Prenatal Exposure to Air Pollution and Pre-Labor Rupture of Membranes in a Prospective Cohort Study: The Role of Maternal Hemoglobin and Iron Supplementation

Abstract

Background: Exposure to air pollution in prenatal period is associated with prelabor rupture of membranes (PROM). However, the sensitive exposure time windows and the possible biological mechanisms underlying this association remain unclear.

Objective: We aimed to identify the sensitive time windows of exposure to air pollution for PROM risk. Further, we examined whether maternal hemoglobin levels mediate the association between exposure to air pollution and PROM, as well as investigated the potential effect of iron supplementation on this association.

Method: From 2015 to 2021, 6,824 mother-newborn pairs were enrolled in the study from three hospitals in Hefei, China. We obtained air pollutant data [particulate matter (PM) with aerodynamic diameter $\le 2.5\mu m$ (${\mathrm{PM}}_{2.5}$), PM with aerodynamic diameter $\le 10\mu m$ (${\mathrm{PM}}_{10}$), sulfur dioxide (${\mathrm{SO}}_2$), and carbon monoxide (CO)] from the Hefei City Ecology and Environment Bureau. Information on maternal hemoglobin levels, gestational anemia, iron supplementation, and PROM was obtained from medical records. Logistic regression models with distributed lags were used to identify the sensitive time window for the effect of prenatal exposure to air pollutant on PROM. Mediation analysis estimated the mediated effect of maternal hemoglobin in the third trimester, linking prenatal air pollution with PROM. Stratified analysis was used to investigate the potential effect of iron supplementation on PROM risk.

Results: We found significant association between prenatal exposure to air pollution and increased PROM risk after adjusting for confounders, and the critical exposure windows of ${\mathrm{PM}}_{2.5}$, ${\mathrm{PM}}_{10}$, ${\mathrm{SO}}_2$ and CO were the 21th to 24th weeks of pregnancy. Every $10\text{-}{\mu g/m}^3$ increase in ${\mathrm{PM}}_{2.5}$ and ${\mathrm{PM}}_{10}$, $5\text{-}{\mu g/m}^3$ increase in ${\mathrm{SO}}_2$, and $0.1{\text{-mg}/m}^3$ increase in CO was associated with low maternal hemoglobin levels [$-0.94g/L$ (95% confidence interval (CI): $-1.15$, $-0.73$), $-1.31g/L$ (95% CI: $-1.55$, $-1.07$), $-2.96g/L$ (95% CI: $-3.32$, $-2.61$), and $-1.11g/L$ (95% CI: $-1.31$, $-0.92$), respectively] in the third trimester. The proportion of the association between air pollution and PROM risk mediated by hemoglobin levels was 20.61% [average mediation effect (95% CI): 0.02 (0.01, 0.05); average direct effect (95%): 0.08 (0.02, 0.14)]. The PROM risk associated with exposure to low-medium air pollution could be attenuated by maternal iron supplementation in women with gestational anemia.

Conclusions: Prenatal exposure to air pollution, especially in the 21st to 24th weeks of pregnancy, is associated with PROM risk, which is partly mediated by maternal hemoglobin levels. Iron supplementation in anemia pregnancies may have protective effects against PROM risk associated with exposure to low-medium air pollution. https://doi.org/10.1289/EHP11134.

Figure 1.

The PROM risk in association with week-specific prenatal air pollution exposure during pregnancy. Week-specific estimates are provided as the OR of PROM (with 95% CI) for a $10\text{-}{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$ increment of ${\mathrm{PM}}_{2.5}$ exposure (A). Week-specific estimates are provided as the OR of PROM (with 95% CI) for a $10\text{-}{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$ increment of ${\mathrm{PM}}_{10}$ exposure (B). Week-specific estimates are provided as the OR of PROM (with 95% CI) for a $5\text{-}{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$ increment of ${\mathrm{SO}}_2$ exposure (C). Week-specific estimates are provided as the OR of PROM (with 95% CI) for a $0.1{\text{-mg}/\mathrm{m}}^3$ increment of CO exposure (D). Models were based on a distributed lag (nonlinear) model and adjusted for age, education, income, parity, activity, passive smoking, folic acid supplementation, iron supplementation, prepregnancy BMI, hypertension during pregnancy, gestational diabetes mellitus, vaginitis, and temperature. The numerical results are presented in Supplement Table 3. Note: BMI, body mass index; CI, confidence interval; CO, carbon monoxide; OR, odds ratio; PROM, prelabor rupture of membranes.

Figure 2.

The association among air pollution exposure, hemoglobin levels, and PROM risk. The estimated change in hemoglobin levels was calculated for each quartile and each unit increment in ${\mathrm{PM}}_{2.5}$, ${\mathrm{PM}}_{10}$, ${\mathrm{SO}}_2$, and CO during the second and third trimesters in linear regression model (A). The model was based on the line regression model and adjusted for age, education, income, activity, passive smoking, iron supplementation, prepregnancy BMI, hypertension during pregnancy, gestational diabetes mellitus, and temperature. The hemoglobin level per increase in ${\mathrm{PM}}_{2.5}$ and ${\mathrm{PM}}_{10}$ was $10{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$, the hemoglobin level per increase in ${\mathrm{SO}}_2$ was $5{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$, and the hemoglobin level per increase in CO was $0.1{\mathrm{mg}/\mathrm{m}}^3$. The numerical results are presented in Supplement Table 8. The relationship between hemoglobin levels and PROM (B). The model was based on the logistic regression model and adjusted for age, education, income, parity, activity, passive smoking, folic acid supplementation, iron supplementation, prepregnancy BMI, hypertension during pregnancy, gestational diabetes mellitus, vaginitis, and temperature. Air pollution was in the second and third trimesters. The numerical results are presented in Supplement Table 10. Note: BMI, body mass index; CO, carbon monoxide; PROM, prelabor rupture of membranes.

Figure 3.

The relationship between air pollution and PROM risk in different hemoglobin levels. Air pollution was in the second and third trimesters. The hemoglobin level per increase in ${\mathrm{PM}}_{2.5}$ and ${\mathrm{PM}}_{10}$ was $10{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$, the hemoglobin level per increase in ${\mathrm{SO}}_2$ was $5{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$, and the hemoglobin level per increase in CO was $0.1{\mathrm{mg}/\mathrm{m}}^3$. Models adjusted for age, education, income, parity, activity, passive smoking, folic acid supplementation, iron supplementation, prepregnancy BMI, hypertension during pregnancy, gestational diabetes mellitus, vaginitis, and temperature. Note: BMI, body mass index; CO, carbon monoxide; Hb, hemoglobin; PROM, prelabor rupture of membranes.