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Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons

BMJ 2017; 357 doi: (Published 14 June 2017) Cite this as: BMJ 2017;357:j2563
  1. Martina Persson, consultant1 2,
  2. Sven Cnattingius, professor1,
  3. Eduardo Villamor, professor1 3,
  4. Jonas Söderling, statistician1,
  5. Björn Pasternak, senior researcher1 4,
  6. Olof Stephansson, consultant1 5,
  7. Martin Neovius, professor1
  1. 1Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, SE-171 76 Stockholm, Sweden
  2. 2Department of Diabetes and Endocrinology, Sachsska Children’s Hospital, Södersjukhuset, Stockholm, Sweden
  3. 3Department of Epidemiology, School of Public Health and Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USA
  4. 4Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
  5. 5Division of Obstetrics and Gynecology, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
  1. Correspondence to: M Persson Martina.Persson{at}
  • Accepted 24 May 2017


Objective To estimate the risks of major congenital malformations in the offspring of mothers who are underweight (body mass index (BMI) <18.5), overweight (BMI 25 to <30), or in obesity classes I (BMI 30 to <35), II (35 to <40), or III (≥40) compared with offspring of normal weight mothers (BMI 18.5 to <25) in early pregnancy.

Design Population based cohort study.

Setting Nationwide Swedish registries.

Participants 1 243 957 liveborn singleton infants from 2001 to 2014 in Sweden. Data on maternal and pregnancy characteristics were obtained by individual record linkages.

Exposure Maternal BMI at the first prenatal visit.

Main outcome measures Offspring with any major congenital malformation, and subgroups of organ specific malformations diagnosed during the first year of life. Risk ratios were estimated using generalised linear models adjusted for maternal factors, sex of offspring, and birth year.

Results A total of 43 550 (3.5%) offspring had any major congenital malformation, and the most common subgroup was for congenital heart defects (n=20 074; 1.6%). Compared with offspring of normal weight mothers (risk of malformations 3.4%), the proportions and adjusted risk ratios of any major congenital malformation among the offspring of mothers with higher BMI were: overweight, 3.5% and 1.05 (95% confidence interval 1.02 to 1.07); obesity class I, 3.8% and 1.12 (1.08 to 1.15), obesity class II, 4.2% and 1.23 (1.17 to 1.30), and obesity class III, 4.7% and 1.37 (1.26 to 1.49). The risks of congenital heart defects, malformations of the nervous system, and limb defects also progressively increased with BMI from overweight to obesity class III. The largest organ specific relative risks related to maternal overweight and increasing obesity were observed for malformations of the nervous system. Malformations of the genital and digestive systems were also increased in offspring of obese mothers.

Conclusions Risks of any major congenital malformation and several subgroups of organ specific malformations progressively increased with maternal overweight and increasing severity of obesity. For women who are planning pregnancy, efforts should be encouraged to reduce adiposity in those with a BMI above the normal range.


  • Contributors: MN and JS had full access to all of the data in the study and take full responsibility for the integrity of the data and the accuracy of the data analysis. SC, MN, BP, MP, OS, and EV conceived and designed the study. All authors acquired, analysed, and interpreted the data and critically revised the manuscript for important intellectual content. SC, MN, and MP drafted the manuscript. MN and JS carried out the statistical analysis. SC, MN, and OS obtained funding and provided administrative, technical, or material support. MN and JS are the guarantors.

  • Funding: Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award number R01DK105948. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders were not involved in the design and conduct of the study; collection, management, analysis, or interpretation of the data; and preparation, review, or approval of the manuscript. This study was also funded by the Swedish Research Council for Health, Working Life and Welfare (grant No 2014-0073) and an unrestricted grant from Karolinska Institutet (distinguished professor award to SC). MP was supported by Stockholm County Council (clinical post-doctoral position). OS was supported by the Swedish Research Council (grant No 2013-2429). BP was supported by the Danish Medical Research Council. MN was supported by the Swedish Research Council (grant No 2013-3770) and the National Institutes of Health (award No R01DK105948).

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. MN reports being a member of the scientific advisory board for Itrim (<$5000 (£3876; €4430)/year).

  • Ethical approval: This study was approved by the regional research ethics committee in Stockholm, Sweden (No 2012/1813-31/4).

  • Data sharing: No additional data available.

  • Transparency The lead author (MP) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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