A quality improvement initiative standardizing the antibiotic treatment and feeding practices in patients with medical necrotizing enterocolitis.

OBJECTIVE: Evaluate the impact of a multidisciplinary guideline standardizing antibiotic duration and enteral feeding practices following medical necrotizing enterocolitis (mNEC). STUDY DESIGN: For preterm infants with Bell Stage 2 A mNEC and negative blood culture, antibiotic treatment was standardized to 7 days. Trophic feeds of unfortified human milk began 72 h after resolution of pneumatosis. Feeds were advanced by 20 cc/kg/day starting on the last day of antibiotics. Primary outcomes were antibiotic days and days to full feeds, defined as 120 cc/kg/day of enteral nutrition. Secondary outcomes included central line days and length of stay (LOS). RESULTS: Antibiotic duration decreased 23%. Time to start trophic feeds and time to full feeds decreased 33 and 16% respectively. Central line use dropped (98 to 72% of infants) and central line days were reduced by 59%. CONCLUSION: Implementation of a mNEC QI package reduced antibiotic duration, time to full feeds, central line use and CL days.

Variability in antibiotic duration for necrotizing enterocolitis and outcomes in a large multicenter cohort.

OBJECTIVES: To evaluate variability in antibiotic duration for necrotizing enterocolitis (NEC) and associated clinical outcomes. STUDY DESIGN: Five-hundred ninety-one infants with NEC (315 medical; 276 surgical) were included from 22 centers participating in Children's Hospitals Neonatal Consortium (CHNC). Multivariable analyses were used to determine predictors of variability in time to full feeds (TFF) and length of stay (LOS). RESULTS: Median (IQR) antibiotic duration was 12 (9, 17) days for medical and 17 (14, 21) days for surgical NEC. Wide variability in antibiotic use existed both within and among centers. Duration of antibiotic therapy was associated with longer TFF in both medical (OR 1.04, 95% CI [1.01, 1.05], p < 0.001) and surgical NEC (OR 1.02 [1, 1.03] p = 0.046); and with longer LOS in medical (OR 1.03 [1.02, 1.04], p < 0.001) and surgical NEC (OR 1.01 [1.01, 1.02], p = 0.002). CONCLUSION: Antibiotic duration for both medical and surgical NEC remains variable within and among high level NICUs.

Does the initial surgery for necrotizing enterocolitis matter? Comparative outcomes for laparotomy vs. peritoneal drain as initial surgery for necrotizing enterocolitis in infants <1000 g birth weight.

PURPOSE: Quantify short-term outcomes associated with initial surgery [laparotomy (LAP) vs. peritoneal drain (PD)] for necrotizing enterocolitis (NEC) in extremely-low-birth-weight (ELBW) infants. METHODS: Using the Children's Hospitals Neonatal Database, we identified ELBW infants <32 weeks' gestation with surgical NEC (sNEC). Unadjusted and multivariable regression analyses were used to estimate the associations between LAP (or PD) and death/short bowel syndrome (SBS) and length of stay (LOS). RESULTS: LAP was the more common initial procedure for sNEC (n = 359/528, 68%). Infants receiving LAP were older and heavier. Initial procedure was unrelated to death/SBS in both bivariate (LAP: 43% vs PD: 46%, p = 0.573) and multivariable analyses (OR = 0.89, 95% CI = 0.57, 1.38, p = 0.6). LAP was inversely related to mortality (29% vs. 41%, p < 0.007) in bivariate analysis, but not significant in multivariable analysis accounting for markers of preoperative illness severity. However, the association between LAP and SBS (14% vs. 5%, p = 0.012) remained significant in multivariable analyses (adjusted OR = 2.25, p = 0.039). LOS among survivors was unrelated to the first surgical procedure in multivariable analysis. CONCLUSION: ELBW infants who undergo LAP as the initial operative procedure for sNEC may be at higher risk for SBS without a clear in-hospital survival advantage or shorter hospitalization. LEVEL OF EVIDENCE: Level II.

Pulmonary hemorrhage in very low birth weight infants: a case-control analysis.

In this case-control analysis, pulmonary hemorrhage cases (n = 22) were more likely than gestational age-matched controls (n = 44) to be small for gestational age, have moderate-to-large patent ductus arteriosus, extubate rapidly, and develop grade III-IV intraventricular hemorrhage (P < .05). Cases were more likely to die (P = .000), especially if not exposed to indomethacin (P = .007).

Superior mesenteric artery blood flow velocities following medical treatment of a patent ductus arteriosus.

We examined superior mesenteric artery blood flow velocity in response to feeding in infants randomized to trophic feeds (n = 16) or nil per os (n = 18) during previous treatment for patent ductus arteriosus. Blood flow velocity increased earlier in the fed infants, but was similar in the 2 groups at 30 minutes after feeding.

Hemodynamic effects of delayed cord clamping in premature infants.

BACKGROUND AND OBJECTIVE: Delayed cord clamping (DCC) has been advocated during preterm delivery to improve hemodynamic stability during the early neonatal period. The hemodynamic effects of DCC in premature infants after birth have not been previously examined. Our objective was to compare the hemodynamic differences between premature infants randomized to either DCC or immediate cord clamping (ICC). METHODS: This prospective study was conducted on a subset of infants who were enrolled in a randomized controlled trial to evaluate the effects of DCC versus ICC. Entry criteria included gestational ages of 24(0) to 31(6) weeks. Twins and infants of mothers with substance abuse were excluded. Serial Doppler studies were performed at 6 ± 2, 24 ± 4, 48 ± 6, and 108 ± 12 hours of life. Measurements included superior vena cava blood flow, right ventricle output, middle cerebral artery blood flow velocity (BFV), superior mesenteric artery BFV, left ventricle shortening fraction, and presence of a persistent ductus arteriosus. RESULTS: Twenty-five infants were enrolled in the DCC group and 26 in the ICC group. Gestational age, birth weight, and male gender were similar. Admission laboratory and clinical events were also similar. DCC resulted in significantly higher superior vena cava blood flow over the study period, as well as greater right ventricle output and right ventricular stroke volumes at 48 hours. No differences were noted in middle cerebral artery BFV, mean superior mesenteric artery BFV, shortening fraction, or the incidence of a persistent ductus arteriosus. CONCLUSIONS: DCC in premature infants is associated with potentially beneficial hemodynamic changes over the first days of life.

Blood transfusion alters the superior mesenteric artery blood flow velocity response to feeding in premature infants.

Packed red blood cell transfusion may increase the risk of necrotizing enterocolitis in premature infants. We hypothesize that the postprandial increase in mesenteric blood flow velocity (MBFV) would not be altered by a blood transfusion in premature infants. Infants born at 25 to 32 weeks and feeding at least 60 mL/kg/d who required a transfusion were randomized within each of two weight strata to feed or not feed during the transfusion. Mean, peak systolic, and end diastolic Doppler MBFV was measured 30 minutes before and after feedings at baseline (anemic) and with the first feeding posttransfusion. Twenty-two infants (27.3 +/- 2.3 weeks' gestational age; hemoglobin [HgB] 9.3 +/- 1.3 g/dL) were studied on day of life 3 to 71 (mean 31.2 days) and a corrected gestational age of 31.8 +/- 2.9 weeks. In the entire cohort, the peak systolic ( P = 0.02) and the mean ( P = 0.01) MBFV increased in response to feeding in the anemic but not the transfused state. On subgroup analysis, only anemic infants > 1250 g ( N = 12, HgB 8.6 +/- 0.9 g/dL) had an increase in peak systolic ( P = 0.04) and mean ( P = 0.006) MBFV with feeding. In conclusion, the MBFV increases in response to feeding in anemic preterm infants > 1250 g. We speculate that the lack of response to feeding in the immediate posttransfusion state may contribute to the development of transfusion-associated necrotizing enterocolitis.

Effect of preeclampsia on blood pressure in newborn very low birth weight infants.

OBJECTIVE: To test the hypothesis that very low birth infants born to mothers with preeclampsia have higher blood pressure over the first week of life than infants whose mothers did not have preeclampsia. METHOD: Infants born at<1,350 g who survived at least one week were stratified by gestational age ( or= 29 completed weeks) and grouped by the presence or absence of preeclampsia. Highest and lowest systolic and mean and diastolic blood pressures were recorded for each of the first seven days of life. Serial blood pressures were analyzed by repeated measures ANOVA: The presence of hypertension (defined as >or= 3 days with the highest systolic blood pressure>90th percentile for gestational age stratum and day-specific range) was analyzed by binary logistic regression. RESULTS: Infants >or= 29 weeks gestational age born to mothers with preeclampsia had higher blood pressures than did controls. Infants or= 29 weeks gestation. The long-term significance of this finding is not known.

Asymmetry of cerebral blood flow velocity in low birth weight infants.

BACKGROUND: In premature infants, intraventricular hemorrhage occurs more commonly in the left than the right hemisphere. We have demonstrated previously that cerebral blood flow velocity is lower in the left than the right middle cerebral artery in the first few hours after birth. This may be due to the open ductus arteriosus. OBJECTIVE: To test the hypothesis that blood flow velocity is lower in the left than the right middle cerebral artery only when the ductus arteriosus is open. STUDY DESIGN: Infants born at 25-33 weeks' gestation were enrolled. Middle cerebral artery blood flow velocities and coefficients of variation were measured on the left, followed by the right, on days 1 and 7 of life. Echocardiography identified 67 infants (25-33 weeks, 517-2,371 g) whose ductus arteriosus was open on day 1 and closed on day 7. RESULTS: Systolic (26.4 +/- 7.4 vs. 29.6 +/- 7.2 cm/s), mean (12.4 +/- 4.0 vs. 15.6 +/- 4.6 cm/s) and end-diastolic (5.3 +/- 2.2 vs. 6.8 +/- 2.9 cm/s) blood flow velocities were lower (p < 0.01) and the corresponding coefficients of variation were higher (p < 0.01) on the left on day 1. Neither the absolute Doppler blood flow velocities nor the coefficients of variation differed between the left and right sides on day 7. CONCLUSIONS: Blood flow velocity is lower and more variable in the left compared to the right middle cerebral artery on day 1 of life in premature infants. These differences are not found on day 7. We speculate that this difference is due to the associated ductus arteriosus patency.

Low blood pressure among very-low-birth-weight infants with fetal vessel inflammation.

OBJECTIVE: To test the hypothesis that fetal vessel inflammation (FVI: funisitis and/or fetal vasculitis) is associated with lower blood pressure (BP) over the first week of life and an increased risk of periventricular leukomalacia (PVL) among premature infants. STUDY DESIGN: A total of 255 infants born at <1350 g to normotensive mothers were stratified by gestational age (GA) and grouped by presence/absence of FVI on placental pathology. Daily highest (Hi) and lowest (Lo) systolic BP (BP(sys)), mean BP (BP(mn)) and diastolic BP (BP(dia)) over first 7 days of life were analyzed by repeated measures ANOVA and regression analysis. Cranial ultrasounds were obtained at 2 weeks of life. RESULTS: Infants > or =30 weeks gestation with FVI had lower HiBP(sys), HiBP(mn), HiBP(dia), LoBP(sys), LoBP(mn) and LoBP(dia) (p<0.001) than did infants without FVI. Infants with PVL (all < or =27 weeks gestation) had lower LoBP(mn) and LoBP(dia) (p<0.01) than controls. FVI did not increase the risk of PVL in these infants. CONCLUSION: FVI and PVL are associated with reduced BP over the first week of life.

Prophylactic indomethacin reduces grades III and IV intraventricular hemorrhages when compared to early indomethacin treatment of a patent ductus arteriosus.

OBJECTIVE: To determine the relative risk of severe intraventricular hemorrhage (IVH) between two very early indomethacin treatment strategies. STUDY DESIGN: Retrospective chart review of infants <29 weeks gestation and <1350 g who received either indomethacin prophylaxis or very early echocardiography with indomethacin treatment only if the ductus arteriosus was patent. RESULTS: A total of one hundred and two infants received prophylactic indomethacin (pINDO). Echochardiography was performed on 158 infants, of whom 117 received indomethacin. Infants receiving pINDO had lower gestational age, but similar birth weight, gender, race, antenatal steroid exposure, delivery mode, Apgar scores, and need for resuscitation as infants evaluated by echocardiography. Grades III to IV IVH was observed less frequently in infants who received pINDO (OR 0.27, 95% CI 0.10 to 0.77, p=0.014). Frequency of side effects and recurrent patent ductus arteriosus did not differ between treatment groups. CONCLUSION: pINDO reduces severe IVH when compared to an early echocardiography strategy.

Hemodynamic disturbances in premature infants born after chorioamnionitis: association with cord blood cytokine concentrations.

Chorioamnionitis and elevated cord blood inflammatory cytokine concentrations are associated with detectable disturbances of systemic and cerebral hemodynamics in premature newborns. Fifty-five infants (25-31 wk gestation) were enrolled. Chorioamnionitis was defined by placental histology. IL-6, IL-1beta, and tumor necrosis factor-alpha were quantified by ELISA. Blood pressure, heart rate, cardiac output, stroke volume, fractional shortening, and middle cerebral artery blood flow velocities were measured at 3 +/- 1 h after birth. Chorioamnionitis was evident in 22 placentas and was associated with increased IL-6 (p < 0.001), IL-1beta (p = 0.035), and heart rate (p = 0.027); and with decreased mean and diastolic blood pressure (p = 0.026 and p = 0.019, respectively). IL-6 concentration correlated inversely with systolic, mean, and diastolic blood pressures. Right ventricular cardiac output was elevated (p = 0.028) in infants with fetal vessel inflammation. Maternal temperature >or=38.0 degrees C and newborn immature-to-total white blood cell ratio >or=0.4 were associated with significant decreases in left ventricular fractional shortening (p = 0.001 and p = 0.005, respectively). Neither chorioamnionitis nor elevated cytokine concentrations were associated with changes in middle cerebral artery Doppler blood flow velocities. Chorioamnionitis and elevated cord blood IL-6 concentrations are associated with decreased blood pressure in premature newborns. Inflammation of the fetal vessels and nonspecific indicators of infection are associated with disturbances in cardiac function. Infants with chorioamnionitis and elevated cytokine concentrations do not manifest changes in cerebral Doppler indices within the first few postnatal hours. We speculate that cytokine-associated systemic hemodynamic disturbances in premature infants born after chorioamnionitis predispose such infants to perinatal brain injury.