• Maria Carolina Borges, Gemma L Clayton, Rachel M Freathy, Janine F Felix, Alba Fernández-Sanlés, Ana Gonçalves Soares, Fanny Kilpi, Qian Yang, McEachanRosemary R CRRCBradford Institute for Health Research, Bradford Teaching Hospitals NHS Trust, Bradford, UK., Rebecca C Richmond, Xueping Liu, Line Skotte, Amaia Irizar, Andrew T Hattersley, Barbara Bodinier, Denise M Scholtens, Ellen A Nohr, Tom A Bond, M Geoffrey Hayes, Jane West, Jessica Tyrrell, John Wright, Luigi Bouchard, Mario Murcia, Mariona Bustamante, Marc Chadeau-Hyam, Marjo-Riitta Jarvelin, Martine Vrijheid, Patrice Perron, Per Magnus, Romy Gaillard, JaddoeVincent W VVWVThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., William L Lowe, Bjarke Feenstra, Marie-France Hivert, SørensenThorkild I ATIADepartment of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Novo Nordisk Foundation Center for Basic Metabolic Diseases, Faculty of Health and Medical S, Siri E Håberg, Sylvain Serbert, Maria Magnus, and Deborah A Lawlor.
• MRC Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK. m.c.borges@bristol.ac.uk.
• Bmc Med. 2024 Jan 29; 22 (1): 3232.

BackgroundHigher maternal pre-pregnancy body mass index (BMI) is associated with adverse pregnancy and perinatal outcomes. However, whether these associations are causal remains unclear.MethodsWe explored the relation of maternal pre-/early-pregnancy BMI with 20 pregnancy and perinatal outcomes by integrating evidence from three different approaches (i.e. multivariable regression, Mendelian randomisation, and paternal negative control analyses), including data from over 400,000 women.ResultsAll three analytical approaches supported associations of higher maternal BMI with lower odds of maternal anaemia, delivering a small-for-gestational-age baby and initiating breastfeeding, but higher odds of hypertensive disorders of pregnancy, gestational hypertension, preeclampsia, gestational diabetes, pre-labour membrane rupture, induction of labour, caesarean section, large-for-gestational age, high birthweight, low Apgar score at 1 min, and neonatal intensive care unit admission. For example, higher maternal BMI was associated with higher risk of gestational hypertension in multivariable regression (OR = 1.67; 95% CI = 1.63, 1.70 per standard unit in BMI) and Mendelian randomisation (OR = 1.59; 95% CI = 1.38, 1.83), which was not seen for paternal BMI (OR = 1.01; 95% CI = 0.98, 1.04). Findings did not support a relation between maternal BMI and perinatal depression. For other outcomes, evidence was inconclusive due to inconsistencies across the applied approaches or substantial imprecision in effect estimates from Mendelian randomisation.ConclusionsOur findings support a causal role for maternal pre-/early-pregnancy BMI on 14 out of 20 adverse pregnancy and perinatal outcomes. Pre-conception interventions to support women maintaining a healthy BMI may reduce the burden of obstetric and neonatal complications.FundingMedical Research Council, British Heart Foundation, European Research Council, National Institutes of Health, National Institute for Health Research, Research Council of Norway, Wellcome Trust.© 2024. The Author(s).

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