Birju Shah

Neonatal sepsis: an old problem with new insights.

Neonatal sepsis continues to be a common and significant health care burden, especially in very-low-birth-weight infants (VLBW <1500 g). Though intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal infection dramatically, it still remains a major cause of neonatal sepsis. Moreover, some studies among VLBW preterm infants have shown an increase in early-onset sepsis caused by Escherichia coli. As the signs and symptoms of neonatal sepsis are nonspecific, early diagnosis and prompt treatment remains a challenge. There have been a myriad of studies on various diagnostic markers like hematological indices, acute phase reactants, C-reactive protein, procalcitonin, cytokines, and cell surface markers among others. Nonetheless, further research is needed to identify a biomarker with high diagnostic accuracy and validity. Some of the newer markers like inter α inhibitor proteins have shown promising results thereby potentially aiding in early detection of neonates with sepsis. In order to decrease the widespread, prolonged use of unnecessary antibiotics and improve the outcome of the infants with sepsis, reliable identification of sepsis at an earlier stage is paramount.

Prospective research on infants with mild encephalopathy: the PRIME study

Objective:To determine short-term outcomes of infants with evidence of hypoxia–ischemia at birth and classified as mild neonatal encephalopathy (NE) at <6 h of age.Study Design:Prospective multicenter study. Mild NE was defined as ⩾1 abnormal category in modified Sarnat score. Primary outcome was any abnormality on early amplitude integrated electroencephalogram (aEEG) or seizures, abnormal brain magnetic resonance imaging (MRI) or neurological exam at discharge.Results:A total of 54/63 (86%) of enrolled infants had data on components of the primary outcome, which was abnormal in 28/54 (52%): discontinuous aEEG (n=4), MRI (n=9) and discharge exam (n=22). Abnormal tone and/or incomplete Moro were the most common findings. MRI abnormalities were confined to cerebral cortex but two infants had basal ganglia and/or thalamus involvement. The 18 to 24 months follow-up is ongoing.Conclusions:A larger than expected proportion of mild NE infants with abnormal outcomes was observed. Future research should evaluate safety and efficacy of neuroprotection for mild NE.

Blood Level of Inter-Alpha Inhibitor Proteins Distinguishes Necrotizing Enterocolitis From Spontaneous Intestinal Perforation

Objective To examine circulating levels of inter‐alpha inhibitor protein (IaIp) in infants with necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP), and matched controls to assess the diagnostic accuracy of IaIp to differentiate NEC from SIP and to compare receiver operating characteristics of IaIp for NEC with C‐reactive protein (CRP). Study design A prospective, nested case‐control study of infants with feeding intolerance was carried out. Blood and clinical data were collected from 27 infants diagnosed with NEC or SIP and from 26 matched controls admitted to our unit. Infants with modified Bell criteria stage 2 or greater were included as NEC. Clinical, radiologic, and/or surgical findings were used to identify infants with SIP. Controls were matched for gestational age, postnatal age, sex, and birth weight. Results Mean ± SD IaIp blood levels were 147 ± 38 mg/L, 276 ± 67 mg/L, and 330 ± 100 mg/L in infants with NEC, SIP, and matched controls, respectively (P < .004 and P < .01). Receiver operating characteristics analysis to establish the predictive value of NEC demonstrated areas under curve of 0.98 and 0.63 for IaIp and CRP, respectively. Conclusions IaIp levels were significantly decreased in infants with NEC compared with SIP and matched controls. The diagnostic accuracy of IaIp for NEC was superior to that of CRP.

Prospective research in infants with mild encephalopathy identified in the first six hours of life: neurodevelopmental outcomes at 18–22 months

BackgroundStudies of early childhood outcomes of mild hypoxic-ischemic encephalopathy (HIE) identified in the first 6 h of life are lacking.ObjectiveTo evaluate neurodevelopmental outcomes at 18–22 months of PRIME study.Study designMulticenter, prospective study of mild HIE defined as ≥1 abnormality using the modified Sarnat within 6 h of birth and not meeting cooling criteria. Primary outcome was disability with mild: Bayley III cognitive 70–84 or ≥85 and either Gross Motor Function Classification System (GMFCS) 1 or 2, seizures, or hearing deficit; moderate: cognitive 70–84 and either GMFCS 2, seizures, or hearing deficit; severe: cognitive <70, GMFCS 3–5.ResultsOf the 63 infants enrolled, 51 (81%) were evaluated at 19 ± 2 months and 43 (68%) completed Bayley III. Of the 43 infants, 7 (16%) were diagnosed with disability, including 1 cerebral palsy and 2 autism. Bayley scores < 85 in either cognition, motor, or language were detected in 17 (40%): 14 (32%) language, 7 (16%) cognitive, and 6 (14%) motor domain. Infants with disability had more abnormalities on discharge examination and brain MRI, with longer hospital stay (p < 0.001).ConclusionsIn this contemporary untreated cohort of mild HIE, disability occurred in 16% of infants at 18–22 months.

Vitamin D and associated perinatal–neonatal outcomes among extremely low-birth-weight infants

ObjectiveTo evaluate vitamin D inadequacy among extremely low-birth-weight (ELBW, <1000 g) infants and the association between circulating vitamin D concentrations and perinatal–neonatal outcomes.Study designProspective cohort study of ELBW infants in the neonatal ICU. Blood was collected within the first 3 days after birth after obtaining informed consent. Circulating 25-hydroxyvitamin D concentrations (25(OH)D) were quantified using liquid chromatography–tandem mass spectroscopy and classified as vitamin D deficient, insufficient, or adequate ( < 20, 20–30, or > 30 ng/mL, respectively). Associations between 25(OH)D and perinatal–neonatal outcomes were determined by multivariable regression, adjusted for covariates that differ in the bivariate analysis.ResultsOf the 60 ELBW infants enrolled, 13 (22%) were vitamin D deficient, 15 (25%) were insufficient, and 32 (53%) were adequate. 25(OH)D levels were positively associated with fetal growth restriction and prolonged rupture of the membranes.ConclusionsVitamin D inadequacy was frequent among ELBW infants. Circulating vitamin D concentrations were significantly associated with perinatal outcomes in this contemporary cohort.