Maternal risk factors for congenital anomalies of the kidney and urinary tract: A case-control study

Congenital anomalies of the kidney and urinary tract (CAKUT) are significant causes of pediatric morbidity and mortality. The spectrum of CAKUT can be part of a syndrome, but most of these abnormalities occur as isolated and sporadic forms. The etiology of human CAKUT is unknown in the majority of cases. This case-control study aimed to investigate the association between maternal characteristics and the occurrence of CAKUT and specific CAKUT phenotypes.In this case-control study, 29,653 newborns were evaluated consecutively in a tertiary neonatal unit using the Latin American Collaborative Study of Congenital Malformations (ECLAMC) registry. Newborns without congenital anomalies were matched to CAKUT cases by sex, date, and place of birth at a ratio of 3:1. For analysis purposes, the cases were stratified into four subgroups: upper tract abnormalities (UTA), including ureteropelvic junction obstruction, vesicoureteral reflux, primary megaureter and others (n = 239), lower urinary tract obstruction (LUTO) (n = 79), cystic diseases (n = 59) and agenesis/hypodysplasia (n = 28). Multivariable logistic regression analyses were used to calculate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for associations between the maternal risk factors and the presence of CAKUT.The prevalence of non-syndromic CAKUT in our sample was 13 per 1000 live births. Data records allowed the analysis of 405 cases and 1208 controls. After adjustment by the binary regression logistic, three covariates remained associated as risk factors for the entire spectrum of CAKUT: consanguinity (Odds ratio [OR], 7.1, 95%CI, 2.4-20.4), family history of CAKUT (OR, 6.4, 95%CI, 1.9-21.3), and maternal chronic hypertension (OR, 14.69, 95%CI, 3.2-67.5) (Figure). These risk factors persisted consistently across the various CAKUT phenotypes with minor variations. Consanguinity was the only factor consistently associated with almost all CAKUT phenotypes. Maternal hypertension was associated with all phenotypes except for the agenesis/hypodysplasia group. The prevalence of CAKUT cases was 15 times higher in hypertensive mothers (3%) compared to normotensive mothers (0.2%).Our study suggests that an increased risk of CAKUT is associated with consanguinity, a positive family history of CAKUT, and maternal hypertension. However, the prevalence of these risk factors in our cohort was rare and most cases presented as sporadic forms.