Unpublished completed obstetric randomized clinical trials registered at ClinicalTrials.gov: how big is this issue?

BACKGROUND: A portion of obstetrical randomized clinical trials registered on ClinicalTrials.gov are not published in peer-reviewed journals. OBJECTIVE: This study aimed to compare the characteristics of completed published vs unpublished randomized clinical trials in obstetrics registered on ClinicalTrials.gov and to identify barriers to publication. STUDY DESIGN: This cross-sectional study queried ClinicalTrials.gov for all completed obstetrical randomized clinical trials registered between January 1, 2009, and December 31, 2018. For each completed obstetrical randomized clinical trial, we abstracted the following registration fields from ClinicalTrials.gov: ClinicalTrials.gov identifier, recruitment status, trial start and completion dates, study results, type of intervention, study phase, enrollment size, funder type, location, and facilities. Calculated variables included time to completion. In May 2021, we used PubMed and Google Scholar to identify the publication status of completed trials, and we compared the characteristics of published vs unpublished randomized clinical trials. The corresponding authors' e-mail addresses for the unpublished studies were collected from ClinicalTrials.gov and departmental websites. Between September 2021 and March 2022, the authors of these completed but unpublished obstetrical randomized clinical trials were contacted and invited to respond to a survey examining perceptions of barriers to publication, responses of which were collected and presented as counts and percentages. RESULTS: Of the 647 obstetrical randomized clinical trials marked as completed on ClinicalTrials.gov, 378 (58%) were published, and 269 (42%) were unpublished. Unpublished trials were more likely to have an enrollment size of <50 participants (14.5% published vs 25.3% unpublished; P<.001) and less likely to be conducted at multiple sites (25.4% published vs 17.5% unpublished; P<.02). The main barriers to publication reported in the survey by authors whose trials were not published included lack of time (30%), change in employment or completion of training (25%), and results that were not of statistical significance (15%). CONCLUSION: Among the obstetrical randomized clinical trials registered and marked as completed on ClinicalTrials.gov, more than 40% were unpublished. Unpublished trials were more likely to be smaller studies, conducted by researchers who reported experiencing a lack of time as the most common barrier to study publication.

Birthweight is increasing in the United States.

OBJECTIVE: The rates of obesity and diabetes mellitus have increased over the last several decades.1,2 This has resulted in a higher number of large-for-gestational-age (LGA) neonates.3 The US cesarean delivery rate has increased over the same period; LGA fetuses may be a contributing factor.4 This study aimed to establish whether birthweights in the United States have increased over time. STUDY DESIGN: This was a retrospective cohort study conducted using live birth data of singleton pregnancies from the US National Vital Statistics between January 1972 and December 2020. These data are deidentified and publicly available; therefore, the study was deemed exempt from our institutional review board. Singleton births between 37 0/7 and 42 6/7 weeks of gestation were included. Multiple pregnancies and deliveries which had unknown gestational age or birthweight, were excluded. The mean birthweight by each gestational age week for the years 1972-2020 was calculated at selected years (1972, 1982, 1992, 2002, 2012, 2018, and 2020). Of note, 2018 was included to account for differences in the dataset that might be due to the COVID-19 pandemic. Using R statistical software, a linear model was fit for each gestational age week. A t test was performed to determine whether the slope was statistically different from zero (indicating whether there was a trend of rising or decreasing birthweights over time). RESULTS: A total of 19,730,588 individuals met the inclusion criteria. However, <1% of the data were excluded because of missing data. Birthweight at 39, 40, 41, and 42 weeks of gestation showed a statistically significant increase over time (Figure). There was a significant decrease in birthweight at 37 weeks of gestation. Data on Hispanic ethnicity became available in 1992. After 1992, birthweight by race or ethnicity group was examined. Each race or ethnicity group echoes the overall trends observed. However, for 39, 40, 41, and 42 weeks of gestation, the non-Hispanic Black and Hispanic groups have higher increases in birthweight than the non-Hispanic White group. There were fluctuations in the overall combined mean for 37 to 42 weeks of gestation (Table). CONCLUSION: Although the overall mean birthweight did not increase over the study period, it increased for each gestational age week at ≥39 weeks of gestation. The birthweight at 37 weeks of gestation decreased. The reason for the decrease in birthweight is unclear. Contributing factors may include changes in guidelines on the timing of delivery and method of calculation of gestational age. Increases in the rates of obesity and diabetes mellitus could be contributing to the birthweight increase from 39 weeks of gestation.1,2 There was an increase in the rate of gestational diabetes mellitus from 3% to 8% in our study population from 1992 to 2020 and an increase in mean body mass index from 26.3 to 27.5 from 2012 to 2020. The publicly available birthweight data have limitations. Data collection evolved during the study period. The estimates for gestational age have become more accurate with first-trimester dating ultrasounds. In summary, birthweight is increasing among those born from 39 to 42 weeks of gestation. These increasing birthweights may be a factor in persistently high cesarean delivery rates despite national campaigns.5.

Risk of Stillbirth in Pregnancies Complicated by Diabetes, Stratified by Fetal Growth.

OBJECTIVE: To compare stillbirth rates per week of expectant management stratified by birth weight in pregnancies complicated by gestational diabetes mellitus (GDM) or pregestational diabetes mellitus. METHODS: A national population-based retrospective cohort study of singleton, nonanomalous pregnancies complicated by pregestational diabetes or GDM was performed using national birth and death certificate data from 2014 to 2017. Stillbirth rates per 10,000 patients (stillbirth incidence at gestational age week/ongoing pregnancies-[0.5×live births at gestational age week]) were determined for each week of pregnancy from 34 to 39 completed weeks of gestation. Pregnancies were stratified by birth weight, categorized as having small-for-gestational-age (SGA), appropriate-for-gestational-age (AGA), or large-for-gestational-age (LGA) fetuses, assigned by sex-based Fenton criteria. Relative risk (RR) and 95% CI for stillbirth were calculated for each gestational age week compared with the GDM-related AGA group. RESULTS: We included 834,631 pregnancies complicated by either GDM (86.9%) or pregestational diabetes (13.1%) in the analysis, with a total of 3,033 stillbirths. Stillbirth rates increased with advancing gestational age for pregnancies complicated by both GDM and pregestational diabetes regardless of birth weight. Compared with pregnancies with AGA fetuses, those with both SGA and LGA fetuses were significantly associated with an increased risk of stillbirth at all gestational ages. Ongoing pregnancies at 37 weeks of gestation complicated by pregestational diabetes with LGA or SGA fetuses had respective stillbirth rates of 64.9 and 40.1 per 10,000 patients. Pregnancies complicated by pregestational diabetes had an RR of stillbirth of 21.8 (95% CI 17.4-27.2) for LGA fetuses and 13.5 (95% CI 8.5-21.2) for SGA fetuses compared with GDM-related AGA at 37 weeks of gestation. The greatest absolute risk of stillbirth was in pregnancies complicated by pregestational diabetes at 39 weeks of gestation with LGA fetuses (97/10,000). CONCLUSION: Pregnancies complicated by both GDM and pregestational diabetes affected by pathologic fetal growth have an increased risk of stillbirth with advancing gestational age. This risk is significantly higher with pregestational diabetes, especially pregestational diabetes with LGA fetuses.

Fetal Autopsy Rates in the United States: Analysis of National Vital Statistics.

OBJECTIVE: To identify rates of fetal autopsy in the United States as well as demographic and clinical characteristics related to consent to autopsy after stillbirth. METHODS: This is a population-based retrospective cohort study using U.S. fetal death certificates for stillborn fetuses (20 weeks of gestation or more) delivered between January 2014 and December 2016. Multiple gestations were excluded. Fetal autopsy rates were calculated by gestational age, maternal age, self-reported race and ethnicity, education, and having at least one living child. Multivariate logistic regression to adjust for potential confounders was performed. RESULTS: There were 60,328 stillbirths meeting inclusion criteria. Overall, fetal autopsy was performed in 20.9% of stillbirths. Non-Hispanic Black women had the highest rate of fetal autopsy (22.9%, 95% CI 22.3-23.6%), compared with non-Hispanic White women (20.4%, 95% CI 20.0-20.9%) and Hispanic women (19.6%, 95% CI 19.0-20.3%) ( P <.001). After adjusting for potential confounders, maternal non-Hispanic Black race (adjusted odds ratio [aOR] 1.22, 95% CI 1.16-1.29), higher education (graduate degree: aOR 1.62, 95% CI 1.47-1.79), and higher gestational age (term: aOR 2.08, 95% CI 1.95-2.23) were associated with increased aORs for fetal autopsy. Maternal age 40 years or older (aOR 0.77 95% CI 0.63-0.92) and having at least one living child (aOR 0.74, 95% CI 0.71-0.78) were associated with a decreased aOR of having a fetal autopsy. Women of American Indian or Alaska Native decent had decreased uptake of fetal autopsy compared with non-Hispanic White women (aOR 0.72, 95% CI 0.58-0.90). CONCLUSION: Fetal autopsy rates are low throughout the United States. The reasons for low autopsy rates warrant further exploration to inform strategies to increase availability and uptake.

Comprehensive serologic profile and specificity of maternal and neonatal cord blood SARS-CoV-2 antibodies.

BACKGROUND: Initial studies on COVID-19 in pregnancy have demonstrated a range of neutralizing activity, but little has been published on the full profile of SARS CoV-2 related antibodies in maternal and cordblood. OBJECTIVE: This study aimed to describe the profile and specificity of maternal and neonatal cord blood antibody profiles in response to SARS-CoV-2 virus exposure. STUDY DESIGN: This was a prospective cohort study of delivering patients at Thomas Jefferson University Hospital from April 2020 to February 2021. The primary objective was to describe unique maternal and fetal antibody epitope titers and specificity in patients with COVID-19 history. Serologic profile was assessed with a multiplex platform. Antigens used were hemagglutinin trimer influenza A (Hong Kong H3); spike trimers for SARS-CoV-2, SARS-CoV-1, Middle East respiratory syndrome coronavirus, and betacoronaviruses HKU-1 and OC43; and spike N-terminal domain, spike receptor-binding domain, and nucleocapsid protein (full length) for SARS-CoV-2. RESULTS: Here, 112 maternal samples and 101 maternal and cord blood pairs were analyzed. Of note, 37 patients had a known history of COVID-19 (positive polymerase chain reaction test) during pregnancy. Of 36 patients, 16 (44%) were diagnosed with COVID-19 within 7 days of delivery. Moreover, 15 of the remaining 76 patients (20%) without a known diagnosis had positive maternal serology. For those with a history of COVID-19, we identified robust immunoglobulin G response in maternal blood to CoV-2 nucleocapsid, spike (full length), and spike (receptor-binding domain) antigens with more modest responses to the spike (N-terminal domain) antigen. In contrast, the maternal blood immunoglobulin M response seemed more specific to spike (full length) epitopes than nucleocapsid, spike (receptor-binding domain), or spike (N-terminal domain) epitopes. There were significantly higher maternal and cord blood immunoglobulin G responses not only to CoV-2 spike (127.1-fold; standard deviation, 2.0; P<.00001) but also to CoV-1 spike (21.1-fold higher; standard deviation, 1.8; P<.00001) and Middle East respiratory syndrome spike (6.9-fold higher; standard deviation, 2.5; P<.00001). In contrast, maternal immunoglobulin M responses were more specific to CoV-2 spike (15.8-fold; standard deviation, 2.1; P<.00001) but less specific to CoV-1 (2.5-fold higher; standard deviation, 0.71; P<.00001) and no significant difference for Middle East respiratory syndrome. Maternal and cord blood immunoglobulin G antibodies were highly correlated for both spike and nucleocapsid (R2=0.96 and 0.94, respectively). CONCLUSION: Placental transfer was efficient, with robust nucleocapsid and spike responses. Both nucleocapsid and spike antibody responses should be studied for a better understanding of COVID-19 immunity. Immunoglobulin G antibodies were cross-reactive with related CoV-1 and Middle East respiratory syndrome spike epitopes, whereas immunoglobulin M antibodies, which cannot cross the placenta to provide neonatal passive immunity, were more SARS-CoV-2 specific. Neonatal cord blood may have significantly different fine specificity than maternal blood, despite the high efficiency of immunoglobulin G transfer.

Meconium-stained amniotic fluid and the risk of postcesarean surgical site infection.

OBJECTIVE: To investigate the association between meconium-stained amniotic fluid (MSAF) and postcesarean surgical site infections. METHODS: This was a secondary analysis of the Maternal-Fetal Medicine Units Network (MFMU) Cesarean Registry. Women with a singleton pregnancy attempting labor or induction of labor, who ultimately had a cesarean delivery, were included in the study. Pregnancies complicated by MSAF (n = 4262) and those who did not have MSAF (n = 13,850) were compared. The primary outcome was the incidence of SSI. RESULTS: A total of 18,112 patients were included in the study. 4262 (38%) had meconium-stained amniotic fluid. After accounting for potential confounders in a multivariable logistic regression, meconium-stained amniotic fluid was associated with an increased risk of postoperative surgical site infection (odds ratio 1.16, 95% CI 1.03-1.30). CONCLUSIONS: Meconium-stained amniotic fluid may be associated with an increased risk of postoperative surgical site infection.

The compliance with a patient-safety bundle for management of placenta accreta spectrum†.

OBJECTIVE: Our objective was to evaluate the compliance with a patient-safety bundle for placenta accreta spectrum (PAS) by comparing the implementation of the components of the patient-safety bundle in the pre- and post-protocol time periods as a quality improvement project. STUDY DESIGN: This is a before and after retrospective cohort study as a quality improvement report examining compliance with a multidisciplinary delivery approach for patients with suspected PAS between 2007 and 2018. This bundle involved a multidisciplinary approach with maternal-fetal medicine, gynecologic oncology, intervention radiology, obstetric anesthesia, neonatology, and blood bank. The primary outcome was incorporation of all six of the components of the bundle into a PAS procedure: (1) betamethasone, (2) gynecologic oncology intraoperative consult, (3) preoperative balloon catheters, (4) cell salvage technology in the operating room, (5) vertical skin incision, and (6) fundal or high transverse hysterotomy. Demographic, delivery, and patient outcome data were also collected. RESULTS: There were 39 patients included in the study, 17 were pre-protocol and 22 were post-protocol. Patients were more likely to have a PAS suspected in the antenatal period during post protocol period (23.5 versus 90.9%, p < .0001), as well as having a placenta previa (35.3 versus 81.8%, p = .003), and receive betamethasone prior to delivery (23.5 versus 86.3%, p < .0001). Patients were delivered at an earlier gestational age in post protocol period (36.8 ± 2.52 versus 33.87 ± 2.4, p = .001). The primary outcome, adherence to all components of the patient-safety bundle, was more likely to occur in the post protocol period (0 versus 40.9%, p < .0001). Maternal and postoperative outcomes were not significantly different between groups. CONCLUSIONS: We have successfully implemented a patient-safety bundle for PAS and have standardized the execution of multidisciplinary management for PAS at our institution.

Timing of Repeat Cesarean Delivery for Women with a Prior Classical Incision.

OBJECTIVE: This study aimed to compare neonatal outcomes for delivery at 36 weeks compared with 37 weeks in women with prior classical cesarean delivery (CCD). STUDY DESIGN: This was a secondary analysis of the prospective observational cohort of the Eunice Kennedy National Institute for Child and Human Development's Maternal-Fetal Medicine Unit Network Cesarean Registry. Data on cases of repeat cesarean delivery (RCD) in the setting of a prior CCD were abstracted and used for analysis. This study compared outcomes of women who delivered at 360/7 to 366/7 versus 370/7 to 376/7 weeks. The primary outcome was a composite of adverse neonatal outcomes that included neonatal intensive care unit (NICU) admission, respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), hypoglycemia, mechanical ventilation, sepsis, length of stay ≥5 days, and neonatal death. A composite of maternal outcomes that included uterine rupture, blood transfusion, general anesthesia, cesarean hysterectomy, venous thromboembolism, maternal sepsis, intensive care unit admission, and surgical complications was also evaluated. RESULTS: There were 436 patients included in the analysis. Women who delivered at 36 weeks (n = 176) were compared those who delivered at 37 weeks (n = 260). There were no differences in baseline characteristics. Delivery at 37 weeks was associated with a reduction in composite neonatal morbidity (24 vs. 34%, adjusted odds ratio [aOR] = 0.61 [0.31-0.94]), including a decrease in NICU admission rates (20 vs. 29%, aOR = 0.63 [0.40-0.99]), hospitalization ≥5 days (13 vs. 24%, aOR = 0.48 [0.29-0.8]), and RDS or TTN (9 vs. 19%, aOR = 0.43 [0.24-0.77]). There was no difference in adverse maternal outcomes (7 vs. 7%, aOR = 0.98 [0.46-2.09]). CONCLUSION: Delivery at 37 weeks for women with a history of prior CCD is associated with a decrease in adverse neonatal outcomes, compared with delivery at 36 weeks. KEY POINTS: · Classical cesarean section may have increased risk of uterine rupture in future pregnancies.. · This study compares outcomes of delivery at 370/7 to 376/7 versus 360/7 to 366/7 weeks.. · Delivery at 370/7 to 376/7 weeks was associated with decreased neonatal morbidity..

Obstetric anal sphincter injuries: strategies for prevention, diagnosis, and management.

Obstetric anal sphincter injuries (OASIS) are one of the most common causes of anal incontinence (AI) in women of reproductive age and can have a significant impact on quality of life. However, many women do not report symptoms to their physicians because of embarrassment and shame. Therefore, prevention and diagnosis of the tear is essential. Diagnostic strategies have evolved considerably in recent years, with an increase in prevalence of OASIS as a consequence. The use of 3D endoanal (3D-EAUS) and 4D transperineal ultrasound (4D-TPUS), in addition to standard clinical examination have enhanced the detection of OASIS. Once identified, adequate repair by a skilled practitioner and optimal postpartum management should be ensured in order to reduce the risk of anal incontinence. This review presents the available evidence on strategies for prevention, diagnosis, and management of OASIS.

Phrenic nerve injury secondary to extracorporeal membrane oxygenation in pregnancy: A case report.

Extracorporeal membrane oxygenation (ECMO) is used to provide acute respiratory and/or hemodynamic support to patients with severe, refractory respiratory failure. Phrenic nerve injury with subsequent hemidiaphragm paralysis should be included in the differential diagnosis of pregnant women with persistent hypoxia after ECMO cannulation.

Labor and delivery guidance for COVID-19.

This document addresses the current coronavirus disease 2019 (COVID-19) pandemic for providers and patients in labor and delivery (L&D). The goals are to provide guidance regarding methods to appropriately screen and test pregnant patients for COVID-19 prior to, and at admission to L&D reduce risk of maternal and neonatal COVID-19 disease through minimizing hospital contact and appropriate isolation; and provide specific guidance for management of L&D of the COVID-19-positive woman, as well as the critically ill COVID-19-positive woman. The first 5 sections deal with L&D issues in general, for all women, during the COVID-19 pandemic. These include Section 1: Appropriate screening, testing, and preparation of pregnant women for COVID-19 before visit and/or admission to L&D Section 2: Screening of patients coming to L&D triage; Section 3: General changes to routine L&D work flow; Section 4: Intrapartum care; Section 5: Postpartum care; Section 6 deals with special care for the COVID-19-positive or suspected pregnant woman in L&D and Section 7 deals with the COVID-19-positive/suspected woman who is critically ill. These are suggestions, which can be adapted to local needs and capabilities.

Fetal Movement Counting and Perinatal Mortality: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the association of fetal movement counting with perinatal mortality. DATA SOURCES: Electronic databases (ie, MEDLINE, ClinicalTrials.gov, ScienceDirect, the Cochrane Library at the CENTRAL Register of Controlled Trials) were searched from inception until May 2019. Search terms used were: "fetal movement," "fetal movement counting," "fetal kick counting," "stillbirth," "fetal demise," "fetal mortality," and "perinatal death." METHODS OF STUDY SELECTION: We included all randomized controlled trials comparing perinatal mortality in those women randomized to receive instructions for fetal movement counting compared with a control group of women without such instruction. TABULATION, INTEGRATION AND RESULTS: The primary outcome was perinatal mortality. Five of 1,290 identified articles were included, with 468,601 fetuses. Definitions of decreased fetal movement varied. In four of five studies, women in the intervention group were asked to contact their health care providers if they perceived decreased fetal movement; the fifth study did not provide details. Reported reduction in fetal movement usually resulted in electronic fetal monitoring and ultrasound assessment of fetal well-being. There was no difference in the incidence of perinatal outcome between groups. The incidence of perinatal death was 0.54% (1,252/229,943) in the fetal movement counting group and 0.59% (944/159,755) in the control group (relative risk [RR] 0.92, 95% CI 0.85-1.00). There were no statistical differences for other perinatal outcomes as stillbirths, neonatal deaths, birth weight less than 10th percentile, reported decreased fetal movement, 5-minute Apgar score less than 7, neonatal intensive care unit admission or perinatal morbidity. There were weak but significant increases in preterm delivery (7.6% vs 7.1%; RR 1.07, 95% CI 1.05-1.10), induction of labor (36.6% vs 31.6%; RR 1.15, 95% CI 1.09-1.22), and cesarean delivery (28.2% vs 25.3%; RR 1.11, 95% CI 1.10-1.12). CONCLUSION: Instructing pregnant women on fetal movement counting compared with no instruction is not associated with a clear improvement in pregnancy outcomes. There are weak associations with some secondary outcomes such as preterm delivery, induction of labor, and cesarean delivery. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019123264.

Is It Safe to Manage Acute Cholecystitis Nonoperatively During Pregnancy?: A Nationwide Analysis of Morbidity According to Management Strategy.

OBJECTIVES: To compare cholecystectomy (CCY) and nonoperative treatment (no-CCY) for acute cholecystitis in pregnancy. SUMMARY OF BACKGROUND DATA: Current Society of Gastrointestinal and Endoscopic Surgery guidelines recommend CCY over nonoperative management of acute cholecystitis during pregnancy, and the American College of Obstetricians and Gynecologists recommend medically necessary surgery regardless of trimester. This approach has been recently questioned. METHODS: Pregnant women admitted with acute cholecystitis were identified using the Nationwide Readmission Database 2010-2015. Propensity-score adjusted logistic regression models were used to compare CCY and no-CCY. The primary outcome was a composite measure of adverse maternal-fetal outcomes (intrauterine death/stillbirth, poor fetal growth, abortion, preterm delivery, C-section, obstetric bleeding, infection of the amniotic fluid, venous thromboembolism). RESULTS: There were 6390 pregnant women with acute cholecystitis: 38.2% underwent CCY, of which 5.1% were open. Patients were more likely to be managed operatively in their second trimester (First 43.9%, Second 59.1%, Third 34.2%; P < 0.01). Patients managed with CCY did not differ in age, insurance, income, Charlson Comorbidity Index, diabetes or obesity when compared to no-CCY (all P > 0.05), but were less likely to have a previous C-section, gestational diabetes, preeclampsia/eclampsia or be in the third trimester (P ≤ 0.01). Risk-adjusted analyses showed that no-CCY was associated with significantly increased maternal-fetal complications during the index admission [odds ratio 3.0 (95% confidence interval 2.08-4.34), P < 0.01] and 30-day readmissions [odds ratio 1.61 (confidence interval % CI 1.12-2.32), P < 0.01]. CONCLUSIONS: Contrary to current guidelines, most pregnant women admitted in the US with acute cholecystitis are managed nonoperatively. This is associated with over twice the odds of maternal-fetal complications in addition to increased readmissions.

Tenascin-X in amniotic fluid and reproductive tissues of pregnancies complicated by infection and preterm prelabor rupture of membranes†.

Preterm prelabor rupture of membranes (PPROM), which can precede or follow intra-amniotic infection/inflammation (IAI), is a poorly understood pregnancy complication. Tenascin-X (TNX) is a connective tissue extracellular matrix protein that regulates fibrillogenesis of collagens I, III, and V. Our goal was to investigate the presence and level of soluble TNX (sTNX) in amniotic fluid (AF) and TNX expression in reproductive tissues of pregnancies complicated by PPROM and IAI. We prospectively recruited 334 women pregnant with singletons who had a clinically indicated amniocentesis for genetic karyotyping, lung maturity testing, or rule-out IAI in the presence or absence of PPROM. We quantified TNX expression in fetal membranes, myometrium, cervix, and placenta using immunological methods and qRT-PCR. In pregnancies with normal outcomes, AF sTNX levels were GA-regulated with lower levels toward term. IAI significantly upregulated AF sTNX levels independent of membrane status. AF sTNX levels inversely correlated with fetal membranes tenascin XB (TNXB) mRNA level, which was significantly downregulated by IAI. Western blotting identified characteristic ∼75 and ∼140 kDa sTNX forms in both AF and fetal membranes. Fetal membranes, placenta, and cervix constitutively express TNX with the highest abundance in the amnion. Amnion TNX richness is significantly lost in the setting of IAI. Our results suggest that fetal membranes may be a source of AF sTNX whereby protein and mRNA expression seem to be significantly impacted by inflammation independent of fetal membrane status. A more thorough understanding of TNX changes may be valuable for understanding spontaneous PPROM and to potentially develop therapeutic targets.

Preterm Birth and Gestational Length in Four Race-Nativity Groups, Including Somali Americans.

OBJECTIVE: To compare preterm birth rates and gestational length in four race-nativity groups including Somali Americans. METHODS: Using a retrospective cohort study design of Ohio birth certificates, we analyzed all singleton births between 2000 and 2015 from four groups of women categorized as U.S.-born, non-Hispanic white (USBW), U.S.-born, non-Hispanic black (USBB), African-born black (ABB, primarily of West African birth country), and Somalia-born (SB). An algorithm trained on maternal names was used to confirm Somali ethnicity. Gestational length was analyzed as completed weeks or aggregated by clinically relevant periods. Risk of spontaneous and health care provider-initiated preterm birth was calculated in a competing risk model. RESULTS: Births to women in the designated groups accounted for 1,960,693 births (USBW n=1,638,219; USBB n=303,028; ABB n=10,966, and SB n=8,480). Women in the SB group had a lower preterm birth rate (5.9%) compared with women in the USBB (13.0%), ABB (8.4%), and USBW (7.9%) groups (P<.001). Women in the SB group had a higher frequency of postterm pregnancy (5.8% vs less than 1%, P<.001 for all groups). The lower rate of preterm birth in the SB group was unrelated to differences in parity or smoking or whether preterm birth was spontaneous or health care provider-initiated. The lower rate of preterm birth and tendency for prolonged gestation was attenuated in ethnic Somali women born outside Somalia. CONCLUSION: We report a positive disparity in preterm birth and a tendency for prolonged gestation for ethnic Somali women in Ohio. Etiologic studies in multiethnic cohorts aimed to uncover the sociobiological determinants of gestational length may lead to practical approaches to reduce prematurity in the general population.

Patterns of Empiric Antibiotic Administration for Presumed Early-Onset Neonatal Sepsis in Neonatal Intensive Care Units in the United States.

Objective To evaluate current patterns in empiric antibiotic use for early-onset neonatal sepsis (EONS). Study Design Retrospective population-based cohort study of newborns admitted on postnatal day 0 to 1 and discharged from NICUs participating in the Pediatric Health Information System (PHIS 2006-2013). Analyses included frequency of antibiotic initiation within 3 days of birth, duration of first course, and variation among hospitals. Results Of 158,907 newborns, 118,624 (74.7%) received antibiotics on or before postnatal day 3. Within 3 days of treatment, 49.4% (n = 58,610) were discharged home or remained hospitalized without antibiotics. There was marked interhospital variation in the proportion of infants receiving antibiotics (range: 52.3-90.9%, mean 77.9%, SD 11.0%) and in treatment days (range: 3.2-8.6, mean 5.3, SD 1.4). Facilities with higher number of newborns started on antibiotics had longer courses (r = 0.643, p < 0.001). The cost of admissions for infants born at ≥35 weeks started on antibiotics and discharged home after no more than 3 days of antibiotics was $76,692,713. Conclusion Site variation in antibiotic utilization suggests antibiotic overtreatment of infants with culture unconfirmed EONS is common and costly.