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Background: The exposome is a novel research paradigm offering promise for understanding the complexity of human exposures, including endocrine-disrupting chemicals (EDCs) and pregnancy outcomes. The physiologically active state of pregnancy requires understanding temporal changes in EDCs to better inform the application of the exposome research paradigm and serve as the impetus for study.Methods: We randomly selected 50 healthy pregnant women with uncomplicated pregnancies from a pregnancy cohort who had available serum/urine samples in each trimester for measuring 144 persistent and 48 nonpersistent EDCs. We used unsupervised machine-learning techniques capable of handling hierarchical clustering of exposures to identify EDC patterns across pregnancy, and linear mixed-effects modeling with false-discovery rate correction to identify those that change over pregnancy trimesters. We estimated the percent variation in chemical concentrations accounted for by time (pregnancy trimester) using Akaike Information Criterion-based R methods.Results: Four chemical clusters comprising 80 compounds, of which six consistently increased, 63 consistently decreased, and 11 reflected inconsistent patterns over pregnancy. Overall, concentrations tended to decrease over pregnancy for persistent EDCs; a reverse pattern was seen for many nonpersistent chemicals. Explained variance was highest for five persistent chemicals: polybrominated diphenyl ethers #191 (51%) and #126 (47%), hexachlorobenzene (46%), p,p'-dichloro-diphenyl-dichloroethylene (46%), and o,p'-dichloro-diphenyl-dichloroethane (36%).Conclusions: Concentrations of many EDCs are not stable across pregnancy and reflect varying patterns depending on their persistency underscoring the importance of timed biospecimen collection. Analytic techniques are available for assessing temporal patterns of EDCs during pregnancy apart from physiologic changes. [ABSTRACT FROM AUTHOR]

Objective: To assess the morbidity associated with continuing the second-stage duration of labor, weighing the probability of spontaneous vaginal birth without morbidity compared with birth with serious maternal or neonatal complications.Methods: In a retrospective cohort, we analyzed singleton, vertex births at 36 weeks of gestation or greater without prior cesarean delivery (n=43,810 nulliparous and 59,605 multiparous women). We calculated rates of spontaneous vaginal birth and composite serious maternal or neonatal complications. Results were stratified by parity (nulliparous or multiparous) and epidural status (yes or no). Competing risks models were created for 1) spontaneous vaginal birth with no morbidity, 2) birth with maternal or neonatal morbidity, and 3) no spontaneous vaginal birth and no morbidity, and our main interest was in comparing number 1 against number 2.Results: Rates of spontaneous vaginal birth without morbidity were slightly higher after the first half hour (greater than 0.5-1.0 hours) for nulliparous women, after which rates decreased with increasing second-stage duration. For multiparous women, rates of spontaneous vaginal birth without morbidity decreased with increasing second-stage duration. For illustration, for a nulliparous woman with an epidural at 3.0 hours of the second stage of labor who extended by another 1.0 hour, her likelihood of delivering by spontaneous vaginal birth was 31.4% compared with her likelihood of birth with any serious complication in the subsequent hour, which was 7.6%. The percentage of cesarean deliveries for nonreassuring fetal heart rate tracing were higher for women without compared with women with an epidural.Conclusion: Rates of spontaneous vaginal birth without serious morbidity steadily decreased for increasing second-stage duration except for the first half hour for nulliparous women. We did not observe an inflection point at a particular hour mark for either spontaneous vaginal delivery without morbidity or births with morbidity. Our findings will assist in decision-making for extending second-stage duration. [ABSTRACT FROM AUTHOR]

Background: Perfluoroalkyl substances have been associated with changes in menstrual cycle characteristics and fecundity, when modeled separately. However, these outcomes are biologically related, and we evaluate their joint association with exposure to perfluoroalkyl substances.Methods: We recruited 501 couples from Michigan and Texas in 2005-2009 upon their discontinuing contraception and followed them until pregnancy or 12 months of trying. Female partners provided a serum sample on enrollment and completed daily journals on menstruation, intercourse, and pregnancy test results. We measured seven perfluoroalkyl substances in serum using liquid chromatography-tandem mass spectrometry. We assessed the association between perfluoroalkyl substances and menstrual cycle length using accelerated failure time models and between perfluoroalkyl substances and fecundity using a Bayesian joint modeling approach to incorporate cycle length.Results: Menstrual cycles were 3% longer comparing women in the second versus first tertile of perfluorodecanoate (PFDeA; acceleration factor [AF] = 1.03, 95% credible interval [CrI] = [1.00, 1.05]), but 2% shorter for women in the highest versus lowest tertile of perfluorooctanoic acid (PFOA; AF = 0.98, 95% CrI = [0.96, 1.00]). When accounting for cycle length, relevant covariates, and remaining perfluoroalkyl substances, the probability of pregnancy was lower for women in second versus first tertile of perfluorononanoate (PFNA; odds ratio [OR] = 0.6, 95% CrI = [0.4, 1.0]) although not when comparing the highest versus lowest (OR = 0.7, 95% CrI = [0.3, 1.1]) tertile.Conclusions: In this prospective cohort study, we observed associations between two perfluoroalkyl substances and menstrual cycle length changes, and between select perfluoroalkyl substances and diminished fecundity at some (but not all) concentrations. See video abstract at, http://links.lww.com/EDE/B136. [ABSTRACT FROM AUTHOR]

Background: The reliability of retrospective time to pregnancy (TTP) has been established, but its validity has been assessed in only 1 study, which had a short follow-up.Methods: Ninety-nine women enrolled a decade earlier in a prospective TTP study were queried by means of mailed questionnaires about the duration of time they had required to become pregnant. Their responses were compared with their earlier data from daily diaries (gold standard).Results: One-third of women could not recall their earlier TTP either in menstrual cycles or calendar months. Only 17%-19% of women recalled their TTP exactly. Agreement increased to 41%-51%, 65%-72%, and 72%-77% when defined as +/-1, +/-2, and +/-3 months, respectively. Women with longer observed TTPs or previous pregnancies were more likely to under-report their TTP.Conclusions: The findings raise questions about the commonly assumed validity of self-reported TTP. Recalled TTP may introduce error when estimating fecundability or classifying couples' fecundity status. [ABSTRACT FROM AUTHOR]

Objective: To assess neonatal and maternal outcomes when the second stage of labor was prolonged according to American College of Obstetricians and Gynecologists guidelines., Methods: Electronic medical record data from a retrospective cohort (2002-2008) from 12 U.S. clinical centers (19 hospitals), including 43,810 nulliparous and 59,605 multiparous singleton deliveries at 36 weeks of gestation or greater, vertex presentation, who reached 10-cm cervical dilation were analyzed. Prolonged second stage was defined as: nulliparous women with epidural greater than 3 hours and without greater than 2 hours and multiparous women with epidural greater than 2 hours and without greater than 1 hour. Maternal and neonatal outcomes were compared and adjusted odds ratios calculated controlling for maternal race, body mass index, insurance, and region., Results: Prolonged second stage occurred in 9.9% and 13.9% of nulliparous and 3.1% and 5.9% of multiparous women with and without an epidural, respectively. Vaginal delivery rates with prolonged second stage compared with within guidelines were 79.9% compared with 97.9% and 87.0% compared with 99.4% for nulliparous women with and without epidural, respectively, and 88.7% compared with 99.7% and 96.2% compared with 99.9% for multiparous women with and without epidural, respectively (P<.001 for all comparisons). Prolonged second stage was associated with increased chorioamnionitis and third-degree or fourth-degree perineal lacerations. Neonatal morbidity with prolonged second stage included sepsis in nulliparous women (with epidural: 2.6% compared with 1.2% [adjusted odds ratio (OR) 2.08, 95% confidence interval (CI) 1.60-2.70]; without epidural: 1.8% compared with 1.1% [adjusted OR 2.34, 95% CI 1.28-4.27]); asphyxia in nulliparous women with epidural (0.3% compared with 0.1% [adjusted OR 2.39, 95% CI 1.22-4.66]) and perinatal mortality without epidural (0.18% compared with 0.04% for nulliparous women [adjusted OR 5.92, 95% CI 1.43-24.51]); and 0.21% compared with 0.03% for multiparous women (adjusted OR 6.34, 95% CI 1.32-30.34). However, among the offspring of women with epidurals whose second stage was prolonged (3,533 nulliparous and 1,348 multiparous women), there were no cases of hypoxic-ischemic encephalopathy or perinatal death., Conclusions: Benefits of increased vaginal delivery should be weighed against potential small increases in maternal and neonatal risks with prolonged second stage., Level of Evidence: : II.

Background: Environmental chemicals may be associated with endometriosis. No published research has focused on the possible role of perfluorochemicals (PFCs) despite their widespread presence in human tissues., Methods: We formulated two samples. The first was an operative sample comprising 495 women aged 18-44 years scheduled for laparoscopy/laparotomy at one of 14 participating clinical sites in the Salt Lake City or San Francisco area, 2007-2009. The second was a population-based sample comprising 131 women matched to the operative sample on age and residence within a 50-mile radius of participating clinics. Interviews and anthropometric assessments were conducted at enrollment, along with blood collection for the analysis of nine PFCs, which were quantified using liquid chromatography-tandem mass spectrometry. Endometriosis was defined based on surgical visualization (in the operative sample) or magnetic resonance imaging (in the population sample). Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for each PFC (log-transformed), adjusting for age and body mass index, and then parity., Results: Serum perfluorooctanoic acid (PFOA; OR = 1.89 [95% CI = 1.17-3.06]) and perfluorononanoic acid (2.20 [1.02-4.75]) were associated with endometriosis in the operative sample; findings were moderately attenuated with parity adjustment (1.62 [0.99-2.66] and 1.99 [0.91-4.33], respectively). Perfluorooctane sulfonic acid (1.86 [1.05-3.30]) and PFOA (2.58 [1.18-5.64]) increased the odds for moderate/severe endometriosis, although the odds were similarly attenuated with parity adjustment (OR = 1.50 and 1.86, respectively)., Conclusions: Select PFCs were associated with an endometriosis diagnosis. These associations await corroboration.

Objective: To examine labor patterns in a large population and to explore an alternative approach for diagnosing abnormal labor progression., Methods: Data from the National Collaborative Perinatal Project were used. A total of 26,838 parturients were selected who had a singleton term gestation, spontaneous onset of labor, vertex presentation, and a normal perinatal outcome. A repeated-measures analysis was used to construct average labor curves by parity. An interval-censored regression was used to estimate duration of labor stratified by cervical dilation at admission and centimeter by centimeter., Results: The median time needed to progress from one centimeter to the next became shorter as labor advanced (eg, from 1.2 hours at 3-4 cm to 0.4 hours at 7-8 cm in nulliparas). Nulliparous women had the longest and most gradual labor curve; multiparous women of different parities had very similar curves. Nulliparas may start the active phase after 5 cm of cervical dilation and may not necessarily have a clear active phase characterized by precipitous dilation. The deceleration phase in the late active phase of labor may be an artifact in many cases., Conclusion: The active phase of labor may not start until 5 cm of cervical dilation in multiparas and even later in nulliparas. A 2-hour threshold for diagnosing labor arrest may be too short before 6 cm of dilation, whereas a 4-hour limit may be too long after 6 cm. Given that cervical dilation accelerates as labor advances, a graduated approach based on levels of cervical dilation to diagnose labor protraction and arrest is proposed., Level of Evidence: III.