Gina Lim

Early Caffeine Use in Very Low Birth Weight Infants and Neonatal Outcomes: A Systematic Review and Meta-Analysis

The use of caffeine citrate for treatment of apnea in very low birth weight infants showed short-term and long-term benefits. A systematic review and meta-analysis of the literature was undertaken to document the effect providing caffeine early (0-2 days of life) compared to providing caffeine late (≥3 days of life) in very low birth weight infants on several neonatal outcomes, including bronchopulmonary dysplasia (BPD). We searched MEDLINE, the EMBASE database, the Cochrane Library, and KoreaMed for this meta-analysis. The quality of the included studies was assessed using the Newcastle-Ottawa Scale and Jadads scale. Studies were included if they examined the effect of the early use of caffeine compared with the late use of caffeine. Two reviewers screened the candidate articles and extracted the data from the full-text of all of the included studies. We included a total of 59,136 participants (range 58,997-59,136; variable in one study) from a total of 5 studies. The risk of death (odds ratio [OR], 0.902; 95% confidence interval [CI], 0.828 to 0.983; P=0.019), bronchopulmonary dysplasia (BPD) (OR, 0.507; 95% CI, 0.396 to 0.648; P<0.001), and BPD or death (OR, 0.526; 95% CI, 0.384 to 0.719; P<0.001) were lower in the early caffeine group. Early caffeine use was not associated with a risk of necrotizing enterocolitis (NEC) and NEC requiring surgery. This meta-analysis suggests that early caffeine use has beneficial effects on neonatal outcomes, including mortality and BPD, without increasing the risk of NEC.

A Simplified Formula Using Early Blood Gas Analysis Can Predict Survival Outcomes and the Requirements for Extracorporeal Membrane Oxygenation in Congenital Diaphragmatic Hernia

The aims of this study were to investigate whether early arterial blood gas analysis (ABGA) could define the severity of disease in infants with congenital diaphragmatic hernia (CDH). We conducted a retrospective study over a 21-yr period of infants diagnosed with CDH. Outcomes were defined as death before discharge, and extracorporeal membrane oxygenation requirements (ECMO) or death. A total 114 infants were included in this study. We investigated whether simplified prediction formula [PO2-PCO2] values at 0, 4, 8, and 12 hr after birth were associated with mortality, and ECMO or death. The area under curve (AUC) of receiver operating characteristic curve was used to determine the optimum ABGA values for predicting outcomes. The value of [PO2-PCO2] at birth was the best predictor of mortality (AUC 0.803, P < 0.001) and at 4 hr after birth was the most reliable predictor of ECMO or death (AUC 0.777, P < 0.001). The value of [PO2-PCO2] from ABGA early period after birth can reliably predict outcomes in infants with CDH.

Penile length, digit length, and anogenital distance according to birth weight in newborn male infants

Purpose Anogential distance (AGD) and the 2:4 digit length ratio appear to provide a reliable guide to fetal androgen exposure. We intended to investigate the current status of penile size and the relationship between penile length and AGD or digit length according to birth weight in Korean newborn infants. Materials and Methods Between May 2013 and February 2014, among a total of 78 newborn male infants, 55 infants were prospectively included in this study. Newborn male infants with a gestational age of 38 to 42 weeks and birth weight>2.5 kg were assigned to the NW group (n=24) and those with a gestational age<38 weeks and birth weight<2.5 kg were assigned to the LW group (n=31). Penile size and other variables were compared between the two groups. Results Stretched penile length of the NW group was 3.3±0.2 cm, which did not differ significantly from that reported in 1987. All parameters including height, weight, penile length, testicular size, AGD, and digit length were significantly lower in the LW group than in the NW group. However, there were no significant differences in AGD ratio or 2:4 digit length ratio between the two groups. Conclusions The penile length of newborn infants has not changed over the last quarter century in Korea. With normal penile appearance, the AGD ratio and 2:4 digit length ratio are consistent irrespective of birth weight, whereas AGD, digit length, and penile length are significantly smaller in newborns with low birth weight.

Thyroid dysfunctions of prematurity and their impacts on neurodevelopmental outcome1)

Abstract 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.

Early discontinuation of thyroxine therapy is possible in most very low‐birthweight infants with hypothyroidism detected by screening

To determine the feasibility of discontinuing thyroid hormone treatment earlier than recommended by the current guidelines for congenital hypothyroidism.

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

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.

Perinatal factors and the development of childhood asthma

BACKGROUND Perinatal factors are suspected to have a significant impact on the development of asthma; however, sufficiently powered studies have not been performed to investigate this issue. OBJECTIVE To evaluate whether perinatal factors and other risk factors have an independent or combined effect on the development of asthma. METHODS This study involved 3,770 children (mean age 9.1 years, range 5.68-12.16 years; 51.9% boys) who were enrolled in the Elementary School Student Cohort (2009-2014) in Ulsan University Hospital (Ulsan, Korea). Subjects were divided into an asthma group (n = 514) and a non-asthma group (n = 3,256). RESULTS Multivariate analyses showed that early life (within first week) oxygen therapy (adjusted odds ratio [aOR] 1.864, 95% confidence interval [CI] 1.156-3.004) and breastfeeding (aOR 0.763, 95% CI 0.606-0.960) were 2 significant perinatal factors influencing the development of asthma. Environmental tobacco smoke (aOR 1.634, 95% CI 1.298-2.058) and parental allergic disease (aOR 1.882, 95% CI 1.521-2.328) also were identified as risk factors. Using subgroup analyses, combined effects on asthma development were observed between perinatal factors (early life oxygen therapy and breastfeeding) and other risk factors (vicinity to major roadway [traffic-related air pollution], environmental tobacco smoke, parental allergic disease, and atopy). CONCLUSION Early life oxygen therapy and breastfeeding were identified as 2 important perinatal factors influencing the development of asthma. Furthermore, these factors showed combined effects with other risk factors (environmental tobacco smoke, traffic-related air pollution, parental allergic disease, and atopy) on the development of asthma.

Determination of reference range of gamma glutamyl transferase in the neonatal intensive care unit

Abstract Objective: We aimed to establish the reference range of gamma glutamyl transferase (GGT) in the first week of life at each gestational age (GA). Methods: This retrospective study included infants born and admitted before 7 days of age with no apparent congenital liver disease during four consecutive years. Early GGT levels measured at 3–7 days of age were analyzed according to GA. Differences according to sex, mode of delivery, small for gestational age, and the predictability for cholestasis were analyzed. Results: We analyzed early GGT values in 2091 neonates. The average reference value in neonates (156.7 ± 98.2 IU/L) was much higher than that in adults. The GGT values were significantly higher in preterm than in term infants and in male infants than in female infants. Mode of delivery and small for gestational age were not significantly related to GGT level. Early GGT had no predictive value for cholestasis occurrence. Conclusions: Early GGT levels were much higher in neonates, especially preterm infants with GA of 31–35 weeks.

Prophylactic Systemic Antifungal Agents to Prevent Mortality and Morbidity in Very Low Birth Weight Infants

Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection in infants who received systemic antifungal prophylaxis (typical risk ratio (RR) 0.41, 95% confidence interval (CI) 0.27–0.61; risk difference (RD) –0.09, 95% CI –0.14 to –0.05). The average incidence of invasive fungal infection in the control groups of the trials (16%) was much higher than that generally reported from large cohort studies (<5%). Meta-analysis did not find a statistically significant difference in the risk of death prior to hospital discharge (typical RR 0.74, 95% CI 0.52–1.05; RD –0.04, 95% CI –0.08 to 0.01). Very limited data on long-term neurodevelopmental outcomes were available. Two trials that compared systemic versus oral or topical non-absorbed antifungal prophylaxis did not detect any statistically significant effects on invasive fungal infection or mortality. Two trials that compared different dose regimens of prophylactic intravenous fluconazole did not detect any significant differences in infection rates or mortality.

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.