Sarah Keene

Association of Red Blood Cell Transfusion, Anemia, and Necrotizing Enterocolitis in Very Low-Birth-Weight Infants

IMPORTANCE Data regarding the contribution of red blood cell (RBC) transfusion and anemia to necrotizing enterocolitis (NEC) are conflicting. These associations have not been prospectively evaluated, accounting for repeated, time-varying exposures. OBJECTIVE To determine the relationship between RBC transfusion, severe anemia, and NEC. DESIGN, SETTING, AND PARTICIPANTS In a secondary, prospective, multicenter observational cohort study from January 2010 to February 2014, very low-birth-weight (VLBW, ≤1500 g) infants, within 5 days of birth, were enrolled at 3 level III neonatal intensive care units in Atlanta, Georgia. Two hospitals were academically affiliated and 1 was a community hospital. Infants received follow-up until 90 days, hospital discharge, transfer to a non-study-affiliated hospital, or death (whichever came first). Multivariable competing-risks Cox regression was used, including adjustment for birth weight, center, breastfeeding, illness severity, and duration of initial antibiotic treatment, to evaluate the association between RBC transfusion, severe anemia, and NEC. EXPOSURES The primary exposure was RBC transfusion. The secondary exposure was severe anemia, defined a priori as a hemoglobin level of 8 g/dL or less. Both exposures were evaluated as time-varying covariates at weekly intervals. MAIN OUTCOMES AND MEASURES Necrotizing enterocolitis, defined as Bell stage 2 or greater by preplanned adjudication. Mortality was evaluated as a competing risk. RESULTS Of 600 VLBW infants enrolled, 598 were evaluated. Forty-four (7.4%) infants developed NEC. Thirty-two (5.4%) infants died (all cause). Fifty-three percent of infants (319) received a total of 1430 RBC transfusion exposures. The unadjusted cumulative incidence of NEC at week 8 among RBC transfusion-exposed infants was 9.9% (95% CI, 6.9%-14.2%) vs 4.6% (95% CI, 2.6%-8.0%) among those who were unexposed. In multivariable analysis, RBC transfusion in a given week was not significantly related to the rate of NEC (adjusted cause-specific hazard ratio, 0.44 [95% CI, 0.17-1.12]; P = .09). Based on evaluation of 4565 longitudinal measurements of hemoglobin (median, 7 per infant), the rate of NEC was significantly increased among VLBW infants with severe anemia in a given week compared with those who did not have severe anemia (adjusted cause-specific hazard ratio, 5.99 [95% CI, 2.00-18.0]; P = .001). CONCLUSIONS AND RELEVANCE Among VLBW infants, severe anemia, but not RBC transfusion, was associated with an increased risk of NEC. Further studies are needed to evaluate whether preventing severe anemia is more important than minimizing RBC transfusion.

Predicting death or extended length of stay in infants with congenital diaphragmatic hernia

Objective:To predict mortality or length of stay (LOS) >109 days (90th percentile) among infants with congenital diaphragmatic hernia (CDH).Study Design:We conducted a retrospective analysis using the Childrens Hospital Neonatal Database during 2010 to 2014. Infants born >34 weeks gestation with CDH admitted at 22 participating regional neonatal intensive care units were included; patients who were repaired or were at home before admission were excluded. The primary outcome was death before discharge or LOS >109 days. Factors associated with this outcome were used to develop a multivariable equation using 80% of the cohort. Validation was performed in the remaining 20% of infants.Results:The median gestation and age at referral in this cohort (n=677) were 38 weeks and 6 h, respectively. The primary outcome occurred in 242 (35.7%) infants, and was distributed between mortality (n=180, 27%) and LOS >109 days (n=66, 10%). Regression analyses showed that small for gestational age (odds ratio (OR) 2.5, P=0.008), presence of major birth anomalies (OR 5.9, P<0.0001), 5- min Apgar score ⩽3 (OR 7.0, P=0.0002), gradient of acidosis at the time of referral (P<0.001), the receipt of extracorporeal support (OR 8.4, P<0.0001) and bloodstream infections (OR 2.2, P=0.004) were independently associated with death or LOS >109 days. This model performed well in the validation cohort (area under curve (AUC)=0.856, goodness-of-fit (GF) χ2, P=0.16) and acted similarly even after omitting extracorporeal support (AUC=0.82, GF χ2, P=0.05).Conclusions:Six variables predicted death or LOS ⩾109 days in this large, contemporary cohort with CDH. These results can assist in risk adjustment for comparative benchmarking and for counseling affected families.

Early feeding factors associated with exclusive versus partial human milk feeding in neonates receiving intensive care

Objective:To evaluate early feeding factors associated with exclusive human milk (EHM) feeding at discharge in a cohort of human milk-fed infants admitted to the neonatal intensive care unit (NICU).Study Design:Retrospective cohort of consecutively discharged infants from two NICUs over a 12-month period who received any human milk during the 24 h before hospital discharge. We used logistic regression to evaluate early feeding factors associated with EHM feeding at discharge.Result:We evaluated a total of 264 infants. EHM-fed infants were twice as likely to receive human milk at the first feeding compared with partial human milk-fed infants (65% vs 32%; P<0.01). In multivariable analysis, including adjustment for race and type of maternal insurance, infants receiving human milk as the initial feeding, compared with formula, had a greater odds of EHM feeding at hospital discharge (adjusted odds ratio (OR)=3.41; 95% confidence interval (CI)=1.82 to 6.39; P<0.001).Conclusion:Among infants admitted to the NICU whose mothers provide human milk, those receiving human milk as the first feeding were more likely to receive EHM feeding at discharge.

Identical Twins with Lethal Congenital Pulmonary Airway Malformation Type 0 (Acinar Dysplasia): Further Evidence of Familial Tendency

We report a case of identical twins with lethal congenital pulmonary airway malformation (CPAM) type 0. Twin A expired several hours after birth, and twin B was sustained by extra-corporeal membrane oxygenation (ECMO) support; however, care was withdrawn from twin B following the autopsy of twin A, which revealed a diagnosis of CPAM type 0. Both twins showed pulmonary hypoplasia, histologically consistent with CPAM type 0 and pulmonary hypertension. Furthermore, the family also had a previous male who presented with pulmonary hypoplasia and respiratory failure and died shortly after birth; however, no autopsy was performed to confirm a diagnosis of CPAM. Here, in discussing our case, as well as previously reported cases, we demonstrate CPAM type 0s high prevalence among females (9:1 ratio). From the reported cases, it appears that CPAM type 0s tendency to recur in families is up to 40%, suggesting an autosomal recessive inheritance pattern. However, the actual tendency of familial recurrence is hard to assess due to the rarity of the disease and the potential lack of reporting CPAM type 0 cases. To our knowledge, our report represents the first description of CPAM type 0 in identical twins.

An overview of medical ECMO for neonates

Extracorporeal membrane oxygenation (ECMO), a life-saving therapy for respiratory and cardiac failure, was first used in neonates in the 1970s. The indications and criteria for ECMO have changed over the years, but it continues to be an important option for those who have failed other medical therapies. Since the Extracorporeal Life Support Organization (ELSO) Registry was established in 1989, more than 29,900 neonates have been placed on ECMO for respiratory failure, with 84% surviving their ECMO course, and 73% surviving to discharge or transfer. In this chapter, we will review the basics of ECMO, patient characteristics and criteria, patient management, ECMO complications, special uses of neonatal ECMO, and patient outcomes.

Predicting Mortality or Intestinal Failure in Infants with Surgical Necrotizing Enterocolitis

Objective To compare existing outcome prediction models and create a novel model to predict death or intestinal failure (IF) in infants with surgical necrotizing enterocolitis (NEC). Study design A retrospective, observational cohort study conducted in a 2‐campus health system in Atlanta, Georgia, from September 2009 to May 2015. Participants included all infants ≤37 weeks of gestation with surgical NEC. Logistic regression was used to model the probability of death or IF, as a composite outcome, using preoperative variables defined by specifications from 3 existing prediction models: American College of Surgeons National Surgical Quality Improvement Program Pediatric, Score for Neonatal Acute Physiology Perinatal Extension, and Vermont Oxford Risk Adjustment Tool. A novel preoperative hybrid prediction model was also derived and validated against a patient cohort from a separate campus. Results Among 147 patients with surgical NEC, discrimination in predicting death or IF was greatest with American College of Surgeons National Surgical Quality Improvement Program Pediatric (area under the receiver operating characteristic curve [AUC], 0.84; 95% CI, 0.77–0.91) when compared with the Score for Neonatal Acute Physiology Perinatal Extension II (AUC, 0.60; 95% CI, 0.48–0.72) and Vermont Oxford Risk Adjustment Tool (AUC, 0.74; 95% CI, 0.65–0.83). A hybrid model was developed using 4 preoperative variables: the 1‐minute Apgar score, inotrope use, mean blood pressure, and sepsis. The hybrid model AUC was 0.85 (95% CI, 0.78–0.92) in the derivation cohort and 0.77 (95% CI, 0.66–0.86) in the validation cohort. Conclusions Preoperative prediction of death or IF among infants with surgical NEC is possible using existing prediction tools and, to a greater extent, using a newly proposed 4‐variable hybrid model.

The Vanishing Twin Syndrome

Two cases of devastating fetal malformations associated with vanished monochorionic twins were identified upon review of pathology files. A 35-year-old G1P0 woman and 36-year-old G3P1 woman were both diagnosed with an intrauterine twin gestation via transvaginal ultrasound at 10 weeks. The spectrum of fetal anomalies ranged from omphalocele, bilateral upper extremity, and unilateral lower extremity hypoplasia, to craniofacial malformation with diaphragmatic hernia. On histopathologic examination, the placentas demonstrated vascular anastomoses between the surviving co-twin and the “vanished” fetal sac. We propose anastomotic placental vasculature as a contributing factor to the observed fetal malformations. Additionally, genetic or teratogenic factors may have been attributed to the demise of the first twin and the anomalies seen in the other twin. While such instances are rare, they are important to consider when counseling patients regarding outcomes associated with a monochorionic vanished twin.

Predicting Risk of Infection in Infants with Congenital Diaphragmatic Hernia

Objective To predict incident bloodstream infection and urinary tract infection (UTI) in infants with congenital diaphragmatic hernia (CDH). Study design We conducted a retrospective analysis using the Childrens Hospital Neonatal Database during 2010‐2016. Infants with CDH admitted at 22 participating regional neonatal intensive care units were included; patients repaired or discharged to home prior to admission/referral were excluded. The primary outcome was death or the occurrence of bloodstream infection or UTI prior to discharge. Factors associated with this outcome were used to develop a multivariable equation using 80% of the cohort. Validation was performed in the remaining 20% of infants. Results Median gestation and postnatal age at referral in this cohort (n = 1085) were 38 weeks and 3.1 hours, respectively. The primary outcome occurred in 395 patients (36%); and was associated with low birth weight, low Apgar, low admission pH, renal and associated anomalies, patch repair, and extracorporeal membrane oxygenation (P < .001 for all; area under receiver operating curve = 0.824; goodness of fit χ2 = 0.52). After omitting death from the outcome measure, admission pH, patch repair of CDH, and duration of central line placement were significantly associated with incident bloodstream infection or UTI. Conclusions Infants with CDH are at high risk of infection which was predicted by clinical factors. Early identification and low threshold for sepsis evaluations in high‐risk infants may attenuate acquisition and the consequences of these infections.

Acquired Infection and Antimicrobial Utilization During Initial NICU Hospitalization in Infants with Congenital Diaphragmatic Hernia

Background: In addition to substantial medical and surgical intervention, neonates with congenital diaphragmatic hernia often have concurrent concerns for acquired infection. However, few studies focus on infection and corresponding antimicrobial utilization in this population. Methods: The Children’s Hospital Neonatal Database was queried for congenital diaphragmatic hernia infants hospitalized from January 2010 to February 2016. Patient charts were linked to the Pediatric Health Information Systems database. Descriptive clinical data including delivery history, cultures sent, diagnosed infection, antimicrobial use and outcomes were reported. Results: A total of 1085 unique patients were identified after data linkages; 275 (25.3%) were born at <37 weeks’ gestation. Bacteremia at delivery (2/1085) and in the first 7 days of life (8/1085) was less common than later infection, but 976 patients (89.9%) were treated with antibiotics. Median number of days on antibiotics was 6 [3,11] for those without a documented infection and 21 [13,36] for those with positive cultures. Incidence of urinary tract infection, bacteremia and pneumonia increased significantly over time and was most common after 28 days. Antibiotic use, conversely, decreased over time (92% of infants in week 1 to 44% in week 4 and beyond). Conclusions: Although culture positivity increased with age, risk of these selected infections was relatively low for a population in neonatal intensive care unit. An important mismatch is observed between culture negativity and high rates of antibiotic utilization. These data identify opportunities for antibiotic stewardship quality improvement programs.