Journal of Neonatal-Perinatal Medicine

Being a rare condition, the incidence of chylothorax among neonates is low, but the mortality rate is high. In a dire effort to reduce the risk of death, octreotide treatment is used to effectively treat acquired and congenital chylothorax. Octreotide is proven to effectively treat chylothorax in pre-term and full-term neonates. However, previous studies have not consistently demonstrated the optimal dose of octreotide or the best mode of administration. The objectives of this work were to review previous literature to determine the outcomes of administering high doses of octreotide compared to lower dose regimens in neonates with chylothorax and to determine best practices.

A literature search was performed using electronic databases using the key words neonates, chylothorax, and octreotide.

Octreotide has been administrated in doses ranging from 0.5μg/kg/h to > 20μg/kg/h. Both low- and high-doses of octreotide are effective in resolving chylothorax with little to no side effects. When side effects were reported, neonates experienced side effects that are less significant in nature and scope.

We recommend that the dose of octreotide in neonatal chylothorax can be titrated safely to a maximum of 20μg/kg/h without significant side effects.

Increasing rates of maternal opioid use disorder has led to greater number of opioid exposed newborns (OENs). Maternal enrollment in medication for opioid use disorder (MOUD) program improves short term neonatal outcomes. This study aimed at assessing neurobehavioral outcomes for OENs.

Retrospective observational cohort study of OENs between Jul 2006 and Dec 2018. Two study groups were identified as initiation of medication for opioid use disorder (MOUD) prior to diagnoses of pregnancy or after. Primary outcome variables were enrollment in and duration of EI services. Secondary outcome variable was diagnoses of a behavioral and/or developmental disorder (BDD) during the study period.

Of 242 infants, 113 were enrolled in EI and BDD diagnoses data was available for all infants [age range 6 to 12 years], 82% infants had exposure to maternal MOUD, while 18% were exposed to either maternal prescription non-MOUD opioids or illicit opioids. Maternal MOUD initiation prior to pregnancy was associated with improved short term outcomes for OENs. Almost a third of infants were diagnosed with a BDD with no differences between the two study groups.

Early initiation of maternal MOUD improved short term outcomes and discharge disposition for OENs. Prolonged in-utero exposure to opioids presents a potential for negative impact on neurodevelopmental and behavioral outcomes. These risks must be considered to increase access and adherence to EI services, as well as to focus on non-opioid based maternal MOUD. Longitudinal studies assessing the safety of MOUD on short and long-term child health outcomes are needed.

Pregnant mothers with opioid dependency commonly receive maintenance treatment of opioid (OMT), either as buprenorphine (BMT) or methadone maintenance treatment (MMT). We investigated, whether OMT adversely affects standardized neonatal anthropometric outcomes and whether BMT is potentially safer than MMT in this regard.

Retrospective chart review of mother infant dyad, with and without OMT. Infant’s absolute and standardized (z-score) anthropometric outcomes at birth were first compared, between OMT and control group (negative meconium drug screen), and then between BMT and MMT group. These outcomes were also compared between infants who did or did not require treatment after birth for neonatal abstinence syndrome (NAS).

A total of 1479 participants with MDS were included [Control = 1251; OMT = 228 (MMT = 181; BMT = 47)]. Both the z-scores of birth weight (BW) and head circumference (HC) was lower in OMT group (p < 0.001). Among the OMT group, GA at delivery was slightly higher in the BMT group (p = 0.05). There was an inverse correlation between maternal dose at the time of delivery and anthropometric z-scores in the BMT group, mainly in female infants (BW: p = 0.006; HC: p = 0.003). Furthermore, In BMT group, infants with lower HC were more likely to require treatment for NAS (p = 0.01).

HC and BW when comparing Z-scores were not different between MMT and BMT. High maternal dosing of buprenorphine is associated with lower BW and HC Z-scores but dose effect is not seen with methadone. In addition, there seems to be an association between NAS severity and HC, especially in the BMT group.

It is known that small for gestational age (SGA) babies may be at an increased risk of cardiovascular diseases during adulthood. There is paucity of literature regarding comparative cardiac functions of SGA and appropriate for gestational age (AGA) babies in neonatal period. The present study was conceived to compare the cardiac function of term small and appropriate for gestational age (AGA) babies through a relatively novel echocardiographic index in early neonatal period.

To compare values of myocardial performance index (MPI) index (MPI = IVCT + IVRT/ET) at 48–72 hours of age among AGA and SGA babies.

Morphological and anthropometric assessment of serially born term babies was done at time of birth to recruit hundred each of AGA and SGA babies. Tissue Doppler Imaging (TDI) was done between 48–72 hours for each enrolled baby to assess both right and left ventricle MPI in each group.

Mean±SD values for right ventricular MPI in AGA and SGA groups were 0.268 + 0.007 and 0.30 + 0.026 respectively (p < 0.001). Mean±SD values for left ventricular MPI in AGA and SGA groups were 0.25 + 0.012 and 0.30 + 0.017 respectively (p < 0.001). There was significant negative correlation between MPI values for either ventricles and the birth weight (spearmen’s rho of –0.66) (p < 0.001). Mean±SD values for LVET in AGA and SGA group were 0.304 + 0.026 and 0.266 + 0.032 respectively (p < 0.001).

MPI had a higher absolute value in the SGA babies as compared to AGA babies. These observations point towards suboptimal cardiac performance among SGA babies as compared to AGA babies on the basis of myocardial performance index.

To determine the association between plasma hemoglobin (HB) at three time-points (birth, postnatal days 0–3 and 0–10) and spontaneous closure of the ductus arteriosus (sDAC).

A retrospective case-control study of preterm infants born (2013–2016) between 24 and 29 weeks of gestational age (GA) was conducted in a level three perinatal center in Switzerland. We collected hemoglobin at birth, between days 0–3 and 0–10 in two distinct groups: (i) patients treated for a PDA and (ii) patients with spontaneous closure of the ductus arteriosus (sDAC). Antenatal and postnatal demographic data and neonatal morbidity were collected. Bivariate analysis was performed and a stepwise logistic regression was done to investigate factors associated with sDAC.

We reviewed the medical chart of 184 premature infants of whom 146 (79.3%) satisfied eligibility criteria. Of these, 74 (51%) were classified as sDAC. Patients with sDAC were older (GA: 28 vs 27, p < 0.001), more stable (clinical risk index for babies score (CRIB score): 2 vs 5, p < 0.001) and had better clinical outcomes than patients who received treatment for a PDA. Infants in the sDAC group had a higher level of hemoglobin during the first ten postnatal days. Multiple logistic regression analysis revealed that lower HB level (day 0–10) were associated with failure of sDAC (p < 0.05).

This is one of the first studies to highlight a potential association between hemoglobin during the transitional period and sDAC. The biological nature of this observation requires prospective clarification.

Less invasive surfactant replacement therapy (SRT) methods have been linked to better respiratory outcomes. The primary aim of this study was to determine if Less Invasive Surfactant Administration (LISA) altered the rate of bronchopulmonary dysplasia (BPD) in preterm infants. Secondary objectives were to determine if LISA compared to Intubation Surfactant Extubation (InSurE) resulted in different respiratory outcomes and hospital course.

In this retrospective chart review, outcomes were compared in two preterm infant groups (25–32 weeks gestation). Infants in Group 1 received surfactant replacement therapy (SRT) via InSurE method, while infants in Group 2 received SRT via LISA method.

Regardless of SRT method utilized, there were no significant differences in rates of BPD between the two groups in infants born at 25–32 weeks gestation (30.6% vs 33.3%; P = 0.47).

Despite using LISA method rather than InSurE for SRT, premature infants continue to be at high risk for BPD. LISA shows promise as a safe, noninvasive SRT alternative to invasive methods like InSurE.

Asymmetric Dimethyl Arginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) is important in different diseases characterized by decreased nitric oxide (NO) availability. We aimed to assess the serum ADMA level in preterm infants suffering from respiratory distress syndrome (RDS) and its relationship with pulmonary outcomes.

This prospective study included 50 preterm neonates suffering from RDS aging≤32 weeks and weighing≤1500  gm. Serum ADMA levels were estimated in the 1st and 28th day of life by ELISA, and its correlation with surfactant requirement, duration of ventilation, and development of BPD was assessed.

Fifty preterm infants with RDS were included, 30 infants were treated with surfactant within 12 hours after birth, the 1stday ADMA level was higher significantly in infants who required surfactant treatment than infants without surfactant treatment, At 36 weeks postmenstrual age, 16 infants were diagnosed with BPD, the 28th day ADMA level was significantly higher in infants with BPD than others without BPD. 1st-day ADMA level was significantly correlated with days on mechanical ventilation but there were no significant correlations between 1st day ADMA and days on CPAP and days on supplemental O2.

Elevated serum ADMA level in preterm neonates with RDS estimated in the 1st and 28th day of life is a good predictor for pulmonary morbidities such as surfactant requirement, duration of mechanical ventilation, and development of BPD.

The optimal oxygen saturation target in preterm infants is not known. In this study, we aimed to assess the effect of lower oxygen saturation targets on the rate of bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and pulmonary hypertension (PH) in preterm infants.

Retrospective cohort study comparing BPD, ROP, and PH incidence among two cohorts of infants born at≤32 weeks gestation with different oxygen saturation targets at≥34 weeks post-menstrual age (PMA): cohort 1, 94–98% (n = 126); cohort 2, 92–97% (n = 121). Groups compared by Chi-square test, t-test, and multivariable logistic regression.

When comparing cohort 1 (average gestational age 29.8 weeks, average birth weight 1271g) with cohort 2 (average gestational age 29.6 weeks, average birth weight 1299g), there was no difference in rate of BPD (24% vs. 19%, p = 0.38), ROP (4% vs. 3%, p = 0.49), or PH (2% vs. 4%, p = 0.44).

An oxygen saturation target of 92–97% at≥34 weeks PMA was not associated with a higher rate of PH or lower rate of BPD or ROP when compared with a higher target of 94–98%.

Postnatal exposure to red blood cell transfusion (RBCT) in premature infants is an important risk factor for Retinopathy of Prematurity (ROP) progression. We hypothesized that higher number and earlier timing of RBCT are associated with worse ROP severity and result in laser treatment at an earlier postmenstrual age (PMA) in very low birth weight (≤1500 g, VLBW) infants.

A retrospective medical record review of 631 VLBW infants over a 5-year period was performed. Demographic features and potential clinical risk factors including number of RBCT, ROP severity, and progression to laser treatment were collected to evaluate predictors of severe ROP. ANCOVA, pairwise post-hoc analyses, and multivariate regression were used to determine associations between frequency and timing of RBCT and ROP severity.

Of the 456 eligible infants, 61 developed severe ROP (13%). There was significant correlation between number of RBCTs and ROP severity, adjusted for gestational age and birthweight (Adjusted R² = 0.53; p < 0.001). Compared to infants with No/Mild and Type 2 ROP, infants with Type 1 ROP received more RBCTs, with higher number of RBCTs per week during the first month of life (mean RBCT in ROP No/Mild 5.7±0.4 vs Type 2 16.3±1.8 vs Type 1 22.4±1.5, p = 0.042). Laser-treated infants received a higher number of RBCTs than non-treated infants (mean RBCT 22.3 vs. 6.5, p < 0.001) but no correlation was observed between number of RBCTs and PMA at time of laser treatment.

Higher number of RBCTs in early postnatal life of VLBW infants was associated with more severe ROP.

There is no consensus on how to wean infants from Nasal Continuous Positive Airway Pressure (NCPAP). We hypothesized that ceasing NCPAP abruptly would decrease the duration required, compared with a gradual wean.

This retrospective chart review included preterm infants requiring NCPAP for over 48 hours. Cohort1 weaned NCPAP by cycling on and off, while cohort 2 ceased NCPAP abruptly. The primary outcome was total days on NCPAP. Secondary outcomes included rate of bronchopulmonary dysplasia, weight gain, duration of hospital stay, and compliance with the use of stability criteria.

81 infants met inclusion criteria in cohort one, and 89 in cohort two. Median days on NCPAP were 17.0 and 11.0 days, respectively, not significant. There was no significant difference in secondary outcomes.

There was no significant association between the two NCPAP weaning protocols and the outcomes studied.

To determine the predictors of mortality following early rescue surfactant therapy in preterm babies with respiratory distress syndrome.

Prospective cohort study enrolling babies between 28 weeks to 34 weeks with respiratory distress syndrome requiring early rescue surfactant therapy. For statistical analysis babies were further divided into two subgroups: survivors and non-survivors. Maternal and neonatal variables were compared between the two groups to find out the predictors of mortality.

Out of total 110 babies, 72 (65.45%) survived. The mean birth weight and mean gestational age of the study population was 1614.36 (±487.86) g and 31.40 (±2.0)1 weeks, respectively. Birth weight < 1500 g, gestational age < 32 weeks, primiparity, vaginal delivery, prolonged rupture of membranes, lack of antenatal steroid cover, bag and mask ventilation at birth, sepsis, apneic episodes and mechanical ventilation were significantly associated with death on univariate analysis. On multivariate analysis, very low birth weight, vaginal delivery, lack of antenatal steroid cover, bag and mask ventilation at birth and mechanical ventilation were found to be independent predictors of mortality.

Some of the identified predictors of mortality are modifiable and can be used to draw up a screening tool to predict the clinical severity and mortality among these babies.

In premature infants, clinical changes frequently occur due to sepsis or non-infectious conditions, and distinguishing between these is challenging. Baseline risk factors, vital signs, and clinical signs guide decisions to culture and start antibiotics. We sought to compare heart rate (HR) and oxygenation (SpO₂) patterns as well as baseline variables and clinical signs prompting sepsis work-ups ultimately determined to be late-onset sepsis (LOS) and sepsis ruled out (SRO).

At three NICUs, we reviewed records of very low birth weight (VLBW) infants around their first sepsis work-up diagnosed as LOS or SRO. Clinical signs prompting the evaluation were determined from clinician documentation. HR-SpO₂ data, when available, were analyzed for mean, standard deviation, skewness, kurtosis, and cross-correlation. We used LASSO and logistic regression to assess variable importance and associations with LOS compared to SRO.

We analyzed sepsis work-ups in 408 infants (173 LOS, 235 SRO). Compared to infants with SRO, those with LOS were of lower GA and BW, and more likely to have a central catheter and mechanical ventilation. Clinical signs cited more often in LOS included hypotension, acidosis, abdominal distension, lethargy, oliguria, and abnormal CBC or CRP

(p < 0.05). HR-SpO₂ data were available in 266 events. Cross-correlation HR-SpO₂ before the event was associated with LOS after adjusting for GA, BW, and postnatal age. A model combining baseline, clinical and HR-SpO₂ variables had AUC 0.821.

In VLBW infants at 3-NICUs, we describe the baseline, clinical, and HR-SpO₂ variables associated with LOS versus SRO.

In the developing countries, neonatal sepsis is the most common complication in neonatal period. It is as a systemic inflammatory response because of infection. Laboratory indicators, do not have satisfactory sensitivity. Thus, early identification of sepsis is still needed. Because PTX3 may be a faster acute-phase protein that is not liver-dependent, it is probable that it is superior to traditional biomarkers for mirroring rapid inflammatory courses.

A prospective case control study design was used to determine the sensitivity of pentraxin 3 in the diagnosis of neonatal sepsis to allow early diagnostic tool. This study was carried out on neonatal ICU unit in Suez Canal University Hospital and the studied population were divided into two groups, including patients diagnosed with neonatal sepsis, based on clinical, laboratory and positive blood culture results, and control group

The study found that there was statistically significant differences between both groups in serum CRP values in diseased and control group (Mean = 49.3±37.4 mg/L, 26.8±17.2 mg/L, p < 0.05), and pentraxin values in diseased and control group (Mean = 5.2±3.7 mg/L, 2.3±0.78 mg/L, p < 0.0001). In addition, there were statistically significant correlations between pentraxin and serum CRP concentrations (p < 0.05) in diseased group. ROC curve showed that serum CRP demonstrated good diagnostic accuracy in predicting neonatal sepsis AUC = 0.875 with sensitivity of 100% and specificity of 92.3%.

Serum PTX3 may be a promising acute-phase protein for interpretation of affected newborns with symptoms and signs of sepsis.

Early empiric antibiotic exposure appears to negatively influence feeding tolerance in preterm infants. However, the effect of prolonged antibiotic treatment is unknown. The objective of this study was to investigate whether prolonged antibiotics impact the time to full enteral feed in infants less than 29 weeks of gestational age with negative blood cultures.

Retrospective data for infants less than 29 weeks gestation age were retrieved from the PEARL-Peristat perinatal registry in Qatar. Exclusion criteria were major congenital anomalies, conditions requiring surgery in the first 10 days of life, positive blood cultures in the first 48 hours of life, and death within the first week of life. Antibiotic courses were categorized as prolonged if continued more than 48 hours. The primary outcome was the duration of total parenteral nutrition.

Of 199 study infants, 185 (92.9%) underwent antibiotic treatment for > 48 hours despite negative blood cultures. The median duration of parenteral nutrition was not significantly different between the prolonged and short antibiotic groups (25 and 22 days, respectively; p = 0.139). Infants with prolonged antibiotic courses experienced non-significantly higher levels of necrotizing enterocolitis (7.1% and 18.4%, respectively), bronchopulmonary dysplasia (28.6% and 45.4%, respectively), and retinopathy of prematurity (14.3% and 38.4%, respectively). There were no differences in the late-onset sepsis rate (78.6% and 82.1%, respectively) and the in-hospital death rate (7.1% and 7.6%, respectively).

Prolonged antibiotic treatment in infants less than 29 weeks gestation with negative blood cultures has no significant impact on the time to full enteral feed.

Wide variation in the care practices and survival rates of neonates born at peri-viable gestational ages of 22⁺⁰ – 24⁺⁶ weeks. This study elucidates the postnatal risk factors for morbidity/mortality, contrasts the care practices and short-term outcomes of this vulnerable group of preterm neonates from a single center with others.

Retrospective study of neonates born at 22⁺⁰ –24⁺⁶ weeks in a level 3 neonatal intensive care unit in UK, over a period of 4 years (2016–2019).

94 neonates given active care were studied. Survival until discharge was 51.1%(22–23 wks –44%, 24 wks –59.1%) and survival with no major brain injury (MBI) [grade III/IV IVH, cystic periventricular leukomalacia] was 38.3%(22–23 wks –32%, 24 wks –45.4%). Of those who survived until discharge, 75%had no MBI (22–23 wks –72.7%, 24 wks –76.9%). Neonates requiring significant respiratory support within first 72 hours as well as needing rescue high frequency ventilation had significantly high risk of mortality or MBI [aOR –7.17 (2.24–25.79), p = 0.00; 4.76 (1.43–20.00), p = 0.01].

Survival rate differed from other centres. MBI was low amongst survivors. Severe respiratory disease in the initial days was associated with a higher risk of death or MBI.

Micro-premature newborns, gestational age (GA) ≤ 25 weeks, have high rates of mortality and morbidity. Literature has shown improving outcomes for extremely low gestational age newborns (ELGANs) GA ≤ 29 weeks, but few studies have addressed outcomes of ELGANs ≤ 25 weeks.

To evaluate the trends in outcomes for ELGANs born in New Jersey, from 2000 to 2018 and to compare two subgroups: GA 23 to 25 weeks (E1) and GA 26 to 29 weeks (E2).

Thirteen NICUs in NJ submitted de-identified data. Outcomes for mortality and morbidity were calculated.

Data from 12,707 infants represents the majority of ELGANs born in NJ from 2000 to 2018. There were 3,957 in the E1 group and 8,750 in the E2 group. Mortality decreased significantly in both groups; E1, 43.2% to 30.2% and E2, 7.6% to 4.5% over the 19 years. The decline in E1 was significantly greater than in E2. Most morbidities also showed significant improvement over time in both groups. Survival without morbidity increased from 14.5% to 30.7% in E1s and 47.2% to 69.9% in E2s. Similar findings held for 501–750 and 751–1000g birth weight strata.

Significant declines in both mortality and morbidity have occurred in ELGANs over the last two decades. These rates of improvements for the more immature ELGANs of GA 23⁰ to 25⁶ weeks were greater than for the more mature group in several outcomes. While the rates of morbidity and mortality remain high, these results validate current efforts to support the micro-premature newborn.

Diabetes insipidus (DI) is a disease resulting from defects in the arginine vasopressin system responsible for regulating body water homeostasis. It is characterized by polyuria with increased serum osmolality and sodium and can result from congenital or acquired disorders.

A baby was admitted to NICU for extreme prematurity (25 weeks gestation), extreme low birth weight (900 grams) and respiratory distress. He received one dose of Surfactant and was ventilated using high frequency jet ventilation for development of pulmonary interstitial emphysema. After nine days, he still required high settings with development of early chronic lung changes in the form of atelectasis. Therefore, he was started on a course of dexamethasone following the DART study protocol (Dexamethasone: A Randomized Trial). However, after six days (cumulative dose of 0.75 mg/kg/day) he developed polyuria (7.4 ml/kg/h) with increased serum sodium (150 mmol/L) and osmolality (348 mmol/L). He lost 85 grams of his weight in 24 hours, which represented a 9.8 %weight loss. The findings were suggestive of DI and given there were no apparent causes other than dexamethasone, it was discontinued. Over the following 48 hours, polyuria and hypernatremia gradually resolved, reaching 3.5 ml/kg/h, and 140 mmol/L respectively.

The use of dexamethasone is not an uncommon practice in tertiary care neonatal units. To our knowledge, our case is the first report of neonatal DI secondary to the use of dexamethasone. We recommend closely monitoring urine output and serum electrolytes in preterm infants receiving dexamethasone.