Association between treatment for retinopathy of prematurity and blood monocyte counts.

PURPOSE: To investigate blood monocyte counts as a risk factor for retinopathy of prematurity (ROP) treatment. DESIGN: Retrospective cohort study. METHODS: Infants who underwent ROP screening at Shiga University of Medical Science Hospital between January, 2011 and July, 2021 were included in this study. Screening criteria were a gestational age (GA) < 32 weeks or birth weight (BW) < 1500 g. The week with the largest difference in monocyte counts between the infants with and without type 1 ROP determined based on the effect size. Multivariate logistic regression analysis was applied to investigate whether the monocyte counts constituted an independent risk factor for type 1 ROP. The objective variable was type 1 ROP, and the explanatory variables were GA, BW, infants' infection, and Apgar score at 1 min and monocyte counts in the week with the largest monocyte-counts difference between the with- and without type 1 ROP groups. RESULTS: In total, 231 infants met the inclusion criteria. The monocyte counts in the fourth week after birth (4w MONO) exhibited the largest difference between infants with and without type 1 ROP. The analysis was performed on 198 infants, excluding 33 infants without 4w MONO data. Thirty-one infants had type 1 ROP, whereas 167 infants did not. BW and 4w MONO were significantly associated with type 1 ROP (odds ratio: 0.52 and 3.9, P < .001 and 0.004, respectively). CONCLUSIONS: The 4w MONO was an independent risk factor for type 1 ROP and may be useful in follow-up of infants with ROP.

Surgical treatment of traction retinal detachment associated with compound heterozygous congenital protein C deficiency.

Purpose: Congenital protein C deficiency leads to a prothrombotic state that may result in potentially sight- and life-threatening thromboembolic attacks. In this report, we report two cases of infants with compound heterozygous protein C deficiency who underwent lensectomies and vitrectomies for the treatment of traction retinal detachments (TRDs). Observations: One two-month-old and one three-month-old female neonates with leukocoria and purpura fulminans received a diagnosis of protein C deficiency and were referred to ophthalmology. In both cases, the right eye had a total retinal detachment that was considered inoperable, while the left eye had a partial TRD for which surgery was performed. Of the two operated eyes, one resulted in a total retinal detachment, while the other eye has remained stable with no retinal detachment progression three months after surgery. Conclusions: Compound heterozygous congenital protein C deficiency may lead to the rapid development of severe TRDs with poor visual and anatomical prognoses. Early diagnosis and surgery for the treatment of partial TRDs with low disease activity may help prevent progression towards total retinal detachments in these infants.

Blood neutrophil-to-lymphocyte ratio as a risk factor in treatment for retinopathy of prematurity.

PURPOSE: To investigate the blood neutrophil-to-lymphocyte ratio (NLR) as a risk factor for retinopathy of prematurity (ROP) development or treatment. METHODS: Retrospective cohort study. Infants who underwent ROP screening at Shiga University of Medical Science Hospital and Omihachiman Community Medical Center between April 2010 and December 2021 were included in this study. Screening criteria were gestational age (GA) < 32 weeks or birth weight (BW) < 1500 g. Multivariate logistic regression analysis was applied to investigate whether the NLR constituted an independent risk factor for ROP development or treatment. The objective variable was ROP development or treatment, and the explanatory variables were GA, BW, NLR, maternal infection or clinical chorioamnionitis and corticosteroid use by the mother. Maternal infection or clinical chorioamnionitis and corticosteroid use by the mother was included in the explanatory variables to adjust for factors affecting the NLR. RESULTS: In total, 220 infants met the inclusion criteria, of whom 125 developed ROP, whereas 95 infants did not display ROP. GA was significantly associated with ROP development (odds ratio (OR): 0.41, p < 0.001); however, the NLR was not significantly associated with ROP development (OR: 1.0, p = 0.74). Thirty-eight infants received treatment for ROP, whereas 182 infants had no such treatment. BW and the NLR were significantly associated with ROP treatment (OR: 1.6 and 0.66, p < 0.001 and 0.003, respectively). CONCLUSION: The NLR was not a risk factor for ROP development but was a risk factor for ROP treatment.

Changes in fetal growth restriction and retinopathy of prematurity during the coronavirus disease 2019 pandemic: A cross-sectional study.

PURPOSE: To investigate changes in the number of preterm infants, low birth weight infants, and infants with fetal growth restriction (FGR) or retinopathy of prematurity (ROP) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this retrospective cross-sectional study, we reviewed the medical records of infants born and admitted to the neonatal intensive care unit and growth care unit of Shiga University of Medical Science Hospital before the COVID-19 pandemic (April 1, 2019 to September 30, 2019) and during the pandemic (April 1, 2020 to September 30, 2020). Medical records of infants' mothers were also collected. Preterm infants, low birth weight infants, infants with FGR, infant and maternal factors associated with FGR, and infants requiring treatment for ROP were compared between the two periods. RESULTS: There were fewer infants born at < 28 weeks of gestation, infants with birth weight < 1,500 g, and infants with FGR during the pandemic period than the pre-pandemic period (pre-pandemic: n = 4 vs. during pandemic: n = 0, P = 0.048; pre-pandemic: n = 15 vs. during pandemic: n = 6, P = 0.02; and pre-pandemic: n = 31 vs. during pandemic: n = 12, P = 0.0002, respectively). There were no significant differences in any infant or maternal factors associated with FGR. The number of infants requiring treatment for ROP decreased during the pandemic, although this difference was not statistically significant (pre-pandemic: n = 3 vs. during pandemic: n = 0, P = 0.08). CONCLUSIONS: Our findings showed a reduction in the number of infants with FGR during the COVID-19 pandemic. The number of infants born at < 28 weeks of gestation and infants with birth weight < 1,500 g also decreased during the pandemic period. There was a trend toward fewer infants requiring treatment for ROP during the COVID-19 pandemic.

Chronological changes of serum exosome in preterm infants: A prospective study.

BACKGROUND: Exosomes, which are observed in all human fluid, including serum, are nanosized extracellular vesicles with a mechanism of intercellular communication. Potential clinical applications of exosomes in neonatal diseases have recently been discussed. However, the characteristics of exosomes in serum during early infancy is unclear. METHODS: In this prospective study, we evaluated the chronological changes in the concentration of serum-derived exosomes of 20 infants for 12 months after birth. RESULTS: The average concentration of serum-derived exosomes was 4.6 × 1010 particles/mL at birth and increased significantly until the age of 48 weeks. There was a moderate correlation between the gestational age and the concentration of serum-derived exosomes both at birth (r = 0.54, P = 0.01) and during the 8 weeks after birth (r = 0.48, P < 0.001). A multivariable analysis showed that gestational age at birth was associated with the concentration of serum-derived exosomes at birth (partial regression coefficient, 0.86; 95% confidence interval, 0.37-1.37; P = 0.002). CONCLUSIONS: The concentration of serum-derived exosomes in preterm infants increased both chronologically and by gestational age after birth. These basic data may help to further understand physiology of exosomes in preterm infants.

Effect of intravitreal bevacizumab for retinopathy of prematurity on weight gain.

PURPOSE: To evaluate the short-term effect on body weight (BW) gain after intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP). METHODS: This was a retrospective 1:1 matched case-control study. Infants with ROP treated by IVB or photocoagulation (PC) at Shiga University of Medical Science Hospital between April 2010 and December 2019 were included in the study. To match BWs at treatment between the IVB and PC groups, 1:1 matching for BWs at treatment within 100 g was performed. The BW gains for the 7 days before treatment (pre-treatment week), the 7 days after treatment (first post-treatment week), and the period from 7 to 14 days after treatment (second post-treatment week) were compared between the IVB and PC groups. RESULTS: Following 1:1 matching, 13 infants in both groups were enrolled in the analysis. The weekly BW gain for the first post-treatment week was significantly lower in the IVB group compared with the PC group (86 g vs. 145 g; P = 0.046), whereas the weekly BW gains for the pre-treatment week (173 g vs. 159 g; P = 0.71) and the second post-treatment week (154 g vs. 152 g; P = 0.73) were comparable between the two groups. The short-term inhibitive effect of IVB on BW gain was particularly observed in infants weighing less than 1500 g at treatment (<1500 g: 47 g vs. ≥1500 g: 132 g; P = 0.03). CONCLUSION: IVB could have a short-term inhibitive effect on BW gain in infants with ROP, and this effect is more likely to occur in infants with a lower BW at the time of treatment.

Systemic adverse events after screening of retinopathy of prematurity with mydriatic.

PURPOSE: To evaluate systemic adverse events after screening for retinopathy of prematurity (ROP) performed with mydriatic. METHODS: This was a retrospective case series study. Medical records of consecutive patients who underwent screening for ROP with 0.5% phenylephrine and 0.5% tropicamide eyedrops were retrospectively reviewed. The score of abdominal distention (0-5), volume of milk sucked and volume of stool, along with systemic details (pulse and respiration rates, blood pressure and number of periods of apnea) were collected at 1 week and 1 day before ROP examination, and at 1 day after examination. Results were compared between the days before and after examination. Correlation between body weight at the time of examination and the score of abdominal distention was examined. The numbers of infants with abdominal and/or systemic adverse events were compared between pre- and post-examination periods. RESULTS: Eighty-six infants met the inclusion criteria. The score of abdominal distention increased from 2.0 at 1 day before examination to 2.3 at 1 day after examination (p = 0.005), and the number of infants who had worsened abdominal distension increased after examination (p = 0.01). Infants with lower body weight had a higher score of abdominal distention (p < 0.0001, r = -0.57). The number of infants with reduced milk consumption increased after examination (p = 0.0001), as did the number of infants with decreased pulse rate (p = 0.0008). CONCLUSIONS: Screening for ROP with mydriatic may have adverse effects on systemic conditions. Infants should be carefully monitored after ROP screening with mydriatic.

Short-Term Changes in Intraocular Pressure After Intravitreal Injection of Bevacizumab for the Treatment of Retinopathy of Prematurity.

PURPOSE: To evaluate short-term changes in intraocular pressure after intravitreal injection of bevacizumab for retinopathy of prematurity. PATIENTS AND METHODS: This study was a prospective case-series. Consecutive infants underwent intravitreal injection with bevacizumab for type 1 retinopathy of prematurity at a university hospital. Intraocular pressure was measured with tonometer at baseline, at 1 min, and at 3, 10, 30 and 60 mins after injection. RESULTS: Five patients (four boys) were enrolled in this study. Mean (± standard deviation) intraocular pressure was 8.0 ± 2.4 mmHg (range: 6-11.5 mmHg) just before the intravitreal injection, and the pressures were 19.8 ± 2.8 mmHg (16.4-23.9 mmHg), 14.6 ± 4.4 mmHg (7.6-18.4 mmHg), 11.2 ± 4.2 mmHg (6.4-16.5 mmHg), 9.3 ± 3.5 mmHg (5.8-13.2 mmHg), and 8.2 ± 1.4 mmHg (6.9-10.0 mmHg) at 1 min, 3, 10, 30 and 60 mins after the injection, respectively. Mean intraocular pressure after 1 min was significantly higher than intraocular pressure before injection (p = 0.02). Pressures decreased between 1 min and 3 mins after intravitreal injection, although there was no statistically significant difference between the pressures at those time-points. Intraocular pressures after 3, 10, 30 and 60 mins were not significantly different from the pressure before injection. CONCLUSION: Intraocular pressure elevation after intravitreal injection of bevacizumab for neonatal infants may be mild, so there may be a limited risk due to intraocular pressure after intraocular injection of bevacizumab for retinopathy of prematurity.

Poor Bifidobacterial Colonization Is Associated with Late Provision of Colostrum and Improved with Probiotic Supplementation in Low Birth Weight Infants.

This study aimed to evaluate the association between bifidobacterial colonization in low birth weight infants and perinatal factors, including the timing of initial colostrum and the effect of probiotics on this colonization. In this non-randomized controlled trial, we enrolled 98 low-birth-weight infants from a neonatal intensive care unit (NICU) in Japan. Infants were divided into three groups: group N (no intervention), group H (received non-live bifidobacteria), and group L (received live bifidobacteria). The number of bifidobacteria in the infants' stools at 1 month of age was measured using real-time polymerase chain reaction (PCR). We divided infants into "rich bifidobacteria" (≥104.8 cells/g feces) and "poor bifidobacteria" (<104.8 cells/g feces) subgroups. The ratio of "rich bifidobacteria" infants was 20/31, 34/36, and 30/30 in groups N, H, and L, respectively. In group N, the "rich bifidobacteria" group received first colostrum significantly earlier than the "poor bifidobacteria" group (1 day vs. 4 days, P < 0.05). Compared with the N group, both groups H and L had a significantly high proportion of "rich bifidobacteria" infants (P < 0.05). Bifidobacterial colonization was poor in premature infants at 1 month compared with term infants, and the level of colonization was associated with the timing of initial provision of colostrum. Providing probiotics to premature infants can improve bifidobacterial colonization.

The histological findings in transposition of the great artery with severe persistent pulmonary hypertension of the newborn.

The combination of persistent pulmonary hypertension of the newborn (PPHN) and transposition of the great arteries (TGA) has serious impacts on treatment and prognosis, often with adverse outcomes. We report the case of a male full-term newborn with TGA with intact ventricular septum and severe PPHN who died 2 h after birth; further, we examined his vascular histology. On autopsy, lung histology showed mild fibrous hypertrophy in the intima and moderate medial hypertrophy of the minimal pulmonary artery. Hypoplasia of the pulmonary artery was not detected. Pulmonary congestion was detected and pneumatization was poor. Debris was present in the alveoli. Hemosiderin deposition was detected, suggesting prenatal hemostasis or hemorrhage. Severe PPHN may have occurred because of pulmonary arterial spasm accompanying pulmonary congestion which had been in the fetal stage. A wide range of lesions can be present in the pulmonary vascular bed in TGA. The pathologies of pulmonary vascular tissues with TGA and PPHN are not uniform. .

Bilirubin Uridine Diphosphate-glucuronosyltransferase Polymorphism as a Risk Factor for Prolonged Hyperbilirubinemia in Japanese Preterm Infants.

OBJECTIVE: To determine whether a variant of the bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1*6) is a risk factor for prolonged hyperbilirubinemia in preterm infants. STUDY DESIGN: UGT1A1 genotypes in 46 Japanese preterm infants (<37 weeks of gestation) were compared with UGT1A1 genotypes in 38 control infants, using polymerase chain reaction-direct sequencing. Prolonged unconjugated hyperbilirubinemia was defined as serum total bilirubin concentration of >150 µmol/L (8.77 mg/dL) beyond 14 days of life. RESULTS: In the case group, 41 of 46 infants (89.1%) had a polymorphic variant, c.211G>A, p.G71R (UGT1A1*6). In the control group, 7 of 38 (18.4%) had UGT1A1*6. The allele frequency of UGT1A1*6 was 0.641 in the prolonged hyperbilirubinemia group, which was significantly higher than in the control group (0.092; P < .001). In total, 39 of 46 infants in the case group were breast fed, and only 10 infants in the control group were breast fed. CONCLUSIONS: These data suggest that UGT1A1*6 is a risk factor for prolonged unconjugated hyperbilirubinemia in preterm infants in Japan. Given the different rate of breast feeding in this study, additional data are necessary for drawing a definitive conclusion.

Bifidobacterium bifidum OLB6378 Simultaneously Enhances Systemic and Mucosal Humoral Immunity in Low Birth Weight Infants: A Non-Randomized Study.

Probiotic supplementation has been part of the discussion on methods to enhance humoral immunity. Administration of Bifidobacterium bifidum OLB6378 (OLB6378) reduced the incidence of late-onset sepsis in infants. In this non-randomized study, we aimed to determine the effect of administration of live OLB6378 on infants' humoral immunity. Secondly, we tried to elucidate whether similar effects would be observed with administration of non-live OLB6378. Low birth weight (LBW) infants weighing 1500-2500 g were divided into three groups: Group N (no intervention), Group L (administered live OLB6378 concentrate), and Group H (administered non-live OLB6378 concentrate). The interventions were started within 48 h after birth and continued until six months of age. Serum immunoglobulin G (IgG) levels (IgG at one month/IgG at birth) were significantly higher in Group L than in Group N (p < 0.01). Group H exhibited significantly higher serum IgG levels (p < 0.01) at one month of age and significantly higher intestinal secretory immunoglobulin A (SIgA) levels (p < 0.05) at one and two months of age than Group N. No difference was observed in the mortality or morbidity between groups. Thus, OLB6378 administration in LBW infants enhanced humoral immunity, and non-live OLB6378, which is more useful as a food ingredient, showed a more marked effect than the viable bacteria.

Possible Prevention of Neonatal Death: A Regional Population-Based Study in Japan.

PURPOSE: The neonatal mortality rate in Japan has currently been at the lowest level in the world. However, it is unclear whether there are still some potentially preventable neonatal deaths. We, therefore, aimed to examine the backgrounds of neonatal death and the possibilities of prevention in a region of Japan. MATERIALS AND METHODS: This is a population-based study of neonatal death in Shiga Prefecture of Japan. RESULTS: The 103 neonatal deaths in our prefecture between 2007 and 2011 were included. After reviewing by a peer-review team, we classified the backgrounds of these neonatal deaths and analyzed end-of-life care approaches associated with prenatal diagnosis. Furthermore, we evaluated the possibilities of preventable neonatal death, suggesting specific recommendations for its prevention. We analyzed 102 (99%) of the neonatal deaths. Congenital malformations and extreme prematurity were the first and the second most common causes of death, respectively. More than half of the congenital abnormalities (59%) including malformations and chromosome abnormality had been diagnosed before births. We had 22 neonates with non-intensive care including eighteen cases with congenital abnormality and four with extreme prematurity. Twenty three cases were judged to have had some possibility of prevention with one having had a strong possibility of prevention. Among specific recommendations of preventable neonatal death, more than half of them were for obstetricians. CONCLUSION: There is room to reduce neonatal deaths in Japan. Prevention of neonatal death requires grater prenatal care by obstetricians before birth rather than improved neonatal care by neonatologists after birth.

Genotype of UGT1A1 and phenotype correlation between Crigler-Najjar syndrome type II and Gilbert syndrome.

BACKGROUND AND AIMS: Hereditary unconjugated hyperbilirubinemias, Crigler-Najjar syndrome type I, Crigler-Najjar syndrome type II (CN-2), and Gilbert syndrome (GS) all result from mutations of the bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase gene (UGT1A1). Often, to distinguish between CN-2 and GS is difficult because the borderline of the two syndromes is unclear. We analyzed the genotypes and phenotypes of 163 Japanese patients with CN-2 or GS. METHODS: Japanese patients (99 males and 64 females) with unconjugated hyperbilirubinemia were analyzed. Their serum bilirubin concentrations varied from 1.2 to 22.2 mg/dL (20 to 379 µM). Genetic analysis of UGT1A1 was performed by PCR-amplified direct sequencing. Association between serum bilirubin concentrations and genotypes group (typical CN-2, intermediate group, and typical GS) was studied. RESULTS: Most patients had biallelic mutations of UGT1A1. Moreover, many of them (78.5%) had multiple mutations. The mutation in typical CN-2 was a homozygous double missense mutation of p.[G71R:Y486D]. In typical GS group, four prevalent genotypes were detected: homozygous UGT1A1*28, UGT1A1*6/UGT1A1*28, and homozygous UGT1A1*6, and UGT1A1*27/UGT1A1*28. In the intermediate group, three genotypes, p.[G71R:Y486D]/UGT1A1*7, p.[G71R:Y486D]/UGT1A1*6, and homozygous UGT1A1*7, were detected. Serum bilirubin concentrations of typical CN-2, intermediate group, and typical GS are respectively 12.9 ± 5.1, 5.2 ± 2.2, and 2.8 ± 1.1 mg/dL. Serum bilirubin concentration among the three groups is statistically different (P < 0.0001). CONCLUSIONS: The serum bilirubin concentration varied continuously from GS to CN-2 depending on genotypes. Because of the combination of the mutations and polymorphisms, many patients showed intermediate serum bilirubin concentration between two syndromes. Clinically, it is difficult to distinguish clearly between the two syndromes.

Neonatal Meckel diverticulum: Obstruction due to a short mesodiverticular band.

This is the first report of symptomatic Meckel diverticulum in a newborn, in which direct compression by a short mesodiverticular band (MDB) caused intestinal obstruction. A short MDB can cause intestinal obstruction due to direct compression. There are two mechanisms by which Meckel diverticulum with MDB can cause intestinal obstruction: internal hernia and direct compression. Onset of intestinal obstruction due to direct compression by a short MDB might be earlier than that for internal hernia with long MDB.

Suspected fetal onset of neonatal transient eosinophilic colitis and development of respiratory distress.

Neonatal transient eosinophilic colitis (NTEC) is a new disease concept within eosinophilic gastroenteritis, which was proposed by Ohtsuka et al. It causes hematochezia as a result of eosinophilia, in neonates who have not yet started to receive enteral nutrition, although the whole-body status of the infant is in fact relatively good. To date, there have been no reports of this disease in which abnormalities were noted during gestation, and the clinical phenomena surrounding it, along with any complications, are not yet clear. We encountered a suspected case of NTEC causing respiratory distress with aspiration of hematochezia, in which dilated bowel was noted during gestation. This case indicates that NTEC may occur at the fetal stage and be complicated by respiratory distress.

Bilirubin uridine diphosphate-glucuronosyltransferase variation is a genetic basis of breast milk jaundice.

OBJECTIVE: To evaluate the role of bilirubin UDP-glucuronosyltransferase family 1, polypeptide A1 (UGT1A1) gene variations on prolonged unconjugated hyperbilirubinemia associated with breast milk feeding (breast milk jaundice [BMJ]). STUDY DESIGN: UGT1A1 gene allelic variation was analyzed in 170 Japanese infants with BMJ with polymerase chain reaction-direct sequencing, and their genotypes compared with serum bilirubin concentrations. In 62 of 170 infants, serum bilirubin concentration was followed after 4 months of life. Genotypes were examined in 55 infants without BMJ. RESULTS: Of 170 infants with BMJ, 88 (51.8%) were homozygous UGT1A1*6. Serum bilirubin concentrations (21.8 ± 3.65 mg/dL) were significantly greater than in infants with other genotypes (P < .0001). The Gilbert UGT1A1*28 allele was not detected in infants with BMJ, except in an infant who was compound heterozygous with UGT1A1*6. At 4 months of age, serum bilirubin concentration improved to >1 mg/dL, except in 2 infants who were homozygous UGT1A1*7. Homozygous UGT1A1*6 was not detected in the control group. CONCLUSION: One-half of the infants with BMJ were homozygous UGT1A1*6 and exhibited a serum bilirubin concentration significantly greater than other genotypes. This finding indicates that UGT1A1*6 is a major cause of BMJ in infants in East Asia. Previous finding have demonstrated that 5ß-pregnane-3α,20ß-diol present in breast milk inhibits p.G71R-UGT1A1 bilirubin glucuronidation activity. Thus, prolonged unconjugated hyperbilirubinemia may develop in infants with UGT1A1*6 who are fed breast milk.

Efficacy of bronchial fiberscope in esophageal fistula caused by necrotizing bronchitis.

Neonatal necrotizing bronchitis is a disease that occurs in premature and low-birthweight infants who are subject to artificial respiratory management, and which has a poor prognosis, because it progresses suddenly and can result in death. There have been no reports of survival to date in cases of tracheo-esophageal fistula caused by necrotizing bronchitis, and no swift and effective management method has yet been reported. This report describes a case in which the use of a bronchial fiberscope in making an early diagnosis facilitated appropriate management and survival. The proactive use of a bronchial fiberscope in regard to this disease, which has a high fatality rate, may save lives.