Neonatal hypoglycemia is a common metabolic disorder in newborns, which may present with non-specific symptoms or even be asymptomatic. Current guidelines recommend screening for hypoglycemia in at-risk babies (late preterm, small for gestational age, large for gestational age, and infants of diabetic mothers). Past studies have suggested other potential risk factors, such as maternal obesity, gestational hypertension, cesarean section, etc. In this study, we aim to identify additional prenatal and perinatal maternal/fetal characteristics associated with early asymptomatic hypoglycemia in term and late preterm babies. We performed a retrospective review on medical charts of all newborns, born between January, 2017 and December, 2020, in the well-baby newborn nursery of a tertiary medical center. We identified newborns who had received blood glucose concentration monitor after birth. Detailed prenatal and perinatal maternal/newborn information were collected for analysis. In the study period, 841 newborns had received blood glucose screening after birth. After matching by sex and indication for postnatal blood glucose screen (SGA, LGA, and GDM), 148 newborns were included in the "hypoglycemia group" and 296 newborns were included in the "euglycemia group". In the univariate analysis, parity, insulin treatment for gestational diabetes mellitus (GDM), and cesarean section were associated with an increased risk for neonatal hypoglycemia. Factors associated with decreased risk included higher gestational age, longer duration of skin-to-skin contact, neonatal hyperthermia, higher maternal labor pain score, and epidural anesthesia administration. By multivariable analysis, insulin treatment for GDM was identified as an independent factor associated with increased risk for neonatal hypoglycemia. Our study showed insulin treatment for GDM to be independently associated with neonatal hypoglycemia. Other risk factors noted in the univariate analysis, such as decreased skin-to-skin contact duration, hypothermia, Cesarean section, and preterm delivery, would require further investigation to confirm the findings.

Background: The mucopolysaccharidoses (MPSs) are a group of rare lysosomal storage disorders characterized by the accumulation of glycosaminoglycans (GAGs) and which eventually cause progressive damage to various tissues and organs. We developed a feasible MPS screening algorithm and established a cross-specialty collaboration platform between medical geneticists and other medical specialists based on at-risk criteria to allow for an earlier confirmative diagnosis of MPS. Methods: Children (<19 years of age) with clinical signs and symptoms compatible with MPS were prospectively enrolled from pediatric clinics between July 2013 and June 2018. Urine samples were collected for a non-specific total GAG analysis using the dimethylmethylene blue (DMB) spectrophotometric method, and the quantitation of three urinary GAGs (dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS)) was performed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). The subjects with elevated urinary GAG levels were recalled for leukocyte enzyme activity assay and genetic testing for confirmation. Results: Among 153 subjects enrolled in this study, 13 had a confirmative diagnosis of MPS (age range, 0.6 to 10.9 years—three with MPS I, four with MPS II, five with MPS IIIB, and one with MPS IVA). The major signs and symptoms with regards to different systems recorded by pediatricians at the time of the decision to test for MPS were the musculoskeletal system (55%), followed by the neurological system (45%) and coarse facial features (39%). For these 13 patients, the median age at the diagnosis of MPS was 2.9 years. The false negative rate of urinary DMB ratio using the dye-based method for these 13 patients was 31%, including one MPS I, two MPS IIIB, and one MPS IVA. However, there were no false negative results with urinary DS, HS and KS using the MS/MS-based method. Conclusions: We established an at-risk population screening program for MPS by measuring urinary GAG fractionation biomarkers using the LC-MS/MS method. The program included medical geneticists and other medical specialists to increase awareness and enable an early diagnosis by detecting MPS at the initial onset of clinical symptoms.

Precocious puberty in girls is defined as the onset of pubertal changes before 8 years of age, and gonadotropin-releasing hormone (GnRH) agonist treatment is available for central precocious puberty (CPP). The gold standard for diagnosing CPP is the GnRH stimulation test. However, the GnRH stimulation test is time-consuming, costly, and requires repeated blood sampling. We aimed to develop an artificial intelligence (AI) prediction model to assist pediatric endocrinologists in decision making regarding the optimal timing to perform the GnRH stimulation test. We reviewed the medical charts of 161 girls who received the GnRH stimulation test from 1 August 2010 to 31 August 2021, and we selected 15 clinically relevant features for machine learning modeling. We chose the models with the highest area under the receiver operating characteristic curve (AUC) to integrate into our computerized physician order entry (CPOE) system. The AUC values for the CPP diagnosis prediction model (LH ≥ 5 IU/L) were 0.884 with logistic regression, 0.912 with random forest, 0.942 with LightGBM, and 0.942 with XGBoost. For the Taiwan National Health Insurance treatment coverage prediction model (LH ≥ 10 IU/L), the AUC values were 0.909, 0.941, 0.934, and 0.881, respectively. In conclusion, our AI predictive system can assist pediatric endocrinologists when they are deciding whether a girl with suspected CPP should receive a GnRH stimulation test. With proper use, this prediction model may possibly avoid unnecessary invasive blood sampling for GnRH stimulation tests.

Infants and children with feeding difficulties have swallowing dysfunction and high risk of aspiration, which could be silent without choking, resulting in recurrent pneumonia and long-term respiratory morbidity. Videofluoroscopic swallow study (VFSS) is a useful tool for real-time visualization of the swallowing process and airway aspiration. This study reported a single-institutional 10-year experience of VFSS in pediatric patients with feeding difficulties and the efficacy of swallowing therapy. From 2011 to 2020, 30 infants and children with feeding difficulties received VFSS examinations in a medical center at a median age of 19 months (range 7 days-8 years). The images of the swallowing process (oral phase, triggering of pharyngeal swallowing, and pharyngeal phase) under videofluoroscopy were analyzed by a radiologist and a speech-language pathologist. Aspiration severity was assessed from VFSS observations and rated by an eight-point Penetration-Aspiration-Scale (PAS), with higher scores indicating increased severity. Swallowing therapy was performed by experienced speech-language therapists, and follow-up of oral feeding tolerance and risk of aspiration pneumonia was done. Of the 30 patients, 24 (80%) had neurological deficits. High PAS scores (6-8) were observed in 25 (83.4%) patients, and 22 had a PAS score of 8, indicating silent aspiration. Of the 25 patients with high PAS scores, 19 (76%) had neurological deficits, and 18 (72%) depended on tube feeding at a median age of 20 months. Swallowing problems occurred most frequently during the pharyngeal phase in the patients with high PAS scores. VFSS-based swallowing therapy improved oral feeding ability and reduced aspiration episodes. Infants and children with swallowing dysfunction and neurological deficits had high risk of severe aspiration. Swallowing problems in the pharyngeal phase were the most common VFSS findings in patients with severe aspiration. VFSS may help guide problem-oriented swallowing therapy to reduce the risk of recurrent aspiration.

Whole-exome sequencing (WES) has advantages over the traditional molecular test by screening 20,000 genes simultaneously and has become an invaluable tool for genetic diagnosis in clinical practice. Here, we reported a family with a child and a fetus presenting undiagnosed skeletal dysplasia phenotypes, while the parents were asymptomatic. WES was applied to the parents and affected fetus to identify the genetic cause of the phenotypes. We identified novel compound heterozygous mutations consisting of a single-nucleotide variant (SNV) and a large deletion in the CRTAP gene (NM_006371.4:c.1153-3C > G/hg19 chr3:g.32398837_34210906del). Genetic alterations of CRTAP are known to cause osteogenesis imperfecta (OI) in an autosomal recessive manner. Further examination of the proband’s elder sibling who was diagnosed as OI after birth found that she shares the inherited compound heterozygous mutations of CRTAP; thus, the findings support the disease-causing role of CRTAP mutations. Through the in vitro molecular test and in silico analysis, the deleterious effects of the splicing-altering SNV in CRTAP (c.1153-3C > G) on gene product were confirmed. Collectively, our WES-based pathogenic variant discovery pipeline identifies the SNVs and copy number variation to delineate the genetic cause on the proband affected with OI. The data not only extend the knowledge of mutation spectrum in patients with skeletal dysplasia but also demonstrate that WES holds great promise for genetic screening of rare diseases in clinical settings.

The aim of this long-term longitudinal study in Taiwan was to estimate and compare the prevalence of cerebral palsy (CP) and to identify the age of CP diagnosis of term-born and preterm children with different birthweights. Records of 1494 extremely low birth weight (ELBW, <1000 g), 3961 very low birth weight (VLBW, 1000–1499 g), 19,612 low birth weight (LBW, 1500–2499 g) preterm, and 100,268 matched term-born children were retrieved from Taiwan′s National Health Insurance Research Database. According to a 12-year retrospective data review, the results showed the highest prevalence of CP in preterm ELBW children (147.3 cases per 1000 neonatal survivors), followed by preterm VLBW (97.2 cases), preterm LBW (27.7 cases), with the lowest prevalence in term-born children (2.5 cases). Regardless of the birthweight group, 90% of preterm children with CP were diagnosed by 4 years of age, but it was 7 years before 90% of term-born children with CP were diagnosed. After removing the children whose CP was caused by brain infections, injuries, or cerebrovascular accidents after 4 months of age, there were similar mean ages at the initial CP diagnosis (1.58–1.64 years of age) across birthweight groups born prematurely, but initial diagnosis occurred at an older age (2.41 years of age) in term-born children. The results indicate that birthweight is reversely correlated with the prevalence of CP in preterm children. Although the three preterm birthweight groups received different types of developmental follow-up programs after birth, it did not influence their age at the initial diagnosis of CP. Furthermore, we suggest that follow-up for at least 4 years after birth for preterm children, and 7 years for term-born children, is optimal for estimating CP prevalence. In order to identify and provide early intervention for term-born children with CP earlier, it is suggested that parents routinely fill out a self-reported motor developmental screening questionnaire and pediatricians conduct a motor developmental examination on term-born children at each time of scheduled vaccination injections.