Prenatal exposure to particulate matter and term low birth weight: systematic review and meta-analysis

To evaluate the relationships between maternal particulate matter exposure and offspring birth weight. Studies were categorized into three subgroups: term low birth weight (TLBW) among full-term births and all births (regardless of gestational age) and low birth weight (LBW) among all births, based on the search results of MEDLINE and the Web of Science from the inception of the database to April 2022. Subgroup analyses were conducted based on the economic status, region, exposure assessment, risk of bias, and adjustment. Sixty-one studies involving 34,506,975 singleton live births in 15 countries were analyzed. Overall, the risk of bias for most studies (75%) was low. In 39 of 47 term birth studies, the pooled odds ratio of TLBW among term births for per interquartile range (IQR) increases throughout the entire pregnancy was 1.02 (1.01 to 1.03) for PM2.5 and 1.03 (1.01 to 1.05) for PM10 after adjustment for covariates. No significant relevance was detected across each trimester period for PM2.5. A stronger effect was observed during the second trimester (1.03, 1.01 to 1.06) for PM10. There was no increased risk of TLBW in all births associated with IQR increases in PM2.5 and PM10. LBW was associated with PM2.5 exposure in 4 of 7 studies, but statistical heterogeneity was considerable. In the TLBW subgroup analysis, the effects of PM2.5 and PM10 were both greater in studies conducted in advanced countries, studies with low bias, and studies that adjusted for maternal age, infant sex, and parity. Stronger effects were present for PM2.5 exposure collected from monitoring stations and PM10 exposure interpolated from the inverse distance weighting model. TLBW may be associated with prenatal exposure to particulate matter, but no critical windows were identified. Stronger associations were observed in advanced countries. Future original study designs need to consider the impact of different exposure assessment modalities and all possible confounding factors. Supplementary Information The online version contains supplementary material available at 10.1007/s11356-023-26831-7.

Comparison group appropriateness refers to having similar baseline characteristics between the groups aside from the exposures and outcomes under study.

Confounding bias Q2: Did the study design or analysis account for important confounding and modifying variables?
Note: a parallel question under detection bias addresses reliability of the measurement of confounding variables. Q3: Did researchers adjust or control for other exposures that are anticipated to bias results? Performance bias Q4: Did researchers adhere to the study protocol? Attrition/exclusion bias Q5: Were outcome data complete without attrition or exclusion from analysis?
Attrition rates are required to be similar and uniformly low across groups with respect to withdrawal or exclusion from analysis.

Detection bias
Q6: Were the outcome assessors blinded to study group or exposure level? Blinding requires that outcome assessors do not know the study group or exposure level of the human subject or animal when the outcome was assessed.

Q7: Were confounding variables assessed consistently across groups using valid and reliable measures?
Consistent application of valid, reliable, and sensitive methods of assessing important confounding or modifying variables is required across study groups. 8 Note: a parallel question under selection bias addresses whether design or analysis account for confounding. Q8: Can we be confident in the exposure characterization?
Confidence requires valid, reliable, and sensitive methods to measure exposure applied consistently across groups. Q9: Can we be confident in the outcome assessment?
Confidence requires valid, reliable, and sensitive methods to assess the outcome and the methods should be applied consistently across groups.

Selective reporting bias
Q10: Were all measured outcomes reported?
Note: Six risk-of-bias domains were assessed for each study, and each domain was in in the form of specific questions. Each question is rated with one of four options as low, moderate, unclear (or not applicable), or high risk, rated as 1,2,3 and 4, respectively. Studies will get a "low" tier 1 risk of bias, if they score a low risk of bias rating in most of the domains. We will use tier 3 "high" risk of bias for studies that score a high risk of bias rating in all three key domains (Selection/ Confounding/ reporting). Studies that do not receive a tier 1 or tier 3 rating will be rated as tier 2. Region-specific analyses revealed significant associations between PM2.5 and LBW in all regions, and significant associations between PM2.5 and PTB in Western and Southern Africa. Subgroup analyses revealed that the association between PM2.5 and LBW was present in all subgroups, and stronger associations were observed in female infants, while the association between PM2.5 and PTB was larger in subgroups of older individuals living in urban areas. Zou (2021) China 2527  75 In the multivariate logistic regression analyses, exposures to outdoor NO2 were consistently associated with the higher odds of LBW and T-LBW. These associations were generally stronger for early months than for later months of the gestation.
This association was stronger in girls, renters, and children whose mothers≥30 yearsold, with household dampness-related exposures, and with parental smoking during pregnancy Goyal (2021)  For term low birthweight, the associations with PM2.5 were slightly less than the null among those living in urban environments and null among those living in less urban areas. However, the opposite was observed for O3 concentrations and term low birthweight. Associations between third trimester O3 concentration and term low birthweight were observed among those living in urban environments, whereas the associations was smaller among those living in less urban environments. Shang (2021) China 321521  4369 During the whole pregnancy, maternal exposure to PM2.5, PM10, SO2, and CO all significantly reduced the term birth weight and increased the risk of TLBW. However, NO2 and O3 exposure have significantly increased the term birth weight, and O3 even increased the risk of macrosomia significantly. Those effects were also observed in the first and second trimesters of pregnancy. But during the third trimester, high level of air quality index (AQI) and maternal exposure to PM2.5, PM10, SO2, NO2, and CO increased the term birth weight and the risk of macrosomia, while O3 exposure was contrary to this effect. Liang ( Associations were reduced considerably after adjustment for individual covariates and neighbourhood per cent visible minority, but remained significant for SGA (odds ratio 1.04, 95%CI 1.02-1.06 per 20 ppb NO2) and term birth weight (16.2 g reduction, 95% CI 13.6-18.8 g per 20 ppb NO2).
Associations with NO2 were of greater magnitude in a sensitivity analysis using monthly monitoring data, and among births to mothers born in Canada, and in neighbourhoods with higher incomes and a lower proportion of visible minorities. Laurent (2016) USA 3534708 72632 Term LBW was positively and significantly associated with interpolated measurements of ozone but not total fine PM or nitrogen dioxide. No significant association was observed between term LBW and primary PM from all sources grouped together. Balsa (2016) Uruguay 72920 1939 Exposures were not consistently associated with birth weight or low birth weight among term births, though second-trimester exposures were associated with higher birth weight, contrary to expectations. There were no consistent dose-response relationships between the pollutants and TLBW. Ozone exposure was associated with a higher risk of TLBW only in the first trimester, but these results were not statistically significant. Exposure to the third quartile of ozone for the full gestational period had negative associations with TLBW (odds ratio = 0.86; 95% confidence interval, 0.81-0.92) Laurent (2014) USA 960945 22420 Increased LBW risks were associated with the mass of primary fine and ultrafine PM. Hyder (2014) USA 628131  11641 Overall, the exposure assessment method modified the magnitude of the effect estimates of PM2.5 on birth outcomes. change in birth weight per interquartile range (2.41 μg/m3) increase in PM2.5 was −6 g (95% confidence interval = −8 to −5), −16 g (−21 to −11), and −19 g (−23 to −15), using the monitor, satellite (1), and satellite (2)  The association between exposure to air pollutants and the risk of LBW was significant Silva (2014) for the 4th quartile of PM2.5 concentrations in the 2nd trimester (OR = 1.51, 95% CI = 1.04 to 2.17) and in the 3rd trimester, and for the 4th quartile of CO concentrations in the 2nd trimester only, in adjusted analysis. Ebisu (2012) USA 1207800 34038 Several PM2.5 chemical components were associated with LBW. Risk increased 4.9% (95% CI: 3.4, 6.5%), 4.7% (3.2, 6.2%), 5.7% (2.7, 8.8%), and 5.0% (3.1, 7.0%) per interquartile range increase of PM2.5 aluminum, elemental carbon, nickel, and titanium, respectively. Other PM2.5 chemical components and gaseous pollutants showed associations, but were not statistically significant in multipollutant models. The trimester associated with the highest relative risk differed among pollutants.
Effect estimates for PM2.5 elemental carbon and nickel were higher for infants of white mothers than for those of African-American mothers, and for males than females.
Araban (2012) Iran 225  35 The results showed a significant association between exposure to CO and LBW (OR = 2.08, 95% CI: After adjustment for potential confounders such as demographics, medical and lifestyle factors PM2.5 exposures in all trimesters were found to be significantly and positively associated with the risk of all adverse birth outcomes. Second-trimester exposure had the strongest effects. For an interquartile range (IQR) increase in PM2.5 during the second trimester, the risk of term LBW, PTB and VPTB increased by 3% [95% confidence interval (CI): 1-6%)], 12% (11-14%) and 22% (18-25%), respectively. O3 was also found to be positively associated with PTB and VPTB with the strongest effects over the whole pregnancy period [3% (1-5%) for PTD and 13% (7-19%) for VPTB for each IQR increase]. However, O3 was observed to have protective effects on term LBW. Results were consistent for multi-pollutant models. Dadvand (2014) Spain 6438 190 During the whole pregnancy, maternal exposure to PM2.5, PM10, SO2, and CO all significantly reduced the term birth weight and increased the risk of TLBW. However, NO2 and O3 exposure have significantly increased the term birth weight, and O3 even increase Basu (2014) USA 646296 NA Higher full gestational exposures to PM2.5 mass and several PM2.5 constituents were significantly associated with reductions in term birth weight. The largest reductions in birth weight were associated with exposure to vanadium, sulfur, sulfate, iron, elemental carbon, titanium, manganese, bromine, ammonium, zinc, and copper. Several of these PM2.5 constituents were associated with increased risk of term LBW.
Reductions in birth weight were generally larger among younger mothers and varied by race/ethnicity.

Dugandzic (2006)
Canada 74284 1193 In the analyses unadjusted for year of birth, first trimester exposures in the highest quartile for SO2 and PM10 suggested an increased risk of delivering a LBW infant (relative risk = 1.36,95% confidence interval = 1.04 to 1.78 for SO2 exposure and relative risk = 1.33, 95% confidence interval = 1.02 to 1.74 for PM10). After adjustment for birth year, the relative risks were attenuated somewhat and not statistically significant. A dose-response relationship for SO2 was noted with increasing levels of exposure. No statistically significant effects were noted for ozone. Laurent (2013) USA 74416 NA Increased risks of LBW were associated with ambient O3 concentrations as measured by monitoring stations, as well as traffic density and proximity to major roadways. LBW was not significantly associated with other air pollution metrics, except that a decreased risk was associated with ambient NO2 concentrations as measured by monitoring stations. Bell (2010) USA 76788 NA Road dust and related constituents such as silicon and aluminum were associated with lower birth weight, as were the motor-vehicle-related species such as elemental carbon and zinc, and the oil-combustion-associated elements vanadium and nickel. An interquartile range increase in exposure was associated with low birthweight for zinc (12% increase in risk), elemental carbon (13%), silicon (10%), aluminum (11%), vanadium (8%), and nickel (11%).Analysis by trimester showed effects of third-trimester exposure to elemental carbon, nickel, vanadium, and oil-combustion PM2.5. Wilhelm (2005) USA 136134  2778 For women residing within a 1-mi dis-tance, we observed a 27% increase in risk for high (≥ 75th percentile) first-trimester CO exposures and preterm birth and a 36% increase for high third-trimester pregnancy CO exposures and term LBW. For particles, we observed similar size effects during early and late pregnancy for both term LBW and preterm birth. In contrast, smaller or no effects were observed beyond a 1-mi distance of a residence from a station. Associations between CO and PM10 averaged over the whole pregnancy and term LBW were generally smaller than effects for early and late pregnancy. These new results for 1994-2000 generally confirm our previous observations for the period 1989-1993, again linking CO and particle exposures to term LBW and preterm birth. Salam (2005) USA 3901 72 Results from linear mixed-effects regression models showed that a 12-ppb increase in 24hr ozone averaged over the entire pregnancy was associated with 47.2 g lower birth weight [95% confidence interval (CI), 27.4-67.0 g], and this association was most robust for exposures during the second and third trimesters. A 1.4-ppm difference in firsttrimester carbon monoxide exposure was associated with 21.7 g lower birth weight (95% CI,1.1-42.3 g) and 20% increased risk of intrauterine growth retardation (95% CI, 1.0-1.4). First-trimester CO and third-trimester O3 exposures were associated with 20% increased risk of intrauterine growth retardation. A 20-µg/m3 difference in levels of particulate matter ≤ 10 µm in aerodynamic diameter (PM10) during the third trimester was associated with a 21.7-g lower birth weight (95% CI, 1.1-42.2 g), but this association was reduced and not significant after adjusting for O3. Lin (2004)  ROC  92288  2069 This study suggested a 26% increase in term LBW risk given maternal ambient exposure to SO2 concentration exceeding 11.4 ppb during pregnancy compared to low exposure (o7.1 ppb) (OR=1.26, 95% CI=1.04-1.53). Since the relative risk of term LBW was reassessed according to exposure level in each trimester, mothers exposed to 412.4 ppb of SO2 in the last trimester showed 20% higher risk (OR=1.20, 95% CI=1.01-1.41) of term LBW delivery than mothers with lower exposure (o6.8 ppb). No significant elevation ORs was observed for other air pollutants. Lee (2003) Korea 388105 NA The monthly analyses suggested that the risks for LBW tended to increase with carbon monoxide (CO) exposure between months 2-5 of pregnancy, with exposure to particles <10 mm (PM10) in months 2 and 4, and for sulphur dioxide (SO2) and nitrogen dioxide (NO2) exposure between months 3-5. Chen (2002) USA 36305 893 PM10 was not found to be related with the risk of LBW from logistic regression.CO and O3 were not found to be associated with birth weight or risk of LBW of newborns by the same modeling procedure. Maisonet (2001) USA 89557 Our results suggest that exposures to ambient CO and SO2 increase the risk for term LBW. This risk increased by a unit increase in CO third trimester average concentration [adjusted odds ratio (AOR) 1.31; 95% confidence interval (CI)1.06,1.62]. Infants with SO2 second trimester exposures falling within the 25 and < 50th (AOR 1.21;CI 1.07,1.37), the 50 to < 75th (AOR 1.20; CI 1.08,1.35), and the 75 to < 95th (AOR 1.21; CI 1.03,1.43) percentiles were also at increased risk for term LBW when compared to those in the reference category (< 25th percentile). There was no indication of a positive association between prenatal exposures to PM10 and term LBW. Morello-Frosch (2010) USA 3545177 NA In multivariate models, pollutants were associated with decreased birth weight; -5.4 grams (95% confidence interval -6.8 g, -4.1 g) per ppm carbon monoxide, -9.0 g (-9.6 g, -8.4 g) per pphm nitrogen dioxide, -5.7 g (-6.6 g, -4.9 g) per pphm ozone, -7.7 g (-7.9 g, -6.6 g) per 10 μg/m3 particulate matter under 10 μm, -12.8 g (-14.3 g, -11.3 g) per 10 μg/m3 particulate matter under 2.5 μm, and -9.3 g (-10.7 g,-7.9 g) per 10 μg/m3 of coarse particulate matter. With the exception of carbon monoxide, estimates were largely unchanged after controlling for co-pollutants. Effect estimates for the third trimester largely reflect the results seen from full pregnancy exposure estimates; greater variation in results is seen in effect estimates specific to the first and second trimesters.

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Supplementary Table S6c. Results of studies assessing associations between prenatal exposure to particulate matter and term low birth weight among total births In the multivariate logistic regression analyses, exposures to outdoor NO2 were consistently associated with the higher odds of LBW and T-LBW. These associations were generally stronger for early months than for later months of the gestation.