Protective factors against preterm infants to develop significant patent ductus arteriosus.

BACKGROUND: Identifying preterm infants with a higher likelihood of spontaneous patent ductus arteriosus (PDA) closure would be desirable. This study aimed to examine daily PDA status during the first week of life for very low birthweight (VLBW, <1500 g) preterm infants and to develop a scoring system to predict spontaneous PDA closure. METHODS: We enrolled VLBW infants admitted between January 2016 and January 2017 and performed daily echocardiographic screening for PDA existence. Oxygen index (OI, mean airway pressure × fraction of inspired oxygen/partial pressure of arterial oxygen) was applied to represent the respiratory condition. RESULTS: A total of 215 VLBW infants were enrolled, and the accumulative incidence of spontaneous PDA closure by age 1 week was 80%, 70%, and 34% for infants born of gestational age (GA) ≥30, 28-29, and ≤27 weeks, respectively. Of these 215 infants, 184 infants entered the second phase to establish the scoring system. Infants with spontaneous PDA closure were more mature (GA 29.2 ± 2.3 vs. 26.9 ± 2.3 weeks, p < 0.001), had lower OI (2.8 ± 2.2 vs. 5.6 ± 5.3, p < 0.001) and were less likely to need endotracheal intubation (23% vs. 68%, p < 0.001). Using the receiver operating characteristics curve, OI <2.5 was determined favoring higher PDA closure incidence. The score was calculated based on the odds ratio generated in multiple regression: 4, 3 and 1 points for GA ≥30, 28-29 and ≤27 weeks, 2 and 1 points for OI <2.5 and ≥2.5, and 3 and 1 points for without and with endotracheal intubation. Using score ≥6 to predict PDA closure, the sensitivity and specificity were 0.77 and 0.72. CONCLUSION: A score made up of GA, OI and need for intubation was proposed to predict spontaneous PDA closure by age 1 week, which could be helpful to clinicians in the management of PDA in preterm infants.

Staged Management of Congenital Chylothorax With Hydrops Fetalis: An Insight Into EXIT Related Procedures.

Background: Idiopathic congenital chylothorax is a rare but serious disease. Advancement in perinatal care and the renovated treatment modalities have brought about significant improvement in patient outcome. Objective: To describe the clinical course of severe forms of idiopathic congenital chylothorax, focusing on the development of recent treatment modalities and their impacts. Design: A retrospective cohort by review of medical records in the NICU of a perinatal referral center in Taiwan. Study period was from January 2006 to June 2017. Neonates with the diagnosis of idiopathic congenital chylothorax with non-immune hydrops fetalis were enrolled. Clinical relevant including demographic data, perinatal interventions, post-natal course, and treatment outcome were described and analyzed. Results: Twenty-eight neonatal patients were included. The median gestational age at birth was 34 (range 27-36) weeks and median birth weight was 2,369 (range 1,430-3,608) g. Prenatal intervention was performed in 39.3% of the patients. Besides, 11 out of the 28 neonates developed tension pneumothorax in the first 24 h and 4 (36.4%) of them died. Sepsis was documented in two patients (7.1%). Overall survival rate was 71.4%. There were five patients enrolled during the last 2 years of the study period. EXIT with intubation was performed in two and octreotide was given to four of these most recent neonates, and all of them survived. Conclusion: Recent advances in the management of these neonates, specifically EXIT with intubation and use of octreotide. Both of them improved patient survival in our cohort, but the evidence of impact has yet to be validated.

Prospective investigation of serial ultrasound for transient tachypnea of the newborn.

BACKGROUND: Transient tachypnea of the newborn (TTN), which is diagnosed using typical clinical course and radiographic findings, is the most common cause of respiratory distress in late-preterm and term neonates. Lung ultrasound (LUS) is increasingly used to identify TTN according to the distinct characteristics of the disease. However, few studies have reported the application of LUS to monitor the clinical evolution of TTN. Using serial LUS, this prospective study assessed and monitored TTN severity. METHODS: From November 2018 to October 2019, neonates ≥34 weeks of gestation admitted to the newborn center of Chang Gung Memorial Hospital were enrolled. Neonates diagnosed with TTN and requiring respiratory support comprised the TTN group (n = 29), whereas those without respiratory disease served as the control group (n = 23). LUS was performed and scored in both groups within 4 h of admission and followed up at 24 and 48 h. RESULTS: A total of 65 infants were screened for enrollment and 13 were excluded. Most of the enrollees in both groups exhibited a peak LUS score on the first day, which then gradually declined thereafter. In comparison with the control group, the LUS score of the TTN group was higher on day 1 and day 2, and it had a significantly greater decrease from day 1 to day 2. In the TTN group, LUS scores moderately correlated with respiratory severity scores. CONCLUSION: We conducted a serial and quantitative LUS investigation in late-preterm and term infants with TTN. The LUS score mirrored the respiratory status relatively well, and it can help to monitor the clinical course of TTN, in the case of either resolution or deterioration.

Middle cerebral artery velocity is associated with the severity of MRI brain injury in neonates received therapeutic hypothermia.

BACKGROUND: No previous study has investigated the relationship between middle cerebral artery (MCA) flow velocity and the severity of hypoxic ischemic encephalopathy (HIE) evaluated by magnetic resonance imaging (MRI). The aim of this study was to assess the correlation between cerebral blood flow as assessed by transcranial Doppler sonography and the severity of MRI brain injury in asphyxiated neonates with clinical HIE who received therapeutic hypothermia. METHODS: This retrospective cohort study was conducted in the neonatal intensive care unit at Chang Gung Memorial Hospital between April 2011 and May 2014. All neonates with HIE who received therapeutic hypothermia, transcranial Doppler examinations, and brain MRI were eligible. Brain MRI was performed at 11 days of age (interquartile range: 8.5-15 days) and the severity of MRI brain injuries was evaluated using the MR scoring system proposed by Barkovich et al. Serial transcranial Doppler examinations were performed in pre-hypothermia, hypothermia, and post-hypothermia phases. RESULTS: Twenty-six neonates met the eligibility criteria for this study. Neonates with an abnormal MCA mean flow velocity (MFV) during the hypothermia phase had a higher risk of brain MRI abnormalities (77.8% vs. 22.2%, p = 0.017) and neonates with abnormal high MFV of MCA had higher MR scores of basal ganglia (p = 0.022). However, there were no statistical differences between abnormal MFV of MCA and brain MRI abnormalities during pre- and post-hypothermia phases. CONCLUSIONS: During therapeutic hypothermia, mean cerebral blood flow velocity of the MCA was associated with the severity of MRI brain injury in the neonates with clinical HIE.

Acute exacerbation of hepatitis B with hepatic failure during the first trimester of pregnancy: Delivery of a healthy term baby after liver transplantation.

The severe form of acute exacerbation of hepatitis B during pregnancy is a rare but life-threatening condition for both the mother and the fetus. A 32-year-old pregnant woman at 10 weeks of gestation was diagnosed with acute decompensated liver failure due to acute exacerbation of hepatitis B. The Model for End-stage Liver Disease score was up to 37. The patient was managed carefully with antiviral treatment, fluid resuscitation, correction of coagulopathy, close monitoring of hepatic function, and regular assessment of the fetus. She was transplanted with a deceased liver at 14 weeks and 1 day of gestation. With careful post-transplant care and avoidance of medication with risk of miscarriage and teratogenicity, a healthy baby was delivered at 39 weeks and 1 day of gestation. Herein, we report this critical condition of pregnancy that was complicated with liver failure due to acute exacerbation of hepatitis B, but had favorable outcomes for both the mother and the baby after liver transplantation.

A retrospective study on the incidence of acute kidney injury and its early prediction using troponin-I in cooled asphyxiated neonates.

Acute kidney injury (AKI) is a common complication of perinatal asphyxia and is associated with poorer short-term and long-term outcomes. This retrospective study describes the incidence of AKI in asphyxiated neonates who have received therapeutic hypothermia using the proposed modified Kidney Diseases: Improving Global Outcomes (KDIGO) definition and investigates clinical markers that would allow earlier recognition of at-risk neonates. We included asphyxiated  neonates who underwent therapeutic hypothermia between the period of January 2011 and May 2018 in our study. The serum creatinine levels within a week of birth were used in establishing AKI according to the modified KDIGO definition. Demographic data, resuscitation details, laboratory results and use of medications were collected and compared between the AKI and non-AKI groups to identify variables that differed significantly. A total of 66 neonates were included and 23 out of them (35%) were found to have AKI. The neonates with AKI had a lower gestational age (p = 0.006), lower hemoglobin level (p = 0.012), higher lactate level before and after therapeutic hypothermia (p = 0.013 and 0.03 respectively) and higher troponin-I level after therapeutic hypothermia (p < 0.001). After logistic regression analysis, elevated troponin-I after therapeutic hypothermia was independently associated with risk of AKI (OR 1.69, 95% CI 1.067-2.699, p = 0.025). The receiver operating curve showed that troponin-I after therapeutic hypothermia had an area under curve of 0.858 at the level 0.288 ng/ml. Our study concludes that the incidence of AKI among asphyxiated newborns who received therapeutic hypothermia is 35% and an elevated troponin-I level after therapeutic hypothermia is independently associated with an increased risk of AKI in asphyxiated newborns.

Seizures severity during rewarming can predict seizure outcomes of infants with neonatal hypoxic-ischemic encephalopathy following therapeutic hypothermia.

BACKGROUND: The aim of this study was to examine the predictive value of amplitude-integrated electroencephalography (aEEG) on 12-month seizure outcomes of infants with neonatal hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia. METHODS: We conducted this retrospective cohort study in a tertiary neonatal intensive care unit between May 2012 and September 2017. Neonates with HIE who received both therapeutic hypothermia (TH) and aEEG were enrolled. RESULTS: A total of 23 infants (14 boys, nine girls) with a mean gestational age of 38.9 weeks were enrolled. Fifteen (65%) infants had moderate HIE and eight (35%) had severe HIE according to modified Sarnat staging. The mean aEEG recording time was 107.5 h. Twenty (86.9%) infants had seizure activity during the first 24 h after cooling and 14 (60.8%) had seizure activity during the first 24 h after rewarming. At 12 months, five (21.7%) infants had poor seizure outcomes. Repetitive seizures or status epilepticus pattern during the first 24 h after rewarming, but not the first 24 h after cooling, were associated with the presence of epilepsy at 12 months (p = 0.037). CONCLUSIONS: We identified a high incidence of electrographic seizures in infants with neonatal HIE treated with therapeutic hypothermia, and post-neonatal epilepsy in the children who survived after HIE. Repetitive seizures or status epilepticus pattern during the first 24 h after rewarming, but not in the first 24 h after cooling, were associated with the presence of epilepsy at 12 months.

Baseline cardiac output and its alterations during ibuprofen treatment for patent ductus arteriosus in preterm infants.

BACKGROUND: Infants with hemodynamically significant patent ductus arteriosus (PDA) may physiologically compensate with a supranormal cardiac output (CO). As such, a supranormal CO may be a surrogate marker for a significant PDA or indicate a failed response to PDA closure by ibuprofen. Electrical cardiometry (EC) is an impedance-based monitor that can continuously and non-invasively assess CO (COEC). We aimed to trend COEC through ibuprofen treatment for PDA in preterm infants. METHODS: We reviewed our database of preterm infants receiving ibuprofen for PDA closure. Response to ibuprofen was defined as no ductal flow in echocardiography ≤24 h after treatment. Responders were compared with gestational age (GA) and postnatal age matched non-responders and their trends of COEC were compared. Both groups' baseline COEC were further compared to the reference infants without PDA. RESULTS: Eighteen infants (9 responders and 9 non-responders) with median (interquatile range) GA 27.5 (26.6-28.6) weeks, birthweight 1038 (854-1218) g and age 3.5 (3.0-4.0) days were studied. There were positive correlations between COEC and ductal diameter and left atrium/ aortic root ratio (r = 0.521 and 0.374, p < 0.001, respectively). Both responders and non-responders had significantly higher baseline COEC than the reference. Although there was no significant within-subject alteration of COEC during ibuprofen treatment, there was a between-subject difference indicating non-responders had generally higher COEC. CONCLUSIONS: The changes of COEC during pharmacological closure of PDA is less drastic compared to surgical closure. Infants with PDA had higher baseline COEC compared to those without PDA, and non-responders had higher COEC especially at baseline compared to responders.

Renal replacement therapy in the neonatal intensive care unit.

BACKGROUND: Renal replacement therapy (RRT) is becoming increasingly necessary for supporting critically ill neonates. Few studies have reported the use of RRT in the neonatal intensive care unit (NICU). Therefore, we performed a retrospective study to describe the use of RRT in our NICU and its associated efficacy, complications, and outcomes. METHODS: We identified patients requiring RRT between January 2009 and January 2017. Demographic data, mode of RRT, and associated factors were recorded. Efficacy was calculated as the percentage reduction in the blood urea nitrogen (BUN) or toxic metabolite level after 24 h of RRT. Complications including hypotension, electrolyte disturbance, and technical and catheter-related complications were documented. Measures of clinical outcome included in-hospital survival, presence of neurological sequelae, and chronic kidney disease. The chi-square test and Mann-Whitney U test were used for categorical and continuous variables, respectively. RESULTS: We included 17 neonates in our study. The median gestational age at birth was 37 weeks (32-39 weeks), and the median birth weight was 2.7 kg (1.5-3.6 kg). Twelve neonates, including three with inborn errors of metabolism (IEM), received continuous RRT (CRRT), and five neonates underwent peritoneal dialysis (PD). The percentage reduction in ammonia in neonates with IEM who received CRRT was 87.2% at 24 h. The percentage reductions in BUN in the non-IEM neonates in the CRRT and PD groups were 33.7% and 23.7% at 24 h, respectively. The main complication was electrolyte disturbance including hypokalemia, hypocalcemia, and hypophosphatemia. All neonates with IEM survived, whereas the mortality rates for the non-IEM neonates in the CRRT and PD groups were 78% and 80%, respectively. CONCLUSION: Our study findings reveal RRT to be feasible, even in preterm neonates with low birth weight. CRRT had a higher efficacy level, particularly in neonates with IEM, and the complications encountered were transient and correctable.

Electrical Cardiometry to Monitor Cardiac Output in Preterm Infants with Patent Ductus Arteriosus: A Comparison with Echocardiography.

BACKGROUND: Electrical cardiometry (EC) is an impedance-based monitoring that provides noninvasive cardiac output (CO) assessment. Through comparison to transthoracic echocardiography (Echo), the accuracy of EC has been verified. However, left-to-right patent ductus arteriosus (PDA) shunting is a concern because PDA shunts aortic flow to the pulmonary artery and may interfere with EC in measuring CO. OBJECTIVE: To determine the agreement between EC and Echo in preterm infants with a hemodynamically significant PDA (hsPDA). METHODS: We reviewed our hemodynamic database in which simultaneous CO measurements by Echo and EC (Aesculon®) were recorded. Preterm infants with left-to-right shunting hsPDA were enrolled. RESULTS: A total of 105 paired measurements in 36 preterm infants were compared. Infants' median (range) age and weight at measurement were 27+2 weeks (24+0-33+1) and 1,015 g (518-1,880), with mean (95% CI) ductal diameter 2.11 mm (1.99-2.22) or 2.15 mm/kg (2.00-2.30). Mean COEC and COEcho were 252 ± 32 and 258 ± 45 mL/kg/min, respectively, which demonstrated a moderate correlation and without a significant between-measurement difference. Bland-Altman analysis showed a bias, limits of agreement, and error percentage of -5.3 mL/kg/min, -78.3 to 67.7 mL/kg/min, and 28.6%, respectively. There was a trend of increased bias and error percentage of infants with high CO ≥280 mL/kg/min and supported with high-frequency ventilator. CONCLUSIONS: EC and Echo have a wide but clinically acceptable agreement in measuring CO in preterm infants with hsPDA. However, for infants with high CO or ventilated by high-frequency ventilation, interpretation of COEC should be approached with caution.