Exploring applications of non-targeted analysis in the characterization of the prenatal exposome.

Capturing the breadth of chemical exposures in utero is critical in understanding their long-term health effects for mother and child. We explored methodological adaptations in a Non-Targeted Analysis (NTA) pipeline and evaluated the effects on chemical annotation and discovery for maternal and infant exposure. We focus on lesser-known/underreported chemicals in maternal and umbilical cord serum analyzed with liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). The samples were collected from a demographically diverse cohort of 296 maternal-cord pairs (n = 592) recruited in San Francisco Bay area. We developed and evaluated two data processing pipelines, primarily differing by detection frequency cut-off, to extract chemical features from non-targeted analysis (NTA). We annotated the detected chemical features by matching with EPA CompTox Chemicals Dashboard (n = 860,000 chemicals) and Human Metabolome Database (n = 3140 chemicals) and applied a Kendrick Mass Defect filter to detect homologous series. We collected fragmentation spectra (MS/MS) on a subset of serum samples and matched to an experimental MS/MS database within the MS-Dial website and other experimental MS/MS spectra collected from standards in our lab. We annotated ~72 % of the features (total features = 32,197, levels 1-4). We confirmed 22 compounds with analytical standards, tentatively identified 88 compounds with MS/MS spectra, and annotated 4862 exogenous chemicals with an in-house developed annotation algorithm. We detected 36 chemicals that appear to not have been previously reported in human blood and 9 chemicals that were reported in less than five studies. Our findings underline the importance of NTA in the discovery of lesser-known/unreported chemicals important to characterize human exposures.

The association between timing in pregnancy of drought and excess rainfall, infant sex, and birthweight: Evidence from Nepal.

Background: Past research on the impact of climatic events, such as drought, on birth outcomes has primarily been focused in Africa, with less research in South Asia, including Nepal. Existing evidence has generally found that drought impacts birthweight and infant sex, with differences by trimester. Additionally, less research has looked at the impact of excess rain on birth outcomes or focused on the impact of rainfall extremes in the preconception period. Using data from a large demographic surveillance system in Nepal, combined with a novel measure of drought/excess rainfall, we explore the impact of these on birthweight by time in pregnancy. Methods: Using survey data from the 2016 to 2019 Chitwan Valley Study in rural Nepal combined with data from Climate Hazards InfraRed Precipitation with Station, we explored the association between excess rainfall and drought and birthweight, looking at exposure in the preconception period, and by trimester of pregnancy. We also explore the impact of excess rainfall and drought on infant sex and delivery with a skilled birth attendant. We used multilevel regressions and explored for effect modification by maternal age. Results: Drought in the first trimester is associated with lower birthweight (ß = -82.9 g; 95% confidence interval [CI] = 164.7, -1.2) and drought in the preconception period with a high likelihood of having a male (odds ratio [OR] = 1.41; 95% CI = 1.01, 2.01). Excess rainfall in the first trimester is associated with high birthweight (ß = 111.6 g; 95% CI = 20.5, 202.7) and higher odds of having a male (OR = 1.48; 95% CI = 1.02, 2.16), and in the third trimester with higher odds of low birth weight (OR = 2.50; 95% CI = 1.40, 4.45). Conclusions: Increasing rainfall extremes will likely impact birth outcomes and could have implications for sex ratios at birth.

Extreme weather-Wildfires & pregnancy.

As described in the previous chapter, Chapter 4: Air pollution and pregnancy, there is robust literature on the adverse health impacts of ambient air pollution on perinatal outcomes. With climate change contributing to more extreme weather patterns, wildfire events are becoming more intense and frequent. Wildfire smoke is a major contributor to poor air quality and data are beginning to emerge with respect to the negative impact on perinatal outcomes. The aim of this chapter is to provide an overview of the current literature on wildfire smoke exposure in pregnancy and associated adverse outcomes.

Extending Nontargeted Discovery of Environmental Chemical Exposures during Pregnancy and Their Association with Pregnancy Complications-A Cross-Sectional Study.

BACKGROUND: Nontargeted analysis (NTA) methods identify novel exposures; however, few chemicals have been quantified and interrogated with pregnancy complications. OBJECTIVES: We characterized levels of nine exogenous and endogenous chemicals in maternal and cord blood identified, selected, and confirmed in prior NTA steps, including linear and branched isomers perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), monoethylhexyl phthalate, 4-nitrophenol, tetraethylene glycol, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid. We evaluated relationships between maternal and cord levels and between gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy in a diverse pregnancy cohort in San Francisco. METHODS: We collected matched maternal and cord serum samples at delivery from 302 pregnant study participants from the Chemicals in Our Bodies cohort in San Francisco. Chemicals were identified via NTA and quantified using targeted approaches. We calculated distributions and Spearman correlation coefficients testing the relationship of chemicals within and between the maternal and cord blood matrices. We used adjusted logistic regression to calculate the odds of GDM and hypertensive disorders of pregnancy associated with an interquartile range increase in maternal chemical exposures. RESULTS: We detected linear PFOS, PFHxS, octadecanedioic acid, and deoxycholic acid in at least 97% of maternal samples. Correlations ranged between -0.1 and 0.9. We observed strong correlations between cord and maternal levels of PFHxS, linear PFOS, and branched PFOS (coefficient=0.9, 0.8, and 0.8, respectively). An interquartile range increase in linear and branched PFOS, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid was associated with increased odds ratio (OR) of GDM [OR=1.33 (95% CI: 0.89, 2.01), 1.24 (95% CI: 0.86, 1.80), 1.26 (95% CI: 0.93, 1.73), 1.24 (95% CI: 0.86, 1.80), and 1.23 (95% CI: 0.87, 1.75), respectively]. Tridecanedioic acid was positively associated with hypertensive disorders of pregnancy [OR=1.28 (95% CI: 0.90, 1.86)]. DISCUSSION: We identified both exogenous and endogenous chemicals seldom quantified in pregnant study participants that were also related to pregnancy complications and demonstrated the utility of NTA to identify chemical exposures of concern. https://doi.org/10.1289/EHP11546.

Climate Change and Pregnancy: Risks, Mitigation, Adaptation, and Resilience.

Importance: Climate change is affecting the earth, resulting in more extreme temperatures and weather, rising sea levels, more frequent natural disasters, and displacement of populations of plants and animals, including people and insects. These changes affect food and housing security, vector-borne illnesses, and access to clean air and water, all of which influence human health. Evidence and Results: There are a number of adverse health outcomes linked to heat, air pollution from wildfires, stress from natural disasters, and other elements of climate change. Pregnant people are especially vulnerable to the health harms resulting from climate change, namely, preterm birth, small for gestational age, hypertensive disorders of pregnancy, and other adverse reproductive health and birth outcomes. Strategies to minimize these harms include mitigation and adaptation. Conclusions and Relevance: Physicians are in a unique position to protect the health of pregnant persons and children by advocating for policy changes that address climate change and providing clinical recommendations for patients to protect themselves from the health impacts of climate hazards.

Investigating geographic differences in environmental chemical exposures in maternal and cord sera using non-targeted screening and silicone wristbands in California.

BACKGROUND: Differential risks for adverse pregnancy outcomes may be influenced by prenatal chemical exposures, but current exposure methods may not fully capture data to identify harms and differences. METHODS: We collected maternal and cord sera from pregnant people in Fresno and San Francisco, and screened for over 2420 chemicals using LC-QTOF/MS. We matched San Francisco participants to Fresno participants (N = 150) and compared detection frequencies. Twenty-six Fresno participants wore silicone wristbands evaluated for over 1500 chemicals using quantitative chemical analysis. We assessed whether living in tracts with higher levels of pollution according to CalEnviroScreen correlated with higher numbers of chemicals detected in sera. RESULTS: We detected 2167 suspect chemical features across maternal and cord sera. The number of suspect chemical features was not different by city, but a higher number of suspect chemicals in cosmetics or fragrances was detected in the Fresno versus San Francisco participants' sera. We also found high levels of chemicals used in fragrances measured in the silicone wristbands. Fresno participants living in tracts with higher pesticide scores had higher numbers of suspect pesticides in their sera. CONCLUSIONS: Multiple exposure-assessment approaches can identify exposure to many chemicals during pregnancy that have not been well-studied for health effects.

Disparities in chemical exposures among pregnant women and neonates by socioeconomic and demographic characteristics: A nontargeted approach.

BACKGROUND: Exposure to environmental chemicals during pregnancy adversely affects maternal and infant health, and identifying socio-demographic differences in exposures can inform contributions to health inequities. METHODS: We recruited 294 demographically diverse pregnant participants in San Francisco from the Mission Bay/Moffit Long (MB/ML) hospitals, which serve a primarily higher income population, and Zuckerberg San Francisco General Hospital (ZSFGH), which serves a lower income population. We collected maternal and cord sera, which we screened for 2420 unique formulas and their isomers using high-resolution mass spectrometry using LC-QTOF/MS. We assessed differences in chemical abundances across socioeconomic and demographic groups using linear regression adjusting for false discovery rate. RESULTS: Our participants were racially diverse (31% Latinx, 16% Asian/Pacific Islander, 5% Black, 5% other or multi-race, and 43% white). A substantial portion experienced financial strain (28%) and food insecurity (20%) during pregnancy. We observed significant abundance differences in maternal (9 chemicals) and cord sera (39 chemicals) between participants who delivered at the MB/ML hospitals versus ZSFGH. Of the 39 chemical features differentially detected in cord blood, 18 were present in pesticides, one per- or poly-fluoroalkyl substance (PFAS), 21 in plasticizers, 24 in cosmetics, and 17 in pharmaceuticals; 4 chemical features had unknown sources. A chemical feature annotated as 2,4-dichlorophenol had higher abundances among Latinx compared to white participants, those delivering at ZSFGH compared to MB/ML, those with food insecurity, and those with financial strain. Post-hoc QTOF analyses indicated the chemical feature was either 2,4-dichlorophenol or 2,5-dichlorophenol, both of which have potential endocrine-disrupting effects. CONCLUSIONS: Chemical exposures differed between delivery hospitals, likely due to underlying social conditions faced by populations served. Differential exposures to 2,4-dichlorophenol or 2,5-dichlorophenol may contribute to disparities in adverse outcomes.

Perinatal outcomes and 2017 ACC/AHA blood pressure categories.

OBJECTIVE: To evaluate the association of blood pressure category < 20 weeks according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) criteria with adverse perinatal outcomes. STUDY DESIGN: A retrospective cohort study of singleton deliveries between 1/2014 and 10/2017 was undertaken. Blood pressure category assigned by 2017 ACC/AHA criteria applied to blood pressures prior to 20 weeks gestation: normal (systolic < 120 and diastolic < 80), elevated blood pressure (systolic 120-129 and diastolic < 80 mmHg), stage 1 hypertension (systolic 130-139 and/or diastolic 80-89), stage 2 hypertension (prior diagnosis of chronic hypertension or systolic ≥ 140 or diastolic ≥ 90 mmHg). MAIN OUTCOME MEASURES: The primary outcome was preeclampsia. Secondary outcomes included preterm birth and postpartum readmission. Chi-square, ANOVA and Kruskal-Wallis tests and multivariable Poisson regression were used for analysis. RESULTS: Of the 6,067 eligible pregnancies, 3,855 (63.5%) had normotensive blood pressure, 1,224 (20.2%) elevated blood pressure, 624 (10.3%) stage 1 hypertension, and 364 (6.0%) stage 2 hypertension. Compared to 4.6% prevalence of preeclampsia among normotensive pregnancies, higher categories were associated with higher preeclampsia prevalence: elevated blood pressure (10.7%, adjusted relative risk (aRR) 2.2, 95% confidence interval (CI) 1.8-2.6), stage 1 hypertension (15.1%, aRR 2.7, 95% CI 2.2-3.4) and stage 2 hypertension (38.7%, aRR 6.2, 95% CI 5.1-7.4). Non-normal categories were also associated with a higher risk of preterm birth and postpartum readmission. CONCLUSION: Patients with elevated blood pressure and stage 1 and 2 hypertension at < 20 weeks are at increased risk of adverse obstetric perinatal outcomes.

Climate change, women's health, and the role of obstetricians and gynecologists in leadership.

Climate change is one of the major global health threats to the world's population. It is brought on by global warming due in large part to increasing levels of greenhouse gases resulting from human activity, including burning fossil fuels (carbon dioxide), animal husbandry (methane from manure), industry emissions (ozone, nitrogen oxides, sulfur dioxide), vehicle/factory exhaust, and chlorofluorocarbon aerosols that trap extra heat in the earth's atmosphere. Resulting extremes of weather give rise to wildfires, air pollution, changes in ecology, and floods. These in turn result in displacement of populations, family disruption, violence, and major impacts on water quality and availability, food security, public health and economic infrastructures, and limited abilities for civil society to maintain citizen safety. Climate change also has direct impacts on human health and well-being. Particularly vulnerable populations are affected, including women, pregnant women, children, the disabled, and the elderly, who comprise the majority of the poor globally. Additionally, the effects of climate change disproportionally affect disadvantaged communities, including low income and communities of color, and lower-income countries that are at highest risk of adverse impacts when disasters occur due to inequitable distribution of resources and their socioeconomic status. The climate crisis is tilting the risk balance unfavorably for women's sexual and reproductive health and rights as well as newborn and child health. Obstetrician/gynecologists have the unique opportunity to raise awareness, educate, and advocate for mitigation strategies to reverse climate change affecting our patients and their families. This article puts climate change in the context of women's reproductive health as a public health issue, a social justice issue, a human rights issue, an economic issue, a political issue, and a gender issue that needs our attention now for the health and well-being of this and future generations. FIGO joins a broad coalition of international researchers and the medical community in stating that the current climate crisis presents an imminent health risk to pregnant people, developing fetuses, and reproductive health, and recognizing that we need society-wide solutions, government policies, and global cooperation to address and reduce contributors, including fossil fuel production, to climate change.

Prolonged second stage of labor and risk of subsequent spontaneous preterm birth.

BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and death in the United States. Although many risk factors for spontaneous preterm birth have been elucidated, some women with a previous term delivery experience spontaneous preterm birth in the absence of any identifiable risk factors. Cervical trauma during a prolonged second stage of labor has been postulated as a potential contributor to subsequent spontaneous preterm birth. OBJECTIVE: This study was designed to examine the relationship between the length of the second stage of labor in the first pregnancy and the risk of spontaneous preterm birth in the subsequent pregnancy. STUDY DESIGN: This was a retrospective cohort study of all women with 2 consecutive singleton deliveries at a single institution between July 2012 and June 2018, with the first delivery occurring ≥37 weeks of gestation. Multiparous women and those women who did not reach the second stage of labor in the first pregnancy were excluded. Prolonged second stage of labor was defined as ≥4 hours, based on the 75th percentile for this cohort and on recommendations from the National Institute of Child Health and Human Development. Very prolonged second stage of labor was defined as ≥7 hours, based on the 95th percentile for this cohort. The primary outcome was spontaneous preterm birth <37 weeks of gestation in the subsequent pregnancy. The Kruskal-Wallis test compared median values for nonparametric continuous variables; Fisher's exact tests compared proportions for categoric variables, and logistic regression generated odds ratios. RESULTS: A total of 1032 women met criteria for study inclusion, with an overall subsequent spontaneous preterm birth rate of 3.1%. Prolonged second stage of labor of ≥4 hours was identified in 24.4% (252/1032 women) of the cohort, with 70.6% (178/252 women) of this group delivering vaginally. There was no statistically significant difference in rate of spontaneous preterm birth in those with and without prolonged second stage of labor (4.4% [11/252 women] with prolonged labor vs 2.7% [21/780 women] without prolonged labor; P=.21; odds ratio, 1.6; 95% confidence interval, 0.8-3.5). Very prolonged second stage of labor of ≥7 hours was identified in 4.3% (44/1032 women) of the cohort, with 45.4% (20/44 women) of this group delivering vaginally. There was a significantly higher rate of spontaneous preterm birth in those with very prolonged second stage of labor compared with those without prolonged labor (9.1% [4/44 women] with prolonged labor vs 2.8% [28/988 women] without prolonged labor; P=.04; odds ratio, 3.4; 95% confidence interval, 1.1-10.2), although this finding did not persist after we controlled for the mode of first delivery (adjusted odds ratio, 1.55; 95% confidence interval, 0.65-3.73). Spontaneous preterm birth after very prolonged second stage of labor was identified in only 4 patients, all of whom had a cesarean delivery with the first pregnancy. CONCLUSION: A second stage of labor of ≥4 hours in the first pregnancy was not associated with an increased risk of subsequent spontaneous preterm birth and was associated with a high rate (>70%) of vaginal birth. A second stage of labor of ≥7 hours did not appear to be associated with an increased risk of preterm birth, when we adjusted for mode of first delivery. There was a nonsignificant increase in the risk of preterm birth in those who delivered via cesarean section after a second stage of labor of ≥7 hours.

The International Society for Children's Health and the Environment Commits to Reduce Its Carbon Footprint to Safeguard Children's Health.

The Lancet Countdown and the 2018 Intergovernmental Panel on Climate Change declared that the worst impacts of climate change are and will continue to be felt disproportionately by children. Children are uniquely vulnerable to the consequences of climate change, including heat stress, food scarcity, increases in pollution and vector-borne diseases, lost family income, displacement, and the trauma of living through a climate-related disaster. These stressors can result in long-lasting physical and mental health sequelae. Based upon these concerns associated with climate change, the International Society for Children's Health and the Environment developed a statement about ways in which the Society could take action to reduce its contribution of greenhouse gas emissions. The objective of this article is to report our Society's plans in hopes that we may stimulate other scientific societies to take action. https://doi.org/10.1289/EHP6578.

Gender Differences in Academic Rank and NIH Funding among Academic Maternal-Fetal Medicine Physicians in the United States.

OBJECTIVE: This article evaluates gender differences in academic rank and National Institutes of Health (NIH) funding among academic maternal-fetal medicine (MFM) physicians. STUDY DESIGN: This was a cross-sectional study of board-certified academic MFM physicians. Physicians were identified in July 2017 from the MFM fellowship Web sites. Academic rank and receipt of any NIH funding were compared by gender. Data on potential confounders were collected, including years since board certification, region of practice, additional degrees, number of publications, and h-index. RESULTS: We identified 659 MFM physicians at 72 institutions, 312 (47.3%) male and 347 (52.7%) female. There were 246 (37.3%) full, 163 (24.7%) associate, and 250 (37.9%) assistant professors. Among the 154 (23.4%) MFM physicians with NIH funding, 89 (57.8%) were male and 65 (42.2%) were female (p = 0.003). Adjusting for potential confounders, male MFM physicians were twice as likely to hold a higher academic rank than female MFM physicians (adjusted odds ratio [aOR], 2.04 [95% confidence interval, 1.39-2.94], p < 0.001). There was no difference in NIH funding between male and female MFM physicians (aOR, 1.23 [0.79-1.92], p = 0.36). CONCLUSION: Compared with female academic MFM physicians, male academic MFM physicians were twice as likely to hold a higher academic rank but were no more likely to receive NIH funding.

Examining Joint Effects of Air Pollution Exposure and Social Determinants of Health in Defining "At-Risk" Populations Under the Clean Air Act: Susceptibility of Pregnant Women to Hypertensive Disorders of Pregnancy.

Pregnant women are uniquely susceptible to adverse effects of air pollution exposure due to vulnerabilities and health consequences during pregnancy (e.g., hypertensive disorders of pregnancy [HDP]) compared to the general population. Because the Clean Air Act (CAA) creates a duty to protect at-risk groups, the regulatory assessment of at-risk populations has both policy and scientific foundations. Previously, pregnant women have not been specially protected in establishing the margin of safety for the ozone and particulate matter (PM) standards. Due to physiological changes, pregnant women can be at greater risk of adverse effects of air pollution and should be considered an at-risk population. Women with preexisting conditions, women experiencing poverty, and groups that suffer systematic discrimination may be particularly susceptible to cardiac effects of air pollutants during pregnancy. We rigorously reviewed 11 studies of over 1.3 million pregnant women in the United States to characterize the relationship between ozone or PM exposure and HDP. Findings were generally mixed, with a few studies reporting a joint association between ozone or PM and social determinants or pre-existing chronic health conditions related to HDP. Adequate evidence associates exposure to PM with an adverse effect of HDP among pregnant women not evident among non-gravid populations.

Endocrine-Disrupting Chemicals and Reproductive Health.

This review discusses the evidence linking industrial chemicals to a variety of health and reproductive outcomes. Industrial chemical production has increased over the past 30 to 40 years. Basic science, animal models, and epidemiologic data suggest that certain chemicals may act as endocrine disruptors (substances that interfere with normal hormonal action) and may play an etiologic role in a number of conditions whose incidence has also increased during this same period. These include low birth weight, gestational diabetes, obesity, certain cancers, certain birth defects, and neurodevelopmental disorders such as attention deficit disorder and autism. In addition, some environmental chemicals may have epigenetic effects, resulting in transgenerational health impacts. The epidemiologic and experimental evidence that links chemicals such as plasticizers (eg, phthalates and phenols), flame retardants, perfluorinated compounds, and pesticides with adverse reproductive health outcomes is reviewed. Women's health care providers are the liaison between scientific research and their patients; they should educate themselves on the significance of environmental toxins to health. They are ideally positioned, not only to counsel and reassure pregnant women, but also to suggest practicable changes in dietary and lifestyle habits to improve their health. Furthermore, women's health care providers should advocate for regulatory changes that protect women and their families from the health effects of environmental toxins.

Social media messaging in pregnancy: comparing content of Text4baby to content of free smart phone applications of pregnancy.

OBJECTIVE: Text4baby is the only free text-message program for pregnancy available. Our objective was to determine whether content differed between Text4baby and popular pregnancy smart phone applications (apps). METHODS: Researchers enrolled in Text4baby in 2012 and downloaded the four most-popular free pregnancy smart phone apps in July 2013; content was re-extracted in February 2014. Messages were assigned thematic codes. Two researchers coded messages independently before reviewing all the codes jointly to ensure consistency. Logistic regression modeling determined statistical differences between Text4baby and smart phone apps. RESULTS: About 1399 messages were delivered. Of these, 333 messages had content related to more than one theme and were coded as such, resulting in 1820 codes analyzed. Compared to smart phone apps, Text4baby was significantly more likely to have content regarding Postpartum Planning, Seeking Care, Recruitment and Prevention and significantly less likely to mention Normal Pregnancy Symptoms. No messaging program included content regarding postpartum contraception. CONCLUSIONS: To improve content without increasing text message number, Text4baby could replace messages on recruitment with messages regarding normal pregnancy symptoms, fetal development and postpartum contraception.

Clamp late and maintain perfusion (CLAMP) policy: delayed cord clamping in preterm infants.

OBJECTIVE: Randomized controlled trials have demonstrated that delayed umbilical cord clamping (DCC) in preterm infants results in improved neonatal outcomes, including increased hematocrit, and decreased rates of intraventricular hemorrhage (IVH) and packed red blood cell transfusions. We hypothesized that implementation of a DCC policy in preterm infants would result in similarly improved outcomes, despite initial clinician resistance. STUDY DESIGN: A DCC policy (30-60 s) for singleton infants <35 weeks gestation was implemented in September 2011. We conducted a pre-test/post-test analysis of neonatal outcomes among singletons delivered between 24 0/7 weeks and 34 6/7 weeks gestation from 2009 to 2013 (2 years pre-implementation and 2 years post-implementation). The primary outcomes were rates of policy compliance and four neonatal outcomes. RESULTS: Despite multiple routes of policy dissemination, DCC was attempted in only 49% of the deliveries. In spite of this, infants delivered post-policy implementation (n = 196) had a significant decrease in IVH, significant increase in initial hematocrits, and improved temperatures compared with infants delivered pre-implementation (n = 204). CONCLUSION: After implementation of a DCC policy, preterm singleton infants had improved temperatures, increased hematocrits and a decreased prevalence of IVH without significant differences in adverse outcomes, suggesting that the benefits of DCC outweighed the risks.

My Obstetrician Got Me Fired: How Work Notes Can Harm Pregnant Patients and What to Do About It.

Prenatal care providers are frequently asked to provide employment notes for their patients requesting medical leave or changes to work duties. Writing employment notes correctly can help patients negotiate for and obtain medically indicated workplace accommodations, allowing them to continue to work and earn an income. However, a poorly written or poorly timed note can jeopardize a patient's employment and salary. This commentary provides an overview of pregnancy-related employment laws and guidance in writing work accommodations letters that allow pregnant women to keep their jobs while maintaining a healthy pregnancy.

Fetal growth and maternal glomerular filtration rate: a systematic review.

OBJECTIVE: Glomerular filtration rate (GFR) may influence concentrations of biomarkers of exposure and their etiologic significance in observational studies of associations between environmental contaminants and fetal growth. It is unknown whether the size of a developing fetus affects maternal GFR such that a small fetus leads to reduced plasma volume expansion (PVE), reduced GFR and subsequent higher concentrations of biomarkers in maternal serum. Our objective was to answer the question: "Is there an association between fetal growth and maternal GFR in humans?" METHODS: We adapted and applied the Navigation Guide systematic review methodology to assess the evidence of an association between fetal growth and GFR, either directly or indirectly via reduction in PVE. RESULTS: We identified 35 relevant studies. We rated 31 human and two non-human observational studies as "low" quality and two experimental non-human studies as "very low" quality. We rated all three evidence streams as "inadequate". The association between fetal growth and GFR was "not classifiable" according to pre-specified definitions. CONCLUSIONS: There is currently insufficient evidence to support the plausibility of a reverse causality hypothesis for associations between exposure to environmental chemicals during pregnancy and fetal growth. Further research would be needed to confirm or disprove this hypothesis.