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

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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. 


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. 


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.


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.

Original languageEnglish
Article number318
JournalBMC Medicine
Issue number1
Publication statusPublished - 23 Aug 2023

Bibliographical note

Funding Information:
The research reported in this publication was supported by “Stichting Vrienden van Sophia,” Sophia Children’s Hospital, Erasmus MC, University Medical Center, Rotterdam, grant number; WAR-20–47, “Stichting Volksbond Rotterdam,” the Netherlands Organization for Health Research and Development (Aspasia Grant No. 015.016.056), and from the European Union’s Horizon Europe research and innovation program under grant agreement No 101057390. All mentioned funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Funding Information:
The Safe Passage Study was supported by National Institutes of Health grants U01HD055154, U01HD045935, U01HD055155, U01HD045991, and U01AA016501 funded by the National Institute on Alcohol Abuse and Alcoholism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute on Deafness and Other Communication Disorders.

Publisher Copyright:
© 2023, BioMed Central Ltd., part of Springer Nature.


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