A randomized controlled trial of synchronized nasal intermittent positive pressure ventilation in RDS.

OBJECTIVE: Comparison of outcomes of infants with respiratory distress syndrome (RDS), post-surfactant, extubated to synchronized nasal intermittent positive pressure ventilation (SNIPPV) or continued on conventional ventilation (CV). STUDY DESIGN: Prospective post-surfactant randomized controlled trial of primary mode SNIPPV compared with CV in infants (born from July 2000 to March 2005) with birth weights (BW) of 600 to 1250 g. Primary mode SNIPPV was defined as its use in the acute phase of RDS, following the administration of the first dose of surfactant. RESULT: There were no significant differences in the maternal demographics, antenatal steroid use, mode of delivery, BW, gestational age, gender or Apgar at 5 min between infants continued on CV (n=21) and those extubated to primary mode SNIPPV (n=20). Significantly, more babies in the CV group had the primary outcome of bronchopulmonary dysplasia (BPD)/death, compared to the SNIPPV group (52 versus 20%, P=0.03). There was no difference in the incidence of other common neonatal morbidities. There were no differences in the Mental or Psychomotor Developmental Index scores on follow-up between the two groups. CONCLUSION: Infants of BW 600 to 1250 g with RDS receiving surfactant with early extubation to SNIPPV had a significantly lower incidence of BPD/death. Primary mode SNIPPV is a feasible method of ventilation in small premature infants.

Site-specific characteristics of infants developing bronchopulmonary dysplasia.

HYPOTHESIS: Site-specific variables that contribute to the pathogenesis of bronchopulmonary dysplasia (BPD) can be identified. OBJECTIVES: To evaluate the demographic, nutrition and growth characteristics of infants at risk for developing BPD at two neonatal intensive care units (NICUs: sites A and O). STUDY DESIGN: Records of 306 infants of < or = [corrected] 30 weeks gestational age (GA) who survived to at least 36 weeks postmenstrual age were retrospectively reviewed. Data were obtained for maternal and neonatal demographics, weights, total fluids, calories, carbohydrate, protein and fat intake at birth, 7, 14, 21 and 28 days of life. RESULTS: BPD rates were not different at the two sites. No statistical differences were noted in the incidence of maternal chorioamnionitis, pregnancy-induced hypertension or use of antenatal steroids among infants who developed BPD (n = 169) and those who did not (n = 137). White race, birth weight, respiratory distress syndrome requiring surfactant, sepsis and patent ductus arteriosus were significantly associated (all P < or =0.03) with BPD. After controlling for significant confounding variables, infants who developed BPD had significantly (P < 0.001) less weight gain, received less calories and fat in the first postnatal month. In the 26 to 28 weeks GA group, the odds of getting BPD were 5.4 (95%CI: 1.4 to 21.3) times greater for site A than site O (P = 0.017). CONCLUSION: Our analysis suggests that while some decrease in BPD can be achieved by focusing on ventilation/oxygen use, this approach is unlikely to impact on the youngest infants.

Exposure to violence: psychological and academic correlates in child witnesses.

BACKGROUND: Inner-city children are frequently exposed to violence; however, there are few data regarding the psychological and academic correlates of such exposure in young children at school entry. OBJECTIVES: To document exposure to violence in inner-city children aged 7 years; assess their feelings of distress; and evaluate the relationships of exposure to violence with school performance, behavior, and self-esteem. SETTING: A study center in an inner-city hospital. PARTICIPANTS: One hundred nineteen inner-city children evaluated at age 7 years; 119 caregivers (biological and foster). DESIGN: As part of a longitudinal study, children were administered the following by a masked examiner: Things I Have Seen and Heard (TISH) to assess exposure to violence; Levonn, a cartoon-based interview for assessing children's distress symptoms; and the Culture-Free Self-Esteem Inventory, Second Edition. School performance was assessed by school reports and child behavior by the Child Behavior Checklist (CBCL), the Parent Report Form, and the Teacher Report Form. Caregivers for children were administered the parent report version of the Checklist of Children's Distress Symptoms (CCDS-PRV) as well as the CBCL Parent Report Form. MAIN OUTCOME MEASURES: Exposure to violence (TISH); feelings of distress (Levonn); school performance; behavior (CBCL Parent Report Form and CBCL Teacher Report Form); and self-esteem (Culture-Free Self-Esteem Inventory). RESULTS: We found that these children were frequently exposed to violence. For example, 75% had heard gun shots, 60% had seen drug deals, 18% had seen a dead body outside, and 10% had seen a shooting or stabbing in the home (TISH). Many showed signs of depression and anxiety; eg, 61% worried some or a lot of the time that they might get killed or die and 19% sometimes wished they were dead (Levonn). Higher exposure to violence (TISH Total Violence score) was correlated with higher Levonn composite scores for depression and anxiety and with lower self-esteem (P< or =.04), and was also associated with lower grade point average and more days of school absence (P< or =.02). Caregiver assessment of child anxiety correlated poorly with child report of anxiety (P =.58). CONCLUSIONS: Young inner-city children have a high exposure to violence by age 7 years; many show signs of distress that frequently are not recognized by caregivers. Further, higher exposure to violence in children correlates with poorer performance in school, symptoms of anxiety and depression, and lower self-esteem.

Are there neurologic correlates of in utero cocaine exposure at age 6 years?

At age 6 years, a cohort of non-asphyxiated children, 52 with gestational cocaine exposure and 63 control subjects, underwent a neurologic examination. Groups did not differ on any aspect of the examination. This finding, while reassuring, does not exclude the possibility of more subtle deficits.

A prospective comparison of developmental outcome of children with in utero cocaine exposure and controls using the Battelle Developmental Inventory.

Children with in utero cocaine exposure may be at risk for adverse neurodevelopmental outcome. To evaluate such outcome in young children, we administered the Battelle Developmental Inventory (BDI) to a group of inner-city children with (COC) and without (CON) in utero cocaine exposure at ages 3 and 5 years. Sixty-five COC and 68 CON, similar at age of testing, were evaluated at both time points by examiners masked to child group status. Both groups scored poorly and worsened over time. Although Total BDI raw scores were lower in the COC group than in the CON group at 3 years, this difference was related to postnatal environmental factors, caregiver (p = .022), and home environment (p = .010), not to in utero cocaine exposure (p = .88). At 5 years, the Total BDI score was related to the home environment (p < .001) but not to the caregiver (p = .36) or in utero cocaine exposure (p = .83). We conclude that inner-city children are at risk for adverse developmental outcome regardless of in utero cocaine exposure.

Clinical correlations in infants in the neonatal intensive care unit with varying severity of gastroesophageal reflux.

BACKGROUND: Gastroesophageal reflux (GER) is frequently a benign condition in infancy with spontaneous resolution. In the neonatal intensive care unit (NICU), however, it can add to neonatal morbidity if not adequately diagnosed and treated. The objective of the current study was to analyze factors associated with GER in infants in the NICU and correlate them with the severity of the disease. METHODS: All infants in the NICU (n = 150; born November 1994 through April 1999) who were evaluated by a five-channel pH study to rule out GER were included in the study. Infants were grouped as normal, with a reflux index (RI) of less than 6 (n = 66); mild, with RI of 6 to 14 (n = 42); and severe, with RI of more than 14 (n = 42). Maternal and neonatal data were obtained. Clinical GER was defined as the presence of feeding problems (significant gastric residue or emesis) and medical improvement with antireflux measures and medications. RESULTS: There was no difference in birth weight, gestational age; incidence of patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, or chronic lung disease; and treatment with aminophylline or caffeine among the groups. Infants with mild and severe GER (RI 6-14 and >14) had significantly more clinical GER than the normal group (P = 0.0001). Additionally, infants with RI more than 14 had significantly more respiratory distress syndrome, lower hematocrits at the time of study and longer length of stay than those with no or mild GER (P = 0.02). CONCLUSION: Infants with severe GER had lower hematocrits despite receiving more blood transfusions and iron therapy. Infants with severe GER also had prolonged hospital stays. Early diagnosis and aggressive management of GER may decrease neonatal morbidity and result in earlier discharge from the NICU.

Problem-solving ability of inner-city children with and without in utero cocaine exposure.

To evaluate the problem-solving abilities of a cohort of inner-city cocaine-exposed children and controls, children were invited to play with the Goodman Lock Box, a large red and blue box with 10 compartments, each having a different lock and toy. Examiners, blinded to the children's group status, coded the children's activities during the 6.5-minute play period. Nineteen behaviors were collapsed into three outcomes: Aimless Actions, Competence, and Mental Organization. Groups' scores were compared with scores of the Goodman standardization sample of mixed socioeconomic status preschoolers. Seventy-three cocaine-exposed children and 82 controls were evaluated at age 3.5 years; of these, 58 cocaine-exposed and 63 controls were reevaluated at age 4.5 years. The groups' scores did not differ on any outcome at either time point (p > or = .22). However, both groups' Mental Organization scores were consistently lower than the Goodman group at each age (p < .01). This high-risk cohort may experience problems functioning in more complex environments such as the classroom.

Neutral oligosaccharide content of preterm human milk.

Human milk oligosaccharides are known to play a role in protection against certain infectious diseases. Previous reports indicate that the content of human milk oligosaccharides varies widely among individuals at term but such information on preterm milk is lacking. After removal of the fat, protein and most of the lactose from non-pooled human milk samples, a total neutral oligosaccharide fraction was isolated by ion-exchange chromatography followed by gel filtration. A Dionex high-performance anion-exchange chromatography system equipped with a pulsed electrometric detector was then employed to measure the levels of ten neutral oligosaccharides in the individual milk samples. Twenty-three milk samples from thirteen mothers who delivered at a mean gestational age of 29.5 (SD 3.1) weeks were collected between days 0 and 33 of lactation, and compared with three samples of term milk from two mothers. The ranges of the total and individual levels of the ten neutral oligosaccharides in preterm milk were similar to those in term milk. Further, as previously described in term milk, preterm milk exhibited a quantitative individual variation. This variation was independent of the gestational age, day of lactation, and postconceptional age. In conclusion, levels of ten neutral oligosaccharides did not differ between preterm and term human milk.

The effects of maternal magnesium sulfate treatment on newborns: a prospective controlled study.

OBJECTIVE: To evaluate the effects of maternal magnesium sulfate treatment on newborn outcome. METHODS: Subjects were newborn infants delivered at > or = 34 weeks of gestation whose mothers received a minimum of 12 hours of intravenous MgSO4 therapy before delivery. Control infants were the next born infants of similar gestational age. Outcome recorded at delivery included Apgar scores, whether resuscitation was required, and whether respiratory depression or decreased tone were noted by the physician in attendance. Pneumocardiograms on magnesium-exposed and control infants, obtained within 6 to 18 hours after delivery, were analyzed postdischarge by a single investigator who was blinded to group. The nursery course, feeding patterns, time to first stool, and time to first void were recorded. All patient care decisions, including admission to the neonatal intensive care unit (NICU) or term nursery, were independent of study protocol. RESULTS: A total of 26 magnesium-exposed and 26 control infants were enrolled. The mean total dose of MgSO4 before delivery was 51.2+/-24 gm; the mean duration of therapy was 23.1+/-10 hours. The mean maternal serum magnesium level before delivery was 5.8+/-1.1 mg/dl. The infants' mean cord or initial serum magnesium level was 5.2+/-1.0 mg/dl, which correlated with the maternal magnesium level before delivery (r=0.81, p < 0.001). MgSO4-exposed infants had a higher incidence of hypotonia and lower median Apgar scores than control infants (p < 0.001). However, there was no association between adverse outcomes and maternal serum magnesium concentrations at delivery, duration of treatment, or dose of MgSO4. No difference in dose or length of maternal MgSO4 treatment was noted between infants admitted to term nursery and those admitted to NICU. Pneumocardiogram data were similar between MgSO4-exposed and control infants (all p > or = 0.16). There were no significant differences in number of episodes of feeding intolerance or in time to first stool or void between MgSO4-exposed and control infants (all p > or = 0.31). CONCLUSION: Infants born to mothers treated with MgSO4 were more likely to be hypotonic and have lower Apgar scores at birth. Beyond the immediate postdelivery period, there were no additional complications in this cohort attributable to prenatal MgSO4 exposure. We suggest that pediatricians attend deliveries of magnesium-exposed infants.

Inner-city achievers: who are they?

OBJECTIVE: To define characteristics that differentiate inner-city children with Average or above-Average Full Scale IQ scores (> or =90) from those with below-Average scores (<90). DESIGN: As part of a prospective study of children with and without in utero cocaine exposure tested at age 4 years on the Wechsler Preschool and Primary Scales of Intelligence-Revised, we found that, taken together, only 32 (21%) scored at or above 90 whereas 118 (79%) scored below 90. The groups (IQ> or =90 and IQ<90) were compared on prenatal, natal, and postnatal factors. SETTING: A study center in an inner-city hospital. PARTICIPANTS: One hundred-fifty children of low socioeconomic status, 34 weeks' gestational age or older, and nonasphyxiated at birth, who had intelligence testing at age 4 years; 150 caregivers (biological and foster). MAIN OUTCOME MEASURES: Association of Full Scale IQ with prenatal, natal, and postnatal characteristics (including caregiver-child interaction measured by the Parent Caregiver Involvement Scale [PCIS], and home environment measured by the Home Observation for Measurement of the Environment [HOME]). RESULTS: The group of children with IQs at or above 90 (n = 32) did not differ from the group with IQs below 90 (n = 118) in prenatal or natal characteristics (all P> or =.18) or proportion in foster care, attendance at day care or Head Start, continued caregiver cocaine use, or parental IQ. Children with IQs at or above 90 had more developmentally appropriate interaction by caregivers (P=.043) and higher scores on 6 of 8 subscales and Total HOME (P< or =.05) than the group of children with IQs below 90. CONCLUSIONS: Two postnatal factors, home environment and caregiver-child interaction, were associated with Full Scale IQ scores at or above 90 whereas prenatal and natal factors were not. These potentially malleable postnatal factors can be targeted for change to improve cognitive outcome of inner-city children.

Children with in utero cocaine exposure do not differ from control subjects on intelligence testing.

OBJECTIVE: To determine if in utero cocaine exposure affects IQ scores in children at age 4 years. DESIGN: A prospective, longitudinal evaluation by blinded examiners of the IQ scores of cocaine-exposed and control children of low socioeconomic status who have been observed since birth. SETTING: A study center in an inner-city hospital. PARTICIPANTS: One hundred one children with in utero cocaine exposure and 118 control children, all of whom were 34 weeks' gestational age or older and nonasphyxiated at birth. MAIN OUTCOME MEASURE: Intelligence quotient scores on a standardized intelligence test, the Wechsler preschool and Primary Scale of Intelligence--Revised. RESULTS: Seventy-one cocaine-exposed and 78 control children were administered the Wechsler Preschool and Primary Scale of Intelligence--Revised. Maternal, natal, and 30-month characteristics of the children tested did not differ from those not tested. Groups did not differ on mean Performance (83.2 vs 87.0), Verbal (79.0 vs 80.8), or Full Scale (79.0 vs 81.9) IQ scores (all P > or = .10 [values for cocaine-exposed children given first]). None of these 3 scores was associated with cocaine exposure in multivariate linear regressions. Although cocaine-exposed and control groups did not differ in outcome, 93% of cocaine-exposed and 96% of control children had Full Scale IQ scores below 100, the mean IQ score for the test. CONCLUSIONS: In an inner-city cohort, IQ scores did not differ between cocaine-exposed and control children. However, both groups performed poorly.

Is Clostridium difficile a pathogen in the newborn intensive care unit? A prospective evaluation.

OBJECTIVES: The purpose of this study was to investigate (1) the presence of Clostridium difficile toxin in patients in the newborn intensive care unit and (2) the association of C. difficile toxin with gastrointestinal tract symptoms in this population. STUDY DESIGN: A prospective, masked study was done in which twice-weekly stool specimens of subjects hospitalized in a newborn intensive care unit during a 4-month period were analyzed for C. difficile toxin A by enzyme immunoassay. Daily data collection included infant clinical status, stool frequency and character, presence of gastrointestinal tract symptoms, and actions taken for gastrointestinal tract symptoms. Infants hospitalized 5 or more days who had at least two stool assays comprised the study population. For data analysis, an infant with C. difficile toxin-positive status was defined as an infant with two or more toxin-positive stools. RESULTS: Of 87 infants who met study criteria, 42 (48%) had toxin-negative and 45 (52%) toxin-positive results on at least one specimen. Of the infants with toxin-positive findings, 27 (31%) had two or more positive stool assays and comprised the comparison group. The infants with toxin-positive results were smaller, less mature, and had a longer hospital stay than infants with toxin-negative results (p < 0.001). Infants with toxin-positive findings had more days per infant with frequent (> 6) stools and abnormal stools (p < 0.001). The total number of symptom days was 8.2 +/- 5.7 in infants in the toxin-positive group versus 2.2 +/- 2.2 in those in the toxin-negative group (p < 0.001). The mean number of times stools were sent for evaluation and culture was greater in infants with toxin-positive findings (p < or = 0.012) whereas there was no difference in the number of times oral feedings were withheld from infants or infants had abdominal films obtained (p > or = 0.18). CONCLUSIONS: Infants hospitalized in our newborn intensive care unit frequently had stools positive for C. difficile toxin A. When compared with infants with toxin-negative findings, infants with colonization had an increased number of days with gastrointestinal tract symptoms.

A prospective evaluation of early language development in children with in utero cocaine exposure and in control subjects.

A cohort of children of low socioeconomic status, 76 with in utero cocaine exposure and 81 control subjects, was assessed for early language development at 2 1/2 years of age by a masked examiner using the Preschool Language Scale. There were no differences between groups in expressive, receptive, or total language score (all p > or = 0.57). Physicians caring for cocaine-exposed children with early language delay should not automatically ascribe the delay to cocaine exposure but should initiate a standard evaluation for language delay.

Play behavior in toddlers with in utero cocaine exposure: a prospective, masked, controlled study.

Play behavior was compared between toddlers with in utero cocaine exposure and controls of similar low socioeconomic status enrolled at birth in a prospective, masked study. At 18 and 24 months, 83 cocaine-exposed and 93 control toddlers were videotaped playing on their own for 15 minutes. An observer who was off-site and unaware of project purpose or drug exposure status of toddlers recorded the most cognitively complex play activity per 15-second interval. In a total of 315 play sessions, the groups did not differ in middle and highest level of play achieved at either 18 or 24 months (p > or = .27). After controlling for confounders, the proportions of play behavior in each of six play categories were similar in the two groups at both 18 and 24 months (p > or = .42). We conclude that in utero cocaine exposure was not associated with differences in play behavior in this cohort of cocaine-exposed and control toddlers.

Antibody response of low birth weight infants to Haemophilus influenzae type b polyribosylribitol phosphate-outer membrane protein conjugate vaccine.

OBJECTIVE: To evaluate the effectiveness in low birth weight (LBW) infants of the currently recommended immunization schedule for conjugated Haemophilus influenzae type b (HIB) vaccine. METHODS: We quantified antibody responses in 36 preterm infants with a mean birth weight of 1060 g and a mean gestational age of 28 weeks. Infants were immunized with 0.5 mL of HIB vaccine at 2 and 4 months' postnatal age. Specific HIB antibodies were quantified on cord blood, immediately before each immunization and 2 months after the last immunization. RESULTS: Even though the geometric mean titers increased significantly during the study period, they were still markedly lower than values reported in term infants. After the second immunization, only 24 infants (67%) attained antibody concentrations of more than 0.25 micrograms/mL, defined as seropositivity. Also, only 53% of infants achieved antibody concentrations of more than 1.0 micrograms/mL compared with 92% as reported in term infants. Stepwise logistic regression identified gestational age of 27 weeks or less and the amount of intravenous immunoglobulin received as the significant variables influencing the antibody response after the first immunization. The incidence of side effects was negligible. CONCLUSIONS: We conclude that LBW infants, and especially those born at 27 or less weeks' gestation, do not respond as effectively to the HIB vaccine. We speculate that reevaluation of the current immunization schedule may be required for very LBW infants.

Natal status of infants of cocaine users and control subjects: a prospective comparison.

Cocaine use by pregnant women has increased dramatically in recent years. To assess the effect of maternal cocaine use on infant outcome, we enrolled 224 women (105 cocaine users, 119 control subjects) and their infants (all of 34 weeks or more gestational age and nonasphyxiated) in a prospective, blinded study. Results showed that infants exposed to cocaine were more likely to be admitted to the newborn intensive care unit, be treated for congenital syphilis, have a greater length of stay, and be discharged to a person other than the mother (all p < 0.01). Birth weight and head circumference, adjusted for gestational age, were smaller in the infants exposed to cocaine than in control infants (p < 0.001). After statistically controlling for cigarette use and other confounders, however, the odds of infants exposed to cocaine and control infants having birth weight and head circumferences less than the 25th percentile for gestational age did not differ (both p > 0.80). Infants of cocaine-using mothers and control subjects had a similar incidence of abnormal cranial and renal ultrasonographic findings and abnormal pneumocardiograms (all p > or = 0.32). We conclude that in this cohort of nonasphyxiated infants of 34 weeks or more gestational age, infants exposed to cocaine had more medical and social problems than control infants but did not differ statistically in the incidence of severe growth retardation, abnormal cranial or renal ultrasonographic findings, or abnormal pneumocardiograms. We suggest that natal interventions for the nonasphyxiated term and near-term infant exposed to cocaine should include a careful history and physical examination, follow-up plans, and social service involvement.

Cocaine-exposed children: follow-up through 30 months.

This prospective, blinded study evaluates the effect of in utero cocaine exposure on outcome of nonasphyxiated, term and near-term children born to women of low socioeconomic status. Two hundred nineteen children (101 cocaine-exposed and 118 control) with extensive natal evaluations are evaluated at 6-month intervals. We report here growth, performance on the Bayley Scales of Infant Development (BSID) through 30 months of age, and tone and reflexes at 6 and 12 months. To date, subjects have had 816 follow-up visits, with subject retention greater than or equal to 73%. Cocaine-exposed children showed statistically lower mean weights and smaller mean head circumferences than control children over the 30-month follow-up period (p < or = .011). The percentage of children with abnormal tone and reflexes, however, was similar in the two groups at 6 and 12 months (p > or = .34). Mean BSID Mental Development Index (MDI) and Psychomotor Development Index scores did not differ between the two groups (p > or = .16), although both groups' scores decreased over time (p < .001). Of concern, both cocaine-exposed and control groups had lower mean MDI scores than those published for a group of children of higher socioeconomic status. We conclude that, in our cohort of children, low socioeconomic or minority status may have had a substantial influence on BSID scores whereas in utero drug exposure did not.

Use of a beta-agonist in ventilated, very-low-birth-weight babies: a longitudinal evaluation.

To determine if there is a specific postnatal (PNA) or postconceptional age (PCA) at which ventilated preterm infants respond to beta-agonists, we evaluated 15 infants with a mean gestational age of 26.5 +/- 1.5 weeks and mean birth weight of 0.89 +/- 0.23 kg who required mechanical ventilation at 10 days of age. Weekly pulmonary function testing (PFT) was performed before and 1 h after administration of albuterol. Taking the group as a whole, as well as individual babies, regression analysis showed no relationship between positive response and either PNA or PCA. Evaluation of individual infants, however, showed that some consistently responded to beta-agonists whereas others did not. We recommend individual PFT to identify those infants who will benefit from use of beta-agonists.

Avoiding the risk of aspiration in intubated infants.

Aspiration is a potential problem in intubated infants who are fed enterally. In this prospective study, intubated preterm infants were fed orogastrically or oroduodenally. Aspiration was assessed by examining endotracheal aspirates for evidence of blue-colored dye. None of the babies had blue-colored endotracheal secretions when fed by either route. Heart and respiratory rates, blood pressure, and transcutaneous oxygen and carbon dioxide measurements were recorded at each interval of the study. There were no significant differences from baseline for these measurements. These findings indicate that there is no significant aspiration in intubated preterm infants who are fed by the orogastric or the oroduodenal route.