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Maternal age, BMI, and irregular folic acid supplementation are associated with higher birth defect riskFactors like age and folic acid impact risk of birth defects

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Key Takeaway
Note that maternal age, high BMI, and irregular folic acid intake are associated with increased risk of birth defects.

This meta-analysis synthesized data from 25 studies involving 26,019 cases to evaluate the impact of maternal physiological, healthcare, nutritional, and behavioral factors on birth defects in China. The analysis identifies several significant associations between these factors and adverse outcomes.

Maternal age of 35 years or older (OR 1.26; 95% CI: 1.05-1.47) and a BMI over 30 kg/m2 (OR 1.42; 95% CI: 1.25-1.58) were associated with increased risks of birth defects. Additionally, irregular folic acid supplementation was linked to an increased risk of birth defects (OR 1.32; 95% CI: 0.09-2.55) and a significantly higher risk of neural tube defects (OR 2.34; 95% CI: 2.01-2.72). Other factors associated with increased risk included exposure to harmful substances (OR 1.45), contraceptive use within 6 months prior to pregnancy (OR 1.36), and history of fever or medication in early pregnancy.

Conversely, premarital, pregnancy, and birth examinations were each associated with a decreased risk of birth defects. These findings provide evidence for potential intervention measures in the prevention of birth defects, though results are based on observational data and do not establish direct causality.

How this fits prior evidence

This meta-analysis addresses gaps regarding specific maternal factors linked to birth defects by identifying associations with age, BMI, and folic acid intake. It complements previous findings showing a 10% decline in U.S. infant mortality from birth defects (2003-2017) and the known risks of gestational complications for patients with certain skin conditions.

Expecting a child comes with many questions about how to ensure a healthy pregnancy. A large study involving over 26,000 cases looked at various factors that might influence the risk of birth defects, including neural tube defects (problems with the spine or brain).

The research found that certain factors were linked to higher risks. These included being over age 35, having a high body mass index, and irregular folic acid use. The study also noted links between birth defects and things like exposure to harmful substances, history of fever in early pregnancy, and using certain medications or contraceptives shortly before becoming pregnant.

On the other hand, regular medical checkups showed a protective effect. Specifically, premarital, pregnancy, and birth examinations were all linked to lower risks. It is important to remember that these findings show associations, not direct causes. Because this was based on observational data, it highlights areas where consistent care and nutrition can play a role in prenatal health.

What this means for you:
Factors like age, weight, and regular folic acid use are linked to the risk of birth defects.

Common questions

How does folic acid affect pregnancy?

The study found that irregular folic acid supplementation was linked to an increased risk of birth defects. Specifically, it was associated with a higher risk of neural tube defects, which are issues involving the spine and brain.

What maternal factors were linked to higher risks?

Several factors showed an association with higher risk: being age 35 or older, having a body mass index over 30, exposure to harmful substances, and experiencing a fever during early pregnancy.

Can medical checkups help reduce risks?

Yes, the data showed that premarital, pregnancy, and birth examinations were all associated with a decreased risk of birth defects. These routine checks are part of the healthcare services evaluated in the study.

Study Details

Study typeMeta analysis
EvidenceLevel 1
PublishedJul 2026
View Original Abstract ↓
ObjectiveThis study aims to systematically evaluate the primary influencing factors of birth defects in China from 2019 to 2025, providing evidence for decision-making and intervention measures in the prevention of birth defects.MethodsA comprehensive search was conducted in various databases, including CNKI, Wanfang, VIP, China Biomedical Literature Database, PubMed, Web of Science, Embase, Elsevier Science Direct, and CINAHL, covering literature published from January 2019 to December 2025. Two researchers independently performed literature screening, quality assessment, and data extraction. Meta-analysis was conducted using Stata 17.0 software. For factors exhibiting high heterogeneity (I2 ≥ 50%) and with at least four included studies, subgroup analyses were carried out based on the types of birth defects, study regions, or study quality. This review adhered to the PRISMA 2020 guidelines.ResultsA total of 25 studies were included in this analysis, comprising 26,019 cases of birth defects. Seventeen influencing factors were identified. Maternal physiological factors included maternal age ≥35 years (OR = 1.26, 95% CI: 1.05–1.47), maternal BMI > 30 kg/m2 (OR = 1.42, 95% CI: 1.25–1.58), and maternal drug use (OR = 1.06, 95% CI: 0.58–1.54). Healthcare service factors encompassed premarital examinations (OR = 0.36, 95% CI: 0.30–0.43), pregnancy examinations (OR = 0.41, 95% CI: 0.21–0.62), and birth examinations (OR = 0.45, 95% CI: 0.28–0.62). Nutritional and behavioral factors included irregular folic acid supplementation (OR = 1.32, 95% CI: 0.09–2.55; for neural tube defects: OR = 2.34, 95% CI: 2.01–2.72, I2 = 0%), a history of medication in early pregnancy (OR = 1.17, 95% CI: 0.65–1.69), a history of fever in early pregnancy (OR = 1.19, 95% CI: 0.86–1.52), adverse mood during pregnancy (OR = 1.09, 95% CI: 0.17–2.01), exposure to harmful substances (OR = 1.45, 95% CI: 1.04–1.87), and contraceptive use within 6 months prior to pregnancy (OR = 1.36, 95% CI: 1.29–1.44). Other factors included income
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