Linda S. Book

Gastroesophageal reflux causing respiratory distress and apnea in newborn infants

Respiratory distress, apnea, and chronic pulmonary disease since birth were identified in 14 infants who also had symptomatic gastroesophageal reflux. Birth weights varied from 760 to 4,540 gm. All infants had radiographic changes similar to those in bronchopulmonary dysplasia. Cessation of apnea and improvement of pulmonary disease occurred only after medical (8) or surgical (6) control of gastroesophageal reflux. Simultaneous tracings of esophageal pH, heart rate, impedance pneumography, and nasal air flow in five infants demonstrated that reflux preceded apnea. Apnea could be induced by instillation of dilute acid, but not water or formula, into the esophagus. Prolonged monitoring of esophageal pH more than two hours after feeding in 14 other infants less than 6 weeks of age (birth weight 780 to 3,350 gm) without a history of recent vomiting indicated that reflux was not greater than in normal older children.

Serum alpha fetoprotein (AFP) levels in normal infants.

Summary: Serum α-fetoprotein (AFP) levels were monitored in 32 normal babies consecutively from 2 to 3 days, 2 wk, and 2 and 4 months after birth. In addition, serum AFP concentration was also measured in 116 random specimens from infants with normal liver enzymes and 10 infants born immaturely. Results were combined to establish normal AFP levels for infants at various ages. Serum AFP disappeared rapidly after birth. We found that it was not until 8 months of age that the normal AFP level in infants approached adult level. The half-lives of AFP degradation were estimated to be 5.5 days between birth and 2 wk, 11 days between 2 wk to 2 months, and 33 days between 2 and 4 months of age. In contrast to earlier belief, we felt that some AFP synthesis still exists after birth; however, the rate of synthesis may also decrease with age.Speculation: Our results favor the view that some α-fetoprotein (AFP) synthesis exists after birth. The rate of synthesis is slowly decreased with time. Any factor affecting the rate of synthesis may influence the serum AFP level. The wide range of variation in serum AFP levels in infants of various ages indicates that there must be more than one unknown factor affecting the AFP serum level. The normal range will be narrower if these factors become known. By using our age-dependent normal AFP serum levels, it would be interesting to see whether differential diagnosis of neonatal hepatitis from biliary atresia can be unproved and whether infants do have higher and more frequent elevation of serum AFP with hepatic disorders.

Necrotizing enterocolitis in low-birth-weight infants fed an elemental formula

The incidence of necrotizing enterocolitis in the newborn infant has increased within the same time period that increasing emphasis has been placed on oral alimentation of very small infants. A prospective investigation was conducted to determine the nutritional efficacy as well as the incidence of necrotizing enterocolitis of a standard cow milk formula compared with an elemental formula. Sixteen infants who weighed less than 1,200 gm were randomized and fed one of the two formulas. The clinical status of the two groups was similar. Seven of eight (87.5%) infants fed the elemental formula and two of eitht (25%) fed the standard cow milk formula developed necrotizing enterocolitis (p less than 0.02). The hypertonicity of the elemental diet may have contributed to the increased incidence of necrotizing enterocolitis in infants fed this formula.

Prevalence and clinical characteristics of celiac disease in Downs syndrome in a U.S. study

Celiac disease is an autoimmune gastrointestinal disorder characterized by mucosal atrophy of the jejunum on exposure to gluten, a protein found in grains. The purpose of our study was to determine the prevalence of celiac disease in children with Downs syndrome in a U.S.-based Caucasian population. The 97 Downs syndrome children were screened for celiac disease using serum IgA-anti-endomysial antibody testing, which is highly specific and sensitive for the disorder. Children with titers greater than 1:5 (using the IgA endomysial antibody [EMA] test; EMA+) were considered affected. Ten children (10.3%) were EMA+. We examined their HLA DQA1 DQB1 genotype, karyotype, clinical characteristics, and the prevalence of celiac disease in their first-degree relatives. The nine available karyotypes were trisomy 21. Downs syndrome-specific mean height percentile was 64% ± 26% (range <5–99%) and weight percentile was 43% ± 28% (range 5–95%). Presence of diarrhea, constipation, vomiting, and abdominal pain was similar for children with and without celiac disease. Only bloating symptoms were significantly more frequent in those with celiac disease (EMA+). Seven of eight (88%) genotyped EMA+ children had the celiac disease-associated high-risk HLA DQA1*0501 DQB1*0201 genotype as compared with 13/80 (16%) of EMA− children. Five of 48 (10%) first-degree relatives of the celiac disease (EMA+) children were EMA+. In conclusion, celiac disease, as diagnosed by positive endomysial antibody tests, has an increased prevalence in children with Downs syndrome in the U.S. as compared with the general population (1/250). Clinical and growth characteristics do not distinguish between children with and without celiac disease. Based on these observations, it is recommended that children with Downs syndrome be screened for celiac disease.

Prevalence of celiac disease among relatives of sib pairs with celiac disease in U.S. families.

OBJECTIVE:Celiac disease is a familial malabsorptive disorder with an estimated prevalence in first-degree relatives of 10–12%. The prevalence for first-degree and more distant relatives has not been determined in families where there are two affected first-degree relatives. The aim of our investigation was to estimate the prevalence and relative risk for celiac disease in relatives of two siblings diagnosed with celiac disease.METHODS:We ascertained sib pairs with celiac disease, and then identified all living first-degree relatives and available second-degree relatives to minimize ascertainment bias. We measured IgA endomysial antibodies, a highly specific and sensitive assay for celiac disease, in all subjects without a confirmed biopsy diagnosis. For those individuals with positive serologic tests, IgA tissue transglutaminase antibody tests and human leukocyte antigen DQA1 and DQB1 genotyping were performed for additional confirmation. Individuals with positive biopsy and/or serology were considered affected. We calculated the relative risk of being affected with celiac disease using the λR statistic.RESULTS:The prevalence of celiac disease in relatives of affected sib pairs was as follows: 21.3% (13/61) of siblings (λS = 53); 14.7% (10/68) of offspring (λO = 37); 17.2% (28/163) of first-degree relatives; 19.5% (16/82) of second-degree relatives; and 17.8% (52/292) of all relatives (λR = 44.5).CONCLUSIONS:In these families, we identified a sibling risk approximately double that found in previous reports, as well as significant risk for more distant relatives, probably because of sharing of a common gene. In families where at least two siblings have been diagnosed with celiac disease, relatives are at high risk for celiac disease. Screening should be considered for all family members.

Strongly positive tissue transglutaminase antibodies are associated with Marsh 3 histopathology in adult and pediatric celiac disease.

Goals Our objective was to determine whether high serologic IgA tissue transglutaminase antibodies (TTGA) are exclusively associated with celiac disease (CD). Background IgA TTGA are found in the serum of most individuals with CD. This serologic marker is used to screen individuals with suspected CD for duodenal biopsy, the gold standard of CD diagnosis. Data suggest strongly positive IgA TTGA ≥100 units are highly specific for CD histopathology in pediatric patients and may be sufficient for diagnosis. Study Records of adult and pediatric subjects in the celiac study at the University of Utah and University of California Irvine were reviewed for strongly positive TTGA. Pathology reports from duodenal biopsies of subjects with IgA TTGA ≥100 units were graded as 0 to 3 by modified Marsh criteria. Results From a pool of 1882 subjects with IgA TTGA assayed, 208 had IgA TTGA ≥100 units. Seventy-six of these, including 28 children and 48 adults, also had duodenal biopsies. Villous atrophy (Marsh 3 histopathology) was found on biopsy in 73 (96%) of these subjects. The remaining 3 subjects had intermediate Marsh histology. One (Marsh 1) had a complete serologic response to a gluten-free diet and 2 had Marsh 2 lesions and positive endomysium, making early CD most likely. Conclusions IgA TTGA ≥100 units occur almost exclusively in the setting of Marsh 3 duodenal histopathology in adults and children. Rare cases without villous atrophy were marked by intermediate Marsh changes suggestive of early CD. IgA TTGA ≥100 arbitrary units indicate duodenal changes consistent with CD.

Surgery in children with gastroesophageal reflux and respiratory symptoms

We reviewed our seven-year experience in 63 children with an operation to control gastroesophageal reflux and respiratory symptoms. The age at operation, sex, major associated disorders, and control of vomiting in this group of children were compared with another group of 72 children without respiratory symptoms who also had an antireflux operation during the same period. Associated central nervous system, pharyngeal, or esophageal disorders were common in both groups. Vomiting was controlled in 96% of patients. Fifty-six of 61 (92%) children had at least partial relief of respiratory symptoms postoperatively. The complete relief of these symptoms was more likely in patients without major associated disorders (97% vs 59% P = 0.0009). Central nervous system disorders were present in most children with incomplete resolution of respiratory symptoms. It appears that a significant number of affected infants and children may have respiratory difficulties unrelated to the presence of GER.

Primary sclerosing cholangitis, autoimmune hepatitis, and overlap in utah children: Epidemiology and natural history

The epidemiology and natural history of pediatric primary sclerosing cholangitis (PSC), autoimmune sclerosing cholangitis (ASC), and autoimmune hepatitis (AIH) are not well characterized. Using multiple, overlapping search strategies followed by a detailed records review, we identified all cases of pediatric PSC, ASC, AIH, and inflammatory bowel disease (IBD) in a geographically isolated region of the United States. We identified 607 cases of IBD, 29 cases of PSC, 12 cases of ASC, and 44 cases of AIH. The mean age at diagnosis was 13.0 years for PSC, 11.3 years for ASC, and 9.8 years for AIH. The incidence and prevalence of PSC, ASC, and AIH were 0.2 and 1.5 cases, 0.1 and 0.6 cases, and 0.4 and 3.0 cases per 100,000 children, respectively. The mean duration of follow‐up was 5.9 years. The probability of developing complicated liver disease within 5 years of the diagnosis of liver disease was 37% [95% confidence interval (CI) = 21%‐58%] for PSC, 25% (95% CI = 7%‐70%) for ASC, and 15% (95% CI = 7%‐33%) for AIH. The 5‐year survival rates with the native liver were 78% (95% CI = 54%‐91%) for PSC, 90% (95% CI = 47%‐99%) for ASC, and 87% (95% CI = 71%‐95%) for AIH. Cholangiocarcinoma developed in 2 of the 29 PSC patients (6.9%). PSC occurred in 9.9% of patients with ulcerative colitis (UC) and in 0.6% of patients with Crohns disease (CD). ASC occurred in 2.3% of UC patients and 0.9% of CD patients. AIH occurred in 0.4% of UC patients and in 0.3% of CD patients. Liver disease occurred in 39 of 607 IBD patients (6.4%) overall. Conclusion: Immune‐mediated liver diseases are important sources of morbidity in children. Using a population‐based design, this study quantifies the burden and natural history of immune‐mediated liver disease in children. (Hepatology 2013;58:1392–1400)

Elimination of soybean lipid emulsion in parenteral nutrition and supplementation with enteral fish oil improve cholestasis in infants with short bowel syndrome.

BACKGROUND Parenteral nutrition-associated liver disease (PNALD) is a potentially fatal complication for children with intestinal failure. Fish oil-based lipid emulsions have shown promise for the treatment of PNALD but are not readily available. Six cases are presented in which cholestasis resolved after soybean lipid emulsion (SLE) was removed from parenteral nutrition (PN) and enteral fish oil was given. METHODS A retrospective review at a tertiary childrens hospital (July 2003 to August 2008) identified 6 infants with intestinal failure requiring PN for >6 months who developed severe hepatic dysfunction that was managed by eliminating SLE and providing enteral fish oil. RESULTS Twenty-three infants with short bowel syndrome requiring prolonged PN developed cholestasis. SLE was removed in 6 of these patients, and 4 of the 6 received enteral fish oil. Standard PN included 2-3 g/kg/d SLE with total PN calories ranging from 57 to 81 kcal/kg/d at the time of SLE removal. Hyperbilirubinemia resolved after elimination of SLE within 1.8-5.4 months. Total PN calories required to maintain growth generally did not change. CONCLUSIONS Temporary elimination of SLE and supplementation with enteral fish oil improved cholestasis in PN-dependent infants. Further trials are needed to evaluate this management strategy.

Patterns of postcibal gastroesophageal reflux in symptomatic infants

Symptomatic infants displayed three patterns of gastroesophageal reflux after drinking apple juice (20 ml/kg or 300 ml/m2 of body surface area). The type I pattern occurred in patients who had continuous postcibal gastroesophageal reflux, large hiatal hernias and frequently required an antireflux operation. A functional motility disorder suggesting delayed gastric emptying appeared to be important in infants with discontinuous reflux (type II pattern). These infants had frequent gastroesophageal reflux for only 2 3/4 hours postcibally, antral-pylorospasm, increased low esophageal sphincter pressures, and a high incidence of pulmonary symptoms and non-specific watery diarrhea. The mixed (type III) pattern of gastroesophageal reflux occurred in a small number of infants and exhibited features of both type I and II patterns.