Risk Factors for Pneumothorax and Its Association with Ventilation in Neonates.

OBJECTIVE: The mode of ventilation that is implicated in pneumothorax is the one at the time of its diagnosis. Although there is evidence that air leak starts many hours before it is clinically evident, there are no prior studies that have investigated the association of pneumothorax with the mode of ventilation few hours before rather than at the time of its diagnosis. STUDY DESIGN: A retrospective case-control study was conducted in the neonatal intensive care unit (NICU) between 2006 and 2016 where cases of neonates with pneumothorax were compared with gestational age-matched control neonates without pneumothorax. Respiratory support associated with pneumothorax was classified as the mode of ventilation 6 hours before the clinical diagnosis of pneumothorax. We investigated the factors that were different between cases and controls, and between cases of pneumothorax on bubble continuous positive airway pressure (bCPAP) and invasive mechanical ventilation (IMV). RESULT: Of the 8,029 neonates admitted in the NICU during the study period, 223 (2.8%) developed pneumothorax. Among these, 127 occurred among 2,980 (4.3%) neonates on bCPAP, 38 among 809 (4.7%) neonates on IMV, and the remaining 58 among 4,240 (1.3%) neonates on room air. Those with pneumothorax were more likely to be male, have higher body weight, require respiratory support and surfactant administration, and have bronchopulmonary dysplasia (BPD). Among those who developed pneumothorax, there were differences in the gestational age, gender, and use of antenatal steroids between those who were on bCPAP as compared to those on IMV. IMV was associated with increased odds of pneumothorax as compared to those on bCPAP in a multivariable regression analysis. Cases on IMV had higher incidence of intraventricular hemorrhage, retinopathy of prematurity, BPD, and necrotizing enterocolitis, as well as longer length of stay as compared to those on bCPAP. CONCLUSION: Neonates who require any respiratory support have higher incidence of pneumothorax. Among those on respiratory support, those on IMV had higher odds of pneumothorax and worse clinical outcomes as compared to those on bCPAP. KEY POINTS: · The process of air leak leading to pneumothorax in majority of neonates starts much before it is clinically diagnosed.. · It is possible to detect the air leak early in the process by subtle changes in the signs, symptoms and changes in lung function.. · True association of the ventilation associated with pneumothorax is not at the time of diagnosis of pneumothorax but few hours before it is diagnosed.. · There is higher incidence of pneumothorax in neonates on any respiratory support.. · There is significantly higher incidence of pneumothorax among neonates on invasive ventilations as compared to noninvasive ventilation after correction for all other clinical factors..

Recurrent acute kidney injury in preterm neonates is common and associated with worse outcomes and higher mortality.

BACKGROUND: Acute kidney injury (AKI) in preterm neonates is associated with poor outcomes that may worsen in the setting of recurrent episodes of AKI. This study defines and studies the incidence, risk factors, and outcomes of recurrent AKI (rAKI). METHODS: Retrospective chart review of the neonates born at a gestational age of ≤28 weeks admitted to the neonatal intensive care unit (NICU) between January 2014 and December 2018. We identified AKI based on the serum creatinine (Scr) concentrations using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. rAKI was defined as the occurrence of AKI after Scr from the prior AKI had returned to baseline. RESULTS: Forty-nine of the 205 (24%) preterm neonates developed rAKI. An earlier diagnosis (<7 days old) and a higher KDIGO stage (stage 3) at the initial episode of AKI was associated with rAKI (p = 0.03). Preterm neonates with rAKI had higher mortality as compared to those with a single episode of AKI (sAKI) (adjusted odds ratio (aOR) 4.55, 95% confidence interval (CI), 1.12-18.51). Length of stay (LOS) was longer among neonates with rAKI as compared to those with sAKI by 36 days (95% CI 24.9-47.1). CONCLUSIONS: Recurrent AKI in preterm neonates was associated with earlier episodes and higher KDIGO stage of the initial AKI episode. Neonates with rAKI had higher mortality and longer LOS compared to those with sAKI. IMPACT: Definition and study of the incidence of rAKI and its associated outcomes among preterm neonates. Recurrent AKI is common among preterm neonates and may contribute to worse outcomes for premature neonates in the NICU. Early recognition of the risk factors for AKI, and effective management of initial AKI and early phase of recurrent AKI may improve outcomes of these preterm neonates.

Plasma Citrulline as a Biomarker for Early Diagnosis of Necrotizing Enterocolitis in Preterm Infants.

OBJECTIVE: Citrulline synthesized by healthy enterocytes and decreases with injury. This work aimed to study plasma citrulline concentrations (CITs) as a biomarker to differentiate among infants presenting with early nonspecific signs and symptoms of necrotizing enterocolitis (NEC) with those who will develop NEC. Further to study the correlation between posttreatment CIT with time to full feeds (TTFF) and length of stay (LOS). STUDY DESIGN: This is a prospective study which included infants < 32 weeks gestational age (GA) with 9 infants each in Group 1 (stage 2/3 NEC), Group 2 (with stage 1 NEC-like presentation), and Group 3 (healthy GA-matched infants). CIT was measured in Groups 1 and 2 within 24 hours of presentation and again in Group 1 after treatment. RESULTS: The three groups were similar in clinical characteristics. Median CIT (µmol/L) in Group 1 (15.4 [interquartile range, IQR: 7.3-18.0]) was lower than Group 2 (22.2 [IQR: 18.3-27.3], p = 0.02) and Group 3 (24.9 [IQR: 19.8-31.9], p = 0.009). Posttreatment CIT in Group 1 did not correlate with TTFF (r = 0.15; p = 0.69) and LOS (r = - 0.33; p = 0.38). CONCLUSION: CIT was lower in infants with NEC as compared with healthy controls and those infants with nonspecific signs of NEC. CIT after treatment does not correlate with TTFF and LOS. KEY POINTS: · Citrulline is produced by enterocytes.. · It is decreased in infants with necrotizing enterocolitis early in disease.. · It can be used as a biomarker for early diagnosis of necrotizing enterocolitis..

Simulations of Deliveries of SARS-CoV-2 Positive Pregnant Women and Their Newborn Babies: Plan to Implement a Complex and Ever-Changing Protocol.

Management of severe acute respiratory Syndrome corona virus-2 (SARS-CoV-2) infected pregnant women at time of delivery presents a unique challenge. The variability in the timing and the method of delivery, ranging from normal vaginal delivery to an emergent cesarean section, adds complexity to the role of the health care providers in the medical care of the patient and in the interactions, they have with other providers. These variations are further influenced by the availability of isolation rooms in the facility and adequacy of personal protective equipment. The protocols already set in place can be further challenged when the facility reaches its capacity to manage the patients.To fulfill the goal of providing adequate management to the SARS-CoV-2 infected pregnant women and their infants, avoid variation from suggested guidelines, and decrease risk of exposure of the health care workers, the health care provider team needs to review the variations regularly. While familiarity can be achieved by reviewing the guidelines, clinical case simulations provide a more hands-on approach.Using case-based simulations and current guidance from the Center for Disease Control, American Academy of Pediatrics, and recent reviews, we discuss a management guideline developed at our institution to facilitate provision of care to SARS-CoV-2 infected pregnant women during delivery and to their infants, while protecting health care providers from exposure, and in keeping with the local facility logistics. KEY POINTS: · Simulation of delivery of SARS-CoV-2 positive pregnant women can minimize the risk of exposure to healthcare professionals.. · Four common scenarios of delivery as described can be adapted for the evolving guidelines for the management of SARS-CoV-2 positive pregnant women.. · Integrating simulations of management of SARS-CoV-2 positive pregnant women is feasible in daily clinical routine..

Late onset neonatal acute kidney injury: results from the AWAKEN Study.

BACKGROUND: Most studies of neonatal acute kidney injury (AKI) have focused on the first week following birth. Here, we determined the outcomes and risk factors for late AKI (>7d). METHODS: The international AWAKEN study examined AKI in neonates admitted to an intensive care unit. Late AKI was defined as occurring >7 days after birth according to the KDIGO criteria. Models were constructed to assess the association between late AKI and death or length of stay. Unadjusted and adjusted odds for late AKI were calculated for each perinatal factor. RESULTS: Late AKI occurred in 202/2152 (9%) of enrolled neonates. After adjustment, infants with late AKI had higher odds of death (aOR:2.1, p = 0.02) and longer length of stay (parameter estimate: 21.9, p < 0.001). Risk factors included intubation, oligo- and polyhydramnios, mild-moderate renal anomalies, admission diagnoses of congenital heart disease, necrotizing enterocolitis, surgical need, exposure to diuretics, vasopressors, and NSAIDs, discharge diagnoses of patent ductus arteriosus, necrotizing enterocolitis, sepsis, and urinary tract infection. CONCLUSIONS: Late AKI is common, independently associated with poor short-term outcomes and associated with unique risk factors. These should guide the development of protocols to screen for AKI and research to improve prevention strategies to mitigate the consequences of late AKI.

c-KIT-Positive Fatal Diffuse Cutaneous Mastocytosis With Systemic Manifestations in a Neonate.

Diffuse cutaneous mastocytosis is a rare variant of mastocytosis in the neonatal period. We describe a case of c-KIT (DV) mutation-positive fatal diffuse cutaneous mastocytosis with systemic involvement of the gastrointestinal tract and associated malabsorption and hepatosplenomegaly associated with mast cell mediator release symptoms.

Use of serum citrulline concentrations from routine newborn screen as a biomarker for necrotizing enterocolitis.

PURPOSE: Necrotizing enterocolitis (NEC), a leading cause of mortality and morbidity in preterm neonates, lacks a reliable biomarker. Citrulline is primarily produced by enterocytes and correlates with intestinal function. Serum citrulline concentration (CIT) is routinely measured in routine newborn screening (NBS). The purpose of the study is to test if CIT from NBS may predict the occurrence of NEC and whether it correlates with the time to full feeds (TTFF) and length of stay (LOS), serving as a biomarker of NEC and intestinal health. METHODS: In a retrospective case control study conducted on neonates with gestational age of 26-32 weeks, we compared CIT levels between cases (neonates with NEC) and controls (next-born neonate). NBS was collected within first 24 h, at day 5 and when the neonates achieved full feeds and were compared using non-parametric tests. RESULTS: There was no difference in CIT between the controls and cases on day 1 [11.42 (7.42-14.84 vs. 11.93 (6.85-18.8) µmol/L, p = 0.55], on day 5 [11.99 (7.99-16.55) vs. 13.70 (7.42-26.83) µmol/L, p = 0.05], or at full feeds [14.86 (6.85-25.69) vs. 15.7 (7.42-26.26) µmol/L, p = 0.87]. CIT on day 1 did not correlate with TTFF (r = 0.08, p = 0.53) or LOS (r = 0.23, p = 0.06), respectively). CONCLUSIONS: CIT from routine NBS does not serve as a biomarker to predict NEC in preterm neonates.

Randomized control trial comparing physiologic effects in preterm infants during treatment with nasal continuous positive airway pressure (NCPAP) generated by Bubble NCPAP and Ventilator NCPAP: a pilot study.

OBJECTIVES: Nasal continuous positive airway pressure (NCPAP) is an accepted form of non-invasive ventilation in preterm infants. Few, if any, studies have shown an advantage of one type of NCPAP over another. It has been theorized that bubble-generated NCPAP may be advantageous for the preterm neonate versus traditionally used ventilator-generated NCPAP. The aim of this study was to examine for any short-term differences in physiologic parameters in preterm subjects receiving these two different methods of NCPAP. METHODS: We conducted a randomized, prospective, cross-over pilot study of preterm infants being treated with NCPAP in the neonatal intensive care unit. Subjects were continuously monitored for several physiologic parameters including heart rate, respiratory rate, oxygen saturation, cerebral tissue oxygen saturation and cerebral fractional oxygen extraction using routine neonatal monitors and near-infrared spectroscopy (NIRS) while on 2 h of bubble NCPAP and 2 h of ventilator NCPAP. Subjects were randomized to be monitored while either starting on bubble NCPAP and then switching to ventilator NCPAP or starting on ventilator NCPAP and switching to bubble NCPAP. RESULTS: Eighteen subjects were included. We found no statistically significant difference in any of the physiologic parameters while subjects were receiving bubble NCPAP versus ventilator NCPAP during the monitoring time periods. While on bubble NCPAP, subjects showed a trend toward decreasing respiratory rate and decreasing cerebral fractional oxygen extraction over time, but this did not reach statistical significance. CONCLUSION: There appears to be no difference in immediate physiologic effects between bubble NCPAP and ventilator NCPAP. This does not preclude the possibility of potential long-term differences, but any differences seen would likely be based on mechanisms that take more time to develop. A larger prospective trial is warranted to confirm our findings.

Neonatal serum magnesium concentrations are determined by total maternal dose of magnesium sulfate administered for neuroprotection.

BACKGROUND: Antenatal magnesium in preterm labor for neuroprotection decreases the incidence of cerebral palsy. However, there are no guidelines on the dose and duration of magnesium infusion for neuroprotection. As increased neonatal serum magnesium concentrations may be related to higher risk of morbidity and mortality, the role of total amount of magnesium and maternal serum magnesium concentrations associated with safe neonatal serum magnesium concentrations is not known. METHODS: A retrospective study was conducted on 289 mothers who received antenatal magnesium for neuroprotection as a loading dose of 4-6 g infused over 30 min, followed by a maintenance infusion of 1-2 g/h. Total magnesium dose infused to the mother and maternal serum magnesium concentrations were correlated with neonatal serum magnesium concentrations. RESULTS: Of the 289 mothers, 192 mother/baby dyads had all three measurements (maternal total magnesium dose, and maternal and neonatal serum magnesium concentrations). Magnesium infusion was continued beyond 24 h in 60 mothers. Total maternal magnesium dose at 24 and 48 h of infusion correlated with neonatal serum magnesium concentrations (r=0.55, P<0.0001 and r=0.35, P<0.0001, respectively), but not with maternal serum magnesium concentrations (r=0.004, P=0.98 and r=0.14, P=0.21). However, there was no correlation between the maternal and neonatal serum magnesium concentrations (r=0.10, P=0.15). CONCLUSION: Total dose of magnesium infused to the mother correlates with neonatal serum magnesium concentrations. To keep neonatal serum magnesium concentrations within a range that is effective for neuroprotection and safe for the neonates, the total dose received by the mother needs to be monitored and limited.

Incidence, Risk Factors, and Outcomes Associated With Recurrent Neonatal Acute Kidney Injury in the AWAKEN Study.

Importance: The incidence and associated outcomes of recurrent acute kidney injury (rAKI) in neonates remain largely unknown. Objective: To determine the incidence, risk factors, and clinical outcomes associated with rAKI in critically ill neonates. Design, Setting, and Participants: This cohort study was a secondary analysis of the multicenter, international Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates retrospective study. Comparisons were made among neonates with no AKI, a single AKI episode (sAKI), and rAKI. All neonates younger than 14 days who were admitted between January 1 and March 31, 2014, to 24 participating level II to IV neonatal intensive care units and received intravenous fluids for at least 48 hours were considered for inclusion. Neonates with congenital heart disease requiring surgery within the first week of life, lethal chromosomal anomalies, death within 48 hours of admission, or severe congenital kidney abnormalities were excluded. Data were analyzed from May 23, 2022, to December 8, 2023. Exposure: Recurrent AKI using the neonatal Kidney Disease: Improving Global Outcomes criteria. Determination of each rAKI required a complete return to the baseline serum creatinine level that defined the prior AKI episode. Main Outcomes and Measures: Incidence and risk factors of rAKI and associations of rAKI with length of stay (LOS; ie, birth to hospital discharge) and mortality. Results: The study cohort (n = 2162) included 1233 male neonates (57.0%). Gestational age distribution was less than 29 weeks for 276 neonates (12.8%), 29 to less than 36 weeks for 958 (44.3%), and 36 weeks or older for 928 (42.9%). Of 605 neonates with AKI, 133 (22.0%) developed rAKI with risk factors including younger gestational age, lower birthweight, and higher stage of initial AKI. Infants with rAKI experienced longer median LOS (no AKI, 17 [IQR, 8-34] days; sAKI, 18 [IQR, 9-45] days; rAKI, 60 [IQR, 25-109] days; P < .001). Time-varying Cox proportional hazards regression models suggest rAKI is independently associated with a lower hazard of discharge (adjusted hazard ratio, 0.7 [95% CI, 0.6-0.9]; P = .01) when compared with sAKI, but mortality did not differ between groups (adjusted hazard ratio, 1.4 [95% CI, 0.6-3.0]; P = .44). Conclusions and Relevance: In this cohort study, neonatal rAKI was independently associated with longer LOS when compared with sAKI, suggesting that rAKI in neonates may be an important clinical distinction warranting further study and careful monitoring after an initial AKI episode.

Investigating changes in atmospheric aerosols properties over the Indo-Gangetic Plain during different phases of COVID-19-induced lockdowns.

Impact of COrona VIrus Diseases 2019 (COVID-19) restrictive measures on aerosol optical depth (AOD) and black carbon (BC) concentration is investigated for the western, central, and eastern Indo-Gangetic Plain (IGP) using satellite-based observations. Due to COVID-19-induced lockdown measures, a noticeable decline in AOD and BC concentrations was observed across the IGP when compared to pre-lockdown period of 2020 and the lockdown concurrent period of 2015-2019. During the total lockdown period, a maximum drop in AOD and BC was observed in the central IGP (26.5 % and 10.1 %), followed by western IGP (24.9% and 5.2%) and eastern IGP (23.2 % and 4.9 %) with respect to the same period of 2015-2019. We have removed seasonal influences on aerosol properties during the COVID-19 lockdown, by taking average seasonal variations during the period of 2015-2019 as reference and projecting the hypothetical AOD and BC for the lockdown period under normal scenario. The difference between the hypothetical AOD and BC (under normal scenario) and the retrieved AOD and BC for the lockdown period is the absolute percentage change in AOD and BC concentration due to the lockdown alone. This elimination of seasonal influence is a novel approach. Central IGP showed an absolute decrease in AOD and BC of 38.5% and 18.2% during the lockdown period followed by western IGP (34.6% and 7.7%) and eastern IGP (25.9% and 11.5%). The observed absolute reduction in AOD, 26-39 %, is significantly higher than the global average reduction in AOD of 2-5%. CALIPSO-derived aerosol sub-types over major location of the western, central, and eastern IGP suggests prevalence of anthropogenic activities during pre- and post-lockdown periods. During the lockdown, IGP was influenced by aerosols from natural sources, with mineral dust and polluted dust in the western and central IGP, and aerosols from marine regions in the eastern IGP. Replenishment of aerosols within the boundary layer were far quicker when compared to total column during post-lockdown. Overall, the study reveals a reduction in anthropogenic emissions during the COVID-19-induced lockdowns, leading to temporary improvements in air quality over the IGP. Our study presents a comprehensive analysis of COVID-19 lockdown impact on aerosols properties over the IGP and highlights unprecedented reductions in AOD (~ 40 %) and BC (~ 20 %), due to imposition of lockdown and subsequent cessation of aerosol sources, by removing seasonal influences.

Complications associated with incorrect use of nasal CPAP.

Nasal continuous positive airway pressure (nCPAP) is a safe, effective, non-invasive respiratory modality to deliver positive end expiratory pressure in neonates. Many studies have established its associated improved respiratory outcomes without increase in major morbidities associated with preterm neonates. In contrast, there is paucity in literature addressing complications such as nasal injury, abdominal distention, air leak syndromes (especially pneumothorax), hearing loss, heat and chemical burns, swallowing and aspiration of small components of the nasal interface and delay in escalation of respiratory support associated with the use of nCPAP, most frequently due to its incorrect use. This is a comprehensive review that seeks to address the different complications that are associated with the incorrect use of nCPAP highlighting that these are operator-related and not device-related.

Carnitine supplementation increases serum concentrations of free carnitine and total acylcarnitine in preterm neonates: A retrospective cohort study.

OBJECTIVE: Our goal was to determine the efficacy of the American Society for Parenteral and Enteral Nutrition's recommended carnitine dosage of 5 mg/kg/day in maintaining normal serum free carnitine and total acylcarnitine levels in preterm neonates receiving parenteral nutrition (PN). STUDY DESIGN: A retrospective cohort study was conducted on neonates born <30 weeks gestation and weighing <1250 g, comparing those who received carnitine supplementation to those without supplementation. Free carnitine and total acylcarnitine data were collected from routine newborn screens in the first days of life and on full enetral feeds. Univariate analysis was performed, and those factors that were significantly different between the two groups were adjusted for using mixed effects analysis. RESULTS: There were 108 supplemented and 45 unsupplemented neonates in the study. At baseline, free carnitine (19.8 ± 3.3 vs 18.9 ± 3.7 µmol/L, P = 0.53) and total acylcarnitine (26.6 ± 5.1 vs 22.5 ± 7.1 µmol/L, P = 0.11) were similar between the two groups. At full enteral feeds, compared with unsupplemented group, supplemented infants had significantly higher free carnitine (27.1 ± 16.4 vs 17.1 ± 8.5 µmol/L, P < 0.001) and total acylcarnitine (30.3 ± 11.5 vs 20.2 ± 10.1 µmol/L, P < 0.001). None of the supplemented neonates developed biochemical carnitine deficiency as compared with 18% in the unsupplemented group (P < 0.001). No difference was observed in time to reach full lipid provision, and there were no differences in the change in the triglyceride levels from baseline to the time on full PN lipid provision (P = 0.39). CONCLUSION: Preterm neonates routinely supplemented with parenteral carnitine at 5 mg/kg/day demonstrated higher free carnitine and total acylcarnitine levels at full feeds, with none developing biochemical carnitine deficiency.

The Epidemiology and Mechanisms of Lifetime Cardiopulmonary Morbidities Associated With Pre-Pregnancy Obesity and Excessive Gestational Weight Gain.

Obesity has reached pandemic proportions in the last few decades. The global increase in obesity has contributed to an increase in the number of pregnant women with pre-pregnancy obesity or with excessive gestational weight gain. Obesity during pregnancy is associated with higher incidence of maternal co-morbidities such as gestational diabetes and hypertension. Both obesity during pregnancy and its associated complications are not only associated with immediate adverse outcomes for the mother and their newborns during the perinatal period but, more importantly, are linked with long-term morbidities in the offsprings. Neonates born to women with obesity are at higher risk for cardiac complications including cardiac malformations, and non-structural cardiac issues such as changes in the microvasculature, e.g., elevated systolic blood pressure, and overt systemic hypertension. Pulmonary diseases associated with maternal obesity include respiratory distress syndrome, asthma during childhood and adolescence, and adulthood diseases, such as chronic obstructive pulmonary disease. Sequelae of short-term complications compound long-term outcomes such as long-term obesity, hypertension later in life, and metabolic complications including insulin resistance and dyslipidemia. Multiple mechanisms have been proposed to explain these adverse outcomes and are related to the emerging knowledge of pathophysiology of obesity in adults. The best investigated ones include the role of obesity-mediated metabolic alterations and systemic inflammation. There is emerging evidence linking metabolic and immune derangements to altered biome, and alteration in epigenetics as one of the intermediary mechanisms underlying the adverse outcomes. These are initiated as part of fetal adaptation to obesity during pregnancy which are compounded by rapid weight gain during infancy and early childhood, a known complication of obesity during pregnancy. This newer evidence points toward the role of specific nutrients and changes in biome that may potentially modify the adverse outcomes observed in the offsprings of women with obesity.

Antenatal factors for neonatal seizures among late preterm births*.

OBJECTIVE: The objective of this study was to evaluate for antenatal risk factors for neonatal seizures among late preterm births. STUDY DESIGN: This was a case control study which included late preterm births without anomaly from the United States Natality database. Cases were infants with neonatal seizures, while the controls consisted of infants without neonatal seizures. Maternal and pregnancy characteristics were compared. Multivariable logistic regression was performed to investigate risk factors for neonatal seizures. RESULTS: Of the 943,580 late preterm births, 512 (0.05%) developed neonatal seizures. Significant risk factors associated with neonatal seizures among late preterm births included number of prenatal visits (adjusted odds ratio [aOR] 0.94, 95% CI [0.92-0.96]), smoking history (aOR 1.78, 95% CI [1.41-2.25]), chorioamnionitis (aOR 4.37, 95% CI [2.65-7.21]), non-Hispanic White race (aOR 1.41, 95% CI [1.13-1.76]), and cesarean birth (aOR 2.31, 95% CI [1.91-2.80]). CONCLUSION: Number of prenatal visits, history of smoking, chorioamnionitis, non-Hispanic white race, and cesarean birth are risk factors for neonatal seizures at late preterm gestation.

Drop in platelet counts in extremely preterm neonates and its association with clinical outcomes.

BACKGROUND: Thrombocytopenia is a common finding among preterm neonates and has been associated with mortality and morbidities. In recent studies in adults, the drop in platelet numbers has been shown to be a predictor of clinical outcomes. Although drop in the platelet counts with or without thrombocytopenia has also been observed in neonates, its association with mortality and morbidity has not been investigated in the preterm population. OBJECTIVE: To study the prevalence of a ≥ 30% drop in platelet counts in preterm neonates and its association with clinical outcomes. METHODS: Retrospective chart review was done on neonates born at gestational age ≤ 28 weeks and survived for ≥ 7 days. As with the adult studies, a ≥30% drop in platelet numbers were identified at 7 days and 28 days of age and their association with mortality, morbidities, and length of stay (LOS) was investigated. RESULTS: Two hundred eighty-six patients included in the study had a mean gestational age of 26.3 weeks (range, 23 to 28 wk) and birth weight of 899 ± 215 grams. A ≥ 30% drop in platelet counts occurred in 68.1% neonates. It was significantly associated with mortality (P < 0.001), morbidities at both 7 and 28 days [intraventricular bleed (P < 0.01)], retinopathy of prematurity (P<0.01), necrotizing enterocolitis (P < 0.05) and gram-positive infections (P < 0.05), and LOS (P < 0.01). Only those neonates who had a ≥ 30% drop in the platelet numbers developed gram negative and fungal infections. These associations of clinical morbidities and mortality with a ≥ 30% drop in platelet counts were independent of thrombocytopenia. CONCLUSIONS: A ≥ 30% drop in platelet counts is associated with increased mortality, morbidities, and LOS in preterm neonates, independent of thrombocytopenia. As the drop occurs before the onset of clinical morbidity, one potential application is its use to predict the onset of morbidities including necrotizing enterocolitis, intraventricular hemorrhage, and retinopathy of prematurity, and a prolonged LOS and mortality.

NCI classification of thrombocytopenia in extremely preterm neonates and its association with mortality and morbidity.

BACKGROUND: Thrombocytopenia (TP) is a common finding among preterm neonates and has been associated with mortality and morbidities. Yet, there is no consistent classification for neonatal TP. TP in adults has recently been graded by the National Cancer Institute (NCI) Common Toxicity Criteria and has been shown to predict clinical outcomes. OBJECTIVE: To use the NCI classification for TP in preterm neonates and elucidate its association with clinical outcomes. METHODS: Retrospective chart review was done on neonates born at gestational age (GA) ≤28 weeks and survived for ≥7 days. TP was classified as per NCI guidelines at 7 days and 28 days of age and their association with mortality, major morbidities and hospital length of stay (LOS) were investigated. RESULTS: A total of 286 patients were included in the study with a mean GA of 26.3±1.5 weeks and birth weight of 899±215 g. NCI TP grades at 7 days were significantly (P<0.001) associated with mortality, LOS, intraventricular hemorrhage and Gram negative infections. In addition to these outcomes, necrotizing enterocolitis, Gram positive and fungal infections were also significantly associated with NCI TP grades at 28 days. CONCLUSIONS: Classification of TP using the NCI criteria in extreme preterm neonates is clinically applicable. This grading system of platelet counts is significantly associated with mortality, morbidity and LOS in preterm neonates.

Immediate clinical outcomes in preterm neonates receiving antenatal magnesium for neuroprotection.

BACKGROUND: Antenatal magnesium sulfate can potentially reduce the risk of cerebral palsy in neonates delivered between 24 and 32 weeks of gestational age. Some studies using high-dose magnesium sulfate for neuroprotection have reported increased perinatal mortality. METHODS: A retrospective study was conducted on 475 neonates born between 24 and 32 weeks of gestational age. Serum magnesium level in the first 24 h of life was used to stratify the neonates treated with antenatal magnesium into four subgroups: A (<2.5 mEq/L), B (≥2.5 to <3.5 mEq/L), C (≥3.5 to <4.5 mEq/L), and D (≥4.5 mEq/L). Primary outcome of survival without intraventricular hemorrhage (IVH) and/or periventricular leukomalacia (PVL) along with secondary outcomes, such as Apgar scores, resuscitation, intubation, broncho-pulmonary dysplasia, retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), time to reach full feeds, length of stay (LOS), and mortality during immediate neonatal period were studied. RESULTS: Of the 475 neonates included in the study, 289 (61%) received antenatal magnesium sulfate. Primary outcome of survival without IVH and/or PVL among the preterm neonates was 70.9% in those receiving and 74.2% in those not receiving antenatal magnesium (P=0.25). There were higher incidences of ROP (P=0.02), PDA (P=0.01), greater time to reach full feeds (P=0.03), and increased LOS (P=0.01) in neonates who had received antenatal magnesium. These findings were not statistically significant when the data were corrected for gestational age and birth weight. Among the subgroups, there was a significantly increased mortality rate (P<0.05) with increasing magnesium levels (5% vs. 16.9%, P<0.05 in groups A vs. D) and a trend toward higher intubation rate (P=0.1) and PDA (P=0.14). CONCLUSION: Antenatal magnesium is safe in the immediate postnatal period; however, in the subset of preterm neonates with serum magnesium levels >4.5 mEq/L, there is increased mortality independent of birth weight and gestational age. Identification of these neonates and appropriate dosing for their antenatal neuroprotection needs to be studied.

Relationship of patent ductus arteriosus management with neonatal AKI.

OBJECTIVE: Investigate relationship between management of patent ductus arteriosus (PDA) and acute kidney injury (AKI) in very low birthweight neonates. STUDY DESIGN: Retrospective cohort study of neonates, <1500 g, admitted to 24 NICUs, 1/1/14 - 3/31/14. AKI diagnosed using the neonatal modified KDIGO definition; diagnosis and treatment of PDA extracted from the medical record. Demographics, clinical characteristics, and AKI stage compared using chi-square and analysis of variance. A general estimating equation logistic regression used to estimate adjusted odds ratios. RESULTS: Of 526 neonates with sufficient data to diagnose AKI, 157 (30%) had PDA (61 conservative management, 62 pharmacologic treatment only, 34 surgical ligation). In analyses adjusted for sex, birthweight, gestational age, caffeine, nephrotoxin exposure, vasopressor and mechanical ventilation use, with conservative management as reference, there were no differences among treatment cohorts in the odds of AKI. CONCLUSION: The underlying physiology of PDA, not management strategy, may determine the likelihood of AKI in neonates <1500 g.

Congenital Diarrheal Diseases.

Early diagnosis of diarrhea is critical to prevent disease progression. Diarrhea in newborns can be congenital or acquired; acquired diarrheas are the major cause in infants. Congenital diarrheal diseases are rare and include defects in digestion, absorption, and transport of nutrients, and electrolytes; disorders of enterocyte differentiation and polarization; defects of enteroendocrine cell differentiation; dysregulation of the intestinal immune response; and dysfunction of the immune system. This review discusses the clinical approach that may help in early identification and management of different congenital diarrheal diseases.