Search

BACKGROUND: We determined the role of risk and protective factors on the trajectories of behavior problems associated with high prenatal cocaine exposure (PCE)/polydrug exposure. METHODS: The Maternal Lifestyle Study enrolled 1388 children with or without PCE, assessed through age 15 years. Because most women using cocaine during pregnancy also used other substances, we analyzed for the effects of 4 categories of prenatal drug exposure: high PCE/other drugs (OD), some PCE/OD, OD/no PCE, and no PCE/no OD. Risks and protective factors at individual, family, and community levels that may be associated with behavior outcomes were entered stepwise into latent growth curve models, then replaced by cumulative risk and protective indexes, and finally by a combination of levels of risk and protective indexes. Main outcome measures were the trajectories of externalizing, internalizing, total behavior, and attention problems scores from the Child Behavior Checklist (parent). RESULTS: A total of 1022 (73.6%) children had known outcomes. High PCE/OD significantly predicted externalizing, total, and attention problems when considering the balance between risk and protective indexes. Some PCE/OD predicted externalizing and attention problems. OD/no PCE also predicted behavior outcomes except for internalizing behavior. High level of protective factors was associated with declining trajectories of problem behavior scores over time, independent of drug exposure and risk index scores. CONCLUSIONS: High PCE/OD is a significant risk for behavior problems in adolescence; protective factors may attenuate its detrimental effects. Clinical practice and public health policies should consider enhancing protective factors while minimizing risks to improve outcomes of drug-exposed children.

OBJECTIVE: This study examined the NICU Network Neurobehavioral Scale (NNNS) as a predictor of negative medical and behavioral findings at 1 month to 4.5 years of age. METHODS: The sample included 1248 mother–infant dyads (42% born at RESULTS: Five discrete behavioral profiles were reliably identified; the most extreme negative profile was found in 5.8% of the infants. The profiles showed statistically significant associations with prenatal drug exposure; GA and birth weight; head ultrasound; neurologic and brain disease findings; and abnormal scores on measures of behavior problems, school readiness, and IQ through 4.5 years of age. CONCLUSIONS: The NNNS may be useful to identify infant behavioral needs to be targeted in well-infant pediatric care, as well as for referrals to community-based early intervention services.

OBJECTIVE. We examined the trajectory of childhood behavior problems after prenatal cocaine exposure.METHODS. The Maternal Lifestyle Study, a longitudinal cohort study, enrolled children between 1993 and 1995 at 4 centers. Prenatal cocaine exposure was determined from mothers who admitted use and/or meconium results. Exposed children were matched with a group of nonexposed children within site and by gestational age, gender, race, and ethnicity. The study began at the 1-month corrected age with a total of 1388 children enrolled. A total of 1056 were assessed for internalizing, externalizing, and total behavior problems at ages 3, 5, and 7 years using the Child Behavior Checklist. Longitudinal hierarchical linear models were used to determine the effect of prenatal cocaine exposure on behavior problem trajectories while controlling for other prenatal exposures; time-varying covariates, including ongoing caregiver use of legal and illegal substances; demographic factors; family violence; and caregiver psychological distress.RESULTS. High prenatal cocaine exposure was associated with the trajectory of internalizing, externalizing, and total behavior problems; these effects were independent of and less than the significant combined effect of prenatal and postnatal tobacco and alcohol exposures. Caregiver depression and family violence had independent negative influence on all behavior outcomes.CONCLUSIONS. Prenatal cocaine exposure has a negative impact on the trajectories of childhood behavior outcomes. When they co-occur with prenatal cocaine exposure, prenatal and postnatal tobacco and alcohol exposures have added negative effects on behavior outcomes.

OBJECTIVE:The study goal was to determine whether clonidine treatment of neonatal abstinence syndrome (NAS) would result in a better neurobehavioral performance compared with morphine.METHODS:This pilot study prospectively enrolled infants ≥35 weeks’ gestational age admitted for treatment of NAS. After informed consent was obtained, infants were randomized to receive morphine (0.4 mg/kg per day) or clonidine (5 μg/kg per day) divided into 8 doses. A 25% dose escalation every 24 hours was possible per protocol (maximum of 1 mg/kg per day for morphine and 12 μg/kg per day for clonidine). After control of symptoms, the dose was tapered by 10% every other day. Clinical staff monitored infants by using Finnegan scoring. Masked research staff administered the NICU Network Neurobehavioral Scale (NNNS) at 1 week and at 2 to 4 weeks after initiation of treatment and the Bayley Scales III, and Preschool Language Scale IV, at 1-year adjusted age. Analyses included descriptive statistics, repeated measures analysis of variance, and Wilcoxon tests.RESULTS:Infants treated with morphine (n = 15) versus clonidine (n = 16) did not differ in birth weight or age at treatment. Treatment duration was significantly longer for morphine (median 39 days) than for clonidine (median 28 days; P = .02). NNNS summary scores improved significantly with clonidine but not with morphine. On subsequent assessment, those receiving clonidine had lower height of arousal and excitability (P < .05). One-year motor, cognitive, and language scores did not differ between groups.CONCLUSIONS:Clonidine may be a favorable alternative to morphine as a single-drug therapy for NAS. A multicenter randomized trial is warranted.

Objective. In this prospective, observational study, we determined whether serum C-reactive protein (CRP) correlated with necrotizing enterocolitis (NEC) stages II and III. We hypothesized that serial CRP measurement if used as an adjunct to abdominal radiographs would improve the identification of infants with NEC.Methods. Serum CRP level was measured every 12 hours for 3 measurements and, when abnormal, once daily. When clinical signs persisted and the initial abdominal radiographs were abnormal, follow-up radiographs were obtained.Results. Of 241 infants who were evaluated for gastrointestinal signs, 11 had ileus or benign pneumatosis intestinalis with persistently normal CRP; gastrointestinal manifestations resolved within 48 hours, antibiotics were discontinued in Conclusions. In infants with suspected NEC, normal serial CRP values would favor aborted antibiotic therapy and early resumption of feedings. CRP becomes abnormal in both stage II and stage III NEC. In infants with NEC, persistently elevated CRP after initiation of appropriate medical management suggests associated complications, which may require surgical intervention.

Objective. The diagnosis of persistent pulmonary hypertension (PPHN) can often be difficult to make, especially in a clinical setting in which pediatric echocardiography is not readily available. A noninvasive test that could differentiate PPHN from other cardiorespiratory disease would be very useful in the early management of the disease, because it would allow rapid identification of those infants at greatest risk of requiring the services of a level 3 nursery. Brain-type natriuretic peptide (BNP) is an endogenous peptide hormone secreted by the cardiac ventricles in response to increased wall stress and related ventricular filling pressures. The purpose of this study was to determine if BNP levels are elevated in newborns with PPHN and therefore may be used as a marker for differentiating PPHN from other forms of respiratory disease during the early newborn period. Method. We used a prospective cohort design with 3 groups. One group was diagnosed with PPHN by clinical and echocardiographic criteria (PPHN group: n = 15). The second group had been diagnosed with respiratory disease; however, PPHN had been ruled out by having no evidence of elevated pulmonary pressure by echocardiography (RD group: n = 17). The third group had no respiratory disease and was breathing room air (RA group: n = 15). BNP levels were measured with a point-of-care fluorescence immunoassay at various time intervals between birth and 150 hours of life. Results. There were no differences between groups for birth weight, gestational age, gender, race, Apgar scores at 1 minute, or age at time of initial blood sampling. Initial BNP levels (pg/mL) were elevated in the PPHN group relative to both the RA and RD groups (median [25%, 75%]: PPHN group = 1610 [1128, 1745]; RD group = 132 [76, 327]; RA group = 248 [127, 395]). There was no difference in the initial BNP level between the RA and RD groups. BNP levels remained elevated in the PPHN group over both groups for the first 4 days of life. BNP levels correlated with the gradient of the tricuspid regurgitation jet and with the ratio of tricuspid regurgitation jet gradient to mean blood pressure. BNP levels were not affected by administration of dopamine or dobutamine. BNP weakly correlated with the oxygenation index but not with the alveolar-arterial oxygenation gradient. Conclusions. Our findings indicate that BNP levels are elevated in infants with PPHN but not in infants with other forms of respiratory distress not associated with PPHN. Elevated BNP levels in term or near-term infants with respiratory distress should increase the suspicion of PPHN. Serial determination may also be helpful in monitoring the clinical course of such infants.

Descriptive statistics for the Neonatal Intensive Care Unit Network Neurobehavioral Scale summary scores are provided based on data from 1388 1-month-old infants in the Maternal Lifestyle Study (MLS) of prenatal drug exposure and child outcome. The multisite MLS is described, followed by tables with descriptive statistics and percentile for the Neonatal Intensive Care Unit Network Neurobehavioral Scale summary scores. The tables include data for the entire MLS sample as well as tables by drug exposure status, gestational age, poverty status, sex, race and ethnicity, and MLS study site. These tables can be used as quasinorms for comparison with other infants of this age.

Objective. This was a prospective longitudinal multisite study of the effects of prenatal cocaine and/or opiate exposure on neurodevelopmental outcome in term and preterm infants at 1 month of age.Methods. The sample included 658 exposed and 730 comparison infants matched on race, gender, and gestational age (11.7% born Results. On the NICU Network Neurobehavioral Scale, cocaine exposure was related to lower arousal, poorer quality of movement and self-regulation, higher excitability, more hypertonia, and more nonoptimal reflexes with most effects maintained after adjustment for covariates. Some effects were associated with heavy cocaine exposure, and effects were also found for opiates, alcohol, marijuana, and birth weight. Acoustic cry characteristics that reflect reactivity, respiratory, and neural control of the cry sound were also compromised by prenatal drug exposure, including cocaine, opiates, alcohol, and marijuana and by birth weight. Fewer cry effects remained after adjustment for covariates.Conclusions. Cocaine effects are subtle and can be detected when studied in the context of polydrug use and level of cocaine exposure. Effects of other drugs even at low thresholds can also be observed in the context of a polydrug model. The ability to detect these drug effects requires a large sample and neurobehavioral tests that are differentially sensitive to drug effects. Long-term follow-up is necessary to determine whether these differences develop into clinically significant deficits.

Objective.The objective of this study was to describe drug use by pregnant women participating in the 4-site Maternal Lifestyle Study of in utero cocaine and/or opiate exposure.Methods.Meconium specimens of 8527 newborns were analyzed by immunoassay with GC/MS confirmation for metabolites of cocaine, opiates, cannabinoids, amphetamines, and phencyclidine. Maternal self-report of drug use was determined by hospital interview.Results.The prevalence of cocaine/opiate exposure in the 4 sites was 10.7% with the majority (9.5%) exposed to cocaine based on the combination of meconium analysis and maternal self-report. However, exposure status varied by site and was higher in low birth weight infants (18.6% for very low birth weight and 21.1% for low birth weight). Gas chromatography/mass spectrometry (GC/MS) confirmation of presumptive positive cocaine screens was 75.5%. In the cocaine/opiate-exposed group, 38% were cases in which the mother denied use but the meconium was positive. There was 66% agreement between positive meconium results and positive maternal report. Only 2% of mothers reported that they used only cocaine during pregnancy and mothers were 49 times more likely to use another drug if they used cocaine.Conclusion.Accurate identification of prenatal drug exposure is improved with GC/MS confirmation and when the meconium assay is coupled with a maternal hospital interview. However, the use of GC/MS may have different implications for research than for public policy. We caution against the use of quantitative analysis of drugs in meconium to estimate the degree of exposure. Our study also highlights the polydrug nature of what used to be thought of as a cocaine problem.

BACKGROUND: Some maternal infections are associated with impaired infant cognitive and motor performance. Periodontitis results in frequent bacteremia and elevated serum inflammatory mediators. OBJECTIVE: The purpose of this study was to determine if periodontitis treatment in pregnant women affects infant cognitive, motor, or language development. METHODS: Children born to women who had participated in a previous trial were assessed between 24 and 28 months of age by using the Bayley Scales of Infant and Toddler Development (Third Edition) and the Preschool Language Scale (Fourth Edition). Information about the pregnancy, neonatal period, and home environment was obtained through chart abstractions, laboratory test results, and questionnaires. We compared infants born to women treated for periodontitis before 21 weeks' gestation (treatment group) or after delivery (controls). In unadjusted and adjusted analyses, associations between change in maternal periodontal condition during pregnancy and neurodevelopment scores were tested by using Student's t tests and linear regression. RESULTS: A total of 411 of 791 eligible mother/caregiver-child pairs participated. Thirty-seven participating children (9.0%) were born at .5). Results were similar in adjusted analyses. Children of women who experienced greater improvements in periodontal health had significantly higher motor and cognitive scores (P = .01 and .02, respectively), although the effect was small (∼1-point increase for each SD increase in the periodontal measure). CONCLUSION: Nonsurgical periodontitis treatment in pregnant women was not associated with cognitive, motor, or language development in these study children.

Objective. This study was performed to determine prospectively whether, in the presence of proved or presumed bacterial infection, the sensitivity of serum C-reactive protein (CRP) response could be enhanced by serial rather than single determinations. We also sought to assess CRP responses to clinically identified noninfectious disorders. Design. The CRP responses of 491 infants on 691 occasions of suspected infection were assessed. CRP levels were measured initially and twice again at 12-hour intervals (rate immunonephelometry). Assessments also included a blood culture, complete blood cell count, and chest radiograph and culture of spinal fluid when appropriate. CRP responses were correlated with four designated clinical groups: (1) positive blood or cerebrospinal fluid cultures (n = 190); (2) negative blood culture-definite infection (necrotizing enterocolitis stages 2 and 3, pneumonia, subcutaneous abscess) (n = 52); (3) negative blood culture-possible infection (antenatal risk factors, meconium aspiration, positive urine group B streptococcus antigen, necrotizing enterocolitis stage 1, febrile infants) (n = 287); and (4) negative blood culture-no infection (respiratory distress syndrome, transient tachypnea of the newborn, patent ductus arteriosus, tissue trauma) (n = 160). Diagnoses were made before CRP results were known. Results. In all, 187 (27%) of the blood cultures were positive. A single organism was recovered from 174 of these; two organisms from 13. Among the single-organism cultures, 50 (29%) were Gram-negative, 120 (69%) were Gram-positive, and 4 (2%) were budding yeasts. CRP levels were elevated in various groups as follows: in the positive blood culture group (by organism), Gram-negative rods, 92% (46/50); group B streptococcus, 92% (12/13); Staphylococcus aureus, 89% (8/9); group D streptococcus, 71% (10/14); Streptococcus viridans, 60% (6/10); Staphylococcus epidermidis, 55% (40/73). In the negative blood culture-definite infection group, CRP levels were abnormal in 88%; in the negative culture-possible infection group, CRP was elevated in 33%; and in the negative blood culture-no infection group, CRP was elevated in 9%. Serial determinations of CRP resulted in enhanced sensitivity in the positive blood culture group, the negative blood culture-definite infection group, and the negative blood culture-possible infection group. Initial determinations by themselves were inadequatey sensitive. Serial determinations did not enhance sensitivity of the negative blood culture-no infection group. High specificity (91%) is suggested by the low incidence of abnormal CRP levels among infants who were not infected. Conclusions. These data suggest that it would be appropriate to conduct a cautious, controlled trial to assess the safety of discontinuing antibiotic therapy if three serial CRP measurements are normal and if there are no other clinical factors suggestive of infection. The data also indicate the necessity for serial determinations of CRP for optimal sensitivity.

Follow-up studies relating prenatal cocaine and other substance exposures to behavioral problems during childhood typically use a behavioral teratology model.1–4 The goal here is to isolate the effects of a teratogen by controlling for effects of potential confounding variables through study design such as matching and/or statistics in which confounding variables are covaried. The variance in outcome explained by the confounding variables is essentially removed from the analysis, and the left over unexplained variance is attributed to the teratogen. For example, we found effects of prenatal cocaine exposure on trajectories of behavior problems from 3 to 7 years independent of the effects of prenatal exposure to alcohol and tobacco, as well as other potentially confounding variables.5 The behavioral teratology model is critically important because it enables us to determine, not only if there is a unique drug effect (i.e., drugs affect outcome when confounding factors are controlled), but also the magnitude of the drug effect (i.e., variability in the outcome measure explained by the drug alone). A limitation of the behavioral teratology approach, however, is that it does not lend itself to study the developmental processes that lead from exposure to developmental outcome. In addition to direct drug effects there may be indirect effects that suggest how factors mediate the relationship between teratogenic effects and developmental outcome. In a developmental model, effects that are removed as confounding variables can be studied as factors that explain more of the variability in developmental outcome in the presence of teratogenic effects. In other words, these factors are included rather than controlled or removed. In addition, other factors that are hypothesized to be involved in these developmental models can also be included. Statistical techniques such as path analysis or structural equation modeling (SEM) are often used to study these pathways. In previous work, path models have shown that growth deficits associated with prenatal cocaine exposure are mediated, in part, by gestational age.6 In addition to direct effects of prenatal cocaine exposure on IQ, there are indirect effects mediated by head circumference, child behavior, and the home environment.7 In our work, the relationship between prenatal cocaine exposure and hypertension was mediated by body mass index.8 In the present study, we used SEM to test a developmental model relating prenatal cocaine and other substance exposure to behavior problems at age 7. The primary hypothesis was that prenatal exposure to cocaine and other substances would result in neurobehavioral dysregulation in infancy (i.e., problems with arousal and reactivity), which would predict externalizing and internalizing behavior problems in childhood. Externalizing and internalizing behavior problems are part of the neurobehavioral disinhibition profile that includes cognitive, emotional, and behavioral disturbances.9 This profile reflects diminished inhibitory control and is related to early onset of substance use.9–11 In the present study, we were interested in the behavioral antecedents of neurobehavioral disinhibition. Therefore, we predicted children who showed signs of neurobehavioral dysregulation at one month would have a difficult temperament at 4 months, leading to behavior problems at 3 and 7 years of age. Our long-term goal is to delineate developmental pathways in which children with prenatal cocaine exposure are at increased risk for adolescent substance use.

Increased use of cocaine in the United States in the 1980s turned the scientific community toward studying the children of mothers who used cocaine during pregnancy. Initial legal and social stigma attached to mothers who abused cocaine during pregnancy and their “crack kids” who were feared to be “brain damaged”1,2 has been tempered by evidence that the risk for serious congenital malformations or medical complications in newborns with prenatal cocaine exposure (PCE) is minimal3; however, little is known about the potential long-term neurodevelopmental effects of PCE. Previous studies revealed varying effects of PCE on behavior4–6 and cognitive outcomes.7–13 Longitudinal follow-up studies of the intelligence of these children suggested that cocaine effects are apparent but more subtle than originally feared.14 Inconsistencies in the cocaine literature have been described and may be attributable to methodologic issues such as small sample size; confounding of cocaine exposure with exposure to other drugs; lack of biochemical verification for exposure status and levels; and lack of adequate control for demographic variables such as prenatal care, socioeconomic status (SES), and out-of-home placement.14,15 There are few studies of school function in children with PCE. Teacher rating of school behavior suggested increased behavior problems in children with PCE in some5,6,16 but not all studies.17 Studies have reported adverse effects of PCE on language in children aged 2.5 to 9.5 years,14,18–24 whereas others have not25,26; however, there are no studies of use of school-based speech and language services in this group. One study of school performance showed no effects of PCE on grade progression, grade point average, or standardized test.27 We provide the first report of enrollment in special education of children with PCE. These services require significant school funding and teacher resources. On the basis of these findings, we hypothesized that PCE is associated with higher rates of enrollment in special education and the need for support services at 7 years, especially speech and language services.

The blood pressure (BP) and transcutaneous Po2, (TcPo2) changes associated with intensive care procedures were evaluated to determine whether responses differ between babies with and without periventricular-intraventricular hemorrhage (PV-IVH). Fifty-three inborn babies ≤1500 g were studied using a microcomputer-based monitoring system. With almost any procedure including a seemingly benign one such as a diaper change, peak systolic BP increased and TcPo2 decreased. However, responses to interventions did not differ between babies with PV-IVH and those without PV-IVH. Neither did these responses differ between those with birth weight ≤1000 g and >1000 g. When each baby's record was scanned for the highest peak systolic BP before diagnosis of PV-IVH or within 48 hours in those with no PV-IVH and their BP points plotted against birth weight, a stable region was evident wherein PV-IVH occurred at a lower incidence (13%). When peak systolic BP was beyond this stable region, the incidence of PV-IVH was significantly higher, 70% (P < .0001). The stability boundary for the maximum systolic BP is birth weight-dependent; the limit for the highest tolerable peak systolic BP is lower for the low-birth-weight infant. In over 70% of instances the highest peak systolic BP was associated with motor activities either induced by nursery procedures or spontaneous. We speculate that decreasing the frequency of intensive care interventions may decrease episodic BP increases to levels beyond the birth weight-dependent stability boundary where PV-IVH is likely to occur.

Objective. To determine the effects of patterns of drug use during term pregnancy on infant growth parameters at birth. Methods. Histories of cocaine, opiate, alcohol, tobacco, and marijuana use during the 3-month period before pregnancy and the 3 trimesters of pregnancy were recorded at the infants’ 1-month visit. Patterns of use were categorized as consistently high, moderate, or low/none or increasing/decreasing, and effects on growth parameters were analyzed in multivariate linear regression analyses, with adjustment for clinical site, maternal age, prepregnancy weight, multidrug use, and socioeconomic status. Results. A total of 241 cocaine-exposed women and 410 non–cocaine-exposed women participated in the study. In the cocaine-exposed group, 75% used alcohol, 90% used tobacco, and 53% used marijuana; in the non–cocaine-exposed group, 57% used alcohol, 34% used tobacco, and 19% used marijuana. Birth weight, birth length, and head circumference were significantly greater among infants born to women who used no drugs, compared with women with any cocaine, opiate, alcohol, tobacco, or marijuana use, and were greater among infants born to cocaine nonusers, compared with cocaine users. With adjustment for confounders, birth weight was significantly affected by cocaine (deficit of 250 g with consistently low pattern) and tobacco (deficits of 232 g with consistently high pattern, 173 g with consistently moderate pattern, 153 g with decreasing pattern, and 103 g with consistently low pattern). Head size was affected by cocaine (deficit of 0.98 cm with consistently moderate pattern) and tobacco (deficits of 0.72 cm with consistently high pattern and 0.89 cm with consistently moderate pattern). Birth length was affected by tobacco use only (deficits of 0.82 cm with consistently high pattern and 0.98 cm with decreasing use). Conclusion. Patterns of tobacco use during pregnancy affect birth weight, length, and head circumference, whereas cocaine affects birth weight and head size, when adjustments are made for confounders, including multidrug use.

Objective. To evaluate the direct effects of prenatal cocaine exposure and prenatal opiate exposure on infant mental, motor, and behavioral outcomes longitudinally between 1 and 3 years old.Methods. As part of a prospective, longitudinal, multisite study, the Bayley Scales of Infant Development II were administered to 1227 infants who were exposed to cocaine (n = 474), opiates (n = 50), cocaine and opiates (n = 48), and neither substance (n = 655) at 1, 2, and 3 years of corrected age by certified, masked examiners. Hierarchic linear modeling of the 1-, 2-, and 3-year scores was conducted using cocaine and opiate exposure as predictors with and without controlling for covariates.Results. Overall retention was 88.4% and did not differ by cocaine or opiate exposure. Overall (at 1, 2, and 3 years), cocaine-exposed infants scored 1.6 Mental Development Index points below infants who were not exposed to cocaine. Opiate-exposed infants scored 3.8 Psychomotor Development Index points below infants who were not exposed to opiates. Neither the cocaine nor the opiate effect remained significant after controlling for covariates. Neither cocaine nor opiate exposure was associated with the Behavioral Record Score during the examination. Low birth weight and indices of nonoptimal caregiving were associated with lower Mental Development Index, Psychomotor Development Index, and Behavioral Record Score scores for all groups of infants.Conclusions. In the largest at-risk sample observed longitudinally to date, infant prenatal exposure to cocaine and to opiates was not associated with mental, motor, or behavioral deficits after controlling for birth weight and environmental risks.

Descriptive statistics for the Neonatal Intensive Care Unit Network Neurobehavioral Scale summary scores are provided based on data from 1388 1-month-old infants in the Maternal Lifestyle Study (MLS) of prenatal drug exposure and child outcome. The multisite MLS is described, followed by tables with descriptive statistics and percentile for the Neonatal Intensive Care Unit Network Neurobehavioral Scale summary scores. The tables include data for the entire MLS sample as well as tables by drug exposure status, gestational age, poverty status, sex, race and ethnicity, and MLS study site. These tables can be used as quasinorms for comparison with other infants of this age.

Objective. To determine the efficacy of tolazoline as a rescue treatment for hypoxemia in preterm infants with respiratory distress syndrome.Methods. Retrospective chart review on case series of infants weighing Results. Forty-three infants with a mean gestational age and birth weight of 24 weeks and 581 g, respectively, received tolazoline. All infants were mechanically ventilated and required a fraction of inspired oxygen of 1.0. Oxygenation improved in 72% (31/43) of infants with a tolazoline dose of 0.5 to 1.0 mg/kg. Of those who responded, Pao2 values (mean ± standard deviation) pretolazoline and posttolazoline were 32 ± 7.5 mm Hg and 156 ± 114.9 mm Hg, respectively. In all responders, oxygen saturation increased to ≥90% within 30 minutes of tolazoline administration. Improvement in pH, pCO2, oxygenation index, and mean airway pressure was also noted. Among nonresponders, pH decreased and pCO2 increased after tolazoline. Minimal change in blood pressure was noted in both responders and nonresponders. Heart rate decreased by 19 beats per minute among nonresponders compared with an increase of 3 beats per minute in those who responded to tolazoline.Conclusion. Tolazoline is an effective treatment of severe resistant hypoxemia in preterm infants who are already on vigorous ventilatory support.

Objective. We report our experience with routine immunization of 89 premature infants in the neonatal intensive care unit because 1) a substantial number of them developed abnormal clinical signs, and 2) all but one of those who received diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccine responded with elevations of interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations that are otherwise characteristic of bacterial disease.Methodology. We hypothesized that the elevated IL-6 and CRP levels were solely a response to immunization and that treatment with antibiotics was not necessary. We performed this study in two consecutive parts. In part 1, we prospectively evaluated 79 consecutive premature infants who were immunized with DTwP, Haemophilusb conjugate vaccine, hepatitis B vaccine, and inactivated polio vaccine, (Hib, HBV, and IPV). IL-6 and CRP were determined before immunization and every 12 hours on three occasions after immunization. In part 2, we studied an additional 10 infants who received acellular pertussis vaccine (DTaP) and who, 2 days later, received Hib, HBV, and IPV immunization simultaneously. We followed the same schedule of IL-6 and CRP determinations as in part 1.Results. In part 1, 24 infants (30%) developed abnormal cardiorespiratory signs within 24 hours after immunization. CRP and IL-6 values rose to abnormal levels after immunization in all but one infant; that infant was later shown to have a T-cell abnormality. In part 2, 3 infants had abnormal cardiorespiratory signs after simultaneous immunization with Hib, HBV, and IPV, but not after DTaP. IL-6 and CRP levels remained normal in all 10 infants.Conclusions. Part 1 demonstrates clearly the temporal relationship between IL-6 and CRP increments after DTwP, Hib, HBV, and IPV vaccines. In part 2 (DTaP was substituted for DTwP), there were no elevations of IL-6 or CRP, thus indicating that whole-cell pertussis component of DTwP was responsible for IL-6 and CRP elevations. Abnormal cardiorespiratory signs occurred frequently after immunizations in part 1, but they were unrelated to the magnitude of IL-6 and CRP elevations. The frequency of cardiorespiratory difficulty and its occasional severity suggest a need to monitor premature infants for ∼48 hours after routine immunization.

Periventricular-intraventricular hemorrhage (IVH) remains a significant cause of long-term morbidity among premature infants1. Clinical trials2-4 have shown that prophylactic indomethacin is associated with a decreased incidence of IVH, including the severe form. In this issue of Pediatrics, Ment et al5 report on the long-term outcome of children who received indomethacin prophylaxis for IVH. Incidence of cerebral palsy (8%) was similar between the indomethacin-and placebo-treated groups; mean IQ scores determined from the Stanford-Binet Intelligence Scale (Form L-M, 1972) did not differ. IQ scores were significantly related to IVH, birth weight, and maternal education; ie, lower IQ scores with IVH and higher scores with higher birth weight and years of education.

In Reply.— We appreciate the interest and comments of Drs Puccio and Soliani regarding our article "Blood Pressure Increase, Birth Weight Dependent Stability Boundary and Intraventricular Hemorrhage."1 In response, we address the following points: 1. Although mean blood pressure (BP) values greater than 100 mm Hg were observed in some of our patients, these were quite rare. The mean BP was found to be less than 60 mm Hg 99% of the time. Thus, unless one is recording BPs through long periods and sampling quite often, the brief spikes likely would not be observed.

We appreciate Dr Philip's sharing his experience on the use of serial C-reactive protein (CRP) for monitoring neonates with sepsis or pneumonia due to group B streptococcus. In his letter, Dr Philip alluded to the use of normal serial CRP within 24 to 48 hours of life as a guide to discontinuing antibiotic therapy when cultures are negative. Our current practice is carried further. Based on our published data and our continuing experience, we discontinue antibiotic therapy in asymptomatic infants, even in those with positive blood cultures.

The applanation transducer was used to measure intracranial pressure (ICP) through the intact fontanel. The method is painless, rapid, and accurate. The pressures recorded with this fontogram were correlated with direct measurements of ICP. The correlation coefficient of the 21 paired determinations was .98—a very good correlation. Fontanel pressure was determined in 35 normal newborn infants. The mean pressure was 7.37 mm Hg with an SD of ± 1.45 (range, 3.5 to 9.5 mm Hg). Three clinical cases are presented to illustrate the usefulness of this apparatus in the detection of increased ICP and in monitoring the effectiveness of treatment.