Parental conditions, modifiable lifestyle factors, and first trimester growth and development: a systematic review
Authors: Naomi Graafland, Melek Rousian, Merle L de Zwart, Regine P M Steegers-Theunissen, Eric A P Steegers, Anke G Posthumus
Journal: Human Reproduction Update (2025)

The embryonic period in human development is the foundation of lifelong and even transgenerational health. Although previously believed to be uniform, there is increasing evidence that embryonic growth is influenced by the conditions and modifiable lifestyle factors of parents in the periconception period. In ongoing pregnancies, a delay in growth in the first trimester has been associated with miscarriages, malformations, low birth weight, preterm birth, and small for gestational age at birth. This has stimulated research on factors associated with variations in human embryonic growth. However, there is still no consensus on which parental conditions and modifiable lifestyle factors affect first trimester growth and development and to what extent. A systematic review was undertaken according to PRISMA guidelines to provide an overview of literature on the associations between parental conditions and lifestyle factors in the periconception period and first trimester growth and development, with an aim to identify existing evidence gaps. A systematic search of the literature concerning articles on embryonic growth and lifestyle factors published between 1900 and 2024 was performed in six electronic databases. Studies were eligible for inclusion if they reported on the association between periconception parental conditions and/or modifiable lifestyle factors and an in vivo measure of first trimester growth or development (i.e. crown-rump length, embryonic volume and/or Carnegie stage) between 6 + 0 and 13 + 6 weeks gestational age in singleton pregnancies. Parental conditions and modifiable lifestyle factors were defined as ex utero determinants divided into characteristics (age, ethnicity, BMI, blood pressure), lifestyle risk factors (caffeine intake, alcohol consumption, and smoking), nutrition (dietary patterns and food groups), vitamins (vitamin B9/B11, vitamin B12, vitamin D, and supplements), and the ambient environment (air pollution, noise exposure, and neighborhood deprivation). Risk of bias of the included studies was assessed using the Newcastle-Ottawa Scale. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to assess the evidence level of the studies included in the review. A total of 4708 unique records were identified, of which 34 studies were included in the systematic review. The majority of studies investigating smoking and BMI suggested an inverse association with embryonic growth and development, while maternal age, folic acid supplement use, and folate levels were positively associated with embryonic growth and development. Studies on blood pressure, ethnicity, vitamin B12, vitamin D, alcohol consumption, caffeine consumption, and ambient environment were too limited to conclude an association with embryonic growth and development. Reported effect estimates were heterogeneous for all determinants. Based on the GRADE criteria, the quality of evidence for the results of this review was considered low or very low. Some periconceptional parental conditions and modifiable lifestyle factors are associated with first trimester growth and development and should be considered in clinical preconception care. To advance our understanding and establish strong, high-level evidence-based recommendations, future research should prioritize methodological quality and focus on lifestyle intervention studies. PROSPERO (ID: CRD42021240618).