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Objective: To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18-22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants., Study Design: Evaluation of infants at 18-22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index and the Psychomotor Developmental Index. NDI was defined as moderate or severe cerebral palsy, Mental Developmental Index or Psychomotor Developmental Index <70, blindness, or hearing impairment., Results: Death or NDI at 18-22 months corrected age was similar in the dexamethasone and placebo groups (65% vs 66%, P = .99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50% vs 41%, P = .42 for weight less than 10th percentile); 49% of infants in the placebo group received treatment with corticosteroid compared with 32% in the dexamethasone group (P = .02)., Conclusion: The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: To determine if early developmental intervention (EDI) improves developmental abilities in resuscitated children., Study Design: This was a parallel group, randomized controlled trial of infants unresponsive to stimulation who received bag and mask ventilation as part of their resuscitation at birth and infants who did not require any resuscitation born in rural communities in India, Pakistan, and Zambia. Intervention infants received a parent-implemented EDI delivered with home visits by parent trainers every other week for 3 years starting the first month after birth. Parents in both intervention and control groups received health and safety counseling during home visits on the same schedule. The main outcome measure was the Mental Development Index (MDI) of the Bayley Scales of Infant Development, 2nd edition, assessed at 36 months by evaluators unaware of treatment group and resuscitation history., Results: MDI was higher in the EDI (102.6 ± 9.8) compared with the control resuscitated children (98.0 ± 14.6, 1-sided P = .0202), but there was no difference between groups in the nonresuscitated children (100.1 ± 10.7 vs 97.7 ± 10.4, P = .1392). The Psychomotor Development Index was higher in the EDI group for both the resuscitated (P = .0430) and nonresuscitated children (P = .0164)., Conclusions: This trial of home-based, parent provided EDI in children resuscitated at birth provides evidence of treatment benefits on cognitive and psychomotor outcomes. MDI and Psychomotor Development Index scores of both nonresuscitated and resuscitated infants were within normal range, independent of early intervention., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To determine whether resuscitation of infants who failed to develop effective breathing at birth increases survivors with neurodevelopmental impairment., Study Design: Infants unresponsive to stimulation who received bag and mask ventilation at birth in a resuscitation trial and infants who did not require any resuscitation were randomized to early neurodevelopmental intervention or control groups. Infants were examined by trained neurodevelopmental evaluators masked to both their resuscitation history and intervention group. The 12-month neurodevelopmental outcome data for both resuscitated and non-resuscitated infants randomized to the control groups are reported., Results: The study provided no evidence of a difference between the resuscitated infants (n = 86) and the non-resuscitated infants (n = 115) in the percentage of infants at 12 months with a Mental Developmental Index <85 on the Bayley Scales of Infant Development-II (primary outcome; 18% versus 12%; P = .22) and in other neurodevelopmental outcomes., Conclusions: Most infants who received resuscitation with bag and mask ventilation at birth have 12-month neurodevelopmental outcomes in the reference range. Longer follow-up is needed because of increased risk for neurodevelopmental impairments., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: To determine if selected pro-inflammatory and anti-inflammatory cytokines and/or mediators of inflammation reported to be related to the development of cerebral palsy (CP) predict neurodevelopmental outcome in extremely low birth weight infants., Study Design: Infants with birth weights ≤1000 g (n = 1067) had blood samples collected at birth and on days 3 ± 1, 7 ± 1, 14 ± 3, and 21 ± 3 to examine the association between cytokines and neurodevelopmental outcomes. The analyses were focused on 5 cytokines (interleukin [IL] 1β; IL-8; tumor necrosis factor-α; regulated upon activation, normal T-cell expressed, and secreted (RANTES); and IL-2) reported to be most predictive of CP in term and late preterm infants., Results: IL-8 was higher on days 0-4 and subsequently in infants who developed CP compared with infants who did not develop CP in both unadjusted and adjusted analyses. Other cytokines (IL-12, IL-17, tumor necrosis factor-β, soluble IL rα, macrophage inflammatory protein 1β) were found to be altered on days 0-4 in infants who developed CP., Conclusions: CP in former preterm infants may, in part, have a late perinatal and/or early neonatal inflammatory origin., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objectives: To compare the rates of adverse neurodevelopmental outcome or death at 18 to 22 months among extremely low birth weight (ELBW) infants born to mothers >or=4 0 years to the corresponding rates among infants of younger mothers., Study Design: Prospective evaluation of ELBW infants to quantify the relative risks of maternal age and multiple birth for death or adverse neurodevelopmental outcome., Results: The sample consisted of 14 671 live ELBW births divided into maternal age groups: <20, 20 to 29, 30 to 39, and >or= 40 years. Of infants born to mothers >or= 40 years, 20% were multiples. Mothers >or= 40 years had high rates of obstetric interventions and medical morbidities compared with mothers <40 years. ELBW live births of mothers >or= 40 years were 22% more likely to survive and had a 13% decreased risk of neurodevelopmental impairment or death compared with mothers <20. Multiple birth, however, was associated with a 10% greater risk of neurodevelopmental impairment or death., Conclusion: Although mothers >or= 40 years had high pregnancy-related morbidities, we found no overall increased risk of the composite outcome of death or NDI. Multiple birth, however, was a predictor of all adverse outcomes examined, regardless of maternal age.

Objective: To evaluate the effectiveness of the American Academy of Pediatrics Neonatal Resuscitation Program (NRP) in improving knowledge, skills, and self-efficacy of nurse midwives in low-risk delivery clinics in a developing country., Study Design: We used the content specifications of the NRP material applicable to college-educated nurse midwives working in low-risk clinics in Zambia to develop performance and self-efficacy evaluations focused on principles of resuscitation, initial steps, ventilation, and chest compressions. These evaluations were administered to 127 nurse midwives before and after NRP training and 6-months later., Results: After training, written scores (knowledge evaluation) improved from 57%+/-14% to 80%+/-12% (mean+/-SD; P< .0001); performance scores (skills evaluation) improved the most from 43%+/-21% to 88%+/-9% (P< .0001); self-efficacy scores improved from 74%+/-14% to 90%+/-10% (P< .0001). Written and performance scores decreased significantly 6 months after training, but self-efficacy scores remained high., Conclusions: As conducted, the NRP training improved educational outcomes in college-educated practicing nurse midwives. Pre-training knowledge and skills scores were relatively low despite the advanced formal education and experience of the participants, whereas the self-efficacy scores were high. NRP training has the potential to substantially improve knowledge and skills of neonatal resuscitation.

Objective: To report the neurodevelopmental outcome of infants enrolled in a randomized multicenter trial of early inhaled nitric oxide (iNO) in term and near-term neonates with hypoxic respiratory failure and pulmonary hypertension., Study Design: Neonates born at > or = 34 weeks gestation who required assisted ventilation and had an oxygenation index > or = 15 and < 25 were randomized to an early iNO group or a control group. A comprehensive neurodevelopmental assessment of survivors was performed at age 18 to 24 months., Results: The trial enrolled 299 infants, of which 266 (89%) survived to age 18 to 24 months (136 in the early iNO group and 130 in the control group). Follow-up evaluations were done on 234 (88%) of surviving infants. There were no differences between the 2 groups in the incidence of neurodevelopmental impairment (early iNO, 27%; control, 25%) and hearing impairment (early iNO, 23%; control, 24%). Mental development index scores were similar in the 2 groups; however, psychomotor developmental index scores were significantly higher in the control group (early iNO, 89 +/- 17.7; control, 93.5 +/- 18.4)., Conclusions: Early iNO therapy for hypoxic respiratory failure in term and near-term infants is not associated with an increase in neurodevelopmental impairment or hearing loss at 18 to 24 months postnatal age.

Objective: To compare duration of ventilation to mortality and adverse neurodevelopmental outcomes among extremely low birth weight (ELBW; 501-1000 g) infants., Study Design: Retrospective analysis of prospectively collected data from 5364 infants with a birthweight of 501 to 1000 g born at National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers from 1995 to 1998. The main outcome measures were: survival, duration of mechanical ventilation, and neurodevelopmental outcome., Results: Overall survival was 71%. The median duration of ventilation for survivors was 23 days; 75% were free of mechanical ventilation by 39 days, and 7% were ventilated for > or = 60 days. Of those ventilated for > or = 60 days, 24% survived without impairment. Of those ventilated for > or = 90 days, only 7% survived without impairment. Of those ventilated > or = 120 days, all survivors were impaired., Conclusions: The prognosis for ELBW with protracted ventilation remains grim. The cohort who remain intubated have diminished survival and high rates of impairment. Parents of these infants should be informed of changes in prognosis as the time of ventilation increases.

Objective: To study absolute and interpeak latencies of the auditory brain response in infants exposed to cocaine and/or opiates in utero.Study design The sample included 477 exposed and 554 comparison infants matched for race, sex, and gestational age. Mothers were recruited at 4 urban university-based centers; most were black, receiving public assistance, and had received adequate prenatal care. Exposure was determined by meconium assay and self-report with alcohol, marijuana, and tobacco present in both groups. At 1 month, infants were tested by masked examiners with the auditory brain response., Results: Analyses were conducted for exposed and comparison groups and for level of prenatal cocaine exposure with adjustment for covariates (alcohol, marijuana, tobacco, gestational age at birth, social class, and site). Heavy prenatal cocaine exposure (>/=3 days per week, first trimester) led to an increase in the I-III, I-V, and III-V interpeak latencies and to a shorter latency to peak I. Infants with prenatal opiate exposure showed a longer latency to peak V and a longer III-V interpeak latency., Conclusions: Prenatal cocaine and/or opiate exposure affects neural transmission. Detection of these effects requires a large sample with control for gestational age, other drugs, and level of cocaine use.

Objective: To determine whether minimal ventilation decreases death or bronchopulmonary dysplasia (BPD)., Study Design: Infants with birth weight 501 g to 1000 g and mechanically ventilated before 12 hours were randomly assigned to minimal ventilation (partial pressure of carbon dioxide [PCO(2)] target >52 mm Hg) or routine ventilation (PCO(2) target <48 mm Hg) and a tapered dexamethasone course or saline placebo for 10 days, using a 2 x 2 factorial design. The primary outcome was death or BPD at 36 weeks' postmenstrual age., Results: After enrollment of 220 patients, the trial was halted because of unanticipated nonrespiratory adverse events related to dexamethasone therapy. The relative risk for death or BPD at 36 weeks in the minimal versus routine ventilation groups was 0.93 (95% CI, 0.77-1.12; P =.43). Ventilator support at 36 weeks was 1% in the minimal versus 16% in the routine group (P <.01). Major morbidities and long-term outcome were comparable in both treatment groups., Conclusions: With the sample size studied, minimal ventilation did not reduce the incidence of death or BPD. The reduced ventilator support at 36 weeks in the minimal ventilation group warrants further study of this intervention.

Objective: Ballard scores are commonly used to estimate gestational age (GA). The purpose of this study was to determine the accuracy of the New Ballard Score (NBS) for infants <28 weeks GA by accurate menstrual history and to evaluate NBS as an outcome predictor., Methods: Infants weighing 401 to 1500 g in 12 National Institute of Child Health and Human Development Neonatal Research Network centers had NBS performed before age 48 hours. Accuracy of NBS estimates of GA was assessed for infants with GA determined by accurate menstrual history. In a larger cohort of infants, NBS was included in regression models of the association of NBS and death, poor outcome, and duration of hospital stay., Results: At each week from 22 to 28 weeks GA by accurate menstrual history, NBS estimates exceeded GA by dates by 1.3 to 3.3 weeks, and estimates varied widely (range of widths of 95% CIs for the observations, 6.8 to 11.9 weeks). NBS did not contribute significantly to regression models of death, poor outcome, or duration of hospital stay., Conclusions: Inaccuracies in GA determined by the NBS should be considered when treating extremely premature infants, particularly in decisions to forego or administer intensive care. Refinement of GA scoring systems is needed to optimize clinical benefit.

Objective: Late-onset sepsis (occurring after 3 days of age) is an important problem in very low birth weight (VLBW) infants. To determine the current incidence of late-onset sepsis, risk factors for disease, and the impact of late-onset sepsis on subsequent hospital course, we evaluated a cohort of 7861 VLBW (401 to 1500 gm) neonates admitted to the 12 National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers during a 32-month period (1991 to 1993)., Methods: The NICHD Neonatal Research Network maintains a prospectively collected registry of all VLBW neonates cared for at participating centers. Data from this registry were analyzed retrospectively., Results: Of 6911 infants who survived beyond 3 days, 1696 (25%) had one or more episodes of blood culture-proven sepsis. The vast majority of infection (73%) were caused by gram-positive organisms, with coagulase-negative staphylococci accounting for 55% of all infections. Rate of infection was inversely related to birth weight and gestational age. Complications of prematurity associated with an increased rate of infection included intubation, respiratory distress syndrome, prolonged ventilation, bronchopulmonary dysplasia, patent ductus arteriosus, severe intraventricular hemorrhage, and necrotizing enterocolitis. Among infants with bronchopulmonary dysplasia, those with late-onset sepsis had a significantly longer duration of mechanical ventilation (45 vs 33 days; p <0.01). Late-onset sepsis prolonged hospital stay: the mean number of days in the hospital for VLBW neonates with and without late-onset sepsis was 86 and 61 days, respectively (p <0.001). Even after adjustment for other complications of prematurity, including intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia, infants with late-onset sepsis had a significantly longer hospitalization (p <0.001). Moreover, neonates in whom late-onset sepsis developed were significantly more likely to die than those who were uninfected (17% vs 7%; p <0.000 1), especially if they were infected with gram-negative organisms (40%) or fungi (28%). Deaths attributed to infection increased with increasing chronologic age. Whereas only 4% of deaths in the first 3 days of life were attributed to infection, 45% of deaths after 2 weeks were related to infection., Conclusions: Late-onset sepsis is a frequent and important problem among VLBW preterm infants. Successful strategies to decrease late-onset sepsis should decrease VLBW mortality rates, shorten hospital stay, and reduce costs.

Objective: Early-onset sepsis (occurring within 72 hours of birth) is included in the differential diagnosis of most very low birth weight (VLBW) neonates. To determine the current incidence of early-onset sepsis, risk factors for disease, and the impact of early-onset sepsis on subsequent hospital course, we studied a cohort of 7861 VLBW neonates (401 to 1500 gm) admitted to the 12 National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers during a 32-month period (1991-1993)., Methods: The NICHD Neonatal Research Network maintains a prospectively collected registry on all VLBW neonates born or cared for at participating centers. Data from this registry were analyzed retrospectively., Results: Blood culture-proven early-onset sepsis was uncommon, occurring in only 1.9% of VLBW neonates. Group B streptococcus was the most frequent pathogen associated with early-onset sepsis (31%), followed by Escherichia coli (16%) and Haemophilus influenzae (12%). Decreasing gestational age was associated with increased rates of infection. Antibiotic therapy for suspected sepsis is frequently initiated at birth in VLBW neonates. Almost half of the infants in this cohort were considered to have clinical sepsis and continued to receive antibiotics for 5 or more days, despite a negative blood culture result in 98% of cases. These findings underscore the difficulty of ruling out sepsis in the symptomatic immature neonate and the special concern for culture-negative clinical sepsis in the face of maternal antibiotic use. Neonates with early-onset sepsis were significantly more likely to have subsequent comorbidities, including severe intraventricular hemorrhage, patent ductus arteriosus, and prolonged assisted ventilation. Although 26% of VLBW neonates with early-onset sepsis died, only 4% of the 950 deaths that occurred in the first 72 hours of life were attributed to infection. For those infants discharged alive, early-onset sepsis was associated with a significantly prolonged hospital stay (86 vs 69 days; p <0.02)., Conclusions: Early-onset sepsis remains an important but uncommon problem among VLBW preterm infants. Improved diagnostic strategies are needed to enable the clinician to distinguish between the infected and the uninfected VLBW neonate with symptoms and to target continued antibiotic therapy to those who are truly infected.

Objective: To compare the efficacy of two surfactants, Exosurf Neonatal (Burroughs Wellcome Co.) and Survanta (Ross Laboratories), for the treatment of neonatal respiratory distress syndrome., Design: Multicenter randomized trial., Setting: Eleven tertiary care university neonatal intensive care units participating in the National Institute of Child Health and Human Development Neonatal Research Network., Patients: Newborn infants (n = 617) weighing 501 to 1500 gm with respiratory distress syndrome who were receiving assisted ventilation with 30% oxygen or more within 6 hours of birth were enrolled between January 1991 and January 1992., Interventions: Infants were randomly assigned to receive up to four intratracheal doses of either Exosurf Neonatal (n = 309) or Survanta (n = 308)., Main Outcome Measures: The occurrence of death or bronchopulmonary dysplasia 28 days after birth and the average fraction of inspired oxygen (FIO2) and mean airway pressure (MAP) during the first 72 hours after treatment., Results: Death or bronchopulmonary dysplasia occurred in 67% of the infants in the Exosurf group and 62% of those in the Survanta group (adjusted relative risk, 1.07; 95% confidence interval, 0.96 to 1.20). During the 72 hours after the first surfactant dose, the average FIO2 (+/- SEM) was 0.50 +/- 0.01 for Exosurf and 0.42 +/- 0.01 for Survanta (difference, 0.08; 95% confidence interval, 0.05 to 0.11); the average MAP (+/- SEM) was 7.64 +/- 0.21 cm H2O for Exosurf and 6.93 +/- 0.21 cm H2O for Survanta (difference, 0.71 cm H2O; 95% confidence interval, 0.13 to 1.29 cm H2O). There was no difference between the groups in the incidence of other neonatal morbidities or in the duration of hospitalization, assisted ventilation, or supplemental oxygen administration., Conclusion: We found no difference between treatment groups in the incidence of death or bronchopulmonary dysplasia, although we did observe a difference in the initial response to treatment as measured by FIO2 and MAP.

We studied the occurrence of necrotizing enterocolitis in 2681 very low birth weight infants during an 18-month period to characterize the biodemographic and clinical correlates. Proven necrotizing enterocolitis (Bell stage II and beyond) occurred in 10.1% of study infants; necrotizing enterocolitis was suspected in 17.2% of study infants. Positivity of blood cultures was related to necrotizing enterocolitis staging. The mortality rate increased only for stage III necrotizing enterocolitis (54% died). Logistic regression identified medical center of birth, race, gender, birth weight, maternal hemorrhage, duration of ruptured membranes, and cesarean section as significant risk factors. For one center the odds ratio was 3.7, whereas for another center it was only 0.3. For black boys, the odds ratio was 2.3 relative to nonblack boys; for girls, race did not affect prevalence of necrotizing enterocolitis. Age at onset was related to birth weight and gestational age. Intercenter differences in necrotizing enterocolitis prevalence were related to time required to regain birth weight and other indicators of fluid management. Gram-positive organisms predominated in positive blood cultures for stage I and II necrotizing enterocolitis; enteric bacteria were isolated more frequently in infants with stage III disease. We conclude that necrotizing enterocolitis prevalence varies greatly among centers; this may be related to early clinical practices of neonatal care.

A comparison of the accuracy and practicality of two new latex agglutination tests for the rapid identification of group A beta-hemolytic streptococci directly from throat swabs was performed in a busy pediatric office. The Directigen Group A Strep Test kit had a sensitivity of 84%, specificity 99%, positive predictive value 99%, and negative predictive value 93% when compared with blood agar cultures. The Culturette Brand 10-Minute Group A Strep ID Kit had a sensitivity of 83%, a specificity 99%, positive predictive value 97%, and negative predictive value 93% when compared with blood agar cultures. When cultures with less than 10 colonies of group A beta-hemolytic streptococci per plate were not considered positive, both rapid tests had a sensitivity of 95%. The Culturette Brand test required considerably less time, equipment, supplies, and skill than the Directigen test. Only the Culturette Brand test appeared to be practical for routine use in a pediatrician's office. Further investigations of the accuracy of both of these rapid tests need to be performed before either is accepted as a substitute for the throat culture.

To determine if a single daily dose of cefadroxil would be effective in the treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis, 196 patients with GABHS pharyngitis were randomly assigned to receive either penicillin V 250 mg three times daily or cefadroxil 30 mg/kg once daily, for 10 days. Outcome was measured by the ability to isolate GABHS from the upper respiratory tract 18 to 24 hours after the onset of therapy, the impact on the clinical course, and the bacteriologic treatment failure rate. There was no significant difference in the number of patients in the cefadroxil and penicillin V treatment groups with throat cultures positive for GABHS at the 18 to 24-hour follow-up visit (0% and 2%, respectively), and the clinical responses of the patients in the two treatment groups were similar. Of the 99 patients in the three times daily penicillin V group, six (6%) had strains of GABHS isolated on one of the follow-up cultures that were identical to the strains isolated from their initial throat cultures and were considered to have bacteriologic treatment failures. Of the 96 patients in the once daily cefadroxil group, two (2%) were considered to have bacteriologic treatment failures. A single daily dose of cefadroxil appears to be as effective in the treatment of GABHS pharyngitis in this population as penicillin V given three times daily.

The effects of ductal closure on range-gated pulsed Doppler cerebral blood flow velocity (CBFV) patterns in the internal carotid, anterior cerebral, and middle cerebral arteries were studied in 10 normal term infants (mean birth weight 3302 +/- 294 g (SD) and mean gestational age 39.6 +/- 1.3 weeks). Pulsatility was calculated from flow velocities and used as an estimate of cerebral blood flow (CBF). Ductal closure was associated with a rise in mean blood pressure from 45.0 +/- 4.2 to 51.3 +/- 6.5 mm Hg (P less than 0.05) and a significant decrease in pulsatility in all three vessels (mean = 0.77 +/- 0.07 vs 0.70 +/- 0.05 (P less than 0.02]. Changes in pulsatility were correlated with changes in mean blood pressure (P less than 0.02), providing evidence that systemic blood pressure may influence postnatal cerebral arterial pulsatility indices. We also noted significant differences in the velocity and pulsatility of individual vessels that were independent of blood pressure, suggesting that Doppler flow studies may be useful in describing regional CBF patterns. The temporal association between ductal closure and decreased pulsatility suggests that CBFV patterns reflect ductal shunting in normal term newborn infants. Diastolic runoff and reduced systemic blood pressure in the presence of ductal shunting appear to reduce diastolic flow velocity and increase CBFV pulsatility in normal term infants during the first days of life. Normal mechanisms of cerebral autoregulation compensate for decreased flow with vasodilation; therefore the increased pulsatility associated with ductal shunting may be due to diastolic runoff rather than increased cerebrovascular resistance.

The clinical significance of false-negative results on antigen detection tests for group A beta-hemolytic streptococcal (GABHS) pharyngitis (negative test results and positive culture) has yet to be determined. We recently compared the Culturette Brand Ten-Minute Group A Strep ID Kit with blood agar cultures in 313 patients with pharyngitis, 257 (82%) of whom had positive throat cultures for GABHS. The Culturette Brand test had a sensitivity of 88%, specificity of 96%, a positive predictive value of 99%, and negative predictive value of 64%. More than half of the false-negative Culturette Brand test results occurred in children with less than 10 GABHS colonies on throat culture (1+ culture). When these 1+ cultures were not considered positive, the sensitivity of the Culturette Brand test was 93%. The sensitivity of the Culturette Brand test increased with an increased degree of positivity of the corresponding throat culture. Of the 31 children with false-negative Culturette Brand test results, 14 (45%) had a significant streptococcal antibody response; of the 224 children with true-positive Culturette Brand test results (positive test results and positive culture) from whom serologic data were available, 114 (51%) had a significant streptococcal antibody response. This difference is not statistically significant. These findings suggest that almost half of patients with false-negative results on antigen detection tests for GABHS pharyngitis have true infections (positive culture and antibody rise) and are not merely streptococcal carriers.