Association of ambient air pollution with depressive and anxiety symptoms in pregnant women: A prospective cohort study.
International journal of hygiene and environmental health
BACKGROUND:Air pollution is associated with depressive and anxiety symptoms in the general population. However, this relationship among pregnant women remains largely unknown. OBJECTIVE:To evaluate the association between pregnancy air pollution exposure and maternal depressive and anxiety symptoms during the third trimester assessed using the Center for Epidemiologic Studies-Depression and State-Trait Anxiety Inventory scales, respectively. METHODS:We analyzed 1481 pregnant women from a cohort study in Seoul. Maternal exposure to particulate matter with an aerodynamic diameter <2.5 μm (PM) and <10 μm (PM), as well as to nitrogen dioxide (NO) and ozone (O) for each trimester and the entire pregnancy was assessed at participant's residential address by land use regression models. We estimated the relative risk (RR) and corresponding confidence interval (CI) of the depressive and anxiety symptoms associated with an interquartile range (IQR) increase in PM, PM, NO, and O using modified Poisson regression. RESULTS:In single-pollutant models, an IQR increase in PM, PM, and NO during the second trimester was associated with an increased risk of depressive symptoms (PM RR = 1.15, 95% CI: 1.04, 1.27; PM RR = 1.13, 95% CI: 1.04, 1.23; NO RR = 1.15, 95% CI: 1.03, 1.29) after adjusting for relevant covariates. Similarly, an IQR increase in O during the third trimester was associated with an increased risk of depressive symptoms (RR = 1.09, 95% CI: 1.01, 1.18), while the IQR increase in O during the first trimester was associated with a decreased risk (RR = 0.89, 95% CI: 0.82, 0.96). Exposure to PM, PM, and NO during the second trimester was significantly associated with anxiety symptoms. The associations with PM and O in single-and multi-pollutant models were consistent. CONCLUSIONS:Our findings indicate that increased levels of particulate matter, NO, and O during pregnancy may elevate the risk of depression or anxiety in pregnant women.
10.1016/j.ijheh.2021.113823
Maternal body mass index, offspring body mass index, and blood pressure at 18 years: a causal mediation analysis.
International journal of obesity (2005)
OBJECTIVE:Understanding the natural history of hypertension is key to identifying prevention strategies. Previous work suggests that in utero exposures and offspring anthropometrics may play a role. This study examined the relationship between maternal pre-pregnancy body mass index (BMI) and the mediating role of childhood and adolescent BMI on offspring blood pressure at 18 years. METHODS:We performed multivariable regression and causal mediation analyses within 3217 mother - offspring pairs from the Avon Longitudinal Study of Parents and Children prospective birth cohort. The main exposure was maternal pre-pregnancy BMI, and the outcome was offspring blood pressure at 18 years of age categorized as normal or elevated. Latent trajectory analysis was used to quantify the mediator, offspring BMI trajectories, derived from multiple measurements throughout childhood and adolescence. Mediation analyses were repeated using current offspring BMI at 18 years as a continuous variable. RESULTS:Multivariable logistic regression revealed that for every 1 unit increase in maternal BMI, the risk of elevated blood pressure at 18 years of age increased by 5% (aOR: 1.05, 95% CI: 1.03-1.07; p < 0.001). The strength of this association was reduced after adjusting for offspring BMI trajectory (aOR: 1.03, 95% CI: 1.00-1.05; p = 0.017) and eliminated after adjusting for offspring BMI at 18 years (aOR: 1.00; 95% CI: 0.98-1.03; p = 0.70). Causal mediation analysis confirmed offspring BMI at 18 years as a mediator, where BMI trajectory accounted for 46% of the total effect of maternal BMI on elevated offspring blood pressure and current BMI account for nearly the entire effect. CONCLUSIONS:Maternal pre-pregnancy BMI is associated with an increased risk of elevated blood pressure in offspring at 18 years of age although it appears to be entirely mediated by offspring BMI.
10.1038/s41366-021-00930-2
Exposome and foetoplacental vascular dysfunction in gestational diabetes mellitus.
Molecular aspects of medicine
A balanced communication between the mother, placenta and foetus is crucial to reach a successful pregnancy. Several windows of exposure to environmental toxins are present during pregnancy. When the women metabolic status is affected by a disease or environmental toxin, the foetus is impacted and may result in altered development and growth. Gestational diabetes mellitus (GDM) is a disease of pregnancy characterised by abnormal glucose metabolism affecting the mother and foetus. This disease of pregnancy associates with postnatal consequences for the child and the mother. The whole endogenous and exogenous environmental factors is defined as the exposome. Endogenous insults conform to the endo-exposome, and disruptors contained in the immediate environment are the ecto-exposome. Some components of the endo-exposome, such as Selenium, vitamins D and B, adenosine, and a high-fat diet, and ecto-exposome, such as the heavy metals Arsenic, Mercury, Lead and Copper, and per- and polyfluoroakyl substances, result in adverse pregnancies, including an elevated risk of GDM or gestational diabesity. The impact of the exposome on the human placenta's vascular physiology and function in GDM and gestational diabesity is reviewed.
10.1016/j.mam.2021.101019
Influence of ambient temperature and diurnal temperature variation on the premature rupture of membranes in East China: A distributed lag nonlinear time series analysis.
Yang Dongjian,Chen Lei,Yang Ya,Shi Jingjin,Xu Jingjing,Li Cheng,Wu Yanting,Ji Xinhua
Environmental research
BACKGROUND:Extreme ambient temperature has an adverse effect on pregnancy outcomes, but the conclusions have been inconsistent. The influence of ambient temperature and diurnal temperature variation on the premature rupture of membranes (PROM) needs further study. METHODS AND FINDINGS:The daily data of PROMs, daily meteorological and air pollutant were obtained. After controlling for potential confounding factors, the quasi-Poisson generalized additive model (GAM) combined with the distributed lag nonlinear model (DLNM) was used to analyze the association between temperature or diurnal temperature variation and PROM, including preterm premature rupture of membranes (PPROM) and term premature rupture of membranes (term PROM). Compared with the median temperature(18.7 °C), the mean temperature of 5-7 days lagging beyond 31.5 °C and below -1.5 °C was positively correlated with PROM; the mean temperature had more sensitive effect on the term PROM. Exposure to extremely high temperatures (97.5th percentile, 32 °C) had a 6-day lagging relative risk (RR) (95% CI: 1.005-1.160) of 1.08 for PROM and a 6-day lagging RR of 1.079 (95% CI: 1.005-1.159) for term PROM; Exposure to a high diurnal temperature variation (diurnal temperature variation greater than 16 °C) was positively correlated with the term PROM. Compared with the 2.5th percentile diurnal temperature variation (2 °C), exposure to the 95th percentile diurnal temperature variation (17 °C) significantly increased the risk of term PROM (RR: 1.229, 95% CI: 1.029-1.467). CONCLUSIONS:Exposure to a high-temperature and a high diurnal temperature variation environment will increase the relative risks of PROM. For pregnant women in the 3rd trimester, it is important to reduce exposure to extremely high-temperatures and greater diurnal temperature changes.
10.1016/j.envres.2021.111145
Prenatal exposure to maternal stressful life events and earlier age at menarche: the Raine Study.
Bräuner E V,Koch T,Juul A,Doherty D A,Hart R,Hickey M
Human reproduction (Oxford, England)
STUDY QUESTION:Is there an association between prenatal exposure to stressful life events and age at menarche, and does childhood BMI mediate this association? SUMMARY ANSWER:Girls exposed to prenatal stress had a slightly earlier age at menarche, but this association did not show a dose-response effect and was not mediated by childhood offspring BMI. WHAT IS ALREADY KNOWN:Prenatal stress may impact on reproductive function in females including age at menarche, but human data are very limited. High childhood BMI is known to be associated with earlier age at menarche. Only one small study has measured the association between maternal stress and age at menarche and reported that childhood BMI mediated the association between maternal stress and earlier age at menarche. However, neither maternal stress nor age at menarche was prospectively recorded and the study was limited to 31 mother-daughter pairs. STUDY DESIGN, SIZE, DURATION:The Raine Study is a large prospective population-based pregnancy cohort study (n = 1414 mother-daughter pairs) continuously followed from prenatal life through to adolescence. In the present study, we examined the association between exposure to maternal stressful life events during early, late and total gestation and age at menarche in offspring using 753 mother-daughter pairs with complete case information. PARTICIPANTS/MATERIALS, SETTING, METHODS:Mothers prospectively reported stressful life events during pregnancy at 18 and 34 weeks using a standardized 10-point questionnaire. Exact date of menarche was assessed using a purpose-designed questionnaire at 8, 10, 14 and 17 years of age. Complete information on exposure, outcome and confounding variables was obtained from 753 mothers-daughter pairs. Multivariate linear regression complete case analysis was used to examine associations between maternal stressful life event exposure and age at menarche. Potential selection bias was evaluated using multiple imputations (50 datasets). The mediating effects of offspring childhood BMI (ages 5, 8, or 10 years) on these associations were measured in separate sub-analyses. MAIN RESULTS AND ROLE OF CHANCE:Most (580/753, 77%) daughters were exposed to at least one prenatal stressful life event. Exposure to maternal stressful life events during the entire pregnancy was associated with a non-linear earlier age at menarche. Exposure to one event and two or more psychological stressful events was associated with a 3.5 and 1.7-month earlier onset of puberty, respectively when compared to the reference group with no exposure maternal stressful life events. The estimates from multiple imputation with 50 datasets were comparable with complete case analysis confirming the existence of an underlying effect. No separate significant effects were observed for exposure during early or late gestation. The association between prenatal stressful events and age at menarche was not mediated by childhood BMI in the offspring. LIMITATIONS, REASONS FOR CAUTION:Stressful life events may have affected pregnant women in different ways and self-perceived maternal stress severity may have provided a more precise estimate of gestational psychological stress. The observed non-linear U-shape of the association between maternal psychological stress and age at menarche did not reflect a dose-response. This suggests that the first exposure to prenatal stress exerts a greater effect on fetal reproductive development. A potential mechanism is via dramatic initial activation of the hypothalamic-pituitary-adrenal (HPA) axis following the first stressful life event which is greater than that observed following subsequent exposure to two or more maternal stressful life events. Whilst we adjusted for a priori chosen confounders, we cannot exclude residual confounding or confounding by factors we did not include. Maternal age at menarche was not available so the effects of familial history/genetics could not be assessed. There was a large loss due to the number of girls with no information on date of menarche and missing confounder information implying risk of selection bias and multiple imputation analyses did not fully exclude this risk (similar direction but slightly weaker estimate magnitude). WIDER IMPLICATIONS OF THE FINDINGS:Menarche is a sentinel reproductive event and earlier age at menarche carries implications for psychological, social and reproductive health and for long-term risk of common non-communicable diseases. Understanding the factors regulating age at menarche has extensive health implications. This is the first population-based cohort study in humans to demonstrate that prenatal psychological stress might directly modify age at menarche. STUDY FUNDING/COMPETING INTEREST(S):Dr. Bräuner and Trine Koch's salaries were supported by Doctor Sofus Carl Emil Friis and spouse Olga Doris Friis foundation, The Danish Cancer Society (Kræftens Bekæmpelse, RP15468, R204-A12636, Denmark) and The Danish Health Foundation (Helsefonden, F-22181-23, Denmark). Martha Hickey was funded by NHMRC Practitioner Fellowships. The funding bodies played no role in the design, collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. Dr. Hart has received personal fees in his function as the Medical Director of Fertility Specialists of Western Australia and received educational sponsorship grants from MSD, Merck-Serono and from Ferring Pharmaceuticals. Dr Hart has also received personal fees from Shareholders in Western IVF outside the submitted work. TRIAL REGISTRATION NUMBER:NA.
10.1093/humrep/deab039
Gestational exposures to outdoor air pollutants in relation to low birth weight: A retrospective observational study.
Zou Zhijun,Liu Wei,Huang Chen,Cai Jiao,Fu Qingyan,Sun Chanjuan,Zhang Jialing
Environmental research
Findings for impacts of outdoor air pollutants on birth outcomes were controversial. We performed a retrospective observational study in 2527 preschoolers of Shanghai, China and investigated associations of duration-averaged concentrations of outdoor sulphur dioxide (SO), nitrogen dioxide (NO), and particulate matter with an aerodynamic diameter ≤ 10 μm (PM) in different months and trimesters of gestation, with preterm birth (PB), low birth weight (LBW), term low birth weight (T-LBW), and small for gestational age (SGA). Daily concentrations of outdoor air pollutants were collected in each residence-located district. Parents reported health information. In the multivariate logistic regression analyses, exposures to outdoor NO were consistently associated with the higher odds of LBW and T-LBW. These associations were generally stronger for early months than for later months of the gestation. Adjusted odds ratios generally were larger in multi-pollutant model than in single-pollutant model. Exposure to NO in the first month of the gestation was significantly associated with T-LBW (adjusted OR, 95%CI: 1.91, 1.02-3.58 for increment of interquartile range (18.5 μg/m); p-value = 0.044) in multi-pollutant model. This association was stronger in girls, renters, and children whose mothers ≥30 years-old, with household dampness-related exposures, and with parental smoking during pregnancy. Our results indicate that exposure to NO during gestation perhaps is a risk factor for LBW and T-LBW, and effects of NO exposures could be greater during early periods than during later periods of gestation.
10.1016/j.envres.2020.110354
Maternal life and work stressors during pregnancy and asthma in offspring.
Pape Kathrine,Liu Xiaoqin,Sejbæk Camilla Sandal,Andersson Niklas Worm,Larsen Ann Dyreborg,Bay Hans,Kolstad Henrik Albert,Bonde Jens Peter Ellekilde,Olsen Jørn,Svanes Cecilie,Hansen Kirsten Skamstrup,Rugulies Reiner,Hougaard Karin Sørig,Schlünssen Vivi
International journal of epidemiology
BACKGROUND:Maternal stressors during pregnancy are potential risk factors for asthma in offspring. However, previous studies have been limited by the use of self-reported data focusing on stressors either in private life or at work. This study examined the association between maternal stressors both in private life and at work during pregnancy and asthma in offspring. METHODS:In the Danish National Birth Cohort, 75 156 live-born singletons born during 1996-2002 were identified. Maternal information on job title were available around weeks 12-16 of gestation. Data on maternal bereavement, life-threatening illness, suicide attempt and alcohol or drug abuse of a close relative and offspring childhood asthma (3-10 years of age) were obtained from Danish nationwide registers. Maternal psychosocial work stressors (job control, psychological job demands, emotional job demands, work-related violence and threats of work-related violence) were estimated by the use of job-exposure matrices. The association between maternal stress and childhood asthma was analysed in Cox models adjusted for maternal age, comorbidity and parity. RESULTS:Neither private-life nor work stressors were related to onset of asthma in offspring. Separate analyses by parental atopy or onset of asthma in offspring supported the main findings. CONCLUSIONS:This study does not support an elevated risk of childhood asthma related to exposure to stress during pregnancy.
10.1093/ije/dyaa133
Prepregnancy renal function and risk of preterm birth and related outcomes.
Harel Ziv,Park Alison L,McArthur Eric,Hladunewich Michelle,Dirk Jade S,Wald Ron,Garg Amit X,Ray Joel G
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne
BACKGROUND:Prepregnancy kidney dysfunction has been associated with preterm birth, which is the leading cause of neonatal morbidity and mortality; however, the relation is not well understood. We determined the risk of preterm birth in women with prepregnancy kidney dysfunction, defined using pregnancy-specific serum creatinine cut points. METHODS:This population-based cohort study in the province of Ontario, Canada, involved women aged 16 to 50 years who had a singleton birth between 2006 and 2016 and measurement of serum creatinine within 10 weeks preceding their estimated conception date. The exposure was abnormally elevated prepregnancy serum creatinine, defined as greater than the 95th percentile (> 77 μmol/L), a value derived from a population-based sample of women without known kidney disease who became pregnant soon after the measurement was obtained. The main outcome was any preterm birth from 23 to 36 weeks' gestation. Secondary outcomes included provider-initiated preterm birth before 37 weeks' gestation and spontaneous preterm birth before 37 weeks. RESULTS:Among 55 946 pregnancies, preterm birth before 37 weeks' gestation occurred in 3956 women (7.1%). The risk of preterm birth before 37 weeks was higher among women with prepregnancy creatinine above the 95th percentile, relative to those with prepregnancy creatinine at or below the 95th percentile (9.1% v. 7.0%; adjusted relative risk [RR] 1.23, 95% confidence interval [CI] 1.09 to 1.38). The effect was significant for provider-initiated preterm birth (adjusted RR 1.30, 95% CI 1.11 to 1.52) but not for spontaneous preterm birth (adjusted RR 1.12, 95% CI 0.91 to 1.37). INTERPRETATION:Given that prepregnancy kidney dysfunction conferred an increased risk of preterm birth, measurement of serum creatinine (a relatively inexpensive blood test) may form part of the assessment of risk for preterm birth among those planning pregnancy.
10.1503/cmaj.200089
Ambient air pollution exposure during the late gestational period is linked with lower placental iodine load in a Belgian birth cohort.
Neven Kristof Y,Wang Congrong,Janssen Bram G,Roels Harry A,Vanpoucke Charlotte,Ruttens Ann,Nawrot Tim S
Environment international
BACKGROUND:Adequate intake of iodine is required for the production of thyroid hormones and contributes in pregnant women to a healthy brain development and growth in their offspring. To date, some evidence exists that fine particulate air pollution is linked with the fetal thyroid hormone homeostasis. However, possible effects of air pollutants on the placental iodine storage have not been investigated so far. OBJECTIVES:We investigated the association between air pollution exposure to particulate matter with a diameter less than 2.5 µm (PM), NO, and black carbon and the placental iodine load. METHODS:The current study is part of the ENVIRONAGE birth cohort and included 470 mother-newborn pairs. Iodine concentrations were measured in placental tissue. A high-resolution air pollution model was used to estimate the daily exposure to PM, NO, and black carbon over the entire pregnancy based on the maternal residential addresses. Distributed lag nonlinear models (DLNMs) were used to estimate gestational week-specific associations between placental iodine concentrations and the air pollutants to understand the impact of specific exposure windows. RESULTS:PM showed a positive association with placental iodine concentration between the 16 and 22 week of gestation. In contrast, a significant inverse association between PM and placental iodine concentration was observed in gestational weeks 29-35. The effect estimate, for a 5 µg/m increment in PM concentration, was the strongest at week 32 (β -0.11 µg/kg; 95%CI: -0.18 to -0.03). No associations were observed between placental iodine concentrations and NO or black carbon. Assuming causality, we estimated that placental iodine mediated 26% (-0.33 pmol/L; 95%CI: -0.70 to 0.04 pmol/L) of the estimated effect of a 5 µg/m increment in PM exposure on cord blood free thyroxine (FT) concentrations. CONCLUSION:In utero exposure to particulate matter during the third trimester of pregnancy is linked with a lower placental iodine load. Furthermore, the effect of air pollution on cord blood FT levels was partially mediated by the placental iodine load.
10.1016/j.envint.2020.106334
Exposures to phthalates and bisphenols in pregnancy and postpartum weight gain in a population-based longitudinal birth cohort.
Philips Elise M,Jaddoe Vincent W V,Deierlein Andrea,Asimakopoulos Alexandros G,Kannan Kurunthachalam,Steegers Eric A P,Trasande Leonardo
Environment international
BACKGROUND:Experimental evidence suggests that exposures to phthalates and bisphenols may interfere with processes related to glucose and lipid metabolism, insulin sensitivity, and body weight. Few studies have considered the possible influence of chemical exposures during pregnancy on maternal weight gain or metabolic health outcomes postpartum. OBJECTIVE:To examine the associations of early and mid-pregnancy bisphenol and phthalate urine concentrations with maternal weight gain 6 years postpartum. METHODS:We analyzed urine samples for bisphenol, phthalate and creatinine concentrations from early and mid-pregnancy in 1192 women in a large, population-based birth cohort in Rotterdam, the Netherlands, and examined postpartum weight gain using maternal anthropometrics before pregnancy and 6 years postpartum. We have used covariate-adjusted linear regressions to evaluate associations of early and mid-pregnancy bisphenols and phthalate metabolites with weight change. Mediator and interaction models have been used to assess the role of gestational weight gain and breastfeeding, respectively. Sensitivity analysis is performed among women without subsequent pregnancies. RESULTS:Among all 1192 mothers included in the analysis, each log unit increase in the average bisphenol A and all assessed phthalate groupings were associated with increased maternal weight gain. As a proxy for phthalate exposure, each log unit increase in averaged phthalic acid was associated with 734 g weight gain (95% CI 273-1196 g) between pre-pregnancy and 6 years postpartum. Mediation by gestational weight gain was not present. Breastfeeding and ethnicity did not modify the effects. Stratification revealed these associations to be strongest among overweight and obese women. Among women without subsequent pregnancies (n = 373) associations of bisphenols, HMW phthalate metabolites and di-2-ethylhexylphthalate metabolites attenuated. For phthalic acid, LMW phthalate metabolites and di-n-octylphthalate metabolites associations increased. Similarly to the whole group, stratification yielded significant results among overweight and obese women. DISCUSSION:In a large population-based birth cohort, early and mid-pregnancy phthalate exposures are associated with weight gain 6 years postpartum, particularly among overweight and obese women. These data support ongoing action to replace phthalates with safer alternatives.
10.1016/j.envint.2020.106002
Exposure to multiple metals and prevalence for preeclampsia in Taiyuan, China.
Wang Ying,Wang Keke,Han Tianbi,Zhang Ping,Chen Xi,Wu Weiwei,Feng Yongliang,Yang Hailan,Li Mei,Xie Bingjie,Guo Pengge,Warren Joshua L,Shi Xiaoming,Wang Suping,Zhang Yawei
Environment international
BACKGROUND:Several studies with small sample size have reported inconsistent associations between single metal and preeclampsia (PE). Very few studies have investigated metal mixtures and PE. METHODS:Blood concentrations of chromium (Cr), cadmium, mercury (Hg), arsenic (As), lead (Pb), nickel, cobalt, and antimony were measured using inductively coupled plasma-mass spectrometry among 427 PE women and 427 matched controls from Taiyuan, China. Multivariate logistic regression models, weighted quantile sum (WQS) regression, and principal component analysis were employed to examine exposure to single metals and metal mixtures in relation to PE. RESULTS:An increased prevalence of PE was associated with Cr (OR = 1.76, 95% CI: 1.18, 2.62 and 1.90, 1.22, 2.93 for the middle and high vs. low), Hg (OR = 1.60, 95% CI: 1.08, 2.38 for the high vs. low) and As (OR = 1.64, 95% CI: 1.07, 2.52 for the middle vs. low). The WQS index, predominated by Cr, Hg, Pb, and As, was positively associated with PE. A principal component characterized by Cr and As also exhibited excessive association with PE. The highest PE prevalence was found among women who were overweight/obese before pregnancy and had high Cr levels compared to women who had pre-pregnancy normal body mass index (BMI) and low Cr levels. CONCLUSIONS:Our study provided evidence that exposure to multiple metals was associated with increased prevalence of PE, and the observed association with multiple metals was dominated by Cr, As. Our study also suggested that pre-pregnancy BMI might modify the association between Cr and PE.
10.1016/j.envint.2020.106098
Assessing the effects of non-optimal temperature on risk of gestational diabetes mellitus in a cohort of pregnant women in Guangzhou, China.
Zhang Huanhuan,Wang Qiong,Benmarhnia Tarik,Jalaludin Bin,Shen Xiaoting,Yu Zengli,Ren Meng,Liang Qianhong,Wang Jingzhe,Ma Wenjun,Huang Cunrui
Environment international
Previous observational studies have shown that exposure to ambient temperature and air pollution were associated with the incidence of gestational diabetes mellitus (GDM). However, the susceptible time window of non-optimal temperature on GDM is still unknown, and the interaction with air pollution has not been examined. We conducted a prospective cohort study in Guangzhou, China to investigate the windows of susceptibility of temperature extremes and variability on the risk of GDM and to explore any interaction effect with air pollution. Daily maximum (T), minimum temperature (T) and diurnal temperature range (DTR) were obtained from Guangdong Meteorological Service. Distributed lag non-linear models with a logistic regression were applied to assess the effect of temperature extremes and DTR in different weeks of gestation on GDM. To examine the interaction effect, relative excess risk due to interaction index, attributable proportion and synergy index were calculated. There were 5,165 pregnant women enrolled, of which 604 were diagnosed with GDM (11.7%). Compared with a reference temperature (50th percentile of T), we found that extreme high temperature (99th percentile of T) exposure during 21st and 22nd gestational weeks was associated with an increased risk of GDM. Extreme low temperature (1st percentile of T) exposure during 14th to 17th weeks increased the risk of GDM. We observed that per 1 °C increment of DTR during 21st to 24th weeks was associated with an elevated GDM risk. No interaction effect of temperature extremes or variability with air pollution on GDM were observed. Our results suggested that non-optimal temperature is an independent risk factor of GDM. The time window of susceptibility for extreme temperatures and DTR exposure on the risk of GDM generally occurred in second trimester of pregnancy. In the context of climate change, our study has important implications for reproductive health and justifies more research in different climate zones.
10.1016/j.envint.2021.106457
The association between maternal exposure to outdoor air pollutants, inflammatory response, and birth weight in healthy women.
Environmental research
Increased maternal inflammatory response has been noted in women with pregnancies complicated by preterm birth and small-for-gestational age infants. However, the association between gestational exposure to air pollutants, maternal inflammatory response, and fetal growth remains unclear. In this study, we aimed to investigate the association between exposure to air pollutants during pregnancy and the concentration of inflammatory indicators in maternal and fetal circulations, as well as fetal growth. We recruited 108 healthy pregnant women living in northern (n = 55) and southern (n = 53) areas of Taiwan and prospectively collected information of exposure to outdoor air pollutants throughout gestation. Maternal blood from each trimester and umbilical cord blood after delivery were collected and analyzed for inflammatory indicators including high sensitivity C-reactive protein (hs-CRP), interleukin-1β (IL-1β), and tumor necrosis factor (TNF)-α. Our results showed that exposure to particulate matter less than or equal to 10 μm (PM) and ozone (O) during the first trimester had a direct effect on reduction of birth weight, but the direct effect of PM mediated by hs-CRP and the direct effect of O mediated by TNF-α on fetal birth weight were not significant. Exposure to PM and PM during the second and third trimesters also directly affected birth weight. Furthermore, exposure to sulfur dioxide (SO) caused changes in the concentrations of TNF-α in maternal blood during the second trimester, which subsequently resulted in reduced fetal weight. Together, these results indicate that exposure to air pollutants may cause both direct and indirect effects on the reduction of fetal weight.
10.1016/j.envres.2021.110921
Ambient air pollution and stillbirth: An updated systematic review and meta-analysis of epidemiological studies.
Zhang Huanhuan,Zhang Xiaoan,Wang Qiong,Xu Yuanzhi,Feng Yang,Yu Zengli,Huang Cunrui
Environmental pollution (Barking, Essex : 1987)
Stillbirth has a great impact on contemporary and future generations. Increasing evidence show that ambient air pollution exposure is associated with stillbirth. However, previous studies showed inconsistent findings. To clarify the effect of maternal air pollution exposure on stillbirth, we searched for studies examining the associations between air pollutants, including particulate matter (diameter ≤ 2.5 μm [PM] and ≤10 μm [PM]) and gaseous pollutants (sulfur dioxide [SO], nitrogen dioxide [NO], carbon monoxide [CO] and ozone [O]), and stillbirth published in PubMed, Web of Science, Embase and Cochrane Library until December 11, 2020. The pooled effect estimates and 95% confidence intervals (CI) were calculated, and the heterogeneity was evaluated using Cochran's Q test and I statistic. Publication bias was assessed using funnel plots and Egger's tests. Of 7546 records, 15 eligible studies were included in this review. Results of long-term exposure showed that maternal third trimester PM and CO exposure (per 10 μg/m increment) increased the odds of stillbirth, with estimated odds ratios (ORs) of 1.094 (95% CI: 1.008-1.180) and 1.0009 (95% CI: 1.0001-1.0017), respectively. Entire pregnancy exposure to PM was also associated with stillbirth (OR: 1.103, 95% CI: 1.074-1.131). A 10 μg/m increment in O in the first trimester was associated with stillbirth, and the estimated OR was 1.028 (95% CI: 1.001-1.055). Short-term exposure (on lag day 4) to O was also associated with stillbirth (OR: 1.002, 95% CI: 1.001-1.004). PM, SO and NO exposure had no significant effects on the incidence of stillbirth. Additional well-designed cohort studies and investigations regarding potential biological mechanisms are warranted to elaborate the suggestive association that may help improve intergenerational inequality.
10.1016/j.envpol.2021.116752
Safety of Antimicrobials During Pregnancy: A Systematic Review of Antimicrobials Considered for Treatment and Postexposure Prophylaxis of Plague.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND:The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for plague during pregnancy. METHODS:We searched 5 scientific literature databases for primary sources on the safety of 9 antimicrobials considered for plague during pregnancy (amikacin, gentamicin, plazomicin, streptomycin, tobramycin, chloramphenicol, doxycycline, sulfadiazine, and trimethoprim-sulfamethoxazole [TMP-SMX]) and abstracted data on maternal, pregnancy, and fetal/neonatal outcomes. RESULTS:Of 13 052 articles identified, 66 studies (case-control, case series, cohort, and randomized studies) and 96 case reports were included, totaling 27 751 prenatal exposures to amikacin (n = 9), gentamicin (n = 345), plazomicin (n = 0), streptomycin (n = 285), tobramycin (n = 43), chloramphenicol (n = 246), doxycycline (n = 2351), sulfadiazine (n = 870), and TMP-SMX (n = 23 602). Hearing or vestibular deficits were reported in 18/121 (15%) children and 17/109 (16%) pregnant women following prenatal streptomycin exposure. First trimester chloramphenicol exposure was associated with an elevated risk of an undescended testis (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.7). Doxycycline was associated with cardiovascular malformations (OR 2.4, 95% CI 1.2-4.7) in 1 study and spontaneous abortion (OR 2.8, 95% CI 1.9-4.1) in a separate study. First trimester exposure to TMP-SMX was associated with increased risk of neural tube defects (pooled OR 2.5, 95% CI 1.4-4.3), spontaneous abortion (OR 3.5, 95% CI 2.3-5.6), preterm birth (OR 1.5, 95% CI 1.1-2.1), and small for gestational age (OR 1.6, 95% CI 1.2-2.2). No other statistically significant associations were reported. CONCLUSIONS:For most antimicrobials reviewed, adverse maternal/fetal/neonatal outcomes were not observed consistently. Prenatal exposure to streptomycin and TMP-SMX was associated with select birth defects in some studies. Based on limited data, chloramphenicol and doxycycline may be associated with adverse pregnancy or neonatal outcomes; however, more data are needed to confirm these associations. Antimicrobials should be used for treatment and PEP of plague during pregnancy; the choice of antimicrobials may be influenced by these data as well as information about the risks of plague during pregnancy.
10.1093/cid/ciz1231
Prenatal exposure to phthalates and maternal metabolic outcomes in a high-risk pregnant Latina population.
Zukin Helen,Eskenazi Brenda,Holland Nina,Harley Kim G
Environmental research
BACKGROUND:Phthalates are a group of endocrine disrupting chemicals that are heavily used throughout industry in flexible plastic and personal-care products. As a result, detectable levels of their metabolites are readily found in humans. Some studies have shown associations of phthalates with diabetes, but associations with gestational diabetes mellitus (GDM) are less clear. OBJECTIVE:To investigate the association of 11 prenatal urinary phthalate metabolites and development of GDM, impaired glucose tolerance (IGT), continuous plasma glucose level, and excessive gestational weight gain (GWG) in a population of pregnant Latina women (N = 415) enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study. METHODS:Phthalate metabolite levels were measured via mass spectrometry from two urine samples collected in the end of the first and second trimester. Maternal plasma glucose levels, prior diabetes diagnosis, GDM diagnosis, and weight gain were abstracted from medical records. Multiple regression was used to evaluate the association between the average of the two urinary phthalate metabolites levels and maternal metabolic outcomes. In our sensitivity analysis, phthalate levels were categorized by level (as quartiles of exposure) and by timing of urine sample collection (as taken in first and second half of pregnancy). RESULTS:Consistent with findings from a nationally representative sample, all of the individual phthalate metabolites were detected in majority of mothers. Thirty-one mothers (7.5%) were diagnosed with GDM, 49 mothers (14.7%) displayed IGT, and 223 mothers (55.1%) gained an excessive amount of weight during their pregnancy. MEP concentrations were associated with an increased odds of excessive GWG (OR: 1.1, 95% CI: 1.0 to 1.3). We did not find an association between any phthalate metabolite and any maternal glucose outcome. CONCLUSION:Contrary to previous studies, our findings do not support an association of prenatal phthalate levels and increased odds for hyperglycemia, IGT, or GDM. But, we did find an increased odds of excessive GWG, a well-known risk factor for GDM.
10.1016/j.envres.2021.110712
Chronic exposure to air pollution and risk of mental health disorders complicating pregnancy.
Environmental research
BACKGROUND:Air pollution is associated with mental health in the general population, but its influence on maternal mental health during pregnancy has not been assessed. OBJECTIVE:We evaluated the relationship between unspecified mental disorders complicating pregnancy and depression with average air pollution exposure during 3-months preconception, first trimester and whole pregnancy. METHODS:Ambient air pollution was derived from a modified Community Multiscale Air Quality model and mental health diagnoses were based on electronic intrapartum medical records. Logistic regression models assessed the odds of unspecified mental disorder complicating pregnancy (n = 11,577) and depression (n = 9793) associated with an interquartile range increase in particulate matter (PM) less than 2.5 μm (PM), PM, carbon monoxide (CO), nitrogen dioxide (NO), nitrogen oxide (NO), sulfur dioxide (SO), and ozone (O). Pregnancies without mental health disorders were the reference group (n = 211,645). Models were adjusted for maternal characteristics and study site; analyses were repeated using cases with no additional mental health co-morbidity. RESULTS:Whole pregnancy exposure to PM, PM, NO, and NO was associated with a 29%-74% increased odds of unspecified mental disorders complicating pregnancy while CO was associated with 31% decreased odds. Results were similar for depression: whole pregnancy exposure to PM, PM, NO, and NO was associated with 11%-21% increased odds and CO and O were associated with 16%-20% decreased odds. SO results were inconsistent, with increased odds for unspecified mental disorders complicating pregnancy and decreased odds for depression. While most findings were similar or stronger among cases with no co-morbidity, PM and NO were associated with reduced risk and SO with increased risk for depression only. DISCUSSION:Whole pregnancy exposure to PM, PM, NO, and NO were associated with unspecified mental disorder complicating pregnancy and depression, but some results varied for depression only. These risks merit further investigation.
10.1016/j.envres.2021.110937
Exposure to perfluoroalkyl substances and blood pressure in pregnancy among 1436 women from the Odense Child Cohort.
Environment international
BACKGROUND:Previous studies of association between exposure to poly- and perfluoroalkyl substances (PFAS) and gestational hypertension (GH) and preeclampsia (PE) have shown conflicting results, but most dichotomized outcome and did not study continuous blood pressure (BP) changes. OBJECTIVES:To study the association between PFAS exposure in early pregnancy and maternal BP trajectories in pregnancy, gestational hypertension and preeclampsia. METHODS:1436 women were enrolled in the Odense Child Cohort in early pregnancy and had a serum sample drawn, from which perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) were measured using LC-MS/MS. Repeated BP measurements through pregnancy and information on PE were obtained from hospital files. Adjusted linear mixed models were used to investigate association between PFAS exposure and BP trajectory. Associations between PFAS and PE and GH were assessed by Cox proportional hazards model. RESULTS:All women had measurable concentrations of PFAS. In all of many comparisons higher PFAS exposure (apart from PFHxS) was associated with higher systolic (SBP) and diastolic (DBP) blood pressures, although not all were significant, which is unlikely to be due to chance. After adjustment, each doubling in PFOS or PFOA exposure was associated with 0.47 mmHg (95% CI: -0.13; 1.08) and 0.36 mmHg (-0.19; 0.92) higher SBP; and 0.58 mmHg (0.13; 1.04) and 0.37 mmHg (-0.05; 0.79) higher DBP. No clear associations between PFAS exposure and PE or GH were found. DISCUSSION:The magnitude of the association between PFAS exposure and BP might appear small, statistically non-significant and the possible clinical importance low. However, at a population level this may slightly shift the distribution of BP towards an increased incidence of GH. If BP increases in pregnancy, it may have long-term impact on health not only of the pregnant woman but also of her offspring.
10.1016/j.envint.2021.106442
Prenatal Exposure to Specific PM Chemical Constituents and Preterm Birth in China: A Nationwide Cohort Study.
Cai Jing,Zhao Yan,Kan Julia,Chen Renjie,Martin Randall,van Donkelaar Aaron,Ao Junjie,Zhang Jun,Kan Haidong,Hua Jing
Environmental science & technology
Exposure to fine particulate matter (PM) during pregnancy has been associated with preterm birth (PTB). However, the existing evidence is inconsistent, and the roles of specific PM chemical constituents remain unclear. Based on the China Labor and Delivery Survey, we included birth data from 89 hospitals in 25 provinces in mainland China, and conducted a national multicenter cohort study to examine the associations of PM and its chemical constituents with PTB risk in China. We applied satellite-based models to predict prenatal PM mass and six main component exposure. Multilevel logistic regression analysis was used to examine the associations, controlling for sociodemographic characteristics, seasonality, and spatial variation. We observe an increased PTB risk with an increase in PM mass and the most significant association is found during the third trimester when the adjusted odds ratio (OR) per interquartile range increases in PM total mass is 1.12 (95% confidence Interval, CI: 1.05-1.20). Infants conceived by assisted reproductive technology (ART) show greater PTB risk associated with PM exposure (OR = 1.33, 95% CI: 1.05-1.69) than those conceived naturally (OR = 1.11, 95% CI: 1.03-1.19). We also find black carbon, sulfate, ammonium and nitrate, often linked to fossil combustion, have comparable or larger estimates of the effect (OR = 1.07-1.14) than PM. Our findings provide evidence that components mainly from fossil fuel combustion may have a perceptible influence on increased PTB risk associated with PM exposure in China. Additionally, compared to natural conception, conception through ART may be more susceptible to PM exposure.
10.1021/acs.est.0c02373
Urinary antibiotic exposure across pregnancy from Chinese pregnant women and health risk assessment: Repeated measures analysis.
Geng Menglong,Liu Kaiyong,Huang Kun,Zhu Yitian,Ding Peng,Zhang Jingjing,Wang Baolin,Liu Wenwen,Han Yan,Gao Hui,Wang Sheng,Chen Guanjun,Wu Xiaoyan,Tao Fangbiao
Environment international
Multiple antibiotics are widely used in clinic practice and livestock husbandry, but exposure data based on repeated measurements are scarce among pregnant women. Here, we biomonitored 41 antibiotics and their two metabolites in urine samples from 3235 pregnant women over three trimesters. Spearman's correlation coefficient, intraclass correlation coefficient (ICC), percentile analysis and linear mixed models were employed to evaluate the correlations, variability, co-exposure patterns and predictors of antibiotics, respectively. Pregnant urinary creatinine-adjusted concentrations of antibiotics were used to estimate daily exposure dose and assessed health risks. The target antibiotics were detected in more than 90% of urine samples, primarily as preferred as veterinary antibiotics (PVAs), and the 95th percentile urinary concentrations of each individual antibiotics were range from below the limits of detection to 5.74 ng/mL. We observed considerable within-subject variation (ICC: 0.05-0.63) of urinary antibiotics concentrations during pregnancy. More than half pregnant women were co-exposed to two or more antibiotics of different usage classes, while both co-exposure to high percentiles of three usage antibiotics at one trimester or exposure to single usage antibiotics at high-dose through three trimesters were infrequent in the study population, and most pregnant women were continuously exposed to low-dose PVAs across pregnancy. A total of 4.5% samples were showed hazard index values exceeding 1 during entire pregnancy. Urinary levels of antibiotics associated with residence, maternal age and education, pre-pregnancy BMI, household income and gestational week, especially vary by sampling seasons. Taken together, most pregnant women were frequently exposure to low-dose PVAs across pregnancy and some were in a health risk associated with the disturbance of gut microbiota. Multiple measurements of urinary antibiotic concentrations are essential to more accurate charactering the exposure levels during pregnancy. Several predictors of urinary antibiotics should be taken into consideration in future researches.
10.1016/j.envint.2020.106164
Psychosocial status modifies the effect of maternal blood metal and metalloid concentrations on birth outcomes.
Environment international
BACKGROUND:Metal exposure and psychosocial stress in pregnancy have each been associated with adverse birth outcomes, including preterm birth and low birth weight, but no study has examined the potential interaction between them. OBJECTIVES:We examined the modifying effect of psychosocial stress on the association between metals and birth outcomes among pregnant women in Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) birth cohort study. METHODS:In our analysis of 682 women from the PROTECT study, we measured 16 essential and non-essential metals in blood samples at two time points. We administered questionnaires to collect information on depression, perceived stress, social support, and life experience during pregnancy. Using K-means clustering, we categorized pregnant women into one of two groups: "good" and "poor" psychosocial status. We then evaluated whether the effect of blood metals (geometric average) on adverse birth outcomes (gestational age, preterm birth [overall and spontaneous], birth weight z-score, small for gestation [SGA], large for gestation [LGA]) vary between two clusters of women, adjusting for maternal age, maternal education, pre-pregnancy body mass index (BMI), and second-hand smoke exposure. RESULTS:Blood manganese (Mn) was associated with an increased odds ratio (OR) of overall preterm birth (OR/interquartile range [IQR] = 2.76, 95% confidence interval [CI] = 1.25, 6.12) and spontaneous preterm birth (OR/IQR: 3.68, 95% CI: 1.20, 6.57) only among women with "poor" psychosocial status. The association between copper (Cu) and SGA was also statistically significant only among women having "poor" psychosocial status (OR/IQR: 2.81, 95% CI: 1.20, 6.57). We also observed associations between nickel (Ni) and preterm birth and SGA that were modified by psychosocial status during pregnancy. CONCLUSIONS:Presence of "poor" psychosocial status intensified the adverse associations between Mn and preterm birth, Cu and SGA, and protective effects of Ni on preterm. This provides evidence that prenatal psychosocial stress may modify vulnerability to metal exposure.
10.1016/j.envint.2021.106418
Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women.
mSystems
Bacterial vaginosis (BV) affects 20% of women worldwide and is associated with adverse reproductive health outcomes and increased risk for HIV. Typically, BV represents a shift in the vaginal microbiome from one that is dominated by to one that is diverse. Persistent racial differences in BV and diverse vaginal microbiome composition overlap with racial disparities in risks for HIV and sexually transmitted infection, especially among women of African descent. Risk factors for BV and nonoptimal vaginal microbiome include sexual practices, yet racial differences persist when adjusted for behavioral factors, suggesting a host genetic component. Here, we perform a genome-wide association study on vaginal microbiome traits in Kenyan women. Linear regression and logistic regression were performed, adjusting for age and principal components of genetic ancestry, to evaluate the association between , , , Shannon diversity index, and community state type (CST) with host genetic single nucleotide polymorphisms (SNPs). We identified novel genomic loci associated with the vaginal microbiome traits, though no SNP reached genome-wide significance. During pathway enrichment analysis, Toll-like receptors (TLRs), cytokine production, and other components of innate immune response were associated with , , and CST. Multiple previously reported genomic loci were replicated, including (Shannon, CST), (, Shannon), (Shannon, CST), (, , CST), and (, Shannon). These genetic associations suggest a role for the innate immune system and cell signaling in vaginal microbiome composition and susceptibility to nonoptimal vaginal microbiome. Globally, bacterial vaginosis (BV) is a common condition in women. BV is associated with poorer reproductive health outcomes and HIV risk. Typically, BV represents a shift in the vaginal microbiome from one that is dominated by to one that is diverse. Despite many women having similar exposures, the prevalence of BV and nonoptimal vaginal microbiome is increased for women of African descent, suggesting a possible role for host genetics. We conducted a genome-wide association study of important vaginal microbiome traits in Kenyan women. We identified novel genetic loci and biological pathways related to mucosal immunity, cell signaling, and infection that were associated with vaginal microbiome traits; we replicated previously reported loci associated with mucosal immune response. These results provide insight into potential host genetic influences on vaginal microbiome composition and can guide larger longitudinal studies, with genetic and functional comparison across microbiome sites within individuals and across populations.
10.1128/mSystems.00502-20
Vaginal Biomarkers That Predict Cervical Length and Dominant Bacteria in the Vaginal Microbiomes of Pregnant Women.
Witkin Steven S,Moron Antonio F,Ridenhour Benjamin J,Minis Evelyn,Hatanaka Alan,Sarmento Stephanno G P,Franca Marcelo S,Carvalho Francisco H C,Hamamoto Tatiana K,Mattar Rosiane,Sabino Ester,Linhares Iara M,Rudge Marilza V C,Forney Larry J
mBio
In many impoverished regions of the world, it may not be possible to assess two major risk factors for preterm birth: a short cervical length and the depletion of vaginal lactobacilli. We determined whether measuring specific compounds in vaginal fluid might be a simple, noninvasive, and cost-effective way to predict the bacteria that dominate the vaginal microbiome and indicate the presence of a shortened cervix (<25 mm). Vaginal fluid samples were prospectively collected from mid-trimester pregnant women, and the concentrations of d- and l-lactic acid, tissue inhibitor of matrix metalloproteinases TIMP-1 and TIMP-2, matrix metalloproteinases MMP-2 and MMP-8, the 70-kDa heat shock protein, a2 isoform of vacuolar ATPase, and sequestrome-1 were quantified by an enzyme-linked immunosorbent assay (ELISA). The compositions of vaginal microbiomes were assessed by analysis of the V1-V3 regions of 16S rRNA genes, while cervical length was determined by transvaginal ultrasonography. The vaginal microbiomes could be clustered into five community state types (CSTs), four of which were dominated by a single species. The dominance of or in the vaginal microbiome predicted the level of d-lactic acid present. Several of the biomarkers, especially TIMP-1, in combination with the subject's age and race, were significantly associated with cervical length. Using piecewise structural equation modeling, we established a causal network that links CST to cervical length via biomarkers. We concluded that measuring levels of TIMP-1 and d-lactic acid in vaginal secretions might be a straightforward way to assess the risk for preterm birth due to a short cervix and microbiome composition. Premature birth and its complications are the largest contributors to infant death in the United States and globally. A short cervical length and the depletion of species are known risk factors for preterm birth. However, in many resource-poor areas of the world, the technology to test for their occurrence is unavailable, and pregnant women with these risk factors are neither identified nor treated. In this study, we used path analysis to gain an unprecedented understanding of interactions between vaginal microbiome composition, the concentrations of various compounds in vaginal secretions, and cervical length. We identified low-cost point-of-care measures that might be used to identify pregnant women at risk for preterm birth. The use of these measures coupled with appropriate preventative or treatment strategies could reduce the incidence of preterm births in poor areas of the world that lack access to more sophisticated diagnostic methods.
10.1128/mBio.02242-19
Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients.
Haahr T,Jensen J S,Thomsen L,Duus L,Rygaard K,Humaidan P
Human reproduction (Oxford, England)
STUDY QUESTION:What is the diagnostic performance of qPCR assays compared with Nugent scoring for abnormal vaginal microbiota and for predicting the success rate of IVF treatment? SUMMARY ANSWER:The vaginal microbiota of IVF patients can be characterized with qPCR tests which may be promising tools for diagnosing abnormal vaginal microbiota and for prediction of clinical pregnancy in IVF treatment. WHAT IS KNOWN ALREADY:Bacterial vaginosis (BV) is a common genital disorder with a prevalence of approximately 19% in the infertile population. BV is often sub-clinical with a change of the vaginal microbiota from being Lactobacillus spp. dominated to a more heterogeneous environment with anaerobic bacteria, such as Gardnerella vaginalis and Atopobium vaginae. Few studies have been conducted in infertile women, and some have suggested a negative impact on fecundity in the presence of BV. STUDY DESIGN, SIZE, DURATION:A cohort of 130 infertile patients, 90% Caucasians, attending two Danish fertility clinics for in vitro fertilization (IVF) treatment from April 2014-December 2014 were prospectively enrolled in the trial. PARTICIPANTS/MATERIALS, SETTING AND METHODS:Vaginal swabs from IVF patients were obtained from the posterior fornix. Gram stained slides were assessed according to Nugent's criteria. PCR primers were specific for four common Lactobacillus spp., G. vaginalis and A. vaginae. Threshold levels were established using ROC curve analysis. MAIN RESULTS AND THE ROLE OF CHANCE:The prevalence of BV defined by Nugent score was 21% (27/130), whereas the prevalence of an abnormal vaginal microbiota was 28% (36/130) defined by qPCR with high concentrations of Gardnerella vaginalis and/or Atopobium vaginae. The qPCR diagnostic approach had a sensitivity and specificity of respectively 93% and 93% for Nugent-defined BV. Furthermore, qPCR enabled the stratification of Nugent intermediate flora. Eighty-four patients completed IVF treatment. The overall clinical pregnancy rate was 35% (29/84). Interestingly, only 9% (2/22) with qPCR defined abnormal vaginal microbiota obtained a clinical pregnancy (P = 0.004). LIMITATIONS, REASONS FOR CAUTION:Although a total of 130 IVF patients were included in the study, a larger sample size is needed to draw firm conclusions regarding the possible adverse effect of an abnormal vaginal microbiota in relation to the clinical pregnancy rate and other reproductive outcomes. WIDER IMPLICATIONS OF THE FINDINGS:Abnormal vaginal microbiota may negatively affect the clinical pregnancy rate in IVF patients. If a negative correlation between abnormal vaginal microbiota and the clinical pregnancy rate is corroborated, patients could be screened and subsequently treated for abnormal vaginal microbiota prior to fertility treatment. STUDY FUNDING/COMPETING INTERESTS:This study was funded by The AP Møller Maersk Foundation for the advancement of Medical Science and Hospital of Central Jutland Research Fund, Denmark. No competing interests. TRIAL REGISTRATION NUMBER:The project was registered at clinicaltrials.gov (file number NCT02042352).
10.1093/humrep/dew026
Association of Maternal Use of Folic Acid and Multivitamin Supplements in the Periods Before and During Pregnancy With the Risk of Autism Spectrum Disorder in Offspring.
Levine Stephen Z,Kodesh Arad,Viktorin Alexander,Smith Lauren,Uher Rudolf,Reichenberg Abraham,Sandin Sven
JAMA psychiatry
Importance:The association of maternal use of folic acid and multivitamin supplements before and during pregnancy with the risk of autism spectrum disorder (ASD) in offspring is unclear. Objective:To examine the associations between the use of maternal folic acid and multivitamin supplements before and during pregnancy and the risk of ASD in offspring. Design, Setting, and Participants:A case-control cohort study of 45 300 Israeli children born between January 1, 2003, and December 31, 2007, were followed up from birth to January 26, 2015, for the risk of ASD. The cases were all children diagnosed with ASD and the controls were a random sample of 33% of all live-born children. Exposures:Maternal vitamin supplements were classified for folic acid (vitamin B9), multivitamin supplements (Anatomical Therapeutic Chemical A11 codes vitamins A, B, C, and D), and any combination thereof exposed in the intervals before and during pregnancy. Main Outcomes and Measures:The association between maternal vitamin supplementation and the risk of ASD in offspring was quantified with relative risks (RRs) and their 95% CIs fitting Cox proportional hazards regression models adjusted for confounders. Sensitivity analyses were performed to test the robustness of the results. Results:Of the 45 300 children in the study (22 090 girls and 23 210 boys; mean [SD] age, 10.0 [1.4] years at the end of follow-up), 572 (1.3%) received a diagnosis of ASD. Maternal exposure to folic acid and/or multivitamin supplements before pregnancy was statistically significantly associated with a lower likelihood of ASD in the offspring compared with no exposure before pregnancy (RR, 0.39; 95% CI, 0.30-0.50; P < .001). Maternal exposure to folic acid and/or multivitamin supplements during pregnancy was statistically significantly associated with a lower likelihood of ASD in offspring compared with no exposure during pregnancy (RR, 0.27; 95% CI, 0.22-0.33; P < .001). Corresponding RRs were estimated for maternal exposure to folic acid before pregnancy (RR, 0.56; 95% CI, 0.42-0.74; P = .001), maternal exposure to folic acid during pregnancy (RR, 0.32; 95% CI, 0.26-0.41; P < .001), maternal exposure to multivitamin supplements before pregnancy (RR, 0.36; 95% CI, 0.24-0.52; P < .001), and maternal exposure to multivitamin supplements during pregnancy (RR, 0.35; 95% CI, 0.28-0.44; P < .001). The results generally remained statistically significant across sensitivity analyses. Conclusions and Relevance:Maternal exposure to folic acid and multivitamin supplements before and during pregnancy is associated with a reduced risk of ASD in the offspring compared with the offspring of mothers without such exposure.
10.1001/jamapsychiatry.2017.4050
Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development.
Immunity
Successful pregnancy requires carefully-coordinated communications between the mother and fetus. Immune cells and cytokine signaling pathways participate as mediators of these communications to promote healthy pregnancy. At the same time, certain infections or inflammatory conditions in pregnant mothers cause severe disease and have detrimental impacts on the developing fetus. In this review, we examine evidence for the role of maternal and fetal immune responses affecting pregnancy and fetal development, both under homeostasis and following infection. We discuss immune responses that are necessary to promote healthy pregnancy and those that lead to congenital disorders and pregnancy complications, with a particular emphasis on the role of interferons and cytokines. Understanding the contributions of the immune system in pregnancy and fetal development provides important insights into the pathogenesis underlying maternal and fetal diseases and sheds insights on possible targets for therapy.
10.1016/j.immuni.2018.07.017