Characteristics Of The Included Studies
A total of 888 non-duplicate works were identified through the literature search, including 12 manually retrieved from systematic reviews and reference lists of identified studies. After title/abstract screening and full-text screening, 37 articles were included for the current systematic review (Fig. 1).
Eleven out of the 37 studies (30%) were conducted in the USA, followed by Ethiopia (11%) and the Netherlands (11%). These included studies were conducted between 1984 and 2019. The sample sizes of these studies varied from 105 [16] to 2,963,888 [17]. The prevalence of alcohol consumption during pregnancy among different samples varied between 0.2% (China) [18] to 73.9% (SCOPE study) [19].
The main outcome of 29 out of the 37 articles was PE. In these 29 studies, 7 were prospective cohort studies, 7 were retrospective cohort studies, and 15 were case-control studies. Eight of the 37 articles were used to analyze the association between alcohol consumption during pregnancy and HDP.
We evaluated the 35 cohort and case-control studies by the NOS (Table 1). Two cross-sectional studies were assessed by an 11-item checklist recommended by Agency for Healthcare Research and Quality (AHRQ). Of these, 5 case-control studies, 6 prospective cohort studies, and 1 cross-sectional study were considered high quality. The main aspect responsible for the lower quality of these cohort studies is comparability as the most of these studies only provide crude odds ratios (OR), without adjustment for confounding factors. The reasons for low quality of case-control studies include the control group were selected from hospitalized population (not community controls), and ascertainment of exposure was not blinded or only based on medical record and self-report.
Table 1
Characteristics of Studies in Systematic Review
Author | study design | exposure ascertainment | country | study year | Quality assessment |
PE as outcome |
Bandoli 2018[17] | retrospective population-based cohort | birth certificate and hospital discharge record | USA | 2007–2012 | 6 |
Bobic 2015[16] | case-control | - | Croatia | 2015 | 6 |
Bommarito 2019[34] | prospective | At the first visit (median, 10 weeks gestation), women completed detailed questionnaires of demographic information | USA | 2006–2008 | 7 |
Chedraui 2014[35] | csae control | - | Ecuador | 2014 | 5 |
Coolman 2012[36] | population-based prospective cohort study | alcohol consumption was assessed by questionnaires in each trimester. | Netherlands | 2002–2006 | 7 |
Cota 2006[37] | case-contro | medical records postpartum | Brazil | 2004 | 4 |
Endeshaw 2014[38] | Case-Control | interview after delivery | Ethiopia | 2014 | 6 |
Eskenazi 1991[39] | case-control | abstracted from medical charts | Northern California(USA) | 1984–1985 | 5 |
Fang 2009[40] | case-control | a 45- minute in-person interview in which trained research personnel used a structured questionnaire | Thailand | 2006–2007 | 7 |
Grum 2017[41] | unmatched case control study | using pretested interviewer administered questionnaire | Ethiopia | 2015–2016 | 7 |
Jhee 2019[42] | retrospective study | retrieved from electronic medical records | Korea | 2005–2017 | 6 |
Kharkova 2017[43] | retrospective study | alcohol abuse as diagnosed by a doctor based on medical record | Russia | 2006–2011 | 6 |
Kiondo 2012[44] | case control | the women were interviewed about their socio-demographic characteristics | Uganda | 2008–2009 | 7 |
KLONOFF-COHEN 1996[45] | case-control | obtained from a standardized telephone interview | USA | 1984–1987 | 7 |
KURKI 2000[46] | prospective population-based study | by a structured questionnaire at at their first prenatal visit between 8–17 weeks’ gestation | Finland | 2000 | 7 |
Lafaurie 2020[47] | case control | obtained from hospital information systems and medical records | Colombia | 2019 | 4 |
Laine 2015[48] | nested case-control | based on self report at either baseline or postpartum examination interview. | USA | 2004–2007 | 4 |
Lardoeyt 2013[22] | case-control study | in-depth interviews were conducted using an instrument designed for the study | Cuba | 2007–2009 | 5 |
Leemaqz 2016[19] | prospective cohort | dietary and lifestyle questionnaires were recorded at 15 weeks’ and 20 weeks’ gestation | Australia, New Zealand,Ireland, United Kingdom | 2004–2011 | 8 |
Meertens 2019[49] | prospective cohort study | by a web-based questionnaire before 16 weeks of gestation (pregnancy questionnaire) | Netherlands | 2013–2015 | 7 |
Mekie 2020[50] | Age matched case-control study | collected through an interview using a questionnaire | Ethiopia | 2018 | 7 |
Nobles 2019[51] | retrospective cohort | abstracted from delivery electronic medical records(yes/no) | USA | 2002–2010 | 6 |
RUDRA 2005[52] | case-control study | an in-person structured interview questionnaire to collect information | USA | 1998–2002 | 5 |
Salihu 2011[20] | retrospective cohort | Missouri vital record system | USA | 1989–2005 | 6 |
Sandström 2019[53] | prospectively population-based cohort study | Alcohol consumption at registration are self-reported | Sweden | 2008–2013 | 6 |
Thompson 2014[54] | prospective cohort study | interview in which trained research personnel used a structured questionnaire before 20 weeks’ gestation | USA(Swedish Medical Center) | 1996–2008 | 7 |
Wang 2015[18] | birth cohort study | in-person interviews at the hospital using a standardized and structured questionnaire after dilivery | China | 2010–2012 | 6 |
Xiong 2000[55] | retrospective cohort | data were derived from delivery record | Canada | 1995–1997 | 6 |
Xiong 2009[56] | case–control | obtained during personal interviews | canada | 2003–2006 | 4 |
HDP as outcome |
Baugh 2016[57] | national population-based survey (retrospective) | contacted by mail and/ or telephone to participate 2–4 months after giving birth | USA | 2000–2010 | 6 |
Chada 2007[58] | case-control | Two midwives administered questionnaires on the day of delivery | Argentina | 2007 | 4 |
Iwama 2019[59] | prospective birth cohort study | obtained from the two questionnaires, namely, T1(16.5 weeks) and T2༈27.9 weeks༉ | Japan | 2011–2014 | 9 |
Masho 2015[60] | prospective cohort | contacted by mail and/ or telephone to participate 2–4 months after giving birth | USA | 2004–2011 | 5 |
Mutsaerts 2014[61] | population-based prospective birth-cohort study | Shortly after delivery, the midwife or gynaecologist guiding the pregnancy completed a questionnaire on maternal alcohol use | Netherlands | 2006–2007 | 6 |
Nugteren 2012[62] | prospective cohort | alcohol consumption was assessed by questionnaires in each trimester. | Netherlands | 2002–2006 | 7 |
Walle 2019[63] | cross-sectional study | using interviewer administered semi structured questioner | Ethiopia | 2017 | 8 |
Ye 2014[64] | cross-sectional study | All information was collected on the basis of standardized antenatal, obstetric and neonatal records. | China | 2011 | 7 |
Figure 1: Flow-chart of study selection. |
Alcohol Consumption During Pregnancy And Pe
We analyzed the association between maternal alcohol consumption with PE by using alcohol during pregnancy as a dichotomous variable, regardless of dosage, pattern, and time in the pregnancy. The total study population was 4,434,003 women with 170,481 PE cases in 29 studies. There was no significant association between alcohol consumption during pregnancy and incidence of PE (OR = 0.93, 95% CI: 0.73–1.20), with statistically significant heterogeneity among studies (I 2 = 91%, P < 0.00001) (Fig. 2). Among the subgroup of prospective cohort studies (n = 7), the pooled results showed that alcohol consumption during pregnancy had a protective effect on PE (OR = 0.64, 95% CI: 0.54–0.76), without statistically significant heterogeneity among these studies (I2 = 0%, P = 0.56). The results from the subsets of retrospective cohort studies (n = 7) and case-control studies, in which alcohol exposure during pregnancy was determined through postpartum interviews or medical records, were consistent with the conclusion that alcohol consumption during pregnancy was not associated with PE, with an odds of 1.07 (0.65–1.74) and 1.02 (0.64–1.61), respectively. By visual inspection of the funnel plot, there was no significant publish bias (Fig. 3)
In the prospective subgroup, sensitivity analysis showed that the pooled results were stable. In the subgroup of retrospective cohort studies, when Salihu's study (2011)[20] was removed, the subtotal OR was changed to 1.47 (1.36–1.58), and the heterogeneity was eliminated (I2 = 0%, p = 0.45). In case-control studies subgroup, heterogeneity and pooled OR values did not change even when we removed studies in which the number of cases exposed to alcohol was less than 10 or low quality of the studies.
The literature identified on the dose-response and time-response relationship and quasi-experimental studies between maternal alcohol consumption and PE was limited and insufficient for meta-analysis, so we describe the relevant results as follows.
Regarding the time-response relationship between alcohol consumption, Leemaqz [19] et al reported that alcohol consumption at 15 weeks’ gestation has a protective effect for PE with borderline significance 0.72 (0.53–0.99). At 20 weeks’ gestation, there was not association with PE in a large prospective cohort study with 5588 nulliparous women (SCOPE).
When it comes to the dose-response relationship, McCarthy[21] reported that alcohol consumption of occasional to binge drinking before 15 weeks’ gestation was not associated with the development of PE with an adjusted OR of 0.73 (0.51–1.06) for occasional to low drinking and 0.66 (0.39–1.14) for moderate to heavy alcohol consumption compared with abstinence in pregnancy. However, Salihu [20] used the Missouri maternally-linked cohort data files and the result showed that 1–2 drinks per week had protective effect for PE with an adjusted OR of 0.82 (0.74–0.90). The protective effect disappeared for women consuming three to four drinks per week [OR 0.85 (95% CI: 0.64–1.14)] and more than five drinks per week [OR 1.05 (95% CI: 0.79–1.40)].
Mendelian randomization (MR), and family-based designs are approaches that can be used to improve causal inference. Only one study was family-based design. Lardoeyt et al[22] found a 16-fold increased risk of developing PE (OR 16) when first-degree family history (OR for sister with PE history is 1.61 alone) and alcohol consumption (OR is 4.44 alone) coexisted.
Alcohol Consumption During Pregnancy And Hdp
The 8 studies that had outcome variable of HDP. The total study population was 467,055 women with 41,708 cases of HDP. The pooled estimates OR was 0.98 (95%CI: 0.75–1.29) with significant heterogeneity (I2 = 90% P < 0.00001) (Fig. 4). The funnel plot of the odds ratios for HDP shows an asymmetrical distribution, which indicates some publish bias (Fig. 5).