Cue-based oral feeding clinical pathway results in earlier attainment of full oral feeding in premature infants.

OBJECTIVE: To study whether a cue-based clinical pathway for oral feeding initiation and advancement of premature infants would result in earlier achievement of full oral feeding. STUDY DESIGN: Age of achievement of full oral intake was compared for two groups of preterm infants; a prospective study group vs historic cohort controls. Study infants had oral feedings managed by nurses using a clinical pathway that relied on infant behavioral readiness signs to initiate and advance oral feedings. Controls had oral feedings managed by physician orders. RESULT: Fifty-one infants (n=28 study and n=23 control) were studied. Gender distribution, gestational age, birth weight and ventilator days were not different between groups. Study infants reached full oral feedings 6 days earlier than controls (36+/-1 3/7 weeks of postmenstrual age (PMA) vs 36 6/7+/-1 4/7 weeks of PMA, P=0.02). CONCLUSION: The cue-based clinical pathway for oral feeding initiation and advancement of premature infants resulted in earlier achievement of full oral feeding.

D-Penicillamine administration and the incidence of retinopathy of prematurity.

OBJECTIVE: We compared the development of retinopathy of prematurity (ROP) among 49 preterm neonates:; 15 who were treated during the first 2 weeks of life with D-penicillamine and 34 who were not. METHODS: During a 15-month period beginning 1 March, 2005, 15 preterm neonates <1000 g birth weight or < or =29 weeks gestation enterally received a 14-day course of D-penicillamine, and 34 did not, in an open-label non-randomized trial. We compared the outcomes of developing 'ROP any stage' and 'ROP requiring surgery' in the recipients vs the non-recipients. Potential toxicities of the D-penicillamine were examined by comparing specific laboratory tests, growth velocities, transfusion requirements, discharge hemoglobin concentrations and supplemental O(2) at discharge. RESULTS: The 34 non-treated and the 15 D-penicillamine treated patients were of similar gestational age (26.5+/-1.8 vs 26.6+/-2.2 weeks, mean+/-s.d.) and birth weight (887+/-222 vs 849+/-187 g). Four of the 34 non-recipients died. Eighteen of the 30 survivors (60%) developed ROP and seven of the 30 (23%) had ROP surgery. One of the 15 D-penicillamine recipients died. Three of the 14 survivors (21%) developed ROP (P=0.01 vs non-recipients) and all three had ROP laser surgery. No increase in elevated creatinine, direct or indirect bilirubin, thrombocytopenia or neutropenia was apparent in those treated with D-penicillamine. The D-penicillamine recipients did not receive more transfusions and did not have lower hemoglobin concentrations at discharge. They did not have lower velocities of weight gain at 14, 28 and 56 days, and were not discharged on supplemental O(2) at a rate exceeding that of the non-recipients. CONCLUSIONS: In this non-randomized, single-centered comparison analysis, a 14-day course of D-penicillamine resulted in no apparent short-term toxicity. The treatment was associated with elimination of Stage I and Stage II ROP, decreasing the overall odds of developing ROP from 60 to 21%. However, this approach did not reduce the odds of ROP surgery. Perhaps higher doses of D-penicillamine or longer treatment periods or other prophylactic approaches will be required to reduce ROP surgery among the most immature neonates.

Treating feeding intolerance with an enteral solution patterned after human amniotic fluid: a randomized, controlled, masked trial.

OBJECTIVE: Feeding intolerance is a common problem in the neonatal intensive care unit (NICU) and some cases might be causally related to atrophic changes in the small bowel mucosa. We speculated that for such patients, feeding tolerance might improve after oral administration of enterocyte growth factors in a sterile, isotonic solution patterned after amniotic fluid. STUDY DESIGN: Twenty neonates meeting criteria for feeding intolerance were eligible for this trial. They were randomized to either Group 1 (test solution) or Group 2 (control). Group 1 received 2.5 ml of test solution/kg every 3 h by oral-gastric or nasal-gastric (OG/NG) tube. This was begun when the patient was NPO because of feeding intolerance and continued until 80 ml/k/day of milk feedings were tolerated, or for a maximum of 7 days. Group 2 received a sham OG/NG administration every 3 h, until 80 ml/k/day of milk feedings were tolerated, or for a maximum of 7 days. Only the bedside nurse and the NICU pharmacist were aware which patients received the test solution and which received the sham administrations. The volumes of milk feedings were increased by order of the attending neonatologist and nurse practitioner. The study outcome was enteral calories/kg/day during and for 7 days after the cessation of the treatments. RESULTS: Eleven patients were randomized to receive the test solution and nine to receive sham administrations. At study entry, the two groups were not different in gestational age, postnatal age, signs of feeding intolerance or cal/k/day taken enterally during the previous 3 days. The study doses were given for an average of just under 6 days (range, 2 to 7 days). During the week following the administrations, the test solution recipients trended toward more enteral calories. Specifically, they had an increase averaging 78+/-20.8 cal/k/day more than before the study, whereas the sham recipients had an increase averaging 55.9+/-33 cal/k/day more than before the study (P=0.05 for a one-sided test and P=0.10 for a two-sided test). The test solution recipients also had a trend toward fewer formula changes than did the sham recipients (P=0.10). In this small, randomized, controlled, masked trial, the administration of a sterile, non-caloric, growth factor containing solution patterned after human amniotic fluid was associated with trends that we interpret as reflecting better tolerance of milk feedings. On this basis, we suggest that a phase III efficacy trial should be accomplished, using the present data for sample size calculations.

A pilot trial testing the feasibility of administering D-penicillamine to extremely low birth weight neonates.

OBJECTIVE: We enterally administered a 14-day course of 3-mercapto-D-valine (D-penicillamine) to five extremely low birth weight (ELBW) neonates, as a step toward assessing this therapy as a means of reducing the incidence or severity of retinopathy of prematurity (ROP). METHODS: The study drug (100 mg/ml) was given by nasogastric tube at a dose of 100 mg/k every 8 h for three days, and then 50 mg/k once per day for 11 additional days. Logbooks were maintained by the bedside nurses to record signs of possible immediate intolerance. Laboratory tests assessed hepatic, renal, and hematologic toxicity. ROP was scored according to the ICROP guidelines. Comparisons were with a cohort of 139 consecutive recent neonates of the same birth weight and gestational age range. RESULTS: Five neonates were enrolled in the study, and all received the full course of study drug as planned. Signs of immediate intolerance of the study drug were not observed in any. The study patients did not have a higher incidence, than that of the cohort group, in creatinine elevation, thrombocytopenia, neutropenia, hyperbilirubinemia, or abnormal liver function test. Four of the five had no ROP and one developed transient stage 1, compared with a 54% occurrence of ROP in the cohort. CONCLUSIONS: It is feasible to enterally administer a 14-day course of 3-mercapto-D-valine to ELBW neonates and the suspension appears to be well tolerated. These results suggest that phase II safety and preliminary efficacy trials can be undertaken.

Testing for fetal exposure to illicit drugs using umbilical cord tissue vs meconium.

OBJECTIVE: We assessed the agreement of testing for fetal exposure to illicit drugs contrasting paired specimens of meconium vs umbilical cord tissue. METHODS: We obtained paired samples of meconium and umbilical cord tissue from 118 pregnancies with high suspicion of illicit drug use by the mothers. Each specimen was tested for amphetamines, opiates, cocaine, cannabinoids, and phencyclidine using drug class-specific immunoassays. RESULTS: The agreement of drug screening results between cord and meconium was above 90% for all drugs tested. Meconium identified 21 cases as positive for amphetamines. The paired cord identified 20 of these, and in addition identified three other positives that the meconium labeled as negative. Gas chromatography-mass spectrometry confirmed these three cord samples as methamphetamine positive. Meconium identified 97 samples that were negative for amphetamines, while the cord identified 94 of these as negative but three as positive. Agreement of cord with meconium for amphetamines was 96.6%. The concordance for opiates was 94.9%, for cocaine was 99.2%, and for cannabinoids was 90.7%. CONCLUSIONS: Umbilical cord tissue performs as well as meconium in assessing fetal drug exposure to amphetamines, opiates, cocaine, and cannabinoids. Results of studies using the cord may have a more rapid return to the clinician, because waiting for meconium to be passed sometimes requires several days. Moreover, in some cases the meconium is passed in utero making collection impossible, whereas cord should always be available for drug testing.

High rates of multiple antibiotic resistance in Streptococcus pneumoniae from healthy children living in isolated rural communities: association with cephalosporin use and intrafamilial transmission.

OBJECTIVE: Streptococcus pneumoniae is one of the most clinically significant pathogens with emerging antibiotic resistance. We performed a surveillance study in isolated rural populations of healthy children to estimate the prevalence of pneumococcal resistance and to contrast factors that predict pneumococcal carriage with those that specifically predict resistant pneumococcal carriage. METHODS: The study was conducted in 1998 in 2 rural communities in Utah. Families were recruited directly for participation through community canvassing. Surveillance nasopharyngeal cultures were obtained from children who were younger than 8 years. Antibiotic usage and information on other potential risk factors were obtained from questionnaires and local pharmacy records. Resistance was determined by testing isolates for susceptibility to penicillin, cefaclor, trimethoprim-sulfamethoxazole, erythromycin, ceftriaxone, and trovafloxacin. Selected resistant isolates were characterized further by serotyping, pulsed field gel electrophoresis, and Southern blot with DNA probes specific for the pneumococcal lytA gene and for antibiotic resistance genes. RESULTS: In April 1998, surveillance nasopharyngeal cultures were obtained from 368 children aged

Challenging generally accepted contraindications to vaginal hysterectomy.

OBJECTIVE: A number of preexisting clinical conditions are generally accepted as contraindications to vaginal hysterectomy. The purpose of this study was to evaluate the validity of this concept. STUDY DESIGN: The study vaginal hysterectomy group consisted of 250 consecutive patients undergoing vaginal hysterectomy. These patients (1) had a large uterus (>180 g), (2) either were nulliparous or had no previous vaginal delivery, or (3) had a previous cesarean delivery or pelvic laparotomy. Three control groups used for comparison underwent (1) laparoscopically assisted vaginal hysterectomy, (2) vaginal hysterectomy, or (3) abdominal hysterectomy. The records for all patients were analyzed for age, weight, parity, primary diagnosis, uterine size, operative time, blood loss, analgesia, hospital stay, resumption of diet, incidence of morcellation, and surgical complications. Sample size calculations were based on previous studies of complications associated with vaginal hysterectomy (alpha =.05; beta =.20). RESULTS: Hysterectomy was successfully completed by the intended vaginal route in all study patients. Major and minor complications (3.2%) were significantly less (P <.001) than in the other groups as follows: vaginal hysterectomy, 10.4%; laparoscopically assisted vaginal hysterectomy, 11.6%; and abdominal hysterectomy, 13.6%. The decrease in hematocrit was 5.7% in the study vaginal hysterectomy group compared with 6.2% for vaginal hysterectomy, 6.5% for abdominal hysterectomy (P =.009), and 6.6% for laparoscopically assisted vaginal hysterectomy (P =.002). Hospital stay was shorter for the study group (2.1 days) than for vaginal hysterectomy (2.3 days; P <.001) and abdominal hysterectomy (2.7 days; P <.001). Operative time was shorter in the study vaginal hysterectomy group (49 minutes) than with laparoscopically assisted vaginal hysterectomy (76 minutes; P <.001) or abdominal hysterectomy (61 minutes; P <.001), although morcellation was carried out more frequently in the study group (34%) than with vaginal hysterectomy (4%) or laparoscopically assisted vaginal hysterectomy (11%). CONCLUSION: Our data indicate that a large uterus, nulliparity, previous cesarean delivery, and pelvic laparotomy rarely constitute contraindications to vaginal hysterectomy.

Bone mineral status in prepubertal children with cystic fibrosis.

OBJECTIVES: To determine whether osteopenia is evident in prepubertal children with cystic fibrosis (CF) and, if so, whether it is caused by a deficiency in bone formation or increased bone resorption. STUDY DESIGN: With the use of a prospective case control study design, we investigated 11 prepubertal children with CF between the ages of 8 and 12 years old and a non-CF control group matched by weight and sex. Bone density at the radius, ulnar, trochanter, femoral neck, and lumbar spine, biochemical markers of bone metabolism, calcium, vitamin D metabolites, and intact parathyroid hormone were measured in all subjects. Comparisons between the 2 groups were performed with Wilcoxon matched pairs and Fisher exact tests. RESULTS: Intake of total calories, calcium, phosphorus, and vitamin D was significantly greater in the CF group than in the control group. Serum 25(OH)vitamin D levels were significantly lower in the CF group: median 22 ng/mL for the CF group and 39 ng/mL for the control group (P =.02). 1,25(OH)(2) vitamin D levels were borderline or low in 7 subjects in the CF group and 2 members of the control group (P =.08, Fisher exact test). Intact parathyroid hormone levels were higher than the upper limit of normal in 4 subjects of the CF group and 1 member of the control group. Despite these biochemical abnormalities, we found no evidence of bone mineral deficiency in the CF group. CONCLUSIONS: Prepubertal children with CF do not have bone mineral deficit compared with a weight- and sex-matched control group; however, their lower vitamin D levels may portend problems with bone mineralization during adolescence and adulthood.