Advanced Parental Age and Perinatal Risks in Twins Conceived Through In Vitro Fertilization

OBJECTIVE: To evaluate the associations between advanced parental age and perinatal risks in twins. METHODS: We analyzed 7514 twin pairs conceived through in vitro fertilization. The exposure was advanced parental age (≥ 35 years), analyzed separately for mothers and fathers. Primary outcomes included birth weight discordance, small for gestational age, large for gestational age, macrosomia, low birth weight, very low birth weight, preterm birth, very preterm birth, and extremely preterm birth. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. Additionally, parental age was analyzed both as a categorical variable and with a restricted cubic spline. The combined effect of advanced age in both parents was further evaluated. RESULTS: Advanced paternal age (≥ 35 years) was associated with increased odds of birth weight discordance (adjusted OR, 1.20; 95% CI, 1.01-1.42). A graded dose-response association was evident (p for trend = 0.026), with adjusted ORs for birth weight discordance progressively increasing across paternal age categories: 1.02 (95% CI, 0.83-1.25) for ages 30-34, 1.18 (95% CI, 0.91-1.52) for ages 35-39, and 1.41 (95% CI, 1.02-1.96) for ages ≥ 40 years, all compared to the < 30 years reference group. Restricted cubic spline analysis identified 37 years as a threshold beyond which paternal age significantly elevated birth weight discordance risk. Similarly, advanced maternal age (≥ 35 years) was significantly associated with increased small for gestational age odds (adjusted OR, 1.21; 95% CI, 1.04-1.41), with a significant trend (p for trend = 0.012) and a restricted cubic spline-derived threshold at 30 years. When both parents were over 35, the odds of birth weight discordance (adjusted OR, 1.37; 95% CI, 1.15-1.63) and small for gestational age (adjusted OR, 1.30; 95% CI, 1.13-1.50) were significantly elevated compared to both being under 35. CONCLUSIONS: Advanced parental age was associated with elevated risks of birth weight discordance and small for gestational age in twins, suggesting it as a contributing factor to perinatal risk.