Sonographic Predictors of Antepartum Bleeding in Placenta Previa.

OBJECTIVE: To evaluate the association between sonographic features of placenta previa and vaginal bleeding (VB). STUDY DESIGN: Retrospective cohort study of women with placenta previa identified on ultrasound between 160/7 and 276/7 weeks gestation. Placental distance past the cervical os (DPO), placental thickness, edge angle, and cervical length (CL) were measured. The primary outcome was any VB and the secondary outcome was VB requiring delivery. Median values of the sonographic features were compared for each of the outcomes using the Mann-Whitney U test. Receiver operating characteristic curves were used to compare the predictive value of sonographic variables markers and to determine optimal cut points for each measurement. Logistic regression was used to estimate the association between each measure and the outcomes while controlling for confounders. RESULTS: Of 149 women with placenta previa, 37% had VB and 15% had VB requiring delivery. Women with VB requiring delivery had significantly more episodes of VB than those who did not require delivery for VB (1.5, interquartile range [IQR] [1-3] vs 1.0 [1-5]; p = 0.001). In univariate analysis, women with VB had decreased CL (3.9 vs. 4.2 cm; p < 0.01) compared with those without. Women with VB requiring delivery had increased DPO (2.6 cm IQR [1.7-3.3] vs. 1.5 cm [1.1-2.4], p = 0.01) compared with those without. After adjusting for confounders, only CL < 4 cm remained independently associated with increased risk of VB (adjusted odds ratio: 2.27, 95% confidence interval [1.12-4.58], p = 0.01). None of the measures were predictive of either outcome (area under the curve < 0.65). CONCLUSION: Decreased CL may be associated with risk of VB in placenta previa. KEY POINTS: · Placenta previa is associated with VB.. · Sonographic markers of placenta previa are associated with VB.. · CL is associated with VB in placenta previa, whereas placental DPO is associated with higher rates of bleeding leading to delivery..

Characterization of Patients with Frequent Utilization of the Obstetric Triage Unit: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to identify characteristics of patients with frequent obstetric triage visits ("superusers") compared to those with fewer visits and to evaluate the association of frequent obstetric triage visits with preterm birth and cesarean delivery. STUDY DESIGN: This retrospective cohort included patients presenting to the obstetric triage unit at a tertiary care center from March through April 2014. Superusers were defined as individuals having four or more triage visits. Participant characteristics, including demographic, clinical, visit acuity, and health care characteristics of superusers and nonsuperusers, were summarized and compared. In the subset of patients where data were available regarding prenatal care, prenatal visit patterns were analyzed and compared between the two groups. The outcomes of preterm birth and cesarean were compared between groups using modified Poisson regression to control for confounding. RESULTS: Of the 656 patients evaluated in the obstetric triage unit during the study period, 648 patients met the inclusion criteria. Factors associated with frequent triage use included race/ethnicity, multiparity, insurance status, high-risk pregnancy, and a prior preterm birth. Superusers were more likely to present at an earlier gestational age and had a higher proportion of visits for hypertensive disease. Patient acuity scores were not different between the groups. In the subset of patients receiving prenatal care at the institution, prenatal visit patterns were similar. The risk of preterm birth (adjusted risk ratio [aRR]: 1.06; 95% confidence interval [CI]: 0.66-1.70) did not differ between groups; however, the risk of a cesarean delivery was increased in superusers (aRR: 1.39; 95% CI: 1.01-1.92) when compared to nonsuperusers. CONCLUSION: Superusers, compared to nonsuperusers, have distinct clinical and demographic characteristics and are more likely to be seen in the triage unit at earlier gestational ages. Superusers tended to have a higher proportion of visits for hypertensive disease and had an increased risk of cesarean delivery. KEY POINTS: · Patients with frequent triage visits did not have an increased risk of preterm birth.. · Patients with frequent triage visits were more likely to undergo cesarean delivery.. · Acuity scales were similar for patients with frequent visits compared to those with few visits..

A Comparison of Vaginal and Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth.

OBJECTIVE: This study aimed to examine whether vaginal progesterone is noninferior to 17-α hydroxyprogesterone caproate (17OHP-C) in the prevention of recurrent preterm birth (PTB). STUDY DESIGN: This retrospective cohort study included singleton pregnancies among women with a history of spontaneous PTB who received prenatal care at a single tertiary center from 2011 to 2016. Pregnancies were excluded if progesterone was not initiated prior to 24 weeks or the fetus had a major congenital anomaly. The primary outcome was PTB <37 weeks. A priori, noninferiority was to be established if the upper bound of the adjusted two-sided 90% confidence interval (CI) for the difference in PTB fell below 9%. Inverse probability of treatment weighting (IPTW) was used to carefully control for confounding associated with choice of treatment and PTB. Adjusted differences in PTB proportions were estimated via IPTW regression, with standard errors adjustment for multiple pregnancies per woman. Secondary outcomes included PTB <34 and <28 weeks, spontaneous PTB, neonatal intensive care unit admission, and gestational age at delivery. RESULTS: Among 858 pregnancies, 41% (n = 353) received vaginal progesterone and 59% (n = 505) were given 17OHP-C. Vaginal progesterone use was more common later in the study period, and among women who established prenatal care later, had prior PTBs at later gestational ages, and whose race/ethnicity was neither non-Hispanic white nor non-Hispanic Black. Vaginal progesterone did not meet noninferiority criteria compared with 17-OHPC in examining PTB <37 weeks, with an IPTW adjusted difference of 3.4% (90% CI: -3.5, 10.3). For secondary outcomes, IPTW adjusted differences between treatment groups were generally small and CIs were wide. CONCLUSION: We could not conclude noninferiority of vaginal progesterone to 17OHP-C; however, women and providers may be willing to accept a larger difference (>9%) when considering the cost and availability of vaginal progesterone versus 17OHP-C. A well-designed randomized trial is needed. KEY POINTS: · Vaginal progesterone is not noninferior to 17OHP-C.. · PTB risk may be 10% higher with vaginal progesterone.. · Associations did not differ based on obesity status..

Association between Diabetes in Pregnancy and Shoulder Dystocia by Infant Birth Weight in an Era of Cesarean Delivery for Suspected Macrosomia.

OBJECTIVE: We estimated the association between diabetes and shoulder dystocia by infant birth weight subgroups (<4,000, 4,000-4,500, and >4,500 g) in an era of prophylactic cesarean delivery for suspected macrosomia. STUDY DESIGN: A secondary analysis from the National Institute of Child Health and Human Development U.S. Consortium for Safe Labor of deliveries at ≥24 weeks with a nonanomalous, singleton fetus with vertex presentation undergoing a trial of labor. The exposure was either pregestational or gestational diabetes compared with no diabetes. The primary outcome was shoulder dystocia and secondarily, birth trauma with a shoulder dystocia. We calculated adjusted risk ratios (aRRs) with modified Poison's regression between diabetes and shoulder dystocia and the number needed to treat (NNT) to prevent a shoulder dystocia with cesarean delivery. RESULTS: Among 167,589 assessed deliveries (6% with diabetes), pregnant individuals with diabetes had a higher risk of shoulder dystocia at birth weight <4,000 g (aRR: 1.95; 95% confidence interval [CI]: 1.66-2.31) and 4,000 to 4,500 g (aRR: 1.57; 95% CI: 1.24-1.99), albeit not significantly at birth weight >4,500 g (aRR: 1.26; 95% CI: 0.87-1.82) versus those without diabetes. The risk of birth trauma with shoulder dystocia was higher with diabetes (aRR: 2.29; 95% CI: 1.54-3.45). The NNT to prevent a shoulder dystocia with diabetes was 11 and 6 at ≥4,000 and >4,500 g, versus without diabetes, 17 and 8 at ≥4,000 and >4,500 g, respectively. CONCLUSION: Diabetes increased the risk of shoulder dystocia, even at lower birth weight thresholds than at which cesarean delivery is currently offered. Guidelines providing the option of cesarean delivery for suspected macrosomia may have decreased the risk of shoulder dystocia at higher birth weights. KEY POINTS: · >Diabetes increased the risk of shoulder dystocia, even at lower birth weight thresholds than at which cesarean delivery is currently offered.. · Cesarean delivery for suspected macrosomia may have decreased the risk of shoulder dystocia at higher birth weights.. · These findings can inform delivery planning for providers and pregnant individuals with diabetes..

Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix: The TOPS Randomized Clinical Trial.

Importance: A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. Objective: To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. Design, Setting, and Participants: We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. Interventions: Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. Main Outcome and Measures: The primary outcome was delivery or fetal death prior to 37 weeks. Results: A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). Conclusions and Relevance: Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02901626.

A One-Year Cross Sectional Analysis of Emergency Medical Services Utilization and Its Association with Hypertension in Pregnancy.

Objective: To evaluate the prehospital obstetric population that utilizes emergency medical services (EMS) and their association with hypertensive disorders of pregnancy. Methods: We conducted a retrospective evaluation of one year of all medical calls from a large, municipal, midwestern fire department. Inclusion criteria included all pregnant patients transported to a hospital by EMS. Descriptive statistics were calculated to evaluate prehospital event information (e.g., zip code, time, and duration of call), patient characteristics, and clinical management data regarding blood pressure. Census data were used to compare neighborhood information with poverty rates. Results: Of the 1,575 identified patients, 64.4% (1015/1575) presented with obstetric complaints, 57.4% (700/1220) were in their third trimester and 72.7% (686/944) were multiparous. The median call duration was 17 (interquartile range 12-22) minutes. In the areas where EMS usage was highest, one quarter of individuals lived below the poverty level. Of the studied population, 32.0% (504/1575) were found to be hypertensive; 14.9% (75/504) of hypertensive patients were found to have severe hypertension. Only one patient (1/1575, 0.06%) presented with a chief complaint of hypertension; the rest were discovered by EMS. The highest rates of hypertension were noted in wealthier areas of the city. Patients with severe hypertension were more likely to present with seizures, consistent with eclampsia. Conclusion: Hypertension is common in the obstetric population using EMS. Prehospital management of hypertensive disorders of pregnancy may focus on identification and treatment of severe pre-eclampsia or eclampsia. Areas with longer call times may consider treatment of severe hypertension. Prehospital treatment of hypertensive disorders of pregnancy could be optimized.

Obstetric History and Risk of Short Cervix in Women with a Prior Preterm Birth.

OBJECTIVE: We aimed to assess the relationship between obstetric history and incidence of short cervical length (CL) at <24 weeks gestational age (GA) in women with a prior spontaneous preterm birth (PTB). STUDY DESIGN: Women with a singleton gestation and a history of spontaneous PTB on progesterone who received prenatal care at a single center from 2011 to 2016 were included. Those who did not undergo screening or had a history-indicated cerclage were excluded. The associations between short CL (<25 mm) before 24 weeks and obstetrical factors including: number of prior PTBs, history of term birth, and GA of earliest spontaneous PTB were estimated through modified Poisson regression, adjusting for confounding factors. Multiple pregnancies for the same woman were accounted for through robust sandwich standard error estimation. RESULTS: Among 773 pregnancies, 29% (n = 224) had a CL <25 mm before 24 weeks. The number of prior PTBs was not associated with short CL, but a prior full-term delivery conferred a lower risk of short CL (absolute risk reduction or aRR 0.79, 95% CI 0.63-1.00). Earliest GA of prior spontaneous PTB was associated with short CL. The strongest association was observed in women with a prior PTB at 160/7 to 236/7weeks (aRR 1.98, 95% CI: 1.46-2.70), compared with those with deliveries at 340/7 to 366/7 weeks. Yet, even women whose earliest PTB was 340/7 to 366/7 weeks remained at risk for a short CL, as 21% had a CL <25 mm. The number of prior PTBs did not modify the effect of GA of the earliest prior PTB (interaction test: p = 0.70). CONCLUSION: GA of earliest spontaneous PTB, but not the number of prior PTBs, is associated with short CL. Nevertheless, women with a history of later PTBs remain at sufficiently high risk of having a short CL at <24 weeks gestation that we cannot recommend modifications to existing CL screening guidelines in this group of women. KEY POINTS: · Prior 16 to 236/7 weeks birth is a key risk factor for CL <25 mm.. · One in five women with prior late PTB had a short CL.. · Number of PTBs is a less important risk factor..

Trends in Active Treatment of Live-born Neonates Between 22 Weeks 0 Days and 25 Weeks 6 Days by Gestational Age and Maternal Race and Ethnicity in the US, 2014 to 2020.

Importance: Birth in the periviable period between 22 weeks 0 days and 25 weeks 6 days' gestation is a major source of neonatal morbidity and mortality, and the decision to initiate active life-saving treatment is challenging. Objective: To assess whether the frequency of active treatment among live-born neonates in the periviable period has changed over time and whether active treatment differed by gestational age at birth and race and ethnicity. Design, Setting, and Participants: Serial cross-sectional descriptive study using National Center for Health Statistics natality data from 2014 to 2020 for 61 908 singleton live births without clinical anomalies between 22 weeks 0 days and 25 weeks 6 days in the US. Exposures: Year of delivery, gestational age at birth, and race and ethnicity of the pregnant individual, stratified as non-Hispanic Asian/Pacific Islander, non-Hispanic Black, Hispanic/Latina, and non-Hispanic White. Main Outcomes and Measures: Active treatment, determined by whether there was an attempt to treat the neonate and defined as a composite of surfactant therapy, immediate assisted ventilation at birth, assisted ventilation more than 6 hours in duration, and/or antibiotic therapy. Frequencies, mean annual percent change (APC), and adjusted risk ratios (aRRs) were estimated. Results: Of 26 986 716 live births, 61 908 (0.2%) were periviable live births included in this study: 5% were Asian/Pacific Islander, 37% Black, 24% Hispanic, and 34% White; and 14% were born at 22 weeks, 21% at 23 weeks, 30% at 24 weeks, and 34% at 25 weeks. Fifty-two percent of neonates received active treatment. From 2014 to 2020, the overall frequency (mean APC per year) of active treatment increased significantly (3.9% [95% CI, 3.0% to 4.9%]), as well as among all racial and ethnic subgroups (Asian/Pacific Islander: 3.4% [95% CI, 0.8% to 6.0%]); Black: 4.7% [95% CI, 3.4% to 5.9%]; Hispanic: 4.7% [95% CI, 3.4% to 5.9%]; and White: 3.1% [95% CI, 1.1% to 4.4%]) and among each gestational age range (22 weeks: 14.4% [95% CI, 11.1% to 17.7%] and 25 weeks: 2.9% [95% CI, 1.5% to 4.2%]). Compared with neonates born to White individuals (57.0%), neonates born to Asian/Pacific Islander (46.2%; risk difference [RD], -10.81 [95% CI, -12.75 to -8.88]; aRR, 0.82 [95% CI, [0.79-0.86]), Black (51.6%; RD, -5.42 [95% CI, -6.36 to -4.50]; aRR, 0.90 [95% CI, 0.89 to 0.92]), and Hispanic (48.0%; RD, -9.03 [95% CI, -10.07 to -7.99]; aRR, 0.83 [95% CI, 0.81 to 0.85]) individuals were significantly less likely to receive active treatment. Conclusions and Relevance: From 2014 to 2020 in the US, the frequency of active treatment among neonates born alive between 22 weeks 0 days and 25 weeks 6 days significantly increased, and there were differences in rates of active treatment by race and ethnicity.

Proactive neonatal treatment at 22 weeks of gestation: a systematic review and meta-analysis.

OBJECTIVE: The objective of this study was to provide a systematic review and meta-analysis to quantify prognosis and identify factors associated with variations in reported mortality estimates among infants who were born at 22 weeks of gestation and provided proactive treatment (resuscitation and intensive care). DATA SOURCES: PubMed, Scopus, and Web of Science databases, with no language restrictions, were searched for articles published from January 2000 to February 2020. STUDY ELIGIBILITY CRITERIA: Reports on live-born infants who were delivered at 22 weeks of gestation and provided proactive care were included. The primary outcome was survival to hospital discharge; secondary outcomes included survival without major morbidity and survival without neurodevelopmental impairment. Because we expected differences across studies in the definitions for various morbidities, multiple definitions for composite outcomes of major morbidities were prespecified. Neurodevelopmental impairment was based on Bayley Scales of Infant Development II or III. Data extractions were performed independently, and outcomes agreed on a priori. STUDY APPRAISAL AND SYNTHESIS METHODS: Methodological quality was assessed using the Quality in Prognostic Studies tool. An adapted version of the Grading of Recommendations Assessment, Development and Evaluation approach for prognostic studies was used to evaluate confidence in overall estimates. Outcomes were assessed as prevalence and 95% confidence intervals. Variabilities across studies attributable to heterogeneity were estimated with the I2 statistic; publication bias was assessed with the Luis Furuya-Kanamori index. Data were pooled using the inverse variance heterogeneity model. RESULTS: Literature searches returned 21,952 articles, with 2034 considered in full; 31 studies of 2226 infants who were delivered at 22 weeks of gestation and provided proactive neonatal treatment were included. No articles were excluded for study design or risk of bias. The pooled prevalence of survival was 29.0% (95% confidence interval, 17.2-41.6; 31 studies, 2226 infants; I2=79.4%; Luis Furuya-Kanamori index=0.04). Survival among infants born to mothers receiving antenatal corticosteroids was twice the survival of infants born to mothers not receiving antenatal corticosteroids (39.0% vs 19.5%; P<.01). The overall prevalence of survival without major morbidity, using a definition that includes any bronchopulmonary dysplasia, was 11.0% (95% confidence interval, 8.0-14.3; 10 studies, 374 infants; I2=0%; Luis Furuya-Kanamori index=3.02). The overall rate of survival without moderate or severe impairment was 37.0% (95% confidence interval, 14.6-61.5; 5 studies, 39 infants; I2=45%; Luis Furuya-Kanamori index=-0.15). Based on the year of publication, survival rates increased between 2000 and 2020 (slope of the regression line=0.09; standard error=0.03; P<.01). Studies were highly diverse with regard to interventions and outcomes reported. CONCLUSION: The reported survival rates varied greatly among studies and were likely influenced by combining observational data from disparate sources, lack of individual patient-level data, and bias in the component studies from which the data were drawn. Therefore, pooled results should be interpreted with caution. To answer fundamental questions beyond the breadth of available data, multicenter, multidisciplinary collaborations, including alignment of important outcomes by stakeholders, are needed.

The Importance of Clinical Presentation in Risk and Management of Recurrent Preterm Birth.

OBJECTIVE: This study aimed to compare the risk of recurrent spontaneous preterm birth (sPTB), as well as cerclage efficacy, between groups stratified by phenotype of the index sPTB. STUDY DESIGN: This is a retrospective cohort study of women with a history of sPTB. Included were women with a history of singleton sPTB who received progesterone in a subsequent pregnancy. Multifetal gestations and abdominal cerclage were excluded. Exposure groups were based upon the presenting symptom that preceded their first sPTB and included painless cervical dilation (PCD), preterm premature rupture of membranes (PPROM), and painful dilation (preterm labor [PTL]). Primary outcome was delivery <34 weeks in a subsequent pregnancy. Secondary outcomes included delivery <28 and <37 weeks. Rates were compared using the Chi-square test. Multivariable Poisson regression was used to adjust for confounders. RESULTS: A total of 723 women were included. A total of 114 (16%) presented with PCD, 305 (42%) with PPROM, and 304 (42%) with PTL in their first sPTB. Cerclage in subsequent pregnancy was highest in the PCD group (42%) when compared with the PPROM (16%) and PTL (12%) groups. Rates of sPTB <34 and 37 weeks were similar among the groups. After adjusting for confounders, PCD was found to significantly increase the risk of recurrent sPTB <28 weeks (incidence rate ratio: 3.46 [1.09-11.0]; p = 0.04). Of the 121 women who underwent cerclage, there were no significant differences in rates of sPTB between the clinical presentation groups. CONCLUSION: PCD as a specific phenotype of sPTB impacts recurrence of delivery before 28 weeks, but not at later gestational ages. In contrast, there was no significant association between clinical presentation of index sPTB and gestational latency in women who also underwent cerclage placement in a subsequent pregnancy. Our data suggest that clinical presentation is important with regards to recurrence of early sPTB, but not sPTB at later gestational ages. KEY POINTS: · Phenotype is critical to understanding PTB.. · Phenotype is associated with recurrent PTB.. · Painless dilation is associated with recurrent PTB..

The Hepatobiliary System: An Overview of Normal Function and Diagnostic Testing in Pregnancy.

Pregnancy is associated with physiological adaptions that affect every organ system. Changes in liver function in pregnancy have important effects on nutrient metabolism, protein synthesis, and the biotransformation of substances in preparation for excretion. A clear understanding of the anatomic and functional changes of the hepatobiliary system is necessary for the diagnosis and evaluation of disease, as well as understanding how these changes predispose women to pregnancy-specific hepatic conditions. In this review, the effect of gestational changes in hepatobiliary function on laboratory tests and the role of diagnostic imaging of the liver and gallbladder in pregnancy will be discussed.

Prenatal cigarette smoking as a mediator between racism and depressive symptoms: The Biosocial Impact on Black Births Study.

OBJECTIVE: This study examined whether cigarette smoking mediated the association of racial discrimination with depressive symptoms among pregnant Black women. DESIGN: Cross-sectional. SAMPLE: Two hundred Black women at 8-29 weeks gestation. MEASUREMENTS: Women completed questionnaires including the Experiences of Discrimination and the Center for Epidemiologic Studies-Depression (CES-D) scales, as well as questions about sociodemographic characteristics and cigarette smoking. RESULTS: The mean age of the sample was 26.9 ± 5.7 years and the mean gestational age at data collection was 15.6 ± 5.7 weeks. Approximately 17% of women reported prenatal cigarette smoking; 27% had prenatal CES-D scores ≥23, which have been correlated with depression diagnoses; and 59% reported ever (lifetime) experiencing discrimination in at least one situation (e.g., at work). Path analysis results indicated that the standardized indirect effect of experiences of racial discrimination on CES-D scores through prenatal smoking was statistically significant (standardized indirect effect = 0.03; 95% CI: 0.001, 0.094; p = .042). CONCLUSION: Cigarette smoking during pregnancy partially mediated the association between lifetime experiences of racial discrimination and prenatal depressive symptoms among pregnant Black women. Smoking cessation programs should focus on identifying and treating depressive symptoms among pregnant Black women.

Genetic variation associated with preterm birth in African-American women.

BACKGROUND: Preterm birth is considered a multifactorial condition; however, emerging evidence suggests that genetic variation among individuals may have an important role. Prior studies have suggested that single-nucleotide polymorphisms associated with genes related to the immune system, and particularly the maternal inflammatory response, may be associated with an increased risk of preterm delivery. OBJECTIVE: The objective of the study was to identify single-nucleotide polymorphisms associated with spontaneous preterm birth <37 weeks within a cohort of African-American women. STUDY DESIGN: This is a secondary analysis of a randomized trial that evaluated periodontal disease and preterm birth. Women were enrolled between 6 and 20 weeks' gestation at 3 prenatal care clinics between 2004 and 2007. Maternal DNA samples were collected and analyzed using a custom 1536 single-nucleotide polymorphismgenotyping array designed to assess genes involved in inflammation. Women were included in this study if they self-identified as African American. We excluded women with a multiple gestation or an indicated preterm delivery. We performed allele- and genotype-based analyses to evaluate the association between spontaneous preterm birth and tag single-nucleotide polymorphisms. We used a logistic regression to adjust for prior preterm birth in our genotype-based analysis. In a subgroup analysis, we compared women who delivered at <34 weeks' gestation to women who delivered at term. Within the microarray, we identified ancestry informative markers and compared global ancestry estimates among women who delivered preterm with those who delivered at term. RESULTS: Of the 833 African-American women in the study with genotype data, 77 women (9.2%) had a spontaneous preterm birth, whereas 756 women delivered at term. In an allele-based analysis, 4 single-nucleotide polymorphisms related to the genes for protein kinase C-α (PRKCA) were associated with increased risk of spontaneous preterm birth <37 weeks, whereas a single single-nucleotide polymorphism related to fms-related tyrosine kinase 1 (FLT1) was associated with spontaneous preterm birth <34 weeks. A genotype-based analysis revealed similar associations between single-nucleotide polymorphisms related to the PRKCA genes and spontaneous premature delivery. Additionally, single-nucleotide polymorphisms related to matrix metalloproteinase-2 (MMP2), tissue inhibitor of matrix metalloproteinase-2 (TIMP2), and interleukin 16 (IL16) genes were associated with spontaneous preterm birth <37 weeks in genotype-based analysis. Genetic variants related to MMP2, matrix metalloproteinase-1 (MMP1), and leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1) genes were associated with higher rates of preterm birth <34 weeks. Ancestry estimates were similar between the women who had a spontaneous preterm birth and those who delivered at term. CONCLUSION: We identified tag single-nucleotide polymorphisms related to 7 genes that are critical to inflammation, extracellular remodeling, and cell signaling that were associated with spontaneous preterm birth in African-American women. Specifically, we found a strong association with the PRKCA gene. Genetic variation in these regions of the genome may be important in the pathogenesis of preterm birth. Our results should be considered in the design of future genomic studies in prematurity.

Optimal Admission Cervical Dilation in Spontaneously Laboring Women.

OBJECTIVE: To estimate the impact of admission cervical dilation on the risk of cesarean in spontaneously laboring women at term. STUDY DESIGN: Secondary analysis of a prospective cohort study of women admitted in term labor with a singleton gestation. Women with rupture of membranes before admission, induction of labor, or prelabor cesarean were excluded. The association between cesarean and cervical dilation at admission was estimated, and results were stratified by parity. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated, using cervical dilation ≥ 6 cm as the reference group. Cesarean for arrest was secondarily explored. RESULTS: A total of 2,033 spontaneously laboring women met inclusion criteria. Women admitted at <6 cm dilation had an increased risk of cesarean compared with those admitted at ≥6 cm (13.2 vs. 3.5%; RR 3.73; 95% CI 1.94-7.17). The increased risk was noted in nulliparous (16.8 vs. 7.1%; RR 2.35; 95% CI 0.90-6.13) and multiparous (11.0 vs. 2.5%; RR 4.36; 95% CI 1.80-10.52) women, but was statistically significant only in multiparous women. CONCLUSIONS: Decreasing cervical dilation at admission, particularly <6 cm, is a modifiable risk factor for cesarean, especially in multiparous women. This should be considered in the decision-making process about timing of admission in term labor.

Neonatal morbidity associated with shoulder dystocia maneuvers.

OBJECTIVE: We sought to examine neonatal morbidity associated with different maneuvers used among term patients who experience a shoulder dystocia. STUDY DESIGN: We conducted a retrospective cohort study of all women who experienced a clinically diagnosed shoulder dystocia at term requiring obstetric maneuvers at a single tertiary care hospital from 2005 through 2008. We excluded women with major fetal anomaly, intrauterine death, multiple gestation, and preterm. Women exposed to Rubin maneuver, Wood's screw maneuver, or delivery of the posterior arm were compared to women delivered by McRoberts/suprapubic pressure only, which served as the reference group. The primary outcome was a composite morbidity of neonatal injury (defined as clavicular or humeral fracture or brachial plexus injury) and neonatal depression (defined as Apgar <7 at 5 minutes, arterial cord pH <7.1, continuous positive airway pressure use, intubation, or respiratory distress). Logistic regression was used to adjust for nulliparity and duration of shoulder dystocia, defined as time from delivery of fetal head to delivery of shoulders. RESULTS: Among the 231 women who met inclusion criteria, 135 were delivered by McRoberts/suprapubic pressure alone (57.9%), 83 women were exposed to Rubin maneuver, 53 women were exposed to Wood's screw, and 36 women were exposed to delivery of posterior arm. Individual maneuvers were not associated with composite morbidity, neonatal injury, or neonatal depression after adjusting for nulliparity and duration of shoulder dystocia. CONCLUSION: We found no association between shoulder dystocia maneuvers and neonatal morbidity after adjusting for duration, a surrogate for severity. Our results demonstrate that clinicians should utilize the maneuver most likely to result in successful delivery.

Interpreting category II fetal heart rate tracings: does meconium matter?

OBJECTIVE: Category II fetal heart rate (FHR) tracings are considered indeterminate; thus, improved risk stratification of category II FHR tracings is needed. We estimated whether the presence of meconium increased the risk of adverse neonatal outcomes. STUDY DESIGN: This study was conducted within a prospective cohort of 5000 women with singleton pregnancies who were admitted in labor at term. Pregnancies with category II FHR in the 60 minutes before delivery were included. FHR data were extracted by trained nurses who were blinded to clinical outcome. The exposure was the presence of meconium. The primary outcome was a composite neonatal morbidity defined as ≥1 of the following: neonatal death, neurologic morbidity, respiratory morbidity, hypotension that required treatment, and sepsis. Secondary outcomes were nursery admission, cord pH, 5-minute Apgar score, and components of the composite. Logistic regression was used to adjust for confounders. RESULTS: Of the 3257 women with category II FHR tracings, 693 women (21.3%) had meconium, and 2564 women (78.7%) did not. Meconium was associated with higher risk of the composite morbidity (adjusted odds ratio, 2.49; 95% confidence interval, 1.78-3.48) and increased risks of the secondary outcomes. The associations remained significant when infants with meconium aspiration syndrome were excluded. Thick meconium was associated significantly with the composite morbidity. CONCLUSION: The presence of meconium is associated with an increased risk of neonatal morbidity in women with category II FHR pattern. This clinical factor may assist clinicians in managing category II FHR patterns in labor.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Expression of flotillins in the human placenta: potential implications for placental transcytosis.

A proteomics survey of human placental syncytiotrophoblast (ST) apical plasma membranes revealed peptides corresponding to flotillin-1 (FLOT1) and flotillin-2 (FLOT2). The flotillins belong to a class of lipid microdomain-associated integral membrane proteins that have been implicated in clathrin- and caveolar-independent endocytosis. In the present study, we characterized the expression of the flotillin proteins within the human placenta. FLOT1 and FLOT2 were coexpressed in placental lysates and BeWo human trophoblast cells. Immunofluorescence microscopy of first-trimester and term placentas revealed that both proteins were more prominent in villous endothelial cells and cytotrophoblasts (CTs) than the ST. Correspondingly, forskolin-induced fusion in BeWo cells resulted in a decrease in FLOT1 and FLOT2, suggesting that flotillin protein expression is reduced following trophoblast syncytialization. The flotillin proteins co-localized with a marker of fluid-phase pinocytosis, and knockdown of FLOT1 and/or FLOT2 expression resulted in decreased endocytosis of cholera toxin B subunit. We conclude that FLOT1 and FLOT2 are abundantly coexpressed in term villous placental CTs and endothelial cells, and in comparison, expression of these proteins in the ST is reduced. These findings suggest that flotillin-dependent endocytosis is unlikely to be a major pathway in the ST, but may be important in the CT and endothelium.