Accelerated removal of antibody-coated red blood cells from the circulation is accurately tracked by a biotin label.

BACKGROUND: Safe, accurate methods to reliably measure circulating red blood cell (RBC) kinetics are critical tools to investigate pathophysiology and therapy of anemia, including hemolytic anemias. This study documents the ability of a method using biotin-labeled RBCs (BioRBCs) to measure RBC survival (RCS) shortened by coating with a highly purified monomeric immunoglobulin G antibody to D antigen. STUDY DESIGN AND METHODS: Autologous RBCs from 10 healthy D+ subjects were labeled with either biotin or (51) Cr (reference method), coated (opsonized) either lightly (n = 4) or heavily (n = 6) with anti-D, and transfused. RCS was determined for BioRBCs and for (51) Cr independently as assessed by three variables: 1) posttransfusion recovery at 24 hours (PTR(24) ) for short-term RCS; 2) time to 50% decrease of the label (T(50) ), and 3) mean potential life span (MPL) for long-term RCS. RESULTS: BioRBCs tracked both normal and shortened RCS accurately relative to (51) Cr. For lightly coated RBCs, mean PTR(24) , T(50) , and MPL results were not different between BioRBCs and (51) Cr. For heavily coated RBCs, both short-term and long-term RCS were shortened by approximately 17 and 50%, respectively. Mean PTR(24) by BioRBCs (84 ± 18%) was not different from (51) Cr (81 ± 10%); mean T(50) by BioRBCs (23 ± 17 days) was not different from (51) Cr (22 ± 18 days). CONCLUSION: RCS shortened by coating with anti-D can be accurately measured by BioRBCs. We speculate that BioRBCs will be useful for studying RCS in conditions involving accelerated removal of RBCs including allo- and autoimmune hemolytic anemias.

Red blood cell (RBC) volume can be independently determined in vivo in humans using RBCs labeled at different densities of biotin.

BACKGROUND: Anemia is a serious problem in critically ill neonates. To investigate the pathophysiology of anemia and responses to red blood cell (RBC) transfusions and erythropoietin therapy, repeated measurement of red blood cell volume (RCV) and blood volume is useful. To extend our previous sheep study in which RBCs were labeled at four different biotin densities, we assessed the validity of this multidensity method for in vivo measurement of circulating RCV in humans. STUDY DESIGN AND METHODS: In eight healthy adults, autologous RBCs were biotinylated at each of four biotin densities (6, 18, 54, and 162 µg biotinylation reagent/mL RBC), mixed, and infused intravenously; blood was sampled at 10, 20, and 60 minutes. At each time, RCV was calculated from dilution of individual RBC populations enumerated by flow cytometry. RCV measurements from the population of RBCs biotinylated at 6 µg/mL were chosen as the reference values because this density had been previously validated against the 51Cr method in vitro and in vivo in humans. RESULTS: Values for RCVs were not significantly different among the four densities of biotinylated RBCs at any of the three time points and did not change over 60 minutes. CONCLUSIONS: These studies provide evidence that four densities of biotinylated RBCs can be used in vivo for simultaneous, independent, accurate measurements of RCV in humans. We speculate that this method will also be useful for repeated measurement of RCV and blood volume in infants and other patient populations in whom radioactive labels should be avoided.

Red blood cell (RBC) volume can be independently determined in vivo in the sheep using ovine RBCs labeled at different densities of biotin.

BACKGROUND: To investigate the pathophysiology of anemia and responses to red blood cell (RBC) transfusions and erythropoietin, repeated measurement of the circulating red blood cell volume (RCV) would be useful. Ovine erythropoiesis is similar to human erythropoiesis. Accordingly, a method for measuring RCV using either human or sheep RBCs labeled at different biotin densities has been previously validated in vitro. Here preclinical studies validating this method for in vivo measurement of circulating RCV in sheep are reported. STUDY DESIGN AND METHODS: For each sheep, autologous RBCs were biotinylated were at four discrete densities (12, 24, 48, and 96µg biotinylation reagent/mL RBCs). The densities were mixed and infused intravenously. Blood was sampled five times over 1 hour beginning at 4 minutes. RCV values were determined based on dilution of each population of biotinylated RBCs and by the [(14) C]cyanate method. RESULTS: There was no difference among RCVs measured at all densities through 16 minutes; however, by 60 minutes, RBCs biotinylated at the highest density overestimated RCV by 7.6%. RCV values increased 41% over the hour, consistent with equilibration with a pool of RBCs sequestered in the spleen. RCV by the [(14) C]cyanate method paralleled results by the biotin method but averaged 8% greater. CONCLUSIONS: These studies provide evidence that all four densities of biotinylated RBCs can be used in sheep to simultaneously and independently determine RCV. We speculate that the multidensity biotinylation method will be useful both for multiple simultaneous measurements and for repeated measurement of circulating RCV and blood volume in humans.

Red blood cell volume can be independently determined in vitro using sheep and human red blood cells labeled at different densities of biotin.

BACKGROUND: The development of valid methods for repeatedly measuring red blood cell (RBC) volume (RCV) in the same individual would be useful in furthering understanding of the physiology and pathophysiology of the pregnant woman, fetus, and infant under a variety of conditions. STUDY DESIGN AND METHODS: Small volumes (5 to 100 mL) of either sheep or human blood were used to test the hypothesis that there is no significant difference in RCV and blood volume determined in vitro using as many as five populations of RBCs labeled at distinct biotin densities. By varying the mass of biotinylating reagent, the density of biotin on the surface of RBCs was incrementally increased to produce discrete populations as assessed by flow cytometric enumeration. Calculation of RCV for each biotin-labeled RBC population was based on the dilution principle. RESULTS: All biotin densities, except the most densely labeled, where variance was the greatest, accurately quantitated the in vitro blood volume to within 10 percent of the correct value. There was no bias of either overestimation or underestimation in the determination of the blood volume using either sheep or human RBCs. CONCLUSION: These in vitro results provide evidence that the multidensity biotin labeling method is sufficiently accurate to utilize in vivo for repeated determination of circulating RCV and blood volume.

Red cell volume can be accurately determined in sheep using a nonradioactive biotin label.

The sheep has served as an informative animal model for investigation of human fetal and newborn erythropoiesis and red blood cell (RBC) kinetics. We previously validated the permanent label (14C)cyanate for measuring red cell volume (RCV) in sheep. Here, we validate biotin labeling of RBCs as a nonradioactive method for measuring RCV in sheep with the anticipation that it can be applied in studies of human infants. The RCV was determined simultaneously using two techniques for quantitation of the biotin label. The first one quantified total blood concentration of biotin label on biotin-labeled RBCs using (125I)streptavidin. The second one enumerated biotin-labeled RBCs by flow cytometry after incubation with fluorescein-conjugated avidin. RCV measurements made using the two biotin quantitation techniques were validated against both (14C)cyanate and 51Cr as reference methods. Both biotin techniques produced RCV values that agreed well with the reference methods and with each other, producing correlation coefficients averaging >or =0.93. Sequential repetitive measurements in the same animal also agreed with the (14C)cyanate method and each other (average difference <10%). These results establish biotin-labeled RBCs as an accurate method for performing RCV measurements in sheep. This biotin method can be applied in studies that model neonatal erythropoiesis.

Sleep duration and body mass index in a rural population.

BACKGROUND: A growing body of epidemiological evidence suggests an association between short sleep duration and obesity. Recently, potential hormonal links have been observed that may account for the relationship. The possible connection between sleep duration and body mass index (BMI) has not been explored in rural populations. Rural populations are of interest because obesity rates are high and lifestyle patterns of nutrition, physical activity, work hours, and sleep may differ from those in urban and suburban populations. We conducted this study to determine whether short sleep duration is related to BMI and obesity in a rural population in southeast Iowa. METHODS: We conducted a cross-sectional analysis of data collected in the Keokuk County Rural Health Cohort Study, 1999-2004. Study participants were from a population-based sample consisting of 990 employed adults in a rural community in southeastern Iowa. The main outcome measure was BMI. Multiple linear regression modeling was used to adjust for potential confounding variables. RESULTS: Self-reported sleep duration on weeknights was negatively correlated (beta = -0.42; 95% confidence interval, -0.77 to -0.07) with higher BMI after adjusting for sex, age, educational achievement, physical job demand, household income, depressive symptoms, marital status, alcohol consumption, and snoring. CONCLUSION: These data support an association between short sleep duration and higher BMI in this rural population, which is consistent with the relationship found in other settings.

Workforce Characteristics and Attitudes Regarding Participation in Worksite Wellness Programs.

PURPOSE: To estimate workforce participation characteristics and employees' attitudes regarding participation in workplace wellness programs. DESIGN: Data from a statewide stratified random sample were used to compare small (<50 employees) and larger (50+ employees) workplaces to estimate participation in screening programs and likelihood of participation in workplace wellness programs. SETTING: A telephone survey of employed Iowans registered to vote. SUBJECTS: Surveyed were 1171 employed Iowans registered to vote, ages 18 to 65. MEASURE: Among questionnaire survey modules were items from the Wellness Council of America Employee Needs and Interest Survey, the U.S. Census Bureau for employment documentation, and the World Health Organization Health and Work Performance Questionnaire for assessment of sickness absenteeism and presenteeism. ANALYSIS: Prevalence of participation in screening and wellness programs was analyzed by employment size and levels of likeliness to participate, and multivariable analyses of employee baseline characteristics regarding participation in screening programs and likelihood of participation in wellness programs was presented as top and bottom quartiles. RESULTS: Those employed in smaller workplaces participated less often in screening programs. Multivariable models identified male gender and those with an abnormal body mass index were associated with nonparticipation, while having a primary care physician was associated with participation. Very few items showed significant statistical difference in willingness to participate. CONCLUSION: Workforce characteristics and access to health care may influence participation in screening and wellness programs. Employment size is not a determining factor for willingness to participate in wellness programs.

Asthma and farm exposures in a cohort of rural Iowa children.

Epidemiologic studies of farm children are of international interest because farm children are less often atopic, have less allergic disease, and often have less asthma than do nonfarm children--findings consistent with the hygiene hypothesis. We studied a cohort of rural Iowa children to determine the association between farm and other environmental risk factors with four asthma outcomes: doctor-diagnosed asthma, doctor-diagnosed asthma/medication for wheeze, current wheeze, and cough with exercise. Doctor-diagnosed asthma prevalence was 12%, but at least one of these four health outcomes was found in more than a third of the cohort. Multivariable models of the four health outcomes found independent associations between male sex (three asthma outcomes), age (three asthma outcomes), a personal history of allergies (four asthma outcomes), family history of allergic disease (two asthma outcomes), premature birth (one asthma outcome), early respiratory infection (three asthma outcomes), high-risk birth (two asthma outcomes), and farm exposure to raising swine and adding antibiotics to feed (two asthma outcomes). The high prevalence of rural childhood asthma and asthma symptoms underscores the need for asthma screening programs and improved asthma diagnosis and treatment. The high prevalence of asthma health outcomes among farm children living on farms that raise swine (44.1%, p = 0.01) and raise swine and add antibiotics to feed (55.8%, p = 0.013), despite lower rates of atopy and personal histories of allergy, suggests the need for awareness and prevention measures and more population-based studies to further assess environmental and genetic determinants of asthma among farm children.

Agricultural pesticide use, familial cancer, and risk of non-Hodgkin lymphoma.

To investigate whether the association between agricultural pesticide use and the risk of non-Hodgkin's lymphoma (NHL) is modified by a family history of hematopoietic cancer, including leukemia, myeloma, and lymphoma, we analyzed pooled data on white men from three population-based, case-control studies of NHL conducted in Iowa/Minnesota, Kansas, and Nebraska. Information on the agricultural use of insecticides, fungicides, and herbicides; a family history of cancer; and other risk factors was obtained by interviewing 973 cases and 2,853 controls or, if deceased, their next-of-kin (37% of cases, 43% of controls). The NHL risk was estimated by odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, state of residence, type of respondent, and use of hair dye. Compared to men with no family history of cancer, the ORs (95% CIs) of NHL was 1.5 (1.3-1.8) for men with a family history of nonhematopoietic cancer, and 2.7 (1.9-3.7) for those with a history of hematopoietic cancer among first-degree relatives. This positive association was noted for each group of NHL defined according to the Working Formulation, and was most pronounced for small lymphocytic NHL. Among direct respondents, farmers who used pesticides and had a positive family history of cancer or hematopoietic cancer were not at elevated risk of NHL, compared to nonfarmers who had no family cancer history. However, among proxy respondents, ORs were elevated for farmers who had a positive family history of hematopoietic cancer and used animal insecticides (OR = 4.6; 1.9-11.2), crop insecticides (OR = 4.7; 1.6-13.4), or herbicides (OR = 4.9; 1.7-14.2), although the interaction of family history of cancer and agricultural pesticide use was not statistically significant. In summary, the joint effects of the family cancer history and pesticide use were limited to proxy respondents with wide CIs and, thus, provide little evidence that a family history of cancer modifies the association of agricultural exposures with NHL.

Racial differences in factors that influence the willingness to participate in medical research studies.

PURPOSE: The relative absence of racial/ethnic minorities among medical research subjects is receiving considerable attention because of recent government mandates for their inclusion in all human subject research. We examined racial differences in the prevalence of sociocultural barriers as a possible explanation for the underrepresentation of African Americans in medical research studies. METHODS: During 1998-1999, a total of 198 residents of the Detroit Primary Metropolitan Statistical Area (PMSA) participated in a survey that examined impediments to participation in medical research studies. Chi square tests and logistic regression analyses were used to examine the association between race, issues related to trust of medical researchers, and the willingness to participate in medical research studies. RESULTS: Study results indicate that African Americans and whites differ in their willingness to participate in medical research. Racial differences in the willingness to participate in a medical research are primarily due to the lower level of trust of medical research among African Americans. African American respondents were also somewhat less willing to participate if they attribute high importance to the race of the doctor when seeking routine medical care, believed that minorities bear most of the risks of medical research, and if their knowledge of the Tuskegee Study resulted in less trust in medical researchers. CONCLUSION: These data reiterate the need for medical researchers to build trusting relationships with minority communities. Researchers can begin by acknowledging the previous medical abuse of minority research participants, discussing their specific plans to assure the protection of study participants, and explaining the need for the participation of racial/ethnic minorities including studies that specifically target or that are likely to result in disproportionate representation of racial/ethnic minorities among study participants.

Alcohol consumption, family history of hematolymphoproliferative cancer, and the risk of non-Hodgkin's lymphoma in men.

PURPOSE: To investigate the association between alcohol consumption and the risk of non-Hodgkin's lymphoma (NHL) and to examine whether the association is modified by a family history of hematolymphoproliferative cancer (HLPC). METHODS: Data on white men from two population-based case-control studies of NHL conducted in Iowa/Minnesota and Kansas were pooled for this analysis. Information on alcohol consumption, family history of HLPC, and other factors was obtained by interviewing 792 cases and 2193 controls or, if deceased, their next-of-kin. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There was no clear association between NHL and the use of alcohol, beer, hard liquor, or wine. The relationship, however, may differ according to a family history of HLPC. Alcohol use was not associated with the risk of NHL in men without a family history of HLPC (ORs = 0.8 and 0.9 for men consuming alcohol < or = median and > median, respectively), the presence of a family history in the absence of alcohol use was associated with a slightly increased risk (OR = 1.4; 95% CI 0.8-2.5), whereas risks of NHL among men with a positive family history were 2.1 (CI 1.0-4.7) for men consuming alcohol < or = median (13.7 g/day) and 2.8 (1.3-5.9) for men consuming alcohol greater than median. CONCLUSIONS: The present data found no clear association between alcohol consumption and the risk of NHL among men without a family history of HLPC, whereas alcohol intake was associated an elevated risk in men with a positive family history. The finding of effect modification of the alcohol-NHL association by a family history of HLPC is novel and requires confirmation.

Methodologic issues in a population-based health survey of Gulf War veterans.

This report describes the principal methods used in the development, conduct, and analysis of the research study "Health Assessment of Persian Gulf War Veterans from Iowa" (Iowa Gulf War Study). The methods presented include an outline of the organizational structure, study timeline, hypotheses, outcome definitions, and study design. Adhering to a strict timeline, the study protocol and instruments were developed, and a stratified sample of 3,695 military personnel (76% participation) was located and surveyed by structured telephone interview. The study tracked personnel from all service branches residing nationally and internationally, including those discharged from service. This study required development and implementation of methods appropriate to analysis of data collected in a complex sampling framework and methodological procedures to ensure scientific rigor in a highly public and politicized environment. Statistical analyses were conducted on a priori health outcomes and required development of methods to compute Cochran-Mantel-Haenszel adjusted rate differences. This environment facilitated rapid implementation, critique by scientific and public advisors, a high participation rate, and rapid publication.

Risk factors for animal-related injury among Iowa large-livestock farmers: a case-control study nested in the Agricultural Health Study.

CONTEXT: Although farmers are at risk for injuries from contact with large livestock, few previous studies have examined risk factors for animal-related injuries. PURPOSE: This case-control study, nested in the Agricultural Health Study, aimed to assess risk factors for animal-related injury among Iowa large-livestock farmers. METHODS: A screener questionnaire sent to 6999 farmers identified 116 farmers with large livestock who had an animal-related injury requiring medical advice/treatment in the previous year. Several possible risk factors for injury were assessed by comparing these farmers with 342 farmers who had livestock but were not injured in the previous year. FINDINGS: A multiple logistic regression analysis showed significant associations between animal-related injury and the use of a hearing aid (odds ratio [OR] = 5.4 [95% CI, 1.6 to 18.0]), doctor-diagnosed arthritis or rheumatism (OR = 3.0 [95% CI, 1.7 to 5.2]), education beyond high school (OR = 1.8 [95% CI, 1.1 to 2.8]), and a younger age. Farmers engaged in off-farm work were less likely to sustain animal-related injuries (OR = 0.4 [95% CI, 0.2 to 0.8]). CONCLUSIONS: This is the first study to show associations between animal-related injury and a younger age, hearing difficulties, and doctor-diagnosed arthritis. Hearing loss and arthritis, which are more common among farmers than among other workers, may be particularly important risk factors to address in future preventive studies.

Chronic disease and injury in an agricultural county: The Keokuk County Rural Health Cohort Study.

The Keokuk County Rural Health Study (KCRHS) was designed as a 20-year, prospective cohort study focusing on chronic disease and injury in an agricultural southeastern Iowa county. The goals of the KCRHS are to prospectively describe, measure, and analyze prevalent rural and agriculturally related adverse health outcomes and their respective risk factors and to provide the basis for future community-based intervention programs to reduce disease and injury incidence. Methods of data collection included in-person interviews, medical screenings, and environmental assessments of homes and farms. All households studied were rural; comparisons were made among farm, rural nonfarm, and town households, between men and women, and between smokers and nonsmokers. The present paper reports selected adult baseline data from Round 1 of this study. Residents of farm households were somewhat younger and better educated than residents of rural nonfarm and town households; smoked less; were more likely to have ridden an all-terrain vehicle; and were more likely to report firearms in the home. Eighty-nine percent of the men and 66% of the women engaged in farming or did so in the past. Men more often reported hearing loss, were more often overweight and obese, more often reported an injury, less often reported asthma, and less often saw a medical practitioner. Women reported poorer emotional health and higher rates of depression symptoms. The KCRHS has identified several modifiable health outcomes and risk factors as candidates for further analysis and targets for community-based prevention and intervention programs.

Risk factors for machinery-related injury among Iowa farmers: a case-control study nested in the Agricultural Health Study.

Farm machinery is a major cause of injury morbidity and mortality among farmers. This case-control study assessed risk factors for machinery-related injuries among Iowa farmers. A screener questionnaire sent to 6,999 farmers in 1998 identified 205 farmers who had machinery-related injuries requiring medical advice/treatment in the previous year. Possible risk factors for injury were assessed among these farmers compared with 473 farmers with no injury in the previous year. A multiple logistic regression analysis showed significant associations between machinery-related injury and hours per week spent on farmwork (OR = 2.02; 95% CI 1.38-2.94), fewer years of farming experience (OR = 1.79; 95% CI 1.14-2.79), wearing a hearing aid (OR = 4.37; 95% CI 1.55-12.25), and a high CAGE score suggesting problem drinking (OR = 2.49; 95% CI 1.00-6.19). This is the first study to show associations between machinery-related injury and hearing impairment, problem drinking, and fewer years of farming experience. These findings may be useful for future interventions to decrease injuries related to farm machinery.

The numbers game: evaluation of statistics by obstetrics & gynecology.

Statistical analysis has become integral to the planning, conduct, and reporting of modern medical research. Attention to the statistical aspects of manuscripts submitted to Obstetrics & Gynecology goes back approximately 40 years and the process used in their evaluation has evolved over that time. For the past 20 years, submissions with any type of statistics and being seriously considered for acceptance have routinely been reviewed by a Statistical Editor who judges the work on a number of statistical and design characteristics. Findings of the statistical design review (which has been done by one Statistical Editor over the entire 20-year period) are integrated into the editorial decision about acceptance. The statistical review generally leads to rejection of approximately 16-25% of manuscripts and in a larger proportion, it identifies less serious problems, the correction of which improves the final product.

Employment status matters: a statewide survey of quality-of-life, prevention behaviors, and absenteeism and presenteeism.

OBJECTIVE: To estimate quality-of-life (QoL), primary care, health insurance, prevention behaviors, absenteeism, and presenteeism in a statewide sample of the unemployed, self-employed, and organizationally employed. METHODS: A statewide survey of 1602 Iowans included items from the Centers for Disease Control and Prevention QoL and Behavioral Risk Factor Surveillance System Survey prevention behavior questionnaires used to assess employee well-being; their indicator results are related to World Health Organization's Health and Work Performance Questionnaire-derived absenteeism and presenteeism scores. RESULTS: The unemployed exhibited poorer QoL and prevention behaviors; the self-employed exhibited many better QoL scores due largely to better prevention behaviors than those employed by organizations. Higher QoL measures and more prevention behaviors are associated with lower absenteeism and lower presenteeism. CONCLUSIONS: Employment status is related to measures of well-being, which are also associated with absenteeism and presenteeism.

At what age should children engage in agricultural tasks?

PURPOSE: We compared parents' perceived-as-appropriate ages with actual-performance ages for their children engaging in selected agricultural tasks or practices, and we examined the factors associated with age discrepancy. METHODS: We analyzed data from the Keokuk County Rural Health Study collected among parents of children age 17 or younger. Parents were interviewed separately regarding the age of their children's involvement in 14 selected agricultural tasks and their opinions about appropriate age of involvement. FINDINGS: Of the 264 families included, 86.5% with a son and 69.8% with a daughter reported having children involved in at least 1 of 14 selected agricultural tasks. The average actual-performance ages for children to be involved in any of the tasks were younger than those that parents perceived appropriate. Furthermore, in 6 of the 9 North American Guidelines for Children's Agricultural Tasks (NAGCAT) that we assessed, parents' perceived-as-appropriate ages were younger than minimum ages recommended by the NAGCAT. Driving an all-terrain vehicle (ATV) was the most common task with actual-performance age younger than the NAGCAT-recommended age; 53.0% of boys (n = 106) and 36.1% of girls (n = 61) did so under the recommended age. Boys and children who live on a farm, or whose parents have been or are farmers, were significantly more likely to perform agricultural tasks at earlier ages. CONCLUSIONS: Our results suggest farm parents and other rural stakeholders need to be better educated and encouraged to follow the NAGCAT guidelines, and that multilevel interventions need to be developed to ensure protection of children from agricultural injury and death.

Challenges of conducting a large rural prospective population-based cohort study: the Keokuk County Rural Health Study.

The Keokuk County Rural Health Study (KCRHS) is a population-based, prospective study of health status and environmental exposures of a large stratified random sample of residents in one rural Iowa county. The study focuses on injury and respiratory disease and monitors health care delivery, geriatric health, mental health, and other health outcomes, as well as behavioral risk factors for disease and injury. Injury and disease prevalence is investigated in relation to occupational, agricultural, and other environmental exposures. The KCRHS enrolled 1004 families in Round 1 (1994 to 1998) and 1002 families in Round 2 (1999 to 2004). Participants range in age from newborn to 98 years of age and are about equally divided between males and females. The families live in farm, rural nonfarm, and town households, representing men, women, and children, the elderly, farmers, and nonfarmers. The KCRHS is currently in Round 3 (2006-2011). Although the sample is stratified by residence type, the entire county is, by definition, rural, because the largest town has fewer than 2500 residents. Using the Keokuk County Rural Health Study as an example, this paper describes the methodological challenges faced in conducting a large rural prospective population-based cohort study. Some of these challenges are inherent in any large cohort study; others are unique to rural cohort studies. Topics considered include planning the study, developing the protocol, sampling, recruiting and tracking subjects, data collection and management, sustaining funding, relating to the community, and sharing data.

A randomized clinical trial comparing immediate versus delayed clamping of the umbilical cord in preterm infants: short-term clinical and laboratory endpoints.

BACKGROUND: Most neonates less than 1.0 kg birth weight need red blood cell (RBC) transfusions. Delayed clamping of the umbilical cord 1 minute after delivery transfuses the neonate with autologous placental blood to expand blood volume and provide 60 percent more RBCs than after immediate clamping. This study compared hematologic and clinical effects of delayed versus immediate cord clamping. STUDY DESIGN AND METHODS: After parental consent, neonates not more than 36 weeks' gestation were randomly assigned to cord clamping immediately or at 1 minute after delivery. The primary endpoint was an increase in RBC volume/mass, per biotin labeling, after delayed clamping. Secondary endpoints were multiple clinical and laboratory comparisons over the first 28 days including Score for Neonatal Acute Physiology (SNAP). RESULTS: Problems with delayed clamping techniques prevented study of neonates of less than 30 weeks' gestation, and 105 neonates 30 to 36 weeks are reported. Circulating RBC volume/mass increased (p = 0.04) and weekly hematocrit (Hct) values were higher (p < 0.005) after delayed clamping. Higher Hct values did not lead to fewer RBC transfusions (p > or = 0.70). Apgar scores after birth and daily SNAP scores were not significantly different (p > or = 0.22). Requirements for mechanical ventilation with oxygen were similar. More (p = 0.03) neonates needed phototherapy after delayed clamping, but initial bilirubin levels and extent of phototherapy did not differ. CONCLUSIONS: Although a 1-minute delay in cord clamping significantly increased RBC volume/mass and Hct, clinical benefits were modest. Clinically significant adverse effects were not detected. Consider a 1-minute delay in cord clamping to increase RBC volume/mass and RBC iron, for neonates 30 to 36 weeks' gestation, who do not need immediate resuscitation.