To Örebro University

Background and aims: Young maternal age is thought to be associated with adverse metabolic outcomes in offspring that may persistin to adulthood. Previous studies have utilised longitudinal designs including cohort studies to assess these associations, but may have been limited by unmeasured or residual confounding. Here we use a longitudinal sibling comparison design (to tackle familial genetic and environmental confounding), to evaluate the association between maternal age <16 years at delivery and type 2 diabetes (T2D) in adult-hood among offspring.

Materials and methods: Using Swedish Register data from 1964 to 2018, we defined young mothers as maternal age at delivery <16 years and assessed T2D in offspring from 30 years. Demographic information was provided by Statistics Sweden; T2D by the Patient Register, Prescribed Drug Register, and Cause of Death Register using ICD 9 and ICD 10 codes; and death information by the Cause of Death Register. We estimated person-time from birth to diagnosis of T2D, emigration, death, loss to follow-up, or the end of the follow-up on December 31, 2018, whichever came first. After ruling out birth order effect, we associated maternal age at birth (<16 vs ≥16) with T2D, utilising Cox regression for conventional and models stratified by family (biological mother) for sibling comparison. We adjusted these models for sex (men vs women) and socioeconomic index (high, low, agriculture, and others vs middle).

Results: There were 5,719,176 mothers who gave birth to offspring comprising 2,661,535 groups of siblings. Of these, 6,020 children were born when their mothers were <16 years old; 13.93% developed T2D among these compared to 5,713,156 children who were born when their mothers were ≥ 16 years; 10.59% developed T2D among these. Using conventional analysis, both in unadjusted and adjusted analysis, offspring of young mothers compared with their siblings born after their mother was aged 16 years, had statistically significantly higher hazard ratios (with 95% confidence intervals) for T2D (HR [95% CI]: 1.63 [1.52, 1.75] and 1.52 [1.42, 1.65]). In comparison, sibling models ,both in unadjusted and adjusted analysis, found offspring of young mothers compared with their siblings born after their mother was aged 16 years, had significantly decreased hazard ratios for T2D (0.28 [0.21, 0.38] and 0.25 [0.20, 0.33]).

Conclusion: The raised risk of T2D born to young mothers compared with their siblings born after their mother was aged 16 years is confounded by familial characteristics.