Abstract
PurposeWhile it is well documented that maternal adverse exposures contribute to a series defects on offspring health according to the Developmental Origins of Health and Disease (DOHaD) theory, paternal evidence is still insufficient. Advanced paternal age is associated with multiple metabolism and psychiatric disorders. Birth weight is the most direct marker to evaluate fetal growth. Therefore, we designed this study to explore the association between paternal age and birth weight among infants born at term and preterm (<37 weeks gestation).MethodsA large retrospective study was conducted using population-based hospital data from January 2015 to December 2019 that included 69,964 cases of singleton infant births with complete paternal age data. The primary outcome was infant birth weight stratified by sex and gestational age including small for gestational age (SGA, 10th percentile) and large for gestational age (LGA, 90th percentile). Birth weight percentiles by gestational age were based on those published in the INTERGROWTH-21st neonatal weight-for gestational-age standard. Logistic regression analysis and linear regression model were used to estimate the association between paternal age and infant birth weight.ResultsAdvanced paternal age was associated with a higher risk for a preterm birth [35–44 years: adjusted odds ratio (OR) = 1.13, 95%CI (1.03 to 1.24); >44 years: OR = 1.36, 95%CI (1.09 to 1.70)]. Paternal age exerted an opposite effect on birth weight with an increased risk of SGA among preterm infants (35–44years: OR = 1.85, 95%CI (1.18 to 2.89) and a decreased risk among term infant (35–44years: OR = 0.81, 95%CI (0.68 to 0.98); >44 years: OR = 0.50, 95%CI (0.26 to 0.94). U-shaped associations were found in that LGA risk among term infants was higher in both younger (<25 years) (OR = 1.32; 95%CI, 1.07 to 1.62) and older (35–44 years) (OR = 1.07; 95% CI, 1.01 to 1.14) fathers in comparison to those who were 25 to 34 years old at the time of delivery.ConclusionsOur study found advanced paternal age increased the risk of SGA among preterm infants and for LGA among term infants. These findings likely reflect a pathophysiology etiology and have important preconception care implications and suggest the need for antenatal monitoring.
Highlights
While it is well documented that advanced age among women is an important risk factor for infertility, miscarriage, and offspring genetic defects [1], less is known about the effects of advanced age on reproductive impairment among men
The primary outcome was infant birth weight stratified by sex and gestational age including small for gestational age (SGA, 10th percentile) and large for gestational age (LGA, 90th percentile)
Paternal age exerted an opposite effect on birth weight with an increased risk of Small for gestational age (SGA) among preterm infants (35–44years: OR = 1.85, 95%CI (1.18 to 2.89) and a decreased risk among term infant (35–44years: OR = 0.81, 95%CI (0.68 to 0.98); >44 years: OR = 0.50, 95%CI (0.26 to 0.94)
Summary
While it is well documented that advanced age among women is an important risk factor for infertility, miscarriage, and offspring genetic defects [1], less is known about the effects of advanced age on reproductive impairment among men. From 1972 to 2015, the National Vital Statistics System data has shown that the mean paternal age has increased from 27.4 to 30.9 years in US [3]. Researchers have shown that the risk increase in incontrovertible paternal age-related adverse conditions starts around 35 years old of paternal age [4]. There is preliminary evidence to suggest that advanced paternal age may increase the occurrence of adverse pregnancy outcomes such as miscarriage [5], stillbirth [6] or preterm birth [7]. The adverse offspring outcomes include higher rates of congenital malformations [8], malignancies [9], early onset schizophrenia [10], autism [11] and other psychiatry or academic morbidities [12]
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