case study on hypertension in pregnancy

Case Study: Treating Chronic Hypertension in Pregnancy

Chronic hypertension during pregnancy increases the risk of poor pregnancy and birth outcomes.

Case: A 35-year-old female presents to clinic. She is actively trying for pregnancy and already stopped her birth control. Her medical history includes a 5-year history of hypertension treated with an ACE inhibitor.

Today her blood pressure is 124/68 mmHg and BMI 27 kg/ m 2 . What recommendations do you have for management of this patient’s situation?

Chronic hypertension in pregnancy is defined as >140/90mmHg. 1 The prevalence of hypertension in pregnant women is estimated to be around 3%, with potential association with women having children at a later age. 4

Chronic hypertension during pregnancy increases the risk of poor pregnancy and birth outcomes. 3,4 Although consensus exists to use antihypertensive therapy to treat severe hypertension (systolic ≥160, diastolic ≥105-110 mmHg) during pregnancy, the benefits and safety for treating mild chronic hypertension during pregnancy are unclear.

According to the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy, the controversy in mild to chronic hypertension in pregnancy is due to the lack of evidence to guide therapy. 1

Methyldopa, a centrally acting alpha agonist has traditionally been first line for hypertension in pregnancy. 3 But a common adverse effect (AE) of methyldopa is somnolence.

Drs Seely and Ecker, authors of “Chronic Hypertension in Pregnancy” recommend labetalol. Labetalol, a combined alpha and beta blocker, has fewer AEs than methyldopa. 3 A common AE of labetalol is dizziness. 2

Nifedipine, a long-acting calcium channel blocker, was also an alternative antihypertensive drug. 3,4 ACEis/ARBs are contraindicated because they cause oligohydramnios from impaired fetal growth. 3

The Chronic Hypertension and Pregnancy (CHAP) trial looked at treatment of mild chronic hypertension in pregnancy. This multi center, open label, randomized, controlled trial enrolled 2408 women with mild chronic hypertension and singleton fetus at <23 weeks’ gestation.

The active treatment group had 1202 women and wanted to achieve a systolic blood pressure <140/<90mmHg. The standard treatment group, also 1202 women, received no treatment unless severe hypertension developed ≥160/≥105 mmHg.

The active treatment group received labetalol or extended release nifedipine, or other drugs such as amlodipine or methyldopa by preference. 4 Doses were escalated to the maximum dose to achieve the target blood pressure.

The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth before 35 weeks, placental abruption, or fetal or neonatal death. The active treatment group’s primary outcome was significantly lower than standard treatment, with an approximate incidence of 30.2% versus 37.0%. 4

The safety outcome of the incidence was small for gestational age birth weight below the 10th percentile and did not differ significantly between the active treatment group and standard treatment group. 4 In an analysis of secondary outcomes, composites of serious maternal complications or serious neonatal complications occurred infrequently.

The results suggest lower rates of pre-eclampsia and preterm birth with antihypertensive therapy. 4 Some limitations were that women were aware of their treatment, there was a high ratio of women screened to women enrolled, and this trial was not powered to see treatment effects across subgroups. The authors conclude that treating mild chronic hypertension during pregnancy reduced adverse pregnancy outcomes without impairing fetal growth. 4

Based on this information, the patient in our case should be counseled on contraception until she has her pre-pregnancy evaluation. If she has a reversible cause of chronic hypertension, that should be addressed along with changing her ACE inhibitor to a drug that is safe in pregnancy such as methyldopa, labetalol, or nifedipine. She should also be closely followed during her pregnancy, receive interdisciplinary care from obstetrics and gynecology practitioners, and be educated on pre-eclampsia.

About the Author

Momi Talukdar, PharmD candidate, Northeast Ohio Medical University, Class of 2024, 2022 Mayo Clinic pharmacy intern.

• Hypertension in Pregnancy. American College of Obstetricians and Gynecologists . 2013;122(5):1122-1133. Accessed June 27, 2022. https://oce.ovid.com/article/00006250-201311000-00036/PDF
• Labetalol. Lexi-Drugs. Lexicomp. Wolters Kluwer Health. Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed July 3, 2022
• Seely,E., Ecker, J. 2011. Chronic Hypertension in Pregnancy | NEJM . [online] New England Journal of Medicine. Available at: <https://www/nejm.org/doi/full/10.1056/NEJMcp0804872> [Accessed 27 June 2022].
• Tita, A., Szychowski, J. and Boggess, K., 2022. Treatment for Mild Chronic Hypertension during Pregnancy | NEJM . [online] New England Journal of Medicine. Available at: <https://www.nejm.org/doi/full/10.1056/NEJMoa2201295> [Accessed 24 June 2022].

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• Published: 20 June 2022

Hypertensive disorders of pregnancy: definition, management, and out-of-office blood pressure measurement

• Hirohito Metoki 1 , 2 ,
• Noriyuki Iwama 2 , 3 ,
• Hirotaka Hamada 3 ,
• Michihiro Satoh 1 , 2 ,
• Takahisa Murakami 1 , 2 ,
• Mami Ishikuro 2 &
• Taku Obara 2 , 4  

Hypertension Research volume  45 ,  pages 1298–1309 ( 2022 ) Cite this article

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Hypertensive disorders of pregnancy increase the risk of adverse maternal and fetal outcomes. In 2018, the Japanese classification of hypertensive disorders of pregnancy was standardized with those of other countries, and a hypertensive disorder of pregnancy was considered to be present if hypertension existed during pregnancy and up to 12 weeks after delivery. Strategies for the prevention of hypertensive disorders of pregnancy have become much clearer, but further research is needed on appropriate subjects and methods of administration, and these have not been clarified in Japan. Although guidelines for the use of antihypertensive drugs are also being studied and standardized with those of other countries, the use of calcium antagonists before 20 weeks of gestation is still contraindicated in Japan because of the safety concerns that were raised regarding possible fetal anomalies associated with their use at the time of their market launch. Chronic hypertension is now included in the definition of hypertensive disorders of pregnancy, and blood pressure measurement is a fundamental component of the diagnosis of hypertensive disorders of pregnancy. Out-of-office blood pressure measurements, including ambulatory and home blood pressure measurements, are important for pregnant and nonpregnant women. Although conditions such as white-coat hypertension and masked hypertension have been reported, determining their occurrence in pregnancy is complicated by the gestational week. This narrative review focused on recent reports on hypertensive disorders of pregnancy, including those related to blood pressure measurement and classification.

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Introduction.

In Japan, “pregnancy toxemia”, with three main features, “hypertension,” “proteinuria,” and “edema”, was defined and classified in 1982 [ 1 ] and then again in 1984 [ 2 ]. This term was widely used until 2005, when it was changed to “pregnancy-induced hypertension.” In 2018, the classification was standardized with those of other countries, and “hypertensive disorders of pregnancy (HDP)” were considered to be present if hypertension existed during pregnancy and up to 12 weeks after delivery [ 3 ]. High blood pressure before pregnancy (chronic hypertension) is now included in the definition of HDP. Among the various hypotheses explaining the etiology of HDP, the two-stage theory and angiogenesis imbalance are the most plausible. The two-stage theory of the etiology of HDP may have led to the novel possibility of treatment/prevention for HDP. Furthermore, assessing the circulating levels of angiogenic factors may have diverse clinical roles in preventing adverse outcomes in HDP [ 4 ]. This narrative review focused on recent reports on HDP, including those related to blood pressure measurement and classification.

Classification and definition of hypertensive disorders of pregnancy

HDP are classified into four types: preeclampsia, gestational hypertension, superimposed preeclampsia, and chronic hypertension [ 5 ]. Preeclampsia is defined as hypertension after 20 gestational weeks with proteinuria, organ damage, or uteroplacental dysfunction. Gestational hypertension is similar to preeclampsia; however, the condition is defined as hypertension alone after 20 gestational weeks. Based on the Japan Society for the Study of Hypertension in Pregnancy (JSSHP), superimposed preeclampsia is defined as hypertension accompanied by organ damage or proteinuria [ 3 , 5 ].

In normal pregnancy, spiral artery remodeling occurs, where trophoblastic cells invade the decidua and replace the endothelial cells and vascular smooth muscle of the decidua spiral artery. As a result, the maternal blood vessels begin to perfuse into the interchorionic space, which increases the partial pressure of oxygen in the placenta and reduces systemic vascular resistance (Fig.  1A ). Angiogenic factors, vascular endothelial growth factors (VEGFs), and placental growth factors (PlGFs) affect angiogenesis intracellularly through the receptor VEGFR-1 (Fig.  1B ). Uterine natural killer (uNK) cells and regulatory T cells are essential for maintaining pregnancy and inhibiting allogeneic responses toward the fetus [ 6 , 7 ]. Decidual uNK cells control trophoblast invasion by producing interleukin-8 and interferon-inducible protein-10 chemokines and secrete a series of angiogenic factors [ 8 ]. Early vascular changes resulting from desquamation, such as intimal vacuolation and disintegration, and thinning of the tunica media occur before trophoblastic cells are present near the spiral arteries of the uterus [ 9 ].

Schematic diagram of the two-stage theory of preeclampsia. In normal pregnancy, appropriate EVT invasion into the maternal endometrium (red arrow) leads to sufficient maternal blood flow from the spiral artery ( A ). PlGF, which is secreted from the placenta, activates VEGF and maintains a healthy endothelium ( B ). On the other hand, in preeclamptic pregnancy, incomplete invasion of the EVT (blue arrow) leads to insufficient maternal blood flow from the spiral artery and subsequent placental hypoxia ( C ). sFlt1 is then secreted from the placenta, which suppresses VEGF, resulting in systemic endothelial dysfunction and the appearance of various clinical symptoms ( D ). HELLP syn. hemolysis, elevated liver enzymes, low platelet count syndrome, FGR fetal growth restriction, NK cells natural killer cells, EVT extravillous trophoblast, PlGF placental growth factor, sFlt1 soluble fms-like tyrosine kinase-1, VEGF vascular endothelial growth factor

Preeclampsia

Preeclampsia is a complex medical disorder [ 10 ]. According to recent guidelines in Japan [ 5 ] and other countries [ 10 , 11 , 12 , 13 , 14 ], preeclampsia is characterized by hypertension with maternal acute kidney injury, liver dysfunction, neurological features, hemolysis or thrombocytopenia, or fetal growth restriction. Preeclampsia is thought to originate from the placenta because of the rapid improvement of clinical symptoms of preeclampsia after placenta delivery [ 15 ], while retained placenta leads to the development of preeclampsia; the removal of the placenta by intrauterine curettage results in disappearance of the symptoms [ 16 ].

Insufficient angiogenesis and remodeling cause an incomplete increase in the partial pressure of oxygen in the fetal placental circulation (Fig.  1C ), resulting in placental ischemia and damage [ 17 ]. Stimulated soluble VEGFR-1 (sFlt-1) production in trophoblast cells inhibits PlGF production and soluble endoglin (sEng) production [ 18 ]. Inhibition of VEGF and PlGF by sFlt-1 suppresses the invasion of trophoblastic cells into the shed membrane and damages vascular endothelial cells (Fig.  1D ). By binding and antagonizing TGF-β, sEng inhibits the invasion of cytotrophoblast cells [ 19 ]. The transition of these factors into maternal circulation causes the maternal symptoms of preeclampsia [ 20 , 21 ]. Placental abnormalities in early pregnancy may cause chronic uteroplacental insufficiency, local ischemia, and the release of inflammatory cytokines, resulting in earlier maternal hypertension in early-onset preeclampsia [ 22 , 23 , 24 ]. In contrast, late-onset preeclampsia is more frequently based on placental dysfunction associated with chronic oxidative stress due to maternal metabolic abnormalities such as obesity and insulin resistance [ 22 , 23 , 25 ]. At the same time, there is much overlap in placental pathology and continuous features in desmoplastic vascular lesion pathology among the four HDP subtypes [ 26 ].

Superimposed preeclampsia

Superimposed preeclampsia is defined as chronic hypertension or kidney disease that progresses to preeclampsia [ 3 ]. It should be noted that in countries other than Japan, it basically refers only to superimposed chronic hypertension [ 10 , 11 , 12 , 13 , 14 ]. Vascular endothelial dysfunction is reported to predict the development of superimposed preeclampsia in chronic hypertension [ 27 ]. In preeclampsia following de novo gestational hypertension, early placental calcification and weight gain precede preeclampsia [ 28 ]. Pregnant women with IgA nephropathy [ 29 ] and chronic kidney disease [ 30 ] had 7.3- and 10.4-fold greater risks of preeclampsia than others, respectively.

Chronic hypertension in pregnancy

Blood pressure during early pregnancy seems important in pregnancies complicated by hypertension [ 31 , 32 ]. A systolic blood pressure <130 mmHg within 14–15 weeks of gestation was reported to reduce the risk of early-onset superimposed preeclampsia in women with chronic hypertension [ 33 ]. As described in a later section on white-coat hypertension, it is essential to diagnose whether a patient has sustained or white-coat hypertension. Because chronic hypertension is a risk factor for perinatal mortality in both early and late gestation, a planned delivery at 37 to 38 weeks of gestation is reported to be a superior balance of risk [ 34 ].

Maternal outcomes

Regarding the risk of developing cardiovascular diseases later in life, although there are differences among HDP subtypes, Veerbeek et al. [ 35 ] reported that all types of HDP seem to be associated with high risks. Gestational hypertension is reported to be associated with a 4.2-fold higher risk for future chronic hypertension [ 36 ] and a greater risk of cardiovascular disease, coronary heart disease, and heart failure [ 37 ]. Preeclampsia is associated with a fourfold increased risk of future heart failure and a twofold increased risk of coronary heart disease, stroke, and death due to coronary heart or cardiovascular disease [ 38 ]. Women with HDP were reported to have a 6.3-fold higher risk for future hypertension within 2 years postpartum compared to controls [ 39 ] and a 4.9-fold higher risk of chronic kidney disease in later life [ 40 ].

Birth outcomes

Maternal cardiac output in early pregnancy has been associated with being small for gestational age (SGA) [ 41 ]. Maternal hypertension-related factors were associated with infant growth via placental factors based on the genome wide association study summary statistics of BioBank Japan data and compared with cohort data [ 42 ]. The Hokkaido study showed that women with HDP had 2.1-, 3.5-, and 3.6-fold higher risks of having SGA infants, preterm birth, and infants with low birth weight than those with normotensive pregnancy [ 43 ]. Home [ 44 ] and ambulatory [ 45 ] blood pressure measurements have been shown to be more associated with birth weight than clinic blood pressure; these are reviewed in subsequent sections. The trajectory of maternal blood pressure during pregnancy is also an indicator of infant birth weight [ 46 , 47 , 48 ].

Long-term outcomes of offspring

According to a meta-analysis of eight studies, HDP were associated with a 1.2-fold higher risk of asthma in offspring [ 49 ]. In a study, offspring exposed to HDP had a 1.4- and 1.3-fold higher risk for autism spectrum disorders and attention-deficit hyperactivity disorder, respectively [ 50 ]. The Helsinki Birth Cohort Study reported that offspring exposed to maternal gestational hypertension in utero had an increased risk of type 2 diabetes in late adulthood after adjustment for low birth weight or small for gestational age infants [ 51 ].

The results of studies in Japan on the long-term prognosis of pregnant women with HDP and their children exposed to HDP are now being reported. The TMM BirThree Cohort Study reported that women with superimposed preeclampsia had a 1.8-fold increased risk of having children with autistic behavior at 2 years old compared to normotensive women [ 52 ]. The Hokkaido Birth Cohort Study reported that male children exposed to HDP caught up with their growth and gained more weight by 7 years of age than male children who were not exposed to HDP [ 53 ]. According to observations in the Japan Environment and Children’s Study (JECS), HDP were not a risk factor for offspring regardless of the sensitivity analyses using possible mediating factors such as cesarean delivery, birth weight, and gestational age [ 54 ].

When examining the association between HDP and prognosis, there is no need to adjust for preterm birth and low birth weight because they are included in HDP outcomes and are mediators rather than confounders when considering their impact on the long-term prognosis of offspring [ 49 , 50 , 52 , 53 ]. On the other hand, as mentioned earlier, several studies have performed sensitivity analyses considering the role of HDP as mediators [ 51 , 54 ]. Based on the results of the ongoing mediator analysis and other studies, future studies need to examine possible intervention points for the association between HDP and child outcomes and develop better intervention methods.

Prediction, prevention, and treatment

Associated factors and prediction.

The Fetal Medicine Foundation (FMF) first-trimester prediction model (the FMF triple test) has high detection rates of 90% and 75% for the prediction of early and preterm preeclampsia, respectively, with a 10% false-positive rate [ 55 ]. This FMF triple test consists of a combination of maternal factors and measurements of mean arterial pressure, the uterine artery pulsatility index, and serum placental growth factor. An Asia-wide study using an algorithm developed by the FMF in Asian people confirmed the validity of the FMF triple test with a detection rate of 64% for the prediction of preterm preeclampsia with a 10% false-positive rate [ 56 ].

In addition to the FMF triple test, several predictors have been reported in individual studies, and those presented in this study are listed in Table  1 .

The JECS is a cohort study that started in 2011 to investigate the relationship between environmental exposure and child health. Several studies on HDP have been conducted with the JECS cohort. Higher levels of HbA1c at a nondiabetic level [ 57 ], both lower and higher Na intake before pregnancy [ 58 ], elevated serum IgE levels during the first trimester [ 59 ], higher caffeine intake [ 60 ], working a schedule of ≥36 h per week with night shifts [ 61 ], smoking [ 62 ], alcohol consumption [ 63 ], and becoming pregnant with in vitro fertilization and embryo transfer [ 64 ] were associated with the risk of hypertensive disorders of pregnancy. Moreover, coffee intake was associated with a decreased risk of HDP [ 60 ]. Although this is a large cohort study, some studies reported that no association between the exposures and outcomes can be found, such as calcium intake and HDP among primiparas [ 65 ]. The JECS involves a novel approach to adjunct studies. The peak areas of N-dimethylglycine and S-methylcysteine were significantly higher in the first-trimester serum of patients with early-onset HDP than in controls [ 66 ].

Sleep quality in early pregnancy may help predict elevated systolic blood pressure in the first trimester [ 67 ], and overnight oxygen saturation screening ~1 month before the due date may be useful in predicting late-onset gestational hypertension [ 68 ]. Unmodifiable factors include twin pregnancy [ 69 , 70 ] and residing in a high-altitude area (>2500 m) [ 71 , 72 ]. Blood pressure is known to be elevated in twin pregnancy [ 69 ], regardless of whether the pregnancy is a dichorionic or monochorionic diamniotic twin pregnancy [ 70 ]; therefore, pregnant women with unmodifiable factors should be followed up as high-risk pregnancies.

Several efforts to perform comprehensive metabolomic analysis in samples of pregnant women have been reported, such as the C-MATCH [ 73 ] and HELIX studies [ 74 ]. The metabolite profiles of women who developed HDP were comparable to those of women with normal pregnancies with longer gestation in the Maternity Log study, which is an adjunct to the BirThree cohort study [ 75 ].

Aspirin administration has been described in various guidelines as effective in preventing the onset of preeclampsia. The ASPRE study showed that aspirin treatment for pregnant women at high risk for preeclampsia reduced the incidence of preeclampsia to 0.38 [ 76 ]. The NICE [ 11 ], ACOG [ 12 ], USPSTF [ 77 ], SOGC [ 13 ], SOMANZ [ 14 ], and ISSHP [ 10 ] guidelines state that aspirin should be administered to high-risk pregnant women. However, the Japanese guidelines from the JSSHP that were issued in 2015 state that aspirin should be given to a limited number of women [ 78 ], while those that were issued in 2021 state that aspirin should be considered for women with preeclampsia to prevent recurrence in subsequent pregnancy [ 5 ]. In Asian women, the dose-dependent efficacy of low-dose aspirin [ 79 ] and its efficacy in women with blood pressure of 130–139/80–89 mmHg, which is included in the American College of Cardiology/American Heart Association definition of Stage 1 hypertension or mild hypertension [ 80 ], have also been reported. However, a study reported that aspirin has poor efficacy when started at 12–20 weeks gestation [ 81 ]. The ADA guidelines also strongly recommended aspirin for women with diabetic pregnancies until 2020 [ 82 ]; moreover, the recommendations became weaker in the 2021 edition and later editions [ 83 ]. A recent study reported limited efficacy of aspirin in preventing preeclampsia among women with diabetic pregnancies [ 84 ]. Future studies are warranted on eligible subjects and administration methods.

In principle, in Japan, inpatient management is recommended for HDP patients with blood pressure of 160/110 mmHg or higher, antihypertensive treatment should be given if a patient’s blood pressure is repeatedly found to be 160/110 mmHg or higher, and antihypertensive treatment is considered if a patient’s blood pressure is 140/90 mmHg or higher. Furthermore, if a patient has recurrent blood pressure of 160/110 mmHg or higher or has preeclamptic symptoms, magnesium sulfate should be administered to prevent eclampsia, and if management at the patient’s own facility is difficult, referral to a higher-level medical facility should be considered [ 5 ].

There are concerns that antihypertensive treatment during pregnancy may increase the risk of placental abruption and preterm delivery [ 85 ]. Data from Scotland showed a 2.3-fold increase in congenital defects with the use of antihypertensive drugs [ 86 ]. However, untreated hypertension, not antihypertensive medication, is a risk to the child [ 87 ]. The CHIPS study reported no significant group differences in the risk of pregnancy loss, high-level neonatal care, or overall maternal complications between less-tight (target office diastolic blood pressure of 100 mmHg) and tight (target office diastolic blood pressure of 85 mmHg) control of hypertension in pregnancy [ 88 ]. A recent meta-analysis showed that blood pressure-lowering treatment significantly prevented not only severe hypertension, preeclampsia, and severe preeclampsia but also placental abruption and preterm birth, while the risk of SGA was increased [ 89 ].

Currently, Japanese guidelines refer to methyldopa, hydralazine, and labetalol as oral antihypertensive drugs that can be used during pregnancy, while nifedipine can only be used after 20 weeks of pregnancy [ 5 ]. Guidelines for the use of different antihypertensive drugs have not been developed. There is a possibility of improved maternal prognosis with physiological nomogram-guided care and tailored pharmacological intervention [ 90 ]. In Japan, the use of calcium antagonists in early pregnancy is still not approved on the package label, and deviation from the guidelines is a concern [ 91 ]. However, in Japan, the most frequently prescribed oral antihypertensive drug during pregnancy is nifedipine, followed by methyldopa, hydralazine, and furosemide [ 92 ]. It has been reported that the risk of birth defects due to amlodipine use in the first trimester was not significantly different compared to the risk of the use of other antihypertensives in a case–control study in Japan [ 93 ]; more extensive observation is urgently needed.

Similar concerns have been raised regarding long-term prognosis. A comparison of the long-term prognosis of infants between treatment groups in a historical cohort study also reported the possibility of attention-deficit hyperactivity disorder and sleep disorders in infants whose mothers received drug interventions for gestational hypertension [ 94 ]. On the other hand, studies examining the effects of antihypertensive medications may not have examined baseline blood pressure levels [ 86 ], or baseline blood pressure levels may be obviously different [ 94 ]; hence, the risk of antihypertensive medication use must be carefully assessed. Such concerns are expected to be clarified by national-scale cohort studies.

Blood pressure measurement during pregnancy

There are several debates regarding how blood pressure should be measured during pregnancy [ 95 ]. Reports suggest that blood pressure values in pregnant women with preeclampsia vary depending on the measurement environment [ 96 ]. Hurrell et al. conducted a detailed review of blood pressure measurements in pregnant women [ 97 ]. A recent meta-analysis also confirmed that both systolic and diastolic blood pressure decrease by ~4 mmHg in the second trimester [ 98 ]; the results were very similar to those of a single cohort study investigating the use of home blood pressure [ 99 ].

Ambulatory blood pressure measurement

Ambulatory blood pressure measurement is valuable for diagnosing masked or white-coat hypertension (16) and assessing diurnal variations in blood pressure in pregnant women [ 100 , 101 ]. Normal daytime values for ambulatory blood pressure monitoring in pregnant women have been reported to be less than 130/77 mmHg at ≤22 weeks, 133/81 mmHg at 26–30 weeks, and 135/86 mmHg after 30 weeks [ 102 ]. Diurnal variations in blood pressure during pregnancy have been reported to be nocturnal declines of 12–14%/18–19% in systolic/diastolic blood pressure [ 100 ]. It has also been reported that nocturnal declines in blood pressure are attenuated before gestational hypertension nephropathy becomes apparent [ 101 ]. Among 146 Japanese pregnant women with suspected HDP, ambulatory blood pressure monitoring was more strongly associated with SGA infants, with an odds ratio of 1.74 times for every 10 mmHg increase (95% CI: 1.28–2.38; P  = 0.001) compared with office blood pressure measurement (OR: 1.40; 95% CI: 0.92–2.13; P  = 0.11) [ 45 ].

Home blood pressure measurement

Home blood pressure measurement is suitable for detecting long-term and seasonal variations in blood pressure. In a 2008 statement on home blood pressure measurement, the American Heart Association noted that “Home blood pressure measurement is theoretically ideal for monitoring changes in blood pressure during pregnancy because it is the best technique for providing multiple readings recorded at the same time of day over prolonged periods of time.” [ 103 ]. Furthermore, a report from the consensus meeting of the European Council on Hypertension issued around the same time stated that “Home blood pressure monitoring, although at present not commonly practiced in this setting, has considerable potential in improving the management of pregnant women.” [ 104 ]. According to the Japanese Society of Hypertension guidelines, for general (nonpregnant) patients, if the results of office blood pressure and home blood pressure measurements are different, the home blood pressure result has priority for treatment [ 91 ]. In pregnancy, home blood pressure measurements may be taken by pregnant women before recommendations are made by health care providers. Using home blood pressure monitoring, seasonal blood pressure [ 99 ] and hemodynamic changes are well observed. In a study that simultaneously included both home and clinic blood pressure levels in early pregnancy, the adjusted odds ratios for having a baby that was 500 g smaller per standard deviation increase in mean and diastolic blood pressure were 1.29 (95% CI: 1.04–1.59) and 1.28 (95% CI: 1.04–1.58) for home blood pressure and 1.02 (95% CI: 0.83–1.24) and 1.06 (95% CI: 0.87–1.30) for clinic blood pressure, respectively, with only home blood pressure measurements having a significant association [ 44 ]. Furthermore, the maternal blood pressure trajectory during pregnancy was an indicator of infant birth weight [ 46 ]. However, no study has determined whether interventions based on home blood pressure measurements improve outcomes.

Several values have been proposed as the diagnostic threshold of home blood pressure based on population distribution and regression with office blood pressure values. Using the standard major axis method, the home blood pressure values reported to be equivalent to a clinical blood pressure of 140/90 mmHg were 120.8/83.5 mmHg, 126.0/85.2 mmHg, and 136.3/89.3 mmHg in the first, second, and third trimesters, respectively [ 105 ]. However, no consensus value has been established [ 106 ].

A meta-analysis reported in 2020 summarized nine studies and noted that the use of home blood pressure measurements in the antenatal period was associated with a reduced risk of induction of labor, hospitalization before delivery, and diagnosis of preeclampsia and that the number of prenatal visits was significantly lower in the home blood pressure group, but there was no significant difference in the combined maternal, fetal, or neonatal outcomes compared to conventional care [ 107 ].

Clinical significance of white-coat hypertension

White-coat hypertension is a condition in which a patient has high blood pressure in the office but normal blood pressure outside the office. Generally, 24-h ambulatory blood pressure monitoring or home blood pressure monitoring may be used to identify white-coat hypertension. Ishikuro et al. reported that among pregnant women who were normotensive, the white-coat effect during pregnancy was 4.1/3.8, 3.4/1.6, and 1.8/2.4 mmHg in early, mid-, and late pregnancy, respectively [ 108 ]. When the factors affecting the white-coat effect were examined in the same population, no significant differences were found for body mass in sex, age, or family history of hypertension. However, the effect was significantly greater in primiparas than in multiparas in early pregnancy for systolic blood pressure and in late pregnancy for diastolic blood pressure [ 109 ]. A meta-analysis of 16 studies on the white-coat effect showed that office blood pressure measurements were 4/3 (3–6/2–4) mmHg higher than home blood pressure measurements [ 106 ]. White-coat hypertension is prevalent in women with preexisting diabetes and may indicate an increased risk of developing pregnancy-induced hypertensive disorders later in life [ 110 ].

Based on ambulatory blood pressure monitoring in early pregnancy, it has been reported that 22% of pregnant women have sustained hypertension, and 8% of those with white-coat hypertension develop preeclampsia; thus, white-coat hypertension in pregnancy may have a relatively good prognosis [ 102 ]. It is essential to recognize that hypertension in the office may not necessarily require antihypertensive treatment if the blood pressure outside the office is normal. However, 42% of pregnant women with white-coat hypertension in early pregnancy showed hypertension both in the office and out of the office until delivery [ 102 ]; therefore, careful follow-up is necessary in such cases.

Clinical significance of masked hypertension

There are few studies on masked hypertension in pregnant women. Salazar et al. reported that masked hypertension is a prevalent and high-risk condition. An office blood pressure of ≥125/75 mmHg in the second half of gestation seems appropriate for indicating out-of-office measurements in women with high-risk pregnancies [ 111 ]. Pregnant women with masked hypertension had a 7.8 times higher risk of preeclampsia than those who were normotensive [ 112 ]. Unlike white-coat hypertension, masked hypertension cannot be detected unless all pregnant women who are at risk receive out-of-office blood pressure measurements. Therefore, further study is needed to determine which women should undergo blood pressure measurement outside the office.

Present blood pressure monitoring situations in clinical practice

According to a survey reported in 2021, 89.3% of obstetricians took blood pressure measurements in an outpatient setting only once per occasion if a woman’s blood pressure was normal. However, if the pregnant women had hypertension, 54.8% took a second measurement, and 40.3% repeated blood pressure measurements until a stable reading was obtained [ 113 ]. Furthermore, 62.8% of the obstetricians recorded the lowest value when they measured blood pressure twice, and 69.0% of the physicians recorded the last measurement when the blood pressure was measured until it stabilized [ 113 ]. Therefore, when conducting research based on databases, researchers need to recognize some variation in the measurements recorded on each measurement occasion. On the other hand, blood pressure measurements for research purposes at a venue different from that of the antenatal checkup was reported to be equivalent to home blood pressure measurements and significantly lower than those at antenatal checkups, and the possibility of a stressful environment during the antenatal checkup causing an increase in blood pressure should be considered [ 114 ].

A survey of family medicine and obstetrics/gynecology physicians providing prenatal care at a tertiary obstetrics hospital in Canada found that obstetricians were more likely to use home blood pressure monitoring. In contrast, family physicians were more likely to use 24 h ambulatory blood pressure monitoring as a diagnostic aid. While obstetricians were more likely than family physicians to use effective home blood pressure monitoring during pregnancy and monitor hypertension with home blood pressure monitoring, family physicians were significantly more likely than obstetricians to target “tight” blood pressure control [ 115 ].

In a survey of 128 patients conducted in the United States, postpartum women perceived a telehealth technology remote intervention as a safe and easy-to-use method, with an acceptable burden of care and an overall satisfactory method of monitoring blood pressure in the postpartum period [ 116 ]. A survey conducted in Belgium reported that 80% of midwives and 67% of obstetricians who used remote blood pressure monitoring in pregnancy perceived digital technologies as an important component of prenatal monitoring [ 117 ]. The results of an online survey of obstetricians in the United Kingdom showed that the percentage of obstetricians who thought that home blood pressure measurements and urinalysis were helpful indicators of clinical diagnosis rose from 88% before the COVID-19 pandemic to 96% after the pandemic. In addition, 47% of the obstetricians agreed that pregnant women would change their predetermined medications based on their measured blood pressure levels [ 118 ].

Novel attempt at blood pressure telemonitoring

In 2008, the transmission of home blood pressure measurements was discussed [ 119 ], but the explorations of remote monitoring are rapidly progressing during the COVID-19 pandemic. A study examined current practices and attitudes concerning home-based blood pressure and cardiotocography monitoring and telemonitoring in high-risk pregnancies requiring maternal and fetal monitoring and reported that home-based monitoring and telemonitoring were offered in 26% and 23% of hospitals, respectively, in the Netherlands [ 120 ]. In a retrospective comparison, the digital platform among high-risk pregnancies significantly reduced prenatal visits, ultrasounds, and hypertension-related hospitalizations compared to usual care without self-monitoring.

As mentioned earlier, the Maternity Log study [ 75 ] attempted to collect life logs, including home blood pressure measurements. There have been text-based attempts at blood pressure management in the postpartum period [ 121 ]. A study attempted to use a smartphone application to monitor home blood pressure in Belgium [ 122 ]. A prospective, randomized, controlled trial, called BP-PRESELF, using home blood pressure measurements is ongoing to assess whether home blood pressure monitoring in women with a history of preeclampsia/HELLP syndrome during pregnancy is a valuable tool for the early detection of chronic hypertension [ 123 ].

Blood pressure measurement during pregnancy is crucial in diagnosing HDP. The precise measurement and evaluation of blood pressure, including its variability, will continue to play an essential role in determining the prognosis and elucidating the pathogenesis of HDP.

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Acknowledgements

All authors have significantly contributed to and agree with the content of the manuscript. We would like to thank Editage ( www.editage.com ) for English language editing.

This study was supported by Grants for Scientific Research [16H05243, 19H03905, 10632242, 19K18659] from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Japan Agency for Medical Research and Development (AMED) Birthday [grant number: JP21gk0110039]; and a Grant-in-Aid (19DA1001) from the Ministry of Health, Labor and Welfare, Health Research on Children, Youth and Families, Japan.

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Hirohito Metoki, Michihiro Satoh & Takahisa Murakami

Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan

Hirohito Metoki, Noriyuki Iwama, Michihiro Satoh, Takahisa Murakami, Mami Ishikuro & Taku Obara

Department of Obstetrics and Gynecology, Tohoku University Hospital, Sendai, Japan

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HM concurrently holds the noncompensated subdirectorship at the Tohoku Institute for Management of Blood Pressure, which is supported by Omron Health Care Co. Ltd., and is involved in collaborative research with Omron Health Care in another study. HM has also received grants or scholarships from Academic Contributions from Pfizer Japan Inc., Astellas Research Support, Daiichi Sankyo Co. Ltd., Bayer Academic Support, Otsuka Pharmaceutical Co., Ltd, Takeda Research Support, Eli Lilly Japan K.K., Baxter Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., and Teijin Pharma Limited. These companies were not involved in this review article.

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Metoki, H., Iwama, N., Hamada, H. et al. Hypertensive disorders of pregnancy: definition, management, and out-of-office blood pressure measurement. Hypertens Res 45 , 1298–1309 (2022). https://doi.org/10.1038/s41440-022-00965-6

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• Antihypertensive Agents
• Blood Pressure
• Hypertension
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• Masked Hypertension
• White-Coat Hypertension

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• Published: 06 January 2020

Risk factors associated with hypertensive disorders in pregnancy in Nekemte referral hospital, from July 2015 to June 2017, Ethiopia: case-control study

• Leta Hinkosa 1 ,
• Almaz Tamene 2 &
• Negeso Gebeyehu 3  

BMC Pregnancy and Childbirth volume  20 , Article number:  16 ( 2020 ) Cite this article

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Hypertension is the most common medical problem encountered in pregnancy and is a leading cause of perinatal and maternal morbidity and mortality. However, its magnitude and risk factors yet not adequately assessed at the study area.

Facility-based retrospective unmatched case-control study was conducted to identify risk factors associated with Hypertensive disorders of pregnancy in Nekemte Referral Hospital just two years back from study period July 1, 2015, to June 30, 2017. Bivariate logistic regression was considered for inclusion in to the multivariate logistic regression. Finally, multi varaite analysis were done to identify risk factors of hypertensive disorders of pregnancy.

Among 6826 total delivery records from July 2015 –June 2017, 199 women developed hypertension during pregnancy. Among 199 women 153(76.9%) were pre-eclampsia/eclampsia,28(14.1%) were gestational hypertension, 14(0.7%) were superimposed hypertension and 4 (2.9%) were chronic hypertension.

Age ≥ 35 (AOR: 2.51, 95% CI: 1.08, 5.83), rural residential area (AOR: 1.79, 95% CI: 1.150, 2.799), prim gravida (AOR: 3.39, 95% CI: 2.16, 5.33), null parity (AOR: 4.35, 95% CI: 2.36, 8.03), positive history of abortion (AOR: 4.39, 95% CI: 1.64, 11.76), twin pregnancy (AOR: 3.78, 95% CI: 1.52, 9.39), lack of ANC follow up (AOR: 3.05, 95% CI: 1.56, 5.96) as well as positive pre-existing hypertension (AOR: 3.81, 95% CI: 1.69, 8.58), positive family history of hypertension (AOR: 5.04, 95% CI: 2.66, 9.56) and positive history of diabetes mellitus (AOR: 5.03, 95% CI: 1.59, 15.89) were risk factors for hypertensive disorders during pregnancy.

This study found that Women with hypertension during pregnancy have a greater risk of developing adverse pregnancy outcome as compared to normotensive pregnant women. so, identification of these risk factors would be useful for early diagnosis of hypertension disorders during pregnancy to give appropriate clinical monitoring and treatments and timely managing maternal and perinatal complications.

Peer Review reports

Hypertension is a clinical term used to describe high blood pressure [ 1 , 2 ]. Hypertension in pregnancy is defined as: “Systolic blood pressure greater than or equal to 140 mmHg and/or diastolic blood pressure greater than or equal to 90 mmHg which usually confirmed within four hours apart measurement” [ 2 ].

Hypertension disorder of pregnancy encompasses a spectrum of conditions including pre-existing hypertension, gestational hypertension, preeclampsia/eclampsia, and superimposed hypertension.

These conditions range from a mild increase in blood pressure at term with no additional signs or symptoms to severe complications with potential for significant maternal, fetal and neonatal harm [ 3 ]. Globally, a significant number of women die every year from pregnancy-related causes and more than half of these deaths occur in sub-Saharan Africa [ 4 ]. Approximately 12% of the maternal deaths are associated with hypertensive disorders in pregnancy such as pregnancy-induced hypertension [ 1 , 2 , 3 , 4 ,]. For that reason, hypertension complications are among the main public health issues worldwide.

A Hospital-based cross-sectional study conducted in Jimma University Specialized Hospital in Ethiopia showed that the overall prevalence of hypertensive disorders of pregnancy was 8.5% of which severe preeclampsia and eclampsia accounted for 51.9 and 23.4%, respectively [ 5 ]. Moreover, the study done in Debre Brehan Referral Hospital indicated that among 8626 pregnant women who obtained delivery services, 340(3.9%) of them had hypertensive disorders with an increasing trend from 1.8% in 2011 to 5.7% in 2014 [ 6 ].

On the other hand, though in Ethiopia, the efforts have been done to identify the risk factors of hypertension and to overcome its effect, its prevalence and risk factors were increasing in the country. The study area population was found in the western part of the country. The study area was the place where the population was highly affected by hypertension disorders during pregnancy. Besides, there is a scarcity of study conducted on risk factors associated with HDP in Nekemte Referral Hospital.

Therefore, it is essential to undertake this study to determine the risk factors and its complications both on mothers and on new-borne in the Hospital.

The facility-based retrospective case-control study was conducted to identify risk factors associated with hypertensive disorders of pregnancy in Nekemte Referral Hospital from July 1, 2015, to June 30, 2017.

Source population

All mothers who delivered in Nekemte Referral hospital.

Study population

Cards of mothers who gave birth in Nekemte referral hospital from of July 2015 to June 2017 and found to have hypertensive disorders during pregnancy.

Control group

Cards of mothers who gave birth in the hospital and not identified to have hypertensive disorders during pregnancy.

Sample size determination

The sample size was determined on the assumptions of the ratios of 1:2, (cases to controls) power 80%, alpha value 95%, and odd ratio 2 by considering relevant factors from other studies that have significant association with hypertension [ 7 , 8 , 9 , and].

From Table 1 , The final sample size was taken from diabetes by adding 10% for incomplete record reviews for the control group since it is the maximum for case (243) and for control (534) the total sample size was 777.

Sampling technique and procedure

Among 6826 records of pregnant mothers who gave birth in the study areas, from July 2015 to June 2017 were first sorted for hypertension and without hypertension. Then, based on 1:2 ratios of samples of cases and controls, respectively, 534 (including 10% for incomplete records) normotensive deliveries were randomly selected.

Out of 777 selected records, 44 cases and 136 controls were excluded from analysis for incomplete of the necessary information. The final data of the study were collected from 199 (81.9%) cases and 398 (74.5%) controls which adds to up 597 women by inclusion criteria.

Variables of the study

A. Dependent variable : Hypertensive disorder of pregnancy.

B. Independent variables.

Demographic variables : Age, Residential area, Marital status, Plan of pregnancy.

Obstetric factors : Gravida. Parity. Abortion history, ANC follow up, Multiplicity of pregnancy.

Medical Disease factors : Pre-existing hypertension, Family history of hypertension. History of diabetes mellitus.

Data collection

Data was collected from record review using a structured and pre-tested checklist. The training was given for both data collectors and supervisors. Three midwives were assigned to collect the data, one supervisor was assigned to supervise the quality data collection.

Data analysis procedures

Records that shows hypertension during pregnancy were taken as case group and the remaining registries were taken as a control group. Then, to identify the sample and control group, the medical record was retrieved and checked for hypertension during pregnancy.

Accordingly, records that show one of the four of HDP types (gestational hypertension, chronic hypertension, pre-eclampsia/ eclampsia or superimposed hypertension) were taken as case group first and then from the remaining registries control group was randomly obtained.

The criteria were an elevation of blood pressure for gestational hypertension whereas blood pressure, protein urea and other laboratory investigations were used as a criterion for other types of hypertensive disorders. Then finally descriptive statics and logistic regression were used. Descriptive statistics such as frequency, a measure of central tendency and measure of dispersion where were calculated to describe the study sample and presented with tables and figures. To determine factors that were significantly associated with hypertension, the first bivariate logistic regression was done. Then, multiple logistic analysis was performed for those variables identified as significant on bivariate analysis.

Among 6826 of the total delivery records during the study period, 243 (3.56%) women had HDP. Of 777 selected records, 44 cases and 136 controls were excluded from analysis for incomplete of necessary information. The final data of the study were collected from 199 (81.9%) of cases and 398 (74.5%) of controls which adds to up 597 women.

Demographic characteristics of women with and without HDP

The mean age of cases was 26.1(SD: ±6.1) which was higher than that of the controls 24.4(SD: ±4.9). Eighty-six (43.2%) of the cases and 218(54.8%) of the controls were below the age of 25 years whereas 28(14.1%) of the cases and 19(4.8%) of the controls were above the age of 35 years ( Table 2 ).

Medical disease history of women with and without HDP

Concerning to medical disease factors, 35(17.6%) of cases and 15(3.8%) of controls had positive pre-existing hypertension whereas 164(82.4%) of cases and 383(96.2%) of controls had not pre-existing hypertension.

Obstetric history characteristics of women with and without HDP

Among study participants, 109 (54.8%) of the case group and 102(25.6%) of the control group were identified for prim gravida while 90(45.2%) cases and 296(74.4%) of controls were of multigravida pregnancies ( Table 3 ). Regarding parity, 64(32.2%) of cases and 24(6.0%) of controls were found to be nulliparous whereas 135(67.8%) of cases and 374(94.0%) controls were of parity greater or equal to 1. The parity difference between two groups was significant (χ2 (1, n  = 597) =70.02, p  = .00, phi = −.35).

As it showed in Fig. 1 : there were 153 (76.9%) pre-eclampsia/ eclampsia, 28 (14.1%) gestational hypertension, 14(7.0%) superimposed hypertension, and 4(2.0%) chronic hypertension (Fig. 1 ).

Percentage of Prevalence of Hypertension disorders among cases of the study

Multivariate analysis of risk factors for women with and without HDP

The multivariate analysis revealed that, the age category of 35 years and above (AOR: 2.51, 95% CI: 1.08, 5.83), rural dwellers (AOR: 1.79, 95% CI: 1.15, 2.80), prim gravida pregnancies (AOR: 3.39, 95% CI: 2.16, 5.33),null parity (AOR: 4.35, 95% CI: 2.36, 8.03),women who had positive history of abortion (AOR: 4.39, 95% CI: 1.64, 11.76),Twin pregnancies (AOR: 3.78, 95% CI: 1.52, 9.39), ANC follow up (AOR: 3.05, 95% CI: 1.56, 5.96), positive pre-existing history of hypertension (AOR: 3.81, 95% CI: 1.69, 8.58),family history of hypertension (AOR: 5.04, 95% CI: 2.66, 9.56) History of diabetes mellitus (AOR: 5.03, 95% CI: 1.59, 15.89) were risk factors for hypertension disorders during pregnancy ( Table 4 ).

Differences in maternal outcomes between women with and without HDP

Regarding the onset of labor, induced labor or C/S 108(54.3%) for cases and 48(12.1%) controls. The difference of onset of labor between those with and without HDP groups was significant (χ2 (1, n  = 597) = 123.50, p  = .000, phi = .46) ( Table 5 ).

Normal and instrumental deliveries were higher among controls (60.8%) and (44.2%) than cases (29.9%) and (16.1%) respectively.

Differences in perinatal outcomes between women with and without HDP

There was low birth weight for 72(36.2%) cases and 15(3.8%) controls (Fig. 2 ).

Delivery modes for women with and without Hypertension disorders of pregnancy

The difference of number of low birth weight between both groups was significant (χ2 (1, n  = 597) = 123.76, p  = .000, phi = .46) ( Table 6 .)

Risk factors of hypertension disorders during pregnancy

This study was conducted to identify the possible risk factors, maternal and perinatal outcomes of hypertensive disorders in pregnancy in Nekemte Referral Hospital, Ethiopia. The study revealed that the proportion of hypertensive disorders of pregnancy was 3.56%, which was lower than the study conducted in Tikur Anbessa Hospital, Jimma University Specialized Hospital and Debre Berhan Referral Hospital [ 3 , 5 , 6 , 10 ]. The reason might be due to the development of awareness creation made on controlling danger signs of maternal health by extension health workers in the current study than earlier study in a rural area.

This study showed that the extreme ages of reproductive years were found to be risk factors for hypertension during pregnancy with high incidence rates in old ages of greater than 35 years in comparison with the age range of 25–29 years. Concerning the current study, a hospital-based cross-sectional study conducted in Dassie Referral Hospital [ 11 ] and in Derashe, woreda [ 7 ] in Ethiopia reported that late age 30 years in some cases and age greater than 35 years in most cases were significantly associated with Hypertensive disorders of pregnancy.

About two folds of cases of HDP (64.8%) were living in a rural area comparing to urban residence for this study. Then the rural residential area was found to be one of the risk factors of HDP.

This finding was similar to a study done in Jimma hospital of a similar country [ 5 ].

In the current study, those women with prim gravida pregnancies had 3.40 times higher odds of developing hypertension disorders as compared with their counterparts. Also, the occurrence of HDP was reported more serious in prim gravida mothers of case groups than the control group [ 12 ]. This is maybe because getting pregnancy for the first time likely induces psychological stress and physical boredom that make women at risk of the development of HDP.

In this study, women with previous abortions had 4.40 times higher odds of more likely to develop hypertensive disorders than with no previous abortion. Which is inconsistent with the current findings. For instance, a study conducted in Iran reported a noticeable effect of the history of abortion on increasing the risk of mild preeclampsia [ 13 ]. further noted that there was no significant difference in the incidence of preeclampsia between women with no history of previous abortion and term pregnancy and women who had previous preterm birth [ 14 , 15 ].

This study indicated that twin pregnancies had more than three folds of developing hypertension during pregnancy as compared with having singleton pregnancies. This result is in line with the research conducted in Northeastern Ethiopia [ 11 ]. This study has shown that lack of antenatal care had more likely associated with hypertension disorder during pregnancy. A similar finding was found in Egypt [ 16 ] in which preeclampsia was higher in women who had not ANC follow up. This could be due to women who had ANC follow up might get preventive measures for preeclampsia from health care providers during their ANC follow up.

The present study revealed that the positive previous history of preeclampsia was significantly associated with the development of hypertension. Women who had pre-existing hypertension were more likely to develop hypertensive disorders compared to women who had a negative family history of hypertension.

This study coincides with the findings reported as women presenting preeclampsia/eclampsia constituted a high-risk group for developing long term chronic hypertension [ 17 ]. Besides, there is consensus in the literature regarding the role of the previous history of preeclampsia as a contributing factor for preeclampsia [ 8 , 10 , 18 ].

In this study, a family history of hypertension had also a significant relationship with hypertensive disorders of pregnancy. Women who had a positive family history of hypertension were more likely to develop hypertensive disorders compared to women who had a negative family history of hypertension. More similar studies including in the Tigray region, Ethiopia revealed that a positive family history of chronic hypertension was a risk factor for HDP [ 8 , 10 , 15 , 18 , 19 , 20 , 21 , 22 ].

From these findings, it seems that both maternal and fetal genes play a role in this syndrome. Therefore, for pregnant women with a family history of HDP, it should be monitored carefully both perinatally and in the postpartum period.

Another finding showed that gestational diabetes mellitus was significantly associated with hypertension disorders during pregnancy. It is supported by numerous studies that diabetes mellitus was considerable risk factors for the development of preeclampsia [ 10 , 23 , 24 , 25 ].

In this study, diabetes Mellitus was found to be an important risk factor for developing HDP. It was 5.03 times higher for the positive history of diabetes mellitus. Thus, actions in public health focused to prevent these diseases are important to also prevent preeclampsia.

Differences in pregnancy outcomes between women with and without HDP

Cases and control of this study found to have significant differences in maternal and perinatal comes. Accordingly, induced labor or cesarean sections (CS) was significantly higher in cases 81(40.7%) than in controls 8(2.0%). Besides, data obtained on the mode of delivery show that Cesarean Section was higher in cases than in controls were as normal spontaneous vaginal delivery and instrumental deliveries were more common in controls than in cases.

The difference between the prevalence of abruption placenta complication between women with and without HDP was found to be significant.

The magnitude of the abruption placenta was more than three-fold in cases compared to in controls. Corresponding to this finding, it was reported that placental abruption was a common complication of mothers experiencing any type of hypertension during pregnancy [ 26 , 27 ].

A considerable number of studies have reported that preterm birth was significantly higher in women with HDP than without. For instance, a study conducted in China indicated that 29.36% of women who had HDP gave birth before 37 weeks of gestation than 6.78% of women without HDP [ 26 ]. Besides, a study in Portugal showed a statistically significant association between preterm delivery and severity of HDP [ 28 ].

Of course, it is very important to conducted further studies with adequate samples in different parts of our country to determine the magnitude of difference that case and control groups have on giving preterm births.

A study conducted in Mettu Karl Referral Hospital reported that 120.37 perinatal mortality per 1000 deliveries, 10.2% stillbirth rate,30.5% low birth weight, low 18.5% APGAR score and 31.4% preterm delivery outcomes in women with HDP [ 29 ].

Besides Tesfaye A and Tilahun M. indicated 21.2% of infants of women with HDP were admitted in a neonatal intensive care unit [ 30 ].

Regarding pregnancy complications, among women with HDP in this study, 24.6, 9.5, 8.0, 3.5, and 3.5% of them had developed complications of eclampsia, abruption placenta, DIC, acute renal failure, and pulmonary edema, respectively.

To this end, many studies reported similar findings [ 1 , 6 , 31 , 32 , 33 ]. The findings show that both maternal and fetal morbidity and mortality were higher in HDP. That is, maternal and perinatal complications women with HDP are common elsewhere in our world with a more severe rate in developing countries. Thus, improving antenatal care for pregnant mothers in our country is indispensable.

Strength and limitation of the study

This study was done on the hypertensive disorders during pregnancy, which is one of the major maternal and perinatal cause of death. The use of a case-control study design helped to compare the effect of hypertension disorder between women with and without HDP.

We utilized secondary data; which might be encountered to lack some of variables.

There were missed variables such as socio-demographic characteristic such as maternal education level, maternal weight, and height, smoking status of mothers.

Conclusions and recommendations

Women with hypertension during pregnancy have a greater risk of having adverse pregnancy outcomes as compared to normotensive pregnant women. Old age, rural residential area, being single, nulliparity, positive history of abortion, twin pregnancy, lack of ANC follows up, positive pre-existing hypertension, positive family history of hypertension and positive diabetes mellitus were identified as risk factors for developing hypertensive disorders of pregnancy.

Recommendation

Based on the findings the following recommendations were given.

Strengthening ANC service to strengthen counseling and managing the complication early.

Strengthening neonatal intensive care unit (including expansion) in health facilities could be an important input in reducing neonatal complications.

Availability of data and materials

The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Antenatal care

Adjusted odd ratio

Cesarean section

Confident Interval

Disseminated intravascular coagulopathy

Hypertension disorders during pregnancy

Standard Deviation

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The researcher acknowledges to Wollega University, College of Health Science, Department of Midwifery, and Nekemte specialized Hospital card room, Obstetric, and Gynecologic Department for their support during data collection.

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Almaz Tamene

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Negeso Gebeyehu

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Hinkosa, L., Tamene, A. & Gebeyehu, N. Risk factors associated with hypertensive disorders in pregnancy in Nekemte referral hospital, from July 2015 to June 2017, Ethiopia: case-control study. BMC Pregnancy Childbirth 20 , 16 (2020). https://doi.org/10.1186/s12884-019-2693-9

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• Risk factors
• Hypertension disorders

BMC Pregnancy and Childbirth

ISSN: 1471-2393

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• Introduction
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Data are from analyses adjusted for covariates in model 3, including maternal age, paternal age, maternal educational level, maternal residence, household annual income, mode of conception, singleton, offspring sex, offspring age, mode of delivery, gestational week at birth, birth weight, and offspring refractive error. ARR indicates adjusted relative risk; NA, not applicable.

eTable 1. Comparisons of Characteristics Between the Included and Excluded Offspring and Their Parents

eTable 2. The ICD-10 Codes Used to Identify Different Types of Maternal HDP

eTable 3. Missing Data for Covariates

eTable 4. Comparisons of Characteristics Between Offspring With Complete and Incomplete Data of Covariates Adjusted in Model 2

eTable 5. Comparisons of Characteristics Between Offspring With Complete and Incomplete Data of Covariates Adjusted in Model 3

eTable 6. Relative Risks for the Association Between Maternal DIP and Overall and Specific Types of Strabismus in Offspring

eTable 7. Relative Risks for the Association Between Maternal HDP and Overall and Specific Types of Strabismus Restricted to Offspring Without Exposure to Maternal Alcohol Consumption During Pregnancy

eTable 8. Relative Risks for the Association Between Maternal HDP and Overall and Specific Types of Strabismus Restricted to Offspring Without Exposure to Maternal Smoking During Pregnancy

eTable 9. Relative Risks for the Association Between Maternal HDP and Overall and Specific Types of Strabismus Restricted to Offspring With Normal Apgar Score

eTable 10. Relative Risks for the Association Between Maternal HDP and Overall and Specific Types of Strabismus Restricted to Offspring Without Congenital Abnormality

eTable 11. Relative Risks for the Association Between Maternal HDP and Overall and Specific Types of Strabismus Restricted to Offspring With Normal Head Circumference

eTable 12. Relative Risks for the Association Between Maternal HDP and Overall and Specific Types of Strabismus Restricted to Offspring Born to Primipara

eTable 13. Relative Risks for the Association Between Maternal HDP and Overall and Specific Types of Strabismus Restricted to Term-Born Children of Normal Birth Weight

eTable 14. Relative Risks for the Association Between Maternal HDP and Overall and Specific Types of Strabismus After Excluding Children With Exposure to Paternal Hypertension or Diabetes Before Pregnancy

eTable 15. Relative Risks for the Association Between Maternal HDP and Overall and Specific Types of Strabismus Restricted to Children Born to Mothers With Prepregnancy BMI <24

eTable 16. Relative Risks for the Association Between Maternal HDP and Overall and Specific Types of Strabismus After PSM

eTable 17. Direct Comparisons of Overall Strabismus Risk in Offspring Between Different HDP Types, BP Control Levels, or Their Combinations

eFigure. Directed Acyclic Graph Documenting Assumptions About the Association Between Covariates, Exposure, and Outcome

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Zhu H , You X , Jing Y, et al. Maternal Hypertensive Disorder in Pregnancy and Childhood Strabismus in Offspring. JAMA Netw Open. 2024;7(7):e2423946. doi:10.1001/jamanetworkopen.2024.23946

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Maternal Hypertensive Disorder in Pregnancy and Childhood Strabismus in Offspring

• 1 Department of Ophthalmology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
• 2 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
• 3 Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
• 4 Department of Maternal, Child and Adolescent Health, School of Public Health, Nanjing Medical University, Nanjing, China
• 5 State Key Laboratory of Reproductive Medicine (Suzhou Centre), The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
• 6 Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China

Question   Is there an association between maternal hypertensive disorder of pregnancy (HDP) and childhood strabismus in offspring?

Findings   In this cohort study that included 3117 children, offspring born to mothers with HDP had an 82% higher overall risk of strabismus at 3 years of age, and offspring with maternal preeclampsia and poorly controlled blood pressure had the highest risk.

Meaning   These findings suggest that early screening of strabismus might be recommended for offspring born to mothers with HDP, especially those with maternal preeclampsia or poorly controlled blood pressure.

Importance   Maternal hypertensive disorder in pregnancy (HDP) might affect ocular health in offspring; however, its association with strabismus remains unclear.

Objective   To examine the association of maternal HDP with overall and type-specific strabismus in offspring.

Design, Setting, and Participants   In the Jiangsu Birth Cohort study, a population-based study in China, pregnant women were recruited from April 24, 2014, to November 30, 2018. A total of 6195 offspring had maternal HDP diagnosis information, of whom 3078 were excluded due to having no information on ocular alignment or due to having ocular diseases other than strabismus or refractive error. Offspring underwent ocular examinations at 3 years of age, completed May 21, 2022. Data were analyzed from May 28, 2022, through December 15, 2023.

Exposure   Maternal HDP, categorized into hypertension and preeclampsia or with blood pressure (BP) well controlled (systolic BP, <130; diastolic BP, <80 mm Hg) and poorly controlled (systolic BP, ≥130; diastolic BP, ≥80 mm Hg).

Main Outcomes and Measures   The primary outcome was the incidence of strabismus in offspring. Poisson generalized linear mixed models were used to estimate the association between maternal HDP and strabismus.

Results   Among the included 3117 children (mean [SD] age, 36.30 [0.74] months; 1629 boys [52.3%]), 143 (4.6%) were exposed to maternal HDP and 368 (11.8%) had strabismus. Offspring exposed to maternal HDP had an 82% increased risk of overall strabismus (relative risk [RR], 1.82 [95% CI, 1.21-2.74]), an 82% increased risk of exophoria (RR, 1.82 [95% CI, 1.11-3.00]), and a 136% increased risk of intermittent exotropia (RR, 2.36 [95% CI, 1.13-4.93]) compared with unexposed offspring. When considering the type of maternal HDP, the risk for all strabismus was high for offspring exposed to preeclampsia (RR, 2.38 [95% CI, 1.39-4.09]) compared with unexposed offspring. When considering the BP control level of maternal HDP, the risk for all strabismus was high for offspring born to mothers with HDP and poorly controlled BP (RR, 2.07 [95% CI, 1.32-3.24]) compared with unexposed offspring.

Conclusions and Relevance   These findings suggest that maternal HDP is associated with an increased risk of offspring strabismus. Early screening of strabismus might be recommended for offspring with maternal HDP. Further exploration of the underlying mechanism of the association between HDP and strabismus is warranted.

Strabismus, which is defined as a deviation from ideal ocular alignment, is one of the most common childhood ocular disorders. It can cause amblyopia, impaired appearance, and psychosocial problems. 1 If the deviation is absent when both eyes are open for viewing, it is considered latent strabismus; otherwise, it is considered manifest strabismus. The prevalence rate ranges from 4% to 58.3% for latent strabismus 2 - 7 and from 0.8% to 5.7% for manifest strabismus. 8 - 13 The etiology and pathogenesis of childhood strabismus remain to be elucidated. 14 Previous studies have found that perinatal factors, including gestational weeks of age, 15 - 18 birth weight, 15 , 16 , 19 Apgar score, 20 congenital abnormality, 21 and parental exposures such as maternal smoking and alcohol consumption during pregnancy, 17 , 22 , 23 are associated with childhood strabismus. These findings imply that aberrant fetal growth and suboptimal intrauterine environments may contribute to the onset of strabismus.

Hypertensive disorder in pregnancy (HDP) is one of the most common cardiometabolic disorders during pregnancy, affecting 5% to 10% of pregnancies worldwide, leading to aberrant fetal growth and intrauterine oxidative stress. 24 Growing evidence 25 - 30 has shown that maternal HDP might be related to ocular abnormalities and diseases in offspring, including narrower retinal microvasculature, thinner retina, larger optic cup, refractive error, retinopathy of prematurity, and amblyopia. Some studies 16 , 21 , 29 , 30 have explored the association of maternal HDP with offspring strabismus, but the findings were preliminary and inconsistent. Recent evidence also suggests that maternal diabetes in pregnancy (DIP) is associated with offspring refractive error. 31 Therefore, the impact of maternal HDP complicated with maternal DIP on offspring strabismus warrants investigation.

In this prospective birth cohort study, we investigated the association of maternal HDP with overall and type-specific strabismus in offspring at 3 years of age. We further evaluated whether the association differed by the type of HDP and level of blood pressure (BP) control and whether the risk increased when HDP was complicated with DIP.

This cohort study was approved by the Human Research Ethics Committee of Nanjing Medical University, and written informed consent was obtained from all participants. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline.

The Jiangsu Birth Cohort study, a subset of the China National Birth Cohort study, aims to assess the influence of perinatal and early life exposure on child health in Jiangsu, China. 32 In brief, women who were in the first trimester of pregnancy after spontaneous conception or receiving assisted reproductive technology (ART) treatment were recruited, and their children were followed up regularly.

This study included children born in Nanjing who fulfilled the following criteria: (1) singleton or twin live birth, (2) having information on maternal HDP diagnosis, and (3) undergoing ocular examinations at 33 to 39 months of age. From April 24, 2014, to November 30, 2018, 6195 live births had maternal HDP diagnosis information, of whom 3078 were excluded due to having no information on ocular alignment (n = 2978) or having other ocular diseases than strabismus or refractive error (n = 100). Comparisons of characteristics between the included and excluded offspring and their parents are provided in eTable 1 in Supplement 1 .

Exposure data were acquired from electronic medical records (EMR), including HDP, BP during labor, and DIP. Codes from the International Statistical Classification of Diseases, Tenth Revision , used to identify different types of maternal HDP are provided in eTable 2 in Supplement 1 . Maternal HDP was divided into hypertension (including chronic hypertension and gestational hypertension) and preeclampsia, as well as well-controlled BP (systolic blood pressure [SBP] <130 mm Hg and diastolic blood pressure [DBP] <80 mm Hg) and poorly controlled BP (SBP ≥130 mm Hg or DBP ≥80 mm Hg) during labor.

To assess ocular alignment, the Hirschberg light reflex test was performed at a distance of 33 cm, followed by cover-uncover test and alternate cover test at distances of both 33 cm and 6 m. Ocular motility was examined at 9 diagnostic positions of gaze. Strabismus was defined as the presence of any latent or manifest ocular deviation and classified according to the primary direction of the deviation. If the manifest deviation was constant at both near and distance fixation, it was considered constant; otherwise, it was intermittent.

Perinatal information on parents and offspring was extracted from questionnaires and the EMR, including maternal age, maternal prepregnancy body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) (<24 or ≥24), parity (primipara or multipara), maternal smoking or alcohol consumption during pregnancy (yes or no), maternal educational level (≤12 or >12 years), maternal residence (city or country), household annual income in Chinese yuan (<¥100 000 [<$13 792], ¥100 000-¥200 000 [$13 792-$27 583], or >¥200 000 [>$27 583]), paternal age, paternal hypertension or diabetes before pregnancy (yes or no), mode of conception (ART or spontaneous), singleton (yes or no), mode of delivery (cesarean or natural delivery), gestational week at birth, birth weight, offspring Apgar score at 1 and 5 minutes (≤7 or >7), offspring sex (male or female), and offspring congenital abnormality (yes or no). Offspring head circumference was measured using ultrasonography during late pregnancy and classified as less than 10th, 10th to 90th, and greater than 90th percentile according to the International Fetal and Newborn Growth Consortium for the 21st Century standards. 33 Offspring age was calculated according to the date of ocular examinations and birth date. Offspring refractive error was detected by refractive screening at 3 years of age and defined as the presence of any of the following conditions: (1) spherical equivalent refraction (SER) of less than −1.25 diopters (D) in either eye; (2) SER of greater than 2.5 D in either eye; (3) intereye difference in SER of greater than 1.0 D; and (4) cylindrical refraction of greater than 1.75 D in either eye. 34 Data on race and ethnicity were not collected. Follow-up was completed on May 21, 2022.

Data were analyzed from May 28, 2022, through December 15, 2023. Poisson generalized linear mixed model with a random intercept for each mother was used to estimate the relative risks (RRs) and 95% CIs for the association between maternal HDP and offspring strabismus, given the nonindependence of observations from twins. 35 Further, we examined whether the association differed by the type of HDP and level of BP control and whether the risk increased when HDP was complicated with DIP.

A directed acyclic graph (eFigure in Supplement 1 ) was developed to inform our staged modeling approach. 36 Model 1 was unadjusted. Model 2 was adjusted for 9 confounders, including maternal age, paternal age, maternal educational level, maternal residence, household annual income, mode of conception, singleton, offspring sex, and offspring age. Model 3 was additionally adjusted for 4 covariates suspected to lie on the causal pathway, including mode of delivery, gestational week of age, birth weight, and offspring refractive error.

Several sensitivity analyses were performed by limiting consideration to a specific subgroup of participants. Since maternal alcohol consumption or smoking during pregnancy, abnormal offspring Apgar score, offspring congenital abnormality, and offspring head circumference were not present or measured in many children, these covariates were evaluated only in sensitivity analyses. These analyses were restricted to children without exposure to maternal alcohol consumption during pregnancy, without exposure to maternal smoking during pregnancy, with normal Apgar scores (defined as >7 at both 1 and 5 minutes), without congenital abnormality, and with normal head circumference (10th-90th percentile). Another 5 sensitivity analyses were performed that were restricted to children born at full term with normal birth weight (defined as ≥2.5 kg), conducted after excluding children with exposure to paternal hypertension or diabetes before pregnancy, restricted to children born to mothers with prepregnancy BMI of less than 24, restricted to children born to primipara, and conducted after propensity score matching between the HDP and non-HDP groups according to all covariates in model 3, using 1:4 nearest neighbor matching without replacement.

Information on missing covariate data is given in eTable 3 in Supplement 1 . We handled missing data (<10% of participants) using complete case analysis and compared characteristics between offspring with and without complete data (eTables 4 and 5 in Supplement 1 ). All analyses were conducted using R software, version 4.1.2 (R Project for Statistical Computing), with a 2-sided P  < .05 considered statistically significant.

Among the 3117 children (mean [SD] age, 36.30 [0.74] months; 1488 girls [47.7%] and 1629 boys [52.3%]) born to 3005 mothers (mean [SD] age, 30.40 [3.76] years; mean [SD] prepregnancy BMI, 21.38 [3.01]) included in the analysis, 143 (4.6%) were exposed to maternal HDP, including 78 with maternal hypertension and 65 with maternal preeclampsia. Among these 143 children, maternal BP was well controlled in 33, poorly controlled in 103, and unknown in 7. Compared with the non-HDP group, the HDP group had older parents; a higher maternal prepregnancy BMI; more frequent conception through ART, twins, cesarean delivery, and maternal urban residence; and lower gestational age, birth weight, household income, and maternal educational level ( Table 1 ).

Among the 3117 children, 368 (11.8%) were found to have strabismus, including 265 (8.5%) with latent strabismus and 103 (3.3%) with manifest strabismus. Among the 265 children with latent strabismus, 260 (98.1%) had exophoria and 5 (1.9%) had esophoria. Among the 103 children with manifest strabismus, 95 (92.2%) had intermittent exotropia, 4 (3.9%) had constant exotropia, 1 (1.0%) had intermittent esotropia, and 3 (2.9%) had constant esotropia.

Offspring exposed to maternal HDP had an 82% increased risk of overall strabismus compared with unexposed offspring (model 3 RR, 1.82 [95% CI, 1.21-2.74]); this pattern was similar for type-specific strabismus, with an 82% increased risk for exophoria (model 3 RR, 1.82 [95% CI, 1.11-3.00]) and a 136% increased risk for intermittent exotropia (model 3 RR, 2.36 [95% CI, 1.13-4.93]) ( Table 2 ). When considering the type of maternal HDP, the risk for all strabismus was high for offspring exposed to preeclampsia (model 3 RR, 2.38 [95% CI, 1.39-4.09]) compared with unexposed offspring; this trend was apparent in exophoria (model 3 RR for preeclampsia, 2.68 [95% CI, 1.42-5.03]) but not in intermittent exotropia (model 3 RR for preeclampsia, 2.51 [95% CI, 0.87-7.25]) ( Table 2 ).

When considering the BP control level of maternal HDP, the risk for all strabismus was high for offspring born to mothers with HDP and poorly controlled BP (model 3 RR, 2.07 [95% CI, 1.32-3.24]) compared with unexposed offspring; this trend was apparent both in exophoria (model 3 RR for poorly controlled BP, 2.13 [95% CI, 1.24-3.65]) and intermittent exotropia (model 3 RR for poorly controlled BP, 2.61 [95% CI, 1.15-5.93]) ( Figure ). When considering both the type of maternal HDP and level of BP control, the highest risk was observed in offspring exposed to preeclampsia and poorly controlled BP (model 3 RR, 2.45 [95% CI, 1.37-4.39]) ( Table 3 ).

No association between maternal DIP and strabismus was found (eTable 6 in Supplement 1 ). Compared with offspring with neither exposure, the fully adjusted RRs for all strabismus were 1.77 (95% CI, 1.08-2.89) in offspring exposed only to maternal HDP, 0.94 (95% CI, 0.72-1.22) in offspring exposed to only maternal DIP, and 1.83 (95% CI, 0.89-3.73) in offspring exposed to both ( Table 4 ).

When we restricted the analysis to children without exposure to maternal alcohol consumption or smoking during pregnancy, with normal Apgar scores at 1 and 5 minutes, without congenital abnormality, with normal head circumference, or born to primipara, we obtained similar results to those of the main analyses (eTables 7-12 in Supplement 1 ). We observed almost identical results to those of the main analyses when we restricted the analysis to children born full-term with normal birth weight (eTable 13 in Supplement 1 ), after excluding children with exposure to paternal hypertension or diabetes before pregnancy (eTable 14 in Supplement 1 ), or to children born to mothers with prepregnancy BMI of less than 24 (eTable 15 in Supplement 1 ). In addition, results of analyses after propensity score matching were consistent with those of the main analyses (eTable 16 in Supplement 1 ).

In this cohort study, offspring born to mothers with HDP were found to have increased risks of overall and type-specific strabismus, including exophoria and intermittent exotropia, at 3 years of age. The highest risk was observed in offspring born to mothers with preeclampsia and poorly controlled BP.

The origins of strabismus are widely considered to be abnormalities in binocular vision. 14 , 37 Binocular vision is a complex process in the brain to combine 2 images—1 from each eye—into a single image that is formed under the conditions of good vision, normal ocular motility, and a well-developed brain. 14 , 37 Maternal HDP might increase the risk of strabismus by damaging binocular vision through the following mechanisms. First, placental hypoxia related to HDP may lead to permanent structural changes in the fetal brain. 38 Animal experiments have shown that even brief periods of hypoxia can result in neuronal death, white matter damage, and reduced growth of neural processes in the fetus. 39 Second, HDP, especially preeclampsia, can lead to increased inflammation and exaggerated oxidative stress in fetal circulation, which may damage fetal neurons, 40 , 41 leading to negative effects on the development of the brain in offspring. 42 - 45 Third, the oxidative stress led by HDP might cause degeneration of photoreceptors and other cells in retina. 46 In one cohort study, children exposed to maternal HDP were found to have thinner retina, 28 supporting the adverse influence of HDP on retina development. Fourth, maternal HDP might also impact offspring vision through inducing refractive error. 25 Finally, maternal HDP would increase the risk of cesarean delivery, 47 preterm birth, 48 and low birth weight 49 in offspring, all of which have potential adverse effects on the development of the brain and vision. 50 - 52

Four previous studies 16 , 21 , 29 , 30 have explored the association between maternal HDP and offspring strabismus but with different methods. A cross-sectional study of 14 980 children aged 3 years 16 found no association between maternal increased BP during pregnancy and parental reported strabismus of offspring; however, increased BP is not the same as HDP, and some types of strabismus, especially latent strabismus and intermittent exotropia, are not easily recognized by parents due to small change in appearance. One cohort study (n = 96 842) 21 showed that offspring exposed to maternal preeclampsia had a slightly higher risk of manifest strabismus. The influence of other HDP types was not analyzed, and the outcome was obtained by reviewing ophthalmological records in this study, which might underestimate the strabismus rate. One small study of 78 preterm children aged 5 years 29 failed to find any difference in the rates of latent and manifest strabismus, obtained through ocular examinations, between children born to mothers with and without preeclampsia. While another cohort study (n = 1125) also using ocular examinations to detect strabismus 30 found that maternal chronic hypertension was related to an increased risk of exotropia at 20 years old, some offspring with strabismus might have been treated during childhood and therefore were regarded as normal, because strabismus usually develops during early childhood. To our knowledge, our study is the first prospective cohort study to evaluate the association of maternal HDP with overall and type-specific strabismus in early childhood, with the outcomes measured by ocular examinations and HDP classified into different types and levels of BP control. As mentioned above, maternal HDP might increase the risk of strabismus in offspring through its influence on refractive error, cesarean delivery, gestational week of age, and birth weight. We applied a staged modeling approach to clarify the role of these possible intermediate factors, and our findings indicate the association between maternal HDP and strabismus may be independent of these factors.

The findings of the current study suggest that preeclampsia was associated with a higher risk of offspring strabismus than hypertension. These findings are understandable given that preeclampsia is a multisystemic disorder that targets several vital organs and is characterized by proteinuria or evidence of systemic disease, rather than just high BP. 53 We also found that the increased risk of strabismus is more pronounced among offspring exposed to maternal HDP with poorly controlled BP than well-controlled BP, indicating the importance of controlling BP. Mothers with SBP of 130 to 139 mm Hg or DBP of 80 to 89 mm Hg have been found to have increased risk of preterm birth in offspring. 54 , 55 Similarly, a higher risk of cardiovascular mortality was observed in pregnant women with DBP of at least 80 mm Hg than those with DBP of less than 80 mm Hg in a cohort study. 56

Maternal HDP and DIP might have shared pathological processes. 24 One prospective study found that maternal DIP was associated with a high risk of refractive error in offspring, 31 indicating that DIP might also influence offspring ocular health. However, we failed to find associations between maternal DIP and offspring strabismus or an increased risk of offspring strabismus when maternal HDP was complicated with DIP. More research is needed to clarify the reason for this discrepancy.

The primary strength of our study is the prospective cohort design, allowing for collecting accurate data on exposure, outcome, and covariates. Ocular examinations were performed by ophthalmologists who were unaware of maternal HDP diagnosis. Possible influence of various covariates has been adjusted in multivariable models or evaluated in sensitivity analyses.

Several limitations should also be noted. First, residual confounding might exist, such as postnatal environmental exposures and family history of strabismus. Second, other strabismus types could not be analyzed, since no children exposed to maternal HDP had strabismus other than exophoria and intermittent exotropia. Larger sample studies are warranted to explore the influence of maternal HDP on other strabismus types. Third, although chronic hypertension and gestational hypertension might have different associations with offspring strabismus, we combined chronic hypertension and gestational hypertension for our analyses due to the small sample size with chronic hypertension. Fourth, we categorized maternal HDP into different levels of BP control according to BP measured during labor; however, BP might vary from pregnancy to delivery, and more frequent measurements of BP at different time points might be better. Fifth, the number of children with exposure to maternal HDP and strabismus was relatively small, limiting direct comparisons between different HDP types, levels of BP control, or their combinations. However, the trend shown in exploratory analyses supported our findings (eTable 17 in Supplement 1 ). Sixth, there might be bias due to the exclusion of offspring with missing outcomes data. Seventh, ascertainment bias might be caused by the differences of birth weight and gestational age between offspring with and without complete data, although we included them in model 3 and performed a sensitivity analysis among children born full-term with normal birth weight. Eighth, coding errors might exist in the EMR, which cause possible misclassification of exposure. However, this misclassification is likely to be nondifferential and weaken the risk estimates.

The findings of this cohort study suggest that maternal HDP was associated with increased risks of overall and type-specific strabismus, including exophoria and intermittent exotropia, in offspring at 3 years of age. Offspring born to mothers with HDP might be recommended for early screening of strabismus, especially those with maternal preeclampsia or poorly controlled BP. The underlying mechanism of the association between maternal HDP and strabismus in offspring warrants further exploration.

Accepted for Publication: May 26, 2024.

Published: July 22, 2024. doi:10.1001/jamanetworkopen.2024.23946

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2024 Zhu H et al. JAMA Network Open .

Corresponding Authors: Jiangbo Du, PhD, Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian St, Nanjing 211166, Jiangsu, China ( [email protected] ); Hu Liu, PhD, Department of Ophthalmology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Rd, Nanjing 210029, Jiangsu, China ( [email protected] ).

Author Contributions: Drs Zhu and Du had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr Zhu and Mss You and Jing served as co–first authors.

Concept and design: Zhu, Ma, Hu, H. Liu, Du.

Acquisition, analysis, or interpretation of data: Zhu, You, Jing, Y. Chen, Yangqian Jiang, Lin, T. Jiang, Qin, Lv, Lu, C. Liu, X. Xu, Y. Liu, Sun, M. Jiang, B. Xu, Han, J. Chen, Yue Jiang, X. Liu, Zhou, Jin, H. Liu, Du.

Drafting of the manuscript: Zhu, Du.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Zhu, You, T. Jiang, J. Chen, Yue Jiang, Du.

Obtained funding: Lv, Lu, Hu, H. Liu, Du.

Administrative, technical, or material support: Lin, Qin, Zhou, Jin, H. Liu, Du.

Supervision: Jin, Ma, H. Liu, Du.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by grant 2021YFC2700705 from the National Key Research & Development Program of China; grants 82273159, 82103919, 82103854, and 82003415 from the National Natural Science Foundation of China; and grant BK20210533 from the Natural Science Foundation of Jiangsu Province.

Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: A complete list of investigators in the China National Birth Cohort Study Group is found in Supplement 2 .

Data Sharing Statement: See Supplement 3 .

Additional Contributions: We thank all the members of the collaborative group of the Jiangsu Birth Cohort, all the study participants for their support, and all staff who provided technical assistance or made contributions to this cohort study.

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Peer-reviewed

Research Article

Associations of hypertension and antenatal care-seeking with perinatal mortality: A nested case-control study in rural Bangladesh

Roles Conceptualization, Data curation, Formal analysis, Methodology, Writing – original draft, Writing – review & editing

* E-mail: [email protected]

Current address: International Development Division, Abt Associates, Rockville, Maryland, United Stated of America

Affiliation Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United Stated of America

Roles Conceptualization, Validation, Writing – review & editing

Affiliation Division of General Internal Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United Stated of America

Roles Data curation, Formal analysis, Methodology, Software, Visualization

Roles Data curation, Investigation, Project administration, Writing – review & editing

Affiliation Division of Maternal and Child Health, International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh

Roles Funding acquisition, Investigation, Methodology, Resources, Software, Supervision, Writing – review & editing

Roles Funding acquisition, Investigation, Project administration, Resources, Supervision, Writing – review & editing

Roles Formal analysis, Funding acquisition, Investigation, Methodology, Supervision, Writing – review & editing

• Allyson P. Bear, 
• Wendy L. Bennett, 
• Joanne Katz, 
• Kyu Han Lee, 
• Atique Iqbal Chowdhury, 
• Sanwarul Bari, 
• Shams El Arifeen, 
• Emily S. Gurley

• Published: July 22, 2024
• https://doi.org/10.1371/journal.pone.0287622
• Peer Review
• Reader Comments

Maternal hypertension may be an underrecognized but important risk factor for perinatal death in low resource settings. We investigated the association of maternal hypertension and perinatal mortality in rural Bangladesh. This nested, matched case-control study used data from a 2019 cross-sectional survey and demographic surveillance database in Baliakandi, Bangladesh. We randomly matched each pregnancy ending in perinatal death with five pregnancies in which the neonate survived beyond seven days based on maternal age, education, and wealth quintile. We estimated associations of antenatal care-seeking and self-reported hypertension with perinatal mortality using conditional logistic regression and used median and interquartile ranges to assess the mediation of antenatal care by timing or frequency. Among 191 cases and 934 matched controls, hypertension prevalence was 14.1% among cases and 7.7% among controls. Compared with no diagnosis, the probability of perinatal death was significantly higher among women with a pre-gestational hypertension diagnosis (OR 2.90, 95% CI 1.29, 6.57), but not among women with diagnosis during pregnancy (OR 1.68, 95% CI 0.98, 2.98). We found no association between the number of antenatal care contacts and perinatal death (p = 0.66). Among women with pre-gestational hypertension who experienced a perinatal death, 78% had their first antenatal contact in the sixth or seventh month of gestation. Hypertension was more common among rural women who experience a perinatal death. Greater effort to prevent hypertension prior to conception and provide early maternity care to women with hypertension could improve perinatal outcomes in rural Bangladesh.

Citation: Bear AP, Bennett WL, Katz J, Lee KH, Chowdhury AI, Bari S, et al. (2024) Associations of hypertension and antenatal care-seeking with perinatal mortality: A nested case-control study in rural Bangladesh. PLoS ONE 19(7): e0287622. https://doi.org/10.1371/journal.pone.0287622

Editor: Sayedur Rahman, Projahnmo Research Foundation, BANGLADESH

Received: June 10, 2023; Accepted: July 8, 2024; Published: July 22, 2024

Copyright: © 2024 Bear et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Relevant variables for this analysis are available from the Dryad database ( https://doi.org/10.5061/dryad.9kd51c5mk ).

Funding: This work was supported by the Bill & Melinda Gates Foundation, Seattle, WA ( https://www.gatesfoundation.org/ ) under grant number OPP1126780 held by SEA and ESG. The funder of the study had no role in the study design, data collection, data analysis, data interpretation, the writing of the report, and in the decision to submit the article for publication.

Competing interests: The authors declare that they have no competing interests.

Introduction

Hypertensive disorders of pregnancy include maternal chronic hypertension, pregnancy-induced hypertension, pre-eclampsia, and eclampsia. Globally, these conditions are estimated to complicate 5–10% of all pregnancies and are responsible for 16% of the estimated 2.6 million stillbirths and 50% of the estimated 2.9 million neonatal deaths each year [ 1 – 6 ]. In 2010, an estimated 224 million women of reproductive age across the world had chronic hypertension [ 7 ].

Between 2011 and 2018, the prevalence of hypertension in Bangladeshi women over the age of 35 increased from 32% to 45% [ 8 , 9 ]. In 2018, the prevalence of hypertension in women aged 18–34 was 12.5% [ 8 ]. The burden of pregnancy-induced or chronic hypertension in pregnancy is less well understood in the Bangladesh context, as is its impact on the fetus or neonate. In 2018, neonatal mortality in Bangladesh accounted for two-thirds of child mortality (3% of live births). Perinatal mortality, or death occurring from 28 weeks’ gestation through the seventh day of life, occurred in 4.8% of pregnancies in Bangladesh, of which 52% were stillbirths [ 8 , 9 ].

Women are encouraged to seek early and regular antenatal care from a medically qualified provider to ensure a healthy pregnancy and safe birth [ 10 ]. In Bangladesh, between 2014 and 2018, the percentage of women receiving any antenatal care from a medically qualified provider increased from 64% to 82% [ 8 , 11 ]. In 2018, 42% of women in rural areas received four or more antenatal care contacts during pregnancy, although this increase in care seeking has not corresponded with a reduction in perinatal mortality [ 8 , 12 ]. The objective of this study was to investigate the association between maternal hypertension and the risk of perinatal mortality in rural Bangladesh, and whether that association was mediated by antenatal care.

Materials and methods

Study setting and study design.

This nested, matched case-control study was a sub-study of the Child Health and Mortality Prevention Surveillance (CHAMPS) project site in the Baliakandi sub-district of Bangladesh. CHAMPS Bangladesh began active population-based demographic surveillance in September 2017 in Baliakandi on a population of approximately 220,000. The details of CHAMPS methods have been published elsewhere [ 13 , 14 ]. Ethical approval for the study was provided by the Ethical Review Committee of the International Centre for Diarrhoeal Disease Research, Bangladesh.

Cross sectional survey.

From April to August 2019, we conducted a single survey among married women of reproductive age in the CHAMPS Baliakandi demographic surveillance system. The survey tool was based on the Demographic and Health Survey (DHS) Program and the WHO STEPwise approach to surveillance surveys [ 15 , 16 ]. The questions were translated into Bengali and validated through prior national surveys [ 8 , 9 , 11 , 17 ]. All married women of reproductive age living in households with a child (living or dead) under five years of age, or a woman currently pregnant or pregnant within the previous 12 months, were eligible to participate. One week prior to the start of data collection in each block of the demographic surveillance system, a listing of households meeting the eligibility criteria was generated using CHAMPS data. Data collectors conducted face-to-face interviews after taking written informed consent from the woman. If the woman was under 18 years of age, informed assent was taken and witnessed by a guardian from the household. Data collectors conducted up to nine follow-up visits to complete the data collection, with women self-reporting previous screenings, diagnoses of diabetes and hypertension and timing of any diagnoses, the numbers of antenatal care contacts they had during current and recent pregnancies, and the location, type of health care provider, and services rendered. No medical records were available to confirm the self-reported information.

Demographic surveillance databases from parent cohort study.

We used the CHAMPS demographic surveillance database dated February 26, 2020 to identify all singleton pregnancy outcomes among survey respondents to include those outcomes which took place up to one year before or 14 days after the date of the survey. We only considered singleton pregnancies for this analysis, as multiparity is an independent risk factor for perinatal death [ 12 , 18 ]. We extracted demographic, socio-economic and pregnancy history information for each woman with an eligible pregnancy from the CHAMPS demographic surveillance database by linking unique identification numbers.

Outcome: Perinatal death.

Perinatal death was defined as a pregnancy ending in the death of the offspring between the completion of 28 weeks gestation and seven days following delivery [ 19 ]. Deaths occurring after 28 weeks of pregnancy, but before or during birth were classified as a stillbirth; those occurring between 0 and 7 completed days after birth were classified as early neonatal deaths [ 19 ].

Exposure: Hypertension

• Any hypertension: Any self-reported diagnosis of hypertension, regardless of timing.
• Presumed pre-gestational (chronic) hypertension: Self-reported diagnosis of hypertension at any time prior to the index pregnancy.
• Presumed gestational hypertension: Self-reported diagnosis of hypertension during or after the index pregnancy, in the absence of any self-reported previous diagnosis of hypertension. We assumed that hypertension diagnosed post-partum was likely due to unresolved hypertension that was present during pregnancy.

Data analysis

Selection of cases and controls..

Cases of pregnancies ending in a perinatal death were identified by comparing the date of pregnancy outcome and date of the woman’s last menstrual period preceding the pregnancy. Eligibility to serve as a matched control was defined as a pregnancy ending in a live birth in which the neonate survived beyond seven days, such a pregnancy being identified by the absence of a reported death within the first seven days of life in the CHAMPS demographic surveillance system. Among cases and eligible controls, we excluded pregnancies in women who reported no previous screening for hypertension and pregnancies for which we had no antenatal care information. For women who had more than one eligible pregnancy, we selected the pregnancy with an outcome closest to the survey date.

Based on a literature review of confounders for the relationship between hypertensive disorders of pregnancy and perinatal mortality we matched on the following characteristics: age group (<20, 20–24, 25–29, 30–34, 35–39, 40+), wealth quintile, and educational attainment (none, primary, secondary, post-secondary) [ 8 , 20 – 25 ]. The wealth quintile was constructed using the DHS wealth index score [ 26 , 27 ]. We randomly matched, without replacement, each case with up to five controls. For cases with fewer than five matched controls, we conducted the analysis with the controls as matched.

Using summary statistics and chi-squared tests, we examined the differences in demographic, hypertension, and pregnancy characteristics between cases and controls. We then used conditional logistic regression in the matched case-control groups to estimate probability ratios for perinatal death by any hypertension diagnosis, nature of hypertension, and number of antenatal care contacts with a qualified provider (0, <4, 4+) for the index pregnancy. Looking at median and interquartile ranges for antenatal care timing and frequency, we explored the relationship between antenatal care-seeking, the type of hypertension, and perinatal death. P<0.05 was considered statistically significant for all analyses.

A total of 4,550 pregnancies met the eligibility criteria for inclusion in the study, including 201 perinatal deaths ( Fig 1 ). The overall perinatal mortality rate was 44 per 1,000 pregnancies (4.4%), which was consistent with national surveys [ 8 , 11 ]. Among women with eligible pregnancies, 97.5% reported screening for hypertension at least once in their lifetimes. Of those screened, 415 (9.4%) reported a diagnosis of hypertension. A total of 216 (4.7%) pregnancies met exclusion criteria, leaving 4,333 unique women with pregnancies eligible for matching, including 191 cases of perinatal death ( Fig 1 ). After matching, 10 cases had greater than one but fewer than five matched controls. The final analysis included 191 cases and 934 matched controls ( Fig 1 ). There were no cases of perinatal death among 19 pregnancies in women over 40 years of age. This age group was dropped from the analysis.

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https://doi.org/10.1371/journal.pone.0287622.g001

Among women who experienced a perinatal death, 79% (151/191) were under 30 years of age, and over two-thirds (69%, 131/191) had completed secondary education or higher ( Table 1 ). There were fewer cases of perinatal death among women in the highest wealth quintile (12.6%) compared with lower wealth quintiles. Slightly more than half (56%) of perinatal deaths were classified as stillbirths ( Table 1 ). Women who experienced a perinatal death were more likely to report being diagnosed with hypertension compared with controls (14.1% vs. 7.7%, p<0.01), and to have pre-gestational high blood pressure (5.2% vs. 2.0%, p = 0.01). The proportion of women who had no contact with a qualified health care provider during pregnancy was similar between cases (18.5%) and controls (20.1%) ( Table 1 ).

https://doi.org/10.1371/journal.pone.0287622.t001

Hypertension and perinatal death

Women who reported any hypertension diagnosis were more likely to experience perinatal death, and risk of perinatal death differed by timing of hypertension diagnosis. Women with pre-gestational hypertension experienced a 2.9-fold greater risk of perinatal death (OR 2.90, 95% CI 1.29, 6.57) than women who reported no diagnosis. Women with presumed gestational hypertension experienced a 68% increased probability of perinatal death (OR 1.68, 95% CI 0.98, 2.98) than women who reported no diagnosis, but this was not statistically significant.

Antenatal care service contacts.

We found no association between the number of antenatal care contacts with a qualified provider and perinatal death ( Table 2 ). Among women who experienced a perinatal death, 81% sought antenatal care at least once from a medically qualified provider. We evaluated the frequency and timing of antenatal care among women with any hypertension diagnosis by perinatal outcome ( Fig 2 ). Across all categories of perinatal outcome and hypertension status, the total number of contacts with qualified health care providers in each pregnancy was below both the national standard of four and the WHO recommendation of eight antenatal care visits [ 10 ]. Women with presumed gestational hypertension had a higher median number of contacts with medically qualified providers (median 3, IQR 1,4) than women with presumed pre-gestational hypertension (median 2, IQR 1,3) and women never diagnosed with hypertension (median 2, IQR 1,3), and this difference was statistically significant (p = 0.02). The median number of contacts with a qualified health care provider did not differ significantly by perinatal outcome within hypertension groups (p = 0.66).

https://doi.org/10.1371/journal.pone.0287622.g002

https://doi.org/10.1371/journal.pone.0287622.t002

Among women who sought any care during pregnancy, 33% (339/1,023) obtained their first antenatal service from a non-qualified provider. Most of these service contacts (90%, 306/339) took place at home in median month four (IQR 2,5) or at a satellite clinic close to home at median month three (IQR 3,5). Among women who sought care with a medically qualified provider, the median first antenatal care contact was in the second trimester of pregnancy in all groups ( Fig 3 ). We found no difference in median timing of first contact with a medically qualified provider by pregnancy outcome among women with no history of hypertension (p = 0.42) ( Fig 3 ). Women with presumed pre-gestational hypertension who experienced a perinatal death had their median first contact with a qualified provider later than any other group, in the sixth month of gestation (IQR 6, 8) ( Fig 3 ), and 89% of these women sought this care in a health care facility (clinic or hospital). There was high variation in timing of first antenatal service contact within almost all groups, the exception being the group of women with presumed pre-gestational hypertension who experienced a perinatal death, 78% (7 out of 9) of which had their first antenatal service contact with a qualified care provider in the sixth or seventh month of pregnancy.

https://doi.org/10.1371/journal.pone.0287622.g003

This retrospective case-control study of 1,125 women found that any pre-pregnancy history of hypertension was a significant risk factor for perinatal death in Baliakandi sub-district, Bangladesh. Antenatal care was suboptimal in timing and frequency among all groups of women regardless of hypertension status or pregnancy outcome, and the frequency of antenatal care-seeking was not associated with fetal or newborn survival.

Chronic hypertension in younger women has not been well studied in Bangladesh. The first national hypertension prevalence survey of women 18–34 years of age was published in 2020 [ 8 ]. Pre-eclampsia is a well-recognized complication of pregnancy in Bangladesh, and previous studies have found that pre-eclampsia contributes to 24% of maternal mortality, 7% of stillbirths, and 2.9% of neonatal deaths [ 12 , 28 , 29 ]. Khanam et. al found that probable pregnancy-induced hypertension was a significant risk factor for stillbirth (IRR = 1.8, 95% CI 1.3–2.5) in Sylhet, Bangladesh [ 30 ]. This study suggests that underlying chronic high blood pressure may be contributing more significantly to perinatal death than has been previously recognized in Bangladesh. Future studies looking at the etiology of perinatal death should attempt to better differentiate between underlying chronic disease and pregnancy-induced disease in order to inform the development of effective public health and medical interventions for preventing adverse pregnancy outcomes.

In all rural areas of Bangladesh, 21% of women seek no antenatal care in pregnancy, and only 20% are seen four or more times by a qualified health care provider [ 8 ]. Our study found similar antenatal care-seeking patterns among women in Baliakandi [ 8 ]. Baliakandi women in our study who experienced a perinatal death had the same median number of antenatal care visits (three) from a qualified antenatal care provider as rural women elsewhere in Bangladesh, with the median timing of first contact with a qualified health care provider taking place in the fourth month of pregnancy [ 29 ]. Our study suggests that this timing and frequency of antenatal care is insufficient to prevent adverse perinatal outcomes. Additional research is needed to understand why this contact with the health care system did not have a protective effect. Possible explanations could be related to poor quality of care by the health care provider, late onset of care-seeking, or weak referral systems once complications were identified [ 31 – 34 ].

Women with a history of hypertension predating pregnancy and who experienced a perinatal death sought care late in their pregnancies, possibly spurred by the onset of hypertension-induced complications. Further qualitative research is needed to understand why women with pregnancies complicated by hypertension, including women with a known history of disease, did not have more frequent contact, as per national guidelines, with the health care system in order to effectively manage their high-risk pregnancy [ 35 ]. Focused efforts to identify women with a history of disease and encourage them to seek early and regular antenatal care from a hospital-level facility equipped to treat high-risk pregnancies could be an effective intervention for improving outcomes in this high-risk group, but only if those facilities are equipped with the personnel, equipment, supplies, and essential medicines to effectively manage hypertension in pregnancy [ 2 , 6 , 34 ].

A limitation of this study is the potential for misclassification due to the absence of direct measurement or medical records to confirm self-reported information on hypertension diagnosis and antenatal care-seeking. We posit that a woman’s ability to correctly recall a pre-pregnancy diagnosis of hypertension is independent of perinatal outcome, in which case misclassification would result in our findings being an underestimate of the true magnitude of the association between hypertension and perinatal death. It is possible, in the effort to understand the causes of adverse events, that women who experienced a perinatal death were more likely to be correctly identified as hypertensive than those with a healthy outcome, leading to differential misclassification by outcome and an overestimate of the association between hypertension diagnosis, either during or after pregnancy, and perinatal death. The marginal association between presumed gestational hypertension and perinatal death (OR 1.68, 95% CI 0.98, 2.98) suggests a clear association that would have been statistically significant with a larger sample size. These data provide a baseline for future longitudinal research to both investigate the temporality of hypertension and further elucidate how hypertension affects pregnancy outcomes throughout a woman’s childbearing years in rural, resource-constrained settings.

The Government of Bangladesh is committed to reducing the neonatal mortality rate to 12 deaths per 1,000 live births by 2030 [ 36 ]. In order to achieve both this goal and that of similar reductions in stillbirths, greater emphasis should be placed on identification of women with a history of hypertension and improving their access to and utilization of skilled antenatal and delivery care. Consistent with national guidelines, antenatal care for women with pre-gestational hypertension should be early, frequent, and take place in hospital settings with the trained personnel, equipment, supplies, and medicines necessary for effective management of complicated pregnancies [ 35 ]. Raising community awareness of the dangers of hypertension in pregnancy, especially when there is a diagnosis of hypertension prior to pregnancy, should be included in any programs introduced to address low care-seeking among these high-risk women [ 35 ].

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Effect of vitamin d deficiency on arterial stiffness in pregnant women with preeclampsia and pregnancy-induced hypertension and implications for fetal development.

1. Introduction

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Iurciuc, M.; Buleu, F.; Iurciuc, S.; Petre, I.; Popa, D.; Moleriu, R.D.; Bordianu, A.; Suciu, O.; Tasdemir, R.; Dragomir, R.-E.; et al. Effect of Vitamin D Deficiency on Arterial Stiffness in Pregnant Women with Preeclampsia and Pregnancy-Induced Hypertension and Implications for Fetal Development. Biomedicines 2024 , 12 , 1595. https://doi.org/10.3390/biomedicines12071595

Iurciuc M, Buleu F, Iurciuc S, Petre I, Popa D, Moleriu RD, Bordianu A, Suciu O, Tasdemir R, Dragomir R-E, et al. Effect of Vitamin D Deficiency on Arterial Stiffness in Pregnant Women with Preeclampsia and Pregnancy-Induced Hypertension and Implications for Fetal Development. Biomedicines . 2024; 12(7):1595. https://doi.org/10.3390/biomedicines12071595

Iurciuc, Mircea, Florina Buleu, Stela Iurciuc, Izabella Petre, Daian Popa, Radu Dumitru Moleriu, Anca Bordianu, Oana Suciu, Rabia Tasdemir, Ramona-Elena Dragomir, and et al. 2024. "Effect of Vitamin D Deficiency on Arterial Stiffness in Pregnant Women with Preeclampsia and Pregnancy-Induced Hypertension and Implications for Fetal Development" Biomedicines 12, no. 7: 1595. https://doi.org/10.3390/biomedicines12071595

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Associations of hypertension and antenatal care-seeking with perinatal mortality: A nested case-control study in rural Bangladesh

Affiliations.

• 1 Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United Stated of America.
• 2 Division of General Internal Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United Stated of America.
• 3 Division of Maternal and Child Health, International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh.
• PMID: 39037995
• PMCID: PMC11262631
• DOI: 10.1371/journal.pone.0287622

Maternal hypertension may be an underrecognized but important risk factor for perinatal death in low resource settings. We investigated the association of maternal hypertension and perinatal mortality in rural Bangladesh. This nested, matched case-control study used data from a 2019 cross-sectional survey and demographic surveillance database in Baliakandi, Bangladesh. We randomly matched each pregnancy ending in perinatal death with five pregnancies in which the neonate survived beyond seven days based on maternal age, education, and wealth quintile. We estimated associations of antenatal care-seeking and self-reported hypertension with perinatal mortality using conditional logistic regression and used median and interquartile ranges to assess the mediation of antenatal care by timing or frequency. Among 191 cases and 934 matched controls, hypertension prevalence was 14.1% among cases and 7.7% among controls. Compared with no diagnosis, the probability of perinatal death was significantly higher among women with a pre-gestational hypertension diagnosis (OR 2.90, 95% CI 1.29, 6.57), but not among women with diagnosis during pregnancy (OR 1.68, 95% CI 0.98, 2.98). We found no association between the number of antenatal care contacts and perinatal death (p = 0.66). Among women with pre-gestational hypertension who experienced a perinatal death, 78% had their first antenatal contact in the sixth or seventh month of gestation. Hypertension was more common among rural women who experience a perinatal death. Greater effort to prevent hypertension prior to conception and provide early maternity care to women with hypertension could improve perinatal outcomes in rural Bangladesh.

Copyright: © 2024 Bear et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Conflict of interest statement

The authors declare that they have no competing interests.

Fig 1. Sample selection of women, nested…

Fig 1. Sample selection of women, nested case-control study, hypertension and perinatal mortality in Baliakandi,…

Fig 2. Number of antenatal service contacts…

Fig 2. Number of antenatal service contacts by nature of hypertension and pregnancy outcome, Baliakandi,…

Fig 3. Month of first contact with…

Fig 3. Month of first contact with a medically qualified provider during pregnancy, by nature…

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UB and Oishei Hospital Part of Clinical Trial on Pregnancy-Related Hypertension

Fron left, Thaddeus P. “Ted” Waters, MD, and Pamela D. Reed, MD, both of the Jacobs School of Medicine and Biomedical Sciences, and Pauline Mendola, PhD, from the School of Public Health and Health Professions. They are among the UB investigators on a clinical trial that will test two health care delivery models’ effectiveness in treating postpartum hypertension. 

By David J. Hill

Published December 14, 2023

The University at Buffalo is among three institutions selected for a major new clinical trial aimed at curbing hypertension and mental health issues in postpartum women, particularly those from marginalized populations.

The study will enroll 6,000 postpartum women from priority populations — mostly Black and Latinx women — in three medical centers: Yale New Haven Hospital, UMass Medical Center and Kaleida Health’s John R. Oishei Children’s Hospital.

The project is being funded through a $18.8 million grant from the Patient-Centered Outcomes Research Institute (PCORI), with UB receiving $3.7 million. Study recruitment is underway.

“Women who have hypertensive disorders during pregnancy are at higher risk throughout their lives for adverse cardiovascular outcomes,” says Vanessa Barnabei, MD, professor emerita in the Department of Obstetrics and Gynecology  in the  Jacobs School of Medicine and Biomedical Sciences , who played a critical role in securing the funding for UB before retiring.

Study Undertaking Patient-Centered Approach

The adverse health impacts have a more profound effect for Black, American Indian/Alaskan Native and Latinx women due to social determinants of health.

“Maternal health is one of the most important health priorities for the African American community. Hypertension, as well as the social determinants of health, have created unacceptable birth outcomes in the community,” says the Rev. George F. Nicholas, pastor of Lincoln Memorial United Methodist Church in Buffalo and co-convener of the African American Health Equity Task Force, a partner on the research project.

“This grant will enable us to obtain important information on how to improve birth outcomes for women and children in the community,” Nicholas says.

“This study takes a patient-centered approach focusing on patient needs and preferences of care delivery with the hope of improving the physical health and mental well-being of women while also addressing health care inequities in our community,” notes Pamela D. Reed, MD, senior research project director for the study.

“Funding for this type of work is so important if we are to decrease the inequities in our current health care delivery system,” Reed adds.

The UB investigators on the research project are:

• Thaddeus P. “Ted” Waters, MD , Amol S. Lele Clinical Professor and division chief of maternal-fetal medicine in the Department of Obstetrics and Gynecology , Jacobs School. He is also medical director for the maternal-fetal medicine and regional perinatal program at Oishei Children’s Hospital.
• Pauline Mendola, PhD, chair of the Department of Epidemiology and Environmental Health, School of Public Health and Health Professions

Other UB collaborators include Michael J. LaMonte, PhD, research professor, and Lina Mu, PhD, associate professor, both in the Department of Epidemiology and Environmental Health; and Heather Link, MD, clinical assistant professor, and J’Leise Sosa, MD, clinical assistant professor of obstetrics and gynecology, from Kaleida Health.

The study is being led by the Yale School of Public Health.

Researchers will compare with the current standard of care, and with each other, the effectiveness of two health care delivery models focused on early detection and control of postpartum hypertension, as well as the social and mental health factors known to impact maternal outcomes. The two models are:

• A remote medical model that incorporates standard procedures along with home blood pressure monitoring and treatment, weekly virtual visits from a medical professional for six to 12 weeks, and screening for social determinants of health and anxiety/depression, with referrals for mental health services if needed.
• A community health model, which incorporates standard of care and the remote model with community health workers trained in a strength-based, trauma-informed approach that respects the influences of a patient’s past experiences when addressing their current health needs.

“The goal of the study is to have a lasting impact on long-term health,” Waters said. “If the study is successful, the model used in the trial can be brought to more patients and meaningfully address post-delivery morbidity and mortality, which disproportionately affects our community.”

Leveraging Community Health Workers

A key part of the study calls for leveraging a community-based approach toward treating postpartum women. The community health worker model has been recognized by the World Health Organization and other agencies for its effectiveness in addressing health inequities due to the fact that community health workers are uniquely poised to play a role in providing better care by sharing the language, socioeconomic status and life experiences of their clients.

“The incorporation of the community health care worker is a model for the future,” Waters says. “We believe this study will demonstrate the value of this approach by addressing the gaps in care for patients at high risk of complications after delivery and improving long-term outcomes related to cardiovascular and mental health.”

Researchers will be working with project partner Cicatelli Associates Inc. (CAI), a New York-based nonprofit with a local Buffalo office that helps organizations improve health care and social services for marginalized communities.

CAI will be central to the delivery of asynchronous e-learning modules and synchronous virtual instructor‐led trainings to the health care providers and community health workers and doulas involved in study. Sample training topics will include the impact of systemic racism on health disparities among women and pregnant women, and trauma through an anti‐racist lens to understand sensitivity and reactivity to stress within the study population.

“Pregnancy risks are unacceptably high among women in priority populations who have been historically underserved and who have experienced discrimination and racism,” says Lindsay Senter, CAI vice president of research and evaluation. “We are thrilled to take part in groundbreaking research that places community voices front and center to ensure that members of marginalized communities are engaged and have a voice in creating the systems that serve them.”

The team will recruit and train community health workers to perform mental health assessments and work with patients directly in their neighborhoods. Nurse practitioners will conduct follow-ups with patients who’ve been identified as having continued high blood pressure postpartum to set them up with additional treatment.

In addition, CAI is leading development of a local community advisory board to help inform the implementation of the trial.

Goal of Improving Clinical Outcomes

The study’s primary objective is to improve clinical outcomes, including mental health outcomes, among postpartum, at‐risk women experiencing health disparities by increasing awareness, detection and timely care of postpartum hypertension, mental health and cardiovascular complications.

“This is a topic that is near and dear to my heart,” Mendola notes. “Postpartum is a very vulnerable time, and it is really important for women’s health and neonatal health, yet it doesn’t get the attention that it really deserves due to its long-term health impacts. We as a clinical community are excited about the opportunity to address some of these issues and help women during a time in which they really need that help but have trouble accessing it.”

The focus on women who identify as Black, Latinx or American Indian/Alaska Native is especially significant, Mendola says. “This study provides another avenue to try to address the striking disparities in maternal mortality and morbidity by race. Black moms are two to three times more likely to die from hypertension during pregnancy than white moms, and their hypertension typically occurs at a much higher rate than mothers of other races and ethnicities.”

Hypertension, or high blood pressure, as well as mental health, are of particular concern during the postpartum period, especially since most new mothers will receive checkups only at two and six weeks postpartum. In fact, at Oishei Children’s Hospital, the numbers continue to climb: In 2021, 16% of women who gave birth there had one of the four types of high blood pressure during pregnancy, up from around 5% in 2009.

“This is a really key time in women’s lives, and it makes a difference for their lifespan and continued health,” Mendola says. “Some of the things we may be able to address in this study and deal with in a proactive way will help improve the women’s cardiometabolic health for the rest of their lives.”

Leadership at Oishei Children’s Hospital is thrilled the hospital was chosen to be one of the three study sites.

“As the region’s only state-designated Regional Perinatal Center, Oishei Children’s Hospital provides the most comprehensive specialized care for our community’s highest risk moms and babies,” says Stephen J. Turkovich, MD, president and chief medical officer of Oishei Children’s Hospital.

“Beyond the four walls of the hospital, our robust network of maternal-fetal medicine specialists and community-based clinics are uniquely positioned to provide complex care services for pregnant moms throughout Western New York. I’m optimistic that through investments in research and alternative care models for postpartum at‐risk women, we can help close the health-disparities gap and improve health outcomes,” says Turkovich, a clinical assistant professor of  pediatrics at the Jacobs School.

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• Ethiop J Health Sci
• v.29(1); 2019 Jan

Pregnancy Induced Hypertension and Associated Factors among Women Attending Delivery Service at Mizan-Tepi University Teaching Hospital, Tepi General Hospital and Gebretsadik Shawo Hospital, Southwest, Ethiopia

Tesfaye abera gudeta.

1 MizanTepi University, College of Health science, Department of Nursing, Maternal Health Nursing Unit

Tilahun Mekonnen Regassa

2 MizanTepi University, College of Health Science, Department of Nursing, adult Health Hursing Unit

Disorders of pregnancy induced hypertensive are a major health problem in the obstetric population as they are one of the leading causes of maternal and perinatal morbidity and mortality. The World Health Organization estimates that at least one woman dies every seven minutes from complications of hypertensive disorders of pregnancy. The objective of this study is to assess pregnancy induced hypertension and its associated factors among women attending delivery service at Mizan-Tepi University Teaching Hospital, Gebretsadikshawo Hospital and Tepi General Hospital.

A health facility based cross-sectional study was carried out from October 01 to November 30/2016. The total sample size (422) was proportionally allocated to the three hospitals. Systematic sampling technique was used to select study participants. Variables with p-value of less than 0.25 in binary logistic regression were entered into the multivariable logistic regression to control cofounding. Odds ratio with 95% confidence interval was used. P-value less than 0.05 was considered as statistically significant.

The prevalence of pregnancy induced hypertension was 33(7.9%); of which 5(15.2%) were gestational hypertension, 12 (36.4%) were mild preeclampsia, 15(45.5%) were severe preeclampsia and 1 (3%) eclampsia. Positive family history of pregnancy induced hypertension [AOR5.25 (1.39–19.86)], kidney diseases (AOR 3.32(1.04–10.58)), having asthma [AOR 37.95(1.41–1021)] and gestational age (AOR 0.096(0.04-.23)) were predictors of pregnancy induced hypertension.

The prevalence of pregnancy induced hypertension among women attending delivery service was 7.9%. Having family history of pregnancy induced hypertension, chronic kidney diseases and gestational age were predictors of pregnancy induced hypertension.

Introduction

Hypertension in pregnancy is a systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or both. Both systolic and diastolic blood pressure raises are important in the identification of Pregnancy induced hypertension ( 1 ). Pregnancy induced hypertension (PIH) is hypertension that occurs after 20 weeks of gestation in women with previously normal blood pressure. The broad classification of pregnancy-induced hypertension during pregnancy is gestational hypertension, pre-eclampsia and eclampsia ( 2 ).

Severe preeclampsia in pregnancy is a systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg or both. Eclampsia is a severe type of pregnancy induced hypertension, and it happens in about one in 1,600 pregnancies and develops near the end of pregnancy ( 4 ). The three primary characteristics of pregnancy induced hypertension conditions are high blood pressure, protein in the urine and pathologic edema ( 3 – 5 ).

Pregnancy induced hypertension is a major contributors to maternal and perinatal morbidity and mortality. In the United States, about 15% of maternal deaths are attributable to hypertension, making it the second leading cause of maternal mortality. Severe hypertension increases the mother's risk of cardiac failure, heart attack, renal failure and cerebral vascular accidents. In addition, the fetus is at increased risk from complications like poor placental transfer of oxygen, growth restriction, preterm birth, placental abruption, stillbirth and neonatal death ( 2 ). Hypertensive disorders represent the most common medical complications of pregnancy with a reported incidence of 5–10% ( 6 , 7 ).

Globally, preeclampsia is a leading cause of maternal and neonatal mortality and morbidity, predominantly in developing countries. The disorder is usually diagnosed in late pregnancy by the presence of high blood pressure with proteinuria and/or edema. Prevention of any disease process needs awareness of its prevalence, etiology and pathogenesis ( 8 ). The World Health Organization estimates that at least one woman dies every seven minutes from complications of pregnancy induced hypertension disorders. Pregnancy complicated with hypertensive disorder is related with increased risk of adverse fetal, neonatal and maternal outcome ( 9 ).

Null parity, multiple pregnancies, history of chronic hypertension, gestational diabetes, fetal malformation , obesity, extreme maternal age (less than 20 or over 40 years), history of PIH in previous pregnancies and chronic diseases like renal disease, diabetes mellitus, cardiac disease, unrecognized chronic hypertension, positive family history of PIH which shows genetic susceptibility, psychological stress, alcohol use, rheumatic arthritis, extreme underweight and overweight, asthma and low level of socioeconomic status are the risk factors for PIH ( 5 , 10 , 11 ). According to a study in South Africa, the incidence of hypertensive disorders of pregnancy was 12%, and it was the commonest cause of maternal death which contributed 20.7% of maternal deaths ( 12 ).

As the Ethiopian Demographic Health survey (EDHS) 2016 reported, maternal mortality ratio is 412 deaths per 100,000 live births, and pregnancy induced hypertension has a countless role for this maternal death ( 13 ). A review study conducted on the causes of maternal mortality in Ethiopia indicated that the proportion of maternal mortality in Ethiopia due to hypertensive disorders between the year of 1980 and 2012 was in an increased trend from 4%–29% ( 14 ).

The Federal Ministry of Health has applied multi-pronged approaches to reducing maternal and newborn morbidity and mortality by improving access to and strengthening facility-based maternal and newborn services but the maternal morbidity and mortality due to pregnancy induced hypertension was in an increasing trend ( 15 ).

Despite the fact that pregnancy induced hypertension is a leading causes of maternal morbidity and mortality during pregnancy, little is known about the current magnitude of PIH, its associated factors among women attending delivery service in Ethiopia and specifically in study areas. Therefore, the objective of this study was to assess pregnancy induced hypertension and its associated factors among women attending delivery service at Mizan Tepi University Teaching Hospital, Gebretsadikshawo Hospital and Tepi General Hospital, Southwest Ethiopia.

Materials and Methods

Study area and period : The study was conducted in Mizan Tepi University Teaching Hospital, Tepi General Hospital and Gebretsadikshawo Hospital found in Benchi Maji, Sheka and Kefa zones from October 01-November 30/2016. Mizan Tepi University Teaching Hospital is located in Bench Maji Zone 560 kms far from Addis Ababa, and Gebretsadikshawo is found 441 kms from Addis Ababa in Kefa Zone and Tepi General Hospital is located in Sheka Zone 565 kms from the capital city of Ethiopia, Addis Ababa.

Study design: Health facility based cross-sectional study design with quantitative data collection method was used.

Source and study population : All women who attended delivery service in Mizan Tepi University teaching Hospital, Tepi General Hospital and Gebretsadikshawo Hospital were considered as source population whereas all sampled women were considered as study population.

Inclusion and exclusion criteria : All admitted women in delivery ward with gestational age greater than 28 weeks were included to the study whereas women with known chronic hypertension and those who were critically ill and unable to communicate after full course of treatment were excluded from the study. A woman who was critically ill due to PIH was waited until she recovered from her illness.

Sample size and sampling technique : The sample size was calculated by using a single population proportion sample size calculation formula by considering the following assumptions: d = margin of error of 5% with 95% confidence interval and P=50% in order to maximized the sample size. By considering 10% none response rate, the final sample size became 422.

The total sample size was proportionally allocated to the three public hospitals based on their source population from each hospital. The source population of each hospital was taken from six-month delivery reports. Then, the average was considered as source population (1030). Afterwards, the study participants were systematically selected from each hospital, and admitted mothers for delivery who were eligible to the study were included until the required sample size was obtained ( Figure 1 ).

Schematic presentation of sampling procedure

Pregnancy induced hypertension (PIH) : A pregnant women attending delivery service with high blood pressure (≥140/90mmHg) after 28 weeks of gestation was measured two times six hours apart by trained data collectors and with or without proteinuria. The diagnosis of PIH was confirmed by a physician working in labour ward. Pregnancy induced hypertension includes gestational hypertension, pre-eclampsia and eclampsia.

Psychological stress : A woman who scored greater than the mean score was considered as psychologically stressed.

Data collection instruments : The data was collected by using pre-tested structured questionnaire adapted from a validated questionnaire ( 16 , 17 ). The questionnaire was first adapted in English and translate into Amharic by an expert and translated back to English to see the consistency of the item. The questionnaire contains sections for assessing demographics and associated factors. The questions and statements were grouped and arranged according to the particular objectives that they were aimed to address. Six data collectors who were degree-holding midwives in qualification fluent in speaking, writing and reading Amharic language were recruited purposefully from their respective facilities to maintain the quality of the data. also Three supervisors were recruited for the same purpose.

Data collection procedure : Data was collected through face-to-face interview, measurements and reviewing of medical records of the mother using pretested structured questionnaire by trained data collectors. Data were collected day and night in order not to miss the cases. Blood pressure reading was taken while the woman was seated in the upright position and supine position using a mercury sphygmomanometer apparatus, and for referred women, BP and protein urea at time of diagnosis were taken from referral form.

Data processing and analysis : EPI data statistical software version 3.1 and Statistical Package for Social Sciences (SPSS) software version 21.0 were used for data entry and analysis. After organizing and cleaning the data, frequencies and percentages were calculated to all variables that were related to the objectives of the study. Variables with p-value less than 0.25 in binary logistic regression analysis were entered into the multivariable logistic regression analysis to control confounders. Odds ratio with 95% confidence interval was used to examine associations between dependent and independent variables. P-value less than 0.05 was considered significant. Finally, the result was presented by using tables and narrative forms.

Data quality control measures : The quality of the data was assured by using validated and pretested questionnaire. Prior to the actual data collection, pre-testing was done on 5% of the total study subjects at Chena Hospital which was not included in the actual study, and based on the findings necessary amendments were made. Reliability of the questions used to measure psychological stress of mothers was tested by Cronbach's alpha test (0.89). Data collectors were trained for one day intensively on the study instrument and data collection procedure that included the relevance of the study, the objective of the study, confidentiality of the information, informed consent and interview technique. The data collectors worked under close supervision of the supervisors to ensure adherence to correct data collection procedures. The supervisors reviewed the filled questionnaires at the end of data collection every day for completeness.

Every morning, the supervisors and the data collectors conducted a morning session to solve problem, if encountered, as early as possible and to take corrective measures accordingly. Moreover, the data was carefully entered and cleaned before the analysis.

Ethical considerations : The study did not involve any experiment, and no harm was expected on human subjects, exception of benefit. Ethical clearance from Mizan Tepi University and permission from respective authorities and written consent of respondents' were obtained before the data collection. To get full co-operation, respondents were reassured about the confidentiality of their responses. They were also informed their voluntarily participation and right to take part or terminate at any time they wanted. Since the subjects of the study could raise ethical issues, care was taken in the design of the questionnaire.

Socio-demographic characteristics : Among the total study participants, 155(37.3%) were aged between 20–24 years, more than half 236(56.7%)of the respondents were orthodox in religion, and 403(96.9%) were married. Almost half of the participants were from rural areas, 214(51.4%). Regarding their educational level, 150(36.1%) of the respondents attended primary school, the majority 276(66.3%) were housewives, and 230(55.3) of the family sizes of the participants were between 3–4 ( Table 1 ).

Distribution of the study participants by their socio- demographic characteristics at MTUTH, Tepi and Gebretsadikshawo hospitals, south west Ethiopia, Nov, 2016

Prevalence of pregnancy induced hypertension : The prevalence of pregnancy induced hypertension among women attending delivery service in the three hospitals of this study was 33(7.9%). The mean of systolic blood pressure was 110.72±15.315 with range of 90 mmHg to 210 mmHg, and the mean of diastolic blood pressure was 72.71±13.093 with range of 50 mmHg to160 mmHg. The result of proteinuria ranged from negative to 3+ in dipstick test. Out of the total of women who had pregnancy induced hypertension, 5(15.2%) were gestational hypertension, 12(36.4%) were mild preeclampsia, 15(45.5%) were severe preeclampsia and 1(3%) were eclampsia.

Variables related to obstetric conditions : Out of the pregnant women who participated in study, 408(98.1%) of the pregnancy were wanted, and 224(53.8%) of pregnancy were multigravida. Regarding parity of the women, 261(62.7%) had parity of 1–4, and the majority, 309(74.3%) of gestational ages were between 37 and 42 weeks. Only 5(1.3%) of the pregnant mothers who were admitted for delivery had previous history of PIH, only 3(0.8) of them had history of gestational diabetic mellitus while 20(4.8%) of the pregnancies were multiple ones ( Table 2 ).

Frequency distribution of variables related to obstetric conditions among women attending delivery service at MTUTH, Tepi and Gebretsadikshawo hospitals, southwest Ethiopia, 2016

NB : GDM=Gestational Diabetic Mellitus

Medical and family history related variables : Regarding medical and family histories of illness, out of the total, 43(10.3%) had family history of chronic hypertension, 16(3.8%) of them had family history of pregnancy induced hypertension commonly from their mothers, 11(84.6). Regarding kidney diseases, 32(7.7%) of the respondents had history of kidney diseases during the current pregnancy, and only 7(1.7%) of them had history of chronic diabetic mellitus. From the study participants, only 36(8.7%) of them had family history of diabetic mellitus and 2 (0.5%) of them had history of asthma ( Table 3 ).

Distributions of medical and family history risk factors among delivered women at MTUTH, Tepi and Gebretsadikshawo hospitals, South west Ethiopia, 2016

Variables related to personal risks : Among the respondents, 9(2.2%) had history of smoking cigarette, of which 2(0.5%) were current smokers while 23(5.5%) of the family members smoked cigarette, mostly the husbands, 20 (87%). From the total of the mothers attending delivery service, 350(84.1%) had mid upper arm circumference ≥21cm whereas 66(15.9%) them were <21cm.

Regarding sleeping pattern of women during current pregnancy, more than half, 250(60.1%), of them sleep ≥9 hours per night, and 164(39.4%) of women were doing scheduled regular physical exercise during their current pregnancy. Based on the nine items used to assess psychological stress, 171(41.1%) of the women had psychological stress during current pregnancy ( Table 4 ).

Distribution of the study subjects by their personal risk factors among women attending delivery service at MTUTH, Tepi and Gebretsadikshawo hospitals, Southwest Ethiopia, Nov, 2016

Variables related to health facility utilization : According to this study, 406(97.6%) of the pregnant mothers utilized health facility for ANC follow-up, of which 8(2%) attended first visit of their routine ANC follow-up and 398 (98%) attended ANC more than twice. Regarding utilization of health facilities for health problems other than the current pregnancy, only 132(31.7%) utilized health facilities for gynecology, surgical and medical problems.

Predictors of pregnancy induced hypertension : In the multivariable logistic regression analysis, factors contributing to pregnancy induced hypertension were identified: Positive family history of pregnancy induced hypertension, kidney diseases during pregnancy, asthma and gestational age had statistically significant associations with pregnancy induced hypertension ( Table 5 ).

Multivariable logistic regression analysis of pregnancy induced hypertension and associated factors among women attending delivery service at MTUTH, Tepi and Gebretsadikshawo hospital, Southwestern 11 Ethiopia, 2016

The pregnant women attending delivery service with family history of pregnancy induced hypertension were five times more likely to develop pregnancy induced hypertension than those who did not have family history of pregnancy induced hypertension (AOR=5.25 at 95%CI= (1.39–19.86).

As this study showed, having kidney diseases during pregnancy was 3.25 times more likely to develop pregnancy induced hypertension as compared to pregnant mothers who did not have kidney diseases during pregnancy (AOR=3.32 at 95%CI= (1.04–10.58). Women who had asthma more likely develop pregnancy induced hypertension by 38 times as compared with women those attending delivery service did not have asthma (at 95% CI, AOR=37.95(1.41–1021).

In this study, gestational was age identified as predictor, indicating that women with gestational age greater than or equal to 37 weeks were less likely to develop pregnancy induced hypertension by 9.6% as compared to women gestational age less than 37 weeks (AOR=0.096 at 95% CI(0.04–0.23) ( Table 5 ).

The prevalence of pregnancy induced hypertension among women attending delivery service in this study was 33(7.9%). This might increase the morbidity and mortality of the mother and the fetus. If appropriate preventive measures are not taken for the risk of pregnant women, in long term, it might be the first cause of maternal mortality. The prevalence of PIH in this study is similar with the study conducted in India which was 7.8 % ( 18 ). However, it is slightly lower than the findings of studies done in Iran 9.8% ( 19 ), in Jimma University Specialized Hospital (8.48%) and Dessie Referal Hospital, 8.4%( 20 , 21 ).

This difference might be attributed to differences in the study period and study design. The population might also be different in lifestyle and culture. However, the prevalence in this study is still greater than the study done in Ethiopia at Tikur Anbessa Hospital which was 5.3% and Mettu Karl Hospital, 2.4% ( 7 , 22 ).

This discrepancy might be because of differences in the study period, study design and health seeking behaviors of pregnant women. In addition, the gap might be due to current health policy which focuses on implementation of focused ANC and exempted service for maternal care which increases the health care seeking behavior of pregnant women and delivery at health facility which increases detection of the case.

In this study, some associated factors of pregnancy induced hypertension were also identified. Having family history of pregnancy induced hypertension had about five times greater odds of developing pregnancy induced hypertension. This is consistent with the study conducted in Ghana ( 23 ) and in the textbook of current diagnosis and treatment in obstetrics and gynecology ( 2 ). This might have occurred due to genetic factors that contribute to the physiologic predisposition of pregnancy induced hypertension.

This study revealed that having kidney diseases during pregnancy increases the likelyhood of pregnancy induced hypertension. This finding was similar with the study conducted in Public Health facility of Dirashe Woreda which showed that preexisting renal diseases had statistically significant associations with pregnancy induced hypertension ( 24 ). Other theories also support that renal physiological function had direct relationship with cardiovascular system ( 2 ).

This study also showed that women who had asthma are at more risk to develop pregnancy induced hypertension than those who did not have asthma. This is in line with the study conducted in New York and Canada ( 25 , 26 ). The other variable associated with PIH in this study was gestational age, which showed that women with gestational age greater than or equal to 37 weeks were less likely to develop pregnancy induced hypertension than women with gestational age less than 37 weeks. However this is inconsistent with the literature. This might be due to the fact that the population of this study was women attending delivery service so that more women with PIH might be delivered before and around 37 weeks of gestational age to reduce the risk of maternal and fetal complication.

As any other cross-sectional study, this study has strength and weakness. The possible limitations may arise from women's readiness and ability to provide every information about themselves and their family correctly based on which PIH was related and; recall and social desirability bias may be introduced during data collection from the pregnant women as they were self-referred. However, measure has been taken to minimize these limitations by using targeted questions.

The other limitation of this study was few variables have small observation which causes lower precision, so it was carefully interpreted. Inclusion of all hospitals from the three zones was strength of this study.

The prevalence of pregnancy induced hypertension among women attending delivery service was 7.9% which indicates that a significant number of women attending delivery services at Mizan Tepi Teaching Hospital, Gebretsadikshawo and Tepi Hospital developed pregnancy induced hypertension. Among pregnancy induced hypertensions, severe preeclampsia was the most common. Having family history of pregnancy induced hypertension, chronic renal diseases (kidney diseases) and gestational age were the factors associated with pregnancy induced hypertension.

Acknowledgment

We are extremely grateful to the Mizan Tepi University for grant fund, study subjects involved in the study, data collectors and supervisors.

Determinants of Hypertensive Disorders of Pregnancy in Rural Women in Central India: A Community-Based Cohort Study

• Original Article
• Published: 16 July 2024

Cite this article

• Shuchi M. Jain 1 ,
• Pradeep Deshmukh 2 ,
• Shreya Sharad Mor 1 ,
• Poonam Varma Shivkumar 1 &
• Amardeep Tembhare 3  

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This prospective cohort study was planned to elucidate the magnitude and epidemiological determinants for hypertensive disease in pregnancy (HDP) in a cohort of rural women of central India.

It was a community-based prospective cohort study of rural pregnant women. 1650 eligible women were recruited at less than 20 weeks of gestation by pretrained field workers in 100 villages of Wardha District. Baseline socio-demographic factors of all subjects were recorded with the help of open-ended pre-designed and tested questionnaire. They were screened for high risk factors. The woman was followed up till delivery for development of hypertensive disorder of pregnancy.

The overall incidence of hypertensive disorders in pregnancy was 7.15%. On univariate analysis, significant determinants of HDP were education, occupation, socio-economic status, interval from previous pregnancy, BMI, calcium intake, stress, and family history of hypertension. Odds of HDP increased by 1.075 times with every additional year of age (95%CI: 1.001 to 1.154), by 1.165 times if BMI increases by one unit (95%CI: 1.165 to 1.168), by 1.168 times if stress score increases by one (95%CI: 1.091 to 1.252), and reduced by 0.736 if haemoglobin increases by one gm/dl (95%CI: 0.632 to 0.858). Family history of hypertension doubles the odds of HDP (95%CI: 1.075 to 3.813).

Conclusions

This study helped us to know the burden and various epidemiological determinants of hypertensive disorders. It helped us in identifying the modifiable high risk factors that stakeholders should give due attention to formulate preventive strategies for improving obstetric outcome.

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Acknowledgements

We would like to thank all our patients who gave consent to be a part of this study. We would also like to thank all colleagues, juniors and staff who helped us with this study.

Funding was received from Indian Council of Medical Research. (ICMR).

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Department of Community Medicine, AIIMS, Nagpur, Maharashtra, India

Pradeep Deshmukh

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Amardeep Tembhare

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Dr. Shuchi M. Jain is a Professor and Head of Department in Obstetrics and Gynaecology; Dr. Pradeep Deshmukh is a Professor and Head of Department in Community Medicine; Dr. Shreya Sharad Mor is a Assistant Professor; Dr. Poonam Varma Shivkumar is a Director Professor and Dr. Amardeep Tembhare is an Associate Professor.

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Jain, S.M., Deshmukh, P., Mor, S.S. et al. Determinants of Hypertensive Disorders of Pregnancy in Rural Women in Central India: A Community-Based Cohort Study. J Obstet Gynecol India (2024). https://doi.org/10.1007/s13224-024-02027-y

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Received : 22 March 2023

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Published : 16 July 2024

DOI : https://doi.org/10.1007/s13224-024-02027-y

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