Life satisfaction for adolescents with developmental and behavioral disabilities during the COVID-19 pandemic.

BACKGROUND: This study aimed to identify contextual factors associated with life satisfaction during the COVID-19 pandemic for adolescents with mental, emotional, behavioral, and developmental (MEBD) disabilities. METHODS: Data were collected from a sample of 1084 adolescents aged 11-21 years from April 2020 to August 2021. This cross-sectional study used a sequential machine learning workflow, consisting of random forest regression and evolutionary tree regression, to identify subgroups of adolescents in the Environmental influences on Child Health Outcomes (ECHO) consortium who demonstrated enhanced vulnerability to lower life satisfaction as described by intersecting risk factors, protective factors, and MEBD disabilities. RESULTS: Adolescents with a history of depression, anxiety, autism, and attention-deficit/hyperactivity disorder were particularly susceptible to decreased life satisfaction in response to unique combinations of stressors experienced during the COVID-19 pandemic. These stressors included decreased social connectedness, decreased family engagement, stress related to medical care access, pandemic-related traumatic stress, and single-caregiver households. CONCLUSION: Findings from this study highlight the importance of interventions aimed specifically at increasing adolescent social connectedness, family engagement, and access to medical support for adolescents with MEBD disabilities, particularly in the face of stressors, such as a global pandemic. IMPACT: Through a machine learning process, we identified contextualized risks associated with life satisfaction among adolescents with neurodevelopmental disabilities during the COVID-19 pandemic. The COVID-19 pandemic resulted in large-scale social disruptions for children and families. Such disruptions were associated with worse mental health outcomes in the general pediatric population, but few studies have examined specific subgroups who may be at heightened risk. We endeavored to close that gap in knowledge. This study highlights the importance of social connectedness, family engagement, and access to medical support as contributing factors to life satisfaction during the COVID-19 pandemic for adolescents with neurodevelopmental disabilities.

Low-dose aspirin, maternal cardiometabolic health, and offspring respiratory health 9 to 14 years after delivery: Findings from the EAGeR Follow-up Study.

BACKGROUND: Accumulating evidence shows that peri-conceptional and in-utero exposures have lifetime health impacts for mothers and their offspring. OBJECTIVES: We conducted a Follow-Up Study of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial with two objectives. First, we determined if women who enrolled at the Utah site (N = 1001) of the EAGeR trial (2007-2011, N = 1228) could successfully be contacted and agree to complete an online questionnaire on their reproductive, cardio-metabolic, and offspring respiratory health 9-14 years after original enrollment. Second, we evaluated if maternal exposure to low-dose aspirin (LDA) during pregnancy was associated with maternal cardio-metabolic health and offspring respiratory health. METHODS: The original EAGeR study population included women, 18-40 years of age, who had 1-2 prior pregnancy losses, and who were trying to become pregnant. At follow-up (2020-2021), participants from the Utah cohort completed a 13-item online questionnaire on reproductive and cardio-metabolic health, and those who had a live birth during EAGeR additionally completed a 7-item questionnaire on the index child's respiratory health. Primary maternal outcomes included hypertension and hypercholesterolemia; primary offspring outcomes included wheezing and asthma. RESULTS: Sixty-eight percent (n = 678) of participants enrolled in the follow-up study, with 10% and 15% reporting maternal hypertension and hypercholesterolemia, respectively; and 18% and 10% reporting offspring wheezing and asthma. We found no association between maternal LDA exposure and hypertension (risk difference [RD] -0.001, 95% confidence interval [CI] -0.05, 0.04) or hypercholesterolemia (RD -0.01, 95% CI -0.06, 0.05) at 9-14 years follow-up. Maternal LDA exposure was not associated with offspring wheezing (RD -0.002, 95% CI -0.08, 0.08) or asthma (RD 0.13, 95% CI 0.11, 0.37) at follow-up. Findings remained robust after considering potential confounding and selection bias. CONCLUSIONS: We observed no association between LDA exposure during pregnancy and maternal cardiometabolic or offspring respiratory health.

Incidence rates of childhood asthma with recurrent exacerbations in the US Environmental influences on Child Health Outcomes (ECHO) program.

BACKGROUND: Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse. OBJECTIVES: This study hypothesized that IRs for ARE would vary by time, geography, age, and race and ethnicity, irrespective of parental asthma history. METHODS: The investigators leveraged data from 17,246 children born after 1990 enrolled in 59 US with 1 Puerto Rican cohort in the Environmental Influences on Child Health Outcomes (ECHO) consortium to estimate IRs for ARE. RESULTS: The overall crude IR for ARE was 6.07 per 1000 person-years (95% CI: 5.63-6.51) and was highest for children aged 2-4 years, for Hispanic Black and non-Hispanic Black children, and for those with a parental history of asthma. ARE IRs were higher for 2- to 4-year-olds in each race and ethnicity category and for both sexes. Multivariable analysis confirmed higher adjusted ARE IRs (aIRRs) for children born 2000-2009 compared with those born 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR = 15.36; 95% CI: 12.09-19.52), and for males versus females (aIRR = 1.34; 95% CI 1.16-1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR = 2.51; 95% CI 2.10-2.99; and aIRR = 2.04; 95% CI: 1.22-3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than those born in the West (P < .01 for each comparison). Children with a parental history of asthma had rates nearly 3 times higher than those without such history (aIRR = 2.90; 95% CI: 2.43-3.46). CONCLUSIONS: Factors associated with time, geography, age, race and ethnicity, sex, and parental history appear to influence the inception of ARE among children and adolescents.

Prenatal exposure to environmental toxins and comprehensive dental findings in a population cohort of children.

Environmental toxins are known to have many impacts on growth and development in humans, starting in utero. Alterations in amelogenesis, caused by chemical and physical trauma that occur during the antenatal, perinatal and postnatal time periods, may result in developmental defects in deciduous and permanent tooth enamel, as demonstrated in animal studies. These defects can be clinically visible and result in a variety of morphological and functional problems in the dentition. Since enamel does not remodel after formation, it may serve as a permanent record of insults during organ development.Our primary purpose was to investigate any possible relationship between intrauterine exposure to endocrine disrupting chemicals (phenols and phthalates) and developmental defects in enamel in children, while also accounting for fluoride exposure. Our secondary purpose was to report descriptively on findings from comprehensive dental examinations performed on 356 children that were drawn from the general paediatric population. A cohort of children from the Utah Children's Project (N = 356) that had full medical exams, comprehensive medical and family histories and available biospecimens were given extraoral and intraoral examinations. They also completed an oral health questionnaire. Standardized intraoral photographs were taken of the teeth and viewed by standardised examiners and the dental observations were recorded for a full inventory of findings, including: tooth morphology, caries, restorations, colorations, attrition, erosion, fractures and hypomineralization. Perinatal maternal urine samples were assessed for the concentration of fluoride, phenols and phthalates, including bisphenol A (BPA).Pairwise statistical analyses were done to correlate the dental findings with one another and with the presence of environment chemicals found in the urine samples. Hypomineralization was the most common finding (96% of children; 37% of deciduous teeth, 42% of permanent teeth), consistent with molar incisor hypomineralization (MIH) described in other human populations. No consistent correlations were seen between dental findings and the presence of phenols and phthalates in prenatal urine, but the number of samples available for the assessment was limited (n = 35).In conclusion, we found a high proportion of dental hypomineralization in a population based paediatric cohort, but did not find an association with prenatal exposure to phenols and phthalates.

Large-Scale Data Harmonization Across Prospective Studies.

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.

Contributions of cancer treatment, comorbidities, and obesity to aging-related disease risks among non-Hodgkin lymphoma survivors.

PURPOSE: It is unknown whether cancer treatment contributes more to long-term disease risk than lifestyle factors and comorbidities among B-cell non-Hodgkin lymphoma (B-NHL) survivors. METHODS: B-NHL survivors were identified in the Utah Cancer Registry from 1997 to 2015. Population attributable fractions (PAF) were calculated to assess the role of clinical and lifestyle factors for six cardiovascular, pulmonary, and renal diseases. RESULTS: Cancer treatment contributed to 11% of heart and pulmonary conditions and 14.1% of chronic kidney disease. Charlson Comorbidity Index (CCI) at baseline contributed to all six diseases with a range of 9.9% of heart disease to 26.5% of chronic kidney disease. High BMI at baseline contributed to 18.4% of congestive heart failure and 7.9% of pneumonia, while smoking contributed to 4.8% of COPD risk. CONCLUSION: Cancer treatment contributed more to heart disease, COPD, and chronic kidney disease than lifestyle factors and comorbidities among B-NHL survivors. High BMI at baseline contributed more to congestive heart failure and pneumonia than cancer treatment, whereas smoking at baseline was not a major contributor in this B-NHL survivor cohort. Baseline comorbidities consistently demonstrated high attributable risks for these diseases, demonstrating a strong association between preexisting comorbidities and aging-related disease risks.

The Role of Childhood Asthma in Obesity Development: A Nationwide US Multicohort Study.

RATIONALE: Asthma and obesity often co-occur. It has been hypothesized that asthma may contribute to childhood obesity onset. OBJECTIVES: To determine if childhood asthma is associated with incident obesity and examine the role of asthma medication in this association. METHODS: We studied 8,716 children between ages 6 and 18.5 years who were nonobese at study entry participating in 18 US cohorts of the Environmental influences on Child Health Outcomes program (among 7,299 children with complete covariate data mean [SD] study entry age = 7.2 [1.6] years and follow up = 5.3 [3.1] years). MEASUREMENTS AND MAIN RESULTS: We defined asthma based on caregiver report of provider diagnosis. Incident obesity was defined as the first documented body mass index ≥95th percentile for age and sex following asthma status ascertainment. Over the study period, 26% of children had an asthma diagnosis and 11% developed obesity. Cox proportional hazards models with sex-specific baseline hazards were fitted to assess the association of asthma diagnosis with obesity incidence. Children with asthma had a 23% (95% confidence intervals [CI] = 4, 44) higher risk for subsequently developing obesity compared with those without asthma. A novel mediation analysis was also conducted to decompose the total asthma effect on obesity into pathways mediated and not mediated by asthma medication use. Use of asthma medication attenuated the total estimated effect of asthma on obesity by 64% (excess hazard ratios = 0.64; 95% CI = -1.05, -0.23). CONCLUSIONS: This nationwide study supports the hypothesis that childhood asthma is associated with later risk of obesity. Asthma medication may reduce this association and merits further investigation as a potential strategy for obesity prevention among children with asthma.

Prospectively assessed perceived stress associated with early pregnancy losses among women with history of pregnancy loss.

STUDY QUESTION: What is the association between perceived stress during peri-conception and early pregnancy and pregnancy loss among women who have experienced a prior pregnancy loss? SUMMARY ANSWER: Daily perceived stress above the median is associated with over a 2-fold risk of early pregnancy loss among women who have experienced a prior loss. WHAT IS KNOWN ALREADY?: Women who have experienced a pregnancy loss may be more vulnerable to stress while trying to become pregnant again. While prior research has indicated a link between psychological stress and clinically confirmed miscarriages, research is lacking among a pre-conceptional cohort followed prospectively for the effects of perceived stress during early critical windows of pregnancy establishment on risk of both hCG-detected pregnancy losses and confirmed losses, while considering important time-varying confounders. STUDY DESIGN, SIZE, DURATION: Secondary data analysis of the EAGeR trial (2007-2011) among women with an hCG-detected pregnancy (n = 797 women). PARTICIPANTS/MATERIALS, SETTING, METHODS: Women from four US clinical centers enrolled pre-conceptionally and were followed ≤6 cycles while attempting pregnancy and, as applicable, throughout pregnancy. Perceived stress was captured via daily diaries and end-of-month questionnaires. Main outcome measures include hCG-detected and clinically recognized pregnancy losses. MAIN RESULTS AND THE ROLE OF CHANCE: Among women who had an hCG-confirmed pregnancy, 188 pregnancies (23.6%) ended in loss. Women with high (>50th percentile) versus low (≤50th percentile) peri-implantation or early pregnancy weekly perceived stress had an elevated risk of experiencing any pregnancy loss (hazard ratio (HR): 1.69, 95% CI: 1.13, 2.54) or clinical loss (HR: 1.58, 95% CI: 0.96, 2.60), with higher risks observed for women experiencing an hCG-detected loss (HR: 2.16, 95% CI: 1.04, 4.46). Models accounted for women's age, BMI, employment, marital status, income, education, race, parity, prior losses, exercise and time-varying nausea/vomiting, caffeine, alcohol and smoking. LIMITATIONS, REASONS FOR CAUTION: We were limited in our ability to clearly identify the mechanisms of stress on pregnancy loss due to our sole reliance on self-reported perceived stress, and the lack of biomarkers of different pathways of stress. WIDER IMPLICATIONS OF THE FINDINGS: This study provides new insight on early pregnancy perceived stress and risk of pregnancy loss, most notably hCG-detected losses, among women with a history of a prior loss. Our study is an improvement over past studies in its ability to account for time-varying early pregnancy symptoms, such as nausea/vomiting, and lifestyle factors, such as caffeine, alcohol and smoking, which are also risk factors for psychological stress and pregnancy loss. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract numbers: HHSN267200603423, HHSN267200603424, HHSN267200603426, HHSN275201300023I). Additionally, K.C.S. was supported by the National Institute on Aging of the National Institutes of Health under Award Number K01AG058781. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: #NCT00467363.

Endometriosis diagnosis, staging and typology and adverse pregnancy outcome history.

BACKGROUND: Women with endometriosis may have an increased risk of adverse pregnancy outcomes. Research has focused on infertility clinic populations limiting generalisability. Few studies report differences by endometriosis severity. OBJECTIVES: We investigated the relationships between endometriosis diagnosis, staging and typology and pregnancy outcomes among an operative and population-based sample of women. METHODS: Menstruating women ages 18-44 years enrolled in the ENDO Study (2007-2009), including the operative cohort: 316 gravid women undergoing laparoscopy/laparotomy at surgical centres in Utah and California; and the population cohort: 76 gravid women from the surgical centres' geographic catchment areas. Pregnancy outcomes were ascertained by questionnaire and included all pregnancies prior to study enrolment. Endometriosis was diagnosed via surgical visualisation in the operative cohort and pelvic magnetic resonance imaging in the population cohort. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) were estimated using generalised linear mixed models for pregnancy outcomes, adjusting for women's age at study enrolment and at pregnancy, surgical site, body mass index and lifestyle factors. RESULTS: Women in the operative cohort with visualised endometriosis (n = 109, 34%) had a lower prevalence of live births, aPR 0.94 (95% CI 0.85, 1.03) and a higher prevalence of miscarriages, aPR 1.48 (95% CI 1.23, 1.77) compared with women without endometriosis. The direction and magnitude of estimates were similar in the population cohort. Women with deep endometriosis were 2.98-fold more likely (95% CI 1.12, 7.95) to report a miscarriage compared with women without endometriosis after adjusting for women's age at study enrolment and at pregnancy, surgical site and body mass index. No differences were seen between endometriosis staging and pregnancy outcomes. CONCLUSIONS: While there was no difference in number of pregnancies among women with and without endometriosis in a population-based sample, pregnancy loss was more common among women with endometriosis, notably among those with deep endometriosis.

Sexual dysfunction among gynecologic cancer survivors in a population-based cohort study.

Treatment for gynecologic cancer is associated with sexual dysfunction, which may present during and/or after treatment. The aim of this study was to investigate the risk of sexual dysfunction among gynecologic cancer survivors compared to cancer-free women in a population-based cohort study. We identified a cohort of 4863 endometrial, ovarian, and cervical cancer survivors diagnosed between 1997 and 2012 in the Utah Cancer Registry. Up to five cancer-free women were matched to cancer survivors (N = 22,693). We used ICD-9 codes to identify sexual dysfunction. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for sexual dysfunction with adjustment for potential confounders. Approximately 6.6% of gynecologic cancer survivors had sexual dysfunction diagnoses 1-5 years after cancer diagnosis. Gynecologic cancer survivors had higher risks of overall sexual dysfunction (HR: 2.51, 95% CI: 2.16, 2.93), dyspareunia (HR: 3.27, 95% CI: 2.63, 4.06), and vaginal dryness (HR: 2.63, 95% CI: 2.21, 3.12) compared to a general population of women, 1-5 years after cancer diagnosis. Sexual dysfunction was associated with advance cancer stage (HRRegional vs. Localized: 1.61, 95% CI: 1.19, 2.31), radiation therapy (HR: 1.73, 95% CI: 1.29, 2.31), and chemotherapy (HR: 1.80, 95% CI: 1.30, 2.50). This large cohort study confirms that there is an increased risk of sexual dysfunction among gynecologic cancer survivors when compared to the general population. Further investigation is needed to address the risk factors for sexual dysfunction and to improve patient-provider communication, diagnosis, documentation, and treatment of sexual dysfunction among gynecologic cancer survivors.

Does a short luteal phase correlate with an increased risk of miscarriage? A cohort study.

BACKGROUND: Miscarriage is defined as spontaneous loss of pregnancy prior to 20 weeks gestation. With an estimated risk of 15% of clinically confirmed pregnancies ending in miscarriage, it is the most common adverse event in pregnancy. Woman's age is the primary risk factor for miscarriage, while medical conditions, including hormonal abnormalities, are also associated. Progesterone is essential for maintaining pregnancy. A short luteal phase may reflect inadequate levels of progesterone production, but it is unclear whether a short luteal phase correlates with an increase in the risk of miscarriage. METHODS: Using a cohort study design, we conducted a secondary data analysis from four cohorts of couples who used a standardized protocol to track biomarkers of the female cycles. A short luteal phase was defined as less than 10 days, with < 11, < 9, and < 8 days as alternate definitions in sensitivity analyses. We included women who experienced a pregnancy with a known outcome, identified the length of the luteal phase in up to 3 cycles prior to conception and assessed the relationship with miscarriage using a modified Poisson regression analysis, adjusting for demographic characteristics, smoking, alcohol use and previous pregnancy history. RESULTS: In our sample of 252 women; the overall miscarriage rate was 18.7%. The adjusted incident risk ratio of miscarriage in women who had at least one short luteal phase < 10 days, compared to those who had none, was 1.01 (95% CI: 0.57, 1.80) Similar null risk was found when assessing alternative lengths of short luteal phase. Women who had short luteal phases < 10 days in all 3 cycles prior to the conception cycle had an incident risk ratio of 2.14 (95% CI: 0.7, 6.55). CONCLUSIONS: Our study found that a short luteal phase in the three cycles prior to conception was not associated with higher rates of miscarriage in an international cohort of women tracking their cycles, but our sample size was limited. Further research to determine if short luteal phases or luteal phase deficiency is associated with early pregnancy losses among preconception cohorts with daily tracking of cycle parameters, in addition to progesterone and human chorionic gonadotropin levels, is warranted. Additionally, future studies should include women with recurrent short luteal phases as a more likely risk factor than isolated short luteal phases.

This study looks at whether women have a higher risk of miscarriage if the second half of their menstrual or reproductive cycle is shorter than normal. The second half of the cycle, referred to as the luteal phase, is normally 11 to 16 days long. If the luteal phase is too short this may suggest a woman does not have enough progesterone, the hormone essential for maintaining pregnancy.This study included 252 pregnant women for whom we had data on the length of at least one luteal phase prior to pregnancy and for whom we knew the outcome of the pregnancy. Almost one-fifth of the women in our study had a miscarriage. However, we found there was no difference in the risk for miscarriage if women had a short or a normal luteal phase.

Fertility treatments and the risk of preterm birth among women with subfertility: a linked-data retrospective cohort study.

BACKGROUND: In vitro fertilization (IVF) births contribute to a considerable proportion of preterm birth (PTB) each year. However, there is no formal surveillance of adverse perinatal outcomes for less invasive fertility treatments. The study objective was to describe associations between fertility treatment (in vitro fertilization, intrauterine insemination, usually with ovulation drugs (IUI), or ovulation drugs alone) and preterm birth, compared to no treatment in subfertile women. METHODS: The Fertility Experiences Study (FES) is a retrospective cohort study conducted at the University of Utah between April 2010 and September 2012. Women with a history of primary subfertility self-reported treatment data via survey and interviews. Participant data were linked to birth certificates and fetal death records to asses for perinatal outcomes, particularly preterm birth. RESULTS: A total 487 birth certificates and 3 fetal death records were linked as first births for study participants who completed questionnaires. Among linked births, 19% had a PTB. After adjustment for maternal age, paternal age, maternal education, annual income, religious affiliation, female or male fertility diagnosis, and duration of subfertility, the odds ratios and 95% confidence intervals (CI) for PTB were 2.17 (CI 0.99, 4.75) for births conceived using ovulation drugs, 3.17 (CI 1.4, 7.19) for neonates conceived using IUI and 4.24 (CI 2.05, 8.77) for neonates conceived by IVF, compared to women with subfertility who used no treatment during the month of conception. A reported diagnosis of female factor infertility increased the adjusted odds of having a PTB 2.99 (CI 1.5, 5.97). Duration of pregnancy attempt was not independently associated with PTB. In restricting analyses to singleton gestation, odds ratios were not significant for any type of treatment. CONCLUSION: IVF, IUI, and ovulation drugs were all associated with a higher incidence of preterm birth and low birth weight, predominantly related to multiple gestation births.

Infertility treatments such as in vitro fertilization are associated with preterm birth, but less is known about how other less invasive treatments contribute to preterm birth. This study compares different types of fertility treatments and rates of preterm birth with women who are also struggling with infertility but did not use fertility treatments at the time of their pregnancy. 490 women were recruited at the University of Utah between 2010 and 2012. Participants were asked to complete a survey and were linked to birth certificate and fetal death certificate data. Women who used in vitro fertilization were 4.24 times more likely to have a preterm birth than those who used no treatment. Use of intrauterine insemination were 3.17 times more likely to have a preterm birth than those who used no treatment at time of conception. Ovulation stimulating drugs were 2.17 times more likely to have a preterm birth. Having female factor infertility was also associated with higher odds of having preterm birth. For those who are having trouble conceiving, trying less invasive treatments to achieve pregnancy might reduce their risk of preterm birth.

Cervical mucus patterns and the fertile window in women without known subfertility: a pooled analysis of three cohorts.

STUDY QUESTION: What is the normal range of cervical mucus patterns and number of days with high or moderate day-specific probability of pregnancy (if intercourse occurs on a specific day) based on cervical mucus secretion, in women without known subfertility, and how are these patterns related to parity and age? SUMMARY ANSWER: The mean days of peak type (estrogenic) mucus per cycle was 6.4, the mean number of potentially fertile days was 12.1; parous versus nulliparous, and younger nulliparous (<30 years) versus older nulliparous women had more days of peak type mucus, and more potentially fertile days in each cycle. WHAT IS KNOWN ALREADY: The rise in estrogen prior to ovulation supports the secretion of increasing quantity and estrogenic quality of cervical mucus, and the subsequent rise in progesterone after ovulation causes an abrupt decrease in mucus secretion. Cervical mucus secretion on each day correlates highly with the probability of pregnancy if intercourse occurs on that day, and overall cervical mucus quality for the cycle correlates with cycle fecundability. No prior studies have described parity and age jointly in relation to cervical mucus patterns. STUDY DESIGN, SIZE, DURATION: This study is a secondary data analysis, combining data from three cohorts of women: 'Creighton Model MultiCenter Fecundability Study' (CMFS: retrospective cohort, 1990-1996), 'Time to Pregnancy in Normal Fertility' (TTP: randomized trial, 2003-2006), and 'Creighton Model Effectiveness, Intentions, and Behaviors Assessment' (CEIBA: prospective cohort, 2009-2013). We evaluated cervical mucus patterns and estimated fertile window in 2488 ovulatory cycles of 528 women, followed for up to 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were US or Canadian women age 18-40 years, not pregnant, and without any known subfertility. Women were trained to use a standardized protocol (the Creighton Model) for daily vulvar observation, description, and recording of cervical mucus. The mucus peak day (the last day of estrogenic quality mucus) was used as the estimated day of ovulation. We conducted dichotomous stratified analyses for cervical mucus patterns by age, parity, race, recent oral contraceptive use (within 60 days), partial breast feeding, alcohol, and smoking. Focusing on the clinical characteristics most correlated to cervical mucus patterns, linear mixed models were used to assess continuous cervical mucus parameters and generalized linear models using Poisson regression with robust variance were used to assess dichotomous outcomes, stratifying by women's parity and age, while adjusting for recent oral contraceptive use and breast feeding. MAIN RESULTS AND THE ROLE OF CHANCE: The majority of women were <30 years of age (75.4%) (median 27; IQR 24-29), non-Hispanic white (88.1%), with high socioeconomic indicators, and nulliparous (70.8%). The mean (SD) days of estrogenic (peak type) mucus per cycle (a conservative indicator of the fertile window) was 6.4 (4.2) days (median 6; IQR 4-8). The mean (SD) number of any potentially fertile days (a broader clinical indicator of the fertile window) was 12.1 (5.4) days (median 11; IQR 9-14). Taking into account recent oral contraceptive use and breastfeeding, nulliparous women age ≥30 years compared to nulliparous women age <30 years had fewer mean days of peak type mucus per cycle (5.3 versus 6.4 days, P = 0.02), and fewer potentially fertile days (11.8 versus 13.9 days, P < 0.01). Compared to nulliparous women age <30 years, the likelihood of cycles with peak type mucus ≤2 days, potentially fertile days ≤9, and cervical mucus cycle score (for estrogenic quality of mucus) ≤5.0 were significantly higher among nulliparous women age ≥30 years, 1.90 (95% confidence interval (CI) 1.18, 3.06); 1.46 (95% CI 1.12, 1.91); and 1.45 (95% CI 1.03, 2.05), respectively. Between parous women, there was little difference in mucus parameters by age. Thresholds set a priori for within-woman variability of cervical mucus parameters by cycle were examined as follows: most minus fewest days of peak type mucus >3 days (exceeded by 72% of women), most minus fewest days of non-peak type mucus >4 days (exceeded by 54% of women), greatest minus least cervical mucus cycle score >4.0 (exceeded by 73% of women), and most minus fewest potentially fertile days >8 days (found in 50% of women). Race did not have any association with cervical mucus parameters. Recent oral contraceptive use was associated with reduced cervical mucus cycle score and partial breast feeding was associated with a higher number of days of mucus (both peak type and non-peak type), consistent with prior research. Among the women for whom data were available (CEIBA and TTP), alcohol and tobacco use had minimal impact on cervical mucus parameters. LIMITATIONS, REASONS FOR CAUTION: We did not have data on some factors that may impact ovulation, hormone levels, and mucus secretion, such as physical activity and body mass index. We cannot exclude the possibility that some women had unknown subfertility or undiagnosed gynecologic disorders. Only 27 women were age 35 or older. Our study participants were geographically dispersed but relatively homogeneous with regard to race, ethnicity, income, and educational level, which may limit the generalizability of the findings. WIDER IMPLICATIONS OF THE FINDINGS: Patterns of cervical mucus secretion observed by women are an indicator of fecundity and the fertile window that are consistent with the known associations of age and parity with fecundity. The number of potentially fertile days (12 days) is likely greater than commonly assumed, while the number of days of highly estrogenic mucus (and higher probability of pregnancy) correlates with prior identifications of the fertile window (6 days). There may be substantial variability in fecundability between cycles for the same woman. Future work can use cervical mucus secretion as an indicator of fecundity and should investigate the distribution of similar cycle parameters in women with various reproductive or gynecologic pathologies. STUDY FUNDING/COMPETING INTEREST(S): Funding for the three cohorts analyzed was provided by the Robert Wood Johnson Foundation (CMFS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (TTP), and the Office of Family Planning, Office of Population Affairs, Health and Human Services (CEIBA). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Polycystic ovary syndrome and postpartum depression symptoms: a population-based cohort study.

BACKGROUND: Women with polycystic ovary syndrome are more likely to experience several pregnancy complications including hypertensive disorders, gestational diabetes mellitus, and preterm births than women without polycystic ovary syndrome. However, at present, there is limited research on whether polycystic ovary syndrome is associated with both anxiety and depression during pregnancy and whether this augments a woman's risk of postpartum depression, particularly among high-risk populations who have limited access to care. OBJECTIVE: Our primary objective was to assess the association between prepregnancy polycystic ovary syndrome and postpartum depression, considering important baseline confounding factors. Our secondary objective was to evaluate the mediating role of prenatal depression and anxiety on the association between polycystic ovary syndrome and postpartum depression. STUDY DESIGN: This study involved a population-based sample of 3906 postpartum (2-6 months) women who completed the Utah Pregnancy Risk Assessment Monitoring System Phase 8 questionnaire (2016-2018). Weighted adjusted prevalence ratios were used to assess the association between polycystic ovary syndrome and postpartum depression, considering potential confounding factors and assessing mediating effects of depression and anxiety experienced during pregnancy. RESULTS: Following the exclusion criteria, 8.2% of women reported clinical polycystic ovary syndrome and 19.1%, 6.2%, and 4.4% reported irregular periods and acne, irregular periods and hirsutism, and all 3 symptoms, respectively. Moreover, 17.7% and 23.5% reported experiencing prenatal depression and anxiety and 9.5% and 10.2% reported experiencing postpartum depressed mood and anhedonia, respectively. Clinical polycystic ovary syndrome was associated with a 1.76 higher adjusted prevalence ratio (95% confidence interval, 1.03-3.00) for postpartum depressed mood or anhedonia after taking into consideration age, prepregnancy body mass index, race/ethnicity, education, and marital status. A similar higher prevalence was seen for irregular periods and acne (adjusted prevalence ratio, 1.65; 95% confidence interval, 1.13-2.41), irregular periods and hirsutism (adjusted prevalence ratio, 1.40; 95% confidence interval, 0.82-2.40), and all 3 symptoms (adjusted prevalence ratio, 1.75; 95% confidence interval, 0.96-3.19) and postpartum depressed mood or anhedonia. Prenatal depression and anxiety mediated 20% and 32% of the effect of clinical polycystic ovary syndrome on postpartum depressed mood and anhedonia, respectively. CONCLUSION: Clinical polycystic ovary syndrome is associated with postpartum depressed mood and symptoms among this population-based sample inclusive of high-risk mothers. Prenatal depression and anxiety mediate this association, emphasizing the importance of prenatal psychological screening among women with polycystic ovary syndrome. An additional important clinical and public health implication of this study lies in the finding that nearly 20% of women in this population-based sample who reported at least 2 polycystic ovary syndrome symptoms (including at-risk women who may not have access to care) had not received a clinical diagnosis for polycystic ovary syndrome.

Sporadic anovulation is not an important determinant of becoming pregnant and time to pregnancy among eumenorrheic women: A simulation study.

BACKGROUND: Attaining pregnancy is conditional upon a series of complex processes, including adequately timed intercourse, ovulation, fertilisation, and implantation. Anovulation is a first-line treatment target for couples with difficulty conceiving and is frequently examined in studies of fecundability. OBJECTIVES: To identify whether sporadic anovulation is an important determinant of cumulative pregnancy rates and time to pregnancy among fertile women with regular menstrual cycles. METHODS: We simulated cumulative pregnancy rates and time to pregnancy for 12 consecutive menstrual cycles among 100 000 women based on data-driven probabilities of implantation, fertilisation, ovulation, and intercourse occurring in the fertile window. We assumed anovulation probabilities of 1%, 8%, or 14.5% and intercourse averaging once per week, every other day, or daily. The model incorporated reductions in implantation and fertilisation rates for successive cycles of non-pregnancy. RESULTS: After 12 cycles, a reduction in the per cycle incidence of anovulation from 14.5% to 1% resulted in a 4.0% higher cumulative pregnancy rate (86.7% vs 90.7%) and similar time to pregnancy (1-cycle median difference). In contrast, increasing mean unscheduled sexual intercourse frequency from weekly to every other day was associated with a 5-cycle median reduction in time to pregnancy (weekly: 7 cycles; every other day or daily: 2 cycles) and a 28.9% increase in the cumulative pregnancy rate (weekly: 59.9%, every other day: 88.8%; daily: 91.6%). CONCLUSIONS: In presumed fertile women with regular menstrual cycles, routine investigation of anovulation may not be an informative outcome in studies of fecundability, and routine testing to ensure ovulation and treatment of anovulation are unlikely to be medically necessary. While biomarkers or cervical fluid may help time intercourse to the fertile window, time to pregnancy can also be improved through increasing the frequency of unscheduled intercourse. These findings need corroboration in large preconception time to pregnancy studies.

The risk of clinical complications and death among pregnant women with COVID-19 in the Cerner COVID-19 cohort: a retrospective analysis.

BACKGROUND: Pregnant women are potentially a high-risk population during infectious disease outbreaks such as COVID-19, because of physiologic immune suppression in pregnancy. However, data on the morbidity and mortality of COVID-19 among pregnant women, compared to nonpregnant women, are sparse and inconclusive. We sought to assess the impact of pregnancy on COVID-19 associated morbidity and mortality, with particular attention to the impact of pre-existing comorbidity. METHODS: We used retrospective data from January through June 2020 on female patients aged 18-44 years old utilizing the Cerner COVID-19 de-identified cohort. We used mixed-effects logistic and exponential regression models to evaluate the risk of hospitalization, maximum hospital length of stay (LOS), moderate ventilation, invasive ventilation, and death for pregnant women while adjusting for age, race/ethnicity, insurance, Elixhauser AHRQ weighted Comorbidity Index, diabetes history, medication, and accounting for clustering of results in similar zip-code regions. RESULTS: Out of 22,493 female patients with associated COVID-19, 7.2% (n = 1609) were pregnant. Crude results indicate that pregnant women, compared to non-pregnant women, had higher rates of hospitalization (60.5% vs. 17.0%, P < 0.001), higher mean maximum LOS (0.15 day vs. 0.08 day, P < 0.001) among those who stayed < 1 day, lower mean maximum LOS (2.55 days vs. 3.32 days, P < 0.001) among those who stayed ≥1 day, and higher moderate ventilation use (1.7% vs. 0.7%, P < 0.001) but showed no significant differences in rates of invasive ventilation or death. After adjusting for potentially confounding variables, pregnant women, compared to non-pregnant women, saw higher odds in hospitalization (aOR: 12.26; 95% CI (10.69, 14.06)), moderate ventilation (aOR: 2.35; 95% CI (1.48, 3.74)), higher maximum LOS among those who stayed < 1 day, and lower maximum LOS among those who stayed ≥1 day. No significant associations were found with invasive ventilation or death. For moderate ventilation, differences were seen among age and race/ethnicity groups. CONCLUSIONS: Among women with COVID-19 disease, pregnancy confers substantial additional risk of morbidity, but no difference in mortality. Knowing these variabilities in the risk is essential to inform decision-makers and guide clinical recommendations for the management of COVID-19 in pregnant women.

Restorative reproductive medicine for infertility in two family medicine clinics in New England, an observational study.

BACKGROUND: Restorative reproductive medicine (RRM) seeks to identify and correct underlying causes and factors contributing to infertility and reproductive dysfunction. Many components of RRM are highly suitable for primary care practice. We studied the outcomes amongst couples who received restorative reproductive medicine treatment for infertility in a primary care setting. METHODS: Two family physicians in Massachusetts trained in a systematic approach to RRM (natural procreative technology, or NaProTechnology) treated couples with infertility. We retrospectively reviewed the characteristics, diagnoses, treatments, and outcomes for all couples treated during the years 1989 to 2014. We compared pregnancy and live birth by clinical characteristics using Kaplan-Meier analysis. We employed the Fleming-Harrington weighted Renyi test or the logrank test to compare the cumulative proportion with pregnancy or with live birth. RESULTS: Among 370 couples beginning treatment for infertility, the mean age was 34.8 years, the mean prior time trying to conceive was 2.7 years, and 27% had a prior live birth. The mean number of diagnoses per couple was 4.9. Treatment components included fertility tracking with the Creighton Model FertilityCare System (80%); medications to enhance cervical mucus production (81%), to stimulate ovulation (62%), or to support the luteal phase (75%); and referral to female laparoscopy by a surgeon specializing in endometriosis (46%). The cumulative live birth rate at 2 years was 29% overall; this was significantly higher for women under age 35 (34%), and for women with body mass index < 25 (40%). There were 2 sets of twins and no higher-order multiple gestations. Of the 63 births with data available, 58 (92%) occurred at term. CONCLUSIONS: Family physicians can provide a RRM approach for infertility to identify underlying causes and promote healthy term live births. Younger women and women with body mass index < 25 are more likely to have a live birth.

Identifying barriers to accessing skilled maternal health care in rural Morocco.

Over the past 30 years, the Moroccan government has made enormous strides towards improving maternal health care for Moroccan women, but outcomes for rural women remain much worse than those of their urban counterparts. This study aimed to understand the experiences of women giving birth in rural Morocco, and to identify the barriers they face when accessing facility-based maternity care. Fifty-five participants were recruited from villages in Morocco's rural south to participate in focus group discussions (FGDs), using appreciative inquiry as the guiding framework. Several themes emerged from the analysis of the focus group data. Women felt well-cared for and safe giving birth both at home and in the large, tertiary care hospitals, but not in the small, primary care hospitals. Women who gave birth at the primary care hospitals reported a shortage of some equipment and supplies and poor treatment at the hands of hospital staff. Locating and paying for transportation was identified as the biggest hurdle in accessing maternity care at any hospital. The findings of this study indicate the need for change within primary care health facilities.

Fecundability in relation to use of mobile computing apps to track the menstrual cycle.

STUDY QUESTION: To what extent does the use of mobile computing apps to track the menstrual cycle and the fertile window influence fecundability among women trying to conceive? SUMMARY ANSWER: After adjusting for potential confounders, use of any of several different apps was associated with increased fecundability ranging from 12% to 20% per cycle of attempt. WHAT IS KNOWN ALREADY: Many women are using mobile computing apps to track their menstrual cycle and the fertile window, including while trying to conceive. STUDY DESIGN, SIZE, DURATION: The Pregnancy Study Online (PRESTO) is a North American prospective internet-based cohort of women who are aged 21-45 years, trying to conceive and not using contraception or fertility treatment at baseline. PARTICIPANTS/MATERIALS, SETTING, METHODS: We restricted the analysis to 8363 women trying to conceive for no more than 6 months at baseline; the women were recruited from June 2013 through May 2019. Women completed questionnaires at baseline and every 2 months for up to 1 year. The main outcome was fecundability, i.e. the per-cycle probability of conception, which we assessed using self-reported data on time to pregnancy (confirmed by positive home pregnancy test) in menstrual cycles. On the baseline and follow-up questionnaires, women reported whether they used mobile computing apps to track their menstrual cycles ('cycle apps') and, if so, which one(s). We estimated fecundability ratios (FRs) for the use of cycle apps, adjusted for female age, race/ethnicity, prior pregnancy, BMI, income, current smoking, education, partner education, caffeine intake, use of hormonal contraceptives as the last method of contraception, hours of sleep per night, cycle regularity, use of prenatal supplements, marital status, intercourse frequency and history of subfertility. We also examined the impact of concurrent use of fertility indicators: basal body temperature, cervical fluid, cervix position and/or urine LH. MAIN RESULTS AND THE ROLE OF CHANCE: Among 8363 women, 6077 (72.7%) were using one or more cycle apps at baseline. A total of 122 separate apps were reported by women. We designated five of these apps before analysis as more likely to be effective (Clue, Fertility Friend, Glow, Kindara, Ovia; hereafter referred to as 'selected apps'). The use of any app at baseline was associated with 20% increased fecundability, with little difference between selected apps versus other apps (selected apps FR (95% CI): 1.20 (1.13, 1.28); all other apps 1.21 (1.13, 1.30)). In time-varying analyses, cycle app use was associated with 12-15% increased fecundability (selected apps FR (95% CI): 1.12 (1.04, 1.21); all other apps 1.15 (1.07, 1.24)). When apps were used at baseline with one or more fertility indicators, there was higher fecundability than without fertility indicators (selected apps with indicators FR (95% CI): 1.23 (1.14, 1.34) versus without indicators 1.17 (1.05, 1.30); other apps with indicators 1.30 (1.19, 1.43) versus without indicators 1.16 (1.06, 1.27)). In time-varying analyses, results were similar when stratified by time trying at study entry (<3 vs. 3-6 cycles) or cycle regularity. For use of the selected apps, we observed higher fecundability among women with a history of subfertility: FR 1.33 (1.05-1.67). LIMITATIONS, REASONS FOR CAUTION: Neither regularity nor intensity of app use was ascertained. The prospective time-varying assessment of app use was based on questionnaires completed every 2 months, which would not capture more frequent changes. Intercourse frequency was also reported retrospectively and we do not have data on timing of intercourse relative to the fertile window. Although we controlled for a wide range of covariates, we cannot exclude the possibility of residual confounding (e.g. choosing to use an app in this observational study may be a marker for unmeasured health habits promoting fecundability). Half of the women in the study received a free premium subscription for one of the apps (Fertility Friend), which may have increased the overall prevalence of app use in the time-varying analyses, but would not affect app use at baseline. Most women in the study were college educated, which may limit application of results to other populations. WIDER IMPLICATIONS OF THE FINDINGS: Use of a cycle app, especially in combination with observation of one or more fertility indicators (basal body temperature, cervical fluid, cervix position and/or urine LH), may increase fecundability (per-cycle pregnancy probability) by about 12-20% for couples trying to conceive. We did not find consistent evidence of improved fecundability resulting from use of one specific app over another. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by grants, R21HD072326 and R01HD086742, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA. In the last 3 years, Dr L.A.W. has served as a fibroid consultant for AbbVie.com. Dr L.A.W. has also received in-kind donations from Sandstone Diagnostics, Swiss Precision Diagnostics, FertilityFriend.com and Kindara.com for primary data collection and participant incentives in the PRESTO cohort. Dr J.B.S. reports personal fees from Swiss Precision Diagnostics, outside the submitted work. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Peri-implantation intercourse does not lower fecundability.

STUDY QUESTION: Does sexual intercourse in the implantation time window (5-9 days after ovulation) reduce fecundability? SUMMARY ANSWER: After adjustment for intercourse in the fecund window and clustering by couple, there was no association between intercourse in the implantation time window and fecundity. WHAT IS KNOWN ALREADY: Previous research has suggested an association between intercourse in the peri-implantation time window (5-9 days after estimated ovulation) and reduced fecundability. STUDY DESIGN, SIZE, DURATION: We used data from the FERTILI study, a prospective observational study conducted in five European countries, with data collected from 1992 to 1996. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who were experienced in fertility awareness tracking kept a daily diary of cervical mucus observations, basal body temperature measurements, coitus and clinically identified pregnancy. We estimated the day of ovulation as cycle length minus 13 days. From 661 women, 2606 cycles had intercourse during the fecund window (from 5 days before to 3 days after the estimated day of ovulation), resulting in 418 pregnancies (conception cycles). An established Bayesian fecundability model was used to estimate the fecundability ratio (FR) of peri-implantation intercourse on fecundability, while adjusting for each partner's age, prior pregnancy, the couple's probability of conception and intercourse pattern(s). We conducted sensitivity analyses estimating ovulation as cycle length minus 12 days, or alternatively, as the peak day of estrogenic cervical mucus. MAIN RESULTS AND THE ROLE OF CHANCE: There was no effect of peri-implantation intercourse on fecundability: adjusted FR for three or more acts of peri-implantation intercourse versus none: 1.00, 95% credible interval: 0.76-1.13. Results were essentially the same with sensitivity analyses. There was an inverse relationship between frequency of intercourse in the fecund window and intercourse in the peri-implantation window. LIMITATIONS, REASONS FOR CAUTION: Women with known subfertility were excluded from this study. Many couples in the study were avoiding pregnancy during much of the study, so 61% of otherwise eligible cycles in the database were not at meaningful risk of pregnancy and did not contribute to the analysis. Some couples may not have recorded all intercourse. WIDER IMPLICATIONS OF THE FINDINGS: We believe the current balance of evidence does not support a recommendation for avoiding intercourse in the peri-implantation period among couples trying to conceive. STUDY FUNDING/COMPETING INTEREST(S): No external funding. The authors have no potential competing interests. TRIAL REGISTRATION NUMBER: N/A.