Fetal Smoke Exposure and Kidney Outcomes in School-Aged Children

Abstract

Background: Fetal smoke exposure may result in developmental adaptations that permanently affect the developing kidney. In this study, the associations of maternal and paternal smoking during pregnancy with childhood kidney size and function were assessed.

Study design: Prospective cohort study from fetal life onward.

Setting & participants: This study was conducted in a group of 5,622 children in Rotterdam, the Netherlands.

Predictors: Maternal and paternal smoking were assessed during pregnancy by questionnaires.

Outcomes & measurements: At a median age of 6.0 (5th-95th percentile, 5.6-7.9) years, we measured childhood kidney volumes, estimated glomerular filtration rate (eGFR), and albumin-creatinine ratio.

Results: The confounder model, which included size at birth, shows that compared with children from mothers who did not smoke during pregnancy, those from mothers who continued smoking during pregnancy had smaller combined kidney volumes at the age of 6 years. The strongest effect estimate was observed for mothers who smoked 5 or more cigarettes per day during pregnancy (difference for combined kidney volume, -2.80 [95% CI, -5.15 to -0.45] cm(3)). Similarly, continued maternal smoking during pregnancy also was associated with a lower eGFR in childhood (difference, -2.25 [95% CI, -3.70 to -0.79] mL/min/1.73 m(2)). First-trimester-only smoking was associated with a higher risk of increased albumin-creatinine ratio (OR, 1.45; 95% CI, 1.05-2.01). Among mothers who did not smoke during pregnancy, paternal smoking was associated with smaller childhood combined kidney volume (difference, -1.78 [95% CI, -3.48 to -0.07] cm(3)), but not with childhood kidney function measures.

Limitations: Smoking behavior was measured with questionnaires. Follow-up measurements were available for only 70% of the children.

Conclusions: Continued maternal smoking during pregnancy is associated with smaller combined kidney volume and lower eGFR in school-aged children. Stronger effect estimates for maternal versus paternal smoking suggest that intrauterine adaptive responses may play a role as underlying mechanisms.

Keywords: Generation R Study; Maternal smoking; albumin-creatinine ratio (ACR); cigarette exposure; epidemiology; fetal influences; glomerular filtration rate (GFR); intrauterine development; kidney development; kidney size; kidney ultrasound; nephrogenesis; nephron number; paternal smoking; pregnancy; renal function; tobacco use.