Newborn screening algorithm distinguishing potential symptomatic isovaleric acidemia from asymptomatic newborns.

Newborn screening (NBS) for isovaleric acidemia (IVA) reduces mortality and morbidity; however, it has also resulted in the detection of individuals with an asymptomatic or mild presentation for which early detection via newborn screening has not been proven to alter neurological outcome. We reevaluated biochemical and molecular data for newborns flagged positive for IVA in aim of developing a new screening algorithm to exclude the latter from positive screening. Among 2 794 365 newborns underwent routine newborn screening in Israel, 412 flagged positive for IVA, of which, 371 were false positives on recall sample testing and 41 positive newborns were referred to the clinic. 38/41 have biochemical and molecular confirmation in keeping with IVA. Among the 38 patients, 32% (12/38) were classified as symptomatic while, 68% (26/38) were classified as asymptomatic. 69% of the latter group harbor the known variant associated with mild potentially asymptomatic phenotype, c.932C>T; p. Ala311Val. Among asymptomatic patients, only 46% (12/26) are currently treated. Two novel variants have been detected in the IVD gene: c.487G>A; p. Ala163Thr and c.985A>G; p. Met329Val. Cut-off recalculation, of referred newborns' initial biochemical results, after classifying the referred patients to two binary groups of symptomatic and asymptomatic, resulted in an improved NBS algorithm comprising of C5 >5 µM and C5/C2>0.2 and C5/C3>4 flagging only those likely to have the classic symptomatic phenotype.

The role of orotic acid measurement in routine newborn screening for urea cycle disorders.

Urea cycle disorders (UCDs), including OTC deficiency (OTCD), are life-threatening diseases with a broad clinical spectrum. Early diagnosis and initiation of treatment based on a newborn screening (NBS) test for OTCD with high specificity and sensitivity may contribute to reduction of the significant complications and high mortality. The efficacy of incorporating orotic acid determination into routine NBS was evaluated. Combined measurement of orotic acid and citrulline in archived dried blood spots from newborns with urea cycle disorders and normal controls was used to develop an algorithm for routine NBS for OTCD in Israel. Clinical information and genetic confirmation results were obtained from the follow-up care providers. About 1147986 newborns underwent routine NBS including orotic acid determination, 25 of whom were ultimately diagnosed with a UCD. Of 11 newborns with OTCD, orotate was elevated in seven but normal in two males with early-onset and two males with late-onset disease. Orotate was also elevated in archived dried blood spots of all seven retrospectively tested historical OTCD patients, only three of whom had originally been identified by NBS with low citrulline and elevated glutamine. Among the other UCDs emerge, three CPS1D cases and additional three retrospective CPS1D cases otherwise reported as a very rare condition. Combined levels of orotic acid and citrulline in routine NBS can enhance the detection of UCD, especially increasing the screening sensitivity for OTCD and differentiate it from CPS1D. Our data and the negligible extra cost for orotic acid determination might contribute to the discussion on screening for proximal UCDs in routine NBS.

Improving newborn health in countries exposed to political violence: An assessment of the availability, accessibility, and distribution of neonatal health services at Palestinian hospitals.

INTRODUCTION: Geopolitical segregation of Palestine has left a fragile healthcare system with an unequal distribution of services. Data from the Gaza Strip reflect an increase in infant mortality that coincided with a significant increase in neonatal mortality (12.0 to 20.3 per 1,000 live births). OBJECTIVE: A baseline study was carried out to evaluate available resources in neonatal units throughout Palestine. STUDY DESIGN: A cross-sectional, hospital-based study was conducted in 2017 using the World Health Organization's "Hospital care for mothers and newborn babies: quality assessment and improvement tool." Data on the main indicators were updated in 2018. RESULTS: There were 38 neonatal units in Palestine: 27 in the West Bank, 3 in East Jerusalem, and 8 in the Gaza Strip. There was an uneven geographic distribution of incubators in relation to population and births that was more marked in the Gaza Strip; 79% of neonatal units and 75% of incubators were in the West Bank. While almost all hospitals with neonatal units accepted very and extremely low birth weight and admitted out-born neonatal cases, there was a shortage in the availability of incubators with humidifiers, high-frequency oscillatory ventilation, mechanical ventilators with humidifiers and isolation wards. There was also a considerable shortage in neonatologists, neonatal nurses, and pediatric subspecialties. CONCLUSION: Almost all the neonatal units accepted extremely low birth weight neonatal cases despite not being ready to receive these newborns due to considerable shortages in human resources, equipment, drugs, and essential blood tests, as well as frequent disruptions in the availability of based amenities. Together, these factors contribute to the burden of providing quality care to newborns, which is further exacerbated by the lack of referral guidelines and challenges to timely referrals resulting from Israeli measures. Ultimately, this contributes to suboptimal care for neonates and negatively impacts future health outcomes.

Intrauterine upper limb ischemia: an unusual presentation of fetal thrombophilia-a case report and review of the literature.

Upper limb ischemia presenting in neonatal period is extremely rare. Moreover, presenting newborn with evidence of intrauterine upper limb vascular occlusion is even rarer. It needs prompt intervention to restore perfusion and avoid morbidity. We present a newborn with right upper limb brachial artery thrombosis causing ischemia that was noted at birth and appeared later to be homozygous for factor V Leiden and glycoprotein IIIa with no other identifiable risk factors. In this report, we present the case, its successful medical management, proper counseling, and review of the literature. We recommend investigating the neonates and their parents for thrombophilia mutations when they present with unusual vascular occlusion site as newborns.

Epidemiological and microbiological characteristics of an outbreak caused by OXA-48-producing Enterobacteriaceae in a neonatal intensive care unit in Jerusalem, Israel.

This study describes the course of an OXA-48-producing Enterobacteriaceae (OPE) outbreak that started in March 2012 in a neonatal intensive care unit (NICU) in Jerusalem, Israel. During the peak of the outbreak (January to August 2012), there were 49 patients who had proven or suspected acquisition of OPE in the NICU, including 16 with invasive infections, out of a total of 156 patients who were hospitalized during that period. Three children hospitalized in the pediatric ICU were identified as carriers of OPE. Three patients with a previous stay in the affected NICU were identified as OPE carriers upon admission to another hospital. The Ministry of Health was notified and then intervened in July 2012. Intervention included cohorting colonized patients, conducting frequent rectal-culture surveillance, and improving the implementation of infection control practices. As a result, the incidence of OPE acquisition declined to 5 cases in the first 4 months, followed by no new cases in the next 3 months. Thirty-one patient-unique isolates were available for analysis: 29 Klebsiella pneumoniae isolates, all belonging to a single clone (sequence type 39 [ST39]), and 2 isolates from Enterobacter cloacae. All isolates possessed the blaOXA-48 and blaCTX-M-14 genes, which are located on the same plasmid. This plasmid, similar to the global blaOXA-48-harboring vector, has now acquired blaCTX-M-14, leading to resistance to all ß-lactam agents.