Determinants of pregnancy-induced hypertension on maternal and foetal outcomes in Hossana town administration, Hadiya zone, Southern Ethiopia: Unmatched case-control study.

BACKGROUND: Globally, 292,982 women die due to the complications of pregnancy and childbirth per year, out of those deaths 85% occurs in Sub Saharan Africa. In Ethiopia, pre-eclampsia accounts for 11% of direct maternal deaths.
OBJECTIVE: To determine maternal and foetal outcomes of pregnancy-induced hypertension among women who gave birth at health facilities in Hossana town administration.
METHODS: Institutional based unmatched case-control study was conducted among women, who gave birth at health facilities from May 20 to October 30, 2018. By using Epi-Info version 7; 207 sample size was estimated, for each case two controls were selected. Two health facilities were selected using a simple random sampling method. Sample sizes for each facility were allocated proportionally. All cleaned & coded data were entered into Epi-info version 3.5.1 and analysis was carried out using SPSS version 20. Multivariate analysis was performed to determine predictors of pregnancy-induced hypertension at a p-value of <0.05. RESULT: Women between 18 to 41 years old had participated in the study with the mean age of 26.00(SD ±4.42), and 25.87(SD ±5.02) for cases and controls respectively. Out of participants 21(30.4%) among cases and 21(15.2%) among controls had developed at least one complication following delivery. 12 (17.4%) and 8 (5.7%) foetal deaths were found in cases and controls groups respectively whereas 15.6% from cases and 3.6% from controls groups women gave birth to the foetus with intra-uterine growth retardation. Women gravidity AOR = 0.32 [95% CI (0.12 0.86)], Previous history of pregnancy-induced hypertension AOR = 22.50 [95% CI (14.95 16.52)] and educational status AOR = 0.32[95% CI (0.12, 0.85)] were identified as predictor of pregnancy-induced hypertension.
CONCLUSION: Women with a previous history of pregnancy-induced hypertension had increased risk of developing pregnancy-induced hypertension, whilst ≥ 3 previous pregnancies and informal educational status decrease odds of developing pregnancy-induced hypertension.

Introduction

Pregnancy and childbirth are natural processes, which comes up with multiple consequences. A hypertensive disorder is one of the pregnancy consequences which is a major alarming cause for maternal, perinatal morbidity and mortalities [1]. The term hypertension in pregnancy is commonly used to describe a wide spectrum of the patient who may have only mild elevations in blood pressure to severe organ dysfunction. Thus, it is accompanied by minor to major complications. Worldwide hypertensive disorder in pregnancy/HDP affects 5–22% and it is responsible for 5–10% of complications in all pregnancies [2-4].

Among four classes of HDP, preeclampsia remains a leading cause, which needs rigorous public intervention for better outcome of foetus and mother, and Preeclampsia affects up to 5–8% out of all pregnancies [5]. Also, preeclampsia is a unique form of hypertension during pregnancy which usually occurs after 20 weeks of gestation. If the early investigation and appropriate management are not undertaken for the women diagnosed with pre-eclampsia. It progress to a severe form called eclampsia, which end-up with maternal as well as foetal adverse outcomes like abruption placenta, acute renal failure/ARF, intravascular coagulation, intra-uterine growth retardation/IUGR, and stillbirth [6]. Therefore, the origin for eclampsia is pre-eclampsia (Eclampsia is the definition of Preeclampsia plus ≥ +2 proteinuria plus the occurrence of convulsion or coma) [7].

Studies suggested that either pre-existing pregnancy-induced hypertension/PIH or pregnancy changes could be responsible for the occurrence of pre-eclampsia. In a multicentre study approximately, 30% of hypertensive disorders of pregnancy were occurred due to chronic hypertension while 70% of the cases were diagnosed as gestational hypertension or pre-eclampsia [8]. Regardless of new-onset or pre-existing occurrences, the harmful effects of preeclampsia and eclampsia upraised from mother to child, family to the country and its severity is from trivial to life-threatening. Still, it has remained a significant public health threat in both developed and developing countries [9].

PIH denotes women’s systolic blood pressure/SBP ≥ 140mmHg, and diastolic blood pressure/DBP ≥ 90mmHg on two or more consecutive measures without proteinuria after 20 weeks of gestation; pre-eclampsia is characterized as when pregnant women presented with SBP ≥ 140mmHg and DBP ≥ 90mmHg on two or more consecutive measures within 4 hours interval with the presence of proteinuria that occurs after 20 weeks of gestation whereas eclampsia denotes the occurrence of convulsion plus proteinuria +2 or more and sign and symptom of severe pre-eclampsia for the women who fulfil the definition of PIH [10-12].

Pre-eclampsia and eclampsia are the second direct cause for maternal death which accounts for 10 to 15% of maternal deaths worldwide [13]. The incidence of pre-eclampsia has significant variation in different parts of the continents. For instance, 4% in Africa, 3.8% in Europe, and 4.2% in the western Pacific region [14]. Moreover, the prevalence of pre-eclampsia throughout the country has vast variation, in Jima University specialized hospital, it was 51.8%, three southwest Ethiopia hospitals 6.3% [15], and in seven Tigray hospitals 50% [16].

Globally, 292,982 women died due to the complications of pregnancy and childbirth. Out of those deaths, 85% have occurred in Sub Saharan Africa/ SSA, yet the majority of those deaths occurred in low resource settings, and most of them could have been preventable [17, 18]. Furthermore, the highest share of maternal death has been reported in Africa as compared to other regions. Maternal death due to pregnancy-related causes is 1 in 4,000 in Europe and 1 in 16 in African countries [18, 19]. Likewise, The probability of a 15 year-old girl eventually dying from a maternal cause in Africa was as high as 1 in 37- as compared to 1 in 3400 in the European region [20].

According to the latest joint trend review study in maternal mortality conducted by United Nation Population Division/UNPD, World health organization/WHO and World Bank, the proportion of mothers dying per 100,000 live births has declined from 380 to 210 in 1990 to 2013 [21]. Besides, there was a slight reduction in maternal mortalities in the last three consecutive Ethiopian demographic health surveys/EDHs; MMR was 667, 665 and 412 per 100,000 life birth and all those deaths might have happened as a result of direct or indirect causes [22]. On the other hand, a trend review study from 1980 to 2012 in Ethiopia, on maternal death reported that as a result of hypertensive disorder of pregnancy/HDP, maternal death has increased from 4%-29%. In-addition to the death trend, the review pointed out the major direct obstetric complications (sepsis, haemorrhage, unsafe abortion, obstructed labour) including pre-eclampsia, accounts for 85% of maternal death. Whereas pre-eclampsia solely accounts for 11% of maternal death [23, 24]. Whilst pre-eclampsia and Eclampsia contribute to 53% of maternal and 62.7% of perinatal complications during pregnancy and birth [25].

HDP especially preeclampsia, in primigravida women is 2 times more risky than multigravida [26, 27]. Impacts of pre-eclampsia and eclampsia are disproportional in both developed and developing countries which are seven times higher in developing countries than in developed worldwide [28].

Impacts of Pre-eclampsia and eclampsia on maternal and foetal outcomes are enormous, which results in life-threatening events to death. For instance, it increases the risk of placenta abruption, postpartum haemorrhage/PPH and intra-uterine growth retardation. According to the WHO multicentre survey, the risk of perinatal death among women with preeclampsia and eclampsia increased 3 and 5 folds respectively, as compared to women with no preeclampsia or eclampsia [26, 29, 30]. Still, preeclampsia is one of the major causes of perinatal death in developing countries, accounts for 20–50% of deaths [31]. In Ethiopia, eclampsia accounts for 35.7% of maternal death [32, 33].

Studies were done abroad and our country revealed that pregnancy-induced hypertension has been associated with poor maternal and prenatal outcomes and loos of life [34]. Case control hospital-based study done in India reported that 10, 8, 3 and 2 complications of Haemolysis, Elevated Liver enzymes, and Low Platelet count/HELLP syndrome, PPH, Infection and ARF respectively [35]. On another case control study conducted by Guduri GB revealed that there were 18%, 2% PPH and 36%, 7% preterm complication, among cases and controls respectively [36].

Studies done in different regional hospitals, Ethiopia reported various proportions of maternal complications and deaths following delivery occurred as a result of pre-eclampsia/eclampsia. The Eastern part of, Ethiopia finding revealed that 53% maternal and 62.7% perinatal complication with a fatality rate of 11% [25], in Woliata Sodo University teaching Hospital 48.89% perinatal complication and 8.89% perinatal deaths [37]. In Zewuditu Memorial Hospital, among women had developed PIH, 131 (52.4%) of them developed complication whilst 31.1% of them experienced with HELLP syndrome [38].

Different studies noted that previous history of pregnancy-induced hypertension, age, and educational status were independent risk factors for the development of preeclampsia. In addition to these, occupation, gravidity, family history of hypertension, gestational diabetic Mellitus and residence had a significant statistical association with preeclampsia [39-42].

Yet, there have been different studies conducted to explore PIH in Ethiopia, but there was no study conducted on predictors of pregnancy-induced hypertension in the study area. Thus, to come up with effective public as well as clinical intervention approach and strong policy development direction, conducting root cause identification research is essential. Therefore, the main objective of this study is to determine maternal and foetal outcomes of pregnancy-induced hypertension among women who gave birth at Public health facility in Hossana town administration, Hadiya zone, Southern Ethiopia: unmatched case control [Fig 1].

Fig 1

Conceptual frame work of PIH and factors (source from literature review).

Legend: PIH: Pregnancy-induced hypertension, HDP: hypertensive disorder of pregnancy, Hx: history, ANC: antenatal care, GA: gestational age.

Methods and material

Study area

The study was conducted in Hossan town administration, Hadiya Zone, South Nation Nationality and People Regional state/SNNPR, Ethiopia. Hadiya zone has ten woredas and two town administrations. According to the Hadiya Zone Finance and Economic Development office statistics, the total population of the zone was 2,486,242 of which 1,218,258 were men whereas 1,267,983 of them were female.

Hossana town is located in the northern part of SNNPR state. It is 232 KM far from the country’s capital city to the south and 120 KM from the regional capital town. The town administration is classified into 3 subs administrative with a total of 8 kebeles. According to the Hossana town administrative office, the current (2018/2019) projection estimated total population was 104,053 whereas 50,986 males and 53, 067 of them were females. Among the total town population, women within the reproductive age group encompass 24,244 from them the estimated number of women who are eligible to be pregnant in the current physical year were 8,388 [43].

The town has one teaching hospital which has been serving more than 3, 548,800 million people from the entire Hadiya Zone and partial part of kembeta and Silte Zone. As well, the town has three health centres, one private surgical hospital, and more than 15 private clinics.

Study design and period

Institutional based unmatched case control study was conducted in OB/GYN department of the selected public health facilities, from May 20/2018 to October 30/2018.

Cases

All pregnant women who were on follow up after 20 weeks gestational age and visit health facilities for delivery service and screened as of having pregnancy-induced hypertension registered in the OB/GYN departments of the respective facilities.

Controls

Pregnant women who have no PIH in the same period and the same health facilities and who came for delivery service after 20 weeks of gestational age.

Source population

The source population of the study were all women, who have been on follow-up care unit and visit facilities for delivery service in Public Health facilities those resided in Hossana town administration.

Study population

All women who were selected using systematic sampling method applying population proportionate to sample size (PPS) from randomly selected public health facilities among women who had been on follow-up care unit and visit the health facility for delivery service whose gestational age above 20 weeks.

Eligibility criteria

Inclusion criteria

All pregnant women who were on flow up and visited selected public health facility for delivery service whose gestational age above 20 weeks were included. For women representing cases, they diagnosed having Pregnancy-induced hypertension as of her SBP ≥140mmHg and DBP ≥90 mmHg on two separate reading which measure within at least four hours apart, plus a dipstick reading +1 and above. For women represent Controls, women within the same health facilities who were attending delivery care was not diagnosed as having Pregnancy-induced hypertension.

Exclusion criteria

Women who didn’t indweller in respective town administrative sub towns and no longer stay at Hossan town administration for more than six months.

Women with a known diagnosis for Epilepsy and women who were not voluntary to give consent also excluded from the study.

Simple size and sampling technique

Sample size

The sample size for this study was computed based on the comparison of proportion for case control study by using Epi-info version 7 for windows. According to a study conducted by Eskeziaw Agedew [39], by considering the factors gravidity and maternal age had an association with PIH. Being multigravida and age during current pregnancy between 25–30 years which have a significant association with pregnancy-induced hypertension with case to control ratio 1:2 and Odds ratio (OR) = 4 and using the following assumptions: power 80%, confidence level 95% (Table 1). The final sample size was taken from the women who were multigravida by adding 10% non-response rate. Thus, an estimated sample was employed for case 69 and 138 for controls yielding a total sample of 207.

Table 1

Sample size calculation for second specific objective for PIH effect on maternal and foetal health among women gave birth in public health facilities.

Variables	Expected frequency of control among exposed	Case	Control	OR	Total sample size
Multigravida	10.1%	63	126	4	207
Age 25–30	38.4%	16	155	4.59	171

OR: Odds ratio

Sampling technique

To select a study unit two Public Health facilities were selected randomly among four facilities. Considering the two months report data from the health management information system/HMIS office sample size allocated proportionally by using proportionate to population size for cases and controls. All newly registered pregnant women who were more than 20 gestational weeks suffered from pregnancy-induced hypertension were selected representing the cases. For each case, women who registered for ANC follow up and had given delivery whose gestational age ≥20 weeks, but hadn’t experienced with PIH at the same time in the same facilities were taken as control. To select controls, a list of total women the MCH department registration book for those who have ANC follow up after 20 weeks of gestation age was considered as a sampling frame. The estimated sample size for this study (n) was divided by a total number of women (N) registered in randomly selected HFs during the last two months which yield proportionate (P). Then through multiplying proportionate value with two months sample, a proportional sample was allocated for each selected health facilities. Finally, by employing a systematic sampling method based on the kth value sampling unit was traced in respective facilities. The sampling procedure was presented (Fig 2).

Fig 2

Sampling procedure scheme of mother who gave birth in public health facility, Hossana town administrative, Southern Ethiopia, 2018.

HC: health centre, NEMMTH: Nigest Eleni Mohomod Memorial Teaching Hospital, n: proportional allocated sample size.

Data collection method, tools and procedures

Structured and pretested questionnaires which was prepared in English and translated to Amharic and then translated back into English again to assure consistency of tool, which developed from reviewing different literature was used in this study.

Data were collected by 4 BSc midwives, 2 BSc Nurses supervised and monitored during the data collection phase by using structured questionnaires whereas the principal investigator undertakes the overall coordination. Data were collected from women who gave birth in the OB/GYN department, for each case, two controls were interviewed on the same day and health facilities. Participant’s medical charts were also reviewed to obtain biomedical laboratory data at the same time.

Data quality control measures and management

Training

Before the actual data collection date, data collectors & supervisors were trained concerning the overall issue of data collection format like, in time data collection following delivery, completeness, participant confidentiality and consistency.

Pre-test

One week before the actual data collection date, research tool was tested on 13 women who gave birth at Doyogena primary hospital, validity checked then a lot amendment was undertaken.

Every day, the principal investigator and supervisors were checked data for completeness and incomplete questionnaires were discarded. Cross-checked and coded data were entered into Epi-info software version 3.5.1. For further analysis and data cleaning, it was exported to SPSS (statistical package for social science) version 20.

Data analysis

To identify the proportion of the pregnancy induce hypertension impact on maternal and foetal outcome in-relation to outcome variable cross-tabulation frequencies were done. Cross tabulation was also employed to test the relation of variables against with outcome variable. Bivariate logistic regression was conducted to select candidate variables for multivariate analysis at P-value < 0.05. Finally, to determine predictors of outcome variables multivariate analysis was employed.

Data was described and presented using cross-tabulation value to for descriptive findings and interpreted by looking at a variable that has an association with outcome variables on multivariate analysis with a 95% confidence interval for AOR.

Study variables

Dependent variable

Foeto-maternal outcomes of Pregnancy Induced Hypertension

Independent variable

Socio demographic variables. Maternal age, residence, educational status, occupation and monthly income.

Obstetrics variables. Gravidity, number of parity, gestational age at delivery, number ANC follow up, number of babies (twin).

Medical variables. Previous history of pregnancy induced HTN, History of D/M, anaemia and renal disease.

Hypertensive disorder sign and symptoms of pregnancies on admission. Level of blood pressure during admission/presentation, vomiting, proteinuria, typical symptoms (oedema, blurred vision, headache and epigastric pain).

Ethical consideration

Ethical approval was obtained from IRB of WCU, Official letter for zonal/woreda health department was written from University research and community service V/P office and a cooperation letter was written from respective woreda office managers to the randomly selected health facilities.

Operational definitions of terms

Hypertensive disorders of pregnancy

Includes chronic hypertensive and pregnancy induced hypertension, regardless of previous history of hypertensive disorder.

Pregnancy-induced hypertension

Hypertension developed after 20 weeks of gestation where SBP ≥ 140mmHg and DBP ≥ 90mmHg, within two consecutive reading which measured 4–6 hours apart without proteinuria among mothers who were attended delivery unit at health facilities among previously normotensive women.

Preeclampsia

The new onset of hypertension with SBP ≥ 140 and DBP ≥ 90 mmHg, within two reading which measured 4–6 hours interval with the presence of proteinuria with or without oedema which occurred after 20 weeks of gestation.

Eclampsia

Mother with DBP greater than or equal to 110mmHg after 20 weeks of gestation and in-addition to the features of pre-eclampsia having one or more episode of convulsion or coma plus proteinuria +2 or more.

Pregnancy outcome

Any women who had at least one prenatal as well as maternal unfavourable outcome after delivery

Maternal complication

Any mothers had at least one complication among who had attended delivery at Hospital.

Gestational age

The duration of gestation is measured from the first day of last menstrual period more than 20 weeks for this study.

Foetal outcomes

Any diagnosed complication or death confirmed after delivery.

Result

Socio-demographic characteristics

Among a total of 207 participants, 69 cases and 139 controls women have participated in the study. Women from the age of 18–41 participated in the study while their mean age was 26.00 (SD ± 4.42), 25.87 (SD ± 5.02) for cases and controls respectively. Two women were participated in the study where their age was below legally eligible for marriage. The majority 97 (47.3%) participants’ were house-hold wives, 9(4.3% of them were students and 69 (42.9%) had no formal education.

Reproductive history and pre-existing medical illness during current pregnancy

Among women who had ANC visits three and above, 34 (52.3%) from cases and 72 (55.0%) from control were not developed PIH. Women with a high frequency of ANC follow-Up had a low proportion of becoming hypertensive on current pregnancy while among women who had no ANC follow-up, 4 from cases and 10 from controls groups had developed pregnancy-induced hypertension.

More than one-third of the study participants were primigravida among them 34 (31.5%) were not know their LNMP. However, 180 (86.9%) didn’t attend the minimum expected ANC follow up, only 16 (7.7%) had four and above ANC follow up. Seven women among cases and 44 women from control groups gave birth by caesarean section, but the largest proportion 62 (89.8%) of women from cases gave birth via spontaneous vaginal delivery/SVD as compared with controls 94 (68.1%).

Among all interviewed women, 29 (14.0%) were experienced with pre-existing medical illness includes: diabetic Mellitus, anaemia and non-pregnancy induced hypertension 4.3%, 5.3% and 3.9% respectively. A high proportion of women from cases 14 (20.3%) had medical problems as compared to controls 15 (10.9%). Out of the total cases that participated in this study; twenty-four women had a previous history of PIH. On the occasion of health facility arrival, 120 (57.9%) women were admitted with pushing labour pain, but the remaining were came up with one or more features rather than labour pain (

Even though the DBP range from 90 to 144 mmHg among cases the mean DBP, 104.13 (SD ± 9.20) was above the cut-off point of the normotensive women. Perinatal delivered from women with cases experienced with an average of 0.7 complications. On the occasion of reception for delivery service and follow-up care in addition to having high blood pressure, every woman from cases was admitted with at least of two suggestive clinical features for PIH whereas controlled had less than 1 clinical feature (Table 3).

Table 3

Mean score and proportion of selected items among women gave birth in Hossana town administration, southern Ethiopia, 2018.

		Case	Control
Mean age of the respondents		26. 00 (SD ± 4.42)	25.87 (SD ± 5.02)
Mean score of the SBP		157.32 (SD ± 18.89) mmHg	126.02 (SD ± 13.75) mmHg
Mean score of the DBP		104.13 (SD ± 9.20) mmHg	76.31 (SD ± 7.68) mmHg
Average number of suggestive CF for PIH on admission		2.5 (SD ± 1.14)	0.22 (SD ± 0.59)
Number of maternal complication		0.66 (SD ± 0.74)	0.60 (SD ±0.74)
Average number of Perinatal complication		0.65 (SD ± 0.95)	0.54 (SD ± 0.83)
Parity	0	13	97
	1 and above	56	41
Mode of delivery	SVD	62	94
	CS	7	44

CF: clinical feature, CS: cesarean section, SD: Standard Deviation

Maternal and fetal outcomes

A total of 69 women with cases participated in the study and showed a potential effect on maternal and perinatal health. Among the interviewed cases, 11 (15.9%) of them were developed eclampsia. On the occasion of the arrival to health facility among women who had developed eclampsia, only 3 (27.2%) of them were comatose on the occasion of the arrival of health facility. For all Women who developed PIH urine test was performed and a test result had shown a minimum +1 proteinuria for the dipstick test.

Among the total of interviewed cases, 21(30.4%) women have developed at least one complication following delivery. The majority of complications were 13 PPH and 7 disseminated intravascular coagulopathy/DIC. Moreover, PIH has a potential effect on maternal as well as perinatal outcomes; perinatal borne from women with PIH more likely to develop complication than normotensive women. Out of 55, alive births among cases 32 (58.2%) had at least one complication, but out of total alive births, 32.9% (n = 68) perinatal hadn’t any complication. From 20 perinatal deaths, 12 (17.4%) was reported from women who had developed PIH. Among 13 foetal IUGR, 8 of them were from cases as far as women diagnosed for PIH 3.7 times more risky to causes foetal IUGR than normotensive women (Table 4).

Table 4

Maternal and foetal outcome among women gave birth in Hossana town administration, southern Ethiopia, 2018.

Variable	Category	Maternal and fetal outcome among both group		OR	95% CI	P value
		Case n = (%)	Control n = (%)
Maternal complication	Yes	21 (30.4)	21 (15.2)	2.83	1.30, 6.15 *	0.01
	No	48 (69.6)	117 (84.5)
Perinatal complication	Yes	32 (58.2)	78 (63.4)	2.23	0.87, 5.74	0.10
	No	23 (41.8)	45 (36.6)
HEELP syndrome	Yes	4 (8.2)	1 (1.2)	0.14	0.02, 1.25	0.09
	No	45 (91.8)	83 (99.8)
PPH	Yes	13 (27.7)	13 (15.5)	2.09	0.87, 4.99	0.10
	No	34 (72.3)	71 (84.5)
Neonatal death	Yes	12 (17.4)	8 (5.7)	3.42	1.32, 8.82 *	0.01
	No	57 (82.6)	130 (94.2)
IUGR	Yes	8 (15.6)	5 (3.6)	3.71	1.16,11.88 *	0.03
	No	53 (76.8)	123 (89.3)
Birth weight	Normal	35 (63.6)	91 (71.1)	1.41	0.72, 2.74	0.32
	LBW	20 (36.4)	37 (28.9)
Gestational age at the delivery	Pre-term	8 (11.6)	6 (4.4)	2.84	0.95, 8.55	0.06
	Term	61 (88.4)	130 (95.6)

*statistically significant at 95% CI with P value < 0.05, OR: odds ratio, CI: confidence interval

Pregnancy-induced hypertension and associated factors

Binary logistic regression with a confidence level of 95%, (α = 0.05) was conducted and variables which have statistically significant at p-value < 0.05 were selected as candidate variable for the last model that determine predictors of pregnancy-induced hypertension among women gave birth at health facilities.

Finally, variables entered into the last model and multivariate analysis was performed. The Previous history of pregnancy-induced hypertension increased odds of developing pregnancy-induced hypertension by 22 folds, [95% CI (6.313, 80.204)], three and above previous pregnancies decreases odds of pregnancy-induced hypertension AOR = 0.32 [95% CI (0.12, 0.86)] and women who had no formal education, 68.4% [95% CI (0.12, 0.85)] less likely to develop PIH than women had primary and above educational status. Thus, the model was identified; gravidity, educational status, and previous history of pregnancy-induced hypertension were determinant factors for pregnancy-induced hypertension. Furthermore, Pregnancy-induced hypertension had an impact on inducing maternal complication, perinatal death and Intra-Uterine growth retardation/IUGR (Table 5).

Table 5

Predictors of PIH among women gave birth at Hossana town administration, Southern Ethiopia, 2018.

Variable	Category	COR 95% CI	AOR 95% CI
Number of pregnancy/gravid	1 times	1	1
	2 times	2.07 (1.04, 4.13)	1.09 (0.51, 2.34)
	≥3 times	0.80 (0.37, 1.74)	0.32 (0.12, 0.86)**
Educational status	College and above	1	1
	Primary–high school	0.48 (0.22, 1.04)	0.54 (0.21, 1.39)
	No formal education	0.45 (0.21, 0.97) *	0.32 (0.12, 0.85)**
Previous history of PIH	No	1	1
	Yes	17.87 (5.87, 54.27)	22.50 (6.31, 80.20)**

*statistically significant in bivariate analysis

** statistically significant in multivariate analysis, COR: crude odds ratio, AOR: adjusted odds ratio.

Discussion

This study revealed that 21(30.4%) among cases and 21(15.2%) women in control groups had developed at least one complication following delivery. The finding is supported by the study conducted in India 54% among case and 9% from controls developed maternal complications [36]. Also, a study done by Kapil Dev revealed that among cases 24% of women developed at least one maternal complication, but there was no maternal complication in controls [37]. A lower proportion of maternal complication in this study could be due to living style and women in the study area had less history of medical complications.

The commonest maternal complications in this study were postpartum haemorrhage/PPH 13 (18.8%), which is higher than the study done in India [35]. The lower proportion reported from elsewhere might be a better management approach and health care setups in those facilities were more intensive and organized as compared to our study area.

This study showed that perinatal complications were more prevalent among controls (63.4%) as compared to cases (58.2%). The finding is supported by the study done by Aleem Arshad, only 1 and 13 low birth weight reported from cases and control, respectively [44]. In this study, neonatal death was the second leading outcome of PIH, 17.4% from cases and 5.7% controls deaths were reported. Concerning perinatal complications, this study reported that 15.6% IUGR from cases and 3.6% from control which was lower than a study conducted in India; 29% and 71% IUGR were reported from women who had developed PIH and normotensive, respectively [36]. The possible reason for the low proportion could be socio-demographic factors and women in our study area affected by low superimposed medical problems.

Out of the cases, group preeclampsia accounted for 58(84.1%) whereas eclampsia comprises 11(15.9%). A study was done in Harare, Zimbabwe reported the proportion of pre-eclampsia and eclampsia were 1.7% & 0.3% respectively [9], but the proportion was lower than a study conducted by Selemawit, 121 women developed Pre-eclampsia and 17 of them Eclampsia [45]. The difference might be due to early identification and alerting women during ANC visits which decrease the possible occurrences of preeclampsia and eclampsia. Other study carried in three south-west hospitals, Ethiopia and tertiary care hospital of Visakhapatnam, India reported in the prevalence of pre-eclampsia and eclampsia were 7.9%, 3% and 16%, 36% respectively among cases [36, 46].

In this study gravidity has an association with PIH, women with gravidity 3 and above were 68% [95% CI (0.12, 0.86)], less likely to develop Pregnancy-induced hypertension as compared to their counterparts. This study is in-line with a study done in Darashe Special woreda [39] and Kombolicha, Ethiopia [41]. Whereas, the finding is in contrast with the study done in Addis Ababa, Ethiopia and Colombia; primigravida women were 2.7 times more likely to develop PIH than multigravida [24], and 36.9% of primigravida women among cases had developed PIH [47], the possible reason might be due to difference in assigning the reference group.

History of previous pregnancy-induced hypertension was significantly associated with PIH. In our study previous history of pregnancy-induced hypertension had 22 times increased odds of pregnancy-induced hypertension as compared to previous normotensive women. Out of the total interviewed women who had previous history of pregnancy-induced hypertension, 34.8% in cases and 2.9% in controls groups developed PIH in the current pregnancy. This finding is in-line with the studies done in Addis Ababa, Ethiopia and Karnataka, India. Women with a previous history of pregnancy-induced hypertension were 4 times more likely to develop PIH during current conception, which reported 28.95% women among cases and 10.9% among control had developed PIH in Karnataka, India. Women with a previous history of PIH were 58 times odds of developing PIH, out of the total interviewed cases 60% and controls 2.50% of women developed PIH during current pregnancy [36]. However, the finding of this study contradicts with the study done in Jaipur, India [40].

In this study, multivariable analysis revealed that previous history of medical illness had no statistical association with PIH, but studies conducted in Tigray, Kombolicha in Ethiopia, and Southern India reported that women with diabetic Mellitus were 5.4, 11 and 5 times more likely to develop PIH respectively [16, 41, 48]. The possible reason for this discrepancy could be that the number of women with a pre-existing medical problem in this study was fewer than those studies conducted elsewhere.

In addition to the maternal complication, this study singled-out that perinatal complications such as low birth weight, IUGR, and pre-term were higher in the cases than controls. Also, the study demonstrated that there was no association between PIH and birth weight which is in contrast with the study done in Zimbabwe where women with PIH were 3 times more likely to have a baby with low birth weight [9]. However, this study is in-line with a study done by Eskzyiaw [39]. Major perinatal complications reported in this study were LBW (31.1%), IUGR (6.9%) and preterm (6.8%).

Conclusion and recommendation

Conclusion

Pregnancy-induced hypertension yet has been seen as a burning issue, which provokes adverse health impact on mothers and their babies. In this study, both maternal and perinatal outcomes were significantly different in both groups (cases & control). Women with PIH were at higher risk for a maternal and perinatal adverse outcome as compared to normotensive women. Women with a previous history of PIH had increased risk of developing PIH whilst women who had ≥ 3 previous pregnancies and with informal education were less likely to develop pregnancy-induced hypertension.

Recommendation

For women diagnosed with a previous history of pregnancy-induced hypertension, health care providers should have taken especial attention and focused care to tackle the adverse effect of PIH on their current conception. Furthermore, concerning governing bodies and partners engaged in maternal service should have facilitated basic setups like on-job training on early screening skills and managements, tax-free transportation. When gravidity increased women may not caution as like the first conception so that clinical expertise gave attention to alerting women regarding early warning sign and improve health service delivery strategies. Principal governing bodies and concern partners should have facilitated maternal waiting room/village for better health, good perinatal and maternal outcome.

(DOCX)

Click here for additional data file.

(DOCX)

Click here for additional data file.

26 May 2020

PONE-D-20-09595

Determinants of pregnancy induced hypertension on maternal and foetal outcomes in Hossana town administration, Hadiya zone, Southern Ethiopia: Unmatched case-control study.

PLOS ONE

Dear Dr. Babore,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

SPECIFIC ACADEMIC EDITOR COMMENTS: An expert reviewer in the field handled your manuscript. Although interest was found in your study, several major comments arose during review that require your attention. These comments include, but are not limited to, the necessity to improve the readability of your manuscript and the conclusions need to be better supported by the major results of this study.

Please submit your revised manuscript by Jul 10 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Frank T. Spradley

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The paper entitled “Determinants of pregnancy induced hypertension on maternal and foetal outcomes in Hossana town administration, Hadiya zone, Southern Ethiopia: Unmatched case controlstudy,” is reporting on a case control study undertaken in Hossana town administration, Hadiya zone, Southern Ethiopia, to determine maternal and fetal outcomes of pregnancy induced hypertension.

It is commendable that the authors are researching how to improve care for women and their babies during pregnancy in a low-income country with limited resources. I congratulate them on conducting a case control study under these circumstances. The finding that women with ≥3 pregnancies, previous history of pregnancy-induced hypertension, and informal educational status were associated with pregnancy-induced hypertension adds to knowledge in this area and may support early diagnosis and improve management and pregnancy outcomes. These findings offer local evidence on which to base future public health interventions in this population and may have important implications for future research and practice. However, the paper requires modifications before it is ready for publication.

Major:

1. The abstract conclusion and the paper conclusion are not consistent with the reported results. The results report that having a previous history of pregnancy-induced hypertension is associated with increased odds of pregnancy-induced hypertension in the pregnant women in this study, and having ≥3 previous pregnancies, and no formal education, is associated with reduced odds of pregnancy-induced hypertension. However, the abstract conclusion and paper conclusion report that ‘women with multigravida, previous history of PIH and with informal educational status were prone to develop pregnancy-induced hypertension.’ Please modify the abstract conclusion and paper conclusion so that they accurately reflect the results.

2. The background and discussion contain considerable detail about other studies, which is most interesting. However, the readability of the paper would be improved if the background and discussion were restructured, so that the focus is on information that is directly related to the objectives and findings of this study. In addition, some comparisons made with other studies would benefit from rechecking to ensure that the comparisons reported in this paper are accurate.

Minor:

3. The authors may wish to consider having the paper professionally edited for English language to assist understanding.

4. The background reports ‘Pregnancy induced hypertension also known as Preeclampsia…’ Please revise this definition, so that the reader understands that while pregnancy-induced hypertension may lead to preeclampsia, they are not the same condition.

5. When reporting the results of the multivariable analysis (which are odds ratios) in the text, please consider describing the association of the assessed factors as ‘increased odds of pregnancy-induced hypertension’ or ‘decreased odds,’ rather than ‘likelihood’ or ‘prone to.’

6. Where percentages have been provided in the text, please also report the numbers to support the readers understanding.

7. Please provide abbreviations in full the first time they are reported.

8. The authors may wish to consider combining some of the result tables and adding a column for the univariable odds ratios for all factors in Table 2 to support understanding. The addition of text below the tables to explain abbreviations in the tables would also be helpful.

9. Please consider providing a copy of the data collection tool (the structured and pretested questionnaire) as an attachment, as this would assist understanding of the work that has been undertaken for this study and would be of considerable interest to readers.

Thank you for the opportunity to review this most interesting and important case control study that is researching the determinants of pregnancy-induced hypertension in order to improve care for women and their babies in Ethiopia. I believe that after some modifications, this paper will provide valuable local evidence on which to base future public health interventions in this population.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

22 Sep 2020

All authors of this manuscript read and took any effort to revise the whole manuscript based on the comment given by peer review. For all forwarded minor and major comments authors gave response as follows.

1. We assure you that all components (manuscript, tables, figures, abstract and abbreviations) of this article was prepared based on the PLOS ONE guide line.

2. My ORCID is 0000-0002-7214-4025

3. Abstract in the manuscript and online submission in-terms of character and contents were revised and identical.

4. For all listed figure (figure_1 & Figure_2) in the main part of the manuscript their copies uploaded separately.

5. Copy of tables (table 1-5), which referred in the text were uploaded immediately next to the each paragraph in the manuscript.

Reviewer #1: The finding of this study revealed that women with previous history of pregnancy induced hypertension more likely to develop pregnancy induced hypertension on current conception whereas women with > 3 number of pregnancies and informal education status were decreased odds of pregnancy induced hypertension. Thus, research team/authors recommend that concern bodies should have facilitate basic setups to make conducive environment (women waiting village, in-service training, and tax free transportation) for better management of the cases where as health care providers should have increased early diagnosis and on time intervention rather than managing complication. Therefore, our paper conclusion part is modified as like aforementioned.

Major comment

1. Conclusion in abstract and paper regarding factors revised based on the finding of the multivariate logistic regression. Variables description: women with previous history of pregnancy induced hypertension increased odds of developing PIH in current conception whereas number of pregnancies > 3 and women having informal education status are 67.7%, 68.4% less likely to develop pregnancy induced hypertension/PIH respectively, this implies they associated with reduced odds of developing PIH. From the point of epidemiology, if the odd ratio/OR < 1 a factor has protective effect of likelihood occurrence of event. Therefore, both number of pregnancies > 3 and women having informal education status reduced odds of developing pregnancy induced hypertension/PIH.

2. In fact, background of this manuscript contains detail about others studies, but for seek of readers better understanding and readability background of the manuscript was revised based on the stated objectives and its finding. As you have reviewed the back ground of the manuscript contained detail about the previously studied articles, but the revised background contain about Pregnancy induced hypertension of preeclampsia and eclampsia and maternal and foetal outcomes in details. Moreover, discussion part also restructured through focusing on Objectives (predictors of PIH and foeto-maternal outcomes) and for more understanding almost all comparison was made with case control studies. We assure you that all comparison made based on the reference which in-line with our study. For further accuracy and consistent you can crosscheck according to the cited reference.

Minor comment

3. The manuscript for better readability and understanding edited by English language professionals who is PhD candidate in Addis Ababa University, Ethiopia. If you have further enquires you can communicate through this address. Email negatuhabitamu@gmail.com cell phone +251912191000.

4. Pregnancy induced hypertension and preeclampsia differ according to the ‘operational definition given in this manuscript. In-addition, Pregnancy induced hypertension is a broad definition and according to the latest American college of obstetrics and gynaecologist preeclampsia is one category of Pregnancy Induced hypertension/PIH. In-fact, Preeclampsia may lead to ecalmpsia but not Pregnancy induced hypertension lead to preeclampsia. A woman diagnosed with preeclampsia who experienced with convulsion with or without coma can be diagnosed as eclampsia.

5. Words ‘likelihood’, ‘prone’ used to describe finding of the multivariate analysis are revised according the given comment. In main manuscript multivariable analysis finding (Odds ratio) revised as previous history of pregnancy induced hypertension is increases odds of developing PIH in current conception whereas informal educational status decrease odds of PIH or less likely develop pregnancy induced hypertension.

6. For all reported percentages in the text cross-ponding ‘numbers’ also added. For further confirmation you can check highlighted text under revised manuscript.

7. Standard Abbreviation appears first in text fully described and appears in text less than three times were excluded.

8. As our understanding if we combine any one of the table; readers may be confused because their descriptions and contents are different. For those abbreviations in the table which are not described under abbreviation explanations in text are given the tables.

9. All structured and pretested questionnaires are uploaded as supporting document.

Submitted filename: Response to reviewer .docx

Click here for additional data file.

14 Oct 2020

PONE-D-20-09595R1

Determinants of pregnancy induced hypertension on maternal and foetal outcomes in Hossana town administration, Hadiya zone, Southern Ethiopia: Unmatched case-control study.

PLOS ONE

Dear Dr. Babore,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

There are still revisions that need to be addressed by the authors. You must respond all of the reviewer's comments in your revised manuscript.

Please submit your revised manuscript by Nov 28 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Frank T. Spradley

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The revised paper entitled “Determinants of pregnancy induced hypertension on maternal and foetal outcomes in Hossana town administration, Hadiya zone, Southern Ethiopia: Unmatched case control study,” is reporting on a case control study undertaken in Hossana town administration, Hadiya zone, Southern Ethiopia, to determine maternal and fetal outcomes of pregnancy induced hypertension.

Thank you for the opportunity to review this interesting and important case control study that is researching the determinants of pregnancy-induced hypertension in order to improve care for women and their babies in Hadiya zone, Southern Ethiopia.

The work by the authors to revise the manuscript based on previous feedback is appreciated, however, further changes are required before the paper is ready for publication. Following changes, this paper will provide valuable local evidence on which to base future public health interventions in this population.

Major:

1. The authors have had the manuscript edited for readability and understanding for English language from a professional who is PhD candidate in Addis Ababa University, Ethiopia. However, it is essential that the authors have the paper edited again for English language by a person who is skilled in this area. English spelling and language improvements are necessary throughout every section of the paper, so that the information is clear and understandable and the data is not misinterpreted by the reader.

Minor:

To assist with the recommended changes to the paper, the authors may find previously published papers in their reference list, on the same topic of hypertension in Ethiopia, are a helpful guide.

Introduction:

• This section would benefit from being shorter and clearer. English spelling and language improvements may assist with this.

• The information provided on hypertension, pre-eclampsia and eclampsia is important as background to the paper, however, the way it is currently written is confusing to the reader. Please revise so that the reader is clear about the definition of pregnancy induced hypertension and how it relates to pre-eclampsia and eclampsia, and maternal and fetal outcomes. Some papers in your reference list may be helpful with this, e.g. Berhe, A.K., Kassa, G.M., Fekadu, G.A. et al. Prevalence of hypertensive disorders of pregnancy in Ethiopia: a systemic review and meta-analysis. BMC Pregnancy Childbirth 18, 34 (2018). https://doi.org/10.1186/s12884-018-1667-7.

Results:

• Please note that this reviewer is not an expert on statistical analysis, therefore is unable to comment on the sample size and process of analysis.

• Table 4 and Table 5, please change the ORs, CIs, and p=values in the tables from 3 decimal places to 2 decimal places (e.g. Table 4, Maternal complication, please change to OR 2.83, 95% C 1.30, 6.15, P 0.01).

• Table 5, “Number of pregnancy/gravid” requires “>3 times” to be changed to ≥ 3 times.

• While Table 5 shows that having ≥3 previous pregnancies is associated with reduced odds of pregnancy-induced hypertension, the text reports that ‘Number of pregnancy women with three and above pregnancies increased odds of pregnancy induced hypertension with AOR=0.32 [95% CI (0.121, 0.864)] than two and below.” Please change the text so that it matches the data in the table.

Discussion:

• It is recommended that the first paragraph of the discussion describes if the objectives of the paper have been met.

• Comparisons made with findings from other studies are useful, but not always understandable, and would benefit from English language improvements to improve reader understanding.

Conclusion:

This conclusion is unclear. English language improvements would help to ensure that the study findings are not misinterpreted by the reader.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

27 Nov 2020

All authors of this manuscript read and took any effort to revise the whole manuscript based on the comment given by the reviewer. All authors try to incorporate the given comment in the entire manuscript. For all forwarded minor and major comments authors gave response as follows.

All authors rigorously tried to address all points answered by reviewer, which stated from 1-7. Then major improvements were made from abstract to recommendation.

Reviewer #1:

Major

In addition to previous edition made by English language professional who is PhD candidate in Addis Ababa University, Ethiopia, in this round additional edition to improve readability and understanding made by Dr. Feleke Doyore (PhD, health promotion and communication) Who is lecturer in Wachemo University) and English language professional Mr Yirga H. (BA, MA) currently, who is teaching in Bobicho preparatory school, Hossan, Ethiopia.

Minor

Regarding Pregnancy Induced Hypertension, Pre-eclampis and eclampsia; to improve readability and understanding for the reader, detail definition written in the background part (from line number 85-94). In addition to this, for further understanding detail definition is also described in the operational definition part (line number 324-332).

The relation between pregnancy induced hypertension with preeclampsia and eclampsia is one is the inclusive the other; when a women diagnosed for eclampsia also fulfil diagnosis criteria of preeclampsia as well women diagnosed for preeclampsia fulfil diagnosis criteria of pregnancy induced hypertension. Therefore, eclampsis = definition of Preeclampsia + occurrence of convulsion or coma + >+2 proteinuria whereas preeclampsia = definition of pregnancy Induced hypertension + presence of proteinuria in dipstick test with or without oedema.

The effect of the pre-eclampsia and eclampsia on the maternal and foetal health explained in detail in the background part (from line number 132-153), which reflect the related outcomes of preeclampsia and eclampsia.

Sample size calculation was performed by using statistical software EPI-Info V 7 for window considering all statistical assumptions and others those needed to estimate sample size. Thus, software sample size estimation is more recommendable and it gives large sample size than manual calculation.

All figures of the ORs, CIs and P values in the tables 4 and 5 are changed to the 2 decimal places from 3 decimal places.

Table 5 finding and text report regarding having >3 previous pregnancies and its odds ratio edited as ‘’ decrease odds of pregnancy induced hypertension.’’

Discussion

Discussion based on the objective of the study revised rigorously. It is the fact that, the first objective of this study is to measure the outcomes of the pregnancy induced hypertension among cases and controls group. Hence, the outcomes of pregnancy induced hypertension on maternal and foetal health explained in detail and based on the multivariate analysis predictors of pregnancy induced hypertension discussed one by one.

Conclusion

To improve understanding and readability for the readers, major amendment undertaken in conclusion part based on the objective of the study and finding of multivariate analysis.

Submitted filename: Response to reviewres.doc

Click here for additional data file.

6 Jan 2021

PONE-D-20-09595R2

Determinants of pregnancy induced hypertension on maternal and foetal outcomes in Hossana town administration, Hadiya zone, Southern Ethiopia: Unmatched case-control study.

PLOS ONE

Dear Dr. Babore,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

ACADEMIC EDITOR: The reviewer and I still have major issues with the readability of this manuscript. The reviewer has kindly offered suggestions to improve this issue. However, it is requested that the authors contact a copyeditor to help with improvement and proof of English grammar and syntax. Failure to do so will prohibit acceptance of this manuscript. Please provide a markup of changes within your revised manuscript.

Please submit your revised manuscript by Feb 20 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Frank T. Spradley

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The third draft of the revised paper entitled “Determinants of pregnancy-induced hypertension on maternal and foetal outcomes in Hossana town administration, Hadiya zone, Southern Ethiopia: Unmatched case control study,” is reporting on a case control study undertaken in Hossana town administration, Hadiya zone, Southern Ethiopia, to determine maternal and foetal outcomes of pregnancy-induced hypertension.

The work by the authors to revise the manuscript based on previous feedback is appreciated. However, despite the authors’ revisions, the paper is still not presented in an intelligible fashion. To be clear, there are English language corrections required in every section (abstract, introduction, methods and material, result, discussion and conclusion), every sub-section, every paragraph, and every sentence in this paper.

In addition, the paper is still too long, with unnecessary repetition, and many sentences still do not make sense. The definition of pregnancy-induced hypertension and how it is related to pre-eclampsia and eclampsia must be revised and clarified.

Spelling corrections required throughout the paper include, but are not limited to:

- Please correct the spelling of the word ‘sever’ to ‘severe’ (note that several corrections are required).

- Please correct the spelling of the word ‘per-eclampsia’ and ‘preeclampsia’ to ‘pre-eclampsia’ (note that several corrections are required).

- Please correct the spelling of the abbreviation ‘HEELP’ to ‘HELLP’ (note that several corrections are required).

- Please correct the spelling of the word ‘pregnancy induced hypertension’ and ‘pregnancy-induced hypertension (note that several corrections are required).

- Please correct the spelling of the word ‘case-control’ to ‘case control’ (note that several corrections are required).

- Please correct the spelling of ‘dipstic’ to ‘dipstick’.

- Please correct the spelling of ‘Intra uterine growth retardation’ to ‘Intra uterine growth restriction’ (note that several corrections are required, although following the first use of IUGR abbreviation in the introduction, they can be abbreviated to IUGR).

- Please remove unnecessary capital letters in the middle of sentences (note that several corrections are required).

Abbreviation corrections required include, but are not limited to:

- Introduction, paragraph three, first sentence: This is the first time the words ‘pregnancy-induced hypertension’ appear in the main body of the paper. Please add the abbreviation PIH here. That is, the sentence should say, ‘Studies suggested that either pre-existing pregnancy-induced hypertension (PIH) or pregnancy changes could be responsible for preeclampsia occurrence.’

- Introduction, paragraph seven, second sentence: This is the first time the abbreviation ‘HDP’ appears in the main body of the paper. It should appear the first time the words ‘hypertensive disorders of pregnancy’ appear in the main body of the paper (which is in the first paragraph of the introduction).

- Introduction, paragraph eleven, second sentence: This is the first time the abbreviation ‘HEELP’ (which must be corrected to HELLP) appears in the main body of the paper. Please add the definition here. That is, the sentence should include that HELLP syndrome includes Haemolysis, Elevated Liver enzymes, and Low Platelets.

In summary, there are English language corrections required in every section (abstract, introduction, methods and material, result, discussion and conclusion), every sub-section, every paragraph, and every sentence in this paper. Until these English language corrections are made, the paper is shorter, and the sentences make sense, I cannot recommend this paper for publication.

**********

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Reviewer #1: No

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2 Apr 2021

Response to reviewers

Under the guidance of corresponding authors, all authors read for long period and they brought the revised manuscript to the table and revision was made together. The whole manuscript revised based on the comment given by the reviewer though using copyedit and others language academicians. For all forwarded major and minor comments authors gave response as follows.

All authors rigorously tried to address all points answered by reviewer, which stated from 1-6. Then major improvements were made from abstract to recommendation according the points raised by reviewers.

Reviewer #1:

In addition to previous edition made by English language professional who is instructor at Bobicho high school, Hossana, Ethiopia, Mr Yirga H. (BA, MA) in this round additional edition in every section (abstract to Conclusion) to improve readability and understanding made by Amanuel Tirkaso (MA, PhD candidate) Who is lecturer at English department, college of social science, Wachemo University, Hossan

In order to avoid unnecessary repetition, exhaustive reading and formatting few lines were undertaken. To minimize paper length, total words in main body of the manuscript (introduction to conclusion) reduced from 5674 to 5,222 words.

Regarding Pregnancy Induced Hypertension, Pre-eclampis and eclampsia definition and relation; to improve readability and understanding for the reader, detail definition written in the background part (from line number 83-89). In addition to this, for further understanding detail definition is also described in the operational definition part (line number 289--298).

The relation between pregnancy induced hypertension with preeclampsia and eclampsia is one is the inclusive the other; a woman diagnosed for pre-eclampsia characterised with elevated blood pressure (SBP > 140 & DBP > 90mmHg) without presence of proteinuria which developed after 20 weeks of gestation. Preeclampsia: two reading of SBP > 140 mmHg & DBP > 90mmHg 4-6 hours apart after twenty weeks of gestation with proteinuria 2+ or more whereas eclampsia is women with signs and symptoms of preeclampsia plus convulsion with or without coma. Oligohdrouia or anuria is present. Therefore, eclampsis = definition of preeclampsia + occurrence of convulsion or coma + >+2 proteinuria whereas preeclampsia = definition of pregnancy-induced hypertension + presence of proteinuria in dipstick test with or without oedema.

All miss spelt words edited appropriately. Abbreviation correction in case of first appearance revised through out of the main body of the manuscript. Regarding Intra uterine growth retardation/IUGR the right word is retardation but not restriction.

Discussion

Discussion based on the stated objective of the study revised rigorously. More focuses of the discussion done considering studies done using case control design. Hence, the outcomes of pregnancy induced hypertension on maternal and foetal health explained in detail and based on the multivariate analysis predictors of pregnancy induced hypertension discussed one by one.

Conclusion

Based on the objective of the study, conclusion focus adverse outcomes of PIH on maternal and foetal health and multivariate analysis findings.

Submitted filename: Response to reviewres.doc

Click here for additional data file.

12 Apr 2021

Determinants of pregnancy induced hypertension on maternal and foetal outcomes in Hossana town administration, Hadiya zone, Southern Ethiopia: Unmatched case-control study.

PONE-D-20-09595R3

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20 Apr 2021

PONE-D-20-09595R3

Determinants of pregnancy induced hypertension on maternal and foetal outcomes in Hossana town administration, Hadiya zone, Southern Ethiopia: Unmatched case-control study.

Dear Dr. Babore:

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Table 2

Cross tabulation of socio-demographic and RH among women gave birth at public health facilities, in Hossana town administration, Southern Ethiopia, 2018.

Variable	Category	Participants
Age of the women		Case n = 69 (%)	Control n = 138 (%)
	15–24 year	25 (36.2)	60 (43.5)
	25–34 year	40 (58.0)	71 (51.4)
	35–44 year	4 (5.8)	7 (5.1)
Educational status	No formal education	26 (37.7)	63 (45.7)
	Literate	43 (62.3)	75 (54.3)
Marital status	Single	0	1 (0.7)
	Married	67 (97.1)	120 (87.0)
	Divorced	2 (2.9)	17 (12.3)
Gravidity	Primgravida	20 (28.6)	50 (71.4)
	Multigravida	49 (35.8)	88 (92.8)
ANC	Yes	65 (94.2)	128 (92.)
	No	4 (5.8)	10 (7.2)
Maternal complication	Yes	21 (30.4)	21 (15.2)
	No	48 (69.6)	117 (84.8)
Number ANC visit	1–2	31 (47.7)	59 (45)
	>3 and above	34 (52.3)	72 (55.0)
History of medical illness	Yes	14 (20.3)	15 (10.9)
	No	55 (79.7)	123 (89.1)
History of previous PIH	Yes	24 (34.8)	4 (2.9)
	No	45 (65.2)	134 (97.1)

PIH: pregnancy-induced hypertension, ANC: antenatal care