Environmental Factor of Unborn Babies Seeing in Womb

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• Open Access
• Published: 15 January 2013

Environmental risk factors of pregnancy outcomes: a summary of recent meta-analyses of epidemiological studies

• Payam Dadvand^1,2,three,
• James Grellier^1,2,3,
• David Martinez^one,2,3 &
• Martine Vrijheid^1,two,three

Environmental Health book 12, Article number:six (2013) Cite this article

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Abstract

Background

Various epidemiological studies have suggested associations between environmental exposures and pregnancy outcomes. Some studies have tempted to combine information from various epidemiological studies using meta-analysis. Nosotros aimed to describe the methodologies used in these contempo meta-analyses of environmental exposures and pregnancy outcomes. Furthermore, nosotros aimed to written report their master findings.

Methods

Nosotros conducted a bibliographic search with relevant search terms. We obtained and evaluated xvi recent meta-analyses.

Results

The number of studies included in each reported meta-assay varied profoundly, with the largest number of studies available for environmental tobacco smoke. Just a small number of the studies reported having followed meta-analysis guidelines or having used a quality rating arrangement. Generally they tested for heterogeneity and publication bias. Publication bias did not occur oftentimes.

The meta-analyses found statistically significant negative associations between ecology tobacco smoke and stillbirth, nativity weight and whatsoever congenital anomalies; PM_two.5 and preterm birth; outdoor air pollution and some congenital anomalies; indoor air pollution from solid fuel employ and stillbirth and birth weight; polychlorinated biphenyls (PCB) exposure and birth weight; disinfection by-products in water and stillbirth, small for gestational age and some congenital anomalies; occupational exposure to pesticides and solvents and some congenital anomalies; and agent orange and some congenital anomalies.

Conclusions

The number of meta-analyses of ecology exposures and pregnancy outcomes is pocket-sized and they vary in methodology. They reported statistically significant associations between environmental exposures such as environmental tobacco fume, air pollution and chemicals and pregnancy outcomes.

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Background

Environmental exposures play an important role in the causation of affliction. The developing foetus is thought to exist specially susceptible to ecology pollutants. Diverse epidemiological studies accept suggested associations betwixt ecology exposures such as air pollution, ecology tobacco smoke, pesticides, solvents, metals, radiation, water contaminants (disinfection by-products, arsenic, and nitrates) and chemicals (persistent organic pollutants (POPs), Bisphenol A, phthalates, and perfluorinated compounds (PFOS, PFOA)) and pregnancy outcomes such equally pregnancy loss, stillbirth, fetal growth, preterm birth and congenital anomalies. These were described and evaluated recently in a number of reviews on ecology exposures and pregnancy outcomes [1–3]. Furthermore there have been a large number of (systematic) reviews on specific ecology exposures and pregnancy outcomes. In general the authors have suggested that while in that location is evidence supporting specific associations betwixt environmental exposures and agin pregnancy outcomes, evidence for other environmental exposures is limited. The latter may be partly due to the limited number of studies available, conflicting results from unlike studies, likewise as the usual issues in epidemiological studies of bias and confounding, risk findings and limitations in exposure assessment.

Ane way to accost some, but not all, of these bug is by combining information from various epidemiological studies and conducting a meta and/or pooled analyses to obtain overall summary estimates for an association between an environmental exposure and pregnancy outcome, and to evaluate any heterogeneity in the results. This may lead to a further insight into and/or ameliorate understanding of the association, improvement of methodology and, ultimately, to improve run a risk management and policy making.

We aimed to draw the methodologies used in recent meta-analyses of ecology exposures and pregnancy outcomes. Furthermore, we aimed to report their principal findings.

Methods

A bibliographic search was carried out in Dec 2011 using MEDLINE (National Library of Medicine 2010). We limited our search to papers published in English and in the concluding 10 years. Initially we searched on "air pollution", "environmental tobacco smoke", "second manus fume", "persistent organic pollutants" (POPs), "PCB", "pesticide", "organic solvents", "heavy metals", "occupational exposure", "radiation", water contaminants such as "disinfection by-products", "arsenic", and "nitrates" and chemicals such every bit "Bisphenol A", "phthalate", and "PFOS PFOA" and "stillbirth", "fetal growth", "nativity weight", "preterm birth", "gestational age" and "congenital anomalies" in PUBMED based on terminology used in recent reviews [ane–3]. In this subset nosotros viewed all the titles and abstracts and searched for the term "meta-analyses". Furthermore we reviewed reports generated past the ENRIECO (Environmental Risks in European Birth Cohorts) project (http://www.enrieco.org). We only included studies that conducted meta-analyses to obtain summary estimates and evaluated heterogeneity betwixt different studies. We did not include spontaneous abortion/miscarriage in the evaluation.

We reviewed each meta-analysis according to: the databases they used, whether meta-analysis guidelines were used (Meta-assay Of Observational Studies in Epidemiology (MOOSE) or [iv] Quality of Reporting of Meta-analyses (Quorom) statement, 2009 [5, 6]), whether included studies were rated on quality (east.g. Newcastle-Ottawa scale [7] or Cochrane Handbook guidelines [8]), the statistics used to examination for heterogeneity in the data (Cochran's Q [nine] or I²[10]), whether fixed [eleven] or random furnishings models [12] were used in the pooling of private studies, and which tests of publication bias were used (funnel plots [13], Egger'southward test [14], or Begg'southward test [15]). Furthermore nosotros checked whether sensitivity analyses had been carried out e.g. for influential studies by leaving one study out at the time, or analyses defined by subgroups.

Results

Bibliographic search

In total we identified 5,315 papers in our search (Figure 1). After scanning the titles and conducting a further search for "meta-analyses", we found 61 potentially eligible papers. We excluded 37 papers after reviewing the abstract because no meta-analysis was actually conducted, eight because the meta-analyses were for dietary supplement utilize, one because of double entry, and one subsequently reading the paper and established that it contained no meta-analysis results on environmental exposures. Furthermore, we found two papers with meta-analyses through other sources [16, 17]. Sixteen papers remained for detailed review (Tabular array 1).

Figure 1

Flow diagram included and excluded studies.

Full size paradigm

Table one Characteristics and methods used in the evaluated meta-analysis papers

Full size tabular array

The number of studies evaluated in the meta-analyses varied from 5 upward to 76 (Tabular array 1). The most used databases were MEDLINE/PUBMED and EMBASE. Just a minority reported following guidelines and using a quality rating system. Cochran's Q was the most used test for testing for heterogeneity while near half the studies used Iⁱⁱ. Some studies reported using both. Half the studies reported using Funnel plots or the Egger test for evaluating publication bias, while only two used Begg'south test. All studies reported some form of sensitivity analyses. The topic with the most studies included was ecology tobacco smoke. A summary of results of the meta-analyses are given in Tables 2 and 3.

Table 2 Associations based on meta-analyses of air pollutants and birth outcomes

Total size table

Table 3 Associations (95% CI) based on meta-analyses of contaminants and occupation and birth outcomes

Full size table

Ecology tobacco fume

Leonardi-Bee et al. conducted meta-analyses to determine the effects of ecology tobacco smoke (ETS) exposure on birth outcomes (birth weight and proportion of premature infants) [xx]. Fifty eight studies were included; 53 used cohort design, 23 ascertaining ETS exposure prospectively and 30 retrospectively; and 5 used instance–control design. In prospective studies, ETS exposure was associated with a 33 g (95% confidence interval (CI): xvi, 51; I²=34%) reduction in mean birth weight, and in retrospective studies a 40 g (95% CI: 26, 54; I²=38.5%) reduction. ETS exposure was also associated with an increased risk of low birth weight (LBW, nascence weight <2500 thou; prospective studies: odds ratio (OR) ane.32, 95% CI: one.07, 1.63; I²=54.seven%); retrospective studies: OR: 1.22; 95% CI: 1.08, 1.37; I²=0%). The hazard of small for gestational age (SGA, defined in the original studies as baby nascence weight beneath the 10^th percentile for gestational age) was significantly associated with ETS exposure merely in retrospective studies (OR: 1.21; 95% CI: one.06, 1.37). There was no effect of ETS exposure on gestational historic period. They did non report on publication bias.

Salmasi et al. conducted extensive meta-analyses to determine whether there was an effect of ETS on pregnancy outcomes [19]. They simply included studies comparing ETS-exposed pregnant women with those unexposed which adequately addressed agile maternal smoking. Seventy-six studies were included with a total of 48,439 ETS exposed women and xc,918 unexposed women. Their primary outcome was perinatal mortality. The four master secondary outcomes were birth weight, gestational age at commitment, preterm birth (PTB) (< 37 weeks gestation), and LBW. Other secondary outcomes included were SGA (the tenth), intrauterine growth restriction (IUGR), built anomalies, stillbirth, and a number of others that nosotros do non review hither. ETS-exposed infants weighed less (−sixty chiliad; 95% CI: –80, –39 g) with a trend towards increased LBW (Relative take chances (RR): 1.sixteen; 95% CI: 0.99, 1.36; N=9), although the duration of gestation and preterm delivery were like (0.02 weeks, 95% CI: –0.09, 0.12 weeks; n=17, and RR: 1.07; 95% CI: 0.93, 1.22; Due north=seven). ETS-exposed infants had increased risks of congenital anomalies (OR: 1.17; 95% CI: 1.03, 1.34). The heterogeneity in the summary risk estimates of their outcomes ranged from an I² exam of 0–100%, and generally exceeded 75%, which is considered loftier. The heterogeneity was likely due to a diverseness of factors, including varying patient selection and the range of sample sizes. Further sensitivity analyses were carried out and these showed that in the analyses for birth weight, for example, infants built-in to mothers with cocky-reported ETS exposure had more heterogeneity (I^two=100%) compared to those assessed biochemically (Iⁱⁱ=54%). No further attempts were made to explore the heterogeneity. Except in the assay for birth weight, funnel plots were relatively symmetrical, which suggests that publication bias was unlikely.

Leonardi-Bee et al. also conducted meta-analyses to decide the risk of adverse pregnancy outcomes due to ETS exposure in nonsmoking meaning women [eighteen]. The main outcome measures were spontaneous abortion, perinatal and neonatal decease, stillbirth, and congenital anomalies. Nineteen studies were identified investigating these potential associations. ETS exposure significantly increased the risk of stillbirth (OR: 1.23, 95% CI: 1.09, ane.38; N=iv; I²=0%) and congenital anomalies (OR: i.13, 95% CI: 1.01, 1.26; Due north=7; Iⁱⁱ=3%), although none of the associations with specific congenital abnormalities were individually meaning. The number of studies included was generally small-scale though. The degree of between-study heterogeneity was generally depression (encounter above); publication bias results were non reported for stillbirth and congenital anomalies analyses.

Outdoor air pollution

Sapkota et al. performed meta-analyses to quantify the association between maternal exposure to particulate matter with aerodynamic diameter 2.5 and 10 μm (PM_two.5 and PM₁₀) during pregnancy and the chance of LBW and PTB. They included twenty peer-reviewed articles providing quantitative gauge of exposure and outcome that met defined selection criteria [sixteen]. They estimated a 15% increase in the chance of PTB for each 10- μg/grand³ increase in PM_2.5 (OR: 1.15; 95% CI: 1.14, 1.16), although with unlikely tight confidence intervals. The magnitude of take a chance associated with PM₁₀ exposure was smaller (2% per ten-μg/mⁱⁱⁱ increase) and similar in size for both LBW and PTB, neither reaching formal statistical significance. They observed meaning heterogeneity amongst studies that used PM₁₀ as the exposure metric (LBW: I²=54%, p=0.01; PTB: Iⁱⁱ= 73%, p<0.01), but not for studies that reported findings for PM_2.5 (LBW, I^two=57%, p=0.07; PTB: I²= 0.i%, p=0.42). They observed no significant publication bias, with p>0.05 based on both Begg'southward and Egger'southward bias tests.

Vrijheid et al. systematically reviewed epidemiologic studies on ambient air pollution and built anomalies and conducted meta-analyses for a number of air pollutant–anomaly combinations [21]. They identified 10 original epidemiologic studies. Meta-analyses were conducted if at to the lowest degree four studies published chance estimates for the same pollutant and bibelot group. Summary take a chance estimates were calculated for a) risk at loftier versus low exposure level in each study and b) gamble per unit increase in continuous pollutant concentration. They conducted meta-analyses for eighteen combinations of pollutants and cardiac anomaly groups and found that nitrogen dioxide (NO₂) and sulphur dioxide (So_two) exposures were related to increases in the take a chance of coarctation of the aorta (OR per 10 ppb NO₂: 1.20; 95% CI: i.00, ane.44; OR per 1 ppb SO_ii: i.04; 95% CI: 1.00, one.08) and tetralogy of Fallot (OR per 10 ppb NO₂: 1.25; 95% CI: i.02, ane.51; OR per one ppb So₂: ane.04; 95% CI: 1.00, 1.08), and PM_ten exposure was related to an increased take chances of atrial septal defects (OR per ten μg/one thousand³: 1.xiv; 95% CI, 1.01, i.28). Between study heterogeneity was identified (p < 0.10) in fewer than one-half of the analyses conducted, most consistently related to analyses of ventricular septal defects (VSDs). Egger test p-values were statistically significant for simply 3 of the 68 meta-analyses they conducted, indicating that publication bias was unlikely.

Indoor air pollution (solid fuel use)

Pope et al. conducted meta-analyses to quantify the relation of indoor air pollution from solid fuel use with birth weight and stillbirth [22]. They compared women using solid fuel with those using cleaner fuel. They found that solid fuel apply was associated with increased risks of LBW (OR: 1.38; 95% CI: 1.25, ane.52) and stillbirth (OR: 1.51; 95% CI: 1.23, 1.85), and with reduced mean nascency weight (-96.6 g; 95% CI: -68.5, -124.7). Heterogeneity was depression (I² = 0%) and in that location was no bear witness for publication bias.

Water contaminants-disinfection by-products

Hwang et al. conducted meta-analyses of chlorination by-products and birth defects [25]. They included six different studies from five publications and found an increased risk for VSD (OR: 1.59; 95% CI: one.21, ii.07). They identified between-study heterogeneity for some built anomalies groups but did not test for publication bias.

Grellier et al. carried out a systematic review and meta-assay of epidemiologic studies featuring original peer-reviewed data on the association of residential total trihalomethane (TTHM) exposure and health outcomes related to fetal growth and prematurity [23]. Fifteen studies were selected for the extraction of relative risks associating adverse nascence outcomes to TTHM exposure. On a subset of viii studies, they constitute some evidence for an association betwixt the third trimester TTHM exposure and SGA (OR: 1.01; 95%CI: 1.00, 1.02 per 10 μg/L TTHM). The Cochran test for homogeneity indicated a lack of heterogeneity amidst the studies, in contrast to a qualitative review of heterogeneity. The results of Egger's regression test (both weighted and unweighted) demonstrated that the results appeared to be unaffected by publication bias, although low study numbers limited the robustness of this examination. Similarly, funnel plots representing the results of such a low number of studies were considered hard to translate.

Nieuwenhuijsen et al. conducted meta-analyses of disinfection by-products and stillbirth [17]. They found a summary OR of one.09 (95% CI: 1.02, one.17) when comparing the highest exposed group with the lowest exposed group. They did non study on heterogeneity and publication bias.

Nieuwenhuijsen et al. conducted meta-analyses for chlorination disinfection by-products (DBPs) and congenital anomalies [24]. They included 15 epidemiologic studies that evaluated a relationship between an alphabetize of DBP exposure (handling, water source, DBP measurements, and both DBP measurements and personal characteristics) and risk of congenital anomalies. For all congenital anomalies combined, the meta-assay gave a statistically significant backlog risk for high versus low exposure to water chlorination or TTHM (OR: i.17; 95% CI: 1.02, ane.34) based on a small number of studies. The meta-assay also suggested a statistically significant excess chance for VSDs (OR: ane.58; 95% CI: ane.21–2.07), simply this was based on only three studies, and there was petty evidence of an exposure–response human relationship. Four of the 17 analyses showed statistically pregnant heterogeneity. They found little evidence for publication bias, except for urinary tract defects and fissure lip and palate.

POPs

Govarts et al. conducted meta-analyses of associations between POPs in maternal and cord blood and breast milk samples and gestational age and nativity weight in 7,990 women enrolled in 15 study populations from 12 European birth cohorts between 1990 and 2008, which were part of the ENRIECO consortium (http://www.enrieco.org) [26]. Using identical variable definitions, they performed for each cohort linear regression of birth weight on cord serum concentrations of PCB 153 and p,p'-DDE while adjusting for gestational age and a priori selected covariates. The meta-analysis including all cohorts indicated a birth weight decrease of 150 g (95% CI: fifty, 250 g) per 1 μg/L increase of PCB153, which was close to the range of exposure levels across the cohorts. They reported heterogeneity for the association between PCB153 and birth weight. No statistically significant association was found for DDE. They did not study on publication bias.

Occupational exposure

Logman et al. conducted a meta-analysis to appraise the risks of spontaneous abortions and major congenital anomalies following paternal exposure to organic solvents [27]. Vi studies were included for major congenital anomalies, and they included quality scoring of the studies. Odds ratios were 1.47 (95% CI: ane.18, 1.83) for major built anomalies, 1.86 (95% CI: 1.40, ii.46) for any neural tube defect, 2.18 (95% CI: one.52, iii.11) for anencephaly, and 1.59 (95% CI: 0.99, two.56) for spina bifida. They did not observe heterogeneity in the analyses. They did non written report on publication bias.

Romitti et al. carried out meta-analyses to evaluate the take chances of orofacial clefts associated with pesticide exposure [28]. Nineteen studies were included in the final analysis. For all phenotypes combined, maternal occupational pesticide exposure was associated with an increased risk of orofacial clefts (OR: 1.37; 95% CI: one.04, 1.81). They reported that there was no statistically meaning heterogeneity in the information merely did non report on publication bias.

Rochelau et al. conducted meta-analyses of hypospadias associated with occupational maternal and parental exposure to pesticides [29]. Nine studies were included. Elevated but marginally meaning risks of hypospadias were associated with maternal occupational exposure (RR: 1.36; 95% CI: 1.04, ane.77), and paternal occupational exposure (RR: 1.xix; 95% CI: 1.00, one.41). They found no heterogeneity in the reported risks by the studies. They establish piddling evidence of publication bias.

Pesticides

Ngo et al. conducted meta-analyses of studies looking at associations betwixt the herbicide agent orange and congenital malformations [30]. They included 22 studies (205,102 subjects). The overall gauge of the RR of congenital anomalies in the Agent Orange exposed group equally compared with the non-exposed group was i.95 (95% CI: ane.59, ii.39). There was a significant variability across studies, with the heterogeneity Q statistic being 163 (P <0.001) and Iⁱⁱ of 0.87. The magnitude of association was higher in the Vietnamese population (RR: iii.0; 95% CI: 2.19, 4.12) than in non-Vietnamese veterans (RR: i.29; 95% CI: i.04, 1.59). In the Vietnamese studies, the magnitude of association was lower in cohort studies than in case–control studies. However, in not-Vietnamese populations, the association between Agent Orangish and congenital anomalies was merely found in cohort studies, not in case–command studies. In either cohort or example–command studies, significant heterogeneity of run a risk estimates was observed. Iⁱⁱ for all Vietnamese studies was 0.78 (P <0.001) and for the international veterans study was 0.85 (P < 0.001). They conducted sub-grouping meta-analyses stratified by intensity and elapsing of exposure. Funnel plots of all studies revealed a severely asymmetrical distribution, suggesting the presence of publication bias with the absence of small-scale studies producing no statistically significant effects (Egger'due south test: intercept = three.75; P < 0.001). When studies were stratified by location of studies, the funnel plots and Egger's examination indicate the possibility of publication bias amongst Vietnamese studies (intercept = 3.06; P < 0.001) simply not among non-Vietnamese studies (intercept = 3.xiii; P = 0.225). Moreover, the funnel plot and Egger's examination suggest some testify of publication bias amongst all published studies (intercept = 3.fourscore; P = 0.096).

Ngo et al. conducted meta-analyses of the herbicide agent orange and spina bifida [31]. Vii studies, encompassing two Vietnamese and 5 non-Vietnamese studies, were included. The overall RR for spina bifida associated with paternal exposure to agent orangish was two.02 (95% CI: 1.48, two.74), with no statistical evidence of heterogeneity across studies. Non-Vietnamese studies showed a slightly college summary RR (RR: 2.22; 95% CI: 1.38, 3.56) than Vietnamese studies (RR: 1.92; 95% CI: ane.29, 2.86). When analyzed separately, the overall association was statistically meaning for the three case–control studies (OR: ii.25, 95% CI: 1.31, 3.86) and the cross exclusive studies (RR: 1.97, 95% CI: ane.31, 2.96), but not for the three accomplice studies (RR: 2.11; 95% CI: 0.78–5.73). Funnel plots revealed a symmetrical distribution with no show of publication bias (Egger's test: intercept = 0.03; P = 0.96) for all studies including those not published, equally well equally for published studies only Egger'southward exam: intercept = 1.00, P = 0.6).

Word

We have described the methodology used and main findings reported by meta-analyses of epidemiological studies investigating associations between environmental exposures and pregnancy outcomes conducted over the last ten years and reported in the English language literature. In total we identified and described xvi meta-analyses meeting our inclusion criteria. The number of studies included in the reported meta-analyses varied greatly, with the largest number of studies available for environmental tobacco smoke. Only a small-scale number of the studies reported to be following meta-analyses guidelines or using a quality rating organisation. Heterogeneity was reported in a number of the studies. Publication bias did not appear to occur ofttimes. The meta-analyses suggested statistically significant associations between ETS and stillbirth, birth weight and any congenital anomalies, PM_2.5 and PTB, outdoor air pollution and possibly some congenital anomalies, indoor air pollution from solid fuel use and stillbirth and birth weight, PCB exposure and birth weight, disinfection by-products in water and stillbirth, SGA and perchance some congenital anomalies, occupational exposure to pesticides and solvents and some congenital anomalies, and agent orangish and some congenital anomalies. Nonetheless the number of studies included in the meta-analyses was oft small, the exposure assessment limited and quality variable.

The relatively pocket-sized number of meta-analyses (North=16) is at kickoff glance mayhap surprising given the number of years of research in the area of environmental exposures and pregnancy outcomes. However every bit the meta-analyses showed, often there are not many studies with comparable data to conduct meta-analyses, except mayhap for ETS. Outcomes such every bit stillbirth and built anomalies studies are fairly rare and large numbers of subjects are needed, and for congenital anomalies the boosted problem is example ascertainment and classification that can vary considerably between studies. Outcomes such as gestational age, nascency weight, PTB, and LBW occur more frequently and are easier to study and compare amid studies.

The principal challenge to pooling studies using meta-analytical techniques is often thought to lie in the difficulties of combining studies with differences in exposure assessment, and therefore in obtaining comparable indices for meta-analyses. The ETS studies compared simple indices such as ETS exposed vs. non ETS exposed women [18–20] in the majority of studies retrospectively and to a groovy extent self-reported which may pb to exposure misclassification. Notwithstanding, in the (sensitivity) analyses at that place was little difference in the observed associations whether the information were obtained retrospectively or prospectively, or by cocky-report and/or some biochemical marker [xix, xx], which provides increased conviction in the results. Unfortunately there was little exploration of the importance of level and duration of the ETS exposure.

For outdoor air pollution, mostly regulatory ambient measurements were used to derive exposure indices providing some numerical concentration values for the exposure response relationships. However there were considerable differences in terms of, for example, the temporal resolution of measurements or the distance of maternal home address to the measurements stations, which could atomic number 82 to some doubt to how representative these were for the population.

The studies on disinfection by-products frequently used regulatory monitoring data of trihalomethanes in h2o, but generally did non include h2o intake measures or concentrations of other DBPs, which probably lead to exposure misclassification errors [17, 23–25]. In some cases, analyses focused on high vs. low exposed groups which were non always directly comparable betwixt studies.

The occupational exposure studies relied to a big extent on cocky reported job title and some assignment of exposure to the job title possibly leading to a considerable exposure misclassification [27–29]. Merely Govarts et al. used biomonitoring data of POPs from different studies but had to employ conversion factors to brand comparable indices because POPs were measured in different media (Maternal blood, cord blood, and breast milk) [26]. Over again this may increment measurement error. Furthermore they focused only on some specific POPs and not the whole Pop mixture.

In full general, with various exceptions, non-differential measurement error/exposure misclassification may pb to attenuation in gamble estimates and/or loss in ability just could be compensated in the increased numbers of subjects in the combined studies [32]. A further option is to stratify analyses past the quality of the exposure assessment.

A further limitation of any meta-analysis of observational studies is residual confounding. Although the bulk of individual studies had attempted to match or command for some of import confounding variables such as maternal age, parity, socioeconomic status, alcohol, and drug use, the covariates included varied betwixt studies. Since this may have resulted in residual confounding structures differing among the studies, it may have led to inappropriate pooling of heterogeneous study results in the meta-assay. On the other hand, where studies with different underlying confounder structures bear witness similar results, this will lead to increased confidence in the results.

Few studies reported having followed meta-analyses guidelines (MOOSE) or using a quality scoring system. Fifty-fifty though some did not report following guidelines, their arroyo appeared to be following the guidelines. 1 of the reasons for not following guidelines or using quality scores is probably the small number of studies included in general in the meta-analyses with the authors being familiar with the studies in the field. The few studies that included quality scores in their analysis did not see any difference in take chances estimates between higher and lower quality studies [19, xx].

The well-nigh used method to notice heterogeneity in the data was Cochran's Q test. Only a small number of studies identified heterogeneity in their studies and this may be partly due to the fact that the tests for heterogeneity are non very powerful when the number of included studies is low [33, 34]. If heterogeneity existed, generally no strategy was used in an attempt to reduce heterogeneity, for case past making subgroups probably considering of the small number of studies; however, some studies had already decided beforehand to bear meta-analyses by subgroup (eastward.yard. study pattern blazon). Salmasi et al. conducted meta-analyses overall and and then stratified by the type of exposure assessment (cocky reported vs. biochemical) and thereby reduced the heterogeneity [xix]. Sapkota et al. plant less heterogeneity in studies of PM_2.5 than PM₁₀, suggesting that the former may exist a better exposure index, since in PM₁₀ may be acting as an imperfect surrogate for PM_ii.5 with differences between areas in how good to the surrogate is [16]. Of course, other explanations are too possible, including for example large variability in toxicity. At times a priori, or after testing fifty-fifty if there was no heterogeneity in the information, the meta-analyses used random effects models to accept business relationship of possible underlying departure betwixt studies. This may have resulted at times in more conservative consequence estimates (i.due east. larger conviction intervals), merely may improve reflect the reality, where heterogeneity exist but may non be detected considering of a small numbers of studies.

One result to note is that authors ofttimes use I² to estimate heterogeneity and we have referred to it every bit such here too. However I² is not a measure of the magnitude of the between-report heterogeneity, nor a betoken estimate of between-study heterogeneity. Information technology represents the judge proportion of total variability in bespeak estimates that tin be attributed to heterogeneity [35]. The total variation depends importantly on the within-study precisions (substantially the sample sizes of the individual studies). Therefore, so must I^two. Furthermore, I² does not guess a meaningful parameter, so should be regarded as a descriptive statistic rather than a point gauge [35]. Authors often omit to mention that the magnitude of heterogeneity can be quantified, using a point estimate of the among-study variance of true furnishings, oft called τ² (tau-squared). Thus, I² may be viewed every bit the proportion of variability in the bespeak estimates that is due to τ² rather than within-written report mistake [35]. A more appropriate descriptor for I² would exist a measure of inconsistency, since information technology depends on the extent of overlap in confidence intervals across studies.

Funnel plots and the Egger test were mostly used to detect publication bias. There was little publication bias observed. 1 of the reasons may be that many of the studies were time consuming and difficult to carry and that therefore authors made great efforts to get the information published. Furthermore, a sufficient number of studies are needed to be able to detect publication bias, and where few studies are bachelor, it may not be possible. Sensitivity analyses by and large consisted of some subgroup analyses or leaving one study out at the fourth dimension to determine if at that place were some influential studies. Generally the results did not modify appreciably, suggesting that the results presented were robust.

Conclusions

The number of meta-analyses of environmental exposures and pregnancy outcomes is minor and they vary in methodology. Just a small number of the studies reported having followed meta-analysis guidelines or having used a quality rating organization. Nevertheless, they mostly tested for heterogeneity and publication bias. Publication bias did not occur ofttimes. The available meta-analyses reported statistically meaning associations betwixt environmental exposures such as ETS, air pollution and chemicals and pregnancy outcomes like PTB, LBW, SGA, and congenital anomalies. We recommend futurity meta-analyses of the associations between environmental exposure and pregnancy outcomes to follow the bachelor guidelines and report not only the combined consequence estimates, but likewise the measures of heterogeneity, the method they apply to account for heterogeneity (e.grand. stratification of analyses or use of random furnishings models), and publication bias. The findings of these meta-analyses could provide a farther insight into and/or better understanding of the association, comeback of methodology and, ultimately, to better take chances management and policy making.

Abbreviations

ETS:

Ecology tobacco smoke

PCB:

Polychlorinated biphenyls

PFOS:

Perfluorooctane sulfonate

PFOA:

Perfluorooctanoic acrid

POPs:

persistent organic pollutants

LBW:

Low nativity weight

PTB:

Preterm birth

SGA:

Small for gestational age

ppb:

Parts per billion

VSD:

Ventricular septal defect

TTHM:

Total trihalomethanes

OR:

Odds ratio

RR:

Relative adventure

95%CI:

95% confidence interval.

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Acknowledgements

Payam Dadvand is funded by a Juan de la Cierva fellowship (JCI-2011-09937) awarded past the Spanish Ministry building of Science and Innovation.

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Affiliations

1. Middle for Inquiry in Environmental Epidemiology (CREAL), Barcelona Biomedical Research Park, Dr. Aiguader 88, Barcelona, 08003, Spain

   Mark J Nieuwenhuijsen, Payam Dadvand, James Grellier, David Martinez & Martine Vrijheid

2. Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona Biomedical Inquiry Park, Dr. Aiguader 88, Barcelona, 08003, Spain

   Mark J Nieuwenhuijsen, Payam Dadvand, James Grellier, David Martinez & Martine Vrijheid

3. CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Kingdom of spain

   Mark J Nieuwenhuijsen, Payam Dadvand, James Grellier, David Martinez & Martine Vrijheid

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Correspondence to Mark J Nieuwenhuijsen.

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The authors declared no competing involvement with respect to the authorship and/or publication of this article.

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All authors contributed to the concept and design of the written report, the review and revision of the article, and have approved the concluding version of the paper. MN carried out the database search and drafted the article.

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Nieuwenhuijsen, K.J., Dadvand, P., Grellier, J. et al. Environmental take chances factors of pregnancy outcomes: a summary of contempo meta-analyses of epidemiological studies. Environ Health 12, 6 (2013). https://doi.org/10.1186/1476-069X-12-six

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• Received: 27 August 2012

• Accustomed: 08 Jan 2013

• Published: 15 Jan 2013

• DOI : https://doi.org/10.1186/1476-069X-12-6

Keywords

• Meta-analysis
• Pregnancy
• Nativity weight
• Gestational age
• Stillbirth
• Congenital anomalies
• Gestational age
• Environmental exposures
• Environmental tobacco smoke
• Air pollution
• Pesticides

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