Spring-mediated distraction enterogenesis may alter the course of adaptation in porcine short bowel syndrome.

Introduction: Severe forms of short bowel syndrome (SBS) resulting in chronic intestinal failure (IF) have limited therapeutic options, all of which are associated with significant morbidities. Spring-mediated distraction enterogenesis (SMDE) uses an intraluminal self-expanding spring to generate mechanical force to induce intestinal stretching and sustained axial growth, providing a promising novel approach for patients with SBS. Previous studies have established this method to be safe and effective in small and large animal models. However, SMDE has previously not been implemented in a large, clinically relevant animal model. Methods: Juvenile mini-Yucatan pigs with 75% of their small intestine resected had intraluminal springs placed after an initial adaptive period. Morphological and histological assessments were performed on SMDE segments compared to the control region of the intestine undergoing normal adaptive responses to resection. Results: While the initial histologic adaptive response observed following resection was attenuated after a month, the SMDE segments instead augmented these adaptive changes. Specifically, intestinal length increased 2-fold in SMDE segments, and the widths of the epithelial, muscularis, and serosal layers were enhanced in SMDE compared with control segments of the same animal. This data suggests that morphologic intestinal adaptation may be enhanced with SMDE in the setting of SBS. Discussion: Here we demonstrate the successful and reproducible implementation of SMDE in a large animal model in the setting of prior intestinal resection, making SMDE a viable and novel approach for SBS to be explored further.

Paneth cell ontogeny in term and preterm ovine models.

Introduction: Paneth cells are critically important to intestinal health, including protecting intestinal stem cells, shaping the intestinal microbiome, and regulating host immunity. Understanding Paneth cell biology in the immature intestine is often modeled in rodents with little information in larger mammals such as sheep. Previous studies have only established the distribution pattern of Paneth cells in healthy adult sheep. Our study aimed to examine the ontogeny, quantification, and localization of Paneth cells in fetal and newborn lambs at different gestational ages and with perinatal transient asphyxia. We hypothesized that ovine Paneth cell distribution at birth resembles the pattern seen in humans (highest concentrations in the ileum) and that ovine Paneth cell density is gestation-dependent. Methods: Intestinal samples were obtained from 126-127 (preterm, with and without perinatal transient asphyxia) and 140-141 (term) days gestation sheep. Samples were quantified per crypt in at least 100 crypts per animal and confirmed as Paneth cells through in immunohistochemistry. Results: Paneth cells had significantly higher density in the ileum compared to the jejunum and were absent in the colon. Discussion: Exposure to perinatal transient asphyxia acutely decreased Paneth cell numbers. These novel data support the possibility of utilizing ovine models for understanding Paneth cell biology in the fetus and neonate.

Acute Bowel Ischemia in a Premature Neonate with Miller-Dieker Syndrome and Anomalous Right Coronary Artery From the Pulmonary Artery.

Miller-Dieker syndrome (MDS) is a rare disease characterized by type I lissencephaly, craniofacial dysmorphisms, intellectual disability, seizures, and death in early childhood. We report a case of a premature infant with MDS with an anomalous right coronary artery from the pulmonary artery who developed sudden bowel ischemia. This case prompts the reconsideration of cardiovascular involvement in patients with MDS. In addition, this review highlights key clinical features and reviews the critical manifestations of MDS that persist into childhood. [Pediatr Ann. 2023;52(8):e283-e291.].

State-of-the-art review and update of in vivo models of necrotizing enterocolitis.

NEC remains one of the most common causes of mortality and morbidity in preterm infants. Animal models of necrotizing enterocolitis (NEC) have been crucial in improving our understanding of this devastating disease and identifying biochemical pathways with therapeutic potential. The pathogenesis of NEC remains incompletely understood, with no specific entity that unifies all infants that develop NEC. Therefore, investigators rely on animal models to manipulate variables and provide a means to test interventions, making them valuable tools to enhance our understanding and prevent and treat NEC. The advancements in molecular analytic tools, genetic manipulation, and imaging modalities and the emergence of scientific collaborations have given rise to unique perspectives and disease correlates, creating novel pathways of investigation. A critical review and understanding of the current phenotypic considerations of the highly relevant animal models of NEC are crucial to developing novel therapeutic and preventative strategies for NEC.

Overview of Congenital Hypopituitarism for the Neonatologist.

Congenital hypopituitarism is the deficiency in 1 or more hormones produced by the anterior pituitary or released by the posterior pituitary and has an estimated incidence of 1 in 4,000 to 10,000. Due to the critical role the pituitary plays in growth, metabolic, and reproductive processes, early diagnosis is essential to prevent devastating and often preventable outcomes. However, in neonates with congenital hypopituitarism, symptoms are often nonspecific and tend to overlap with other disease processes, making diagnosis extremely challenging in the neonatal period. This review highlights the embryology and organogenesis of the pituitary gland, genetic causes of hypopituitarism, clinical presentations in the neonatal period, and methods to diagnose and treat select deficiencies with a focus on anterior pituitary hormones.

Congenital Syphilis Epidemiology, Prevention, and Management in the United States: A 2022 Update.

Congenital syphilis (CS) has dramatically increased in the United States (US) in the past decade despite the widespread availability of penicillin. Once considered an infection on the verge of elimination, CS has re-emerged as a familiar neonatal pathogen in US hospitals. This rise in cases has prompted the evaluation of potential causes and updates in prevention and management guidelines. Following a structured narrative approach, we reviewed CS data reports, peer-reviewed research articles, and updated management guidelines from state health departments over the past two decades. Our main search criteria centered on the treatment and prevention of CS, with a focus on prenatal health disparities. We identified geographical regions reporting disproportionate rates of CS, examined state laws regarding maternal syphilis testing, and evaluated potential reasons for the recent rise in cases. This article examines the current epidemiology, screening, and management recommendations for perinatal and CS in the US. It also reviews pathogenesis and clinical features in perinatal and pediatric populations. Finally, it highlights the likely contributing factors to increased CS rates and identifies areas for future research. Dramatically rising CS cases in certain regions and racial groups reflect gaps in the prevention, timely diagnosis, treatment, and management of perinatal syphilis and CS. Healthcare providers attending to mothers and children should recognize the re-emergence of this pathogen and be familiar with new screening and management guidelines. Increased federal funding for targeted interventions and research that address vulnerable populations is critical to curbing the re-emergence of this infection.

Craniosynostosis: Neonatal Perspectives.

Craniosynostosis is the premature fusion of 1 or more sutures that normally separate the bony plates of an infant's skull and occurs in about 1 in 2,000 to 2,500 live births. Primary or congenital craniosynostoses represent the majority of cases and consist of single-suture and multisuture synostoses. Multisuture synostoses are typically associated with distinct craniofacial syndromes, including Muenke syndrome, Apert syndrome, Crouzon syndrome, and Pfeiffer syndrome, and are thus categorized under syndromic craniosynostoses. Secondary causes of craniosynostoses include metabolic or hematologic disorders that affect bone metabolism and typically present much later than primary synostoses. The severity of the deformity and the presence of increased intracranial pressure dictate the need for early surgical intervention, prompting the importance of early recognition and timely referral. Infants with craniosynostosis are also at increased risk for neurodevelopmental impairment and thus require close follow-up and monitoring. The early recognition and referral of craniosynostosis is imperative for the optimization of management and minimization of potential neurologic impairments that may develop.

Rash and Mucositis Associated With Mycoplasma pneumoniae and Chlamydophila pneumoniae: A Recurrence of MIRM?

INTRODUCTION: A new concept has come to light recently, that is, Mycoplasma-induced rash and mucositis (MIRM). Here, we report the first case of recurrent rash, mucositis, and conjunctivitis involving Mycoplasma pneumoniae and C. pneumoniae that fits under the criteria of what is currently defined as MIRM. CASE PRESENTATION: A patient aged 12 years with a history of recurrent aphthous ulcers presented in 2013 with worsening oral lesions, conjunctivitis, and vesicular rash. Her respiratory polymerase chain reaction (PCR) panel was positive for M. pneumoniae. She was diagnosed with Stevens-Johnson syndrome (SJS) secondary to M. pneumoniae and treated with a macrolide, acyclovir, and intravenous immunoglobulin (IVIG). The same patient returned 3 years later with an identical constellation of symptoms, at which time her PCR was positive for C. pneumoniae. In addition to IVIG and a macrolide, a corticosteroid treatment was administered. DISCUSSION: Here, we present the case of a pediatric patient with a recurrence of mucocutaneous disease that is more consistent with MIRM than the proposed SJS or erythema multiforme (EM) documented via histology. Our patient's symptoms were controlled with azithromycin and IVIG and, in the second episode, with corticosteroids as well. This case adds to that of Mayor-Ibarguren et al, providing further evidence that C. pneumonia may also be a trigger for MIRM. Patients will benefit from expanding the definition of MIRM, as the pathogenesis differs from SJS and EM and could result in more specific treatment options.

Orthotopic transplantation of a tissue engineered diaphragm in rats.

The currently available surgical options to repair the diaphragm are associated with significant risks of defect recurrence, lack of growth potential and restored functionality. A tissue engineered diaphragm has the potential to improve surgical outcomes for patients with congenital or acquired disorders. Here we show that decellularized diaphragmatic tissue reseeded with bone marrow mesenchymal stromal cells (BM-MSCs) facilitates in situ regeneration of functional tissue. A novel bioreactor, using simultaneous perfusion and agitation, was used to rapidly decellularize rat diaphragms. The scaffolds retained architecture and mechanical properties and supported cell adhesion, proliferation and differentiation. Biocompatibility was further confirmed in vitro and in vivo. We replaced 80% of the left hemidiaphragm with reseeded diaphragmatic scaffolds. After three weeks, transplanted animals gained 32% weight, showed myography, spirometry parameters, and histological evaluations similar to native rats. In conclusion, our study suggested that reseeded decellularized diaphragmatic tissue appears to be a promising option for patients in need of diaphragmatic reconstruction.

Fetal production of growth factors and inflammatory mediators predicts pulmonary hypertension in congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) represents a spectrum of lung hypoplasia, and consequent pulmonary hypertension (PH) is an important cause of postnatal morbidity and mortality. We studied biomarkers at the maternal-fetal interface to understand factors associated with the persistence of PH. METHODS: Maternal and cord blood samples from fetuses with CDH and unaffected controls were analyzed using a human 39plex immunoassay kit. Cellular trafficking between the mother and the fetus was quantified using quantitative real-time PCR for nonshared alleles. Biomarker profiles were then correlated with CDH severity on the basis of the degree of PH. RESULTS: Cord blood levels of epidermal growth factor, platelet-derived growth factor, and several inflammatory mediators increased significantly as the severity of CDH increased, whereas maternal levels of growth factors and mediators decreased significantly with CDH severity. Maternal cells were increased in fetuses with severe CDH as compared with controls, with elevated levels of the CXC chemokine ligand-10 in patients with the highest trafficking. CONCLUSION: Patients with CDH demonstrate proinflammatory and chemotactic signals in fetal blood at the time of birth. Because some of these molecules have been implicated in the development of PH, prenatal strategies targeting specific molecular pathways may be useful adjuncts to current fetal therapies.

Alterations in maternal-fetal cellular trafficking after fetal surgery.

BACKGROUND/PURPOSE: Bidirectional trafficking of cells between the mother and the fetus is routine in pregnancy and a component of maternal-fetal tolerance. Changes in fetal-to-maternal cellular trafficking have been reported in prenatal complications, but maternal-to-fetal trafficking has never been studied in the context of fetal intervention. We hypothesized that patients undergoing open fetal surgery would have altered maternal-fetal cellular trafficking. METHODS: Cellular trafficking was analyzed in patients with myelomeningocele (MMC) who underwent open fetal surgical repair (n = 5), patients with MMC who had routine postnatal repair (n = 6), and healthy control healthy patients (n = 9). As an additional control for the fetal operation, trafficking was also analyzed in patients who were delivered by an ex utero intrapartum treatment procedure (n = 6). Microchimerism in maternal and cord blood was determined using quantitative real-time polymerase chain reaction for nonshared alleles. RESULTS: Maternal-to-fetal trafficking was significantly increased in patients who underwent open fetal surgery for MMC compared with healthy controls, patients who underwent postnatal MMC repair, and patients who underwent ex utero intrapartum treatment. There were no differences in fetal-to-maternal cell trafficking among groups. CONCLUSION: Patients undergoing open fetal surgery for MMC have elevated levels of maternal microchimerism. These results suggest altered trafficking and/or increased proliferation of maternal cells in fetal blood and may have important implications for preterm labor.