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Background: Amniogenesis is a key event in biochemical pregnancy, and its failure may result in human embryonic death. However, whether and how environmental chemicals affect amniogenesis remain largely unknown. OBJECTIVES: The objective of the present study was to screen chemicals that may disrupt amniogenesis in an amniotic sac embryoid model and to investigate the potential mechanism of amniogenesis failure, with a focus on organophosphate flame retardants (OPFRs). Methods: This study developed a high-throughput toxicity screening assay based on transcriptional activity of octamer- binding transcription factor 4 (Oct4). For the two positive OPFR hits with the strongest inhibitory activity, we used time-lapse and phase- contrast imaging to assess their effects on amniogenesis. Associated pathways were explored by RNA-sequencing and western blotting, and potential binding target protein was identified through a competitive binding experiment. Results: Eight positive hits exhibiting Oct4 expression were identified, with 2-ethylhexyl-diphenyl phosphate (EHDPP) and isodecyl diphenyl phosphate (IDDPP) showing the strongest inhibitory activity. EHDPP and IDDPP were found to disrupt the rosette-like structure of the amniotic sac or inhibit its development. Functional markers of squamous amniotic ectoderm and inner cell mass were also found disrupted in the EHDPP- and IDDPP-exposed embryoids. Mechanistically, embryoids exposed to each chemical exhibited abnormal accumulation of phosphorylated nonmuscle myosin (p-MLC-II) and were able to bind to integrin [beta]1 (ITG[beta]1). Conclusion: The amniotic sac embryoid models suggested that OPFRs disrupted amniogenesis likely by inhibiting the ITG[beta]1 pathway, thus providing direct in vitro evidence associating OPFRs with biochemical miscarriage. https://doi.org/10.1289/EHP11958, Introduction Miscarriage has been recognized as the most noticeable complication during human pregnancy (1) and has sharply increased globally over the past decades. (2,3) About 23 million miscarriages occurred annually [...]

Objectives To investigate whether adverse childhood experiences are associated with miscarriage. Methods The Gulf Resilience on Women's Health Consortium recruited from clinics and community organizations in Southern Louisiana, 2011-2016. Data from 1511 reproductive-aged women with at least one pregnancy were analyzed. Adverse childhood experiences including abuse, neglect, and family dysfunction, as a child (< age 12), and as an adolescent (12-17), were assessed. Outcome measures were self-reported miscarriage at first pregnancy and at any pregnancy, analyzed with logistic regression with adjustment for maternal age at pregnancy, race, BMI, education, marital and smoking status. Results Women reporting four or more adversities as a child and as a teen had higher odds of experiencing miscarriage at first pregnancy (AOR.sub.child 1.71, 95% CI 1.00-2.90; AOR.sub.teen 1.73, 95% CI 1.05-2.87) and miscarriage at any pregnancy (AOR.sub.child 1.74, 95% CI 1.16-2.62; OR.sub.teen 1.65, 95% CI 1.10-2.45) compared to those with no adverse childhood experiences. Similar patterns of association were seen for other ACE sub-categories. Conclusions Childhood adversities were associated with miscarriage. Further research is needed on the pathways which created this association, including psychological, behavioral, and physiological mechanisms and factors which can mitigate the effects of these outcomes., Author(s): Shweta Kerkar [sup.1] , Arti Shankar [sup.2] , Renee Boynton-Jarrett [sup.3] , Emily W. Harville [sup.4] Author Affiliations: (1) grid.64337.35, 0000 0001 0662 7451, Department of Epidemiology, Louisiana State [...]

Background Insomnia is common and associated with adverse pregnancy and perinatal outcomes in observational studies. However, those associations could be vulnerable to residual confounding or reverse causality. Our aim was to estimate the association of insomnia with stillbirth, miscarriage, gestational diabetes (GD), hypertensive disorders of pregnancy (HDP), perinatal depression, preterm birth (PTB), and low/high offspring birthweight (LBW/HBW). Methods and findings We used 2-sample mendelian randomization (MR) with 81 single-nucleotide polymorphisms (SNPs) instrumenting for a lifelong predisposition to insomnia. Our outcomes included ever experiencing stillbirth, ever experiencing miscarriage, GD, HDP, perinatal depression, PTB (gestational age Conclusions In this study, we observed some evidence in support of a possible causal relationship between genetically predicted insomnia and miscarriage, perinatal depression, and LBW. Our study also found observational evidence in support of an association between insomnia in pregnancy and perinatal depression, with no clear multivariable evidence of an association with LBW. Our findings highlight the importance of healthy sleep in women of reproductive age, though replication in larger studies, including with genetic instruments specific to insomnia in pregnancy are important., Author(s): Qian Yang 1,2,*, Maria Carolina Borges 1,2, Eleanor Sanderson 1,2, Maria C. Magnus 1,2,3, Fanny Kilpi 1,2, Paul J. Collings 4, Ana Luiza Soares 1,2, Jane West 4, Per [...]

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Although evidence tends to suggest that high levels of lead exposure increase the risk of spontaneous abortion, we do not yet know whether moderate-to low-level exposure elevates risk. Among 351 women (aged 16 to 35 Fears, with single pregnancies) who were registered for a longitudinal study, 15 (4.3%) women experienced spontaneous abortion after the 12th week of gestation and before the 20th week. We collected participants' blood samples during the first trimester of pregnancy (8-12 weeks)for lead measurement by inductively coupled plasma-mass spectrometry. Mean [+ or -] standard deviation of blood lead was 3.8 [+ or -] 2.0 [micro]g/dl (range 1.0-20.5 [micro]g/dl) with a geometric mean of 3.5 [micro]g/dl. Mean blood lead concentrations did not differ significantly between spontaneous abortion cases and ongoing pregnancies (3.51 [+ or -] 1.42 and 3.83 [+ or -] 1.99 [micro]g/dl, respectively). The findings suggest that in apparently healthy women, low blood lead levels (mean KEYWORDS lead, pregnancy, spontaneous abortion, human reproduction DOI: 10.1080/03630242.2010.532760

Motivated by the need to understand and predict early pregnancy loss using hormonal indicators of pregnancy health, this article proposes a semiparametric Bayesian approach for assessing the relationship between functional predictors and a response. A multivariate adaptive spline model is used to deseribe the functional predictors, and a generalized linear model with a random intercept describes the response. Through specifying the random intercept to follow a Dirichlet process jointly with the random spline coefficients, we obtain a procedure that clusters trajectories according to shape and according to the parameters of the response model for each cluster. This very flexible method allows for the incorporation of covariates in the models for both the response and the trajectory. We apply the method to postovulatory progesterone data from the Early Pregnancy Study and find that the model successfully prediets early pregnancy loss. KEY WORDS: Bayesian clustering Dirichlet process; Early pregnancy loss; Joint modeling; Progesterone.

Despite research documenting high rates of violence during pregnancy, few studies have examined the impact of physical abuse, psychological abuse, and posttraumatic stress disorder (PTSD) on miscarriage. Secondary analysis of data collected by the Chicago Women's Health Risk Study permitted an exploration of the relationships among physical abuse, psychological abuse, PTSD, and miscarriage among 118 primarily ethnic minority women. The interaction between maximum severity of abuse and age provided the best multivariate predictor of miscarriage rate, accounting for 26.9% of the variance between live birth and miscarriage outcome. Mean scores of psychological abuse, physical violence, forced sex, and PTSD were significantly higher in the miscarriage group than in the live birth group. Women who experience physical violence and psychological abuse during pregnancy may be at greater risk for miscarriage. Prospective studies can confirm findings and determine underlying mechanisms. Routine screening for traumatic stress and PTSD may reduce rates of miscarriage. Keywords: posttraumatic stress disorder; PTSD; psychological abuse; physical abuse; miscarriage

Uterine decidualization, a process that occurs in response to embryo implantation, is critical for embryonic survival and thus is a key event for successful pregnancy. Here we show that the [...]

This study proposed that maternal bereavement in women who experienced miscarriage and women who terminated for fetal abnormality would differ related to the existence of a grief reaction, and to identify the factors that differentiated the two groups. There were no significant grief differences between the miscarriage group and termination group. The groups were then combined to analyze within group factors. Six fixed variables were found to be related to vulnerability for a grief reaction. Factors included: time since the most recent loss; intervention of counseling; employment outside the home; feeling responsible for the perinatal loss; age of the mother as related to guilt; and gestational length of pregnancy.

Byline: Amira Y. El-Bastawissi (1), Tanya K. Sorensen (1), Clarisse K. Akafomo (1), Ihunnaya O. Frederick (1), Rong Xiao (1), Michelle A. Williams (1,2) Keywords: preterm delivery; reproductive history; miscarriage; fetal loss Abstract: Objective: To evaluate the association between maternal reproductive history and preterm delivery. Methods: The 312 preterm delivery cases, studied in aggregate, and in subgroups (spontaneous preterm labor, preterm premature rupture of membranes, medically induced preterm delivery, moderate preterm delivery [gestational age at delivery 34--36 weeks], and very preterm delivery [gestational age at delivery &lt 34 weeks]), were compared with 424 randomly selected women who delivered at term. Maternal medical records provided information on maternal reproductive history, pregnancy outcome, as well as sociodemographic characteristics. Using multivariate logistic regression, we derived maximum likelihood estimates of adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: A history of 2+ miscarriages was ( OR = 2.2 95% CI 1.2--3.9), but a history of 2+ prior induced abortions (OR = 1.2 95% CI 0.7--2.0) was not, associated with preterm delivery in the index pregnancy. Analyses of preterm delivery subgroups indicated that a history of 2+ miscarriages was associated with an increasedrisk of spontaneous preterm labor (OR = 2.6 95% CI 1.2--2.8), preterm premature rupture of membrane (OR = 1.8 95% 0.7--4.4), and medically induced preterm delivery (OR = 1.9 95% CI 0.8--4.2), though only the former approached statistical significance. Excess risk of preterm delivery was associated with maternal prior history of delivering a stillborn infant (OR = 10.7), a prior history of delivering a newborn that later died during the neonatal period (OR = 3.2), and a prior history of having a pregnancy complicated by spontaneous preterm delivery (OR = 6.0). Generally these associations were evident for each subgroup of preterm delivery, though inferences were often hindered by our relatively small sample size. Conclusions: These results support the hypothesis that maternal adverse reproductive history is associated with an increased risk of preterm labor and delivery. Author Affiliation: (1) Center for Perinatal Studies, Swedish Medical Center, Seattle, Washington (2) Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington Article History: Registration Date: 07/10/2004

Pregnant women with low blood folate levels have an increased risk of a miscarriage, according to a study of 468 pregnant women who had a miscarriage and 921 pregnant women who did not. Folate is a naturally occurring substance in the body that has also been linked to birth defects in women with a folate deficiency.

Caffeine may increase the risk of miscarriage in non-smoking pregnant women. This was the conclusion of a study of 562 pregnant women who had a miscarriage and 953 pregnant women who did not. The risk increased as the amount of caffeine ingested increased and the risk of miscarriage only occurred in non-smokers.

Pregnant women with the factor V Leiden gene mutation or the prothrombin gene mutation have three times the risk of miscarriage compared to women without these mutations. This was the conclusion of a study of 232 women with a normal pregnancy and 67 who had a miscarriage. Both mutations cause abnormal blood clotting.

Moderate amounts of coffee do not appear to increase the risk of miscarriage. Researchers measured a metabolite of caffeine called paraxanthine in blood samples from 591 pregnant women who had a miscarriage and 2,558 pregnant women who had a normal pregnancy and live birth. Over 80% of both groups had paraxanthine in their blood, but only women with very high blood levels had an increased risk of miscarriage. Compared to women with 50 nanograms or less of paraxanthine per milliliter, those with blood levels over 1,800 nanograms per milliliter had twice the risk of miscarriage.

In most pregnant women, the fertilized egg implants into the uterus between 8 and 10 days after fertilization. Implantation after that time increases the risk of miscarriage. This was the conclusion of a study of 221 women who were trying to get pregnant. Daily urine samples were analyzed for biological markers of fertilization and implantation. Of the 189 women who became pregnant, 84% experienced uterine implantation between 8 and 10 days after fertilization. The rates of miscarriage were 13% in those who implanted on day 9, 26% on day 10, 52% on day 11 and 82% after day 11.

Cocaine or cigarette use may increase the risk of miscarriage. Researchers measured the levels of cocaine in hair samples and nicotine metabolites in blood samples from 970 pregnant women, 400 of whom had a miscarriage during their pregnancy. Cocaine use as detected in hair samples increased the risk of a miscarriage 40% and tobacco use as detected in urine samples almost doubled the risk. Some women did not report their use of cocaine, indicating that hair analysis may be necessary. Both cocaine and nicotine decrease blood flow to the uterus.

Background/Objectives: Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in childbearing aged women and pregnancy loss (PL) in the first trimester. Subjects/Methods: This is a cross-sectional study. Plasma was collected from 60 nulliparous women with singleton at 7-9 weeks of gestation (30 with viable gestation and 30 with PL) and 60 non-gravid childbearing aged women (30 with a successful pregnancy history, and 30 with one or more spontaneous first-trimester PL history). Quantitation of serum 25-hydroxyvitamin D (25(OH)D) and 25-hydroxyvitamin D-1 alpha hydroxylase (CYP27B1) was assayed. Results: By pregnancy/non-gravid, normal pregnant women had higher 25(OH)D (49.32 [mu]g/l) and CYP27B1 (82.00 pg/ml) than PL women (34.49 [mu]g/l and 37.87 pg/ml, both P [less than] 0.01); the non-gravid women with a successful pregnancy history also had higher 25(OH)D (39.56 [mu]g/l) and CYP27B1 (39.04 pg/ml) than women with PL history (12.30 [mu]g/l and 12.35 pg/ml, both P [less than] 0.01). The 96.7% of non-gravid women with PL history and 43.3% of PL women had serum 25(OH)D concentrations below 30 [mu]g/l. There was a strong association between low vitamin D levels and PL (odds ratio 1.71; 95% confidence interval: 1.2-2.4, P [less than] 0.001). The regression analyses showed that PL was significantly inversely correlated with 25(OH)D (P [less than] 0.01) and CYP27B1 levels (P [less than] 0.01). Conclusions: Vitamin D deficiency associated with PL in the first trimester of pregnancy. Decreased serum vitamin D levels among childbearing aged women with the failed clinical pregnancies history may predispose to increased risk for PL. European Journal of Clinical Nutrition (2016) 70, 1004-1008; doi: 10.1038/ejcn.2016.83; published online 25 May 2016, Author(s): W Hou [1, 2]; X-t Yan [1]; C-m Bai [2]; X-w Zhang [1, 3]; L-y Hui [4]; X-w Yu [1] Introduction Pregnancy loss (PL) is an adverse outcome of [...]

The risk of miscarriage in a daughter is not determined by low and high maternal age and short preceding birth intervals. This was indicated by results of a study of the role of conditions at conception in the risk of miscarriage, using data from 234 women with at least two consecutive miscarriages after conceptions from the same partner. The women were asked to furnish the birth dates of their mothers and their live or stillborn siblings and the occurrence of any maternal miscarriages. Results also indicate the influence of seasonally varying factors on risk of miscarriage.