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Our multi-institutional university consortium implemented a gastroschisis pathway in 2015 to standardize and improve care by promoting avoidance of routine intubation and paralysis during silo placement, expeditious abdominal wall closure, discontinuation of antibiotics/narcotics within 48 h of closure, and early initiation/advancement of feeds.Adherence to the gastroschisis pathway was prospectively monitored. Outcomes for the contemporary cohort (2015-2018) were compared with a historical cohort (2007-2012).Good adherence to the pathway was observed for 70 cases of inborn uncomplicated gastroschisis. The contemporary cohort had significantly lower median mechanical ventilator days (2 versus 5; p 0.01) and antibiotic days (5.5 versus 9; p 0.01) as well as earlier days to initiation of feeds (12 versus 15; p 0.01). However, no differences were observed in length of stay (28 versus 29 days; p = 0.70). A skin closure technique was performed in 66% of the patients, of which 46% were performed at bedside without intubation, the assistance of an operating-room team, or general anesthesia.In this study, adherence to a clinical pathway for gastroschisis across different facilities was feasible and led to reduction in exposure to mechanical ventilation and antibiotics. The adoption of a bedside skin closure technique appears to facilitate compliance with the pathway.Level II/III TYPE OF STUDY: Prospective comparative study with historical cohort.

Necrotizing enterocolitis (NEC) has been recognized for well over 5 decades yet remains the most common life-threatening surgical emergency in the newborn. The incidence of NEC has decreased steadily in preterm and very-low-birthweight infants over several decades and is typically uncommon in term newborns and infants with a birthweight greater than 2,500 g. Evidence accumulating during the past decade, however, suggests that practitioners should consider NEC in this broader subset of term infants with chromosomal and congenital anomalies complicated by heart or gastrointestinal defects when signs and symptoms of feeding intolerance, abdominal illness, or sepsis are present. The short- and long-term consequences of NEC are devastating in all infants, and although early disease recognition and treatment are essential, promoting human milk feeding as a primary modality in prevention is critical. This article highlights our current understanding of the pathophysiology, the clinical presentation, the risk factors for NEC in term infants compared with premature infants, and the treatment of NEC and discusses strategies in the prevention of NEC. Finally, we review the long-term consequences of NEC and the importance of primary care practitioners in the long-term care of infants after hospitalization for NEC.

Objective: Articles previously published by Sullivan et al. and Cristofalo et al. were reanalyzed using the proportion of cow milk-based nutrition received to determine whether that affected clinical outcomes during hospitalization for infants birth weight 500–1250 g. Abrams et al. showed in the same cohort incidences of necrotizing enterocolitis (NEC), NEC requiring surgery and sepsis increased proportionally to the amount of dietary cow milk. Methods: The data from the two studies conducted under essentially the same protocol were combined yielding a cohort of 260 infants receiving a diet ranging from 0% to 100% cow milk. Data analysis utilized negative binomial regression which mitigates differences between subjects in terms of their time on study by incorporating that number into the statistical model. The percent of cow milk-based nutrition was the only predictor investigated. Results: For all outcomes the larger the amount of cow's milk in the diet the greater the number of days of that intervention required. A trend toward statistical significance was seen for ventilator days; however, only parenteral nutrition (PN) days and days to full feeds achieved statistical significance. Conclusions: Incorporation of any cow milk-based nutrition into the diet of extremely premature infants correlates with more days on PN and a longer time to achieve full feeds. There was a nonstatistically significant trend toward increased ventilator days. These represent additional clinical consequences of the use of any cow milk-based protein in feeding EP infants.

Michael P. Sherman, MD, PhD (doctor honoris causa), FAAP (Fig 1), passed away peacefully on September 22, 2017, following complications from a stroke. Michael was a mentor, colleague, and collaborator to many and a respected educator, dedicated scientist, and physician to all. Dr Sherman was a superb neonatologist and world-renowned scientist focusing on infection and immunity in the newborn. He was Professor Emeritus of Child Health, University of Missouri, Columbia, MO, and Professor Emeritus of Pediatrics, University of California, Davis (UC-Davis). Dr Sherman’s scientific accomplishments extended over decades, with notable contributions in the fields of microbiology, immunology, genetics, and neonatal intensive care. He was born on June 8, 1942. Michael’s intellectual reach was enviable, and his passion for understanding and curing disease will be greatly missed. Figure 1. Dr Michael P. Sherman June 8, 1942–September 22, 2017. Dr Sherman attended California State Polytechnic University in San Luis Obispo, CA, and graduated in 1965 as a member of the Beta Beta Beta Honor Society with honors in Microbiology. He was a member of Alpha Omega Alpha National Medical Honor Society and graduated cum laude from the Medical College of Wisconsin, Milwaukee, WI (formerly Marquette School of Medicine) in 1969. He completed his pediatric internship and residency at the University of Michigan and was a Senior and Chief Resident in the Department of Pediatrics, University of California San Diego. Michael was particularly proud of his training in San Diego with the late Louis Gluck, MD, and fondly remembered these years by his membership in the “Gluck Club.” Michael served as a Major in the Air Force and as the Chief of Pediatric Services at Vandenberg US Air Force Hospital in San Diego, CA, from 1972 to 1974. He completed a fellowship in …

The purpose of this study is to evaluate the effects of enteral lactoferrin on the fecal microbiome and contrast those influences with the neonatal intensive care unit (NICU) environment. We theorized that lactoferrin and the NICU habitat shape the fecal microbial composition of very preterm infants. Although functions attributed to lactoferrin include intestinal immune system development and emergence of a healthy gut microbiota, evidence is limited. Twenty-one very low birth weight (VLBW1500 g) infants received twice-daily talactoferrin (TLf, a drug designation for recombinant human lactoferrin) or its excipient by gastric gavage from day 1-28 of life. Twenty-four-hour fecal samples were collected on day 21 of life and compared with fecal operational taxonomy units (OTUs) in treated and control infants in 2 NICUs. Workflow included fecal DNA isolation, generation of amplicons for the V1-V3 region of bacterial 16S ribosomal RNA, and sequencing of a gel-purified multiplex amplicon library using a Roche 454 GS FLX Titanium (Roche, Branford, Connecticut) platform and protocols. Fecal OTUs per infant were higher in NICU 1 vs NICU 2 (P .001), consistent with fewer antibiotic days (P .02) and a shorter duration of parenteral nutrition (P .007) in NICU 1. Proteobacteria and Firmicutes were the major phyla in infants treated with TLf and placebo. Among Enterobacteriaceae, TLf prophylaxis reduced Enterobacter and Klebsiella, but increased Citrobacter in feces of VLBW infants. Citrobacter caused no neonatal infections in the study population. OTUs for Clostridiaceae increased in NICU 1 among infants treated with TLf. Importantly, OTUs of staphylococci were barely detectable in both NICUs among infants fed TLf. Fewer hospital-acquired infections occurred in infants treated with TLf vs controls, although the reduction was seen mostly in coagulase-negative staphylococci-related bloodstream and central line infections (P = .06). TLf modified the fecal microbiome in VLBW infants, but care practices in the NICU habitat also contributed. Future research must establish whether elimination vs enrichment of gut-related microbiota reduces clinically significant hospital-acquired infections and promotes a healthy commensal microflora in the intestines of VLBW infants.ClinicalTrials.gov: NCT00854633.

Congenital hypothyroidism (CH) is the most common endocrine disorder affecting the newborn. Universal newborn screening (NBS) has virtually eliminated the static encephalopathy and devastating neurodevelopmental syndrome known as cretinism. This report describes the presentation of an infant referred by the primary pediatrician to our hospital at 12 days of age for confirmatory testing after the NBS was consistent with CH. The infant had hypoglycemia secondary to lethargy and poor feeding and required transfer to the neonatal intensive care unit for worsening abdominal distension despite normalization of serum thyroid function tests following hormone replacement. In particular, the recalcitrant ileus and secondary bowel obstruction resulted in an additional diagnostic workup and lengthened hospital day. Our report highlights the acute gastrointestinal consequences of hypothyroidism despite evidence of effective treatment. We believe that the preclinical detection and immediate therapy for CH have lessened the prevalence of this presentation in general practice, and hence practitioners are less likely to be familiar with its natural history and management.

Purpose of review There is an intense interest among neonatal caregivers as to whether lactoferrin given enterally may reduce the incidence of necrotizing enterocolitis in preterm infants. This review presents scientific and clinical evidence that lactoferrin alleviates or prevents this life-threatening disease. Recent findings Preclinical studies in neonatal rats showed that lactoferrin given orally before enteral infection with pathogenic Escherichia coli reduced bacteremia and mortality. A multicentered clinical trial found that very low-birth weight preterm infants given bovine lactoferrin had a significant reduction in late-onset sepsis; there was also a trend towards a diminished incidence of necrotizing enterocolitis. Although multicentered trials of lactoferrin use in preterm infants are near completion, regulatory burdens required to bring lactoferrin to the bedside may limit its availability. Summary Extremely preterm infants should receive colostrum, a natural lactoferrin concentrate, immediately after birth and, ideally, continue on breast milk throughout the hospital stay. This practice appears well tolerated, but additional experience will tell us whether this practice reduces the prevalence of necrotizing enterocolitis.

Incessant crying is one of the most common caregiver complaints during emergency department (ED) visits in the first few months of the child's life. Although the majority of cases are attributed to normal infant behavior, the differential diagnosis remains broad. Moreover, the potential for the negative impact of incessant crying on the mental well-being of caregivers as well as the infants necessitates that complaints be taken seriously and that “red flags” for underlying organic causes be ruled out and caregiver anxiety quelled. In addition, the apparent triviality of incessant crying in the face of the life-threatening illnesses or injuries that confront practitioners in the ED necessitates a high level of due diligence in the evaluation of these infants and their families. Ensuring the availability of family support is essential in the discharge planning. Families should also perceive the empathy of the physician and feel reassured about their safe discharge home. Although it is a challenge to examine an incessantly crying infant in all care settings, the failure to recognize the small percentage of infants that present with incessant crying as a manifestation of an underlying organic illness may have grave consequences. [ Pediatr Ann . 2016;45(11):e394–e398.]

To evaluate the safety and explore the efficacy of recombinant human lactoferrin (talactoferrin [TLf]) to reduce infection.We conducted a randomized, double blind, placebo-controlled trial in infants with birth weight of 750-1500 g. Infants received enteral TLf (n = 60) or placebo (n = 60) on days 1 through 28 of life; the TLf dose was 150 mg/kg every 12 hours. Primary outcomes were bacteremia, pneumonia, urinary tract infection, meningitis, and necrotizing enterocolitis (NEC). Secondary outcomes were sepsis syndrome and suspected NEC. We recorded clinical, laboratory, and radiologic findings, along with diseases and adverse events, in a database used for statistical analyses.Demographic data were similar in the 2 groups of infants. We attributed no enteral or organ-specific adverse events to TLf. There were 2 deaths in the TLf group (1 each due to posterior fossa hemorrhage and postdischarge sudden infant death), and 1 death in the placebo group, due to NEC. The rate of hospital-acquired infections was 50% lower in the TLf group compared with the placebo group (P .04), including fewer blood or line infections, urinary tract infections, and pneumonia. Fourteen infants in the TLf group weighing1 kg at birth had no gram-negative infections, compared with only 3 of 14 such infants in the placebo group. Noninfectious outcomes were not statistically significantly different between the 2 groups, and there were no between-group differences in growth or neurodevelopment over a 1-year posthospitalization period.We found no clinical or laboratory toxicity and a trend toward less infectious morbidity in the infants treated with TLf.ClinicalTrials.gov: NCT00854633.

Human milk is the ideal nutrient for neonates. Breastfeeding exposes neonates to maternal microflora, provides host protection, and has proteins that mediate immune system development. Lactoferrin (LF) is the major whey protein in mammalian milk, and its multifunctional characteristics have shown importance in preventing infections. Ferric iron binding and natural peptide antibiotic properties of LF likely promote a healthy intestinal microbiome that prevents bacterial translocation and mediates optimal epithelial growth and differentiation. An established asset of LF is stimulation of naïve dendritic cells; this initiates the emergence of neonatal Th1 helper cells, thereby reversing the Th2 bias associated with pregnancy. Moreover, LF promotes development of Peyer patches, which leads to enhanced IgA secretion into the intestinal lumen. The anti-inflammatory properties of LF involve its binding of endotoxin and other proinflammatory molecules released by intestinal pathogens. LF also blocks receptors that microbes use for epithelial invasion, and thus LF mitigates a proinflammatory response by the host during infection. These properties of LF are known from basic science research and preclinical investigations, and they have resulted in the enteral use of bovine and recombinant human LF to prevent neonatal late onset sepsis. Bovine LF has been shown to reduce the incidence of late onset sepsis in extremely preterm infants, but Food and Drug Administration approval of LF for use in the NICU has not taken place. Because LF is currently available only for scientific investigations, the feeding of a mother's milk is encouraged shortly after birth because the concentration of LF is highest in colostrum.

A 4-month-old premature infant with a history of tracheoesophageal fistula ligation at birth presents with right-side chest wall prominence 1 month after repair of the esophageal atresia. ### Birth History and Early Hospital Course On day 2, the infant underwent division and ligation of the fistula with gastrostomy tube placement. Surgery was complicated by the development of a right-sided chylothorax requiring chest tube placement for drainage and octreotide therapy, which resolved by age 3½ months. The patient underwent right thoracotomy and esophageal atresia repair at age 3 …

Immunologic defense mechanisms of the adaptive and innate immune systems coordinate a balance between host defense and overreaction to the proinflammatory stimuli of the resident microflora in the intestinal tract. Among cells of the intestinal innate immune system, Paneth cells, located in the small intestinal crypts of Lieberkühn, have evolved to provide immediate responses to bacteria as well as shape the composition of commensal bacterial flora in the small intestine. Paneth cells release secretory granules rich in a variety of proteins involved in host defense and inflammation, including alpha-defensins. Alpha-defensins are small, cationic peptides that exhibit a broad spectrum of antimicrobial actions. In addition, Paneth cell granules contain other antibacterial substances, including lysozyme, secretory phospholipase A2, lectins, and a variety of immunomodulatory cytokines. Paneth cell secretion is stimulated by bacteria or by components of bacterial cell envelopes, such as lipopolysaccharide and lipoteichoic acid. The number of Paneth cells, their expression of alpha-defensins, and their expression of proteins involved in the detection of luminal bacteria are reduced in fetuses compared with term newborns and adults. Hence, reduced Paneth cell numbers and immaturity in the production of antibacterial products or their ability to detect bacteria may predispose newborns, and preterm infants in particular, to pathogenic bacterial overgrowth and translocation, contributing to the development of bacteremia, sepsis, and intestinal inflammation in diseases such as necrotizing enterocolitis.

The conceptual framework for a gut-brain axis has existed for decades. The Human Microbiome Project is responsible for establishing intestinal dysbiosis as a mediator of inflammatory bowel disease, obesity, and neurodevelopmental disorders in adults. Recent advances in metagenomics implicate gut microbiota and diet as key modulators of the bidirectional signaling pathways between the gut and brain that underlie neurodevelopmental and psychiatric disorders in adults. Evidence linking intestinal dysbiosis to neurodevelopmental disease outcomes in preterm infants is emerging. Recent clinical studies show that intestinal dysbiosis precedes late-onset neonatal sepsis and necrotizing enterocolitis in intensive care nurseries. Moreover, strong epidemiologic evidence links late-onset neonatal sepsis and necrotizing enterocolitis in long-term psychomotor disabilities of very-low-birth-weight infants. The notion of the gut-brain axis thereby supports that intestinal microbiota can indirectly harm the brain of preterm infants. In this review, we highlight the anatomy and physiology of the gut-brain axis and describe transmission of stress signals caused by immune-microbial dysfunction in the gut. These messengers initiate neurologic disease in preterm infants. Understanding neural and humoral signaling through the gut-brain axis will offer insight into therapeutic and dietary approaches that may improve the outcomes of very-low-birth-weight infants.

Background and aims The effects of lactoferrin [LF] on neonatal gut bacteria is unknown. We theorised LF has a greater impact on gut microbiota than the NICU environment. Methods Ten very preterm infants received enteral recombinant human lactoferrin [rhLF], while 11 infants received placebo for the first 28 days of life. We collected a faecal sample on day 21. We sequenced amplicons made from the V1 – V3 region of bacterial 16 S rRNA in faeces. QIIME and mothur processed filtered reads to classify operational taxonomy units [OTUs] with >97% sequence similarity. Statistical analyses used SPSS. Results Mean faecal OTUs per infant were higher in NICU1 (mean = 63,284) versus NICU2 (48,080, p Veillonella as a marker of gut microbiome maturity was higher in NICU1 (mean OTUs = 13,146 versus NICU2 = 1909, p Enterobacter hormaechei in the faeces. Infants given placebo had more E. hormaechei (mean OTUs = 23,661) versus rhLF-treated babies (mean = 2330, p S. aureus and Pseudomonas , were lower in the faeces of rhLF-treated infants (p Conclusions rhLF modulates gut bacteria of preterm infants. The NICU habitat also significantly affects the intestinal microbiome. Research must show if bovine LF also reduces faecal pathogens in very preterm infants.