Biomedical subjects

Mark A Klebanoff

Publications and source records attributed to Mark A Klebanoff.

At least 19 recordsLinked to original sources

PubMed2006

Maternal hormone levels and perinatal characteristics: implications for testicular cancer.

PURPOSE: It was hypothesized that the risk for testicular germ cell tumors (TGCTs) is associated with maternal hormone levels. To examine the hypothesis, some studies used perinatal factors as surrogates for hormone levels. To determine the validity of this assumption, hormone-perinatal factor relationships were examined in the Collaborative Perinatal Project. METHODS: Maternal estradiol, estriol, and testosterone levels in first- and third-trimester serum samples were correlated with perinatal factors in 300 mothers representative of populations at high (white Americans) or low (black Americans) risk for TGCT. RESULTS: For white participants, testosterone levels were associated negatively with maternal height (p < 0.01) and age (p = 0.02) and positively with maternal weight (p = 0.02) and body mass index (BMI; p < 0.01), whereas estradiol levels were associated negatively with height (p = 0.03) and positively with son's birth weight (p = 0.04). For black participants, estriol levels were associated negatively with maternal weight (p = 0.01), BMI (p = 0.02), and gestational age p < 0.01) and positively with son's birth weight (p < 0.01), length (p = 0.04), and head circumference (p = 0.03). CONCLUSIONS: These findings indicate that use of perinatal characteristics as surrogates for hormone levels should be limited to a specific ethnic group. For white men, previously reported associations of TGCT with maternal weight and age may be caused by lower maternal testosterone levels.

Black or African American↗

PubMed2006

Racial disparities in the association between birth weight in the term infant and blood pressure at age 7 years: results from the collaborative perinatal project.

BP has been inversely associated with birth weight in studies worldwide, but few studies have included black individuals. The US National Collaborative Perinatal Project followed 58,960 pregnant women and their resultant offspring for 7 yr. In this post hoc analysis, all term white or black children without kidney or heart disease were included (n = 29,710). The effect of birth weight and other risk factors on systolic (SBP) and diastolic BP (DBP) was evaluated at 7 yr. Mean birth weight and body mass index at 7 yr were slightly lower for black compared with white children (birth weight 3.14 +/- 0.48 versus 3.32 +/- 0.46 kg [P < 0.001]; body mass index 15.8 +/- 2.0 versus 16.3 +/- 2.0 [P < 0.001]). Compared with white mothers, black mothers were less likely to smoke (41 versus 52%), were more anemic (23 versus 7%), and were more likely to live in poverty (72 versus 39%). In linear regression, there was significant interaction between race and birth weight in predicting SBP (P = 0.002). In bivariate analysis, birth weight was positively associated with SBP (beta = 0.87) and DBP (beta = 1.14) in black children (P < 0.001) but not associated with either in white children. With maternal poverty, educational level, and anemia during pregnancy added to the model, birth weight remained a significant positive predictor of SBP (beta = 0.89, P < 0.001) in black but not in white children (beta = 0.02, P = 0.17). The association between birth weight and SBP differs between black and white children. The cause of intrauterine growth restriction-associated hypertension seems to be race sensitive; therefore, future studies of racial disparities in the "Barker hypothesis" may help in the understanding of the mechanism of fetal programming of hypertension.

Adult↗

PubMed2006

The association between intrauterine growth restriction in the full-term infant and high blood pressure at age 7 years: results from the Collaborative Perinatal Project.

OBJECTIVE: To use neonatal and placental anthropometry as proxy measures of intrauterine growth restriction (IUGR) and to relate these to blood pressure later in childhood. STUDY DESIGN: A post hoc analysis of full-term white and black children from the Collaborative Perinatal Project, followed from birth until age 7 years (n = 29,710). Blood pressure above the 90th percentile by gender and race was considered high blood pressure. Anthropometric measures at birth included birth weight, ponderal index (PI, birth weight/birth length(3)), head to chest circumference (HCC) ratio, and placental ratio percentage (PRP, placental weight(*)100/birth weight). RESULTS: Among anthropometric measures, PI, HCC, and birth weight were not associated with high systolic blood pressure at age 7 years, but PRP was. In multiple logistic regression, high systolic blood pressure and widened pulse pressure were both predicted by increased PRP [odds ratio (OR) 1.03 and 1.04, P < 0.001] but not by birth weight, when adjusted for gender, race, and maternal education. High diastolic blood pressure was weakly predicted by birth weight (OR 1.10, P = 0.05) but not by PRP. CONCLUSIONS: PRP is associated with an increased risk for high systolic blood pressure and pulse pressure later in childhood, whereas birth weight, PI, and HCC are not. The proportion of placental weight to birth weight is a useful marker of IUGR for studying the developmental origins of adult disease hypothesis.

Adult↗

PubMed2006

Prenatal exposure to 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene (p,p'-DDE) in relation to child growth.

OBJECTIVE: To examine the relation between prenatal 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) exposure (a metabolite of the insecticide DDT) and child growth during the first 7 years of life. Design Prospective cohort study. Participants 1,712 children born between 1959 and 1966 with measured p,p'-DDE concentrations in their mother's serum samples from pregnancy. Setting Multicenter US Collaborative Perinatal Project (CPP). RESULTS: The highest prenatal concentrations of p,p'-DDE (>or=60 microg/l), as compared with the lowest (<15 microg/l), were associated with decreased height at age 1 year [adjusted coefficient (SE) = -0.72 cm (0.37), n = 1,540], 4 years [-1.14 cm (0.56), n = 1,289], and 7 years [-2.19 (0.46), n = 1,371]. Among subjects in lower categories of exposure no association was observed. CONCLUSIONS: The findings suggest that high prenatal exposure to p,p'-DDE decreases height in children. Impaired growth may be a general indicator of toxicity and suggests that specific organ systems (e.g. endocrine) could be affected.

Adult↗

PubMed2006

Risk factors for cryptorchism among populations at differing risks of testicular cancer.

BACKGROUND: Cryptorchism is strongly associated with the development of testicular germ cell tumours (TGCTs), possibly owing to a common aetiology. However, while TGCT incidence varies greatly between white and black men, little variability has been reported between the two groups in cryptorchism prevalence. This may suggest that cryptorchism risk factors differ by ethnicity. METHODS: To examine this hypothesis, a prospective analysis was conducted among black and white participants in the US Collaborative Perinatal Project. White participants included 238 cryptorchid sons and 12,296 non-cryptorchid sons, while black participants included 188 cryptorchid sons and 11,942 non-cryptorchid sons. RESULTS: While cryptorchism was significantly more common among white sons (1.90% vs 1.55%; P = 0.04), the difference was incompatible with the 5-fold difference in TGCT rates. The principal maternal risk factors among white sons were age (P = 0.03), hypertension/proteinuria (P = 0.006), and length of time to become pregnant (P = 0.055), while major maternal risk factors among black sons were age (P = 0.06), height (P = 0.007), weight (P = 0.06), and radiation exposure (P = 0.02). Only maternal height, however, had a different relationship with risk among black and white sons. Neonatal associations with risk (shorter gestational age, lower birthweight, shorter length) were similar in the two groups. CONCLUSIONS: These results do not support the hypothesis that the risk factors for cryptorchism vary dramatically by ethnicity but may suggest that cryptorchism is not as closely linked to TGCT among black men as among white men.

Birth Weight↗

PubMed2006

The association of psychosocial stress and bacterial vaginosis in a longitudinal cohort.

OBJECTIVE: The purpose of this study was to assess the association of psychosocial stress with bacterial vaginosis in a longitudinal sample of nonpregnant women. STUDY DESIGN: A 1-year prospective longitudinal design was used. Nonpregnant women (n = 3614) aged 15 to 44 years were recruited at routine health care visits. Assessments were conducted quarterly for 1 year and included a standardized pelvic examination, an assessment of clinical symptoms, and an extensive self-report interview. RESULTS: Psychosocial stress was associated with overall prevalence of (adjusted odds ratio, 1.10; 95% CI, 1.01-1.20) and an increased incidence of (adjusted odds ratio, 1.29; 95% CI, 1.12-1.48) bacterial vaginosis. The association between stress and bacterial vaginosis incidence was not changed appreciably by the control for behavioral and demographic characteristics and was magnified (odds ratio, 2.05; 95% CI, 1.15-3.66) in a case-crossover analysis. CONCLUSION: Increased psychosocial stress is associated with greater bacterial vaginosis prevalence and incidence independent of other risk factors.

Adolescent↗

PubMed2006

Midpregnancy genitourinary tract infection with Chlamydia trachomatis: association with subsequent preterm delivery in women with bacterial vaginosis and Trichomonas vaginalis.

OBJECTIVE: The objective of the study was to estimate whether midpregnancy genitourinary tract infection with Chlamydia trachomatis is associated with an increased risk of subsequent preterm delivery. STUDY DESIGN: Infection with C. trachomatis was determined using a ligase chain reaction assay (performed in batch after delivery) of voided urine samples collected at the randomization visit (16(0/7) to 23(6/7) weeks' gestation) and the follow-up visit (24(0/7) to 29(6/7) weeks) among 2470 gravide women with bacterial vaginosis or Trichomonas vaginalis infection enrolled in 2 multicenter randomized antibiotic treatment trials (metronidazole versus. placebo). RESULTS: The overall prevalence of genitourinary tract C. trachomatis infection at both visits was 10%. Preterm delivery less than 37 weeks' or less than 35 weeks' gestational age was not associated with the presence or absence of C. trachomatis infection at either the randomization (less than 37 weeks: 14% versus 13%, P=.58; less than 35 weeks: 6.4% versus 5.5%, P=.55) or the follow-up visit (less than 37 weeks: 13% versus 11%, P=.33; less than 35 weeks: 4.4% versus 3.7, P=.62). Treatment with an antibiotic effective against chlamydia infection was not associated with a statistically significant difference in preterm delivery. CONCLUSION: In this secondary analysis, midtrimester chlamydia infection was not associated with an increased risk of preterm birth. Treatment of chlamydia was not associated with a decreased frequency of preterm birth.

Anti-Bacterial Agents↗

PubMed2006

Aspirin use and miscarriage risk.

BACKGROUND: Recent research has found nonsteroidal antiinflammatory drugs, including aspirin, to increase the risk of miscarriage. The objective of the present study was to evaluate the association between aspirin use and miscarriage. METHODS: We conducted a case-control study using data from the Collaborative Perinatal Project. This prospective cohort study recruited approximately 54,000 pregnant women at 12 sites in the United States from 1959 to 1965. Women who had miscarriages (n = 542) were matched by clinic and time in pregnancy when they came under observation to 2587 women who had live births. Participants were interviewed at each prenatal visit. Data on aspirin use were collected prospectively by in-person interviews and medical record review. Aspirin use among controls was considered only for the duration of pregnancy when the matched cases remained pregnant. The outcome of interest was miscarriage, defined as spontaneous pregnancy loss at less than 140 days from the last menstrual period. RESULTS: Twenty-nine percent of cases and 34% of controls used aspirin during pregnancy. Aspirin use was not associated with an increased risk of miscarriage. Adjusted odds ratios ranged from 0.64 to 0.92 (95% confidence intervals = 0.48-1.38) for individual lunar months and combinations of lunar months. CONCLUSIONS: Use of aspirin during pregnancy is not associated with an increased risk of miscarriage.

Abortion, Spontaneous↗

PubMed2006

A pilot study of vaginal flora changes with randomization to cessation of douching.

OBJECTIVES: The objectives of this study were to determine whether women who douche regularly would enter a randomized trial of douching cessation or continuation, whether they would adhere to the assigned behavior, and whether there was a dramatic impact on vaginal flora. GOAL: The goal of this study was to determine the feasibility of a large, definitive trial of douching cessation. STUDY DESIGN: Women who douched at least weekly and who had either bacterial vaginosis or normal flora by Gram stain were assigned at random either to continue douching or to stop for 8 weeks. Vaginal Gram stains were obtained every 7 days from each woman. RESULTS: Forty-eight women were randomized. Those assigned to continue reported douching during 77% of study weeks; those assigned to stop denied douching in 94% of weeks. No dramatic differences in flora were observed between women in the continue versus stop groups. CONCLUSION: A large randomized trial of douching cessation is feasible.

Bacteria↗

PubMed2006

Is conception delay a risk factor for reduced gestation or birthweight?

Previous studies have suggested an association between delays in conception and adverse perinatal outcomes, specifically, low birthweight and preterm birth. We investigated the relationship between conception delay (defined as >6 months to become pregnant) and three perinatal outcomes: low birthweight (LBW; <2500 g), preterm birth (PTB; <37 weeks), and small-for-gestational-age (SGA; <10th percentile weight for given gestational age) using data from the Collaborative Perinatal Project. The study cohort was limited to pregnancies with a known time-to-pregnancy (n = 8465; 15%). Generalised estimating equations were used to estimate odds ratios (OR) and 95% confidence intervals [CI] for risk of adverse perinatal outcomes accounting for the clustering of pregnancy outcomes for women with more than one pregnancy. After adjusting for confounders, all ORs were close to the null (LBW, OR = 1.01; 95% CI = 0.86, 1.20), (PTB, OR = 1.10; 95% CI = 0.95, 1.27), (SGA, OR = 1.06; 95% CI = 0.91, 1.25). Thus, we found no evidence to support an adverse relationship between conception delay and decrements in gestation or birthweight among this select sample of fertile women, even after varying the cut-point for defining conception delay.

Adult↗

PubMed2005

Maternal smoking during pregnancy in relation to child overweight: follow-up to age 8 years.

BACKGROUND: Data from several studies indicate that children of mothers who smoked during pregnancy may be at a risk of overweight compared with children of non-smoking mothers. The size of this relation, however, is unclear, as is the age at which it becomes detectable. METHODS: Prospective data for 34 866 children enrolled in the US Collaborative Perinatal Project were analysed to examine maternal pregnancy smoking in relation to weight, height, and body mass index (BMI) in offspring at ages 1, 3, 4, 7, and 8 years. RESULTS: Compared with offspring of non-smokers, children of smokers had (i) weight that was lower at birth but then quickly equalled or exceeded that of non-smokers, (ii) consistently decreased height, and (iii) increased risk of overweight, particularly in girls. For example, at age 7 years, the adjusted odds ratio of BMI>or=85th percentile in boys of mothers who smoked on an average>or=20 cigarettes per day while pregnant was 1.22 (95% confidence interval 1.03-1.46), and in girls it was 1.30 (1.08-1.56). CONCLUSIONS: In these data, maternal smoking during pregnancy was associated with a modest increase in risk of overweight in children before the age of 8 years.

Birth Weight↗

PubMed2005

Maternal serum levels of polychlorinated biphenyls and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and time to pregnancy.

Polychlorinated biphenyls (PCBs), once used widely in transformers and other applications, and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), the main metabolite of the pesticide 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), are hormonally active agents. Changes in menstrual cycle functioning associated with PCBs and DDE, and increased odds of spontaneous abortion associated with DDE, suggest that these compounds could affect fertility. The authors investigated the association between PCB and DDE exposure and time to pregnancy by using serum levels measured in 390 pregnant women in the Collaborative Perinatal Project enrolled at 12 study centers in the United States from 1959 to 1965. They estimated adjusted fecundability odds ratios by using Cox proportional hazards modeling for discrete time data. Compared with time to pregnancy for women in the lowest exposure category (PCBs < 1.24 microg/liter, DDE < 14 microg/liter), time to pregnancy increased for women in the highest exposure category in terms of both PCBs (fecundability odds ratio for PCBs > or = 5.00 microg/liter = 0.65, 95% confidence interval: 0.36, 1.18) and DDE (fecundability odds ratio for DDE > or = 60 microg/liter = 0.65, 95% confidence interval: 0.32, 1.31). Overall, time to pregnancy increased with increasing serum PCB levels but was less suggestive of an association with DDE. Both trends were imprecise and attenuated when expressed on a lipid basis. Overall, evidence of an association between PCB or DDE exposure and time to pregnancy was weak and inconclusive.

Adult↗

PubMed2005

In utero exposure to background levels of polychlorinated biphenyls and cognitive functioning among school-age children.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants. In utero exposure to background levels of PCBs has been associated with intellectual impairment among children in most, but not all, studies. The authors evaluated prenatal PCB exposure in relation to cognitive test (intelligence quotient (IQ)) scores on the Wechsler Intelligence Scale for Children at age 7 years. Pregnant women were recruited from 12 US study centers from 1959 to 1965, and their children were followed until age 7 years (the Collaborative Perinatal Project). Third trimester serum was analyzed for PCBs in 1997-1999 for 732 women selected at random and for an additional 162 women whose children had either a low or a high IQ score. The PCB-IQ association was examined in multivariate models. Among those in the lowest exposure category (<1.25 microg of PCB/liter of serum), the fully adjusted mean IQ score was 93.6 (standard error: 1.8); among those in the highest category (> or =5 microg of PCB/liter), the mean IQ was 97.6 (standard error: 1.2); and overall the increase in IQ per unit increase in PCB level (microg/liter) was 0.22 (95% confidence interval: -0.28, 0.71). In these data, in utero exposure to background levels of PCBs was not associated with lower IQ at age 7 years.

Abnormalities, Drug-Induced↗

PubMed2005

Is bacterial vaginosis a stronger risk factor for preterm birth when it is diagnosed earlier in gestation?

OBJECTIVE: It is stated commonly that the earlier in pregnancy bacterial vaginosis is diagnosed, the greater is the increase in risk of preterm birth compared with women without bacterial vaginosis. However, this contention is based on small numbers of women. STUDY DESIGN: In this analysis of 12,937 women who were screened for bacterial vaginosis as part of a previously conducted clinical trial, the odds ratio of preterm birth (<7 weeks of gestation) for asymptomatic bacterial vaginosis-positive versus bacterial vaginosis-negative women was evaluated among women who were screened from 8 to 22 weeks of gestation. RESULTS: The odds ratio of preterm birth among bacterial vaginosis-positive versus bacterial vaginosis-negative women ranged from 1.1 to 1.6 and did not vary significantly according to the gestational age at which bacterial vaginosis was screened. The odds ratio for preterm birth did not vary significantly by gestational age at diagnosis when bacterial vaginosis was subdivided into Gram stain score 7 to 8 or 9 to 10. CONCLUSION: Although bacterial vaginosis was associated with an increased risk of preterm birth, the gestational age at which bacterial vaginosis was screened for and diagnosed did not influence the increase.

Female↗

PubMed2005

Is a change in the vaginal flora associated with an increased risk of preterm birth?

OBJECTIVE: The purpose of this study was to determine if a change in the vaginal flora was associated with an increased risk of preterm birth, and to determine if metronidazole therapy before 32 weeks increased the risk of preterm birth. STUDY DESIGN: We compared cultures taken at 23 to 26 weeks of gestation with cultures taken at delivery from women enrolled in the Vaginal Infections and Preterm Birth study to analyze the association of changes in the vaginal flora with preterm birth. RESULTS: Metronidazole therapy before 32 weeks was associated with an increased risk of preterm birth (OR 1.5, 95%CI 1.05-2.1) in an unadjusted model. A change to heavy growth of Escherichia coli or Klebsiella pneumoniae at delivery was found to be associated with preterm birth (OR 2.4, 95%CI 1.6-3.8). After controlling for race, parity, prepregnancy weight <100 pounds, smoking or drinking during pregnancy, Trichomonas vaginalis, bacterial vaginosis, chlamydia, mycoplasmas, group B streptococcus, metronidazole therapy before 32 weeks, vaginal pH >5.0, and an increase in E coli or K pneumoniae , only prepregnancy weight <100 pounds (adjusted odds ratio [AOR] 2.07, 95%CI 1.01-4.21) and increased E coli or K pneumoniae in the vagina at delivery (AOR 2.99, 95%CI 1.37-6.53) were found to be significantly associated with preterm birth. CONCLUSION: An increase in E coli or K pneumoniae in the vagina is an independent risk factor for preterm birth. Changes in the vaginal flora may explain the increased risk of preterm birth seen with vaginal clindamycin or oral metronidazole therapy.

Administration, Intravaginal↗

PubMed2005

Issues in clinical trial design: stopping a trial early and the large and simple trial.

During the conduct of a clinical trial, a primary function of the Data Safety and Monitoring Committee is to select the trial conduct and the accumulating data to determine whether the trial should continue or be discontinued earlier than planned. Reasons for early discontinuation of a trial include: evidence of benefit, evidence of harm, and evidence of futility. More than 1 of these elements will often be present. These principles will be illustrated with examples from National Institute of Child Health and Human Development-Maternal-Fetal Medicine Units clinical trials. The "large and simple clinical trial" is a study design rarely undertaken in the United States but commonly used elsewhere. The principles of this type of trial will be introduced and contrasted with those of the "conventional clinical trial."

Clinical Trials Data Monitoring Committees↗

PubMed2005

Childhood cancer following neonatal oxygen supplementation.

OBJECTIVE: To evaluate the relationship between neonatal oxygen supplementation (O2) and childhood cancer in the Collaborative Perinatal Project (CPP). STUDY DESIGN: The CPP consisted of 54,795 children born between 1959 and 1966 and followed to age 8 years. We used Cox proportional hazards modeling to examine the association between history of neonatal O2 and cancer (n = 48). RESULTS: The hazard ratio (HR) for any O2 was 1.77 (95% confidence interval [CI] = 0.94 to 3.35). The HR for continuous duration of O2 was near 1 and not significant. However, the HRs were 0.69 (95% CI = 0.17 to 2.88) and 2.87 (95% CI = 1.46 to 5.66) when comparing 0 to 2 and 3 or more minutes of O2, respectively, to no O2. The latter association was weaker (HR = 2.00; 95% CI = 0.88 to 4.54) and not significant ( P = .10) when analysis was restricted to cancers diagnosed after age 1 year (n = 41). CONCLUSIONS: These findings are consistent with an association between O 2 for 3 minutes or longer and cancer in childhood, and should serve as a basis for further study.

Child↗

PubMed2005

Maternal serum level of the DDT metabolite DDE in relation to fetal loss in previous pregnancies.

Use of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) continues in about 25 countries. This use has been justified partly by the belief that it has no adverse consequences on human health. Evidence has been increasing, however, for adverse reproductive effects of DDT, but additional data are needed. Pregnant women who enrolled in the Collaborative Perinatal Project (United States, 1959-1965) were asked about their previous pregnancy history; blood samples were drawn and the serum frozen. In 1997-1999, the sera of 1717 of these women who had previous pregnancies were analyzed for 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), the major breakdown product of DDT. The odds of previous fetal loss was examined in relation to DDE level in logistic regression models. Compared with women whose DDE level was <15 microg/L, the adjusted odds ratios of fetal loss according to category of DDE were as follows: 15-29 microg/L, 1.1; 30-44 microg/L, 1.4; 45-59 microg/L, 1.6; and 60+ microg/L, 1.2. The adjusted odds ratio per 60 microg/L increase was 1.4 (95% confidence interval 1.1-1.6). The results were consistent with an adverse effect of DDE on fetal loss, but were inconclusive owing to the possibility that previous pregnancies ending in fetal loss decreased serum DDE levels less than did those carried to term.

Abortion, Spontaneous↗