Associations of gestational age and intrauterine growth with systolic blood pressure in a family-based study of 386,485 men in 331,089 families

BACKGROUND: We conducted a family-based study to explore mechanisms underlying the associations of birth weight and gestational age with systolic blood pressure measured at 17 to 19 years of age. METHODS AND RESULTS: A record linkage study of 386,485 singleton-born men from 331,089 families was undertaken. Birth weight was inversely associated with systolic blood pressure within siblings, with a mean difference (adjusted for age at examination, examination center, and year of examination) within siblings per 1-SD difference in birth weight of -0.21 mm Hg (95% CI, -0.33 to -0.08) and between nonsiblings of -0.12 (95% CI, -0.16 to -0.08). Gestational age was inversely associated with systolic blood pressure within siblings (-0.18 mm Hg; 95% CI, -0.25 to -0.11, per week of gestational age) and between nonsiblings (-0.26 mm Hg; 95% CI, -0.29 to -0.24). Adjustment for socioeconomic position and maternal characteristics did not alter these within- or between-family associations. Furthermore, the associations were not affected by adjustment for paternal height, body mass index, or systolic blood pressure. CONCLUSIONS: Our present findings suggest that the inverse associations of birth weight and gestational age with systolic blood pressure are not explained by confounding resulting from family socioeconomic position or other factors that are shared by siblings. Variations in maternal metabolic or vascular health during pregnancy or placental implantation and function may explain these associations.