Outcomes of High-Dose Inhaled Nitric Oxide and Oxygen Administration for Severe Pulmonary Hypertension With Bronchopulmonary Dysplasia.

Pulmonary hypertension (PH) with bronchopulmonary dysplasia (BPD) is fraught with high infant mortality rates. However, the intervention strategy for severe PH is unclear. This case report discusses the utility of long-term high-dose inhaled nitric oxide (iNO) administration and that of oxygen therapy for the prevention of PH deterioration. A male infant weighing 864 g was delivered at a gestational age of 24 weeks and three days. The patient who had severe BPD was diagnosed with PH at a corrected gestational age (CGA) of 43 weeks. Although oxygen was administered to prevent PH, the patient still developed severe PH. Despite long-term high-dose (iNO) administration, the patient could not survive. The abovementioned treatment may exacerbate PH, and oxygen administration is less effective for the prevention of PH deterioration with BPD.

Intrapartum prophylactic efficacy of ampicillin versus clindamycin in preventing vertical transmission of group B Streptococcus.

AIM: To compare the prophylactic efficacy of ampicillin and clindamycin against vertical transmission of group B Streptococcus from mothers to their infants by evaluating the rates of group B Streptococcus colonisation. METHODS: We retrospectively extracted data for mothers who delivered at Showa University Northern Yokohama Hospital between 1 October 2017 and 31 March 2021 and tested positive for antepartum group B Streptococcus, and their infants. The chi-square test was used to compare the rates of group B Streptococcus colonisation, sepsis, and meningitis. We conducted a multivariate logistic regression analysis, including the time interval between membrane rupture and delivery, chorioamnionitis, and maternal intrapartum fever (≥38.0°C). RESULTS: Two hundred fifty-nine mothers and their infants were eligible. Ampicillin and clindamycin were administered to 150 and 109 mothers, respectively. In the ampicillin and clindamycin groups, 12.0% (18/150) and 37.6% (41/109) infants were group B Streptococcus positive, respectively. The rate of group B Streptococcus colonisation among infants was significantly lower in the ampicillin group (p < 0.001). Multivariate regression analysis showed similar results (p < 0.001). No sepsis or meningitis cases were observed in either group. CONCLUSION: Prophylactic efficacy of clindamycin against the vertical transmission of group B Streptococcus is lower than that of ampicillin.

DHA Supplementation Attenuates Inflammation-Associated Gene Expression in the Mammary Gland of Lactating Mothers Who Deliver Preterm.

BACKGROUND: In a randomized trial of DHA supplementation to lactating mothers who delivered preterm, there were significant increases in DHA status in the mother and her infant. OBJECTIVES: Our objective here was to characterize the mammary gland transcriptomes from the above study. We hypothesized that proinflammatory gene expression would be attenuated in the increased DHA group compared with the standard DHA group. METHODS: In the original trial, mothers delivering at <29 wk gestation at the University of Cincinnati Medical Center and intending to express their milk were randomly assigned to supplementation with 200 mg/d DHA (standard group: STD) or 1000 mg/d DHA (experimental group: EXP) within 7 d of delivery. Here, we conducted RNA-seq transcriptome analysis of n = 5 EXP and n = 4 STD extracellular mammary mRNA samples extracted from the fat layer of milk samples obtained 4 wk postenrollment. Transcripts were assessed for differential expression (false discovery rate adjusted P value <0.05) and clustering between EXP compared with STD groups. Ontological analysis of all differentially expressed genes (DEGs) was performed with Toppcluster. RESULTS: There were 409 DEGs. We observed 5 main groups of biological processes that were upregulated, including those associated with improved immune regulation and management of oxidative stress; and 3 main groups of biological processes that were downregulated, including 1 associated with immune dysregulation. For example, we observed upregulation of inflammation-inhibiting genes including NFKB inhibitor alpha (NFKBIA; fold-change (FC), adjusted P value: FC = 1.70, P = 0.007) and interleukin-18 binding protein (IL18BP: FC = 2.2, adjusted P = 0.02); and downregulation of proinflammatory genes including interleukin 7 receptor (IL7R: FC = -1.9, adjusted P = 0.02) and interleukin 1 receptor like 1 (IL1RL1: FC = -13.0, adjusted P = 0.02). CONCLUSIONS: Increased DHA supplementation during lactation can modulate the expression of inflammation-related genes within the mammary gland. This might translate to milk composition with a more optimal inflammasome profile. Future research with a larger clinical trial and greater interrogation of clinical outcomes is warranted.

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.

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.

The Relation between Breast Milk Sodium to Potassium Ratio and Maternal Report of a Milk Supply Concern.

We report that, among exclusively breastfeeding mothers at day 7 postpartum, those with milk supply concerns were significantly more likely to exhibit biochemical evidence of less progress toward mature lactation (elevated ratio of breast milk sodium to potassium concentration). Furthermore, an elevated ratio of breast milk sodium to potassium concentration was predictive of early weaning.

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.

Is fat content of human milk decreased by infusion?

BACKGROUND: Human milk (HM) is the optimum nutrition for preterm infants. Previous studies showed that tube infusion decreased the fat content in thawed HM. The aim of this study was to determine if freezing­thawing is the main reason for decrease of fat content. In neonatal intensive care units, thawed HM is used in general, therefore the aim of this study was to investigate fat loss during tube infusion with regard to changes in tube size, material, and infusion rate. METHODS: First, pre-infusion and post-infusion fat content was measured in 15 fresh HM, 10 thawed HM and 6 formula samples. We compared post-infusion and pre-infusion fat content as well as the percent decrease in fat concentration among fresh HM, thawed HM and formula samples. Second, we measured the fat content of 160 thawed HM samples infused via four different diameters (3­6 Fr), two types of material (DEHP-free and PVC-free), and two infusion rates (30 or 60 min). We compared the percent decrease in fat concentration among four different tube sizes, between DEHP-free and PVC-free tubes, and between 30 and 60 min infusion durations. RESULTS: Post-infusion fat content was significantly decreased compared to before infusion in thawed HM and fresh HM but not in formula. Given that thawed HM resulted in larger decrease in fat content, we performed a second experiment and found no difference regarding differing size, materials or infusion rate. CONCLUSIONS: There was a far greater decrease in the post-infusion fat content of thawed HM compared to fresh HM under all test conditions.

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.

Is there a difference in gastric emptying between myotonic dystrophy type 1 patients with and without gastrointestinal symptoms?

Gastrointestinal symptoms are frequent complaints in patients with myotonic dystrophy type 1 (MyD1) and may be associated with reduced gastrointestinal motility caused by smooth muscle dysfunction. Although previous studies have found delayed gastric emptying (GE) in MyD1 patients, the relationship between GE and symptoms has been unclear. We investigated GE in 23 MyD1 patients and 20 healthy volunteers using the 13C-acetate breath test. The MyD1 patients were divided into two groups: those with gastrointestinal symptoms (n = 9) and those without gastrointestinal symptoms (n = 14). The GE function was estimated using the 13C-acetate breath test as half-emptying time (HET) and peak time of the 13C-%-dose-excess curve (T max). GE (HET and T max) was more significantly delayed in patients with MyD1 than in the controls. The GE in MyD1 patients with gastrointestinal symptoms was significantly delayed compared to those without gastrointestinal symptoms. The GE in MyD1 patients with gastrointestinal symptoms was more significantly delayed than in the controls. The GE was significantly delayed in MyD1 patients with gastrointestinal symptoms for >5 years as compared to those with the disease for <5 years, while GE of MyD1 patients without gastrointestinal symptoms did not correlate with the duration of the disease. The GE in MyD1 patients did not correlate with the muscular disability rating scale. These findings suggest that impairment of GE evolves over time and that the progression of delayed GE and skeletal muscle impairment are independent. Smooth muscle impairment may be affected at an earlier stage in MyD1.

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.

Is there delayed gastric emptying in patients with multiple system atrophy? An analysis using the (13)C-acetate breath test.

Autonomic failure is one of the criteria according to the second consensus statement for the diagnosis of multiple system atrophy (MSA). Gastrointestinal symptoms are frequent complaints in patients with MSA and may be associated with reduced gastrointestinal motility due to autonomic nervous system dysfunction. However, there are few reports on gastric emptying in patients with MSA. We investigated gastric emptying in 25 patients with MSA, 20 patients with sporadic adult-onset ataxia of unknown etiology (SAOA), and 20 healthy volunteers using the (13)C-acetate breath test. Gastric emptying function is estimated by this test as the half-emptying time (HET) and peak time of the (13)C-%-dose-excess curve (T (max)), with expirations collected for 4 h after a test meal and determination of (13)CO(2) content using an infrared (IR) spectrophotometer. The HET and T (max) of gastric emptying were significantly delayed in patients with MSA as compared to those in SAOA and controls (p < 0.01). The HET and T (max) were not significantly different between SAOA and controls. No correlation existed between the HET or T (max) and the duration or severity of the disease in MSA patients. These results suggested that gastric emptying was significantly delayed in patients with MSA, and the delay already appeared in the early stage of the disease. Delayed gastric emptying is one of the autonomic failures and may be a clinical marker of MSA.

Is there a delayed gastric emptying of patients with early-stage, untreated Parkinson's disease? An analysis using the 13C-acetate breath test.

During the pre-symptomatic stage of Parkinson's disease (PD), the idiopathic PD related abnormal synuclein immunostaining is confined to the medulla oblongata and olfactory bulb, according to Braak. In the study of the enteric nervous system of PD, it has reported that Lewy bodies were found in the Auerbach's and Meissner's plexuses. These lesions may cause dysfunction of the gastrointestinal tract (GI) as pre-clinical symptoms of PD. However, because L: -dopa therapy itself may worsen the symptoms of the digestive tract function, it is needed to evaluate the gastrointestinal tract function in patients with early-stage, untreated (de novo) PD. In the present study, using the (13)C-acetate breath test ((13)C-ABT), we investigated gastric emptying in 20 untreated, early-stage PD patients and 40 treated, advanced-stage PD patients, and 20 healthy volunteers. Gastric emptying was examined by the (13)C-ABT [the half emptying time (HET), the peak time of the (13)C% dose-excess curve (T (max))]. The T (max) and HET of gastric emptying as assessed using the (13)C-ABT was significantly delayed in untreated, early-stage PD patients as compared to the controls (P < 0.001). The T (max) and HET of gastric emptying were not significantly delayed in untreated, early-stage PD patients as compared to treated, advanced-stage PD patients. The results demonstrated that delay in gastric emptying did not differ between untreated, early-stage and treated, advanced-stage PD patients. Gastric emptying of untreated, early-stage PD is already delayed. Delayed gastric emptying may be one of markers of the pre-clinical stage of PD.

Is increased fat content of hindmilk due to the size or the number of milk fat globules?

BACKGROUND: It is known that the fat content of breast milk is higher in hindmilk than in foremilk. However, it has not been determined if this increased fat content results from an increase in the number of milk fat globules (MFGs), an increase in the size of MFGs, or both. This study aims to determine which factor plays the most important role. METHODS: Thirteen breastfeeding mothers were enrolled in the study and we obtained 52 samples from 26 breasts before (foremilk) and after (hindmilk) a breastfeeding session. The fat content was evaluated by creamatocrit (CrCt) values. MFG size was measured with the laser light scattering method. We compared CrCt values and MFG size between foremilk and hindmilk. RESULTS: Although the CrCt values were higher in the hindmilk (8.6 +/- 3.6%) than in the foremilk (3.7 +/- 1.7%), the MFG size did not change (4.2 +/- 1.0 mum and 4.6 +/- 2.1 mum, foremilk and hindmilk, respectively). There was no relationship between the changes in CrCt versus MFG size from foremilk to hindmilk. CONCLUSION: The results indicate that the increase in fat content results mainly from the increased number of MFGs, which may be released into the milk flow as the mammary lobe becomes progressively emptied.

Is there a difference in gastric emptying between Parkinson's disease patients under long-term L-dopa therapy with and without motor fluctuations? An analysis using the 13C-acetate breath test.

The mechanism underlying the motor fluctuations that develop after long-term L-dopa therapy is not fully known. It has been speculated that malabsorption of L-dopa from the small intestine occurs. It was reported that gastric retention in Parkinson's disease (PD) patients with motor fluctuations is increased as compared with that in PD without fluctuations. Because L-dopa therapy may worsen the symptoms of delayed gastric emptying (GE), it was not clear whether the delayed GE of PD patients with motor fluctuation was affected by L-dopa therapy. We assessed GE in PD patients with and without motor fluctuations. We investigated GE in 40 patients with PD under long-term L-dopa therapy, 20 fluctuators with "delayed-on" and "noon" phenomena, 20 nonfluctuators, and 20 healthy volunteers. GE was examined by the 13C-acetate breath test ((13)CABT) [the half emptying time (HET), the peak time of the (13)C-%-dose-excess curve (T(max))], with expirations collected for 4 h after a test meal and analyzed for (13)CO(2) using an infrared (IR) spectrophotometer. The T(max) of GE as assessed using the (13)C-ABT was significantly delayed in all PD patients as compared with controls (P = 0.002). The HET was significantly delayed in all PD patients as compared with controls (P < 0.001). The T(max) and HET were not significantly delayed in PD patients with motor fluctuations as compared with PD patients without motor fluctuations. These results demonstrated that GE is commonly delayed in PD patients with long-term L-dopa therapy. Delayed GE does not differ between PD patients with and without motor fluctuations. This finding demonstrated that the motor fluctuation in PD may not be influenced by GE.

Comparison of creamatocrit and protein concentration in each mammary lobe of the same breast: does the milk composition of each mammary lobe differ in the same breast?

OBJECTIVE: We sought to determine if different mammary lobes produce milk of varying composition. STUDY DESIGN: Seventeen mothers were enrolled in this study. Foremilk was obtained from three nipple openings on each breast. After the breastfeeding session, hindmilk was sampled in the same manner. We measured creamatocrit (CrCt) and analyzed the protein concentration. Data were analyzed with the paired t test and Wilcoxon signed-rank sum test where appropriate. Coefficient of variance (COV) was calculated to identify the variation of protein content among different mammary lobes. RESULTS: The fat and protein contents of the foremilk and hindmilk from each milk duct differed despite being expressed from the same breast. When we compared the CrCt values and protein content obtained from three ducts, a greater than 5% difference between the maximum and minimum value was observed in 64 out of 68 breasts (94%) for CrCt and in 61 out of 68 breasts (91%) for protein content. The mean COV of protein content in each breast was 13.2 +/- 8.0 (range, 1.2-45.3). CONCLUSIONS: These study results demonstrate that milk synthesis differs in each mammary lobe, even in the same breast. The degree of fullness in each mammary lobe seems to play the most important role in the fat content. The protein content in the milk from each mammary lobe is determined by other factors, presumably by the feedback inhibitor of lactation, accumulated in the corresponding mammary lobe.

Bedside analysis of human milk for adjustable nutrition strategy.

AIM: Mother's milk is optimum for preterm infants, but human milk fortifier is required at times, because some nutrients are sometimes insufficient for infant growth. It is important to measure the nutrients in breast milk at bedside so that the amount of nutrients that need to be supplemented can be determined. A human milk analyser (HMA, Miris) is currently available. We examined if the macronutrient values measured by human milk analyser are comparable with those measured by conventional methods. We also sought to discover whether we could dilute the milk sample used for the human milk analyser measurement if the amount of milk available for testing was insufficient. SUBJECTS AND METHODS: First, the results of protein, fat and lactose content in breast milk samples obtained using the human milk analyser and conventional methods were compared. Second, we measured diluted samples and compared the values with nondiluted samples. RESULTS: When comparing the human milk analyser and conventional methods, all three nutrients exhibited a significantly positive correlation (p < 0.001); lactose content was reliable on the condition that it is 6-7 g/dL. The lactose content measured by the HPLC method was obtained by 3.05 x human milk analyser value - 13.4. When comparing diluted and nondiluted samples, fat and protein had expected values after dilution whereas lactose did not. CONCLUSION: The human milk analyser can inform us about the amount of major nutrients in breast milk: fat, protein and lactose. However, when human milk is diluted, the lactose content measured by the human milk analyser is overestimated.

The important role of deep attachment in the uniform drainage of breast milk from mammary lobe.

AIM: To determine if the degree of attachment affects uniformity in the drainage of breast milk from mammary lobe during breastfeeding. METHODS: Thirty-seven pairs of healthy breast-fed infants and mothers were the subjects. A total of 48 measurements were obtained. Foremilk was obtained from three nipple openings. After the breastfeeding session, hindmilk was sampled from the same three nipple openings and creamatocrit (CrCt) was measured. The difference in CrCt values of hindmilk, which corresponds to the degree of emptying of the lobe, and the difference in CrCt values between fore- and hindmilk samples (delta CrCt), which corresponds to the change in the degree of emptying among the lobe were calculated. RESULTS: The maximum difference in the CrCt value of hindmilk samples among nipple ducts was 7.0 +/- 4.1% in the shallow attachment (S) group (n = 23) and 2.9 +/- 1.2% in the deep attachment (D) group (n = 25) in the left breast and 5.4 +/- 2.2% in the S group (n = 21) and 3.6 +/- 1.9% in the D group (n = 27) in the right breast. The mean maximum difference in delta CrCt values among nipple ducts was 7.6 +/- 2.9% and 2.6 +/- 1.3% in the left and 5.8 +/- 2.3% and 3.4 +/- 1.4% in the right breast, in the S group and D group, respectively. These differences were significantly smaller in the D group than the S group (p < 0.01). CONCLUSION: The results revealed that deep attachment is helpful in draining milk from all mammary lobe uniformly, which may contribute to successful breastfeeding.