How Can We Prevent Mother-to-Child Transmission of HTLV-1?

The perception of human T-cell leukemia virus type 1 (HTlV-1) infection as a "silent disease" has recently given way to concern that its presence may be having a variety of effects. HTLV-1 is known to cause adult T-cell leukemia (ATL), an aggressive cancer of peripheral CD4 T cells; however, it is also responsible for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Most patients develop ATL as a result of HTLV-1 mother-to-child transmission. The primary route of mother-to-child transmission is through the mother's milk. In the absence of effective drug therapy, total artificial nutrition such as exclusive formula feeding is a reliable means of preventing mother-to-child transmission after birth, except for a small percentage of prenatal infections. A recent study found that the rate of mother-to-child transmission with short-term breastfeeding (within 90 days) did not exceed that of total artificial nutrition. Because these preventive measures are in exchange for the benefits of breastfeeding, clinical applications of antiretroviral drugs and immunotherapy with vaccines and neutralizing antibodies are urgently needed.

Mortality and morbidity of extremely low birth weight infants in Japan, 2015.

BACKGROUND: In Japan, the mortality rate of extremely low birth weight (ELBW) infants is notably low in comparison with other developed countries, but the prevalence of chronic lung disease (CLD) and retinopathy of prematurity (ROP) is relatively high. This study aimed to estimate the mortality and morbidity of ELBW infants born in 2015 who were admitted to neonatal intensive care units (NICUs) in Japan and to examine the factors that affected the short-term outcomes of these infants. We also compared the mortality of ELBW infants born in 2005, 2010, and 2015. METHODS: We analyzed the mortality, morbidity, and factors related to short-term outcomes of ELBW infants, using data from 2782 infants born in 2015 and registered at NICUs in Japan. RESULTS: The mortality rates during NICU stays were 17.0%, 12.0%, and 9.8% for ELBW infants born in 2005, 2010, and 2015, respectively. Among ELBW infants born in 2015, multiple logistic regression analysis showed that short gestational age and low birthweight Z-score contributed to the increased risk of death. Births by cesarean section and antenatal corticosteroid administration were significantly associated with a reduced risk of death. Among infants who survived, CLD was observed in 53.1% and ROP requiring treatment was observed in 30.4%. CONCLUSIONS: Mortality in ELBW infants decreased significantly from 2005 to 2015. As CLD and ROP may affect quality of life and long-term outcomes of infants who survived, prevention strategies and management for these complications are critical issues in neonatal care in Japan.

Experience using donor human milk: A single-center cohort study in Japan.

BACKGROUND: Donor human milk (DHM) became available in Japan when the first human milk bank was established in 2017. This study investigated the effects of DHM on enteral nutrition (EN) in very low birth weight (VLBW) infants in the single center in Japan. METHODS: Seventy-six VLBW infants hospitalized between April 2017 and March 2020 at Showa University Hospital were included in the study. We retrospectively evaluated age (hours) at which EN was initiated and age (days) until complete feeding (EN > 100 mL/kg/day) was achieved. We compared the DHM and non-DHM groups, or the early human milk (EHM) and non-EHM groups. The EHM group was defined as those in which EN was initiated with the mother's own milk or DHM within 12 h of birth. RESULTS: In 30 extremely low birth weight (ELBW) infants, EN was initiated at significantly earlier postnatal hours in the DHM group compared to those in the non-DHM group. Complete feeding was achieved at significantly earlier ages in the EHM group after adjusting for gastrointestinal complications and gestational age. Additionally, the changes in body weight z-scores from birth to term-equivalent age were significantly greater in the EHM group after adjusting for exclusive breastfeeding and small for gestational age, compared to the non-EHM group. Statistical significance was not noted in 46 subjects (birth weight, 1000-1500 g). CONCLUSION: The use of DHM may contribute to earlier initiation and achievement of EN, resulting in greater early postnatal growth in ELBW infants in Japan.

Human milk-based fortifier is associated with less alteration of milk fat globule size than cow milk-based fortifier.

We aimed to evaluate if human milk-based fortifier (HMBF) affects human milk fat globule (MFG) size less than cow milk-based fortifier (CMBF), which may impact overall infant feeding tolerance. Measurements of donated human milk were performed before fortification as well as at 1 hour, 24 hours, and 48 hours after fortification with CMBF or HMBF. MFG size in each sample of fortified milk was measured by laser light scattering. MFG size in the fortified milks increased gradually over time. At 24 and 48 hours after fortification, MFG size in the milk with CMBF was larger than that in the milk with HMBF (4.8 ± 0.5 vs 4.3 ± 0.3 µm, p<0.01, 5.1 ± 0.7 vs 4.5 ± 0.4 µm, p = 0.03, respectively). HMBF is associated with less alteration of MFG size than CMBF. This may have an impact on feeding tolerance of very preterm infants.

Mother-to-Child Transmission of Human T-Cell Leukemia Virus Type 1: Mechanisms and Nutritional Strategies for Prevention.

Approximately 95% of mother-to-child transmission (MTCT) of human T-cell leukemia virus type-1 (HTLV-1) is derived from prolonged breastfeeding, which is a major cause of adult T-cell leukemia (ATL). Exclusive formula feeding (ExFF) is therefore generally used to prevent MTCT. A recent cohort study revealed that 55% of pregnant carriers chose short-term breastfeeding for ≤3 months in Japan. Our meta-analysis showed that there was no significant increase in the risk of MTCT when breastfeeding was carried out for ≤3 months compared with ExFF (pooled relative risk (RR), 0.72; 95% confidence interval (CI), 0.30-1.77), but there was an almost threefold increase in risk when breastfeeding was carried out for up to 6 months (pooled RR, 2.91; 95% CI, 1.69-5.03). Thus, short-term breastfeeding for ≤3 months may be useful in preventing MTCT. Breastmilk is the best nutritional source for infants, and any approach to minimizing MTCT by avoiding or limiting breastfeeding must be balanced against the impact on the child's health and mother-child bonding. To minimize the need for nutritional interventions, it is necessary to identify factors that predispose children born to carrier mothers to MTCT and thereby predict MTCT development with a high degree of accuracy.

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.

Changes in mortality rates among extremely preterm infants born before 25 weeks' gestation: Comparison between the 2005 and 2010 nationwide surveys in Japan.

BACKGROUND: There is no consensus as to whether the outcomes of extremely preterm infants born <25 weeks' gestation have been constantly improving. AIMS: Our study aimed to clarify changes in mortality during hospitalization among extremely preterm infants. STUDY DESIGN: Comparison of mortality rates between the 2005 and 2010 retrospective nationwide surveys in Japan. SUBJECTS: Extremely preterm infants born <25 weeks' gestation in Japan and registered in the nationwide surveys, 802 infants in 2005 and 797 in 2010, respectively. OUTCOMES: Mortality rates stratified by gestational age. RESULTS AND CONCLUSION: Mortality rates <25 weeks' gestation decreased from 36.4% to 25.6% (difference - 10.8% [95% confidence interval {CI}: -15.3%, -6.2%]) in 2010 compared to 2005. Gestational age-specific mortality rates were lower in 2010 compared to 2005, except for 24 weeks' gestation: 66.0% vs. 50.0% (difference: -16% [95% CI: -29.8%, -21.2%]) and 45.7% vs. 25.5% (difference: -20.2%, [95% CI: -28.1, -12.3%]) at 22, and 23 weeks' gestation, respectively. After adjusting for explanatory variables, the probability of death during hospitalization in 2010 was significantly lower in infants born <25 weeks' gestation (adjusted odds ratio [aOR] 0.597 [95% CI: 0.471, 0.757], but when stratified by gestational age, it was only significant for infants born at 23 weeks' gestation (aOR 0.439 [95% CI: 0.303, 0.636]). In conclusion, the mortality rates among infants born <25 weeks' gestation have been steadily improving from 2005 to 2010 in Japan, but the practice for infants born at 22 weeks' gestation is still challenging.

Issues of infant feeding for postnatal prevention of human T-cell leukemia/lymphoma virus type-1 mother-to-child transmission.

BACKGROUND: Nationwide antenatal human T-cell leukemia/lymphoma virus type-1 (HTLV-1) antibody screening has been conducted in Japan. The purpose of our study was to clarify the issues related to feeding options to prevent postnatal mother-to-child transmission. METHODS: Of the pregnant carriers at 92 facilities in Japan between 2012 and 2015, 735 were followed prospectively. Among the children born to them, 313 (42.6%) children were followed up to the age of 3 and tested for HTLV-1 antibodies. The mother-to-child transmission rate was calculated for each feeding option selected before birth. RESULTS: Among the 313 pregnant carriers, 55.0, 35.1, 6.1, and 3.8% selected short-term breast-feeding (≤3 months), exclusive formula feeding, frozen-thawed breast-milk feeding, and longer-term breast-feeding, respectively. Despite short-term breast-feeding, 8-18% of the mothers continued breast-feeding for 4-6 months. The mother-to-child transmission rate with short-term breast-feeding was 2.3% (4/172), and its risk ratio compared with that of exclusive formula feeding was not significantly different (0.365; 95% CI: 0.116-1.145). Because of the small number of children who were fed by frozen-thawed breast-milk, their mother-to-child transmission rate was not statistically reliable. CONCLUSIONS: Pregnant HTLV-1 carriers tended to select short-term breast-feeding in Japan. While short-term breast-feeding was not always easy to wean within 3 months, it may be a viable option for preventing postnatal mother-to-child transmission because the vertical transmission rate with short-term breast-feeding was not significantly higher than that with exclusive formula feeding. Increasing the follow-up rates for children born to pregnant carriers may provide clearer evidence of preventative effects by short-term breast-feeding and frozen-thawed breast-milk feeding.

A Nationwide Antenatal Human T-Cell Leukemia Virus Type-1 Antibody Screening in Japan.

Japan has been running a nationwide antenatal human T-cell leukemia virus type-1 (HTLV-1) antibody screening program since 2010 for the prevention of HTLV-1 mother-to-child transmission. As part of the program, pregnant women are invited to take an HTLV-1 antibody screening test, usually within the first 30 weeks of gestation, during regular pregnancy checkups. Pregnant women tested positive on the antibody screening test undergo a confirmatory test, either western blotting or line immunoassay. In indeterminate case, polymerase chain reaction (PCR) is used as a final test to diagnose infection. Pregnant women tested positive on a confirmatory or PCR test are identified as HTLV-1 carriers. As breastfeeding is a predominant route of postnatal HTLV-1 mother-to-child transmission, exclusive formula feeding is widely used as a postnatal preventive measure. Although there is insufficient evidence that short-term breastfeeding during ≤3 months does not increase the risk of mother-to-child transmission compared to exclusive formula feeding, this feeding method is considered if the mother is eager to breastfeed her child. However, it is important that mothers and family members fully understand that there is an increase in the risk of mother-to-child transmission when breastfeeding would be prolonged. As there are only a few clinical studies on the protective effect of frozen-thawed breastmilk feeding on mother-to-child transmission of HTLV-1, there is little evidence to recommend this feeding method. Further study on the protective effects of these feeding methods are needed. It is assumed that the risk of anxiety or depression may increase in the mothers who selected exclusive formula feeding or short-term breastfeeding. Thus, an adequate support and counseling for these mothers should be provided. In addition to raising public awareness of HTLV-1 infection, epidemiological data from the nationwide program needs to be collected and analyzed. In most cases, infected children are asymptomatic, and it is necessary to clarify how these children should be followed medically.

Unsupervised breastfeeding was related to sudden unexpected postnatal collapse during early skin-to-skin contact in cerebral palsy cases.

AIM: This study aimed to identify the clinical features of infants who were healthy at birth, but developed sudden unexpected collapse and were then diagnosed with cerebral palsy before 5 years of age. METHODS: We retrospectively analysed 1182 records from the no-fault Japan Obstetric Compensation System for Cerebral Palsy database up to 2016. This identified 45 subjects (3.8%) who were subsequently diagnosed with severe cerebral palsy due to sudden unexpected postnatal collapse (SUPC). They were all healthy at birth, based on the criteria of five-minute Apgar scores of seven or more, with normal umbilical cord blood gases and no need for neonatal resuscitation within five minutes of birth. RESULTS: The median birth weight of the 45 subjects (26 males) was 2770 g (range 2006-3695 g). Of these, 10 developed SUPC during early skin-to-skin contact (SSC). Medical personnel were not present in all 10 cases: nine were being breastfed at the time and eight of the mothers did not notice their infant's abnormal condition until medical staff alerted them. CONCLUSION: This national study of children with cerebral palsy who appeared healthy at birth found that unsupervised breastfeeding was a common factor in cases of SUPC during early SSC.

Feeding interval and use of donor breast milk for very low birthweight infants: A nationwide survey in Japan.

BACKGROUND: Enteral feeding is critical for postnatal growth of very low birthweight infants (VLBWI); however, a standard feeding strategy has not been established in Japan. A 2- or 3-h feeding interval is generally used, but no clear evidence supports either approach. Additionally, there is no nationwide breast milk bank in Japan and no consensus exists on the use of donor breast milk (DBM). To clarify the current feeding strategies for VLBWI in Japan, we undertook a nationwide survey. METHODS: We sent a questionnaire to the 382 NICUs included in the Neonatal Research Network in Japan. We sought information on NICU size, number of admissions, necrotizing enterocolitis (NEC) incidence, feeding interval, and use of DBM. RESULTS: We received responses from 217 NICUs (56.8%), including 76 tertiary centers and 140 regional centers. We only analyzed data obtained from tertiary perinatal centers with a high response rate (77.6%) owing to the insufficient response rate of lower-level facilities (<50%). Most NICUs (71.1%) used a 3-h feeding interval. Only 9.2% used a 2-h interval for all VLBWI. Most NICUs (64.5%) never used DBM, which is not routinely pasteurized. DBM was used in 27 NICUs (35.5%), with and without limitations. Data from 14,233 VLBWI were analyzed; 258 infants (1.8%) were diagnosed with NEC from 2011 to 2015. The incidence of NEC was higher in NICUs that used a 2-h interval (2.7%) than in others. No association was found between NEC and the use of DBM. The NEC incidence did not differ between centers using the most common strategy of a 3-h interval without DBM and those using other strategies. CONCLUSION: Most NICUs in Japan use a 3-h feeding interval and do not use DBM for VLBWI. Further prospective studies including multiple confounders are required to clarify the relationship between feeding strategy and the incidence of NEC.

Body length and occipitofrontal circumference may be good indicators of neurodevelopment in very low birthweight infants - secondary publication.

AIM: The aim of this study was to predict the neurological prognosis of very low birthweight (VLBW) infants. We examined the relationship between nutritional status, brain volume measured by magnetic resonance imaging (MRI) and anthropometric measurements of VLBW infants at term-equivalent age (TEA). METHODS: We evaluated 27 VLBW infants, born at Showa University Hospital in Japan between April 2012 and August 2013, who underwent brain MRI at TEA. Based on their clinical data, we analysed their protein and energy intake. RESULTS: Median values for the 27 VLBW infants were as follows: gestational age, 29.7 weeks; birthweight 1117 g; protein intake 2.7 g/kg/day and energy intake 97.9 kcal/kg/day. At TEA, the standard deviation scores (SDSs) of body weight, body length and the occipitofrontal circumference (OFC) were -0.8, -1.4 and 0.7, respectively. Multiple regression analysis revealed that the SDSs of body length and the OFC at TEA were significant determinants of white matter volume, but that the SDS of body weight at TEA was not. CONCLUSION: Our findings suggest that the SDSs of body length and the OFC at TEA may be better indicators than body weight for predicting the development of the central nervous system in VLBW infants receiving nutritional management.

Hyperinsulinemic hypoglycemia in Beckwith-Wiedemann, Sotos, and Kabuki syndromes: A nationwide survey in Japan.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.

PROSPECTIVE MULTICENTER SURVEY ON PREDICTIVE FACTORS FOR POSITIVE ORAL FOOD CHALLENGE TESTS IN DIAGNOSIS OF GASTROINTESTINAL FOOD ALLERGY IN NEONATES.

OBJECTIVE: To assess predictors of positive oral food challenge test (OFC) in neonates that are suggestive of gastrointestinal food allergy. METHODS: A prospective case accumulations study on neonates suspected of having gastrointestinal food allergy was conducted in 126 neonatal intensive care units in Japan between April 2010 and September 2011. Neonates who underwent an OFC for the diagnosis of gastrointestinal food allergy were enrolled. Clinical backgrounds, clinical symptoms, and laboratory findings were compared between neonates with a positive OFC and those with a negative OFC. RESULTS: An analysis was performed in 32 neonates. The OFC results were positive in 9 neonates (28.1%), pseudo-positive in 4, and negative in 19. There were no significant differences in clinical backgrounds between the positive OFC group and the negative OFC group. Vomiting and bloody stool were frequently observed in both groups (approximately 70%), although there were no significant differences in the clinical symptoms between the two groups. Additional diagnostic tests included those for eosinophils in the peripheral blood and stool mucus and allergen-specific lymphocyte stimulation test. There were no significant differences in laboratory findings between the two groups, and many neonates showed pseudo-positive in all of the tests. CONCLUSION: It was difficult to predict OFC results based on clinical symptoms and additional diagnostic test results. In order to obtain an accurate diagnosis of gastrointestinal food allergy in neonates, OFC should be performed proactively under conditions that enable complete understanding of risks to neonates.

[SAFETY OF INFLUENZA VACCINATION IN CHILDREN WITH SEVERE ALLERGY TO HEN'S EGGS: A PROSPECTIVE CASE SERIES STUDY].

BACKGROUND: Influenza vaccination guidelines have recommended that pediatricians should consult with allergists in the case of for children with histories of anaphylaxis to hen's eggs. On the other hand, whether such children can be safely vaccinated is unclear. OBJECTIVE: To evaluate the safety of influenza vaccination for children severely allergic to eggs. METHODS: The study population consisted severe egg-allergic children that had never been immunized with influenza vaccine. The inclusion criteria of severe egg-allergic children included evidence of serum specific IgE antibodies to egg white or an ovomucoid level of class4 or more and complete elimination of dietary intake of eggs, or occurrence of Sampson Grade 3 to 5 anaphylactic reactions upon egg ingestion. Patients underwent skin prick tests, and received 0.1ml of influenza vaccine, followed in 30 minutes if no reaction with the remainder of an age-appropriate dose. We observed the subjects for 30 minutes afterwards, and they were observed by their patients during the subsequent 24 hours. RESULTS: A total of 17 patients were enrolled. All patients received influenza vaccination without an allergic reaction. CONCLUSIONS: Influenza vaccination is safe even in children with histories of severe egg allergy. influenza vaccination without an allergic reaction.

Predictors of low milk volume among mothers who delivered preterm.

BACKGROUND: Factors associated with successful provision of mother's own milk (MOM) for premature infants in a Japanese neonatal intensive care unit (NICU) context are not well known. OBJECTIVE: We determined the independent risk factors for low milk volume at day 4 postpartum and formula feeding at the time of NICU discharge. METHODS: We reviewed the medical records of mothers who delivered at < 32 weeks' gestation. We determined maternal, premature infant, and milk expression variables predictive of (1) day 4 postpartum milk volume being less than the cohort median and (2) formula feeding at the time of NICU discharge, reported as adjusted odds ratios (95% confidence interval). RESULTS: Among 85 dyads, median (quartile range) milk volume on day 4 postpartum was 153 (34-255) mL. The rate of formula feeding at discharge was 42%. Mothers delivering by cesarean (vs vaginal) delivery had 4.3-fold (1.5-12.4) greater odds of day 4 milk volume < median (P < .01). Pregnancy-induced hypertension, delayed milk expression initiation, and low pumping frequency were strongly associated with cesarean delivery. Subsequently, mothers with day 4 milk volume < median (vs ≥ median) had 7.1-fold (2.6-19.5) greater odds of formula feeding at discharge (P < .01). CONCLUSION: Cesarean delivery is associated with lower milk volume on day 4 but may represent a composite of underlying risk factors for low milk volume in the early postpartum period. Further, low milk volume on day 4 is a strong correlate of lack of exclusive breast milk feeding at NICU discharge.

[Effects of measurement position on the forced oscillation technique values].

BACKGROUND: Cheek support and subject's arm position can influence on lung function values measured with forced oscillation technique. We examined resistance and reactance by different methods using a new forced oscillation technique machine called MostGraph (Chest Co. Ltd., Tokyo, Japan). METHODS: We evaluated nineteen adults. Four methods are measured. 1: the subjects support their cheeks with their hands. 2: the tester support the subject's cheeks with their hands. 3: the subjects stiffen their cheeks without any cheek support. 4: subject relax their cheeks without any cheek support. R5, R20, R5-R20, X5, Fres and ALX were compared between four methods. RESULTS: In resistance values, R20 was the lowest in the fourth method, and it was significantly different from the first (p<0.01) and the second (p<0.01) method. R5-R20 was the lowest in the second method, and it was significantly different from the third (p<0.01) and forth (p<0.01) methods. In reactance values, X5 was the highest in the second method. All ractance values in the second method were significantly different from the first and the fourth method. CONCLUSION: Measurement values using Mostgraph was influenced by methods of supporting cheeks and subject's arm position. Measurement method should be unify and the first method is ideal and practical.

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.

Retrospective multicenter survey on food-related symptoms suggestive of cow's milk allergy in NICU neonates.

BACKGROUND: Cow's milk allergy (CMA) is one of the causes of gastrointestinal symptoms in neonates. A relationship between non-immunoglobulin (Ig) E mediated allergic reactions and CMA in early infancy has been proposed, but the clinical features and pathogenesis have not been established. The objective of this study is to determine the clinical characteristics of the neonates found in the earlier study to have food-related symptoms that suggested CMA. METHODS: A second questionnaire was sent to 53 NICUs, as a follow-up to the earlier study, to collect information on the background, onset age, clinical features, and results of clinical examinations. RESULTS: The median birth weight was 2614g and the median gestational age was 36.9 weeks. Symptoms developed within 6 days after birth in 40% of cases. Gastrointestinal symptoms were seen in 90% of cases and were mainly vomiting, bloody stool and abdominal distention. A specific IgE test, a lymphocyte stimulation test, and a fecal eosinophil test were conducted in 88%, 23% and 55% of cases, respectively, and the positive rates were 30%, 84%, and 75%, respectively. An oral food challenge (OFC) test was performed in 26% for confirmation of the diagnosis. CONCLUSIONS: We confirmed that the clinical manifestations of food-related symptoms suggestive of CMA in neonates were distinctly different from those of common immediate type food allergy and were largely affected by underlying factors such as prematurity and gastroenterological surgery. Further OFC-based prospective accumulation of cases of CMA in neonates will be particularly important to reveal the full clinical features of this disease.

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.