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Wang R, Chen C, Huang J, Jia B, Shi Q. Association of Maternal History of Preterm Birth With Congenital Anomalies in Offspring. JAMA Netw Open. 2022;5(7):e2223614. doi:10.1001/jamanetworkopen.2022.23614
Congenital anomalies (CAs) are the leading cause of infant mortality, accounting for more than 20% of infant deaths in the US in 2017.1 Several parental risk factors of CAs, including diabetes before pregnancy and maternal smoking, have been identified.2,3 However, data on the associations of maternal history of previous pregnancy outcomes with the risk of CAs are sparse. To further elucidate potential risk factors, we evaluated maternal history of preterm birth (PTB) and offspring CAs.
This retrospective population-based cohort study used birth data from the US National Vital Statistics System from January 1, 2016, to December 31, 2019, including all women with a live singleton birth. Data analysis was conducted from February 1 to February 15, 2022. Because deidentified data are publicly available, ethics approval was not required by the institutional review board of Children’s Hospital of Fudan University. This study is reported following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Information on maternal history of PTB and 12 subtypes of CAs was retrieved from birth certificates. Because of low incidence of the outcome, proportions are expressed in parts per thousand (‰). The associations of maternal history of PTB with neonatal CAs were estimated as risk differences, crude odds ratios (ORs), and adjusted ORs (aOR) with 95% CIs. Stratified analyses according to baseline characteristics were performed. Adjustments were made for potential confounders, including maternal age, race and ethnicity, educational levels, marital status, parity, smoking before and during pregnancy, prepregnancy body mass index categories, timing of initiation of prenatal care, prepregnancy hypertension, prepregnancy diabetes, gestational hypertension, gestational diabetes, and infant sex. A description of methods and potential confounders is available in the eMethods in the Supplement. All P values were 2-sided, and P < .05 was considered statistically significant. Statistical analyses were performed using Stata, version 15.0 (StataCorp LLC).
A total of 14 774 946 mother-neonate pairs with live singleton birth were included in the final analysis; the mean (SD) age of the mothers was 28.86 (5.81) years. The prevalence of CAs was 3.19‰ (47 205 of 14 774 946). Neonates born to mothers with a history of PTB had a higher prevalence in parts per thousand of CAs than did neonates born to mothers without a PTB history (5.25‰ [2554 of 486 894] vs 3.13‰ [44 651 of 14 288 052]; risk difference, 2.12; 95% CI, 1.91-2.33; crude OR, 1.68; 95% CI, 1.62-1.75). After full adjustment, the OR of CAs was 1.47 (95% CI, 1.42-1.54) for maternal history of PTB. For specific subtypes of CAs, maternal history of PTB was associated with an increased risk of nearly all subtypes except anencephaly (aOR, 1.25; 95% CI, 0.87-1.79). For example, the aOR of cyanotic congenital heart disease was 1.76 (95% CI, 1.60-1.93) for maternal history of PTB (Table 1).
Subgroup analyses by maternal age, race and ethnicity, educational level, parity, smoking before and during pregnancy, time of initiation of prenatal care, prepregnancy body mass index, prepregnancy hypertension, prepregnancy diabetes, gestational hypertension, gestational diabetes, and neonate sex were conducted. The neonates who were born to mothers with a history of PTB had a higher risk of CAs in all subgroups after full adjustment (Table 2).
The findings of this study suggest that maternal history of PTB increased the risk of birth CAs in offspring. The mechanisms underlying the association between maternal history of PTB and birth CAs are yet to be elucidated. Previous PTB may be related to defects of the placenta and metabolic disorders of the mothers,4,5 which may involve the development of CAs. Limitations of this study include potential unmeasured confounding factors. Neonates born to mothers with a history of PTB may have an increased risk of CAs. These findings may help to identify neonates at high risk of CAs.
Accepted for Publication: May 31, 2022.
Published: July 25, 2022. doi:10.1001/jamanetworkopen.2022.23614
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Wang R et al. JAMA Network Open.
Corresponding Authors: Qiqi Shi, MD, PhD (email@example.com), and Bing Jia, MD, PhD, Department of Pediatric Cardiothoracic Surgery, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Rd Shanghai, P.R. China (firstname.lastname@example.org).
Author Contributions: Drs Wang and Shi had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: All authors.
Acquisition, analysis, or interpretation of data: Wang, Shi.
Drafting of the manuscript: Wang, Huang, Shi.
Critical revision of the manuscript for important intellectual content: Chen, Jia.
Statistical analysis: Wang, Shi.
Administrative, technical, or material support: Chen.
Supervision: Chen, Jia.
Conflict of Interest Disclosures: None reported.