Preconception paternal comorbidities and offspring birth defects: Analysis of a large national data set

Abstract

Background Despite the fact that the father contributes half the genome to a child, associations between paternal factors and birth defects are poorly understood. Objectives To investigate the association between preconception paternal health and birth defects in the offspring. Materials and Methods We conducted analysis of a national cohort study utilizing the IBM Marketscan Research Database, which includes data on reimbursed private healthcare claims in the United States from 2007 to 2016. The potential association between paternal comorbidities, as measured by the components of metabolic syndrome (MetS), and any birth defect in the offspring was analyzed. Results Of the 712,774 live births identified, 21.2% of children were born to fathers with at least one component of the metabolic syndrome (MetS ≥1) prior to conception. Compared to infants born to fathers with no components of the metabolic syndrome, a modestly higher percentage of infants with cardiac birth defects were born to fathers with more components of MetS (MetS = 1, OR [95% CI]: 1.07 [1.01–1.13]; MetS ≥2, 1.17 [1.08–1.26], in comparison to MetS = 0) after adjusting for maternal and paternal factors. Similarly, a higher percentage of infants with respiratory defects were born to fathers with two or more components of metabolic syndrome (MetS ≥2, OR [95% CI]: 1.45 [1.22–1.71]). Discussion and Conclusion In this private insurance claims‐based study, we found that fathers with metabolic syndrome‐related diseases before conception were at increased risk for having a child affected by birth defects, especially cardiac and respiratory defects, and this association was not influenced by paternal age or assessed maternal factors.

The association of preconception paternal metabolic syndrome on early childhood emergency department visits and hospitalizations

“…Paternal obesity and its associated metabolic disturbances are common diseases found in fathers that have the potential to cause adverse alterations in sperm epigenetics including DNA methylation and sperm mRNA profiles 9,10 . Recently it has been shown that fathers with more metabolic syndrome‐related comorbidities are at higher risk of fathering children with cardiac and respiratory defects 11 . However, the association of a father's health with his children beyond the perinatal and infant (i.e., until age one 12 ) periods remains uncertain.…”