Exploring the Genetic Causes for Postnatal Growth Failure in Children Born Non-Small for Gestational Age.

The most common causes of short stature (SS) in children are familial short stature (FSS) and idiopathic short stature (ISS). Recently, growth plate dysfunction has been recognized as the genetic cause of FSS or ISS. The aim of this study was to investigate monogenic growth failure in patients with ISS and FSS. Targeted exome sequencing was performed in patients categorized as ISS or FSS and the subsequent response to growth hormone (GH) therapy was analyzed. We found 17 genetic causes involving 12 genes (NPR2, IHH, BBS1, COL1A1, COL2A1, TRPS1, MASP1, SPRED1, PTPTN11, ADNP, NADSYN1, and CERT1) and 2 copy number variants. A genetic cause was found in 45.5% and 35.7% of patients with FSS and ISS, respectively. The genetic yield in patients with syndromic and non-syndromic SS was 90% and 23.1%, respectively. In the 11 genetically confirmed patients, a gain in height from -2.6 to -1.3 standard deviations after 2 years of GH treatment was found. The overall diagnostic yield in this study was 41.7%. We identified several genetic causes involving paracrine signaling, the extracellular matrix, and basic intracellular processes. Identification of the causative gene may provide prognostic evidence for the use of GH therapy in non-SGA children.

Outcomes of singleton preterm very low birth weight infants born to mothers with pregnancy-induced hypertension.

The association between maternal pregnancy-induced hypertension (PIH) and neonatal mortality and morbidities in preterm infants has not been consistent. This study aimed to evaluate the influence of maternal PIH on mortality and morbidities in singleton infants with very low birth weight born before 30 weeks of gestational age using the Korean Neonatal Network (KNN) database. A total of 5340 singleton infants with very low birth weight were registered in the KNN registry, who were born at 23+0 to 29+6 weeks of gestational age between January 2015 and December 2020. Baseline characteristics and neonatal mortality and morbidities were compared between infants with PIH and non-PIH mothers. After adjustment for potential confounders, infants with PIH mothers had significantly higher odds of respiratory distress syndrome (OR 1.983; 95% CI 1.285-3.061, p = 0.002) and bronchopulmonary dysplasia (OR 1.458; 95% CI 1.190-1.785, p < 0.001), and severe bronchopulmonary dysplasia (OR 1.411; 95% CI 1.163-1.713, p < 0.001) than infants with non-PIH mothers, while there were no significant differences in severe intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or death during neonatal intensive care unit admission between infants with PIH and non-PIH mothers. This study showed that preterm infants with PIH mothers had an increased risk of neonatal respiratory morbidities, including respiratory distress syndrome and bronchopulmonary dysplasia.

Prevalence of asthma in preterm and associated risk factors based on prescription data from the Korean National Health Insurance database.

We retrospectively analyzed National Health Insurance claims data (January 2002-December 2018) to determine the asthma prevalence and risk factors among preterm infants born in Korea. Patients with asthma were defined as those with a history of asthma medication prescriptions at least twice per year with International Classification of Diseases, Tenth Edition codes J45 and J46. We enrolled 99,139 preterm infants. The prevalence of asthma among preterm and term infants was 32.7% and 26.9%, 21.2% and 19.1%, 6.7% and 5.9%, 2.0%, and 1.6%, and 2.4% and 1.6% at 2, 5, 10, 15, and 16 years of age, respectively. The relative risk (RR) of asthma in preterm infants was 1.1-fold that in female preterm infants. The RR of asthma medication prescriptions for infants with extreme prematurity was 1.92-fold that of infants with moderate/late pre-term status. Among preterm with bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS) without comorbidities, the RRs for the number of asthma medication prescriptions were 1.34 and 1.06, respectively. This study revealed a higher prevalence of asthma among preterm infants than that in term infants. Male sex, extreme prematurity, BPD, and RDS were identified as risk factors for asthma medication prescriptions in preterm infants.

Neonatal seizures: diagnostic updates based on new definition and classification.

Neonatal seizures are the most common neurological symptoms caused by various etiologies in the neonatal period, but their diagnosis and treatment are challenging because their pathophysiology and electroclinical manifestations differ from those of patients in older age groups. Many seizures present as electrographic-only events without clinical signs or as obscure clinical manifestations that are difficult to distinguish from other neonatal behaviors. Accordingly, a new definition and classification of neonatal seizures was recently proposed by the International League Against Epilepsy Task Force on neonatal seizures, highlighting the role of electroencephalography in diagnosing and treating neonatal seizures. Neonatal seizures are defined as electrographic events with sudden, paroxysmal, and abnormal alteration of activity and divided into electroclinical seizures and electrographic-only seizures according to their clinical signs, thus excluding clinical events without an electrographic correlation. Seizure types are described by their predominant clinical features and divided into motor (automatisms, clonic, epileptic spasms, myoclonic, tonic, and sequential), nonmotor (autonomic and behavioral arrest), and unclassified. Although many neonatal seizures are acute reactive events caused by hypoxic-ischemic encephalopathy or vascular insults, structural, genetic, or metabolic etiologies of neonatal-onset epilepsy should also be thoroughly evaluated to determine their appropriate management.

The association of low body mass index with neonatal morbidities in preterm infants.

Little is known about the association between body proportionality at birth and neonatal outcomes in preterm infants. Body mass index (BMI) is one of the weigh-for-length ratios that represent body proportionality. The objective of this study was to examine whether BMI at birth affects neonatal outcomes in preterm infants. We assessed 3115 preterm (< 30 weeks), very low birth weight (< 1500 g) infants born between January 2013 and December 2016 and registered in the Korean Neonatal Network database. Using gender-specific BMI for gestational age curves, z-scores of BMI at birth were calculated. Low-, normal-, and high-BMI were defined as BMI z-scores of less than - 1, from - 1 to 1, and greater than 1, respectively. Neonatal morbidities and mortality in low- and high-BMI groups were compared to those in normal-BMI group. The low-BMI group had an increased risk of bronchopulmonary dysplasia, bronchopulmonary dysplasia or death, and necrotizing enterocolitis after adjusting for baseline characteristics and the birth weight z-score. High-BMI group had comparable neonatal outcomes to those of normal-BMI group. Low BMI at birth was associated with an increased risk of bronchopulmonary dysplasia and necrotizing enterocolitis, whereas High BMI at birth was not associated with adverse neonatal outcomes.

Association Between Korean-Style Balanced Diet and Risk of Abdominal Obesity in Korean Adults: An Analysis Using KNHANES-VI (2013-2016).

Abdominal obesity is a critical factor for metabolic diseases, and specific eating patterns such as the Mediterranean diet help prevent metabolic diseases. This study aimed to investigate the association between the modified Korean health eating index (MKHEI), including a Korean-balanced diet, and abdominal obesity risk according to genders in adults aged 20-64 years (4,886 males and 7,431 females), using the Korea National Health and Nutrition Examination Survey VI (2013-2016). Adjusted means and 95% confidence intervals of MKHEI scores and nutrient intake estimated using the 24-h recall method were calculated according to abdominal obesity (waist circumference ≥90 cm for men and ≥85 cm for women) after adjusting for age, residence area, region, education, income, drinking status, smoking status, marital status, and exercise. Adjusted odds ratios (ORs) for abdominal obesity were measured according to MKHEI tertiles using logistic regression analysis while controlling for covariates. Individuals aged >50 years, married, below high school, lower-income, heavy alcohol drinkers, past and current smokers, and males living in the southern areas had a higher risk of abdominal obesity. In both genders, the scores of all MKHEI components were lower in the abdominal obesity group (n = 2,895) than in the control group (n = 9,422). Further, the scores of fruits with and without fruit juice and those of beans, including fermented beans, were lower in the abdominal obesity group only in females but not in males. Further, the scores of fast foods were higher in the abdominal obesity group than in the control group only in females. After adjusting for covariates, the adjusted OR for abdominal obesity was inversely associated with Korean balanced diet (KBD) related to KHEI scores. Unlike KBD, MKHEI of Western-style diet was not associated with abdominal obesity in either gender. In conclusion, KBD can lower the risk of abdominal obesity in females and should thus be recommended to prevent abdominal obesity.

Comparison of NIV-NAVA and NCPAP in facilitating extubation for very preterm infants.

BACKGROUND: Various types of noninvasive respiratory modalities that lead to successful extubation in preterm infants have been explored. We aimed to compare noninvasive neurally adjusted ventilatory assist (NIV-NAVA) and nasal continuous positive airway pressure (NCPAP) for the postextubation stabilization of preterm infants. METHODS: This retrospective study was divided into two distinct periods, between July 2012 and June 2013 and between July 2013 and June 2014, because NIV-NAVA was applied beginning in July 2013. Preterm infants of less than 30 weeks GA who had been intubated with mechanical ventilation for longer than 24 h and were weaned to NCPAP or NIV-NAVA after extubation were enrolled. Ventilatory variables and extubation failure were compared after weaning to NCPAP or NIV-NAVA. Extubation failure was defined when infants were reintubated within 72 h of extubation. RESULTS: There were 14 infants who were weaned to NCPAP during Period I, and 2 infants and 16 infants were weaned to NCPAP and NIV-NAVA, respectively, during Period II. At the time of extubation, there were no differences in the respiratory severity score (NIV-NAVA 1.65 vs. NCPAP 1.95), oxygen saturation index (1.70 vs. 2.09) and steroid use before extubation. Several ventilation parameters at extubation, such as the mean airway pressure, positive end-expiratory pressure, peak inspiratory pressure, and FiO2, were similar between the two groups. SpO2 and pCO2 preceding extubation were comparable. Extubation failure within 72 h after extubation was observed in 6.3% of the NIV-NAVA group and 37.5% of the NCPAP group (P = 0.041). CONCLUSIONS: The data in the present showed promising implications for using NIV-NAVA over NCPAP to facilitate extubation.

Surgical Necrotizing Enterocolitis versus Spontaneous Intestinal Perforation in White Matter Injury on Brain Magnetic Resonance Imaging.

BACKGROUND: White matter injury (WMI) is the most common form of brain injury in preterm infants. It could be induced by a systemic inflammatory response in preterm infants. OBJECTIVES: We hypothesized that surgical necrotizing enterocolitis (surgNEC) results in more severe WMI than spontaneous intestinal perforation (SIP) on brain magnetic resonance imaging (MRI) at term-equivalent age (TEA). METHODS: The medical records of 33 preterm infants born at less than 32 weeks of gestation who underwent surgery due to either NEC or SIP were reviewed retrospectively. White matter abnormality (WMA) on brain MRI was scored according to the diagnosis of surgNEC or SIP. RESULTS: Nine patients were diagnosed with SIP and 24 with surgNEC. The median (range) gestational age of the SIP and surgNEC groups was 26+6 (23+3-27+6) and 25+5 weeks (23+3-31+2), respectively (p = 0.454). There were no differences in 1- and 5-min Apgar scores, mode of delivery, use of antenatal steroids, histologic chorioamnionitis, or incidence of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) between the two groups. Males were more prevalent in the surgNEC group (75.0 vs. 33.3%, p = 0.044), and the incidence of sepsis was higher in the surgNEC group than in the SIP group (75.0 vs. 33.3%, p = 0.044). Multivariate regression showed that the difference in WMA scores between the two groups remained significant (estimated difference = 2.418; 95% CI 0.107-4.729). CONCLUSION: In preterm infants at less than 32 weeks of gestation, those with surgNEC showed more severe WMI than infants with SIP on brain MRI at TEA.

Induction of phenylalanine ammonia-lyase gene expression by paraquat and stress-related hormones in Rehmannia glutinosa.

Rehmannia glutinosa is a medicinal herb that is tolerant to the non-selective herbicide paraquat. Acteoside, a phenolic compound present in the plant, has been shown to inhibit paraquat. To understand regulation of the phenylpropanoid pathway that produces the acteoside moiety, we isolated a phenylalanine ammonia-lyase (PAL) cDNA clone (RgPAL1) and used it to examine PAL expression. The deduced 712 amino acid sequence of the open reading frame contains the conserved active site and potential phosphorylation sites of other plant PALs. RgPAL1 mRNA was detected in the leaves, flowers and roots of healthy plants, and the level of the mRNA was higher in leaves than in flowers and roots. RgPAL1 mRNA was induced in leaves by paraquat, H2O2, UV light, wounding, yeast extract, jasmonic acid and ethephon. The transcript level and enzyme activity increased gradually from 6 to 24 h after exposure to paraquat or jasmonic acid. Induction of RgPAL1 by paraquat and stress-related phytohormones suggests that it is involved in the regulation of the phenylpropanoid pathway under oxidative stress.