TY - JOUR

T1 - Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes

AU - Borges, Maria Carolina

AU - Clayton, Gemma L

AU - Freathy, Rachel M

AU - Felix, Janine F

AU - Fernández-Sanlés, Alba

AU - Soares, Ana Gonçalves

AU - Kilpi, Fanny

AU - Yang, Qian

AU - McEachan, Rosemary R C

AU - Richmond, Rebecca C

AU - Liu, Xueping

AU - Skotte, Line

AU - Irizar, Amaia

AU - Hattersley, Andrew T

AU - Bodinier, Barbara

AU - Scholtens, Denise M

AU - Nohr, Ellen A

AU - Bond, Tom A

AU - Hayes, M Geoffrey

AU - West, Jane

AU - Tyrrell, Jessica

AU - Wright, John

AU - Bouchard, Luigi

AU - Murcia, Mario

AU - Bustamante, Mariona

AU - Chadeau-Hyam, Marc

AU - Jarvelin, Marjo-Riitta

AU - Vrijheid, Martine

AU - Perron, Patrice

AU - Magnus, Per

AU - Gaillard, Romy

AU - Jaddoe, Vincent W V

AU - Lowe, William L

AU - Feenstra, Bjarke

AU - Hivert, Marie-France

AU - Sørensen, Thorkild I A

AU - Håberg, Siri E

AU - Serbert, Sylvain

AU - Magnus, Maria

AU - Lawlor, Deborah A

N1 - © 2024. The Author(s).

PY - 2024

Y1 - 2024

N2 - BACKGROUND: Higher maternal pre-pregnancy body mass index (BMI) is associated with adverse pregnancy and perinatal outcomes. However, whether these associations are causal remains unclear.METHODS: We 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.RESULTS: All 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.CONCLUSIONS: Our 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.FUNDING: Medical Research Council, British Heart Foundation, European Research Council, National Institutes of Health, National Institute for Health Research, Research Council of Norway, Wellcome Trust.

AB - BACKGROUND: Higher maternal pre-pregnancy body mass index (BMI) is associated with adverse pregnancy and perinatal outcomes. However, whether these associations are causal remains unclear.METHODS: We 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.RESULTS: All 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.CONCLUSIONS: Our 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.FUNDING: Medical Research Council, British Heart Foundation, European Research Council, National Institutes of Health, National Institute for Health Research, Research Council of Norway, Wellcome Trust.

KW - Infant, Newborn

KW - Pregnancy

KW - Female

KW - Humans

KW - Cesarean Section

KW - Body Mass Index

KW - Hypertension, Pregnancy-Induced/epidemiology

KW - Diabetes, Gestational

KW - Pre-Eclampsia/epidemiology

U2 - 10.1186/s12916-023-03167-0

DO - 10.1186/s12916-023-03167-0

M3 - Journal article

C2 - 38281920

VL - 22

JO - BMC Medicine

JF - BMC Medicine

SN - 1741-7015

M1 - 32

ER -