The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD).

In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). Fetal AChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicentre cohort (n = 46 cases) associated with maternal fAChR antibodies, including 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established myasthenia gravis (MG) diagnosis. All mothers (n = 30) had AChR antibodies and, when tested, binding to fAChR was often much greater than that to the adult AChR isoform. Offspring death occurred in 11/46 (23.9%) cases, mainly antenatally due to termination of pregnancy prompted by severe AMC (7/46, 15.2%), or during early infancy, mainly from respiratory failure (4/46, 8.7%). Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors. Other unexpected features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/37 (43.2%) offspring resulted in symptom improvement in 13/16 (81.3%). Combining our series with all previously published cases, we identified 21/85 mothers treated with variable combinations of immunotherapies (corticosteroids/intravenous immunoglobulin/plasmapheresis) during pregnancy either for maternal MG symptom control (12/21 cases) or for fetal protection (9/21 cases). Compared to untreated pregnancies (64/85), maternal treatment resulted in a significant reduction in offspring deaths (P < 0.05) and other complications, with treatment approaches involving intravenous immunoglobulin/ plasmapheresis administered early in pregnancy most effective. We conclude that presentations due to in utero exposure to maternal (fetal) AChR antibodies are more common than currently recognized and may mimic a wide range of neuromuscular disorders. Considering the wide clinical spectrum and likely diversity of underlying mechanisms, we propose 'fetal acetylcholine receptor antibody-related disorders' (FARAD) as the most accurate term for these presentations. FARAD is vitally important to recognize, to institute appropriate management strategies for affected offspring and to improve outcomes in future pregnancies. Oral salbutamol is a symptomatic treatment option in survivors.

Risk factors and clinical outcomes of extubation failure in very early preterm infants: a single-center cohort study.

BACKGROUND: Early extubation success (ES) in preterm infants may reduce various mechanical ventilation-associated complications; however, extubation failure (EF) can cause adverse short- and long-term outcomes. Therefore, the present study aimed to identify differences in risk factors and clinical outcomes between ES and EF in very early preterm infants. METHODS: This retrospective study was conducted between January 2017 and December 2021. Premature infants born at 32 weeks' gestational age in whom extubation had failed at least once were assigned to the EF group. Successfully extubated patients with a similar gestational age and birth weight as those in the EF group were assigned to the ES group. EF was defined as the need for re-intubation within 120 h of extubation. Various variables were compared between groups. RESULTS: The EF rate in this study was 18.6% (24/129), and approximately 80% of patients with EF required re-intubation within 90.17 h. In the ES group, there was less use of inotropes within 7 days of life (12 [63.2%] vs. 22 [91.7%], p = 0.022), a lower respiratory severity score (RSS) at 1 and 4 weeks (1.72 vs. 2.5, p = 0.026; 1.73 vs. 2.92, p = 0.010), and a faster time to reach full feeding (18.7 vs. 29.7, p = 0.020). There was a higher severity of bronchopulmonary dysplasia BPD (3 [15.8%] vs. 14 [58.3%], p = 0.018), longer duration of oxygen supply (66.5 vs. 92.9, p = 0.042), and higher corrected age at discharge (39.6 vs. 42.5, p = 0.043) in the EF group. The cutoff value, sensitivity, and specificity of the respiratory severity score (RSS) at 1 week were 1.98, 0.71, and 0.42, respectively, and the cutoff value, sensitivity, and specificity of RSS at 4 weeks were 2.22, 0.67, and 0.47, respectively. CONCLUSIONS: EF caused adverse short-term outcomes such as a higher BPD severity and longer hospital stay. Therefore, extubation in very early preterm infants should be carefully evaluated. Using inotropes, feeding, and RSS at 1 week of age can help predict extubation success.

Early prediction of need for invasive mechanical ventilation in the neonatal intensive care unit using artificial intelligence and electronic health records: a clinical study.

BACKGROUND: Respiratory support is crucial for newborns with underdeveloped lung. The clinical outcomes of patients depend on the clinician's ability to recognize the status underlying the presented symptoms and signs. With the increasing number of high-risk infants, artificial intelligence (AI) should be considered as a tool for personalized neonatal care. Continuous monitoring of vital signs is essential in cardiorespiratory care. In this study, we developed deep learning (DL) prediction models for rapid and accurate detection of mechanical ventilation requirements in neonates using electronic health records (EHR). METHODS: We utilized data from the neonatal intensive care unit in a single center, collected between March 3, 2012, and March 4, 2022, including 1,394 patient records used for model development, consisting of 505 and 889 patients with and without invasive mechanical ventilation (IMV) support, respectively. The proposed model architecture includes feature embedding using feature-wise fully connected (FC) layers, followed by three bidirectional long short-term memory (LSTM) layers. RESULTS: A mean gestational age (GA) was 36.61 ± 3.25 weeks, and the mean birth weight was 2,734.01 ± 784.98 g. The IMV group had lower GA, birth weight, and longer hospitalization duration than the non-IMV group (P < 0.05). Our proposed model, tested on a dataset from March 4, 2019, to March 4, 2022. The mean AUROC of our proposed model for IMV support prediction performance demonstrated 0.861 (95%CI, 0.853-0.869). It is superior to conventional approaches, such as newborn early warning score systems (NEWS), Random Forest, and eXtreme gradient boosting (XGBoost) with 0.611 (95%CI, 0.600-0.622), 0.837 (95%CI, 0.828-0.845), and 0.0.831 (95%CI, 0.821-0.845), respectively. The highest AUPRC value is shown in the proposed model at 0.327 (95%CI, 0.308-0.347). The proposed model performed more accurate predictions as gestational age decreased. Additionally, the model exhibited the lowest alarm rate while maintaining the same sensitivity level. CONCLUSION: Deep learning approaches can help accurately standardize the prediction of invasive mechanical ventilation for neonatal patients and facilitate advanced neonatal care. The results of predictive, recall, and alarm performances of the proposed model outperformed the other models.

Longitudinal changes in insulin resistance in children with epilepsy on ketogenic diet: Prevalence and risk factors.

INTRODUCTION: The aim of the study was to evaluate the incidence of insulin resistance (IR) and the associated risk factors in children with epilepsy on a ketogenic diet (KD). METHODS: This longitudinal cohort study analyzed data of children with epilepsy on KD. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). The HOMA-IR value, fasting serum insulin levels, fasting glucose (FG) levels, and lipid profiles were measured before the initiation of the KD and at 6- to 12-month intervals. RESULTS: A total of 28 children were enrolled. The median age at the initiation of KD was 2.7 ±â€¯2.4 years, and the median follow-up duration was 2.1 ±â€¯1.4 years. The median HOMA-IR (HOMA-IR-1) value before the initiation of KD was 1.2 ±â€¯0.2, which significantly increased to 1.8 ±â€¯0.3 at the last follow-up (HOMA-IR-2; ∆HOMA-IR = 0.6 ±â€¯0.3, p < 0.001). The following factors were associated with patients with higher HOMA-IR-2 values (≥1.9): younger age at seizure onset (0.3 ±â€¯0.2 years, p < 0.001), at the initiation of antiepileptic drugs (AEDs; 0.3 ±â€¯0.3 years, p < 0.001), and at the initiation of KD (1.3 ±â€¯0.5 years, p < 0.001) and higher serum alanine transaminase (ALT; 84.0 ±â€¯17.8 U/L, p = 0.022), total cholesterol (TC; 245.0 ±â€¯20.1 mg/dL, p = 0.001), low-density lipoprotein cholesterol (LDL-C, 103.0 ±â€¯6.7 mg/dL, p = 0.003), and triglyceride (387.0 ±â€¯28.8 mg/dL, p < 0.001) levels. Multivariate regression analysis revealed that the age at seizure onset (p = 0.002), at initiation of AEDs (p = 0.021), and at initiation of KD (p = 0.022) and serum levels of LDL-C (p = 0.012) and triglycerides (p = 0.026) were associated with a significantly high HOMA-IR-2 value. CONCLUSION: Close monitoring of serum lipids levels, especially at younger age, may aid in detecting exacerbation of IR.

Meconium peritonitis resulting from different etiologies in siblings: a case report.

BACKGROUND: Meconium peritonitis is defined as aseptic chemical inflammation caused by intrauterine bowel perforation. The underlying causes of bowel perforation include intestinal atresia, midgut volvulus, intussusception, congenital bands, and meconium ileus. CASE PRESENTATION: Siblings with prenatally diagnosed meconium peritonitis of different etiologies were found. The elder sister was born at 36 + 6 weeks gestation with a birth weight of 3110 g. She was diagnosed with meconium peritonitis caused by ileal atresia. Two years later, the younger brother was born at 34 + 3 weeks gestation with a birth weight of 2850 g. He was diagnosed with meconium peritonitis caused by midgut volvulus. CONCLUSIONS: Among the previously reported cases of meconium peritonitis, familial occurance of meconium peritonitis is extremely rare. We present a case of prenatally diagnosed meconium peritonitis in siblings to promote further understanding of its etiology and clinical course.

Extracerebral choroid plexus papilloma in the pharynx with airway obstruction in a newborn: a case report.

BACKGROUND: Choroid plexus papillomas (CPPs) are rare, usually benign, neoplasms originating in the central nervous system. In this study, we present the first case of a giant airway-obstructing CPP in the pharynx of a newborn. CASE PRESENTATION: A cystic mass located in the pharynx was noted in a fetus at the 29th week of gestation. Elective cesarean section was performed at the 38th week of gestation with successful intubation and ex utero intrapartum treatment. On computed tomography, there was a huge airway-obstructing cystic mass in the choana and pharynx. Elective surgery with total excision was performed, and histological examination confirmed the diagnosis of CPP. CONCLUSION: We report the first case of an extracerebral airway-obstructing CPP in the pharynx of a newborn. Radiologic examinations are not enough for the diagnosis of CPPs, and complete excision of the tumor with histological confirmation is indispensable for accurate diagnosis and treatment.

Bart's Syndrome with Novel Frameshift Mutations in the COL7A1 Gene.

INTRODUCTION: Bart's syndrome, a hereditary mechanobullous disorder characterized by aplasia cutis congenita (ACC) with epidermolysis bullosa (EB), has not been genotyped frequently. CASE REPORT: A full-term female neonate had well-demarcated absence of skin on both legs at birth, with blisters and erosive patches developing immediately after birth. Electron microscopy showed blister formation under the lamina densa layer. Genetic studies revealed two heterogenous frameshift mutations in exons 31 and 109 of COL7A1. A diagnosis of Bart's syndrome, recessive dystrophic EB with ACC, was made. There was no pyloric atresia or ureteral stenosis, but congenital hypothyroidism was diagnosed 42 days after birth. CONCLUSION: The novel frameshift mutations in COL7A1 may result in Bart's syndrome and suggest the importance of genetic testing in diagnosis of this disease.

Chylous Ascites in an Infant with Thanatophoric Dysplasia Type I with FGFR3 Mutation Surviving Five Months.

BACKGROUND: Thanatophoric dysplasia (TD) results from sporadic de novo mutations in the FGFR3 gene. Upon confirming intrauterine diagnosis of this perinatal disease, pregnancy termination is recommended. There is limited information on the natural history of longer-term survivors with type 1 TD. CASE REPORT: A full-term neonate was confirmed via postnatal genetic testing to have type 1 TD. At 28 days, chylous ascites developed. Medium-chain triglyceride use improved the ascites. Cerebral ventriculomegaly worsened throughout life. Death due to respiratory failure occurred at age 5 months. CONCLUSION: The chylous ascites in this child with type 1 TD and survival past the neonatal stage suggests that type 1 TD may be accompanied by abnormalities of the lymphatic channels. Moreover, ventriculomegaly can be progressive.

Neonatal Iliopsoas Abscess: The First Korean Case.

Iliopsoas abscess (IPA) is rare in neonates. We present a case of neonatal IPA that was initially believed to bean inguinal hernia. A 20-day-old male infant was referred to our hospital for herniorrhaphy after a 2-day history of swelling and bluish discoloration of the left inguinal area and leg without limitation of motion. Abdominal and pelvic ultrasonography suggested a femoral hernia, but the anatomy was unclear. Abdominal computed tomography revealed a multi-septated cystic mass extending into the psoas muscle from the lower pole of the left kidney to the femur neck. Broad spectrum antibiotics were initiated, and prompt surgical exploration was planned. After opening the retroperitoneal cavity via an inguinal incision, an IPA was diagnosed and surgically drained. Culture of the abscess fluid detected Staphylococcus aureus, sensitive to methicillin. The patient was discharged without complication on the 17th postoperative day.

Enterococcal bacteremia in children: Clinical Significance of vancomycin resistance.

BACKGROUND: We aimed to describe the clinical and microbiological characteristics of enterococcal bacteremia, as well as the effect of Enterococcus resistance against vancomycin on clinical outcomes in Korean children. METHODS: We retrospectively reviewed the medical records of children diagnosed with enterococci isolated from blood cultures at Pusan National University Children's Hospital between December 2009 and November 2021. RESULTS: In total, 64 patients were enrolled in the study. The median age was 0 years (range 0-15), and 43 (67.2%) patients were male. Enterococcus faecalis (50%) was the most commonly identified bacterial strain. Significant underlying diseases were present in 60 patients (93.8%), and the source of bacteremia was identified in 36 patients (56.3%). Among these, intravascular device was the most common identifiable source. Fifty-six (87.5%) patients had previously received broad-spectrum antibiotics and 54 (84.4%) patients were nosocomial in origin. Twenty-nine (45.3%) strains were resistant to ampicillin, and 16 (25%) strains were resistant to vancomycin. All patients with vancomycin-resistant enterococci (VRE) had underlying disease (P = 0.199), and focus of bacteremia was significantly more frequent in VRE patients (P = 0.014). Of all the patients, after appropriate antibiotic treatment, five (7.8%) patients had recurrent enterococcal bacteremia, and seven (10.9%) patients were diagnosed with bacteremia, defined as other pathogens from blood culture. The 30-day mortality rate was 7.8%. CONCLUSION: Enterococcal bacteremia in children is usually nosocomial and occurs in children with serious underlying diseases. Because the number of enrolled patients and mortality were small in our study, it is difficult to identify whether the factor that determines prognosis in patients with enterococcal bacteremia is VRE or an underlying disease. Further studies with a large number of patients in a specific group are needed.