Effect of pregnancy induced hypertension on adverse perinatal outcomes in Tigray regional state, Ethiopia: a prospective cohort study

A prospective cohort study was conducted in multiple hospitals of Tigray regional state. Tigray regional state is located in the northern part of Ethiopia bordered by Eritrea to the north, Sudan to the west, Afar region to the east and Amhara region to the south. The source population for this study was all pregnant women who attend antenatal care at general hospitals located in Tigray from February 2018 to February 2019. General hospitals provide outpatient and inpatient services to the general population which includes medical, surgical, pediatric, accident and emergency services, maternal and child health (MCH), and obstetric and gynecological care, and other relevant services. In addition, general hospitals serve as a referral center to primary health care units. There are fifteen general hospitals in Tigray regional state from those the following eight hospitals entirely distributed in the region namely Lemlem Carl, Mekelle, Adigrat, Adwa, Saint Marry Axum, Suhul Shire, and Kahsay Abera hospitals were included in this study. Those selected hospitals can represent the larger region since more than 50 % of the hospitals in the region were included in this study. General hospitals provide both basic and comprehensive emergency obstetric and newborn care. The average number of delivery in each hospital is around 1600 per year. All the hospitals included in this study provide comprehensive diagnostic and management services for hypertensive disorders of pregnancy starting from the mild form of gestational hypertension to the severe forms of preeclampsia/eclampsia.

Women with PIH and normotensive women in each antenatal care clinic of the hospitals were enrolled to study by reviewing their blood pressure level and proteinuria. Pregnancy-induced hypertension was defined as new hypertension (systolic BP ≥140 mmHg and/or diastolic BP ≥ 90 mmHg) that appears at 20 weeks or more gestational age of pregnancy with or without proteinuria (includes preeclampsia, eclampsia, and gestational hypertension). Pregnant mothers diagnosed with PIH during the data collection period in the selected antenatal care clinic of the hospitals were included as exposed participants and women without PIH during the same period were also enrolled as a non-exposed participant. Pregnant women with chronic hypertension, critically ill women who could not give consent, women who could not respond to the interview and those pregnant women likely to become “lost” e.g., planning to move, unwilling to return for the prospective follow up period were excluded from this study at the time of enrollment. There were no other restrictions (like maternal age, singleton pregnancies, etc.).

A double population proportion formula was used to calculate the sample size. The maximum sample for this study was calculated from the outcome variable stillbirth by considering the following assumptions; two-sided confidence level of 95%, the power level = 80%, r = the ratio of exposed to unexposed group 1 to 2, p₁ = proportion of stillbirth among women with PIH 5.4% [23], p2 = proportion of stillbirth among normotensive pregnant women 1.3%) [23]. With the consideration of a 10% loss to follow up a total of 798 study participants (266 participants with PIH and 532 normotensive participants) were finally included in this study.

From a total of fifteen general hospitals providing maternal health services like antenatal care, delivery and postnatal care services in Tigray regional state, randomly eight hospitals were selected using a simple random sampling technique. The calculated sample size was proportionally allocated to selected hospitals based on the number of pregnant mothers attending antenatal care in each hospital. Women with PIH were recruited consecutively until we get the required sample and two normotensive women next to diagnosed PIH cases were selected by a systematic sampling method using antenatal care registration as a frame list.

A structured questionnaire containing information on socio-demographic characteristics (maternal age, residence, educational status, and employment), obstetric and reproductive health history information’s like gravidity, prior history of PIH, maternal undernutrition ((MUAC< 23 cm), history of anemia, current PIH status, and perinatal outcomes were used to collect the data. Wealth index of participants was assessed using socioeconomic variables like durable asset ownership, ownership of housing, type of floor and roof materials, ownership of farmland, farm animals, number of people in a household, number of rooms in the household, access to utilities and infrastructure (sanitation facility and source of water supply). The questionnaire was prepared by reviewing research articles, demographic health survey (DHS) tools, WHO survey tools and published works on PIH then adapted to the local context [21, 23, 27‐36]. Overall the questionnaire of this study was initially prepared in English version and translated to the local language called Tigrigna by a language expert and back converted again to English by another person to check the consistency.

Midwives and nurses having experience in research assistance were involved in the data collection and supervision. Training was provided for all data collectors and supervisors before the commencement of the actual data collection. The training focused on the objectives of the study, ethical issues, interviewing techniques, inclusion criteria of the study, follow up procedures of the study and overall contents of the data collection instrument. Before starting the actual data collection, a pretest was done for the data collection instruments. Necessary corrections on the data collection instrument were made based on the result of the pretest.

The recruitment of study participants was carried out from February to November 2018. Women who fulfill the inclusion criteria were enrolled in the study during antenatal care. Participants were enrolled at 28–35 weeks of their gestational age. The follow-up period varies between participants depending on the time of enrollment to the study and the gestational age at enrollment. However, the overall follow up period was from February 2018 to February 2019. All selected women were followed by data collectors prospectively through pregnancy, delivery and the postnatal period to assess adverse perinatal outcomes of PIH. Data regarding maternal socio-demographic characteristics, medical and obstetric history using an interviewer-administered questionnaire and PIH status using medical records were collected during enrollment. At the second phase within 24 h of delivery, information about the adverse perinatal outcomes such as birth asphyxia, birth weight, and gestational age at delivery, stillbirth and early neonatal death were collected from medical records. During the third phase within the postnatal period of three to 7 days, data regarding early neonatal death and early neonatal admission to NICU were collected from medical records. The definition of outcomes was based on world health organization and other related literature [37‐39]. Close supervision and checking of filled-in questionnaires were done by the field supervisors deployed with the data collectors. The overall data collection process was coordinated and supervised by the principal investigator.

The adverse perinatal outcome was defined as a newborn with the occurrence of any of the following outcomes low birth weight, birth asphyxia, small for gestational age, preterm delivery, admission to neonatal intensive care unit and perinatal death. Birth asphyxia was defined as a baby with trouble in breathing (gasping or breathing very irregularly or no breathing). Stillbirth was defined as a baby born with no signs of life at or after 28 weeks’ gestation [37]. Small for gestational age of pregnancy defined as a birth weight of newborn below the tenth percentile of weight distribution at the specified gestational age of a pregnancy [39]. Low birth weight was defined as a baby with a birth weight less than 2500 g [38]. Preterm delivery was defined as the delivery of the baby below 37 weeks gestation [38]. Low Apgar score defined as a newborn baby with an Apgar score of less than 7 at 1 and 5 min.

Descriptive statistics, frequencies and percentage for categorical variable and summary statistics for continuous data (mean with standard deviation in normally distributed data or median with IQR if the data was not normally distributed) were used to characterize the study population. The normality distribution test was done using the Kolmogorov-Smirnov test and we considered as normally distributed if p-value > 0.05. Independent t-test was used to assess the mean difference between groups. The wealth index of participants was computed using principal component analysis (PCA) from socioeconomic variables. Due to the convergent problem in log-binomial regression analysis, a modified Poisson regression model with robust standard errors was used to calculate relative risk using STATA version 14 software (research resource identifiers (RRIDs: SCR_012763)) to identify the effect of PIH on adverse perinatal outcomes. Maternal age, wealth status, educational status, residence, gravidity, type of pregnancy (single or multiple births) and mode of delivery, anemia status, maternal undernutrition variables were controlled in the statistical models. After adjusted for confounders relative risk with 95% confidence interval and p-value < 0.05 was considered to declare statistical significance.

Overall a total of 260(97.7%) women with PIH and 522(98.1%) normotensive pregnant women had completed the study (Fig. 1). The reasons for the loss-to-follow-up study were traveling to other places for assistance during pregnancy and delivery. The mean maternal age of women with PIH and normotensive women was more or less similar (27.27 vs 27.34 years respectively). Women with PIH were more likely residing in rural areas than normotensive women (31.5% vs 16.7%). The proportion of primigravidas were more likely higher among women with PIH than normotensive women (41.2% vs 31.8%). In addition, women PIH were less likely to be in the highest wealth status than normotensive women (20.1% vs 40.0%). The proportion of history of anemia was higher among women with PIH than normotensive women (27.3% vs 10%). (Table 1).

Nearly 66.4% of women with PIH and 22.2% of normotensive women developed adverse perinatal outcomes in their newborns. The incidence of birth asphyxia was higher among newborn babies delivered from women with PIH than normotensive women (46.5% vs11.3%). Similarly, low birth weight babies were higher among women with PIH than normotensive women (37.7% vs 6.1%). The mean birth weight of babies born from women with PIH was 2647.2 g and 3176 g among normotensive pregnant women (t-test = − 11.66, p-value < 0.001). In addition, 36.7% of babies born from women with PIH and 10.7% from normotensive women were small for gestational age. The proportions of admission to the neonatal intensive care unit were higher among newborns delivered from women with PIH than normotensive women (28.8% vs 5.4%). Additionally, higher preterm births occurred among pregnant women with PIH than normotensive pregnant women (40.8% vs 5.6%). Women with PIH were more likely to have a lower gestational age at delivery than normotensive women (37.3 ± 2.5 weeks vs. 39.0 ± 1.6 weeks, p = 0.001).

Stillbirths occurred in 10.0% of women with PIH and 1.7% normotensive pregnant women respectively. The stillbirth rate among women with PIH was 100/1000 live births.

Moreover, early neonatal death occurred in 5.0% of mothers with PIH and 1.0% of normotensive mothers. Overall perinatal death occurred in 15.0% women with PIH and 2.5% normotensive pregnant women. Similarly, the perinatal mortality rate among women with PIH was 150 per 1000 live births and 25 per 1000 live births among normotensive pregnant women (Fig. 2).

The risk of birth asphyxia (adjusted relative risk (aRR) = 2.69, 95%CI (1.91,3.80)), low birth weight (aRR = 5.13 (3.36,7.84)), preterm newborn (aRR = 5.19(3.37,7.99)), small for gestational age (aRR = 3.3(2.3,4.6)), admission to NICU (aRR = 3.29(2.33,4.65)), stillbirth (aRR = 3.46(1.40,8.54)) and perinatal mortality (aRR = 3.67(1.83,7.38)) were significantly higher in women with pregnancy-induced hypertension compared to normotensive women after adjusted by maternal age, wealth status, educational status, residence, gravidity, mode of delivery, anemia and maternal undernutrition status (Table 2).