Impact of concomitant necrotizing enterocolitis on mortality in very low birth weight infants with intraventricular hemorrhage.

OBJECTIVE: To evaluate the impact of necrotizing enterocolitis (NEC) on mortality in very low birth weight (VLBW) infants with intraventricular hemorrhage (IVH). STUDY DESIGN: Data were collected on VLBW infants born 2014-2018 at Vermont Oxford Network (VON) centers. NEC and IVH were categorized by severity. Adjusted risk ratios (ARR) for in-hospital mortality were calculated. RESULTS: This study included 187 187 VLBW infants. Both medical and surgical NEC increased mortality risk compared to those without NEC. Stratification by IVH severity modified this effect (no IVH: ARR 3.04 (95%CI 2.74-3.38) for medical NEC and 4.17 (3.84-4.52) for surgical NEC; mild IVH: ARR 2.14 (1.88-2.44) for medical NEC and 2.49 (2.24-2.78) for surgical NEC; severe IVH: ARR 1.14 (1.03-1.26) for medical NEC and 1.10 (1.02-1.18) for surgical NEC). CONCLUSION: The relative impact of NEC on mortality decreased as IVH severity increased. Given the frequent coexistence of NEC and IVH, these data inform multidisciplinary management of these complex patients.

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.

The effect of daily probiotics on the incidence and severity of necrotizing enterocolitis in infants with very low birth weight.

BACKGROUND: Necrotizing enterocolitis remains a leading cause of morbidity and mortality in premature infants. The role of prophylactic probiotics in its prevention is unclear. This study evaluates the effect of routine probiotics on the incidence and severity of necrotizing enterocolitis in infants with very low birth weight in the neonatal intensive care unit. METHODS: This retrospective cohort study compared infants cared for at a single institution before and after implementation of routine probiotic administration (2014- 2018). Babies born after July 2016 received probiotics containing Bifidobacterium and Lactobacillus daily until 35 weeks corrected gestational age. Baseline characteristics, necrotizing enterocolitis incidence and severity, infections, mortality, and length of stay were compared between groups. RESULTS: Of the 665 infants included in the study, 310 received probiotics and 355 did not. The 2 groups did not differ with regard to gestational age, birth anthropometrics, mode of delivery, comorbidities, and type of enteral feed. The incidence of necrotizing enterocolitis (Bell's stage 2 of 3) was similar between groups (4% v. 5%, p = 0.35), as was its severity (p = 0.10). In addition, there were no significant differences in mortality and length of stay between the groups. Significantly fewer infants receiving probiotics developed infections (27% v. 34%, p = 0.046), with the rate of urinary tract infections having the largest reduction. CONCLUSION: The routine use of Bifidobacterium and Lactobacillus probiotics in infants with very low birth weight did not significantly affect the incidence and severity of necrotizing enterocolitis. However, the use of probiotics was associated with fewer overall infections.

Initial Laparotomy Versus Peritoneal Drainage in Extremely Low Birthweight Infants With Surgical Necrotizing Enterocolitis or Isolated Intestinal Perforation: A Multicenter Randomized Clinical Trial.

OBJECTIVE: The aim of this study was to determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP). SUMMARY BACKGROUND DATA: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown. METHODS: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18 to 22 months corrected age, analyzed using prespecified frequentist and Bayesian approaches. RESULTS: Of 992 eligible infants, 310 were randomized and 96% had primary outcome assessed. Death or NDI occurred in 69% of infants in the laparotomy group versus 70% with drainage [adjusted relative risk (aRR) 1.0; 95% confidence interval (CI): 0.87-1.14]. A preplanned analysis identified an interaction between preoperative diagnosis and treatment group (P = 0.03). With a preoperative diagnosis of NEC, death or NDI occurred in 69% after laparotomy versus 85% with drainage (aRR 0.81; 95% CI: 0.64-1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference <0) for a preoperative diagnosis of NEC was 97%. For preoperative diagnosis of IP, death or NDI occurred in 69% after laparotomy versus 63% with drainage (aRR, 1.11; 95% CI: 0.95-1.31); Bayesian probability of benefit with laparotomy = 18%. CONCLUSIONS: There was no overall difference in death or NDI rates at 18 to 22 months corrected age between initial laparotomy versus drainage. However, the preoperative diagnosis of NEC or IP modified the impact of initial treatment.

Association of Blood Donor Sex and Age With Outcomes in Very Low-Birth-Weight Infants Receiving Blood Transfusion.

Importance: There are conflicting data on the association between blood donor characteristics and outcomes among patients receiving transfusions. Objective: To evaluate the association of blood donor sex and age with mortality or serious morbidity in very low-birth-weight (VLBW) infants receiving blood transfusions. Design, Setting, and Participants: This is a cohort study using data collected from 3 hospitals in Atlanta, Georgia. VLBW infants (≤1500 g) who received red blood cell (RBC) transfusion from exclusively male or female donors were enrolled from January 2010 to February 2014. Infants received follow-up until 90 days, hospital discharge, transfer to a non-study-affiliated hospital, or death. Data analysis was performed from July 2019 to December 2020. Exposures: Donor sex and mean donor age. Main Outcomes and Measures: The primary outcome was a composite outcome of death, necrotizing enterocolitis (Bell stage II or higher), retinopathy of prematurity (stage III or higher), or moderate-to-severe bronchopulmonary dysplasia. Modified Poisson regression, with consideration of covariate interactions, was used to estimate the association between donor sex and age with the primary outcome, with adjustment for the total number of transfusions and birth weight. Results: In total, 181 infants were evaluated, with a mean (SD) birth weight of 919 (253) g and mean (SD) gestational age of 27.0 (2.2) weeks; 56 infants (31%) received RBC transfusion from exclusively female donors. The mean (SD) donor age was 46.6 (13.7) years. The primary outcome incidence was 21% (12 of 56 infants) among infants receiving RBCs from exclusively female donors, compared with 45% (56 of 125 infants) among those receiving RBCs from exclusively male donors. Significant interactions were detected between female donor and donor age (P for interaction = .005) and between female donor and number of transfusions (P for interaction < .001). For the typical infant, who received a median (interquartile range) of 2 (1-3) transfusions, RBC transfusion from exclusively female donors, compared with male donors, was associated with a lower risk of the primary outcome (relative risk, 0.29; 95% CI, 0.16-0.54). The protective association between RBC transfusions from female donors, compared with male donors, and the primary outcome increased as the donor age increased, but decreased as the number of transfusions increased. Conclusions and Relevance: These findings suggest that RBC transfusion from female donors, particularly older female donors, is associated with a lower risk of death or serious morbidity in VLBW infants receiving transfusion. Larger studies confirming these findings and examining potential mechanisms are warranted.

Association of High-Mobility Group Box 1 (HMGB1) Gene Polymorphisms with Susceptibility and Better Survival Prognosis in Chinese Han Neonatal Necrotizing Enterocolitis.

BACKGROUND High-mobility group box 1 (HMGB1) plays a crucial role in a variety of diseases, including neonatal necrotizing enterocolitis (NEC). The purpose of this study was to investigate the association of HMGB1 gene single-nucleotide polymorphisms (SNPs) with susceptibility and survival prognosis in Chinese Han neonates with NEC. MATERIAL AND METHODS The HMGB1 gene rs1360485, rs1045411, and rs2249825 site SNPs were genotyped in all participants. The mRNA expression of serum HMGB1 was examined using quantitative reverse transcription-polymerase chain reaction. The correlation of the HMGB1 rs1360485 SNP with NEC neonatal survival prognosis was evaluated by univariate analysis and logistic multivariate regression analysis. RESULTS The TC and CC genotype and C allele distribution frequencies of the rs1360485 SNP were lower in the NEC group, and the differences were statistically significant (all P<0.05). Individuals carrying the TC and CC genotype or C allele had a low risk of being affected by NEC. However, the genotype and allele distributions of rs1045411 and rs2249825 were not significantly different between the patient and control groups (P>0.05). NEC neonates with HMGB1 gene rs1360485 site mutations had lower mRNA levels of serum HMGB1 than those with rs1360485 site wild-type, and the rs1360485 genotypes TC and CC could independently predict better survival outcomes in NEC neonates. CONCLUSIONS This study demonstrated that the rs1360485 SNP of the HMGB1 gene is associated with susceptibility of NEC in neonates, and the rs1360485 genotypes TC and CC may affect HMGB1 expression and are associated with the survival prognosis of neonates with NEC.

Mortality and Morbidities according to Time of Birth in Extremely Low Birth Weight Infants.

BACKGROUND: Although the overall quality of high-risk neonatal care has improved recently, there is still concern about a difference in the quality of care when comparing off-hour births and regular-hour births. Moreover, there are no data in Korea regarding the impact of time of birth on mortality and morbidities in preterm infants. METHODS: A total of 3,220 infants weighing < 1,000 g and born at 23-34 weeks in 2013-2017 were analyzed based on the Korean Neonatal Network data. Mortality and major morbidities were analyzed using logistic regression according to time of birth during off-hours (nighttime, weekend, and holiday) and regular hours. The institutes were sub-grouped into hospital group I and hospital group II based on the neonatal intensive care unit (NICU) care level defined by the mortality rates of < 50% and ≥ 50%, respectively, in infants born at 23-24 weeks' gestation. RESULTS: The number of births during regular hours and off-hours was similar. In the total population and hospital group I, off-hour births were not associated with increased neonatal mortality and morbidities. However, in hospital group II, increased early mortality was found in the off-hour births when compared to regular-hour births. CONCLUSION: Efforts to improve the overall quality of NICU are required to lower the early mortality rate in off-hour births. Also, other sensitive indexes for the evaluation of quality of NICU care should be further studied.

Feeding during neonatal therapeutic hypothermia, assessed using routinely collected National Neonatal Research Database data: a retrospective, UK population-based cohort study.

BACKGROUND: Therapeutic hypothermia is standard of care in high-income countries for babies born with signs of hypoxic ischaemic encephalopathy, but optimal feeding during treatment is uncertain and practice is variable. This study aimed to assess the association between feeding during therapeutic hypothermia and clinically important outcomes. METHODS: We did a population-level retrospective cohort study using the UK National Neonatal Research Database. We included all babies admitted to National Health Service neonatal units in England, Scotland, and Wales between Jan 1, 2010, and Dec 31, 2017, who received therapeutic hypothermia for 72 h or died during this period. For analysis, we created matched groups using propensity scores and compared outcomes in babies who were fed versus unfed enterally during therapeutic hypothermia. The primary outcome was severe necrotising enterocolitis, either confirmed at surgery or causing death. Secondary outcomes include pragmatically defined necrotising enterocolitis (a recorded diagnosis of necrotising enterocolitis in babies who received at least 5 consecutive days of antibiotics while also nil by mouth during their neonatal unit stay), late-onset infection (pragmatically defined as 5 consecutive days of antibiotic treatment commencing after day 3), survival to discharge, measures of breastmilk feeding, and length of stay in neonatal unit. FINDINGS: 6030 babies received therapeutic hypothermia, of whom 1873 (31·1%) were fed during treatment. Seven (0·1%) babies were diagnosed with severe necrotising enterocolitis and the number was too small for further analyses. We selected 3236 (53·7%) babies for the matched feeding analysis (1618 pairs), achieving a good balance for all recorded background variables. Pragmatically defined necrotising enterocolitis was rare in both groups (incidence 0·5%, 95% CI 0·2-0·9] in the fed group vs 1·1% [0·7-1·4] in the unfed group). The enterally fed group had fewer pragmatically defined late-onset infections (difference -11·6% [95% CI -14·0 to -9·3]; p<0·0001), higher survival to discharge (5·2% [3·9-6·6]; p<0·0001), higher proportion of breastfeeding at discharge (8·0% [5·1-10·8]; p<0·0001), and shorter neonatal unit stays (-2·2 [-3·0 to -1·2] days; p<0·0001) compared with the unfed group. INTERPRETATION: Necrotising enterocolitis is rare in babies receiving therapeutic hypothermia. Enteral feeding during hypothermia is safe and associated with beneficial outcomes compared with not feeding, although residual confounding could not be completely ruled out. Our findings support starting milk feeds during therapeutic hypothermia. FUNDING: UK National Institute for Health Research Health Technology Assessment programme 16/79/13.

Neonatal surgical outcomes: a prospective observational study at a Tertiary Academic Hospital in Johannesburg, South Africa.

PURPOSE: The neonatal period is the most vulnerable period for a child. There is a paucity of data on the burden of neonatal surgical disease in our setting. The aim of this study was to describe the frequency with which index neonatal surgical conditions are seen within our setting and to document the 30-day outcome of these patients. METHODS: This was a single-centre prospective observational study in which all neonates with paediatric surgical pathology referred to the paediatric surgical unit with a corrected gestational age of 28 days were included. RESULTS: Necrotising enterocolitis was the most frequent reason for referral to the paediatric surgical unit (n = 68, 34.34%). Gastroschisis was the most frequent congenital anomaly referred (n = 20, 10.10%). The overall morbidity was 57.58%. Surgical complications contributed to 18.51% of morbidities. The development of gram negative nosocomial sepsis was the most frequent cause of morbidity (n = 98, 50.78%). Mortality at 30 days was 21.74% (n = 40). Sepsis contributed to mortality in 35 patients (87.5%), 16 of which had gram negative sepsis. CONCLUSION: Gram-negative sepsis was a major contributing factor in the development of morbidity and mortality in our cohort. Prevention and improvement in infection control are imperative if we are to improve outcomes in our surgical neonates.

C-reactive protein/albumin ratio is a prognostic indicator for predicting surgical intervention and mortality in neonates with necrotizing enterocolitis.

PURPOSE: The role of hypoalbuminemia and raised C-reactive protein (CRP) levels in predicting critical prognosis has been described extensively in adult literature. However, there are limited studies in pediatrics, particularly neonates. The CRP/albumin (CRP/ALB) ratio is often associated with higher mortality, organ failure and prolonged hospital stay. We hypothesized that the serum CRP/ALB ratio has a prognostic value in predicting surgery and mortality in neonates with necrotizing enterocolitis (NEC). METHODS: Retrospective review of all neonates with clinical and radiological evidence of non-perforated NEC that were treated in a tertiary-level referral hospital between 2009 and 2018. General patient demographics, laboratory parameters and outcomes were recorded. Receiver operating characteristics analysis was performed to evaluated optimal cut-offs and area under the curve (AUC) with 95% confidence intervals (CI). RESULTS: A total of 191 neonates were identified. Of these, 103 (53.9%) were born at ≤ 28 weeks of gestation and 101 (52.9%) had a birth weight of ≤ 1000 g. Eighty-four (44.0%) patients underwent surgical intervention for NEC. The overall survival rate was 161/191 (84.3%). A CRP/ALB ratio of ≥ 3 on day 2 of NEC diagnosis was associated with a statistically significant higher likelihood for surgery [AUC 0.71 (95% CI 0.63-0.79); p < 0.0001] and mortality [AUC 0.66 (95% CI 0.54-0.77); p = 0.0150], respectively. CONCLUSIONS: A CRP/ALB ratio of ≥ 3 on day 2 is indicative of a critical pathway in neonates with radiologically confirmed, non-perforated NEC. This could be used as an additional criterion to guide parental counselling in NEC for surgical intervention and mortality.

Severe acute kidney injury in neonates with necrotizing enterocolitis: risk factors and outcomes.

BACKGROUND: To study the risk factors and outcomes of severe acute kidney injury (AKI) in neonates with necrotizing enterocolitis. METHODS: Retrospective chart review of 202 neonates with necrotizing enterocolitis (NEC) (Bell stage >IIa) from 2013 to 2018. AKI was defined as per-modified neonatal Kidney Disease: Improving Global Outcomes criteria. Demographic, clinical, and outcome data were compared between neonates without severe AKI (stage 0 and 1 AKI) and those with severe AKI (stage 2 and 3 AKI). RESULTS: Severe AKI occurred in 66/202 (32.6%) of neonates after NEC diagnosis and after 61/104 (58.7%) of surgical NEC diagnoses. On adjusted model, surgical NEC [adjusted odds ratio (aOR) = 30.6; 95% confidence interval (CI) = 8.9, 130.6], outborn [aOR = 3.9; 95% CI = 1.54, 11.0], exposure to antenatal steroids [aOR = 3.0; 95% CI = 1.1, 8.9], and positive blood culture sepsis [aOR = 3.5; 95% CI = 1.3, 10.0] had increased odds for severe AKI. Those with severe AKI required longer hospitalization [124 days (interquartile range (IQR) 88-187) vs. 82 days (IQR 42-126), p < 0.001]. CONCLUSIONS: Severe AKI is common in neonates with NEC who require surgical intervention, are outborn, have positive blood culture sepsis, and receive antenatal steroids. Severe AKI is associated with a significantly longer length of hospitalization. IMPACT: Neonates with NEC, who are transferred from outside hospitals, require surgical NEC management, and/or have a positive blood culture at NEC onset are at the highest odds for severe (stages 2 and 3) AKI. Assessment of urine output is important for patients with NEC. Without it, 11% of those with severe AKI would have been misdiagnosed using serum creatinine alone. Kidney-protective strategies in the pre-, peri-, and postoperative period may improve the morbidity and mortality associated with severe AKI in neonates with NEC.

Neurodevelopmental outcomes following neonatal late-onset sepsis and blood culture-negative conditions.

OBJECTIVE: Determine risk of death or neurodevelopmental impairment (NDI) in infants with late-onset sepsis (LOS) versus late-onset, antibiotic-treated, blood culture-negative conditions (LOCNC). DESIGN: Retrospective cohort study. SETTING: 24 neonatal centres. PATIENTS: Infants born 1/1/2006-31/12/2014, at 22-26 weeks gestation, with birth weight 401-1000 g and surviving >7 days were included. Infants with early-onset sepsis, necrotising enterocolitis, intestinal perforation or both LOS and LOCNC were excluded. EXPOSURES: LOS and LOCNC were defined as antibiotic administration for ≥5 days with and without a positive blood/cerebrospinal fluid culture, respectively. Infants with these diagnoses were also compared with infants with neither condition. OUTCOMES: Death or NDI was assessed at 18-26 months corrected age follow-up. Modified Poisson regression models were used to estimate relative risks adjusting for covariates occurring ≤7 days of age. RESULTS: Of 7354 eligible infants, 3940 met inclusion criteria: 786 (20%) with LOS, 1601 (41%) with LOCNC and 1553 (39%) with neither. Infants with LOS had higher adjusted relative risk (95% CI) for death/NDI (1.14 (1.05 to 1.25)) and death before follow-up (1.71 (1.44 to 2.03)) than those with LOCNC. Among survivors, risk for NDI did not differ between the two groups (0.99 (0.86 to 1.13)) but was higher for LOCNC infants (1.17 (1.04 to 1.31)) compared with unaffected infants. CONCLUSIONS: Infants with LOS had higher risk of death, but not NDI, compared with infants with LOCNC. Surviving infants with LOCNC had higher risk of NDI compared with unaffected infants. Improving outcomes for infants with LOCNC requires study of the underlying conditions and the potential impact of antibiotic exposure.

Effect of Feeding Strategies on the Development of Fulminant Necrotizing Enterocolitis.

INTRODUCTION: Necrotizing enterocolitis (NEC) causes significant neonatal morbidity. A subset of infants experience precipitous decline and death from fulminant-NEC (F-NEC). We sought to determine the effect of feeding practices on the development of this more virulent form of NEC. MATERIALS AND METHODS: Premature neonates developing Bell's stage II or III NEC between May 2011 and June 2017 were reviewed. Infants were stratified as having NEC or F-NEC, defined as NEC-totalis or NEC causing rapid decline and death within 72 hours. Risk factors extracted included demographics, gestational age, and weight at NEC diagnosis. Feeding data extracted included age at first feed, caloric density, type of feed (breast milk or formula), and whether full volume feeds were reached. Univariate analysis and multivariate analysis were performed. RESULTS: A total of 98 patients were identified, of which 80 were included. In total, 57 patients had NEC and 23 had F-NEC. Reaching full volume feeds was associated with F-NEC on both univariate and multivariate analysis (37.9 vs. 4.5%; odds ratio: 67, 95% confidence interval: 6.606-2041, p = 0.003). Infants developing F-NEC achieved full feeds earlier (22.5 vs. 19.8 days, p = 0.025) on univariate but not multivariate analysis. There was no difference in the rates of NEC and F-NEC among infants receiving breast milk (standard or fortified) or formula (standard or increased caloric density; p = 0.235). CONCLUSION: Among premature neonates with NEC, reaching full volume feedings was associated with a nearly 70-fold increased risk of F-NEC. Assuming it was possible to predict an infant's development of NEC, alternative feeding regimens might reduce the risk of F-NEC in this population.

Withholding or withdrawing life-sustaining treatment in extremely low gestational age neonates.

OBJECTIVE: To identify sociodemographic and clinical factors associated with withholding or withdrawing life-sustaining treatment (WWLST) for extremely low gestational age neonates. DESIGN: Observational study of prospectively collected registry data from 19 National Institute of Child Health and Human Development Neonatal Research Network centres on neonates born at 22-28 weeks gestation who died >12 hours through 120 days of age during 2011-2016. Sociodemographic and clinical factors were compared between infants who died following WWLST and without WWLST. RESULTS: Of 1168 deaths, 67.1% occurred following WWLST. Withdrawal of assisted ventilation (97.4%) was the primary modality. WWLST rates were inversely proportional to gestational age. Life-sustaining treatment was withheld or withdrawn more often for non-Hispanic white infants than for non-Hispanic black infants (72.7% vs 60.4%; 95% CI 1.00 to 1.92) or Hispanic infants (72.7% vs 67.2%; 95% CI 1.32 to 3.72). WWLST rates varied across centres (38.6-92.6%; p<0.001). The centre with the highest rate had adjusted odds 4.89 times greater than the average (95% CI 1.18 to 20.18). The adjusted odds of WWLST were higher for infants with necrotiing enterocolitis (OR 1.77, 95% CI 1.21 to 2.59) and severe brain injury (OR 1.98, 95% CI 1.44 to 2.74). CONCLUSIONS: Among infants who died, WWLST rates varied widely across centres and were associated with gestational age, race, ethnicity, necrotiing enterocolitis, and severe brain injury. Further exploration is needed into how race, centre, and approaches to care of infants with necrotiing enterocolitis and severe brain injury influence WWLST.

Quality Improvement Efforts Reduce Incidence of Surgical Necrotizing Enterocolitis and Related Deaths.

OBJECTIVE: The aim of this study was to determine whether a regional quality improvement (QI) initiative decreased incidence and severity of surgical necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. STUDY DESIGN: A retrospective review of all VLBW infants who received care at one of the three hospitals involved in a NEC QI initiative from 2011 to 2016. Primary outcome was the number of surgical NEC cases per year. Secondary outcomes included associated outcomes and mortality. RESULTS: Sixty-three infants with either a diagnosis of Stage III NEC (n = 40) or spontaneous intestinal perforation (SIP) (n = 23) were included. The incidence of medical and surgical NEC and the mortality rate of infants with surgical NEC decreased over time. Incidence and mortality of SIP did not significantly change. CONCLUSION: A regional QI bundle to reduce the overall incidence of NEC also significantly decreased the incidence of surgical NEC and all-cause mortality of infants diagnosed with surgical NEC. KEY POINTS: · QI reduces surgical necrotizing enterocolitis.. · Reduction in NEC rate improves mortality.. · Human milk does not change SIP incidence..

Incomplete resection of necrotic bowel may increase mortality in infants with necrotizing enterocolitis.

BACKGROUND: Infants with advanced necrotizing enterocolitis (NEC) often need surgical resection of necrotic bowel. We hypothesized that incomplete resection of NEC lesions, signified by the detection of necrotic patches in margins of resected bowel loops, results in inferior clinical outcomes. METHODS: We reviewed the medical records of infants with surgical NEC in the past 15 years for demographic, clinical, and histopathological data. We also developed statistical models to predict mortality and hospital stay. RESULTS: Ninety infants with surgical NEC had a mean (±standard error) gestational age of 27.3 ± 0.4 weeks, birth weight 1008 ± 48 g, NEC onset at 25.2 ± 2.4 days, and resected bowel length of 29.2 ± 3.2 cm. Seventeen (18.9%) infants who had complete resection of the necrosed bowel had fewer (4; 23.5%) deaths and shorter lengths of hospital stay. In contrast, a group of 73 infants with some necrosis within the margins of resected bowel had significantly more (34; 46.6%) deaths and longer hospital stay. The combination of clinical and histopathological data gave better regression models for mortality and hospital stay. CONCLUSION: In surgical NEC, incomplete resection of necrotic bowel increased mortality and the duration of hospitalization. Regression models combining clinical and histopathological data were more accurate for mortality and the length of hospital stay. IMPACT: In infants with surgical NEC, complete resection of necrotic bowel reduced mortality and hospital stay. Regression models combining clinical and histopathological information were superior at predicting mortality and hospital stay than simpler models focusing on either of these two sets of data alone. Prediction of mortality improved with the combination of antenatal steroids, chorioamnionitis, and duration of post-operative ileus, with severity of inflammation and hemorrhages in resected intestine. Length of hospital stay was shorter in infants with higher gestational ages, but longer in those with greater depth of necrosis or needing prolonged parenteral nutrition or supervised feedings.

Safety and efficacy of human milk-based fortifier in enterally fed preterm and/or low birthweight infants: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of the efficacy and safety of fortification of human milk with human milk-based fortifier versus cow's milk-based fortifier for use in preterm and/or very low birthweight infants. DESIGN: Randomised or quasi-randomised controlled trials comparing the effect of human milk fortification with human milk-based milk fortifier versus cow's milk-based fortifier in infants born <34 weeks' gestation and/or with birth weight <1500 g were identified by searching databases, clinical trial registries and reference lists until 5 November 2019. Two authors independently extracted data and assessed evidence quality. Meta-analyses were conducted using fixed or random effects models, as appropriate. MAIN OUTCOME MEASURES: Necrotising enterocolitis (Bell's stage II or higher) and late-onset sepsis. RESULTS: Of 863 unique records identified, 16 full-text trials were screened and 2 trials involving 334 infants were included. Primary outcome data were available for 332 infants. Use of human milk-based fortifier compared with cow's milk-based fortifier reduced the risk of necrotising enterocolitis (risk ratio 0.47, 95% CI 0.22 to 0.98). There was no clear evidence of an effect on late-onset sepsis or any other outcomes. The quality of evidence was low to very low due to imprecision and lack of blinding in one study. CONCLUSIONS: Findings suggest that there is a reduction in the incidence of necrotising enterocolitis with human milk-based fortifiers compared with cow's milk-based fortifiers. The overall quality of evidence is low. Further appropriately powered trials are required before this intervention can be routinely recommended for preterm infants.

Effects of Probiotics in Preterm Infants: A Network Meta-analysis.

CONTEXT: Probiotics have proven to be effective in promoting premature infants' health, but the optimal usage is unknown. OBJECTIVE: To compare probiotic supplements for premature infants. DATA SOURCES: We searched PubMed, Embase, Cochrane, and ProQuest from inception of these databases to June 1, 2020. STUDY SELECTION: Randomized trials of probiotic supplement intervention for preterm infants were screened by 2 reviewers independently. The primary outcomes were mortality and the morbidity of necrotizing enterocolitis (NEC). Secondary outcomes were morbidity of sepsis, time to achieve full enteral feeding, and length of hospital stay. DATA EXTRACTION: The data of primary and secondary outcomes were extracted by 2 reviewers and pooled with a random-effects model. RESULTS: The meta-analysis included 45 trials with 12 320 participants. Bifidobacterium plus Lactobacillus was associated with lower rates of mortality (risk ratio 0.56; 95% credible interval 0.34-0.84) and NEC morbidity (0.47; 0.27-0.79) in comparison to the placebo; Lactobacillus plus prebiotic was associated with lower rates of NEC morbidity (0.06; 0.01-0.41) in comparison to the placebo; Bifidobacterium plus prebiotic had the highest probability of having the lowest rate of mortality (surface under the cumulative ranking curve 83.94%); and Lactobacillus plus prebiotic had the highest probability of having the lowest rate of NEC (surface under the cumulative ranking curve 95.62%). LIMITATIONS: In few studies did authors report the data of infants with a lower birth weight or gestational age. CONCLUSIONS: The efficacy of single probiotic supplements is limited, compared to combined use of probiotics. To achieve optimal effect on premature infant health, combined use of prebiotic and probiotic, especially Lactobacillus or Bifidobacterium, is recommended.

Survival and causes of death in extremely preterm infants in the Netherlands.

OBJECTIVE: In the Netherlands, the threshold for offering active treatment for spontaneous birth was lowered from 25+0 to 24+0 weeks' gestation in 2010. This study aimed to evaluate the impact of guideline implementation on survival and causes and timing of death in the years following implementation. DESIGN: National cohort study, using data from the Netherlands Perinatal Registry. PATIENTS: The study population included all 3312 stillborn and live born infants with a gestational age (GA) between 240/7 and 266/7 weeks born between January 2011 and December 2017. Infants with the same GA born between January 2007 and December 2009 (N=1400) were used as the reference group. MAIN OUTCOME MEASURES: Survival to discharge, as well as cause and timing of death. RESULTS: After guideline implementation, there was a significant increase in neonatal intensive care unit (NICU) admission rate for live born infants born at 24 weeks' GA (27%-69%, p<0.001), resulting in increased survival to discharge in 24-week live born infants (13%-34%, p<0.001). Top three causes of in-hospital mortality were necrotising enterocolitis (28%), respiratory distress syndrome (19%) and intraventricular haemorrhage (17%). A significant decrease in cause of death either complicated or caused by respiratory insufficiency was seen over time (34% in 2011-2014 to 23% in 2015-2017, p=0.006). CONCLUSIONS: Implementation of the 2010 guideline resulted as expected in increased NICU admissions rate and postnatal survival of infants born at 24 weeks' GA. In the years after implementation, a shift in cause of death was seen from respiratory insufficiency towards necrotising enterocolitis and sepsis.