I W Booth

Parenteral nutrition—Related cholestasis in postsurgical neonates: Multivariate analysis of rick factors

The medical records of 74 neonates dependent on parenteral nutrition for at least 21 days after emergency abdominal surgery (performed between 1988 and 1992) were reviewed respectively. The role of enteral starvation, prematurity, composition and duration of parenteral nutrition, and sepsis in the evolution of parenteral nutrition-related cholestasis was evaluated by multiple regression analysis. The most important factors for cholestasis were low gestational age (median, 34 weeks), early exposure to parenteral nutrition, and sepsis. Episodes of sepsis were associated with a 30% increase in the bilirubin level. Enteral starvation and composition and the duration of parenteral nutrition solutions did not correlate significantly with the development of cholestasis. Prevention of sepsis should be the priority in minimising cholestasis in postsurgical neonates who are dependent on parenteral nutrition.

Congenital anterior abdominal wall defects in England and Wales 1987–93: retrospective analysis of OPCS data

Abstract Objectives: Analysis of incidence and characteristics of congenital abdominal wall defects, with special reference to the differences between the incidence of gastroschisis and exomphalos (omphalocele). Design: Retrospective analysis using data from the Office of Population Censuses and Surveys (recoded to differentiate exomphalos and gastroschisis) and the National Congenital Malformation Notification Scheme. Setting: England and Wales, 1987 to 1993. Results: 1043 congenital anterior abdominal wall defects were notified within the seven year study period. Of these, 539 were classified as gastroschisis, 448 as exomphalos, 19 as “prune belly syndrome,” and 37 as “unclassified.” Gastroschisis doubled in incidence from 0.65 in 1987 to 1.35 per 10 000 total births in 1991, with little further change; the incidence of exomphalos decreased from 1.13 to 0.77 per 10 000 births. The overall incidence of notified congenital abdominal wall defects was 2.15 per 10 000 total births. Gastroschisis was associated with a lower overall maternal age than exomphalos and with a significantly lower proportion of additional reported congenital malformations (5.0%) than in the cohort with exomphalos (27.4%) (odds ratio 0.14, 95% confidence interval 0.09 to 0.22; P<0.001). The sex ratio of the two cohorts was the same. The incidence of gastroschisis and exomphalos was higher in the northern regions of England than in the south east of the country. Conclusions: The national congenital malformation notification system showed an increasing trend in the incidence of fetuses born with gastroschisis and a progressive decreasing incidence of exomphalos in England and Wales between 1987 and 1993. Although the reasons for this are likely to be multifactorial, a true differential change seems likely. The observed increase in incidence of gastroschisis relative to exomphalos and the differentiation in maternal age have implications for resource management within the NHS and warrant further epidemiological monitoring. Regional differences may be due to a dietary or environmental factor, which requires further study. Key messages Gastroschisis was also associated with a significantly lower proportion of additional reported congenital malformations Younger mothers are significantly more likely than older mothers to have a child with gastroschisis The incidence of congenital abdominal wall defects seemed to be higher in the regions in the north than in the south east of England

Gut blood flow velocities in the newborn: effects of patent ductus arteriosus and parenteral indomethacin.

The effects on gut blood flow velocities of parenteral indomethacin (0.2 mg/kg) given either quickly as a bolus or slowly as an infusion were compared in consecutive studies of two groups of infants with symptomatic patent ductus arteriosus. In the presence of patent ductus arteriosus the range of velocities in the superior mesenteric artery before indomethacin was given was characterised by pronounced abnormalities including absent--or in some cases even retrograde--diastolic flow. In eight subjects the first rapidly given bolus dose of indomethacin (duration 20 seconds or less) caused a pronounced and sustained fall in the velocity of the superior mesenteric artery blood flow (mean peak systolic velocity (cm/second): before 74; after 38; median time to maximum fall 7.4 minutes; median time to recovery 50 minutes). A further 10 subjects received their first dose of indomethacin by slow infusion (duration 30-35 min) and the percentage fall in peak systolic velocity was both substantially less (22% compared with 47%) and later (median time to maximum fall 37.3 minutes) than after rapid infusion. Qualitatively similar but smaller changes were seen in the coeliac axis. Return of antegrade end diastolic flow in the superior mesenteric artery within one hour of the first dose of indomethacin was a good predictor of subsequent closure of the ductus. These data suggest that there is a profound disturbance in mid gut perfusion in infants with patent ductus, which is exacerbated by indomethacin given rapidly by intravenous bolus. They may also provide a rational explanation for the well recognised association between necrotising enterocolitis and both patent ductus arteriosus and indomethacin administration. The unwanted effects of the indomethacin are abrogated by slow infusion, without loss of efficacy in closure of the ductus.

Six months of exclusive breast feeding: how good is the evidence?

The recommendation that UK mothers should exclusively breast feed for six months is a controversial area in infant nutrition. Mary Fewtrell and colleagues review the evidence and ask if the time is right for reappraisal of this advice

Gastro-oesophageal reflux in preterm infants.

Gastro-oesophageal reflux in very low birthweight infants was studied using a new 1 mm monocrystalline antimony oesophageal pH electrode. Gastro-oesophageal reflux was detected in 30 (85%) subjects. The mean (SEM) number of episodes of reflux in 24 hours was 12.1 (2.1), and 3.2 (0.6) lasted over five minutes. The mean reflux index was 4.5 (1.0)%, and the longest episode 17.1 (4.6) 17.1. Reflux was unrelated to postconceptional age or to resting lower oesophageal sphincter pressure. The mean reflux index was low at rest before feeds, being 1.8 (0.6)%, and increased slightly after feeds (3.8 (1.0)%), but was significantly increased after nursing care to 16.4 (3.0)%, and while xanthines were being given (5.9 (1.6)%. A subgroup of seven infants with xanthine resistant apnoea had severe gastro-oesophageal reflux that was not clinically apparent (reflux index 27.4 (3.6)%). Successful treatment of the reflux (reflux index: 3.6 (1.2)%) was associated with cessation of the apnoea. We conclude that gastro-oesophageal reflux is common, and is usually not clinically apparent, even when severe. It is important to consider gastro-oesophageal reflux in the differential diagnosis of xanthine resistant apnoea in preterm infants.

Gastric emptying in preterm infants.

An ultrasonic technique was used to compare gastric emptying after a feed of expressed breast milk and formula milk in a blind, cross over study of preterm infants. Fourteen infants (median gestational age 33 weeks) were studied on 46 occasions. Each infant received a nasogastric feed of either expressed breast milk or formula milk, and the alternative at the next feed. Real time ultrasound images of the gastric antrum were obtained and measurements of antral cross sectional area (ACSA) were made before the feed and then sequentially after its completion until the ACSA returned to its prefeed value. The half emptying time (50% delta ACSA) was calculated as the time taken for the ACSA to decrease to half the maximum increment. On average, expressed breast milk emptied twice as fast as formula milk: mean 50% delta ACSA expressed breast milk 36 minutes; formula milk 72 minutes. The technique was reproducible and there was no significant difference between the emptying rates of feeds of the same type for an individual infant. These data show that breast milk has a major effect on gastric emptying, which may have important implications for preterm infants who have a feed intolerance due to delayed gastric emptying.

Abnormal gut blood flow velocities in neonates at risk of necrotising enterocolitis.

Duplex pulsed Doppler ultrasound was used to determine blood flow velocities in the coeliac axis and superior mesenteric artery in three groups of neonates: a group at high risk of developing necrotising enterocolitis (n = 27) and two control groups, i.e., a nonasphyxiated, appropriately grown group of preterm infants (n = 18) and a group of nonasphyxiated term infants (n = 14). Subjects were studied on the first, second, and fourth days of life. The median peak systolic velocities in the superior mesenteric artery were between 20 and 51% lower in the at-risk group than in the term control group on all 3 days of measurement (p < 0.05 – p < 0.002). The ratio of peak systolic velocity in the coeliac axis to that in superior mesenteric artery, an index of relative downstream vascular resistance in the superior mesenteric artery, was 42–65% greater in the at-risk group compared with the other two groups on days 1 and 2 (p < 0.05 – p < 0.001) and significantly greater than the term group on day 4 (73%, p < 0.002). These data demonstrate that neonates at risk of developing necrotising enterocolitis have abnormal gut blood flow velocities. Furthermore, they provide evidence that an alteration in the splanchnic circulation may be an important factor in the final common pathway that links diverse risk factors for necrotising enterocolitis with clinical disease.

Enteral nutrition after bone marrow transplantation

Nutritional insult after bone marrow transplantation (BMT) is complex and its nutritional management challenging. Enteral nutrition is cheaper and easier to provide than parenteral nutrition, but its tolerance and effectiveness in reversing nutritional depletion after BMT is poorly defined. Nutritional status, wellbeing, and nutritional biochemistry were prospectively assessed in 21 children (mean age 7.5 years; 14 boys) who received nasogastric feeding after BMT (mean duration 17 days) and in eight children (mean age 8 years, four boys) who refused enteral nutrition and who received dietetic advice only.  Enteral nutrition was stopped prematurely in eight patients. Greater changes in weight and mid upper arm circumference were observed in the enteral nutrition group, while positive correlations were found between the duration of feeds and increase in weight and in mid upper arm circumference. Vomiting and diarrhoea had a similar incidence in the two groups, while fever and positive blood cultures occurred more frequently in the dietetic advice group. Diarrhoea occurring during enteral nutrition was not associated with fat malabsorption, while carbohydrate malabsorption was associated with rotavirus infection only. Enteral feeding did not, however, affect bone marrow recovery, hospital stay, general wellbeing, or serum albumin concentrations. Hypomagnesaemia, hypophosphataemia, zinc and selenium deficiency were common in both groups. In conclusion, enteral nutrition, when tolerated, is effective in limiting nutritional insult after BMT. With existing regimens nutritional biochemistry should be closely monitored in order to provide supplements when required.

The clinical value of solid marker transit studies in childhood constipation and soiling

Assessment of constipation in childhood is difficult, particularly when the presenting symptom is spurious diarrhoea or faecal incontinence. We have therefore assessed the clinical usefulness, reliability and acceptibility of a solid marker transit technique in 52 patients with constipation (median age 8.0 years; range 2–13.5 years) at two referral centres. Median duration of symptoms was 60 months. Soiling was a prominent feature in 43 children (83%). Ten, 3 mm pieces of 6FG radio-opaque Silastic tubing were given orally at 9am on days 1, 2 and 3 and a plain abdominal film taken on day 5. Laxative treatment was not interrupted. Each film was divided into right colon, left colon and rectosigmoid areas, using bony landmarks, and the marker content of each area counted. The coefficient of variation of intra and inter-observer errors was 3.1% and 2.1% respectively. By day 5, 7% (group median) of markers were still in the right colon, 17% in the left colon and 42% in the rectosigmoid. Twenty-one patients(40%) had normal transit, 4 (8%) mild delay, 9 (17%) moderate and 18 (35%) severe transit delay. Marker distribution indicated slow pancolonic transit in 29% and slow segmental transit in 10%. In 21%, clustering of markers in the rectosigmoid suggested outlet obstruction. A significant correlation was found between both transit delay and marker distribution and the severity of clinical symptoms of constipation and soiling. Repeat studies in six children following colonic evacuation revealed significant improvement (P< 0.05) in marker transit. The test was well tolerated and was useful in establishing the diagnosis of constipation in children with soiling or spurious diarrhoea and in assessment of its severity and its response to treatment.

Mutations in TTC37 Cause Trichohepatoenteric Syndrome (Phenotypic Diarrhea of Infancy)

BACKGROUND & AIMS Trichohepatoenteric syndrome (THES) is an autosomal-recessive disorder characterized by life-threatening diarrhea in infancy, immunodeficiency, liver disease, trichorrhexis nodosa, facial dysmorphism, hypopigmentation, and cardiac defects. We attempted to characterize the phenotype and elucidate the molecular basis of THES. METHODS Twelve patients with classic THES from 11 families had detailed phenotyping. Autozygosity mapping was undertaken in 8 patients from consanguineous families using 250,000 single nucleotide polymorphism arrays and linked regions evaluated using microsatellite markers. Linkage was confirmed to one region from which candidate genes were analyzed. The effect of mutations on protein production and/or localization in hepatocytes and intestinal epithelial cells from affected patients was characterized by immunohistochemistry. RESULTS Previously unrecognized platelet abnormalities (reduced platelet alpha-granules, unusual stimulated alpha granule content release, abnormal lipid inclusions, abnormal platelet canalicular system, and reduced number of microtubules) were identified. The THES locus was mapped to 5q14.3-5q21.2. Sequencing of candidate genes showed mutations in TTC37, which encodes the uncharacterized tetratricopeptide repeat protein, thespin. Bioinformatic analysis suggested thespin to be involved in protein-protein interactions or chaperone. Preliminary studies of enterocyte brush-border ion transporter proteins (sodium hydrogen exchanger 2, sodium hydrogen exchanger 3, aquaporin 7, sodium iodide symporter, and hydrogen potassium adenosine triphosphatase [ATPase]) showed reduced expression or mislocalization in all THES patients with different profiles for each. In contrast the basolateral localization of Na/K ATPase was not altered. CONCLUSIONS THES is caused by mutations in TTC37. TTC37 mutations have a multisystem effect, which may be owing to abnormal stability and/or intracellular localization of TTC37 target proteins.