Hrev_master [page 46] [Healthcare in Low-resource Settings 2013; 1:e12] Risk factors for pre-eclampsia among women at antenatal booking in Kano, Northern Nigeria Ibrahim A. Yakasai,1 Imran O. Morhason-Bello2 1Department of Obstetrics and Gynaecology, Bayero University Kano/Aminu Kano Teaching Hospital, Kano; 2Department of Obstetrics and Gynaecology, University College Hospital, Ibadan, Nigeria Abstract Pre-eclampsia (PE) is an important cause of maternal mortality. There have been several studies on risk factors assessment with con- flicting reports across the globe on this dis- ease; however, rigorous recent evaluation of these factors is uncommon in this region. The aim of the present study was to determine the risks factors in the early-onset PE in Aminu Kano Teaching Hospital (AKTH), Kano (Northern Nigeria). We conducted a case-con- trol study in Nigeria between April 2009 and January 2010 to identify the risk factors asso- ciated with the early-onset PE in women attending antenatal clinic in AKTH. Information on socio-cultural characteristics, medical history, previous obstetrics history, level of stress at home, and type of family were obtained and recorded in a proforma designed for the study. Multiple logistic regression analysis was used to determine the risk factors for PE at 95% confidence level. Pregnant women with early-onset PE (150 in each case and control group). Risk factors associated with increased risk of early-onset PE were: his- tory of pre-eclampsia/eclampsia (PE/E) in a previous pregnancy [adjusted odds ratio (AOR) 2.09]; exposure to passive smoking (AOR 1.34); inadequate antenatal supervision (AOR 15.21); family history of hypertension in one or more 1st-degree relative (AOR 8.92); liv- ing in a joint family (AOR 6.93); overweight (120% to 150% of pre-pregnancy ideal body weight, AOR 4.65). Risk factors among women in Northern Nigeria are similar to those reported from other studies. Good antenatal cares, early detection, reduction of stressful conditions at home are the most important preventive measures of early-onset severe PE among these women. Introduction Pre-eclampsia (PE) is a major cause of maternal and fetal mortality and morbidity. In general, the incidence of PE ranges between 2 and 10% worldwide.1 In an average UK popula- tion, the incidence of PE is less than 1 in 20 women.2 According to the National Institute of Clinical Excellence (NICE) antenatal guide- lines, a woman’s level of risk for PE in a given pregnancy should be assessed at the first ante- natal visit by identifying the presence of one or more predisposing historical risk factors, and they should be supervised more vigilantly and managed at centers with facilities for special- ized neonatal and maternal intensive care.1 In the guidelines, some of the risk factors for the development of PE are: first pregnancy; previ- ous PE; >10 years since last baby; age >40 years; body mass index (BMI) >35; family his- tory of PE; booking diastolic blood pressure (BP) 80 mmHg; proteinuria at booking of +1 on more than one occasion or 300 mg/24 h; multiple pregnancy; and underlying medical conditions. Different populations and ethno-geographi- cal groups may have different risk factors.2 It is important to establish the individual contribu- tion of the various risk factors for the develop- ment of PE, most relevant to the particular pop- ulation. Such studies in African women are limited. The incidence of PE in Nigeria is not known. It has never been evaluated on a large randomized trial to give a true national inci- dence. Beside the study by Anorlu and col- leagues there is none available to the best of our knowledge that attempts to estimate the incidence of PE in Lagos state. Most studies from Nigeria dealt with the incidence on eclampsia, and these vary in different geo- graphical areas. It is as low as 0.3%/100 deliv- ery in Calabar (Southern Nigeria) to as high as 5-9%/100 in Kano (Northern Nigeria). Rates are generally higher in the north than the south. Several other studies have been carried out on eclampsia.3-5 In general, the diagnostic criteria for PE are hypertension (HT) and significant proteinuria. The degree of these criteria is a major deter- minant to the progression of the disease. Women who have had a pregnancy complicat- ed by PE and endured significant maternal or perinatal morbidity require specific counseling regarding recurrence (range 0-5% and up to 47%) in order to make decisions about future reproduction. The screening tests to predict PE are also available and they are biophysical and bio- chemical. The most promising biophysical test is uterine artery Doppler scan. Though inex- pensive in the western world, it is rarely per- formed in developing countries due to cost and manpower.6 Therefore, identification of clini- cal, laboratory and historical risk factors for the development of PE in a particular popula- tion group will guide the healthcare providers during counseling of such women and possibly reduce the recurrence risk of PE if some mod- ifiable risk factors (like obesity and insulin- resistance) are present. The present study is proposed to identify the clinical and historical risk factors in women with early-onset PE (defined as having symptoms of PE before 34 weeks’ pregnancy)7 attending a tertiary care hospital in North Nigeria, and compare these risk factors with those in women in a control group without HT. Materials and Methods This case-control study was conducted between April 2009 and January 2010 in the Department of Obstetrics and Gynaecology of Aminu Kano Teaching Hospital (AKTH) Kano, Nigeria. In this study PE is defined as a rise blood pressure of 140/90mmHg and 300 mg of protein in a 24-hour urine sample in the sec- ond half of pregnancy. Severe PE is defined as a BP over 160/110 with or without additional symptoms. The study group was comprised of 150 women seen at the clinic and admitted with early-onset (34 weeks) PE with a systolic BP of 160 mmHg or a diastolic of 110 mmHg after 20 weeks’ gestation, plus proteinuria of 2.0 g/24 h (or 2+ on qualitative examination), according to the National guidelines and the departmen- tal protocol.1,8 The control group was comprised of 150 women admitted without HT and a BP less than 140/90 obtained on two occasions at least 6 h apart, for first time during pregnancy Healthcare in Low-resource Settings 2013; volume 1:e12 Correspondence: Ibrahim Yakasai, Department of Obstetrics and Gynaecology, Aminu Kano Teaching Hospital, Hospital Road, PMB 3452, Kano, Nigeria. Tel./Fax: +234.802.751.3292. E-mail: ibrahimyakasai57@hotmail.com Key words: hypertension, pre-eclampsia, risk fac- tors, Nigeria. Contributions: the authors contributed equally. Conflict of interests: the authors declare no potential conflict of interests. Received for publication: 11 December 2012. Revision received: 9 Febraury 2013. Accepted for publication: 16 Febraury 2013. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). ©Copyright I.A. Yakasai and I. Mohassan Bello, 2013 Licensee PAGEPress, Italy Healthcare in Low-resource Settings 2013; 1:e12 doi:10.4081/hls.2013.e12 No n- co mm er cia l u se on ly [Healthcare in Low-resource Settings 2013; 1:e12] [page 47] after 34 weeks’ gestation and no proteinuria, which delivered during the same period. The control groups were normotensive women matched with the study group in terms of ges- tational age, parity and age. Women with uncertain gestational age, poor compliance for follow-up, whose data did not contain platelet count, renal and liver functions, were exclud- ed. All women gave written informed consent and the study was approved by the Research Ethics Committee of the Institute. The researchers took the medical history and fill the proformas: data was collected by the princi- pal investigator and research assistant, using a pre-tested interviewer-administered ques- tionnaire. A detailed history, including past, personal and family history, pregnancy out- come, including delivery details and perinatal outcome and available investigations were recorded. If BP records in the 1st trimester were not available, the women were examined after 12 weeks of delivery to note the presence of high BP. Though PE and HT may have differ- ent pathology, patients with existing HT were included, in order to determine those who develop superimposed PE and the role if any and influence of pre-existing HT in women who go on to develop PE. Data also exist show- ing that, pre-eclamptic women were more like- ly to have a family history of HT.9,10 The stress at work was calculated by a five- level activity score, based on the distance and transportation from home to workplace, type and physical intensity of work and weekly working hours adapted from a study by Anorlu et al.11 The nature of work among the employed women in the present study was classified into sedentary, moderate and intense physical activity.12 Anorlu et al. had calculated the stress at home in terms of lack of home help, number of young children, stress from husband and number of extended family members living with the patient. They assess factors regarding stress at home and its role as a risk factor in PE. No particular score was given to these fac- tors, but found stress from lack of home help to be the most important factor. The score is not validated but useful in assessing risk factors in PE among pregnant Nigerian women. We therefore chose to use it in this study. These factors were modified to be suitable for the population enrolled in the present study and included availability of home help, resting hours and family type. The minimum sample size was calculated to be 138 using this validated formula:13 n = z2p(1-p)/d2 (1) where n=minimum sample required; z=stan- dard normal deviation=1.96 (at 95% confi- dence level); d=sample error=5%=0.05; p=incidence of women with PE (obtained from other studies) 10%.1 Therefore:n=(1.96)2(0.10)(1-0.10)/(0.05)2 n=3.84x0.10x0.90/0.0025 n=0.3456/0.0025 n=345/2.5 n=138.2 To account for failed or incomplete response, the minimum sample size was increased to 150. Consecutive sampling method was used to recruit study participants Data were analyzed using software SPSS version 11 for Windows. Analysis was done to check for range and consistency of data to determine the risk factors associated with severe PE. Odds ratio (OR) and 95% confi- dence interval (CI) was calculated for each risk factor. A P value <0.05 was considered signifi- cant. Results During the study period, there was a total of 2920 deliveries, of which 250 women had high diastolic BP (mild PE 38, 15.2%; severe PE 120, 48%; eclampsia 78, 31.2%; chronic HT 14, 5.6%). Among the 150 study patients, 110 women had early-onset severe PE, 30 had eclampsia and 10 had superimposed PE on the underlying HT. All the women in the control group had normal BP at 6 weeks’ postpartum. The mean age of cases and controls were 26.03 and 26.46 years, respectively. The socio- demographic characteristics of patients are shown in Table 1. The study group had signifi- cantly more multigravid women as compared with the control group [crude odds ratio (COR) 1.92; 95% CI 1.05-3.52]. The socio-economic status was categorized into five classes accord- ing to Olusanya’s classification.14 In the study group, 81% of women belong to the lower and lower-middle classes as compared with only 43% in the control group, which is statistically significant. Table 2 shows the medical and obstetric characteristics of patients. In the present study, the mean gestation at which women developed severe PE/E was 34 weeks, while none among the control developed it. The peri- natal mortality in the study group was 42% as compared with none in the control group. The study group women had severe disease, as 70% had BP 4180/120; 68% had urine albumin 3+; 35% had HELLP syndrome; 17% had deranged renal functions and 25% had eclampsia. The frequencies of antenatal visits are cate- gorized into adequate, intermediate and inad- equate, according to Kessner index criteria.15 The mean weight of cases and controls were 68.03 + 5.61 kg (range 50-81 kg) and 66.58 + 8.48 kg (range 44-95 kg), respectively. Since there are no nomograms of BMI during preg- nancy, and the pre-pregnancy weight is not always recorded, these women were catego- rized into four groups on the basis of the cur- rent pregnancy weight expressed as a percent- age of the pre-pregnancy ideal body weight.16 Two women in the study group had gestational diabetes mellitus (GDM) controlled on diet and four had frank diabetes (type 1). A history of previous PE/E was associated with more than 18 times increased risk of developing PE (COR 18.86; 95% CI 2.55- 389.25). As smoking has been found to be a factor that reduces the risk of PE/E, we consid- ered exposure to passive smoking to represent this factor, since none of the participants in the study group gave a history of smoking. Exposure to passive smoking is defined as the involuntary exposure to a combined but dilut- ed cigarette side-stream smoke and the exhaled smoke from the smokers.17 The level of stress at home and at work is shown in Table 3. Resting hours were defined as the availability of resting time for 2 h in the day and 7 h at night. A monogamous family consists of the married couple and their dependent children occupying the same dwelling place. The polygamous consists of a number of wives married to one man living with their children; other members of the fam- ily related may also be living in the same com- pound. Pre-pregnancy HT was taken as a significant risk factor for the development of early-onset severe PE on the basis of a highly significant P value (P<0.0003). Article Table 1. Demographic data of women in study and control groups. Variables Cases (n=150) Controls (n=150) OR 95% CI P value n % n % Age (years) <20 10 6.67 14 9.33 0.69 0.28-1.73 0.5 20-34 122 81.33 126 84 0.83 0.44-1.57 0.65 ≥35 18 12 10 6.67 1.91 0.80-4.63 0.16 Gravidity Primigravidae 66 44 75 50 0.6 0.37-0.97 0.04 Multigravidae 84 56 75 50 1.27 0.79-2.06 0.35 OR, odds ratio; CI, confidence interval. No n- co mm er cia l u se on ly [page 48] [Healthcare in Low-resource Settings 2013; 1:e12] Discussion In this study the finding revealed that a his- tory of PE, pre-existing diabetes, multiple preg- nancies, and family history, a raised BMI greater than 35 at booking, maternal age greater than 35 years, underlying renal dis- ease, HT, more than 5 years since last pregnan- cy, and raised BP at booking all increased the risk of women developing PE. The study further shows that exposure to passive smoking is a significant risk factor for the early-onset severe PE. However, other stud- ies have reported that cigarette smoking dur- ing pregnancy was associated with a 32% and 35% reduction in the risk of PE.9,18 The biolog- ic mechanism by which cigarette smoking dur- ing pregnancy may reduce the risk of PE is not clear. It may be possible that smoking leads to the earlier termination of pregnancies – mis- carriage, preterm delivery, or abruption – which would otherwise be destined to manifest as PE.17 Family history of PE was reported to be a risk factor and nearly triples the risk for PE.17 However, in another study, it did not emerge as a significant risk factor.19 History of pre-preg- nancy HT was a significant risk factor associ- ated with early-onset severe PE in univariate analysis (RR 2.14), which is in agreement with other studies. Brown and colleagues20 found that the prevalence of chronic HT was higher in women who develop PE than women who do not (12.1% vs 0.3%). The results of the present study regarding the stress-related factors shows that women of lower socio-economic status and living in a joint family have an increased risk of severe early-onset PE. It is likely that these women may have increased household work due to more family members in a joint family leading to increased physical and mental stress, which may predispose them to develop severe early- onset PE. Chronic autoimmune disease like hypothy- roidism in this study remained a significant risk factor in the development of PE. In a matched case-controlled study Wolfberg et al.21 found that women who develop PE were more likely to have an autoimmune disease. In the present study, of the 150 women with severe PE, 4/8 women with hypothyroidism had chron- ic HT as compared to 26/92 euthyroid women (50 vs 28%). The final verdict as to whether hypothyroidism per se is a significant risk fac- tor for PE or whether it is a contributory factor due to its association with chronic HT will be clarified by larger studies. Risk factors may be specific to the mother or the pregnancy. Some such as primigravidity or past history of PE are well known. Primigravidae are 15 times more likely to develop protienuric PE than parous women,21 which is similar to the present study where nulliparity almost triples the risk for PE. However, Sibai et al.22 showed that HDP are more frequent in multigravidae suggesting that multigravidae are more likely to have early-onset and severe disease. In the present study, only a few women were employed during pregnancy in both the study (6%) and the control (15%) groups; and being unemployed appeared to be a risk factor for early-onset severe PE in univariate analysis (COR 2.76). On the other hand, some authors have reported that employment during preg- nancy is a significant risk factor for developing PE.12,23 This difference may be due to a lesser number of employed women in both groups. The present population of Northern Nigeria women represents a group, among which most women are not formally employed, but may be working much harder in large joint families, which was a significant risk factor for severe early-onset PE (AOR 6.93). Article Table 2. Medical and obstetric characteristics of women in study and control groups. Variables Cases (n) Controls (n) OR 95% CI P value Kessner index criteria Adequate 28 101 0.11 0.06-0.2 <0.0001 Intermediate 43 49 0.83 0.49-4.28 0.5 Inadequate 69 44 2.05 1.24-3.4 0.004 Antenatal complications Multiple pregnancy (twins) 12 8 1.54 0.57-4.28 - Gestational diabetes 9 20 0.41 0.17-1.00 - Abruptio placenta 25 0 - - - Placenta praevia 4 0 - - - PROM 7 4 1.79 0.46-7.44 - BMI/Pregnancy weight categories Normal weight (80-120%) 39 76 0.34 0.2-0.57 <0.0001 Overweight (>120-150%) 105 66 0.92 0.6-1.42 0.77 Obese (>150%) 6 8 0.74 0.22-2.42 0.78 Medical disorders Pre-pregnancy HT 24 0 - - <0.0001 Diabetes mellitus 4 0 - - 0.06 Renal disease 5 0 - - 0.03 Hypothyroidism 2 0 2.01 0.14-56.69 0.5 Previous obstetric outcome Abortions 38 40 0.93 0.54-1.61 0.9 PE/E 32 2 20.1 4.56-123.7 <0.0001 Gestational HT 12 3 4.26 1.09-19.45 0.03 Family history of medical disorders HT 84 36 4.03 2.39-6.82 <0.0001 Diabetes mellitus 38 42 0.87 0.5 -1.50 0.7 PE/E 12 6 2.09 0.7-6.44 0.22 Smoking YES 4 3 1.34 0.25-7.7 0.5 NO 146 147 - - - OR, odds ratio; CI, confidence interval; Kessner index criteria, adequacy of prenatal care; PROM, prelabor rupture of membranes; BMI/Pregnancy weight categories, current weight expressed as a percentage of ideal pre-pregnancy weight; BMI, body-mass index; HT, hypertension; PE/E, pre-elcampsia/eclampsia. Table 3. Level of stress at home and at work of women in study and control groups. Variables Cases (n) Controls (n) OR 95% CI P value Employment during pregnancy YES 25 34 0.68 0.37-1.26 0.25 NO 125 116 - - - Availability of home help (housemaid/relations) YES 60 111 0.23 0.14-0.39 <0.0001 NO 90 39 - - - Family type Monogamous 68 67 1.03 0.64-1.66 0.1 Polygamous 82 83 0.97 0.6-1.57 0.1 OR, odds ratio; CI, confidence interval. No n- co mm er cia l u se on ly [Healthcare in Low-resource Settings 2013; 1:e12] [page 49] There have been conflicting reports on the impact of maternal age on PE. We did not find age to be a significant risk factor, which is con- sistent with a similar study by Eskenazi et al. who conducted their study in North California (USA) among black pregnant women attend- ing antenatal clinic.24 However, a Nationwide US data suggest that the risk of PE increases by 30% for every additional year of age after 34 years.25 This may be probably due to the fact that the majority of our study participants con- cluded their childbearing by the age of 30. Furthermore, multiple pregnancy as a signifi- cant risk factor was also observed in this study. Several studies have shown that when a woman is pregnant with twins her risk of PE nearly triples, neither the chronicity nor zygos- ity alter this increased risk.11,26,27 In summary, factors which emerged to be significant in the multivariate analysis were: history of PE/E in a previous pregnancy (AOR 71.40); exposure to passive smoking (AOR 16.40); inadequate antenatal supervision (AOR 15.21); family history of HT in one or more 1st-degree relatives (AOR 8.92); living in a joint family (AOR 6.93); overweight (4120- 150% of pre-pregnancy ideal body weight, AOR 4.65) and lower socio-economic class (Olusanya’s class III-V) (AOR 3.00). The results of the present study are in agreement with other studies.10,19,24,28 A history of previous PE/E was associated with more than 18 times increased risk of developing PE, while pre-pregnancy ideal body weight found to be least associated with PE. Conclusions Based on the presence of risk factors identi- fied in the present study, women may be coun- seled prior to or during pregnancy and advised to have adequate antenatal supervision in a hospital with appropriate facilities for caring of women with severe PE and pre-term neonates. This may help to constitute a risk model as practice in other units, thereby reducing the attendant maternal and perinatal complications. References 1. National Institute for Health and Care Excellence. NICE Guidelines CG6 Antenatal care-routine care for the healthy pregnant woman. London: NICE Publ.; 2003. 2. Milne F, Redman C, Walker J, et al. The pre-eclampsia community guideline (PRE- COG): how to screen for and detect onset of pre-eclampsia in the community. Brit Med J 2005;330:576-80. 3. Adamu YM, Salihu HM, Sarthiakumar N, Alexandra R. Maternal mortality in Northern Nigeria: a population based study. Eur J Obstet Gyn R B 2003;109:153- 9. 4. Yakasai IA, Gaya SA. 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