Dataset Information

Association of Maternal History of Spontaneous Abortion and Stillbirth With Risk of Congenital Heart Disease in Offspring of Women With vs Without Type 2 Diabetes.

ABSTRACT:

Importance

The associations of maternal history of spontaneous abortion (SA) and stillbirth with congenital heart disease (CHD) remain elusive.

Objective

To evaluate the associations of maternal history of pregnancy loss with CHD in offspring and the role of maternal type 2 diabetes.

Design, setting, and participants

This population-based cohort study included singleton live offspring born between January 1, 1977, and December 31, 2016, identified through Danish national health registries. Statistical analysis was performed from October 1, 2019, through September 1, 2021.

Exposures

Maternal history of SA, with frequency varying from 1 or 2 to 3 or more episodes, and maternal history of single and multiple stillbirths.

Main outcomes and measures

Overall CHD identified by hospital diagnosis. Cox proportional hazard regression was used to estimate the hazard ratio (HR) of CHD. Diabetes was evaluated as a potential confounder and a potential effect modifier.

Results

Among 1 642 534 included offspring (mean [SD] age, 14.11 [8.39] years; 843 265 male [51.35%]), 246 669 (15.02%) were born to mothers with a history of SA and 9750 (0.59%) were born to mothers with a history of stillbirth. The HRs of CHD were 1.16 (95% CI, 1.13-1.20) for offspring with a maternal history of SA and 1.49 (95% CI, 1.32-1.68) for offspring with a maternal history of stillbirth. Significant dose-response associations were observed among offspring with a maternal history of 3 or more episodes of SA (HR, 1.60; 95% CI, 1.39-1.84) and those with maternal history of multiple stillbirths (HR, 2.75; 95% CI, 1.63-4.65). If only inpatient CHD cases were included, the risk of CHD was higher than that found in the main analysis, with HRs of 1.24 (95% CI, 1.19-1.30) for maternal history of SA and 1.78 (95% CI, 1.51-2.11) for maternal history of stillbirth. The observed associations were strengthened by maternal prepregnancy type 2 diabetes (HR for maternal history of SA, 1.65 [95% CI, 1.37-1.97]; HR for maternal history of stillbirth, 1.74 [95% CI, 1.06-2.85]).

Conclusions and relevance

These findings suggest that offspring born to mothers with a previous SA or stillbirth, especially multiple episodes, or with prepregnancy type 2 diabetes were at a higher risk of being diagnosed with CHD. These findings may help identify women at increased risk in whom detailed fetal heart assessment may be cost-effective and highlight the importance of screening for type 2 diabetes in women of reproductive age.

SUBMITTER: Ji H

PROVIDER: S-EPMC8581719 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Maternal History of Spontaneous Abortion and Stillbirth With Risk of Congenital Heart Disease in Offspring of Women With vs Without Type 2 Diabetes.

Ji Honglei H Liang Hong H Yu Yongfu Y Wang Ziliang Z Yuan Wei W Qian Xu X Mikkelsen Ellen Margrethe EM Laursen Anne Sofie Dam ASD Fang GuangHong G Huang Guoying G Miao Maohua M Li Jiong J

JAMA network open 20211101 11

<h4>Importance</h4>The associations of maternal history of spontaneous abortion (SA) and stillbirth with congenital heart disease (CHD) remain elusive.<h4>Objective</h4>To evaluate the associations of maternal history of pregnancy loss with CHD in offspring and the role of maternal type 2 diabetes.<h4>Design, setting, and participants</h4>This population-based cohort study included singleton live offspring born between January 1, 1977, and December 31, 2016, identified through Danish national he ...[more]

PMID: 34757411

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Project description:ImportanceThe association of folate supplementation with congenital heart disease (CHD) prevention is controversial.ObjectiveTo examine the association of maternal serum folate levels at early to midpregnancy with CHD risk in offspring.Design, setting, and participantsThis case-control study recruited participants from one of China's largest cardiac referral centers between 2015 and 2018. CHD cases and non-CHD controls were matched according to maternal age at a ratio of 1:4. Data were analyzed from May to August 2023.ExposuresMaternal serum levels of folate, vitamin B12, and homocysteine were measured around the gestational age of 16 weeks.Main outcomes and measuresThe primary outcome was CHD, which was confirmed using echocardiography. The association between CHD risk in offspring with maternal folate levels was measured using adjusted odds ratios (aORs) with 95% CIs in conditional logistic regression analyses. Interactions between folate, vitamin B12, and homocysteine and CHD were estimated on a multiplicative scale.ResultsA total of 129 CHD cases with ventricular septal defect as the most common phenotype and 516 matched controls were included. The mean (SD) maternal age at pregnancy was 31.6 (5.3) years. There was a U-shaped association between maternal serum folate levels at early to midpregnancy and CHD risk in offspring. Compared with the offspring in the second and third quartiles of maternal folate, those in the lowest (aOR, 3.09; 95% CI, 1.88-5.08) and highest quartiles (OR, 1.81; 95% CI, 1.07-3.06) had increased odds of CHD. The ORs were higher when applying the World Health Organization criteria to determine the normal range for serum folate levels. Interaction analyses suggested that the adverse associations between low and high maternal folate and CHD risk might be further magnified by vitamin B12 deficiency or elevated homocysteine.Conclusions and relevanceIn this case-control study of CHD, low maternal serum folate levels in early to midpregnancy were associated with an increased CHD risk in offspring, and excessively high folate levels were also associated with an elevated CHD risk. Further investigation is needed to make causal inferences for the observed associations and elucidate the underlying mechanisms.

Dataset Information

Association of Maternal History of Spontaneous Abortion and Stillbirth With Risk of Congenital Heart Disease in Offspring of Women With vs Without Type 2 Diabetes.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Association of Maternal History of Spontaneous Abortion and Stillbirth With Risk of Congenital Heart Disease in Offspring of Women With vs Without Type 2 Diabetes.

Similar Datasets

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