Intestinal Oxygenation and Survival After Surgery for Necrotizing Enterocolitis: An Observational Cohort Study.

OBJECTIVE: To assess whether regional intestinal oxygen saturation (rintSO2) and regional cerebral oxygen saturation (rcSO2) measurements aid in estimating survival of preterm infants after surgery for NEC. SUMMARY OF BACKGROUND DATA: Predicting survival after surgery for NEC is difficult yet of the utmost importance for counseling parents. METHODS: We retrospectively studied prospectively collected data of preterm infants with surgical NEC who had available rintSO2 and rcSO2 values measured via near-infrared spectroscopy 0-24 hours preoperatively. We calculated mean rintSO2 and rcSO2 for 60-120 minutes for each infant. We analyzed whether preoperative rintSO2 and rcSO2 differed between survivors and non-survivors, determined cut-off points, and assessed the added value to clinical variables. RESULTS: We included 22 infants, median gestational age 26.9 weeks [interquartile range (IQR): 26.3-28.4], median birth weight 1088 g [IQR: 730-1178]. Eleven infants died postoperatively. Preoperative rintSO2, but not rcSO2, was higher in survivors than in non-survivors [median: 63% (IQR: 42-68) vs 29% (IQR: 21-43), P < 0.01), with odds ratio for survival 4.1 (95% confidence interval, 1.2-13.9, P = 0.02) per 10% higher rintSO2. All infants with rintSO2 values of >53% survived, whereas all infants with rintSO2 <35% died. Median C-reactive protein [138 mg/L (IQR: 83-179) vs 73 mg/L (IQR: 12-98), P < 0.01), lactate [1.1 mmol/L (IQR: 1.0-1.6) vs 4.6 mmol/L (IQR: 2.8-8.0), P < 0.01], and fraction of inspired oxygen [25% (IQR: 21-31) vs 42% (IQR: 30-80), P < 0.01] differed between survivors and non-survivors. Only rintSO2 remained significant in the multiple regression model. CONCLUSIONS: Measuring rintSO2, but not rcSO2, seems of added value to clinical variables in estimating survival of preterm infants after surgery for NEC. This may help clinicians in deciding whether surgery is feasible and to better counsel parents about their infants' chances of survival.

Plasma citrulline during the first 48 h after onset of necrotizing enterocolitis in preterm infants.

BACKGROUND: Levels of plasma citrulline (citrulline-P), a biomarker for enterocyte function, might be useful for the monitoring the course of necrotizing enterocolitis (NEC). Our aim was to evaluate whether citrulline-P levels during the first 48 h (h) after NEC onset were associated with need for surgery, survival, and intestinal recovery. METHODS: In preterm infants with NEC (Bell's stage ≥2) we measured citrulline-P levels during the first 48 h after NEC onset. Categorizing the measurements into 0-8 h, 8-16 h, 16-24 h, 24-36 h, and 36-48 h, we determined the course of citrulline-P using linear regression analyses. Next, we analyzed whether citrulline-P levels measured at 0-24 h and 24-48 h differed between conservative and surgical treatment, survivors and nonsurvivors, and equal/below and above total group's median time to full enteral feeding (FEFt). RESULTS: We included 48 infants, median gestational age 28.3 [IQR:26.0-31.4] weeks, birth weight 1200 [IQR:905-1524] grams. Citrulline-P levels decreased the first 48 h (B per time interval: -1.40 µmol, 95% CI, -2.73 to -0.07, p = 0.04). Citrulline-P was not associated with treatment, nor with survival. Citrulline-P at 0-24 h, but not 24-48 h, was higher in infants with FEFt ≤20 days than in infants with FEFt >20 days (20.7 [IQR:19.9-25.3] µmol/L (n = 13) vs. 11.1 [IQR:8.4-24.0] µmol/L (n = 11), p = 0.049), with a citrulline-P cut-off value of 12.3 µmol/L. CONCLUSION: Citrulline-P levels decreased the first 48 h after NEC onset, suggesting on-going intestinal injury. In survivors, measuring citrulline-P in the first 24 h after NEC onset may provide an indication for intestinal recovery rate.

Predicting intestinal recovery after necrotizing enterocolitis in preterm infants.

BACKGROUND: Intestinal recovery after NEC is difficult to predict in individuals. We evaluated whether several biomarkers predict intestinal recovery after NEC in preterm infants. METHODS: We measured intestinal tissue oxygen saturation (rintSO2) and collected urinary intestinal-fatty acid binding protein (I-FABPu) levels 0-24 h and 24-48 h after NEC onset, and before and after the first re-feed. We assessed intestinal recovery in two ways: time to full enteral feeding (FEFt; below or equal/above group's median) and development of post-NEC complications (recurrent NEC/post-NEC stricture). We determined whether the rintSO2, its range, and I-FABPu differed between groups. RESULTS: We included 27 preterm infants who survived NEC (Bell's stage ≥ 2). Median FEFt was 14 [IQR: 12-23] days. Biomarkers only predicted intestinal recovery after the first re-feed. Mean rintSO2 ≥ 53% combined with mean rintSO2range ≥ 50% predicted FEFt < 14 days with OR 16.7 (CI: 2.3-122.2). The rintSO2range was smaller (33% vs. 51%, p < 0.01) and I-FABPu was higher (92.4 vs. 25.5 ng/mL, p = 0.03) in case of post-NEC stricture, but not different in case of recurrent NEC, compared with infants without complications. CONCLUSION: The rintSO2, its range, and I-FABPu after the first re-feed after NEC predicted intestinal recovery. These biomarkers have potential value in individualizing feeding regimens after NEC.

The effect of enteral bolus feeding on regional intestinal oxygen saturation in preterm infants is age-dependent: a longitudinal observational study.

BACKGROUND: The factors that determine the effect of enteral feeding on intestinal perfusion after preterm birth remain largely unknown. We aimed to determine the effect of enteral feeding on intestinal oxygen saturation (rintSO2) in preterm infants and evaluated whether this effect depended on postnatal age (PNA), postmenstrual age (PMA), and/or feeding volumes. We also evaluated whether changes in postprandial rintSO2 affected cerebral oxygen saturation (rcSO2). METHODS: In a longitudinal observational pilot study using near-infrared spectroscopy we measured rintSO2 and rcSO2 continuously for two hours on postnatal Days 2 to 5, 8, 15, 22, 29, and 36. We compared preprandial with postprandial values over time using multi-level analyses. To assess the effect of PNA, PMA, and feeding volumes, we performed Wilcoxon signed-rank tests or logistic regression analyses. To evaluate the effect on rcSO2, we also used logistic regression analyses. RESULTS: We included 29 infants: median (range) gestational age 28.1 weeks (25.1-30.7) and birth weight 1025 g (580-1495). On Day 5, rintSO2 values decreased postprandially: mean (SE) 44% (10) versus 35% (7), P = .01. On Day 29, rintSO2 values increased: 44% (11) versus 54% (7), P = .01. Infants with a PMA ≥ 32 weeks showed a rintSO2 increase after feeding (37% versus 51%, P = .04) whereas infants with a PMA < 32 weeks did not. Feeding volumes were associated with an increased postprandial rintSO2 (per 10 mL/kg: OR 1.63, 95% CI, 1.02-2.59). We did not find an effect on rcSO2 when rintSO2 increased postprandially. CONCLUSIONS: Our study suggests that postprandial rintSO2 increases in preterm infants only from the fifth week after birth, particularly at PMA ≥ 32 weeks when greater volumes of enteral feeding are tolerated. We speculate that at young gestational and postmenstrual ages preterm infants are still unable to increase intestinal oxygen saturation after feeding, which might be essential to meet metabolic demands. TRIAL REGISTRATION: For this prospective longitudinal pilot study we derived patients from a larger observational cohort study: CALIFORNIA-Trial, Dutch Trial Registry NTR4153 .

Red Blood Cell Transfusions Affect Intestinal and Cerebral Oxygenation Differently in Preterm Infants with and without Subsequent Necrotizing Enterocolitis.

OBJECTIVE: To assess intestinal and cerebral oxygenation during and after red blood cell (RBC) transfusions in preterms with or without subsequent transfusion-associated necrotizing enterocolitis (TANEC). STUDY DESIGN: In preterms of < 32 weeks' gestational age, we measured intestinal and cerebral regional tissue oxygen saturation (rintSO2, rcSO2) and their variabilities using near-infrared spectroscopy during and after transfusions. We compared eight infants who developed TANEC 6 to 48 hours after RBC transfusions with 16 controls. RESULTS: In TANEC infants, rcSO2 was lower during and after RBC transfusions than in controls, median (interquartile range) 55% (50-62) versus 72% (65-75), p < 0.01. There were no differences regarding rintSO2. Individual rintSO2 and rcSO2 ranges were smaller after transfusions in TANEC infants, 28% (9-36) versus 49% (40-65), p < 0.01, and 17% (14-33) versus 36% (26-57), p = 0.01, as was short-term rintSO2 variability. For each 10% higher rcSO2, the risk of developing TANEC decreased (odds ratio 0.09; 95% confidence interval 0.01-0.63). The smaller the rintSO2 range after transfusion, the higher the risk of developing TANEC. CONCLUSION: In preterm infants lower rcSO2, but not rintSO2, values during and after RBC transfusions are associated with TANEC. Lower rintSO2 and rcSO2 variabilities after RBC transfusions may represent a diminished capacity for vascular adaptation, possibly leading to TANEC.

Preterm infants undergoing laparotomy for necrotizing enterocolitis or spontaneous intestinal perforation display evidence of impaired cerebrovascular autoregulation.

BACKGROUND: Preterm infants requiring surgery are at risk of impaired neurocognitive development caused, possibly, by cerebral ischemia associated with impaired cerebrovascular autoregulation (CAR). We evaluated CAR before, during, and after laparotomy. STUDY DESIGN: This was a hypothesis generating prospective observational cohort study. SUBJECTS: We included preterm infants requiring surgery for necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP). Before, during, and after surgery we measured cerebral oxygen saturation using NIRS and calculated cerebral fractional tissue oxygen extraction (cFTOE). OUTCOME MEASURES: Impaired CAR was defined if correlation coefficients (rho) between mean cFTOE and mean arterial blood pressure values were ≤-0.30 with P < .05. We used logistic regression analyses to determine factors associated with impaired CAR. RESULTS: Nineteen infants with median (IQR) GA 27.6 weeks (26.6-31.0), birth weight 1090 g (924-1430), and postnatal age 9 days (7-12) were included. CAR was impaired more often during surgery than before (12 versus 3, P = .02) or after (12 versus 0, P < .01). A higher PCO2 level was associated with impaired CAR during surgery (OR 3.04, 95% CI, 1.11-8.12 for every 1 kPa increase). CONCLUSIONS: More than half of preterm infants with NEC or SIP displayed evidence of impaired CAR during laparotomy. Further research should focus on mechanisms contributing to impaired CAR in preterm infants during surgery.

Amplitude-integrated electroencephalography during the first 72 h after birth in neonates diagnosed prenatally with congenital heart disease.

BackgroundLittle is known on amplitude-integrated electroencephalography (aEEG) during the first few days after birth in neonates with congenital heart disease (CHD). Our aim was, therefore, to assess electrocortical activity using aEEG within the first 72 h after birth in neonates diagnosed prenatally with CHD, and to define independent prenatal and postnatal predictors for abnormal aEEG.MethodsNeonates with CHD who were admitted to the neonatal intensive care unit between 2010 and 2017 were retrospectively included. We assessed aEEG background patterns, sleep-wake cycling, and epileptic activity during the first 72 h after birth and defined prenatal and postnatal clinical parameters associated with aEEG patterns.ResultsSeventy-two neonates were included. Twenty-six (36%) had mildly abnormal and six (8%) had severely abnormal aEEG background patterns at some point during the study period. Sleep-wake cycling was present in 97% of the neonates. Subclinical seizures were common (15%), whereas none of the neonates had clinical seizures. Only treatment with sedatives was a significant predictor for abnormal aEEG background patterns, explaining 56% of the variance.ConclusionAbnormal aEEG background patterns are common and are strongly associated with treatment with sedatives in neonates with prenatally diagnosed CHD. Future studies should assess the association between early postnatal aEEG abnormalities and neurodevelopmental outcome.