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.

Variants in KIF2A cause broad clinical presentation; the computational structural analysis of a novel variant in a patient with a cortical dysplasia, complex, with other brain malformations 3.

Cortical dysplasia, complex, with other brain malformations 3 (CDCBM3) is a rare autosomal dominant syndrome caused by Kinesin family Member 2A (KIF2A) gene mutation. Patients with CDCBM3 exhibit posterior dominant agyria/pachygyria with severe motor dysfunction. Here, we report an 8-year-old boy with CDCBM3 showing a typical, but relatively mild, clinical presentation of CDCBM3 features. Whole-exome sequencing identified a heterozygous mutation of NM_001098511.2:c.1298C>A [p.(Ser433Tyr)]. To our knowledge, the mutation has never been reported previously. The variant was located distal to the nucleotide binding domain (NBD), in which previously-reported variants in CDCBM3 patients have been located. The computational structural analysis showed the p.433 forms the pocket with NBD. Variants in KIF2A have been reported in the NBD for CDCBM3, in the kinesin motor 3 domain, but not in the NBD in epilepsy, and outside of the kinesin motor domain in autism spectrum syndrome, respectively. Our patient has a variant, that is not in the NBD but at the pocket with the NBD, resulting in a clinical features of CDCBM3 with mild symptoms. The clinical findings of patients with KIF2A variants appear restricted to the central nervous system and facial anomalies. We can call this spectrum "KIF2A syndrome" with variable severity.

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.

A Follow-Up Report of an Infant Born to a Mother Receiving Tamoxifen.

Tamoxifen, an estrogen receptor antagonist, is contraindicated in pregnant women due to its teratogenic activity. In the present study, we report the case of an infant whose mother received tamoxifen for breast cancer while unaware of the pregnancy. The infant, born at 29 weeks and 6 days of gestational age with a birth weight of 1664 g, had no congenital anomalies. This case presents detailed information on the development of an infant with placental transfer of tamoxifen. The infant has grown and developed normally throughout a 5-year follow-up period, but long-term vigilance continues.

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.

Fibroblast growth factor-2 inhibits CD40-mediated periodontal inflammation.

Fibroblast growth factor-2 (FGF-2) stimulates periodontal regeneration by a broad spectrum of effects on periodontal ligament (PDL) cells, such as proliferation, migration, and production of extracellular matrix. A critical factor in the success of periodontal regeneration is the rapid resolution of inflammatory responses in the tissue. We explored an anti-inflammatory effect of FGF-2 during periodontal regeneration and healing. We found that FGF-2 on mouse periodontal ligament cells (MPDL22) markedly downregulated CD40 expression, a key player of inflammation. In addition, FGF-2 inhibited CD40 signaling by the non-canonical nuclear factor-kappa B2 (NFκB2) pathway, resulting in decreased production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which have the potential to recruit immune cells to inflamed sites. Furthermore, in vivo treatment of FGF-2 enhanced healing of skin wounds by counteracting the CD40-mediated inflammation. These results reveal that FGF-2 has an important function as a negative regulator of inflammation during periodontal regeneration and healing.

Cord blood insulin-like growth factor (IGF)-1, IGF-binding proteins and adiponectin, and birth size in offspring of women with mild gestational diabetes.

OBJECTIVE: To clarify the impact of a mild form of gestational diabetes mellitus (GDM) on neonatal birth size, and on insulin-related hormones and adiponectin (AdipoQ) in cord blood. METHODS: Two hundred and sixteen Japanese pregnant women diagnosed as having normal glucose tolerance according to the JSOG criteria were enrolled. Of the 216 women, 38 women were reclassified into a mild GDM (mGDM) group according to the IADPSG criteria. Of the remaining 178 women, 135 women with normal 50-g glucose challenge test were reclassified into a normal glucose tolerance (NGT) group. Cord blood insulin-like growth factor (IGF)-1, IGF-binding proteins (IGFBPs) and AdipoQ were measured in the offspring of the two groups. RESULTS: Birth weight and its SD scores were larger in the mGDM group than in the NGT group. The incidence of large-for-gestational age (LGA) newborns was higher in the mGDM than in the NGT group. No differences in cord blood free IGF-1, IGFBP-1, IGFBP-2 or AdipoQ levels were observed between the mGDM and NGT groups. CONCLUSIONS: Our study suggests that mild GDM reclassified according to the IADPSG criteria influences neonatal birth size, but neither the IGF-IGFBP axis nor AdipoQ can account for the changes of birth size in offspring of women with mild GDM.

Association of adiponectin polymorphism with cord blood adiponectin concentrations and intrauterine growth.

To assess whether adiponectin gene (ADIPOQ) polymorphism is associated with intrauterine fetal growth and cord blood adiponectin, we investigated eight single-nucleotide polymorphisms (SNPs; rs182052, rs710445, rs16861205, rs12495941, rs1501299, rs3774261, rs2082940 and rs266729) in ADIPOQ and birth weight and cord blood adiponectin in 526 healthy neonates. We found that the neonates carrying the G allele of rs266729 had a significantly greater birth weight s.d. score than those homozygous for the C allele (CC: -0.06±0.75 versus CG: 0.20±0.64 versus GG: 0.07±0.78; P=1.65 × 10(-3), adjusted P=9.90 × 10(-3)). However, this difference was not significant after adjustment for cord blood adiponectin (P=0.04, adjusted P=0.26). The rs266729 SNP was strongly associated with cord blood adiponectin; neonates with rs266729 GG had the highest adiponectin (CC: 34.1±20.2 versus CG: 44.3±26.1 versus GG: 54.1±36.7 µg ml(-1), P=2.80 × 10(-9), adjusted P=1.68 × 10(-8)). This association remained after adjustment for birth weight s.d. score (P=6.63 × 10(-8), adjusted P=3.98 × 10(-7)). Our results suggest that the influence of the rs266729 SNP in ADIPOQ on birth weight may be dependent on circulating adiponectin.