Preconception Phthalate Exposure and Women's Reproductive Health: Pregnancy, Pregnancy Loss, and Underlying Mechanisms.

BACKGROUND: Phthalates are endocrine-disrupting chemicals linked to adverse pregnancy outcomes. Despite the sensitivity of female reproductive processes to oxidation-reduction reaction stress and endocrine disruption, evidence for the impact of women's phthalate exposure on the ability to establish and maintain pregnancy has been inconclusive. OBJECTIVES: We aimed to determine the relationship of preconception phthalate metabolite exposure with a) fecundability and pregnancy loss and b) markers of potential biological mechanisms, including reproductive hormones, inflammation, and oxidative stress. METHODS: Data were collected from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, a preconception study following 1,228 women who were attempting pregnancy, for up to six menstrual cycles and throughout pregnancy if they became pregnant. Twenty phthalate metabolites were measured in a consecutive 3-d pooled urine sample at enrollment. Pregnancy was determined through urinary human chorionic gonadotropin (hCG) at the expected date of menses during each cycle and pregnancy loss as an observed loss following positive hCG. Highly sensitive C-reactive protein (hsCRP) and isoprostanes were measured at enrollment, and reproductive hormones were measured during the follicular phase, ovulation, and luteal phase. Discrete-time Cox proportional hazards models evaluated the relationship of phthalate metabolites with fecundability and weighted Poisson models with robust variance evaluated the risk of pregnancy loss. RESULTS: An interquartile range (IQR) higher mono-(2-ethylhexyl) phthalate [fecundability odds ratio (FOR)=0.88; 95% confidence interval (CI): 0.78, 1.00], mono-butyl phthalate (FOR=0.82; 95% CI: 0.70, 0.96), and mono-benzyl phthalate (FOR=0.85; 95% CI: 0.74, 0.98) was associated with lower fecundability. No consistent associations were observed with pregnancy loss. Preconception phthalates were consistently associated with higher hsCRP and isoprostanes, as well as lower estradiol and higher follicle-stimulating hormone across the menstrual cycle. DISCUSSION: Women's preconception exposure to phthalates was associated with lower fecundability, changes in reproductive hormones, and increased inflammation and oxidative stress. The pre- and periconception periods may represent sensitive windows for intervening to limit the reproductive toxicity of phthalate exposure. https://doi.org/10.1289/EHP12287.

The Relationship of Preconception and Early Pregnancy Isoprostanes with Fecundability and Pregnancy Loss.

BACKGROUND: Although redox stress likely plays an important role in reproductive health, the utility of peripheral biomarkers of oxidative stress, such as isoprostanes, during the periconception period remains underexplored. We evaluated the relationship between isoprostanes during preconception and gestational week 4 and women's reproductive health outcomes. METHODS: The Effects of Aspirin in Gestation and Reproduction trial (2007-2011) enrolled 1228 women attempting pregnancy and followed them for up to 6 menstrual cycles and throughout pregnancy if they became pregnant. We measured creatinine-adjusted, log-transformed isoprostanes 8-iso-prostaglandin F 2α (8-iso-PGF2α), its metabolite 2,3-dinor-iPF2α-III, and stereoisomers 5-iso-PGF2α-VI and 8,12-iso-iPF2α-VI in urine during preconception and 4 weeks gestation. We evaluated pregnancy among participants in each menstrual cycle using human chorionic gonadotropin (hCG) and defined pregnancy loss as observed loss following positive hCG. We calculated fecundability odds ratios (FOR) and 95% confidence intervals (CI) using discrete-time Cox proportional hazards models and relative risk of pregnancy loss using adjusted log-binomial models. RESULTS: Higher preconception isoprostane levels were associated with lower fecundability [e.g., FOR = 0.89; 95% CI = 0.81, 0.97 per interquartile range (IQR) increase in 8-iso-PGF2α]. Among 797 pregnancies, isoprostane levels increased from preconception to 4 weeks gestation (e.g., mean difference = 0.12; 95% CI = 0.10, 0.14 ng/mL for 8-iso-PGF2α) and higher isoprostanes at 4 weeks gestation were associated with lower risk of pregnancy loss (e.g., RR = 0.79; 95% CI = 0.62, 1.00 per IQR increase in 8-iso-PGF2α). CONCLUSIONS: Preconception urinary isoprostanes may identify redox stress pathways associated with lower fecundability. However, the increase in isoprostanes into gestational week 4 and the associated lower risk of pregnancy loss may suggest confounding by latent factors in early pregnancy.

Asthma Medication Regimens in Pregnancy: Longitudinal Changes in Asthma Status.

OBJECTIVE: This study aimed to assess the impact of common asthma medication regimens on asthma symptoms, exacerbations, lung function, and inflammation during pregnancy. STUDY DESIGN: A total of 311 women with asthma were enrolled in a prospective pregnancy cohort. Asthma medication regimen was categorized into short-acting ß agonist (SABA) alone, SABA + inhaled corticosteroid (ICS), SABA + ICS + long-acting ß agonist (LABA), and no asthma medications (reference). We evaluated asthma control at enrollment (< 15 weeks' gestation) and its change into trimesters 2 and 3, including per cent predicted forced expiratory volume in 1 second (%FEV1) and peak expiratory flow (%PEF), pulse oximetry, fractional exhaled nitric oxide (FeNO), asthma symptoms (asthma attacks/month, night symptoms/week), and severe exacerbations. Linear mixed models adjusted for site, age, race, annual income, gestational age, body mass index, and smoking, and propensity scores accounted for asthma control status at baseline. RESULTS: Women taking SABA + ICS and SABA + ICS + LABA had better first trimester %PEF (83.5% [75.7-91.3] and 84.6% [76.9-92.3], respectively) compared with women taking no asthma medications (72.7% [66.0-79.3]). Women taking SABA + ICS + LABA also experienced improvements in %FEV1 (+11.1%, p < 0.01) in the third trimester and FeNO in the second (-12.3 parts per billion [ppb], p < 0.01) and third (-11.0 ppb, p < 0.01) trimesters as compared with the trajectory of women taking no medications. SABA + ICS use was associated with increased odds of severe exacerbations in the first (odds ratio [OR]: 2.22 [1.10-4.46]) and second (OR: 3.15 [1.11-8.96]) trimesters, and SABA + ICS + LABA use in the second trimester (OR: 7.89 [2.75-21.47]). Women taking SABA alone were similar to those taking no medication. CONCLUSION: Pregnant women taking SABA + ICS and SABA + ICS + LABA had better lung function in the first trimester. SABA + ICS + LABA was associated with improvements in lung function and inflammation across gestation. However, both the SABA + ICS and SABA + ICS + LABA groups had a higher risk of severe exacerbation during early to mid-pregnancy. KEY POINTS: · Medication regimens may affect perinatal asthma control.. · Intensive regimens improved lung function/inflammation.. · Women on intensive regimens had more acute asthma events..

The Safety of Low-Dose Aspirin on the Mode of Delivery: Secondary Analysis of the Effect of Aspirin in Gestation and Reproduction Randomized Controlled Trial.

OBJECTIVE: This study aimed to examine whether prenatal low-dose aspirin (LDA) therapy affects risk of cesarean versus vaginal delivery. STUDY DESIGN: This study is a secondary analysis of the randomized clinical effects of aspirin in gestation and reproduction (EAGeR) trial. Women received 81-mg daily aspirin or placebo from preconception to 36 weeks of gestation. Mode of delivery and obstetric complications were abstracted from records. Log-binomial regression models estimated relative risk (RR) of cesarean versus vaginal delivery. Data were analyzed among the total preconception cohort, as well as restricted to women who had a live birth. RESULTS: Among 1,228 women, 597 had a live birth. In the intent-to-treat analysis, preconception-initiated LDA was not associated with risk of cesarean (RR = 1.02; 95% confidence interval [CI]: 0.98-1.07) compared with placebo. Findings were similar in just women with a live birth and when accounting prior cesarean delivery and parity. CONCLUSION: Preconception-initiated daily LDA was not associated with mode of delivery among women with one to two prior losses. KEY POINTS: · Aspirin was not associated with risk of cesarean section.. · Aspirin was not associated with mode of delivery.. · No increased risk of bleeding with use of aspirin..

A Data-Based Approach to Evaluating Representation by Gender and Affiliation in Key Presentation Formats at the Annual Meeting of the Society for Epidemiologic Research.

The annual meeting of the Society for Epidemiologic Research (SER) is a major forum for sharing new research and promoting the career development of participants. Because of this, evaluating representation in key presentation formats is critical. For the 3,257 presentations identified at the 2015-2017 SER annual meetings, we evaluated presenter characteristics, including gender, affiliation, subject area, and h-index, and representation in 3 highlighted presentation formats: platform talks (n = 382), invited symposium talks (n = 273), and chairing a concurrent contributed session or symposium (n = 188). Data were abstracted from SER records, abstract booklets, and programs. Gender was assessed using GenderChecker software, and h-index was determined using the Scopus application programming interface. Log-binomial models were adjusted for participant characteristics and conference year. In adjusted models, women were less likely than men to present an invited symposium talk (relative risk = 0.60, 95% confidence interval: 0.45, 0.81) compared with all participants with accepted abstracts. Researchers from US public universities, US government institutions, and international institutions were less likely to present a symposium talk or to chair a concurrent contributed session or symposium than were researchers from US private institutions. The research areas that were most represented in platform talks were epidemiologic methods, social epidemiology, and cardiovascular epidemiology. Our findings suggest differences in representation by gender, affiliation, and subject area after accounting for h-index.

The role of maternal preconception vitamin D status in human offspring sex ratio.

Evolutionary theory suggests that some animal species may experience shifts in their offspring sex ratio in response to maternal health and environmental conditions, and in some unfavorable conditions, females may be less likely to bear sons. Experimental data in both animals and humans indicate that maternal inflammation may disproportionately impact the viability of male conceptuses; however, it is unknown whether other factors associated with both pregnancy and inflammation, such as vitamin D status, are associated with the offspring sex ratio. Here, we show that among 1,228 women attempting pregnancy, preconception 25-hydroxyvitamin D concentrations are positively associated with the live birth of a male infant, with notably stronger associations among women with elevated high sensitivity C-reactive protein, a marker of systemic low-grade inflammation. Our findings suggest that vitamin D may mitigate maternal inflammation that would otherwise be detrimental to the implantation or survival of male conceptuses in utero.

Associations between blood cadmium and endocrine features related to PCOS-phenotypes in healthy women of reproductive age: a prospective cohort study.

BACKGROUND: Cadmium is an endocrine disrupting chemical that affects the hypothalamic-pituitary-gonadal axis. Though evidence suggests its potential role in altering androgen synthesis and metabolic pathways that are characteristic of polycystic ovary syndrome (PCOS), its relation in healthy women of reproductive age is largely unknown. As women with mild sub-clinical features of PCOS who do not meet the diagnostic criteria of PCOS may still experience reduced fecundability, investigating associations between cadmium and PCOS-phenotypes among healthy women may provide unique insight into the reproductive implications for many on the PCOS spectrum. Therefore, the objective of this study was to evaluate associations between cadmium and androgens, anti-Müllerian hormone (AMH), and metabolic markers in women of reproductive age. METHODS: This was a prospective cohort study of 251 healthy premenopausal women without self-reported PCOS (mean age 27.3 years and BMI 24.1 kg/m2). Cadmium was measured in blood collected at baseline. Reproductive hormones and metabolic markers were measured in fasting serum 8 times per menstrual cycle for 2 cycles. Linear mixed models and Poisson regression with a robust error variance were used to examine associations between cadmium and reproductive hormones and metabolic markers and anovulation, respectively. RESULTS: Median (interquartile range) blood cadmium concentrations at baseline were 0.30 (0.19-0.43) µg/L. Higher levels of testosterone (2.2 %, 95 % confidence interval [CI] 0.4, 4.1), sex hormone-binding globulin (2.9 %, 95 % CI 0.5, 5.5), and AMH (7.7 %, 95 % CI 1.1, 14.9) were observed per 0.1 µg/L increase in cadmium concentrations. An 18 % higher probability of a mild PCOS-phenotype (95 % CI 1.06, 1.31), defined by a menstrual cycle being in the highest quartile of cycle-averaged testosterone and AMH levels, was also found per 0.1 µg/L increase in cadmium levels. No associations were observed for insulin and glucose. These findings were consistent even after analyses were restricted to non-smokers or further adjusted for dietary factors to account for potential sources of exposure. CONCLUSIONS: Overall, among healthy reproductive-aged women, cadmium was associated with endocrine features central to PCOS, but not with metabolic markers. These suggest its potential role in the hormonal milieu associated with PCOS even at low levels of exposure.

Low Intake of Vegetable Protein is Associated With Altered Ovulatory Function Among Healthy Women of Reproductive Age.

CONTEXT: Diets high in plant-based protein have gained popularity due to increasing health concerns regarding consumption of animal products. Though links between intakes of certain protein-rich foods and reproductive disorders have been suggested, the relationship of overall animal and vegetable proteins with reproductive hormones among reproductive-aged women is unknown. OBJECTIVE: To evaluate the associations between the intake of dietary protein with reproductive hormones and sporadic anovulation among reproductive-aged women. DESIGN: A prospective cohort study, 2005-2007. SETTING: University at Buffalo, western New York, United States. PARTICIPANTS: A total of 259 premenopausal women (18-44 years) without dietary restrictions. MAIN OUTCOME MEASURE(S): Serum reproductive hormones were determined up to 8 times per cycle for 2 cycles. Protein intake was assessed the day prior to hormone assessment at 4 visits/cycle using 24-hour recalls. RESULTS: Overall, 84% of participants met the recommended dietary allowance for total protein set for reproductive-aged women. Neither total nor animal protein intake were associated with reproductive hormones or anovulation. However, vegetable protein intake in the lowest tertile was associated with lower luteal phase progesterone (-18.0%, 95% confidence interval [CI] -30.2, -3.6), higher follicle-stimulating hormone (3.8%, 95% CI 0.2, 7.6), and a higher risk of anovulation (risk ratio [RR] 2.53, 95% CI 1.21, 5.26), compared with the middle tertile. Nuts and seeds were the only protein-rich foods associated with an elevated risk of anovulation (RR 2.12, 95% CI 1.17, 3.85). CONCLUSIONS: Findings suggest that among women who meet the recommended dietary allowance for total protein, low intake of vegetable, but not animal, protein may disturb normal ovulatory function.

Chronic exposure to air pollution and risk of mental health disorders complicating pregnancy.

BACKGROUND: Air pollution is associated with mental health in the general population, but its influence on maternal mental health during pregnancy has not been assessed. OBJECTIVE: We evaluated the relationship between unspecified mental disorders complicating pregnancy and depression with average air pollution exposure during 3-months preconception, first trimester and whole pregnancy. METHODS: Ambient air pollution was derived from a modified Community Multiscale Air Quality model and mental health diagnoses were based on electronic intrapartum medical records. Logistic regression models assessed the odds of unspecified mental disorder complicating pregnancy (n = 11,577) and depression (n = 9793) associated with an interquartile range increase in particulate matter (PM) less than 2.5 µm (PM2.5), PM10, carbon monoxide (CO), nitrogen dioxide (NO2), nitrogen oxide (NOx), sulfur dioxide (SO2), and ozone (O3). Pregnancies without mental health disorders were the reference group (n = 211,645). Models were adjusted for maternal characteristics and study site; analyses were repeated using cases with no additional mental health co-morbidity. RESULTS: Whole pregnancy exposure to PM10, PM2.5, NO2, and NOx was associated with a 29%-74% increased odds of unspecified mental disorders complicating pregnancy while CO was associated with 31% decreased odds. Results were similar for depression: whole pregnancy exposure to PM10, PM2.5, NO2, and NOx was associated with 11%-21% increased odds and CO and O3 were associated with 16%-20% decreased odds. SO2 results were inconsistent, with increased odds for unspecified mental disorders complicating pregnancy and decreased odds for depression. While most findings were similar or stronger among cases with no co-morbidity, PM2.5 and NOx were associated with reduced risk and SO2 with increased risk for depression only. DISCUSSION: Whole pregnancy exposure to PM10, PM2.5, NO2, and NOx were associated with unspecified mental disorder complicating pregnancy and depression, but some results varied for depression only. These risks merit further investigation.

Does maternal race or ethnicity modify the association between maternal psychiatric disorders and preterm birth?

PURPOSE: Preterm birth risk has been linked to maternal racial and ethnic background, particularly African American heritage; however, the association of maternal race and ethnicity with psychiatric disorders and preterm birth has received relatively limited attention. METHODS: The Consortium on Safe Labor (2002-2008) is a nationwide U.S. cohort study with 223,394 singleton pregnancies. Clinical data were obtained from electronic medical records, including maternal diagnoses of psychiatric disorders. Relative risk (RR) and 95% confidence intervals (CI) were estimated for the association between maternal psychiatric disorders and preterm birth (<37 completed weeks) using log-binomial regression with generalized estimating equations. The interaction effect of maternal psychiatric disorders with race and ethnicity was also evaluated. RESULTS: Non-Hispanic White (RR, 1.42; 95% CI, 1.35-1.49), Hispanic (RR, 1.44; 95% CI, 1.29-1.60), and non-Hispanic Black (RR, 1.21, 95% CI, 1.13-1.29) women with any psychiatric disorder were at increased risk for delivering preterm infants, compared with women without any psychiatric disorder. However, non-Hispanic Black women with any psychiatric disorder, depression, bipolar disorder, and schizophrenia had a significantly lower increase in preterm birth risk than non-Hispanic White women. CONCLUSIONS: Despite the significant association between maternal psychiatric disorders and preterm birth risk, psychiatric disorders did not appear to contribute to racial and ethnic disparities in preterm birth.

Adiposity is associated with anovulation independent of serum free testosterone: A prospective cohort study.

BACKGROUND: Obesity, a body mass index (BMI) ≥30 kg/m2 , is linked to infertility, potentially through a greater risk of anovulation due to elevated androgens. Yet, previous studies have not directly assessed the impact of adiposity, or body fat, on anovulation in the absence of clinical infertility. OBJECTIVE: To characterise the associations between adiposity and anovulation among women menstruating on a regular basis. METHODS: Women from the EAGeR trial (n = 1200), a randomised controlled trial of low-dose aspirin and pregnancy loss among women trying to conceive, were used to estimate associations between adiposity and incident anovulation. Participants completed baseline questionnaires and anthropometry, and provided blood specimens. Women used fertility monitors for up to six consecutive menstrual cycles, with collection of daily first morning voids for hormone analysis in the first two menstrual cycles for prospective assessment of anovulation. Anovulation was assessed by urine pregnanediol glucuronide or luteinising hormone concentration or the fertility monitor. Weighted mixed-effects log-binomial regression was used to estimate associations between measures of adiposity and incident anovulation, adjusted for free (bioavailable) testosterone, anti-Mullerian hormone (AMH), serum lipids, and demographic and life style factors. RESULTS: 343 (28.3%) women experienced at least one anovulatory cycle. Anovulation risk was higher per kg/m2 greater BMI (relative risk [RR] 1.03, 95% confidence interval (CI) 1.01, 1.04), cm waist circumference (RR 1.01, 95% CI 1.00, 1.02), mm subscapular skinfold (RR 1.02, 95% CI 1.01, 1.03), and mm middle upper arm circumference (RR 1.04, 95% CI 1.01, 1.06) adjusted for serum free testosterone, AMH, lipids, and other factors. CONCLUSIONS: Adiposity may be associated with anovulation through pathways other than testosterone among regularly menstruating women. This may account in part for reported associations between greater adiposity and infertility among women having menstrual cycles regularly. Understanding the association between adiposity and anovulation might lead to targeted interventions for preventing infertility.

Ambient temperature and stillbirth: Risks associated with chronic extreme temperature and acute temperature change.

BACKGROUND: Ambient temperature events are increasing in frequency and intensity. Our prior work in a U.S. nationwide study suggests a strong association between both chronic and acute temperature extremes and stillbirth risk. OBJECTIVE: We attempted to replicate our prior study by assessing stillbirth risk associated with average whole-pregnancy temperatures and acute ambient temperature changes in a low-risk U.S. METHODS: Singleton deliveries in the NICHD Consecutive Pregnancies Study (Utah, 2002-2010; n = 112,005) were identified using electronic medical records. Ambient temperature was derived from the Weather Research and Forecasting model. Binary logistic regression determined the adjusted odds ratio (aOR) and 95% confidence interval (95% CI) for stillbirth associated with whole-pregnancy exposure to extreme cold (<10th percentile) and hot (>90th percentile) versus moderate (10th-90th percentiles) average temperature, adjusting for maternal demographics, season of conception, hypertensive disorders of pregnancy, and gestational diabetes. In a case-crossover analysis, we estimated the stillbirth aOR and 95% CI for each 1° Celsius increase during the week prior to delivery using conditional logistic regression. In both models, we adjusted for relative humidity, ozone, and fine particulates. RESULTS: We observed 500 stillbirth cases among 498 mothers. Compared to moderate temperatures, whole-pregnancy exposure to extreme cold (aOR: 4.42, 95% CI:3.43, 5.69) and hot (aOR: 5.06, 95% CI: 3.34, 7.68) temperatures were associated with stillbirth risk. Case-crossover models observed a 7% increased odds (95% CI: 1.04, 1.10) associated with each 1° Celsius increase during the week prior to delivery. DISCUSSION: Both chronic and acute ambient temperature were associated with odds of stillbirth in this low-risk population, similar to our prior nationwide findings. Future increases in temperature extremes are likely and the observed risk in a low-risk population suggests this association merits attention.

Recalled maternal lifestyle behaviors associated with anti-müllerian hormone of adult female offspring.

Anti-müllerian hormone (AMH) is an established marker of ovarian reserve that decreases with age. Though the pool of ovarian follicles is established during fetal development, impacts of in utero exposures on AMH are uncertain. Thus, we sought to evaluate associations of in utero exposures with AMH of adult daughters with a prospective cohort study of adult daughters at university medical centers. Women noted their mother's reported use of diethylstilbestrol (DES), vitamins, tobacco, alcohol, and caffeine during pregnancy, and their mother's occupation during pregnancy. All participants were reproductive age women (18-40 years) enrolled in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial. Serum AMH concentrations were measured at baseline prior to conception and categorized using clinical guidelines. Multinomial regression models estimated associations between each exposure and high (>3.5 ng/mL) and low (<1.0 ng/mL) versus normal AMH (1.0-3.5 ng/mL), adjusting for participant's age, mother's age, mother's history of fertility treatment, and mother's use of vitamins. In 1202 women with available data, maternal caffeine use was associated with an increased risk of low AMH, compared to normal (relative risk [RR] 1.90, 95 % confidence interval [CI] 1.09, 3.30). Vitamins were associated with an increased risk of high AMH compared to normal (RR 1.93, 95 % CI 1.24, 3.00). Other exposures were not associated with AMH concentrations in offspring. Maternal caffeine and vitamin use during pregnancy may be associated with ovarian reserve in adult offspring, highlighting the potential importance of pregnancy lifestyle on the reproductive health of daughters.

Low-dose aspirin in reproductive health: effects on menstrual cycle characteristics.

OBJECTIVE: To estimate the effect of daily 81 mg low-dose aspirin (LDA) on menstrual cycle length and hormone profiles. DESIGN: Secondary analysis of a trial evaluating the effect of daily LDA or placebo on live birth among women with one or two previous pregnancy losses. SETTING: University medical centers. PATIENT(S): A total of 915 regularly menstruating women who had at least one menstrual cycle (3,190 total cycles) in which pregnancy did not occur. INTERVENTION(S): Randomized allocation to LDA versus placebo. MAIN OUTCOME MEASURE(S): Menstrual cycle length and follicular and luteal phases were measured. Urinary pregnanediol glucuronide, follicle-stimulating hormone, luteinizing hormone, and estrone-3-glucuronide were assessed up to six times during the first two cycles. Generalized estimating equations estimated relative risk of short (<25th percentile: <27 days) and long (>75th percentile: ≥32 days) versus normal cycle length. Linear mixed models estimated mean hormone level differences with weights used to account for multiple cycles contributed per participant. RESULT(S): There were no significant differences in total menstrual cycle, follicular phase, or luteal phase length between LDA and placebo groups. LDA posed no greater risk of having a short versus normal-length or long versus normal-length follicular phase, or having a short versus normal-length or long versus normal-length luteal phase. There were no significant differences in hormone levels across the menstrual cycle between the LDA and placebo groups. CONCLUSION(S): Daily LDA use did not result in any changes to menstrual cycle, follicular phase, or luteal phase length or hormone levels across the menstrual cycle compared with placebo. CLINICAL TRIAL REGISTRATION NUMBER: NCT00467363.

Family history of autoimmune disease in relation to time-to-pregnancy, pregnancy loss, and live birth rate.

Several autoimmune conditions have adverse effects on reproductive outcomes, but the relationship between family history of autoimmune disease in women without these conditions and pregnancy is uncertain. The objective of this study was to determine if there is an association between a family history of an autoimmune condition and time-to-pregnancy (TTP), pregnancy loss, and live birth. This was a prospective cohort study from a RCT of 1228 adult women ages 18-40, who were healthy, had no history of infertility, were actively attempting to conceive, and had one or two prior pregnancy losses. Of these, 1172 women had data available regarding family history of autoimmune conditions. Women with an affected first-degree relative had similar TTP when compared to those without a FHx (fecundability odds ratio 0.90, 95% confidence interval [CI] 0.70, 1.15). Women with an affected first-degree relative had a lower likelihood of live birth (relative risk [RR] 0.83, 95% CI 0.69, 0.99). Among women who achieved pregnancy, FHx of autoimmune disease was associated with a higher likelihood of pregnancy loss (RR 1.49, 95% CI 1.10, 2.03). Women who had a first-degree relative with an autoimmune disease had a similar TTP as unaffected women but a lower likelihood of live birth and higher risk of pregnancy loss. This information may encourage clinicians to evaluate women with a family history of autoimmune conditions prior to pregnancy and highlights the need for further studies to ascertain the effects of autoimmunity and pregnancy.

Preconception Blood Pressure and Its Change Into Early Pregnancy: Early Risk Factors for Preeclampsia and Gestational Hypertension.

Preeclampsia and gestational hypertension are common complications of pregnancy associated with significant maternal and infant morbidity. Despite extensive research evaluating risk factors during pregnancy, most women who develop a hypertensive disorder of pregnancy are not considered high-risk and strategies for prevention remain elusive. We evaluated preconception blood pressure and its change into early pregnancy as novel risk markers for development of a hypertensive disorder of pregnancy. The EAGeR (Effects of Aspirin in Gestation and Reproduction) trial (2007-2011) randomized 1228 healthy women with a history of pregnancy loss to preconception-initiated low-dose aspirin versus placebo and followed participants for up to 6 menstrual cycles attempting pregnancy and throughout pregnancy if they became pregnant. Blood pressure was measured during preconception and throughout early gestation. The primary outcomes, preterm preeclampsia, term preeclampsia, and gestational hypertension, were abstracted from medical records. Among 586 women with a pregnancy >20 weeks' gestation, preconception blood pressure levels were higher for preterm preeclampsia (87.3±6.7 mm Hg mean arterial pressure), term preeclampsia (88.3±9.8 mm Hg), and gestational hypertension (87.9±9.1 mm Hg) as compared with no hypertensive disorder of pregnancy (83.9±8.6 mm Hg). Change in blood pressure from preconception into very early pregnancy was associated with development of preeclampsia (relative risk, 1.13 [95% CI, 1.02-1.25] per 2 mm Hg increase in mean arterial pressure at 4 weeks' gestation), particularly preterm preeclampsia (relative risk, 1.21 [95% CI, 1.01-1.45]). Randomization to aspirin did not alter blood pressure trajectory or risk of hypertension in pregnancy. Preconception blood pressure and longitudinal changes during early pregnancy are underexplored but crucial windows in the detection and prevention of hypertensive disorders of pregnancy. Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00467363.

Air Pollution Exposure Monitoring among Pregnant Women with and without Asthma.

Background: We monitored exposure to fine particulates (PM2.5), ozone, nitrogen dioxide (NO2), and ambient temperature for pregnant women with and without asthma. Methods: Women (n = 40) from the Breathe-Well-Being, Environment, Lifestyle, and Lung Function Study (2015-2018) were enrolled during pregnancy and monitored for 2-4 days. Daily pollutants were measured using personal air monitors, indoor air monitors, and nearest Environmental Protection Agency's stationary monitors based on GPS tracking and home address. Results: Personal-monitor measurements of PM2.5, ozone, and NO2 did not vary by asthma status but exposure profiles significantly differed by assessment methods. EPA stationary monitor-based methods appeared to underestimate PM2.5 and temperature exposure and overestimate ozone and NO2 exposure. Higher indoor-monitored PM2.5 exposures were associated with smoking and the use of gas appliances. The proportion of waking-time during which personal monitors were worn was ~56%. Lower compliance was associated with exercise, smoking, being around a smoker, and the use of a prescription drug. Conclusions: Exposure did not vary by asthma status but was influenced by daily activities and assessment methods. Personal monitors may better capture exposures but non-compliance merits attention. Meanwhile, larger monitoring studies are warranted to further understand exposure profiles and the health effects of air pollution during pregnancy.

Maternal preconception lipid profile and gestational lipid changes in relation to birthweight outcomes.

In 575 women with 1-2 prior pregnancy losses; total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were evaluated preconception and throughout pregnancy to evaluate whether previously observed associations between third trimester maternal lipid profile and birthweight outcomes are driven by preconception lipids or lipid changes during pregnancy. Lipid trajectories were compared by pre-pregnancy body mass index (BMI) <25 or ≥25 kg/m2; logistic regression models evaluated preconception lipid concentration and change from preconception to 28 weeks with adjusted odds of large- or small-for-gestational age (LGA or SGA) neonate by BMI group. Preconception lipid concentrations and gestational lipid trajectories varied by BMI group (P < 0.001). Preconception lipids were not associated with LGA or SGA in either group. A 10 mg/dL increase in HDL-C change from preconception to 28 weeks was associated with decreased odds of LGA (odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.46, 0.86) and 10 mg/dL increase in TG change associated with increased odds of LGA (OR = 1.05, 95% CI: 1.01, 1.1) overall. For ≥25 BMI only, 10 mg/dL increase in HDL-C change was associated with decreased SGA odds (OR = 0.35, 95% CI: 0.19, 0.64). Gestational lipid trajectories differed by BMI group and were differentially associated with birthweight outcomes, with HDL-C more strongly associated with healthy birthweight in women with BMI ≥25.

Associations Between Preconception Plasma Fatty Acids and Pregnancy Outcomes.

BACKGROUND: Although fatty acids are involved in critical reproductive processes, the relationship between specific fatty acids and fertility is uncertain. We investigated the relationship between preconception plasma fatty acids and pregnancy outcomes. METHODS: We included 1,228 women attempting pregnancy with one to two previous pregnancy losses from the EAGeR trial (2007-2011). Plasma fatty acids were measured at baseline. We used log-binomial regression to assess associations between fatty acids and pregnancy, pregnancy loss, and live birth, adjusting for age, race, smoking, BMI, physical activity, income, parity, treatment arm, and cholesterol. RESULTS: Although total saturated fatty acids (SFAs) were not associated with pregnancy outcomes, 14:0 (myristic acid; relative risk [RR] = 1.10, 95% confidence interval [CI] = 1.02, 1.19, per 0.1% increase) and 20:0 (arachidic acid; RR = 1.05, 95% CI = 1.01, 1.08, per 0.1% increase) were positively associated with live birth. Findings suggested a positive association between total monounsaturated fatty acids (MUFAs) and pregnancy and live birth and an inverse association with loss. Total polyunsaturated fatty acids (PUFAs) were associated with lower probability of pregnancy (RR = 0.97, 95% CI = 0.95, 1.00) and live birth (RR = 0.96, 95% CI = 0.94, 0.99), and increased risk of loss (RR = 1.10, 95% CI = 1.00, 1.20), per 1% increase. Trans fatty acids and n-3 fatty acids were not associated with pregnancy outcomes. CONCLUSIONS: Preconception total plasma MUFAs were positively associated with pregnancy and live birth. PUFAs were inversely associated with pregnancy outcomes. Specific SFAs were associated with a higher probability of live birth. Our results suggest that fatty acids may influence pregnancy outcomes.