Pelvic Floor Symptoms 4 Years After Elective Labor Induction: A Randomized Clinical Trial.

IMPORTANCE: Pelvic floor disorders are common and burdensome. Data on the effect of induction of labor on pelvic floor disorders are sparse and results are mixed. OBJECTIVE: Our aim was to evaluate whether elective labor induction in nulliparous women increases the risks of symptomatic urinary incontinence (UI), anal incontinence (AI), or pelvic organ prolapse (POP) 4 years after delivery. STUDY DESIGN: In this single-site follow-up study of "A Randomized Trial of Induction Versus Expectant Management" (ARRIVE) that randomized low-risk nulliparous women with a singleton fetus to elective induction of labor versus expectant management, we compared pelvic floor symptoms between groups at a median of 4 years (interquartile range, 3.5-5.3) after first delivery using validated questionnaires. RESULTS: Seventy hundred sixty-six of 1,042 (74%) original participants responded, and 647 participants (62%) were included in the analysis after exclusions. The overall prevalence rates of symptomatic moderate to severe UI, AI, and POP were 21%, 14%, and 8%, respectively. There were no significant differences in any of the outcomes between women randomized to induction of labor and those to expectant management, either in unadjusted or adjusted analyses. There were also no differences in secondary outcomes, including subtypes of UI or flatal versus stool incontinence. CONCLUSIONS: In this single-site study, we found no significant differences in any UI, AI, and POP symptoms between nulliparous women randomized to elective induction of labor and to expectant management; however, for the least frequent outcome (POP), meaningful differences cannot be ruled out.

Allostatic load in early pregnancy and sleep-disordered breathing.

OBJECTIVES: To assess the association between allostatic load in early pregnancy and sleep-disordered breathing (SDB) during pregnancy. METHODS: High allostatic load in the first trimester was defined as ≥ 4 of 12 biomarkers (systolic blood pressure, diastolic blood pressure, body mass index, cholesterol, low-density lipoprotein, high-density lipoprotein, high sensitivity C-reactive protein, triglycerides, insulin, glucose, creatinine, and albumin) in the unfavorable quartile. SDB was objectively measured using the Embletta-Gold device and operationalized as "SDB ever" in early (6-15 weeks) or mid-pregnancy (22-31 weeks); SDB at each time point was analyzed as secondary outcomes. Multivariable logistic regression was used to test the association between high allostatic load and SDB, adjusted for confounders. Moderation and sensitivity analyses were conducted to assess the role of allostatic load in racial disparities of SDB and obesity affected the relationship between allostatic load and SDB. RESULTS: High allostatic load was present in 35.0% of the nuMoM2b cohort. The prevalence of SDB ever occurred among 8.3% during pregnancy. After adjustment, allostatic load remained significantly associated with SDB ever (aOR= 5.3; 3.6-7.9), in early-pregnancy (aOR= 7.0; 3.8-12.8), and in mid-pregnancy (aOR= 5.8; 3.7-9.1). The association between allostatic load and SDB was not significantly different for people with and without obesity. After excluding BMI from the allostatic load score, the association decreased in magnitude (aOR= 2.6; 1.8-3.9). CONCLUSION: The association between allostatic load and SDB was independent of confounders including BMI. The complex and likely bidirectional relationship between chronic stress and SDB deserves further study in reducing SDB.

Overactive Bladder in Late Pregnancy to 1 Year After First Vaginal Delivery.

IMPORTANCE: Understanding overactive bladder (OAB) during pregnancy and postpartum may increase our knowledge of pathophysiology. OBJECTIVES: The purpose of this study was to understand the prevalence and severity of OAB during pregnancy through 1 year postpartum as well as the associated factors. STUDY DESIGN: This is a secondary analysis of a prospective cohort study evaluating primiparous women with a singleton term vaginal delivery assessed at the third trimester, 8 weeks postpartum, and 1 year postpartum. Overactive bladder was defined as urinary urgency plus nocturia or frequency, or urgency urinary incontinence (UUI). Overactive bladder severity was defined using average visual analog scores (0-100) from OAB symptoms on the Epidemiology of Prolapse and Incontinence Questionnaire. We evaluated associations with OAB at each time point using logistic regression. RESULTS: Among 579 participants, mean age was 29 years. Overactive bladder prevalence was higher at 8 weeks postpartum (23%) than at the third trimester (18%, P = 0.03) and 1 year postpartum (19%, P = 0.03). Overactive bladder severity was higher at the third trimester (42.2) than at 8 weeks postpartum (23.3, P = 0.008), but not at 1 year postpartum (29.1, P = 0.1). In those with OAB, UUI severity was higher at 1 year postpartum compared with that at the third trimester ( P = 0.02). Younger age was associated with third trimester OAB. At 8 weeks postpartum, OAB was associated with older age, urinary tract infection after delivery, birth weight ≥3,500 g, and third trimester OAB. At 1 year postpartum, OAB was associated with birth weight ≥3,500 g and third trimester OAB. CONCLUSIONS: Overactive bladder affects 1 in 5 primiparous women during pregnancy or after vaginal delivery. The increased severity of UUI postpartum and the association between higher birth weight and OAB postpartum suggest an effect of delivery.

Cannabis Exposure and Adverse Pregnancy Outcomes Related to Placental Function.

Importance: Cannabis use is increasing among reproductive-age individuals and the risks associated with cannabis exposure during pregnancy remain uncertain. Objective: To evaluate the association between maternal cannabis use and adverse pregnancy outcomes known to be related to placental function. Design, Setting, and Participants: Ancillary analysis of nulliparous individuals treated at 8 US medical centers with stored urine samples and abstracted pregnancy outcome data available. Participants in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort were recruited from 2010 through 2013; the drug assays and analyses for this ancillary project were completed from June 2020 through April 2023. Exposure: Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol using frozen stored urine samples from study visits during the pregnancy gestational age windows of 6 weeks and 0 days to 13 weeks and 6 days (visit 1); 16 weeks and 0 days to 21 weeks and 6 days (visit 2); and 22 weeks and 0 days to 29 weeks and 6 days (visit 3). Positive results were confirmed with liquid chromatography tandem mass spectrometry. The timing of cannabis exposure was defined as only during the first trimester or ongoing exposure beyond the first trimester. Main Outcome and Measure: The dichotomous primary composite outcome included small-for-gestational-age birth, medically indicated preterm birth, stillbirth, or hypertensive disorders of pregnancy ascertained by medical record abstraction by trained perinatal research staff with adjudication of outcomes by site investigators. Results: Of 10 038 participants, 9257 were eligible for this analysis. Of the 610 participants (6.6%) with cannabis use, 32.4% (n = 197) had cannabis exposure only during the first trimester and 67.6% (n = 413) had ongoing exposure beyond the first trimester. Cannabis exposure was associated with the primary composite outcome (25.9% in the cannabis exposure group vs 17.4% in the no exposure group; adjusted relative risk, 1.27 [95% CI, 1.07-1.49]) in the propensity score-weighted analyses after adjustment for sociodemographic characteristics, body mass index, medical comorbidities, and active nicotine use ascertained via urine cotinine assays. In a 3-category cannabis exposure model (no exposure, exposure only during the first trimester, or ongoing exposure), cannabis use during the first trimester only was not associated with the primary composite outcome; however, ongoing cannabis use was associated with the primary composite outcome (adjusted relative risk, 1.32 [95% CI, 1.09-1.60]). Conclusions and Relevance: In this multicenter cohort, maternal cannabis use ascertained by biological sampling was associated with adverse pregnancy outcomes related to placental dysfunction.

Thrombotic Markers in Pregnant Patients with and without SARS-CoV-2 Infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with coagulation abnormalities and increased risk for venous and arterial thrombi. This study aimed to evaluate D-dimer levels and lupus anticoagulant (LAC) positivity in pregnant individuals with and without Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. STUDY DESIGN: This was a prospective cohort study of pregnant individuals delivering at a single academic institution from April 2020 to March 2022. Individuals with a positive SARS-CoV-2 result during pregnancy were compared with a convenience sample of those without a positive SARS-CoV-2 result. For individuals with SARS-CoV-2 infection, severity was assessed based on the National Institutes of Health classification system. The primary outcome was D-dimer level measured during delivery admission. The secondary outcomes were LAC positivity and thromboembolic events. Outcomes were compared between individuals with and without a positive SARS-CoV-2 result, and further by disease severity. RESULTS: Of 98 participants, 77 (78.6%) were SARS-CoV-2 positive during pregnancy. Among individuals with SARS-CoV-2 infection, severity was asymptomatic in 20 (26.0%), mild in 13 (16.9%), moderate in 4 (5.2%), severe in 38 (49.4%), and critical in 2 (2.6%). The D-dimer concentration at delivery did not significantly differ between those with a SARS-CoV-2 positive result compared with those without (mean 2.03 µg/mL [95% confidence interval {CI} 1.72-2.40] vs. 2.37 µg/mL [95% CI 1.65-3.40]; p = 0.43). Three individuals (4%) with SARS-CoV-2 infection and none (0%) without infection were LAC positive (p = 0.59). There were no clinically apparent thromboses in either group. D-dimer concentrations and LAC positive results did not differ by COVID-19 severity. CONCLUSION: Thrombotic markers did not differ in pregnant individuals by SARS-CoV-2 infection; however, high rates of LAC positivity were detected. KEY POINTS: · Thrombotic markers did not differ in pregnant individuals by SARS-CoV-2 infection.. · Higher than expected rates of LAC positivity were detected.. · There were no clinically apparent thromboses..

Labour agentry and subsequent adverse mental health outcomes: A follow-up study of the ARRIVE Trial.

OBJECTIVE: Labour can be traumatic for women who perceive they are not involved in decisions affecting their care during labour. Our objective was to assess the relation between labour agentry and subsequent mental health. DESIGN: Follow-up cohort study. SETTING: U.S. Tertiary care center. POPULATION: Participants from Utah who participated in the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial. METHODS: During the ARRIVE trial, participants completed the Labor Agentry Scale twice, a validated questionnaire measuring perceived control of patients during childbirth. ARRIVE participants from Utah subsequently were asked to complete questions about mental health history and stressful events occurring since the trial, as well as surveys including the Primary Care Posttraumatic Stress Disorder (PC-PTSD) screen, Edinburgh Postnatal Depression Scale (EPDS) and Generalised Anxiety Disorder-7 (GAD-7) screen. The lower quartile of both agentry measurements defined a person's ordinal agentry category, used for assessing cohort characteristics by exposure category. Continuous minimum agentry was included in adjusted modelling. MAIN OUTCOME MEASURES: The primary outcome was a mental health composite including a positive screen for depression, anxiety, or PTSD or self-report of a diagnosis or exacerbation since their delivery. RESULTS: In all, 766 of 1042 (74%) people responded to the survey (median 4.4, range 2.5-6.4 years after delivery) and 753 had complete data for analysis. In unadjusted comparisons across ordinal agentry category, lower agentry was significantly associated with the primary composite endpoint, and depressive symptoms (test of trend p = 0.003 primary, p = 0.004 depression). Lower labour agentry scores were associated with incremental odds of the primary endpoint (1 SD [24 units], adjusted odds ratio [aOR] 1.21, 95% CI 1.41-1.03), driven by depressive symptoms or self-reported diagnosis (aOR 1.25, 95% CI 1.47-1.05). CONCLUSIONS: Lower labour agentry at the time of birth was associated with a greater risk for mental health conditions years after delivery, indicating a potential opportunity for primary prevention of subsequent depression.

Maternal Morbidity Risk Factors in Nulliparas.

OBJECTIVE: For every incidence of maternal mortality, maternal morbidity is thought to occur in another 50 to 100 individuals in the United States. Multiple risk factors for severe maternal morbidity have been identified, but counseling about specific risk in pregnancy remains difficult, particularly nulliparous individuals as prior obstetric history is one of the factors influencing risk for severe maternal morbidity. The objective of this study is to examine the association between sociodemographic and laboratory assessments in the first trimester and maternal morbidity in nulliparas. STUDY DESIGN: This was a secondary analysis of a large, multicenter prospective observational cohort of nulliparas. The primary maternal outcome was a composite of hypertensive disorders of pregnancy (HDP), hemorrhage (transfusion, hemorrhage, hysterectomy, other surgery, readmission for bleeding), infection (endometritis, wound infection or dehiscence, pneumonia, sepsis, infection during labor and delivery, readmission for infection through day 14), venous thromboembolic events (VTE) (deep venous thrombosis, or pulmonary embolus), or maternal death within 14 days of delivery. Sociodemographic and clinical factors were compared between people with and without maternal morbidity. Relative risk and 95% confidence interval for maternal morbidity was calculated using log-binomial regression, adjusted for baseline characteristics that had a significant independent relationship with maternal morbidity with a p-value <0.05. RESULTS: Of 9,445 pregnant people in the analysis, 18.2% (n = 1,716) experienced the composite maternal morbidity; the most common component was HDP (13.1%, n = 1,244) followed by infection (4.43%, n = 420), hemorrhage (2.27%, n = 215), VTE (0.12%, n = 11), and death (0.01%, n = 1). In a multivariable model, self-identified Black race, first trimester obesity, pregestational diabetes, chronic hypertension, and chronic kidney disease were significantly associated with the primary maternal outcome. CONCLUSION: More than one in six nulliparas experienced the composite maternal morbidities. Maternal morbidity was associated with self-identified Black race, obesity, and multiple preexisting medical comorbidities. KEY POINTS: · One in six nulliparas experience maternal morbidity in their first pregnancy related to hypertensive disorders of pregnancy, infection, hemorrhage, and venous thromboembolism.. · Risk factors for maternal morbidity in nulliparas include Black race, prepregnancy body mass index, and preexisting medical conditions.. · The preexisting medical conditions with the strongest association with maternal morbidity included pregestational diabetes, chronic hypertension, and chronic kidney disease..

Can allostatic load in pregnancy explain the association between race and subsequent cardiovascular disease risk: A cohort study.

OBJECTIVE: To assess the relationship between allostatic load, a measure of cumulative chronic stress in early pregnancy and cardiovascular disease risk, 2-7 years postpartum, and pathways contributing to racial disparities in cardiovascular disease risk. DESIGN: Secondary analysis of a prospective cohort study. SETTING MULTICENTER POPULATION: Pregnant women. METHODS: Our primary exposure was high allostatic load in the first trimester, defined as at least 4 of 12 biomarkers (systolic blood pressure, diastolic blood pressure, body mass index, cholesterol, low-density lipoprotein, high-density lipoprotein, high-sensitivity C-reactive protein, triglycerides, insulin, glucose, creatinine and albumin) in the unfavourable quartile. Logistic regression was used to test the association between high allostatic load and main outcome adjusted for confounders: time from index pregnancy and follow up, age, education, smoking, gravidity, bleeding in the first trimester, index adverse pregnancy outcomes, and health insurance. Each main outcome component and allostatic load were analysed secondarily. Mediation and moderation analyses assessed the role of high allostatic load in racial disparities of cardiovascular disease risk. MAIN OUTCOME MEASURE: Incident cardiovascular disease risk: hypertension, or metabolic disorders. RESULTS: Cardiovascular disease risk was identified in 1462/4022 individuals (hypertension: 36.6%, metabolic disorder: 15.4%). After adjustment, allostatic load was associated with cardiovascular disease risk (adjusted odds ratio [aOR] 2.0, 95% CI 1.8-2.3), hypertension (aOR 2.1, 95% CI 1.8-2.4) and metabolic disorder (aOR 1.7, 95% CI 1.5-2.1). Allostatic load was a partial mediator between race and cardiovascular disease risk. Race did not significantly moderate this relationship. CONCLUSIONS: High allostatic load during pregnancy is associated with cardiovascular disease risk. The relationships between stress, subsequent cardiovascular risk and race warrant further study.

Association Between Genital Hiatus Size 8 Weeks Postpartum and Pelvic Organ Prolapse 1 Year After the First Vaginal Delivery.

IMPORTANCE: Evidence suggests that genital hiatus (GH) enlargement precedes pelvic organ prolapse development remote from delivery. However, the association of postpartum GH enlargement and prolapse is unknown. OBJECTIVE: The aim of this study was to determine the association between enlarged GH at 8 weeks postpartum and prolapse 1 year after first vaginal delivery. STUDY DESIGN: This is a secondary analysis of the Motherhood and Pelvic Health study, a prospective cohort of women after their first vaginal delivery. Enlarged GH was defined as ≥4 cm. Prolapse was defined as Pelvic Organ Prolapse Quantification points Ba, Bp, or C at or beyond the hymen. Kaplan-Meier analysis and proportional hazards modeling were used to analyze the association between enlarged GH at 8 weeks postpartum and prolapse at 1 year postpartum. Diagnostic test characteristics of enlarged GH were calculated. RESULTS: Five hundred eighty women were included. At 1 year postpartum, the prevalence of prolapse was 3 times higher in women with, versus without, an enlarged GH at 8 weeks postpartum (16% vs 5%, P < 0.001). This was confirmed in a Cox proportional hazards model while adjusting for age, body mass index, and early postpartum prolapse (adjusted hazard ratio, 3.3; 95% confidence interval, 1.85-6.06; P < 0.001). The diagnostic properties of postpartum GH to predict prolapse at 1 year are as follows: sensitivity, 0.63; specificity, 0.67; positive predictive value, 0.17; and negative predictive value, 0.95. CONCLUSIONS: Women with an enlarged GH at 8 weeks postpartum have a 3.3-fold increased risk of prolapse at 1 year. As a screening tool, GH <4 cm at 8 weeks postpartum has high negative predictive value.

Association Between Periviable Delivery and New Onset of or Exacerbation of Existing Mental Health Disorders.

OBJECTIVE: To evaluate whether there is an association between periviable delivery and new onset of or exacerbation of existing mental health disorders within 12 months postpartum. METHODS: We conducted a retrospective cohort study of individuals with liveborn singleton neonates delivered at 22 or more weeks of gestation from 2008 to 2017 in the MarketScan Commercial Research Database. The exposure was periviable delivery , defined as delivery from 22 0/7 through 25 6/7 weeks of gestation. The primary outcome was a mental health morbidity composite of one or more of the following: emergency department encounter associated with depression, anxiety, psychosis, posttraumatic stress disorder, adjustment disorder, self-harm, or suicide; new psychotropic medication prescription; new behavioral therapy visit; and inpatient psychiatry admission in the 12 months postdelivery. Secondary outcomes included components of the primary composite. Those with and without periviable delivery were compared using multivariable logistic regression adjusted for clinically relevant covariates, with results reported as adjusted incident rate ratios (aIRRs). Effect modification by history of mental health diagnoses was assessed. Incidence of the primary outcome by 90-day intervals postdelivery was assessed. RESULTS: Of 2,300,244 included deliveries, 16,275 (0.7%) were periviable. Individuals with periviable delivery were more likely to have a chronic health condition, to have undergone cesarean delivery, and to have experienced severe maternal morbidity. Periviable delivery was associated with a modestly increased risk of the primary composite outcome, occurring in 13.8% of individuals with periviable delivery and 11.0% of individuals without periviable delivery (aIRR 1.18, 95% CI 1.12-1.24). The highest-risk period for the composite primary outcome was the first 90 days in those with periviable delivery compared with those without periviable delivery (51.6% vs 42.4%; incident rate ratio 1.56, 95% CI 1.47-1.66). CONCLUSION: Periviable delivery was associated with a modestly increased risk of mental health morbidity in the 12 months postpartum.

Trends in Attempted and Successful Trial of Labor After Cesarean Delivery in the United States From 2010 to 2020.

The vaginal birth after cesarean (VBAC) delivery rate was last reported as 13.8% in 2019. However, contemporary trends in attempted and successful trial of labor after cesarean (TOLAC) delivery among individuals with prior cesarean delivery have not been evaluated. We performed a repeated cross-sectional analysis of singleton, cephalic, term deliveries in individuals with a history of one or two cesarean deliveries in the National Vital Statistics System from 2010 to 2020. Temporal trends in attempted and successful TOLAC, as well as VBAC, were characterized using joinpoint regression. Overall, 4,277,800 deliveries were included. Attempted TOLAC increased from 15.3% in 2010 to 21.7% in 2020, with an annual percent increase (relative) of 4.25% (95% CI 2.9-5.6%). Successful TOLAC increased from 69.8% to 74.7%, with an annual percent change (relative) of 0.91% (95% CI 0.7-1.2%). The VBAC rate similarly increased such that, by 2020, it was 16.2%.

Hypertensive disorders of pregnancy pre- and postaspirin guideline publication in individuals with pregestational diabetes mellitus.

BACKGROUND: The US Preventive Services Taskforce published guidelines in 2014 recommending that low-dose aspirin be initiated between 12 and 28 weeks of gestation among high-risk patients for preeclampsia prophylaxis. Moreover, low-dose aspirin is recommended by some clinicians for the prevention of preterm birth. OBJECTIVE: This study aimed to evaluate whether there is an association between the US Preventive Services Taskforce aspirin guideline hypertensive disorders of pregnancy and the rates of hypertensive disorders of pregnancy and preterm birth in individuals with pregestational diabetes mellitus. STUDY DESIGN: This was a repeated cross-sectional analysis of individuals with pregestational diabetes mellitus and at least 1 singleton delivery at >20 weeks of gestation with records available in the National Vital Statistics System between 2010 and 2018. The primary outcome was hypertensive disorders of pregnancy, and the secondary outcome was preterm birth. Demographics and clinical characteristics among individuals in the pre-US Preventive Services Taskforce guideline cohort (2010-2013) were compared with that of individuals in the post-US Preventive Services Taskforce guideline cohort (2015-2018). Multivariable regression estimated the odds ratios and 95% confidence intervals for the association between guideline publication and the selected endpoints. Effect modification was assessed for access to prenatal care using the Kotelchuck Index (<80% vs ≥80%). Furthermore, a sensitivity analysis limited to nulliparas was performed. RESULTS: Overall, 224,065 individuals were included. Individuals in the post-US Preventive Services Taskforce guideline cohort were more likely to be older, be obese, and have a history of preterm birth. In unadjusted and adjusted modeling, delivery in the post-US Preventive Services Taskforce guideline cohort was associated with hypertensive disorders of pregnancy (adjusted odds ratio, 1.25; 95% confidence interval, 1.22-1.28) and preterm birth (adjusted odds ratio, 1.10; 95% confidence interval, 1.08-1.12). The adjusted odds ratios for hypertensive disorders of pregnancy and preterm birth were more pronounced among those with less than adequate access to care. The findings were similar in the sensitivity analysis of only nulliparas. CONCLUSION: Delivery after US Preventive Services Taskforce aspirin guideline publication was associated with higher rates of hypertensive disorders of pregnancy and preterm birth in a population of individuals with diabetes mellitus. It is unknown whether patient or practitioner factors, or other changes in obstetrical care, contributed to these findings.

Physician cesarean delivery rates and severe perinatal morbidity among low-risk nulliparas.

OBJECTIVE: To estimate the individual physician cesarean delivery rate associated with serious perinatal morbidity. STUDY DESIGN: Study of nulliparous, term, singleton, vertex deliveries with maternal-neonatal dyad data (2015-2017) in the MarketScan Research Database. An individual cesarean delivery rate was calculated for all delivering physicians. The primary maternal outcome included transfusion of ≥4 units of blood, intensive care unit (ICU) admission, venous thromboembolism, or hysterectomy. The primary neonatal outcome included hypoxic ischemic encephalopathy, seizure, cardiopulmonary resuscitation or ventilator use (within 24 h), or ICU admission. Multivariable modeling of the association between physician cesarean delivery rate and each outcome was performed. RESULTS: Among 77,058 maternal-neonatal dyads, the maternal composite occurred in 1.3% of deliveries and neonatal composite in 3.6% of deliveries. The likelihood of the maternal (aOR 1.03 for each 3% increase in physician cesarean delivery rate, 95% CI 1.021-1.043) and neonatal (aOR 1.02 for each 3% increase, 95% CI 1.014-1.027) composite outcome increased linearly with increasing physician cesarean delivery rate. CONCLUSIONS: Severe perinatal morbidity was associated with increasing individual physician cesarean delivery rates.

Copy number variants and fetal growth in stillbirths.

BACKGROUND: Fetal growth abnormalities are associated with a higher incidence of stillbirth, with small and large for gestational age infants incurring a 3 to 4- and 2 to 3-fold increased risk, respectively. Although clinical risk factors such as diabetes, hypertension, and placental insufficiency have been associated with fetal growth aberrations and stillbirth, the role of underlying genetic etiologies remains uncertain. OBJECTIVE: This study aimed to assess the relationship between abnormal copy number variants and fetal growth abnormalities in stillbirths using chromosomal microarray. STUDY DESIGN: A secondary analysis utilizing a cohort study design of stillbirths from the Stillbirth Collaborative Research Network was performed. Exposure was defined as abnormal copy number variants including aneuploidies, pathogenic copy number variants, and variants of unknown clinical significance. The outcomes were small for gestational age and large for gestational age stillbirths, defined as a birthweight <10th percentile and greater than the 90th percentile for gestational age, respectively. RESULTS: Among 393 stillbirths with chromosomal microarray and birthweight data, 16% had abnormal copy number variants. The small for gestational age outcome was more common among those with abnormal copy number variants than those with a normal microarray (29.5% vs 16.5%; P=.038). This finding was consistent after adjusting for clinically important variables. In the final model, only abnormal copy number variants and maternal age remained significantly associated with small for gestational age stillbirths, with an adjusted odds ratio of 2.22 (95% confidence interval, 1.12-4.18). Although large for gestational age stillbirths were more likely to have an abnormal microarray: 6.2% vs 3.3% (P=.275), with an odds ratio of 2.35 (95% confidence interval, 0.70-7.90), this finding did not reach statistical significance. CONCLUSION: Genetic abnormalities are more common in the setting of small for gestational age stillborn fetuses. Abnormal copy number variants not detectable by traditional karyotype make up approximately 50% of the genetic abnormalities in this population.

Mental health symptom changes in pregnant individuals across the COVID-19 pandemic: a prospective longitudinal study.

BACKGROUND: Initial studies found that mental health symptoms increased in pregnant and postpartum individuals during the COVID-19 pandemic. Less research has focused on if these putative increases persist over time and what factors influence these changes. We examined the longitudinal change in mental health symptoms in pregnant and postpartum individuals and investigated moderation by maternal emotion dysregulation and the incidence of coronavirus. METHODS: Pregnant and postpartum individuals at the University of Utah were invited to join the COVID-19 and Perinatal Experiences (COPE) Study. Beginning on April 23, 2020 participants were sent a survey comprised of demographics, medical and social history, pregnancy information and self-assessments (Time 1). Participants were contacted 90 days later and invited to participate in a follow-up questionnaire (Time 2). Daily coronavirus case counts were accessed from the state of Utah and a 7-day moving average calculated. Within-subject change in mental health symptom scores, as measured by the Brief Symptom Inventory, was calculated. Linear mixed effects regression modeling adjusted for history of substance abuse and mental health disorders. RESULTS: 270 individuals responded between April 23rd, 2020 and July 15th, 2021. Mental health symptom scores improved by 1.36 points (0.7-2.0 p < 0.001). The decrease in mental health symptoms was not moderated by the prevalence of COVID-19 cases (p = 0.19) but was moderated by emotion dysregulation (p = 0.001) as defined by the Difficulties in Emotion Regulation Scale short form. Participants with higher emotion dysregulation also had higher mental health symptom scores. CONCLUSION: Mental health symptoms improved over the course of the pandemic in the same pregnant or postpartum participant. Our findings do not negate the importance of mental health care during the pandemic. Rather, we believe this identifies some aspect of resiliency and adaptability. Examining emotion dysregulation, or asking about a history of mental health, may be helpful in identifying persons at higher risk of heightened responses to stressors.

Allostatic Load and Adverse Pregnancy Outcomes.

OBJECTIVE: To assess the association between allostatic load, as an estimate of chronic stress, and adverse pregnancy outcomes. METHODS: This was a secondary analysis of nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be), a prospective observational cohort study. Our primary exposure was dichotomous high allostatic load in the first trimester, defined as 4 or more of 12 biomarkers in the "worst" quartile. The primary outcome was a composite adverse pregnancy outcome: hypertensive disorders of pregnancy (HDP), preterm birth, small for gestational age (SGA), and stillbirth. Secondary outcomes included components of the composite. Multivariable logistic regression was used to test the association between high allostatic load and adverse pregnancy outcomes, adjusted for potential confounders. Mediation and moderation analyses were conducted to assess the role of allostatic load along the causal pathway between racial disparities and adverse pregnancy outcomes. RESULTS: Among 4,266 individuals, 34.7% had a high allostatic load. Composite adverse pregnancy outcome occurred in 1,171 (27.5%): 14.0% HDP, 8.6% preterm birth (48.0% spontaneous and 52.2% indicated), 11.0% SGA, and 0.3% stillbirth. After adjustment for maternal age, gravidity, smoking, bleeding in the first trimester, and health insurance, high allostatic load was significantly associated with a composite adverse pregnancy outcome (adjusted odds ratio [aOR] 1.5, 95% CI 1.3, 1.7) and HDP (aOR 2.5, 95% CI 2.0-2.9), but not preterm birth or SGA. High allostatic load partially mediated the association between self-reported race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race, but not for a composite adverse pregnancy outcome, preterm birth, or SGA. CONCLUSION: High allostatic load in the first trimester is associated with adverse pregnancy outcomes, particularly HDP. Allostatic load was a partial mediator between race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race.