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 (r(int)SO(2)) 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 r(int)SO(2) affected cerebral oxygen saturation (r(c)SO(2)). Methods In a longitudinal observational pilot study using near-infrared spectroscopy we measured r(int)SO(2) and r(c)SO(2) 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 r(c)SO(2), 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, r(int)SO(2) values decreased postprandially: mean (SE) 44% (10) versus 35% (7), P = .01. On Day 29, r(int)SO(2) values increased: 44% (11) versus 54% (7), P = .01. Infants with a PMA >= 32 weeks showed a r(int)SO(2) increase after feeding (37% versus 51%, P = .04) whereas infants with a 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

Weight shapes the intestinal microbiome in preterm infants:results of a prospective observational study

BACKGROUND: The intestinal microbiome in preterm infants differs markedly from term infants. It is unclear whether the microbiome develops over time according to infant specific factors. METHODS: We analysed (clinical) metadata - to identify the main factors influencing the microbiome composition development - and the first meconium and faecal samples til the 4th week via 16 S rRNA amplican sequencing. RESULTS: We included 41 infants (gestational age 25–30 weeks; birth weight 430-990 g. Birth via Caesarean section (CS) was associated with placental insufficiency during pregnancy and lower BW. In meconium samples and in samples from weeks 2 and 3 the abundance of Escherichia and Bacteroides (maternal faecal representatives) were associated with vaginal delivery while Staphylococcus (skin microbiome representative) was associated with CS. Secondly, irrespective of the week of sampling or the mode of birth, a transition was observed as children children gradually increased in weight from a microbiome dominated by Staphylococcus (Bacilli) towards a microbiome dominated by Enterobacteriaceae (Gammaproteobacteria). CONCLUSIONS: Our data show that the mode of delivery affects the meconium microbiome composition. They also suggest that the weight of the infant at the time of sampling is a better predictor for the stage of progression of the intestinal microbiome development/maturation than postconceptional age as it less confounded by various infant-specific factors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-021-02279-y

Fecal Bile Salts and the Development of Necrotizing Enterocolitis in Preterm Infants

BACKGROUND: Intestinal bile salts (BSs) may be implicated in NEC development. We hypothesized that fecal BS levels are higher in preterm infants at risk for NEC. METHODS: We compared the composition and concentration of fecal BSs in ten preterm infants who developed NEC (Bell's Stage ≥ II) with twenty matched control infants without NEC. Conjugated and unconjugated fecal BSs were measured after birth (T1) and twice prior to NEC (T2, T3). Data are presented as medians and interquartile ranges. RESULTS: GA and BW were similar in all preterms: ~27+4 weeks and ~1010 g. Age of NEC onset was day 10 (8-24). T1 was collected 2 (1-3) days after birth. T2 and T3 were collected 5 (5-6) days and 1 (0-2) day before NEC or at corresponding postnatal ages in controls. The composition of conjugated BSs did not differ between the two groups. Total unconjugated BSs were 3-fold higher before NEC compared to controls at corresponding ages (0.41 μmol/g feces (0.21-0.74) versus 0.14 μmol/g feces (0.06-0.46), p < 0.05). CONCLUSION: Fecal BS concentrations are higher in preterm infants who develop NEC compared to infants without NEC. Further study is needed to determine the predictive value of fecal BSs in the development of NEC

Ostomy Creation in Neonates with Acute Abdominal Disease:Friend or Foe?

Background An ostomy seems a safe alternative in neonates with an acute abdomen when immediate restoration of bowel continuity is deemed undesirable. Faced with several complications in our center, and the feeling we are not the only center with these complications, we decided to assess the rate and type of complications after both ostomy creation and closure. Methods All data regarding neonates ( Results A total of 155 patients who underwent a laparotomy for suspect acute abdomen were identified. Median gestational age was 33 weeks (range 25 to 40) and median birth weight was 1926 g (range 560 to 4380). Median age at laparotomy was 8 days (range 0 to 30). Indications for surgery were necrotizing enterocolitis (n = 38), spontaneous intestinal perforation (n = 11), intestinal atresia (n = 9) or obstruction (n = 5), and volvulus (n = 4). An ostomy was created in 67 patients (67/155: 43%): 38 boys and 29 girls. There were 8 jejuno-, 49 ileo-, and 10 colostomies created. In almost all cases (94%), a mucous fistula was also constructed. In 23 patients (23/67: 34%) ostomy-related complications occurred. Most frequent were high output ostomy (n = 10) and necrosis of the enterostomy (n = 7). Due to either one of the complications, nine patients (9/67: 13%) needed a reoperation. In this study, 11 patients died before ostomy closure could occur. In 53 patients, the ostomy was closed after a median of 107 days (range 4 to 299). After ostomy closure, complications occurred in 13 cases (13/53: 25%). Seven patients (7/53: 13%) needed another reoperation because of anastomotic leakage (n = 4), adhesions (n = 2), or incisional hernia (n = 1). There was no closure-related mortality. Conclusion Although creating a temporary ostomy in newborns is preferable in certain situations, there is a considerable occurrence of complications and reoperations

Serial fecal calprotectin in the prediction of necrotizing enterocolitis in preterm neonates

PURPOSE: To investigate whether serial measurements of fecal calprotectin concentrations enable us to identify infants who will develop NEC prior to development of symptoms. METHODS: Prospective matched case-control study including 100 high-risk neonates. High risk includes 1) gestational age (GA) ≤30 weeks, 2) birth-weight (BW) ≤1000 g, 3) GA 30-32 weeks and BW ≤1250 g, 4) born from a mother who received indomethacin for tocolysis. We matched every NEC subject with three controls for birth weight and gestational age. Fecal calprotectin was measured twice a week from day one until five weeks after birth or until NEC development. We analyzed differences in fecal calprotectin between NEC subjects and controls in the week preceding NEC onset and course of fecal calprotectin within subjects who developed NEC. RESULTS: Of 100 included patients, ten (median GA 27.5 weeks [24.6-29.4], BW 1010 g [775-1630]) developed NEC. The median calprotectin concentration in all samples combined was 332 μg/g [<40-8230] μg/g feces. There were no differences between NEC subjects and controls, with a wide variation in both groups. In NEC subjects, there was no intraindividual rise in calprotectin before clinical symptoms occurred. CONCLUSIONS: There are high concentrations and wide interindividual variations in calprotectin in preterm infants during the first weeks of life. Wide intraindividual variation further precludes the serial use of fecal calprotectin in the early detection or prediction of NEC in high risk infants. LEVEL OF EVIDENCE: III

Serial fecal calprotectin in the prediction of necrotizing enterocolitis in preterm neonates

PURPOSE: To investigate whether serial measurements of fecal calprotectin concentrations enable us to identify infants who will develop NEC prior to development of symptoms.METHODS: Prospective matched case-control study including 100 high-risk neonates. High risk includes 1) gestational age (GA) ≤30 weeks, 2) birth-weight (BW) ≤1000 g, 3) GA 30-32 weeks and BW ≤1250 g, 4) born from a mother who received indomethacin for tocolysis. We matched every NEC subject with three controls for birth weight and gestational age. Fecal calprotectin was measured twice a week from day one until five weeks after birth or until NEC development. We analyzed differences in fecal calprotectin between NEC subjects and controls in the week preceding NEC onset and course of fecal calprotectin within subjects who developed NEC.RESULTS: Of 100 included patients, ten (median GA 27.5 weeks [24.6-29.4], BW 1010 g [775-1630]) developed NEC. The median calprotectin concentration in all samples combined was 332 μg/g [&lt;40-8230] μg/g feces. There were no differences between NEC subjects and controls, with a wide variation in both groups. In NEC subjects, there was no intraindividual rise in calprotectin before clinical symptoms occurred.CONCLUSIONS: There are high concentrations and wide interindividual variations in calprotectin in preterm infants during the first weeks of life. Wide intraindividual variation further precludes the serial use of fecal calprotectin in the early detection or prediction of NEC in high risk infants.LEVEL OF EVIDENCE: III.</p

Early cerebral and intestinal oxygenation in the risk assessment of necrotizing enterocolitis in preterm infants

Background and aim: Predicting necrotizing enterocolitis (NEC) might help in preventing its devastating consequences. We aimed to investigate whether early cerebral and intestinal tissue oxygen saturation (rSO(2)) and fractional tissue oxygen extraction (FTOE) predict the onset of NEC. Study design: Prospective observational case-control study. Subjects: Infants with gestational age (GA) = 70% (odds ratio 9.00 (95% CI 1.33-61.14). Intestinal FTOE was higher in infants who developed NEC compared to controls during the last NIRS measurement at median 2 days (range: 1-7) before NEC onset (median 0.65 vs. 0.44). Conclusions: Cerebral oxygenation monitoring early after birth might be valuable in the risk assessment of NEC development. Additionally, our results suggest that intestinal oxygenation is impaired before the onset of clinical NEC

A Necrotizing Enterocolitis-Associated Gut Microbiota Is Present in the Meconium: Results of a Prospective Study

BACKGROUND: Anomalous intestinal microbiota development is supposedly associated with development of necrotizing enterocolitis (NEC). Our aim in this study was to identify the intestinal microbiota of patients at risk for NEC. METHODS: In a prospective trial that investigated prognostic factors for development of NEC in high-risk neonates (NTR4153), 11 NEC cases were gestational age/birthweight matched with controls (ratio of 1:2). Feces were collected twice a week. We used the first feces sample of each patient (meconium), as well as the last 2 feces samples prior to development of NEC. DNA was extracted, and the bacterial 16S rRNA genes were analyzed on a MiSeq sequencer. RESULTS: The presence and abundance of Clostridium perfringens (8.4%) and Bacteroides dorei (0.9%) in meconium were increased in neonates who developed NEC compared with controls (0.1% and 0.2%; both species, P < .001). In post-meconium samples, the abundance of staphylococci became negatively associated with NEC development (P = .1 and P = .01 for consecutive samples); Clostridium perfringens continued to be more prevalent in NEC cases. Early enteral feeding and, in particular, breast milk were correlated with an increase in lactate-producing bacilli in post-meconium samples (ρ = -0.45; P = .004). CONCLUSIONS: A NEC-associated gut microbiota can be identified in meconium samples; C. perfringens continues to be associated with NEC from the first meconium till just before NEC onset. In contrast, in post-meconium, increased numbers of staphylococci were negatively associated with NEC. These findings suggest causality but this causality should be verified in trials of induced infection in animals, targeted antibiotics, and/or probiotics. CLINICAL TRIALS REGISTRATION: CALIFORNIA trial, registered under trial number NTR4153 in the Dutch Trial Registry

A Hemodynamically Significant Patent Ductus Arteriosus Does Not Affect Cerebral or Renal Tissue Oxygenation in Preterm Infants

BACKGROUND: Patent ductus arteriosus (PDA) is common in preterm infants and is associated with significant morbidity. To determine whether the PDA is hemodynamically significant (HSDA), several echocardiographic parameters have been suggested, including retrograde diastolic blood flow in the descending aorta (Dao). OBJECTIVE: To assess the impact of an HSDA, including retrograde diastolic flow in the Dao, on regional tissue oxygen saturation (rSO2) and extraction measured by near-infrared spectroscopy (NIRS). METHODS: This is a prospective observational cohort study in which we included preterm infants (GA 1.4 and/or left pulmonary artery end-diastolic flow velocity >0.2 m/s and/or retrograde diastolic blood flow in the Dao. RESULTS: Forty-nine infants were included, with a median GA of 27.6 weeks (IQR: 26.1-29.0), birth weight of 980 g (IQR: 800-1,200), and postnatal age of 77 h (IQR: 70-107). Infants with a closed duct (n = 11), a non-HSDA (n = 18), and an HSDA (n = 20) had similar cerebral and renal NIRS measurements. Retrograde diastolic blood flow in the Dao, present in 11 infants with PDA, also did not affect cerebral and renal NIRS measurements. CONCLUSION: In preterm infants with clinical signs of an HSDA within 2 weeks after birth, cerebral and renal oxygen saturation and extraction are not affected by an HSDA or by retrograde diastolic blood flow in the Dao