Journal of Neonatal-Perinatal Medicine

Neonatal hyperbilirubinemia is a common medical emergency in early neonatal period. Unconjugated bilirubin is neurotoxic and can lead to lifelong neurological sequelae in survivors.

To find out the association between serum bilirubin and neurodevelopmental outcome at 1 year of age using Development Assessment Scale for Indian Infants (DASII).

A prospective cohort study was conducted in the Department of Pediatrics of a tertiary care institution of Central India between January 2018 and August 2019. Total 108 term healthy neonates, with at least one serum bilirubin value of >15 mg/dl, were included. Subjects were divided into three groups based on the serum bilirubin; group 1: (15–20 mg/dl) –85(78.7%) cases, group 2: (20–25 mg/dl) –17(15.7%), and group 3: (>25 mg/dl) –6(5.5%). Developmental assessment was done using DASII at 3, 6, 9, 12 months of age.

Out of 108 cases, 101(93.5%) received phototherapy, and 7(6.5%) received double volume exchange transfusion. Severe delay was observed in 5(4.6%) and mild delay in 2(1.9%) cases in the motor domain of DASII at one year. Severe delay in the motor domain was associated with mean TSB of 27.940±2.89 mg/dl and mild delay with mean TSB of 22.75±1.76 mg/dl (p = 0.001). On cluster analysis, delay was observed in locomotion 1 score in 11(13%) cases (p = 0.003) and manipulation score in 6(7.1%) cases in group 1.

Increased serum bilirubin was a significant risk factor for the delayed neurodevelopment in babies with neonatal jaundice. Even a moderate level of bilirubin significantly affects the developmental outcome.

As neonates transition from a relatively hypoxic environment to extra-uterine life, arterial oxygen saturation dramatically increases. This transition occurs while most organs have not fully matured. The ability for immature tissue to adequately extract and utilize oxygen remains largely unknown. With the development of near-infrared spectroscopy (NIRS), measuring specific tissue oxygen saturation (StO2) noninvasively, clinicians can measure StO2 and determine if adequate tissue oxygenation is maintained. The objective of this study is to determine the relationships of NIRS brain and somatic autoregulation function to patients’ severity of illness.

In this prospective cohort pilot study, after parental consent, neonates less than 34 weeks with arterial access, were enrolled. The FORE-SIGHT NIRS probe was placed on the forehead and abdominal wall for 24 hours. Continuous arterial blood pressure, SpO2 and cerebral and somatic NIRS were used to derive autoregulation function.

Data was obtained from 17 neonates (0.540 to 2.37 kg, gestation 23.0 to 33.2 weeks). The autoregulation function categorizes pressure passive index (PPI) values as good, borderline, or poor. For normal autoregulation function, PPI values tend to be low and fairly constant for a range of MAP. The PPI borderline zone is a hypothetical range of PPI values where autoregulation function transitions from good to poor.

Our results show most premature neonates, as long as they maintained normal BP and systemic circulation can autoregulate cerebral perfusion. When BP are above or below the normal MAP for age, the neonate is at risk for losing brain and somatic autoregulation.

Children born prematurely (<37 gestational weeks) are at risk for a variety of adverse medical events. They may experience ischemic and/or hemorrhagic events leading to negative neural sequelae. They are also exposed to repeated stressful experiences as part of life-saving care within the neonatal intensive care unit (NICU). These experiences have been associated with methylation of SLC6A4, a gene which codes for serotonin transport proteins, and is associated with anxiety, depression, and increased incidence of autism spectrum disorders.

The purpose of this study was to examine the effects of altered serotonin levels on behavioral and neuroanatomical outcomes in a neonatal rodent model with or without exposure to hypoxic-ischemic (HI) injury.

Wistar rat pups were randomly assigned to either HI injury or sham groups. Pups within each group were treated with a chronic SSRI (Citalopram HBr) to simulate the effects of SLC6A4 methylation, or saline (NS). Subjects were assessed on behavioral tasks and neuropathologic indices.

HI injured subjects performed poorly on behavioral tasks. SSRI subjects did not display significantly greater anxiety. HI + SSRI subjects learned faster than HI+NS. Histologically, SSRI subjects had predominantly larger brain volumes than NS.

SSRI treated subjects without injury showed patterns of increased anxiety, consistent with theories of SLC6A4 methylation. The paradoxical trend to improved cognition in HI+SSRI subjects relative to HI alone, may reflect an unexpected SSRI neuroprotective effect in the presence of injury, and may be related to serotonin-induced neurogenesis.

Late-onset neonatal sepsis (LONS) detection is problematic as no single examinations (blood culture, c-reactive protein (CRP), procalcitonin (PCT)) are reliable. Toll-like receptors (TLRs), which detect the presence of pathogen-associated molecular patterns is a promising novel biomarker, but less studied in LONS. This study aimed to determine neutrophils and monocytes TLR2 and TLR4 expression in LONS and their diagnostic value.

A cross-sectional study conducted in May and June 2017 involving 52 neonates with clinical late-onset (>72 hours of age) sepsis. We examine complete blood count, I/T ratio, CRP, PCT, as well as TLR2 and TLR4 expression to compared with blood culture as the gold standard. We classified cases into proven or unproven sepsis.

The incidence of LONS was 32.6% in the subjects. The expression of TLR2 was low in LONS, while TLR4 was high. TLR4 neutrophil expression has 88.2% sensitivity, 20% specificity, 34.9% positive predictive value (PPV), 77.8% negative predictive value (NPV), and an AUC of 0.541. TLR4 monocyte expression has 92.1% sensitivity, 11.4% specificity, 34% PPV, 80% NPV, and an AUC of 0.528. The AUC of CRP is increased from 0.608 to 0.843 after combination with TLR4, comparable with CRP + PCT (AUC 0.829).

The increase in TLR4 expression has good sensitivity but low specificity. TLR4 expression, in combination with CRP, could become a reliable biomarker for the diagnosis of LONS.

This study’s aim is to evaluate lung ultrasound (LUS) efficacy in detecting opening and closing lung pressures and its correlation with the tracheal interleukin 6 (IL-6) level.

This single-blinded randomized controlled study was done at Ain Shams University Children’s Hospital neonatal intensive care units, Egypt. It consists of 44 mechanically ventilated preterm neonates with Respiratory Distress Syndrome (RDS). Initial LUS assessment was done followed by randomization to one of 2 groups; group I: 22 patients underwent LUS guided RM and group II: 22 patients underwent non-ultrasound guided RM. Tracheal IL-6 level was measured before and after RM in both groups.

The LUS scores showed a sensitivity of 86.7%, specificity of 62.10% and accuracy of 70.45% at the cut-off point >B1 grade. After RM, there was a higher percentage of changes in mean airway pressure (p = 0.03), FiO2 (p = 0.01), PaO₂/FiO₂ ratio (p = 0.01), and IL-6 (p < 0.01) in group I. The duration of oxygen requirement (6 vs.13.5 days, p = 0.01), invasive ventilation (3 vs.5.5 days, p = 0.03), non-invasive ventilation (2.5 vs. 5 days, p = 0.02) and NICU stay (21.5 vs. 42.5 days, p = 0.03) were less in group I. A positive correlation is found between reaeration score and the duration of O₂ requirement (p = 0.002), duration of invasive ventilation (p = 0.001), NICU length of stay (p = 0.002) and negative correlation with PaO₂/FiO₂ ratio before RM (p = 0.012). The best cut-off point for the reaeration score is >21 with a sensitivity of 75%, specificity of 71.43% and area under the curve of 78.1%.

LUS-guided RM achieved earlier lowest FiO₂, shorter O₂ dependency, lesser NICU stay and marked decrease in lung inflammation by decreasing atelectotrauma and shortening the duration of invasive ventilation.

Prevalence of extubation failure in neonates may be up to 80%, but evidence to determine if a neonate is ready for extubation remains unclear. We aim to evaluate a spontaneous breathing trial accuracy with minimum pressure support to predict success in neonates’ extubation and identify variables related to failures.

This is a diagnostic accuracy study based on a cohort study in an intensive care unit with all eligible newborn infants subjected to invasive mechanical ventilation for at least 24 hours submitted to the trial for 10 minutes before extubations. The outcome was failures of extubations, considered if reintubation was needed until 72 hours.

The incidence of failure was 14.7%among 170 extubations. There were 145 successful extubations; of these, 140 also passed the trial with a sensitivity of 96.5%(95%CI: 92.1–98.9). Of the 25 extubations that eventually failed, 16 failed the test with a specificity of 64.0%(95%CI: 42.5–82.0). The negative predictive value was 76.2%, and the positive predictive value was 94%. In stratifying by weight, the accuracy was >98.7%for neonates weighting >2500 g, but 72.5%for those weighing <1250 g. Extubation failures occurred more frequently in smaller (p = 0.01), preterm infants (p = 0.17), with longer ventilation time (p = 0.05), and having a hemodynamically significant persistent arterial duct (p = 0.01), compared with infants whose extubation was successful.

The spontaneous breathing trial with minimum pressure support ventilation seems to predict extubation success with great accuracy in full-term and larger neonates.

Based on the most recently published recommendations from the Committee on the Fetus and Newborn (COFN), three approaches currently exist for the use of risk factors to identify infants who are at increased risk of early-onset sepsis (EOS). Categorical risk factor assessments recommend laboratory testing and empiric antibiotic therapy for all infants born to mothers with a clinical diagnosis of chorioamnionitis. Risk assessments based on clinical condition recommend frequent examinations and close vital sign monitoring for infants born to mothers with chorioamnionitis. The Kaiser Permanente EOS risk calculator (SRC) is an example of the third approach, multivariate risk assessments. The aim of our study was to compare the three risk stratification approaches recommended by the COFN for management of chorioamnionitis-exposed infants.

Retrospective study of 1,521 infants born ≥35 weeks to mothers with chorioamnionitis. Management recommendations of the SRC were compared to the recommendations of categorical risk assessment and risk assessment based on clinical condition (CCA).

Hypothetical application of SRC and CCA resulted in 79.6% and 76.8–85.1% respectively fewer infants allocated empiric antibiotic therapy. While CCA recommended enhanced observation for all chorioamnionitis-exposed infants, SRC recommended routine care without enhanced observation in 44.3% infants. For the six infants (0.39%) with EOS, SRC and CCA recommended empiric antibiotics only for three symptomatic infants.

The SRC and CCA can reduce antibiotic use but potentially delay antibiotic treatment. The SRC does not recommend enhanced observation with frequent and prolonged vital signs for >44% of chorioamnionitis-exposed infants.

Evidence supports delayed cord clamping (DCC) in preterm infants. However, practice variation exists, and many preterm infants do not receive DCC despite multiple benefits and lack of harm. We aim to 1) study the rate of DCC in preterm infants, 2) compare the difference between infants who received DCC and those who did not receive DCC and 3) investigate the reasons for not performing DCC.

We conducted this retrospective study to evaluate DCC practice at our institution since its implementation in September 2015. We collected and analyzed the data on DCC of 30–45 sec duration in inborn infants < 35 weeks gestation admitted to the neonatal intensive care unit from June 2016- June 2019. The primary outcome was the rate of delayed cord clamping.

Of the 447 infants, 275 (62%) received DCC. The rate of DCC was 36%, 54%, and 66% in infants < 27 weeks, 27–29 weeks and > 30 weeks gestation, respectively (p = 0.001). Infants not receiving DCC were smaller, of lower gestational age, and more likely to be delivered via cesarean section than those who received DCC (p < 0.0001). Infants not receiving DCC had a higher rate of receiving PPV or intubation and a 1minute Apgar score of < 5 compared to those receiving DCC. We could not establish the reason for not performing DCC because of inadequate documentation in the medical records.

The rate of DCC is low in clinical practice, particularly among extremely preterm infants.

Necrotizing enterocolitis (NEC) is a serious, often fatal, disease of neonates. Minimal data exists regarding the optimal method for reintroducing feeds after successful treatment. This study aims to compare outcomes in patients reintroduced to bolus or continuous feeds after treatment for medical NEC.

A retrospective review of infants treated for medical NEC in the neonatal intensive care unit (NICU) from 2011-2018 was performed. Demographics, information about initial feeds, clinical diagnosis data, and information about reintroduction of feeds were recorded. Patients with significant congenital heart disease or those who required procedures for treatment were excluded.

Sixty-one patients were analyzed; 45 were reintroduced to bolus feeds and 16 to continuous feeds. There were no differences between the two groups. Bolus-fed patients reached goal feeds quicker (p = 0.007), required fewer days of parenteral nutrition (p = 0.002), had shorter hospital stays (p = 0.013) and were discharged faster from diagnosis to discharge (p = 0.002). Differences were confirmed with multivariate regression.

Infants given bolus feeds reached goal feeds faster, required less time on PN, and were discharged quicker than those fed continuously. This suggests that, compared to continuous feeding, bolus feeding is associated with superior clinical outcomes among patients treated for medical NEC.

Identify perinatal risk factors associated with SIP

This was a retrospective case-control study of SIP in infants born at ≤28 weeks of gestation and admitted between 1995 and 2016 at a tertiary care NICU. Infants with NEC or other GI abnormalities were excluded. Cases of SIP were matched with gestational age-matched controls with the closest birth date. Maternal, infant and birth related factors were evaluated using univariate analyses and significant factors were evaluated using multiple logistic regression.

25 cases of SIP were matched with 25 controls. No maternal factors reached statistical significance. Being one of twins increased the odds of SIP 29-fold. Birth-order or weight-discrepancy in twin had no association of SIP within twin pairs.

Twins are at significantly higher risk for SIP. The association of SIP and twin gestation was independent of previously reported risk factors of perinatal indomethacin or magnesium sulfate and merits further study.

PICC line use is a common practice in neonatal units, but it is associated with various complications. Catheter migration is the most common complication in neonates. Periodic imaging is recommended to monitor the tip position of the PICCs, but the optimal frequency is undetermined. The incidence, timing and risk factors that are associated with PICC migration have not been fully investigated beyond 24 hrs in neonates. The aim of the study was to determine the incidence, timing and risk factors that are associated with peripherally inserted central venous catheter (PICC) migration in neonates.

This was a single center, retrospective study of 168 PICCs placed in 141 neonates in the neonatal intensive care unit (NICU) between 2015 and 2016. The incidence of catheter migration was determined radiographically at 12–24 hrs and every third day after insertion until it was removed.

Overall incidence of PICC migration was 28%and most commonly was detected within the first three days after PICC placement (83%). The incidence of PICC migration was higher in males. The PICC migration was associated with difficulty advancing the PICC at the time of insertion and PICC dressing change.

Serial evaluation of PICC placement in neonates is required to maintain proper position. Based on our experience in our unit, we recommend periodic imaging at 12–24 hrs and on the third day after PICC placement as most migration occurred within three days after insertion.

Timely delivery and magnesium sulfate (MgSO₄) are mainstay in the treatment of preeclampsia with severe features (PWSF). Premature delivery, severity of illness and mother-infant separation may increase the risk for breastfeeding (BF) initiation failure.

To compare BF initiation among women with late-onset PWSF treated with MgSO₄ to women with late-onset preeclampsia without severe features (WOSF) who did not receive MgSO₄.

Retrospective study of 158 women with PWSF and 104 with WOSF who delivered at ≥34 weeks. Intention to BF, formula feed (FF) or partially BF was declared prenatally. At discharge, exclusive BF included direct BF or direct BF with expressed breast milk (EBM).

PWSF and WOSF groups were similar in age, race, and obstetric history. PWSF and WSOF differed in primiparity (65 & 51%), late preterm births (73 vs 15%), admission to NICU (44 &17%) and mother (5 & 4d) and infant (6 & 3d) hospital stay. Both groups were similar in intention to BF (80 & 84%), to FF (16 & 13%) and to partially BF (5 & 5%). At discharge, exclusive BF (37 & 39%), partial BF (33 & 31%) and FF (30 & 30%) were similar. Exclusive BF in the PWSF group was 43% direct BF, 28% direct BF and EBM and 29% EBM alone whereas in the WOSF group exclusive BF was 93% direct BF and 7% direct BF and EBM.

BF initiation rates for women with PWSF and WOSF were similar. EBM alone or with direct BF enabled infants in the PWSF group to exclusively BF at discharge.

Knowledge on short-term outcomes of preterm infants is important for quality control. Our objective was to analyze the outcomes of very low birth weight infants admitted to our neonatal intensive care unit over a ten years’ period and to compare the results with internationally published data.

We analyzed the outcome measures for all live born infants with birth weight (BW) of 400–1500 grams and gestational age (GA) of 23–32 weeks born at King Faisal Specialist Hospital & Research Centre between 2006 and 2015. Results were compared to data from four international neonatal networks.

During the study period, we admitted 528 infants born at a gestational age of≥23 and≤32 weeks with a very low birth weight (VLBW) of 400–1500 grams. Mean (SD) GA was 28 (2.4) weeks and mean (SD) BW was 1007 (290) grams. A hundred and twenty-nine (24.4%) infants were small for gestational age and major congenital anomalies were present in 56 (10.6 %) infants. The rate of bronchopulmonary dysplasia (BPD) was 24.4 %, necrotizing enterocolitis (NEC) 9.1%, patent ductus arteriosus (PDA) 29.9%, severe intraventricular hemorrhage (IVH)10.8 %, periventricular leukomalacia (PVL) 5.7%, severe retinopathy of prematurity (ROP) 8%, and late-onset sepsis was 18.8%. The incidences of major neonatal outcomes such as CLD, NEC, severe IVH and severe ROP were comparable to the international cohorts.

In our population of preterm infants, survival rates and complications of prematurity were comparable to international data.

The vein of Galen aneurysm (VGAM) is the most common type of arteriovenous malformation in the neonate. These neonates commonly present with high output cardiac failure that may be associated with pulmonary hypertension. The medical management and stabilization of these neonates can be challenging before staged transarterial embolization of the aneurysm is undertaken.

A 2.34 kilogram neonate, antenatally diagnosed to have VGAM, was born at 36 weeks of gestation for fetal distress. The neonate failed to respond to medical management including inotropes, high frequency mechanical ventilation and inhaled nitric oxide. The patient’s high-output heart failure and persistent pulmonary hypertension were stabilized with veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) using central cannulation. Further transarterial staged embolization of the VGAM was undertaken on VA-ECMO support.

There may be a role of VA-ECMO using central cannulation to optimize management of high output cardiac failure and persistent pulmonary hypertension in neonatal VGAM patients who fail medical management to facilitate staged transarterial embolization of the VGAM.

Disseminated intravascular coagulation (DIC) with Kasabach-Merrit syndrome from a large hepatic hemangioma is life-threatening. We report a case of giant hepatic hemangioma of the newborn with KMS.

The patient was born at 37 gestational weeks and 2 days via cesarean section; weight at birth was 2952 g. Congenital duodenal atresia was noted during the fetal period. DIC developed after delivery and a giant liver hemangioma was diagnosed via abdominal CT. The cause of DIC was Kasabach–Merritt syndrome owing to a giant hepatic hemangioma. First, combination therapy of 2 mg/kg/day of prednisolone and 0.2 mg/kg/day of propranolol was initiated form enterostomy. However, the size of the hepatic hemangioma did not alter, as observed via image evaluation. Therefore, 0.3 mg/kg/day of everolimus was administered frorm enterostomy. Subsequently, the size of the hepatic hemangioma was assessed via image evaluation. Although it did not alter, blood flow to the hepatic hemangioma decreased and thrombocytopenia was also suppressed. We performed hepatic lateral segmentectomy, radical operation for duodenal atresia. The pathological diagnosis of the removed tumor was infantile hemangioma.

We report everolimus may be useful when PSL and propranolol are ineffective.

Anal skin tags are commonly seen with anal fissures, haemorrhoids, inflammatory bowel disease and their association have been extensively studied. However the presence of anal skin tag in food protein-induced allergic proctocolitis has rarely been reported in literature. We report a neonate with food protein-induced allergic proctocolitis who presented with blood in stool and anal skin tag.

A 26-day-old baby presented with history of passing intermittent blood in stools for two days. The baby was exclusively breast-fed and was well-appearing with no failure to thrive. Two anal skin tags were present but there was no evidence of anal fissures or haemorrhoids. The biopsy of anal skin tag showed fibroepithelial polyp. Colonoscopy was suggestive of food protein-induced allergic proctocolitis. In view of poor response to elimination diet in the mother and extensively hydrolysed formula, the baby was started on amino acid formula with complete recovery.

Through this case we wish to highlight that clinicians should consider food protein-induced allergic proctocolitis in their differential diagnosis in a neonate presenting with blood in stools and anal skin tag.