Karen Hellenbrand

Heterogeneity in assessing self-reports of caffeine exposure: Implications for studies of health effects

Background. Coffee and its metabolite caffeine are widely studied for their health effects but with inconclusive results. Caffeine is particularly difficult to assess, and therefore we explore heterogeneity of caffeine exposure. Methods. We categorized caffeine exposure among 2,478 pregnant women in southern New England during 1996–2000 by the traditional laboratory-based methods of M. Bunker and M. McWilliams. A subsample was examined to ascertain caffeine levels of brewed or purchased beverages actually consumed. Results. More than half (56.6%) of women drank coffee since becoming pregnant. Serving sizes ranged from 2 to 32 oz and are considerably larger than laboratory standards, which are typically 8–10 oz, as compared with the standard of 5 to 6 oz. Conversely, caffeine content per serving of coffee was one-third the laboratory standard, eg, 100 mg caffeine compared with 300 mg for a 10-oz cup. Tea brewed more than 3 minutes contained 42 mg caffeine as compared with the standard of 94 mg. When the amount of caffeine actually consumed was measured, one-quarter (24.8%) of subjects traditionally classified as consuming 300+ gm caffeine daily were reclassified as consuming 150–299 mg. Conclusion. Misclassification of caffeine consumption increases difficulty in identifying health effects from caffeine. Some combination of more precise consumption data and a biomarker such as paraxanthine may more precisely estimate exposure.

Association of cocaine use with sperm concentration, motility, and morphology

Use of cocaine within 2 years of their first semen analysis has been found to be twice as common among men with sperm counts less than 20 X 10(6) mL (odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.0, 4.6). Duration of cocaine use for five or more years was more common in men with low sperm motility (OR = 2.0, 95% CI 1.0, 4.1) and in those with low concentrations and a large proportion of abnormal forms. Other major risk factors for these three indicators of male subfertility also have been identified, but the cocaine risk factors remained after adjustment for them. This association, together with the high prevalence of cocaine use in the general male population, suggests cocaine may now be related to male subfertility and that history of use should be ascertained during diagnostic interviews.

maternal Caffeine Consumption and Spontaneous Abortion: A Prospective Cohort Study

&NA; We investigated the relation between caffeine beverage consumption and spontaneous abortion in 2,967 pregnant women planning to deliver at Yale‐New Haven Hospital in 1988–1992. We evaluated coffee, tea, and soda drinking in the first month of pregnancy in interviews before the end of the sixteenth week of gestation. We obtained information on 98.2% of the pregnancies (including 2,714 singleton livebirths and 135 spontaneous abortions). As compared with abstention from caffeine beverages (coffee, tea, and soda), the adjusted odds ratios for spontaneous abortion associated with consumption of 1–150, 151–300, and >300 mg caffeine daily were 0.81 [95% confidence interval (CI) = 0.54–1.20], 0.89 (95% CI = 0.48–1.64), and 1.75 (95% CI = 0.88–3.47), respectively. Drinking ≥3 cups of tea or coffee was associated with elevated risks of spontaneous abortion (adjusted odds ratio = 2.33, 95% CI = 0.92–5.85; and adjusted odds ratio = 2.63, 95% CI = 1.29–5.34, respectively). These results, if replicated, suggest that some ingredient (or correlate) of tea or coffee may account for some of the observed association of caffeine with spontaneous abortion. In this study, caffeine consumption is more strongly related to spontaneous abortion than alcohol or cigarette use in early pregnancy.

Conception delay after oral contraceptive use: the effect of estrogen dose.

A significant delay was observed in conception among 248 former oral contraceptive (OC) users compared with women discontinuing other methods of contraception (n = 1,365). The mean time to conception was 5.88 cycles (95% confidence interval [CI] 5.38, 6.38) for former OC users and 3.64 cycles (95% CI 3.49, 3.79) after other contraceptives. Women discontinuing OCs with higher doses of estrogen (greater than or equal to 50 micrograms) had greater conception delays than those on lower estrogen doses who, in turn, had longer delays than other method users. Oral contraceptive use was associated with significant reductions in conception for each of the first six cycles after discontinuation. This study provides further evidence for a direct effect of oral contraception on delayed conception, suggests that the delay lasts longer than previously thought, and finds that the probability of conception after OC discontinuation depends on the estrogen dose of the OC.

Proportional weight gain and complications of pregnancy, labor, and delivery in healthy women of normal prepregnant stature

Detailed reproductive information was obtained through interview at early prenatal visits to hospital clinics, private medical groups, or health maintenance organizations for 4186 women delivered at Yale-New Haven Hospital. From these women, 1,396 were selected who had no preexisting chronic disease, were within their normal prepregnant weight for height as determined by Quetelets Index (weight2/height2), and were delivered of single infants with no major congenital malformations between 37 and 42 weeks. These women were divided into four quartiles according to their proportional weight gain (weight gain/prepregnant weight): quartile 1 = gains less than or equal to 15%; quartile 2 = gains 16% to 25%; quartile 3 = gains 26% to 35%; quartile 4 = gains greater than 35%. Complications of pregnancy, labor, and delivery were recorded within 2 days of delivery. Compared with the women in quartile 2 those in quartile 4 were 3.8 times more likely to develop gestational hypertension and had a fourfold risk of becoming preeclamptic. They were also significantly more likely to require cesarean section. The size of the infant was a significant risk factor for prolonged second stage of labor in primigravid women (greater than 2 hours) but not in multigravid women (greater than 1 hour). Weight gains of more than 35% almost doubled the risk of a prolonged second stage of labor for multigravid women. High proportional gains were not associated with adverse neonatal outcomes. Clinicians should consider proportional weight gain when advising healthy women about weight gain during pregnancy.

Spontaneous Abortion and Exposure to Electric Blankets and Heated Water Beds

We conducted a prospective study (N = 2,967) to evaluate the relation of spontaneous abortion with use of electrically heated beds (electric blankets and heated water beds) during pregnancy. At interview, 61.5% of women were at less than 12 weeks gestation, and 38.5% were between 13 and 16 weeks; thus, very early pregnancy losses would have been excluded. Information regarding exposure to electric beds was obtained for the month of conception and the 7 days before interview. Electric blanket use at conception was associated with an increased risk of spontaneous abortion in the unadjusted analysis [relative risk (RR) = 1.84; 95% confidence interval (CI) = 1.08–3.13], but adjustment for other factors reduced the risk slightly [odds ratio (OR) = 1.74; 95% CI = 0.96–3.15]. Heated water bed use was not associated with an increased risk of spontaneous abortion at conception (OR = 0.59; 95% CI = 0.33–1.07) or at interview (OR = 0.63; 95% CI = 0.36–1.12). Measures of dose response (daily use, hours of use, or temperature setting) were not associated with increased risk. Wire code data were obtained for the first, or only, house lived in during pregnancy. Women living in homes classified as “very high” or “ordinary high” current configuration were not at greater risk than women living in homes with buried wires. Nor was there any trend for increased risk of spontaneous abortion by wire code category. This study does not support the hypothesis that use of electric beds or residence in a high current configuration home increases the risk of spontaneous abortion; however, it indicates that electric blanket use at the time of conception and in early pregnancy may be associated with a slight increase in risk of pregnancy loss.

PDE11A associations with asthma: Results of a genome-wide association scan

Andrew T. DeWan, PhDa, Elizabeth W. Triche, PhDc, Xuming Xu, PhDa, Ling-I Hsu, MPHa, Connie Zhao, PhDd, Kathleen Belanger, PhDb, Karen Hellenbrand, MPHb, Saffron A. G. Willis-Owen, PhDe, Miriam Moffatt, PhDe, William O. C. Cookson, MD, PhDe, Blanca E. Himes, PhDf, Scott T. Weiss, MDf, W. James Gauderman, PhDg, James W. Baurley, MSg, Frank Gilliland, MD, PhDg, Jemma B. Wilk, DSch, George T. O’Connor, MDh, David P. Strachan, PhDi, Josephine Hoh, PhDa, and Michael B. Bracken, PhDb

Whole-exome sequencing of a pedigree segregating asthma

BackgroundDespite the success of genome-wide association studies for asthma, few, if any, definitively causal variants have been identified and there is still a substantial portion of the heritability of the disease yet to be discovered. Some of this “missing heritability” may be accounted for by family-specific coding variants found to be segregating with asthma.MethodsTo identify family-specific variants segregating with asthma, we recruited one family from a previous study of asthma as reporting multiple asthmatic and non-asthmatic children. We performed whole-exome sequencing on all four children and both parents and identified coding variants segregating with asthma that were not found in other variant databases.ResultsTen novel variants were identified that were found in the two affected offspring and affected mother, but absent in the unaffected father and two unaffected offspring. Of these ten, variants in three genes (PDE4DIP, CBLB, and KALRN) were deemed of particular interest based on their functional prediction scores and previously reported function or asthma association. We did not identify any common risk variants segregating with asthma, however, we did observe an increase in the number of novel, nonsynonymous variants in asthma candidate genes in the asthmatic children compared to the non-asthmatic children.ConclusionsThis is the first report applying exome sequencing to identify asthma susceptibility variants. Despite having sequenced only one family segregating asthma, we have identified several potentially functional variants in interesting asthma candidate genes. This will provide the basis for future work in which more families will be sequenced to identify variants across families that cluster within genes.

Changes in the prevalence distribution of hypertension: Connecticut adults 1978–1979 to 1982☆

In the Spring and Summer of 1982 the Second Connecticut Blood Pressure Survey (CBPS-II) was completed. This survey is independent of, but essentially identical in design and implementation to the First Connecticut Blood Pressure Survey reported on by Freeman et al. [1]. This paper compares the results of the two surveys using the same analytic techniques as reported previously [2]. In addition, a model for analyzing the components of hypertension control is utilized in the analysis. Finally, the implications of the survey comparison are discussed in the context of the Connecticut High Blood Pressure Program (CHBP) [3].