Meconium aspiration syndrome in infants of HIV-positive women: a case-control study.

OBJECTIVE: Our aim was to determine whether maternal HIV infection in the current era is associated with an increased incidence of meconium aspiration syndrome (MAS) in their infants. METHODS: Infants born to 149 HIV-positive women at our hospital over a 5-year period were compared with infants born to HIV-negative women in a retrospective case-control study. Charts of all 298 patients included in the study were reviewed for maternal and infant demographics, HIV treatment, vertical transmission and untoward events at delivery or during the hospital course. RESULTS: When compared with HIV-negative women, a greater proportion of HIV-positive women had meconium-stained amniotic fluid (MSAF), 33% vs. 13%, P<0.001; and thick MSAF, 17% vs. 5%, P<0.001, respectively. Seven of 298 infants were admitted to the neonatal intensive care unit for MAS; all seven were born to HIV-positive women (P=0.015). Although in utero exposure to illicit drugs is a reported risk factor for meconium staining of the amniotic fluid and such drug exposure was more common among our HIV-positive sample, controlling for this and other possible covariates did not greatly reduce the association of HIV status with meconium-related complications of delivery. CONCLUSIONS: Infants born to HIV-positive women had significantly more MSAF and MAS than infants born to non-infected women. It is unclear whether this association results from maternal HIV infection itself or from anti-retroviral therapy. Maternal and infant care providers should be prepared for this complication when attending to the deliveries of HIV-positive women.

Comparison of two gentamicin dosing schedules in very low birth weight infants.

BACKGROUND: Several dosing schedules for gentamicin have been recommended for very low birth weight infants during the early neonatal period. We conducted a prospective, randomized, controlled trial to compare efficacy and pharmacokinetics of two dosing schedules in preterm neonates. METHODS: Fifty-eight very low birth weight infants (600 to 1500 g), prescribed gentamicin for treatment of suspected sepsis during the first week after birth, were randomized to receive either the new dosing schedule [every 48 h (q48h)] or the existing dosing schedule [every 24 h (q24h)]. Infants in the "q48h" group received gentamicin at 5.0 or 4.5 mg/kg/dose q48h depending on weight group and infants in the "q24h" group received 2.5 or 3.0 mg/kg/dose q24h. Peak and trough serum gentamicin concentrations were monitored. RESULTS: Peak serum gentamicin concentrations after the first dose were significantly higher in the q48h infants than in q24h infants (8.19 +/- 1.3 vs. 6.04 +/- 2.2, P = 0.00001). Ninety percent of all peak serum gentamicin concentrations in the q48h group were in a higher therapeutic range of 6 to 12 microg/ml as compared with 55% of q24h (P = 0.0005). None of the q48h infants had subtherapeutic serum gentamicin concentrations immediately after administration of the first dose as compared with 36% of q24h infants (P < 0.005). Eighteen percent of q24h infants continued to have peak serum gentamicin concentrations in subtherapeutic range even after the third dose at 48 h. Trough serum gentamicin concentrations were significantly lower in q48h infants than in q24h infants. However, 9 of 30 (30%) q48h infants had trough serum gentamicin concentrations of < or = 0.5 microg/ml before the dose at 48 h and 4 of the 9 had serum gentamicin concentrations of <1 microg/ml at 24 h after the first dose. CONCLUSIONS: The q48h dosing schedule of gentamicin given to very low birth weight infants during the first week after birth achieved therapeutic serum gentamicin concentrations and potentially higher peak to MIC ratios for microorganisms in all infants. However, nearly one-third of the infants had extremely low serum gentamicin concentrations before the next dose. A dosing interval of 36 h might be optimal for bactericidal activity and avoid bacterial growth during prolonged periods of extremely low serum gentamicin concentrations; this dosing interval warrants study.

Comparison of once-daily versus twice-daily gentamicin dosing regimens in infants > or = 2500 g.

OBJECTIVE: There is no uniformity in the current recommendations of dosing regimen of gentamicin for neonates. We conducted a prospective, randomized, controlled trial to compare a once-daily dosing regimen to the twice-daily dosing regimen for neonates > or = 2500 g during the first 7 days after birth. STUDY DESIGN: Infants > or = 2500 g admitted to the Neonatal Intensive Care Unit and prescribed gentamicin for suspected bacterial infection were randomized to receive either 4 mg/kg every 24 hours, study group (n=20), or a standard regimen of 2.5 mg/kg every 12 hours, control group (n=21). Serum gentamicin concentrations (SGCs) were followed and gentamicin pharmacokinetics calculated on all infants. RESULTS: Peak SGC 30 minutes after the first dose was 8.2+/-1.7 microg/ml in the study group, compared to 6.4+/-1.5 microg/ml in the control group (p=0.001). Ninety-five percent of study group infants, compared to 81% of the control group, had peak SGCs in therapeutic range after the first dose. Peak SGC at 48 hours (steady state) was 8.9+/-1.5 in the study group and 6.8+/-1.1 in the control group (p=0.0001). On further analysis, a significantly higher percentage of infants in the study group, compared to the control group, had peak SGCs in higher therapeutic ranges of 6 to 12 microg/ml as well as 8 to 12 microg/ml. None of the study infants, compared to six control infants, had trough SGCs > or = 2 microg/ml at steady state. Thus, none of the study group infants, versus six of the control group infants, needed a dosing adjustment at 48 hours (p=0.02, Fisher's exact test). CONCLUSION: We found that 4 mg/kg gentamicin given every 24 hours achieved significantly higher peak SGCs and safe trough concentrations in all infants, compared to the twice-daily regimen of 2.5 mg/kg. We suggest that SGCs may not need to be followed in term infants prescribed a short course of this once-daily regimen for suspected early-onset sepsis if renal functions are normal.

Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study.

OBJECTIVE: Budesonide is an inhaled steroid with a strong topical effect but with minimal systemic effects; it has been effectively delivered to animal lungs using surfactant as a vehicle. The purposes of this study were to determine whether early intratracheal instillation of budesonide using surfactant as a vehicle would improve pulmonary status, reduce mortality, and reduce chronic lung disease morbidity. PATIENTS AND METHODS: We conducted a prospective, randomized blind trial in 116 very low birth weight infants (< 1500 g) who had severe radiographic respiratory distress syndrome and required mechanical ventilation with fraction of inspired oxygen > or = 0.6 shortly after birth: 60 were in the treated group (intratracheal instillation of a mixture of 0.25 mg/kg of budesonide and 100.00 mg/kg of survanta, every 8 hours) and 56 were in the control group (100 mg/kg of survanta only, every 8 hours). The end point assessment was the number of infants who would die or develop chronic lung disease at 36 weeks' postconceptional age. RESULTS: Infants in the treatment group required significantly lower mean airway pressure on day 1 and day 3 and had significantly lower oxygen index and PCO(2) during the first 3 days than infants in the control group. More infants were extubated in the treatment group than controls at 1 and 2 weeks. The combined outcome of deaths or chronic lung disease was significantly lower in the treatment group than in the control group (19 of 60 vs 34 of 56). No clinically significant adverse effects were observed during the study. CONCLUSIONS: This pilot study indicated that early postnatal intratracheal instillation of budesonide using surfactant as vehicle significantly improved the combined outcome of death or chronic lung disease in small premature infants without causing immediate adverse effects. The results are encouraging, and a large sample multicenter trial is warranted.

Palivizumab use in very premature infants in the neonatal intensive care unit.

OBJECTIVE: The purpose of this study was to determine the ability of young hospitalized premature (born < or =30 weeks' gestational age) infants to achieve serum levels of palivizumab that are protective against RSV infection. METHODS: Palivizumab, 15 mg/kg per dose intramuscularly, was administered every 28 days to stable premature infants who were hospitalized in the neonatal intensive care unit starting at 1 month of postnatal life. Palivizumab concentrations were assayed in serum samples that were drawn from infants who remained in the hospital at 14 days (midpoint concentration) and at 28 days (trough concentration) after each dose was administered. RESULTS: The gestational age of the 24 infants who were enrolled was 27.5 +/- 1.8 weeks (mean +/- standard deviation), and birth weight was 928 +/- 159 g. Midpoint palivizumab concentrations in the 24 infants after the first dose were 45.6 +/- 13.0 microg/mL; 71% (17 of 24) of the infants maintained optimal palivizumab concentrations (> or =40 microg/mL). The concentrations dropped subsequently; trough concentrations just before the second dose were 32.2 +/- 10.5 microg/mL, and only 23% (5 of 22) of the infants had concentrations in the optimal range. Sixteen infants were given 2 doses and 6 were given three doses of palivizumab while in the neonatal intensive care unit. Midpoint concentrations after the second dose were significantly higher than those after the first dose. Likewise, trough concentrations before the third dose were 51.9 +/- 7.8 microg/mL and higher than those before the second dose; the concentrations were >40 microg/ml in all 6 infants tested. CONCLUSIONS: Very premature infants had sustained optimal protective serum concentrations only after the second dose of palivizumab; 77% of infants tested had trough concentrations <40 microg/mL before the second dose. Additional studies are needed to establish the optimal timing of the initial dose and optimal dosing interval of palivizumab in this most vulnerable population.