Grandparental morbidity and mortality patterns are associated with infant birth weight in the Lifeways cross-generation cohort study 2001-2010.

The association of infants' birth weight with maternal cardiovascular morbidity (CVD) and mortality substantiates the foetal origins hypothesis. Few studies to date have investigated grandparent-infant risk association. We prospectively examined this relationship in the Lifeways three-generation familial cohort, contrasting lineage and gender differences to understand mechanisms of intergenerational risk transmission. In 2001, a cohort of 1082 families was established at antenatal stage. A total of 539 families (n = 539 infants) had both a participating grandparent (n = 1054) and information on infants' gestational age. At baseline, grandparents provided their diagnosed CVD status and 79% also underwent a cardiovascular risk factors assessment. In 2005, general practitioners provided an update for 61% grandparents. In 2010, a search of civil register confirmed 77 grandparental deaths in 539 families. Grandchildren's birth weight and grandparental cardiovascular risk factors associations were examined with linear regressions. Grandparental CVD associations were analysed using ANCOVA. Cox proportional hazard ratios (HR) were calculated for all-cause mortality associations. Models were adjusted for infants', mothers' and grandparents' demographic, anthropometric and socio-behavioural characteristics, as appropriate. The paternal grandfathers' (PGF) systolic blood pressure (mmHg) [β (95% CI) = 6.6 (0.8 - 12.5); P = 0.03] and paternal grandmothers' serum triglycerides (mmol/l) [β (95% CI) = 78.8 (7.0 - 150.7); P = 0.03] were linearly predictive of infants' birth weight, which was not observed for maternal grandparents. Mean birth weight for infants of maternal grandmothers with diabetes {-272.7 [(-499.7) - (-45.6)] g; P = 0.02} or stroke {-292.1 [(-544.5) - (-39.6)] g; P = 0.02} was lower than those without diabetes or stroke, a pattern not observed for paternal grandparents. Whereas PGFs' mortality was significantly associated with infants' high birth weight (≥4000 g) [HR (95% CI) = 4.9 (1.2 - 19.9); P = 0.03], maternal grandparents' mortality showed a converse pattern with infants' low birth weight (<2500 g) [HR (95% CI) = 1.7 (0.4 - 8.2); P = 0.7], although not statistically significant. These findings suggest that intergenerational transmission of risk differs in maternal and paternal lines.