Association of sickle cell trait with adverse pregnancy outcomes in a population-based cohort.

INTRODUCTION: Sickle cell trait (SCT) is common in African descendants. Its association with several adverse pregnancy outcomes (APOs) has been reported but remains inconsistent. The objectives of this study are to test associations of SCT with APOs in non-Hispanic Black women, including (1) validate the associations of SCT with previously reported APOs, (2) test novel associations of SCT with broad spectrum of APOs, and (3) estimate the attributable risk of SCT for implicated APOs. MATERIAL AND METHODS: This is a retrospective analysis of a prospectively designed population-based cohort. Women/participants were self-reported non-Hispanic Black women from the UK Biobank (UKB). SCT status was determined based on heterozygous Glu6Val in the HBB gene. Several APOs were studied, including four previously reported SCT-associated APOs (preeclampsia, bacteriuria, pregnancy loss, and preterm delivery), and broad conditions related to pregnancy, childbirth, and the puerperium. APOs were curated by experts' peer review and consensus processes. Associations of SCT with APOs were tested by estimating its relative risk and 95% confidence interval (95% CI), adjusting for number of live births and age at first birth. Attributable risk proportion (ARP) and population attributable risk proportion (PARP) of SCT to APOs were estimated. RESULTS: Among the 4057 self-reported non-Hispanic Black women with pregnancy records in the UKB, 581 (14.32%) were SCT carriers. For four previously reported SCT-associated APOs, two were confirmed at a nominal P < 0.05; relative risk (RR) was 2.39 (95% CI 1.09-5.23) for preeclampsia, and 4.85 (95% CI 1.77-13.27) for bacteriuria. SCT contributed substantially to these two APOs among SCT carriers, with attributable risk proportion estimated at 61.00% and 68.96% for preeclampsia and bacteriuria, respectively. SCT also contributed substantially to these two APOs in the population (self-reported Black UK women), with population attributable risk proportion estimated at 18.30% and 24.14% for preeclampsia and bacteriuria, respectively. In addition, novel associations were found for seven other APOs (nominal P < 0.05). CONCLUSIONS: SCT is significantly associated with APOs in this study and contributes substantially to APOs among self-reported Black women in the UK. Confirmation of these findings in independent study populations is required.

The Association between Maternal Body Mass Index and the Risk of Perinatal Depression.

OBJECTIVE: The aim of this study was to evaluate whether the risk of perinatal depression is associated with body mass index (BMI) category. STUDY DESIGN: We performed a retrospective cohort study of women who completed an Edinburgh Postnatal Depression Scale (EPDS) questionnaire during the antepartum period at an integrated health system from January 2003 to May 2018. Risk of perinatal depression was defined as a score of ≥10 on the EPDS or an affirmative response to thoughts of self-harm. Risk of perinatal depression was compared by first trimester BMI category, defined as underweight (BMI: <18.5 kg/m2), normal weight (BMI: 18.5-24.9 kg/m2), overweight (BMI: 25.0-29.9 kg/m2), or obese (BMI: ≥30.0 kg/m2). Univariable analyses were performed using χ 2, Fisher's exact test, analysis of variance, Kruskal-Wallis, and Wilcoxon rank-sum tests as appropriate to evaluate the association between maternal BMI category, demographic and clinical characteristics, and risk of perinatal depression. Logistic multivariable regression models were performed to adjust for potential confounders identified as variables with p < 0.10 in univariable analysis. RESULTS: Our analysis included 3,420 obese women, 3,839 overweight women, 5,949 normal weight women, and 1,203 underweight women. The overall median gestational age at EPDS administration was 27 weeks (interquartile range: 23-29). Overweight and obese women were more likely to be non-Hispanic Black, Hispanic, multiparous, to have public insurance, prepregnancy diabetes, and chronic hypertension as compared with normal or underweight women (p < 0.001). In univariable analysis, the risk of perinatal depression was not significantly different among underweight (10.8%, odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.79-1.18) or overweight women (12%, OR: 0.96, 95% CI: 0.79-1.18); however, the risk was higher among obese women (14.7%, 95% CI: 1.21-1.55) compared with normal weight women (11.2%). In multivariable analysis, obesity remained associated with an increased risk of perinatal depression (adjusted OR: 1.19, 95% CI: 1.04-1.35). CONCLUSION: Obesity is associated with an increased risk of perinatal depression as compared with women of normal weight. KEY POINTS: · Maternal obesity is associated with an increased risk of perinatal depression.. · Maternal BMI is associated with increased risk of perinatal depression.. · Maternal obesity is an independent risk factor for perinatal depression..

Complications associated with second trimester inductions of labor requiring greater than five doses of misoprostol.

OBJECTIVE: To evaluate outcomes associated with induction at 14 weeks 0 days-23 weeks 6 days gestation that require five or less vs. six or more misoprostol doses. STUDY DESIGN: We performed a retrospective study of vaginal misoprostol inductions from January 2003 to February 2016 to assess complications based on number of misoprostol doses. RESULTS: Among 390 women receiving five or fewer doses and 78 women receiving six or more doses, we found similar rates of chorioamnionitis, postpartum hemorrhage, transfusion and retained placenta. CONCLUSION: Complication rates were comparable in women receiving more than five versus less than five misoprostol doses for labor induction in the second trimester. IMPLICATIONS: Women undergoing second trimester induction undelivered after five doses of misoprostol can receive additional doses without any concern for increased complications.

Recurrent Non Immune Fetal Hydrops Associated With IPEX Syndrome.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is a clinical syndrome associated with mutations in FOXP3 and consequent abnormalities of T regulatory cells. Affected males typically die in infancy or early childhood from a variety of autoimmune conditions. Reports of recurrent pregnancy loss of male fetuses in these families have been accompanied by descriptions of nonimmune fetal hydrops, with or without additional fetal anomalies. Here, we report an additional family affected by IPEX with a novel mutation leading to recurrent second trimester fetal hydrops and intrauterine fetal demise with associated fetal anomalies. This report underscores how careful genetic and pathologic analysis of even midtrimester fetuses can provide important information impacting an entire family. It also further substantiates the use of broad, symptom-targeted genetic screening panels in cases of recurrent pregnancy loss even in the absence of a remarkable pedigree.

Perinatal and obstetric outcomes of dichorionic vs trichorionic triplet pregnancies.

BACKGROUND: Clinical management and outcome of multiple gestation can be affected by chorionicity. In triplet pregnancies, fetal death has been associated with dichorionic (DC) and monochorionic placentation. Studies evaluating triplet pregnancy outcomes in relation to chorionicity have been few and may not reflect contemporary antenatal and neonatal care. OBJECTIVE: The objective of this study was to compare obstetric and perinatal outcomes in DC and trichorionic (TC) triplet pregnancies. STUDY DESIGN: We performed a retrospective cohort study of triplet pregnancies that delivered at ≥20 weeks' gestation at 2 Chicago area hospitals from January 1999 through December 2010. Chorionicity was determined by pathology specimen. Maternal and infant charts were reviewed for obstetric and perinatal outcomes. RESULTS: The study population included 159 pregnancies (477 neonates) of which 108 were TC (67.9%) and 51 were DC (32.1%). Over 94% of mothers in this study had all 3 infants survive to discharge regardless of chorionicity. No difference was found in perinatal mortality rate between DC and TC triplets (3.3% vs 4.6%; P = .3). DC triplets were significantly more likely to be very low birthweight (41.8% vs 22.2%; odds ratio, 2.2; 95% confidence interval, 1.2-4.2; P = .02) and to deliver at <30 weeks (25.5% vs 8.3%; odds ratio, 6.1; 95% confidence interval, 1.9-19.4; P = .002) compared to TC triplets. Criteria for twin-twin transfusion syndrome (TTTS) were present in 3 DC triplet pregnancies (5.9%). Neonates in pregnancies complicated by TTTS were less likely to survive 28 days as compared to neonates from DC pregnancies that were not affected by TTTS (P = .02) or TC neonates (P = .02) Neonatal survival was similar in DC pregnancies not affected by TTTS and TC pregnancies (98.6% and 96.6%; P = .7). CONCLUSION: Although perinatal mortality did not correlate with chorionicity, DC pregnancies were more likely to deliver <30 weeks' gestational age and have very low birthweight neonates. Neonatal mortality appears to be mediated by the presence or absence of TTTS as 28-day survival was worse in DC pregnancies complicated by TTTS, but similar between DC pregnancies not affected by TTTS and TC pregnancies.

Sleep disordered breathing in a high-risk cohort prevalence and severity across pregnancy.

OBJECTIVE: The objective of this study was to determine the prevalence and incidence of sleep disordered breathing (SDB) in pregnancy among high-risk women. STUDY DESIGN: This was a prospective, observational study. We recruited women with a body mass index (BMI) ≥ 30 kg/m(2), chronic hypertension, pregestational diabetes, history of preeclampsia, and/or a twin gestation. Objective assessment of SDB was completed between 6 and 20 weeks and again in the third trimester. SDB was defined as an apnea-hypopnea index (AHI) ≥5, and further grouped into severity categories: mild (5-14.9), moderate (15-29.9) and severe (≥30). Subjects who had a normal AHI at the baseline (AHI < 5), but an abnormal study in the third trimester (AHI ≥5) were classified as having "new-onset" SDB. RESULTS: A total of 128 women were recruited. In early pregnancy 21, 6 and 3% had mild, moderate, or severe SDB, respectively. These frequencies increased to 35, 7, and 5% in the third trimester (p < 0.001). About 27% (n = 34) experienced a worsening of SDB during pregnancy; 26 were cases of new-onset SDB, while the other 8 had SDB in early pregnancy that worsened in severity. The incidence of new-onset SDB was 20%. The majority of these new-onset cases were mild. CONCLUSIONS: SDB in early pregnancy is common in high-risk women and new-onset SDB occurs in 20% of these women.

Implications of sleep-disordered breathing in pregnancy.

OBJECTIVE: The objective of the study was to examine the relationship between sleep-disordered breathing (SDB) and adverse pregnancy outcomes in a high-risk cohort. STUDY DESIGN: This was a planned analysis of a prospective cohort designed to estimate the prevalence and trends of SDB in high-risk pregnant women. We recruited women with a body mass index of 30 kg/m(2) or greater, chronic hypertension, pregestational diabetes, prior preeclampsia, and/or a twin gestation. Objective assessment of SDB was completed between 6 and 20 weeks and again in the third trimester. SDB was defined as an apnea hypopnea index of 5 or greater and further grouped into severity categories: mild SDB (5-14.9), moderate SDB (15-29.9), and severe SDB (≥30). Pregnancy outcomes (preeclampsia, gestational diabetes, preterm birth, infant weight) were abstracted by physicians blinded to the SDB results. RESULTS: Of the 188 women with a valid early pregnancy sleep study, 182 had complete delivery records. There was no relationship demonstrated between SDB exposure in early or late pregnancy and preeclampsia, preterm birth less than 34 weeks, and small-for-gestational-age (<5%), or large-for-gestational-age (>95%) neonates. Conversely, SDB severity in early pregnancy was associated with the risk of developing gestational diabetes (no SDB, 25%; mild SDB, 43%; moderate/severe SDB, 63%; P = .03). The adjusted odds ratio for developing gestational diabetes for moderate/severe SDB was 3.6 (0.6, 21.8). CONCLUSION: This study suggests a dose-dependent relationship between SDB in early pregnancy and the subsequent development of gestational diabetes. In contrast, no relationships between SDB during pregnancy and preeclampsia, preterm birth, and extremes of birthweight were demonstrated.

Clinical implementation of noninvasive prenatal testing among maternal fetal medicine specialists.

OBJECTIVE: To assess the clinical implementation of non-invasive prenatal testing (NIPT) among maternal-fetal medicine (MFM) specialists. METHOD: Practicing MFMs were invited by email to complete questionnaires via SurveyMonkey©. RESULTS: Of 278 respondents, 56% were male, 48% practiced in academic centers, and 94% currently offer NIPT. NIPT is most often being offered 'to specific patients meeting certain criteria' (59.2%), for indications of advanced maternal age (87.5%), abnormal screen results (94.9%), abnormal ultrasound findings (90.2%), and 'when a high-risk patient declines invasive diagnostic testing' (73.7%). Thirteen percent indicated NIPT is being offered as a diagnostic test. Regardless of whether NIPT was presented as a diagnostic or screening test, 65.3% of MFMs estimate 'some' of their patients have undergone invasive testing for confirmation. Responses were mixed concerning appropriate populations and diagnostic capabilities of NIPT, but MFMs generally agree NIPT should be confirmed with invasive testing and will replace conventional screening procedures. CONCLUSION: Assessment indicates NIPT is being adopted by MFMs, largely in accord with recently published American College of Obstetricians and Gynecologists and the Society for MFM guidelines. Cost and test performance remain factors for not adopting NIPT. Further research on clinical management based on NIPT results and patient understanding of NIPT results is suggested.

Development of a pregnancy-specific screening tool for sleep apnea.

STUDY OBJECTIVE: The Berlin Questionnaire and Epworth Sleepiness Scale (ESS) are commonly used to screen for sleep apnea in non-pregnant populations. We sought to evaluate the Berlin and ESS in pregnancy and to determine whether an alternative screening approach could better detect sleep apnea in pregnant women. METHODS: Pregnant women at high risk for sleep apnea (women with chronic hypertension, pre-gestational diabetes, obesity, and/or a prior history of preeclampsia) completed a sleep survey composed of the Berlin and ESS, and participated in an overnight sleep evaluation with the Watch-PAT100 (WP100), a wrist-mounted device designed to diagnose sleep apnea, defined as an apnea hypopnea index ≥ 5. Using multivariable statistics, demographic, clinical, and subjective symptoms that were independently associated with sleep apnea were determined and a prediction rule for the presence of sleep apnea was developed. The predictive capacity of this newly developed system was compared to that of the Berlin and ESS using receiver-operating curve (ROC) statistics. RESULTS: Of the 114 women who participated and had a valid WP100 study, 100 completed the Berlin and 96 the ESS. The Berlin and ESS did not accurately predict sleep apnea in this high-risk pregnancy cohort, with ROC area under the curves (AUC) of 0.54 (p = 0.6) and 0.57 (p = 0.3), respectively. Conversely, a model incorporating frequent snoring, chronic hypertension, age, and body mass index performed significantly better (AUC 0.86, p > 0.001). CONCLUSION: The Berlin and ESS are not appropriate tools to screen for sleep apnea in high-risk pregnant women. Conversely, our four-variable model more accurately predicts sleep apnea in pregnancy.

Lack of increased hepatotoxicity in HIV-infected pregnant women receiving nevirapine compared with other antiretrovirals.

OBJECTIVE: To estimate whether HIV-infected pregnant women were at an increased risk of hepatotoxicity when taking nevirapine (NVP)-containing regimens compared with HIV-infected pregnant women taking antiretroviral therapy (ART) not containing NVP. METHODS: This analysis included HIV-infected pregnant women on ART from two multicenter, prospective cohorts: the Women and Infants Transmission Study and the International Maternal Pediatric Adolescent AIDS Clinical Trials protocol P1025. Multivariate Cox proportional hazards regression models were used to investigate the association between NVP use and hepatotoxicity. NVP use was dichotomized as use or no use and further categorized according to ART exposure history. We investigated two outcomes: any liver enzyme elevation (LEE) (grade 1-4) and severe LEE (grade 3-4). RESULTS: A total of 1229 women with ART use during pregnancy were studied, 218 (17.7%) of whom received NVP. Among the women receiving NVP, 137 (62.8%) were NVP naive. Twenty-nine women (13.3%) who received NVP developed any LEE and one (0.5%) developed severe LEE. Of the 1011 women on non-NVP regimens, 145 (14.3%) developed any LEE and 14 (1.4%) developed severe LEE. There were no maternal deaths. In univariate models, LEE was not significantly associated with CD4 cell count above 250 cells/mul or NVP use. In adjusted multivariate models, no significant increased risk of LEE (any or severe) in women taking NVP was detected as compared to those taking other ART regardless of prior exposure history. CONCLUSION: We did not observe an increased risk of hepatotoxicity among HIV-infected pregnant women on NVP versus other ART, including women who were ART naive.

Obstetric outcomes in pregnant women with congenital heart disease.

BACKGROUND: Predictors of adverse maternal and neonatal outcomes in pregnant women with congenital heart disease (CHD) have been described, but not for obstetrical outcomes. The primary aim of this study was to determine what risk factors predict sustaining adverse obstetric events in pregnant women with CHD. In addition, a secondary aim was to assess the impact of avoiding Valsalva on obstetrical outcomes, an intervention commonly recommended, but never studied. METHODS: A retrospective cohort study examined outcomes in women with CHD who delivered between 1998 and 2005. We examined baseline cardiac characteristics in a multivariate logistic regression model to assess which were associated with adverse obstetric events. We also compared outcomes of women who avoided Valsalva versus those who were allowed to Valsalva. RESULTS: The study included 65 women with 112 pregnancies. An adverse obstetric event occurred in 32.6% (n=32) of ongoing pregnancies, the most common being preterm delivery (n=19), post-partum hemorrhage (n=13), and preterm premature rupture of membranes (n=9). There were no independent predictors for sustaining an adverse obstetric event. Women who avoided Valsalva had increased rates of post-partum hemorrhage and 3rd/4th degree lacerations. CONCLUSIONS: Although one-third of pregnancies were associated with an adverse obstetric outcome, these events could not be predicted by baseline hemodynamic characteristics. The routine practice of avoiding Valsalva may be associated with high rates of post-partum hemorrhage and 3rd/4th degree lacerations.

Increased risk of hepatotoxicity in HIV-infected pregnant women receiving antiretroviral therapy independent of nevirapine exposure.

OBJECTIVE: To estimate whether the association between nevirapine (NVP) and hepatotoxicity differs according to pregnancy status in HIV-infected women. METHODS: The present analysis included HIV-infected pregnant women on antiretroviral therapy (ART) from two multicenter, prospective cohorts - the Women and Infants Transmission Study and the International Maternal Pediatric Adolescent AIDS Clinical Trials protocol P1025 - and HIV-infected nonpregnant women from one multicenter, prospective cohort - the Women's Interagency HIV Study. Using multivariate Cox proportional hazards regression, the interaction between NVP and pregnancy status in terms of hepatotoxicity was investigated. NVP use was dichotomized as use or no use and was further categorized according to ART exposure history. We investigated two outcomes: any liver enzyme elevation (LEE; grade 1-4) and severe LEE (grade 3-4). RESULTS: Data on 2050 HIV-infected women taking ART were included: 1229 (60.0%) pregnant and 821 (40.0%) nonpregnant. Among the pregnant women, 174 (14.2%) developed any LEE and 15 (1.2%) developed severe LEE as compared with 75 (9.1%) and 5 (0.6%), respectively, of the nonpregnant women. In multivariate adjusted models, NVP was not significantly associated with risk of LEE, regardless of pregnancy status; however, pregnancy was associated with an increased risk of any LEE (relative risk 4.7, confidence interval = 3.4-6.5) and severe LEE (relative risk 3.8, confidence interval = 1.3-11.1). The association of pregnancy and LEE was seen, regardless of prior ART and NVP exposure history. CONCLUSION: No significant association between NVP and LEE was observed, regardless of pregnancy status, but pregnancy was significantly associated with increased hepatotoxocity in HIV-infected women.

Obstetric complications of fibroids.

The effect of uterine fibroids on fecundity and pregnancy outcome is difficult to determine with any degree of accuracy; this is due, in large part, to the lack of adequate large clinical trials. In general, the literature tends to underestimate the prevalence of fibroids in pregnancy and overestimate the complications that are attributed to them. In contrast to popular opinion, most fibroids do not exhibit a significant change in volume during pregnancy, although those that do increase in size tend to do so primarily in the first trimester. Although most pregnancies are unaffected by the presence of uterine fibroids, large submucosal and retro-placental fibroids seem to impart a greater risk for complications, including pain (degeneration), vaginal bleeding, placental abruption, IUGR, and preterm labor and birth. Preconception myomectomy to improve reproductive outcome can be considered on an individual basis, but likely has a place only in women who have recurrent pregnancy loss, large submucosal fibroids, and no other identifiable cause for recurrent miscarriage. Antepartum myomectomy should be reserved for women who have subserosal or pedunculated fibroids and intractable fibroid pain that are unresponsive to medical therapy and who are in the first or second trimester of pregnancy. Myomectomy at the time of cesarean delivery is associated with significant morbidity (hemorrhage) and should be pursued with caution and only in select patients.

Pregnancy outcomes in women with congenital heart disease.

BACKGROUND: Pregnant women with congenital heart disease are at increased risk for cardiac and neonatal complications, yet risk factors for adverse outcomes are not fully defined. METHODS AND RESULTS: Between January 1998 and September 2004, 90 pregnancies at age 27.7+/-6.1 years were followed in 53 women with congenital heart disease. Spontaneous abortions occurred in 11 pregnancies at 10.8+/-3.7 weeks, and 7 underwent elective pregnancy termination. There were no maternal deaths. Primary maternal cardiac events complicated 19.4% of ongoing pregnancies, with pulmonary edema in 16.7% and sustained arrhythmias in 2.8%. Univariate risk factors included prior history of heart failure (odds ratio [OR], 15.5), NYHA functional class > or =2 (OR, 5.4), and decreased subpulmonary ventricular ejection fraction (OR, 7.7). Independent predictors were decreased subpulmonary ventricular ejection fraction and/or severe pulmonary regurgitation (OR, 9.0) and smoking history (OR, 27.2). Adverse neonatal outcomes occurred in 27.8% of ongoing pregnancies and included preterm delivery (20.8%), small for gestational age (8.3%), respiratory distress syndrome (8.3%), intraventricular hemorrhage (1.4%), intrauterine fetal demise (2.8%), and neonatal death (1.4%). A subaortic ventricular outflow tract gradient >30 mm Hg independently predicted an adverse neonatal outcome (OR, 7.5). Cardiac risk assessment was improved by including decreased subpulmonary ventricular systolic function and/or severe pulmonary regurgitation (OR, 10.3) in a previously proposed risk index developed in pregnant women with acquired and congenital heart disease. CONCLUSIONS: Maternal cardiac and neonatal complication rates are considerable in pregnant women with congenital heart disease. Patients with impaired subpulmonary ventricular systolic function and/or severe pulmonary regurgitation are at increased risk for adverse cardiac outcomes.