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. 2017 Jun 14:357:j2563.
doi: 10.1136/bmj.j2563.

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

Martina Persson  1   2 , Sven Cnattingius  3 , Eduardo Villamor  3   4 , Jonas Söderling  3 , Björn Pasternak  3   5 , Olof Stephansson  3   6 , Martin Neovius  3
Affiliations

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

Martina Persson et al. BMJ. .

Abstract

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.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf 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).

Figures

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Fig 1 Prevalence of major congenital malformations in Swedish live singleton births between 2001 and 2014 (n=1 243 957)
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Fig 2 Major congenital malformations in liveborn singletons by maternal body mass index (BMI) in underweight (BMI <18.5; n=29 864), normal weight (BMI 18.5 to <25; n=756 432), and overweight (BMI 25 to <30; n=311 339) women, and in women in obesity classes I (BMI 30 to <35; n=103 085), II (BMI 35 to <40; n=31 883), and III (BMI ≥40; n=11 354). Adjustment was made for maternal age (13-24, 25-29, 30-34, ≥35 years), height (130-154, 155-159, 160-164, 165-169, 170-174, 175-200 cm), parity (primiparous, multiparous), early pregnancy smoking status (non-smoker, 1-9, ≥10 cigarettes daily), educational level (<10, 10-12, >12 years), maternal country of birth (Nordic (Sweden, Denmark, Finland, Iceland, and Norway), non-Nordic), family situation (living with partner, not living with partner), and sex of offspring
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Fig 3 Major congenital malformations in nervous system, eye, heart, and oral clefts in liveborn singletons by maternal body mass index (BMI) in underweight (BMI <18.5; n=29 864), normal weight (BMI 18.5 to <25; n=756 432), and overweight (BMI 25 to <30; n=311 339) women, and in women in obesity classes I (BMI 30 to <35; n=103 085), II (BMI 35 to <40; n=31 883), and III (BMI ≥40; n=11 354). Adjustment was made for maternal age (13-24, 25-29, 30-34, ≥35 years), height (130-154, 155-159, 160-164, 165-169, 170-174, 175-200 cm), parity (primiparous, multiparous), early pregnancy smoking status (non-smoker, 1-9, ≥10 cigarettes daily), educational level (<10, 10-12, >12 years), maternal country of birth (Nordic (Sweden, Denmark, Finland, Iceland, and Norway), non-Nordic), family situation (living with partner, not living with partner), and sex of offspring
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Fig 4 Major congenital malformations in digestive, urinary, and genital systems; limbs; and other malformations anliveborn singletons by maternal body mass index (BMI) in underweight (BMI <18.5; n=29 864), normal weight (BMI 18.5 to <25; n=756 432), and overweight (BMI 25 to <30; n=311 339) women, and in women in obesity classes I (BMI 30 to <35; n=103 085), II (BMI 35 to <40; n=31 883), and III (BMI ≥40; n=11 354). Adjustment was made for maternal age (13-24, 25-29, 30-34, ≥35 years), height (130-154, 155-159, 160-164, 165-169, 170-174, 175-200 cm), parity (primiparous, multiparous), early pregnancy smoking status (non-smoker, 1-9, ≥10 cigarettes daily), educational level (<10, 10-12, >12 years), maternal country of birth (Nordic (Sweden, Denmark, Finland, Iceland, and Norway), non-Nordic), family situation (living with partner, not living with partner), and sex of offspring
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