Effect of maturation at birth on the clinical features of neonatal cow's milk protein allergy: A retrospective study.

Neonatal immune regulation transitions from fetal immunity and varies with maturation status, but its role in neonatal cow's milk protein allergy (CMPA) remains unknown. We studied the association between maturation status at birth and neonatal CMPA. Clinical and laboratory data of neonates presenting with CMPA symptoms were retrospectively collected from two tertiary hospitals. Patients were assessed according to gestational age at birth: preterm, late-preterm, and full-term. Fifty-five infants (26 females, 14 preterm, 15 late-preterm, and 26 full-term) were included; 44 were negative for milk-specific IgE. Neonatal CMPA was common during moderately premature periods. Preterm infants exhibited longer latency from initial CM exposure to disease onset, lower incidence of bloody stool, and absence of elevated monocyte counts. However, immunoreactivity to CM antigens was retained in all infants. Neonatal CMPA features varied with infant maturation status at birth. Our results improve the understanding of intestinal immunity development, fetal/neonatal immune regulation, and CMPA pathogenesis.

Effectiveness of ultrasound-guided peripheral arterial cannulation in neonates, including very low birth weight infants who are conventionally difficult-to-cannulate: a case series.

The effectiveness of ultrasound-guided peripheral arterial cannulation (UGPAC) in children has been increasingly been reported. However, to the best of our knowledge, there have been no reports of UGPAC in neonates, including very low birth weight infants (VLBWIs). In this study, we aimed to retrospectively review the results of UGPAC in neonates, including VLBWIs, and assess its effectiveness. This case series was conducted in a tertiary neonatal intensive care unit (NICU) in Japan. We included neonates aged below 28 days who underwent UGPAC in our NICU between April 2021 and October 2022. We extracted the following data from medical records and analysed it retrospectively: patient age (days), postconceptional age, patient weight at the time of cannulation, number of punctures using the conventional technique before ultrasound guidance was performed and number of punctures with the ultrasound-guided technique until successful cannulation. A total of 27 UGPACs were performed in 19 neonates, including 14 cannulations in 10 VLBWIs. In infants weighing > 1500 g and VLBWIs, the success rate within the first three punctures was 100% (13/13) and 79% (11/14), respectively. Overall, 41% (11/27) of UGPACs were performed following failed punctures using conventional methods, with a 100% success rate within the first three attempts. In all cases, no apparent adverse events, such as hypothermia, were noted.  Conclusions: Our results suggest that UGPAC had a high success rate in neonates, including VLBWIs. Further studies are required to compare the effectiveness of UGPAC with conventional methods in neonates. What is Known: • The use of ultrasound guidance for arterial cannulation is recommended in children. • Ultrasound-guided peripheral arterial cannulation (UGPAC) in neonates, including very low birth weight infants (VLBWIs), has not been reported. What is New: • UGPAC in neonates, including VLBWIs, was performed with a high success rate; approximately 40% of UGPACs were performed after the failure of the conventional methods. • This study suggested the effectiveness of UGPAC in neonates, including VLBWIs.

A Neonate with a Diagnosis of Pontocerebellar Hypoplasia Type 6 Treated with Biotin and Developed Biotin Interference with Laboratory Thyroid Function Tests.

BACKGROUND The interference of biotin administration with thyroid function tests has been reported; however, it remains unclear in clinical practice. In this report, we present the case of a neonate with a diagnosis of pontocerebellar hypoplasia type 6 (PCH6) treated with biotin who developed biotin interference with laboratory thyroid function tests. CASE REPORT A 1-day-old male infant with hypothermia, tachypnea, and lactic acidosis had a suspected diagnosis of mitochondrial disease. Biotin and several vitamins were administered to improve his condition. On day 14, his laboratory tests revealed a free triiodothyronine level of 4.7 pg/mL, free thyroxine level of 3.7 ng/dL, thyroid-stimulating hormone level of 0.07 µIU/mL, and thyroid-stimulating hormone receptor antibody (TRAb) level of 37.6 IU/L, suggesting Graves' disease. No goiter or tachycardia developed. The maternal thyroid function was not measured during pregnancy, while the maternal TRAb was negative on the same day. After methimazole administration, the patient's thyroid function normalized, and methimazole was therefore discontinued. All thyroid function tests were conducted using immunoassay methods with avidin and biotin. Later, reduced oxygen consumption under aerobic conditions in skin fibroblasts and compound heterozygous variants of the mitochondrial arginine tRNA synthetase gene were identified, and the patient was diagnosed with PCH6. CONCLUSIONS In this case, the clinical symptoms and physical findings were incompatible with the thyroid function. These laboratory findings could have mimicked Graves' disease due to the biotin interference with immunoassays. Therefore, caution is required when evaluating similar cases.

Comparison of 5-year safety and efficacy of laser photocoagulation and intravitreal bevacizumab injection in retinopathy of prematurity.

PURPOSE: To compare laser photocoagulation and intravitreal injection of bevacizumab (IVB) treatment for retinopathy of prematurity (ROP). METHODS: The study included 52 eyes of 26 patients after ROP treatment who were observed up to 5 years of age. Twenty-eight eyes received laser photocoagulation as the initial treatment (laser group), and twenty-four eyes underwent IVB (IVB group). We collected data on gestational age, birth weight, 1- and 5-min Apgar scores, zone and stage at the time of treatment, recurrence of ROP and best-corrected visual acuity (BCVA) (logMAR), equivalent spherical value (SE), ocular complications, and developmental delay at the age of 5. RESULTS: More zone I low-stage eyes were treated with IVB than laser. There was no difference in BCVA (p = 0.836). Although the mean SE was not different between the groups (p = 0.280), the prevalence of myopia was significantly higher in the laser group (p = 0.020). Developmental delay was observed in 3 of 14 and 3 of 12 cases in the laser and IVB groups, respectively (p = 0.596). Retinal holes were observed in 2 eyes in the IVB group, with 1 developing localized retinal detachment. There were no significant differences between the groups in the other factors. CONCLUSIONS: Compared to laser for ROP, IVB was not inferior in neurodevelopment or visual outcome and was superior in refractive error. As cases in the IVB group showed retinal holes, long-term follow-up with fundus examination is recommended after IVB.

Nationwide survey of late-onset hemolysis in very low birthweight infants.

BACKGROUND: In Japan, some cases of late-onset acute hemolysis in very low birthweight (VLBW) infants have been reported. These cases had common features but the cause of hemolysis was unknown. The incidence and prognosis of this disease are also unknown. However, there are only few reports of such hemolytic episodes in countries other than Japan. Thus, this study aimed to examine the incidence and clinical course of late-onset acute hemolysis and to establish it as a new disease concept. METHODS: A nationwide prospective survey was conducted from 2011 to 2015 as a rare disease surveillance project of the Japan Society for Neonatal Health and Development. RESULTS: Twenty-four cases were confirmed. The median (range) gestational age, birthweight, and onset of hemolytic episodes were 26 weeks and 2 days (23 weeks and 4 days-31 weeks and 2 days), 898 g (627-1,416 g), and 19 days after birth (9-33 days), respectively. Phototherapy, blood transfusion, and exchange transfusion were required in 22 (96%), 24 (100%), and 7 (29%) cases, respectively. During the observation period, no recurrence of the hemolytic episode occurred. All patients survived; however, one case developed kernicterus and suffered severe neurological sequelae. CONCLUSIONS: In this study, at least 1 out of 1,259 VLBW infants developed hemolysis at 9-33 days after birth in Japan. Owing to the risk of kernicterus, this disease should be recognized as among the important pathological conditions of VLBW infants, suggesting the need to manage jaundice and anemia until 5 weeks after birth.

Ideal endotracheal tube insertion depth in neonates with a birthweight less than 750 g.

BACKGROUND: Appropriate management of the endotracheal tube (ETT) insertion depth is important. The depth calculated using Tochen's formula is overestimated in extremely-low- birthweight infants, particularly those with a birthweight <750 g. Gestational age has been shown to be particularly useful in the Neonatal Resuscitation Program, 7th edition.5 However, a randomized trial for estimating the ETT insertion depth failed to show the advantage of using gestational age over birthweight.6 Therefore, we aimed to estimate the appropriate ETT insertion depth in neonates weighing <750 g. METHODS: This was a single-center, retrospective observational study including neonates weighing <750 g who required intubation. The appropriate depth was determined by adjusting the distance between the actual ETT position and the area from the first to the second thoracic vertebra on the radiograph. Correlations between gestational age and physique were investigated using Pearson's correlation coefficient. We examined small-for- gestational-age (SGA) infants and non-SGA infants separately. RESULTS: Forty neonates were enrolled in this study. The mean gestational age and birthweight were 26.3 weeks and 620 g respectively. Twenty infants were SGA. The ETT position was deep in 35 of 40 cases, with the strongest correlation between weight and ETT insertion depth. The correlation with gestational age was not observed in this study. CONCLUSIONS: Our study showed that the ideal ETT insertion depth at birth correlates with birthweight in neonates weighing <750 g. Therefore, determination by gestational age may not be feasible in populations with a high proportion of SGA infants.

Ultrasonographic confirmation of endotracheal intubation in extremely low birthweigh infants - secondary publication.

BACKGROUND: The purpose of this study was to investigate the usefulness of ultrasonography (US) for confirmation of endotracheal tube (ETT) placement during resuscitation in extremely low birthweight (ELBW) infants. METHODS: We conducted a retrospective review of the medical records of ELBW infants in whom ETT position was verified using US between June 2016 and September 2017. We investigated the backgrounds of the patients and US investigators, and the time required for the detection of exhaled carbon dioxide using the colorimetric method and US. RESULTS: Eleven ELBW infants were evaluated using US by four neonatologists. The median duration required to determine the ETT position by the colorimetric method and US were 11 s and 3 s, respectively. In six ELBW infants, we were able to verify the ETT position more rapidly using US than using the colorimetric method, and were able to perform prompt resuscitation. Unnecessary reintubations were avoided in three ELBW infants. CONCLUSION: Ultrasonography allowed the swift confirmation of the tracheal intubations. The colorimetric method yielded false negative results; in such cases, unnecessary reintubation could have been avoided if US was used. We assessed the mechanism of false negative results and performed appropriate resuscitation.

Neonatal outcomes of very low birthweight infants born to mothers with hyperglycaemia in pregnancy: a retrospective cohort study in Japan.

OBJECTIVE: To examine the mortality and morbidities of very low birthweight (VLBW, <1500 g) infants of mothers with hyperglycaemia in pregnancy. DESIGN AND SETTING: We conducted a retrospective cohort study using data from the Neonatal Research Network of Japan, a nationwide registry of VLBW infants (2003-2012). PATIENTS: We studied 29 626 infants born at 23 to 32 weeks without major congenital anomalies, of which 682 (2.3%) infants were from pregnancies affected by maternal hyperglycaemia. MAIN OUTCOME MEASURES: The primary outcome was hospital mortality. Secondary outcomes were neonatal morbidities and their anthropometric values. Associations between maternal hyperglycaemia and each outcome were observed for the overall period, and statistical tests for interaction were conducted to assess whether they differed before or after the adoption of the International Association of Diabetes in Pregnancy Study Group (IADPSG) guidelines in 2010 for the diagnosis of gestational diabetes mellitus. RESULTS: Overall, hospital mortality (4.1% vs 5.2%), composite outcomes of mortality and severe morbidity (54.2% vs 60%), and anthropometric values were not significantly different between infants of mothers with or without hyperglycaemia in pregnancy. However, the incidence of respiratory distress syndrome (RDS) in VLBW infants from mothers with hyperglycaemia was significantly higher than those from mothers without it only before (relative risk (RR) 1.09, 95% CI 1.00 to 1.19) and not after (RR 0.97, 95% CI 0.83 to 1.11) the adoption of the IADPSG guidelines. CONCLUSION: VLBW infants born to mothers with hyperglycaemia in pregnancy do not seem to be at higher risk of mortality and morbidities, except for RDS only before the adoption of the IADPSG guidelines.