ABSTRACT.Objective. Moderate to heavy levels of prenatal alcohol exposure have been associated with alterations in child behavior, but limited data are available on adverse effects after low levels of exposure. The objective of this study was to evaluate the dose-response effect of prenatal alcohol exposure for adverse child behavior outcomes at 6 to 7 years of age.Methods. Beginning in 1986, women attending the urban university-based maternity clinic were routinely screened at their first prenatal visit for alcohol and drug use by trained research assistants from the Fetal Alcohol Research Center. All women reporting alcohol consumption at conception of at least 0.5 oz absolute alcohol/day and a 5% random sample of lower level drinkers and abstainers were invited to participate to be able to identify the associations between alcohol intake and child development. Maternal alcohol, cigarette, and illicit drug use were prospectively assessed during pregnancy and postnatally. The independent variable in this study, prenatal alcohol exposure, was computed as the average absolute alcohol intake (oz) per day across pregnancy. At each prenatal visit, mothers were interviewed about alcohol use during the previous 2 weeks. Quantities and types of alcohol consumed were converted to fluid ounces of absolute alcohol and averaged across visits to generate a summary measure of alcohol exposure throughout pregnancy. Alcohol was initially used as a dichotomous variable comparing children with no prenatal alcohol exposure to children with any exposure. To evaluate the effects of different levels of exposure, the average absolute alcohol intake was relatively arbitrarily categorized into no, low (>0 but <0.3 fl oz of absolute alcohol/day), and moderate/heavy (>0.3 fl oz of absolute alcohol/day) for the purpose of this study. Six years later, 665 families were contacted. Ninety-four percent agreed to testing. Exclusions included children who missed multiple test appointments, had major congenital malformations (other than fetal alcohol syndrome), possessed an IQ >2 standard deviations from the sample mean, or had incomplete data. The Achenbach Child Behavior Checklist (CBCL) was used to assess child behavior. The CBCL is a parent questionnaire applicable to children ages 4 to 16 years. It is widely used in the clinical assessment of children's behavior problems and has been extensively used in research. Eight syndrome scales are further grouped into Externalizing or undercontrolled (Aggressive and Delinquent) behavior and Internalizing or overcontrolled (Anxious/Depressed, Somatic Complaints, and Withdrawn) behaviors. Three syndromes (Social, Thought, and Attention Problems) fit neither group. Higher scores are associated with more problem behaviors. Research assistants who were trained and blinded to exposure status independently interviewed the child and caretaker. Data were collected on a broad range of control variables known to influence childhood behavior and/or to be associated with prenatal alcohol exposure. These included...

Background-Previous studies have suggested that the incidence of retinopathy is lower in preterm infants with exposure to reduced levels of oxygenation than in those exposed to higher levels of oxygenation. However, it is unclear what range of oxygen saturation is appropriate to minimize retinopathy without increasing adverse outcomes.Methods-We performed a randomized trial with a 2-by-2 factorial design to compare target ranges of oxygen saturation of 85 to 89% or 91 to 95% among 1316 infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. The primary outcome was a composite of severe retinopathy of prematurity (defined as the presence of threshold retinopathy, the need for surgical ophthalmologic intervention, or the use of bevacizumab), death before discharge from the hospital, or both. All infants were also randomly assigned to continuous positive airway pressure or intubation and surfactant.Results-The rates of severe retinopathy or death did not differ significantly between the loweroxygen-saturation group and the higher-oxygen-saturation group (28.3% and 32.1%, respectively; relative risk with lower oxygen saturation, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P = 0.21). Death before discharge occurred more frequently in the lower-oxygen-saturation group (in 19.9% of infants vs. 16.2%; relative risk, 1.27; 95% CI, 1.01 to 1.60; P = 0.04), whereas severe retinopathy among survivors occurred less often in this group (8.6% vs. 17.9%; relative risk, 0.52; 95% CI, 0.37 to 0.73; P<0.001). There were no significant differences in the rates of other adverse events.Conclusions-A lower target range of oxygenation (85 to 89%), as compared with a higher range (91 to 95%), did not significantly decrease the composite outcome of severe retinopathy or death, but it resulted in an increase in mortality and a substantial decrease in severe retinopathy among survivors. The increase in mortality is a major concern, since a lower target range of oxygen saturation is increasingly being advocated to prevent retinopathy of prematurity. (ClinicalTrials.gov number, NCT00233324.) Retinopathy of prematurity is an important cause of blindness and other visual disabilities in preterm infants. The incidence of retinopathy of prematurity was increased with exposure to unrestricted oxygen supplementation in preterm infants in randomized, controlled trials NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript performed in the 1950s. 1 In the 1960s, this increase resulted in the practice of restricting the fraction of inspired oxygen (FiO 2 ) to no more than 0.50, which was estimated to result in an excess of 16 deaths per case of blindness prevented. 2 More recent data suggest that levels of oxygen saturation previously thought to be at the upper end of the normal range may increase the risk of retinopathy of prematurity as compared with levels at the lower end of the normal range. [3][4][5] Oxygen toxicity may also increase the risk of death, 6,7 bronchopulmonary dysplasia, 8-...

We have reported feasibility, safety and ranges for rsSO₂ for a small number of preterm infants in the first 2 weeks of life.

Fetal and neonatal inflammation is associated with several morbidities of prematurity. Its relationship to retinopathy of prematurity (ROP) has not been investigated. Our objective was to determine the relationship between cytokine levels and ROP in the first 3 postnatal wks. Data for this study were derived from the NICHD Cytokine Study. Dried blood spots (DBS) were obtained from infants Ͻ1000 g on days 0 -1, 3 Ϯ 1, 7 Ϯ 2, 14 Ϯ 3, and 21 Ϯ 3. Infants were classified into three groups-no, mild, and severe ROP. Multiplex Luminex assay was used to quantify 20 cytokines. Temporal profiles of cytokines were evaluated using mixed-effects models after controlling for covariates. Of 1074 infants enrolled, 890 were examined for ROP and 877 included in the analysis. ROP was associated with several clinical characteristics on unadjusted analyses. Eight cytokines remained significantly different across ROP groups in adjusted analyses. IL-6 and IL-17 showed significant effects in early time periods (D0 -3); TGF-␤, brain-derived neurotrophic factor (BDNF), and regulated on activation, normal T cell expressed and secreted (RANTES) in later time periods (D7-21) and IL-18, C-reactive protein (CRP), and neurotrophin-4 (NT-4) in both early and later time periods. We conclude that perinatal inflammation may be involved in the pathogenesis of ROP. (Pediatr Res 67: 394-400, 2010) R etinopathy of prematurity (ROP), a vasoproliferative disorder of the developing retina, is a major cause of blindness in infancy. ROP is a biphasic disease consisting of an initial phase of blunted vascular growth followed by a second phase of vasoproliferation that is recognized on ophthalmoscopy 4 to 6 wks after birth. Angiogenesis, the fundamental process involved in retinal vascular development, is tightly regulated by a complex network of cytokines, extracellular matrix components, and growth factors the action of which varies in a time-dependent fashion. Although inflammatory cytokines have the ability to modulate angiogenesis, their role in triggering the dysregulated angiogenesis in ROP has not been investigated (1). Abbreviations: BDNF, brain-derived neurotrophic factor; CRP, C-reactive protein; FIRS, fetal inflammatory response syndrome; GM-CSF, granulocyte-macrophage colony-stimulating factor; IVH, intraventricular hemorrhage; MCP-1, monocyte chemoattractant protein-1; MIP-1␣, macrophage inflammatory protein-1␣; MMP-9, matrix metalloproteinase-9; NEC, necrotizing enterocolitis; NT-4, neurotrophin-4; PVL, periventricular leukomalacia; RANTES, regulated upon activation, normal T cell expressed and secreted; ROP, retinopathy of prematurity; sIL-6R, soluble IL-6 receptor 0031-3998/10/6704-0394 PEDIATRIC RESEARCH

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