Maternal Body Mass Index and Risk of Congenital Heart Defects in Infants: A Dose-Response Meta-Analysis

Liu, Xuezhen; Ding, Guoyong; Yang, Weili; Feng, Xiaoshan; Li, Yuejin; Liu, Hua‐Min; Zhang, Qianqian; Ji, Long; Li, Dong

doi:10.1155/2019/1315796

Cited by 18 publications

(25 citation statements)

References 69 publications

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“…Prevention of CHDs in the offspring. It is very well-established that maternal obesity is associated with marginally increased risk of CHDs, and two meta-analyses reported a doseresponse effect on risk of CHDs with increasing BMI [53,80]. But an increase of 20-40% of a very small risk in general may not be clinically significant.…”

Section: Aetiological Considerations and Possible Prevention Of Chdsmentioning

confidence: 99%

Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: A systematic review

et al. 2021

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Background Congenital heart defects (CHDs) are the most common congenital malformations. The aetiology of CHDs is complex. Large cohort studies and systematic reviews and meta-analyses based on these have reported an association between higher risk of CHDs in the offspring and individual maternal metabolic disorders such as obesity, diabetes, hypertension, and preeclampsia, all conditions that can be related to insulin resistance or hyperglycaemia. However, the clinical reality is that these conditions often occur simultaneously. The aim of this review is, in consequence, both to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia and CHDs in the offspring, as well as the significance of combinations, such as metabolic syndrome, as risk factors. Methods A systematic literature search of papers published between January 1, 1990 and January 14, 2021 was conducted using PubMed and Embase. Studies were eligible if they were published in English and were case-control or cohort studies. The exposures of interest were maternal overweight or obesity, hypertension, preeclampsia, diabetes, dyslipidaemia, and/or metabolic syndrome, and the outcome of interest was CHDs in the offspring. Furthermore, the studies were included according to a quality assessment score. Results Of the 2,250 identified studies, 32 qualified for inclusion. All but one study investigated only the individual metabolic disorders. Some disorders (obesity, gestational diabetes, and hypertension) increased risk of CHDs marginally whereas pre-gestational diabetes and early-onset preeclampsia were strongly associated with CHDs, without consistent differences between CHD subtypes. A single study suggested a possible additive effect of maternal obesity and gestational diabetes. Conclusions Future studies of the role of aberrations of the glucose-insulin homeostasis in the common aetiology and mechanisms of metabolic disorders, present during pregnancy, and their association, both as single conditions and–particularly–in combination, with CHDs are needed.

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Section: Aetiological Considerations and Possible Prevention Of Chdsmentioning

confidence: 99%

Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: A systematic review

et al. 2021

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“…It is very well-established that maternal obesity is associated with marginally increased risk of CHDs, and two meta-analyses reported a dose-response effect on risk of CHDs with increasing BMI [52,79]. But an increase of 20-40% of a very small risk in general may not be clinically significant.…”

Section: Discussionmentioning

confidence: 99%

Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: a systematic review

Hedermann

Hedley

Thagaard

et al. 2020

Preprint

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Congenital heart defects (CHDs) are the most common congenital malformation and will, in severe cases, have a serious impact on neonatal mortality and morbidity. The aetiology of CHDs is complex. Large cohort studies have reported an association between increased risk of CHDs in the offspring and individual maternal metabolic disorders such as diabetes, hypertension, preeclampsia, and obesity. All conditions that can be related to insulin resistance and possibly metabolic syndrome (MetS). The aim of this review is to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia, and MetS, or combinations thereof and CHDs in the offspring. A literature search was performed using PubMed and Embase databases. Of the 2,076 potentially relevant identified studies, 30 qualified for inclusion. Only one study dealt with the combination of more than one maternal metabolic condition as risk factor for CHDs in the offspring. All other studies investigated the individual metabolic disorders and their association with CHDs. Some disorders (chronic hypertension, gestational diabetes, and obesity) increased risk of CHDs marginally whereas pregestational diabetes and early-onset preeclampsia were highly associated with CHDs. Future studies on the combination of several metabolic disorders in the same pregnancy and their association with CHDs are needed.

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“…A recent systematic review and meta-analysis of the association of BMI with CHDs found that risk of CHDs was higher in those whose mothers were overweight or obese at the start of pregnancy, compared with those who were normal weight. Results for underweight mothers were not reported 5 , but a large cohort study consisting of >2,000,000 singletons found no clear association for maternal underweight status and CHDs 6 . These results from conventional multivariable approaches may be explained by residual confounding due to incomplete identification or adjustment for confounders.…”

Section: Introductionmentioning

confidence: 95%

The effect of maternal pre-/early-pregnancy BMI and pregnancy smoking and alcohol on congenital heart diseases: a parental negative control study

Taylor¹,

Elhakeem²,

Nader

et al. 2020

Preprint

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Background: Congenital heart diseases (CHDs) are the most common congenital anomaly. The causes of CHDs are largely unknown, but intrauterine mechanisms appear to be important. Higher prenatal body mass index (BMI), smoking and alcohol consumption are associated with increased risk of CHDs. Whether these are causal is unclear. Methods: Seven European birth cohorts including 232,390 offspring were included. We applied negative exposure paternal control analyses to explore the intrauterine effects of maternal BMI, smoking and alcohol consumption during pregnancy, on offspring CHDs and CHD severity. We used logistic regression and combined estimates using a fixed-effects meta-analysis and compared maternal-specific confounder-adjusted associations to similarly adjusted associations of paternal exposures. If there is a causal intrauterine effect of a maternal pregnancy exposure, we would expect to see a maternal-specific association, with no (or weaker) association with the paternal exposure. Results: There were 2,469 CHD cases (1.1%). The association of mean BMI with CHD was null and similar in mothers (adjusted OR per 1kg/m2: 1.00 (95%CI: 0.99, 1.02)) and fathers (OR: 1.01 (0.99, 1.03)). The analyses of BMI categories resulted in similar increased odds of CHD in overweight (mothers OR: 1.15 (1.01, 1.31) and fathers 1.10 (0.96, 1.27)) and obesity (mothers OR: 1.12 (0.93, 1.36) and fathers 1.16 (0.90, 1.50)). Maternal smoking was associated with increased odds of CHD (OR: 1.11 (0.97, 1.25)) but paternal smoking was not (OR: 0.96 (0.85, 1.07)). The difference increased when removing offspring with genetic/chromosomal defects (mothers OR: 1.15 (1.01, 1.32) and fathers 0.93 (0.83, 1.05)). The positive association with maternal pregnancy smoking appeared to be driven by non-severe CHD cases (OR: 1.22 (1.04, 1.44)). Associations with maternal (OR: 1.16 (0.52, 2.58)) and paternal (OR: 1.23 (0.74, 2.06)) moderate/heavy pregnancy alcohol consumption were similar. Conclusions: We have shown that maternal, but not paternal, pregnancy smoking is associated with an increase in odds of offspring CHDs, primarily non-severe CHDs, providing evidence of an intrauterine effect. We found no strong evidence of an intrauterine effect of higher maternal BMI or alcohol consumption on offspring CHDs. Our findings provide further evidence for why smoking cessation is important during pregnancy.

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Maternal Body Mass Index and Risk of Congenital Heart Defects in Infants: A Dose-Response Meta-Analysis

Cited by 18 publications

References 69 publications

Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: A systematic review

Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: A systematic review

Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: a systematic review

The effect of maternal pre-/early-pregnancy BMI and pregnancy smoking and alcohol on congenital heart diseases: a parental negative control study

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