Fatality owing to pulmonary hemorrhage following pamidronate disodium administration in a neonate with osteogenesis imperfecta type 2: A case report.

We report the case of a patient with osteogenesis imperfecta (OI) who developed pulmonary hemorrhage 4 d after pamidronate disodium (PA) administration, despite a relatively stable respiratory status. Bisphosphonates are introduced to reduce osteoclast activity and are now widely used in patients with OI. Bisphosphonates are typically well-tolerated in children, and the standard of care involves cyclic intravenous administration of PA. However, in practice, there is limited experience with the use of PA for severe OI during the neonatal period, and its safety remains uncertain. This report aimed to describe the respiratory events potentially associated with PA in a neonatal patient with OI type 2, suggesting that serious life-threatening complications of pulmonary hemorrhage may occur after PA administration. Further studies are required to assess the relationship between pulmonary hemorrhage and PA administration, aiming to enhance prophylaxis measures.

Assessment of pulmonary artery size at birth as a prognostic factor in congenital diaphragmatic hernia: results of a multicenter study in Japan.

OBJECTIVE: To assess the reliability of pulmonary artery (PA) parameters as a prognostic marker in neonates with isolated left-sided congenital diaphragmatic hernia (IL-CDH). STUDY DESIGN: A retrospective cohort study conducted by the Japanese CDH Study Group (JCDHSG). RESULTS: 323 IL-CDH patients registered with the JCDHSG were included. 272 patients survived to 90 days of age. Right PA (RPA) and left PA (LPA) diameters and pulmonary artery index (PAIndex) at birth were significantly larger in survivors. The cutoff values of RPA and LPA diameters and PAIndex for survival up to 90 days were 3.2 mm, 2.8 mm and 83.7, respectively, and logistic regression analysis showed that these were significantly related to survival. Multiple logistic regression analysis showed that both the PA parameters and liver herniation were significantly related to survival. CONCLUSIONS: The three PA parameters at birth can predict clinical outcomes and are considered as independent risk factors of liver herniation.

Intraoperative Transpyloric Tube Insertion for Congenital Diaphragmatic Hernia: Analysis of Japanese Study Group Data.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a severe congenital disease. Some CDH infants suffer from gastro-esophageal reflux disease (GERD), even after surgical correction of gastric position. A transpyloric tube (TPT) is inserted into CDH patients under direct observation intraoperatively in some hospitals in Japan to establish early enteral feeding. This strategy avoids gastric expansion to maintain a better respiratory condition. However, it is unclear whether the strategy has a secure effect for patient prognosis. This study aimed to evaluate the effectiveness of intraoperative TPT insertion on enteral feeding and postoperative weight gain. METHODS: The Japanese CDH Study Group database was used to identify infants with CDH born between 2011 and 2016, who were then divided into two groups: the TPT group and gastric tube (GT) group. In the TPT group, infants underwent intraoperative TPT insertion; postoperative insertion/extraction of TPT was irrelevant to the analysis. Weight growth velocity (WGV) was calculated using the exponential model. Subgroup analysis was performed using Kitano's gastric position classification. RESULTS: We analyzed 204 infants, of which 99 and 105 were in the TPT and GT groups, respectively. Enteral nutrition (EN) in the TPT and GT groups was 52 ± 39 and 44 ± 41 kcal/kg/day (p = 0.17) at age 14 days (EN14), respectively, and 83 ± 40 and 78 ± 45 kcal/kg/day (p = 0.46) at age 21 days (EN21), respectively. WGV30 (WGV from day 0 to day 30) in the TPT and GT groups was 2.3 ± 3.0 and 2.8 ± 3.8 g/kg/day (p = 0.30), respectively, and WGV60 (WGV from day 0 to day 60) was 5.1 ± 2.3 and 6.0 ± 2.5 g/kg/day (p = 0.03), respectively. In infants with Kitano's Grade 2 + 3, EN14 in the TPT and GT groups was 38 ± 35 and 29 ± 35 kcal/kg/day (p = 0.24), respectively, EN21 was 73 ± 40 and 58 ± 45 kcal/kg/day (p = 0.13), respectively, WGV30 was 2.3 ± 3.2 and 2.0 ± 4.3 g/kg/day (p = 0.76), respectively, and WGV60 was 4.6 ± 2.3 and 5.2 ± 2.3 g/kg/day (p = 0.30), respectively. CONCLUSION: Intraoperative TPT insertion did not improve nutritional intake and WGV30. WGV60 in TPT was less than that in GT. In Grade 2 + 3 subgroup analysis, TPT also had no advantage. We could not recommend routine TPT insertion at surgery. LEVEL OF EVIDENCE: III.

Outcomes of congenital diaphragmatic hernia among preterm infants: inverse probability of treatment weighting analysis.

OBJECTIVES: To evaluate the survival and intact-survival rates among preterm infants with congenital diaphragm hernia (CDH). STUDY DESIGN: Multicenter retrospective cohort study of 849 infants born between 2006 and 2020 at 15 Japanese CDH study group facilities. Multivariate logistic regression analysis adjusted using inverse probability treatment weighting (IPTW) method was used. We also compare trends of intact-survival rates among term and preterm infants with CDH. RESULTS: After adjusting using the IPTW method for CDH severity, sex, APGAR score at 5 min, and cesarean delivery, gestational age and survival rates have a significantly positive correlation [coefficient of determination (COEF) 3.40, 95% confidence interval (CI), 1.58-5.21, p value <0.001] and higher intact-survival rate [COEF 2.39, 95% CI, 1.73-4.06, p value 0.005]. Trends of intact-survival rates for both preterm and term infants had significantly changed, but improvement in preterm infants was much smaller than in term infants. CONCLUSION: Prematurity was a significant risk factor for survival and intact-survival among infants with CDH, regardless of adjustment for CDH severity.

A Neonate with Mucopolysaccharidosis Type VII with Intractable Ascites.

We report a case of a patient with severe fetal hydrops and refractory ascites, diagnosed as mucopolysaccharidosis type VII (MPS VII) by whole-exome sequencing, and discharged at 5 months of age after long-term ventilatory management. A male neonate was born by emergency cesarean section due to fetal distress at 30 1/7 weeks' gestation. Physical examination and X-rays revealed pleural effusion, ascites, and generalized edema, indicating severe fetal hydrops. He underwent tracheal intubation because of respiratory distress that was attributed to massive ascites, pulmonary hypoplasia, and pulmonary hypertension. He received mechanical ventilation and inhaled nitric oxide therapy. Prednisone, octreotide, and a factor XIII preparation were used as the treatment for ascites, and the ascites gradually decreased. He was extubated within 2 months of age. At 4 months of age, the results of whole-exome sequencing of the cord blood showed a compound heterozygous mutation in the GUSB gene, the gene responsible for MPS VII. Enzyme replacement therapy was initiated, and the ascites was resolved. Careful systemic management, including lung-protective respiratory management and the early establishment of nutrition, is important for the long-term survival of infants with fetal hydrops, and early aggressive workup, including whole-genome sequencing for the cause, should be performed in the case of refractory ascites.

Development of mortality prediction models for infants with isolated, left-sided congenital diaphragmatic hernia before and after birth.

BACKGROUND: Mortality prediction of congenital diaphragmatic hernia (CDH) is essential for developing treatment strategies, including fetal therapy. Several researchers have reported prognostic factors for this rare but life-threatening condition; however, the optimal combination of prognostic factors remains to be elucidated. OBJECTIVES: This study aimed to develop the most discriminative prenatal and postnatal models to predict the mortality of infants with an isolated left-sided CDH. METHODS: This multi-institutional retrospective cohort study included infants with CDH born at 15 tertiary hospitals of the Japanese CDH Study Group between 2011 and 2016. We developed multivariable logistic models with every possible combination of predictors and identified models with the highest cross-validated area under the receiver operating characteristic curve (AUC) for prenatal and postnatal predictions. RESULTS: Among 302 eligible infants, 44 died before discharge. The prenatal mortality prediction model was based on the observed/expected lung area to head circumference ratio (O/E LHR), liver herniation, and stomach herniation (AUC, 0.830). The postnatal mortality prediction model was based on O/E LHR, liver herniation, and the lowest oxygenation index (AUC, 0.944). CONCLUSION: Our models can facilitate the prenatal and postnatal mortality prediction of infants with isolated left-sided CDH.

A predictive scoring system for small diaphragmatic defects in infants with congenital diaphragmatic hernia.

PURPOSE: To develop a predictive score for small diaphragmatic defects in infants with congenital diaphragmatic hernia (CDH) for determining thoracoscopic surgery indication. METHODS: The Japanese CDH Study Group cohort was randomly divided into derivation (n = 397) and validation (n = 396) datasets. Using logistic regression, a prediction model and weighted scoring system for small diaphragmatic defects were created from derivation dataset and validated with validation dataset. RESULTS: Six weighted variables were selected: no hydramnios, 1 point; 1 min Apgar score of 5-10, 1 point; apex type of the lung (left lung is detected radiographically in apex area), 1 point; oxygenation index < 8, 1 point; abdominal nasogastric tube (tip of the nasogastric tube is detected radiographically in the abdominal area), 2 points; no right-to-left flow of ductus arteriosus, 1 point. In validation dataset, rates of small diaphragmatic defects for Possible (0-3 points), Probable (4-5 points), and Definite (6-7 points) groups were 36%, 81%, and 94%, respectively (p < 0.001). Additionally, sensitivity, specificity, positive predictive value, and C statistics were 0.78, 0.79, 0.88, 0.76, and 0.45, 0.94, 0.94, 0.70 for Probable and Definite groups, respectively. CONCLUSION: Our scoring system effectively predicted small diaphragmatic defects in infants with CDH.

Prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia: a systematic review and meta-analysis.

PURPOSE: This study aimed to evaluate prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia (CDH). METHODS: A systematic literature search was performed to identify relevant observational studies that evaluated the ability of lung-to-head ratio (LHR), observed-to-expected LHR (o/e-LHR), observed-to-expected total fetal lung volume (o/e-TFLV), lung-to-thorax transverse area ratio (L/T ratio), intrathoracic herniation of the liver and the stomach, and side of diaphragmatic hernia, using a threshold for the prediction of mortality in fetuses with CDH. Study quality was assessed using the QUADAS-2 tool. Hierarchical summary receiver operating characteristic curves were constructed. RESULTS: A total of 50 articles were included in this meta-analysis. The QUADAS-2 tool identified a high risk of bias in more than one domain scored in all parameters. Among those parameters, the diagnostic odds ratio of mortality with o/e-LHR < 25%, o/e-TFLV < 25%, and L/T ratio < 0.08 were 11.98 [95% confidence interval (CI) 4.65-30.89], 11.14 (95% CI 5.19-23.89), and 10.28 (95% CI 3.38-31.31), respectively. The predictive values for mortality were similar between the presence of liver herniation and retrocardiac fetal stomach position. CONCLUSIONS: This systematic review suggests that o/e-LHR, o/e-TFLV, and L/T ratio are equally good predictors of neonatal mortality in fetuses with isolated CDH.

The efficacy of the postnatal nasogastric tube position as a prognostic marker of left-sided isolated congenital diaphragmatic hernia.

PURPOSE: The prenatal diagnosis of the stomach position in congenital diaphragmatic hernia (CDH) has been a reliable prognostic factor, but few studies have focused on the postnatal position. We therefore evaluated the significance of the nasogastric (NG) tube position just after birth. METHODS: The Japanese CDH Study Group database enrolled 1037 CDH neonates over 15 years. In our multicenter retrospective study, 464 cases of left-sided isolated CDH with prenatal diagnoses were divided into two groups: NG tube below the diaphragm (BD; n = 190) or above the diaphragm (AD; n = 274). The primary outcome was the 90-day survival rate, and the secondary outcomes were mechanical ventilation duration, hospitalization duration, and recurrence rate. RESULTS: The BD group had a significantly higher 90-day survival rate (98.4 vs. 89.4%, p < 0.001), shorter mechanical ventilation (11 vs. 19 days, p < 0.001), shorter hospitalization (38 vs. 59 days, p < 0.001), and lower recurrence rate (p = 0.002) than the AD group. A multivariate analysis showed that BD (adjusted odds ratio, 3.68; 95% confidence interval 1.02-13.30) was a favorable prognostic factor for the 90-day survival. CONCLUSION: The assessment of the NG tube position revealed it to be a reliable prognostic factor of left-sided isolated CDH. Therefore, it should be included as a routine assessment.

Long-Term Outcomes of Congenital Diaphragmatic Hernia: Report of a Multicenter Study in Japan.

BACKGROUND: Treatment modalities for neonates with congenital diaphragmatic hernia (CDH) have greatly improved in recent years, with a concomitant increase in survival. However, long-term outcomes restrict the identification of optimal care pathways for CDH survivors in adolescence and adulthood. Therefore, we evaluated the long-term outcomes within the Japanese CDH Study Group (JCDHSG). METHODS: Participants were born with CDH between 2006 and 2018 according to the JCDHSG. Participants were enrolled in the database at 1.5, 3, 6, and 12 years old. Follow-up items included long-term complications, operations for long-term complication, and home medical care. RESULTS: A total of 747 patients were included in this study, with 626 survivors (83.8%) and 121 non-survivors (16.2%). At 1.5, 3, 6, and 12 years old, 45.4%, 36.5%, 34.8%, and 43.6% developed complications, and 20.1%, 14.7%, 11.5%, and 5.1% of participants required home care, respectively. Recurrence, pneumonia, pneumothorax, gastroesophageal reflux disease, and intestinal obstruction decreased with age, and thoracic deformity increased with age. CONCLUSIONS: As CDH survival rates improve, there is a need for continued research and fine-tuning of long-term care to optimize appropriate surveillance and long-term follow-up.

Best pre-ductal PaO2 prior to extracorporeal membrane oxygenation as predictor of mortality in patients with congenital diaphragmatic hernia: a retrospective analysis of a Japanese database.

PURPOSE: Predicting lethal pulmonary hypoplasia in infants with congenital diaphragmatic hernia (CDH) before extracorporeal membrane oxygenation (ECMO) initiation is difficult. This study aimed to predict lethal pulmonary hypoplasia in patients with CDH prior to ECMO. METHODS: This was a multicenter cohort study involving neonates prenatally diagnosed with isolated unilateral CDH (born 2006-2020). Patients who required ECMO due to respiratory insufficiency were included in this study. Patients who underwent ECMO due to transient disorders were excluded from analysis. Blood gas analysis data within 24 h of birth were compared between survivors and non-survivors. Predictive abilities were assessed for factors with significant differences. RESULTS: Overall, 34 patients were included (18 survivors and 16 non-survivors). The best pre-ductal PaO2 was significantly lower in non-survivors than in survivors (50.4 [IQR 30.3-64.5] vs. 67.5 [IQR 52.4-103.2] mmHg, respectively; p = 0.047). A cutoff PaO2 of 42.9 mmHg had a sensitivity, specificity, and positive predictive value of 50.0%, 94.4%, and 88.9%, respectively, to predict mortality. CONCLUSION: The best PaO2 within 24 h after birth predicted mortality following ECMO initiation. This should be shared to families and caregivers to optimize the best interests of the infants with CDH.

Optimal timing of delivery for pregnancies with prenatally diagnosed congenital diaphragmatic hernia: a propensity-score analysis using the inverse probability of treatment weighting.

OBJECTIVE: To evaluate the optimal timing of neonates with prenatally diagnosed congenital diaphragmatic hernia (CDH). METHODS: Data from a retrospective cohort study conducted by the Japanese CDH Study Group between 2011 and 2018 were divided into two groups according to delivery timing: 36-37 and 38-41 weeks of gestation (wg). Death before 90 days as the primary outcome and the duration of hospitalization, oxygen therapy and tube feeding at discharge as the secondary outcomes were analyzed with generalized linear model applying inverse probability of treatment weighting method. We also performed layered analysis according to stomach position. RESULT: Among 493 neonates with prenatally diagnosed, isolated and left CDH, 237 were born at 38-41wg. The duration of hospitalization was significantly shorter in those born at 38-41wg, especially among those with stomach malposition, and the other outcomes showed no difference. CONCLUSIONS: Delivery at 38-41wg could be beneficial for those with high grade stomach position.

Neonatal systemic juvenile Xanthogranuloma with Hydrops diagnosed by Purpura skin biopsy: a case report and literature review.

BACKGROUND: Systemic juvenile xanthogranuloma is a very rare disease typically presents as skin lesions with yellow papules or nodules and is sometimes fatal. We report a case of congenital neonatal systemic juvenile xanthogranuloma with atypical skin appearance that made the diagnosis difficult. CASE PRESENTATION: A preterm Japanese female neonate with prenatally diagnosed fetal hydrops in-utero was born with purpuric lesions involving the trunk and face. Since birth, she had hypoxemic respiratory failure, splenomegaly, anemia, thrombocytopenia, coagulopathy, and was transfusion dependent for red blood cells, fresh frozen plasma, and platelets. Multiple cystic lesions in her liver, part of them with vascular, were detected by ultrasound. A liver biopsy was inconclusive. A skin lesion on her face similar to purpura gradually changed to a firm and solid enlarged non-yellow nodule. Technically, the typical finding on skin biopsy would have been histiocytic infiltration (without Touton Giant cells) and immunohistochemistry results which then would be consistent with a diagnosis of systemic juvenile xanthogranuloma, and chemotherapy improved her general condition. CONCLUSIONS: This case report shows that skin biopsies are necessary to detect neonatal systemic juvenile xanthogranuloma when there are organ symptoms and skin eruption, even if the skin lesion does not have a typical appearance of yellow papules or nodules.

Optimal timing of surgery in infants with prenatally diagnosed isolated left-sided congenital diaphragmatic hernia: a multicenter, cohort study in Japan.

PURPOSE: To date, there is no compelling evidence of the optimal timing of surgery for congenital diaphragmatic hernia (CDH). This study aimed to establish the optimal timing of surgery in neonates with isolated left-sided CDH. METHODS: This multicenter cohort study enrolled 276 patients with isolated left-sided CDH at 15 institutions. Based on the timing of surgery, the patients were classified into four groups [< 24 h (G1), 24-47 h (G2), 48-71 h (G3), and ≥ 72 h (G4)]. The clinical outcomes were compared among the groups using a logistic regression model, after adjusting for potential confounders, such as disease severity. RESULTS: Multivariate analyses showed that G2 also had a lower mortality rate than the other groups. In mild and severe cases, there were no significant differences in mortality across the four groups. In moderate cases, G2 resulted in significantly increased survival rates, compared with G1. CONCLUSION: The study results suggest that surgery within 24 h of birth is not recommended for patients with moderate severity CDH, that there is no benefit in the delay of surgery for more than 72 h in mild severity CDH patients, and that there is no definite optimal time to perform surgery in severe cases of CDH.

Prognosis of conventional vs. high-frequency ventilation for congenital diaphragmatic hernia: a retrospective cohort study.

OBJECTIVE: To determine the appropriate initial ventilatory mode for neonatal congenital diaphragmatic hernia (CDH) by comparing patient prognosis following conventional mechanical ventilation (CMV) versus high-frequency oscillatory ventilation (HFO). STUDY DESIGN: This multicenter retrospective cohort study was performed at 15 participating hospitals in Japan between 2011 and 2016. The 328 eligible CDH infants were classified into CMV (n = 78) and HFO groups (n = 250) to compare mortality and incidence of bronchopulmonary dysplasia (BPD). Propensity score matching was applied to reduce confounding by indication. RESULT: While crude mortality was significantly higher in the HFO than the CMV group, adjusted odds ratio (OR) did not show significant difference in mortality between groups (OR of HFO group: 0.98, 95% confidence interval (CI): 0.57-1.67). Adjusted OR of BPD incidence showed no significant difference between groups (OR of HFO group: 1.66, 95%CI: 0.50-5.49). CONCLUSION: Initial ventilatory mode in CDH patients, whether CMV or HFO, does not affect prognosis.

Branched-chain amino acid supplementation for improving growth and development in term and preterm neonates.

BACKGROUND: Branched-chain amino acids (BCAAs) play a vital role in neonatal nutrition. Optimal BCAA supplementation might improve neonatal nutrient storage, leading to better physical and neurological development and other outcomes. OBJECTIVES: To determine the effect of BCAA supplementation on physical growth and neurological development in term and preterm neonates. We planned to make the following comparisons: parenteral nutrition with and without BCAA supplementation; enteral BCAA supplementation versus no supplementation; and any type of supplementation including enteral, parenteral and both ways versus no supplementation. To investigate the supplementation effectiveness for different dosages assessed in the eligible trials. SEARCH METHODS: We conducted comprehensive searches using Cochrane Neonatal's standard search strategies: Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 6), MEDLINE, Embase and CINAHL (up to July 2016). We updated the search with CENTRAL (2019, Issue 8), MEDLINE, Embase and CINAHL (up to August 2019). We also searched clinical trials registries and reference lists of retrieved articles. SELECTION CRITERIA: We planned to include individual and cluster-randomised and quasi-randomised controlled trials comparing BCAA supplementation versus placebo or no supplementation in term and preterm neonates. We excluded trials presented only as abstracts and cross-over trials. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of all potential studies identified from the search strategy. We planned to extract data using a pilot-tested standard data extraction form and assess risk of bias of the included studies following the methods described in the Cochrane Handbook for Systematic Reviews of Interventions. We planned to analyse treatment effects and report their effect estimates as per dichotomous or continuous data with 95% confidence intervals. We planned to conduct subgroup analysis to investigate heterogeneity, and perform sensitivity analysis where possible. We planned to use fixed-effect meta-analysis to combine data wherever appropriate. We planned to assess evidence quality using the GRADE approach. MAIN RESULTS: We did not identify any potentially eligible studies that met the inclusion criteria in this review. AUTHORS' CONCLUSIONS: We found no trial data to support or refute the idea that BCAA supplementation affects physical and neurological development and other outcomes in term and preterm neonates.

Feasibility and outcomes of fetoscopic endoluminal tracheal occlusion for severe congenital diaphragmatic hernia: A Japanese experience.

AIM: To present the feasibility, safety and outcomes of fetoscopic endoluminal tracheal occlusion (FETO) for the treatment of severe congenital diaphragmatic hernia (CDH). METHODS: This was a single-arm clinical trial of FETO for isolated left-sided CDH with liver herniation and Kitano Grade 3 stomach position (>50% stomach herniation into the right chest). FETO was performed at 27-29 weeks of gestation for cases with observed/expected lung to head ratio (o/e LHR) <25% and at 30-31 weeks for cases with o/e LHR ≥25%. RESULTS: Eleven cases were enrolled between March 2014 and March 2016, and balloon insertion was successful in all cases. The median o/e LHR at entry was 27% (range, 20-33%). The median gestational age at FETO was 30.9 (range, 27.1-31.7) weeks. There were no severe maternal adverse events. One fetus died unexpectedly at 33 weeks of gestation due to cord strangulation by the detached amniotic membrane. There were 3 cases (27%) of preterm premature rupture of membranes. In all 10 cases, balloon removal at 34-35 weeks of gestation was successful. The median gestational age at delivery was 36.5 (range, 34.2-38.3) weeks. The median duration of occlusion and the median interval between balloon insertion and delivery were 26 days (range: 17-49 days) and 43 days (range, 21-66 days), respectively. Both the survival rate at 90 days of age and the rate of survival to discharge were 45% (5/11). CONCLUSION: The FETO is feasible without maternal morbidity in Japan and could be offered to women whose fetuses show severe isolated left-sided CDH to accelerate fetal lung growth.

Risk factors for pneumothorax associated with isolated congenital diaphragmatic hernia: results of a Japanese multicenter study.

PURPOSE: This study aimed to elucidate the clinical characteristics of neonates with congenital diaphragmatic hernia (CDH) associated with pneumothorax and evaluate the risk factors for the development of pneumothorax. METHODS: A retrospective cohort study was conducted in the 15 institutions participating in the Japanese CDH Study Group. A total of 495 neonates with isolated CDH who were born between 2011 and 2018 were analyzed in this study. RESULTS: Among the 495 neonates with isolated CDH, 52 (10.5%) developed pneumothorax. Eighteen (34.6%) patients developed pneumothorax before surgery, while 34 (65.4%) developed pneumothorax after surgery. The log-rank test showed that the cumulative survival rate was significantly lower in patients with pneumothorax than in those without pneumothorax. Univariate analysis revealed significant differences between patients with pneumothorax and those without pneumothorax with regard to the best oxygenation index within 24 h after birth, mean airway pressure (MAP) higher than 16 cmH2O, diaphragmatic defect size, and need for patch closure. Multiple logistic regression analysis indicated that only the MAP was associated with an increased risk of pneumothorax. CONCLUSIONS: The cumulative survival rate was significantly lower in isolated CDH patients with pneumothorax than in those without pneumothorax. A higher MAP was a risk factor for pneumothorax in CDH patients.

An extremely severe case of Aicardi-Goutières syndrome 7 with a novel variant in IFIH1.

We describe herein an extremely severe case of Aicardi-Goutières syndrome 7 (AGS7). The female patient was the daughter of nonconsanguineous parents and developed cardiomegaly, pericardial effusion, splenomegaly, and intracranial calcification during the fetal period. Because her cardiotocogram showed a non-reassuring fetal status, she was delivered at 29 weeks and 4 days of gestation by an emergency cesarean section. After birth, she suffered from respiratory distress, pulmonary hypertension, refractory fever, recurrent thrombocytopenia, and abdominal distention caused by hepatomegaly and ascites. She showed a lenticulostriate vasculopathy, which was compatible with the fetal intracranial calcification. Despite various intensive care procedures, she died of gradually progressive pulmonary hypertension at 3 months of age. After her death, whole exome sequencing on the patient and the parents was performed and revealed a novel, de novo, heterozygous mutation in the IFIH1 gene (IFIH1:NM_022168:exon12:c.2439A > T:p.Glu813Asp). On the basis of the mutation and the clinical features, the diagnosis was AGS7. Although AGS7 has been regarded as a relatively mild subtype of Aicardi-Goutières syndrome, this case indicates that the c.2439A > T variant of AGS7 can be fatal in early infancy.

Effects of Domperidone in Increasing Milk Production in Mothers with Insufficient Lactation for Infants in the Neonatal Intensive Care Unit.

Breast milk is the optimum for all infants, but hospitalization in the neonatal intensive care unit can cause separation of mothers and infants, which often interferes with milk secretion. Some reports show that domperidone is effective in promoting milk secretion. However, the Food and Drug Administration in the United States cautioned to not use domperidone for increasing milk volume because domperidone carries some risk of cardiac events, including QT prolongation, cardiac arrest, and sudden death. In contrast, it is used in Canada, Australia, and the United Kingdom with safety. The pharmacodynamics and pharmacokinetics of drugs may vary by race or ethnic origin, and it is not known whether domperidone is effective or safe for Japanese. In this study we report the effects of domperidone for Japanese mothers with insufficient lactation. Ten mothers were enrolled in a pilot study. After confirming that there were no abnormal findings on the electrocardiogram, the mothers were administered domperidone. Seven of 10 who took domperidone increased their milking volume. Prolactin was increased in 9 of 10 mothers. Adverse events were observed in two mothers, one headache and one abdominal pain; all symptoms were mild and improved promptly; and there were no adverse cardiac events. These results are consistent with reports from other countries. Domperidone may tentatively be considered effective for increasing milk secretion in Japanese mothers as in other populations. Our preliminary study of 10 cases indicates the need for further studies with larger sample sizes to assess the efficacy and safety of domperidone.