Shorter Gestation Is Associated with Renal Biomarkers at 4 Years

Studies suggest that exposure to air pollution and heavy metals during pregnancy may contribute to birth outcomes such as shorter gestation. Since nephron development is not typically complete until 36 weeks of gestation, infants born prematurely may be more susceptible to renal dysfunction. Urine proteins reflect renal health and are predictive of kidney function later in life. We explored the association between gestational age (GA) and nine proteins in spot urine samples collected from 103 children aged 4-6 years participating in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort in Mexico City. The nine urinary proteins: albumin, neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), kidney injury molecule-1 (KIM-1), clusterin, alpha-1-microglobulin, cystatin C, beta-2 microglobulin and trefoil factor 3, were selected based on their use as validated or emerging biomarkers of children’s renal health and measured using the Luminex Milliplex System. We applied linear regression to examine associations between GA with individual proteins and used weighted quantile sum (WQS) regression, a statistical method developed to assess mixtures, to create a composite renal biomarker index of all 9 proteins. We adjusted for body mass index, indoor smoking, socio-economic status, age, gender, and urine creatinine. In the individual protein regressions, each day shorter gestation was associated with 12.9% higher KIM-1 (95% CI[-0.00, 24.00], p<0.06) and 4.4% higher cystatin C (95% CI[-0.33, 8.84], p<0.08). As is in the univariate models, the WQS renal biomarker index was associated with shorter gestation (-0.58; 95% CI[-10.09,-0.06], p<0.03). Weights constructed to parse the contribution of each protein to the result showed that albumin (24%), NGAL (19%), OPN (16%) and KIM-1 (16%) had the highest contribution. Motivated by these results, additional work will assess the interactions with environmental exposures.