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. 2010 Mar;20(3):241-9.
doi: 10.1016/j.annepidem.2009.10.009. Epub 2010 Jan 6.

Association of paternal age and risk for major congenital anomalies from the National Birth Defects Prevention Study, 1997 to 2004

Ridgely Fisk Green  1 , Owen Devine, Krista S Crider, Richard S Olney, Natalie Archer, Andrew F Olshan, Stuart K Shapira; National Birth Defects Prevention Study
Affiliations

Association of paternal age and risk for major congenital anomalies from the National Birth Defects Prevention Study, 1997 to 2004

Ridgely Fisk Green et al. Ann Epidemiol. 2010 Mar.

Abstract

Purpose: The objective of this study was to examine the associations between paternal age and birth defects of unknown etiologies while carefully controlling for maternal age.

Methods: By using 1997 to 2004 data from the National Birth Defects Prevention Study, we fit logistic regression models with paternal and maternal age as continuous variables while adjusting for demographic and other factors.

Results: Elevated odds ratios (ORs) for each year increase in paternal age were found for cleft palate (OR. 1.02, 95% confidence interval [95% CI], 1.00-1.04), diaphragmatic hernia (OR, 1.04; 95% CI, 1.02-1.06), right ventricular outflow tract obstruction (OR, 1.03; 95% CI, 1.01-1.04), and pulmonary valve stenosis (OR, 1.02, 95% CI, 1.01-1.04). At younger paternal ages, each year increase in paternal age correlated with increased odds of having offspring with encephalocele, cataract, esophageal atresia, anomalous pulmonary venous return, and coarctation of the aorta, but these increased odds were not observed at older paternal ages. The effect of paternal age was modified by maternal age for gastroschisis, omphalocele, spina bifida, all orofacial clefts, and septal heart defects.

Conclusions: Our findings suggest that paternal age may be a risk factor for some multifactorial birth defects.

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Figures

Figure 1
Figure 1
Estimated Odds Ratios of the Association Between Paternal Age (Referent = 30) and Gastroschisis (A), Omphalocele (B), Spina Bifida (C), All Orofacial Clefts (D), and Septal Heart Defects (E) From the National Birth Defects Prevention Study 1997–2004. Covariates included in the analyses were maternal age, maternal age2, gravidity, periconceptional folic acid use, maternal body mass index, paternal birthplace, paternal education, paternal race and ethnicity, singleton/multiple birth, maternal smoking, maternal alcohol use, paternal drug use, use of assisted reproductive technology, and previous stillbirth or miscarriage. The following maternal and paternal age interaction terms were included in the logistic regression models for each of the defects listed: maternal age x paternal age (gastroschisis, spina bifida, omphalocele, all orofacial clefts, and all septal defects); maternal age2 × paternal age (gastroschisis, spina bifida, and all septal defects); maternal age × paternal age2 (gastroschisis, omphalocele, and all orofacial clefts) and maternal age2 × paternal age2 (gastroschisis). Cases categorized as complex (mostly Pentalogy of Cantrell or OEIS (Omphalocele, Exstrophy, Imperforate anus, Spinal defects)) were excluded from analyses of omphalocele and spina bifida.
Figure 1
Figure 1
Estimated Odds Ratios of the Association Between Paternal Age (Referent = 30) and Gastroschisis (A), Omphalocele (B), Spina Bifida (C), All Orofacial Clefts (D), and Septal Heart Defects (E) From the National Birth Defects Prevention Study 1997–2004. Covariates included in the analyses were maternal age, maternal age2, gravidity, periconceptional folic acid use, maternal body mass index, paternal birthplace, paternal education, paternal race and ethnicity, singleton/multiple birth, maternal smoking, maternal alcohol use, paternal drug use, use of assisted reproductive technology, and previous stillbirth or miscarriage. The following maternal and paternal age interaction terms were included in the logistic regression models for each of the defects listed: maternal age x paternal age (gastroschisis, spina bifida, omphalocele, all orofacial clefts, and all septal defects); maternal age2 × paternal age (gastroschisis, spina bifida, and all septal defects); maternal age × paternal age2 (gastroschisis, omphalocele, and all orofacial clefts) and maternal age2 × paternal age2 (gastroschisis). Cases categorized as complex (mostly Pentalogy of Cantrell or OEIS (Omphalocele, Exstrophy, Imperforate anus, Spinal defects)) were excluded from analyses of omphalocele and spina bifida.
Figure 1
Figure 1
Estimated Odds Ratios of the Association Between Paternal Age (Referent = 30) and Gastroschisis (A), Omphalocele (B), Spina Bifida (C), All Orofacial Clefts (D), and Septal Heart Defects (E) From the National Birth Defects Prevention Study 1997–2004. Covariates included in the analyses were maternal age, maternal age2, gravidity, periconceptional folic acid use, maternal body mass index, paternal birthplace, paternal education, paternal race and ethnicity, singleton/multiple birth, maternal smoking, maternal alcohol use, paternal drug use, use of assisted reproductive technology, and previous stillbirth or miscarriage. The following maternal and paternal age interaction terms were included in the logistic regression models for each of the defects listed: maternal age x paternal age (gastroschisis, spina bifida, omphalocele, all orofacial clefts, and all septal defects); maternal age2 × paternal age (gastroschisis, spina bifida, and all septal defects); maternal age × paternal age2 (gastroschisis, omphalocele, and all orofacial clefts) and maternal age2 × paternal age2 (gastroschisis). Cases categorized as complex (mostly Pentalogy of Cantrell or OEIS (Omphalocele, Exstrophy, Imperforate anus, Spinal defects)) were excluded from analyses of omphalocele and spina bifida.
Figure 1
Figure 1
Estimated Odds Ratios of the Association Between Paternal Age (Referent = 30) and Gastroschisis (A), Omphalocele (B), Spina Bifida (C), All Orofacial Clefts (D), and Septal Heart Defects (E) From the National Birth Defects Prevention Study 1997–2004. Covariates included in the analyses were maternal age, maternal age2, gravidity, periconceptional folic acid use, maternal body mass index, paternal birthplace, paternal education, paternal race and ethnicity, singleton/multiple birth, maternal smoking, maternal alcohol use, paternal drug use, use of assisted reproductive technology, and previous stillbirth or miscarriage. The following maternal and paternal age interaction terms were included in the logistic regression models for each of the defects listed: maternal age x paternal age (gastroschisis, spina bifida, omphalocele, all orofacial clefts, and all septal defects); maternal age2 × paternal age (gastroschisis, spina bifida, and all septal defects); maternal age × paternal age2 (gastroschisis, omphalocele, and all orofacial clefts) and maternal age2 × paternal age2 (gastroschisis). Cases categorized as complex (mostly Pentalogy of Cantrell or OEIS (Omphalocele, Exstrophy, Imperforate anus, Spinal defects)) were excluded from analyses of omphalocele and spina bifida.
Figure 1
Figure 1
Estimated Odds Ratios of the Association Between Paternal Age (Referent = 30) and Gastroschisis (A), Omphalocele (B), Spina Bifida (C), All Orofacial Clefts (D), and Septal Heart Defects (E) From the National Birth Defects Prevention Study 1997–2004. Covariates included in the analyses were maternal age, maternal age2, gravidity, periconceptional folic acid use, maternal body mass index, paternal birthplace, paternal education, paternal race and ethnicity, singleton/multiple birth, maternal smoking, maternal alcohol use, paternal drug use, use of assisted reproductive technology, and previous stillbirth or miscarriage. The following maternal and paternal age interaction terms were included in the logistic regression models for each of the defects listed: maternal age x paternal age (gastroschisis, spina bifida, omphalocele, all orofacial clefts, and all septal defects); maternal age2 × paternal age (gastroschisis, spina bifida, and all septal defects); maternal age × paternal age2 (gastroschisis, omphalocele, and all orofacial clefts) and maternal age2 × paternal age2 (gastroschisis). Cases categorized as complex (mostly Pentalogy of Cantrell or OEIS (Omphalocele, Exstrophy, Imperforate anus, Spinal defects)) were excluded from analyses of omphalocele and spina bifida.
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