Hallan Stein, Euser Anne M, Irgens Lorentz M, Finken Martijn J J, Holmen Jostein, Dekker Friedo W
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Am J Kidney Dis. 2008 Jan;51(1):10-20. doi: 10.1053/j.ajkd.2007.09.013.
The hypothesis of intrauterine origin of adult disease is debated. We tested whether intrauterine growth restriction is associated with later kidney function.
Prospective cohort study.
SETTING & PARTICIPANTS: 7,457 Norwegian adults aged 20 to 30 years participating in the population-based Nord Trøndelag 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.
Birth weight expressed as an SD score (SDS) to adjust for gestational age and sex. Subjects with a birth weight SDS 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.
Compared with men with birth weight appropriate for gestational age (n = 2,755), odds ratios for low-normal creatinine clearance (<100 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% CI, 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% CI, 1.17 to 2.35) and 2.00 (95% CI, 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% CI, 3.3 to 4.6) in men and 2.9 mL/min (95% CI, 2.2 to 3.5) in women per 1-SDS decrease. Adjusting for possible confounders did not influence results.
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.
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.
成人疾病源于子宫内的假说存在争议。我们测试了子宫内生长受限是否与后期肾功能相关。
前瞻性队列研究。
7457名年龄在20至30岁的挪威成年人参与了基于人群的北特伦德拉格健康研究（1995 - 1997年），挪威医学出生登记处记录了他们的出生体重、孕周以及母亲和围产期风险因素的数据。
以标准差评分（SDS）表示的出生体重，用于校正孕周和性别。出生体重SDS小于 -2.0、-2.0至 -1.3以及 -1.3至1.3的受试者分别被定义为非常小、小以及适于胎龄，分别对应低于第3百分位、第3至第10百分位以及第10至第90百分位。
使用Cockcroft - Gault公式以及可溯源至同位素稀释质谱法的4变量肾脏病饮食改良（MDRD）研究方程估算肾功能。低于特定性别的第10百分位的值被定义为肾功能低正常。
与适于胎龄的男性（n = 2755）相比，胎龄小的男性（n = 261）肌酐清除率低正常（<100 mL/分钟）的比值比为1.66（95%置信区间[CI]，1.16至2.37），而胎龄非常小的男性（n = 101）为2.40（95% CI，1.46至3.94）。使用MDRD研究方程估算的肾功能得出了类似结果。女性（分别为n = 3126、283和112）肌酐清除率低正常（<80 mL/分钟）的比值比为1.65（95% CI，1.17至2.35）和2.00（95% CI，1.21至3.29），而使用MDRD研究方程时该关联不显著。使用线性回归分析，每降低1个SDS，男性肌酐清除率下降4.0 mL/分钟（95% CI，3.3至4.6），女性下降2.9 mL/分钟（95% CI，2.2至3.5）。对可能存在干扰因素进行校正并未影响结果。
选择偏倚可能是一个问题，因为参与率为49%，但在母亲和围产期特征方面，参与者与非参与者之间没有统计学上的显著差异。对于子宫内生长受限的人群，根据体型校正肾功能可能是一个特殊问题。
尽管在青年期影响仍较小，但子宫内生长受限与肾功能低正常显著相关。与男性相比，女性的这种影响较弱且不太一致。
