Impact of definitive surgery for esophageal atresia on long-term outcomes in patients with trisomy 18.

This study investigates the long-term outcomes of palliative and definitive surgeries for esophageal atresia (EA) in patients with trisomy 18 syndrome. A retrospective study included 25 cases undergoing EA surgery at our center between 2008 and 2022. The Palliative group (n = 16) comprised 13 cases with esophageal banding and 3 with tracheoesophageal fistula (TEF) division. The Definitive group (n = 9) included 5 cases with primary repair and 4 with staged repair following TEF division. The patient characteristics exhibited no significant differences between the groups. In the Definitive group, 56% (5/9) were successfully weaned off mechanical ventilation, compared with none in the Palliative group (p = 0.002). Survival-to-discharge rates were 31% (5/16) in the Palliative group and 67% (6/9) in the Definitive group. Home ventilator management was required for all 5 cases that required ventilation in the Palliative group, whereas only 17% (1/6) in the Definitive group needed it. The Palliative group also required continuous oral suction for persistent saliva removal, with two cases undergoing laryngotracheal separation. Overall, definitive surgery for EA in patients with trisomy 18 syndrome may provide enhanced respiratory stability, thereby improving the survival-to-discharge rate and overall quality of life for patients and their families.

Impact of tracheostomies on the long-term survival of patients with trisomy 13 syndrome.

In this retrospective cohort study, we investigated the impact of tracheostomies on the long-term survival of children with trisomy 13 syndrome at a Japanese tertiary pediatric center. We compared survival and survival to discharge rates between patients who underwent tracheostomies during their NICU stays (T group, n = 8) and those who did not (non-T group, n = 11). A total of 19 patients enrolled. Median survival in all patients was 673 (266-1535) days. Significant differences in the 1-, 2-, and 3-year survival rates were found between the T and the non-T groups (100% vs. 46%, p = 0.018; 88% vs. 18%, p = 0.006; 63% vs. 9%, p = 0.041, respectively). The survival to discharge rate was higher in the T versus non-T group (75% vs. 45%, p = 0.352). This study highlights a significantly higher long-term survival of patients with trisomy 13 syndrome who underwent tracheostomies during their NICU stays.

Improving survival in patients with trisomy 18.

The effects of medical and surgical interventions on the survival of patients with trisomy 18 have been reported, leading to changes in perinatal management and decision-making. However, few studies have fully reported the recent changes in survival and treatment of trisomy 18. We examined how treatment and survival of patients with trisomy 18 have changed over a decade in a Japanese pediatric tertiary referral center. This retrospective cohort study included patients with trisomy 18 who were admitted within the first 7 days of life at the Hyogo Prefectural Kobe Children's Hospital between 2008 and 2017. The patients were divided into early period (EP) and late period (LP) groups based on the birth year of 2008-2012 and 2013-2017, respectively. Changes in treatment and survival rates were compared between the two groups. A total of 56 patients were studied (29 in the EP group and 27 in the LP group). One-year survival rates were 34.5% and 59.3% in the EP and LP groups, respectively. The survival to discharge rate significantly increased from 27.6% in the EP group to 81.5% in the LP group (p < 0.001). The proportion of patients receiving surgery, especially for congenital heart defects, significantly increased from 59% in the EP group to 96% in the LP group (p = 0.001). In our single-center study, survival and survival to discharge were significantly improved in patients with trisomy 18, probably because of increased rate of surgical interventions. These findings may facilitate better decision-making by patients' families and healthcare providers.

Gestational Age Dependency of Umbilical Cord Serum IL-6 Levels for Detecting Fetal Inflammation.

OBJECTIVE: The fetal inflammatory response syndrome (FIRS) is characterized by elevated concentrations of inflammatory cytokines in fetal blood, with preterm delivery and morbidity. Umbilical cord serum interleukin-6 (UC-s-IL-6) is an ideal marker for detecting FIRS. However, the effect of gestational age (GA) on UC-s-IL-6 levels has not been reported. This study aimed to determine the relationship between GA and UC-s-IL-6 levels, and GA-dependent cutoff values of UC-s-IL-6 levels for detecting fetal inflammation. STUDY DESIGN: UC-s-IL-6 concentrations were measured in 194 newborns (44 extremely preterm newborns (EPNs) at 22-27 weeks' GA, 68 very preterm newborns (VPNs) at 28-31 weeks' GA, and 82 preterm newborns (PNs) at 32-34 weeks' GA). Linear regression analyses were used to correlate GA and UC-s-IL-6 levels. Receiver operating characteristic (ROC) curves analyses were performed for detecting the presence of funisitis, as the histopathological counterpart of FIRS. RESULTS: A significant negative correlation between GA and UC-s-IL-6 levels was found in newborns with severe funisitis (r s = - 0.427, p = 0.004) and those with mild funisitis (r s = - 0.396, p = 0.025). ROC curve analyses revealed the area under the curve for detecting funisitis were 0.856, 0.837, and 0.622 in EPNs, VPNs, and PNs, respectively. The UC-s-IL-6 cutoff value in EPNs (28.1 pg/mL) exceeded those in VPNs and PNs (3.7 and 3.0 pg/mL, respectively). CONCLUSION: UC-s-IL-6 levels were inversely correlated with GA especially in newborns with funisitis. Such GA dependency of UC-s-IL-6 should be considered for detecting fetal inflammation. KEY POINTS: · IL-6 levels inversely correlate with GA.. · Higher IL-6 levels strongly indicate funisitis.. · Detecting cutoff values differ depending on GA..

Patterns of increases in interleukin-6 and C-reactive protein as predictors for white matter injury in preterm infants.

BACKGROUND: The aim of this study was to determine whether patterns of increases in serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels at birth were associated with the development of white matter injury (WMI) in preterm infants with a fetal inflammatory response (FIR). METHODS: One hundred infants who were born at <32 weeks gestation and had funisitis, as determined by histological evidence of FIR, were studied. Infants were divided into four groups according to IL-6 and CRP levels at birth, with cut-off values of 200 pg/mL and 0.4 mg/dL, respectively. We compared the incidence of WMI, determined by MRI at term-equivalent age, among these groups. RESULTS: The number of infants in each group was 12, 43, 0, and 45 in the high IL-6 and high CRP (HH) group, high IL-6 and low CRP (HL) group, low IL-6 and high CRP (LH) group, and low IL-6 and low CRP (LL) group, respectively. The incidence of WMI was significantly higher in the HH group than in the HL group and LL group (83%, 40%, and 34%, respectively). Multiple logistic regression analysis revealed that a combined elevation in IL-6 and CRP levels was an independent predictor for the development of WMI (odds ratio, 8.3). CONCLUSION: A combined elevation in serum IL-6 and CRP levels at birth was associated with the development of WMI in preterm infants with FIR.

Neonatal leukemoid reaction associated with Candida albicans chorioamnionitis.

Chorioamnionitis due to Candida species is relatively rare, despite the high prevalence (20-25%) of Candida vulvovaginitis during pregnancy. We describe a case of neonatal leukemoid reaction (NLR) associated with Candida albicans chorioamnionitis. A male infant was born at 31 weeks' gestation and weighed 1864 g. Laboratory tests at birth indicated marked leukocytosis (i.e. total leukocyte count 89.8 × 10(9) /L including 66% polymorphonuclear leukocytes and 15% band forms). Samples of the infant's pharyngeal mucus and tracheal aspirate were positive for Candida albicans. On further histopathology of the placenta, C. albicans mycelia had invaded the placenta, chorioamniotic membrane, and umbilical cord. Although it is not very common, C. albicans chorioamnionitis should be considered in preterm infants with NLR.

Effect of hydrocortisone therapy on severe leaky lung syndrome in ventilated preterm infants.

BACKGROUND: The aim of this study was (i) to determine the incidence and risk factors of severe leaky lung syndrome (sLLS), persistent pulmonary edema characterized by massive tracheal secretions and resistance to surfactant therapy, in extremely low gestational age newborns requiring ventilatory support; and (ii) to evaluate the effects of hydrocortisone (HC) therapy for sLLS on tracheal aspirate fluid (TAF) volume and ß2-microglobulin levels in TAF. METHODS: Infants born at <28 weeks gestation requiring ventilation beyond day of life (DOL) 7 were included. Daily TAF volume changes were assessed using a TAF scoring system. Levels of TAF ß2-microglobulin, an indicator of capillary leakage, were measured at DOL0, 7, before, and 4 days after starting HC therapy (started at 4 mg/kg/day; tapered for 1-3 weeks). RESULTS: Of the 54 infants enrolled, 24 (44%) were diagnosed with sLLS. Lower gestational age, lower birthweight, and higher TAF ß2-microglobulin levels at DOL7 were independent risk factors for sLLS. Seventeen infants with sLLS received HC therapy starting at DOL17 (median), with subsequent decreases in TAF volume and ß2-microglobulin levels. CONCLUSIONS: The incidence of sLLS, as defined in this study, was 44% in extremely low gestational age newborns requiring ventilator support beyond a week. HC therapy effectively reduced TAF volume and ß2-microglobulin levels, suggesting suppression of increased permeability of pulmonary capillaries in infants with sLLS.

Time-course effect of a single dose of hydrocortisone for refractory hypotension in preterm infants.

BACKGROUND: The aim of this study was to determine the time-course effect of a single dose of hydrocortisone (HC) on arterial blood pressure in extremely low gestational age newborns (ELGAN) with refractory hypotension during the first 3 days of life. METHODS: We carried out a matched case-control study of a cohort of 116 infants born between 23 and 27 weeks' gestation at a tertiary center. Twelve infants (10%) were treated with HC for refractory hypotension (HC group). HC was administered at a dose of 2 mg/kg when mean arterial pressure (MAP) was below 30 mmHg (25 mmHg for infants <25 weeks of gestational age) despite the use of inotropes and volume expanders. Changes in the MAP after the HC administration were compared with those in the infants who were not treated with HC and matched for gestational age (Control group). RESULTS: The mean MAP before administration of HC was significantly lower in the HC group than that in the control group (24.0 ± 3.2 vs 33.3 ± 4.8 mmHg; P < 0.01). The mean MAP in the HC group increased significantly at 2 h after HC treatment, and then reached levels comparable to those in the Control group at 5 h (31.3 ± 4.0 vs 33.9 ± 4.7 mmHg; P= 0.18), and remained at normal levels until 12 h after HC treatment. CONCLUSION: A single dose of HC treatment induces a rapid and sustained improvement in blood pressure in ELGAN with refractory hypotension.

Prophylactic indomethacin in extremely premature infants between 23 and 24 weeks gestation.

BACKGROUND: In extremely premature infants, the presence of a left-to-right shunt through a patent ductus arteriosus (PDA) increases the risks of pulmonary hemorrhage, intraventricular hemorrhage, necrotizing enterocolitis, renal failure, and chronic lung disease. Conservative management induces spontaneous ductus closure in <20% of extremely premature infants (infants born at <25 weeks of gestation). The aim of the present study was to determine the efficacy and safety of prophylactic indomethacin (INDO) administration for PDA closure in extremely premature infants born between 23 and 24 weeks of gestation. METHODS: A historical case-control study of 30 infants born between 23 and 24 weeks of gestation was carried out. In the prophylactic INDO group, a 12 h-long, 0.01 mg/kg per h dose of INDO was administered within 6 h of life. During the historical control period, only infants with symptomatic PDA were treated with INDO for 1 h. The incidence of symptomatic PDA, mortality and early neonatal morbidity was compared between the two groups on Fisher's exact test and Mann-Whitney rank-sum test. RESULTS: None of the infants in the prophylactic INDO group had symptomatic PDA, while 11 of the 15 infants in the control group showed symptomatic PDA (P < 0.001). There were no significant differences between the mortality rates and the early neonatal morbidities in the two groups. CONCLUSIONS: Prophylactic INDO administration to extremely premature infants born between 23 and 24 weeks of gestation decreased the incidence of symptomatic PDA without increasing the incidence of adverse effects.

[Multidisciplinary treatment for severe syndromic craniosynostosis].

We describe the treatment of patients having syndromic craniosynostosis with severe craniofacial abnormality. One patient had Cruzon's syndrome, one had Beare-Stevenson cutis gyrata syndrome, and four had Pfeiffers syndrome. Anterior cranial deformity in all patients was treated using fronto-orbital advancement (FOA) by gradual distraction. Initially, the frontal and supraorbital bones were removed and remodeled. Next, the frontal bones were fixed loosely to the supraorbital bones with absorbable threads. Then, the supraorbital and temporal bones were connected using distraction devices on both sides. The temporal bones were thereafter reinforced with titanium plates. Distraction was started one week postoperation, and the mean amount of elongation was 28.9 mm. Distraction devices were removed one to five months after the operation. One case required FOA by the traditional method ten months after the initial operation. Local infection was observed in three cases, but there were no majors complications. Posterior cranial remodelings were performed in five cases, with one requiring a second operation. We chose the appropriate procedure according to the degree of cranial deformity and operative findings. We performed decompression of the foramen magnum in five cases and laminectomy of the atlas in two cases. Ventriculoperitoneal shunt for hydrocephalus and tracheotomy for airway obstruction were performed in all cases. Cranial remodeling for treating severe craniofacial abnormality requires careful inspection of abnormalities, proper timing, close attention to the procedure and adequate perioperative care. Multidisciplinary therapy is essential for treating severe syndromic craniosynostosis due to systematic osseocartilaginous aplasia.

A girl with CLOVES syndrome with a recurrent PIK3CA somatic mutation and pancreatic steatosis.

CLOVES syndrome is characterized by congenital lipomatous overgrowth, vascular malformation, epidermal nevi, and scoliosis/spinal malformation. It is caused by somatic mosaicism of gain-of-function variants of PIK3CA. Here, we describe a novel case of a 5-year-old Japanese girl with CLOVES and concurrent pancreatic steatosis. She had a recurrent somatic mutation in PIK3CA (NM_006218.3: c.1357G>A, p.Glu453Lys), elevated HbA1c levels, and pancreatic steatosis. This case indicates that pancreatic screening is critical for PIK3CA-related disorders.

Patient with a novel purine-rich element binding protein A mutation.

There have been several reports on 5q31.3 microdeletion syndrome. The overlapping deleted region includes purine-rich element binding protein A (PURA), which encodes transcriptional activator protein Pur-α. Patients with PURA mutations show moderate to severe neurodevelopmental delay and learning disability. Neonatal hypotonia, respiratory insufficiency, feeding difficulties, and seizures are often seen. Dysmorphic features including myopathic faces are helpful as clinical signs of the diagnosis. We report a patient with a novel PURA mutation detected by whole-exome sequencing. We suggest that PURA abnormality is a recognizable syndrome.

Congenital immature pure erythroid leukemia with E-cadherin expression.

Congenital pure erythroid leukemia is exceedingly rare and poses a diagnostic challenge. We report an atypical case of congenital pure erythroid leukemia that did not express typical erythroid markers. The patient presented with a high white blood cell count with blastic cells at birth. Although flow cytometric analyses of peripheral blood and bone marrow showed a large CD45-negative cell population, we did not identify any evidence of monoclonality. While the circulating blasts decreased with only supportive care, hepatomegaly with multiple nodules was accompanied by liver failure, disseminated intravascular coagulation, and development of hemophagocytic lymphohistiocytosis. Pathological examination of the liver biopsy specimen revealed a small round cell tumor that was negative for nearly all hematopoietic cell markers, including classical erythroid cell markers, and positive for CD43, CD71, and E-cadherin, an early erythroid marker epithelial calcium-dependent adhesion protein, suggesting that these tumor cells originated from an immature erythroblast. We found high ß-catenin and c-Myc protein expression, which were not previously described in pure erythroid leukemia. Cytosine arabinoside temporarily alleviated clinical symptoms; however, the patient died of progressive disease at 8 months of age. This case indicates that E-cadherin is useful for diagnosing pure erythroid leukemia, even in immature cases.

Very Low Birth Weight Monochorionic Diamniotic Twins as a Risk Factor for Symptomatic Patent Ductus Arteriosus.

BACKGROUND: Some prior studies have shown that symptomatic patent ductus arteriosus (sPDA) is highly familial. Although it is estimated that both genetic and environmental factors may contribute to sPDA, evidence is still lacking. OBJECTIVE: The aim of this study was to determine the risk factors for sPDA, focusing on the genetic and in utero environment by analyzing very low birth weight (VLBW) singletons and twins. METHODS: This retrospective case-control study reviewed the medical records of 445 VLBW infants (25 weeks ≤ gestational age <32 weeks, 600 g ≤ birth weight <1,500 g) and compared the incidence of sPDA among monochorionic diamniotic (MD) twins (n = 65), dichorionic diamniotic (DD) twins (n = 66), and singletons (n = 314). RESULTS: Stepwise multiple regression analysis showed that twin siblings (p = 0.001), gestational week (p < 0.001), antenatal steroid use (p = 0.021), and premature rupture of membranes (p = 0.002) were independent predictors of sPDA. Incidence of sPDA in MD twin siblings was significantly higher than that in singletons (p < 0.01), whereas no significant difference was found between singletons and DD twins or between MD and DD twins. CONCLUSIONS: The current results show that being a VLBW MD twin is an independent risk factor for sPDA, and that both genetic and in utero environmental factors may contribute to its development.

Familial Hemophagocytic Lymphohistiocytosis Presenting as Hydrops Fetalis.

Background Familial hemophagocytic lymphohistiocytosis (FLH) is an autosomal recessive disorder of immune regulation that leads to a hyperinflammatory syndrome. Fetal onset FHL is extremely rare and is considered to be the most severe form of FHL. Case We report a preterm case of FHL that presented as hydrops fetalis. The infant was treated with a chemotherapy regimen based on the HLH-2004 protocol from the third day of life. However, he had persistent cytopenia and died on the 18th day of life due to bacteremia. The detection of defective perforin expression in the patient's natural killer cells and mutations in the PRF1 gene resulted in a molecular diagnosis of FHL. Conclusion We suggest that early diagnosis and the development of an appropriate immunosuppressive strategy that can induce and maintain remission until hematopoietic stem cell transplantation can be performed are required to improve the outcomes of fetal onset FHL.

Successful management of an extremely premature infant with congenital candidiasis.

Congenital candidiasis, which presents with a variety of clinical symptoms, is very rare in both term and preterm infants, and less than 100 neonatal cases have been reported in the medical literature. We describe the case of an extremely premature infant with congenital candidiasis, who was successfully treated and survived without major sequelae. A male infant was born at 25 weeks' gestation (weight, 834 g). He exhibited diffuse erythematous papules. Samples of his skin, pharyngeal mucus, gastric fluid, and tracheal aspirate were found to be Candida albicans-positive while blood cultures were negative. Further histopathological examinations revealed that Candida albicans mycelia had invaded the umbilical cord. After prompt antifungal therapy, the patient's skin lesions improved markedly, and he was discharged from hospital without any major complications. This report highlights the importance of characteristic skin lesions for the early diagnosis of Candida infections, especially in extremely premature infants.