Eric Gibson

Sublingual Buprenorphine for Treatment of Neonatal Abstinence Syndrome: A Randomized Trial

OBJECTIVE. In utero exposure to drugs of abuse can lead to neonatal abstinence syndrome, a condition that is associated with prolonged hospitalization. Buprenorphine is a partial μ-opioid agonist used for treatment of adult detoxification and maintenance but has never been administered to neonates with opioid abstinence syndrome. The primary objective of this study was to demonstrate the feasibility and, to the extent possible in this size of study, the safety of sublingual buprenorphine in the treatment of neonatal abstinence syndrome. Secondary goals were to evaluate efficacy relative to standard therapy and to characterize buprenorphine pharmacokinetics when sublingually administered. METHODS. We conducted a randomized, open-label, active-control study of sublingual buprenorphine for the treatment of opiate withdrawal. Thirteen term infants were allocated to receive sublingual buprenorphine 13.2 to 39.0 μg/kg per day administered in 3 divided doses and 13 to receive standard-of-care oral neonatal opium solution. Dose decisions were made by using a modified Finnegan scoring system. RESULTS. Sublingual buprenorphine was largely effective in controlling neonatal abstinence syndrome. Greater than 98% of plasma concentrations ranged from undetectable to ∼0.60 ng/mL, which is less than needed to control abstinence symptoms in adults. The ratio of buprenorphine to norbuprenorphine was larger than that seen in adults, suggesting a relative impairment of N-dealkylation. Three infants who received buprenorphine and 1 infant who received standard of care reached protocol-specified maximum doses and required adjuvant therapy with phenobarbital. The mean length of treatment for those in the neonatal-opium-solution group was 32 compared with 22 days for the buprenorphine group. The mean length of stay for the neonatal-opium-solution group was 38 days compared with 27 days for those in the buprenorphine group. Treatment with buprenorphine was well tolerated. CONCLUSIONS. Buprenorphine administered via the sublingual route is feasible and apparently safe and may represent a novel treatment for neonatal abstinence syndrome.

Revised dose schema of sublingual buprenorphine in the treatment of the neonatal opioid abstinence syndrome.

AIMS More than half of infants exposed to opioids in utero develop neonatal abstinence syndrome (NAS) of severity to require pharmacological therapy. Current treatments are associated with prolonged hospitalization. We sought to optimize the dose of sublingual buprenorphine in the treatment of NAS. DESIGN Randomized, Phase 1, open-label, active-control clinical trial comparing sublingual buprenorphine to oral morphine. SETTING Large, urban, tertiary care hospital. PARTICIPANTS Twenty-four term infants requiring pharmacological treatment for NAS. MEASUREMENTS Outcomes were neonatal safety, length of treatment and length of hospitalization. FINDINGS Sublingual buprenorphine was safe and effective. Infants treated with buprenorphine had a 23-day length of treatment compared to 38 days for those treated with morphine (P = 0.01), representing a 40% reduction. Length of hospital stay in the buprenorphine group was reduced 24%, from 42 to 32 days (P = 0.05). CONCLUSIONS Sublingual buprenorphine was safe in NAS, with a substantial efficacy advantage over standard of care therapy with oral morphine.

Infant Sleep Position Practices 2 Years Into the “Back to Sleep” Campaign

Since the 1992 American Academy of Pediatrics (AAP) recommendation to put babies to sleep in the nonprone position and the subsequent 1994 “Back to Sleep” campaign, the U.S. rate of sudden infant death syndrome (SIDS) has decreased more than 40%. This study reports sleep position practices in the greater Philadelphia area during 1996 and 1997. Four hundred and ten parents of infants 6 months of age or less answered a questionnaire by interview in Philadelphia clinics and private pediatric offikes from December 1995 through February 1997. Sleep position practices and other SIDS risk factors were measured among demographic groups and compared with reported rates in a similar population from 1993 and 1994. Data were analyzed by Chi square after analysis of correlation coefficients. Significance is reported at p<O.05. Seventy-two percent of all infants surveyed slept nonprone (NP) compared to 31.8% in 1993 and 59.1% in 1994. The population was 61% African-American (AA), 62% clinic patients. The breast feeding rate was 31%, maternal smoking 17%, and cosleeping 46%. AA infants (67% vs. 82%), infants receiving care at a clinic (66% vs. 84%), and infants >3 months old (65% vs. 76%) are less likely to be placed nonprone. Most parents who place infants on their back report it was recommended by a medical professional (56%). The majority of those placing infants prone do so because their infant is more comfortable or sleeps better (65%), although 73% said their physician/nurse discussed sleep position with them. Nonprone sleeping continues to increase since the initiation of the “Back to Sleep” campaign. Disparity between some demographic groups persists. An excessive number of African-American families and clinic families still choose a prone sleep position. Many who do so cite increased infant comfort, despite knowledge of the AAP recommendation.

Earlier Discharge of Infants from Neonatal Intensive Care Units: A Pilot Program of Specialized Case Management and Home Care

A multidisciplinary approach using a neonatology independent physicians association, affiliated hospitals, a pediatric home care company, and a health maintenance organization was designed to promote earlier safe discharge of infants from intensive care. This pilot project involved 43 infants who received case management and early discharge home with home oxygen, monitoring, intravenous antibiotics, gavage feedings, phototherapy, or nutritional management for poor weight gain. A staff neonatologist remained the primary physician until the patient would have been discharged according to standard criteria. Two patients had unscheduled readmissions and all infants survived. This approach resulted in an estimated savings of 456 hospital days and

Sudden infant death syndrome rates subsequent to the American Academy of Pediatrics supine sleep position.

329,982; 89% of parents rated the care as good to excellent, and 83% were satisfied with the program and outcome. This study suggests that a prospectively designed program can be designed to promote safe earlier discharge of infants in intensive care.

Documented Home Apnea Monitoring: Effect on Compliance, Duration of Monitoring, and Validation of Alarm Reporting

OBJECTIVES In April 1992, the American Academy of Pediatrics (AAP) recommended that healthy infants be positioned for sleep on their side or back to reduce the risk of Sudden Infant Death Syndrome (SIDS). The authors hypothesized three different forms of the intervention to examine the impact of the recommendation according to theory such as technology diffusion. Seasonality was included in the models to control its effect when testing. METHODS Box and Tiao time-series intervention methodology was used to examine the effect of the AAP recommendation on SIDS rates. Sudden Infant Death Syndrome mortality data from Philadelphia and Chicago were examined separately for white and nonwhite populations over 32 quarters. RESULTS Overall SIDS rates dropped significantly according to an abrupt effect from the intervention. However, the effect appeared to be gradually declining in Philadelphia but permanent in Chicago. In Philadelphia, a decline of 62.3% was estimated in whites in the first quarter after the intervention but decreased to only 5% in the last quarter of 1994. A decline of 35.8% was estimated in nonwhites in the first quarter after the intervention but decreased to only 9.4% in the last quarter of 1994. An abrupt and permanent decrease of 26.7% and 16.5% was found in Chicago for whites and nonwhites, respectively. CONCLUSIONS Evidence of an abrupt adoption of the recommendation can be explained by the authority innovation decision made by the AAP. Some evidence was found that the effect is temporary, perhaps because physicians are reversing earlier decisions. The demonstrated methodology provides a powerful way to test naturally occurring interventions from quasiexperimental designs to test the impact of policy guidelines.

Pseudoreflux Syndrome-Increased Periodic Breathing During the Neonatal Period Presenting as Feeding-Related Difficulties

The objectives of this study were to: (1) measure patient compliance with monitoring, (2) validate parental reports of alarms at home, (3) examine monitoring duration, and (4) compare documented monitor records with the traditional pneumogram to evaluate patients for monitor discontinuation. During the 1-year period fromJanuary through December, 1992, 114 infants were followed up with documented monitoring. Simultaneously, 113 infants were followed up with conventional monitors. Infants were premature, or victims of apparent life-threatening episodes (ALTE), or siblings of SIDS victims. Monitors recorded all episodes of apnea greater than 15 seconds and bradycardia loss than 80 beats per minute. All families were contacted biweekly by telephone. Downloads were performed at regular intervals. Monitor downloads were compared with simultaneous pneumograms to assess the accuracy of a long-term, intermittent event-recording system versus short-term (6-to 12-hour) continuous recording. All families were highly compliant with the use of home monitoring. Although Caucasian families used the monitors more often than non-Caucasian families, all groups used the monitor >75% of the time. True episodes were verified in 38% of patients by monitor downloads. Only 7.4% of all recorded events were true events. Of the real events, 51.2% were apneas of 16-20 seconds. No significant differences were found in overall duration of monitoring between documented and nondocumented monitors. In the premature infants, the duration of monitoring was significantly reduced in those infants found to have no true episodes over those with real events at home. Readmission for ALTE was reduced in infants with documented monitors. Premature infants without events were monitored an average of 24 fewer days (P=0.03). Computerized monitor downloads were found to be equally, if not more, sensitive than pneumograms in evaluating infants for monitor discontinuation. Documented monitoring offers a viable alternative to traditional monitoring and pneumograms in assisting clinicians and families in evaluating their infants progress. By accurately assessing compliance, distinguishing true from false alarms, and decreasing the need for pneumograms, these devices provide valuable information to clinicians and families.

Live births of infants less than 23 weeks gestation disproportionately affect infant mortality rates in the United States

Sixteen infants who presented with symptoms suggestive of gastroesophageal reflux (GER)-associated apnea were evaluated at the Breathing Disorder Center of the Childrens Hospital of Philadelphia. These neonates had a history of occasional emesis and an apparent life-threatening event (ALTE) that occurred while awake which was similar to the presentation of a group of infants previously described. Evaluation of the present group of infants however, revealed increased periodic breathing (12.1 ±1.8 SEM% of total sleep time) as opposed to the obstructive apnea that was typically seen with GER. Pathologic gastroesophageal reflux could not be diagnosed in relationship to apneic events. Infants who present during the first month of life with symptoms suggestive of GER-associated apnea should have careful evaluation of reflux and respiratory patterns to confirm the correct diagnosis. Because of the similarities of these infants to the GER group, we have called their disorder pseudoreflux.

The Incidence of Apnea after Discharge in Infants Less Than 34 Weeks Gestation with Normal Pre-Discharge Pneumocardiograms

Objective: The aim of the study was to determine if states with high infant mortality rates (IMR) have more live births of infants < 23 weeks gestation than states with low IMR, and to determine if there are racial differences in births < 23 weeks in low and high IMR states. Study Design: Data were assessed using United States linked birth and death certificate data from 1997-2000. Ten states with the highest IMR over the 4-year study period were compared to 10 states with the lowest IMR. Statistical analysis was carried out by logistic regression. Results: After controlling for potential confounders, the odds of death from a birth < 23 weeks gestation were significantly higher in the states with the highest overall IMR. IMR was adjusted by removing live births < 23 weeks. African American infants < 23 weeks in high IMR states contributed to a greater percentage of IMR (25%) compared to African American infants in low IMR states (20%), or Caucasian infants in high IMR (15%), or low IMR (13%) states. Conclusions: States with high IMR are more likely to have live births of infants < 23 weeks gestation, compared to those states with low IMR. The contribution to the IMR from births < 23 weeks in high IMR states is disproportionately from African American infants.

Screening Documented Event Monitors in Healthy Premature Infants for Pathologic Apnea and Bradycardia

The Incidence of Apnea after Discharge in Infants Less Than 34 Weeks Gestation with Normal Pre-Discharge Pneumocardiograms