Oluyinka O. Olutoye

Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs

Necrotizing enterocolitis (NEC) remains the most severe gastrointestinal disorder in preterm infants. It is associated with the initiation of enteral nutrition and may be related to immature carbohydrate digestive capacity. We tested the hypothesis that a formula containing maltodextrin vs. a formula containing lactose as the principal source of carbohydrate would predispose preterm pigs to a higher NEC incidence. Cesarean-derived preterm pigs were given total parenteral nutrition for 48 h followed by total enteral nutrition with a lactose-based (n = 11) or maltodextrin-based (n = 11) formula for 36 h. A higher incidence (91% vs. 27%) and severity (score of 3.3 vs. 1.8) of NEC were observed in the maltodextrin than in the lactose group. This higher incidence of NEC in the maltodextrin group was associated with significantly lower activities of lactase, maltase, and aminopeptidase; reduced villus height; transiently reduced in vivo aldohexose uptake; and reduced ex vivo aldohexose uptake capacity in the middle region of the small intestine. Bacterial diversity was low for both diets, but alterations in bacterial composition and luminal concentrations of short-chain fatty acids were observed in the maltodextrin group. In a second study, we quantified net portal absorption of aldohexoses (glucose and galactose) during acute jejunal infusion of a maltodextrin- or a lactose-based formula (n = 8) into preterm pigs. We found lower net portal aldohexose absorption (4% vs. 42%) and greater intestinal recovery of undigested carbohydrate (68% vs. 27%) in pigs acutely perfused with the maltodextrin-based formula than those perfused with the lactose-based formula. The higher digestibility of the lactose than the maltodextrin in the formulas can be attributed to a 5- to 20-fold higher hydrolytic activity of tissue-specific lactase than maltases. We conclude that carbohydrate maldigestion is sufficient to increase the incidence and severity of NEC in preterm pigs.

Prenatal diagnosis and outcome of fetal lung masses

AIM The purpose of this study is to evaluate the accuracy of prenatal diagnostic features, particularly congenital cystic adenomatoid malformation volume ratio (CVR), in predicting outcomes for fetuses with lung masses. METHODS The records and imaging features of all fetuses referred to the Texas Childrens Fetal Center with a fetal lung mass between July 2001 and May 2010 were reviewed retrospectively. Data collected included gestational age (GA) at diagnosis, fetal magnetic resonance imaging findings, CVR, mass size, nature of fetal treatment, surgical findings, pathology, and outcome. Data were analyzed for predicting development of hydrops or the need for fetal therapy using receiver operating characteristic curves. RESULTS Of 82 fetuses (41 male) evaluated for a lung mass, 53 (65%) were left-sided (1 bilateral), and the mean (SD) GA at diagnosis was 21.5 (4.3) weeks. Seventy-three fetuses underwent fetal magnetic resonance imaging at a mean (SD) GA of 26.1 (4.6) weeks. Thirteen fetuses (16%) had fetal treatment. Four fetuses with hydrops underwent open fetal surgical resection, and 3 survived. Six fetuses with large lung masses and persistent mediastinal compression near term underwent ex-utero intrapartum therapy-to-resection procedures, and 3 fetuses with hydrops underwent serial thoracentesis. Congenital cystic adenomatoid malformation volume ratio correlated strongly with the development of hydrops and the need for fetal therapy with an area under the receiver operating characteristic curve of 0.96 (P < .0001) and 0.88 (P < .0001), respectively. Of 18 fetuses with a CVR greater than 2.0 compared with 2 (3%) of 60 with a CVR of 2.0 or less, 10 (56%) required fetal intervention (P < .0001). CONCLUSION Congenital cystic adenomatoid malformation volume ratio correlates strongly with the development of fetal hydrops and the need for fetal intervention. A threshold value of 2.0 yields the most powerful statistical results.

Parameters of Thromboelastography in Healthy Newborns

Thromboelastography (TEG) aids in monitoring a patients global hemostatic system by measuring the rate of clot formation, clot strength, and stability. The usefulness of TEG in pediatric settings, especially with neonates, is limited owing to a lack of neonatal reference values. In this study, neonatal TEG reference intervals were developed and results correlated with other coagulation test parameters. Samples were from women who delivered a neonate after at least 34 weeks of gestation in normal pregnancies. From the recovered placenta, cord blood from the umbilical vein or artery was collected within 30 minutes after delivery and tested. Neonatal TEG reaction time (time clot formation begins), clot firmness (shear elastic modulus strength), and platelet function analysis closure times were significantly lower than those in adult ranges (P< .001). When compared with the values for children, TEG reaction time, angle, coagulation index, clot firmness value, and clot kinetics (time from clot formation to time amplitude reaches 20 mm) were significantly different (P< .001) among neonates. TEG can be used to interpret the data for newborns by using reference values obtained in the present study.

Impact of prenatal evaluation and protocol-based perinatal management on congenital diaphragmatic hernia outcomes

BACKGROUND/PURPOSE Although intuitive, the benefit of prenatal evaluation and multidisciplinary perinatal management for fetuses with congenital diaphragmatic hernia (CDH) is unproven. We compared the outcome of prenatally diagnosed patients with CDH whose perinatal management was by a predefined protocol with those who were diagnosed postnatally and managed by the same team. We hypothesized that patients with CDH undergoing prenatal evaluation with perinatal planning would demonstrate improved outcome. METHODS Retrospective chart review of all patients with Bochdalek-type CDH at a single institution between 2004 and 2009 was performed. Patients were stratified by history of perinatal management, and data were analyzed by Fishers Exact test and Students t test. RESULTS Of 116 patients, 71 fetuses presented in the prenatal period and delivered at our facility (PRE), whereas 45 infants were either outborn or postnatally diagnosed (POST). There were more high-risk patients in the PRE group compared with the POST group as indicated by higher rates of liver herniation (63% vs 36%, P = .03), need for patch repair (57% vs 27%, P = .004), and extracorporeal membrane oxygenation use (35% vs 18%, P = .05). Despite differences in risk, there was no difference in 6-month survival between groups (73% vs 73%). CONCLUSIONS Patients with CDH diagnosed prenatally are a higher risk group. Prenatal evaluation and multidisciplinary perinatal management allows for improved outcome in these patients.

The use of combined ultrasound and magnetic resonance imaging in the detection of fetal anomalies.

To compare the referral diagnosis based on prenatal ultrasound to diagnoses made following combined ultrasound (US) and magnetic resonance imaging (MRI) evaluation at the Texas Childrens Fetal Center (TCFC) and postnatal diagnosis.

Fetal lung volume and quantification of liver herniation by magnetic resonance imaging in isolated congenital diaphragmatic hernia.

To determine associations between fetal lung and liver herniation volumes measured by magnetic resonance imaging (MRI) and mortality/need for extracorporeal membrane oxygenation (ECMO) in cases of isolated congenital diaphragmatic hernia (CDH). A secondary objective was to compare prenatal MRI parameters with two‐dimensional ultrasound lung measurements.

Near-infrared spectroscopy measurement of abdominal tissue oxygenation is a useful indicator of intestinal blood flow and necrotizing enterocolitis in premature piglets

PURPOSE A major objective of necrotizing enterocolitis (NEC) research is to devise a noninvasive method of early detection. We hypothesized that abdominal near-infrared spectroscopy (A-NIRS) readings will identify impending NEC in a large animal model. METHODS Piglets were prematurely delivered and received parenteral nutrition followed by enteral feedings. Serial A-NIRS readings were obtained for 5 days, and animals were monitored for NEC. Separately, A-NIRS readings were obtained in healthy piglets to validate the correlation of A-NIRS with splanchnic oxygen delivery. RESULTS Of 29 piglets, 3 developed NEC. Eleven piglets without NEC died prematurely. Fifteen piglets remained healthy, had normal histologic assessment of their intestines, and served as controls. Abdominal near-infrared spectroscopy readings within 12 hours of birth were significantly lower in animals that developed NEC compared with healthy littermates (4% vs 33%, P = .02). For all time-points measured, A-NIRS readings were significantly lower in the NEC group compared with controls (21% vs 55%, P < .001). Abdominal near-infrared spectroscopy readings correlated with both decreased pulse oximetry readings during apneic episodes (r = 0.96) and increased superior mesenteric artery flow in response to glucagon-like peptide 2 (r = 0.67). CONCLUSION Abdominal near-infrared spectroscopy is capable of detecting alterations in intestinal oxygenation and perfusion in neonatal piglets and may allow early detection of neonates at risk for NEC.

Negative pressure therapy is effective to manage a variety of wounds in infants and children

Negative pressure therapy (NPT) has been accepted as a valuable adjunct for wound closure in adults; however, reports on its effectiveness in young children and infants, including neonates, are limited. A retrospective chart review was conducted on children treated with NPT at a single institution between January 2003 and December 2005. Wound volumetric measurements were calculated at the start and end of therapy. Sixty‐eight patients with 82 wounds were identified. The mean age was 8.5 years (range 7 days–18 years). Twenty patients (29%) were 2 years of age or younger, including eight neonates. Wound types included: pressure ulcers (n=13), extremity wounds (n=18), dehisced surgical wounds (n=19), open sternal wounds (n=10), wounds with fistulas (n=3), and complex abdominal wall defects (n=6). Low suction pressures (<100 mmHg) were generally used in children younger than 4 years of age. Following NPT, 93% of wounds decreased in volume. The average wound volume decrease was 80% (p<0.01, n=56). NPT can be effectively used to manage a variety of wounds in children and neonates. No major complications were identified in our retrospective review. Prospective studies are required to better refine the use of this technology in children.

New generation lipid emulsions prevent PNALD in chronic parenterally fed preterm pigs

Total parenteral nutrition (TPN) is associated with the development of parenteral nutrition-associated liver disease (PNALD) in infants. Fish oil-based lipid emulsions can reverse PNALD, yet it is unknown if they can prevent PNALD. We studied preterm pigs administered TPN for 14 days with either 100% soybean oil (IL), 100% fish oil (OV), or a mixture of soybean oil, medium chain triglycerides (MCTs), olive oil, and fish oil (SL); a group was fed formula enterally (ENT). In TPN-fed pigs, serum direct bilirubin, gamma glutamyl transferase (GGT), and plasma bile acids increased after the 14 day treatment but were highest in IL pigs. All TPN pigs had suppressed hepatic expression of farnesoid X receptor (FXR), cholesterol 7-hydroxylase (CYP7A1), and plasma 7α-hydroxy-4-cholesten-3-one (C4) concentrations, yet hepatic CYP7A1 protein abundance was increased only in the IL versus ENT group. Organic solute transporter alpha (OSTα) gene expression was the highest in the IL group and paralleled plasma bile acid levels. In cultured hepatocytes, bile acid-induced bile salt export pump (BSEP) expression was inhibited by phytosterol treatment. We show that TPN-fed pigs given soybean oil developed cholestasis and steatosis that was prevented with both OV and SL emulsions. Due to the presence of phytosterols in the SL emulsion, the differences in cholestasis and liver injury among lipid emulsion groups in vivo were weakly correlated with plasma and hepatic phytosterol content.

Ex-utero intrapartum treatment procedure for giant neck masses—fetal and maternal outcomes

BACKGROUND/PURPOSE For fetuses with giant neck masses and tracheal obstruction, an ex-utero intrapartum treatment (EXIT) procedure allows for safe nonemergent airway management while on placental support. Our objective was to examine fetal and maternal outcomes after EXIT procedure specifically for giant neck masses. METHODS The medical records of all patients referred to a comprehensive fetal center for a giant neck mass between 2001 and 2010 were reviewed retrospectively. RESULTS Among 24 patients referred, an EXIT procedure was performed in 12 with evidence of tracheal compression. An EXIT procedure was not performed because of minimal tracheal involvement (n = 8), elective abortion (n = 2), fetal demise (n = 1), or obstetric complication (n = 1). In all fetuses, the airway was successfully secured; tracheal intubation was achieved with rigid bronchoscopy (n = 10), direct laryngoscopy (n = 1), and tracheostomy (n = 1). Eleven patients survived to discharge, whereas 1 patient with significant pulmonary hypoplasia died 8 days after emergency EXIT procedure. Of 11 surviving infants, 10 are neurodevelopmentally intact. All mothers who desired future pregnancies have subsequently had uncomplicated deliveries (n = 6). CONCLUSIONS Ex-utero intrapartum treatment procedure for giant neck mass can be performed safely for both mother and child. Most fetuses can be orotracheally intubated with minimal long-term morbidity. The potential for future pregnancies is preserved.