Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway, which degrades heme into equimolar amounts of carbon monoxide, free iron, and biliverdin. Its inducible isoform, HO-1, has multiple protective functions, including immune modulation and pregnancy maintenance, showing dynamic alteration during perinatal periods. As its contribution to the development of perinatal complications is speculated, two functional polymorphisms of the HMOX1 gene, (GT)_n repeat polymorphism (rs3074372) and A(-413)T single nucleotide polymorphism (SNP) (rs2071746), were studied for their association with perinatal diseases. We systematically reviewed published evidence on HMOX1 polymorphisms in perinatal diseases and clarified their possible significant contribution to neonatal jaundice development, presumably due to their direct effect of inducing HO enzymatic activity in the bilirubin-producing pathway. However, the role of these polymorphisms seems limited for other perinatal complications such as bronchopulmonary dysplasia. We speculate that this is because the antioxidant or anti-inflammatory effect is not directly mediated by HO but by its byproducts, resulting in a milder effect. For better understanding, subtyping each morbidity by the level of exposure to causative environmental factors, simultaneous analysis of both polymorphisms, and the unified definition of short and long alleles in (GT)_n repeats based on transcriptional capacity should be further investigated.

To date, the difference in neurodevelopmental outcomes between late preterm infants (LPI) born at 34 and 35 gestational weeks (LPI-34 and LPI-35, respectively) has not been elucidated. This retrospective study aimed to evaluate neurodevelopmental outcomes at 18 months of corrected age for LPI-34 and LPI-35, and to elucidate factors predicting neurodevelopmental impairment (NDI). Records of all LPI-34 (n = 93) and LPI-35 (n = 121) admitted to our facility from 2013 to 2017 were reviewed. Patients with congenital or chromosomal anomalies, severe neonatal asphyxia, and without developmental quotient (DQ) data were excluded. Psychomotor development was assessed as a DQ using the Kyoto Scale of Psychological Development at 18 months of corrected age. NDI was defined as DQ < 80 or when severe neurodevelopmental problems made neurodevelopmental assessment impossible. We compared the clinical characteristics and DQ values between LPI-34 (n = 62) and LPI-35 (n = 73). To elucidate the factors predicting NDI at 18 months of corrected age, we compared clinical factors between the NDI (n = 17) and non-NDI (n = 118) groups. No significant difference was observed in DQ values at 18 months of corrected age between the groups in each area and overall. Among clinical factors, male sex, intraventricular hemorrhage (IVH), hyperbilirubinemia, and severe hyperbilirubinemia had a higher prevalence in the NDI group than in the non-NDI group, and IVH and/or severe hyperbilirubinemia showed the highest Youden Index values for predicting NDI. Based on the results of this study, we can conclude that no significant difference in neurodevelopmental outcomes at 18 months of corrected age was observed between LPI-34 and LPI-35. Patients with severe hyperbilirubinemia and/or IVH should be considered to be at high risk for developing NDI.

(1) Background: Pseudohypoaldosteronism type 1 (PHA-1) is a disorder caused by renal tubular resistance to aldosterone and is characterized by problems with sodium regulation. PHA-1 is typically divided into primary PHA-1, which is caused by genetic mutation, and secondary PHA-1, which is associated with urinary tract abnormality. However, data on the clinical features of PHA-1 among newborn infants are limited. (2) Methods: We conducted a nationwide prospective surveillance study of neonatal PHA in Japan from 1 April 2019 to 31 March 2022 as part of a rare disease surveillance project of the Japan Society for Neonatal Health and Development. (3) Results: Fifteen cases (male:female = 7:8), including four primary, four secondary, and seven non-classified cases, were reported during the study period. The median gestational age and birthweight were 34 weeks (28–41) and 1852 g (516–4610), respectively. At the onset, the median serum Na and K levels were 132 mEq/L (117–137) and 6.3 mEq/L (4.7–8.3), respectively. The median plasma renin activity was 45 ng/mL/h (3.1–310, n = 9), active renin concentration was 1017 pg/mL (123–2909, n = 6), and serum aldosterone concentration was 5310 pg/mL (3250–43,700). (4) Conclusions: Neonatal PHA-1 was more common among preterm infants with no male predominance. It developed immediately after birth in cases without genetic or renal complications.

We report a case of a preterm infant who developed cow’s milk allergy. This male infant presented with recurrent ascites and was successfully treated with donated breast milk. He was born at 24 weeks’ gestation with a birthweight of 506 g. From day 20, infant formula, soy protein-based formula, and casein-hydrolyzed formula were used due to insufficient maternal lactation. This resulted in abdominal distention, generalized edema, and recurrent ascites. We diagnosed him with cow’s milk allergy since these symptoms improved on exclusive breast milk feeding. No recurrence of symptoms occurred when donated breast milk was used in combination with the mother’s own milk. Ascites should be regarded as a clinical symptom of neonatal cow’s milk allergy. Donated breast milk may be effective in the treatment of the allergy if breastfeeding is not available.

Background: Free bilirubin (Bf) is a better marker than total serum bilirubin (TSB) for predicting bilirubin encephalopathy (BE). To date, two UGT1A1 genetic variants (rs4148323 and rs3064744) have been associated with neonatal hyperbilirubinemia; however, the direct association between UGT1A1 variants and Bf levels in newborns has not been elucidated. Methods: We retrospectively analyzed the clinical data of 484 infants, including the genotype data of two UGT1A1 genetic variants. We divided the infants into a high Bf group (Bf ≥ 1.0 µg/dL, n = 77) and a non-high Bf group (Bf < 1.0 µg/dL, n = 407), based on the peak Bf values. Logistic regression analysis was performed to calculate the odds ratios (ORs) for each variant allele compared to wild-type alleles. Results: The frequencies of the A allele in rs4148323 and (TA)₇ allele in rs3064744 in the high Bf group (29% and 4%, respectively) were significantly different from those in the non-high Bf group (16% and 12%, respectively). In logistic regression analysis, for rs4148323, the A allele was significantly associated with an increased risk of hyper-free bilirubinemia over the G allele (adjusted OR: 1.80, 95% confidence interval [CI]: 1.19–2.72, p < 0.01). However, for rs3064744, the (TA)₇ allele was significantly associated with a decreased risk of hyper-free bilirubinemia over the (TA)₆ allele (adjusted OR: 0.42, 95% CI: 0.18–0.95, p = 0.04). Conclusions: This study is the first to show that the A allele in rs4148323 is a risk factor and that the (TA)₇ allele in rs3064744 is a protective factor for developing hyper-free bilirubinemia in Japanese newborns.

Neonatal sepsis is characterized by systemic bacterial invasion followed by a massive inflammatory response. At present, no therapeutic strategy has been found that significantly reduces the mortality of neonatal sepsis. We aimed to investigate the protective role of an initial low-dose septic challenge for the prevention of subsequent lethal sepsis in a mouse model. A stock cecal slurry (CS) solution was prepared from adult ceca. The LD83 (1.5 mg CS/g) was used for all animals. An initial challenge of normal saline (NS) or 0.5 mg CS/g (non-lethal dose) was administered at four days of age, then 1.5 mg CS/g was administered intraperitoneally at seven days of age (72 h post-initial challenge), and survival was monitored. Initial exposure to NS (n = 10) resulted in 90% mortality following exposure to the LD83 CS dose in contrast to an initial exposure to CS (n = 16), which significantly decreased mortality to 6% (p < 0.0001), reduced blood bacterial counts, attenuated inflammatory responses, and suppressed lipid mediators. Initial exposure to a non-lethal CS dose prior to exposure to a lethal CS dose significantly reduces sepsis mortality, a protective effect that might be mediated by modulating abnormal systemic inflammatory responses.