Anemia of prematurity (AOP) is a multifactorial condition associated with congenital iron deficiency, low erythropoietin levels, a short lifespan of red blood cells, and iatrogenic blood loss. AOP is a common complication in premature infants that can adversely affect growth, development, and long-term neurocognitive outcomes. To standardize the diagnosis and treatment of AOP, the Neonatal Clinical Practice Guidelines Expert Committee and the Neonatal Evidence-Based Medicine Group of the Commission of Neonatal Medicine of the Cross-Strait Medical and Health Exchange Association, along with the Editorial Office of the Chinese Journal of Contemporary Pediatrics, have developed the "Clinical practice guidelines for the diagnosis and treatment of anemia of prematurity (2025)", based on the World Health Organization's handbook for guideline development and the formulation/revision principles of Chinese clinical practice guidelines. This guideline addresses eight clinical issues related to AOP, including risk factors, early identification, etiological diagnosis, diagnostic criteria, early prevention, transfusion therapy, strategies to improve prognosis, and post-discharge follow-up. It presents 29 recommendations formed from current evidence and expert consensus, aiming to provide guidance and decision-making support for healthcare professionals in the diagnosis and treatment of AOP.
Humans ; Infant, Newborn ; Infant, Premature ; Anemia, Neonatal/diagnosis* ; Anemia/diagnosis* ; Practice Guidelines as Topic

BACKGROUND: The purpose of this study was to determine prognostic factors that can affect the fetal survival immediate after fetoscopic laser ablation. METHODS: The study population consisted of consecutive twin pregnant women who underwent fetoscopic laser ablation with the diagnosis of twin to twin transfusion syndrome (TTTS) from 2011 to 2018 in Seoul National University Hospital. Fetal survival immediate after procedure was defined as survival to 48 hours after procedure and neonatal survival was defined as survival to 28 days of life. Clinical characteristics and ultrasound findings were compared according to the fetal survival immediate after procedure. RESULTS: A total of 57 pregnant women with TTTS were included, and the overall fetal survival immediate after procedure was 71.1% (81/114) after fetoscopic laser ablation. Fetuses who survived immediate after procedure had higher gestational age at procedure and lower frequency of abnormal Doppler studies than those did not survive. However, the frequency of hydrops was not different between cases with fetal survival and those with fetal death. The earlier gestational age at procedure and the presence of abnormal Doppler studies were significant risk factors for fetal death even after adjustment. CONCLUSION: Based on this data, the fetal survival immediate after procedure (fetoscopic laser treatment) in TTTS can be affected by the gestational age at procedure and the presence of abnormal Doppler studies.
Diagnosis ; Edema ; Female ; Fetal Death ; Fetofetal Transfusion* ; Fetus ; Gestational Age ; Humans ; Laser Therapy* ; Pregnancy ; Pregnant Women ; Risk Factors ; Seoul ; Twins* ; Ultrasonography

OBJECTIVE: To evaluate the initial maternal and perinatal outcomes of fetoscopic laser photocoagulation for the treatment of twin-to-twin transfusion syndrome (TTTS) in a referral center in Brazil. METHODS: This prospective observational study analyzed 24 fetoscopic laser photocoagulation procedures at 18–26 weeks of gestation. TTTS severity was determined using the Quintero classification. Blood vessels that crossed the interamniotic membrane were nonselectively photocoagulated. The χ2 test and Mann-Whitney U test were used for the statistical analysis. RESULTS: The mean (±standard deviation) age of pregnant women, gestational age at surgery, surgical time, gestational age at birth, and newborn weight were 32.2±4.1 years, 20.7±2.9 weeks, 51.8±16.7 minutes, 30.5±4.1 weeks, and 1,531.0±773.1 g, respectively. Using the Quintero classification, there was a higher percentage of cases in stage III (54.2%), followed by stages IV (20.8%), II (16.7%), and I (8.3%). Ten (41.7%) donor fetuses died and 14 (58.3%) donor fetuses survived until the end of gestation. Placental insertion location (anterior vs. posterior) did not affect the incidence of iatrogenic septostomy, surface bleeding, and premature rupture of membranes until the end of gestation. The death rate of donor and recipient fetuses before 24th gestational week increased with severity of TTTS. CONCLUSION: The maternal and perinatal outcomes resulting from the implementation of a new minimally invasive surgical technique are in line with those obtained in major centers worldwide, considering the learning curves and infrastructures.
Blood Vessels ; Brazil* ; Classification ; Female ; Fetofetal Transfusion* ; Fetoscopy ; Fetus ; Gestational Age ; Hemorrhage ; Humans ; Incidence ; Infant, Newborn ; Learning Curve ; Light Coagulation* ; Membranes ; Mortality ; Observational Study ; Operative Time ; Parturition ; Perinatal Mortality ; Pregnancy ; Pregnant Women ; Prospective Studies ; Referral and Consultation ; Rupture ; Tissue Donors

BACKGROUND: The direct/total (d/t) bilirubin ratio can be used to distinguish the causes of jaundice in many patients who have increased levels of direct and indirect bilirubin. However, the reference range of the d/t ratio has not been established, hindering its clinical usefulness. This study assessed the clinical usefulness of the d/t ratio. METHODS: Paired total bilirubin and direct bilirubin tests (N=4,357) of cholestasis, hemolytic anemia, and neonatal jaundice were evaluated. Regression analyses were performed between total bilirubin and direct bilirubin, and between total bilirubin and the d/t ratio for each disease. Theoretical correlation models were established and used to compare the regression analyses data. RESULTS: The theoretical model and regression equation between total bilirubin and direct bilirubin displayed linear correlations for all three cholestatic diseases. The model and regression equation between total bilirubin and the d/t ratio showed reciprocal curve correlations for the cholestatic diseases. When the total bilirubin concentration exceeded approximately 10 mg/dL, the rate of change of the d/t ratio decreased and converged to a constant value between 0.7 and 0.9. CONCLUSIONS: If the total bilirubin concentration exceeds 10 mg/dL, cholestatic diseases can be diagnosed if the d/t ratio is more than 0.7. However, if the total bilirubin concentration is lower than 10 mg/dL, cholestatic diseases should be considered even if the d/t ratio is lower than 0.7. Therefore, use of the d/t ratio with total bilirubin could prove to be valuable in clinical settings.
Anemia, Hemolytic ; Bilirubin* ; Cholestasis ; Humans ; Hyperbilirubinemia ; Infant, Newborn ; Jaundice ; Jaundice, Neonatal ; Models, Theoretical ; Reference Values

OBJECTIVE: To investigate the safety of umbilical cord milking on both the mother and neonate among very preterm deliveries of less than 33 weeks of gestation. METHODS: Pregnant women who were expected to deliver at between 24 0/7 and 32 6/7 weeks of gestation were randomized to either the umbilical cord milking or immediate cord clamping group. Maternal and neonatal data associated with delivery, in addition to neonatal morbidity and mortality data, were collected and analyzed. RESULTS: Of the 66 preterm deliveries included in the study, 34 were randomized into the milking and 32 into the clamping group. Differences between maternal pre- and post-partum hemoglobin levels were 1.35 g/dL in the milking and 1.58 g/dL in the clamping group (P=0.451). Neonatal Apgar scores at both 1 and 5 minutes, initial blood gas analysis results, body temperature at admission, need for early intubation, and maximum bilirubin levels were all similar between the 2 groups. However, neonatal hemoglobin levels at birth (15.79 vs. 14.69 g/dL; P<0.05) and at 24 hours of age (14.83 vs. 13.29 g/dL; P<0.05) were significantly higher in the milking group. Neonates in the clamping group required more blood transfusion (1.78 vs. 0.93; P=0.049), and a higher percentage of neonates in the clamping group required inotropic drugs (63% vs. 29%; P=0.007). The mortality rate was significantly lower in the milking group (6% vs. 28%; P=0.015). CONCLUSION: Umbilical cord milking can be a safe and beneficial procedure for both the mother and the neonate in deliveries of less than 33 weeks of gestation.
Anemia, Neonatal ; Bilirubin ; Blood Gas Analysis ; Blood Transfusion ; Body Temperature ; Constriction ; Female ; Fetomaternal Transfusion ; Humans ; Infant, Newborn* ; Infant, Premature ; Intubation ; Milk* ; Mortality ; Mothers ; Parturition ; Pregnancy ; Pregnant Women ; Umbilical Cord*

PURPOSE: Fetoscopic laser surgery (FLS) is considered an optimal therapeutic strategy for twin-to-twin transfusion syndrome (TTTS). We aimed to determine the clinical outcomes of TTTS patients since the introduction of FLS. METHODS: A retrospective study of TTTS patients born between January 2005 and December 2015 was conducted. Mortality and morbidity were compared in the FLS and non-FLS groups. The FLS group was divided into selective FLS and Solomon technique group, and subgroup analysis was performed. RESULTS: Of 70 pregnancies diagnosed with TTTS during the study period, FLS was performed for 35 (50%). Survival of at least one infant at discharge was achieved in 100% (35/35) of pregnancies in the FLS group and 91.4% (32/35) in the non-FLS group (P=0.028). Subgroup analysis revealed that the Solomon technique group had a higher dual survival rate than the selective FLS group (81.3% vs. 57.9%, P=0.036). Neonatal mortality was significantly lower in the FLS group than in the non-FLS group (1.7% vs. 16.4%, P=0.005). Severe intraventricular hemorrhage more than grade 3 was less frequent in the FLS group than in the non-FLS group (0% vs. 18.2%, P= 0.001). The FLS group showed smaller inter-twin differences in birth weight (24.4% vs. 33.7%, P= 0.032) and lower incidence of twin anemia-polycythemia sequence (0% vs. 43.8%, P<0.001). CONCLUSION: Since the introduction of FLS, the survival rate of TTTS patients has improved. The Solomon technique resulted in better dual survival rates than selective FLS.
Birth Weight ; Female ; Fetofetal Transfusion* ; Fetoscopy ; Hemorrhage ; Humans ; Incidence ; Infant ; Infant Mortality ; Infant, Newborn ; Laser Therapy* ; Mortality ; Pregnancy ; Retrospective Studies ; Survival Rate ; Twins

A full term male infant was admitted to the neonatal intensive care unit due to jaundice and mild hemolytic anemia within the first 24 hours of his life. The total serum bilirubin level was 11.2 mg/dL at 24 hours of age. The patient was RhD positive and blood group A, and his mother was RhD positive and blood group B. The direct and indirect antiglobulin tests of the infant were all positive. On antibody screening and identification tests, anti-S antibodies were identified from both the infant and mother. The RBC phenotyping for S antigen revealed positive for infant and negative for mother. This report documents the first case of hemolytic disease of the fetus and newborn due to the anti-S antibody in Korea.
Anemia, Hemolytic ; Antibodies ; Bilirubin ; Coombs Test ; Fetus* ; Humans ; Infant ; Infant, Newborn* ; Intensive Care, Neonatal ; Jaundice ; Korea* ; Male ; Mass Screening ; Mothers

Infantile osteopetrosis is a rare congenital disorder caused by abnormal bone resorption. Patients with osteopetrosis can have severe anemia, thrombocytopenia, hepatosplenomegaly, rickets, visual impairment, and deafness. Cytomegalovirus also can cause a congenital infection with anemia, thrombocytopenia, hepatosplenomegaly, and calcifications in the brain. We report a 38-day-old infant with severe hepatosplenomegaly, thrombocytopenia, hypocalcemia, and growth failure. Real time polymerase chain reaction detected cytomegalovirus in the plasma. Skeletal radiography revealed generalized bone sclerosis. He was diagnosed with osteopetrosis along with cytomegalovirus infection. Only the test for mutation of the CLCN7 gene, representing the most common and heterogeneous form of osteopetrosis, was available, and the result was negative. With supportive care and antiviral treatment, severe thrombocytopenia due to the cytomegalovirus infection almost normalized despite the possible immunosuppression caused by osteopetrosis. We present the first report of an infant who suffered from osteopetrosis and CMV infection which was successfully treated by long term antiviral agent therapy.
Anemia ; Bone Resorption ; Brain ; Congenital, Hereditary, and Neonatal Diseases and Abnormalities ; Cytomegalovirus Infections* ; Cytomegalovirus* ; Deafness ; Humans ; Hypocalcemia ; Immunosuppression ; Infant ; Infant, Newborn* ; Osteopetrosis* ; Plasma ; Radiography ; Real-Time Polymerase Chain Reaction ; Rickets ; Sclerosis ; Thrombocytopenia ; Vision Disorders

OBJECTIVE: To demonstrate the safety of fetal delivery through placental incision in a placenta previa pregnancy. METHODS: We examined the medical records of 80 women with singleton pregnancy diagnosed with placenta previa who underwent cesarean section between May 2010 and May 2015 at the Department of Obstetrics and Gynecology, Chungbuk National University Hospital. Among the women with placenta previa, those who did not have the placenta in the uterine incision site gave birth via conventional uterine incision, while those with anterior placenta previa or had placenta attached to the uterine incision site gave birth via uterine incision plus placental incision. We compared the postoperative hemoglobin level and duration of hospital stay for the mother and newborn of the two groups. RESULTS: There was no difference between the placental incision group and non-incision group in terms of preoperative and postoperative hemoglobin change, the amount of blood transfusions required by the mother, newborns with 1-min or 5-min Apgar scores below 7 points or showing signs of acidosis on umbilical cord blood gas analysis result of pH below 7.20. Moreover, neonatal hemoglobin levels did not differ between the two groups. CONCLUSION: Fetal delivery through placental incision during cesarean section for placenta previa pregnancy does not negatively influence the prognosis of the mother or the newborn, and therefore, is considered a safe surgical technique.
Acidosis ; Anemia, Neonatal ; Blood Transfusion ; Cesarean Section ; Chungcheongbuk-do ; Female ; Fetal Blood ; Gynecology ; Humans ; Hydrogen-Ion Concentration ; Infant, Newborn ; Length of Stay ; Medical Records ; Mothers ; Obstetrics ; Parturition ; Placenta Previa* ; Placenta* ; Pregnancy ; Prognosis

Massive fetomaternal hemorrhage (FMH) is a major cause of unexplained fetal death and neonatal anemia. FMH can be diagnosed using the Kleihauer-Betke test or flow cytometry by identifying the presence of fetal red cells in the maternal blood. However, timely diagnosis is a challenge because many hospitals lack the equipment needed to perform such tests. The authors experienced a case of FMH diagnosed via high-performance liquid chromatography (HPLC) which is generally used in measuring glycated hemoglobin (HbA1c) in a patient with unexplained neonatal anemia. A girl aged 2 days was transferred to our hospital for showing pallor and a hemoglobin level of 5.0 g/dL. HPLC revealed 3% fetal hemoglobin (HbF) in the maternal blood. HPLC is a quick test for quantifying HbF that is readily available in many hospitals and could serve as a promising alternative for diagnosing FMH.
Anemia, Neonatal ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Diagnosis ; Female ; Fetal Death ; Fetal Hemoglobin ; Fetomaternal Transfusion ; Flow Cytometry ; Hemoglobin A, Glycosylated ; Humans ; Infant, Newborn ; Pallor ; Pregnancy ; Prothrombin Time