Cognitive and Behavioral Outcomes of School-aged Children Born Extremely Preterm: a Korean Single-center Study with Long-term Follow-up

Background@#School-aged children born very preterm have been suggested to have worse cognitive and behavioral outcomes than children born full-term. Executive function (EF) is a higher level of cognitive function related to academic achievement. The present study aimed to evaluate the cognitive (including EF) and behavioral outcomes of Korean children born extremely preterm (EP) and to analyze any biological or socioeconomic risk factors for poor cognitive outcomes in this population. @*Methods@#A total of 71 infants weighing < 1,000 g at birth or born before 30 weeks of gestation (EP group) who were admitted to the neonatal intensive care unit from 2008 to 2009 were included in this study and compared with 40 term-birth controls. The Korean Wechsler Intelligence Scale for Children-Fourth Edition, Advanced Test of Attention (ATA), Stroop test, Children's Color Trails Test (CCTT), and Wisconsin Card Sorting Test (WCST) were used.Additionally, the Korean Child Behavior Checklist (K-CBCL) and Korean ADHD Rating Scale (K-ARS) were completed. Perinatal and demographic data were collected and analyzed. @*Results@#The mean full-scale intelligence quotient (FSIQ) score in the EP group was significantly lower than that of the term control group (89.1 ± 18.3 vs. 107.1 ± 12.7; P < 0.001).In the EP group, 26 (37%) children had an FSIQ score below 85, compared to only one child (3%) in the control group. Furthermore, the EP group showed significantly worse EF test results (ATA, Stroop test, CCTT, WCST). Except for the higher social immaturity subscore in the EP group, the K-CBCL and K-ARS scores were not different between the two groups. EP children who received laser treatment for retinopathy of prematurity (ROP) had an 8.8-fold increased risk of a low FSIQ score, and a 1-point increase in the discharge weight Z-score decreased the risk of a low FSIQ score by approximately half in this EP cohort. @*Conclusion@#This is the first Korean study to investigate the cognitive and behavioral outcomes of school-aged children born EP. In the study cohort, EP children exhibited significantly lower FSIQ scores and EF than their full-term peers, and 37% of them had cognitive problems. Nonetheless, except for social immaturity, the behavioral problems werenot different in EP children. Severe ROP and low discharge weight Z-score were identified as independent risk factors for low FSIQ score after adjusting for birth weight.

Cognitive and Behavioral Outcomes of School-aged Children Born Extremely Preterm: a Korean Single-center Study with Long-term Follow-up

Background@#School-aged children born very preterm have been suggested to have worse cognitive and behavioral outcomes than children born full-term. Executive function (EF) is a higher level of cognitive function related to academic achievement. The present study aimed to evaluate the cognitive (including EF) and behavioral outcomes of Korean children born extremely preterm (EP) and to analyze any biological or socioeconomic risk factors for poor cognitive outcomes in this population. @*Methods@#A total of 71 infants weighing < 1,000 g at birth or born before 30 weeks of gestation (EP group) who were admitted to the neonatal intensive care unit from 2008 to 2009 were included in this study and compared with 40 term-birth controls. The Korean Wechsler Intelligence Scale for Children-Fourth Edition, Advanced Test of Attention (ATA), Stroop test, Children's Color Trails Test (CCTT), and Wisconsin Card Sorting Test (WCST) were used.Additionally, the Korean Child Behavior Checklist (K-CBCL) and Korean ADHD Rating Scale (K-ARS) were completed. Perinatal and demographic data were collected and analyzed. @*Results@#The mean full-scale intelligence quotient (FSIQ) score in the EP group was significantly lower than that of the term control group (89.1 ± 18.3 vs. 107.1 ± 12.7; P < 0.001).In the EP group, 26 (37%) children had an FSIQ score below 85, compared to only one child (3%) in the control group. Furthermore, the EP group showed significantly worse EF test results (ATA, Stroop test, CCTT, WCST). Except for the higher social immaturity subscore in the EP group, the K-CBCL and K-ARS scores were not different between the two groups. EP children who received laser treatment for retinopathy of prematurity (ROP) had an 8.8-fold increased risk of a low FSIQ score, and a 1-point increase in the discharge weight Z-score decreased the risk of a low FSIQ score by approximately half in this EP cohort. @*Conclusion@#This is the first Korean study to investigate the cognitive and behavioral outcomes of school-aged children born EP. In the study cohort, EP children exhibited significantly lower FSIQ scores and EF than their full-term peers, and 37% of them had cognitive problems. Nonetheless, except for social immaturity, the behavioral problems werenot different in EP children. Severe ROP and low discharge weight Z-score were identified as independent risk factors for low FSIQ score after adjusting for birth weight.

The First Report on Clinical Manifestation of Cryopyrin-Associated Periodic Syndrome in Korean Children

PURPOSE: The aim of this study was to evaluate the clinical characteristics of children diagnosed as cryopyrin-associated periodic syndrome (CAPS) in Korea. METHODS: Diagnosis was made based on clinical features and confirmed by a mutation in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene. Especially, osteocartilaginous overgrowth in the patella or distal femur was so characteristic that its presence warranted a diagnosis of chronic infantile neurologic cutaneous and articular/NOMID. RESULTS: We observed the clinical features of 9 Korean CAPS patients. All the patients suffered from an urticarial rash with recurrent fever. Among the 9 patients, 6 presented with rash and 4 with fever on the 1st or 2nd days of birth. Eight patients showed myalgia, and 7 patients showed arthralgia in the joints, and 6 patients showed radiologic findings of arthropathy including cupping of the metaphysis, excessive growth of the epiphysis, osteopenia or overgrowth of the cartilage. Four patients showed brain atrophy, enlarged ventricles or leptomeningeal enhancement on magnetic resonance imaging. Intellectual disability was observed in 1 patient. Five patients had eye involvement as conjunctivitis, uveitis, chorioretinitis, avascular area or papillary edema, and 3 patients showed progressive hearing loss. All 9 patients showed increased C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). CONCLUSIONS: All the patients carried a mutation on exon 3 of the CIAS1 gene. After the anakinra (interleukin-1 receptor antagonist) therapy, the fever and rash immediately disappeared, and CRP and ESR were improved.

Influence of Routine Probiotic Supplementation on the Incidence of Necrotizing Enterocolitis and Late Onset Sepsis

PURPOSE: This study aimed to investigate the influence of routine probiotic supplementation on causes of neonatal morbidity and mortality, such as necrotizing enterocolitis (NEC) and late onset sepsis. METHODS: All neonates born at <32 weeks of gestation and weighing <1,500 g admitted to the neonatal intensive care unit during the study period were included. The study period was divided into the pre-probiotic period, between January 2009 and February 2011, and the probiotic period, between November 2012 and December 2014. The probiotic given was a mixture of Lactobacillus plantarum, L. rhamnosus, Bifidobacterium lactis and B. longum, administered at the time of the first feeding over 2 mL once daily. RESULTS: A total of 358 infants were screened for enrollment, with 149 infants included in the pre-probiotic group (mean birth weight 937 g, mean gestational age 27.9 wk), and 158 in the probiotic group (1,040 g, 28.6 wk). Probiotics had no statistically significant impact on NEC and late onset sepsis. However, three cases of probiotic related sepsis occurred after the infants were routinely administered probiotics in our unit. CONCLUSION: Routine probiotic supplementation did not reduce the incidence of NEC in very low birth weight (VLBW) infants. However, severe sepsis was caused by strains in the probiotic administered to patients. Therefore, routine prophylactic use of probiotic in VLBW infants should be performed cautiously.

Decolonization of Methicillin resistant Staphylococcus aureus: Role in the Neonatal Intensive Care Unit

PURPOSE: We aimed to assess the incidence of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection in a neonatal intensive care unit (NICU) by using various decolonization methods and to evaluate their efficacy. METHODS: Medical records of all neonates who were admitted to the NICU of Seoul National University Children's Hospital were retrospectively reviewed. Surveillance culture were obtained for all neonates in the NICU 48 hours after admission. Three periods with different decolonization methods were compared; Period 1 was without any decolonization measures (July 1, 2009 to August 26, 2010). In period 2, intranasal mupirocin and chlorhexidine gluconate bathing were administered to MRSA-colonized neonates (August 27, 2010 to September 6, 2011). In period 3, only chlorhexidine bathing was performed for MRSA-colonized infants (September 7, 2011 to August 31, 2012). RESULTS: A total of 1,378 infants were admitted to the NICU during the study period. Baseline demographic and clinical characteristics were similar among the 3 periods. The incidence of MRSA colonization per 1,000 patient-days was 6.27 for period 1, 7.02 for period 2, and 6.29 for period 3; however, these values were not significantly different. The incidence of MRSA infection was highest in period 3, with 0.69 cases per 1,000 patient-days; however, this finding was not significant. The MRSA infection/colonization ratio also did not differ significantly among the 3 study periods. CONCLUSION: Decolonization of MRSA in the NICU with the application of chlorhexidine gluconate bathing alone or in combination with intranasal mupirocin were not effective in decreasing the incidence of MRSA colonization and infection.

Characteristics of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants according to the Timing of Dexamethasone Administration / 대한주산의학회잡지

PURPOSE: Corticosteroids has been used for treatment and prophylaxis of bronchopulmonary dysplasia (BPD) in preterm infants. However, administration of corticosteroids could be delayed due to its potential harmful effects on neurodevelopment. The aim of this study was to evaluate the adequate dexamethasone administration timing in very low birth weight infants. METHODS: Medical records of 56 VLBW infants who were admitted to neonatal intensive care unit of Seoul National University Children's Hospital and Seoul National University Bundang Hospital between January 2008 and September 2014 were collected retrospectively. Study population were divided into early administration group (dexamethasone administration before 4 weeks of postnatal days) and late administration group (after 4 weeks) and respiratory morbidities were compared between groups. RESULTS: There were no significant differences in clinical characteristics between early administration group (n=30) and late administration group (n=26). Respiratory severity score and oxygen needs at 7 days after birth and before administering dexamethasone were comparable. Extubation was done earlier postnatal days in early administration group. Incidence of severe BPD was higher in the late administration group. There was no significant difference in diagnosed with cerebral palsy (CP) at 12 months of corrected age. When adjusting for multiple risk factors, administration of dexamethasone 4 weeks after birth and severe of BPD showed a significant association (adjusted OR 17.14 [1.29-227.52], P=0.031). CONCLUSION: Administration of dexamethasone in order to minimize ventilator care and to reduce severe BPD might be done between 1 week and 4 weeks after birth in very low birth weight infants.

Comparison of Enteral Feeding in Early Neonatal Period in Very Low Birthweight Infants with Hypothyroidism / 대한주산의학회잡지

PURPOSE: We investigated the effects of hypothyroidism on feeding advancement in very low birth weight infants (VLBW). METHODS: This study was a retrospective case-control study of 14 very low birth weight infants (VLBWIs) diagnosed with hypothyroidism and other 14 infants were recruited as age- and weight-matched controls without hypothyroidism or hypothyroxinemia in Seoul National University Children's Hospital between January 2007 and August 2009. We examined whether these infants gained weight more, achieved full-volume enteral feedings sooner, had fewer episodes of increased pre-gavage residuals, and had fewer days of parenteral nutrition. RESULTS: Until full enteral feeding (120 mL/kg/day) was not statistically significant between the groups. In the hypothyroidism group, during the first 14 days after birth, the volume of feeding was smaller [14.7 (0.5-84.0) mL/kg/day, P=0.041], the episodes of increased pre-gavage residuals were frequently observed [16.7 (0.2-78) times, P=0.036], and the duration of central line was significantly longer [18 (10-50) days, P=0.018]. In hypothyroidism group, mean day at first L-thyroxine supplementation was 24.2+/-10.2 days after birth. L-thyroxine administration boosted thyroid function for hypothyroidism infants, helped them tolerate a larger amount of enteral feeding [from 89.5 (2.9-160.8) to 146.9 (31.8-178.8) mL/kg/day, P=0.002] and decreased episodes of excessive gastric residuals [from 5.5 (0-41.6) to 0 (0-44) time, P=0.026]. However, no more weight gain was statistically found. CONCLUSION: In VLBW infants, hypothyroidism may induce feeding intolerance. L-thyroxine supplementation was effective in feeding advancement on preterm infants with hypothyroidism.

A Case of a Preterm Infant with Prenatally Diagnosed Intrauterine Midgut Volvulus / 대한주산의학회잡지

Intrauterine midgut volvulus is a rare and potentially life-threatening congenital disease that can lead to intestinal ischemia, sepsis and peritonitis caused by bowel perforation and meconium obstruction. Early detection and immediate treatment is crucial to improve the outcome. Herein, we report a preterm infant of 30 weeks of gestation with intrauterine midgut volvulus associated with meconium peritonitis who survived after cesarean delivery and immediate postnatal surgical intervention. The outcome of in-utero intestinal volvulus depends on optimal delivery timing and adequate postnatal treatment. Therefore, prompt multidisciplinary consultation and planning with obstetricians, neonatologists and pediatric surgeons is necessary to reduce the morbidity and mortality associated with fetal midgut volvulus, especially in the preterm period.

Timing of Liberation from Ventilation Assistance and Decannulation in Preterm Infants with Bronchopulmonary Dysplasia after Tracheostomy

PURPOSE: We aimed to evaluate the clinical outcomes of preterm infants with bronchopulmonary dysplasia after tracheostomy. METHODS: We retrospectively examined 24 preterm infants with bronchopulmonary dysplasia who were admitted to the neonatal intensive care unit of Seoul National University Hospital and treated with tracheostomy between January 1999 and December 2013. We collected data on the age at tracheostomy, indication for the tracheostomy, and the long-term outcomes. RESULTS: Of the admitted patients, 1.0% were treated with tracheostomy, and the median age at tracheostomy was 185 days. Fifteen patients (62.5%) were weaned from mechanical ventilation. Of these, 56.5% patients were weaned from positive pressure ventilation (PPV) within 24 months, and 81.3% were weaned from PPV within 60 months. The median time from the tracheostomy procedure to independent PPV was 15.9 months. Decannulation was achieved in 8 patients (33.3%); of these, 41.5% were decannulated within 24 months, and 69.9% were decannulated within 60 months. The median time from the tracheostomy procedure to decannulation was 48.8 months. In patients without airway disease, the time from the tracheostomy procedure to independent PPV and decannulation was 15.6 months. In patients with airway disease, the time from the tracheostomy procedure to independent PPV and decannulation was found to be extended. However, the presence of airway disease was not significantly associated with the duration of mechanical ventilation, or with the time to decannulation. The 5-year survival rate was 80.2%; the patients who did not survive died within 12 months of the tracheostomy procedure. CONCLUSION: Infants with moderate or severe bronchopulmonary dysplasia occasionally require tracheostomy tube placement for mechanical ventilation. In cases with airway disease, the time from the tracheostomy procedure to independent PPV and decannulation tended to be increased, although this increase was not significant.

Risk Factor for Massive Pulmonary Hemorrhage Occurring during the First Five Days after Birth in Extremely Low Birth Weight Infants

PURPOSE: Massive pulmonary hemorrhage(MPH) within the first five days after birth is a major cause of early death in extremely low birth weight(ELBW) infants. The objective of this study was to determine risk factors for MPH in ELBW infants. METHODS: Data were retrospectively collected from 115 ELBW infants admitted to Seoul National University Bundang Hospital between January 2007 and September 2012. MPH was defined as the presence of hemorrhagic fluid in the trachea accompanied by acute respiratory failure within the first five days after birth. Initial echocardiography and cranial ultrasonography were performed in all subjects before MPH. Clinical characteristics of ELBW infants with and without MPH were compared and the risk factors for MPH were investigated. RESULTS: MPH occurred at 54+/-30 h after birth and was more frequent in ELBW infants with lower gestational age and lesser birth weight. Older maternal age was also associated with MPH. The presence of patent ductus arteriosus diagnosed using initial echocardiography was not significantly associated with MPH. The presence of intraventricular hemorrhage diagnosed using serial cranial ultrasonography was significantly associated with MPH. Logistic regression analysis indicated that among the variables that preceded MPH, only lower gestational age was independently associated with MPH. CONCLUSION: Lower gestational age was found to be a risk factor for MPH within the first five days after birth in ELBW infants.

Respiratory Morbidities in Newborn Infants by Gestational Age Following Elective Cesarean Section beyond 35 Weeks of Gestation / 대한주산의학회잡지

PURPOSE: We evaluate respiratory morbidities in infants beyond 35 weeks of gestation born via elective cesarean section by gestational age. METHODS: This is a retrospective study of 443 infants who were born at Seoul National University Hospital by elective cesarean section beyond 35 weeks of gestation from January 2011 to December 2012. We compared respiratory morbidities in four groups classified by gestational age (35(+0)-36(+6) weeks, 37(+0)-37(+6) weeks, 38(+0)-38(+6) weeks, 39(+0)-40(+6) weeks). RESULTS: There were significantly lower Apgar scores in the late-preterm infant group (35-36 weeks) compared to other term infant groups and the proportion of infants born from mothers with preeclampsia gradually decreased as gestational age increased. There were significant differences in O2 supplement, duration of O2 (>24 hours), checked chest radiography, transient tachypnea of newborn (TTN), transfer to neonatal intensive care unit (NICU), endotracheal intubation, and ventilator uses including nasal continuous positive airway pressure in four groups (P<0.05). By logistic regression analysis, compared to births at 38 weeks, births at 35-36 weeks and at 37 weeks were associated with an increased risk of respiratory morbidities [odds ratios (OR) and 95% confidence intervals (CI) for births at 35-36 weeks, 122.5 (17.4-863.4) for TTN; 54.0 (10.1-289.4) for transfer to NICU; 99.5 (14.9-666.2) for ventilator apply; OR and 95% CI for births at 37 weeks, 8.8 (1.6-50.1) for TTN; 5.3 (1.1-24.7) for transfer to NICU; 8.4 (1.5-47.7) for ventilator apply; P<0.05]. There were no significant differences in respiratory morbidities between births at 38 weeks and births at 39-40 weeks. CONCLUSION: Postponing the timing of elective cesarean section to beyond 38 weeks of gestation would be helpful in reducing the neonatal respiratory morbidities.

Optimal Timing of the First Screening Examination for Retinopathy of Prematurity

PURPOSE: In the present study, we aimed to evaluate the suitability of the first screening examination for retinopathy of prematurity (ROP) in a tertiary neonatal intensive care unit (NICU). METHODS: A retrospective analysis of ROP screening records of 459 infants admitted to the NICU of Seoul National University Children's Hospital between January 2006 and December 2011 was performed. The first examination was performed at 31-32 weeks of postmenstrual age (PMA) or 4-5 weeks of postnatal age (PNA), whichever was earlier. The infants were divided into subgroups according to the gestational age (GA), and the time of the first examination, time of onset of ROP, and time of laser surgery were assessed with regard to the PMA and PNA. RESULTS: Of the 459 infants, 139 infants developed ROP, with the mean PMA at onset of ROP being 34+2+/-2+3 weeks. Type I ROP developed in 57 infants, with the median PMA at laser surgery being 36+0 weeks. The median PMAs at the time of onset and the time of surgery did not significantly differ between groups divided according to GA. Infants with a GA of or =26 weeks. None of the infants with a GA of <26 weeks were diagnosed with ROP at the first examination, and none of the patients in either group missed treatment. Six infants developed ROP before 31 weeks of PMA, at which time the first screening for ROP is generally performed. CONCLUSION: We suggest that the timing of the initial examination for ROP should be based on PMA or PNA, whichever is earlier, particularly in infants with GA of <26 weeks.

Posterior Chamber Intraocular Lens Implantation Combined with Pars Plana Lensectomy and Intraocular Foreign Body Removal

Four patients with intraocular foreign bodies and traumatic cataracts underwent combined pars plana lensectomy, vitrectomy, and intraocular foreign body removal. During pars plana lensectomy, anterior lens capsule and zonules were left intact. At the end of surgery, a posterior chamber intraocular lens was placed in the sulcus in front of the anterior capsule through a 7-mm limbal incision. This procedure was performed in selected cases of combined anterior and posterior segment trauma. Combining pars plana lensectomy and posterior chamber intraocular lens implantation with posteior segment procedures allows rapid visual rehabilitation and functional unaided vision. We therefore suggest that this technique is effective in treating selected patients with both cataract and vitreoretinal diseases.

Causes of Failure after Initial Vitreoretinal Surgery

We reviewed the records of 23 patients who underwent repeat operation after initial vitreoretinal surgery in Chungnam National University Hospital between January 1993 and December 1993. Of 193 eyes who underwent vitreoretinal surgery in that period, 23(12%) had undergone reoperation. The most common cause of initial anatomic failure and reoperation was either new or recurrent proliferative vitreoretinopathy(10 eyes). Other causes included iatrogenic retinal tears(5 eyes), hidden retinal breaks(4 eyes), vitreous traction(1 eye), inappropriate chorioretinal adhesion(1 eye), and new break(1 eye). We performed vitreous base dissection on all 9 eyes with anterior proliferative vitreoretinopathy. With additional surgery and after a mean follow-up period of 10.4 months, 21(91%) of 23 retinas were reattached. The final cause of anatomic failure was anterior proliferative vitreoretinopathy. Of the 23 reoperated eyes, 20(87%) had postoperative visual acuity of 0.05 or better.

A Case of Cilioretinal Artery Occlusion Associated with Central Retinal Vein Occlusion

A cilioretinal artery occlusion associated with a central retinal vein occlusion is a rare condition and has been reported to have a good visual prognosis. We report a young patient with this condition who also demonstrated prolonged filling of the branch retinal arteries with fluorescein angiography. Her initial visual acuity was 0.03 in the affected eye. Two months later, normal central retinal artery inflow resumed. Her visual acuity has improved to 0.5 over the three years' follow-up.

A Study on Hepatitis B Surface Antigen in Tear of Hepatitis Patients

We performed the radioimmunoassay to detect the hepatitis B surface antigen(HBsAg) in the tear. Among 70 patients who have positive reactions for HBsAg in blood, 53 patients(75.71%) were positive for HBsAg in tear. Among the various groups of hepatitis, the most positive reaction for HBsAg in tear was higher in serum HBeAg positive group(92.68%) than in serum HBeAg negative group(51.72%). So we emphasize the possibility of transmission of hepatitis B virus infection via tear.

A Study on Hepatitis B Surface Antigen in Tear of Hepatitis Patients

We performed the radioimmunoassay to detect the hepatitis B surface antigen (HBsAg) in the tear. Among 70 patients who have positive reactions for HBsAg in blood, 53 patients (75.71 %) were positive for HBsAg in tear. Among the various groups of hepatitis, the most positive reaction for HBsAg in tear was higher in serum HBeAg positive group (92.68%) than in serum HBeAg negative group (51.72%). So we emphasize the possibility of transmission of hepatitis B virus infection via tear.