Low Birth Weight and Kidney Function in Middle-Aged Men and Women: The Netherlands Epidemiology of Obesity Study

Abstract

Rationale & objective: Chronic kidney disease (CKD), defined as estimated glomerular filtration rate (eGFR)<60mL/min/1.73m², is a risk factor for cardiovascular morbidity and mortality. Little is known about low birth weight and risk for CKD in middle-aged adults in the general population. We estimated the causal association between birth weight and eGFR in a Dutch cohort of middle-aged men and women.

Study design: Retrospective cohort study.

Setting & participants: 6,671 participants in the Netherlands Epidemiology of Obesity (NEO) Study. Replication study using data for 133,814 participants studied by the CKDGen consortium.

Exposure: Birth weight was self-reported and also based on an instrumental variable, 59 birth weight-associated genetic variants, derived from an independent data source.

Outcome: eGFR at the age of 45 to 65 years.

Analytical approach: We assessed the association between self-reported birth weight and eGFR in the NEO Study using multivariable linear regression, adjusted for age, sex, education, smoking, and alcohol use. The effect of the instrument on eGFR was estimated using separate 2-sample Mendelian randomization analyses: one using individual data from the NEO cohort and one using summary data from the CKDGen consortium.

Results: At baseline, mean eGFR was 86±12.4 (SD) mL/min/1.73m². After multivariable adjustment, self-reported birth weight was not associated with kidney function in middle age. Two-sample Mendelian randomization analysis showed that in the NEO cohort, for each 500-g lower birth weight defined using genetic variants, there was a 3.7 (95% CI, 0.5-6.9)-mL/min/1.73m² lower eGFR at the age of 45 to 65 years. However, using CKDGen summary-level data, there was a smaller nonsignificant relationship between birth weight and eGFR.

Limitations: Birth weight was self-reported.

Conclusions: Lower birth weight defined using genetic variants was associated with lower eGFRs in Dutch middle-aged adults. However, this finding was not replicated within the CKDGen consortium.

Keywords: Birth weight; Mendelian randomization; albuminuria; chronic kidney disease (CKD); delayed effects; eGFR decline; epidemiology; estimated glomerular filtration rate (eGFR); fetal programming; glomerular mass; intrauterine environment; kidney function; middle age; nephron deficit; prenatal exposure.