Antenatal Magnesium Sulfate Is Not Associated With Improved Long-Term Neurodevelopment and Growth in Very Low Birth Weight Infants

Background@#Though antenatal magnesium sulfate (MgSO4 ) is widely used for fetal neuroprotection, suspicions about the long-term neuroprotection of antenatal MgSO4 have been raised. @*Methods@#We investigated short- and long-term outcomes of antenatal MgSO4 use for 468 infants weighing < 1,500 g with a gestational age of 24–31 weeks. @*Results@#Short-term morbidities and the risk of developmental delay, hearing loss, and cerebral palsy at a corrected age of 18–24 months and 3 years of age did not decrease in the MgSO4 group (infants who were exposed to MgSO4 for any purpose) or neuroprotection group (infants who were exposed to MgSO4 for fetal neuroprotection) compared with the control group (infants who were not exposed to MgSO4 ). The z-scores of weight, height, and head circumference did not increase in the MgSO4 group or neuroprotection group compared with the control group. @*Conclusion@#Antenatal MgSO4 including MgSO4 for neuroprotection did not have beneficial effects on long-term neurodevelopmental and growth outcomes.

Neonatal Diabetes Mellitus Due to KCNJ11 (KIR6.2) Mutation Successfully Treated with Sulfonylurea

Neonatal diabetes mellitus (NDM) is a rare disease that occurs at less than 6 months of age and is presumably caused by a mutation in the gene that affects pancreatic beta-cell function. Approximately 80% of NDM cases reveal a known genetic mutation, and mutations in potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) and ABCC8 affecting the pancreatic beta-cell adenosine triphosphate-sensitive potassium channel may be treated with oral sulfonylurea. Early recognition of mutations in KCNJ11 and ABCC8 is important because early administration of sulfonylurea can not only control blood glucose levels but also improve neurodevelopmental outcomes. In the present study, we report a case of NDM that initially presented as diabetic ketoacidosis at the age of 1 month, accompanied by seizures during hospitalization. After confirmation of the KCNJ11 gene mutation (c.989A>C), we started administering oral sulfonylurea (glimepiride) at the age of 2 months. After gradually increasing the dosage of glimepiride, insulin was discontinued at the age of 3 months. To date, the infant’s blood glucose levels have been well controlled without significant hypoglycemic events. No further episodes of seizures have occurred, and his developmental status is favorable.

Mortality and Morbidities according to Time of Birth in Extremely Low Birth Weight Infants

Background@#Although the overall quality of high-risk neonatal care has improved recently, there is still concern about a difference in the quality of care when comparing off-hour births and regular-hour births. Moreover, there are no data in Korea regarding the impact of time of birth on mortality and morbidities in preterm infants. @*Methods@#A total of 3,220 infants weighing < 1,000 g and born at 23–34 weeks in 2013–2017 were analyzed based on the Korean Neonatal Network data. Mortality and major morbidities were analyzed using logistic regression according to time of birth during off-hours (nighttime, weekend, and holiday) and regular hours. The institutes were sub-grouped into hospital group I and hospital group II based on the neonatal intensive care unit (NICU) care level defined by the mortality rates of < 50% and ≥ 50%, respectively, in infants born at 23–24 weeks' gestation. @*Results@#The number of births during regular hours and off-hours was similar. In the total population and hospital group I, off-hour births were not associated with increased neonatal mortality and morbidities. However, in hospital group II, increased early mortality was found in the off-hour births when compared to regular-hour births. @*Conclusion@#Efforts to improve the overall quality of NICU are required to lower the early mortality rate in off-hour births. Also, other sensitive indexes for the evaluation of quality of NICU care should be further studied.

Neonatal Diabetes Mellitus Due to KCNJ11 (KIR6.2) Mutation Successfully Treated with Sulfonylurea

Neonatal diabetes mellitus (NDM) is a rare disease that occurs at less than 6 months of age and is presumably caused by a mutation in the gene that affects pancreatic beta-cell function. Approximately 80% of NDM cases reveal a known genetic mutation, and mutations in potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) and ABCC8 affecting the pancreatic beta-cell adenosine triphosphate-sensitive potassium channel may be treated with oral sulfonylurea. Early recognition of mutations in KCNJ11 and ABCC8 is important because early administration of sulfonylurea can not only control blood glucose levels but also improve neurodevelopmental outcomes. In the present study, we report a case of NDM that initially presented as diabetic ketoacidosis at the age of 1 month, accompanied by seizures during hospitalization. After confirmation of the KCNJ11 gene mutation (c.989A>C), we started administering oral sulfonylurea (glimepiride) at the age of 2 months. After gradually increasing the dosage of glimepiride, insulin was discontinued at the age of 3 months. To date, the infant’s blood glucose levels have been well controlled without significant hypoglycemic events. No further episodes of seizures have occurred, and his developmental status is favorable.

Mortality and Morbidities according to Time of Birth in Extremely Low Birth Weight Infants

Background@#Although the overall quality of high-risk neonatal care has improved recently, there is still concern about a difference in the quality of care when comparing off-hour births and regular-hour births. Moreover, there are no data in Korea regarding the impact of time of birth on mortality and morbidities in preterm infants. @*Methods@#A total of 3,220 infants weighing < 1,000 g and born at 23–34 weeks in 2013–2017 were analyzed based on the Korean Neonatal Network data. Mortality and major morbidities were analyzed using logistic regression according to time of birth during off-hours (nighttime, weekend, and holiday) and regular hours. The institutes were sub-grouped into hospital group I and hospital group II based on the neonatal intensive care unit (NICU) care level defined by the mortality rates of < 50% and ≥ 50%, respectively, in infants born at 23–24 weeks' gestation. @*Results@#The number of births during regular hours and off-hours was similar. In the total population and hospital group I, off-hour births were not associated with increased neonatal mortality and morbidities. However, in hospital group II, increased early mortality was found in the off-hour births when compared to regular-hour births. @*Conclusion@#Efforts to improve the overall quality of NICU are required to lower the early mortality rate in off-hour births. Also, other sensitive indexes for the evaluation of quality of NICU care should be further studied.

Comparison of Respiratory Outcomes between Less Invasive Surfactant Administration and the IntubationSurfactant-Extubation Technique in Premature Infants with Respiratory Distress Syndrome

Purpose@#To compare respiratory outcomes between less invasive surfactant admi nistration (LISA) and the intubation-surfactant-extubation (INSURE) technique in premature infants with respiratory distress syndrome (RDS). @*Methods@#We performed a retrospective medical chart review for 75 premature in fants who were born at a gestational age (GA) of ≤34 weeks (between January 2017 and December 2019) and developed RDS after birth. Data on the demographic and outcome variables, including respiratory outcomes, were collected and compared between the infants who received LISA and those who received INSURE as a rescue therapy for RDS. @*Results@#No signifcant differences in GA, birth weight, and other demographic characteristics were found between the LISA and INSURE groups (GA: 28.7 weeks vs.28.8 weeks, P=0.449; birth weight: 1,236 g vs. 1,124 g, P=0.714). At the delivery room, although the infants showed no significant difference in positive pressure ventilation rate after birth, the LISA group showed a higher rate of continuous positive airway pressure application than the INSURE group. The infants in the LISA group presented a higher risk of requiring multiple doses of surfactant for RDS than the infants in the INSURE group (57% vs. 17.5%, P=0.001). However, the duration of invasive and/ or noninvasive respiratory support and incidence of bronchopulmonary dysplasia showed no signifciant difference between the two groups. @*Conclusion@#In the present study, no significant differences in the incidence of inhospital respiratory outcomes such as bronchopulmonary dysplasia were found between the LISA and INSURE groups. These results suggest that LISA can be an alternative therapeutic option for treating RDS to avoid intubation and mechanica ventilation in premature infants.

Continuous Renal Replacement Therapy in Preterm Infants

PURPOSE: Despite the increasing use of continuous renal replacement therapy (CRRT) in the neonatal intensive care unit (NICU), few studies have investigated its use in preterm infants. This study evaluated the prognosis of preterm infants after CRRT and identified risk factors of mortality after CRRT. MATERIALS AND METHODS: A retrospective review was performed in 33 preterm infants who underwent CRRT at the NICU of Samsung Medical Center between 2008 and 2017. Data of the demographic characteristics, predisposing morbidity, cardiopulmonary function, and CRRT were collected and compared between surviving and non-surviving preterm infants treated with CRRT. Univariable and multivariable analyses were performed to identify factors affecting mortality. RESULTS: Compared with the survivors, the non-survivors showed younger gestational age (29.3 vs. 33.6 weeks), lower birth weight (1359 vs. 2174 g), and lower Apgar scores at 1 minute (4.4 vs. 6.6) and 5 minutes (6.5 vs. 8.6). At the initiation of CRRT, the non-survivors showed a higher incidence of inotropic use (93% vs. 40%, p=0.017) and fluid overload (16.8% vs. 4.0%, p=0.031). Multivariable analysis revealed that fluid overload >10% at CRRT initiation was the primary determinant of mortality after CRRT in premature infants, with an adjusted odds ratio of 14.6 and a 95% confidence interval of 1.10–211.29. CONCLUSION: Our data suggest that the degree of immaturity, cardiopulmonary instability, and fluid overload affect the prognosis of preterm infants after CRRT. Preventing fluid overload and earlier initiation of CRRT may improve treatment outcomes.

The Impact of Surgical Intervention on Neurodevelopmental Outcomes in Very Low Birth Weight Infants: a Nationwide Cohort Study in Korea

BACKGROUND: To investigate the incidence of surgical intervention in very low birth weight (VLBW) infants and the impact of surgery on neurodevelopmental outcomes at corrected ages (CAs) of 18–24 months, using data from the Korean Neonatal Network (KNN). METHODS: Data from 7,885 VLBW infants who were born and registered with the KNN between 2013 to 2016 were analyzed in this study. The incidences of various surgical interventions and related morbidities were analyzed. Long-term neurodevelopmental outcomes at CAs of 18–24 months were compared between infants (born during 2013 to 2015, n = 3,777) with and without surgery. RESULTS: A total of 1,509 out of 7,885 (19.1%) infants received surgical interventions during neonatal intensive care unit (NICU) hospitalization. Surgical ligation of patent ductus arteriosus (n = 840) was most frequently performed, followed by laser therapy for retinopathy of prematurity and laparotomy due to intestinal perforation. Infants who underwent surgery had higher mortality rates and greater neurodevelopmental impairment than infants who did not undergo surgery (P value < 0.01, both). On multivariate analysis, single or multiple surgeries increased the risk of neurodevelopmental impairment compared to no surgery with adjusted odds ratios (ORs) of 1.6 with 95% confidence interval (CI) of 1.1–2.6 and 2.3 with 95% CI of 1.1–4.9. CONCLUSION: Approximately one fifth of VLBW infants underwent one or more surgical interventions during NICU hospitalization. The impact of surgical intervention on long-term neurodevelopmental outcomes was sustained over a follow-up of CA 18–24 months. Infants with multiple surgeries had an increased risk of neurodevelopmental impairment compared to infants with single surgeries or no surgeries after adjustment for possible confounders.

A novel de novo mosaic mutation in PHEX in a Korean patient with hypophosphatemic rickets

X-linked hypophosphatemic rickets is caused by loss-of-function mutations in PHEX, which encodes a phosphate-regulating endopeptidase homolog. We report a 26-year-old man with X-linked hypophosphatemic rickets who showed decreased serum phosphate accompanied by bilateral genu valgum and short stature. He had received medical treatment with vitamin D (alfacalcidol) and phosphate from the age of 3 to 20 years. He underwent surgery due to valgus deformity at the age of 14 and 15. Targeted gene panel sequencing for Mendelian genes identified a nonsense mutation in PHEX (c.589C>T; p.Gln197Ter) and a mosaic pattern where only 38% of sequence reads showed the variant allele. This mutation was not found in his mother, who had a normal phenotype. This is a case of a sporadic nonsense mutation in PHEX and up to date, this is the first case of a mosaic mutation in PHEX in Korea.