Emily A. Oliver

Development and Validation of an Algorithm to Determine Spontaneous versus Provider-Initiated Preterm Birth in US Vital Records.

BACKGROUND Determining whether initiation of preterm birth was spontaneous, or through labour induction or caesarean without labour or membrane rupture is critical in surveillance and aetiological research on preterm birth, although this information is not explicitly included on the US Birth Certificate. Algorithms combining several fields from birth certificates have been developed to infer the initiating event, but none has been validated against manual review of original obstetric records. Our objective was to develop a birth certificate-based algorithm to determine initiation of preterm birth and validate it by manual review of original records. METHODS We developed an algorithm from the 2003 US Standard Birth Certificate to determine spontaneous vs. indicated preterm birth. The algorithm was first tested on obstetrical records from 80 preterm (<37 weeks) births in Columbus OH (2006-12) abstracted by an obstetrics research nurse and reviewed by an obstetrician-gynecologist. Onset of delivery was spontaneous if the initiating event was premature rupture of membranes (PROM) or contractions, or indicated if the initiating event was induction or caesarean without labour or PROM. The algorithm was validated in an independent sample of 100 preterm births from four hospitals. RESULTS Codes for tocolysis, fetal intolerance of labour, and anaesthesia during labour did not predict labour and were dropped. The final algorithm correctly classified 73/80 cases, kappa = 0.83. In the validation, 86/100 cases were correctly classified. The kappa statistic was 0.68 (0.52, 0.83); predictive values for spontaneous and indicated onset were 85% (75%, 92%) and 89% (71%, 98%). CONCLUSIONS The algorithm distinguished spontaneous from indicated preterm birth, using birth certificates, with good accuracy.

High Mobility Group-Box 1 (HMGB1) levels are increased in amniotic fluid of women with intra-amniotic inflammation-determined preterm birth, and the source may be the damaged fetal membranes

BACKGROUND High Mobility Group Box-1 (HMGB1) is considered a prototype alarmin molecule. Upon its extracellular release, HMGB1 engages pattern recognition receptors and the Receptor for Advanced Glycation End-products (RAGE) followed by an outpouring of inflammatory cytokines, including interleukin (IL)-6. METHODS We assayed the amniotic fluid (AF) levels of HMGB1 and IL-6 in 255 women that either had a normal pregnancy outcome or delivered preterm. Immunohistochemistry on fetal membranes was used for cellular localization and validation of immunoassay findings. HMGB1 also was analyzed in amniochorion tissue explants subjected to endotoxin. RESULTS AF HMGB1 levels are not gestational age regulated but are increased in women with intra-amniotic inflammation and preterm birth. The likely source is the damaged amniochorion, as demonstrated by immunohistochemistry and explant experiments. CONCLUSIONS Our research supports a role for HMGB1 in the inflammatory response leading to preterm birth. As a delayed phase cytokine, in utero exposure to elevated AF HMGB1 levels may have an impact on the newborn beyond the time of birth.

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

Tenascin-x in Amniotic Fluid and Reproductive Tissues of Pregnancies Complicated by Infection and Preterm Prelabor Rupture of Membranes†

76,692,713. Conclusion Site variation in antibiotic utilization suggests antibiotic overtreatment of infants with culture unconfirmed EONS is common and costly.

Strengthening Health Systems of Developing Countries: Inclusion of Surgery in Universal Health Coverage

Abstract 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.