Biomedical subjects

David A Savitz

Publications and source records attributed to David A Savitz.

At least 37 records · Page 2Linked to original sources

PubMed2005

Measures of placental growth in relation to birth weight and gestational age.

Fetal growth depends in part on placental growth. The authors tested placental measures derived from digital images for reliability and to evaluate their association with birth weight and gestational age. A total of 628 women recruited into the Pregnancy, Infection, and Nutrition Study, a prospective cohort study of preterm birth in central North Carolina between 2002 and 2004, delivered singleton liveborn infants after 24 completed weeks' gestation. Novel chorionic plate morphometric parameters captured off digital images of the gross placenta were analyzed as estimators of gestational age and birth weight. Without acknowledgment to placental weight, digitally obtained lateral chorionic plate growth measures accounted for 17 percent of gestational age variance and 35 percent of birth weight variance, overall. Chorionic plate measures accounted for 10 percent of birth weight variance beyond that accounted for by placental weight alone. Among preterm births, 34 percent of gestational age variance and 63 percent of birth weight variance were accounted for by lateral chorionic plate growth measures. Intraclass correlation coefficients for the novel digital measures ranged from 0.96 to 0.98. Reliable digital measures of lateral chorionic plate growth estimate birth weight variance more strongly than gestational age, project variance that is not accounted for by placental weight, and project these outcomes to a greater degree in preterm births than at term.

Birth Weight↗

PubMed2005

The impact of water consumption, point-of-use filtration and exposure categorization on exposure misclassification of ingested drinking water contaminants.

The use of population-level indices to estimate individual exposures is an important limitation of previous epidemiologic studies of disinfection by-products (DBPs). We examined exposure misclassification resulting from the use of system average DBP concentrations to estimate individual-level exposures. Data were simulated (n=1000 iterations) for 100 subjects across 10 water systems based on the following assumptions: DBP concentrations ranged from 0-99 microg/L with limited intra-system variability; water intake ranged from 0.5-2.5 L/day; 20% of subjects used bottled water exclusively; 20% of subjects used filtered tap water exclusively; DBP concentrations were reduced by 50% or 90% following filtration. DBP exposure percentiles were used to classify subjects into different exposure levels (e.g., low, intermediate, high and very high) for four classification approaches. Compared to estimates of DBP ingestion that considered daily consumption, source type (i.e., unfiltered tap, filtered tap, and bottled water), and filter efficiency (with 90% DBP removal), 48-62% of subjects were misclassified across one category based on system average concentrations. Average misclassification across at least two exposure categories (e.g., from high to low) ranged from 4-14%. The median classification strategy resulted in the least misclassification, and volume of water intake was the most influential modifier of ingestion exposures. These data illustrate the importance of individual water use information in minimizing exposure misclassification in epidemiologic studies of drinking water contaminants.

Chlorine↗

PubMed2005

Pregnancy intendedness, maternal psychosocial factors and preterm birth.

OBJECTIVES: This study examined associations between reported pregnancy intendedness and several maternal psychosocial factors in relation to preterm birth (<37 weeks' completed gestation). METHODS: Women were recruited into a prospective cohort study between the 24th and 29th weeks of pregnancy in central North Carolina from 1996 to 2000. Prior to delivery, participants responded to questions about pregnancy intendedness, life events impacts, depressive symptoms, and coping style. RESULTS: Women who reported not intending their pregnancy had increased odds of reporting low, medium and high levels of perceived stress during pregnancy (OR = 1.4 [95% CI: 1.1, 1.9], OR = 2.2 [95% CI: 1.7, 2.8], and OR = 3.4 [95% CI: 2.6, 4.5], respectively, relative to very low), medium and high levels of depressive symptoms (OR = 2.2 [95% CI: 1.8, 2.9] and OR = 3.1 [95% CI: 2.4, 3.9], respectively), and medium and high levels of several coping styles. Reporting not intending the pregnancy was not associated with increased risk of preterm birth (Risk Ratio [RR] = 1.0, 95% CI: 0.8, 1.1), but reporting the highest quartile of perceived stress (RR = 1.6, 95% CI: 1.1, 2.3) and the highest tertile of distancing coping style (compared with lowest quartile) was associated with preterm birth (RR = 1.4, 95% CI: 1.1, 1.9). Interactions between pregnancy intendedness and the psychosocial variables perceived stress, depression or coping style did not modify the psychosocial variable's associations with preterm birth. CONCLUSIONS: Pregnancy intendedness remains an important concept in the reproductive health literature integrally tied to indicators of maternal mental health, but not necessarily to pregnancy outcomes.

Adaptation, Psychological↗

PubMed2005

The epidemiology of threatened preterm labor: a prospective cohort study.

OBJECTIVE: The purpose of this study was to describe the occurrence, timing, and outcomes of hospital-based diagnoses of preterm labor. STUDY DESIGN: Administrative records identified hospital admissions for preterm labor among 2534 women in an ongoing cohort study. Factors that were considered risks for prematurity were examined by logistic regression for an association with any preterm labor diagnosis, a preterm labor diagnosis <33 weeks of gestation, or > or =33 weeks of gestation. RESULTS: Of 234 women (9%) who experienced hospitalization for preterm labor, 90 women (38%) were delivered in the first episode. Previous preterm birth consistently was associated with a diagnosis of preterm labor. Reporting a sexually transmitted infection (odds ratio, 1.8; 95% CI, 1.1-3.0) or bacterial vaginosis (odds ratio, 2.6; 95% CI, 1.7-4.1) early in pregnancy was associated with hospitalization for preterm labor between 24 and 32 weeks of gestation. CONCLUSION: The incidence of first-time hospitalization for preterm labor was 9%, with most episodes not resulting in preterm birth. Previous preterm birth was associated therefore with a preterm labor diagnosis.

Adolescent↗

PubMed2005

A quantitative analysis of fish consumption and coronary heart disease mortality.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of fish consumption on coronary heart disease (CHD) mortality and nonfatal myocardial infarction (MI). Other papers quantify stroke risk and the impacts of both prenatal MeHg exposure and maternal intake of n-3 PUFAs on cognitive development. This analysis identified articles in a recent qualitative review appropriate for the development of a dose-response relationship. Studies had to satisfy quality criteria, quantify fish intake, and report the precision of the relative risk estimates. Relative risk results were averaged, weighted proportionately by precision. CHD risks associated with MeHg exposure were reviewed qualitatively because the available literature was judged inadequate for quantitative analysis. Eight studies were identified (29 exposure groups). Our analysis estimated that consuming small quantities of fish is associated with a 17% reduction in CHD mortality risk, with each additional serving per week associated with a further reduction in this risk of 3.9%. Small quantities of fish consumption were associated with risk reductions in nonfatal MI risk by 27%, but additional fish consumption conferred no incremental benefits.

Adult↗

PubMed2005

A quantitative analysis of fish consumption and stroke risk.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of fish consumption on stroke risk. Other papers quantify coronary heart disease mortality risk and the impacts of both prenatal MeHg exposure and maternal intake of n-3 PUFAs on cognitive development. This analysis identified articles in a recent qualitative literature review that are appropriate for the development of a dose-response relationship between fish consumption and stroke risk. Studies had to satisfy quality criteria, quantify fish intake, and report the precision of the relative risk estimates. The analysis combined the relative risk results, weighting each proportionately to its precision. Six studies were identified as appropriate for inclusion in this analysis, including five prospective cohort studies and one case-control study (total of 24 exposure groups). Our analysis indicates that any fish consumption confers substantial relative risk reduction compared to no fish consumption (12% for the linear model), with the possibility that additional consumption confers incremental benefits (central estimate of 2.0% per serving per week).

Adult↗

PubMed2005

A quantitative risk-benefit analysis of changes in population fish consumption.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish, while recommendations encourage fish consumption among the general population because of nutritional benefits. To investigate the aggregate impacts of hypothetical shifts in fish consumption, the Harvard Center for Risk Analysis convened an expert panel (see acknowledgements). Effects investigated include prenatal cognitive development, coronary heart disease mortality, and stroke. Substitution of fish with high MeHg concentrations with fish containing less MeHg among women of childbearing age yields substantial developmental benefits and few negative impacts. However, if women instead decrease fish consumption, countervailing risks substantially reduce net benefits. If other adults (mistakenly and inappropriately) also reduce their fish consumption, the net public health impact is negative. Although high compliance with recommended fish consumption patterns can improve public health, unintended shifts in consumption can lead to public health losses. Risk managers should investigate and carefully consider how populations will respond to interventions, how those responses will influence nutrient intake and contaminant exposure, and how these changes will affect aggregate public health.

Adolescent↗

PubMed2005

Regression models for clustered binary responses: implications of ignoring the intracluster correlation in an analysis of perinatal mortality in twin gestations.

PURPOSE: Dependent binary responses, such as health outcomes in twin pairs or siblings, frequently arise in perinatal epidemiologic research. This gives rise to correlated data, which must be taken into account during analysis to avoid erroneous statistical and biological inferences. METHODS: An analysis of perinatal mortality (fetal deaths plus deaths within the first 28 days) in twins in relation to cluster-varying (those that are unique to each fetus within a twin pregnancy such as birthweight) and cluster-constant (those that are identical for both twins within a sibship such as maternal smoking status) risk factors is presented. Marginal (ordinary logistic regression [OLR] and logistic regression using generalized estimating equations [GEE]) and cluster-specific (conditional and random-intercept logistic regression models) regression models are fit and their results contrasted. The United States "matched multiple data" file of twin births (1995-1997), which includes 285,226 twins from 142,613 pregnancies, was used to examine the implications of ignoring of clustering on regression inferences. RESULTS: The OLR models provide variance estimates for cluster constant covariates that ranged from 7% to 71% smaller than those from GEE-based models. This underestimation is even more pronounced for some cluster-varying covariates, ranging from 21% to 198%. CONCLUSIONS: Ignoring the cluster dependency is likely to affect the precision of covariate effects and consequently interpretation of results. With widespread availability of appropriate software, statistical methods for taking the intracluster dependency into account are easily implemented and necessary.

Cluster Analysis↗

PubMed2005

Maternal pre-pregnancy overweight and obesity and the risk of cesarean delivery in nulliparous women.

PURPOSE: To examine the effect of maternal pre-pregnancy overweight and obesity on the risk of term cesarean delivery in nulliparous women. METHODS: The authors examined data from 641 nulliparous women with a term pregnancy that participated in the Pregnancy, Infection, and Nutrition Study from 1995 to 2002. Unadjusted and adjusted risk ratios and 95% confidence intervals (CI) were computed for normal weight (BMI 19.8-26.0 kg/m(2)), overweight (BMI 26.1-29.0 kg/m(2)), and obese (BMI>29.0 kg/m(2)) women. Normal weight women served as the referent population. RESULTS: The unadjusted risk ratio for cesarean delivery for overweight women compared with normal weight women was 1.4 (95% CI, 0.97, 2.1) and for obese women compared with normal weight women was 1.4 (95% CI, 1.03, 2.0). After controlling for maternal height, education, weight gain during pregnancy, and labor induction, the adjusted risk ratio for cesarean delivery among overweight women was 1.2 (95% CI, 0.8, 1.8). The adjusted risk ratio for obese women was 1.5 (95% CI, 1.05, 2.0). CONCLUSION: Our analysis confirms that there is a moderate association between maternal pre-pregnancy obesity and an unplanned term cesarean delivery. However, the risk is not as large as previously reported.

Adolescent↗

PubMed2005

Urbanization and breast cancer incidence in North Carolina, 1995-1999.

PURPOSE: Breast cancer incidence rates are reported to be higher in urban compared with rural areas in the United States. We investigated the relationship between urbanization and breast cancer in North Carolina (1995-1999), and considered hospital characteristics as an explanation. METHODS: We calculated age-adjusted in situ and invasive female breast cancer incidence rates stratified by race, urbanization (Urban Influence Codes), and the presence of a hospital with a cancer registry and cancer program approval in a county. RESULTS: For white women, incidence rate ratios (IRRs) comparing the most urban with the most rural counties were 1.60 for in situ and 1.18 for invasive cancer. For non-white women, IRRs were 1.27 and 0.99, respectively. IRRs for incidence in registry hospital counties versus those without were all > 1.00 and differences were greater for in situ cancer than invasive. For most strata, urban excesses were attenuated when further stratified by registry hospital status. CONCLUSIONS: For most strata, we observed excess incidence in urban counties, but it appeared to be explained through the urban preponderance of registry hospitals. Counties with these hospitals may have higher incidence because of increased detection. Area hospital characteristics should be considered when evaluating geographic patterns of breast cancer incidence.

Adult↗

PubMed2005

Maternal urine albumin excretion and pregnancy outcome.

BACKGROUND: Vascular dysfunction has been hypothesized as a causal pathway for preeclampsia, impaired fetal growth, and early parturition. The relationship between increased urine albumin excretion (albuminuria), a marker of endothelial dysfunction, and preterm birth has not been fully evaluated. METHODS: We conducted a nested case-control study of 404 pregnancies from 1998 to 2000 within the Pregnancy, Infection and Nutrition cohort. Cases consisting of live births delivered before 37 weeks of gestation (preterm birth, n = 111) were compared with term births from the same cohort (n = 293). Albumin-creatinine ratio (in milligrams per gram) was measured in urine collected around 27 weeks of gestation. We compared risks for preterm birth in mothers with albuminuria with albumin levels of 3 to 20 mg/g and greater than 20 mg/g relative to those with albumin levels less than 3 mg/g by using logistic regression. RESULTS: Median albuminuria was albumin level of 2.7 and 4.3 mg/g for term and preterm births, respectively. Albuminuria was strongly associated with preterm birth in a dose-response fashion, with adjusted odds ratios of 1.9 (95% confidence interval, 1.1 to 3.1) and 4.7 (95% confidence interval, 1.7 to 12.6) for albuminuria with albumin of 3 to 20 mg/g and greater than 20 mg/g, respectively. The association was present for both spontaneous and medically induced preterm births, but the effect was decreased and the dose-response relationship was eliminated by excluding high-risk groups and those with pregnancy complications. CONCLUSION: Low levels of albuminuria are associated with preterm birth. The mechanism underlying this association warrants additional exploration.

Adult↗

PubMed2005

Diagnosis of bacterial vaginosis from self-obtained vaginal swabs.

OBJECTIVE: To determine the concordance between vaginal fluid Gram stains and pH obtained at speculum exam with similar stains and pH prepared from self-obtained vaginal swabs. METHODS: Using vaginal fluid Gram stain, 129 pregnant women were screened for bacterial vaginosis at 24 to 29 weeks' gestation. Two smears were collected from each woman during the same prenatal visit: the first was prepared from a self-obtained vaginal swab and the second from a physician-obtained speculum examination. Vaginal pH was recorded for each swab. Kappa coefficient was used to quantify agreement between the two sets of results. RESULTS: When compared with the physician-obtained smear, the ability of the self-obtained Gram stain to diagnose bacterial vaginosis had a sensitivity of 77%, specificity of 97%, positive predictive value of 71% and negative predictive value of 97%. There was substantial agreement (weighted kappa=0.82) between the two techniques in the ability to determine the grade of vaginal flora. CONCLUSION: When compared with physician-obtained vaginal smears, self-obtained smears have substantial agreement in the diagnosis of bacterial vaginosis.

Adolescent↗

PubMed2005

Physical exertion at work and the risk of preterm delivery and small-for-gestational-age birth.

OBJECTIVE: To assess whether exposure to standing, lifting, night work, or long work hours during 3 periods of pregnancy are associated with an increased risk of preterm or small-for-gestational-age birth. METHODS: The Pregnancy, Infection and Nutrition study is a prospective cohort with a nested case-control component that was conducted through clinic and hospital settings in Central North Carolina. A total of 1,908 women pregnant with a singleton gestation were recruited during prenatal visits from January 1995 through April 2000 and provided information during telephone and face-to-face interviews about physical exertion for the 2 longest-held jobs during pregnancy. RESULTS: No significant elevations in preterm delivery were observed among women who lifted repeatedly or stood at least 30 hours per week, with no changes in risk estimates over the course of pregnancy. A 50% elevation in the risk of preterm delivery (relative risk 1.5, 95% confidence interval 1.0-2.0; first trimester) was observed among women who reported working at night (10:00 PM to 7:00 AM), whereas a 40% reduction in risk was observed among women working at least 46 hours per week (relative risk 0.6, 95% confidence interval 0.4-0.9; first trimester), regardless of period of exposure. No elevations in small-for-gestational-age birth were observed among women exposed to any of the 4 types of occupational exertion. CONCLUSION: Physically demanding work does not seem to be associated with adverse pregnancy outcomes, whereas working at night during pregnancy may increase the risk of preterm delivery. Studies to examine the effect of shift work on uterine activity would help to clarify the possibility of a causal effect on preterm birth.

Adult↗

PubMed2005

Reducing misclassification in assignment of timing of events during pregnancy.

BACKGROUND: Perinatal epidemiology studies often collect only the calendar month in which an event occurs in early pregnancy because it is difficult for women to recall a specific day when queried later in pregnancy or postpartum. Lack of day information may result in incorrect assignment of completed gestational month because calendar months and pregnancy months are not aligned. METHODS: To examine the direction and magnitude of misclassification, we compared 3 methods for assignment of completed gestational month: 1) calendar month difference, 2) conditional month difference, and 3) imputed month midpoint. We used data from the Pregnancy, Infection, and Nutrition Study for simulations. RESULTS: Calendar month difference misclassified 54% of events as 1 month later in pregnancy compared with the actual completed month of gestation. Each of the other 2 methods misclassified approximately 12% of events to 1 month earlier and 12% to 1 month later. CONCLUSIONS: Calendar month difference, a common method, has the greatest misclassification. Conditional month difference and imputed month midpoint, which require little effort to implement, are superior to calendar month difference for reducing misclassification.

Cohort Studies↗

PubMed2005

Risk of small-for-gestational age is associated with common anti-inflammatory cytokine polymorphisms.

BACKGROUND: Anti-inflammatory cytokines play a key role in pregnancy maintenance. Genetic variation in anti-inflammatory cytokines could influence a woman's risk of adverse reproductive outcomes. METHODS: We investigated the relationship of polymorphisms in interleukin 4 (IL4), IL5, IL10, IL13, and transforming growth factor (TGFbeta1) with spontaneous preterm birth and small-for-gestational age (SGA) in a nested case-control study of a prospective pregnancy cohort. Women were recruited between 24 and 29 weeks' gestation at the Wake County and University of North Carolina, Chapel Hill obstetric clinics between February 1996 and June 2000. We inferred haplotypes using the EM algorithm and the Bayesian method, PHASE. Semi-Bayesian hierarchical logistic regression was used to obtain odds ratio (OR) estimates and 95% confidence intervals (CIs) for each polymorphism. RESULTS: African-American mothers who carried the IL4 GCC haplotype had greater risk of spontaneous preterm birth (OR = 2.9; 95% CI = 1.2-7.4). In white mothers, carriers of the "low-producing" IL4 CC and IL10 ATA haplotypes had markedly reduced risk of SGA (for the CC haplotype, 0.2 [0.0-1.2]; for the ATA haplotype, 0.5 [0.3-0.8]), whereas carriers of the "high-producing" IL4(-589)T variant had increased risk of SGA in both African-American and white mothers. CONCLUSIONS: Variants related to decreased anti-inflammatory cytokine production may lower risk of SGA. Furthermore, the same mechanism that protects against SGA might increase risk of spontaneous preterm birth.

Black or African American↗

PubMed2005

Risk of spontaneous preterm birth is associated with common proinflammatory cytokine polymorphisms.

BACKGROUND: Preliminary data suggest that common genetic variation in immune response genes can contribute to the risk for spontaneous preterm birth and possibly small-for-gestational age (SGA). METHODS: We investigated the relationship of polymorphisms in 6 cytokine genes associated with inflammation-interleukin (IL)1alpha, IL1beta, IL2, IL6, tumor necrosis factor (TNF), and lymphotoxin alpha (LTA)-with spontaneous preterm and SGA birth in a nested case-control study drawn from a prospective pregnancy cohort. Women were recruited between 24 and 29 weeks' gestation at the Wake County and University of North Carolina, Chapel Hill obstetric clinics between February 1996 and June 2000. We inferred haplotypes using the EM algorithm and the Bayesian method, PHASE. We then compared haplotype frequency distributions and implemented semi-Bayesian hierarchical logistic regression analyses to obtain odds ratio (OR) estimates and 95% confidence intervals (CIs) for each polymorphism. RESULTS: Two haplotypes spanning the TNF/LTA genes were associated with increased risk for spontaneous preterm birth in white subjects (for the AGG haplotype, OR = 1.5 [95% CI=0.8-2.6]; for the GAC haplotype, 1.6 [0.9-2.9]). Additionally, carriers of the GAG haplotype were found to have decreased risk of spontaneous preterm birth (0.6; 0.3-1.0). The TNF(-488)A and LTA(IVS1-82)C variants, constituents of the AGG and GAC haplotypes respectively, were also strongly associated with increased risk of spontaneous preterm birth. CONCLUSIONS: Our results suggest that common genetic variants in proinflammatory cytokine genes could influence the risk for spontaneous preterm birth. Selected TNF/LTA haplotypes were associated with spontaneous preterm birth in both African-American and white subjects. Our data do not support an inflammatory etiology for SGA.

Black or African American↗

PubMed2005

Should spontaneous and medically indicated preterm births be separated for studying aetiology?

An increasing proportion of preterm births result from medical interventions, and the practice of aggregating all preterm births vs. splitting into spontaneous and medically indicated preterm births is inconsistent. While mechanistic and clinical arguments can be offered for either approach, we empirically evaluated the predictiveness of a range of risk factors for preterm birth in the Pregnancy, Infection, and Nutrition Study. Most influences were shared across the two subsets - African-American ethnicity, advancing age, delivery at a university medical centre, prior preterm birth and smoking. Medically indicated preterm births appeared to be associated with intensity of medical care, higher in the university medical centre and lower for the poorest women. Body mass index was positively associated with medically indicated preterm birth and inversely with spontaneous preterm birth. Given the complexity of the aetiological pathways, both aggregation and disaggregation are well justified and should be included in studies of the causes of preterm birth.

Adult↗

PubMed2005

Probability samples of area births versus clinic populations for reproductive epidemiology studies.

Studies of pregnancy outcome are generally based either on geographically defined populations, often from birth records, or on clinic or hospital populations. We compared women recruited into a clinic-based study, the Pregnancy, Infection, and Nutrition (PIN) Study, with women who resided in the geographical area of the study (Alamance, Orange, and Wake Counties in North Carolina) and gave birth over the corresponding time period (1996-2000). Clinic participants were more likely to be Black, younger, have lower education, be unmarried, have a more frequent history of adverse pregnancy outcome, obtain prenatal care later, and smoke more cigarettes. Despite that profile, the proportion of clinic participants delivering preterm was somewhat lower than among area women overall (10.8% vs. 11.3%). Black/White risk ratios for preterm birth were markedly different for area (1.6) vs. clinic women (1.1), whereas other predictors were similar. Patterns may differ across groups for many reasons, including self-selection of clinics and varying clinical practices.

Adult↗