The Youngest Survivor with Gestational Age of 21(5/7) Weeks

The decision whether or not to resuscitate extremely low gestational age (GA) infants is recommended to be individualized according to antenatal counseling with parents, neonatologists, and obstetricians. A GA of 22(0/7)–23(6/7) weeks is generally considered as the lower end of the range where infants can be candidates for selective resuscitation. Below this lower end of periviable gestation, resuscitation is usually not considered and survivors are rarely reported. To date, the youngest survivor is an infant with a GA of 21(6/7) weeks reported in the English medical literature. Here, we report the case of a female infant, the first twin conceived through in vitro fertilization, with a GA of 21(5/7) weeks, who was resuscitated initially according to strong parental wishes after antenatal counseling and is still surviving at 43 months of age with fairly good neurodevelopmental outcome.

A Novel De Novo Pathogenic Variant in FOXF1 in a Newborn with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is an autosomal dominant, fatal developmental disorder of the lungs, with a mortality rate of about 100%. ACD/MPV is caused by mutations in FOXF1. Herein, we describe a newborn boy with ACD/MPV carrying a novel pathogenic variant of FOXF1. The patient developed respiratory distress and severe pulmonary hypertension on the first day of life. Despite aggressive cardiorespiratory management, including veno-venous extracorporeal membrane oxygenation, his condition deteriorated rapidly, and he died within the first month of his life. Lung histology showed the characteristic features of ACD/MPV at autopsy. Sequence analysis of FOXF1 from genomic DNA obtained from autopsied lung tissue revealed that the patient was heterozygous for a novel missense variant (c.305T>C; p.Leu102Pro). Further analysis of both parents confirmed the de novo occurrence of the variant. To the best of our knowledge, this is the first report of genetically confirmed ACD/MPV in Korea.

Delayed Cord Clamping Compared with Cord Milking in Preterm Neonates

PURPOSE: To evaluate the safety and feasibility of delayed cord clamping compared with umbilical cord milking in premature infants less than 32 weeks of gestation. METHODS: This study was performed by 1:2 case-control match. Infants received delayed cord clamping (DCC) for one minute (DCC group, n=10, May 2014-October 2015) were compared with perinatal factors-matching controls, who received umbilical cord milking (CM, CM group, n=20, May 2014-October 2015) or who received immediate cord clamping (ICC, ICC group, n=20, January 2008-December 2008). The primary outcome was hematocrit during the first 28 days. Secondary outcomes included delivery room management, selected neonatal morbidities and mortality. RESULTS: Baseline characteristics were comparable in all the three groups. The median hematocrit level at 1st day and 3rd day was significantly higher in the DCC group (54.3±6.2%, 53.6±5.6%) as compared with the CM group (48.0±7.7%, 43.2±7.8%) or ICC group (47.2±7.5%, 45.8±6.3%). The DCC group had reductions in red blood cell transfusion within the first two weeks of life compared to the CM group (10% vs. 50%, P=0.03). The DCC group compared to the CM group had no increment in respiratory intervention in the delivery room and hypothermia on admission. There was no difference between DCC and CM in mortality, intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, severe retinopathy of prematurity and sepsis. CONCLUSION: Delayed cord clamping for 1 minute in preterm infants may be a safe and feasible method to increase initial hematocrit and reduce transfusion compared with umbilical cord milking.

Clinical Characteristics of Early Onset Sepsis in Micropreemie Born at 25 or Less than 25 Weeks of Gestational Age / 대한주산의학회잡지

PURPOSE: The aim of this study is to determine the clinical characteristics of early onset sepsis (EOS) in micropreemie. METHODS: We retrospectively reviewed medical records of 107 extremely preterm infants born at 25 or less than 25 weeks of gestation and admitted to the neonatal intensive care unit of Samsung Medical Center from January 2013 to August 2015. Infants were divided into two groups based on the presence of culture-proven EOS in the first 7 days of life. Retrospective analysis of perinatal factors and laboratory findings within the first week of life was done between two groups. We compared the neonatal outcomes among two groups. RESULTS: Culture-proven EOS was diagnosed in 11 of 107 infants (10.3%). Main pathogen of EOS was Staphylococcus epidermidis (45.5%). There were no significant differences between control group and EOS group in gestational age, birth weight, Apgar score, delivery type and pathologic chorioamnionitis. Among 11 infants with EOS, 9 showed fetal tachycardia (P=0.001). And EOS group presented lower platelet count at 3rd day and 7th day of life than that of control group (P=0.033, P=0.045). Neonatal outcomes in EOS group were compatible with control group. Main cause of death was sepsis in EOS group. CONCLUSION: In micropreemie, EOS is important factor of mortality. Our data suggest that fetal tachycardia and low platelet count during the first 7 days of life were associated with EOS.

Clinical Characteristics of Early Onset Sepsis in Micropreemie Born at 25 or Less than 25 Weeks of Gestational Age / 대한주산의학회잡지

PURPOSE: The aim of this study is to determine the clinical characteristics of early onset sepsis (EOS) in micropreemie. METHODS: We retrospectively reviewed medical records of 107 extremely preterm infants born at 25 or less than 25 weeks of gestation and admitted to the neonatal intensive care unit of Samsung Medical Center from January 2013 to August 2015. Infants were divided into two groups based on the presence of culture-proven EOS in the first 7 days of life. Retrospective analysis of perinatal factors and laboratory findings within the first week of life was done between two groups. We compared the neonatal outcomes among two groups. RESULTS: Culture-proven EOS was diagnosed in 11 of 107 infants (10.3%). Main pathogen of EOS was Staphylococcus epidermidis (45.5%). There were no significant differences between control group and EOS group in gestational age, birth weight, Apgar score, delivery type and pathologic chorioamnionitis. Among 11 infants with EOS, 9 showed fetal tachycardia (P=0.001). And EOS group presented lower platelet count at 3rd day and 7th day of life than that of control group (P=0.033, P=0.045). Neonatal outcomes in EOS group were compatible with control group. Main cause of death was sepsis in EOS group. CONCLUSION: In micropreemie, EOS is important factor of mortality. Our data suggest that fetal tachycardia and low platelet count during the first 7 days of life were associated with EOS.

Trends in Survival and Incidence of Bronchopulmonary Dysplasia in Extremely Preterm Infants at 23-26 Weeks Gestation

The aim of this study was to investigate the relationship between survival and incidence of bronchopulmonary dysplasia (BPD) in extremely premature infants, and identify clinical factors responsible for this association. Medical records of 350 infants at 23-26 weeks gestation from 2000 to 2005 (period I, n = 137) and 2006 to 2010 (period II, n = 213) were retrospectively reviewed. The infants were stratified into 23-24 and 25-26 weeks gestation, and the survival, BPD incidence, and clinical characteristics were analyzed. BPD was defined as oxygen dependency at 36 weeks postmenstrual age. The overall survival rate was significantly improved in period II compared to period I (80.3% vs. 70.0%, respectively; P = 0.028), especially in infants at 23-24 weeks gestation (73.9% vs. 47.4%, respectively; P = 0.001). The BPD incidence in survivors during period II (55.0%) was significantly decreased compared to period I (67.7%; P = 0.042), especially at 25-26 weeks gestation (41.7% vs. 62.3%, respectively; P = 0.008). Significantly improved survival at 23-24 weeks gestation was associated with a higher antenatal steroid use and an improved 5-minute Apgar score. A significant decrease in BPD incidence at 25-26 weeks gestation was associated with early extubation, prolonged use of less invasive continuous positive airway pressure, and reduced supplemental oxygen. Improved perinatal and neonatal care can simultaneously lead to improved survival and decreased BPD incidence in extremely premature infants.

Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Associated with Acetaminophen Use during Viral Infections

An association between drug treatment for viral infections and severe cutaneous adverse reactions has been noted. We investigated six patients diagnosed with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after being prescribed acetaminophen for suspected viral illnesses. Multiplex analysis was performed to measure cytokine levels in sera before and after treatment. IL-2Rα levels significantly decreased during the convalescence phase. Although acetaminophen is relatively safe, the drug can trigger SJS/TEN in patients with suspected viral infections. T-cells and monocytes may be key components of the link between viral infection and acetaminophen-induced SJS/TEN.

Comparison of Clinical Manifestation and Prognosis of Preterm and Full-Term Infants with Down Syndrome

PURPOSE: To investigate and compare the clinical manifestation and prognosis of preterm and full-term infants with Down syndrome (DS). METHODS: We retrospectively reviewed 80 patients diagnosed with DS and confirmed by chromosomal study at the Samsung Medical Center between January 1994 and July 2014. Data on demographic characteristics, associated anomalies, treatment, prognosis and cause of death were compared between preterm and full-term DS infants. RESULTS: Of the 80 confirmed DS patients, there were 49 (61%) full-term and 31 (38%) preterm DS infants. The mean gestational age of full-term DS infants was 38(+1)+/-0(+2) weeks (range, 37(+0)-40(+0) weeks) and the mean birth weight was 3,007+/-418 g (range, 1,930-4,100 g). The mean gestational age of preterm infants was 34(+1)+/-2(+1) weeks (range, 29(+1)-36(+6) weeks) and the mean birth weight was 2,181+/-598 g (range, 890-3,500 g). There were no differences in demographics, associated anomalies, mortality or related factors, or the rate of active treatment between full-term and preterm DS infants. CONCLUSION: In this single center study, the mortality rate of preterm DS infants was comparable to that of full-term DS infants. Larger national cohort studies might be needed to further investigate the prognosis of preterm DS infants.

Immunologic Evaluation of Patients with Cefotetan-Induced Anaphylaxis

Cefotetan is a commonly prescribed second-generation cephalosporin that acts against a wide range of bacteria. However, cefotetan-induced hypersensitivity has rarely been reported. We report 2 cases of cefotetan-induced anaphylaxis with immunologic evaluation. The first case was a 70-year-old asthmatic woman who had dyspnea and hypotension during administration of cefotetan, in which high serum-specific IgE to cefotetan-human serum albumin (HSA) conjugate was detected by enzyme-linked immunosorbent assay. The second case was a 63-year-old asthmatic woman who complained of chest tightness and dyspnea during cefotetan infusion, in which high serum-specific IgG1 and IgG4 with no serum specific IgE to cefotetan-HSA conjugate was detected. The basophil activation test using basophils from the patient showed a significant up-regulation of CD63 with the addition of anti-IgG4 antibody compared with that in non-atopic healthy controls. In conclusion, cefotetan can induce anaphylaxis, which may involve both IgE- and IgG4-mediated responses in the pathogenic mechanism.

KAAACI Work Group report on the management of chronic urticaria

Chronic urticaria (CU) is defined by the presence of urticaria that has been continuously or intermittently for a period of 6 weeks or longer. The prevalence of CU in the general population has been estimated to range from 0.5% to 5%. Correct diagnosis and proper management for CU is essential to improve the quality of care. To date, several practical guidelines have been available for practitioners. In this article, we reviewed and summarized the epidemiology, pathogenesis, diagnosis, and management based on case reports and studies of CU from Korea and the other part of world, and recently published guidelines. Although there are many controversies, this report for CU would provide a clinical guidance for healthcare professionals in Korea.

Prevention of Cytomegalovirus Transmission via Breast Milk in Extremely Low Birth Weight Infants

PURPOSE: Extremely low birth weight infants (ELBWIs) have a high risk of acquiring cytomegalovirus (CMV) infection via breast milk and consequently developing serious symptoms. We evaluated whether freeze-thawing or pasteurization could prevent postnatal CMV infection transmitted through breast milk in ELBWIs. MATERIALS AND METHODS: Medical records of 385 ELBWIs with whole milk feeding, and freeze-thawed or pasteurized breast milk feeding were reviewed retrospectively. Postnatally acquired CMV infection was defined as an initial negative and a subsequent positive on follow-up urine CMV DNA polymerase chain reaction screening tests. The incidence, clinical characteristics, symptoms, sequelae, and long-term outcome at corrected age [(CA): 2 years of CMV infection] were analyzed. RESULTS: While no infant developed CMV infection with whole milk (0/22) or pasteurized breast milk (0/62) feeding, postnatal CMV infection was diagnosed in 8% (27/301) of ELBWIs who were fed freeze-thawed breast milk. Gestational age in the CMV group was significantly lower than the control group. In 82% (22/27) of cases, CMV infection was symptomatic and was associated with increased ventilator days and > or =moderate bronchopulmonary dysplasia (BPD). Neurodevelopmental outcome and growth status at CA 2 years were not different between the study groups. Lower gestational age and freeze-thawed breast milk feeding >60% of total oral intake during the first 8 postnatal weeks were independent risk factors for acquiring postnatal CMV infection. BPD (> or =moderate) was the only significant adverse outcome associated with this CMV infection. CONCLUSION: Pasteurization but not freeze-thawing of breast milk eradicated the postnatal acquisition of CMV infection through breast milk.

Effect of Prophylactic Palivizumab on Admission Due to Respiratory Syncytial Virus Infection in Former Very Low Birth Weight Infants with Bronchopulmonary Dysplasia

The aim of this study was to observe the effects of prophylactic palivizumab on hospitalization secondary to respiratory syncytial virus (RSV) infection (RSVhospitalization) in former very low birth weight infants (VLBWI) with bronchopulmonary dysplasia (BPD). This study also sought to identify the risk factors of RSVhospitalizationin this particular infant population. A prospective observational study was conducted between September 2007 and April 2008 in seven Korean hospitals. Children with a history of very low birth weight, a diagnosis of BPD and who were <2 yr old at the onset of the RSV season were included in this study. Palivizumab injections were administered monthly for a maximum of five months during the RSV season. RSVhospitalization rates were reviewed, and RSVhospitalization rates between subgroups were categorized by gestational age, birth weight, and duration of ventilator care. A total of 90 subjects completed the follow-up interviews. The mean gestational age at birth was 26.1+/-1.7 weeks, and the mean birth weight was 889.4+/-222.2 g. The incidence of RSVhospitalization in the study population was 8.9% (8/90), and the mean hospital stay was 11.0+/-5.5 days, including one death. There were no statistically significant differences in the patients' demographic characteristics or risk factors for RSV hospitalization. When subgroup analyses were conducted, there were still no statistically significant differences. The administration of palivizumab prophylaxis during the entire RSV season is important in VLBWI with BPD, regardless of their gestational age and birth weight, or previous ventilator dependency.

The Prevalence of Serum Specific IgE to Superantigens in Asthma and Allergic Rhinitis Patients

Staphylococcus aureus is the most common bacterium present in upper respiratory tract, and the toxins it produced are involved in allergic inflammation pathogenesis. In this study, we investigated the clinical significance of IgE in association with staphylococcal superantigens in allergic asthma with rhinitis (BAwAR) and allergic rhinitis alone (AR). We recruited 100 patients with BAwAR (group I), 100 patients with AR (group II), and 88 healthy controls (group III). Patients were clinically diagnosed by physicians, and were sensitized to house dust mites. Specific IgE antibodies to staphylococcal superantigen A (SEA), B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured using the ImmunoCAP system. Other clinical parameters were retrospectively analyzed. All specific IgE antibodies to SEA, SEB, and TSST-1 were detected most frequently in group I (22%, 21%, and 27%), followed by group II (11%, 14%, and 21%) and group III (4.5%, 3.4%, and 2.3%). Absolute values of serum specific IgE to SEA, SEB, and TSST-1 were also significantly higher in group I (0.300+/-1.533 kU/L, 0.663+/-2.933 kU/L, and 0.581+/-1.931 kU/L) and group II (0.502+/-2.011 kU/L, 0.695+/-3.337 kU/L, and 1.067+/-4.688 kU/L) compared to those in group III (0.03+/-0.133 kU/L, 0.03+/-0.14 kU/L, and 0.028+/-0.112 kU/L). The prevalence of serum specific IgE to SEA was significantly higher in group I compared to group II (P=0.025). Blood eosinophil counts were significantly higher in patients with specific IgE to SEA or SEB, and higher serum levels of specific IgE to house dust mites were noted in patients with specific IgE to TSST-1. In conclusion, the present study suggested that IgE responses to staphylococcal superantigens are prevalent in the sera of both BAwAR and AR patients. This may contribute to an augmented IgE response to indoor allergens and eosinophilic inflammation.

Neonatal Presentation and Follow-up of Goldenhar Syndrome / 대한주산의학회잡지

PURPOSE: Expression patterns, associated anomalies and progress of the patients with Goldenhar syndrome from the neonatal period were systematically investigated. This allows us to evaluate the need for early diagnosis. METHODS: This is a retrospective study of 29 infants with Goldenhar syndrome whose diagnosed in Samsung Medical Center between 1994 and 2013. Associated anomalies and procedures between neonatal group (n=13) and non-neonatal group (n=16) were systematically compared. RESULTS: Mean gestational age in the neonatal group were 38+1+/-2+4 weeks and 3 patients (23%) were preterm infants. The average birth weight in the neonatal group were 2,853+/-544 grams. Goldenhar syndrome was mainly diagnosed by ear and face anomalies during the neonatal period. The associated anomalies in neonatal group were cardiovascular anomaly (54%), genitourinary anomaly (30%), vertebral anomaly (15%), and others (31%). About 40% of patients who had long-term follow-up revealed hearing abnormalities and about 1/4 of all patients had bilateral hearing problem, which resulted in requiring hearing aid devices. In addition, the most common procedure performed during follow-up was preauricular skin tag removal. And other procedures or surgery related to oral, eyes, and others were performed in each 1/4 of the patients. Cardiac surgery was done in 15% of total patients. Frequency of associated anomalies and performed procedures between the patients diagnosed at neonatal and non-neonatal period was not significantly different. CONCLUSION: A multidisciplinary approach should be undertaken by multi-departments when evaluating patients with Goldenhar syndrome. In particular if the patient has an ear anomaly, careful hearing test is required in early life.

Clinical features of elderly chronic urticaria

BACKGROUND/AIMS: Chronic urticaria (CU) is defined as itchy wheals lasting 6 weeks or more. As the aged population increases worldwide, it is essential to identify the specific features of this disease in the elderly population. METHODS: We investigated the prevalence and clinical features of CU in elderly patients. Medical records of 837 CU patients from the outpatient Allergy Clinic of Ajou University Hospital, Korea were analyzed retrospectively. Patients with chronic spontaneous urticaria according to the EAACI/GA2LEN/EDF/WAO guidelines were included. Patients older than 60 years were defined as elderly. RESULTS: Of the 837 patients, 37 (4.5%) were elderly. In elderly versus nonelderly CU patients, the prevalence of atopic dermatitis (AD) was significantly higher (37.8% vs. 21.7%, respectively; p = 0.022), while that of aspirin intolerance was lower (18.9% vs. 43.6%, respectively; p = 0.003) in terms of comorbid conditions. The prevalences of serum specific immunoglobulin E antibodies to staphylococcal enterotoxin A and staphylococcal enterotoxin B were considerably higher in elderly CU patients with AD than in those without AD (37.5% vs. 0%, respectively). CONCLUSIONS: Elderly patients with CU had a higher prevalence of AD. Therefore, there is a need to recognize the existence of AD in elderly CU patients.

Clinical Outcome of Infants Who Underwent Tracheostomy in Neonatal Intensive Care Unit: 16 years' Experience in a Single Center

PURPOSE: This study was designed to review the clinical outcome of infants who underwent tracheostomy in the neonatal intensive care unit (NICU) of a single center in Korea during 16 years. METHODS: We retrospectively reviewed medical records of 33 patients who underwent tracheostomy in NICU of Samsung Medical Center between January, 1997 and December, 2013. We collected data on timing, indications, clinical outcomes, and complications of tracheostomy in the study patients. We also compared these variables with those in another single center study (study A) recently showing the outcome of infants who underwent tracheostomy in a NICU of USA during 10 years. RESULTS: The median gestational age and birth weight of the study patients were 35 weeks, and 3,200 g, respectively. Gestational age of the study patients was greater than that of study A (35 weeks vs. 27 weeks). The most common indication for tracheostomy was airway disease (69.7%) in our study. Bronchopulmonary dysplasia (9%) was less frequent indication for tracheostomy in our study when compared with in the study A (41%). Granuloma formation was the most common complication of tracheostomy (48%) and decannulation was accomplished in nine patients (27.3%). Although the mortality rate was 12.1%, no patient died from tracheostomy-related complications. CONCLUSION: Main causes of tracheostomy in our NICU are airway problems and neuromuscular diseases rather than bronchopulmonary dysplasia itself. For better clarification of clinical courses and outcomes related to tracheostomy performed in NICU in Korea, further study in a larger population will be needed.

Survival of Patients with Trisomy 18 Based on the Treatment Policy at a Single Center in Korea

PURPOSE: Although discussion about active treatment of trisomy 18 is increasing, there are no previous articles regarding this subject in Korea. In order to provide objective data about the clinical characteristics and survival of patients with trisomy 18, based on the treatment policy, to medical teams and parents with trisomy 18, we reviewed the medical records of such patients at a single center in Korea. METHODS: This is a retrospective study of 22 patients diagnosed with trisomy 18 at the Samsung Medical Center between 1995 and 2013. We collected data about the clinical characteristics, including demographics, birth history, diagnosis method, and associated anomalies. We analyzed the survival in days, according to three broad categories of treatment policy: give-up, conservative management and active treatment. RESULTS: Of the 22 patients with confirmed trisomy 18, the majority were female (19, 86%). The median gestational age was 39 weeks (range, 31-41 weeks) and the median birth weight is 2,029 g (range, 1,130-2,990 g). Among the anomalies associated with trisomy 18, ventricular septal defect (86%) and patent ductus arteriosus (81%) were the most common cardiac anomalies; giant cisterna magna (59%) was the most common central nervous system anomaly; and clenched hands (73%) and low set ears (59%) were the most common structural anomalies. The survival based on the treatment policy was the highest in the active treatment group, followed by the conservative management group. The give-up group had the lowest survival. CONCLUSION: It is possible to achieve an improvement in both survival and symptom relief for patients with trisomy 18, despite poor neurological outcome and high mortality. Medical personnel need to provide objective data on trisomy 18 to the parents, and determine the treatment policy through careful discussion.

Retinopathy of Prematurity in Infants with Birth Weights Greater than 1,000 Grams

PURPOSE: To understand the incidence of retinopathy of prematurity (ROP) in preterm infants with birth weights more than 1,500 g or gestational age 30 weeks, and/or unstable clinical course, we investigated the highest gestational age and birth weight of preterm infants who require ROP treatment and those who do not. METHODS: The subjects were preterm infants admitted in Samsung medical center between January 1, 2000 and December 31, 2013. We retrospectively reviewed the medical records of 847 premature infants whose birth weights were more than 1,000 g. RESULTS: Of the 847 infants, 105 (12.4%) had stage 1 ROP, 54 (6.4%) had stage 2, 31 (3.7%) had stage 3, 0 had stage 4, and 2 (0.2%) had stage 5 ROP. Thirty-three (3.9%) of the 847 infants developed stage 3-5 ROP. Twenty (2.4%) of these 33 (3.9%) stage 3-5 ROP infants required treatment. Among the stage 1-3 ROP infants who did not require treatment, the highest gestational age was 37(+1) weeks (stage 1) and birth weight was 2,362 g (stage 1). Among the stage 3-5 ROP infants who needed treatment, the highest gestational age was 32 weeks and birth weight was 1,495 g. CONCLUSIONS: Newborn infants with gestational age more than 38 weeks or birth weight more than 2,400 g did not develop ROP even if they had an unstable clinical course. In our study, no preterm infants with gestational age more than 33 weeks or birth weight more than 1,500 g required ROP treatment.

Letter to the Editor: Two Major Phenotypes of Sulfite Hypersensitivity: Asthma and Urticaria

No abstract available.

The Timing of Surgical Ligation for Patent Ductus Arteriosus Is Associated with Neonatal Morbidity in Extremely Preterm Infants Born at 23-25 Weeks of Gestation

The purpose of this study was to evaluate prognostic factors associated with surgical ligation for patent ductus arteriosus (PDA) in extremely preterm infants born at the limits of viability. Ninety infants who were born at 23-25 weeks of gestation and who received surgical ligation were included and their cases were retrospectively reviewed. Infants were classified into two different groups: survivors with no major morbidity (N), and non-survivors or survivors with any major morbidity (M). Clinical characteristics were compared between the groups. Possible prognostic factors were derived from this comparison and further tested by logistic regression analysis. The mean gestational age and the mean birth weight of M were significantly lower than those of N. Notably, the mean postnatal age at time of ligation in N was significantly later than that of the other group (17+/-12 vs 11+/-8 days in N and M, respectively). An adjusted analysis showed that delayed ligation (>2 weeks) was uniquely associated with a significantly decreased risk for mortality or composite morbidity after surgical ligation (OR, 0.105; 95% CI, 0.012-0.928). In conclusion, delayed surgical ligation for PDA (>2 weeks) is associated with decreased mortality or morbidities in extremely preterm infants born at 23-25 weeks of gestation.