Summer Hospitalization and Bronchial Asthma Make Treatment of Respiratory Syncytial Virus Infection Difficult: A Retrospective Study in Japan.

In recent years, epidemics of respiratory syncytial virus (RSV) have been seen in the summer in Japan. Patients hospitalized in the summer used a high-flow oxygen administration device more frequently than patients hospitalized in the winter. This study was a retrospective study to examine the variables associated with duration of oxygen therapy and severe cases. Subjects were pediatric patients diagnosed with RSV infection and hospitalized for treatment during the 5 years from April 2014 to March 2019. Data from 292 patients were analyzed. Duration of oxygen therapy was significantly associated with bronchial asthma (partial regression coefficient: 0.897, P = .004). Hospitalization in summer was significantly associated with severe condition (adjusted odds ratio: 4.07, 95% confidence interval: 1.16-14.27). The present study showed that bronchial asthma is a risk factor for prolonged oxygen therapy and infection in summer is a risk factor for progression to severe condition in cases of RSV infection.

The Effect of Early Postnatal Nutrition on Human T Cell Leukemia Virus Type 1 Mother-to-Child Transmission: A Systematic Review and Meta-Analysis.

The main route of mother-to-child transmission (MTCT) of human T cell leukemia virus type 1 is vertical transmission via breastfeeding. Although the most reliable method for preventing MCTC is exclusive formula feeding (ExFF), short-term breastfeeding (STBF) or frozen-thawed breast milk feeding (FTBMF) has been offered as an alternative method if breastfeeding is strongly desired. The aim of this review was to clarify the pooled risk ratio of MCTC of STBF and FTBMF compared with ExFF. This study was registered with PROSPERO (number 42018087317). A literature search of PubMed, CINAHL, the Cochrane Database, EMBASE, and Japanese databases through September 2018 identified 1979 articles, 10 of which met the inclusion criteria. Finally, 11 articles, including these 10 studies and the report of a recent Japanese national cohort study, were included in the meta-analysis. The pooled relative risks of STBF ≤3 months, STBF ≤6 months, and FTBMF compared with ExFF were 0.72 (95% confidence interval (CI): 0.30-1.77; p = 0.48), 2.91 (95% CI: 1.69-5.03; p = 0.0001), and 1.14 (95% CI: 0.20-6.50; p = 0.88), respectively. This meta-analysis showed no statistical difference in the risk of MTCT between STBF ≤3 months and ExFF, but the risk of MTCT significantly increased in STBF ≤6 months.

A Preterm Case of Cow's Milk Allergy Presenting with Recurrent Ascites Treated with Donor Breast Milk.

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.

Midazolam Intoxication in a Premature Neonate.

PURPOSE: We report the case of a male neonate with a respiratory disorder who developed adverse cardiorespiratory symptoms after the continuous infusion of midazolam. METHODS: To clarify the cause of cardiogenic shock, we performed whole exome sequencing and screened relative single-nucleotide variants of 2 cytochrome P450 (CYP) isoforms, CYP3A4 and CYP3A5, which play a dominant role in the metabolic elimination of midazolam. We measured endogenous cortisol 6ß-hydroxylation clearance to phenotypically assess CYP3A activity. FINDINGS: The CYP3A activity level in the patient was significantly lower than the mean CYP3A activity level in healthy adults. Three intronic mutations in the CYP3A4 and CYP3A5 isoforms were detected in the patient. IMPLICATIONS: Our findings suggest that the midazolam concentration in plasma was achieved at above the steady-state concentration during continuous infusion used to sedate neonates receiving mechanical ventilatory support. Evaluation of the drug-metabolizing ability based on CYP3A might be useful if adverse electrophysiologic variables or the induction of tachycardia occur because of delayed elimination.

Policy statement of enteral nutrition for preterm and very low birthweight infants.

For preterm and very low birthweight infants, the mother's own milk is the best nutrition. Based on the latest information for mothers who give birth to preterm and very low birthweight infants, medical staff should encourage and assist mothers to pump or express and provide their own milk whenever possible. If the supply of maternal milk is insufficient even though they receive adequate support, or the mother's own milk cannot be given to her infant for any reason, donor human milk should be used. Donors who donate their breast milk need to meet the Guideline of the Japan Human Milk Bank Association. Donor human milk should be provided according to the medical needs of preterm and very low birthweight infants, regardless of their family's financial status. In the future, it will be necessary to create a system to supply an exclusive human milk-based diet (EHMD), consisting of human milk with the addition of a human milk-derived human milk fortifier, to preterm and very low birthweight infants.

Survey of a nutrition management method for very low birthweight infants: Status before wide use of breast milk banks in Japan.

BACKGROUND: The importance of breast-feeding for very low birthweight (VLBW) infants has been pointed out. Some overseas studies suggested that the standardization of enteral nutrition (EN) leads to improved prognosis in VLBW infants. In Japan, however, physicians in charge of infants are responsible for making nutrition management decisions on an individual basis. We conducted an online survey to clarify the course of nutrition management of VLBW infants currently implemented in Japan. METHODS: We mailed a notice to 300 representative neonatologists throughout Japan requesting their participation in the online survey. On the survey website, neonatologists responded to questions regarding the nutritional strategy for five birthweight groups (less than 500 g, 500-749 g, 750-999 g, 1,000-1,249 g and 1,250-1,499 g). RESULTS: Responses were recieved from 137 neonatologists. The first choice for EN up to 1 week after birth was breast milk regardless of birthweight (92.0% for 1,250-1,499 g to 95.6% for 500-999 g). More than 30% of the respondents answered that they fast infants who weigh <750 g at birth or feed them with other mothers' breast milk until their own mother's milk becomes available. The lower the birthweight, the later EN is started, and the greater the number of days to establish EN. CONCLUSION: The lower the birthweight, the more difficult it is to feed infants their own mother's milk and the later the EN is started. If donor milk is supplied in a stable manner, it takes fewer days to establish EN.

Necessity of human milk banking in Japan: Questionnaire survey of neonatologists.

BACKGROUND: If their own mother's milk (OMM) is not available, another mother's milk may be used for extremely low-birthweight (ELBW) infants. Human milk is a bodily fluid, however, therefore we have assumed that other mother's milk is currently seldom given to infants despite its superiority to formula. Although the World Health Organization and the American Academy of Pediatrics have recommended using donor human milk (DHM) from a human milk bank (HMB) in the case that OMM is not available, there is no HMB in Japan. To assess whether other mother's milk is used for ELBW infants and whether an HMB is necessary in Japan, we surveyed neonatal intensive care units (NICU) via questionnaire. METHODS: The questionnaire was sent by email to members of the Japanese Neonatologist Association who are responsible for NICU. RESULTS: In total, 126 completed questionnaires (70.7%) were returned and analyzed. One-fourth of NICU give other mother's milk to ELBW infants. The first choice of nutrition is OMM, but other mother's milk or formula is given to infants at 19% of NICU if OMM is unavailable. Approximately three-fourths of NICU would like an HMB. CONCLUSION: Although human milk contains contagious agents and authorities do not recommend giving other mother's milk as a substitute for OMM, other mother's milk is still a choice in NICU in Japan. Many neonatologists, however, would prefer a safer alternative, that is, DHM obtained from an accredited HMB. A well-regulated HMB should be established and safe DHM should be available for all preterm infants if necessary.

Accumulation of subcutaneous fat, but not visceral fat, is a predictor of adiponectin levels in preterm infants at term-equivalent age.

BACKGROUND: Preterm infants have altered fat tissue development, including a higher percentage of fat mass and increased volume of visceral fat. They also have altered adiponectin levels, including a lower ratio of high-molecular-weight adiponectin (HMW-Ad) to total adiponectin (T-Ad) at term-equivalent age, compared with term infants. AIMS: The objective of this study was to investigate the association between adiponectin levels and fat tissue accumulation or distribution in preterm infants at term-equivalent age. STUDY DESIGN: Cross-sectional clinical study. SUBJECTS: Study subjects were 53 preterm infants born at ≤34weeks gestation with a mean birth weight of 1592g. OUTCOME MEASURES: Serum levels of T-Ad and HMW-Ad were measured and a computed tomography (CT) scan was performed at the level of the umbilicus at term-equivalent age to analyze how fat tissue accumulation or distribution was correlated with adiponectin levels. RESULTS: T-Ad (r=0.315, p=0.022) and HMW-Ad levels (r=0.338, p=0.013) were positively associated with subcutaneous fat area evaluated by performing CT scan at term-equivalent age, but were not associated with visceral fat area in simple regression analyses. In addition, T-Ad (ß=0.487, p=0.003) and HMW-Ad levels (ß=0.602, p<0.001) were positively associated with subcutaneous fat tissue area, but they were not associated with visceral fat area also in multiple regression analyses. CONCLUSION: Subcutaneous fat accumulation contributes to increased levels of T-Ad and HMW-Ad, while visceral fat accumulation does not influence adiponectin levels in preterm infants at term-equivalent age.

Abdominal aortic intima-media thickness in preschool children born preterm.

Recently aortic intima-media thickness (IMT) has been used as an earlier marker of preclinical atherosclerosis in high-risk children, such as those with type 1 diabetes mellitus and hypercholesterolemia. Children who were born preterm have an early elevation in insulin resistance, which may be a risk factor for metabolic syndrome in adulthood. However, there is no optimal marker of subsequent cardiovascular disease for children born preterm. In this study, we aimed to evaluate the effect of preterm birth on aortic IMT during the preschool period. Mean aortic IMT was measured by ultrasound in 26 subjects born preterm (gestational age <37 weeks [preterm group]) and 11 control subjects born at term (term group). The mean aortic IMT of the preterm group was significantly thicker than that of the term group (preterm group: median 577 µm, interquartile range (524-599) versus term group: 517 µm (442-544); p = 0.003). Mean aortic IMT may be one of the earlier markers of subclinical vasculopathy in preschool children who were born preterm.

Preterm infants have altered adiponectin levels at term-equivalent age even if they do not present with extrauterine growth restriction.

BACKGROUND/AIMS: This study aimed to investigate total adiponectin (T-Ad) and high-molecular-weight adiponectin (HMW-Ad) levels in preterm infants at term-equivalent age and to assess the relationship between adiponectin levels and early postnatal growth. METHODS: The study included 43 term infants and 58 preterm infants born at 34 weeks' gestation or less. T-Ad and HMW-Ad levels were measured in the preterm infants at birth and at term-equivalent age, and in the term infants at birth. Adiponectin levels were statistically compared between preterm and term infants to evaluate the association between postnatal growth and changes in the adiponectin levels in preterm infants. RESULTS: The T-Ad levels were higher and the ratio of HMW-Ad to T-Ad (HMW%) was lower in preterm infants at term-equivalent age than in term infants. Further, body weight SD score changes were positively associated with T-Ad and HMW-Ad increases in preterm infants from birth to term-equivalent age. The HMW% changes had a negative association only with HMW% in cord blood. CONCLUSION: Preterm infants have altered adiponectin levels at term-equivalent age. Further, postnatal growth may contribute to adiponectin increases from birth to term-equivalent age, although HMW% changes might be regulated before birth at least up to term-equivalent age in preterm infants.

Development of fatty acid calcium stone ileus after initiation of human milk fortifier.

We report a case who was born with extremely low birth weight infant and had experienced abdominal operation for necrotizing enterocolitis, eventually developed ileus due to fatty acid calcium stones after giving human milk fortifier. He had developed necrotizing enterocolitis on day 30 of his age, such that we performed enterectomy and ileostomy. He could not tolerate enteral feeding fully, because intestinal fistula infection was repeated. Although we administered hindmilk, he grew up slowly and he suffered cholestasis as well. We performed end-to-end anastomosis to prevent fistula infections on day 87. After this operation, breast milk feeding volume was increased easily. However, we started to add HMF of half-strength on day 124, because his body weight gain remained very poor. And we confirmed to intensify the ratio of HMF full-strength on day 128. After that his abdomen had distended on day 131. As there is no effect of conservative therapy to occlusive ileus, we did emergency laparotomy on day 139. Intestinal calculi were impacted at anastomic portion. Although all stones were removed, he died on 144 days due to disseminated intravascular coagulation and renal failure. Calculi analysis revealed that all of them were fatty acid calcium stones. There is no report about like our case. We speculate that the construction of fatty acid calcium result from either high concentration of calcium/phosphorus or rapid increase in the fortification. We could have prevented this case happened by slower increment of fortification.

Low HCMV DNA copies can establish infection and result in significant symptoms in extremely preterm infants: a prospective study.

Breast milk (BM) is the main source of human cytomegalovirus (HCMV) infection. We examined whether the number of HCMV DNA copies in BM is related to HCMV infection in very low birth weight (VLBW) infants. We identified 11 pairs of VLBW infants and mothers. BM samples were collected every week until 10 weeks postpartum. Urine samples were collected from the infants within 1 week, at 6 to 8 weeks, at discharge, and whenever HCMV infection was suspected. HCMV DNA in BM was positive in 7 of 11 mothers and reached a peak at 4 to 5 weeks postpartum. Of the 11, 5 infants were determined to be infected from positive HCMV DNA in the urine, despite the fact that BM was used after being frozen. Of the five, four infected infants exhibited symptoms between 35 and 60 days of age. Symptomatic infants had longer stays and slower weight gain. The HCMV infection rate is high in very preterm infants. A new strategy to prevent HCMV infection other than freezing should therefore be established.

Cord serum adiponectin is positively related to postnatal body mass index gain.

BACKGROUND: The roles of adiponectin and leptin in the early stages of life are poorly understood. We previously studied longitudinal changes in these adipocytokines from birth to 12 months of age. The aim of this investigation was to evaluate the correlation between cord serum adipocytokine levels and postnatal growth by 3 years of age. METHODS: A questionnaire was sent to obtain the general physical measurements of 3-year-olds from 56 healthy newborn infants born at a gestational age of 35 weeks or more; 45 valid responses were obtained. The correlations between variables, including cord serum adipocytokine levels at birth and general physical measurements at 3 years, were investigated. RESULTS: Body mass index (BMI) Z-score gain from birth to 3 years was negatively correlated with birthweight SD scores (ß=-0.395, P= 0.019) and gestational age (ß=-0.557, P= 0.016), and positively correlated with cord serum adiponectin levels (ß= 0.253, P= 0.043). BMI Z-score gain from birth to 6 months was negatively correlated with only birthweight SD score (ß=-0.442, P= 0.017). Cord serum leptin levels were not a significant predictor of BMI Z-scores gain in our subjects. BMI Z-scores at 6 months, 12 months, and 3 years of age were not related to cord serum adiponectin or leptin levels. CONCLUSIONS: Birthweight SD score, gestational age, and cord serum adiponectin levels are significant predictors of BMI Z-score gain from birth to 3 years of age in Japanese infants.

Extrauterine growth restriction in preterm infants of gestational age < or =32 weeks.

BACKGROUND: Extrauterine growth restriction (EUGR) in low-birthweight (LBW) infants affects their growth and developmental prognoses as well as their incidence of adult diseases. The aim of the present paper was to determine the frequency and contributing factors of EUGR in infants > or =32 weeks of gestational age. METHODS: The subjects consisted of 416 infants from 22 facilities born between February and October 2002, whose gestational age was > or =32 weeks. For EUGR assessment, subjects whose body measurements in the 37-42 week postmenstrual age (PMA) period were below the 10th percentile of the standard normal distribution, were selected. RESULTS: EUGR incidence rates for weight, length, and head circumference were 57%, 49%, and 6%. In appropriate-for-gestational-age infants, a negative correlation was found between number of gestational weeks and EUGR incidence rates for weight, length, and head circumference, but in small-for-gestational-age infants this was true only for head circumference. Lower gestational age and age in days to achieve complete feeding were among the shared factors contributing to EUGR incidence for weight, length, and head circumference. The significant factors for EUGR incidence for weight and length included whether the infant was small for gestational age, whether oxygen was administered at 36 weeks PMA, age in days at which breast-feeding was initiated, and age in days when the infant regained birthweight. CONCLUSIONS: The growth retardation of preterm LBW infants in the neonatal intensive care unit continues to pose challenges. Relevant factors other than gestational age include intrauterine growth restriction, severe chronic lung disease, and poor nutrition.

Longitudinal follow-up of height up to five years of age in infants born preterm small for gestational age; comparison to full-term small for gestational age infants.

OBJECTIVE: This aims to conduct a comparative study of the height catch-up rate in preterm small for gestational age (SGA) infants during early childhood by gestational age and identify the factors affecting short stature in comparison to full-term SGA infants. METHODS: 449 SGA infants (214 full-term infants, 73 infants with gestation of less than 32 weeks, and 162 infants with gestation of more than 32 weeks but less than 37 weeks) from 25 institutions in Japan were assessed for catch-up (> or = -2SD) rate in growth by measuring for length/height at 1 year, 3 years and 5 years of age and the risk factors for no catch-up (< -2SD) at 5 years. RESULTS: The overall length/height catch-up rate was 68% at 1 year, 89% at 3 years and 88% at 5 years. The catch-up rate at 3 and 5 years of age in the group with gestation of less than 32 weeks had a rate of 74%, which was significantly less than the other two groups (approximately 90%). A significant factor associated with short stature at 5 years in the group with gestation of less than 32 weeks was the lower length SD score at time of birth, and for preterm infants born more than 32 weeks of gestation and full-term infants, significant factors were the lower maternal height and head circumference at birth. CONCLUSION: SGA infants born less than 32 weeks of gestation had a higher risk of no catch-up and different factors affecting catch-up compared to preterm SGA infants of gestation more than 32 weeks and full-term SGA infants.