Prevention of human milk-acquired cytomegalovirus infection in very-low-birth-weight infants.

BACKGROUND: The aim of the study was to determine the rate of cytomegalovirus virolactia in the human milk (HM) of mothers of VLBW infants, compare the CMV infection rates and the changes in CMV DNA viral load and nutrient profile among different HM preparation methods. METHODS: A prospective randomized controlled study was performed in infants with gestational age < 32 weeks or birth-weight < 1500 g admitted to neonatal intensive care unit of Asan Medical Center and Haeundae Paik Hospital who were given mother's own milk. Enrolled infants were randomized into three groups according to the HM preparation methods: freezing-thawing (FT), FT + low-temperature Holder pasteurization (FT + LP), and FT + high-temperature short-term pasteurization (FT + HP). Urine CMV culture and PCR were obtained at birth and at 4, 8, and 12 weeks. HM CMV culture and PCR were obtained at birth and at 3, 6, 9, and 12 weeks. Changes in macronutrients in HM was obtained at 4 ~ 6 weeks. RESULTS: Of 564 infants, 217 mothers (38.5%) produced CMV PCR positive milk. After exclusion, a total of 125 infants were randomized into the FT (n = 41), FT + LP (n = 42), and FT + HP (n = 42) groups, whose rate of HM-acquired CMV infection was 4.9% (n = 2), 9.5% (n = 4), and 2.4% (n = 1), respectively. Out of seven CMV infected infants, two infants fed with FT + LP HM developed CMV infection- associated symptoms. Ages at diagnoses were earlier (28.5 days after birth) and at younger post conceptional age (< 32 weeks) in comparison to infants with asymptomatic CMV infection. CMV DNA viral load significantly decreased after pasturizations, especially in FT + HP group. CONCLUSIONS: HM-acquired symptomatic CMV infection rate is low and its impact on clinical course was not serious in our VLBW infants. However, evidences showing poor neurodevelopmental outcome in later life, we need to generate a guideline to protect VLBW infant form HM transmitted CMV infection. Based on our small sized study, we did not find any superiority in pasteurizing HM with frequently used LP in comparison to frozen or HP HM. More research is needed to determine the method and duration of pasteurization to reduce the HM-acquired CMV infection.

Ultrasound findings of subpial hemorrhage in neonates.

PURPOSE: Subpial hemorrhage (SPH) is a subtype of intracranial hemorrhage characterized by damage to the adjacent brain parenchyma. The aim of this study was to describe the sonographic features of SPH in neonates. METHODS: The cranial ultrasound (US) findings of neonates with SPH confirmed by brain magnetic resonance imaging (MRI) were analyzed retrospectively. Initial and follow-up US and MRI scans were reviewed by two pediatric radiologists who were blinded to both clinical history and outcomes. The US features were compared with the MRI findings. RESULTS: Sixteen patients were included (median gestational age, 38 weeks; range, 26 to 40 weeks; 69% term). SPH was detected most often in the temporal lobe (63%), and multiple SPHs were found in seven of 16 neonates, based on MRI. Acute SPH with an underlying venous infarct (UVI) was detected on US in 15 of 16 patients: small or large fan-shaped hyperechoic lesions (n=7 and 4, respectively) and gyriform hyperechoic lesions (n=4). The sonographic yin-yang sign was observed in three of the four large fan-shaped SPH cases. The accompanying findings on US were intraventricular hemorrhage (four out of six MRI-confirmed cases), and concurrent periventricular venous infarcts (five out of nine MRI-confirmed cases). In five patients, subpial cysts were observed on follow-up US or MRI (n=4 and n=4, respectively). CONCLUSION: Acute SPH with UVI can appear as a peripheral fan-shaped or gyriform hyperechoic lesion on cranial US. SPH can be detected and suspected based on the US features of SPH with the accompanying findings.

The forehead is a better site than the sternum to check transcutaneous bilirubin during phototherapy in sick infants.

BACKGROUND: To confirm the accuracy of transcutaneous bilirubin (TcB) in the neonatal intensive care unit both with and without phototherapy, and compare forehead and sternum as the TcB assessment site. METHODS: We simultaneously assessed the total serum bilirubin (TSB) and TcB at the forehead and sternum, using a JM-103 bilirubinometer. We analyzed the correlation between the TSB and TcB assessed at the forehead and sternum, with measurements classified as 'without phototherapy' (before phototherapy and > 24 hours after phototherapy discontinuation) and 'with phototherapy' (after 24 hours of phototherapy). RESULTS: There were 1,084 paired forehead and sternum TcB measurements, with the corresponding TSB measurement, from 384 infants. Their mean gestational age of 35.4 ± 3.2 weeks (62% were preterm) and a mean birth weight of 2434 ± 768 grams, and TSB was 6.61 ± 3.56 mg/dL. Without phototherapy, TcB values at the forehead and sternum were correlated well to the TSB value (r = 0.925 and 0.915, respectively). With phototherapy, TcB values at the forehead and sternum were significantly correlated with the TSB value, but TcB at the forehead (r = 0.751) was a better match to the TSB than was TcB at the sternum (r = 0.668). Additionally, Bland-Altman plots showed a greater degree of underestimation of the TSB by TcB at the sternum with phototherapy. CONCLUSIONS: TcB was more accurate in infants not receiving phototherapy. During phototherapy, it is better to assess TcB at the forehead rather than at the sternum.

Incidence and risk factors of subclinical umbilical catheter-related thrombosis in neonates.

INTRODUCTION: This study aimed to determine the risk factors for subclinical umbilical catheter-related thrombosis (UCRT) and its association with clinical morbidities. MATERIALS AND METHODS: In infants without any symptoms associated with umbilical catheterization, the presence of thrombosis was monitored using abdominal ultrasonography within 1 week after umbilical catheter removal. The association between UCRT and the clinical variables was analyzed by comparing the groups with and without UCRT. RESULTS: UCRT occurred in 26 (19.0%) of 137 infants. The relative incidence rate of thrombosis was 12.3% at the umbilical artery and 21.7% at the umbilical vein. However, the type of umbilical vessels with a catheter was not associated with thrombosis (P = 0.095). Subclinical UCRT was associated with high serum calcium concentration in the multivariate analysis (95% confidence interval, 1.26-15.32; P = 0.020). UCRT was resolved within 3 weeks in 13 infants (50.0%), although the thrombosis persisted for up to 2 months in 2 infants (7.7%). We found no significant association between the subclinical UCRT and the neonatal morbidities in preterm infants. CONCLUSIONS: Though a rare cause of thrombosis, hypercalcemia should be considered in the assessment of infants with subclinical UCRT, and calcium levels should be routinely checked in infants with umbilical catheters.

Predictive value of the aspartate aminotransferase to platelet ratio index for parenteral nutrition associated cholestasis in extremely low birth weight infants.

BACKGROUND: Parenteral nutrition (PN) improves the survival of premature infants. However, prolonged PN increases the risk of PN-associated cholestasis (PNAC). OBJECTIVE: We aimed to evaluate the predictive value of aspartate aminotransferase (AST)-to-platelet ratio index (APRI) for PNAC in infants with extremely low birth weight (ELBW, birth weight < 1000 g) infants. METHODS: We retrospectively reviewed the medical records of ELBW infants from March 2010 to February 2017. Clinical data and the serial APRI, AST, alanine aminotransferase (ALT), AST-to-ALT ratio, and direct bilirubin (DB) were analyzed. PNAC was diagnosed in infants with a history of PN for at least 2 weeks and direct bilirubin concentrations > 2 mg/dL after other causes of neonatal cholestasis were excluded. RESULTS: Among the 179 eligible ELBW infants, 56 (31.3%) were diagnosed with PNAC. APRI significantly differed between infants with PNAC and those without PNAC. The best APRI cut-off point was 0.410 at 2 weeks after the start of PN (area under the receiver operating characteristic curve = 0.752, p < 0.05; positive predictive value, 50.6%; negative predictive value, 84.1%). CONCLUSION: APRI at 2 weeks after PN could be a reliable predictor of PNAC development in ELBW infants on PN.

Omental calcification, necrotizing enterocolitis, and undescended testes after fetal abdomino-amniotic shunting performed for the management of meconium peritonitis: A case report.

Prenatal ultrasonography (US) in a 39 year-old woman revealed massive fetal ascites. A fetal abdomino-amniotic shunting procedure was performed. Subsequently, plain radiographs demonstrated diffuse gaseous distention of the bowel and multiple punctate calcifications in the left upper abdomen. Postnatal US examination showed multiple echogenic foci in the liver and the left upper abdomen, bowel wall thickening in the right-sided abdomen, and undescended testes. There was no intra-abdominal free air or loculated fluid collections. Medical management was instituted secondary to the clinical suspicion of omental calcification, necrotizing enterocolitis, and undescended testes. Follow-up US examination showed resolution of portal vein gas and bowel wall thickening. The neonate recovered fully.

Clinical description of a neonate carrying the largest reported deletion involving the 10p15.3p13 region.

Chromosome 10p deletion is a rare disorder. This is the largest deletion in chromosome 10p reported to date and the first to be diagnosed in the early neonatal period because of severe clinical manifestations. This rare case might help to understand the genotype-phenotype spectrum in infants with 10p deletion.

Risk factor analysis of parenteral nutrition-associated cholestasis in extremely low birth weight infants.

AIM: Parenteral nutrition (PN) provides an alternative nutrition source for preterm infants who are intolerant of enteral nutrition. However, prolonged PN increases the risk of PN-associated cholestasis (PNAC). We conducted this study to determine the incidence and risk factors of PNAC in extremely low birth weight (ELBW) infants. METHODS: We retrospectively reviewed the medical records of ELBW infants from March 2010 to April 2015. PNAC was diagnosed in infants with a history of PN for at least two weeks and direct bilirubin concentrations >2 mg/dL after other causes of neonatal cholestasis were excluded. RESULTS: Of the 114 eligible ELBW infants, 41 (36%) were diagnosed with PNAC. The multivariate analysis showed that birth weight, sepsis, necrotising enterocolitis, fluconazole prophylaxis and the duration of PN and hospitalisation were independent risk factors for the development of PNAC (p < 0.05). However, parenteral fish oil-based lipid preparation (FOLP) did not reduce the risk of PNAC. Although PNAC was not a direct cause of death, it was associated with an increased risk of mortality. CONCLUSION: PNAC was common in ELBW infants, was associated with various clinical factors and increased the risk of mortality. However, we did not observe the protective effect of FOLP against PNAC.

Feasibility of an Early Discontinuation of Thyroid Hormone Treatment in Very-Low-Birth-Weight Infants at Risk for Transient or Permanent Congenital Hypothyroidism.

BACKGROUND/AIMS: This prospective study was conducted to investigate the feasibility of an early discontinuation of thyroid hormone treatment in very-low-birth-weight (VLBW) infants with congenital hypothyroidism (CH). METHODS: We enrolled VLBW infants between January 2011 and December 2012. The infants were divided into the hypothyroid and normal thyroid function groups according to the results of a thyroid function test. We performed an early off-therapy trial at 24 months of age. RESULTS: Of the 182 VLBW infants enrolled, 15 were lost to follow-up and 167 were finally enrolled. In total, 24 infants (14.4%) were assigned to the hypothyroid function group and were treated with thyroid hormone. Younger gestational age and a lower birth weight were associated with hypothyroid function. In the hypothyroid function group, hypothyroidism (HT) and hyperthyrotropinemia (HTT) were observed in 13 and 11 infants, respectively. There were no differences in the clinical characteristics between the HT and HTT groups. Overall, 24 infants discontinued thyroxine medication at 24 months of age after normal results had been confirmed by radiologic work-ups, including thyroid ultrasonography and technetium-99m scans. All infants were successfully weaned off thyroxine and maintained euthyroid function. CONCLUSION: Early discontinuation of thyroid hormone replacement therapy is possible in the majority of VLBW infants with CH.

Delayed Dexamethasone Therapy and Neurodevelopmental Outcomes in Preterm Infants with Bronchopulmonary Dysplasia.

BACKGROUND: It remains unclear whether the benefit of postnatal corticosteroid as a respiratory rescue therapy outweighs the potential harm of neurodevelopmental impairment (NDI) in very-low-birth-weight infants at risk of bronchopulmonary dysplasia (BPD). METHODS: We reviewed the charts of very-low-birth-weight infants with oxygen dependency for 28 days or more and who survived until 18-22 months' corrected age. Patients were divided into the delayed (≥21 days after birth) dexamethasone therapy (DDT, n=71) and the control (n=60) groups. NDI was defined by the presence of cerebral palsy, Bayley Mental or Psychomotor Developmental Index less than 70, deafness, or blindness. RESULTS: The DDT group was more premature and had worse respiratory morbidities before (ventilator-dependent at 21 days, 69% vs. 17%) and after the DDT (moderate/severe BPD, 41% vs. 15%) than the control group. The risk of NDI did not differ between the DDT and the control groups in the entire cohort (odds ratio and 95% confidence interval, 1.309 [0.530-3.237]) or in the propensity-score-matched cohort (n=62; odds ratio and 95% confidence interval, 1.344 [0.455-3.976]). However, in the subgroup of infants exposed to DDT, the cumulative dexamethasone dose greater than 5.0 mg/kg was significantly associated with NDI. CONCLUSION: Among the very-low-birth-weight infants with BPD, there was no definitely harmful effect of DDT on the neurodevelopmental outcome in the short term. However, considering the potential harm of high cumulative doses of dexamethasone on the developing brain, further studies are needed to determine the optimal dosage of DDT to be administered for the prevention of BPD.

Neonatal Hemoperitoneum Secondary to Hemorrhage from Omental Venous Malformation.

Hemoperitoneum in the neonate is uncommon. We report our experience with a neonate who suddenly developed hemoperitoneum in late gestation. Ascites with right pleural effusion initially suggested fetal hydrops. However, a decrease in hemoglobin with bloody ascites from the paracentesis gave the impression of hemoperitoneum. Ultrasonography and computed tomography showed no abnormality in the solid organs. Using 3-mm laparoscopic exploration, we found the omental mass and excised it. It was histologically confirmed as a venous malformation. Venous malformation of the omentum with significant bleeding requiring exploration is a very rare condition in the neonate, but it should be considered as a cause of neonatal hemoperitoneum.

An accessory limb with an imperforate anus.

Congenital accessory limbs are very rare anomalies with many causative factors. We describe the case of a 1-day-old female neonate-born to a healthy, 27-year-old mother-who presented with an accessory limb (foot) attached to the buttock and an imperforate anus. We also provide a review of the relevant literature.

Establishing a reference range for triiodothyronine levels in preterm infants.

OBJECTIVES: Thyroid dysfunction affects clinical complications in preterm infants and older children. However, thyroid hormone replacement in preterm infants has no proven benefits, possibly owing to the lack of an appropriate reference range for thyroid hormone levels. We aimed to establish a reference range for triiodothyronine (T3) levels at 1-month postnatal age (PNA) in preterm infants. METHODS: This retrospective study included preterm infants born at a tertiary referral neonatal center at gestational age (GA)<35 weeks with no apparent thyroid dysfunction, for 6 consecutive years, with follow-up from PNA 2 weeks to 16 weeks. Using thyroid function tests (TFT), the relationships between T3 levels and thyrotropin (TSH) and free thyroxine (fT4) levels, birth weight, GA, postmenstrual age (PMA), and PNA were examined. The conversion trend for fT4 to T3 was analyzed using the T3/fT4 ratio. RESULTS: Overall, 464 TFTs from 266 infants were analyzed, after excluding 65 infants with thyroid dysfunction. T3 levels increased with fT4 levels, birth weight, GA, PMA, and PNA but not with TSH levels. The T3/fT4 ratio also increased with GA, PNA, and PMA. The average T3 level at 1 month PNA was 72.56 ± 27.83 ng/dL, with significant stratifications by GA. CONCLUSIONS: Relatively low T3 and fT4 levels in preterm infants were considered normal, with T3 levels and conversion trends increasing with GA, PMA, and PNA. Further studies are required to confirm the role of the present reference range in thyroid hormone replacement therapy.

Congenital antral web in premature baby.

Antral web is a rare cause of gastric outlet obstruction in neonate. It is a 2-4 mm thin mucous membrane that can be found anywhere from 1 to 7 cm proximal to the pylorus. The baby was born at gestational age of 32(+1) weeks with 1,880 g as 2nd baby of dizygotic twin. After birth, the baby had constant non-bilious vomiting without feeding while he didn't show abdominal distension or discoloration. The infantogram showed distended stomach with distal small bowel gas. Upper gastrointestinal series revealed that the antrum was abruptly narrowed at 1 cm proximal to pylorus. We performed laparotomy at the 10th day after birth and excised the 2 mm-thick web circumferentially. He began milk feeding after 6 days and discharged uneventfully at postoperative 35 days with corrected age of 38(+4) weeks with body weight 2,420 g. The antral web should be considered in the case of non-bilious vomiting in neonate.

Thyroid dysfunctions of prematurity and their impacts on neurodevelopmental outcome.

BACKGROUND: Thyroid dysfunction is very common and is associated with neurodevelopmental impairments in preterm infants. OBJECTIVES: This study was conducted to determine the incidence and natural course of various thyroid dysfunctions and their impacts on neurodevelopmental outcomes among premature infants. METHODS: A total of 177 infants were enrolled who were born at <34 weeks or whose birth weight was <1500 g and who underwent repeat thyroid function tests. We analyzed how various thyroid dysfunctions affected neurodevelopmental outcomes at 18 months of corrected age. RESULTS: Thyroid dysfunction was noted in 88 infants. Hypothyroxinemia was observed in 23 infants, and their thyroid function was influenced by variable clinical factors. Free T4 levels were all normalized without thyroxine medication, and neurodevelopmental outcomes were not affected. In contrast, hyperthyrotropinemia was not associated with other clinical factors. Among 58 subjects who had hyperthyrotropinemia, only 31 infants showed normal thyroid-stimulating hormone (TSH) levels at follow-up tests. The remaining 27 infants had persistently high TSH levels, which significantly and poorly influenced the neurodevelopmental outcomes. CONCLUSIONS: Thyroid dysfunction is common among preterm infants. With the exception of persistent hyperthyrotropinemia, it generally does not affect neurodevelopmental outcomes. However, the beneficial effects of thyroid hormone therapy in patients with persistent hyperthyrotropinemia merits further study.

Effect of furosemide on ductal closure and renal function in indomethacin-treated preterm infants during the early neonatal period.

BACKGROUND: Furosemide is known to increase renal prostaglandin synthesis. However, its influence on ductal closure and renal toxicities of indomethacin in preterm infants has not been conclusive, especially during the early neonatal period. OBJECTIVES: To identify the effects of furosemide after indomethacin administration on the rate of patent ductus arteriosus (PDA) closure and renal function in preterm infants. METHODS: 68 infants (gestational age <34 weeks and birth weight <2,000 g) receiving indomethacin therapy (one course: 0.2-0.1-0.1 mg/kg q 12 h, mostly started <48 h after birth) were randomly assigned to the furosemide (n = 35) or control (n = 33) group. Each indomethacin dose was followed by furosemide (1.0 mg/kg) or placebo. The primary (PDA closure) and secondary (acute renal failure (ARF) and others) outcomes were assessed. Renal parameters before and 0-12 and 24-36 h after the first course of indomethacin were also investigated. RESULTS: In an intention-to-treat analysis, there were no differences in the PDA closure rate between the furosemide (29/34) and the control (27/29) group (p = 0.437). The incidence of ARF (serum creatinine >1.6 mg/dl) was greater in the furosemide group (20/34) than in the control group (3/29) (p < 0.001). Compared with the control group, serum creatinine and cystatin C levels and fractional excretion of sodium were significantly increased in the furosemide group for 24-36 h after indomethacin therapy (p < 0.01). There were no between-group differences in mortality and other neonatal morbidity rates. CONCLUSIONS: Use of furosemide in combination with indomethacin increased the incidence of ARF but did not affect the PDA closure rate in preterm infants.

Impact of fetal echocardiography on trends in disease patterns and outcomes of congenital heart disease in a neonatal intensive care unit.

BACKGROUND: Congenital heart disease (CHD) is the most common developmental malformation and the leading cause of neonatal mortality and morbidity. The introduction of fetal echocardiography has made prenatal diagnosis of CHD possible. OBJECTIVE: This study was conducted to investigate the impact of fetal echocardiography on the changing disease patterns and outcomes of CHD. METHODS: A retrospective analysis of data from infants with CHD admitted to the neonatal intensive care unit (NICU) of the Asan Medical Center during the time periods was performed. Period I (1994-1996) was considered representative of a period before the introduction of fetal echocardiography, while period II (2004-2006) represented a period of more extensive application of fetal echocardiography. RESULTS: A total of 164 patients were admitted to the NICU during period I and 320 during period II. The number of infants prenatally diagnosed with CHD was 5 of 164 (3.0%) in period I and 219 of 320 (68.4%) in period II (p < 0.05). The overall accuracy of fetal diagnosis was approximately 92%. Of the 3 CHD categories, there was a greater proportion of infants with 'significant' heart disease in period II than I (47 vs. 32%; p < 0.05). In contrast, there was a smaller proportion of infants with 'simple' heart defects in period II than I (22 vs. 40%; p < 0.05). The proportion of infants with 'complex' heart disease was similar in both periods (28% in period I and 31% in period II). The 1-year survival rate of patients with CHD has improved remarkably with time (70.1% in period I to 88.8% in period II). Multivariate analysis showed prenatal diagnosis and planned delivery in a tertiary NICU are factors affecting CHD outcomes, especially when defects are 'complex' (p < 0.01). CONCLUSION: Fetal echocardiography has resulted in an increased frequency of prenatal CHD diagnosis, has altered the disease patterns observed in the NICU, and has resulted in better 1-year outcomes.