Effect of intrauterine growth restriction on kidney function at young adult age: The Nord Trondelag Health (HUNT 2) Study

Background: The hypothesis of intrauterine origin of adult disease is debated. We tested whether intrauterine growth restriction is associated with later kidney function. Study Design: Prospective cohort study. Setting & Participants: 7,457 Norwegian adults aged 20 to 30 years participating in the population-based Nord Trondelag Health Study (1995-1997) with data for birth weight, gestational age, and maternal and perinatal risk factors registered at the Medical Birth Registry of Norway. Predictor: Birth weight expressed as an SID score (SDS) to adjust for gestational age and sex. Subjects with a birth weight SIDS less than -2.0, -2.0 to -1.3, and -1.3 to 1.3 were defined as very small, small, and appropriate for gestational age, corresponding to less than the 3rd, 3rd to 10th, and 10th to 90th percentiles, respectively. Outcome & Measurements: Kidney function estimated using the Cockcroft-Gault and isotope dilution mass spectrometry-traceable 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Values less than the sex-specific 10th percentile were defined as low-normal kidney function. Results: Compared with men with birth weight appropriate for gestational age (n = 2,755), odds ratios for low-normal creatinine clearance (< 1 00 mL/min) were 1.66 (95% confidence interval [CI], 1.16 to 2.37) if small for gestational age (n - 261) and 2.40 (95% Cl, 1.46 to 3.94) if very small for gestational age (n = 101). Kidney function estimated using the MDRD Study equation gave similar results. Women (n = 3,126, 283, and 112, respectively) had odds ratios of 1.65 (95% Cl, 1.17 to 2.35) and 2.00 (95% Cl, 1.21 to 3.29) for low-normal creatinine clearance (< 80 mL/min), whereas the association was not significant using the MDRD Study equation. Using linear regression, creatinine clearance decreased by 4.0 mL/min (95% Cl, 3.3 to 4.6) in men and 2.9 mL/min (95% Cl, 2.2 to 3.5) in women per 1-SDS decrease. Adjusting for possible confounders did not influence results. Limitations: Selection bias could be a problem because the participation rate was 49%, but there were no statistically significant differences between participants and nonparticipants regarding maternal and perinatal characteristics. Adjusting kidney function for body size can be a special problem in people with intrauterine growth restriction. Conclusions: Although effects were still small in young adulthood, intrauterine growth restriction was significantly associated with low-normal kidney function. The effect was weaker and less consistent in women compared with men.