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1.
Sci Total Environ ; 806(Pt 1): 150298, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34844318

RESUMO

BACKGROUND: Prior studies have found that residential proximity to upstream oil and gas production is associated with increased risk of adverse health outcomes. Emissions of ambient air pollutants from oil and gas wells in the preproduction and production stages have been proposed as conferring risk of adverse health effects, but the extent of air pollutant emissions and resulting nearby pollution concentrations from wells is not clear. OBJECTIVES: We examined the effects of upstream oil and gas preproduction (count of drilling sites) and production (total volume of oil and gas) activities on concentrations of five ambient air pollutants in California. METHODS: We obtained data on approximately 1 million daily observations from 314 monitors in the EPA Air Quality System, 2006-2019, including daily concentrations of five routinely monitored ambient air pollutants: PM2.5, CO, NO2, O3, and VOCs. We obtained data on preproduction and production operations from Enverus and the California Geographic Energy Management Division (CalGEM) for all wells in the state. For each monitor and each day, we assessed exposure to upwind preproduction wells and total oil and gas production volume within 10 km. We used a panel regression approach in the analysis and fit adjusted fixed effects linear regression models for each pollutant, controlling for geographic, seasonal, temporal, and meteorological factors. RESULTS: We observed higher concentrations of PM2.5 and CO at monitors within 3 km of preproduction wells, NO2 at monitors at 1-2 km, and O3 at 2-4 km from the wells. Monitors with proximity to increased production volume observed higher concentrations of PM2.5, NO2, and VOCs within 1 km and higher O3 concentrations at 1-2 km. Results were robust to sensitivity analyses. CONCLUSION: Adjusting for geographic, meteorological, seasonal, and time-trending factors, we observed higher concentrations of ambient air pollutants at air quality monitors in proximity to preproduction wells within 4 km and producing wells within 2 km.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , California , Campos de Petróleo e Gás
2.
Sci Total Environ ; : 152150, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34864029

RESUMO

BACKGROUND/OBJECTIVE: Research suggests gestational exposure to particulate matter ≤2.5 µm (PM2.5) and extreme heat may independently increase risk of birth defects. We investigated whether duration of gestational extreme heat exposure modifies associations between PM2.5 exposure and specific congenital heart defects (CHDs). We also explored nonlinear exposure-outcome relationships. METHODS: We identified CHD case children (n = 2824) and non-malformed live-birth control children (n = 4033) from pregnancies ending between 1999 and 2007 in the National Birth Defects Prevention Study, a U.S. population-based multicenter case-control study. We assigned mothers 6-week averages of PM2.5 exposure during the cardiac critical period (postconceptional weeks 3-8) using the closest monitor within 50 km of maternal residence. We assigned a count of extreme heat days (EHDs, days above the 90th percentile of daily maximum temperature for year, season, and weather station) during this period using the closest weather station. Using generalized additive models, we explored logit-nonlinear exposure-outcome relationships, concluding logistic models were reasonable. We estimated joint effects of PM2.5 and EHDs on six CHDs using logistic regression models adjusted for mean dewpoint and maternal age, education, and race/ethnicity. We assessed multiplicative and additive effect modification. RESULTS: Conditional on the highest observed EHD count (15) and at least one critical period day during spring/summer, each 5 µg/m3 increase in average PM2.5 exposure was significantly associated with perimembranous ventricular septal defects (VSDpm; OR: 1.54 [95% CI: 1.01, 2.41]). High EHD counts (8+) in the same population were positively, but non-significantly, associated with both overall septal defects and VSDpm. Null or inverse associations were observed for lower EHD counts. Multiplicative and additive effect modification estimates were consistently positive in all septal models. CONCLUSIONS: Results provide limited evidence that duration of extreme heat exposure modifies the PM2.5-septal defects relationship. Future research with enhanced exposure assessment and modeling techniques could clarify these relationships.

3.
Proc Natl Acad Sci U S A ; 118(51)2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34916285

RESUMO

Spina bifida (SB) is a debilitating birth defect caused by multiple gene and environment interactions. Though SB shows non-Mendelian inheritance, genetic factors contribute to an estimated 70% of cases. Nevertheless, identifying human mutations conferring SB risk is challenging due to its relative rarity, genetic heterogeneity, incomplete penetrance, and environmental influences that hamper genome-wide association studies approaches to untargeted discovery. Thus, SB genetic studies may suffer from population substructure and/or selection bias introduced by typical candidate gene searches. We report a population based, ancestry-matched whole-genome sequence analysis of SB genetic predisposition using a systems biology strategy to interrogate 298 case-control subject genomes (149 pairs). Genes that were enriched in likely gene disrupting (LGD), rare protein-coding variants were subjected to machine learning analysis to identify genes in which LGD variants occur with a different frequency in cases versus controls and so discriminate between these groups. Those genes with high discriminatory potential for SB significantly enriched pathways pertaining to carbon metabolism, inflammation, innate immunity, cytoskeletal regulation, and essential transcriptional regulation consistent with their having impact on the pathogenesis of human SB. Additionally, an interrogation of conserved noncoding sequences identified robust variant enrichment in regulatory regions of several transcription factors critical to embryonic development. This genome-wide perspective offers an effective approach to the interrogation of coding and noncoding sequence variant contributions to rare complex genetic disorders.


Assuntos
Genoma Humano , Disrafismo Espinal/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Biologia de Sistemas , Fatores de Transcrição/genética
4.
BMJ Open ; 11(11): e050963, 2021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824115

RESUMO

OBJECTIVE: This study aimed to develop a blood test for the prediction of pre-eclampsia (PE) early in gestation. We hypothesised that the longitudinal measurements of circulating adipokines and sphingolipids in maternal serum over the course of pregnancy could identify novel prognostic biomarkers that are predictive of impending event of PE early in gestation. STUDY DESIGN: Retrospective discovery and longitudinal confirmation. SETTING: Maternity units from two US hospitals. PARTICIPANTS: Six previously published studies of placental tissue (78 PE and 95 non-PE) were compiled for genomic discovery, maternal sera from 15 women (7 non-PE and 8 PE) enrolled at ProMedDx were used for sphingolipidomic discovery, and maternal sera from 40 women (20 non-PE and 20 PE) enrolled at Stanford University were used for longitudinal observation. OUTCOME MEASURES: Biomarker candidates from discovery were longitudinally confirmed and compared in parallel to the ratio of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) using the same cohort. The datasets were generated by enzyme-linked immunosorbent and liquid chromatography-tandem mass spectrometric assays. RESULTS: Our discovery integrating genomic and sphingolipidomic analysis identified leptin (Lep) and ceramide (Cer) (d18:1/25:0) as novel biomarkers for early gestational assessment of PE. Our longitudinal observation revealed a marked elevation of Lep/Cer (d18:1/25:0) ratio in maternal serum at a median of 23 weeks' gestation among women with impending PE as compared with women with uncomplicated pregnancy. The Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting impending event of PE with superior sensitivity (85% vs 20%) and area under curve (0.92 vs 0.52) from 5 to 25 weeks of gestation. CONCLUSIONS: Our study demonstrated the longitudinal measurement of maternal Lep/Cer (d18:1/25:0) ratio allows the non-invasive assessment of PE to identify pregnancy at high risk in early gestation, outperforming the established sFlt-1/PlGF ratio test.

5.
J Hypertens ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34751169

RESUMO

BACKGROUND: Reducing the prevalence of eclampsia, a major cause of maternal and perinatal morbidity, is a maternal health priority. However, sparse data exist examining trends in the USA prevalence of eclampsia. OBJECTIVE: The aim of this study was to assess temporal trends in the prevalence of eclampsia among live births in the United States from 2009 to 2017. STUDY DESIGN: This population-based cross-sectional study included live births in 41 USA states and the District of Columbia between 2009 and 2017. The prevalence of eclampsia among all women, women with chronic hypertension and hypertensive disorders of pregnancy were reported by 1000 live births. Risk ratios adjusted for maternal characteristics were used to assess temporal trends. RESULTS: Of 27 866 714 live births between 2009 and 2017, 83 000 (0.30%) were associated with eclampsia. The adjusted risk of eclampsia decreased 10% during the 7 most recent years of the cohort, with an adjusted risk ratio of 0.90 [95% confidence interval (95% CI): 0.87-0.93] in 2017 relative to 2009. Relative to 2009, the adjusted risk of eclampsia in 2017 was substantially lower among women with chronic hypertension (adjusted risk ratio: 0.51; 95% CI: 0.46-0.57) and women with hypertensive pregnancy disorders (adjusted risk ratio: 0.43; 95% CI: 0.40-0.47). Among nonhypertensive women, there was a slight increase in the adjusted risk of eclampsia in 2017 relative to 2009 (adjusted risk ratio: 1.14; 95% CI: 1.10-1.17). CONCLUSION: Despite reductions in the eclampsia prevalence among women with chronic hypertension and hypertensive disorders of pregnancy, public health initiatives are needed to reduce the overall eclampsia prevalence, especially in nonhypertensive women.

7.
Pediatr Res ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34671094

RESUMO

BACKGROUND: Hypertensive disorders of pregnancy and maternal diabetes profoundly affect fetal and newborn growth, yet disturbances in intermediate metabolism and relevant mediators of fetal growth alterations remain poorly defined. We sought to determine whether there are distinct newborn screen metabolic patterns among newborns affected by maternal hypertensive disorders or diabetes in utero. METHODS: A retrospective observational study investigating distinct newborn screen metabolites in conjunction with data linked to birth and hospitalization records in the state of California between 2005 and 2010. RESULTS: A total of 41,333 maternal-infant dyads were included. Infants of diabetic mothers demonstrated associations with short-chain acylcarnitines and free carnitine. Infants born to mothers with preeclampsia with severe features and chronic hypertension with superimposed preeclampsia had alterations in acetylcarnitine, free carnitine, and ornithine levels. These results were further accentuated by size for gestational age designations. CONCLUSIONS: Infants of diabetic mothers demonstrate metabolic signs of incomplete beta oxidation and altered lipid metabolism. Infants of mothers with hypertensive disorders of pregnancy carry analyte signals that may reflect oxidative stress via altered nitric oxide signaling. The newborn screen analyte composition is influenced by the presence of these maternal conditions and is further associated with the newborn size designation at birth. IMPACT: Substantial differences in newborn screen analyte profiles were present based on the presence or absence of maternal diabetes or hypertensive disorder of pregnancy and this finding was further influenced by the newborn size designation at birth. The metabolic health of the newborn can be examined using the newborn screen and is heavily impacted by the condition of the mother during pregnancy. Utilizing the newborn screen to identify newborns affected by common conditions of pregnancy may help relate an infant's underlying biological disposition with their clinical phenotype allowing for greater risk stratification and intervention.

8.
J Perinatol ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404925

RESUMO

OBJECTIVE: Investigate the association between maternal homelessness at the time of delivery and perinatal outcomes, with a focus on neonatal health outcomes. STUDY DESIGN: Population-based cohort using California's statewide database included 1,520,253 women with linked birth and maternal discharge data, 2008-2012. Multivariable analysis assessed homelessness at time of delivery on perinatal outcomes, preterm delivery, and neonatal intensive care unit admission. RESULT: A total of 672 women (0.05%) were homeless at the time of delivery. Homelessness was associated with premature delivery at multiple gestational age cutoffs (34w0d-36w6d; 32w0d-33w6d; 28w0d-31w6d; <28w0d) (range of aORs:1.62-2.19), and neonatal intensive care unit admission (aOR = 1.66, 95% CI:1.31-2.09). Among term infants, homelessness remained associated with increased odds of neonatal intensive care unit admission (aOR = 1.84, 95% CI:1.34-2.53), low birthweight (aOR = 1.99, 95% CI:1.36-2.90), neonatal abstinence syndrome (aOR = 2.13, 95% CI:1.35-2.53), hypoxic-ischemic encephalopathy (aOR = 14.38, 95% CI:3.90-53.01), and necrotizing enterocolitis (aOR = 14.94, 95% CI:2.68-83.20). CONCLUSION: Homelessness in pregnancy was associated with adverse perinatal outcomes including increased odds of preterm delivery across all gestational ages, and increased risk of neonatal intensive care unit admission and low birth weight independent of preterm delivery.

9.
Am J Med Genet A ; 185(10): 3028-3041, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34355505

RESUMO

Bladder exstrophy (BE) is a rare, lower ventral midline defect with the bladder and part of the urethra exposed. The etiology of BE is unknown but thought to be influenced by genetic variation with more recent studies suggesting a role for rare variants. As such, we conducted paired-end exome sequencing in 26 child/mother/father trios. Three children had rare (allele frequency ≤ 0.0001 in several public databases) inherited variants in TSPAN4, one with a loss-of-function variant and two with missense variants. Two children had loss-of-function variants in TUBE1. Four children had rare missense or nonsense variants (one per child) in WNT3, CRKL, MYH9, or LZTR1, genes previously associated with BE. We detected 17 de novo missense variants in 13 children and three de novo loss-of-function variants (AKR1C2, PRRX1, PPM1D) in three children (one per child). We also detected rare compound heterozygous loss-of-function variants in PLCH2 and CLEC4M and rare inherited missense or loss-of-function variants in additional genes applying autosomal recessive (three genes) and X-linked recessive inheritance models (13 genes). Variants in two genes identified may implicate disruption in cell migration (TUBE1) and adhesion (TSPAN4) processes, mechanisms proposed for BE, and provide additional evidence for rare variants in the development of this defect.

10.
PLoS One ; 16(7): e0255000, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34280228

RESUMO

BACKGROUND: Most evidence for interpregnancy interval (IPI) and adverse birth outcomes come from studies that are prone to incomplete control for confounders that vary between women. Comparing pregnancies to the same women can address this issue. METHODS: We conducted an international longitudinal cohort study of 5,521,211 births to 3,849,193 women from Australia (1980-2016), Finland (1987-2017), Norway (1980-2016) and the United States (California) (1991-2012). IPI was calculated based on the time difference between two dates-the date of birth of the first pregnancy and the date of conception of the next (index) pregnancy. We estimated associations between IPI and preterm birth (PTB), spontaneous PTB, and small-for-gestational age births (SGA) using logistic regression (between-women analyses). We also used conditional logistic regression comparing IPIs and birth outcomes in the same women (within-women analyses). Random effects meta-analysis was used to calculate pooled adjusted odds ratios (aOR). RESULTS: Compared to an IPI of 18-23 months, there was insufficient evidence for an association between IPI <6 months and overall PTB (aOR 1.08, 95% CI 0.99-1.18) and SGA (aOR 0.99, 95% CI 0.81-1.19), but increased odds of spontaneous PTB (aOR 1.38, 95% CI 1.21-1.57) in the within-women analysis. We observed elevated odds of all birth outcomes associated with IPI ≥60 months. In comparison, between-women analyses showed elevated odds of adverse birth outcomes for <12 month and >24 month IPIs. CONCLUSIONS: We found consistently elevated odds of adverse birth outcomes following long IPIs. IPI shorter than 6 months were associated with elevated risk of spontaneous PTB, but there was insufficient evidence for increased risk of other adverse birth outcomes. Current recommendations of waiting at least 24 months to conceive after a previous pregnancy, may be unnecessarily long in high-income countries.


Assuntos
Intervalo entre Nascimentos , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto , Estudos de Coortes , Países Desenvolvidos , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Estudos Longitudinais , Idade Materna , Gravidez , Nascimento Prematuro/patologia , Adulto Jovem
11.
BMC Pregnancy Childbirth ; 21(1): 478, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215208

RESUMO

BACKGROUND: Some scholars posit that attempts to avert stillbirth among extremely preterm gestations may result in a live birth but an early neonatal death. The literature, however, reports no empirical test of this potential form of left truncation. We examine whether annual cohorts delivered at extremely preterm gestational ages show an inverse correlation between their incidence of stillbirth and early neonatal death. METHODS: We retrieved live birth and infant death information from the California Linked Birth and Infant Death Cohort Files for years 1989 to 2015. We defined the extremely preterm period as delivery from 22 to < 28 weeks of gestation and early neonatal death as infant death at less than 7 days of life. We calculated proportions of stillbirth and early neonatal death separately by cohort year, race/ethnicity, and sex. Our correlational analysis controlled for well-documented declines in neonatal mortality over time. RESULTS: California reported 89,276 extremely preterm deliveries (live births and stillbirths) to Hispanic, non-Hispanic (NH) Black, and NH white mothers from 1989 to 2015. Findings indicate an inverse correlation between stillbirth and early neonatal death in the same cohort year (coefficient: -0.27, 95% CI of - 0.11; - 0.42). Results remain robust to alternative specifications and falsification tests. CONCLUSIONS: Findings support the notion that cohorts with an elevated risk of stillbirth also show a reduced risk of early neonatal death among extremely preterm deliveries. Results add to the evidence base that selection in utero may influence the survival characteristics of live-born cohorts.


Assuntos
Lactente Extremamente Prematuro , Nascido Vivo/epidemiologia , Morte Perinatal , Mortalidade Perinatal/tendências , Natimorto/epidemiologia , Viés , California/epidemiologia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Análise de Séries Temporais Interrompida/tendências , Gravidez
12.
Artigo em Inglês | MEDLINE | ID: mdl-34066190

RESUMO

To investigate preeclampsia etiologies, we examined relationships between greenspace, air pollution, and neighborhood factors. Data were from hospital records and geocoded residences of 77,406 women in San Joaquin Valley, California from 2000 to 2006. Preeclampsia was divided into mild, severe, or superimposed onto pre-existing hypertension. Greenspace within 100 and 500 m residential buffers was estimated from satellite data using normalized difference vegetation index (NDVI). Air quality data were averaged over pregnancy from daily 24-h averages of nitrogen dioxide, particulate matter <10 µm (PM10) and <2.5 µm (PM2.5), and carbon monoxide. Neighborhood socioeconomic (SES) factors included living below the federal poverty level and median annual income using 2000 US Census data. Odds of preeclampsia were estimated using logistic regression. Effect modification was assessed using Wald tests. More greenspace (500 m) was inversely associated with superimposed preeclampsia (OR = 0.57). High PM2.5 and low SES were associated with mild and severe preeclampsia. We observed differences in associations between greenspace (500 m) and superimposed preeclampsia by neighborhood income and between greenspace (500 m) and severe preeclampsia by PM10, overall and among those living in higher SES neighborhoods. Less greenspace, high particulate matter, and high-poverty/low-income neighborhoods were associated with preeclampsia, and effect modification was observed between these exposures. Further research into exposure combinations and preeclampsia is warranted.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Pré-Eclâmpsia , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , California/epidemiologia , Estudos de Casos e Controles , Exposição Ambiental/análise , Feminino , Humanos , Parques Recreativos , Material Particulado/análise , Pré-Eclâmpsia/epidemiologia , Gravidez
13.
Am J Perinatol ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33940645

RESUMO

OBJECTIVE: The study aimed to determine if single year birth certificate data can be used to identify regional and hospital variation in rates of short interpregnancy interval (IPI < 6 months). STUDY DESIGN: IPI was estimated for multiparous women ages 15 to 44 years with singleton live births between 2015 and 2016. Perinatal outcomes, place of birth, maternal race, and data for IPI calculations were obtained by using birth certificates. IPI frequencies are presented as observed rates. RESULTS: The cohort included 562,039 multiparous women. Short IPI rates were similar to those obtained with analyses by using linked longitudinal data and confirmed the association with preterm birth. Short IPI rates varied by race and Hispanic nativity. There was substantial hospital (0.8-9%) and regional (2.9-6.2%) variation in short IPI rates. CONCLUSION: IPI rates can be reliably obtained from current year birth certificate data. This can be a useful tool for quality improvement projects targeting interventions and rapidly assessing their progress to promote optimal birth spacing. KEY POINTS: · Near-real time regional and hospital IPI rates can be reliably obtained from current year birth certificate data.. · Substantial variations in rates of short IPI exist between hospital and perinatal regions.. · IPI rates from individual birth certificates can be a tool to target and assess interventions..

14.
Am J Perinatol ; 2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33934321

RESUMO

OBJECTIVE: The study aimed to describe preterm birth (PTB) rates, subtypes, and risk factors in twins compared with singletons to better understand reasons for the decline in PTB rate between 2007 and 2011. STUDY DESIGN: This was a retrospective population-based analysis using the California linked birth certificates and maternal-infant hospital discharge records from 2007 to 2011. The main outcomes were overall, spontaneous (following spontaneous labor or preterm premature rupture of membranes), and medically indicated PTB at various gestational age categories: <37, <32, and 34 to 36 weeks in twins and singletons. RESULTS: Among the 2,290,973 singletons and 28,937 twin live births pairs included, overall PTB <37 weeks decreased by 8.46% (6.77-6.20%) in singletons and 7.17% (55.31-51.35%) in twins during the study period. In singletons, this was primarily due to a 24.91% decrease in medically indicated PTB with almost no change in spontaneous PTB, whereas in twins indicated PTB declined 7.02% and spontaneous PTB by 7.39%. CONCLUSION: Recent declines in PTB in singletons appear to be largely due to declines in indicated PTB, whereas both spontaneous and indicated PTB declined in twins. KEY POINTS: · The declines in PTB noted between 2006 and 2014 occurred in both singleton and twins.. · Declines were mostly in medically indicated PTB.. · Interventions proposed as causing the declines in singletons would not apply to twins..

15.
Environ Health Perspect ; 129(5): 57001, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33949893

RESUMO

BACKGROUND: Nitrate is a widespread groundwater contaminant and a leading cause of drinking water quality violations in California. Associations between nitrate exposure and select adverse birth outcomes have been suggested, but few studies have examined gestational exposures to nitrate and risk of preterm birth (before 37 wk gestation). OBJECTIVE: We investigated the association between elevated nitrate in drinking water and spontaneous preterm birth through a within-mother retrospective cohort study of births in California. METHODS: We acquired over 6 million birth certificate records linked with Office of Statewide Health Planning and Development hospital discharge data for California births from 2000-2011. We used public water system monitoring records to estimate nitrate concentrations in drinking water for each woman's residence during gestation. After exclusions, we constructed a sample of 1,443,318 consecutive sibling births in order to conduct a within-mother analysis. We used separate conditional logistic regression models to estimate the odds of preterm birth at 20-31 and 32-36 wk, respectively, among women whose nitrate exposure changed between consecutive pregnancies. RESULTS: Spontaneous preterm birth at 20-31 wk was increased in association with tap water nitrate concentrations during pregnancy of 5 to <10mg/L [odds ratio (OR)=1.47; 95% confidence interval (CI): 1.29, 1.67] and ≥10mg/L (OR=2.52; 95% CI: 1.49, 4.26) compared with <5mg/L (as nitrogen). Corresponding estimates for spontaneous preterm birth at 32-36 wk were positive but close to the null for 5 to <10mg/L nitrate (OR=1.08; 95% CI: 1.02, 1.15) and for ≥10mg/L nitrate (OR=1.05; 95% CI: 0.85, 1.31) vs. <5mg/L nitrate. Our findings were similar in several secondary and sensitivity analyses, including in a conventional individual-level design. DISCUSSION: The results suggest that nitrate in drinking water is associated with increased odds of spontaneous preterm birth. Notably, we estimated modestly increased odds associated with tap water nitrate concentrations of 5 to <10mg/L (below the federal drinking water standard of 10mg/L) relative to <5mg/L. https://doi.org/10.1289/EHP8205.


Assuntos
Água Potável , Nitratos , Nascimento Prematuro , California/epidemiologia , Água Potável/química , Feminino , Humanos , Recém-Nascido , Mães/estatística & dados numéricos , Nitratos/efeitos adversos , Nitratos/análise , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos
16.
Sci Transl Med ; 13(592)2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952678

RESUMO

Estimating the time of delivery is of high clinical importance because pre- and postterm deviations are associated with complications for the mother and her offspring. However, current estimations are inaccurate. As pregnancy progresses toward labor, major transitions occur in fetomaternal immune, metabolic, and endocrine systems that culminate in birth. The comprehensive characterization of maternal biology that precedes labor is key to understanding these physiological transitions and identifying predictive biomarkers of delivery. Here, a longitudinal study was conducted in 63 women who went into labor spontaneously. More than 7000 plasma analytes and peripheral immune cell responses were analyzed using untargeted mass spectrometry, aptamer-based proteomic technology, and single-cell mass cytometry in serial blood samples collected during the last 100 days of pregnancy. The high-dimensional dataset was integrated into a multiomic model that predicted the time to spontaneous labor [R = 0.85, 95% confidence interval (CI) [0.79 to 0.89], P = 1.2 × 10-40, N = 53, training set; R = 0.81, 95% CI [0.61 to 0.91], P = 3.9 × 10-7, N = 10, independent test set]. Coordinated alterations in maternal metabolome, proteome, and immunome marked a molecular shift from pregnancy maintenance to prelabor biology 2 to 4 weeks before delivery. A surge in steroid hormone metabolites and interleukin-1 receptor type 4 that preceded labor coincided with a switch from immune activation to regulation of inflammatory responses. Our study lays the groundwork for developing blood-based methods for predicting the day of labor, anchored in mechanisms shared in preterm and term pregnancies.


Assuntos
Início do Trabalho de Parto , Metaboloma , Proteoma , Biomarcadores , Feminino , Humanos , Início do Trabalho de Parto/imunologia , Início do Trabalho de Parto/metabolismo , Estudos Longitudinais , Gravidez
17.
Am J Perinatol ; 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34015838

RESUMO

OBJECTIVES: The aim of the study was to: (1) Identify (early in pregnancy) psychosocial and stress-related factors that predict risk of spontaneous preterm birth (PTB, gestational age <37 weeks); (2) Investigate whether "protective" factors (e.g., happiness/social support) decrease risk; (3) Use the Dhabhar Quick-Assessment Questionnaire for Stress and Psychosocial Factors™ (DQAQ-SPF™) to rapidly quantify harmful or protective factors that predict increased or decreased risk respectively, of PTB. STUDY DESIGN: This is a prospective cohort study. Relative risk (RR) analyses investigated association between individual factors and PTB. Machine learning-based interdependency analysis (IDPA) identified factor clusters, strength, and direction of association with PTB. A nonlinear model based on support vector machines was built for predicting PTB and identifying factors that most strongly predicted PTB. RESULTS: Higher levels of deleterious factors were associated with increased RR for PTB: General anxiety (RR = 8.9; 95% confidence interval or CI = 2.0,39.6), pain (RR = 5.7; CI = 1.7,17.0); tiredness/fatigue (RR = 3.7; CI = 1.09,13.5); perceived risk of birth complications (RR = 4; CI = 1.6,10.01); self-rated health current (RR = 2.6; CI = 1.0,6.7) and previous 3 years (RR = 2.9; CI = 1.1,7.7); and divorce (RR = 2.9; CI = 1.1,7.8). Lower levels of protective factors were also associated with increased RR for PTB: low happiness (RR = 9.1; CI = 1.25,71.5); low support from parents/siblings (RR = 3.5; CI = 0.9,12.9), and father-of-baby (RR = 3; CI = 1.1,9.9). These factors were also components of the clusters identified by the IDPA: perceived risk of birth complications (p < 0.05 after FDR correction), and general anxiety, happiness, tiredness/fatigue, self-rated health, social support, pain, and sleep (p < 0.05 without FDR correction). Supervised analysis of all factors, subject to cross-validation, produced a model highly predictive of PTB (AUROC or area under the receiver operating characteristic = 0.73). Model reduction through forward selection revealed that even a small set of factors (including those identified by RR and IDPA) predicted PTB. CONCLUSION: These findings represent an important step toward identifying key factors, which can be assessed rapidly before/after conception, to predict risk of PTB, and perhaps other adverse pregnancy outcomes. Quantifying these factors, before, or early in pregnancy, could identify women at risk of delivering preterm, pinpoint mechanisms/targets for intervention, and facilitate the development of interventions to prevent PTB. KEY POINTS: · Newly designed questionnaire used for rapid quantification of stress and psychosocial factors early during pregnancy.. · Deleterious factors predict increased preterm birth (PTB) risk.. · Protective factors predict decreased PTB risk..

18.
Semin Perinatol ; 45(4): 151408, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33875265

RESUMO

To understand the disparities in spontaneous preterm birth (sPTB) and/or its outcomes, biologic and social determinants as well as healthcare practice (such as those in neonatal intensive care units) should be considered. Disparities in sPTB have been largely intractable and remain obscure in most cases, despite a myriad of identified risk factors for and causes of sPTB. We still do not know how they lead to the different outcomes at different gestational ages and if they are independent of NICU practices. Here we describe an integrated approach to study the interplay between the genome and exposome, which may drive biochemistry and physiology and lead to health disparities.


Assuntos
Produtos Biológicos , Nascimento Prematuro , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Gravidez , Nascimento Prematuro/epidemiologia , Determinantes Sociais da Saúde
19.
20.
J Expo Sci Environ Epidemiol ; 31(3): 503-513, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33859340

RESUMO

BACKGROUND: Preterm birth is the leading cause of perinatal morbidity and mortality in the U.S. and disparities among racial and ethnic groups persist. While etiologies of preterm birth have not been fully elucidated, it is probable that environmental and social factors play a role. OBJECTIVE: We hypothesized that there is an interactive association between exposure to fine particulate matter (PM2.5) or ozone (O3) and neighborhood socioeconomic factors that increase the risk of preterm birth. METHODS: We conducted a retrospective study using geocoded birth certificate data between 2007 and 2011, daily ambient air quality data on PM2.5 and O3, and American Community Survey (2007-2011 5-year estimates) data to assess census tract-level socioeconomic factors in California urban counties. RESULTS: Our study found a small positive association between maternal exposures to PM2.5 and O3 and preterm birth that varied by gestational exposure period. In mixed-effects models, we found an increase in the risk of preterm birth for a one-unit change in PM2.5 averaged across the entire pregnancy (AOR = 1.02, 95% CI: 1.01, 1.02) and O3 during 3-months pre-pregnancy (AOR = 1.03, 95% CI: 1.02, 1.04). Interaction between census tract-level factors and air pollutants showed an increase in the risk of preterm birth among mothers living in higher socioeconomic areas, though, a fixed cohort bias sensitivity analysis showed these associations were not significant. SIGNIFICANCE: These findings substantiate previous studies that showed associations between air pollution and preterm birth, even as pollution levels have decreased. This study has important implications for policy decisions and may help inform research on potential mechanisms of preterm birth.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Nascimento Prematuro , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , California/epidemiologia , Feminino , Humanos , Recém-Nascido , Exposição Materna/efeitos adversos , Material Particulado/efeitos adversos , Material Particulado/análise , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Fatores Socioeconômicos
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