Judith M. Sondheimer

Infection and cholestasis in neonates with intestinal resection and long-term parenteral nutrition.

OBJECTIVES This retrospective study was conducted to determine the incidence of cholestasis and liver failure in patients with intestinal resection in the neonatal period who subsequently become dependent on parenteral nutrition support and to assess the significance of associated clinical factors--gestational age, birth weight and length; length of bowel resected; presence of ileocecal valve; enteral feeding history; and infection--to the incidence and severity of cholestasis. METHODS Retrospective chart review of all patients in a single institution from May 1984 to February 1997 with neonatal small intestinal resection dependent on parenteral nutrition for at least 3 months. RESULTS Forty-two patients fitting the inclusion criteria were the subjects of this review. Cholestasis developed in 28 (67%) while they were receiving parenteral nutrition (direct serum bilirubin more than 2 mg/dl). In 21, the elevated direct bilirubin normalized while patients continued to receive parenteral nutrition. Seven patients progressed to liver failure. In 14 patients, serum direct bilirubin nerve rose above 2 mg/dl. The cholestatic patients did not differ from the noncholestatic in gestational age, birth weight, and length; primary diagnosis; length of bowel resected; or presence of ileocecal valve. The duration of dependence on parenteral nutrition was longer in noncholestatic (33.2 +/- 9 months) than in cholestatic patients progressing to liver failure (19.4 +/- 3 months) or in cholestatic patients who recovered (16.1 +/- 1.9 months) (p < 0.05). Invasive fungal or bacterial infections occurred in all but one noncholestatic patient. The number of infections per patient was similar in all groups. The mean age (days) at first infection was significantly younger in cholestatic patients progressing to liver failure (28.5 +/- 5) and cholestatic patients who recovered (48.2 +/- 14.2) than in noncholestatic patients (167 +/- 43.2) (p < 0.01). Infection preceded the onset of cholestasis in all but 3 patients by an average of 13.5 days. Infecting organisms and site of first infection were similar in all patients. CONCLUSIONS Cholestasis is common in infants with neonatal intestinal resection. Liver failure develops in 16.6%. Bacterial infection early in life characterized the cholestatic patients, and cholestasis developed shortly after the first infection in 90% of patients.

Gastroesophageal reflux among severely retardedchildren

Of 136 institutionalized severely retarded children, 20 (15%) had recurrent vomiting. Of these 20, 15 had gastroesophageal reflux diagnosed by x-ray examination, acid reflux text, or both. Esophagitis was noted by endoscopy in ten of 14 patients with GER. Four patients were anemic and six had had one or more episodes of aspiration pneumonia in the 12 months prior to study. Reduced basal lower esophageal sphincter pressure was the most common manometric abnormality noted in the patients with GER. Responses of the LES to bethanechol and swallow were normal, as was the basal pressure of the upper esophageal sphincter. Abnormal propagation of esophageal peristalsis was seen in six patients, all of whom had moderate or severe esophagitis. When compared to the nonvomiting retarded patients, the GER patients had significantly lower mental age and higher incidence of scoliosis. Patients with GER who had basal LES pressure less than 10 mm Hg did not improve with medical management. Recurrent vomiting is a common and serious problem in severely retarded children, the organic cause of which can be demonstrated by the application of appropriate investigative techniques.

Outcome of syndromic paucity of interlobular bile ducts (Alagille syndrome) with onset of cholestasis in infancy

OBJECTIVE To determine the outcome, in index patients followed at an American Center, of syndromic paucity of interlobular bile ducts (sPILBD; Alagille syndrome), with onset of cholestasis in infancy. DESIGN Cohort. SETTING Regional referral center for infants and children with liver disease. RESULTS During the past 10 years, 26 unrelated children with sPILBD were identified. Fifteen (58%) are alive without liver transplantation at a median age of 12.1 years. Three (11%) died, all before 2 years of age. Eight patients (31%) underwent liver transplantation at a median age of 6.5 years; all eight are alive a median 5.4 years after transplantation. The most common factors contributing to the decision for transplantation were bone fractures, pruritus, and severe xanthoma. The predicted probability of reaching 19 years of age without transplantation is about 50%; however, with transplantation, the predicted probability of long-term survival is 87%. Of 26 patients 4 (15%) have had significant central nervous system disease, and two of them have died of intracranial hemorrhage. Of the four patients who underwent cholecystoportostomy or portoenterostomy, three required liver transplantation. CONCLUSIONS Children with sPILBD identified in infancy because of cholestasis have a 50% probability of long-term survival without liver transplantation, a worse prognosis than other follow-up studies have reported. In selected patients, liver transplantation provides the opportunity for long-term survival with improved quality of life. Patients with sPILBD are at risk of having intracranial hemorrhage.

Evaluation of infantile acid and nonacid gastroesophageal reflux using combined pH monitoring and impedance measurement.

Objective: Characterize the proportion of acid and nonacid esophageal reflux events in young infants with suspected gastroesophageal reflux (GER) using combined pH-multichannel intraluminal impedance (MII) monitoring. Determine the symptom index correlation with nonacid reflux and acid reflux events. Study Design: Prospective study of children, aged 2 weeks to 1 year, referred to The Childrens Hospital of Denver Gastroenterology Clinic for evaluation of GER. Exclusion criteria were congenital anomalies or syndromes, cerebral palsy, mental retardation, and pulmonary or cardiac disease. The children were admitted to The Childrens Hospital General Clinical Research Center for a 20 hour pH-MII study. Acid suppression was either never used or discontinued 2 weeks before testing. Results: Thirty-four infants were enrolled from February 2004 to February 2005. Ages ranged from 2 months to 11 months, median = 7 (20 females/14 males). One thousand eight hundred ninety reflux events were detected by MII, and 588 reflux events were detected by pH probe alone. The percent of reflux that was acid was 47% (888 events) versus 53% of (1,002 events) nonacid reflux events. The proportion of nonacid reflux decreased with age (P < 0.0001 by Pearson χ2 test) and with increasing time elapsed from last meal. There were 958 total symptoms evaluated. The most frequently reported symptom was fussiness/pain, which correlated with nonacid reflux events 24.6% and acid reflux 25.2%. The proximal height of a reflux was predictive for symptoms of fussiness/pain, arching, and burping. Conclusion: MII detects more reflux events than pH monitoring alone. The proportion of nonacid reflux to acid reflux events in infants is more similar to adults than previously reported. Combined pH-MII esophageal monitoring identifies more reflux events and improves clinical correlation with symptoms.

Continuous gastric pH measurement in young and older healthy preterm infants receiving formula and clear liquid feedings.

Gastric pH was recorded with an intragastric pH electrode for 12 h in two groups of healthy, preterm infants with similar birth weights (range 1.4 to 2.0 kg). Group I infants (n = 13) were less than 7 days old and Group II infants (n = 10) were 7-15 days old. Infants were fed three formula feedings and one clear liquid feeding during the study. In Group I, mean gastric pH measured at 15-min intervals was above 4.0 for 3 h after either feeding. In Group II mean gastric pH was lower particularly after clear liquid feedings, where it remained below pH 4.0 for the entire 3-h postprandial period. The percent of monitored time at gastric pH less than 4.0 was low in Group I--15.2 +/- 4.2% and 20.6 +/- 6.4% after formula and clear liquid, respectively. The percent time was greater in Group II--42.7 +/- 8.0% and 61.9 +/- 7.3% after formula and clear liquid, respectively. In the younger preterm infant, gastric pH does not appear sufficiently low to support peptic activity.

Intestinal function in infants with severe congenital heart disease

We evaluated digestive tract function in 21 young infants with severe congenital heart disease. One group had congestive heart failure and ventricular septal defect or single ventricle; the other had cyanosis and transposition of the great arteries. Enteric protein loss was excessive in eight patients, and steatorrhea was found in five. These abnormalities were mild and not related to the type or severity of the cardiac lesion. Available evidence points to a need of these babies for calories in excess of normal requirements for weight. The present study suggests that in designing dietary regimens for these very sick patients, their potential for defective gastrointestinal function must be considered. Because no consistent pattern of abnormalities in apparent, each patient who fails to thrive may deserve gastroenterologic evaluation.

Simultaneous pH recordings from multiple esophageal sites in children with and without distal gastroesophageal reflux.

We made continuous, simultaneous recordings of esophageal pH from three sites in the esophageal body, for 18-24 h, in 11 children with normal prolonged distal esophageal pH studies (Group I) and in 14 children with abnormal distal esophageal pH recordings (Group II). A flexible catheter housing four antimony microelectrodes was used, and data were stored in a portable recorder. A computer allowed for evaluation of the percent of time esophageal pH was less than 4.0, number of reflux episodes per hour, acid clearance time, and the duration of longest reflux episode. Recordings made while subjects were upright or recumbent could be distinguished and analyzed separately. In the recumbent position, comparison of pH recordings from distal, middle, and proximal esophageal pH electrodes in Group I showed significant decreases in the percent of time spent with pH less than 4.0, reflux episodes per hour, acid clearance time, and duration of longest reflux episode in the proximal esophageal sites, with a near negligible total acid exposure in the most proximal electrode. In Group II subjects, however, comparison of recumbent recordings from distal, middle, and proximal esophagus indicates that the proximal esophagus is highly exposed to acid reflux and that the decrease in acid exposure from distal to proximal esophagus in reflux patients is not proportionally as great as that of Group I. The data suggest that in the recumbent position, the ability of the subjects with abnormal reflux scores to protect the upper esophagus is less than that of subjects with normal amounts of distal esophageal acid exposure.

Anastomotic ulceration: A late complication of ileocolonic anastomosis

Symptomatic ulceration developed at a previous ileocolonic anastomosis in six children. In the neonatal period all patients had had necrotizing enterocolitis that required resection of the terminal ileum, ileocecal valve, and proximal portion of the colon. Gross or occult rectal bleeding, with or without pain and diarrhea, began 5 1/2 years after successful resection and ileocolonic anastomosis. The cause of the ulcers is unknown. They appear inflammatory, both grossly and histologically, but have been uniformly unresponsive to antiinflammatory medications, antibiotics, and immunosuppressive medication. Surgical revision of the anastomosis and ulcer resection in five patients have resulted in rapid recurrence in four. Thirteen similar cases have been reported in the English-language literature. We conclude that ulceration is a long-term complication of neonatal resection of the terminal ileum and ascending colon with ileocolonic anastomosis.

Gastroesophageal reflux with drifting onset in infants : a phenomenon unique to sleep

We have characterized the gastroesophageal reflux (GER) episodes which occurred during sleep in 28 infants with pathologic gastroesophageal reflux and 10 symptomatic age-matched controls without gastroesophageal reflux. We describe three kinds of episodes during the sleeping period-awake episodes which occur completely during electroencephalogram (EEG)-defined wakefulness associated with clinical evidence of the waking state (62 episodes), episodes occurring during EEG-defined sleep which have a rapid drop in pH at their onset (119 episodes), and episodes occurring during EEG-defined sleep in which the esophageal pH drifts down slowly over a period up to 30 min (113 episodes). Only 9 of the 10 control subjects experienced any reflux episodes during monitoring. The total number of episodes of reflux in controls (34) was less than the total number in reflux subjects (260). Controls did, however, experience all three types of reflux episode. Awake episodes all had a rapid drop in pH at their onset and were characterized by a short acid clearance time (2.0 +/- 0.3 min in reflux patients and 1.0 +/- 0.2 min in controls). The sleep episodes with rapid onset had longer mean acid clearance time than the awake episodes, significantly so in GER subjects (20.1 +/- 6.8 min in reflux subjects and 2.6 + 1.3 min in controls). Body movement was noted at the onset of 93.4% of rapid-onset sleep episodes in reflux subjects and 88.9% in controls. Body movement was also common at the termination of rapid-onset sleep episodes (77.8% of rapid-onset episodes in reflux subjects and 80.0% in controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Early effects of bethanechol on the esophageal motor function of infants with gastroesophageal reflux.

Summary Lower esophageal sphincter (LES) pressure, as well as esophageal peristaltic amplitude, duration, and velocity were measured in 16 infants with gastroesophageal reflux before administration of subcutaneous bethanechol, and at 10, 20, and 30 min after. Seven infants received 0.1 mg/kg, and 9 received 0.2 mg/kg. Significant increases in LES pressure occurred at both doses and lasted for 20 min. The amplitude and duration of peristaltic contractions were increased only after the larger bethanechol dose, and the increases were of greater magnitude in the distal esophagus than in the middle esophagus. The velocity of peristalsis decreased significantly in both the lower and middle esophagus, but only after the larger dose of bethanechol. Bethanechol had no effect on any motor function of the upper third of the esophagus. The changes in esophageal peristalsis produced by bethanechol may improve the efficiency of distal esophageal acid clearance and thus may be responsible in part for the therapeutic effect of bethanechol in infants with gastroesophageal reflux.