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.

Maternal depressive symptoms during pregnancy are associated with risk for offspring emotional and behavioral problems, but the mechanisms by which this association occurs are not known. Infant elevated negative affect (increased crying, irritability, fearfulness, etc.) is a key risk factor for future psychopathology, so understanding its determinants has prevention and early intervention potential. An understudied yet promising hypothesis is that maternal mood affects infant mood via maternal prenatal inflammatory mechanisms, but this has not been prospectively examined in humans. Using data from a pilot study of women followed from the second trimester of pregnancy through six months postpartum (N = 68) our goal was to initiate a prospective study as to whether maternal inflammatory cytokines mediate the association between maternal depressive symptoms and infant offspring negative affect. The study sample was designed to examine a broad range of likely self-regulation and mood-regulation problems in offspring; to that end we over-selected women with a family history or their own history of elevated symptoms of attention-deficit/hyperactivity disorder. Results supported the hypothesis: maternal pro-inflammatory cytokines during the third trimester (indexed using a latent variable that included plasma interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1 concentrations as indicators) mediated the effect, such that higher maternal depressive symptoms were associated with higher maternal inflammation, and this mediated the effect on maternal report of infant negative affect (controlling for maternal affect during the infant period). This is the first human study to demonstrate that maternal inflammatory cytokines mediate the association between prenatal depression and infant outcomes, and the first to demonstrate a biological mechanism through which depressive symptoms impact infant temperament.

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.

OBJECTIVE: To evaluate whether C5b-9 concentrations in blood and urine are increased in preeclampsia with severe features. METHODS: The Complement and Preeclampsia in the Americas study is a prospective, multicenter case–control study performed at six centers in Colombia from November 2015 to July 2016. The case group included women with preeclampsia with severe features, and the control group included women who were healthy or had chronic hypertension, gestational hypertension, or preeclampsia without severe features. We enrolled two women in the control group for every woman in the case group. Soluble C5b-9 concentrations were measured by enzyme-linked immunosorbent assays in blood and urine. The primary outcome was C5b-9 concentrations in women in the case group compared with all women in the control group, and the secondary outcome was C5b-9 levels in women in the case group compared with individual control subgroups. Differences were assessed by test of medians, and associations were further evaluated by receiver operating characteristic curve analysis and logistic regression with α=0.05. RESULTS: Three hundred fifty-two patients were enrolled. Plasma C5b-9 concentrations did not differ significantly between women in the case group and those in the control group, but urine C5b-9 concentrations were higher in women in the case group (median [interquartile range] 9.9 [1.6–43.7] vs 1.8 [0.54–4.1] ng/mL, P<.001). In subgroup analysis, plasma C5b-9 concentrations were increased in women in the case group compared with healthy women in the control group (median [interquartile range] 2,778 [1,633–4,230] vs 1,374 [1,064–2,332] ng/mL, P<.001), and urine C5b-9 concentrations were increased in women in the case group compared with all control subgroups (P<.001). Using receiver operating characteristic analysis, urine C5b-9 concentrations differentiated preeclampsia with severe features from hypertensive women in the control group (area under the receiver operating characteristic curve 0.74, 95% CI 0.68–0.80). Urine C5b-9 22 ng/mL or greater (range 0–158.4 ng/mL) was the optimal cut point for diagnosis of preeclampsia with severe features with adjusted odds ratio of 10.0 (95% CI 3.5–28.8, P<.001). CONCLUSION: Urinary excretion of terminal complement effector C5b-9 is higher in women with preeclampsia with severe features compared with women with other hypertensive disorders of pregnancy and women without hypertension.

Hemolysis predisposes to adverse pregnancy outcomes. Yet, there are limited data on hemolysis in hypertensive disorders of pregnancy other than hemolysis, elevated liver enzymes, and low platelet count syndrome. To evaluate the prevalence and impact of hemolysis in hypertensive disorders of pregnancy, we performed a retrospective cohort study at a single center (October 2013-May 2017), among women screened for hemolysis using lactate dehydrogenase (LDH) levels. We compared LDH levels by hypertensive disorder (chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia with severe features) and evaluated impact on adverse pregnancy outcomes. Data were analyzed by χ or test, ANOVA, test of medians, and logistic regression. Among 8645 deliveries, 1188 (13.7%) had a hypertensive disorder. Of these, 812 (68.4%) had LDH measurement before delivery: chronic hypertension (n=152); gestational hypertension (n=209); preeclampsia (n=216); and preeclampsia with severe features (n=235). LDH ≥400 U/L (≥1.6× normal) was more common in preeclampsia with severe features compared with other hypertensive disorders of pregnancy (9.8% versus 2.3%;<0.001); adjusted odds ratio 4.52 (95% confidence interval, 2.2-9.2; <0.001). LDH ≥400 U/L was associated with adverse maternal outcomes (41.7% versus 15.3%; <0.001), adjusted odds ratio 3.05 (95% confidence interval, 1.4-6.7; =0.006), and adverse neonatal outcomes (eg, preterm birth 59.4% versus 22.5%;<0.001). We find that elevated LDH levels are associated with adverse maternal and neonatal outcomes in hypertension and preeclampsia, independent of hemolysis, elevated liver enzymes, and low platelet count syndrome. Therefore, elevated LDH levels (≥1.6× normal or ≥400 U/L) may be considered a severe feature of preeclampsia.

OBJECTIVE We sought to evaluate the frequency of, and factors associated with, the use of 3 evidence-based interventions: antenatal corticosteroids for fetal lung maturity, progesterone for prevention of recurrent preterm birth, and magnesium sulfate for fetal neuroprotection. STUDY DESIGN A self-administered survey was conducted from January through May 2011 among obstetricians from 21 hospitals that included 30 questions regarding their knowledge, attitudes, and practice of the 3 evidence-based interventions and the 14-item short version of the Team Climate for Innovation survey. Frequency of use of each intervention was ascertained from an obstetrical cohort of women between January 2010 and February 2011. RESULTS A total of 329 obstetricians (74% response rate) who managed 16,946 deliveries within the obstetrical cohort participated in the survey. More than 90% of obstetricians reported that they incorporated each intervention into routine practice. Actual frequency of administration in women eligible for the treatments was 93% for corticosteroids, 39% for progesterone, and 71%formagnesiumsulfate. Provider satisfaction with quality of treatment evidence was 97% for corticosteroids, 82% for progesterone, and 57% for magnesium sulfate. Obstetricians perceived that barriers to treatment were most frequent for progesterone (76%), 30% for magnesium sulfate, and 17% for corticosteroids. Progesterone use was more frequent among patients whose provider reported the quality of the evidence was above average to excellent compared with poor to average (42% vs 25%, respectively; P < .001), and they were satisfied with their knowledge of the intervention (41%vs 28%; P = .02), and was less common among patients whose provider reported barriers to hospital or pharmacy drug delivery (31% vs 42%; P = .01). Corticosteroid administration was more common among patients who delivered at hospitals with 24 hours a day–7 days a week maternal-fetal medicine specialist coverage (93% vs 84%; P = .046), CONCLUSION Obstetricians in Maternal-Fetal Medicine Units Network hospitals frequently use these evidence-based interventions; however, progesterone usewas found to be related to their assessment of evidence quality. Neither progesterone nor the other interventions were associated with overall climate of innovation within a hospital as measured by the Team Climate for Innovation. National Institutes of Health Consensus Conference Statements may also have an impact on use; there is such a statement for antenatal corticosteroids but not for progesterone for preterm prevention or magnesium sulfate for fetal neuroprotection.

Contact with the urticating setae from the abdomen of adult females of the neo-tropical moth Hylesia metabus gives rise to an urticating dermatitis, characterized by intense pruritus, generalized malaise and occasionally ocular lesions (lepidopterism). The setae contain a pro-inflammatory glycosylated protease homologous to other S1A serine proteases of insects. Deglycosylation with PNGase F in the presence of a buffer prepared with 40% H2 (18)O allowed the assignment of an N-glycosylation site. Five main paucimannosidic N-glycans were identified, three of which were exclusively α(1-6)-fucosylated at the proximal GlcNAc. A considerable portion of these N-glycans are anionic species sulfated on either the 4- or the 6-position of the α(1-6)-mannose residue of the core. The application of chemically and enzymatically modified variants of the toxin in an animal model in guinea pigs showed that the pro-inflammatory and immunological reactions, e.g. disseminated fibrin deposition and activation of neutrophils, are due to the presence of sulfate-linked groups and not on disulfide bonds, as demonstrated by the reduction and S-alkylation of the toxin. On the other hand, the hemorrhagic vascular lesions observed are attributed to the proteolytic activity of the toxin. Thus, N-glycan sulfation may constitute a defense mechanism against predators.