Adverse short- and long-term outcomes among infants with mild neonatal encephalopathy.

BACKGROUND: Studies in newborns with mild neonatal encephalopathy (mNE) demonstrated normal outcomes, but recent literature suggests otherwise. METHODS: This retrospective cohort study examined inborn infants between 2014 and 2017. Biochemical and clinical characteristics determined the presence of NE and an encephalopathy score categorized infants as Definite or Possible mNE. An Unexposed control group consisted of newborns not meeting the inclusion criteria. Long-term outcomes assessed included cerebral palsy, seizures, developmental disorder, and motor and speech delay. The association of mNE with seizure disorder by 3 years of age was assessed with logistic regression and developmental disorders with Cox proportional hazards models. RESULTS: Of the 156,501 births, we identified 130 with Definite mNE and 445 with Possible mNE (0.8 and 2.8 per 1000 births, respectively). Both groups had significantly higher rates of any developmental disorder and motor and speech delay when compared to the Unexposed (p < 0.05, except for p = 0.07 for motor delay in the Possible NE group). The Definite mNE group had higher rates of developmental disorder and motor and speech delay when compared to the Unexposed with hazard ratios (95% CI) 2.0 (1.2-3.2), 3.7 (1.5-8.8), and 2.1 (1.3-3.5), respectively. CONCLUSIONS: An estimate of short- and long-term consequences of mNE suggests that there may be a higher risk of adverse outcome. IMPACT: Infants with mild NE are at significant risk for adverse short- and long-term outcomes. The risk of having an abnormal long-term outcome at 3 years of age were doubled in the mild NE group compared to the Unexposed group. Randomized clinical trials are needed as neuroprotective strategies may mitigate these.

Prenatal treatment of ornithine transcarbamylase deficiency.

PURPOSE OF STUDY: Patients with neonatal urea cycle defects (UCDs) typically experience severe hyperammonemia during the first days of life, which results in serious neurological injury or death. Long-term prognosis despite optimal pharmacological and dietary therapy is still poor. The combination of intravenous sodium phenylacetate and sodium benzoate (Ammonul®) can eliminate nitrogen waste independent of the urea cycle. We report attempts to improve outcomes for males with severe ornithine transcarbamylase deficiency (OTCD), a severe X-linked condition, via prenatal intravenous administration of Ammonul and arginine to heterozygous carrier females of OTCD during labor. METHODS USED: Two heterozygote OTCD mothers carrying male fetuses with a prenatal diagnosis of OTCD received intravenous Ammonul, arginine and dextrose-containing fluids shortly before birth. Maintenance Ammonul and arginine infusions and high-caloric enteral nutrition were started immediately after birth. Ammonul metabolites were measured in umbilical cord blood and the blood of the newborn immediately after delivery. Serial ammonia and biochemical analyses were performed following delivery. SUMMARY OF RESULTS: Therapeutic concentrations of Ammonul metabolites were detected in umbilical cord and neonatal blood samples. Plasma ammonia and glutamine levels in the postnatal period were within the normal range. Peak ammonia levels in the first 24-48h were 53mcmol/l and 62mcmol/l respectively. The boys did not experience neurological sequelae secondary to hyperammonemia and received liver transplantation at ages 3months and 5months. The patients show normal development at ages 7 and 3years. CONCLUSION: Prenatal treatment of mothers who harbor severe OTCD mutations and carry affected male fetuses with intravenous Ammonul and arginine, followed by immediate institution of maintenance infusions after delivery, results in therapeutic levels of benzoate and phenylacetate in the newborn at delivery and, in conjunction with high-caloric enteral nutrition, prevents acute hyperammonemia and neurological decompensation. Following initial medical management, early liver transplantation may improve developmental outcome.

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.

Therapeutic hypothermia during neonatal transport: current practices in California.

Therapeutic hypothermia initiated at <6 hours of age reduces death and disability in newborns ≥ 36 weeks' gestation with moderate to severe hypoxic ischemic encephalopathy. Given the limited therapeutic window, cooling during transport becomes a necessity. Our goal was to describe the current practice of therapeutic hypothermia during transport used in the state of California. All level III neonatal intensive care units (NICUs) were contacted to identify those units providing therapeutic hypothermia. An electronic questionnaire was sent to obtain basic information. Responses were received from 28 (100%) NICUs performing therapeutic hypothermia; 26 NICUs were cooling newborns and two were in the process of program development. Eighteen (64%) centers had cooled a patient in transport, six had not yet cooled in transport, and two do not plan to cool in transport. All 18 centers use passive cooling, except for two that perform both passive and active cooling, and 17 of 18 centers recommend initiation of cooling at the referral hospital. Reported difficulties include overcooling, undercooling, and bradycardia. Cooling on transport is being performed by majority of NICUs providing therapeutic hypothermia. Clinical protocols and devices for cooling in transport are essential to ensure safety and efficacy.

Neonatal transport in California: findings from a qualitative investigation.

OBJECTIVE: To identify characteristics of neonatal transport in California and which factors influence team performance. STUDY DESIGN: We led focus group discussions with 19 transport teams operating in California, interviewing 158 neonatal transport team members. Transcripts were analyzed using a thematic analysis approach. RESULT: The composition of transport teams varied widely. There was strong thematic resonance to suggest that the nature of emergent neonatal transports is unpredictable and poses several significant challenges including staffing, ambulance availability, and administrative support. Teams reported dealing with this unpredictability by engaging in teamwork, gathering experience with staff at referral hospitals, planning for a wide variety of circumstances, specialized training, debriefing after events, and implementing quality improvement strategies. CONCLUSION: Our findings suggest potential opportunities for improvement in neonatal transport. Future research can explore the cost and benefits of strategies such as dedicated transport services, transfer centers, and telemedicine.