Retrospective evaluations revealed pre-symptomatic citrulline concentrations measured by newborn screening were significantly low in late-onset ornithine transcarbamylase deficiency patients.

INTRODUCTION: Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder. Late-onset OTCD manifests after the neonatal period; therefore, if pre-symptomatic diagnosis and treatment are performed, it can improve the prognosis by preventing hyperammonemia. However, pre-symptomatic diagnosis is unreliable as the specific screening marker of OTCD has not been established yet. This retrospective study aimed to evaluate the pre-symptomatic blood citrulline levels in patients with late-onset OTCD. METHODS: Patients with late-onset OTCD who were born after the newborn screening based on tandem mass spectrometry (MS/MS-NBS) was started and were referred to Hyogo College of Medicine Hospital between 2014 and 2018 were included. Pre-symptomatic blood citrulline levels measured by MS/MS-NBS were retrospectively evaluated. RESULTS: Four patients were included in this study. The pre-symptomatic blood citrulline levels were 2.02, 4.50, 4.97, and 3.75 µmol/l, respectively. Compared with the citrulline levels in all newborns in Hyogo prefecture, these values were significantly low. CONCLUSIONS: These results suggest the possibility that hypocitrullinemia detected by the MS/MS-NBS can be used as a screening marker for some patients with late-onset OTCD. Further retrospective evaluation of pre-symptomatic citrulline levels in patients with late-onset OTCD, as well as prospective monitoring of hypocitrullinemia on the MS/MS-NBS should be conducted.

Hyperbilirubinemia in Term Newborns Needing Phototherapy within 48 Hours after Birth in a Japanese Birth Center.

BACKGROUND: Hyperbilirubinemia in term newborns needing phototherapy within 48 hours after birth, early-onset hyperbilirubinemia, has not been evaluated in recent Japanese healthy birth centers. In this study, we sought to determine the cause of early-onset hyperbilirubinemia in a Japanese healthy birth center and to evaluate the 1992 Kobe University phototherapy treatment criterion requiring total serum bilirubin (TSB) and unbound bilirubin (UB). METHODS: In this retrospective observational study, we collected data on newborns diagnosed with early-onset hyperbilirubinemia between 2009 and 2016 at the Chibune General Hospital. Causes of the disease were investigated, as well as which index (TSB or UB) was used for treatment decisions. RESULTS: Overall, 76 term newborns were included in the analysis. Twenty-seven newborns (36%) found the cause (ABO blood type incompatibility [n=17, 22%], polycythemia [n=8, 11%], and cephalohematoma [n=2, 3%]). However, 49 newborns (64%) did not find any causes (i.e., idiopathic hyperbilirubinemia). Of these, 27 observed more than 5% weight loss from birth weight. Seventy (92%) newborns had abnormal TSB only, and 5 (7%) had abnormal TSB and UB values. Only 1 (1%) newborn with only abnormal UB values received phototherapy. CONCLUSIONS: Altogether, data from this Japanese healthy birth center suggest that many apparently healthy newborns with or without excessive weight loss develop early-onset hyperbilirubinemia. In the 1992 Kobe University phototherapy treatment criterion, TSB, not UB, was the main index used to make treatment decisions in these patients.

Culture-proven neonatal sepsis in Japanese neonatal care units in 2006-2008.

BACKGROUND: Recent Japanese epidemiology of neonatal sepsis and its predominant pathogens has not been reported. It is also unknown whether there are center differences in the incidence of neonatal sepsis, including early-onset sepsis (EOS) and late-onset sepsis (LOS) in Japan. OBJECTIVES: To investigate the morbidity and characteristics of neonatal sepsis in recent years and the differences in the incidence of sepsis among Japanese neonatal care units. METHODS: We retrospectively collected the data of newborn infants with culture-proven sepsis that occurred in five Japanese centers of perinatal care from 2006 to 2008. The incidence of sepsis was calculated, including EOS and LOS, and compared among centers. RESULTS: Morbidity from sepsis occurred in 51/6,894 (0.74%) infants. The incidence of EOS and LOS was 0.13 and 0.61%, respectively. The incidence of total sepsis and LOS in infants <1,000 g of birth weight was significantly higher than that in infants who weighed >1,000 g at birth, whereas there were no significant differences in the incidence of EOS between the different birth weights. Methicillin-resistant Staphylococcus aureus was the most common pathogen involved in morbidity and mortality of neonatal sepsis. Significant center differences were observed in the incidence of LOS, but not EOS. CONCLUSIONS: The majority of culture-proven neonatal sepsis is LOS, which differs among centers, especially in infants who weigh <1,000 g at birth in Japan. We consider that it is important to control nosocomial infection in newborn care units to further reduce the morbidity of neonatal sepsis in Japan.