Maternal Chronic Disease and Congenital Anomalies of the Kidney and Urinary Tract in Offspring: A Japanese Cohort Study

Rationale & Objective: Several maternal chronic diseases have been reported as risk factors for congenital anomalies of the kidney and urinary tract (CAKUT) in offspring. However, these investigations used case-control designs, and cases with isolated genitourinary CAKUT were not distinguished from cases in which CAKUT were present with extrarenal congenital anomalies (complicated CAKUT). We examined the association of maternal diseases with isolated and complicated CAKUT in offspring using data from a prospective cohort study. Study Design: A nationwide prospective birth cohort study. Setting & Participants: 100,239 children enrolled in the Japan Environment and Children's Study between January 2011 and March 2014 at 15 research centers. Physicians’ diagnoses in mothers and children were collected from medical record transcripts and questionnaires. Exposures: Medical histories of maternal noncommunicable diseases, including obesity, hypertension, diabetes mellitus, kidney disease, hyperthyroidism, hypothyroidism, psychiatric disease, epilepsy, cancer, and autoimmune disease. Outcomes: CAKUT diagnosed during the first 3 years of life, classified as isolated or complicated. Analytical Approach: Multivariable Poisson regression with generalized estimating equations accounting for clustering by clinical center. Results: Among the 100,239 children, 560 (0.6%) had CAKUT, comprising 454 (81%) isolated and 106 (19%) complicated forms. The risk of isolated CAKUT was increased in children of mothers who experienced kidney disease (adjusted risk ratio [RR], 1.80 [95% CI, 1.12-2.91]) or cancer (RR, 2.11 [95% CI, 1.15-3.86]). Furthermore, the risk of complicated CAKUT was increased in children of mothers with diabetes mellitus (RR, 3.04 [95% CI, 1.64-5.61]). Limitations: Lack of standardization or prespecification of clinical definitions, diagnostic criteria, measurements, and testing. Genetic testing was not performed. Conclusions: Isolated CAKUTs and complicated CAKUTs were associated with different maternal diseases. The results may inform clinical management of pregnancy and highlight potential differences in the genesis of isolated and complicated forms of CAKUT.