Moderate altitude as a risk factor for isolated congenital malformations. Results from a case–control multicenter–multiregional study

Background

Living in high-altitude regions has been associated with a higher prevalence of some birth defects. Moderate altitudes (1500–2500 m) have been associated with some congenital heart diseases and low birth weight. However, no studies have been conducted for other isolated congenital malformations.

Objectives

To estimate the prevalence at birth of isolated congenital malformations in low and moderate altitudes and to determine if moderate altitudes are a risk factor, such as high altitudes, for isolated congenital malformations adjusted for other factors.

Methods

The study consisted of a case–control multicenter-multiregional study of 13 isolated congenital malformations. Cases included live births with isolated congenital malformations and controls at low (10–1433 m) and moderate altitudes (1511–2426 m) from a Mexican registry from January 1978 to December 2019. Prevalence per 10,000 (95% CI) per altitude group was estimated. We performed unadjusted and adjusted logistic regression models (adjusted for maternal age, parity, malformed relatives, socioeconomic level, and maternal diabetes) for each isolated congenital malformation.

Results

Hydrocephaly and microtia had a higher at-birth prevalence, and spina bifida, preauricular tag, and gastroschisis showed a lower at-birth prevalence in moderate altitudes. Moderate altitudes were a risk factor for hydrocephaly (aOR 1.39), microtia (aOR 1.60), cleft-lip-palate (aOR 1.27), and polydactyly (aOR 1.32) and a protective effect for spina bifida (aOR 0.87) compared with low altitudes.

Conclusions

Our findings provide evidence that moderate altitudes as higher altitudes are an associated risk or protective factor to some isolated congenital malformations, suggesting a possible gradient effect.