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Background: The metabolic changes that ultimately lead to gestational diabetes mellitus (GDM) likely begin before pregnancy. Cannabis use might increase the risk of GDM by increasing appetite or promoting fat deposition and adipogenesis. Objectives: We aimed to assess the association between preconception cannabis use and GDM incidence. Methods: We analysed individual‐level data from eight prospective cohort studies. We identified the first, or index, pregnancy (lasting ≥20 weeks of gestation with GDM status) after cannabis use. In analyses of pooled individual‐level data, we used logistic regression to estimate study‐type‐specific odds ratios (OR) and 95% confidence intervals (CI), adjusting for potential confounders using random effect meta‐analysis to combine study‐type‐specific ORs and 95% CIs. Stratified analyses assessed potential effect modification by preconception tobacco use and pre‐pregnancy body mass index (BMI). Results: Of 17,880 participants with an index pregnancy, 1198 (6.7%) were diagnosed with GDM. Before the index pregnancy, 12.5% of participants used cannabis in the past year. Overall, there was no association between preconception cannabis use in the past year and GDM (OR 0.97, 95% CI 0.79, 1.18). Among participants who never used tobacco, however, those who used cannabis more than weekly had a higher risk of developing GDM than those who did not use cannabis in the past year (OR 2.65, 95% CI 1.15, 6.09). This association was not present among former or current tobacco users. Results were similar across all preconception BMI groups. Conclusions: In this pooled analysis of preconception cohort studies, preconception cannabis use was associated with a higher risk of developing GDM among individuals who never used tobacco but not among individuals who formerly or currently used tobacco. Future studies with more detailed measurements are needed to investigate the influence of preconception cannabis use on pregnancy complications. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between ovarian reserve biomarkers and future fertility among late reproductive-age women.Design: Cohort study of participants enrolled in Time to Conceive (TTC), a time-to-pregnancy cohort study of the ovarian reserve biomarkers.Setting: Community.Patient(s): Women aged 30-44 years without a history of infertility who provided a blood sample at enrollment in TTC and who agreed to future follow-up.Intervention(s): Not applicable.Main Outcome Measure(s): The primary outcomes were probability of achieving a live birth >3 years after enrollment in TTC, diagnosis of infertility at any time, and time-to-pregnancy in future pregnancy attempts.Result(s): Women with diminished ovarian reserve, defined as those with an antimüllerian hormone (AMH) level <0.7 ng/mL or follicle-stimulating hormone (FSH) level ≥10 mIU/mL, did not have low risk of future live birth (relative risk [RR], 1.32; 95% confidence interval [CI], 0.95-1.83 and RR, 1.28; 95% CI, 0.97-1.70, respectively) compared with women with normal ovarian reserve after adjusting for age at blood draw, race, obesity, use of hormonal contraception, and year of enrollment in original study. Among women in the cohort that attempted to conceive, there was not a significant association between diminished ovarian reserve, as measured by AMH or FSH, and risk of future infertility (RR, 0.65; 95% CI, 0.21-2.07 and RR,1.69; 95% CI, 0.86-3.31, respectively). Similarly, there was no association between AMH and FSH levels and future fecundability (fecundability ratio, 0.97; 95% CI, 0.59, 1.60; and fecundability ration, 0.86; 95% CI, 0.55-1.36, respectively).Conclusion: Diminished ovarian reserve is not associated with reduced future reproductive capacity. Given the lack of association, women should be cautioned regarding use biomarkers of ovarian reserve as predictors of their future reproductive capacity. [ABSTRACT FROM AUTHOR]

• Vitamin D status has been inconsistently associated with age of menopause. • We used data from the Sister Study cohort (N=13, 102). • We examined vitamin D or calcium supplement use and 25-hydroxyvitamin D (25OHD) level with the timing of natural menopause. • Concomitant multivitamin and vitamin D use was associated with slightly earlier menopause (HR(CI): 1.10 (0.98, 1.24). • None of the remaining vitamin D or calcium supplement variables meaningfully associated with timing of natural menopause. • Future studies of menopause timing should focus on a life course approach and include 25OHD measures from early mid-life. Vitamin D status has been inconsistently associated with ovarian reserve and menopause. We used data from the Sister Study cohort to examine the associations of vitamin D supplement use, total 25-hydroxyvitamin D (25OHD) level, and calcium supplement use with the timing of natural menopause. Vitamin D and calcium supplement use were assessed on a questionnaire at baseline (mean age: 46) and two follow-up time points, and characterized in multiple ways based on type, dose, and duration of use. Serum samples from a random subset of participants were analyzed for total 25OHD (25OHD 3 + 25OHD 2 + epi-25OHD 3) using liquid chromatography-mass spectrometry. Menopause was assessed at each yearly follow-up with the question "Have you had a menstrual period in the past 12 months?"; if the response was "no", age at last menstrual period was recorded. We censored women at time of hysterectomy or medically induced menopause, death, loss to follow-up or October 2020. We used multivariable Cox proportional hazard models with age as the time scale to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs), adjusting for race/ethnicity, education, body mass index, alcohol use, smoking status, and physical activity. Among the 13,102 eligible premenopausal participants, 8897 experienced natural menopause during follow-up. Concomitant use of a multivitamin and a vitamin D supplement was associated with slightly earlier menopause (HR(CI): 1.10 (0.98, 1.24)). None of the remaining vitamin D or calcium supplement variables (alone or in combination) were meaningfully associated with timing of natural menopause. In a subsample with 25OHD measurements (n = 906), neither total 25OHD nor 25OHD 3 was associated with timing of menopause. Our study includes, on average, 6 years of follow-up from an average age of 46 years and did not find associations between vitamin D or calcium supplement use and timing of menopause. Future studies should focus on a life course approach to this question and include 25OHD measures from early mid-life when examining menopause timing. [ABSTRACT FROM AUTHOR]

BACKGROUND: Vitamin D improves absorption of calcium; however, in animal studies vitamin D also increases the absorption of toxic metals, such as lead and cadmium. OBJECTIVES: We examined maternal and neonatal cord blood levels of lead, cadmium, manganese, and mercury after supplementation with vitamin D during pregnancy. METHODS: The Maternal Vitamin D for Infant Growth trial was a randomized, placebo-controlled, multi-arm study of maternal vitamin D supplementation during pregnancy in Dhaka, Bangladesh (NCT01924013). Women were randomized during their second trimester to blinded weekly doses of placebo or 4,200, 16,800, or 28,000 IU of vitamin D3 throughout pregnancy. Each group had 118–239 maternal blood specimens and 100–201 cord blood samples analyzed. Metals were measured using inductively coupled plasma mass spectrometry. Unadjusted estimates from linear regression models were expressed as percentage differences. Cord blood cadmium was analyzed as detectable or undetectable with log-binomial regression. RESULTS: Maternal cadmium, mercury, and manganese levels were nearly identical across groups. Maternal lead levels were 6.3%, 7.4%, and 6.0% higher in the treatment groups (4,200, 16,800, and 28,000 IU, respectively) vs. placebo; however, 95% confidence intervals (CIs) showed that differences from 4.1% lower to 20% higher were compatible with the data. In treatment groups (4,200, 16,800, 28,000 IU) vs. placebo, neonatal cord blood lead levels were 8.5% (95% CI: -3:5, 22), 16% (95% CI: 3.3, 30), and 11% (95% CI: 0.4, 23) higher and had higher risk of detectable cadmium, relative risk ðRRÞ= 2:2 (95% CI: 1.3, 3.7), RR = 1:4 (95% CI: 0.8, 2.5), RR = 1:7 (95% CI: 1.0, 2.9). DISCUSSION: Vitamin D supplementation from the second trimester of pregnancy did not influence maternal cadmium, mercury, or manganese levels at delivery. Vitamin D was associated with nonsignificant increases in maternal lead and with significant increases in cord blood lead and cadmium. These associations were not dose dependent. Given that there are no safe levels of metals in infants, the observed increases in cord blood lead and cadmium require further exploration. [ABSTRACT FROM AUTHOR]

Study Question: Are serum omega-3 and omega-6 essential fatty acid concentrations associated with the probability of conceiving?Summary Answer: There is no strong association between serum concentrations of omega-3 and omega-6 fatty acids and the probability of conceiving naturally.What Is Known Already: Omega-3 and omega-6 fatty acid serum concentrations have been shown to play an important role in reproduction in animal models, while conflicting results have been reported in human studies of infertile women. It is unknown to what extent omega fatty acid serum concentrations impact natural fertility.Study Design, Size, Duration: A nested, case-control study was conducted consisting of 200 participants [fertile: conceived within 3 cycles of attempt (n = 50), subfertile: conceived within 4 and 12 cycles of attempt (n = 100) and infertile: did not conceive within 12 cycles of attempt (n = 50)] randomly selected from the Time to Conceive cohort, a prospective time-to-pregnancy study (2008 to 2015).Participants/materials, Setting, Methods: In the Time to Conceive study, women aged 30-44 years who were trying to conceive for <3 months and had no history of infertility were recruited and followed until the end of their pregnancy or ~1 year of pregnancy attempt. For this study, serum collected early in the woman's pregnancy attempt was analysed for anti-Müllerian hormone (AMH) and omega-3 and omega-6 fatty acid concentrations by liquid chromatography-mass spectrometry. The primary outcome was a positive home pregnancy test. The secondary outcomes were miscarriage and serum AMH level. A discrete-time Cox proportional hazards model was used to estimate the fecundability ratio. The odds ratios for miscarriage were calculated using logistic regression. The association between serum omega fatty acid concentrations and AMH level (natural log transformed) was analysed using Pearson's Correlation.Main Results and the Role Of Chance: A total of 200 women provided 1321 cycles for analysis.Mean omega-3, omega-6 and omega-6:omega-3 ratios did not significantly differ between the fertile, subfertile and infertile groups. There were no associations (all fecundability ratios ~1.0) between pregnancy and individual omega-3 fatty acid concentrations, including alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, or omega-6 fatty acids, including linoleic acid (LA), dihommo-gamma linolenic acid and arachidonic acid. There was no significant association between any individual omega fatty acid serum concentration and the age-adjusted odds of miscarriage. No association was found between any serum omega fatty acid concentration and AMH.Limitations, Reasons For Caution: This study is limited by the sample size. Omega-3 and omega-6 fatty acid concentrations were derived from serum provided at a single timepoint in the first cycle of enrollment. Serum concentrations may therefore not be representative of all critical timepoints in the menstrual cycle or throughout their attempts to conceive. Additionally, women enrolled in this study were 30 years of age and older, and therefore the findings may not apply to younger women.Wider Implications Of the Findings: These data would suggest that omega-3 and omega-6 serum levels are not associated with natural fertility or risk of miscarriage. However, due to the above-mentioned limitations, future investigation is still needed to determine whether omega-3 fatty acid supplementation may benefit women planning to conceive naturally.Study Funding/competing Interest(s): This study was supported by the Division of Reproductive Endocrinology and Infertility at the University of North Carolina at Chapel Hill, by the NIH/NICHD (R21 HD060229-01 and R01 HD067683-01) and, in part, by the Intramural Research Program of the National Institute of Environmental Health Sciences (Z01ES103333). Dr. Jukic received vitamin D supplements for a research study from Theralogix, Inc. The authors have no other conflicts of interest to disclose.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Abstract Background Phthalates and bisphenol A (BPA) are environmental contaminants that may affect early embryonic development. Objective To assess the association between phthalate metabolites and BPA with early pregnancy endpoints in a cohort of women followed from before conception. Methods We quantified 11 phthalate metabolites and BPA in 137 conception cycles from naturally conceived clinical pregnancies. Phthalate metabolites and BPA concentrations were measured in a pooled sample of three daily morning urine specimens. Daily urinary hormone measurements had previously been used to define ovulation, implantation, and corpus luteum rescue. We assessed associations between conception cycle exposures (phthalate biomarkers and BPA) and 1) time from ovulation to implantation; 2) type of corpus luteum rescue (timing and pattern of rise in progesterone: early, late, or no rise); and 3) rate of initial rise in hCG. Results Mono(3-carboxypropyl) phthalate (MCPP) and mono-isobutyl phthalate (MiBP) were associated with earlier implantation (6–8 days vs. 9 days (the most commonly observed); per natural log-unit, OR (95% CI) = 2.8 (1.2, 6.7) and OR (CI) = 2.1 (1.2, 3.7), respectively). Monoethyl phthalate (MEP) was associated with later implantation (10–12 days vs. 9 days); OR (CI) = 1.5 (1.0, 2.1). Compared with implantation on day 9, BPA was significantly associated with both earlier and later implantation (OR=2.2 for both). Women with concentrations above the median of monobenzyl phthalate (MBzP) (p = 0.04) or above the median of the molar sum of four di(2-ethylhexyl) phthalate metabolites (∑DEHP) (p = 0.08) had a slower initial rise in hCG. Increasing MCPP was associated with an increased odds of a late rise rescue (OR (CI) = 2.9 (1.0, 8.5); late rise vs. early rise), while increasing MEP was associated with a no rise rescue (OR (CI) = 1.6 (0.9, 2.8); no rise vs. early rise). Conclusions The reported associations varied in their direction of effect, some potentially protective, others adverse. This may reflect the complexity with which these potential endocrine disrupting chemicals can be acting, but chance findings are also possible. Given that women continue to be exposed to these compounds (or their precursors), continued research on the effects they may have on pregnancy is warranted. Highlights • Exposure to phthalates and bisphenol A may affect early pregnancy events. • Changes in reproductive hormone levels are required to maintain pregnancy. • Certain chemical biomarkers were associated with adverse early pregnancy endpoints. [ABSTRACT FROM AUTHOR]

Background: Prenatal exposure to metals in private well water may increase the risk of preterm birth (PTB) (delivery < 37 weeks' gestation). In this study, we estimated associations between arsenic, manganese, lead, cadmium, chromium, copper, and zinc concentrations in private well water and PTB incidence in North Carolina (NC). Methods: Birth certificates from 2003–2015 (n = 1,329,071) were obtained and pregnancies were assigned exposure using the mean concentration and the percentage of tests above the maximum contaminant level (MCL) for the census tract of each individuals' residence at the time of delivery using the NCWELL database (117,960 well water tests from 1998–2019). We evaluated associations between single metals and PTB using adjusted logistic regression models. Metals mixtures were assessed using quantile-based g-computation. Results: Compared with those in other census tracts, individuals residing in tracts where > 25% of tests exceeded the MCL for lead (aOR 1.10, 95%CI 1.02,1.18) or cadmium (aOR 1.11, 95% CI 1.00,1.23) had an increased odds of PTB. Conversely, those residing in areas with > 25% MCL for zinc (aOR 0.77 (95% CI: 0.56,1.02) and copper (aOR 0.53 (95% CI: 0.13,1.34)) had a reduced odds of PTB. A quartile increase in the concentrations of a mixture of lead, cadmium, and chromium was associated with a small increased odds for PTB (aOR 1.02, 95% CI 1.01, 1.03). This metal mixture effect was most pronounced among American Indian individuals (aOR per quartile increase in all metals: 1.19 (95% CI 1.06,1.34)). Conclusions: In a large study population of over one million births, lead and cadmium were found to increase the risk of PTB individually and in a mixture, with additional mixtures-related impacts estimated from co-exposure with chromium. This study highlights critical racial and ethnic health disparities in relation to private well water thereby emphasizing the urgent need for improved private well water quality to protect vulnerable populations. [ABSTRACT FROM AUTHOR]

The article comment on a study by Najmabadi and colleagues, examine patterns in menstrual cyclicity and menstrual bleeding, and follicular and luteal phase length. Topics discussed include cycle length differ by race or ethnicity, and associations between exposures and menstrual cycle length may differ within racial groups; using hormonal birth control; and also mentions menstrual cycle apps for women regarding the pregnancy intentions.

Vitamin D is a fat-soluble vitamin that is synthesized in the skin with exposure to sunlight or is ingested from dietary supplements or food. There has been a dramatic increase in research on vitamin D, linking it with health outcomes as varied as reproductive function, infection, cardiovascular disease, and cancer. The study of vitamin D has generated much excitement, partly because there is an ideal intervention: Low levels may be common and can be remedied with widely available supplements. Determination of vitamin D status is complex and has advanced dramatically in the past 5 years. In this paper, we begin by describing important considerations for measurement of total 25-hydroxyvitamin D (25(OH)D), the biomarker traditionally assessed in epidemiologic studies. While 25(OH)D remains the most commonly measured biomarker, emerging evidence suggests that other related analytes may contribute to the characterization of an individual's vitamin D status (e.g., vitamin D-binding protein, bioavailable and free 25(OH)D, the C-3 epimer of 25(OH)D, 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D). The measurement of these analytes is also complex, and there are important considerations for deciding whether their measurement is warranted in new research studies. Herein we discuss these issues and provide the reader with an up-to-date synthesis of research on vitaminD measurement options and considerations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Certain phthalates and bisphenol A (BPA) show reproductive effects in animal studies and potentially affect human ovulation, conception, and pregnancy loss. OBJECTIVES: We investigated these chemicals in relation to follicular- and luteal-phase lengths, time to pregnancy, and early pregnancy loss (within 6 weeks of the last menstrual period) among women attempting pregnancy. METHODS: Women discontinuing contraception provided daily first-morning urine specimens and recorded days with vaginal bleeding for up to 6 months. Specimens had previously been analyzed for estrogen and progesterone metabolites and human chorionic gonadotropin. A total of 221 participants contributed 706 menstrual cycles. We measured 11 phthalate metabolites and BPA in pooled urine from three specimens spaced throughout each menstrual cycle. We analyzed associations between chemical concentrations and outcomes using linear mixed models for follicular- and luteal-phase lengths, discrete-time fecundability models for time to pregnancy, and logistic regression for early pregnancy loss. RESULTS: Higher concentrations of monocarboxyoctyl phthalate (MCOP) were associated with shorter luteal phase [2nd tertile vs. 1st tertile: -0.5 days (95% CI: -0.9, -0.1), 3rd vs. 1st: -0.4 days (95% CI: -0.8, 0.01), p = 0.04]. BPA was also associated with shorter luteal phase [2nd vs. 1st: -0.8 days (95% CI: -1.2, -0.4), 3rd vs. 1st: -0.4 days (95% CI: -0.8, 0.02),p = 0.001]. CONCLUSIONS: BPA and MCOP (or its precursors) were associated with shorter luteal phase. Menstrual cycle--specific estimates of urinary BPA and phthalate metabolites were not associated with detrimental alterations in follicular-phase length, time to pregnancy, or early pregnancy loss, and in fact, DEHP [di(2-ethylhexyl) phthalate] metabolites {MEOHP [mono(2-ethyl-5-oxohexyl) phthalate] and ΣDEHP} were associated with reduced early loss. These findings should be confirmed in future human studies. [ABSTRACT FROM AUTHOR]

Background: In animals, low levels of vitamin D are associated with estrus cycle disturbances, but there are virtually no human data. We examined the association of 25-hydroxyvitamin D (25(OH)D) (a biomarker for vitamin D status) with menstrual cycle characteristics. Methods: Women aged 35-44 were randomly selected from a Washington D.C. health plan and invited to participate in the Uterine Fibroid Study (1996 - 1999). Our analysis includes 636 women (57% were African-American) who provided a blood sample and completed a telephone interview that included gynecologic history. Women were asked their usual cycle length in the preceding year. Women who reported it was "too irregular to estimate" were classified as having irregular cycles (N = 48). Women were excluded if they currently or recently used hormonal contraception or any other medication that influences menstrual cycles. 25(OH)D was measured by radioimmunoassay in stored plasma samples. Results: The median 25(OH)D level was 12.0 ng/mL (interquartile range: 7.6, 19.7 ng/mL). After controlling for age, race, BMI, education, age of menarche, current smoking, alcohol use, and physical activity, a decrease in 25(OH)D of 10 ng/mL was associated with 1.9 times the odds of irregular cycles (Odds ratio (OR) (95% confidence interval (CI)): 1.9 (1.0, 3.4), p = 0.04). 25(OH)D was not associated with the occurrence of short cycles (OR(CI): 1.08 (0.79, 1.48, p = 0.6) or long cycles (OR(CI): 1.31 (0.66, 2.60), p = 0.4). Conclusions: Lower levels of 25(OH)D were associated with irregular cycles, but not with short or long cycles. Vitamin D may play a role in regulating ovulatory function. Further investigation of potential mechanisms is warranted. [ABSTRACT FROM AUTHOR]

Background In rodents, physical activity during pregnancy has been associated with improved learning and memory in the offspring. We used data from the Avon Longitudinal Study of Parents and Children (born in 1991-92) to investigate maternal physical activity during pregnancy and offspring language development. Methods At 18 weeks of gestation, women reported the hours per week they participated in 11 leisure-time physical activities and the hours per week spent in general physical activity (leisure, household and occupational). Caregivers completed a modified Mac Arthur Infant Communication scale at 15 months. Verbal intelligence quotient ( IQ) was measured at age 8 years. Regression analysis was used to examine the associations of physical activity with Mac Arthur score (more than 75th percentile) and verbal IQ. The number of participants available for analyses ranged from 4529 to 7162. Results Children of women in the two highest quintiles of leisure activity (compared with no leisure activity) were more likely to have high 15-month Mac Arthur scores (adjusted odds ratio 1.2 [95% confidence interval 0.9, 1.4] and adjusted odds ratio 1.4 [95% CI 1.1, 1.7], respectively). Leisure activity was not associated with IQ, while general physical activity was linked with lower verbal IQ (1 and 3 points lower for the two highest quintiles). Conclusions The most robust finding was a transient increase in offspring vocabulary score at young ages with maternal leisure activity. Differences in the associations with leisure-time physical activity compared with general physical activity need further exploration. [ABSTRACT FROM AUTHOR]

Abstract: Both delayed gastrointestinal transit and autonomic neuropathy have been documented in patients with diabetes mellitus. The mechanism of neostigmine, an agent that mimics release of acetylcholine from autonomic neurons by prokinetic agents, to contract smooth muscle, despite dysfunctional enteric neural pathways, was determined using isolated ilea from STZ-treated and control guinea pigs. Both bethanechol- and neostigmine-induced contractions were stronger in diabetic ileum. Bethanechol-induced contractions of control but not diabetic ileum were increased by low dose scopolamine suggesting reduced activation of presynaptic muscarinic autoreceptors in diabetic ileum. The muscarinic receptor antagonist 4-DAMP strongly, but the nicotinic receptor antagonist hexamethonium only weakly, reduced neostigmine-induced contractions of control and diabetic ilea. The amount of acetylcholine, inferred from tissue choline content, was increased in diabetic ileum. Nicotinic neural and noncholinergic postjunctional smooth muscle receptors contributed more strongly to neostigmine-induced contractions in diabetic than control ileum. Relaxation of diabetic ileum by exogenous nitric oxide generated from sodium nitroprusside was comparable to control ileum, but smooth muscle relaxation by l-arginine using neuronal nitric oxide synthase to generate nitric oxide was weaker in diabetic ileum with evidence for a role for inducible nitric oxide synthase. Despite autonomic neuropathy, neostigmine strongly contracted ileum from diabetic animals but by a different mechanism including stronger activation of postjunctional muscarinic receptors, greater synaptic acetylcholine, stronger activation of noncholinergic excitatory pathways, and weaker activation of inhibitory pathways. A selective medication targeting a specific neural pathway may more effectively treat disordered gastrointestinal transit in patients with diabetes mellitus. [Copyright &y& Elsevier]

Previous studies of hormone patterns after clinical miscarriage suggest reduced pituitary function. Hormonal effects of very early pregnancy loss (before 6 weeks gestation) have not been described. We used within-woman differences between menstrual cycles in urinary hormone measurements from women in the North Carolina Early Pregnancy Study to describe hormonal changes after very early pregnancy loss ( n = 28 early losses; 80 non-conception comparison cycles). We found lower pre-ovulatory luteinising hormone and shorter luteal phase length after very early pregnancy loss, but the differences were non-significant ( p > 0.3) and smaller than those reported in the spontaneous miscarriage literature. Consistent with the reduced pituitary function reported post-spontaneous miscarriage, we found a slower rate of oestrogen rise ( p = 0.08). There was no evidence of lower mid-luteal steroid levels as has been suggested for post-spontaneous miscarriage cycles. Very early pregnancy losses do not appear to influence subsequent menstrual cycles to the same degree as spontaneous miscarriages. [ABSTRACT FROM AUTHOR]

Vitamin D facilitates the absorption of calcium but may also increase absorption of other metals; the literature is conflicting. To examine whether 25OHD in the first trimester of pregnancy was associated with subsequent metals levels in the late second trimester of pregnancy. We used data from a sample of women in the LIFECODES pregnancy cohort (N = 381). 25-hydroxyvitamin D (25OHD) was measured with a chemiluminescence immunoassay in plasma samples drawn at 10 weeks of gestation. A panel of 17 metals and elements was measured in urine collected at 26 weeks of gestation. We used linear or logistic regression to estimate associations between 25OHD (dichotomous, linear, and in tertiles) and either urinary metal concentrations or the proportion of samples below the limit of detection, respectively. Multivariable models included urinary specific gravity, age, race/ethnicity, education, body mass index, insurance type, gestational age, and season. After multivariable adjustment, low 25OHD was associated with a 47% increase in lead level, a 60% increase in tin level, and 1.58 times the odds of detectable tungsten. A 10 ng/ml increase in 25OHD was associated with a 12% decrease in tin and an 8% increase in molybdenum. While we had a small sample size, we found some evidence of effect modification by race. Women who reported their race as Black or were classified in the other race category, who also had low 25OHD, had 40% higher thallium than women with higher 25OHD and were more likely to have detectable beryllium and tungsten. These metals were not associated with low 25OHD in women who reported their race as White. Tin and lead were higher in women with low 25OHD in all race groups. In total, further research is warranted to determine if vitamin D levels alter metal levels, and to elucidate the shape of the association for each metal across a range of corresponding 25OHD levels, and longitudinally, across pregnancy. This is especially true for pregnant people as exposure to metals during pregnancy has health consequences for the fetus. • Vitamin D facilitates the absorption of calcium but may also increase absorption of other metals. • After adjustment, low 25OHD was associated with 47% higher lead, 60% higher tin, and higher odds of detectable tungsten. • While the sample size was small, there was some evidence of effect modification by race. • Further research is warranted to determine if vitamin D levels alter metal levels longitudinally, particularly during pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: Variability in menstrual cycle length, largely determined by variation in follicular phase length, is related to several health outcomes, yet the causes of this variability are incompletely understood. We sought to identify characteristics associated with follicular phase length. Methods: We used the North Carolina Early Pregnancy Study to describe factors correlated with timing of ovulation (follicular phase length). Women collected daily urine specimens and recorded vaginal bleeding. Specimens were assayed for estrone 3-glucuronide and pregnanediol 3-glucuronide, which in turn were used to estimate the day of ovulation. All other variables were assessed through interview. Associations with follicular phase length were evaluated using a multiple regression model. Results: We determined follicular phase length for the first cycles of 201 women. Women with a history of miscarriage tended to have shorter follicular phases (2.2 days). Longer duration of oral contraceptive (OC) use and recent OC use (in the last 90 days) were both correlated with longer follicular phase. Occasional marijuana users (up to three times in the last 3 months) had a longer follicular phase than nonusers (3.5 days); the follicular phase in frequent users (more than three times) was almost 2 days longer than that of nonusers. Conclusions: The association between marijuana use and longer follicular phase is consistent with prior rhesus monkey research that shows ovulatory delay or inhibition. [ABSTRACT FROM AUTHOR]

To examine the association between serum 25-hydroxyvitamin D [25(OH)D] levels and ovarian reserve as measured using antimüllerian hormone (AMH) levels. Cross-sectional study. Detroit, Michigan area. Data were obtained from a prospective cohort of self-identified Black or African American women aged 23–35 years at the time of enrollment (N = 1,593), who had no prior diagnosis of polycystic ovary syndrome, were not currently pregnant, and were not missing AMH or 25(OH)D level measures. Serum 25(OH)D. The serum AMH level was the main outcome. Linear regression was used to examine the associations between categorical 25(OH)D levels (<12, 12–<20, 20–<30, and ≥30 ng/mL) and continuous natural log-transformed AMH levels. Associations between 25(OH)D and high (upper 10th percentile: >7.8 ng/mL) or low AMH (<0.7 ng/mL) levels were estimated with logistic regression. Models were adjusted for age, age-squared, body mass index (kg/m2), hormonal contraceptive use, smoking, and exercise. The 25(OH)D levels were low; 70% of participants were below 20 ng/mL. In fully adjusted models, compared with 25(OH)D levels <12 ng/mL, those with 25(OH)D levels of 12–<20, 20–<30, and ≥30 ng/mL had an AMH level that was 7% (95% confidence interval [CI]: −4, 20), 7% {95% CI: −6, 22}, or 11% {95% CI: −7, 34} higher, respectively. Moreover, these groups had lower odds of having low AMH levels (odds ratio [95% CI]: 0.63 {0.40, 0.99}, 0.60 {0.34, 1.07}, and 0.76 {0.35, 1.65}, respectively), and the highest category of 25(OH)D levels had higher odds of having high AMH levels (odds ratio [95% CI]: 1.42 {0.74, 2.72}). Exclusion of participants with either irregular cycles or very high AMH (>25 ng/mL) levels did not alter the associations. Taken together, these results indicate that higher levels of 25(OH)D are associated with slightly higher AMH levels, lower odds of low AMH levels, and higher odds of high AMH levels. This evidence is weak, however, because only a small percentage of participants had high 25(OH)D levels. Future studies should examine populations with a wide distribution of 25(OH)D levels (both high and low), with a clinical trial design, or with longitudinal measures of both 25(OH)D and AMH levels. [ABSTRACT FROM AUTHOR]

Background: Environmental exposure to phthalates and bisphenol A (BPA) may have endocrine disrupting effects that alter length of gestation. We assessed the association between the urinary concentrations of 11 phthalate metabolites and BPA with length of gestation in a cohort of women followed from before conception with daily 1st-morning urinary hormone measures that identified day of implantation.Methods: Pre-implantation and post-implantation urinary phthalate metabolites and BPA concentrations were measured in pooled urine samples designed to limit single-measure variability due to the likely episodic nature of these exposures and the short half-life of these compounds. We estimated associations between these exposure biomarkers early in pregnancy with length of gestation from implantation to spontaneous birth. Cox proportional hazards models were used to estimate the hazard of birth among 125 naturally-conceived, singleton live births with censoring for medical interventions that artificially shortened pregnancy.Results: Higher concentrations of mono (2-ethyl-5-hydroxyhexyl) phthalate (a metabolite of di (2-ethylhexyl) phthalate (DEHP)) during the pre-implantation window were associated with reduced probability of birth, i.e., longer gestations (hazard ratio (HR): 0.55, 95% CI: 0.35, 0.86; p = 0.01). The HR for the molar sum of the four DEHP metabolites measured showed a similar association (HR: 0.67, 95% CI: 0.43, 1.05). Higher concentrations of mono (3-carboxypropyl) phthalate (MCPP), a non-specific metabolite of several high molecular-weight phthalates, measured post-implantation were associated with increased risk of earlier birth, i.e. shorter length of gestation, HR: 1.59, CI: 1.02, 2.49.Conclusions: Early gestational exposure to DEHP and possibly other high-molecular weight phthalates, (as reflected by urinary MCPP concentrations) may influence the length of pregnancy. Such effects could have consequences for neonatal and maternal health. [ABSTRACT FROM AUTHOR]

The Preconception Period Analysis of Risks and Exposures Influencing Health and Development (PrePARED) Consortium creates a novel resource for addressing preconception health by merging data from numerous cohort studies. In this paper, we describe our data harmonization methods and results. Individual-level data from 12 prospective studies were pooled. The crosswalk-cataloging-harmonization procedure was used. The index pregnancy was defined as the first postbaseline pregnancy lasting more than 20 weeks. We assessed heterogeneity across studies by comparing preconception characteristics in different types of studies. The pooled data set included 114,762 women, and 25,531 (22%) reported at least 1 pregnancy of more than 20 weeks' gestation during the study period. Babies from the index pregnancies were delivered between 1976 and 2021 (median, 2008), at a mean maternal age of 29.7 (standard deviation, 4.6) years. Before the index pregnancy, 60% of women were nulligravid, 58% had a college degree or more, and 37% were overweight or obese. Other harmonized variables included race/ethnicity, household income, substance use, chronic conditions, and perinatal outcomes. Participants from pregnancy-planning studies had more education and were healthier. The prevalence of preexisting medical conditions did not vary substantially based on whether studies relied on self-reported data. Use of harmonized data presents opportunities to study uncommon preconception risk factors and pregnancy-related events. This harmonization effort laid the groundwork for future analyses and additional data harmonization. [ABSTRACT FROM AUTHOR]

BACKGROUND: Extracellular vesicles (EVs), membrane-bound particles containing a variety of RNA types, DNA, proteins, and other macromolecules, are now appreciated as an important means of communication between cells and tissues, both in normal cellular physiology and as a potential indicator of cellular stress, environmental exposures, and early disease pathogenesis. Extracellular signaling through EVs is a growing field of research for understanding fundamental mechanisms of health and disease and for the potential for biomarker discovery and therapy development. EVs are also known to play important roles in mediating the effects of exposure to environmental stress. OBJECTIVES: This seminar addresses the application of new tools and approaches for EV research, developed in part through the National Institutes of Health (NIH) Extracellular RNA Communication Program, and reflects presentations and discussions from a workshop held 27–28 September 2021 by the National Institute of Environmental Health Sciences (NIEHS) and the National Center for Advancing Translational Sciences (NCATS) on “Extracellular Vesicles, Exosomes, and Cell-Cell Signaling in Response to Environmental Stress.” The panel of experts discussed current research on EVs and environmental exposures, highlighted recent advances in EV isolation and characterization, and considered research gaps and opportunities toward identifying and characterizing the roles for EVs in environmentally related diseases, as well as the current challenges and opportunities in this field. DISCUSSION: The authors discuss the application of new experimental models, particularly organ-on-chip (OOC) systems and in vitro approaches and how these have the potential to extend findings in population-based studies of EVs in exposure-related diseases. Given the complex challenges of identifying cell-specific EVs related to environmental exposures, as well as the general heterogeneity and variability in EVs in blood and other accessible biological samples, there is a critical need for rigorous reporting of experimental methods and validation studies. The authors note that these efforts, combined with cross-disciplinary approaches, would ensure that future research efforts in environmental health studies on EV biomarkers are rigorous and reproducible. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between antimüllerian hormone (AMH), a measure of ovarian reserve, and miscarriage among naturally conceived pregnancies.Design: Prospective cohort study.Setting: Not applicable.Patient(s): Women (n = 533), between 30 and 44 years of age with no known history of infertility, polycystic ovarian syndrome, or endometriosis who conceived naturally.Intervention(s): None.Main Outcome Measure(s): Miscarriage, defined as an intrauterine pregnancy loss before 20 weeks' gestation.Result(s): After adjusting for maternal age, race, history of recurrent miscarriage, and obesity, risk of miscarriage decreased as AMH increased (risk ratio per unit increase in natural log of AMH = 0.83; 95% confidence interval [CI], 0.73, 0.94). Women with severely diminished ovarian reserve (AMH ≤ 0.4 ng/mL) miscarried at over twice the rate of women with an AMH ≥ 1 ng/mL (hazard ratio, 2.3; 95% CI, 1.3, 4.3).Conclusion(s): AMH levels are inversely associated with the risk of miscarriage. Women with severely diminished ovarian reserve are at an increased risk of miscarriage. [ABSTRACT FROM AUTHOR]

Background: Pregnant women in American Samoa have a high risk of complications due to overweight and obesity. Prenatal care can mitigate the risk, however many women do not seek adequate care during pregnancy. Low utilization of prenatal care may stem from low levels of satisfaction with services offered. Our objective was to identify predictors of prenatal care satisfaction in American Samoa.Methods: A structured survey was distributed to 165 pregnant women receiving prenatal care at the Lyndon B Johnson Tropical Medical Center, Pago Pago. Women self-reported demographic characteristics, pregnancy history, and satisfaction with prenatal care. Domains of satisfaction were extracted using principal components analysis. Scores were summed across each domain. Linear regression was used to examine associations between maternal characteristics and the summed scores within individual domains and for overall satisfaction.Result: Three domains of satisfaction were identified: satisfaction with clinic services, clinic accessibility, and physician interactions. Waiting ≥ 2 h to see the doctor negatively impacted satisfaction with clinic services, clinic accessibility, and overall satisfaction. Living > 20 min from the clinic was associated with lower clinic accessibility, physician interactions, and overall satisfaction. Women who were employed/on maternity leave had lower scores for physician interactions compared with unemployed women/students. Women who did not attend all their appointments had lower overall satisfaction scores.Conclusions: Satisfaction with clinic services, clinic accessibility and physician interactions are important contributors to prenatal care satisfaction. To improve patient satisfaction prenatal care clinics should focus on making it easier for women to reach clinics, improving waiting times, and increasing time with providers. [ABSTRACT FROM AUTHOR]

BACKGROUND: Parabens, found in everyday items from personal care products to foods, are chemicals with endocrine-disrupting activity, which has been shown to influence reproductive function. OBJECTIVES: This study investigated whether urinary concentrations of methylparaben, propylparaben, or butylparaben were associated with the urinary metabolome during the periconceptional period, a critical window for female reproductive function. Changes to the periconceptional urinary metabolome could provide insights into the mechanisms by which parabens could impact fertility. METHODS: Urinary paraben concentrations were measured in paired pre- and postconception urine samples from 42 participants in the Early Pregnancy Study, a prospective cohort of 221 women attempting to conceive. We performed untargeted and targeted metabolomics analyses using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. We used principal component analysis, orthogonal partial least-squares discriminant analysis, and permutation testing, coupled with univariate statistical analyses, to find metabolites associated with paraben concentration at the two time points. Potential confounders were identified with a directed acyclic graph and used to adjust results with multivariable linear regression. Metabolites were identified using fragmentation data. RESULTS: Seven metabolites were associated with paraben concentration (variable importance to projection score >1, false discovery rate-corrected 푞-value<0.1). We identified four diet-related metabolites to the Metabolomics Standards Initiative (MSI) certainty of identification level 2, including metabolites from smoke flavoring, grapes, and olive oil. One metabolite was identified to the class level only (MSI level 3). Two metabolites were un-identified (MSI level 4). After adjustment, three metabolites remained associated with methylparaben and propylparaben, two of which were diet-related. No metabolomic markers of endocrine disruption were associated with paraben concentrations. DISCUSSION: This study identified novel relationships between urinary paraben concentrations and diet-related metabolites but not with metabolites on endocrine-disrupting pathways, as hypothesized. It demonstrates the feasibility of integrating untargeted metabolomics data with environmental exposure information and epidemiological adjustment for confounders. The findings underscore a potentially important connection between diet and paraben exposure, with applications to nutritional epidemiology and dietary exposure assessment [ABSTRACT FROM AUTHOR]

Objective: To examine the association between serum 25-hydroxyvitamin D [25(OH)D] and menstrual cycle length and regularity.Design: Community-based, cross-sectional study of serum 25(OH)D (adjusted for seasonal differences in timing of blood draw) and menstrual cycle length. Women aged 23-34 years reported their gynecologic history. Menstrual cycles were described with four independent categories (normal, short, long, irregular). We used polytomous logistic regression to estimate the association between a doubling of seasonally adjusted 25(OH)D and the odds of each cycle category.Setting: Not applicable.Patient(s): A total of 1,102 African American women.Intervention(s): Not applicable.Main Outcome Measure(s): Self-reported menstrual cycle length over the previous 12 months, excluding women who were using cycle-regulating medications over the entire year. Women who reported that their cycles were "too irregular to estimate" were classified as having irregular cycles. A typical cycle length of <27 days was considered "short," >34 days was "long," and 27-34 days was "normal."Result(s): The median 25(OH)D level was 14.7 ng/mL (interquartile range, 10.9-19.6 ng/mL). A doubling of 25(OH)D was associated with half the odds of having long menstrual cycles: adjusted odds ratio (aOR) 0.54, 95% confidence interval (CI) 0.32-0.89. 25-Hydroxyvitamin D was not associated with the occurrence of short (aOR 1.03, 95% CI 0.82-1.29) or irregular (aOR 1.46, 95% CI 0.88-2.41) menstrual cycles. Results were robust to several sensitivity analyses.Conclusion(s): These findings suggest that vitamin D status may influence the menstrual cycle and play a role in ovarian function. Further investigation of 25(OH)D and ovarian hormones, and prospective studies of 25(OH)D and cycle length, are needed. [ABSTRACT FROM AUTHOR]

Background: Intrauterine conditions may be important in the development of cerebral palsy in the child. The hormone, human chorionic gonadotropin (hCG), is synthesized in the placenta, and hCG plays an important role in placental angiogenesis and development. Thus, maternal hCG concentrations may be an indicator of placental function and thereby the intrauterine environment for the offspring. We studied the associations of maternal concentrations of hCG during pregnancy with cerebral palsy in the child.Methods: We performed a case-control study nested within a cohort of 29,948 pregnancies in Norway during 1992-1994. Cases were all women within the cohort who gave birth to a singleton child with cerebral palsy diagnosed before five years of age (n = 63). Controls were a random sample of women with a singleton child without cerebral palsy (n = 182).Results: The adjusted odds ratio (OR) for cerebral palsyin the child was 0.78 (95% CI: 0.55-1.10) per log-transformed unit of maternal hCG in the 1 st trimester, and the OR was 1.42 (95% CI: 0.94-2.16) in the 2nd trimester. Thus, women who did not have high hCG concentrations in the 1 st trimester and low hCG concentrations in the 2nd trimester, had increased risk for giving birth to a child with cerebral palsy. Adjustments were made for pregnancy week of serum sampling, maternal age and parity.Conclusions: The abnormal hCG concentrations in pregnancies with cerebral palsy in the offspring, could suggest placental factors as causes of cerebral palsy. [ABSTRACT FROM AUTHOR]

Objective: To provide female age-related estimates of fecundity and incidence of infertility by history of prior pregnancy among women 30-44 years of age.Design: Prospective, time-to-pregnancy cohort study.Setting: Not applicable.Patient(s): Women, between 30 and 44 years of age, attempting to conceive for ≤3 months, and no known history of infertility, polycystic ovarian syndrome (PCOS), or endometriosis.Intervention(s): Not applicable.Main Outcome Measure(s): Fecundability and incidence of infertility.Result(s): Compared to women aged 30-31 years, fecundability was reduced by 14% in women 34-35 years of age (fecundability ratio [FR] 0.86, 95% confidence interval [CI] 0.68-1.08), 19% in women 36-37 years of age (FR 0.81, 95% CI 0.60-1.08, 30% in women 38-39 years of age (FR 0.70, 95% CI 0.48-1.01), 53% in women 40-41 years of age (FR 0.47, 95% CI 0.28-0.78), and 59% in women 42-44 years of age (FR 0.39, 95% CI 0.16-0.93). Fecundability did not differ between women aged 30-31 years and 32-33 years. In general, fecundability and cumulative probability of pregnancy was lower for women who had never had a prior pregnancy.Conclusion(s): Women experience a significant reduction in fecundity and increase in the probability of infertility in their late thirties. At any age >30 years, women who have never conceived have a lower probability of achieving a pregnancy.Clinical Trial Registration Number: NCT01028365. [ABSTRACT FROM AUTHOR]

Study Question: Are urinary phenol concentrations of methylparaben, propylparaben, butylparaben, triclosan, benzophenone-3, 2,4-dichlorophenol or 2,5-dichlorophenol associated with fecundability and early pregnancy loss?Summary Answer: 2,5-dichlorophenol concentrations were associated with an increased odds of early pregnancy loss, and higher concentrations of butylparaben and triclosan were associated with an increase in fecundability.What Is Known Already: Phenols are chemicals with endocrine-disrupting potential found in everyday products. Despite plausible mechanisms of phenol reproductive toxicity, there are inconsistent results across few epidemiologic studies examining phenol exposure and reproductive function in non-fertility treatment populations.Study Design, Size, Duration: Specimens and data were from the North Carolina Early Pregnancy Study prospective cohort of 221 women attempting to conceive naturally from 1982 to 1986. This analysis includes data from 221 participants across 706 menstrual cycles, with 135 live births, 15 clinical miscarriages and 48 early pregnancy losses (before 42 days after the last menstrual period).Participants/materials, Setting, Methods: Participants collected daily first-morning urine specimens. For each menstrual cycle, aliquots from three daily specimens across the cycle were pooled within individuals and analyzed for phenol concentrations. To assess sample repeatability, we calculated intraclass correlation coefficients (ICCs) for each phenol. We evaluated associations between phenol concentrations from pooled samples and time to pregnancy using discrete-time logistic regression and generalized estimating equations (GEE), and early pregnancy loss using multivariable logistic regression and GEE.Main Results and the Role Of Chance: ICCs for within-person variability across menstrual cycles in pooled phenol concentrations ranged from 0.42 to 0.75. There was an increased odds of early pregnancy loss with 2,5-dichlorophenol concentrations although the CIs were wide (5th vs 1st quintile odds ratio (OR): 4.79; 95% CI: 1.06, 21.59). There was an increased per-cycle odds of conception at higher concentrations of butylparaben (OR: 1.62; 95% CI: 1.08, 2.44) and triclosan (OR: 1.49; 95% CI: 0.99, 2.26) compared to non-detectable concentrations. No associations were observed between these endpoints and concentrations of other phenols examined.Limitations, Reasons For Caution: Limitations include the absence of phenol measurements for male partners and a limited sample size, especially for the outcome of early pregnancy loss, which reduced our power to detect associations.Wider Implications Of the Findings: This study is the first to use repeated pooled measures to summarize phenol exposure and the first to investigate associations with fecundability and early pregnancy loss. Within-person phenol concentration variability underscores the importance of collecting repeated samples for future studies. Exposure misclassification could contribute to differences between the findings of this study and those of other studies, all of which used one urine sample to assess phenol exposure. This study also contributes to the limited literature probing potential associations between environmental exposures and early pregnancy loss, which is a challenging outcome to study as it typically occurs before a pregnancy is clinically recognized.Study Funding/competing Interest(s): This research was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health (award number F31ES030594), the Intramural Research Program of the National Institutes of Health, the National Institute of Environmental Health Sciences (project numbers ES103333 and ES103086) and a doctoral fellowship at the Yale School of Public Health. The authors declare they have no competing interests to disclose.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

• Digital cohort of 125,104 menstrual cycles from 17,427 participants within the US. • Modest seasonal variation of menstrual cycle length from June 2020 to July 2022. • Shorter cycles (<1/5 day) in May–Aug and Sept–Dec compared to Jan–April. • Younger participants <35°N and >40°N with PCOS had strongest seasonal trends. • No seasonal patterns in cycle lengths were found for participants above age 40. [ABSTRACT FROM AUTHOR]

Background: Time to pregnancy (TTP) is a biomarker of fecundability and has been associated with behavioral and environmental characteristics; however, these associations have not been examined in a large population-based sample of application (app) users. Materials and Methods: This observational study followed 5,376 women with an age range of 18 to 45 years who used an app to identify their fertile window. We included women who started trying to conceive between September 30, 2017 and August 31, 2018. TTP was calculated as the number of menstrual cycles from when the user switched to "Plan" mode up to and including the cycle in which they logged a positive pregnancy test. We examined associations with several characteristics, including age, gravidity, body mass index, cycle length and cycle length variation, frequency of sexual intercourse, and temperature measuring frequency. Discrete time fecundability models were used to estimate fecundability odds ratios. Results: For the complete cohort the 6-cycle and 12-cycle cumulative pregnancy probabilities were found to be 61% (95% confidence interval [CI]: 59–62) and 74% (95% CI: 73–76), respectively. The median TTP was four cycles. The highest fecundability was associated with an age of less than 35 years, with cycle length variation <5 days and logging sexual intercourse on at least 20% of days added (the proportion of days in which intercourse was logged) (11.5% [n = 613] of entire sample). This group achieved a 6- and 12-cycle cumulative pregnancy probability of 88% (95% CI: 85–91) and 95% (95% CI: 94–97), respectively, and a TTP of 2 cycles. Conclusions: Natural Cycles was an effective method of identifying the fertile window and a noninvasive educational option for women planning a pregnancy. Women under age 35 with regular cycles showed a high pregnancy rate. [ABSTRACT FROM AUTHOR]

Nongenetic, environmental factors contribute to maternal morbidity and mortality through chemical exposures via air, water, soil, food, and consumer products. Pregnancy represents a particularly sensitive window of susceptibility during which physiological changes to every major organ system increase sensitivity to chemicals that can impact a woman's long-term health. Nonchemical stressors, such as low socioeconomic status, may exacerbate the effects of chemical exposures on maternal health. Racial/ethnic minorities are exposed disproportionately to both chemicals and nonchemical stressors, which likely contribute to the observed health disparities for maternal morbidities and mortality. Epidemiological studies linking exposures to adverse maternal health outcomes underscore the importance of environmental health impacts, and mechanistic studies in model systems reveal how chemicals perturb biological pathways and processes. Environmental stressors are associated with a variety of immediate maternal health impacts, including hypertensive disorders of pregnancy, fibroids, and infertility, as well as long-term maternal health impacts, such as higher risk of breast cancer and metabolic disorders. Identifying and reducing a pregnant woman's environmental exposures is not only beneficial to her offspring but also important to preserve her short- and long-term health. [ABSTRACT FROM AUTHOR]

Background: Preconception health may have intergenerational influences. We have formed the PrePARED (Preconception Period Analysis of Risks and Exposures influencing health and Development) research consortium to address methodological, conceptual, and generalisability gaps in the literature.Objectives: The consortium will investigate the effects of preconception exposures on four sets of outcomes: (1) fertility and miscarriage; (2) pregnancy-related conditions; (3) perinatal and child health; and (4) adult health outcomes.Population: A study is eligible if it has data measured for at least one preconception time point, has a minimum of selected core data, and is open to collaboration and data harmonisation.Design: The included studies are a mix of studies following women or couples intending to conceive, general-health cohorts that cover the reproductive years, and pregnancy/child cohort studies that have been linked with preconception data. The majority of the participating studies are prospective cohorts, but a few are clinical trials or record linkages.Methods: Data analysis will begin with harmonisation of data collected across cohorts. Initial areas of interest include nutrition and obesity; tobacco, marijuana, and other substance use; and cardiovascular risk factors.Preliminary Results: Twenty-three cohorts with data on almost 200 000 women have combined to form this consortium, begun in 2018. Twelve studies are of women or couples actively planning pregnancy, and six are general-population cohorts that cover the reproductive years; the remainder have some other design. The primary focus for four was cardiovascular health, eight was fertility, one was environmental exposures, three was child health, and the remainder general women's health. Among other cohorts assessed for inclusion, the most common reason for ineligibility was lack of prospectively collected preconception data.Conclusions: The consortium will serve as a resource for research in many subject areas related to preconception health, with implications for science, practice, and policy. [ABSTRACT FROM AUTHOR]

Background: We studied associations of number of daily cigarettes in the first trimester with placental weight and birthweight in women who smoked throughout pregnancy, and in women who stopped smoking after the first trimester.Methods: We included all women with delivery of a singleton in Norway (n = 698 891) during 1999-2014, by using data from the Medical Birth Registry of Norway. We assessed dose-response associations by applying linear regression with restricted cubic splines.Results: In total, 12.6% smoked daily in the first trimester, and 3.7% stopped daily smoking. In women who smoked throughout pregnancy, placental weight and birthweight decreased by number of cigarettes; however, above 11-12 cigarettes we estimated no further decrease (Pnon-linearity < 0.001). Maximum decrease in placental weight in smokers compared with non-smokers was 18.2 g [95% confidence interval (CI): 16.6 to 19.7], and for birthweight the maximum decrease was 261.9 g (95% CI: 256.1 to 267.7). In women who stopped smoking, placental weight was higher than in non-smokers and increased by number of cigarettes to a maximum of 16.2 g (95% CI: 9.9 to 22.6). Birthweight was similar in women who stopped smoking and non-smokers, and we found no change by number of cigarettes (Pnon-linearity < 0.001).Conclusions: In women who smoked throughout pregnancy, placental weight and birthweight decreased non-linearly by number of cigarettes in the first trimester. In women who stopped smoking, placental weight was higher than in non-smokers and increased linearly by number of cigarettes; birthweight was almost similar to that of non-smokers. [ABSTRACT FROM AUTHOR]