Neonatal outcomes of non-vigorous neonates with meconium-stained amniotic fluid before and after change in tracheal suctioning recommendation.

OBJECTIVE: To evaluate the short-term outcomes of non-vigorous infants born through meconium-stained amniotic fluid (MSAF) before and after implementation of no-tracheal suctioning guidelines. STUDY DESIGN: Single-center retrospective study of ≥36-week gestation neonates with MSAF. RESULTS: During routine-suction era (9/2013-12/2014), 280/2306 neonates (12%) were born through MSAF and 39 (14%) were non-vigorous. Thirty (77%) of non-vigorous infants underwent tracheal suctioning. In the no-suction era (1/2017-12/2018), 282/2918 neonates (9.7%) were born through MSAF and 30 (10.6%) were non-vigorous and one needed intubation. Admissions for meconium aspiration syndrome (15% vs 53%) and respiratory distress (18% vs 57%) were significantly higher among non-vigorous infants in the no-suction era. CONCLUSIONS: In this single-center study, non-vigorous infants born through MSAF without routine-tracheal suctioning had a higher incidence of NICU admission for MAS and respiratory distress compared to the routine-suction era. Multicenter randomized trials evaluating tracheal suction in non-vigorous infants with MSAF are warranted.

Change in neonatal resuscitation guidelines and trends in incidence of meconium aspiration syndrome in California.

OBJECTIVE: To describe trends in the incidence and severity of meconium aspiration syndrome (MAS) around the release of revised Neonatal Resuscitation Program (NRP) guidelines in 2016. STUDY DESIGN: The California Perinatal Quality Care Collaborative database was queried for years 2013-2017 to describe the incidence and outcomes of infants with MAS. Results were analyzed based on both individual years and pre- vs. post-guideline epochs (2013-15 vs. 2017). RESULT: Incidence of MAS decreased significantly from 2013-15 to 2017 (1.02 to 0.78/1000 births, p < 0.001). Among infants with MAS, delivery room intubations decreased from 2013-15 to 2017 (44.3 vs. 35.1%; p = 0.005), but similar proportion of infants required invasive respiratory support (80.1 vs. 80.8%), inhaled nitric oxide (28.8 vs. 28.4%) or extracorporeal membrane oxygenation (0.81 vs. 0.35%). CONCLUSION: While the study design precludes confirmation of implementation of the recent NRP recommendation, there was no increase in the incidence or severity of MAS following its release.

Magnetic resonance spectroscopy assessment of brain injury after moderate hypothermia in neonatal encephalopathy: a prospective multicentre cohort study.

BACKGROUND: In neonatal encephalopathy, the clinical manifestations of injury can only be reliably assessed several years after an intervention, complicating early prognostication and rendering trials of promising neuroprotectants slow and expensive. We aimed to determine the accuracy of thalamic proton magnetic resonance (MR) spectroscopy (MRS) biomarkers as early predictors of the neurodevelopmental abnormalities observed years after neonatal encephalopathy. METHODS: We did a prospective multicentre cohort study across eight neonatal intensive care units in the UK and USA, recruiting term and near-term neonates who received therapeutic hypothermia for neonatal encephalopathy. We excluded infants with life-threatening congenital malformations, syndromic disorders, neurometabolic diseases, or any alternative diagnoses for encephalopathy that were apparent within 6 h of birth. We obtained T1-weighted, T2-weighted, and diffusion-weighted MRI and thalamic proton MRS 4-14 days after birth. Clinical neurodevelopmental tests were done 18-24 months later. The primary outcome was the association between MR biomarkers and an adverse neurodevelopmental outcome, defined as death or moderate or severe disability, measured using a multivariable prognostic model. We used receiver operating characteristic (ROC) curves to examine the prognostic accuracy of the individual biomarkers. This trial is registered with ClinicalTrials.gov, number NCT01309711. FINDINGS: Between Jan 29, 2013, and June 25, 2016, we recruited 223 infants who all underwent MRI and MRS at a median age of 7 days (IQR 5-10), with 190 (85%) followed up for neurological examination at a median age of 23 months (20-25). Of those followed up, 31 (16%) had moderate or severe disability, including one death. Multiple logistic regression analysis could not be done because thalamic N-acetylaspartate (NAA) concentration alone accurately predicted an adverse neurodevelopmental outcome (area under the curve [AUC] of 0·99 [95% CI 0·94-1·00]; sensitivity 100% [74-100]; specificity 97% [90-100]; n=82); the models would not converge when any additional variable was examined. The AUC (95% CI) of clinical examination at 6 h (n=190) and at discharge (n=167) were 0·72 (0·65-0·78) and 0·60 (0·53-0·68), respectively, and the AUC of abnormal amplitude integrated EEG at 6 h (n=169) was 0·73 (0·65-0·79). On conventional MRI (n=190), cortical injury had an AUC of 0·67 (0·60-0·73), basal ganglia or thalamic injury had an AUC of 0·81 (0·75-0·87), and abnormal signal in the posterior limb of internal capsule (PLIC) had an AUC of 0·82 (0·76-0·87). Fractional anisotropy of PLIC (n=65) had an AUC of 0·82 (0·76-0·87). MRS metabolite peak-area ratios (n=160) of NAA-creatine (<1·29) had an AUC of 0·79 (0·72-0·85), of NAA-choline had an AUC of 0·74 (0·66-0·80), and of lactate-NAA (>0·22) had an AUC of 0·94 (0·89-0·97). INTERPRETATION: Thalamic proton MRS measures acquired soon after birth in neonatal encephalopathy had the highest accuracy to predict neurdevelopment 2 years later. These methods could be applied to increase the power of neuroprotection trials while reducing their duration. FUNDING: National Institute for Health Research UK.

Can Functional Polymorphisms in VEGF and MMP Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?

BACKGROUND: The pathophysiology of intraventricular hemorrhage (IVH) is multifactorial. This study attempts to identify genetic and clinical factors contributing to IVH in newborns with a focus on those born ≤28 weeks of gestation. METHODS: This was a prospective study of 382 consecutive newborns admitted to the neonatal intensive care unit. DNA purification was conducted using standard methods. TaqMan SNP assays were conducted for functional polymorphisms in VEGF (RS699947, RS2010963, RS3025039, and RS1570360) and MMP2 (RS243685 and RS2285053) genes. An RFLP assay was done for a polymorphism in MMP9 (RS3918242). RESULTS: The GG genotype in VEGF RS1570360 (p = 0.013) and the CC genotype in VEGF RS699947 (p = 0.036) were associated with a lower incidence of IVH amongst newborns ≤28 weeks of gestation. Chorioamnionitis, Caucasian race, and patent ductus arteriosus were associated with a higher incidence of IVH. A binary logistic regression analysis of clinical and SNP data that was significant from bivariate analysis demonstrated that VEGF RS1570360 was significantly associated with IVH (p = 0.017). CONCLUSION: This study demonstrated that the GA/AA genotype in VEGF RS1570360 and the AA/AC genotype in VEGF RS699947 were associated with higher incidence rates of IVH in newborns ≤28 weeks of gestation. A future study is warranted to comprehensively examine VEGF polymorphisms in association with IVH.

Impact of interhospital transport on the physiologic status of very low-birth-weight infants.

OBJECTIVES: To evaluate the change in physiologic stability of very low-birth-weight (VLBW) infants following transport using TRIPS (transport risk index of physiologic stability) score as a measure of physiologic stability and compare changes in TRIPS score in groups of VLBW infants who underwent shorter versus longer transport. STUDY DESIGN: Retrospective chart review. RESULTS: Our cohort of 106 infants, 44 (41%) of whom were females, had a mean birth weight of 777 g (standard deviation [SD] 159) and median gestational age of 26 weeks (range 23 to 32 weeks). Mean weight at transfer was 1,610 g (SD 924) and mean postnatal age at transfer was 56 days (SD 45). Median time on transport was 15 minutes (range 10 to 85 minutes). All 106 transports were ground transports. Of the 106 infants, 57 (54%) had deterioration, 20 (19%) had improvement, and 29 (27%) had no change in their physiologic status during transport. Comparison of the two transport duration groups based on median transport time as a cutoff point (i.e., ≤ 15 minutes and > 15 minutes) revealed a higher proportion of infants with deterioration in their physiologic status in the prolonged transport (>15 minutes) group (65% versus 45%; p = 0.03). Temperature change, either alone or in combination with other indices, was responsible for change in TRIPS score (deterioration or improvement) in 79% of these infants. CONCLUSIONS: Interhospital transport of VLBW infants may cause deterioration in their physiologic status, the likelihood of which is increased with longer duration of transport. Better temperature regulation during interhospital transport may decrease the chances of deterioration in physiologic status of VLBW infants.

B-type natriuretic peptide levels in preterm neonates with bronchopulmonary dysplasia: a marker of severity?

RATIONALE FOR THE STUDY: B type natriuretic peptide (BNP) is a hormone released in response to stretching of the ventricular wall. The role of BNP as a biomarker of bronchopulmonary dysplasia (BPD) has not been clarified. OBJECTIVE: To determine if plasma BNP concentrations correlate with the severity of BPD. METHODS: This prospective observational case control study included 60 preterm infants (≤32 weeks); 27 infants had no/mild BPD, 19 had moderate and 14 had severe BPD. BNP levels were measured at 36 ± 2 weeks PMA or within a week of discharge home. Groups were compared using Mann-Whitney's U-test, Kruskal-Wallis, and bivariate regression. RESULTS: Median (IQR) plasma levels of BNP in infants with moderate/severe BPD infants (n = 33) were higher as compared to those with no/mild BPD (n = 27); 27.1 (12.1-43.5) pg/ml versus 9.3 (6-18.5) pg/ml; P < 0.05 (Mann Whitney U). Median (IQR) BNP levels in infants with severe BPD (n = 14), 43.5 (28.4-189) pg/ml differed significantly from levels in those with moderate (n = 19), 22.8 (10.3-27.7) pg/ml; mild (n = 16), 11.5 (6.6-44.5 pg/ml); or no (n = 11), 8.1 (5-12.6 pg/ml) BPD (P < 0.001 Kruskal-Wallis). Based on receiver operating characteristic curves, BNP > 24.4 pg/ml at 36 ± 2 weeks PMA or discharge home was 85.7% sensitive and 76.1% specific for severe BPD. CONCLUSIONS: An elevation in plasma BNP was significantly associated with severe BPD. We speculate that plasma BNP measurement in infants with BPD may aid in risk-stratification and further targeted therapies.

Pneumatoceles in infants in the neonatal intensive care unit: clinical characteristics and outcomes.

OBJECTIVE: To describe the clinical characteristics and outcomes of neonatal intensive care unit patients with a radiographic diagnosis of pneumatocele. STUDY DESIGN: Retrospective chart review. RESULTS: Our cohort (n = 27) had a gestational age of 27 ± 5 weeks, birth weight of 1038 ± 760 g, and a predominance of females (59%) and black infants (74%). All infants were ventilated at the time of diagnosis at a median age of 12 days (range: 5 to 105 days). Endotracheal cultures sent from 25 infants revealed bacteria in 20 (80%). Clinical diagnosis of pneumonia was made in 18 (67%) infants. Pneumatoceles resolved in 17 (63%) infants, but persisted in 10 (37%) infants. Compared with infants with resolution of pneumatoceles, mortality (70% versus 0%, p < 0.001), positive endotracheal cultures (100% versus 67%, p = 0.05), and clinical diagnosis of pneumonia (100% versus 47%, p = 0.005) were significantly higher in infants with persistent pneumatoceles. CONCLUSIONS: In infants with pneumatoceles, positive endotracheal culture is a frequent finding and correlates with persistence. Persistence of pneumatoceles is associated with a higher mortality.

Neonatal thyrotoxicosis presenting as persistent pulmonary hypertension.

Neonatal hyperthyroidism is a rare condition caused either by transplacental passage of thyroid-stimulating immunoglobulins from a mother with Graves' disease or by activating mutations of the thyrotropin receptors and α-subunit of G-protein. The clinical features may vary. We report a case of neonatal thyrotoxicosis in an infant born to a mother with Graves' disease, who presented with cardiorespiratory failure and persistent pulmonary hypertension (PPHN). PPHN resolved with specific antithyroid treatment and extracorporeal membrane oxygenation was not required.

Isolated ruptured appendicitis presenting as pneumatosis intestinalis in a premature neonate.

We report a novel case of ruptured appendicitis in a premature neonate which radiographically mimicked necrotizing enterocolitis with free intraperitoneal air. On exploratory laparotomy, both the large and small intestines were normal.

Point-of-care testing for B-type natriuretic peptide in premature neonates with patent ductus arteriosus.

Patent ductus arteriosus (PDA) is highly prevalent in pre-term neonates (PTN) and has been recognized as a neonatal co-morbidity. The purpose of this study was to determine if levels of brain (or B-type) natriuretic peptide (BNP), a peptide secreted by ventricular myocytes in response to volume or pressure overload, correlate with the size of the PDA. In a prospective design, 52 PTN (no PDA: n=24; PDA: n=28) were studied after obtaining parental consent. Those with genetic anomalies and congenital heart disease, except for PDA and patent foramen ovale, were excluded. Echocardiographic estimates of the diameters of the PDA (or absence of PDA) were made concurrently with capillary blood collection for BNP assay. BNP levels in samples from PTN without PDA were 23.6 ng/L (median); 13.1 to 32.3 ng/L (IQR); initial samples (between days 3 and 7 of life) with small PDA (n=11), median 66.1 ng/L; 55.5 to 85.3 ng/L (IQR); with moderate PDA (n=6) median 284 ng/L; 204 to 622 ng/L (IQR); and with large PDA (n=11) 2410 ng/L median; 420 to 2770 ng/L (IQR). (p< 0.0001 for ANOVA; groupwise: p<0.05 for both no PDA vs. moderate and large PDA); Trend analysis suggested a strong association of BNP with size of PDA (p<0.001). Of 17 subjects with moderate to large PDA, pre and post-treatment (Ibuprofen; per standard protocol) data were obtained on 12 subjects. Pre-treatment BNP ranged from 111 to 5000 ng/L; post-treatment BNP decreased to 5.0 to 262 ng/L (p = 0.0005). Estimates of decision levels for treatment were made by examining dichotomized groups, i.e., no-to-small vs. moderate-to-large and using receiver-operator characteristic (ROC) curve analysis yielding a value of 123 ng/L. BNP may obviate repeated echocardiography as follow up after treatment, or to monitor future course of respiratory distress secondary to PDA in PTN.

Staphylococcal scalded skin syndrome in a preterm newborn presenting within first 24 h of life.

A preterm neonate was noted to have diffuse blanching erythema around the mouth followed by appearance of bullous lesions on the upper back, lower neck and right scapular areas at 23 h of life. The bullae subsequently ruptured leaving an extremely tender, erythematous, denuded area of the skin, which extended over next few hours to involve most of the upper back and right shoulder regions. Nikolsky sign was positive. Clinical diagnosis of staphylococcal scalded skin syndrome was made. The throat, blood, urine and cerebrospinal fluid cultures did not yield any growth, but wound culture was positive for Staphylococcus aureus. Treatment included administration of intravenous fluids and vancomycin for 10 days. The wound area was covered with vaseline and sterile gauge dressings. On day 5 of life, epithelialisation began and was complete on the seventh day of life. She was discharged home with intact skin, without scars, on day 12 of life.