Michael J. Corwin

The Effect of Chronic or Intermittent Hypoxia on Cognition in Childhood: A Review of the Evidence

Objective. A review of the evidence concerning the effect of chronic or intermittent hypoxia on cognition in childhood was performed by using both a systematic review of the literature and critical appraisal criteria of causality. Because of the significant impact of behavioral disorders such as attention-deficit/hyperactivity disorder on certain cognitive functions as well as academic achievement, the review also included articles that addressed behavioral outcomes. Methods. Both direct and indirect evidence were collected. A structured Medline search was conducted from the years 1966-2000 by using the OVID interface. Both English- and non–English-language citations were included. Significant articles identified by the reviewers up to 2003 were also included. To be included as direct evidence, an article needed to be an original report in a peer-reviewed journal with data on cognitive, behavioral, or academic outcomes in children up to 14 years old, with clinical conditions likely to be associated with exposure to chronic or intermittent hypoxia. Indirect evidence from other reviews and publications in closely related fields, including experimental studies in adults, was used to help formulate conclusions. Two reviewers screened abstracts and titles. Each article included as direct evidence received a structured evaluation by 2 reviewers. Adjudication of differences was performed by a group of 2 reviewers and a research consultant. After this review, tables of evidence were constructed that were used as the basis for group discussion and consensus development. Indirect evidence assigned by topic to specific reviewers was also presented as part of this process. A formal procedure was used to rank the studies by design strength. The critical appraisal criteria for causation described in Evidence Based Pediatrics and Child Health (Moyer V, Elliott E, Davis R, et al, eds. London, United Kingdom: BMJ Books; 2000:46–55) were used to develop consensus on causality. Results. A total of 788 literature citations were screened. For the final analysis, 55 articles met the criteria for inclusion in the direct evidence. Of these, 43 (78.2%) reported an adverse effect. Of the 37 controlled studies, 31 (83.8%) reported an adverse effect. Adverse effects were noted at every level of arterial oxygen saturation and for exposure at every age level except for premature newborns. The studies were classified into 5 clinical categories: congenital heart disease (CHD), sleep-disordered breathing (SDB), asthma, chronic ventilatory impairment, and respiratory instability in infants. Two of these categories, CHD and SDB, which accounted for 42 (76.4%) of the included articles, fulfilled the Evidence Based Pediatrics and Child Health criteria for causation. The indirect evidence included 8 reviews, 1 meta-analysis, and 10 original reports covering the fields of adult anoxia, animal research, SDB in adults, natural and experimental high-altitude studies, perinatal hypoxic-ischemic encephalopathy, anemia, and carbon-monoxide poisoning. The studies of high-altitude and carbon-monoxide poisoning provided evidence for causality. Conclusions. Adverse impacts of chronic or intermittent hypoxia on development, behavior, and academic achievement have been reported in many well-designed and controlled studies in children with CHD and SDB as well as in a variety of experimental studies in adults. This should be taken into account in any situation that may expose children to hypoxia. Because adverse effects have been noted at even mild levels of oxygen desaturation, future research should include precisely defined data on exposure to all levels of desaturation.

Efficacy of recombinant human erythropoietin in the critically ill patient: a randomized, double-blind, placebo-controlled trial.

ObjectiveTo determine whether the administration of recombinant human erythropoietin (rHuEPO) to critically ill patients in the intensive care unit (ICU) would reduce the number of red blood cell (RBC) transfusions required. DesignA prospective, randomized, double-blind, placebo- controlled, multicenter trial. SettingICUs at three academic tertiary care medical centers. PatientsA total of 160 patients who were admitted to the ICU and met the eligibility criteria were enrolled in the study (80 into the rHuEPO group; 80 into the placebo group). InterventionsPatients were randomized to receive either rHuEPO or placebo. The study drug (300 units/kg of rHuEPO or placebo) was administered by subcutaneous injection beginning ICU day 3 and continuing daily for a total of 5 days (until ICU day 7). The subsequent dosing schedule was every other day to achieve a hematocrit (Hct) concentration of >38%. The study drug was given for a minimum of 2 wks or until ICU discharge (for subjects with ICU lengths of stay >2 wks) up to a total of 6 wks (42 days) postrandomization. Measurements and Main ResultsThe cumulative number of units of RBCs transfused was significantly less in the rHuEPO group than in the placebo group (p < .002, Kolmogorov-Smirnov test). The rHuEPO group was transfused with a total of 166 units of RBCs vs. 305 units of RBCs transfused in the placebo group. The final Hct concentration of the rHuEPO patients was significantly greater than the final Hct concentration of placebo patients (35.1 ± 5.6 vs. 31.6 ± 4.1;p < .01, respectively). A total of 45% of patients in the rHuEPO group received a blood transfusion between days 8 and 42 or died before study day 42 compared with 55% of patients in the placebo group (relative risk, 0.8; 95% confidence interval, 0.6, 1.1). There were no significant differences between the two groups either in mortality or in the frequency of adverse events. ConclusionsThe administration of rHuEPO to critically ill patients is effective in raising their Hct concentrations and in reducing the total number of units of RBCs they require. (Crit Care Med 1999; 27:2346–2350)

Familial Aggregation of Low Birth Weight among Whites and Blacks in the United States

BACKGROUND Studies have shown that the birth weight of infants is correlated with the birth weights of their siblings and their mothers. We investigated whether the birth weights of mothers and index children were jointly associated with the risk of low birth weight in the siblings of the index children. METHODS We used data on the live-birth cohort of the 1988 National Maternal and Infant Health Survey. The analysis included 1691 white and 1461 black mothers, each of whom had two or more live-born, singleton children. Multiple logistic regression with generalized-estimation equations was used to assess the risk of low birth weight among an index childs siblings. Four groups were studied: that in which neither the mother nor the index child had low birth weight (group 1), that in which only the mother had low birth weight (group 2), that in which only the index child had low birth weight (group 3), and that in which both the mother and the index child had low birth weight (group 4). There was adjustment for other maternal and infant covariates. RESULTS Among white siblings in groups 1, 2, 3, and 4, 3.6, 8.3, 21.2, and 38.9 percent, respectively, had low birth weight, as compared with 8.0, 19.0, 31.1, and 57.1 percent of black siblings. When group 1 was used as the reference group, the adjusted odds ratios (and 95 percent confidence intervals) for low birth weight in groups 2, 3, and 4 were 2.5 (1.4 to 4.3), 6.8 (4.7 to 9.8), and 15.4 (9.2 to 25.5), respectively, among white siblings and 2.6 (1.8 to 3.8), 4.7 (3.5 to 6.4), and 13.9 (9.2 to 20.9) among black siblings. These associations were consistently found for birth weights below 1500 g and those ranging from 1500 to 2499 g in both races and after stratification for the mothers age, parity, education, cigarette-smoking status, and weight and height before pregnancy and the infants sex. CONCLUSIONS Although selection and recall biases cannot be excluded with certainty, our data suggest a strong familial aggregation of low birth weight among both whites and blacks in the United States.

Trends and Factors Associated With Infant Bed Sharing, 1993-2010: The National Infant Sleep Position Study

IMPORTANCE A strong association between infant bed sharing and sudden infant death syndrome or unintentional sleep-related death in infants has been established. Occurrences of unintentional sleep-related deaths among infants appear to be increasing. OBJECTIVES To determine the trends and factors associated with infant bed sharing from 1993 through 2010, including the association of physician advice on bed sharing. DESIGN National Infant Sleep Position study conducted with annual telephone surveys. SETTING The 48 contiguous states. PARTICIPANTS Nighttime caregivers of infants born within 7 months of each survey administration. Approximately 1000 interviews were completed annually. MAIN OUTCOMES AND MEASURES Infant bed sharing as a usual practice. RESULTS Of 18 986 participants, 11.2% reported an infant sharing a bed as a usual practice. Bed sharing increased from 1993 (6.5%) to 2010 (13.5%). Although bed sharing increased significantly among white respondents from 1993 to 2000 (P < .001), the increase from 2001 to 2010 was not significant (P = .48). Black and Hispanic respondents reported an increase in bed sharing throughout the study period, with no difference between the earlier and later periods (P = .63 and P = .77, respectively). After accounting for the study year, factors associated with increase in infant bed sharing as a usual practice included maternal educational level of less than high school compared with college or greater (adjusted odds ratio, 1.42 [95% CI, 1.12-1.79]); black (3.47 [2.97-4.05]), Hispanic (1.33 [1.10-1.61]), and other (2.46 [2.03-2.97]) maternal race or ethnicity compared with white race; household income of less than

Frequency of bed sharing and its relationship to breastfeeding

20,000 (1.69 [1.44-1.99]) and

Trends and factors associated with infant sleeping position: the national infant sleep position study, 1993-2007

20,000 to

Barriers to Following the Supine Sleep Recommendation Among Mothers at Four Centers for the Women, Infants, and Children Program

50,000 (1.29 [1.14-1.45]) compared with greater than

Efficacy of recombinant human erythropoietin in critically ill patients admitted to a long-term acute care facility : A randomized, double-blind, placebo-controlled trial

50,000; living in the West (1.61 [1.38-1.88]) or the South (1.47 [1.30-1.66]) compared with the Midwest; infants younger than 8 weeks (1.45 [1.21-1.73]) or ages 8 to 15 weeks (1.31 [1.17-1.45]) compared with 16 weeks or older; and being born prematurely compared with full-term (1.41 [1.22-1.62]). Almost 46% of the participants reported talking to a physician about bed sharing. Compared with those who did not receive advice from a physician, those who reported their physicians had a negative attitude were less likely to have the infant share a bed (adjusted odds ratio, 0.66 [95% CI, 0.53-0.82]), whereas a neutral attitude was associated with increased bed sharing (1.38 [1.05-1.80]). CONCLUSIONS AND RELEVANCE Our finding of a continual increase in bed sharing throughout the study period among black and Hispanic infants suggests that the current American Academy of Pediatrics recommendation about bed sharing is not universally followed. The factors associated with infant bed sharing may be useful in evaluating the impact of a broad intervention to change behavior.

A Physioacoustic Model of the Infant Cry

ABSTRACT. Bed sharing has been promoted as facilitating breastfeeding but also may increase risks for sudden, unexpected infant deaths. This prospective cohort study was performed to determine the prevalence of adult and infant bed sharing and its association with maternal and infant characteristics. Demographic data were collected from 10,355 infant-mother pairs at birth hospitals in Eastern Massachusetts and Northwest Ohio, and follow-up data were collected at 1, 3, and 6 months by questionnaire. Associations with bed sharing were estimated using odds ratios and 95% confidence intervals from multiple logistic regression models while adjusting for confounding variables. At 1, 3, and 6 months, 22%, 14%, and 13% of infant-mother pairs shared a bed, respectively. On multivariate analysis, race/ethnicity and breastfeeding seemed to have the strongest association with bed sharing. These factors need to be considered in any comprehensive risk to benefit analysis of bed sharing.

Infant Sleep Location: Associated Maternal and Infant Characteristics with Sudden Infant Death Syndrome Prevention Recommendations

OBJECTIVE To determine trends and factors associated with choice of infant sleeping position. DESIGN Annual nationally representative telephone surveys from 1993 through 2007. SETTING Forty-eight contiguous states of the United States. PARTICIPANTS Nighttime caregivers of infants born within the last 7 months; approximately 1000 interviews were given each year. Main Outcome Measure Whether infant is usually placed supine to sleep. RESULTS For the 15-year period, supine sleep increased (P < .001) and prone sleep decreased (P < .001) for all infants, with no significant difference in trend by race. Since 2001, a plateau has been reached for all races. Factors associated with increased supine sleep between 1993 and 2007 included time, maternal race other than African American, higher maternal educational level, not living in Southern states, first-born infant, and full-term infant. The effect of these variables was reduced when variables related to maternal concerns about infant comfort, choking, and advice from physicians were taken into account. Between 2003 and 2007, there was no significant yearly increase in supine sleep. Choice of sleep position could be explained almost entirely by caregiver concern about comfort, choking, and advice. Race no longer was a significant predictor. CONCLUSIONS Since 2001, supine sleep has reached a plateau, and there continue to be racial disparities. There have been changes in factors associated with sleep position, and maternal attitudes about issues such as comfort and choking may account for much of the racial disparity in practice. To decrease sudden infant death syndrome rates, we must ensure that public health measures reach the populations at risk and include messages that address concerns about infant comfort and choking.