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.

Updates in neonatal resuscitation: routine use of laryngeal masks as an alternative to face masks.

Though positive-pressure ventilation (PPV) has traditionally been performed using a face mask in neonatal resuscitation, face mask ventilation has a high failure rate in delivering PPV due to mask leaks, airway obstruction, or gastric inflation. Further, face mask ventilation is compromised during chest compressions. Endotracheal intubation in neonates requires a high skill level, with a first-attempt success rate of <50%. Laryngeal masks can transfer positive pressure more effectively even during chest compressions resulting in lower failure rate of PPV compared to face masks in neonatal resuscitation. Further, inserting a laryngeal mask is easier and more accessible than endotracheal intubation, and there are no differences in the mortality rate between the laryngeal mask and endotracheal intubation in neonatal resuscitation. Therefore, in neonatal resuscitation, laryngeal masks are recommended in infants with gestational age >34 weeks and/or birth weight >2 kg in case of unsuccessful attempts at face mask ventilation (as a primary airway device) or endotracheal intubation (as a secondary airway device, alternative airway). In other words, laryngeal masks are recommended not only when endotracheal intubation fails but also when PPV cannot be achieved. Laryngeal masks are commonly used in anesthetized pediatric patients. However, laryngeal masks are not frequently used in neonatal resuscitation due to limited experience, a preference for endotracheal tubes, or a lack of awareness. Healthcare providers must be aware of the usefulness of laryngeal masks in depressed neonates requiring PPV or endotracheal intubation, which can promptly resuscitate these infants and improve the outcomes of them, resulting in decreased morbidity and mortality.

Proper Depth of Percutaneous Central Venous Catheter via the Great Saphenous Vein for Very Low Birth Weight Infants: A Single-Center, Prospective Cohort Study.

BACKGROUND: A proper depth of percutaneous central venous catheter (PCVC) is very important to reduce procedural time and prevent various complications in very low birth weight (VLBW) infants who require minimal handling or have a sensitive skin. The objective of this study was to suggest a formula for faster and proper insertion of PCVC in VLBWIs to prevent unintended consequences of patients' conditions. METHODS: Prospective data of VLBW infants admitted from June 2015 to January 2018 who had PCVC inserted via the great saphenous vein within seven days after birth were analyzed. Correlations of length of inserted PCVC with body weight, body length, and postmenstrual age at the date of PCVC insertion were determined with a linear regression analysis. Using results of this analysis, a formula to determine the optimal insertion length of PCVC was derived. Coefficient of determination was used to assess how well outcomes were replicated by the formula. RESULTS: The formula to predict the proper insertion length of PCVC via the great saphenous vein at popliteal crease level was obtained as follows: Optimal Length (cm) = 3.8 × Body Weight (kg) + 11.1. With everyday movements such as flexion and extension of the lower extremities, the mean difference in catheter tip position was 7.0 ± 3.9 mm, which was not significant enough to escalate the risk of catheter tip displacement. The rate of catheter-related complications was as low as 4.9% in this study. CONCLUSIONS: The formula derived from this study to predict the optimal PCVC insertion length could benefit VLBW infants by reducing procedural time and lowering the risk of complications.

A thickened formula reduces feeding-associated oxygen desaturation and bradycardia in preterm infants.

BACKGROUND: Although preterm infants often experience desaturation or bradycardia during oral feeding, specific guidelines for its management are lacking. PURPOSE: This study aimed to investigate the effects of a commercial thickened formula (TF) on oxygen saturation and heart rate stabilization during oral feeding in preterm infants. METHODS: This retrospective study included 122 infants born at a median (interquartile range [IQR]) 31+6 weeks (29+4 -34+6 weeks) of gestation weighing 1,725 g (1,353-2,620 g) and fed commercial cornstarch-containing TF due to feeding-associated desaturation or bradycardia. We excluded infants fed TF to treat symptomatic regurgitation. Desaturation and bradycardia events were compared between 3 days prior to the change and 3 days after the change to TF. Desaturation and bradycardia were defined as SpO2 <85% and heart rate <100 beats/min during or immediately after oral bottle feeding, respectively. RESULTS: The median (IQR) postmenstrual age and weight were 36+1 weeks (34+6-38+0 weeks) and 2,395 g (2,160-2,780 g), respectively, at the time of change to TF. The frequency of desaturation significantly decreased after TF feeding (median [IQR]: 2.3 [1.3-3.3] events/day vs. 0.3 [0-1.7] events/day, P< 0.001). Bradycardia also decreased after TF feeding (0.3 [0-1] events/day vs. 0 [0-0.7] events/day, P=0.006). There were no cases of diarrhea or electrolyte abnormalities after TF feeding. Defecation frequency decreased (P=0.037), and polyethylene glycol was prescribed to 27% of the TF-fed infants. In a subgroup analysis of 16 infants with bronchopulmonary dysplasia, the frequency of desaturation was reduced (2.3 [1.8-3.8] events/day vs. 0.5 [0-1.5] events/day, P=0.042), and weight gain improved (22.5 [3.1-36.3] g/day vs. 41.3 [28.1-55.1] g/day, P=0.019), after TF feeding. CONCLUSION: TF feeding significantly reduces oral feeding-associated oxygen desaturation and bradycardia in preterm infants. TF may be useful for stabilizing oxygen saturation and heart rate among preterm infants with difficulties in oral feeding.

Comparison of definitions of bronchopulmonary dysplasia to reflect the long-term outcomes of extremely preterm infants.

Survivors of neonatal bronchopulmonary dysplasia (BPD) have persistent respiratory, neurodevelopmental, and growth impairment over the first few years of life and later childhood, which represents an emerging burden for health systems. Therefore, there is an increasing need for a new definition and grading system of BPD that predicts long-term outcomes of high-risk infants who need timely and proper intervention to improve outcomes. We compared new definitions of BPD (National Institute of Child Health and Human Development [NICHD] 2018 and Neonatal Research Network [NRN] 2019) to the original NICHD 2001 definition at 3 years of age using a nationwide cohort of extreme preterm infants. New definitions and severity grading were clearly related to respiratory, neurodevelopmental, and growth impairments at 3 years of age and at 18-24 months corrected age (CA), whereas the original NICHD 2001 definition was not. Furthermore, the negative effect of BPD on growth was ameliorated at 3 years of age compared to 18-24 months CA. However, the negative effect of BPD in neonates on the respiratory system and neurodevelopment persisted at 3 years of age. These new definitions should be adopted to identify high-risk infants and improve long-term outcomes by exact diagnosis and BPD severity classification.

Serial Long-Term Growth and Neurodevelopment of Very-Low-Birth-Weight Infants: 2022 Update on the Korean Neonatal Network.

BACKGROUND: We aimed to evaluate the long-term growth and neurodevelopmental outcomes of very-low-birth-weight infants (VLBWIs, birth weight < 1,500 g) born between 2013, the establishment of the Korean Neonatal Network (KNN), and 2018, both at 18-24 months of corrected age and three years of age, using a nationwide large cohort, and to evaluate whether these outcomes have improved over time since 2013. METHODS: This study used data from the annual reports of the KNN for 18-24 months of corrected age (follow-up 1) and three years of age (follow-up 2). Follow-up 1 data were collected from 10,065 eligible VLBWIs born between January 1, 2013, and December 31, 2018. Follow-up 2 data were collected from 8,156 eligible VLBWIs born between January 1, 2013, and December 31, 2017. RESULTS: The overall follow-up rates of VLBWIs at follow-ups 1 and 2 were 74.6% (7,512/10,065) and 57.7% (4,702/8,156), respectively. The overall mortality rate between discharge from the neonatal intensive care unit and follow-up 1 was 1% (104/10,065). The overall mortality rate between follow-ups 1 and 2 was 0.049% (4/8,156). Growth restrictions decreased over time, especially weight growth restrictions, which significantly decreased according to era (17% in infants born in 2013-2014 and 13% in infants born in 2017-2018). Fewer infants were re-hospitalized and required rehabilitative support according to era at follow-up 1. More infants had language developmental delays and required language support according to era, both at follow-ups 1 and 2. The incidence of cerebral palsy has significantly decreased over time, from 6% in infants born in 2013-2014 to 4% in infants born in 2017-2018 at follow-up 1, and from 8% in infants born in 2013-2014 to 5% in infants born in 2017 at follow-up 2. CONCLUSION: Long-term outcomes of VLBWIs regarding weight growth and cerebral palsy, the most common motor disability in childhood, have improved serially according to era since 2013. However, the rate of infants with language delays requiring language support has increased according to era. Further studies are required on the increased trends of language delay and language support while improving motor outcomes.

Serial Short-Term Outcomes of Very-Low-Birth-Weight Infants in the Korean Neonatal Network From 2013 to 2020.

BACKGROUND: We aimed to determine the current survival rate and short-term outcomes of very-low-birth-weight infants (VLBWIs) in Korea, as well as whether the survival rate and short-term outcomes have improved over time since 2013, which was when the Korean Neonatal Network (KNN) was launched. METHODS: This study used data from the annual reports of the KNN from 2013 to 2020. A total of 16,351 VLBWIs born at gestational age (GA) ≥ 22 weeks between January 1, 2013, and December 31, 2020, and who were registered in the KNN were enrolled. Serial outcomes were analyzed according to era (2013-14, 2015-16, 2017-18, and 2019-20). RESULTS: More mothers delivered by cesarean section, had diabetes or hypertension during their pregnancy, and received antenatal steroids when analyzed by era. Fewer infants were intubated at birth and had air leaks when analyzed by era. The overall survival rate of VLBWIs between 2013 and 2020 was 87%. The rate of respiratory distress syndrome was 77% and that of bronchopulmonary dysplasia was 32% between 2013 and 2020. The rates of intraventricular hemorrhage (grade ≥ 3), periventricular leukomalacia, and sepsis decreased over time. The survival rate of infants with a GA of 26 weeks has improved serially according to era. CONCLUSION: Since the launch of the KNN in 2013, the survival rates of infants with GA 26 weeks and short-term outcomes have improved, which implies a quality improvement in antenatal and delivery room care. Further studies on the long-term neurodevelopmental outcomes of these KNN registrants are warranted.

Neonatal Abusive Head Trauma without External Injuries: Suspicion Improves Diagnosis.

The term "shaken baby syndrome" has been replaced by "abusive head trauma (AHT)" based on the mechanism of injury. The reported mortality rate of AHT ranges from 10% to 30%. Up to two-thirds of survivors suffer from serious long-term disabilities. Thus, an expeditious and accurate diagnosis is crucial to prevent further abuse that might result in death or serious disabilities. It remains a challenge for physicians to diagnose AHT when parents do not give a history of trauma in preverbal infants without any external signs. Here, we report a case of a 14-day-old boy who presented with a febrile convulsion without evident external injuries nor history of trauma according to his parents. He was diagnosed with AHT based on MRI findings of subacute subdural hemorrhage, multiple cortical hemorrhages, cerebral edema, and diffuse axonal injury. In conclusion, health care providers should keep in mind that the history of trauma provided by the parents or caregivers might not always be true and that reasonable suspicion of abuse is the most important in the diagnosis of AHT, although neuroimaging plays a pivotal role. Reasonable suspicion of AHT in combination with a thorough physical examination, neuroimaging, and skilled neuroradiologist can improve diagnosis and help victims in a timely manner.

Neonatal outcome comparisons between preterm infants with or without early pulmonary hypertension following prolonged preterm premature rupture of membranes before 25 gestational weeks in Korean Neonatal Network.

OBJECTIVE: To determine the outcomes of very low birth weight infants (VLBWIs) following maternal mid-trimester prolonged preterm premature rupture of membranes (PPROM) and subsequent early pulmonary hypertension (PH). DESIGN: Prospective cohort study. SETTING: A nationwide web-based registry of VLBWIs from 67 neonatal intensive care units. PATIENTS: VLBWIs registered on the Korean Neonatal Network and born between 23 and 34 gestational weeks. METHODS: VLBWIs exposed to maternal PPROM prior to 25 gestational weeks and lasting ≥7 days (PPROM25, n = 402) were matched 1:1 with infants not exposed or exposed within 24 h to PPROM (CON, n = 402), using propensity score matching. The PPROM25 group was subdivided into PPROM25 groups with or without early PH, defined as exposure to inhaled nitric oxide or other pulmonary vasodilators to treat PH within 3 days of life. Clinical variables and major outcomes were compared, and risk factors for mortality and morbidities were analyzed. RESULTS: Of 1790 infants with maternal PPROM, the PPROM25 group comprised 402 (22.5%) infants. Survival rates were similar between the CON and PPROM25 groups (71.6% vs 74.4%); however, the incidence of bronchopulmonary dysplasia (BPD) differed (47.8% and 60.2%, p < .05). Infants in the PPROM25 group with early PH had higher mortality (55.6%) and more severe intraventricular hemorrhage (IVH) (31.7%) than infants in the PPROM25 group without early PH (21.9% and 14.3%, respectively; p < .05). In multivariate analysis, lower 5 min Apgar score and the presence of oligohydramnios increased the risk of development of early PH. The presence of PPROM25 was founded to be a significant risk factor for BPD and early PH in relation to mortality and severe IVH, respectively. CONCLUSIONS: In VLBWIs, prolonged exposure to maternal mid-trimester PPROM increased the risk of BPD. Subsequent early PH immediately after birth increased mortality and severe IVH, thus, requires special attention.

Pathophysiology, classification, and complications of common asymptomatic thrombocytosis in newborn infants.

We frequently encounter newborn infants with thrombocytosis in the neonatal intensive care unit. However, neonatal thrombocytosis is not yet fully understood. Thrombocytosis is more frequently identified in newborns and young infants, notably more often in those younger than 2 years than in older children or adults. The production of megakaryocytes (megakaryopoiesis) and platelets (thrombopoiesis) is mainly regulated by thrombopoietin (TPO). Increased TPO levels during infection or inflammation can stimulate megakaryopoiesis, resulting in thrombopoiesis. TPO concentrations are higher in newborn infants than in adults. Levels increase after birth, peak on the second day after birth, and start decreasing at 1 month of age. Initial platelet counts at birth increase with gestational age. Thus, preterm infants have lower initial platelet counts at birth than late-preterm or term infants. Postnatal thrombocytosis is more frequently observed in preterm infants than in term infants. A high TPO concentration and low TPO receptor expression on platelets leading to elevated plasma-free TPO, increased sensitivity of megakaryocyte precursor cells to TPO, a decreased red blood cell count, and immaturity of platelet regulation are speculated to induce thrombocytosis in preterm infants. Thrombocytosis in newborn infants is considered a reactive process (secondary thrombocytosis) following infection, acute/chronic inflammation, or anemia. Thrombocytosis in newborn infants is benign, resolves spontaneously, and, unlike in adults, is rarely associated with hemorrhagic and thromboembolic complications.

Risk factors and screening timing for developmental dysplasia of the hip in preterm infants.

BACKGROUND: The delayed diagnosis of developmental dysplasia of the hip (DDH) requires complex treatment and sometimes progresses to hip osteoarthritis. PURPOSE: This study aimed to evaluate the risk factors and screening time for DDH in preterm infants. METHODS: A total of 155 preterm infants with a gestational age <32 weeks screened for DDH with ultrasonography were enrolled in this retrospective chart review. RESULTS: The incidence of DDH was 6.45% (10 of 155). Gestational age, birth weight, sex ratio, and breech presentation did not differ significantly between infants treated for DDH (n=10) and nontreated infants (n=145) (gestational age, 29.2±1.4 weeks vs. 29.6±2.0 weeks, P=0.583; birth weight, 1,240±237 g vs. 1,295±335 g, P=0.607; female sex, 7 of 10 (70.0%) vs. 77 of 145 (53.1%), P=0.346; and breech presentation, 5 of 10 (50.0%) vs. 43 of 145 (29.7%), P=0.286, respectively). Performing the first ultrasonography earlier than 38 weeks of postmenstrual age (PMA) increased the risk of an abnormal finding by 3.76 times compared to performing it at ≥38 weeks of PMA. These abnormal findings on ultrasonography resolved spontaneously. Breech presentation increased the risk of minor abnormal findings on the first ultrasonography by 3.11 times versus nonbreech presentation and resolved spontaneously. DDH in preterm infants did not occur predominantly on the left side or in infants born with breech presentation. CONCLUSION: Performing ultrasonography screening earlier than 38 weeks of PMA caused unnecessary subsequent ultrasonography and overtreatment. Breech presentation was not a risk factor for DDH in preterm infants. However, breech presentation could increase the risk of minor abnormal findings at the 1st ultrasonography compared to nonbreech presentation, which resolved spontaneously. The etiology and risk factors for DDH in preterm infants are somewhat different from those for DDH in term infants.

Definitions of bronchopulmonary dysplasia and long-term outcomes of extremely preterm infants in Korean Neonatal Network.

New definitions for bronchopulmonary dysplasia (BPD) have recently been suggested, and an accurate diagnosis, including severity classification with proper definition, is crucial to identify high-risk infants for appropriate interventions. To determine whether recently suggested BPD definitions can better predict long-term outcomes of BPD in extremely preterm infants (EPIs) than the original BPD definition, BPD was classified with severity 1, 2, and 3 using three different definitions: definition A (original), National Institute of Child Health and Human Development (NICHD) definition in 2001; definition B, the modified NICHD 2016 definition (graded by the oxygen concentration and the respiratory support at 36 weeks' postmenstrual age [PMA]); and definition C, the modified Jensen 2019 definition (graded by the respiratory support at 36 weeks' PMA). We evaluated 1050 EPIs using a national cohort. Whereas EPIs with grade 2 or 3 BPD as per definition A did not show any increase in the risk, EPIs with BPD diagnosed by definition B and C showed significantly increased risk for poor outcomes, such as respiratory mortality and morbidities, neurodevelopmental delay, and growth restriction at 18-24 months of corrected age. The recently suggested definition and severity grading better reflects long-term childhood morbidities than the original definition in EPIs.

Early pulmonary hypertension is a risk factor for bronchopulmonary dysplasia-associated late pulmonary hypertension in extremely preterm infants.

This study evaluated whether early pulmonary hypertension (PH) in extremely preterm infants (EPIs) at 22-27 weeks of gestation detected clinically with echocardiography at 4-7 postnatal days (PND) is a risk factor for death before 36 weeks post-menstrual age (PMA) or late PH in moderate or severe (m/s) bronchopulmonary dysplasia (BPD) (BPD-PH). We analyzed risk factors for death before 36 weeks PMA or BPD-PH. Among 247 EPIs enrolled, 74 (30.0%) had early PH. Twenty-one (28.4%) infants with early PH and 18 (10.4%) without early PH died before 36 weeks PMA; 14 (18.9%) infants with early PH and 9 (5.2%) without early PH had BPD-PH at 36-38 weeks PMA. Multivariate analysis revealed that early PH (adjusted odds ratio, 6.55; 95% confidence interval, 3.10-13.82, P < 0.05), clinical chorioamnionitis (2.50; 1.18-5.31), intraventricular hemorrhage (grade 3-4) (3.43; 1.26-9.37), and late sepsis (6.76; 3.20-14.28) independently increased the risk of development of death before 36 weeks PMA or BPD-PH. Subgroup analysis among m/s BPD patients revealed that early PH (4.50; 1.61-12.58) and prolonged invasive ventilator care (> 28 days) (4.91; 1.02-23.68) increased the risk for late PH independently. In conclusion, EPIs with early PH at 4-7 PND should be monitored for BPD-associated late PH development.

Intratracheal administration of budesonide with surfactant in very low birth weight infants to prevent bronchopulmonary dysplasia.

BACKGROUND AND OBJECTIVES: Respiratory distress syndrome (RDS) is a major cause of early postnatal death in preterm infants. Bronchopulmonary dysplasia (BPD) is one of the most fatal chronic respiratory complications of preterm infants after management of RDS. Anti-inflammatory therapy with corticosteroid is one of the effective treatments to prevent BPD. However, systemic administration of corticosteroid is not recommended because of long-term adverse effects. We studied the effect of early intratracheal instillation of budesonide with surfactant in preterm infants with severe RDS. METHOD: Very low birth weight infants (VLBWIs) weighing less than 1,500 g who were admitted to the neonatal intensive care unit (NICU) of Busan Paik Hospital between January 2018 and December 2018 and diagnosed with severe RDS were enrolled. The treatment group was given a mixture of budesonide and surfactant (calfactant) while the control group was given surfactant (calfactant) only. RESULTS: Surfactant re-dosing, duration of mechanical ventilation, BPD, mortality, and retinopathy of prematurity (≥ stage 2) were not different between the two groups though there were decreasing trends in the treatment group compared to those in the control group. The duration of hospital stay was longer in the control group with statistical significance. CONCLUSION: Early intratracheal administration of budesonide with surfactant in preterm infants with severe RDS might decrease BPD and mortality without disturbing surfactant function. Further studies with different preparations of surfactants with a large number of preterm infants are required.

Prevalence of Eleven Infectious Viruses Causing Diarrhea in Korea.

Rotavirus and norovirus are well-known causes of viral infectious diarrhea. There are few reports on diarrhea caused by other viruses in Korea, although cases of gastroenteritis attributable to other viruses are increasing worldwide. The aims of this study were to detect various causes of viral diarrhea and to investigate their prevalence. A total of 801 fecal specimens submitted to a clinical microbiology laboratory for the detection of diarrheal viruses were included. We sought to detect rotavirus A/B/C, adenovirus, astrovirus, norovirus GI/GII, sapovirus, Aichi virus, human parechovirus, enterovirus, human cosavirus, human bocavirus, and Saffold virus using multiplex reverse transcription polymerase chain reaction (RT-PCR). At least one diarrheal virus was detected in 223 (27.8%) fecal specimens. Among them, two viruses were detected in 11 specimens. Rotavirus A was most common (17.1%; N = 137), followed by norovirus GII (5.0%; N = 40), enterovirus (4.2%; N = 34), adenovirus (1.0%; N = 8), astrovirus (1.0%; N = 8), human parechovirus (0.6%; N = 5), and human bocavirus (0.2%; N = 2). Rotaviruses B and C, norovirus GI, sapovirus, Aichi virus, human cosavirus, and Saffold virus were not detected. We confirmed that various diarrheal viruses can be detected in fecal specimens. We must consider the possibility of viruses other than rotavirus and norovirus being present in cases of diarrhea.

Comparison of diagnostic and treatment guidelines for undescended testis.

Cryptorchidism or undescended testis is the single most common genitourinary disease in male neonates. In most cases, the testes will descend spontaneously by 3 months of age. If the testes do not descend by 6 months of age, the probability of spontaneous descent thereafter is low. About 1%-2% of boys older than 6 months have undescended testes after their early postnatal descent. In some cases, a testis vanishes in the abdomen or reascends after birth which was present in the scrotum at birth. An inguinal undescended testis is sometimes mistaken for an inguinal hernia. A surgical specialist referral is recommended if descent does not occur by 6 months, undescended testis is newly diagnosed after 6 months of age, or testicular torsion is suspected. International guidelines do not recommend ultrasonography or other diagnostic imaging because they cannot add diagnostic accuracy or change treatment. Routine hormonal therapy is not recommended for undescended testis due to a lack of evidence. Orchiopexy is recommended between 6 and 18 months at the latest to protect the fertility potential and decrease the risk of malignant changes. Patients with unilateral undescended testis have an infertility rate of up to 10%. This rate is even higher in patients with bilateral undescended testes, with intra-abdominal undescended testis, or who underwent delayed orchiopexy. Patients with undescended testis have a threefold increased risk of testicular cancer later in life compared to the general population. Self-examination after puberty is recommended to facilitate early cancer detection. A timely referral to a surgical specialist and timely surgical correction are the most important factors for decreasing infertility and testicular cancer rates.

Development of Swallowing Function in Infants with Oral Feeding Difficulties.

BACKGROUND: Discharge of preterm infants is often delayed because of their oral feeding difficulties. Independent oral feeding is the last obstacle to pass after managing acute and chronic morbidities. We conducted this study to determine the prevalence, characteristics, and risk factors of swallowing dysfunction and suggest proper interventions to reduce aspiration and chronic lung injury. METHODS: Infants admitted to the neonatal intensive care unit (January 2016 to December 2018) who were performed modified barium swallow study due to oral feeding difficulties were enrolled. Modified barium swallow study was done ≥ postmenstrual age 37 weeks to limit radiation exposure. Clinical data were collected retrospectively. Swallowing dysfunction was defined as inadequate epiglottic closure, laryngeal penetration, or tracheal aspiration according to result of the modified barium swallow study. RESULTS: Among a total of 54 infants enrolled, nine (16.7%) were term infants, 13 (24.1%) were late preterm infants (gestational age, 34-36 weeks), and 32 (59.3%) were early preterm infants (gestational age < 34 weeks). Gestational age and birth weight were smaller in infants with swallowing dysfunction. Total duration of mechanical ventilation and duration of invasive ventilation were longer in infants with swallowing dysfunction. The risk of swallowing dysfunction increased by 11.2 times for infants with gestational age < 29 weeks compared to infants with gestational age ≥ 29 weeks. Swallowing dysfunction was improved in most infants after they became matured. They showed different time and rate of maturation with the help of rehabilitation through swallow therapy and dietary modification with thickened formula. CONCLUSION: Preterm infants with gestational age < 29 weeks or with longer ventilation duration are at a higher risk of aspiration. Rehabilitation of swallow therapy and dietary modification with thickened formula can be helpful interventions to prevent aspiration and chronic lung injury and reassure parents until independent oral feeding is possible.

Hypoxia-inducible factor: role in cell survival in superoxide dismutase overexpressing mice after neonatal hypoxia-ischemia.

BACKGROUND: Sixty percent of infants with severe neonatal hypoxic-ischemic encephalopathy die, while most survivors have permanent disabilities. Treatment for neonatal hypoxic-ischemic encephalopathy is limited to therapeutic hypothermia, but it does not offer complete protection. Here, we investigated whether hypoxia-inducible factor (HIF) promotes cell survival and suggested neuroprotective strategies. PURPOSE: HIF-1α-deficient mice have increased brain injury after neonatal hypoxia-ischemia (HI), and the role of HIF-2α in HI is not well characterized. Copper-zinc superoxide dismutase (SOD)1 overexpression is not beneficial in neonatal HI. The expression of HIF-1α and HIF-2α was measured in SOD1 overexpressing mice and compared to wild-type littermates to see if alteration in expression explains this lack of benefit. METHODS: On postnatal day 9, C57Bl/6 mice were subjected to HI, and protein expression was measured by western blotting in the ipsilateral cortex of wild-type and SOD1 overexpressing mice to quantify HIF-1α and HIF-2α. Spectrin expression was also measured to characterize the mechanism of cell death. RESULTS: HIF-1α protein expression did not significantly change after HI injury in the SOD1-overexpressing or wild-type mouse cortex. However, HIF-2α protein expression increased 30 minutes after HI injury in the wild-type and SOD1-overexpressing mouse cortex and decreased to baseline value at 24 hours after HI injury. Spectrin 145/150 expression did not significantly change after HI injury in the SOD1- overexpressing or wild-type mouse cortex. However, spectrin 120 expression increased in both wild-type and SOD1-overexpressing mouse at 4 hours after HI, which decreased by 24 hours, indicating a greater role of apoptotic cell death. CONCLUSION: HIF-1α and HIF-2α may promote cell survival in neonatal HI in a cell-specific and regional fashion. Our findings suggest that early HIF-2α upregulation precedes apoptotic cell death and limits necrotic cell death. However, the influence of SOD was not clarified; it remains an intriguing factor in neonatal HI.

Surfactant preparations for preterm infants with respiratory distress syndrome: past, present, and future.

Following the first successful trial of surfactant replacement therapy for preterm infants with respiratory distress syndrome (RDS) by Fujiwara in 1980, several animal-derived natural surfactants and synthetic surfactants have been developed. Synthetic surfactants were designed to overcome limitations of natural surfactants such as cost, immune reactions, and infections elicited by animal proteins contained in natural surfactants. However, first-generation synthetic surfactants that are protein-free have failed to prove their superiority over natural surfactants because they lack surfactant protein (SP). Lucinactant, a second-generation synthetic surfactant containing the SP-B analog, was better or at least as effective as the natural surfactant, suggesting that lucinactant could act an alternative to natural surfactants. Lucinactant was approved by the U. S. Food and Drug Administration in March 2012 as the fifth surfactant to treat neonatal RDS. CHF5633, a second-generation synthetic surfactant containing SP-B and SP-C analogs, was effective and safe in a human multicenter cohort study for preterm infants. Many comparative studies of natural surfactants used worldwide have reported different efficacies for different preparations. However, these differences are believed to due to site variations, not actual differences. The more important thing than the composition of the surfactant in improving outcome is the timing and mode of administration of the surfactant. Novel synthetic surfactants containing synthetic phospholipid incorporated with SP-B and SP-C analogs will potentially represent alternatives to natural surfactants in the future, while improvement of treatment modalities with less-invasive or noninvasive methods of surfactant administration will be the most important task to be resolved.