Review 2 Mentions
First trimester maternal infections and offspring congenital heart defects: a meta-analysis
Huimin Su•2025
Edie GuoMark Woodward
Top 7% · 93rd Percentile
10 citations · Cardiology and Cardiovascular Medicine
Open Access

TLDR

Illnesses during the first months of pregnancy were linked to a higher chance of heart defects in babies. The link differed by infection and defect, and more research is needed to confirm which illnesses matter most.

Summary

1 Study Aim

The authors aimed to combine current evidence on whether infections during the first trimester (the first three months of pregnancy) are linked to congenital heart defects (structural problems of the heart present at birth). They also examined whether links differed by infection and defect type. The study asked whether early pregnancy illnesses are connected to heart problems in babies.

2 Study Design

The authors conducted a systematic review (a structured search and assessment of research) and meta-analysis (a statistical combination of study results). They searched five research databases through 30 September 2024 and included 30 studies of first-trimester infections, covering 1,732,295 pregnancies. The studies included 24 case-control, three cohort, and three cross-sectional designs. Infection status came from questionnaires in 20 studies, laboratory tests in seven, and medical records in three. Random-effects models combined results while allowing for differences between studies. The researchers combined findings from many studies involving over a million pregnancies.

3 Findings

The authors found that any first-trimester infection was associated with higher odds of a baby having a heart defect: pooled odds ratio (a measure comparing the odds between groups) 1.63, with a 95% confidence interval (a range expressing uncertainty) of 1.41–1.88. Rubella, coxsackievirus, respiratory infections, and influenza were also linked to higher odds. Any infection was associated with ventricular septal defects (a hole between the heart’s lower chambers; 1.59) and atrioventricular septal defects (a problem involving the heart’s central walls and valves; 1.55). Results varied considerably across studies, and possible publication bias reduced the estimated association to 1.32. The authors urge larger studies using laboratory tests to confirm results and investigate causes. Some early pregnancy illnesses may raise the chance of certain heart problems, but better studies are needed to check this.

Abstract

BACKGROUND AND AIMS: Maternal infections have been proposed to play a role in the development of congenital heart defects (CHD). This study aims to synthesize contemporary evidence on the association between first-trimester maternal infection and risk of offspring CHD. METHODS: This systematic review and meta-analysis (PROSPERO number: CRD42024523638) used Embase, PubMed, Web of Science, Scopus, and the Cochrane Library to identify studies investigating first-trimester maternal infection and offspring CHD, published up until 30 September 2024. Human studies with a minimum of 50 cases were eligible. Inverse variance weighted random-effects models were conducted to pool estimates and stratify associations by infection type and heart defect type. RESULTS: A total of 30 studies (24 case-control, 3 cohort, and 3 cross-sectional studies) with 1 732 295 pregnancies were identified. Studies assessed maternal infectious status through self-reported questionnaires (n = 20, 66.7%), laboratory testing (n = 7, 23.3%) or medical records (n = 3, 10.0%). Overall, any first-trimester maternal infection was associated with higher risk of CHD in offspring, with a pooled odds ratio (OR) and 95% confidence interval (CI) of 1.63 (1.41, 1.88). Among specific types of infection, rubella virus, coxsackievirus, respiratory infections, and influenza presented higher risks of offspring CHD, with ORs (95% CI) of 2.78 (2.08, 3.72), 1.57 (1.12, 2.19), 1.57 (1.25, 1.96), and 1.50 (1.20, 1.87), respectively. Studies that reported associations by individual subtype of CHD relied on a comparatively modest number of cases. Pooled ORs for exposure to any first-trimester infection were 1.59 (1.16, 2.20) for ventricular septal defects, 1.55 (1.21, 1.99) for atrioventricular septal defects, and not statistically significant for other subtypes. CONCLUSIONS: First-trimester maternal infections are associated with increased risk of offspring CHD and appear to extend beyond infections commonly tested for during routine pregnancy screening. Larger-scale studies are warranted to confirm these findings using laboratory antibody testing and explore underlying mechanisms.

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