Characteristics of fecal calprotectin as an early marker for suspected necrotizing enterocolitis in newborns exclusively fed maternal breast milk: a case-control study.

Objective: Numerous studies have proposed using fecal calprotectin among many biomarkers associated with necrotizing enterocolitis (NEC) diagnosis. This study aimed to evaluate fecal calprotectin as an early marker for suspected NEC (stage 1) in infants fed exclusively breast milk. Methods: We collected 20 stool samples from newborns admitted to the neonatal intensive care unit at Aswan University Hospital diagnosed with stage I NEC. We compared them with 20 samples from matched healthy newborns. Fecal calprotectin level was measured by enzyme-linked immunosorbent assay. Results: Fecal calprotectin level was higher in cases than in the control group (P < 0.001). Also, there was a positive correlation between fecal calprotectin and C-reactive protein in the studied cases (P = 0.001). However, there were no correlations between fecal calprotectin and sex or postnatal age. Conclusion: Fecal calprotectin levels increase in newborns with stage I NEC. Although not specific, its sensitivity suggests a role as a potential biomarker in the evaluation of suspected NEC.

Enhancing Interpretation of One-Time Body Composition Measurement at Near-Term Gestation in Preterm Infants: An Exploratory Study.

In preterm infants, longitudinal growth patterns have a stronger association with clinical outcomes than cross-sectional metrics. For qualitative growth, a one-time body composition measurement at near term is common, and here we explore the potential use of a novel estimated longitudinal body composition metric (adjusted fat-free mass deficit) using birth anthropometrics. KEY POINTS: · Longitudinal growth patterns are better linked with clinical outcomes in preterm infants.. · Body composition is increasingly used to assess the quality of postnatal growth in preterm infants.. · Single body composition at term adjusted using birth weight may be better predictive for outcomes..

In the grey zone-survival and morbidities of periviable births.

OBJECTIVE: To compare the survival and morbidities of infants born between 22 0/7-25 6/7 weeks of gestation. STUDY DESIGN: This observational cohort study consisted of 187 eligible infants liveborn at a single, Level III Neonatal Intensive Care Unit (NICU) between June 1, 2009, and December 31, 2016, in Cleveland, Ohio. Infants with recognized syndromes or major congenital malformations were excluded from the review. RESULT: The rate of survival to discharge for NICU-admitted infants born at 22- and 23- week was 56% and 54% respectively at our institution. There was no trend observed between gestational ages and incidence of necrotizing enterocolitis (NEC), patent ductus arteriousus (PDA), sepsis, or severe intraventricular hemorrhage (IVH- Grade 3 or 4). The infants born at 22 weeks had a higher incidence of retinopathy of prematurity (ROP) as compared to 25 weeks gestation (p < 0.001). The need for home oxygen was significantly higher in the smallest infants 70% at 22 weeks, 62% and 60% at 23 and 24 weeks versus 33% at 25 weeks gestation (p < 0.007). Those born at 22 weeks had the same rate of survival to discharge with severe IVH as those born at 23 weeks but required fewer VP shunts (p > 0.52). CONCLUSIONS: The course of extremely preterm infants shows no difference between those born at 22 and 23 weeks of gestation in our NICU with regards to both mortality and short-term morbidities, although they differed marginally from 24 week gestation infants and significantly from those born at 25 weeks gestation.

Predicting outcomes of mechanically ventilated premature infants using respiratory severity score.

BACKGROUND: Extremely low birth weight (ELBW) infants have significant morbidities and higher mortality. The major morbidities are bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP). Release of proinflammatory cytokines has been implicated in the development of systemic inflammation that contributes to BPD aND ROP. Also, cumulative oxygen exposure in the first 3 days of life and use of mechanical ventilation was associated with 3-fold increase in severe IVH. Therefore, early ventilation and oxygenation may contribute significantly to morbidities in ELBW infants. Respiratory severity score (RSS), a product of Mean airway pressure (MAP) and FiO2, is a steady-state noninvasive assessment tool useful in infants to monitor the severity of respiratory failure. We used RSS, in the first 3 days of life of ELBW infants, to predict neonatal morbidities and mortality. STUDY DESIGN: In a single-center retrospective cohort study in an urban setting, convenience sampling of ELBW infants meeting the study criteria who were mechanically ventilated at birth for the first 3 days of life were included. Time-weighted average RSS was plotted on receiver-operating characteristic (ROC) curve in the first 3 days of life to predict outcomes. Sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratios were calculated. RESULTS: A total of 69 infants qualified for the study. RSS in the first 3 days significantly predicted the composite outcome of death, ROP, IVH or BPD with an area under the curve (AUC) of 0.82 (p < 0.001). Individually, RSS predicted death, severe ROP and IVH with an AUC of 0.86, 0.77 and 0.71 respectively; but did not predict severe BPD (AUC 0.61). RSS was more sensitive and specific than each of its component; FiO2 and MAP. Weighted RSS in the first 3 days had high-negative predictive value of 98.1% for death between 7 days and 36 weeks, 94.6% for ROP and 91.7% for IVH. CONCLUSIONS: This study is the first to show that RSS in the first 3 days of life is a good predictor of composite neonatal outcomes: severe IVH, BPD, ROP, or mortality. Early RSS had a high positive predictive value for the composite outcome of morbidities/mortality and a high specificity for mortality, ROP, and IVH individually.

Effect of parenteral nutrition duration on patterns of growth and body composition in very low-birth-weight premature infants.

BACKGROUND: Parenteral nutrition (PN) is essential to support premature infants' growth and varies with enteral nutrition (EN) advancement rates. Data on PN duration's impact on premature infants' growth are limited. The aim of this multicenter observational study was to determine the effect of early PN duration on body composition at term corrected gestational age (CGA) in very low-birth-weight (VLBW) premature infants. METHODS: VLBW infants exposed to PN in the first week of life and exposed to significantly different EN regimens were divided into two groups on the basis of early PN duration. Infants with a birth weight (BW) <1000 g and PN duration <28 days and infants with a BW 1000-1500 g and PN duration <14 days were assigned to the "short-PN" group. Infants receiving PN for longer durations were assigned to the "long-PN" group. Body composition was assessed via air displacement plethysmography at term CGA or before discharge. RESULTS: Sixty-two and 53 infants were assigned to the short-PN and long-PN groups, respectively. The two groups were significantly different in BW and GA, so a nested case-control study was conducted after matching 36 infant pairs. Infants in the long-PN group had significantly lower fat-free mass (FFM) z-scores, but both groups had comparable fat mass (FM) z-scores. Long PN was a significant negative predictor of FFM z-score in the multivariate regression analysis. CONCLUSION: In VLBW premature infants, PN duration is negatively associated with FFM z-scores at term CGA without affecting FM z-scores.

Application of Kaiser Sepsis Calculator in culture-positive infants with early onset sepsis.

BACKGROUND: Kaiser Sepsis Calculator (KSC) reduces antibiotic use, testing and intravenous infiltrates but there are concerns about the missed early onset sepsis (EOS) cases. We sought to apply the KSC score for culture-positive infants retrospectively in infants born in the last 10 years in our hospital. METHODS: In a retrospective cohort study, the comparison groups were divided into Group A (no antibiotics recommended by KSC) and Group B (antibiotics recommended). RESULTS: Overall, 17/24 (71%) infants would have been started on antibiotics per KSC but 7/24 (29%) would not. The initial EOS risk was not significantly different between the groups (Group A vs. Group B: 0.44 vs. 0.76, P = 0.41), but the final risk score was (0.33 vs. 9.41, P < 0.001). In Group A (no antibiotics), 3/7 infants became symptomatic between 9 and 42 hours. CONCLUSION: There may be a potential delay in starting antibiotics in infants that are asymptomatic at birth while using KSC.

Infant body composition assessment in the neonatal intensive care unit (NICU) using air displacement plethysmography: Strategies for implementation into clinical workflow.

Nutritional management is integral to infant care in the neonatal intensive care unit (NICU). Recent research on body composition that specifically evaluated fat and fat-free mass has improved our understanding of infant growth and nutritional requirements. The need for body composition monitoring in infants is increasingly recognized as changes in fat mass and fat-free mass associated with early growth can impact clinical outcomes. With the availability of air displacement plethysmography (ADP) as a noninvasive method for assessing infant body composition and published normative gestational age- and sex-specific body composition curves, it is justifiable to integrate this innovation into routine clinical care. Here we describe our experiences in implementing body composition measurement using ADP in routine clinical care in different NICU settings.

Staff perceptions of challenging parent-staff interactions and beneficial strategies in the Neonatal Intensive Care Unit.

AIM: To characterise neonatal intensive care unit (NICU) staff perceptions regarding factors which may lead to more challenging staff-parent interactions, and beneficial strategies for working with families with whom such interactions occur. METHODS: A survey of 168 physician and nursing staff at two NICUs in American teaching hospitals inquired about their perceptions of challenging parent-staff interactions and situations in which such interactions were likely to occur. RESULTS: From a medical perspective, staff perceptions of challenging interactions were noted when infants had recent decompensation, high medical complexity, malformations or long duration of stay in the NICU. From a psychological/social perspective, a high likelihood of challenging interactions was noted with parents who were suspicious, interfere with equipment, or parents who hover in the NICU, express paranoid or delusional thoughts, repeat questions, perceive the staff as inaccessible, are managing addictions, or who require child protective services involvement. Frequent family meetings, grieving opportunities, education of parents, social work referrals, clearly defined rules, partnering in daily care and support groups were perceived as the most beneficial strategies for improving difficult interactions. CONCLUSION: This study delineates what staff perceive as challenging interactions and provides support for an educational and interventional role that incorporates mental health professionals.

Impact of Infant-Polysomnography Studies on Discharge Management and Outcomes: A 5 Year Experience from a Tertiary Care Unit.

OBJECTIVE: To evaluate the impact of infant-polysomnography studies performed in the NICU on management and outcomes. STUDY DESIGN: Retrospective study to collect demographics and data on infant-polysomnography studies between Jan 2010 to Dec 2014. RESULTS: 110 premature neonates had polysomnography study performed at 36.9 ± 2.5 weeks post menstrual age. Almost all the studies were read as abnormal and 95% of the studied infants were discharged home on a cardiorespiratory monitor. 20% of the subjects had apnea >20 s, 18% had apnea of 15-20 s and 50% of infants had apnea of 10-15 s. 24.5% infants were discharged home on caffeine, 28% on metoclopramide and 24% on antacids. There were 11 readmissions for apparent life threatening events with no until 6 month-corrected age. There was no association between polysomnography results and readmission. There was a decline in polysomnography studies performed each year. CONCLUSION: Cardiorespiratory monitoring, medications and polysomnography studies do not predict outcomes.

Human Milk Analysis Using Mid-Infrared Spectroscopy.

BACKGROUND: The composition of human milk is known to vary with length of gestation, stage of lactation, and other factors. Human milk contains all nutrients required for infant health but requires fortification to meet the needs of low-birth-weight infants. Without a known nutrient profile of the mother's milk or donor milk fed to a baby, the composition of the fortified product is only an estimate. Human milk analysis has the potential to improve the nutrition care of high-risk newborns by increasing the information about human milk composition. Equipment to analyze human milk is available, and the technology is rapidly evolving. This pilot study compares mid-infrared (MIR) spectroscopy to reference laboratory milk analysis. METHODS: After obtaining informed consent, we collected human milk samples from mothers of infants weighing <2 kg at birth. Duplicate samples were analyzed for macronutrients by MIR and by reference laboratory analysis including Kjeldahl for protein, Mojonnier for fat, and high-pressure liquid chromatography for lactose. Intraclass correlation coefficients, Bland-Altman scatter plots, and paired t tests were used to compare the two methods. RESULTS: No significant differences were detected between the macronutrient content of human milk obtained by MIR vs reference laboratory analysis. CONCLUSIONS: MIR analysis appears to provide an accurate assessment of macronutrient content in expressed human milk from mothers of preterm infants. The small sample size of this study limits confidence in the results. Measurement of lactose is confounded by the presence of oligosaccharides. Human milk analysis is a potentially useful tool for establishing an individualized fortification plan.

Neonatal Serum Phosphorus Levels and Enamel Defects in Very Low Birth Weight Infants.

BACKGROUND: Very low birth weight (VLBW) infants miss out on the period of greatest mineral accretion that occurs during the last trimester of pregnancy and are at higher risk of enamel defects. No studies have well described the relationship between neonatal nutrition and dental outcomes in preterm, VLBW infants. The objective of this study was to assess the differences in nutrition biomarkers, feeding intake, and comorbidities among VLBW infants with and without enamel defects. METHODS: A retrospective chart review of VLBW infants recruited for an ongoing longitudinal dental study between 2007 and 2010 was done. Participants were classified as cases and controls according to the presence/absence of developmental defects of enamel at 8 and/or 18-20 and/or 36 months. Demographics and medical and nutrition data were abstracted from 76 subjects' medical charts. RESULTS: Of the 76 VLBW subjects, 62% had enamel defects (hypoplasia and/or opacity). The only significant variable in the logistic regression analysis was that infants with a 1-mg/dL increase in serum phosphorus levels had a 68% reduction in the odds of having enamel hypoplasia (odds ratio, 0.322; P = .024). CONCLUSION: Neonatal lower serum phosphorus levels are significantly associated with enamel hypoplasia in VLBW infants younger than 3 years.

A comparison of manual versus automated saturation of peripheral oxygenation in the neonatal intensive care unit.

BACKGROUND: It is vital to maintain the saturation of peripheral oxygenation (SpO2) in a targeted range in extremely premature infants to improve survival without significant morbidities. OBJECTIVES: To compare manual versus automated monitor documentations of daily upper and lower values of SpO2 in premature infants. METHODS: In a prospective observational study, the highest and lowest daily SpO2 manually recorded values from electronic medical records were compared with automatically recorded values from bedside cardiorespiratory monitors. RESULTS: Eighteen infants were monitored for 605 patient days, with a mean birth weight of 859 ± 183 g, and gestational age of 26.0 ± 1.3 wks. Within the lowest SpO2 values, manually recorded values were consistently higher than the simultaneous automatically recorded monitor values. The highest SpO2 point differences in documentation was seen in patients with SpO2 range ≤ 70% (16 ± 13 points), followed by 71-80% (10 ± 7 points) and 81-90% (7 ± 4 points); p < 0.01. CONCLUSIONS: The difference between manually and automatically recorded SpO2 is large in lower SpO2 ranges and small in higher SpO2 ranges. Automated oxygen administering systems should be considered to reduce potential errors.

Improving health care usage in a very low birth weight population.

BACKGROUND: Prematurity is the biggest contributor to admissions in the neonatal intensive care unit (NICU). The period following hospital discharge is a vital continuum for the very low birth weight (VLBW) infant. The objective of this study was to assess the impact of a unique discharge and follow-up process on the outcomes of VLBW infants leaving the NICU. METHODS: All outpatient health care usage by VLBW infants born in the study year (cases) was retrospectively tracked through 12 months of age. A cohort of healthy newborn infants were matched by birthdate to each VLBW infant (controls) and similarly tracked. RESULTS: In this study, there were 85 cases and 85 controls. The mean gestational age at birth for the cases was 29.1 ± 2.7 weeks with a mean birth weight of 1079 ± 263 g. That of the controls was 38.9 ± 1.3 weeks and 3202 ± 447 g. Over 90% of both populations had Medicaid coverage. All VLBW infants received care at the Special Care Developmental Follow-Up Clinic. When compared with the controls, VLBW infants discharged from the NICU made fewer acute, unscheduled visits to the Emergency Department or Urgent Care Clinic (2.3 ± 2.5 vs. 3.7 ± 3.5; P=0.007) despite their high-risk medical and social status. Their growth pattern showed significant "catch-up" and was similar to the matched controls at the last scheduled visit for each group. CONCLUSIONS: Outcomes including health care utilization in high-risk infants can be improved through meticulous discharge planning and follow-up measures that utilize existing hospital infrastructure to provide affordable comprehensive care.

Standardized Slow Enteral Feeding Protocol and the Incidence of Necrotizing Enterocolitis in Extremely Low Birth Weight Infants.

BACKGROUND: Compared with early enteral feeds, the delayed introduction and slow advancement of enteral feedings to reduce the incidence of necrotizing enterocolitis (NEC) are not well studied in extremely low birth weight (ELBW) infants. OBJECTIVE: To study the effects of a standardized slow enteral feeding (SSEF) protocol in ELBW infants. METHODS: ELBW infants who followed an SSEF protocol (September 2009 to December 2012) were compared with a similar group of historical controls (January 2003 to July 2009). Short-term outcomes between the 2 groups were compared by propensity score (PS) analysis. RESULTS: One hundred twenty-five infants in the SSEF group were compared with 294 historical controls. Compared with the controls, feeding initiation day, full enteral feeding day, parenteral nutrition (PN) days, and total central line days were longer in the SSEF group. There was no significant difference in overall NEC (5.6% vs 11.2%, respectively; P = .10) or surgical NEC (1.6% vs 4.8%, respectively; P = .17) between the SSEF group and controls. However, in infants with birth weight <750 g, NEC (2.1% vs 16.2%, respectively; P < .01) or combined NEC/death (12.8% vs 29.5%, respectively; P = .03) was significantly less in the SSEF group compared with controls. In infants who survived to discharge, there was no significant difference in the discharge weight or length of stay in PS-adjusted analysis. CONCLUSIONS: An SSEF protocol significantly reduces the incidence of NEC and combined NEC/death in infants with birth weight <750 g. Despite taking longer to achieve full enteral feeding on this protocol, surviving ELBW infants demonstrated comparable weight gain at discharge without prolonging their hospital stay.

Impact of weight loss between pregnancies on recurrent preterm birth.

OBJECTIVE: Low maternal pre-pregnancy body-mass index (BMI) has been associated with preterm birth (PTB). Women delivering preterm are at increased for recurrent PTB. Our goal was to determine whether change in BMI between pregnancies alters the risk of PTB. STUDY DESIGN: From our electronic perinatal database, we identified women who delivered consecutive pregnancies at our institution. Women were grouped by prepregnancy BMI category (underweight: <18.5, normal: 18.5-24.9, overweight: 25-29.9, obese: >30 kg/m2). They were then grouped based on change in actual BMI ("increase": >5 kg/m2, "stable": within 5 kg/m2, "decrease": >5 kg/m2) and change in BMI category between pregnancies. The risk of PTB was correlated to change in BMI. P < .05 was considered significant. RESULTS: One thousand two hundred forty-one women met inclusion criteria. Women with a PTB in their first pregnancy had more PTB in their second than those with a term birth in their first pregnancy (33.6% vs 8.0%, P < .001). Women whose BMI decreased more than 5 kg/m2 had more frequent PTB in the second pregnancy than those who did not (21.1% vs 9.3%, P = .01). For those with a term birth in the first pregnancy, PTB in the second did not increase with declining BMI. However, for women with a PTB in the first pregnancy, PTB was more frequent in the second if their BMI decreased a BMI category (53.8% vs 27.6%, P = .05) or if BMI decreased more than 5 kg/m2 (80.0% vs 28.2%, P = .01). CONCLUSION: Women whose BMI declines between pregnancies are at increased risk for PTB, particularly if they delivered a prior preterm gestation.

Periviable birth at 20 to 26 weeks of gestation: proximate causes, previous obstetric history and recurrence risk.

OBJECTIVE: Early preterm birth at 20 to 26 weeks of gestation (periviable birth) carries extreme risks of infant death and morbidities. Prevention of periviable birth could improve infant outcomes significantly. We sought to characterize the causes of periviable birth and to determine whether periviable birth can be predicted by previous pregnancy outcome. STUDY DESIGN: We evaluated 104,921 pregnancies (1974-2004) and assessed the frequency and causes of periviable birth. Women who were delivered of both their first and second pregnancies at >20 weeks of gestation at our institution were identified. Predictive values of the first pregnancy outcomes for second pregnancy outcomes were determined. RESULTS: Periviable birth complicated 1981 deliveries (1.9%). Seventy-nine percent of the women with periviable births had no history of periviable births; 44% of the women had no previous deliveries, and 35% of the women had previous term deliveries only. Causes of periviable birth were labor (36%), premature rupture of membranes (34%), bleeding (10%), and preeclampsia (4%). Four percent of the gestations were multiple gestations. Among 7970 pregnancies at >20 weeks of gestation, periviable birth in the first pregnancy was associated with preterm birth and periviable birth in the second pregnancy (35.6%, 6.9%; relative risk, 3.3 and 8.6; P < .0001). Periviable birth and preterm birth in the first pregnancy were insensitive for periviable birth in the second pregnancy (8.8%, 36.8%, respectively). CONCLUSION: Although periviable birth is associated with subsequent periviable birth and preterm birth, preterm birth and periviable birth are insensitive markers for recurrences in the next pregnancy. Early pregnancy or preconceptional markers for prediction of periviable birth are needed.

Perinatal intervention and neonatal outcomes near the limit of viability.

OBJECTIVE: The purpose of this study was to evaluate trends in the level of obstetric and neonatal intervention near the limit of viability and perinatal morbidity and mortality rates over time. STUDY DESIGN: In this retrospective chart review, live-born infants who were delivered at 23 to 26 weeks of gestation and who weighed between 500 and 1500 g between 1990 and 2001 in an urban tertiary care center were identified. Maternal charts were reviewed for clinical characteristics and antenatal and intrapartum course. Neonatal charts were reviewed for short-term morbidities that included respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, and survival. The study group was divided into 2 cohorts (group I:1990-95; group II:1996-2001); the obstetrician's willingness to intervene, neonatal resuscitation efforts, infant mortality (in gestational age subgroups) rate, and short-term morbidity rate were compared. Multivariate analyses, which controlled for obstetrician willingness to intervene, neonatal resuscitation, cohort, and gestational age, were performed to evaluate infant survival in the entire cohort and for morbidity in the survivors. RESULTS: Records for 260 mothers and 293 newborn infants were evaluated. Comparing the 2 cohorts (group I vs II), we found increases over time in intent to intervene for fetal indication (70% vs 89%; P = .0007), cesarean delivery for malpresentation (20% vs 42%; P = .0003), and survival (54% vs 70%; P = .003). Pregnancies in group 1 were less likely to have received antenatal steroids (7.7% vs 60%) or surfactant (39% vs 73%; P <.0001 for each). Survival increased with advancing delivery gestation (24%, 51%, 68%, and 85% at 23, 24, 25, and 26 weeks of gestation, respectively; P <.0001). However, among survivors, the incidences of necrotizing enterocolitis, retinopathy of prematurity, intraventricular hemorrhage, respiratory distress syndrome, sepsis, and bronchopulmonary dysplasia did not decline significantly with advancing gestational age, after controlling for other factors. CONCLUSION: Obstetric intervention and aggressive neonatal resuscitation have increased for pregnancies delivered between 23 and 26 weeks of gestation over the past decade. Although survival has increased over time and with advancing gestational age at delivery, short-term morbidity in survivors is similar, regardless of gestational age in this cohort. A brief delay in delivery of those pregnancies who are at risk for delivery between 23 and 26 weeks of gestation may improve survival, although short-term morbidity in survivors will not be affected substantially.