The association between parental age differences and perinatal outcomes

Hum Reprod. 2024 Feb 1;39(2):425-435. doi: 10.1093/humrep/dead236.

Abstract

Study question: Are there significant associations existing between parental age differences and adverse perinatal outcomes?

Summary answer: Large differences in parental age are associated with adverse perinatal outcomes, particularly with older mothers paired with younger fathers.

What is known already: The association between advanced maternal age and perinatal outcomes is well-documented with women over 35 years showing an increased risk of several adverse outcomes. Other studies have identified potential associations between advanced paternal age and adverse perinatal outcomes.

Study design, size, duration: A historical (retrospective) cohort analysis was performed utilizing a multivariable logistic regression model to evaluate the association between varying differences in parental age and adverse perinatal outcomes while controlling for demographic and health-related covariates. Data were compiled from the National Vital Statistics System for 20 613 704 births between 2012 and 2018.

Participants/materials, setting, methods: Parental age differences, categorized into eleven 4-year intervals, were stratified by seven maternal age categories and evaluated for their associations with adverse perinatal outcomes. Main outcome measures included low birth weight, very low birth weight, preterm birth, very preterm birth, small size for gestational age, low 5-min appearance, pulse, grimace, activity, and respiration score, congenital defects, and chromosomal anomalies.

Main results and the role of chance: Increased parental age differences, in either direction, were associated with significant risks for all adverse outcomes, aside from congenital defects, even when controlling for maternal age. Restricting maternal age to the reference range of 25-29 years, infants born to fathers aged 9-12 years younger (n = 3773) had 27% (odds ratio (OR) 1.27, 95% CI, 1.17-1.37) higher odds of having any adverse perinatal outcome. Infants born to fathers aged >16 years older (n = 98 555) had 14% (OR 1.14, 95% CI, 1.12-1.16) higher odds of having any adverse perinatal outcome.

Limitations, reasons for caution: Data extracted from US birth certificates may be compromised by errors in reporting or documentation. Information regarding the mother's socioeconomic status was estimated using proxy variables and may be susceptible to uncontrolled factors. Use of a pre-compiled dataset may potentially exclude additional maternal comorbidities that could impact perinatal outcomes.

Wider implications of findings: Older mothers paired with younger fathers demonstrated the highest risk, even when maternal age was below the threshold of 35 years. For the clinical setting, parental age differences should be considered alongside maternal and paternal age when assessing risks of adverse perinatal outcomes for potential parents. This is particularly relevant for older women with younger male partners as this may exacerbate the impact of advanced maternal age.

Study funding/competing interest(s): This research was funded by the NIH Research Fellowship T35 Training Grant. There are no competing interests.

Trial registration number: N/A.

Keywords: andrology; counseling; epidemiology; fertilization; infertility; prenatal diagnosis.

MeSH terms

  • Aged
  • Female
  • Humans
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Male
  • Mothers
  • Parturition
  • Pregnancy
  • Premature Birth* / etiology
  • Retrospective Studies