European journal of pediatrics · 2026
Parental and grandparental age in relation to Down syndrome risk and congenital heart disease in affected children: a case-control study in Peru.
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Abarca-Barriga Hugo, Espinosa Suárez Alejandra Paola, Amayo Cabrera Miara Yahaira
Аннотация
UNLABELLED: This study aimed to assess the association between grandparental age and the risk of Down syndrome and evaluate the relationship between paternal age and congenital heart disease (CHD) among affected children in Peru. A retrospective case-control study was conducted at a national pediatric referral center in Peru, including 290 participants (145 cases with free trisomy 21 and 145 controls without genetic disorders). Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Parental ages were higher in cases than in controls, but there were no significant differences in grandparental ages. Maternal age was the strongest risk factor for Down syndrome (OR = 1.16 per additional year; 95% CI: 1.09-1.23). No significant association was found between maternal grandmother's age and Down syndrome (OR = 0.96 per additional year; 95% CI: 0.91-1.02). Paternal age ≥ 32.6 years (categorical analysis based on the Liu-derived cut-off) was associated with an increased risk of congenital heart disease in the presence of FT21, compared with a reference group combining FT21 without CHD and healthy controls (aOR = 3.64; 95% CI: 1.96-6.77).
CONCLUSION: In this Latin American cohort, maternal age remains the primary risk factor for Down syndrome, with no evidence supporting an effect of maternal grandmother's age at the birth of the mother. Notably, advanced paternal age was independently associated with higher odds of congenital heart disease among children with Down syndrome. These findings warrant confirmation in independent populations before being considered for clinical application.
WHAT IS KNOWN: • Advanced maternal age is the main established risk factor for Down syndrome. • The maternal grandmother's age at the birth of the mother remains uncertain, with inconsistent evidence. The contribution of paternal age to congenital heart disease in affected individuals has been insufficiently studied.
WHAT IS NEW: • In this case-control study from a Latin American population, the maternal grandmother's age at the birth of the mother was not associated with DS • Advanced paternal age was independently associated with higher odds of congenital heart disease among children with Down syndrome.
CONCLUSION: In this Latin American cohort, maternal age remains the primary risk factor for Down syndrome, with no evidence supporting an effect of maternal grandmother's age at the birth of the mother. Notably, advanced paternal age was independently associated with higher odds of congenital heart disease among children with Down syndrome. These findings warrant confirmation in independent populations before being considered for clinical application.
WHAT IS KNOWN: • Advanced maternal age is the main established risk factor for Down syndrome. • The maternal grandmother's age at the birth of the mother remains uncertain, with inconsistent evidence. The contribution of paternal age to congenital heart disease in affected individuals has been insufficiently studied.
WHAT IS NEW: • In this case-control study from a Latin American population, the maternal grandmother's age at the birth of the mother was not associated with DS • Advanced paternal age was independently associated with higher odds of congenital heart disease among children with Down syndrome.