Date of Award


Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)


School of Public Health

First Advisor

Zeyan Liew



Introduction: Animal studies have suggested that exposure-induced epigenetic reprogramming of the germlines affects neurodevelopmental outcomes in the next generation, but possible transgenerational effects of parental adverse birth outcomes and offspring autism spectrum disorder (ASD) risk have not been studied in humans.

Objective: To evaluate whether parents being born preterm or low birth weight were associated with risks for ASD in their offspring.

Methods: We conducted a Danish population-based cohort study including mothers and fathers born since 1978 who also have had an offspring registered in Denmark during 1990-2013. Information on gestational age and birth weight were recorded in the Danish Medical Birth Register; ASD diagnoses of the offspring were ascertained using records from the Danish Central Psychiatric Registry. We identified 235,228 mother-child pairs and 161,606 father-child pairs for statistical analyses. We estimated Odds Ratio (OR) and 95% confidence intervals (CI) for ASD according to parental preterm and low birth weight status, with or without adjustment for grand-maternal sociodemographic factors including age, parity and education level.

Results: Of all parents included in the study, 5.4% mothers (12,749) and 4.4 % fathers (7,084) had low birth weight, and approximately 4.0% mothers (9,724) and fathers (7,413) were born preterm. Children of mothers with adverse birth outcomes had about 20% higher risk for ASD (low birth weight, OR=1.19, 95% CI: 1.03-1.38; preterm birth, OR=1.19, 95% CI= 1.01-1.40), compared with mothers born with normal birth weight or born at term. Paternal adverse birth outcomes were also associated with about 30% elevated risks for ASD in the offspring (low birth weight, OR=1.31, 95% CI= 1.07, 1.59; preterm birth, OR=1.29, 95% CI=1.06, 1.57). These associations were slightly attenuated upon adjustment for grandmaternal sociodemographic factors.

Conclusions: Offspring of parents born with adverse outcomes showed slightly elevated risks for ASD. Several etiological pathways could potentially explain this association, including that adverse birth outcomes in parents might act as a proxy indicating complications or harmful in utero exposures that had affected the germlines of the parents, or that parents born disadvantaged also had poorer physical health and lower socioeconomic achievement persisted into adulthood, and that these mechanisms in combined influencing disease risks in their offspring.


This is an Open Access Thesis.

Open Access

This Article is Open Access