Paternal Cardiometabolic Conditions and Perinatal Mortality

Abstract

Background: Studies have suggested that men with cardiometabolic conditions may have an increased risk of offspring perinatal mortality. However, this association remains underexplored.

Objectives: We aimed to study the association between fathers' cardiometabolic conditions and offspring perinatal mortality utilising linked data from national health registries in Norway.

Methods: In this population-based cohort study, males registered in the Medical Birth Registry of Norway (MBRN), born 1967-2005, were linked to their singleton offsprings born 2004-2020. The Norwegian Patient Registry and the Norwegian Prescription Database were used to define study exposures: history of hypertension, diabetes, dyslipidaemia, severe obesity or any of these at any time before/during the year of childbirth while fathers having no such conditions were the reference group. Perinatal mortality was defined as foetal death from 16 weeks' gestation or neonatal deaths within the first month after birth (from the MBRN). We fitted multilevel random-intercept Poisson regression models to account for the clustering of infants born to the same father. We reported incidence rate ratio (IRR) with 95% confidence Intervals (CI).

Results: Of 703,746 infants, 3.6% (n = 25,314) were born to fathers with any condition. Overall, 4827 (0.7%) of them died perinatally. In fully adjusted models, infants of fathers with hypertension had a 29% higher risk of dying perinatally (IRR 1.29, 95% CI 1.05, 1.57) relative to those of fathers without cardiometabolic conditions. Effect estimates for paternal diabetes, severe obesity and any condition also indicated a possible increased perinatal mortality associated with these conditions. In the sex-stratified analysis, the associations were stronger in male offspring (IRR 1.29, 95% CI 1.06, 1.58) than female offspring (IRR 1.01, 95% CI 0.78, 1.29).

Conclusions: The increased perinatal mortality in offspring to fathers with cardiometabolic conditions emphasises fathers' biological role in foetal and placental programming and development. Whether offspring sex impacts these associations needs further investigation.

Keywords: cardiometabolic; late miscarriage; paternal health; perinatal mortality; preconception; stillbirth.

FIGURE 1

Directed acyclic graph of association between father's cardiometabolic conditions and perinatal mortality. Unknown‐2: For example, epigenetic changes of sperm; Immunological incompatibility; Paternal urogenital tract as cytomegalovirus source. Minimal sufficient adjustment sets for estimating the total effect of paternal cardiometabolic conditions on perinatal mortality: Genetic susceptibility, paternal age and socioeconomic status.

FIGURE 2

Number of infants born to fathers with and without cardiometabolic conditions (CMD), 2004–2020, Norway.

FIGURE 3

Associations between father's cardiometabolic conditions and perinatal mortality in their offsprings born 2004–2020, Norway. Perinatal mortality: Intrauterine foetal death from 16 weeks of pregnancy or neonatal death within the first month after birth. Stillbirth: Intrauterine foetal death from 16 weeks of gestation to birth. Neonatal mortality: Death within the first month after birth.