Asymptomatic Infants Research Articles

PIH20 OUTCOME AND ECONOMIC EVALUATION OF NEONATAL SCREENING USING MS/MS FOR INHERITED METABOLIC DISEASES

Neonatal screening aims to detect asymptomatic infants at early stages to prevent the occurrence of body dysfunction and irreversible damage, so as to reduce the rate of infant disability and mortality. Mass spectrometry makes possible the simultaneous measurement of several metabolites and, consequently, the detection of several diseases in one blood spot and in a unique analysis. This study assessed the outcome and cost-effectiveness of neonatal screening using tandem-mass spectrometry (MS/MS). Patients who underwent MS/MS screening for inherited metabolic diseases (IMD) from 2009Q1-2018Q4 were identified with another MS/MS screening plus specified tests and confirmed by gene sequence analysis. All records were extracted from a screening management system in Neonatal Screening Center of Zhejiang province. Direct costs were estimated from the perspective of the Chinese healthcare system. Of the 3,040,815 neonates screened, 26,297(0.86%) neonates were suspected positive after first-round screening and called back to take another MS/MS screening. 25,670(97.62%) of them followed the latter procedures and finally 574(2.24%) cases were diagnosed through gene sequence analysis . The most frequent cause of IMD is fatty acid oxidation disorders (n=248), in most cases organic acidemias (n=211), followed by amino acid diseases(n=115). The costs of MS/MS was RMB$175 for screening and RMB$390 for follow-up, RMB$60 or 116 for specified tests, RMB$3120 for gene sequence analysis and RMB$80 for genetic counselling. The medication expenditures for detection of one single IMD patient was RMB$952,405.04. Overall the cost is huge. Neonatal screening for IMD using MS/MS in common neonates may not be cost-effective, this needs to be confirmed using data on observed mortality and disability reduction.The results prompt the need of prudent consideration for nationwide promotion of IMD neonatal screening using MS/MS.

Perinatal Arterial Ischemic Stroke in Preterm and Term Born Infants: A National Capture- Recapture Calculation Corrected Surveillance Study

Background: We aimed to determine nationwide incidence for perinatal arterial ischemic stroke (PAIS) in term and preterm born newborns and to investigate differences in clinical presentation related to gestational age. Methods: This three-year nationwide surveillance study (2015–2017) estimated incidences for MRI confirmed PAIS diagnosed within the first 28 days of life in term and preterm infants. To correct for underreporting we performed capture-recapture-calculations in one federal state and extrapolated nationwide. Differences in clinical presentation in term and preterm born infants were assessed. Findings: 145 infants were reported of whom 19 were born prematurely. CRC corrected incidence for PAIS was 22·0 per 100,000 live births and 31·9 per 100,000 in preterm born infants (p=0·001). 13 (9%) MRI confirmed PAIS cases were classified as asymptomatic. In symptomatic cases, the incidence estimates did not differ between preterm and term born infants. No differences in risk factors were identified but number of risk factors in premature babies was elevated (mean 3·8 versus 2·9; p=0·01). Median age at diagnosis was increased in preterm born infants (7·9 days versus 3·6 days; p=0·04). Clinical seizures were observed in 88% of term born infants with symptoms compared to 33% in premature infants (p<0·0001). Interpretation: Incidence rates of PAIS in Germany were in the range of other population-based studies suggesting similar rates for PAIS in developed countries. New finding is that symptomatic PAIS in preterm born infants is as common as in term born infants. The detection, however, requires awareness of the specific symptom patterns in preterm born infants. Detection of MRI confirmed PAIS in asymptomatic preterm born infants prompted by suspicious ultrasound findings may hint to a hitherto poorly recognized pathway to disability in preterm born infants. Funding Statement: The sponsor was not involved in any aspect pertinent to the study. Declaration of Interests: All authors stated that they had no interests, which might be perceived as posing a conflict or bias. As well, they all disclose prior publication and submission of the manuscript. Ethical Approval Statement: Due to anonymous reporting in ESPED parental consent was not required. Ethical approval was obtained by the ethics committee of the Medical Faculty of the Ludwig-Maximilians-University, Munich, Germany, Nr 42-15 (05-04-2015).

Prevalence and time course of elevated serum levels of liver enzymes in otherwise healthy Thai infants with breast milk jaundice: a cohort study

Abstract Background Neonatal jaundice and elevated levels of liver enzymes are found in infants with breast milk jaundice (BMJ). Objectives To determine the prevalence and duration of elevated serum levels of liver enzymes in Thai infants with BMJ. Methods We conducted a prospective study of Thai infants with BMJ, excluding those with pathological causes of jaundice. We measured the serum levels of total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT); followed infants with elevated levels; and estimated the time for levels to become normal using Kaplan–Meier analysis. Results We included 42 infants (median age: 17.5 days) with BMJ, and elevated serum levels of at least 1 enzyme were found in 27 (64%) infants. We excluded 4 (10%) infants because they did not continue to be exclusively breastfed, 17 (40%) were lost to follow-up, and 21 (50%) completed the study. We found that 19 (45%) of the 42 infants had elevated GGT, 11 (26%) had elevated ALT, and 9 (21%) each had elevated AST and ALP levels. The median time for enzyme levels to normalize was 291 days (95% confidence interval [CI], 109.8 to 472.2) for ALT, 240 days (95% CI, 139.0 to 340.9) for AST, 184 days (95% CI, 4.4 to 363.6) for ALP, 120 days (95% CI, 74.6 to 164.5) for TB, and 63 days (95% CI, 61.44 to 64.6) for GGT. Infants were otherwise healthy during the follow-up. Conclusion The prevalence of elevated serum levels of liver enzymes in Thai infants was unexpectedly high, but the levels became normal spontaneously despite continued breastfeeding, which endorses a “watchful waiting” strategy in managing asymptomatic infants with BMJ.

Reducing unnecessary neonatal testing in infants of mothers with thyroid disease.

To examine the numbers of asymptomatic infants <8 weeks who had appropriate thyroid function tests (TFTs) in addition to the newborn screening test, because of maternal thyroid disease, before and after the implementation of an updated institutional guideline and staff education. A medical record audit of infants <8 weeks born at a metropolitan teaching hospital, who had TFTs between 1 July 2017 and 31 October 2017 was performed as part of a quality improvement project. Records were reviewed to determine the indication for testing and whether this complied with the current 2011 institutional guideline. A multidisciplinary staff education package was developed to coincide with the publication of an updated guideline in August 2018. Staff education and resources were provided throughout July 2018. A post-intervention audit was repeated between 1 August 2018 and 1 December 2018, assessing compliance with the 2018 guideline. In the baseline period, 40 of 457 infants born had TFTs performed, of which 26 of 40 (65%) were for maternal thyroid disease. Of these 10 of 26 (38%) met the 2011 criteria for testing; 1 of 26 (4%) met the updated 2018 criteria. In the post-intervention period, 14 of 412 infants born had TFTs of which 5 of 14 (36%) were tested due to maternal thyroid disease and all were compliant with the new guideline. Baseline audit revealed unnecessary neonatal thyroid function testing of healthy babies. Implementation of an updated guideline and a brief, targeted education package successfully increased awareness of the updated recommendations, reduced unnecessary testing and led to improved practice.

Assessment of Subtle Myocardial Dysfunction in Asymptomatic Infants of Diabetic Mothers

Abstract Background Cardiovascular abnormalities in infants of diabetic mothers (IDMS) occur in the form of congenital heart diseases (CHD), and hypertrophic cardiomyopathy (HCM). Aim of the Work We hypothesized that two dimensional speckle tracking imaging and pulsed wave tissue Doppler imaging (TM) may uncover subtle myocardial dysfunction in asymptomatic IDMs. Patients and Methods This study was a cross sectional descriptive study conducted at Ain shams University Children’s Hospital Pediatric cardiology unit during the period from June 2017 till January 2018. Thirty IDMs were recruited. IDMs with CHD and HCM were excluded. We further subdivided them into 2 groups; Infants of gestational diabetic mothers (IGDM) and infants of pregestational diabetic mothers (IPGDM). They were all examined using TDI and STI echocardiography in the first week of life. This group was compared to a group of age and sex matched healthy controls. Results All IDMs had normal cardiac dimensions and global cardiac functions as controls, IVS (P = 0.434), LVED (P = 0.318), EF (P = 0.291), LVFS(P = 0.644) and GLS(P = 0.240). However, evidence of LV dysfunction proved by increased Tei index (p = 0.018). This subtle affection of myocardial function was more prominent in infants of IPGDM when compared to IGDMs (P = 0.004). Conclusion Subtle affection of myocardial functions may occur in IDMs even in the absence of morphological cardiac changes. This was detected by TDI. Neither conventional assessment of myocardial functions, nor STI are sensitive tools in detecting these changes. IPGDMs are at risk of more profound affection of myocardial function than infants of IGDMs.

Media Review: The Owlet Smart Sock—a “must have” for the baby registry?

Citation:Malik A, Ehsan Z. Media Review: The Owlet Smart Sock—a “must have” for the baby registry? J Clin Sleep Med. 2020;16(5):839–840.

Viral shedding, and distribution of cytomegalovirus glycoprotein H (UL75), glycoprotein B (UL55), and glycoprotein N (UL73) genotypes in congenital cytomegalovirus infection

BackgroundChildren with congenital CMV infection (cCMV) shed virus in urine and saliva for prolonged periods of time. Outcome of cCMV varies from asymptomatic infection with no sequelae in most cases, to severe longterm morbidity. The factors associated with asymptomatic cCMV are not well defined. We evaluated the viral shedding in a cohort of infants with cCMV identified on newborn screening. In addition, we describe the distribution of viral genotypes in our cohort of asymptomatic infants and previous cohorts of cCMV children in the literature. MethodsStudy population consisted of 40 children with cCMV identified in screening of 19,868 infants, a prevalence of 2/1000. The viral shedding was evaluated at 3 and 18 months of age by real-time CMV-PCR of saliva and plasma, and CMV culture of urine. CMV positive saliva samples were analyzed for genotypes for CMV envelope glycoproteins gB (UL55), and gH (UL75) by genotype specific real-time PCR, and gN (UL73) by cloning and sequencing ResultsAt 3 months age 40/40 saliva and urine samples, and 19/40 plasma samples were positive for CMV. At 18 months age all urine samples tested (33/33), 9/37 of saliva samples, and 2/34 plasma samples were positive for CMV. The genotype distribution did not differ from the published data ConclusionsThe urinary virus shedding is more persistent than salivary shedding in children with cCMV. The genotype distribution was similar to previous literature and does not explain the low disease burden of cCMV in our population.

Preface

An unintended consequence of cystic fibrosis (CF) newborn screening (NBS) is the identification of infants with a positive NBS test but inconclusive diagnostic testing. These infants are classified as CF transmembrane conductance regulator-related metabolic syndrome (CRMS) in the US and CF screen positive, inconclusive diagnosis (CFSPID) in other countries. Diagnostic and management decisions of these infants are challenges for CF healthcare professionals and stressful situations for families. As CF NBS has become more widespread across the world, increased information about the epidemiology and outcomes of these infants is becoming available. These data were reviewed at the 2015 CF Foundation Diagnosis Consensus Conference, and a harmonized definition of CRMS and CFSPID was developed.At the consensus conference, participants reviewed published and unpublished studies of CRMS/CFSPID and used a modified Delphi methodology to develop a harmonized approach to the definition of CRMS/CFSPID.Several studies of CRMS/CFSPID from populations around the world have been published in the past year. Although the studies vary in the number of infants studied, study design, and outcome measures, there have been some consistent findings. CRMS/CFSPID occurs relatively frequently, with CF:CRMS that ranges from 3 to 5 cases of CF for every 1 case of CRMS/CFSPID in regions where gene sequencing is not used. The incidence varies by NBS protocol used, and in some regions more cases of CRMS/CFSPID are detected than cases of CF. The majority of individuals with CRMS/CFSPID do not develop CF disease or progress to a diagnosis of CF. However, between 10% and 20% of asymptomatic infants can develop clinical features concerning for CF, such as a respiratory culture positive for Pseudomonas aeruginosa. Most studies have only reported short-term outcomes in the first 1-3 years of life; the long-term outcomes of CRMS/CFSPID remain unknown. The European CF Society definition of CFSPID and the CF Foundation definition of CRMS differ only slightly, and the consensus conference was able to create a unified definition of CRMS/CFSPID.CRMS/CFSPID is a relatively common outcome of CF NBS, and clinicians need to be prepared to counsel families whose NBS test falls into this classification. The vast majority of infants with CRMS/CFSPID will remain free from disease manifestations early in life. However, a small proportion may develop clinical features concerning for CF or demonstrate progression to a clinical phenotype compatible with a CF diagnosis, and their long-term outcomes are not known. A consistent international definition of CRMS/CFSPID will allow for better data collection for study of outcomes and result in improved patient care.

Current and future diagnosis of cystic fibrosis: Performance and limitations

Cystic fibrosis (CF) is the most frequent genetic disorder in the Caucasian population benefiting from systematic newborn screening tests. It is also the most frequent indication of prenatal and preimplantation genetic diagnosis for a single gene disorder. During the past thirty years, thanks in part to the evolution of diagnostic techniques, our knowledge on CFTR genetics and pathophysiological mechanisms involved in CF have significantly improved. With the implementation of newborn screening in France and in several countries, the diagnosis now often occurs in clinically asymptomatic infants and this has modified the criteria for CF diagnosis. Recently, guidelines for CF diagnosis have been reformulated in Europe and the US, in regard to sweat chloride usual values and disease terminology. This review describes the methods and molecular approaches that are used in routine practice or are being developed to detect CFTR protein dysfunction and to identify disease-causing CFTR variants. Ultimately, an optimal use of all these functional and genetic resources may improve patient care and therapeutic decision-making. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Clinically Asymptomatic Sleep-Disordered Breathing in Infants with Single-Ventricle Physiology

To assess clinically asymptomatic infants with single-ventricle physiology (SVP) for sleep-disordered breathing (SDB) in the supine and car seat positions using polysomnography. Polysomnography results also were compared with results of a standard Car Seat Challenge to measure the dependability of the standard Car Seat Challenge. This was an observational study of 15 infants with SVP. Polysomnography data included Obstructive Index, Central Index, Arousal Index, Apnea Hypopnea Index, and sleep efficiency. Polysomnography heart rate and oxygen saturation data were used to compare polysomnography with the standard Car Seat Challenge. Polysomnography demonstrated that all 15 infants had SDB and 14 had obstructive sleep apnea (Obstructive Index ≥1/hour) in both the supine and car seat positions. Infants with SVP had a statistically significant greater median Obstructive Index in the car seat compared with supine position (6.3 vs 4.2; P=.03), and median spontaneous Arousal Index was greater in the supine position compared with the car seat (20.4 vs 15.2; P=.01). Comparison of polysomnography to standard Car Seat Challenge results demonstrated 5 of 15 (33%) of infants with SVP with abnormal Obstructive Index by polysomnography would have passed a standard Car Seat Challenge. Infants with SVP without clinical symptoms of SDB may be at high risk for SDB that appears worse in the car seat position. The standard Car Seat Challenge is not dependable in the identification of infants with SVP and SDB. Further studies are warranted to further delineate its potential impact of SDB on the clinical outcomes of infants with SVP.

Prevalence and Risk Factors of Incidental Findings in Brain MRIs of Healthy Neonates-The FinnBrain Birth Cohort Study.

Background: Birth is a traumatic event with molding forces directed to the fetal skull, which may result in intracranial hemorrhages. However, the knowledge on prevalence and risk factors of incidental brain magnetic resonance imaging (MRI) findings in infants is still inconclusive.Methods: The prevalence and nature of incidental MRI findings were assessed in a birth cohort of 175 asymptomatic infants. The role of delivery method as well as other potential risk factors for intracranial hemorrhages were evaluated. The infants underwent 3T MRI at the age of 2–5 weeks, and the neurological status of the infants with an incidental finding was evaluated by a pediatric neurologist. Information on the delivery method, duration of delivery, parity, used anesthesia, oxytocin induction, and Apgar score was gathered to evaluate their association with the prevalence of hemorrhages.Results: Incidental intracranial hemorrhages were detected in 12 infants (6.9%), all following spontaneous or assisted vaginal delivery. Vacuum-assistance was found to be a risk factor for subdural hemorrhages with an odds ratio (OR) of 4.7 (95% CI [1.18; 18.9], p = 0.032). All infants were evaluated to develop normally by their clinical status.Conclusions: Incidental intracranial hemorrhages are relatively common among infants born by vaginal delivery. They are often of little clinical significance within the first years of life and have unlikely consequences for later neurodevelopment either. Despite their benign character, investigators should be prepared to share this information with parents competently as the findings can cause parental anxiety, and especially as the popularity of MRI as a research tool is increasing.

Isolated auditory neuropathy at birth in congenital cytomegalovirus infection

BackgroundCongenital cytomegalovirus (cCMV) infection is the most frequent non-genetic cause of sensorineural hearing-loss (SNHL) (i.e., hearing loss due to a cochlear and/or auditory nerve damage). It is widely accepted that SNHL at birth, when associated to cCMV symptomatic infection involving the central nervous system, benefits from antiviral therapy started in the neonatal period. Conversely, there is no consensus for antiviral treatment in congenitally infected infants diagnosed with isolated SNHL (i.e., SNHL in an otherwise asymptomatic infant) at birth.Our aim was to assess the frequency and the auditory outcome of isolated SNHL at birth due to auditory neuropathy (AN) (i.e., SNHL in a patient with normal cochlear function and auditory nerve dysfunction) in infants with cCMV infection.MethodsWe retrospectively reviewed the clinical history of 60 infants, born at term, with cCMV asymptomatic infection, without additional risk factors for SNHL, and exhibiting bilateral “pass” otoacustic emissions (OAE). None of them underwent antiviral therapy.Hearing thresholds were assessed by means of Auditory Brainstem Responses (ABR). AN affected children were followed up until possible normalization of the hearing thresholds or definitive diagnosis of AN. Each infant diagnosed with monolateral or bilateral AN was classified according to the worst ear threshold.ResultsIn our population, the first ABR was performed at a mean age of 5.00 ± 2.79 (SD) months and AN was diagnosed in 16/60 (26.67%) infants; in 4 infants the AN was defined as mild (4/4 monolateral), moderate in 11 (5/11 bilateral), and severe in 1 (bilateral). The mean age at first ABR was 3.69 ± 2.80 (SD) months in the 16 babies with AN and 5.48 ± 2.66 (SD) months in the 44 infants with normal hearing (p = 0.007). All AN cases spontaneously recovered a normal auditory threshold over time. The mean length of the audiological follow-up was 32.44 ± 17.58 (SD) months (range 5–60 months).ConclusionA delayed maturation of the auditory pathways should be considered when a mild/moderate isolated AN at birth is detected in cCMV infected infants. Prospective studies conducted on larger populations, and with a longer audiological follow-up, are needed to confirm our findings.

The outcome of fetuses diagnosed with congenital cystic adenomatous malformation of the lungs: Experience of a regional neonatal center (2004–2016)

Objective: Although much is known about the antenatal course of congenital cystic adenomatous malformation (CCAM), the postnatal course is less well documented. The vast majority of infants remain asymptomatic at birth, with the controversy surrounding the postnatal management of such infants. We reviewed the outcome of fetuses diagnosed with CCAM in our center and evaluated their symptom burden during the 1st year of life. Methods: A retrospective review of maternal and infant medical records of all cases with antenatal diagnosis of CCAM managed in a regional perinatal center over 12 years, and infant outcome at 1 year of age is presented. Results: Forty-two eligible singleton pregnancies/infants were identified. Thirteen babies (30.9%) were symptomatic and 29/42 (69.1%) asymptomatic at birth. 7/13 (53.9%) symptomatic infants had associated antenatal complications. The fetal lesions were more likely to remain static or reduce in size during pregnancy in asymptomatic (26/29; 89.6%) than symptomatic babies (8/13; 61.6%). All babies had chest radiographs after birth, but computed tomography (CT) scan was done in only a few symptomatic babies; 7/42 (16.7%) during the neonatal period and a further 3/42 (7.1%) during infancy. The majority (8/13; 61%) of the symptomatic babies had surgical intervention compared to only 1/29 (3.4%) asymptomatic babies who had surgery. However, most babies remained symptom-free during infancy. Death within the cohort was limited to babies who were symptomatic (4/13; 31%). Conclusion: Most pregnancies diagnosed with CCAM remain uncomplicated. The behavior of the prenatal lesion could help predict the postnatal outcome. Our experience highlights that CCAM persistence cannot be excluded from chest radiographs; hence, the need for chest CT scans. Symptom surveillance should help guide the need for surgery in asymptomatic infants. However, only skilled clinicians who can offer long-term follow-up, until the transition into adulthood should oversee surveillance to ensure safety.

Association of CMV genomic mutations with symptomatic infection and hearing loss in congenital CMV infection

BackgroundCongenital cytomegalovirus (cCMV) infection is the most common congenital infection and a leading cause of long-term neurological and sensory sequelae, the most common being sensorineural hearing loss (SNHL). Despite extensive research, clinical or laboratory markers to identify CMV infected children with increased risk for disease have not been identified. This study utilizes viral whole-genome next generation-sequencing (NGS) of specimens from congenitally infected infants to explore viral diversity and specific viral variants that may be associated with symptomatic infection and SNHL.MethodsCMV DNA from urine specimens of 30 infants (17 asymptomatic, 13 symptomatic) was target enriched and next generation sequenced resulting in 93% coverage of the CMV genome allowing analysis of viral diversity.ResultsVariant frequency distribution was compared between children with symptomatic and asymptomatic cCMV and those with (n = 13) and without (n = 17) hearing loss. The CMV genes UL48A, UL88, US19 and US22 were found to have an increase in nucleotide diversity in symptomatic children; while UL57, UL20, UL104, US14, UL115, and UL35 had an increase in diversity in children with hearing loss. An analysis of single variant differences between symptomatic and asymptomatic children found UL55 to have the highest number, while the most variants associated with SNHL were in the RL11 gene family. In asymptomatic infants with SNHL, mutations were observed more frequently in UL33 and UL20.ConclusionCMV genomes from infected newborns can be mapped to 93% of the genome at a depth allowing accurate and reproducible analysis of polymorphisms for variant and gene discovery that may be linked to symptomatic and hearing loss outcomes.

Induction of labor and early-onset Sepsis guidelines: impact on NICU admissions in Erie County, NY

BackgroundElective delivery prior to term gestation is associated with adverse neonatal outcomes. The impact of American College of Obstetricians and Gynecologists (ACOG) guidelines recommending against induction of labor (IOL) < 39 weeks’ postmenstrual age (PMA) on the frequency of early-term births and NICU admissions in Erie County, NY was evaluated in this study.MethodsThis is a population-based retrospective comparison of all live births and NICU admissions in Erie County, NY between pre-and post-ACOG IOL guideline epochs (2005–2008 vs. 2011–2014). Information on early-term, full/late/post-term births and NICU admissions was obtained. A detailed chart analysis of indications for admission to the Regional Perinatal Center was performed.ResultsDuring the 2005–2008 epoch, early-term births constituted 27% (11,968/44,617) of live births. The NICU admission rate was higher for early-term births (1134/11968 = 9.5%) compared to full/late/post-term (1493/27541 = 5.4%).In the 2011–2014 epoch, early-term births decreased to 23% (10,286/44,575) of live births. However, NICU admissions for early-term (1072/10286 = 10.4%) and full/late/post-term births (1892/29508 = 6.4%) did not decrease partly due to asymptomatic infants exposed to maternal chorioamnionitis admitted for empiric antibiotic therapy as per revised early-onset sepsis guidelines.ConclusionsACOG recommendations against elective IOL or cesarean delivery < 39 weeks PMA were rapidly translated to clinical practice and decreased early-term births in Erie County, NY. This decrease did not translate to reduced NICU admissions partly due to increased NICU admissions for empiric antibiotic therapy.

Blood viral load in the diagnostic workup of congenital cytomegalovirus infection

BackgroundThere is limited data on the role of cytomegalovirus (CMV) blood quantitative polymerase chain reaction (qPCR) in the diagnostic workup of congenital CMV (cCMV) infection. ObjectivesThe objective of this study was to determine if CMV blood qPCR at the time diagnosis could differentiate between symptomatic and asymptomatic infants according to the recent consensus classification. Study designRetrospective study of children diagnosed with cCMV infection at CHU Sainte-Justine, Montreal, Canada, between 2008 and 2016.Cases for whom qPCR was done at baseline (<4 weeks of age) alongside a complete diagnostic workup were included. The association between CMV blood viral load (VL) and clinical severity group was determined. The probability of having moderate to severe symptoms was assessed using univariate logistic regression analysis. ResultsForty-seven patients were included in the analysis. Median VL was significantly higher among infants with moderate to severely symptomatic disease vs. those asymptomatic or asymptomatic with isolated sensorineural hearing loss (SNHL) (13 736 vs. 1876 copies/ml, p = 0.004), infants with moderate to severe disease or asymptomatic with isolated SNHL vs. asymptomatic (17 736 vs. 1496 copies/ml, p < 0.001), and in infants with baseline neurological involvement vs. those without (17 317 vs. 2641 copies/ml, p = 0.03). Using logistic regression, an infant would have a >75 % probability of being moderate to severely symptomatic above 18 770 copies/ml, with a threshold of 100 000 copies/ml approaching a 100 % probability. ConclusionsOur baseline assessment of CMV blood VL suggests that that the level of CMV viremia correlates with symptom severity.

2336. Adherence to Follow-up and CMV Testing in Infants Who Failed Newborn Hearing Screens: Evaluation of New Protocol to Ensure Follow-up and Testing

BackgroundCMV is the most common non-hereditary cause of sensorineural hearing loss (SNHL) in children in the United States. SNHL may be the only presenting symptom in otherwise asymptomatic infants. Several states are making CMV testing mandatory for newborn infants who have a hearing deficit. Testing should be performed before 21 days of life to diagnose congenital CMV infection and provide effective therapy. However, the results of a retrospective 1 year audit of all newborn patients in the nursery of University Hospital of Brooklyn (UHB) who failed their hearing screen found that none were tested for CMV and approximately half failed to follow-up with audiology. Therefor we developed a new protocol to ensure testing and follow-up.MethodsUnder the new protocol, newborns who fail an initial and repeat hearing screen are tested for CMV in urine by culture and the audiology appointment is scheduled before discharge. Patients are tracked by a pediatric infectious disease fellow to ensure adherence to protocol.ResultsThe pre-intervention audit conducted from November 1, 2017 to October 31, 2018 found 37/923 (4%) infants failed their hearing screening tests. Although 34/37 (92%) of these children had audiology appointments made before discharge, only 19 (56%) actually attended. Two (11%) children failed an otoacoustic emissions hearing test. One infant also went on to fail an auditory brainstem response test; both were lost to follow-up. None of these infants was tested for CMV. The new protocol was initiated November 1, 2018, 11/372 (3%) infants failed initial and repeat hearing screening tests. All 11 (100%) of these children had audiology appointments made before discharge, of which 9 (82%) attended. 2 (18%) of these children failed the otoacoustic emissions hearing test at that visit, 1 infant was lost to follow-up; 9 infants who failed hearing test were tested for CMV; 1 (9%) was positive.ConclusionAlthough it has only been in place for 5 months, the new protocol has increased adherence to audiology appointments. CMV testing has increased from 0% to 82% and 1 patient has tested positive for congenital CMV infection. The ongoing success of this protocol could facilitate timely and appropriate treatment of CMV with valgancyclovir. Disclosures All authors: No reported disclosures.

2628. Nasopharyngeal Microbiome in the First Weeks of Life Distinguishes Infants Who Subsequently Develop Lower Respiratory Tract Infections

BackgroundColonization of the nasopharynx (NP) is the initial event in the pathogenesis of lower respiratory tract infections (LRTI). Evidence is accumulating that the NP microbiome influences host immune responses and whether colonization progresses to disease or not. We hypothesized that infants who experience LRTI early in life display distinct NP microbiome characteristics prior to infection, and potentially as early as the newborn period.MethodsAs part of the “Southern Africa Mother Infant Pertussis Study” in Zambia, NP samples were prospectively collected approximately every 2 weeks beginning at birth, through 3 months of age, in conjunction with clinical data. Samples were also collected when an infant experienced respiratory symptoms. We identified infants from the cohort with LRTI and matched with asymptomatic controls. We performed 16S ribosomal DNA amplicon sequencing on DNA extracted from the NP samples using Illumina MiSeq, and analyzed the data using Qiime2 and PathoScope2. We described the NP microbiome characteristics of asymptomatic infants and infants with LRTI and their changes over time and compared between the two populations at each 2-week interval using the R package DESeq2.ResultsTen infants who had LRTI during the study period were matched with 17 healthy asymptomatic controls, together contributing 183 samples with high-quality reads. In asymptomatic infants, Dolosigranulum, Haemophilus and Moraxella’s relative abundance increased over the first 3 months of life, while Corynebacterium and Staphylococcus relative abundance decreased in the NP microbiome (Figure 1). In contrast, infants who developed LRTI had increased abundance of Staphylococcus, Anaerobacillus, and Bacillus, and decreased relative abundance of Dolosigranulum and Moraxella compared with asymptomatic controls (Figure 2). These differences were already present at the time of first sample collection (age 1 week).ConclusionInfants who develop LRTI early in life demonstrate altered NP microbial composition as early as the first week of life. These differences could potentially lead to early identification of at-risk infants. If confirmed, interventions to prevent LRTI in infancy could be evaluated to reduce respiratory mortality and morbidity. Disclosures All authors: No reported disclosures.

Evaluation of clinically asymptomatic high risk infants with congenital cytomegalovirus infection.

ObjectiveTo determine the frequency of abnormal findings on evaluation of neonates with congenital CMV infection who have a normal physical examinationStudy designRetrospective, 2-center study (1996–2017) that reviewed results of complete blood cell count and platelets, serum alanine aminotransferase (ALT) and bilirubin concentrations, eye examination, cranial ultrasonography or other neuroimaging, and brainstem evoked responses performed on neonates with congenital CMV infection and a normal physical examinationResultsOf 34 infants with congenital CMV infection and a normal physical examination, 56% (19/34) had ≥1 abnormality: 39%, elevated ALT concentration; 45%, abnormal neuroimaging (five, lenticulostriate vasculopathy; six, intraventricular hemorrhage; four, calcifications); 12%, anemia; 16%, thrombocytopenia; and 3%, chorioretinitis. Seven (21%) infants had sensorineural hearing loss, and 18 infants received antiviral therapy.ConclusionSome infants with congenital CMV infection and a normal physical examination had abnormalities on laboratory or neuroimaging evaluation, which in some cases prompted antiviral treatment.

Diagnosis and Management of Anomalous Left Anterior Descending Coronary Artery from the Pulmonary Artery in an Asymptomatic Infant.

Anomalous origin of the left anterior descending coronary artery from the pulmonary artery is a rare variant of anomalous origin of the left main coronary artery from the pulmonary artery. We report on a seemingly asymptomatic patient with ALADCAPA and a small restrictive muscular ventricular septal defect diagnosed by echocardiogram in the neonatal period. Our patient underwent elective repair at 3.5months of age after which feeding and growth improved dramatically. Multimodality imaging is helpful to confirm this rare anomaly; however, echocardiographic clues including lack of left coronary branching or an abnormal coronary course should raise suspicion for ALADCAPA. This case provides support for early repair in children with an incidental finding of this anomaly as subclinical ischemia may be under-recognized by available testing but may lead to symptoms later in life.