Alcohol exposure before and during pregnancy is associated with reduced fetal growth: the Safe Passage Study

Pielage et al. BMC Medicine Alcohol exposure before and during pregnancy is associated with reduced fetal growth: the Safe Passage Study Marin Pielage 0 Hanan El Marroun 1 2 Hein J. Odendaal 3 Sten P. Willemsen 0 4 Manon H. J. Hillegers 1 Eric A. P. Steegers 0 Melek Rousian 0 0 Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center , Room Sp-4469, PO Box 2040, 3000 CA Rotterdam , The Netherlands 1 Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center, Sophia Children's Hospital , 3000 CB Rotterdam , the Netherlands 2 Department of Psychology, Education and Child Studies - Erasmus School of Social and Behavioral Sciences, Erasmus University Rotterdam , Rotterdam , The Netherlands 3 Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University , Stellenbosch , South Africa 4 Department of Biostatistics, Erasmus MC, University Medical Center , PO Box 2040, 3000 CA Rotterdam , The Netherlands Background Prenatal alcohol exposure (PAE) is a worldwide public health concern. While PAE is known to be associated with low birth weight, little is known about timing and quantity of PAE on fetal growth. This study investigated the association between periconceptional and prenatal alcohol exposure and longitudinal fetal growth, focusing on timing and quantity in a high exposure cohort. Methods The Safe Passage Study was a prospective cohort study, including 1698 pregnant women. Two-dimensional transabdominal ultrasound examinations were performed to measure fetal femur length, abdominal and head circumference, and biparietal diameter, at three time points during pregnancy. Estimated fetal weight and Z-scores of all parameters were calculated. Trimester-specific alcohol exposure was assessed using the Timeline Followback method. To investigate the associations of specific timing of PAE and fetal growth, two models were built. One with alcohol exposure as accumulative parameter over the course of pregnancy and one trimester specific model, in which PAE was separately analyzed. Linear mixed models adjusted for potential confounders were applied with repeated assessments of both alcohol exposure and fetal growth outcomes. Results This study demonstrated that periconceptional and prenatal alcohol exposure were associated with reduced fetal growth. Effect sizes are displayed as estimated differences (ED) in Z-score and corresponding 95% confidence intervals (95% CIs). When investigated as accumulative parameter, PAE was related to a smaller femur length (ED30; − 0.13 (95% CI; − 0.22; − 0.04), ED36; − 0.14 (95% CI; − 0.25; − 0.04)) and a smaller abdominal circumference (ED36; − 0.09 (95% CI; − 0.18; − 0.01)). Periconceptional alcohol exposure was associated with a smaller abdominal circumference (ED30; − 0.14 (95% CI; − 0.25; − 0.02), ED36; − 0.22 (95% CI; − 0.37; − 0.06)) and a smaller estimated fetal weight (ED36; − 0.22 (95% CI; − 0.38; − 0.05)). Second trimester alcohol exposure was associated with a smaller abdominal circumference (ED30; − 0.49 (95% CI; − 0.86; − 0.12), ED36; − 0.70 (95% CI; − 1.22; − 0.17)) and estimated fetal weight (ED30; − 0.54 (95% CI; − 0.94; − 0.14), ED36; − 0.69 (95% CI; − 1.25; − 0.14)). No additional association of binge drinking was found besides the already observed association of PAE and fetal growth. Conclusions This study demonstrated that PAE negatively affects fetal growth, in particular when exposed during the periconception period or in second trimester. Our results indicate that potential negative consequences of PAE are detectable already before birth. Therefore, healthcare providers should actively address and discourage alcohol use during pregnancy. Background Prenatal alcohol exposure (PAE) is a public health concern, and despite worldwide efforts to avoid PAE, the estimated global prevalence of alcohol consumption during pregnancy is still 10%. The prevalence of alcohol consumption during pregnancy varies between countries, being on average the lowest (0.2%) in countries in the Eastern-Mediterranean region, and on average the highest in countries in the European region (25%) [ 1 ]. In general, the South African population, including men and women, has one of the highest levels of alcohol consumption (28%), including heavy drinking [ 2, 3 ]. The Western Cape is known to be the most problematic area, with the prevalence of any alcohol consumption during pregnancy reaching 38% [4]. PAE has been linked to poor pregnancy outcomes: miscarriage, stillbirth, and premature birth [ 5–8 ]. Furthermore, substantial maternal alcohol consumption causes fetal alcohol spectrum disorders (FASD), a continuum of neurodevelopmental disabilities, craniofacial and somatic anomalies, with a global prevalence of 7.7 per 1000 and 111.1 per 1000 in specific South African communities [ 1, 9, 10 ]. Maternal alcohol consumption leads to fetal exposure by placental diffusion and distribution in the fetal compartment by amniotic fluid accumulation. Additionally, low fetal metabolic enzyme concentrations delays alcohol elimination and along with amniotic reuptake, results in prolonged exposure and potential adverse effects [ 11, 12 ]. Although PAE is thoroughly studied, information on specific associations of timing and quantity of PAE with fetal growth is limited. Many studies on growth impairment due to PAE focus on birth weight and have inconclusive results [ 8, 13–15 ]. Since birth weight is a single measurement, and provides little information on intrauterine growth, it is insufficient to interpret fetal growth. Few studies investigated the association between PAE and fetal growth using longitudinal data, reporting no differences between alcohol-exposed fetuses and controls [ 16–18 ]. However, these studies were performed in small samples, included low exposure groups, or did not investigate associations between periconceptional alcohol exposure and fetal growth later in pregnancy. Periconceptional alcohol exposure was shown to be associated with reduced embryonic growth, reflected by a smaller crown-rump length at 6 and 12  weeks of gestation [19]. Most studies use alcohol exposure as categorized variable, providing limited information on timing and quantity of PAE [ 16–19 ]. A continuous measure provides detailed information on prenatal time-windows in which alcohol could influence fetal growth. Finally, few human studies examined binge drinking (i.e., drinking ≥ 4 consumptions per occasion) during pregnancy, which may cause a higher peak blood concentration (PBC) in a short time span than regular drinking [ 20, 21 ]. Animal studies have shown that PBC may be more important than the total daily alcohol dose influencing fetal development [ 22 ]. As such, we hypothesized that binge drinking during pregnancy has an additional negative effect on fetal growth than moderate alcohol exposure  only. From this background, it is important to (...truncated)