Background
Since 2019, neonatal intensive care units (NICUs) with access to human milk banks (HMBs) have increased in Japan. In this study, using a questionnaire survey, we explored an understanding ...of the purpose, status, and problems of donor human milk (DHM) use and the status of enteral nutrition (EN) in very‐low‐birthweight infants (VLBWIs) in NICUs with access to HMBs.
Methods
A questionnaire was sent to 47 NICUs that had access to HMBs. Participants were surveyed from the begining of January to the end of February 2022.
Results
In total, 37 of 47 (78.9%) NICUs responded to the questionnaire. The most common indications for DHM were gestational age of less than 28 weeks (78.3%) and birthweight of less than 1500 g (100%). Informed consent was obtained from the physicians and most parents accepted DHM. All NICUs responded that EN for VLBWIs should start ideally within 24 h of birth, but in reality, nine NICUs (25%) and 18 NICUs (50%) began EN within 12 and 24 h of birth, respectively. Additionally, seven of the nine NICUs that started EN within 12 h after birth routinely used DHM for VLBWIs. For infants with birthweights of 1000–1499 g, it was not uncommon to start EN within 24 h of birth with formula milk.
Conclusion
All NICUs responded that the indication for DHM was very‐low birthweight and that such infants would receive health benefits from DHM. In Japan, there is a trend of starting EN early in VLBWIs. Accessibility to HMB may be important for starting EN within 24 h of birth.
Pseudohypoaldosteronism (PHA) type II (PHA2) is a genetic disorder that leads to volume overload and hyperkalemic metabolic acidosis. PHA2 and PHA type I (PHA1) have been considered to be genetic and ...pediatric counterparts to type IV renal tubular acidosis (RTA). Type IV RTA is frequently found in adults with chronic kidney disease and is characterized by hyperchloremic hyperkalemic acidosis with normal anion gap (AG). However, we recently observed that PHA1 was not always identical to type IV RTA. In this study, we focused on the acid-base balance in PHA2. Through a literature search published between 2008–2020, 46 molecularly diagnosed cases with PHA2 were identified (median age of 14 years). They comprised 11 sets of familial and 16 sporadic cases and the pathology was associated with mutations in WNK 4 (n = 1), KLHL3 (n = 17), and CUL3 (n = 9). The mean potassium (K+) level was 6.2 ± 0.9 mEq/L (n = 46, range 4.0–8.6 mEq/L), whereas that of chloride (Cl–) was 110 ± 3.5 mEq/L (n = 41, 100–119 mEq/L), with 28 of 41 cases identified as hyperchloremic. More than half of the cases (18/35) presented with metabolic acidosis. Although AG data was obtained only in 16 cases, all but one cases were within normal AG range. Both Cl– and HCO3– levels showed significant correlations with K+ levels, which suggested that the degree of hyperchloremia and acidosis reflect the clinical severity, and is closely related to the fundamental pathophysiology of PHA2. In conclusion, our study confirmed that PHA2 is compatible with type IV RTA based on laboratory findings.
Donor human milk (DHM) is the second-best nutrition for preterm infants when their own mother's milk is unavailable. The nutrient content of human milk is influenced by various factors, including ...gestational and postpartum age, but there are no data regarding DHM composition in Japan. The aim of this study was to determine the protein and immune component content of DHM in Japan and to elucidate the effects of gestational and postpartum age on nutrient composition. From September 2021 to May 2022, 134 DHM samples were collected from 92 mothers of preterm and term infants. Protein concentrations in preterm DHM (
= 41) and term DHM (
= 93) were analyzed using a Miris Human Milk Analyzer. The concentrations of secretory immunoglobulin A (sIgA) and lactoferrin, major immune components, were measured using enzyme-linked immunosorbent assays. Preterm DHM exhibited higher protein content than term DHM (1.2 g/dL and 1.0 g/dL, respectively,
< 0.001), whereas sIgA content was higher in term DHM than in preterm DHM (110 μg/mL and 68.4 μg/mL, respectively,
< 0.001). Gestational age was negatively correlated with protein levels and positively correlated with sIgA and lactoferrin levels. Furthermore, a negative correlation was found between postpartum week and protein, sIgA, and lactoferrin concentrations. Our data suggest that gestational and postpartum age affects protein, sIgA, and lactoferrin concentrations in DHM. These results indicate the importance of nutritional analysis for the appropriate use of DHM in preterm infants.
A questionnaire survey about donor milk and breast milk bank was conducted on baby-friendly hospitals（BFH）. Responses were obtained from 61 obstetricians and 77 pediatricians. Over 70％ of the ...obstetricians and over 80％ of the pediatricians knew the existence of breast milk banks; and also that donor milk is given to extremely premature infants and extremely-low-birth-weight infants in the hospitals. Limited to 55 pediatricians working at BFH with NICU, about 85％ had intention to administer donor milk from the breast milk bank to babies soon after birth, but on the other hand they concerned about insufficiency of information about milk collection, infection through donor milk, the preservation and transportation of donor milk, and how the baby’s mother would feel. They answered they can cooperate in posting information about breast milk bank and distributing leaflet in the hospitals. It is necessary to enhance transmission of information about donor milk and breast milk banks to medical staff working at NICU; and measures are awaited to enable administration of donor milk soon after birth without delay.
Aim: This study aimed to elucidate the gene and lipid profiles of children clinically diagnosed with familial hypercholesterolemia (FH).Methods: A total of 21 dyslipidemia-related Mendelian genes, ...including FH causative genes (LDLR, APOB, and PCSK9) and LDL-altering genes (APOE, LDLRAP1, and ABCG5/8), were sequenced in 33 Japanese children (mean age, 9.7±4.2 years) with FH from 29 families.Results: Fifteen children (45.5%) with pathogenic variants in LDLR (eight different heterozygous variants) and one child (3.0%) with the PCSK9 variant were found. Among 17 patients without FH causative gene variants, 3 children had variants in LDL-altering genes, an APOE variant and two ABCG8 variants. The mean serum total cholesterol (280 vs 246 mg/dL), LDL-cholesterol (LDL-C, 217 vs 177 mg/dL), and non-HDL cholesterol (228 vs 188 mg/dL) levels were significantly higher in the pathogenic variant-positive group than in the variant-negative group. In the variant-positive group, 81.3% of patients had LDL-C levels ≥ 180 mg/dL but 35.3% in the variant-negative group. The mean LDL-C level was significantly lower in children with missense variants, especially with the p.Leu568Val variant, than in children with other variants in LDLR, whereas the LDL-altering variants had similar effects on the increase in serum LDL-C to LDLR p.Leu568Val. Conclusion: Approximately half of the children clinically diagnosed with FH had pathogenic variants in FH causative genes. The serum LDL-C levels tend to be high in FH children with pathogenic variations, and the levels are by the types of variants. Genetic analysis is useful; however, further study on FH without any variants is required.
Reducing the disposal of donated human milk (HM) is important for efficient management of human milk banks (HMBs). The presence of bacteria growth is the main factor that contributes to the disposal ...of donated HM. The bacterial profile in HM is suspected to differ between term and preterm mothers, with HM from preterm mothers containing more bacteria. Thus, elucidation of the causes of bacterial growth in preterm and term HM may help to reduce the disposal of donated preterm HM. This study compared the bacterial profiles of HM between mothers of term infants and mothers of preterm infants.
This pilot study was conducted in the first Japanese HMB, which was initiated in 2017. This study analyzed 214 human milk samples (term: 75, preterm: 139) donated by 47 registered donors (term: 31, preterm: 16) from January to November 2021. Bacterial culture results in term and preterm HM were retrospectively reviewed in May 2022. Differences in total bacterial count and bacterial species count per batch were analyzed using the Mann-Whitney U test. Bacterial loads were analyzed using the Chi-square test or Fisher's exact test.
The disposal rate did not significantly differ between term and preterm groups (p = 0.77), but the total amount of disposal was greater in the preterm group (p < 0.01). Coagulase-negative Staphylococci, Staphylococcus aureus, and Pseudomonas fluorescens were frequently found in both types of HM. Serratia liquefaciens (p < 0.001) and two other bacteria were present in term HM; a total of five types of bacteria, including Enterococcus faecalis and Enterobacter aerogenes (p < 0.001) were present in preterm HM. The median (interquartile range) total bacterial counts were 3,930 (435-23,365) colony-forming units (CFU)/mL for term HM and 26,700 (4,050-334,650) CFU/mL for preterm HM (p < 0.001).
This study revealed that HM from preterm mothers had a higher total bacterial count and different types of bacteria than HM from term mothers. Additionally, preterm infants can receive nosocomial-infection-causing bacteria in the NICU through their mother's milk. Enhanced hygiene instructions for preterm mothers may reduce the disposal of valuable preterm human milk, along with the risk of HM pathogen transmission to infants in NICUs.
Noonan syndrome is characterized by short stature, facial dysmorphia and a wide spectrum of congenital heart defects. Mutations of PTPN11, KRAS and SOS1 in the RAS-MAPK pathway cause ∼60% of cases of ...Noonan syndrome. However, the gene(s) responsible for the remainder are unknown. We have identified five different mutations in RAF1 in ten individuals with Noonan syndrome; those with any of four mutations causing changes in the CR2 domain of RAF1 had hypertrophic cardiomyopathy (HCM), whereas affected individuals with mutations leading to changes in the CR3 domain did not. Cells transfected with constructs containing Noonan syndrome-associated RAF1 mutations showed increased in vitro kinase and ERK activation, and zebrafish embryos with morpholino knockdown of raf1 demonstrated the need for raf1 for the development of normal myocardial structure and function. Thus, our findings implicate RAF1 gain-of-function mutations as a causative agent of a human developmental disorder, representing a new genetic mechanism for the activation of the MAPK pathway.
This study aimed to determine whether neonatal feeding performance can predict the neurodevelopmental outcome of infants at 18 months of age. We measured the expression and sucking pressures of 65 ...infants (32 males and 33 females, mean gestational age 37.8 weeks SD 0.5; range 35.1 to 42.7 weeks and mean birthweight 2722g SD 92) with feeding problems and assessed their neurodevelopmental outcome at 18 months of age. Their diagnoses varied from mild asphyxia and transient tachypnea to Chiari malformation. A neurological examination was performed at 40 to 42 weeks postmenstrual age by means of an Amiel-Tison examination. Feeding performance at 1 and 2 weeks after initiation of oral feeding was divided into four classes: class 1, no suction and weak expression; class 2, arrhythmic alternation of expression/suction and weak pressures; class 3, rhythmic alternation, but weak pressures; and class 4, rhythmic alternation with normal pressures. Neurodevelopmental outcome was evaluated with the Bayley Scales of Infant Development–II and was divided into four categories: severe disability, moderate delay, minor delay, and normal. We examined the brain ultrasound on the day of feeding assessment, and compared the prognostic value of ultrasound and feeding performance. There was a significant correlation between feeding assessment and neurodevelopmental outcome at 18 months (p<0.001). Improvements of feeding pattern at the second evaluation resulted in better neurodevelopmental outcome. The sensitivity and specificity of feeding assessment were higher than those of ultrasound assessment. Neonatal feeding performance is, therefore, of prognostic value in detecting future developmental problems.
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