Pablo J. Sánchez

Detection of Congenital Cytomegalovirus Infection by Real-Time Polymerase Chain Reaction Analysis of Saliva or Urine Specimens

Viral culture of urine or saliva has been the gold standard technique for the diagnosis of congenital cytomegalovirus (CMV) infection. Results of rapid culture and polymerase chain reaction (PCR) analysis of urine and saliva specimens from 80 children were compared to determine the clinical utility of a real-time PCR assay for diagnosis of congenital CMV infection. Results of urine PCR were positive in 98.8% of specimens. Three PCR-positive urine samples were culture negative. Results of saliva PCR and culture were concordant in 78 specimens (97.5%). Two PCR-positive saliva samples were culture negative. These findings demonstrate that PCR performs as well as rapid culture of urine or saliva specimens for diagnosing congenital CMV infection and saliva specimens are easier to collect. Because PCR also offers more rapid turnaround, is unlikely to be affected by storage and transport conditions, has lower cost, and may be adapted to high-throughput situations, it is well suited for targeted testing and large-scale screening for CMV.

Predictive Value of Neonatal MRI Showing No or Minor Degrees of Brain Injury After Hypothermia

BACKGROUNDnMagnetic resonance imaging is a surrogate biomarker for major neurodevelopmental disabilities in survivors of perinatal hypoxic-ischemic encephalopathy because injury to the basal ganglia/thalami is highly predictive of major neuromotor and cognitive problems. Major disabilities and the appearance of neonatal magnetic resonance imaging are improved with therapeutic hypothermia. We evaluated neurodevelopmental outcomes when conventional magnetic resonance imaging showed minimal or no brain injury.nnnMETHODSnInstitutional review board-approved series of 62 infants (≥36 weeks; ≥1800 g; 34 boys/28 girls) cooled for hypoxic-ischemic encephalopathy between 2005 and 2011 who underwent neonatal magnetic resonance imaging and Bayley Scales of Infant and Toddler Development-III at 22 ± 7 months of age. Magnetic resonance imaging at 5-14 (mean 8) days was scored as normal (score = 0), showing focal gray or white matter injury only (score = 1), or basal ganglia/thalamic and/or watershed lesions with or without more extensive hemispheric injury (score = 2). Sensitivity, specificity, and positive and negative predictive values for magnetic resonance scores 0 and 1 and statistical interaction between magnetic resonance imaging score and age at magnetic resonance imaging were determined.nnnRESULTSnMagnetic resonance score = 0 was seen in 35/62 patients; 26/35 (74%) were typically developing, seven (20%) had moderate and two (6%) had severe delay. Magnetic resonance score = 1 was seen in 17/62 (27%) patients; 5/17 (29%) were normal, 11/17 (65%) had moderate delay, and 1/17 (6%) had severe neurodevelopmental delay. Of the 52 patients with magnetic resonance scores of 0 and 1, 40% were abnormal. The negative predictive value of a normal magnetic resonance imaging was 74%. For score 1, sensitivity was 95% (confidence interval 63%-83%), specificity 84% (confidence interval 70%-90%), positive predictive value 84% (confidence interval 71%-93%), and negative predictive value 74% (confidence interval 62%-82%).nnnCONCLUSIONSnCaution is warranted when prognosticating about neurodevelopmental status in early childhood after hypoxic ischemic encephalopathy with cooling, and longer follow-up studies are needed to determine the prognostic significance of a neonatal magnetic resonance imaging showing no or minor degrees of brain injury.

Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial

Importance Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks’ or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. Objective To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. Design, Setting, and Participants A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks’ or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. Interventions Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C). Main Outcomes and Measures The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. Results Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks’ gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, −1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively. Conclusions and Relevance Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness. Trial Registration clinicaltrials.gov Identifier: NCT00614744

Neonatal outcomes of moderately preterm infants compared to extremely preterm infants

BackgroundExtremely preterm infants (EPT, <29 weeks’ gestation) represent only 0.9% of births in the United States; yet these infants are the focus of most published research. Moderately preterm neonates (MPT, 29–336/7 weeks) are an understudied group of high-risk infants.MethodsTo determine the neonatal outcomes of MPT infants across the gestational age spectrum, and to compare these with EPT infants. A prospective observational cohort was formed in 18 level 3–4 neonatal intensive care units (NICUs) in the Eunice Kennedy Shriver NICHD Neonatal Research Network. Participants included all MPT infants admitted to NICUs and all EPT infants born at sites between January 2012 and November 2013. Antenatal characteristics and neonatal morbidities were abstracted from records using pre-specified definitions by trained neonatal research nurses.ResultsMPT infants experienced morbidities similar to, although at lower rates than, those of EPT infants. The main cause of mortality was congenital malformation, accounting for 43% of deaths. Central Nervous System injury occurred, including intraventricular hemorrhage. Most MPT infants required respiratory support, but sequelae such as bronchopulmonary dysplasia were rare. The primary contributors to hospitalization beyond 36 weeks’ gestation were inability to achieve adequate oral intake and persistent apnea.ConclusionsMPT infants experience morbidity and prolonged hospitalization. Such morbidity deserves focused research to improve therapeutic and prevention strategies.

Comparison of saliva PCR assay versus rapid culture for detection of congenital cytomegalovirus infection.

As part of the CMV and Hearing Multicenter Screening (CHIMES) study, 72,239 newborns were screened for cytomegalovirus by rapid culture and real-time PCR of saliva samples. Of the 266 infants with congenital cytomegalovirus infection, discordance between rapid culture and PCR was observed in 14 children, and 13 were identified only by PCR, demonstrating the superiority of the PCR assay.

Newborn Dried Blood Spot Polymerase Chain Reaction to Identify Infants with Congenital Cytomegalovirus-Associated Sensorineural Hearing Loss

Objective To determine the utility of dried blood spot (DBS) polymerase chain reaction (PCR) in identifying infants with cytomegalovirus (CMV) infection–associated sensorineural hearing loss (SNHL). Study design Newborns at 7 US hospitals between March 2007 and March 2012 were screened for CMV by saliva rapid culture and/or PCR. Infected infants were monitored for SNHL during the first 4 years of life to determine sensitivity, specificity, and positive and negative likelihood ratios of DBS PCR for identifying CMV‐associated SNHL. Results DBS at birth was positive in 11 of 26 children (42%) with SNHL at age 4 years and in 72 of 270 children (27%) with normal hearing (P = .11). The sensitivity (42.3%; 95% CI, 23.4%‐63.1%) and specificity (73.3%; 95% CI, 67.6%‐78.5%) was low for DBS PCR in identifying children with SNHL at age 4 years. The positive and negative likelihood ratios of DBS PCR positivity to detect CMV‐associated SNHL at age 4 years were 1.6 (95% CI, 0.97‐2.6) and 0.8 (95% CI, 0.6‐1.1), respectively. There was no difference in DBS viral loads between children with SNHL and those without SNHL. Conclusions DBS PCR for CMV has low sensitivity and specificity for identifying infants with CMV‐associated hearing loss. These findings, together with previous reports, demonstrate that DBS PCR does not identify either the majority of CMV‐infected newborns or those with CMV‐associated SNHL early in life.

The Mortality of Neonatal Herpes Simplex Virus Infection

This retrospective study characterized the clinical course of 13 neonates who died with herpes simplex virus infection from 2001 to 2011, representing a 26% case-fatality rate. Fatal disease developed at ≤ 48 hours of age in one-third of infants, was mostly disseminated disease, and occurred despite early administration of high-dose acyclovir therapy.

Postoperative Regimentation Of Treatment Optimizes Care and Optimizes Length of Stay (PROTOCOL) after pyloromyotomy

BACKGROUND/PURPOSEnA non-standardized approach to caring for infants after pyloromyotomy for pyloric stenosis was associated with prolonged postoperative length of stay (pLOS) at our institution. We studied the impact of a standardized postoperative care protocol on pLOS, patients clinical course, and nursing care.nnnMETHODSnA retrospective chart review identified that 27% of infants who underwent uncomplicated pyloromyotomy had prolonged pLOS, defined as more than one postoperative midnight. A comprehensive postoperative care protocol was developed for infants undergoing pyloromyotomy. Patients were recruited prospectively and those with complications were excluded. A sample size of 70 in each cohort (historic and prospective) allowed 80% power to detect a 50% reduction in the proportion of patients with prolonged pLOS (α=0.05). The prospective group and historic cohort were compared using nonparametric statistics.nnnRESULTSnThe historic cohort had 70 patients and the prospective cohort had 66. Protocol implementation resulted in fewer patients with prolonged pLOS, shorter time to feeds, fewer feeds to discharge, less emesis, and improved nursing documentation.nnnCONCLUSIONnImplementation of a postoperative care protocol improved various aspects of patient care and nursing care studied. Protocols outline a patients course and serve as a common platform for communication among care providers; they can facilitate, expedite, and enhance patient care.

Identification of extremely premature infants at low risk for early-onset sepsis

Delivery characteristics of infants born at 22 to 28 weeks’ gestation can be used to identify those with significantly lower risk of EOS. BACKGROUND: Premature infants are at high risk of early-onset sepsis (EOS) relative to term infants, and most are administered empirical antibiotics after birth. We aimed to determine if factors evident at birth could be used to identify premature infants at lower risk of EOS. METHODS: Study infants were born at 22 to 28 weeks’ gestation in Neonatal Research Network centers from 2006 to 2014. EOS was defined by isolation of pathogenic species from blood or cerebrospinal fluid culture at ≤72 hours age. Infants were hypothesized as “low risk” for EOS when delivered via cesarean delivery, with membrane rupture at delivery, and absence of clinical chorioamnionitis. Frequency of prolonged antibiotics (≥5 days) was compared between low-risk infants and all others. Risks of mortality, EOS, and other morbidities were assessed by using regression models adjusted for center, race, antenatal steroid use, multiple birth, sex, gestation, and birth weight. RESULTS: Of 15u2009433 infants, 5759 (37%) met low-risk criteria. EOS incidence among infants surviving >12 hours was 29 out of 5640 (0.5%) in the low-risk group versus 209 out of 8422 (2.5%) in the comparison group (adjusted relative risk = 0.24 [95% confidence interval, 0.16–0.36]). Low-risk infants also had significantly lower combined risk of EOS or death ≤12 hours. Prolonged antibiotics were administered to 34% of low-risk infants versus 47% of comparison infants without EOS. CONCLUSIONS: Delivery characteristics of extremely preterm infants can be used to identify those with significantly lower incidence of EOS. Recognition of differential risk may help guide decisions to limit early antibiotic use among approximately one-third of these infants.

Herpes Simplex Virus DNAemia Preceding Neonatal Disease

Polymerase chain reaction testing of blood for herpes simplex virus (HSV) is recommended for newborns delivered to mothers with active genital HSV lesions at delivery. We report an infant who had a positive blood HSV polymerase chain reaction test before the onset of clinical signs of HSV disease.