Are paternal or grandmaternal age associated with higher probability of trisomy 21 in offspring? A population-based, matched case-control study, 1995-2015

Karen C Schliep; Marcia L Feldkamp; Heidi A Hanson; Michael Hollingshaus; Alison Fraser; Ken R Smith; Katherine A Panushka; Michael W Varner

doi:10.1111/ppe.12737

Are paternal or grandmaternal age associated with higher probability of trisomy 21 in offspring? A population-based, matched case-control study, 1995-2015

Paediatr Perinat Epidemiol. 2021 May;35(3):281-291. doi: 10.1111/ppe.12737. Epub 2020 Dec 1.

Authors

Karen C Schliep¹, Marcia L Feldkamp², Heidi A Hanson^{3

4}, Michael Hollingshaus⁵, Alison Fraser⁴, Ken R Smith^{4

6}, Katherine A Panushka⁷, Michael W Varner⁷

Affiliations

¹ Department of Family and Preventive Medicine, University of Utah, Salt Lake City, UT, USA.
² Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
³ Department of Surgery, University of Utah, Salt Lake City, UT, USA.
⁴ Department of Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT, USA.
⁵ Kem C. Gardner Policy Institute, University of Utah, Salt Lake City, UT, USA.
⁶ Department of Family and Consumer Studies, University of Utah, Salt Lake City, UT, USA.
⁷ Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA.

Abstract

Background: Fetal aneuploidy risk increases with maternal age, but the majority of pregnancies complicated by trisomy 21 occur in younger women. It has been suggested that grandmaternal and/or paternal age may also play a role.

Objectives: To assess the association between grandmaternal and paternal age and trisomy 21.

Methods: For the grandmaternal assessments, we included all offspring with trisomy 21 in a statewide birth defects surveillance system (1995-2015) that could be linked to 3-generation matrilineal pedigrees in the Utah Population Database. Ten sex/birth year-matched controls were selected for each case (770 cases and 7700 controls). For the paternal assessments, our cohort included all trisomy 21 cases (1995-2015) where both the mother and father resided in Utah at the time of birth (1409 cases and 14 090 controls). Ages were categorised by 5-year intervals (reference: 25-29 years). Conditional logistic regression, adjusting for potential confounding factors, was used to model the association between grandmaternal and paternal age and trisomy 21.

Results: No association between grandmaternal age and trisomy 21 was detected, whether age was assessed continuously (adjusted odds ratio [OR] 1.01, 95% confidence interval [CI] 0.98, 1.03) or categorically after adjusting for grandmaternal and grandpaternal race/ethnicity and grandpaternal age. Compared to fathers aged 20-29 years, fathers <20 years (OR 3.15, 95% CI 1.99, 4.98) and 20-24 years (OR 1.39, 95% CI 1.11, 1.73) had increased odds of trisomy 21 offspring, after adjusting for maternal and paternal race/ethnicity and maternal age. Results were consistent after excluding stillbirths, multiples, and trisomy 21 due to translocation or mosaicism.

Conclusions: Maternal age is an important risk factor for trisomy 21 offspring; however, this population-based study shows that that young paternal age is also associated with trisomy 21, after taking into account maternal age and race/ethnicity.

Keywords: Trisomy 21; case-control study; down syndrome; grandmaternal age; maternal age; paternal age.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Case-Control Studies
Child, Preschool
Down Syndrome* / epidemiology
Down Syndrome* / genetics
Fathers*
Female
Humans
Male
Odds Ratio
Paternal Age
Pregnancy
Risk Factors
Trisomy

Abstract

Publication types

MeSH terms

Grants and funding