Michael A. Posencheg

Adverse neonatal outcomes: examining the risks between preterm, late preterm, and term infants

OBJECTIVE There is a relative paucity of data regarding neonatal outcomes in the late preterm cohort (34 to 36 6/7 weeks). This study sought to assess differences in adverse outcomes between infants delivering 32 to 33 6/7, 34 to 36 6/7 weeks, and 37 weeks or later. STUDY DESIGN Data were collected as part of a retrospective cohort study of preterm labor patients (2002-2005). Patients delivering 32 weeks or later were included (n = 264). The incidence of adverse outcomes was assessed. Significant associations between outcomes and gestational age at delivery were determined using chi(2) analyses and Poisson regression modeled cumulative incidence and controlled for confounders. RESULTS Late preterm infants have increased risk of adverse outcomes, compared with term infants. Controlling for confounders, there was a 23% decrease in adverse outcomes with each week of advancing gestational age between 32 and 39 completed weeks (relative risk 0.77, P < .001, 95% confidence interval, 0.71-0.84). CONCLUSION Further investigation regarding obstetrical management and long-term outcomes for this cohort is warranted.

Improving Delivery Room Management for Very Preterm Infants

BACKGROUND AND OBJECTIVES: Events in the delivery room significantly impact the outcomes of preterm infants. We developed evidence-based guidelines to prevent heat loss, reduce exposure to supplemental oxygen, and increase use of noninvasive respiratory support to improve the care and outcomes of infants with birth weight ≤1250 g at our institution. METHODS: The guidelines were implemented through multidisciplinary conferences, routine use of a checklist, appointment of a dedicated resuscitation nurse, and frequent feedback to clinicians. This cohort study compares a historical group (n = 80) to a prospective group (n = 80, after guidelines were implemented). Primary outcome was axillary temperature at admission to the intensive care nursery. Secondary outcomes measured adherence to the guidelines and changes in clinically relevant patient outcomes. RESULTS: Baseline characteristics of the groups were similar. After introduction of the guidelines, average admission temperatures increased (36.4°C vs 36.7°C, P < .001) and the proportion of infants admitted with moderate/severe hypothermia fell (14% vs 1%, P = .003). Infants were exposed to less oxygen during the first 10 minutes (P < .001), with similar oxygen saturations. Although more patients were tried on continuous positive airway pressure (40% vs 61%, P = .007), the intubation rate was not significantly different (64% vs 54%, P = .20). Median durations of invasive ventilation and hospitalization decreased after the quality initiative (5 vs 1 days [P = .008] and 80 vs 60 days [P = .02], respectively). CONCLUSIONS: We have demonstrated significantly improved quality of delivery room care for very preterm infants after introduction of evidence-based delivery room guidelines. Multidisciplinary involvement and continuous education and reinforcement of the guidelines permitted sustained change.

Proficiency and Retention of Neonatal Resuscitation Skills by Pediatric Residents

BACKGROUND: The basic knowledge and skill base to resuscitate a newborn infant is taught in the Neonatal Resuscitation Program (NRP). We hypothesize that caregivers will perform below current acceptable standards before the recertification period of two years. METHODS: This is a prospective descriptive study evaluating performance of pediatric residents’ NRP knowledge and skills over time. NRP scores are used as baseline data. Follow‐up is performed before the residents first NICU rotation. Differences in the mean scores are analyzed for degree of retention. Subset score analysis is also performed. RESULTS: Eighty-eight subjects completed both evaluations. Knowledge scores maintained close to passing throughout the academic year. Subset evaluation revealed significant deficits within the intubation lesson. Alarming deficits were seen in skills evaluation starting at initial NRP certification with 39.1% residents having failing scores. Mean scores were below passing for every group on follow-up testing. Subgroup analysis of skills revealed deficits in the initial phases of resuscitation (lessons 1–3). CONCLUSIONS: Deterioration of skills is seen shortly after training. It appears that knowledge is generally better retained. Discrepancies between areas of knowledge and skill deterioration indicate that proficiency in one does not necessarily indicate proficiency of the other.

Plasma Biomarkers of Oxidative Stress: Relationship to Lung Disease and Inhaled Nitric Oxide Therapy in Premature Infants

OBJECTIVES. Inhaled nitric oxide treatment for ventilated premature infants improves survival without bronchopulmonary dysplasia. However, there has been no information regarding possible effects of this therapy on oxidative stress. We hypothesized that inhaled nitric oxide therapy would not influence concentrations of plasma biomarkers of oxidative stress. PATIENTS AND METHODS. As part of the Nitric Oxide Chronic Lung Disease Trial, we collected blood samples at specified intervals from a subpopulation of 100 infants of <1250 g birth weight who received inhaled nitric oxide (20 ppm, weaned to 2 ppm) or placebo gas for 24 days. Plasma was assayed for total protein and for 3-nitrotyrosine and carbonylation by using immunoassays. RESULTS. The demographic characteristics and primary outcome for the infants were representative of the entire group of infants who were in the Nitric Oxide Chronic Lung Disease Trial. For all infants at baseline, before receiving study gas, the concentration of total protein was inversely correlated with the respiratory severity score, and plasma carbonyl was positively correlated with severity score, supporting an association between oxidative stress and severity of lung disease. Infants who survived without bronchopulmonary dysplasia had 30% lower protein carbonylation concentrations at study entry than those who had an adverse outcome. At each of 3 time points (1–10 days) during exposure to study gas, there were no significant differences between control and treated infants for concentrations of plasma protein, 3-nitrotyrosine, and carbonylation. CONCLUSIONS. Inhaled nitric oxide treatment for premature infants who are at risk for bronchopulmonary dysplasia does not alter plasma biomarkers of oxidative stress, which supports the safety of this therapy.

Postdischarge Feeding Patterns in Early- and Late-Preterm Infants

Objective. To compare the incidence of postdischarge feeding dysfunction and hospital/subspecialty visits for feeding problems during the first year of life in late (34 to 36 6 7 weeks) and early-preterm (25 to 33 6 7 weeks) infants. Methods. In this prospective study, the authors sent questionnaires to parents of early (n = 319) and late (n = 571) preterm infants at 3, 6, and 12 months corrected age. Parents’ perceptions of infants’ feeding skills, comfort with feeding, and hospital/subspecialty visits for feeding difficulties were obtained. Results were analyzed with χ2 tests and Spearman’s correlations. Results. Early preterms had more oromotor dysfunction at 3 (29% vs 17%) and 12 months (7% vs 4%) and more avoidant feeding behavior at 3 months (33% vs 29%). In both groups, oromotor dysfunction and avoidant feeding behavior improved over time. Frequency of poor appetite and hospitalization/subspecialty visits were similar. Conclusion. Pediatricians should screen all preterm infants for feeding dysfunction during the first year.

Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites

Objective:Inhaled nitric oxide (iNO) is a potential new therapy for prevention of bronchopulmonary dysplasia and brain injury in premature infants. This study examined dose-related effects of iNO on NO metabolites as evidence of NO delivery.Study Design:A subset of 102 premature infants in the NO CLD trial, receiving 24 days of iNO (20 p.p.m. decreasing to 2 p.p.m.) or placebo, were analyzed. Tracheal aspirate (TA) and plasma samples collected at enrollment and at intervals during study gas were analyzed for NO metabolites.Result:iNO treatment increased NO metabolites in TA at 20 and 10 p.p.m. (1.7- to 2.3-fold vs control) and in plasma at 20, 10, and 5 p.p.m. (1.6- to 2.3-fold). In post hoc analysis, treated infants with lower metabolite levels at entry had an improved clinical outcome.Conclusion:iNO causes dose-related increases in NO metabolites in the circulation as well as lung fluid, as evidenced by TA analysis, showing NO delivery to these compartments.

Detection of Echovirus 18 in Human Breast Milk

ABSTRACT We detected enteroviral RNA and cultured infectious virus from a series of banked breast milk samples from the mother of an infant with neonatal sepsis; sequencing of the enterovirus isolate identified it as echovirus type 18. In this case, it is possible that enterovirus transmission occurred through the breast milk.

Placental Transfusion at Birth: Do We Have All of the Answers?

Many questions remain about both delayed cord clamping (DCC) andumbilical cordmilking (UCM). Al-Wassia andShah1 report the firstmeta-analysisofUCMin infants.Wereviewcurrent recommendations and concerns impeding their translation into widespread practice. We next review new meta-analyses in the literature that address someof the remaining knowledge gaps for placental transfusion, including the aforementionedUCMmeta-analysis. Finally,wehighlight some remaining reasons clinicians should proceed cautiously in adopting these practices. In December 2012, the American College of Obstetricians and Gynecologists (ACOG) in association with the American Academy of Pediatrics released a statement titled “Timing of Umbilical Cord Clamping After Birth.”2 This statement concludes for preterm infants, “Evidence exists to support delayed umbilical cord clamping in preterm infants, when feasible. The single most important clinical benefit for preterm infants is the possibility for a nearly 50% reduction in intraventricular hemorrhage.”2 For term infants, they state, “currently, evidence is insufficient to confirmor refute the potential for benefits fromdelayedumbilical cord clamping in term infants, especially in settings with rich resources.”2 However, for both subgroups of infants theremay not yet beuniversalagreement.Forexample, in terminfants, theWorld HealthOrganization recommends the routinedelayofumbilical cord clamping by 1 to 3minutes after delivery of the baby. It also states that this is a particularly relevant intervention in underresourced settings where access to good nutrition and iron is limited during childhood.3 Furthermore, for preterm infants, despite this unequivocally optimistic statement, there appears to be reluctance to adopt thispractice.4,5Most recently, Jelinetal6 surveyedmembers ofACOGand theCollaborativeAmbulatoryResearchNetwork. Eighty-eightpercentof respondents indicated that their hospital did not have an umbilical cord clamping policy and 76% indicated that concern for delayed neonatal resuscitationwas a reason for immediate cord clamping. Although this survey was conducted prior to the 2012 ACOG statement, the underlyingevidencebase for this statementwasavailableprior to the administration of this survey. Anecdotally, neonatologists share the same concern for delayed resuscitation in the most preterm infants.7,8 Two approaches are reported in the literature to prevent delayed resuscitation. The first is the use of a mobile trolley to initiate resuscitation at themother’s bedside. Thomas et al9 presented pilot data on 78 babies with a median gestational age of 34weeks (range, 24-41weeks) resuscitated on amobile trolley. Although there were no adverse events and 77 of the 78 infants had a postresuscitation temperature higher than 36°C, on 18occasions theumbilical cordwas too short to reach the trolley. The randomized Cord Pilot Trial is evaluating this innovative tool and will provide further important data to consider.10Thesecondapproach isUCM,espoused in themodern era by Hosono et al.11 Umbilical cord milking is the act of cutting a long segment of the umbilical cord and stripping it toward the infant to provide placental transfusion more rapidly thanwithDCC. The hope is that UCMwill provide similar benefit while minimizing delay in resuscitation. Indeed, the effect of UCMas comparedwithDCCwas one of thegaps inknowledgehighlightedbyACOGinthe2012statement. The other 2 acknowledged gaps were (1) the ideal duration forumbilical cordclampingespeciallywith regard to cesarean vs vaginal delivery and (2) the need for additional evidence for infants born before 28 weeks’ gestation. While there is not yet additional information to address the questionof durationofDCC, additionalmeta-analyses have examined UCM or DCC strategies in our smallest patients. In considering the ACOG recommendations, the current meta-analysis by Al-Wassia and Shah is important. This is the first systematic review of evidence for UCM in both term and preterm infants. The analysis includes 7 randomized clinical trials, involving 501 infants, evaluating the impact ofUCM.Of these, 5 trials compared UCMwith immediate cord clamping and 2 compared UCMwith DCC.When analyzing the data for preterm infants (<33 weeks’ gestation) only, 5 studies of 277 infantswere included.Theauthors foundareducedriskofoxygen requirement at 36 weeks (risk ratio, 0.42 [95% CI, 0.210.83]) and intraventricular hemorrhage (IVH) overall (risk ratio, 0.62 [95%CI,0.41-0.93]).However, therewasnodifference in severe IVH (grades 3 and 4) or death prior to discharge. Although the initial hemoglobin level was greater in the UCM group (meandifference [MD], 2.0 [95%CI, 1.3-2.7] g/dL [to convert to gramsper liter,multiply by 10.0]), thenumber of blood transfusionswasnot reduced.Most importantly, neurodevelopmental outcomes were not reported. Of these trials, 2 provideddatapooled for 224 infantswith a gestational age of at least 33 weeks. In this subgroup, UCM resulted in higher hemoglobin values at 48 hours after birth (MD, 1.2 [95% CI, 0.8-1.5] g/dL; I2 = 34%). This was without greater peak bilirubin levels or need for phototherapy. In addition, a single study (n = 170) reported higher levels of hemoglobin (MD, 1.1 [95% CI, 0.7-1.5] g/dL) and ferritin (MD, 79 Related article page 18 Opinion

Adverse neonatal outcomes

OBJECTIVE There is a relative paucity of data regarding neonatal outcomes in the late preterm cohort (34 to 36 6/7 weeks). This study sought to assess differences in adverse outcomes between infants delivering 32 to 33 6/7, 34 to 36 6/7 weeks, and 37 weeks or later. STUDY DESIGN Data were collected as part of a retrospective cohort study of preterm labor patients (2002-2005). Patients delivering 32 weeks or later were included (n = 264). The incidence of adverse outcomes was assessed. Significant associations between outcomes and gestational age at delivery were determined using chi(2) analyses and Poisson regression modeled cumulative incidence and controlled for confounders. RESULTS Late preterm infants have increased risk of adverse outcomes, compared with term infants. Controlling for confounders, there was a 23% decrease in adverse outcomes with each week of advancing gestational age between 32 and 39 completed weeks (relative risk 0.77, P < .001, 95% confidence interval, 0.71-0.84). CONCLUSION Further investigation regarding obstetrical management and long-term outcomes for this cohort is warranted.

Incidence and characteristics of positive pressure ventilation delivered to newborns in a US tertiary academic hospital

INTRODUCTION The Neonatal Resuscitation Program (NRP) guidelines recommend positive pressure ventilation (PPV) in the first 60s of life to support perinatal transition in non-breathing newborns. Our aim was to describe the incidence and characteristics of newborn PPV using real-time observation in the delivery unit. METHODS Prospective, observational, quality improvement study conducted at a tertiary academic hospital. Deliveries during randomized weekday/evening 8-h shifts were attended by a trained observer. Intervention data were recorded for all newborns with gestational age (GA) ≥34wks that received PPV. Descriptive summaries and Kruskal-Wallis test for continuous variables and Fishers exact test for categorical variables were used to compare characteristics. RESULTS Of 1135 live deliveries directly observed over 18mos, 64 (6%) newborns with a mean GA 39±2wks received PPV: Median time from birth to warmer was 20s (IQR 15-22s); PPV was initiated within 60s of life in 29 (45%) and between 60 and 90s of life in 17 (27%). PPV duration was <120s in 38 (60%). Seven/21 (33%) newborns that received PPV after vaginal delivery were not pre-identified and resuscitation team was alerted after delivery. We found no association between PPV start time and duration of PPV (p=0.86). CONCLUSION We observed that most (94%) term newborns spontaneously initiate respirations. In over half observed deliveries receiving PPV, time to initiation of PPV was greater than 60s (longer than recommended). Compliance with current NRP guidelines is difficult, and its not clear whether it is the recommendations or the training to achieve PPV recommendations that should be modified.