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

Maria Carolina Borges; Gemma L. Clayton; Rachel M. Freathy; Janine F. Felix; Alba Fernández-Sanlés; Ana Gonçalves Soares; Fanny Kilpi; Qian Yang; Rosemary R.C. McEachan; 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; Vincent W.V. Jaddoe; William L. Lowe; Bjarke Feenstra; Marie France Hivert; Thorkild I.A. Sørensen; Siri E. Håberg; Sylvain Serbert; Maria Magnus; Deborah A. Lawlor

doi:10.1186/s12916-023-03167-0

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

Maria Carolina Borges^*, Gemma L. Clayton, Rachel M. Freathy, Janine F. Felix, Alba Fernández-Sanlés, Ana Gonçalves Soares, Fanny Kilpi, Qian Yang, Rosemary R.C. McEachan, 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 WestJessica Tyrrell, John Wright, Luigi Bouchard, Mario Murcia, Mariona Bustamante, Marc Chadeau-Hyam, Marjo Riitta Jarvelin, Martine Vrijheid, Patrice Perron, Per Magnus, Romy Gaillard, Vincent W.V. Jaddoe, William L. Lowe, Bjarke Feenstra, Marie France Hivert, Thorkild I.A. Sørensen, Siri E. Håberg, Sylvain Serbert, Maria Magnus, Deborah A. Lawlor^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

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.

Original language	English (US)
Article number	32
Journal	BMC Medicine
Volume	22
Issue number	1
DOIs	https://doi.org/10.1186/s12916-023-03167-0
State	Published - Dec 2024

Funding

MCB has received support from MRC Skills Development Fellowship (MR/P014054/1) and the University of Bristol Vice-Chancellor\u2019s Fellowship. DAL is a British Heart Foundation Chair (CH/F/20/90003) and NIHR Senior Investigator (NF-0616\u201310102). JT is supported by an Academy of Medical Sciences (AMS) Springboard Award, which is supported by the AMS, the Wellcome Trust, GCRF, the Government Department of Business, Energy and Industrial Strategy, the British Heart Foundation and Diabetes UK [SBF004\\1079]. RMF was funded by a Wellcome Trust and Royal Society Sir Henry Dale Fellowship (WT104150) and is now funded by a Wellcome Trust Senior Research Fellowship (WT220390). RG received funding from the Dutch Heart Foundation (grant number 2017T013), the Dutch Diabetes Foundation (grant number 2017.81.002), and the Netherlands Organization for Health Research and Development (NWO, ZonMW, grant number 543003109). VWVJ received a Consolidator Grant from the European Research Council (ERC-2014-CoG-648916). XL received support from the Nordic Center of Excellence in Health-Related e-Sciences. LS reports funding from a Carlsberg Foundation postdoctoral fellowship (CF15-0899). BF was supported by an Oak Foundation Fellowship and by a grant from the Novo Nordisk Foundation (12,955). MCM has received funding from the European Research Council (ERC) under the European Union\u2019s Horizon 2020 research and innovation programme (grant agreement number 947684). TAB is supported by the Medical Research Council (MRC) (UK) (MR/K501281/1), the NHMRC (Australia) (GNT1183074 and GNT1157714), and the British Heart Foundation Accelerator Award at the University of Bristol (AA/18/1/34219) and works in/is affiliated with a unit that is supported by the UK Medical Research Council (MC_UU_00011/6). LB is a senior research scholar from the Fonds de la recherche du Qu\u00E9bec-Sant\u00E9 (FRQ-S) and a member of the FRQ-S-funded Centre de recherche du CHUS. MFH was supported by an American Diabetes Association (ADA) Pathways Accelerator Award (1\u201315-ACE-26). SEH and MCM are partly funded by the Research Council of Norway (project no. 320656) and through its Centres of Excellence funding scheme (project No 262700). JW and RMc are supported by the National Institute for Health and Care Research under its Applied Research Collaboration, Yorkshire and Humber (NIHR200166). This study was supported by the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_00032/05), British Heart Foundation (AA/18/1/34219), the European Research Council under the European Union\u2019s Seventh Framework Programme (FP/2007\u20132013)/ERC Grant Agreement (Grant number 669545), the European Union\u2019s Horizon 2020 research and innovation programme under grant agreement No 733206 (LifeCycle), the US National Institutes of Health (R01 DK10324, U01 HG004415), the Bristol NIHR Biomedical Research Centre, and the Research Council of Norway through its Centres of Excellence funding scheme (project number 262700), and the Wellcome Trust [Grant number WT220390]. For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author-Accepted Manuscript version arising from this submission.

Keywords

Body mass index
Mendelian randomisation
Pregnancy
Triangulation

ASJC Scopus subject areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12916-023-03167-0

Cite this

Borges, M. C., Clayton, G. L., Freathy, R. M., Felix, J. F., Fernández-Sanlés, A., Soares, A. G., Kilpi, F., Yang, Q., McEachan, R. R. C., Richmond, R. C., Liu, X., Skotte, L., Irizar, A., Hattersley, A. T., Bodinier, B., Scholtens, D. M., Nohr, E. A., Bond, T. A., Hayes, M. G., ... Lawlor, D. A. (2024). Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes. BMC Medicine, 22(1), Article 32. https://doi.org/10.1186/s12916-023-03167-0

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title = "Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes",

abstract = "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.",

keywords = "Body mass index, Mendelian randomisation, Pregnancy, Triangulation",

author = "Borges, {Maria Carolina} and Clayton, {Gemma L.} and Freathy, {Rachel M.} and Felix, {Janine F.} and Alba Fern{\'a}ndez-Sanl{\'e}s and Soares, {Ana Gon{\c c}alves} and Fanny Kilpi and Qian Yang and McEachan, {Rosemary R.C.} and Richmond, {Rebecca C.} and Xueping Liu and Line Skotte and Amaia Irizar and Hattersley, {Andrew T.} and Barbara Bodinier and Scholtens, {Denise M.} and Nohr, {Ellen A.} and Bond, {Tom A.} and Hayes, {M. Geoffrey} and Jane West and Jessica Tyrrell and John Wright and Luigi Bouchard and Mario Murcia and Mariona Bustamante and Marc Chadeau-Hyam and Jarvelin, {Marjo Riitta} and Martine Vrijheid and Patrice Perron and Per Magnus and Romy Gaillard and Jaddoe, {Vincent W.V.} and Lowe, {William L.} and Bjarke Feenstra and Hivert, {Marie France} and S{\o}rensen, {Thorkild I.A.} and H{\aa}berg, {Siri E.} and Sylvain Serbert and Maria Magnus and Lawlor, {Deborah A.}",

note = "Publisher Copyright: {\textcopyright} 2024, The Author(s).",

year = "2024",

month = dec,

doi = "10.1186/s12916-023-03167-0",

language = "English (US)",

volume = "22",

journal = "BMC Medicine",

issn = "1741-7015",

publisher = "BioMed Central",

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Borges, MC, Clayton, GL, Freathy, RM, Felix, JF, Fernández-Sanlés, A, Soares, AG, Kilpi, F, Yang, Q, McEachan, RRC, Richmond, RC, Liu, X, Skotte, L, Irizar, A, Hattersley, AT, Bodinier, B, Scholtens, DM, Nohr, EA, Bond, TA, Hayes, MG, West, J, Tyrrell, J, Wright, J, Bouchard, L, Murcia, M, Bustamante, M, Chadeau-Hyam, M, Jarvelin, MR, Vrijheid, M, Perron, P, Magnus, P, Gaillard, R, Jaddoe, VWV, Lowe, WL, Feenstra, B, Hivert, MF, Sørensen, TIA, Håberg, SE, Serbert, S, Magnus, M & Lawlor, DA 2024, 'Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes', BMC Medicine, vol. 22, no. 1, 32. https://doi.org/10.1186/s12916-023-03167-0

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.

PY - 2024/12

Y1 - 2024/12

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 - Body mass index

KW - Mendelian randomisation

KW - Pregnancy

KW - Triangulation

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DO - 10.1186/s12916-023-03167-0

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SN - 1741-7015

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JO - BMC Medicine

JF - BMC Medicine

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ER -

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

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