Differences in Growth and Dietary and Nutrient Intake Patterns by Breastfeeding Status Over One Year Among Korean Children Aged 24-35 Months.

BACKGROUND: A previous national study found that Korean children who were breastfed for at least one year had lesser weight gain, lower protein, calcium, and iron intake relative to calories, and different dietary patterns in the second year of life, compared with children weaned before 12 months of age or those who were never breastfed. Therefore, this study aimed to investigate whether growth status, dietary and nutrient intake patterns differed by prolonged breastfeeding (PBF) experience even in the third year of life, when weaning is considered complete. METHODS: This cross-sectional study was based on the data of children aged 24 to 35 months from the National Health and Nutrition Examination Survey (2010-2020). Data on anthropometry, dietary behavior, food and nutrient intake, maternal education, and household income were extracted to analyze the association between PBF and growth, dietary and nutrient intake patterns. RESULTS: In the final analysis, 31.6% of the 931 children with a birth weight of ≥ 2.5 kg continued to breastfeed for at least 12 months of age, and their mean breastfeeding (BF) duration was 15.9 months. Children with PBF had significantly less postnatal weight gain than those without (P = 0.006). Regarding food group intake, PBF was significantly associated with lower legume and soy product intake (ß [95% confidence interval], -10.688 [-19.314, -2.062], P = 0.015) and higher fruit intake (32.978 [3.349, 62.608], P = 0.029), after adjusting for sex, age in month, total caloric intake, maternal education and household income. Regarding nutrient intake, after adjusting for these variables, PBF had significantly associated with higher dietary fiber (ß [95% CI], 1.607 [0.218, 2.996], P = 0.023), iron (0.848 [0.317, 1.380], P = 0.002) and niacin (0.728 [0.222, 1.235], P = 0.005) intake and was significantly associated with lower saturated fatty acid intake (-1.217 [-2.364, -0.071], P = 0.037) and percentage of energy from fat (-1.351 [-2.666, -0.035], P = 0.044). CONCLUSION: Even in the third year of life, children who have been breastfed for over one year continue to have relatively slow growth. However, they do appear to have better intake of some beneficial nutrients, which may be attributed to healthier dietary intake patterns in children with PBF. The results of this study can be used to support the recommendation of long-term BF for Korean infants and toddlers.

Factors associated with the follow-up of high risk infants discharged from a neonatal intensive care unit.

BACKGROUND: The study aimed to identify factors associated with compliance to follow-up (FU) appointments among infants following their discharge from the neonatal intensive care unit (NICU). METHODS: This retrospective cohort study reviewed 657 infants (birth weight <1500 g or gestational age [GA] <32 weeks), born between 2011 and 2015. A total of 525 eligible infants were classified into two groups: the compliant group (n = 360), who attended clinics from 18 to 24 months, and the non-compliant group (n = 165), who were lost to FU before 18 months. RESULTS: The non-compliant group was more likely to have higher usage rate of assisted reproductive technology (p = 0.023), GA (p < 0.001), weight (p < 0.001), height (p < 0.001), and head circumference (p < 0.001) at birth. The sibling number was higher in the non-compliant group (p = 0.011). Moreover, the non-compliant group demonstrated higher Apgar scores at 1 min and 5 min (p = 0.002 and p = 0.031, respectively). The compliant group was more likely to live in metropolitan or larger cities with a borderline significance (p = 0.056). Furthermore, the non-compliant group was less likely to suffer from respiratory distress syndrome (p < 0.001), patent ductus arteriosus (p = 0.002), retinopathy of prematurity (p = 0.007), necrotizing enterocolitis (p = 0.019), and bronchopulmonary dysplasia (p < 0.001). Moreover, it demonstrated lower postmenstrual age at discharge (p = 0.005) and a shorter length of stay in the NICU (p < 0.001). The compliance with FU appointment varied with the assigned doctor (p < 0.001). The multivariate regression analysis mentioned that the birth weight (OR = 0.903), residence in metropolitan or larger cities (OR = 1.495), and an experience of magnetic resonance imaging (OR = 1.920) were associated with compliance. The compliance to FU appointments was different according to the assigned doctor at admission (OR = 0.357). CONCLUSION: The birth weight, residence in metropolitan or larger cities, an experience of MRI, and the assigned doctors were associated with compliance to FU at a corrected age of 18-24 months.

Perinatal risk factors of symptomatic preterm patent ductus arteriosus and secondary ligation.

BACKGROUND: There has been conflicting evidence for the association between antenatal factors and the development of symptomatic patent ductus arteriosus (PDA) or failure of pharmacologic treatment, especially for maternal pregnancy-induced hypertension (PIH) or chorioamnionitis. We assessed the perinatal risk factors of symptomatic PDA in preterm infants and those of secondary ligation in infants with pharmacologic treatment for symptomatic PDA using a national cohort. METHODS: A total of 2961 infants with 22-29 weeks of gestation with symptomatic PDA or no PDA were included from the Korean Neonatal Network database. To identify significant perinatal risk factors associated with symptomatic PDA or secondary ligation, all perinatal factors were included in the univariate and multivariate generalized estimating equation analysis and final model was selected using backward elimination method based on Quasi-likelihood Information Criterion. RESULTS: Lower gestational age (GA), female gender, maternal PIH and surfactant use were significant risk factors of symptomatic PDA. Antenatal corticosteroid use decreased the risk of symptomatic PDA. For secondary ligation, lower GA and cesarean section were significant risk factors. Adjusted odds ratio (aOR) of PIH as a risk factor of symptomatic PDA was 1.56 [95% confidence interval 1.17-2.08]. In the subgroup analysis according to the GA, lower GA, female gender, multiple pregnancy, maternal PIH and surfactant use increased the risk of symptomatic PDA, and histologic chorioamnionitis and antenatal corticosteroid use decreased the risk of symptomatic PDA only in GA 26-29 weeks group. CONCLUSION: Lower GA increased the risk of symptomatic PDA and secondary ligation. Maternal PIH and surfactant use increased the risk of symptomatic PDA; however, antenatal corticosteroid use decreased it. Close observation of the clinical symptoms of PDA is needed in preterm infants with maternal PIH.

Differential Effect of Growth on Development between AGA and SGA Preterm Infants.

Predicting developmental outcomes with growth measurement would be beneficial for primary healthcare or in developing countries with low medical resources. This study aimed to identify physical growth measures that indicate neurodevelopment in very preterm infants. Preterm infants, born at <32 weeks' gestation or weighing <1500 g, were included. We calculated the changes in z-score of weight, length, and head circumference (HC) at different time points: birth, postmenstrual age (PMA) 35 weeks, and 4 and 18 months corrected age (CA). We examined the relationship between growth and Bayley-III scores using linear regression. Among 122 infants, HC at 4 months CA and HC growth between PMA 35 weeks and 4 months CA showed a positive correlation with Bayley-III scores in appropriate-for-gestational-age infants (AGAs). Weight and length increases between birth and 18 months CA were also associated with AGAs' development. In small-for-gestational-age infants (SGAs), only birthweight's z-score was associated with improved neurodevelopmental outcomes. HC at 4 months CA was an important indicator of favorable neurodevelopmental outcomes, and head growth spurt between PMA 35 weeks and 4 months CA contributed to this benefit in preterm AGAs. The period and indices should be monitored differently for SGAs and AGAs.

The Influence of the Variation in Sepsis Rate between Neonatal Intensive Care Units on Neonatal Outcomes in Very-Low-Birth-Weight Infants.

Sepsis is commonly known to affect neonatal outcomes. We assessed how much center-to-center variability of the sepsis rate affects the outcomes of very-low-birth-weight infants (VLBWIs). 7,493 VLBWIs registered in the Korean Neonatal Network from 2013 to 2016 were classified into three groups according to the sepsis rate: low sepsis group (LS) < 25th percentile versus intermediate sepsis group (IS) 25th-75th versus high sepsis group (HS) ≥ 75th. The incidence density of sepsis for the LS, IS, and HS groups were 1.17, 3.17, and 8.88 cases/1,000 person-days. After propensity score matching was done for multiple antenatal and perinatal factors, the odds ratio of death, moderate to severe bronchopulmonary dysplasia and/or death, periventricular leukomalacia, and survival without major morbidities for the HS group were 2.0 (95% confidence interval 1.4-2.8), 1.9 (1.5-2.4), 1.5 (1.1-2.3) and 0.7 (0.5-0.8) when compared with the IS group, and 2.2 (1.6-3.2), 2.3 (1.8-2.9), 2.0 (1.3-2.9), and 0.7 (0.6-0.9) when compared with the LS group. There were no significant differences in those outcomes between the LS and IS groups. Hence, nationwide quality improvements to control the sepsis rate especially in units with a high sepsis rate will be helpful to improve the outcomes of VLBWIs.

Timing of sepsis is an important risk factor for white matter abnormality in extremely premature infants with sepsis.

BACKGROUND: Systemic infection is a major upstream mechanism for white matter abnormality (WMA). Our aim was to evaluate the risk factors for moderate-to-severe WMA in extremely premature infants (gestational age < 28 weeks) with neonatal sepsis. METHODS: Extremely premature infants with culture-proven sepsis between 2006 and 2015 in a tertiary neonatal intensive care unit were classified as having none-to-mild or moderate-to-severe WMA based on WM scores of brain magnetic resonance imaging at the term-equivalent age. Various risk factors for WMA were analyzed. RESULTS: Sixty-three infants (87.5%) had none-to-mild WMA, and nine infants (12.5%) had moderate-to-severe WMA. Multivariate logistic regression analysis revealed that postmenstrual age (PMA) at sepsis diagnosis (OR: 0.640, 95% CI: 0.435-0.941, p = 0.023) and PMA at sepsis diagnosis <28 weeks (OR: 9.232, 95% CI: 1.020-83.590, p = 0.048) were independently associated with moderate-to-severe WMA. PMA at sepsis diagnosis had a significant negative correlation with WM scores (r = -0.243, p = 0.039). CONCLUSION: PMA at sepsis diagnosis might be an important risk factor for moderate-to-severe WMA in extremely premature infants with postnatal sepsis, especially before PMA 28 weeks. Infants who suffer from sepsis before PMA 28 weeks might need additional therapy for neuroprotection.

Prediction of serum theophylline concentrations and cytochrome P450 1A2 activity by analyzing urinary metabolites in preterm infants.

AIMS: The purpose of this study was to explore clinical markers reflecting developmental changes in drug clearance by preterm infants. METHODS: Preterm infants administered aminophylline or theophylline to treat apnoea of prematurity were enrolled in this study. Trough and one of 2 h, 4 h or 6 h post-dose blood samples and urine samples were collected during steady state, to determine the concentrations of theophylline and its targeted metabolites. CYP1A2*1C and CYP1A2*1F genotypes were analyzed. Total, renal and nonrenal clearances of theophylline were calculated, and cytochrome P450 1A2 (CYP1A2) activity was obtained from the ratio of 1-methyluric acid and 3-methylxanthine to theophylline in urine. Multiple linear regression analysis was performed to evaluate the relationships between theophylline clearance and the clinical characteristics of preterm infants. RESULTS: A total of 152 samples from 104 preterm infants were analyzed. A strong association between the serum trough and urine theophylline concentrations was found (P < 0.001). Total, renal and nonrenal clearances of theophylline were 0.50 ± 0.29 ml kg-1  min-1 , 0.16 ± 0.06 ml kg-1  min-1 and 0.34 ± 0.28 ml kg-1  min-1 , respectively. CYP1A2 activity correlated positively with the postnatal age and postmenstrual age. However, CYP1A2 genotype was not associated with CYP1A2 activity, which was significantly associated with nonrenal clearance. CYP1A2 activity, postnatal age , weight and 24-h urine output were significantly associated with total theophylline clearance. CONCLUSIONS: CYP1A2 activity can be monitored using noninvasive random urine samples, and it can be used to assess developmental changes in theophylline clearance by preterm infants.

Comparison of the Mortality and In-Hospital Outcomes of Preterm Infants Treated with Ibuprofen for Patent Ductus Arteriosus with or without Clinical Symptoms Attributable to the Patent Ductus Arteriosus at the Time of Ibuprofen Treatment.

The aim of this study was to assess the differences in the mortality and in-hospital outcomes of preterm infants with < 28 weeks of gestation who received ibuprofen treatment according to the presence of clinical symptoms (any of oliguria, hypotension, or moderate to severe respiratory difficulty) attributable to hemodynamically-significant patent ductus arteriosus (hsPDA) at the time of first ibuprofen treatment. In total, 91 infants born from April 2010 to March 2015 were included. Fourteen infants (15.4%) received ibuprofen treatment when there were clinical symptoms due to hsPDA (clinical symptoms group). In clinical symptoms group, infants were younger (25 [23-27] vs. 26 [23-27] weeks; P = 0.012) and lighter (655 [500-930] vs. 880 [370-1,780] grams; P < 0.001). Also, the clinical risk index for babies (CRIB)-II scores were higher and more infants received invasive ventilator care ≤ 2 postnatal days. More infants received multiple courses of ibuprofen in clinical symptoms group. Although the frequency of secondary patent ductus arteriosus (PDA) ligation and the incidence of bronchopulmonary dysplasia (BPD) was higher in the clinical symptoms group in the univariate analysis, after multivariate logistic regression analysis adjusting for the CRIB-II score, birthweight, birth year, and the invasive ventilator care ≤ 2 postnatal days, there were no significant differences in mortality, frequency of secondary ligation and in-hospital outcomes including necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), BPD or death. Our data suggest that we can hold off on PDA treatment until the clinical symptoms become prominent.

The efficacy and safety of Montelukast sodium in the prevention of bronchopulmonary dysplasia.

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of Montelukast sodium in the prevention of bronchopulmonarydysplasia (BPD). METHODS: The Interventional study was designed as a multicenter, prospective, and randomized trial, with open labeled and parallel-experimental groups, 66 infants were enrolled and allocated to either the case group (n=30) or the control group (n=36) based on gestational age (GA). Infants in the case group were given Montelukast sodium (Singulair) based on their body weight (BW). Zero week was defined as the start time of the study. RESULTS: The incidence of moderate to severe BPD was not different between the groups (case group: 13 of 30 [43.3%] vs. control group: 19 of 36 [52.8%], P=0.912). Additionally, secondary outcomes such as ventilation index, mean airway pressure and resort to systemic steroids were not significantly different. There were no serious adverse drug reactions in either group, and furthermore the rate of occurrence of mild drug related-events were not significantly different (case group: 10 of 42 [23.8%] vs. control group: 6 of 48 (15.8%), P=0.414). CONCLUSION: Montelukast was not effective in reducing moderate or severe BPD. There were no significant adverse drug events associated with Montelukast treatment.

Developmental change of amplitude-integrated electroencephalographic activity in preterm infants with intraventricular hemorrhage.

BACKGROUND: Amplitude-integrated electroencephalography (aEEG) allows continuous brain function monitoring at bedside. OBJECTIVES: This prospective cohort study was designed to longitudinally evaluate aEEG tracings at increased postmenstrual age (PMA) in preterm infants with intraventricular hemorrhage (IVH). METHODS: Biweekly aEEG recordings were performed on preterm infants <32 weeks gestational age from 24 to 36 weeks PMA. The tracings were evaluated according to a scoring system adapted from Burdjalov et al. RESULTS: We analyzed 496 aEEG recordings in 105 preterm infants. The control group consisted of 42 infants with no IVH, whereas the IVH grade I, II, III, and IV groups consisted of 38, 8, 3, and 14 infants, respectively. There were significant differences in the cycling and total maturation scores among the IVH groups at 36 weeks PMA (p = 0.010 and p = 0.006, respectively). The IVH-IV patients maintained low scores in their cycling as their PMA increased, in contrast to their continuity and amplitude scores. The risk factors affecting the aEEG maturation scores at 36 weeks PMA in the IVH-IV patients included seizure events with the administration of antiepileptic drugs and the insertion of external ventricular drains (ß = -0.679 and ß = -0.418, respectively; p = 0.003). CONCLUSIONS: The low cycling scores persisted until 36 weeks PMA in the IVH-IV group.

Population pharmacokinetics of theophylline in premature Korean infants.

OBJECTIVES: The aim of this study was to investigate the population pharmacokinetics of theophylline in premature Korean infants and to assess the influence of clinical covariates. METHODS: Blood samples were first obtained after 1 week of maintenance dosing and then acquired approximately 4 weeks after continuous dosing. The time points were just before dosing and 2, 4, or 6 hours (at randomly assigned time points) after dosing. Two single-nucleotide polymorphism markers, -3860 G>A (CYP1A2*1C) and -163C>A (CYP1A2*1F), were genotyped. Gestational age (GA), postnatal age (PNA), postconceptional age (PCA = GA + PNA), body weight (BW), height, serum AST, serum ALT, serum BUN, serum creatinine, oxygen support, sex, delivery mode, and CYP1A2 genotypes were used for covariate model building. External validation was analyzed using data from an additional 27 patients. RESULTS: A total of 334 serum concentration measurements were made in 100 patients. A one-compartment absorptive model with first-order elimination was fitted to the data in NONMEM (version 7.1.2). The final model included the following parameters: Clearance (L/h) = 0.00492 × (BW)(3.53) + 0.00646 × (PNA), and volume of distribution (L) = 1.53 × (BW). The addition of the CYP1A2*1C or CYP1A2*1F genotypes to the model did not improve the model. The external validation results confirmed the predictive performance without bias in the final model. CONCLUSIONS: The selected covariates were generally consistent with previous studies. However, the mean volume of distribution was higher than the values reported in other population pharmacokinetic studies, which may have been due to the use of 2 sampling time points. The predictive performance was reasonably acceptable. Therefore, the present model may permit more accurate selection of doses to achieve target theophylline concentrations in premature infants.

The efficacy of noninvasive hemoglobin measurement by pulse CO-oximetry in neonates.

OBJECTIVE: To evaluate clinical applicability of noninvasive hemoglobin (Hb) measurement with a pulse CO-oximeter in neonates. DESIGN: Prospective comparison study. SETTING: Neonatal ICU. PATIENTS: Fifty-six preterm and term infants with median age = 20 days (range = 1-98 days) and median weight = 1,440 g (range = 530-4,230 g). INTERVENTIONS: Hb measurements by Pulse CO-Oximetry (Masimo Radical-7) were recorded immediately prior to venous samplings. MEASUREMENTS AND MAIN RESULTS: The collected data were compared with the corresponding venous Hb level obtained in laboratory testing, and a total of 137 data pairs were analyzed. Noninvasive Hb values measured with a pulse CO-oximeter were significantly correlated with the venous Hb levels (correlation coefficient, r = 0.758; p < 0.001). Hb values measured with a pulse CO-oximeter were higher than those measured with a laboratory hematology analyzer (13.3 ± 2.6g/dL vs. 12.5 ± 3.1g/dL). In terms of the agreement between the laboratory analyzer and the pulse CO-oximeter, 94.8% of the measurements fell within two standard deviations of the mean difference. CONCLUSION: Noninvasive Hb measurements with Pulse CO-Oximetry provide clinically acceptable accuracy, and they were significantly correlated with laboratory Hb measurement in neonates. In terms of the clinical applicability, noninvasive Hb monitoring with a pulse CO-oximeter could be useful in the early detection of Hb changes in neonates.

A case of mucolipidosis II presenting with prenatal skeletal dysplasia and severe secondary hyperparathyroidism at birth.

Mucolipidosis II (ML II) or inclusion cell disease (I-cell disease) is a rarely occurring autosomal recessive lysosomal enzyme-targeting disease. This disease is usually found to occur in individuals aged between 6 and 12 months, with a clinical phenotype resembling that of Hurler syndrome and radiological findings resembling those of dysostosis multiplex. However, we encountered a rare case of an infant with ML II who presented with prenatal skeletal dysplasia and typical clinical features of severe secondary hyperparathyroidism at birth. A female infant was born at 37(+1) weeks of gestation with a birth weight of 1,690 g (<3rd percentile). Prenatal ultrasonographic findings revealed intrauterine growth retardation and skeletal dysplasia. At birth, the patient had characteristic features of ML II, and skeletal radiographs revealed dysostosis multiplex, similar to rickets. In addition, the patient had high levels of alkaline phosphatase and parathyroid hormone, consistent with severe secondary neonatal hyperparathyroidism. The activities of ß-D-hexosaminidase and α-N-acetylglucosaminidase were moderately decreased in the leukocytes but were 5- to 10-fold higher in the plasma. Examination of a placental biopsy specimen showed foamy vacuolar changes in trophoblasts and syncytiotrophoblasts. The diagnosis of ML II was confirmed via GNPTAB genetic testing, which revealed compound heterozygosity of c.3091C>T (p.Arg1031X) and c.3456_3459dupCAAC (p.Ile1154GlnfsX3), the latter being a novel mutation. The infant was treated with vitamin D supplements but expired because of asphyxia at the age of 2 months.

Randomized crossover study of neurally adjusted ventilatory assist in preterm infants.

OBJECTIVE: To determine whether neurally adjusted ventilatory assist (NAVA), a new method of mechanical ventilation that delivers pressure assistance that is proportional to the electrical activity of the diaphragm (EAdi), could lower the inspiratory pressure and respiratory muscle load in preterm infants supported with ventilators. STUDY DESIGN: Twenty-six mechanically ventilated preterm infants were randomized to crossover ventilation with NAVA and synchronized intermittent mandatory ventilation (SIMV) with pressure support (PS) for 4 hours each in a randomized order. A 1-hour interval for washout was provided between the 2 modes of ventilation. The ventilator settings were adjusted to maintain similar levels of end-tidal partial pressure of CO(2). The ventilator parameters, vital signs, and gas exchange effects under the 2 ventilatory modes were compared. RESULTS: Nineteen infants completed the 9-hour crossover comparison protocol. Peak inspiratory pressure (PIP), work of breathing, and peak EAdi with NAVA were lower than those in SIMV with PS. Calculated tidal volume to peak EAdi ratio and PIP to peak EAdi ratio were higher with NAVA. There were no significant differences in mean airway pressure, inspiratory oxygen fraction, and blood gas values. The measurements of vital signs did not differ significantly between the 2 modes. CONCLUSION: NAVA lowered PIP and reduced respiratory muscle load in preterm infants at equivalent inspiratory oxygen fraction and partial pressure of CO(2) of capillary blood in comparison with SIMV with PS.

Misdiagnosis of fetus-in-fetu as meconium peritonitis.

Fetus-in-fetu (FIF) is a rare congenital condition in which a fetiform mass is detected in the host abdomen and also in other sites such as the intracranium, thorax, head, and neck. This condition has been rarely reported in the literature. Herein, we report the case of a fetus presenting with abdominal cystic mass and ascites and prenatally diagnosed as meconium pseudocyst. Explorative laparotomy revealed an irregular fetiform mass in the retroperitoneum within a fluid-filled cyst. The mass contained intestinal tract, liver, pancreas, and finger. Fetal abdominal cystic mass has been identified in a broad spectrum of diseases. However, as in our case, FIF is often overlooked during differential diagnosis. FIF should also be differentiated from other conditions associated with fetal abdominal masses.