Background Although preterm birth less than 37 weeks gestation is the leading cause of neonatal morbidity and mortality in the United States, the majority of data regarding preterm neonatal outcomes come from older studies, and many reports have been limited to only very preterm neonates. Delineation of neonatal outcomes by delivery gestational age is needed to further clarify the continuum of mortality and morbidity frequencies among preterm neonates. Objective We sought to describe the contemporary frequencies of neonatal death, neonatal morbidities, and neonatal length of stay across the spectrum of preterm gestational ages. Study Design Secondary analysis of an obstetric cohort of 115,502 women and their neonates who were born in 25 hospitals nationwide, 2008–2011. All live born non-anomalous singleton preterm (23.0–36.9 weeks of gestation) neonates were included in this analysis. The frequency of neonatal death, major neonatal morbidity (intraventricular hemorrhage grade III/IV, seizures, hypoxic-ischemic encephalopathy, necrotizing enterocolitis stage II/III, bronchopulmonary dysplasia, persistent pulmonary hypertension), and minor neonatal morbidity (hypotension requiring treatment, intraventricular hemorrhage grade 1/2, necrotizing enterocolitis stage 1, respiratory distress syndrome, hyperbilirubinemia requiring treatment) were calculated by delivery gestational age; each neonate was classified once by the worst outcome they met criteria for. Results 8,334 deliveries met inclusion criteria. There were 119 neonatal deaths (1.4%). 657 (7.9%) neonates had major morbidity, 3,136 (37.6%) had minor morbidity, and 4,422 (53.1%) survived without any of the studied morbidities. Deaths declined rapidly with each advancing week of gestation. This decline in death was accompanied by an increase in major neonatal morbidity, which peaked at 54.8% at 25 weeks of gestation. As frequencies of death, and major neonatal morbidity fell, minor neonatal morbidity increased, peaking at 81.7% at 31 weeks of gestation. The frequency of all morbidities fell beyond 32 weeks. Neonatal length of hospital stay decreased significantly with each additional completed week of pregnancy; among babies delivered from 26 to 32 weeks of gestation, each additional week in utero reduced the subsequent length of neonatal hospitalization by a minimum of 8 days. The median post-menstrual age at discharge nadired at 35.7 weeks post-menstrual age for babies born at 32–33 weeks of gestation. Conclusions Our data show that there is a continuum of outcomes, with each additional week for gestation conferring survival benefit while reducing the length of initial hospitalization. These contemporary data can be useful for patient counseling regarding preterm outcomes.

OBJECTIVE To describe the prevalence of serious maternal complications following early preterm birth by gestational age (GA), delivery route and type of cesarean incision. STUDY DESIGN Trained personnel abstracted data from maternal and neonatal charts for all deliveries on randomly selected days representing 1/3 of deliveries across 25 US hospitals over 3 years (n=115,502). All women delivering non-anomalous singletons between 23 and 33 weeks’ gestation were included. Women were excluded for antepartum stillbirth and highly morbid conditions for which route of delivery would not likely impact morbidity including non-reassuring fetal status, cord prolapse, placenta previa, placenta accreta, placental abruption, and severe, unstable maternal conditions (cardiopulmonary collapse, acute respiratory distress syndrome, seizures). Serious maternal complications were defined as: hemorrhage (blood loss ≥1500 mL, blood transfusion, or hysterectomy for hemorrhage); infection (endometritis, wound dehiscence, or wound infection requiring antibiotics, reopening or unexpected procedure); ICU admission; or death. Delivery route was categorized as classical cesarean delivery (CCD), low transverse cesarean delivery (LTCD), low vertical cesarean delivery (LVCD), and vaginal delivery (VD). Association of delivery route with complications was estimated using multivariable regression models yielding adjusted relative risks (aRR) controlling for maternal age, race, body mass index, hypertension, diabetes, preterm premature rupture of membranes, preterm labor, GA, and hospital of delivery. RESULTS Of 2659 women who met criteria for inclusion in this analysis, 8.6% of women experienced serious maternal complications. Complications were associated with GA and were highest between 23–27 weeks of gestation. The frequency of complications was associated with delivery route; compared with 3.5% of SVD, 23.0% of CCD (aRR 3.54, 95%CI 2.29–5.48), 12.1% of LTCD (aRR 2.59, 95%CI 1.77–3.77), and 10.3% of LVCD (aRR 2.27, 95%CI 0.68–7.55) experienced complications. There was no significant difference in complication rates between CCD and LTCD (aRR 1.37, 95%CI 0.95–1.97) or between CCD and LVCD (aRR 1.56, 95%CI 0.48–5.07). CONCLUSION The risk of maternal complications after early preterm delivery is substantial, particularly in women who undergo cesarean delivery. Obstetricians need to be prepared to manage potential hemorrhage, infection and ICU admission for early preterm births requiring cesarean delivery.

Background Cesarean delivery in the second stage of labor is common, whereas the frequency of operative vaginal delivery has been declining. However, data comparing outcomes for attempted operative vaginal delivery in the second stage versus cesarean in the second stage are scant. Previous studies that examine operative vaginal delivery have compared it to a baseline risk of complications from a spontaneous vaginal delivery and cesarean delivery. However, when a woman has a need for intervention in the second stage, spontaneous vaginal delivery is not an option she or the provider can choose. Thus, the appropriate clinical comparison is cesarean versus operative vaginal delivery. Objective Our objective was to compare outcomes by the first attempted operative delivery (vacuum, forceps versus cesarean delivery) in patients needing second stage assistance at a fetal station of +2 or below. Study Design Secondary analysis of an observational obstetric cohort in 25 academically-affiliated U.S. hospitals over a three-year period. A subset of ≥37 weeks, non-anomalous, vertex, singletons, with no prior vaginal delivery who reached a station of +2 or below and underwent an attempt at an operative delivery were included. Indications included for operative delivery were: failure to descend, non-reassuring fetal status, labor dystocia or maternal exhaustion. The primary outcomes included a composite neonatal outcome (death, fracture, length of stay ≥3 days beyond mother’s, low Apgar, subgaleal hemorrhage, ventilator support, hypoxic encephalopathy, brachial plexus injury, facial nerve palsy) and individual maternal outcomes (postpartum hemorrhage, third and fourth degree tears [severe lacerations], and postpartum infection). Outcomes were examined by the three attempted modes of delivery. Odds ratios were calculated for primary outcomes adjusting for confounders. Final mode of delivery was quantified. Results 2531 women met inclusion criteria. Vacuum attempt was associated with the lowest frequency of the neonatal composite (4.2% vs. 6.1% vaginal forceps vs. 6.9% cesarean) and maternal complications (Postpartum infection 0.2% vs. 0.9% forceps vs. 5.3% cesarean, Postpartum hemmorhage 1.4% vs. 2.8% forceps vs. 3.8% cesarean), except for severe lacerations (19.1% vs. 33.8% forceps vs. 0% cesarean). When confounders were taken into account, both forceps (odds ratio 0.16, 95%CI 0.05-0.49) and vacuum (odds ratio 0.04, 95%CI 0.01-0.17) were associated with a significantly lower odds of Post partuminfection. The neonatal composite and Postpartum hemmorhage were not significantly different between modes of attempted delivery. Cesarean occurred in 6.4% and 4.4% of attempted vacuum and forceps groups (P=.04). Conclusion In patients needing second stage delivery assistance with a station of +2 or below, attempted operative vaginal delivery was associated with a lower frequency of Postpartum infection, but higher frequency of severe lacerations.

To compare the timing, duration, and severity of corticosteroid-associated hyperglycemia in pregnant women with and without diabetes mellitus (DM). An observational study was conducted of pregnant women with DM and controls who received corticosteroids. Median glucose levels were calculated over 4-hour intervals after the first dose of corticosteroid with a continuous glucose monitor. A glucose level increase of at least 15% above baseline was considered significant. Nine pregnant women participated in this study (six with DM and three without DM). Elevations of glucose levels occurred at hour 20, 44, and 68 in both groups and lasted for up to 4 hours. In those with DM, glucose levels increased 33 to 48%, whereas in those without DM, glucose levels rose 16 to 33%. Several, relatively short episodes of glucose elevation occur in response to corticosteroids, and are more pronounced in diabetic women.

Objective: There is currently no effective medicine or supplement for clearance of high risk- human papillomavirus (HR-HPV) infections. We have taken a systematic approach evaluating the potential use of AHCC supplementation to support clearance of HR-HPV infections. The primary objective of this research was to evaluate AHCC supplementation to modulation of the host immune system to clear HR-HPV infections from bench to bedside.Methods: Cervical cancer cells, CaSki (HPV16+), HeLa(HPV18+), SiHa(HPV16/18+), and C-33A(HPV−), were treated in vitro with AHCC 0.42 mg/mL daily x7 days then observed x7 days with daily sample collection. A confirmatory study in cervical cancer mouse models, SiHa(HPV16/18+) and C-33A(HPV−), was conducted: mice were divided into three groups per cell line then dosed with AHCC 50 mg/kg/d (N = 10), or vehicle alone (N = 10), or no supplementation (N = 10) for a total of 90 days followed by 30 days of observation. Tumors were measured 3x/week and blood samples collected bi-weekly to evaluate interferon (IFN) alpha(α), beta(β), and gamma(γ) and immunoglobulin G(IgG) by immunoassays. Tumors were evaluated for HR-HPV expression by PCR. Two pilot studies of 10 patients each were conducted in women with confirmed persistent HR-HPV+ infections. The 1st study evaluated AHCC 3g from 5 weeks up to 6 months and 2nd study evaluated AHCC 1g < 8 months. HR-HPV DNA status and the immune panel were monitored at each visit.Results: HR-HPV clearance was observed in vitro and confirmed in the animal studies as a durable response. Four of six (66.7%) patients had confirmed HR-HPV clearance after 3–6 months of AHCC 3g. Similarly, 4 of 9 (44%) patients had confirmed HR-HPV clearance after 7 months of AHCC 1g. Suppression of IFNβ <25 pg/mL was observed in those clearing the HR-HPV infection.Conclusion: Pre-clinical in vitro and in vivo studies demonstrated durable clearance of HR-HPV infections. The preliminary data from the two pilot studies suggested that AHCC supplementation supports the host immune system for successful clearance of HR-HPV infections. A confirmatory phase II randomized, double-blinded, placebo-controlled study is ongoing.