Risk factors for prolonged mechanical ventilation in neonates following gastrointestinal surgery.

Background: Prolonged mechanical ventilation (MV) should be avoided in neonates. Noninvasive ventilation (NIV) can facilitate weaning from MV but has risks for patients immediately following foregut surgery due to the potential risk of anastomotic leak. We evaluated the risk factors for prolonged MV following intestinal surgery in neonates. Methods: We retrospectively reviewed 253 neonates undergoing intestinal surgery in 2017-2018 to identify risk factors for prolonged MV, and determine the correlation between NIV and anastomotic leak in a tertiary neonatal intensive care unit that performs the greatest number of neonatal surgeries in Ontario. Results: The most common diagnoses were necrotizing enterocolitis/spontaneous intestinal perforation (NEC/SIP) 21%, intestinal atresia 16%, esophageal atresia/tracheoesophageal fistula 14%, ano-rectal malformation 13%, malrotation/volvulus 11%, gastroschisis 9% and omphalocele 4%. The median (IQR) duration of MV post-surgery was 3 (1-8) days with 25.7 % (n=65) of neonates on MV for >7 days. Compared to infants on MV post-surgery for ≤7 days, those with MV>7 days were of lower gestational age, birth weight and weight at surgery, but a higher proportion underwent stoma creation, had a longer duration of opioid administration and higher rates of moderate to severe bronchopulmonary dysplasia (BPD) and mortality (P<0.05). Generalized linear regression analysis showed lower gestational age (GA) and longer opioid administration were associated with longer duration of MV (P<0.001), but indication for surgery, weight at surgery and stoma creation didn't correlate with longer duration of MV (P>0.05). Of the 122 patients handled by one-stage resection with primary anastomosis, 22.1% (n=27) received NIV with 74.1% (n=20) commenced on NIV after 7 days post-surgery, anastomotic leak was detected in 2.5 % (3/122) patients and didn't correlate with NIV. Conclusions: Lower GA and longer opioid administration were risk factors for prolonged MV in neonates following intestinal surgery. Further research is needed to investigate modifiable practices around pain assessment/ventilation in these patients, and the correlation between NIV and anastomotic leak.

Prenatally diagnosed omphaloceles: Report of 92 cases and association with Beckwith-Wiedemann syndrome.

OBJECTIVE: Describe the prevalence, perinatal and long-term outcomes of Beckwith-Wiedemann syndrome (BWS) among prenatally detected omphaloceles. METHODS: All prenatally diagnosed omphaloceles from 2010 to 2015 within a single tertiary care centre were identified. An echocardiogram and detailed fetal ultrasound were performed, and amniocentesis was offered with karyotype/microarray analysis and BWS molecular testing. Perinatal, neonatal, and long-term outcomes were retrieved for BWS cases. RESULTS: Among 92 omphaloceles, 62 had additional anomalies. Abnormal karyotypes were identified in 23/62 (37%) non-isolated and 2/30 (7%) isolated cases. One BWS case (5%) was identified among non-isolated omphaloceles and six BWS cases (37.5%) were identified among isolated omphaloceles after exclusion of aneuploidy. Among 19 BWS cases, 21% were conceived by ART. All omphaloceles underwent primary closure. Prenatally, macrosomia and polyhydramnios were seen in 42%. Macroglossia and nephromegaly were more commonly detected postnatally. Preterm birth occurred in 10/19 (53%) cases and cesarean deliveries were performed in 7/19 (40%) cases. Overall mortality was 20% (4/19). Embryonal tumors were diagnosed in 2/16 (12.5%) children, and neurodevelopmental outcomes were normal in 9/12 (75%) survivors. CONCLUSIONS: After excluding aneuploidy, BWS was identified in 37.5% and 5% of isolated and non-isolated omphaloceles, respectively. Omphaloceles were small-moderate size with good long-term surgical and neurodevelopmental outcomes when isolated.

Gastrointestinal hemodynamic changes during therapeutic hypothermia and after rewarming in neonatal hypoxic-Ischemic encephalopathy.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is associated with disturbances in visceral blood flow velocities. Therapeutic Hypothermia (TH) is a standard of care; however, its impact on gastrointestinal blood flow in infants with HIE is unknown. The objective of this study was to assess gastrointestinal (GI) blood flow and left ventricle output (LVO) in infants with hypoxic-ischemic encephalopathy during whole body TH and after rewarming. METHODS: Serial echocardiography and Doppler evaluation of intestinal blood flow (celiac (CA) and superior mesenteric (SMA) arteries) were prospectively performed in a cohort of 20 newborn infants with HIE at 4 time points during hypothermia and after rewarming. Demographic, clinical and biochemical data were collected and analyzed for their relevance. RESULTS: Median gestational age and birth weight was 40 weeks (37-41) and 3410 g (2190-4950) respectively. Celiac and mesenteric artery flow remained low during hypothermia and rose significantly after rewarming [peak systolic velocity in CA (0.63 m/s to 0.77 m/s, p = 0.004) and SMA (0.43 m/s to 0.55 m/s, p = 0.001)]. This increase was temporally associated with increased left ventricular output (106 ml/kg/min to 149 ml/kg/min, p < 0.0001). Median age to reach 25% of the feeds was 5 days (1-7 days). All patients survived. CONCLUSIONS: CA and SMA blood flow velocity and LVO did not vary during hypothermia but rose after rewarming. This may suggest protective effect of therapeutic hypothermia on gastrointestinal system. The association of these physiological changes with neonatal outcome needs further assessment.

Outcomes of multi-gestational pregnancies affected by esophageal atresia - tracheoesophageal fistula.

BACKGROUND: Contemporary outcomes of infants with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) from multi-gestational pregnancies compared to those of singleton pregnancies have not been reported. METHODS: A single-center retrospective review of EA/TEF patients born from 1999 to 2013 was performed. Patient demographics, gestational age (GA), birth weight, associated anomalies, requirement for gastrostomy tube and mortality were reviewed. RESULTS: Singleton EA/TEF patients outnumbered those from multi-gestational pregnancies nearly 10:1 (214 vs 22 patients). EA/TEF patients from multi-gestational pregnancies were more likely to be premature (77% vs. 32%), have lower birth weight (mean 1766 g vs. 2695 g), have associated duodenal atresia (18% vs. 6%) and require gastrostomy tube (41% vs. 33%) for feeding challenges compared to EA/TEF singletons. Mortality was also significantly greater for multi-gestational EA/TEF patients compared to singleton EA/TEF patients (18% vs. 6%). CONCLUSION: EA/TEF infants from multi-gestational pregnancies have greater clinical complexity and mortality than singleton EA/TEF patients. Parents of EA/TEF multi-gestational infants should be appropriately counseled and supported.

Neonatal oesophageal perforation: The role for non-operative management.

AIM: Isolated oesophageal perforation in neonates is a rare but potentially life-threatening condition. Although management has historically been operative, conservative management (antibiotics, bowel rest, parenteral nutrition) is now more routinely used. The aim of this study was to evaluate the management of this condition in two large neonatal surgical centres. METHODS: A retrospective cohort study was conducted for neonates admitted to The Hospital for Sick Children (Toronto, Canada) or The Royal Children's Hospital (Melbourne, Australia) with a diagnosis of oesophageal perforation, from 2006 to 2016. Patients with oesophageal atresia or tracheo-oesophageal fistula were excluded. Data were collected from chart review regarding demographics, clinical course, management and outcomes. RESULTS: Eleven neonates with oesophageal perforation were identified over a 10-year period at the two centres. Median gestational age at birth was 25.3 weeks (interquartile range 24.2-28.8) and the majority (7/11, 64%) of neonates were extremely low birthweight. Diagnosis was made on day 1 of life for 9 of 11 (81%) neonates and was secondary to nasogastric tube insertion in 10 of 11 (91%) neonates. Only four (36%) neonates had symptomatic complications. All neonates were managed with bowel rest and intravenous antibiotics for a median of 7 days (interquartile range 7-10); two patients required operative intervention. Three neonates (27%) developed chronic lung disease and two (19%) died prior to discharge. CONCLUSIONS: Oesophageal perforation is severe complication secondary to instrumentation of the upper gastrointestinal tract in neonates. Prompt and accurate diagnosis is crucial. Non-operative management is effective for the majority, though morbidity is common.

Neurodevelopmental outcomes of infants with esophageal atresia and tracheoesophageal fistula.

BACKGROUND: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is a complex disorder, and most outcome data are confined to mortality and feeding-related morbidities. Our objective was to examine mortality, growth and neurodevelopmental outcomes in a large recent cohort of infants with EA/TEF. METHODS: Single center study of EA/TEF infants referred from January 2000 to December 2015. Data collected included associated defects, neonatal morbidity and mortality and growth and neurodevelopmental outcomes at age 12-36months. Multiple regression analysis was used to determine variables associated with adverse outcome. RESULTS: Of the 253 infants identified, 102 infants (40%) were preterm. Overall mortality was 8.3%, the majority from major cardiac malformations (p<0.001) Neurodevelopmental assessments (n=182) showed that 76% were within normal, while some delay was seen in 24%, most often in expressive and receptive language. Nine infants had hearing impairment and 5 had visual impairment. Gastrostomy tubes were required in 47 patients and 15% continued to have weight growth velocities less than the 10th centile. A number of specialist interventions were required, Speech/Language being frequent. CONCLUSION: Mortality in EA/TEF is primarily related to concomitant anomalies, especially cardiac. Multidisciplinary follow up is important for early identification and intervention for growth failure and developmental delay. TYPE OF STUDY: Retrospective study LEVEL OF EVIDENCE: Level II.

Enzyme replacement therapy in perinatal hypophosphatasia: Case report of a negative outcome and lessons for clinical practice.

Enzyme replacement therapy (ERT) is a newly approved disease-modifying treatment for hypophosphatasia (HPP), a rare metabolic bone disorder. With an orphan drug and ultra-rare disease, sharing information about responders and non-responders is particularly important, as any one centre's familiarity with its use will be limited. Nearly all published data in infants and very young children with life-threatening HPP are from three small clinical trials that have reported generally positive outcomes. We describe in detail a patient with perinatal HPP for whom treatment with ERT was not successful. Lessons learned from this case can inform clinical decision-making and provide topics for the research agenda. We also discuss practical and ethical challenges related to treatment of an ultra-rare disease with an expensive new medication in a publicly funded healthcare system.

Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies.

OBJECTIVE: To provide updated information on the pre- and post-conception use of oral folic acid with or without a multivitamin/micronutrient supplement for the prevention of neural tube defects and other congenital anomalies. This will help physicians, midwives, nurses, and other health care workers to assist in the education of women about the proper use and dosage of folic acid/multivitamin supplementation before and during pregnancy. EVIDENCE: Published literature was retrieved through searches of PubMed, Medline, CINAHL, and the Cochrane Library in January 2011 using appropriate controlled vocabulary and key words (e.g., folic acid, prenatal multivitamins, folate sensitive birth defects, congenital anomaly risk reduction, pre-conception counselling). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from 1985 and June 2014. Searches were updated on a regular basis and incorporated in the guideline to June 2014 Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Costs, risks, and benefits: The financial costs are those of daily vitamin supplementation and eating a healthy folate-enriched diet. The risks are of a reported association of dietary folic acid supplementation with fetal epigenetic modifications and with an increased likelihood of a twin pregnancy. These associations may require consideration before initiating folic acid supplementation. The benefit of folic acid oral supplementation or dietary folate intake combined with a multivitamin/micronutrient supplement is an associated decrease in neural tube defects and perhaps in other specific birth defects and obstetrical complications. VALUES: The quality of evidence in the document was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care (Table 1). Summary Statement In Canada multivitamin tablets with folic acid are usually available in 3 formats: regular over-the-counter multivitamins with 0.4 to 0.6 mg folic acid, prenatal over-the-counter multivitamins with 1.0 mg folic acid, and prescription multivitamins with 5.0 mg folic acid. (III) Recommendations 1. Women should be advised to maintain a healthy folate-rich diet; however, folic acid/multivitamin supplementation is needed to achieve the red blood cell folate levels associated with maximal protection against neural tube defect. (III-A) 2. All women in the reproductive age group (12-45 years of age) who have preserved fertility (a pregnancy is possible) should be advised about the benefits of folic acid in a multivitamin supplementation during medical wellness visits (birth control renewal, Pap testing, yearly gynaecological examination) whether or not a pregnancy is contemplated. Because so many pregnancies are unplanned, this applies to all women who may become pregnant. (III-A) 3. Folic acid supplementation is unlikely to mask vitamin B12 deficiency (pernicious anemia). Investigations (examination or laboratory) are not required prior to initiating folic acid supplementation for women with a risk for primary or recurrent neural tube or other folic acid-sensitive congenital anomalies who are considering a pregnancy. It is recommended that folic acid be taken in a multivitamin including 2.6 ug/day of vitamin B12 to mitigate even theoretical concerns. (II-2A) 4. Women at HIGH RISK, for whom a folic acid dose greater than 1 mg is indicated, taking a multivitamin tablet containing folic acid, should be advised to follow the product label and not to take more than 1 daily dose of the multivitamin supplement. Additional tablets containing only folic acid should be taken to achieve the desired dose. (II-2A) 5. Women with a LOW RISK for a neural tube defect or other folic acid-sensitive congenital anomaly and a male partner with low risk require a diet of folate-rich foods and a daily oral multivitamin supplement containing 0.4 mg folic acid for at least 2 to 3 months before conception, throughout the pregnancy, and for 4 to 6 weeks postpartum or as long as breast-feeding continues. (II-2A) 6. Women with a MODERATE RISK for a neural tube defect or other folic acid-sensitive congenital anomaly or a male partner with moderate risk require a diet of folate-rich foods and daily oral supplementation with a multivitamin containing 1.0 mg folic acid, beginning at least 3 months before conception. Women should continue this regime until 12 weeks' gestational age. (1-A) From 12 weeks' gestational age, continuing through the pregnancy, and for 4 to 6 weeks postpartum or as long as breast-feeding continues, continued daily supplementation should consist of a multivitamin with 0.4 to 1.0 mg folic acid. (II-2A) 7. Women with an increased or HIGH RISK for a neural tube defect, a male partner with a personal history of neural tube defect, or history of a previous neural tube defect pregnancy in either partner require a diet of folate-rich foods and a daily oral supplement with 4.0 mg folic acid for at least 3 months before conception and until 12 weeks' gestational age. From 12 weeks' gestational age, continuing throughout the pregnancy, and for 4 to 6 weeks postpartum or as long as breast-feeding continues, continued daily supplementation should consist of a multivitamin with 0.4 to 1.0 mg folic acid. (I-A). The same dietary and supplementation regime should be followed if either partner has had a previous pregnancy with a neural tube defect. (II-2A).

Objectif : Offrir des renseignements à jour sur l'utilisation pré et postconceptionnelle d'acide folique par voie orale, avec ou sans supplément de multivitamines / micronutriments, aux fins de la prévention des anomalies du tube neural et d'autres anomalies congénitales. Ces renseignements aideront les médecins, les sages-femmes, les infirmières et les autres professionnels de la santé à contribuer aux efforts de sensibilisation des femmes quant à l'utilisation et aux posologies adéquates de la supplémentation en acide folique / multivitamines, avant et pendant la grossesse. Résultats : La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans PubMed, Medline, CINAHL et la Cochrane Library en janvier 2011 au moyen d'un vocabulaire contrôlé et de mots clés appropriés (p. ex. « folic acid ¼, « prenatal multivitamins ¼, « folate sensitive birth defects ¼, « congenital anomaly risk reduction ¼, « pre-conception counselling ¼). Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs publiés en anglais entre 1985 et juin 2014. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en juin 2014. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques, et auprès de sociétés de spécialité médicale nationales et internationales. Coûts, risques et avantages : Les coûts financiers sont ceux de la supplémentation quotidienne en vitamines et de la consommation d'un régime alimentaire santé enrichi en folate. Les risques sont ceux qui sont liés à une association signalée entre la supplémentation alimentaire en acide folique et des modifications épigénétiques fœtales / la probabilité accrue d'obtenir une grossesse gémellaire. Ces associations pourraient devoir être prises en considération avant la mise en œuvre d'une supplémentation en acide folique. La supplémentation en acide folique par voie orale (ou l'apport alimentaire en folate combiné à un supplément de multivitamines / micronutriments) a pour avantage de mener à une baisse connexe du taux d'anomalies du tube neural et peut-être même des taux d'autres complications obstétricales et anomalies congénitales particulières. Valeurs : La qualité des résultats est évaluée au moyen des critères décrits par le Groupe d'étude canadien sur les soins de santé préventifs (Tableau). Déclaration sommaire 1. Au Canada, les comprimés de multivitamines comptant de l'acide folique sont habituellement offerts en 3 formats : multivitamines régulières en vente libre comptant de 0,4 à 0,6 mg d'acide folique, multivitamines prénatales en vente libre comptant 1,0 mg d'acide folique et multivitamines d'ordonnance comptant 5,0 mg d'acide folique. (III) Recommandations 1. Les femmes devraient se voir conseiller de maintenir un régime alimentaire santé riche en folate; la mise en œuvre d'une supplémentation en acide folique / multivitamines s'avère cependant requise pour leur assurer l'obtention des taux érythrocytaires de folate qui sont associés à l'octroi d'une protection maximale contre les anomalies du tube neural. (III-A) 2. Toutes les femmes en âge de procréer (12-45 ans) qui sont toujours fertiles (la grossesse demeure possible) devraient se voir offrir, dans le cadre de leurs consultations gynécologiques de dépistage (renouvellement de la contraception, test de Pap, examen gynécologique annuel), des services de counseling au sujet des avantages de l'acide folique administré sous forme d'une supplémentation multivitaminique, et ce, qu'elles envisagent ou non de connaître une grossesse. Puisqu'un si grand nombre de grossesses se manifestent de façon inattendue, cette recommandation s'applique à toutes les femmes qui pourraient devenir enceintes. (III-A) 3. La supplémentation en acide folique est peu susceptible de masquer la carence en vitamine B12 (anémie pernicieuse). La tenue d'explorations (examen ou épreuves de laboratoire) n'est pas requise avant la mise en œuvre d'une supplémentation en acide folique chez les femmes exposées à des risques d'anomalies du tube neural (ou d'autres anomalies congénitales sensibles à l'acide folique) primaires ou récurrentes qui envisagent une grossesse. Il est recommandé que l'acide folique soit administré sous forme de multivitamines comptant également 2,6 µg/jour de vitamine B12, de façon à atténuer toutes les préoccupations (même celles qui sont théoriques). (II-2A) 4. Les femmes exposées à des RISQUES ÉLEVÉS (pour lesquelles une dose d'acide folique supérieure à 1 mg s'avère indiquée) qui prennent des multivitamines contenant de l'acide folique devraient être avisées de respecter les consignes d'utilisation du produit en question et de ne pas prendre plus d'une dose quotidienne de supplément multivitaminique; ces femmes devraient plutôt prendre des comprimés additionnels ne contenant que de l'acide folique pour obtenir la dose requise. (II-2A) 5. Pendant au moins les deux à trois mois précédant la conception, tout au long de la grossesse et pendant de quatre à six semaines à la suite de l'accouchement (ou tant et aussi longtemps que se poursuit l'allaitement), les femmes qui sont exposées à un FAIBLE RISQUE d'anomalie du tube neural ou d'autres anomalies congénitales sensibles à l'acide folique et qui comptent un partenaire masculin également exposé à un faible risque doivent adopter un régime alimentaire composé d'aliments riches en folate et prendre un supplément multivitaminique oral quotidien contenant 0,4 mg d'acide folique. (II-2A) 6. À partir d'au moins trois mois avant la conception, les femmes qui sont exposées à un RISQUE MODÉRÉ d'anomalie du tube neural ou d'autres anomalies congénitales sensibles à l'acide folique et qui comptent un partenaire masculin également exposé à un risque modéré doivent adopter un régime alimentaire composé d'aliments riches en folate et prendre un supplément multivitaminique oral quotidien contenant 1 mg d'acide folique. Ces femmes devraient poursuivre l'utilisation de cette posologie jusqu'à l'atteinte d'un âge gestationnel de 12 semaines. (1-A) À partir de 12 semaines d'âge gestationnel, tout au long du reste de la grossesse et pendant de quatre à six semaines postpartum (ou tant et aussi longtemps que se poursuit l'allaitement), la supplémentation quotidienne utilisée devrait être composée d'une multivitamine contenant de 0,4 à 1,0 mg d'acide folique. (II-2A) 7. Pendant au moins trois mois avant la conception et jusqu'à l'atteinte d'un âge gestationnel de 12 semaines, les femmes qui sont exposées à un RISQUE ÉLEVÉ ou accru d'anomalie du tube neural et qui comptent un partenaire masculin présentant des antécédents personnels d'anomalie du tube neural (ou encore en présence d'antécédents personnels ou familiaux de grossesse affectée par une anomalie du tube neural chez l'un ou l'autre des partenaires) doivent adopter un régime alimentaire composé d'aliments riches en folate et prendre un supplément oral quotidien de 4 mg d'acide folique. À partir de 12 semaines d'âge gestationnel, tout au long du reste de la grossesse et pendant de quatre à six semaines postpartum (ou tant et aussi longtemps que se poursuit l'allaitement), la supplémentation quotidienne utilisée devrait être composée d'une multivitamine contenant de 0,4 à 1,0 mg d'acide folique. (I-A) Le même régime alimentaire et de supplémentation devrait être respecté en présence d'antécédents personnels ou familiaux de grossesse affectée par une anomalie du tube neural chez l'un ou l'autre des partenaires. (II-2A).

Low birthweight, gestational age, need for surgical intervention and gram-negative bacteraemia predict intestinal failure following necrotising enterocolitis.

AIM: Necrotising enterocolitis (NEC) is associated with high morbidity and mortality. The aim of this study was to identify predictors of intestinal failure (IF), morbidity and mortality following NEC. METHODS: We performed a retrospective study of all neonates treated for NEC stage II or greater at a tertiary referral NICU between 2000 and 2009. Demographic data, need for surgery, residual bowel length and rates of bacteraemia, cholestasis, IF and mortality were analysed. RESULTS: During the 10-year period, 301 patients were referred with NEC and 152 had surgical intervention. Overall mortality was 32%. Of the 230 infants who survived >42 days, 97 (42%) had IF at 42 days, decreasing to 15% at >90 days. The rate of IF was significantly higher in the surgical group than the medical group (OR 2.04, 95% CI, 1.25-3.35, p < 0.004), but 23% of the medically treated infants with NEC also developed IF. There was a significant relationship between IF and gram-negative bacteraemia, the need for surgery, cholestasis, liver failure and mortality. CONCLUSION: Intestinal failure occurred in a significant proportion of infants with NEC. Predictors for IF among infants with NEC were low birthweight, low gestational age, need for surgical intervention and gram-negative bacteraemia.

Food fortification and decline in the prevalence of neural tube defects: does public intervention reduce the socioeconomic gap in prevalence?

OBJECTIVE: A significant decline in the prevalence of neural tube defects (NTD) through food fortification has been reported. Questions remain, however, about the effectiveness of this intervention in reducing the gap in prevalence across socioeconomic status (SES). STUDY DESIGN: Using health number and through record linkage, children born in Ontario hospitals between 1994 and 2009 were followed for the diagnosis of congenital anomalies. SES quintiles were assigned to each child using census information at the time of birth. Adjusted rates and multivariate models were used to compare trends among children born in different SES groups. RESULTS: Children born in low SES areas had significantly higher rates of NTDs (RR = 1.25, CI: 1.14-1.37). Prevalence of NTDs among children born in low and high SES areas declined since food fortification began in 1999 although has started rising again since 2006. While the crude decline was greater in low SES areas, after adjustment for maternal age, the slope of decline and SES gap in prevalence rates remained unchanged overtime. CONCLUSIONS: While food fortification is successful in reducing the prevalence of NTDs, it was not associated with removing the gap between high and low SES groups.

The addition of cysteine to the total sulphur amino acid requirement as methionine does not increase erythrocytes glutathione synthesis in the parenterally fed human neonate.

Controversy exists as to whether the parenterally (PN) fed human neonate is capable of synthesizing adequate cysteine from methionine if the total dietary requirement for sulfur amino acid (SAA) is provided as methionine only. The goal of this study was to gather data on whether glutathione (GSH) synthesis is maximized at a methionine intake previously shown to be adequate for protein synthesis in the PN-fed human neonate. We measured GSH concentration, fractional, and absolute synthesis rate in five PN-fed human neonates. Each neonate underwent two isotope infusion studies of 7 h duration after a 2-d adaptation to the total SAA requirement (methionine only) and again after a further 2-d adaptation to the same methionine intake supplemented with cysteine at 10 mg x kg(-1) x d(-1). Cysteine supplementation did not significantly affect GSH synthesis. These data suggest that term infants are capable of synthesizing cysteine from methionine, not only for protein but also for GSH synthesis.

Total sulfur amino acid requirement and metabolism in parenterally fed postsurgical human neonates.

BACKGROUND: Except for tyrosine, the amino acid requirements of human neonates receiving parenteral nutrition (PN) have not been experimentally derived. OBJECTIVES: The objectives were to determine the total sulfur amino acid (TSAA) requirement (methionine in the absence of cysteine) of postsurgical, PN-fed human neonates by using the indicator amino acid oxidation (IAAO) technique with L-[1-(13)C]phenylalanine as the indicator. DESIGN: Fifteen postsurgical neonates were randomly assigned to receive 1 of 18 methionine intakes ranging from 10 to 120 mg x kg(-1) x d(-1), delivered in a customized, cysteine-free amino acid solution. Breath and urine samples were collected for the measurement of (13)CO(2) and amino acid enrichment. Blood samples were collected at baseline and after the test methionine infusion for the measurement of plasma methionine, homocysteine, cystathionine, and cysteine concentrations. RESULTS: Breakpoint analysis determined the mean TSAA requirements to be 47.4 (95% CI: 38.7, 56.1) and 49.0 (95% CI: 39.9, 58.0) mg x kg(-1) x d(-1) with the use of oxidation and F(13)CO(2), respectively. CONCLUSIONS: This is the first study to report the TSAA requirement of postsurgical, PN-fed human neonates. The estimated methionine requirement expressed as a proportion of the methionine content of current commercial pediatric PN solutions was 90% (range: 48-90%) of that found in the lowest methionine-containing PN solution.

Correlation of sonographic findings and outcome in necrotizing enterocolitis.

BACKGROUND: There is little in the literature regarding the use of gray-scale and Doppler sonography of the bowel in necrotizing enterocolitis (NEC) and how findings depicted by this modality might assist in predicting outcome and influence management. OBJECTIVE: To correlate sonographic findings with outcome in NEC. MATERIALS AND METHODS: This was a retrospective analysis of clinical and abdominal ultrasonography (AUS) findings in NEC from January 2003 to December 2005. AUS findings were evaluated for portal venous gas, free gas, peritoneal fluid, bowel wall thickness, echogenicity, perfusion and intramural gas. Patients were categorized into two groups, according to their outcome. RESULTS: A total of 40 infants were identified who had AUS for NEC prior to any surgical intervention. Group A comprised 18 neonates treated medically and recovered fully, and group B comprised 22 neonates who required surgery or died. Free gas (six patients) and focal fluid collections (three patients) were only found in group B. Increased bowel wall echogenicity, absent bowel perfusion, portal venous gas, bowel wall thinning, bowel wall thickening, free fluid with echoes and intramural gas were seen in both groups, but more frequently in group B. Anechoic free fluid was seen more frequently in group A. Increased bowel perfusion was seen equally in both groups. CONCLUSION: An adverse outcome was associated with the sonographic findings of free gas, focal fluid collections or three or more of the following: increased bowel wall echogenicity, absent bowel perfusion, portal venous gas, bowel wall thinning, bowel wall thickening, free fluid with echoes and intramural gas. Sonographic findings are useful in predicting outcome and therefore might help guide management.

Neonatal short bowel syndrome: a cohort study.

BACKGROUND: To date, our knowledge of morbidity and mortality in neonatal short bowel syndrome (SBS) is based on individual case series. Shortcomings of the published literature include long patient recruitment time, selection bias, variable SBS definitions, failure to account for gestational age, and incomplete follow-up. By applying more rigorous methodology, our aim was to determine outcomes of SBS neonates compared with a control group of neonates without SBS. METHODS: A cohort study of all neonates with abdominal pathology requiring laparotomy between January 1, 1997, and December 31, 1998, with observation through July 1, 2001. Short bowel syndrome was defined as patients requiring parenteral nutrition for more than 42 days or residual small bowel length of less than 25% predicted by gestational age. Student's t test, Mann-Whitney U test, and chi2 were used where appropriate. Kaplan-Meier curves were used to determine cumulative survival. Covariates important in the development of SBS were examined using forward step-wise logistic regression. RESULTS: There were 175 patients (with SBS = 40, without SBS = 135) with a mean gestational age of 30.7 +/- 4.6 weeks vs 35.9 +/- 4.8 weeks, respectively (P < .0005). The patients with SBS suffered significantly more morbidity than the group without SBS in all categories of investigation (surgical complications, septic events, central venous line complications, duration to adaptation and parenteral nutrition independence, cholestasis and liver failure, and duration of hospitalization). The case fatality rate was 37.5% in patients with SBS vs 13.3% in patients without SBS (P = .001). Most of the deaths were caused by liver failure or sepsis and occurred within 1 year from the date of surgery. Presence of an ileostomy (exp(B) = 12.29; P < .0005) and a residual small bowel length less than 50% of the original length (exp(B) = 26.84; P < .0005) were the only 2 variables in a logistic regression analysis found to be independently associated with the development of SBS. CONCLUSION: This cohort study clearly illustrates the tremendous morbidity experienced by infants with SBS relative to other surgical neonates. Accurate estimates of the morbidity associated with SBS enables clinicians to appropriately counsel parents, allocate resources and initiate therapeutic trials.

Flaxseed oil and inflammation-associated bone abnormalities in interleukin-10 knockout mice.

Interleukin-10-/- (IL-10) knockout (KO) mice develop an intestinal inflammation that closely mimics human inflammatory bowel disease (IBD) which is accompanied by inflammation-associated bone abnormalities and elevated serum proinflammatory cytokines. The objective of this study was to use the IL-10 KO mouse model to determine whether flaxseed oil (FO) diet, rich in alpha-linolenic acid (ALA), attenuates intestinal inflammation and inflammation-associated bone abnormalities, compared to a corn oil (CO) control diet. Male wild-type (WT) or IL-10 KO mice were fed a 10% CO or 10% FO diet from weaning (postnatal day 28) for 9 weeks. At necropsy, serum, intestine, femurs and lumbar vertebrae were collected and analyzed. IL-10 KO mice fed CO had lower femur bone mineral content (BMC; P<.001), bone mineral density (BMD; P<.001), peak load (P=.033) and lumbar vertebrae BMD (P=.02) compared to WT mice fed either diet. Flaxseed oil had a modest, favorable effect on IL-10 KO mice as femur BMC, BMD and peak load were similar to WT mice fed CO or FO. In addition, lumbar vertebra BMD was similar among IL-10 KO mice fed FO and WT mice fed CO or FO. The fact that FO attenuated serum tumor necrosis factor-alpha (TNF-alpha) among IL-10 KO mice suggests that the positive effects of FO on femur BMC, BMD, peak load and vertebral BMD in IL-10 KO mice may have been partly mediated by changes in serum TNF-alpha. In conclusion, these findings suggest that a dietary level of ALA attainable from a 10% flaxseed oil diet results in modest improvements in some bone outcomes but does not attenuate intestinal inflammation that is characteristic of IL-10 KO mice.

Neonatal short bowel syndrome: population-based estimates of incidence and mortality rates.

BACKGROUND: Congenital or acquired neonatal short bowel syndrome (SBS) carries significant morbidity and mortality rates. No accurate population estimates of incidence and mortality exist because of differences in definition, follow-up, and regional referral patterns. METHODS: A retrospective cohort study was performed involving 175 surgical neonates admitted to our institution from January 1, 1997 to December 31, 1999 and followed up until July 1, 2001. Institution and population-based estimates of incidence and mortality were performed using postcensal population figures (1997) from Statistics Canada. RESULTS: The overall incidence of SBS was 22.1 per 1,000 neonatal intensive care unit (NICU) admissions (95% CI = 15.3, 28.9) and 24.5 per 100,000 live births (95% CI = 12.1, 36.9). The incidence was much greater in premature infants (less than 37 weeks). The SBS case fatality rate was 37.5% (95% CI = 22.5, 52.5) and the cause-specific and proportional mortality rates (for children less than 4 years old) were 2.0 of 100,000 population per year (0.4 to 3.6/100,000/year) and 1.4% (0.3% to 2.6%), respectively. CONCLUSIONS: Patients with neonatal SBS pose a complex management challenge and are responsible for a significant cost to the health care system. To our knowledge, this study represents the first population-based estimates for neonatal SBS incidence and mortality rates. Accurate estimates will assist clinicians in counseling parents, allocating resources, and planning clinical trials.