Older fathers linked to problems with pregnancies, births

Michael Eisenberg, MD

While maternal age remains one of the biggest influencers on infant morbidity, fathers play an important role, too.

Michael Eisenberg, MD, associate professor of Urology and Obstetrics and Gynecology at Stanford University, Stanford, California, and co-author of a new study on paternal age, says the report highlights the fact that the mother’s age isn’t the only one impacting birth outcomes.

“The etiology remains uncertain. Investigators have postulated genetic or epigenetic effects that may occur as the father ages, which may lead to the offspring and maternal outcomes that were observed,” Eisenberg says.

The purpose of the study, published in the BMJ, was conducted to evaluate the effect of paternal age on maternal and perinatal outcomes. Traditionally, maternal age is the primary concern in many cases when assessing the risk status of a pregnancy. However this study shows that higher paternal age was associated with an increased risk of premature birth, low birth weight, and low Apgar scores.¹ More specifically, the research team found that infants born to fathers aged older than 45 years had 14% higher odds of premature birth and 18% higher odds of seizures compared with infants born to fathers aged 25 to 34 years. The odds of a mother developing gestational diabetes were also 34% higher in mothers with the oldest partners, and 13.2% of premature births and 18.2% of gestational diabetes in births were attributed to advanced paternal age.

Paternal age is trending up

Whereas there is a relatively low prevalence of high paternal age in the United States, it is trending up. According to the report, paternal age has doubled in the United States over the past generation, making it increasingly important to understand the impact that paternal age has on outcomes rather than focusing on maternal age.

The number of births to women aged older than 35 years has increased by about 2% each year since the 1970s, according to the report, and births to fathers aged 40 years and older have doubled to 9% over the same period. The effects of maternal age on perinatal outcomes have been studied extensively, but there has been limited information on the effect of paternal age outside congenital diseases. Previously, advanced paternal age and the number of male germ cell divisions in those fathers have been linked to increased prevalence of autism, genetic abnormalities, psychiatric morbidity, and neoplasia in children. However, more recent studies have turned to investigating the paternal effect on perinatal morbidity overall.

Research suggests that epigenetic changes occur within spermatocytes in the same regions that are responsible for several diseases in children of fathers of advanced age. Alterations to developing germ cells could be a precursor to embryonic and placental development, the report notes, with some studies suggesting that paternal imprinting of aging could affect both fetal growth and maternal health during pregnancy.

Given the fact that older fathers are still not all that common in the United States, it has been difficult to provide conclusive data given small samples sizes, the report notes. However, using data from the National Vital Statistics System, researchers investigated more than 40 million live births between 2007 and 2016. After adjusting for multiple other factors that could contribute to infant morbidity, the team found that the oldest fathers were associated with the worst outcomes. Gestational ages were lower in infants whose fathers were aged older than 45 years, and those infants had 45% higher odds of preterm birth. There were no differences when in-vitro fertilization results were excluded.

Fathers’ age impacts mothers, too

The study also investigated the impact of the pregnancy on mothers whose partners were of advanced age. Having a partner aged older than 45 years increased the rate of gestational diabetes in mothers by 28%.

The research team notes that because the study was carried out using data from multiple decades with similar results across the study period, it indicates that the trends seen in this study were not influenced by more recent changes to medical practice.

Overall, the research team attributed 13.2% of premature birth, 14.5% of low-birth-weight births, 15.1% of neonatal intensive care unit admissions, and 18.2% of gestational diabetes cases to fathers who were aged older than 45 years.

Eisenberg says that although this study did not directly compare outcomes between maternal and paternal ages, it is fair to assume that maternal age remains more impactful to infant morbidity. The information in this study, however, highlights that there is a paternal effect present, and the information from this study may help guide future research and decision-making.

“I think the study provides further information to couples about reproduction. Whereas many factors go into deciding when to start a family, the study provides data on how to incorporate the father’s age,” Eisenbergh says. “I think the message is to understand that fertility is a team sport and both members are important.” 

References:

1. Kwandwala YS, Baker VL Shaw GM, Stevenson DK. Lu Y, Eisenberg MI. Association of maternal age with perinatal outcomes between 2007 and 2016 in the United States: population-based cohort study. BMJ. 2018;363:k4372.