A randomized clinical trial of therapeutic hypothermia mode during transport for neonatal encephalopathy.

OBJECTIVE: To determine if temperature regulation is improved during neonatal transport using a servo-regulated cooling device when compared with standard practice. STUDY DESIGN: We performed a multicenter, randomized, nonmasked clinical trial in newborns with neonatal encephalopathy cooled during transport to 9 neonatal intensive care units in California. Newborns who met institutional criteria for therapeutic hypothermia were randomly assigned to receive cooling according to usual center practices vs device servo-regulated cooling. The primary outcome was the percentage of temperatures in target range (33°-34°C) during transport. Secondary outcomes included percentage of newborns reaching target temperature any time during transport, time to target temperature, and percentage of newborns in target range 1 hour after cooling initiation. RESULTS: One hundred newborns were enrolled: 49 to control arm and 51 to device arm. Baseline demographics did not differ with the exception of cord pH. For each subject, the percentage of temperatures in the target range was calculated. Infants cooled using the device had a higher percentage of temperatures in target range compared with control infants (median 73% [IQR 17-88] vs 0% [IQR 0-52], P < .001). More subjects reached target temperature during transport using the servo-regulated device (80% vs 49%, P <.001), and in a shorter time period (44 ± 31 minutes vs 63 ± 37 minutes, P = .04). Device-cooled infants reached target temperature by 1 hour with greater frequency than control infants (71% vs 20%, P < .001). CONCLUSIONS: Cooling using a servo-regulated device provides more predictable temperature management during neonatal transport than does usual care for outborn newborns with neonatal encephalopathy.

Microdeletion of chromosome 15q24.3-25.2 and orofacial clefting.

We report a case of de novo microdeletion of 15q24.3-q25.2 in an infant with orofacial cleft and general hypotonia and suggest that this may be a critical region in orofacial development. In addition, this case highlights the usefulness of comparative genomic microarray in the evaluation of children with congenital anomalies with such defects.

Eliminating Risk of Intubation in Very Preterm Infants with Noninvasive Cardiorespiratory Support in the Delivery Room and Neonatal Intensive Care Unit.

INTRODUCTION: Avoiding intubation and promoting noninvasive modes of ventilator support including continuous positive airway pressure (CPAP) in preterm infants minimizes lung injury and optimizes neonatal outcomes. Discharge home on oxygen is an expensive morbidity in very preterm infants (VPI) with lung disease. In 2007 a standardized bundle was introduced for VPI admitted to the neonatal care unit (NICU) which included delayed cord clamping (DCC) at birth and noninvasive ventilation as first-line cardiorespiratory support in the delivery room (DR), followed by bubble CPAP upon NICU admission. OBJECTIVE: Our goal was to evaluate the risk of (1) intubation and (2) discharge home on oxygen after adopting this standardized DR bundle in VPI born at a regional perinatal center and treated in the NICU over a ten-year period (2008-2017). MATERIALS AND METHODS: We compared maternal and neonatal demographics, respiratory care processes and outcomes, as well as neonatal mortality and morbidity in VPI (< 33 weeks gestation) and extremely low birth weight (ELBW, < 1000 g) subgroup for three consecutive epochs: 2008-2010, 2011-2013, and 2014-2017. RESULTS: Of 640 consecutive inborn VPI, 55% were < 1500 g at birth and 23% were ELBW. Constant through all three epochs, DCC occurred in 83% of VPI at birth. There was progressive increase in maternal magnesium during the three epochs and decrease in maternal antibiotics during the last epoch. Over the three epochs, VPI had less risk of DR intubation (23% versus 15% versus 5%), NICU intubation (39% versus 31% versus 18%), and invasive ventilation (37% versus 30% versus 17%), as did ELBW infants. Decrease in postnatal steroid use, antibiotic exposure, and increase in early colostrum exposure occurred over the three epochs both in VPI and in ELBW infants. There was a sustained decrease in surfactant use in the second and third epochs. There was no significant change in mortality or any morbidity in VPI; however, there was a significant decrease in pneumothorax (17% versus 0%) and increase in survival without major morbidity (15% versus 41%) in ELBW infants between 2008-2010 and 2014-2017. Benchmarked risk-adjusted rate for oxygen at discharge in a subgroup of inborn VPI (401-1500 g or 22-31 weeks of gestation) is 2.5% (2013-2017) in our NICU compared with > 8% in all California NICUs and > 10% in all California regional NICUs (2014-2016). CONCLUSION: Noninvasive strategies in DR and NICU minimize risk of intubation in VPI without adversely affecting other neonatal or respiratory outcomes. Risk-adjusted rates for discharge home on oxygen remained significantly lower for inborn VPI compared with rates at regional NICUs in California. Reducing intubation risk in ELBW infants may confer an advantage for survival without major morbidity. Prenatal magnesium may reduce intubation risk in ELBW infants.

Duration of Cord Clamping and Neonatal Outcomes in Very Preterm Infants.

BACKGROUND: Delayed cord clamping (DCC, ≥30 s) increases blood volume in newborns and is associated with fewer blood transfusions and short-term neonatal complications. The optimal timing of cord clamping for very preterm infants should maximize placental transfusion without interfering with stabilization and resuscitation. AIM: We compared the effect of different durations of DCC, 30-45 s vs. 60-75 s, on delivery room (DR) and neonatal outcomes in preterm infants <32 weeks gestational age (GA). METHODS: This is a single-center prospective observational study. Data were collected prospectively from eligible infants from two groups: 30-45 s DCC group (January 2008 to February 2011, n = 187) and 60-75 s DCC group (March 2011 to April 2014, n = 166). RESULTS: The 60-75 s DCC group compared to the 30-45 s DCC group had higher hematocrits at <2 hours (49.2% vs. 47.4%, p = 0.02). In infants <28 weeks GA, the 12-36 hours hematocrit was higher in the 60-75 s DCC group compared to the 30-45 s DCC group (47.9% vs. 42.1%, p = 0.002). The 60-75 s DCC group had reductions in DR intubation (11% vs. 22%, p = 0.004), hypothermia on admission (1% vs. 5%, p = 0.01), surfactant therapy (13% vs. 28%, p = 0.001), intubation in the first 24 hours (20% vs. 34%, p = 0.004), any intubation (27% vs. 40%, p = 0.007), and any red blood cell transfusion (20% vs. 33%, p = 0.008) during the hospitalization compared to the 30-45 s DCC group. These reductions remained significant after adjusting for GA, gender and >48 hours of antenatal steroid exposure. There was no difference between the two groups in neonatal death, intraventricular hemorrhage, chronic lung disease, late onset sepsis, necrotizing enterocolitis and severe retinopathy of prematurity. CONCLUSION: In this study cohort increasing DCC duration from 30-45 s to 60-75 s is associated with decreased hypothermia on admission, neonatal respiratory interventions and red blood cell transfusions without increase in neonatal mortality and morbidities.

Elimination of admission hypothermia in preterm very low-birth-weight infants by standardization of delivery room management.

CONTEXT: Temperature instability is a serious but potentially preventable morbidity in preterm infants. Admission temperatures below 36°C are associated with increased mortality and late onset sepsis. OBJECTIVE: The goal of our quality-improvement effort was to increase preterm infants' admission temperatures to above 36°C by preventing heat loss in the immediate postnatal period. DESIGN: This quality-improvement initiative used the rapid-cycle Plan-Do-Study-Act approach. Preterm infants born at less than 33 weeks' gestation with very low birth weight less than 1500 g who were born at a Regional Level III Neonatal Intensive Care Unit (NICU) in San Jose, CA, were enrolled. Our intervention involved standardizing the management of thermoregulation from predelivery through admission to the NICU. Data on admission temperature were collected prospectively. MAIN OUTCOME MEASURES: The primary outcome measure was hypothermia, defined as temperature below 36°C on admission to the NICU. RESULTS: The hypothermia rate was reduced from 44% in early 2006 to 0% by 2009. There was a slight increase to 6% in 2010. Subsequently, with further real-time feedback, we were able to sustain 0% hypothermia through 2011. Our hypothermia rate remained substantially lower than state and national hypothermia benchmarks that have shown moderate improvement over the same period. CONCLUSION: We reduced hypothermia in very low-birth-weight infants using a standardized protocol, multidisciplinary team approach, and continuous feedback. Sustaining improvement is a challenge that requires real-time progress evaluation of outcomes and ongoing staff education.

The effectiveness of oral tin mesoporphyrin prophylaxis in reducing bilirubin production after an oral heme load in a transgenic mouse model.

BACKGROUND: Neonatal jaundice is commonly encountered and rarely associated with morbidity and mortality. Nonetheless, infants with glucose-6-phosphate dehydrogenase deficiency often have hemolysis (a heme load) caused by an environmental oxidant trigger, thus increasing their risk for serious morbidity. The use of tin mesoporphyrin (SnMP) has been proposed for interdicting the development of severe hyperbilirubinemia in a variety of conditions. OBJECTIVES: We studied the in vivo effects of prophylactic oral SnMP on heme oxygenase (HO) activity and bilirubin production, as indexed by the excretion rate of carbon monoxide (VeCO), following a subsequent oral heme load. METHODS: Adult mice were exposed serially to heme and assessed for in vivo bilirubin production rates, HO-1 transcription and protein, and HO activity. The effect of prophylaxis with a single oral dose of SnMP prior to an oral heme load was assessed by measuring VeCOand tissue HO activities. RESULTS: After serial heme exposures, VeCO, HO-1 transcription and protein, and liver and spleen HO activities increased incrementally. After pretreatment with oral SnMP, bilirubin production decreased in response to an oral heme load. Also, heme-mediated increases in liver, spleen, and intestine HO activities were significantly dampened. CONCLUSIONS: A single oral dose of SnMP results in durable inhibition of bilirubin production and HO activity for at least 24 h in a mouse model of oral heme loading. Further studies are needed to fully elucidate the duration of this protection against hyperbilirubinemia due to a delayed heme load and any long-term consequences of prophylaxis with SnMP on HO-1 transcription and HO-1 protein.