Hoyt G. Wilson

The NICHD Women's Contraceptive and Reproductive Experiences Study: Methods and Operational Results

PURPOSE This paper presents methods and operational results of a population-based case-control study examining the effects of oral contraceptive use on breast cancer risk among white and black women aged 35-64 years in five U.S. locations. METHODS Cases were women newly diagnosed with breast cancer during July 1994 through April 1998. Controls were identified through random digit dialing (RDD) using unclustered sampling with automated elimination of nonworking numbers. Sampling was density-based, with oversampling of black women. In-person interviews were conducted from August 1994 through December 1998. Blood samples were obtained from subsets of cases and controls, and tissue samples were obtained from subsets of cases. A computerized system tracked subjects through study activities. Special attention was devoted to minimizing exposure misclassification, because any exposure-disease associations were expected to be small. RESULTS An estimated 82% of households were screened successfully through RDD. Interviews were completed for 4575 cases (2953 whites; 1622 blacks) and 4682 controls (3021 whites; 1661 blacks). Interview response rates for cases and controls were 76.5% and 78.6%, respectively, with lower rates for black women and older women. CONCLUSIONS The methodologic details of this large collaboration may assist researchers conducting similar investigations.

Percentage of gestational diabetes mellitus attributable to overweight and obesity.

OBJECTIVES We calculated the percentage of gestational diabetes mellitus (GDM) attributable to overweight and obesity. METHODS We analyzed 2004 through 2006 data from 7 states using the Pregnancy Risk Assessment Monitoring System linked to revised 2003 birth certificate information. We used logistic regression to estimate the magnitude of the association between prepregnancy body mass index (BMI) and GDM and calculated the percentage of GDM attributable to overweight and obesity. RESULTS GDM prevalence rates by BMI category were as follows: underweight (13-18.4 kg/m(2)), 0.7%; normal weight (18.5-24.9 kg/m(2)), 2.3%; overweight (25-29.9 kg/m(2)), 4.8%; obese (30-34.9 kg/m(2)), 5.5%; and extremely obese (35-64.9 kg/m(2)), 11.5%. Percentages of GDM attributable to overweight, obesity, and extreme obesity were 15.4% (95% confidence interval [CI] = 8.6, 22.2), 9.7% (95% CI = 5.2, 14.3), and 21.1% (CI = 15.2, 26.9), respectively. The overall population-attributable fraction was 46.2% (95% CI = 36.1, 56.3). CONCLUSIONS If all overweight and obese women (BMI of 25 kg/m(2) or above) had a GDM risk equal to that of normal-weight women, nearly half of GDM cases could be prevented. Public health efforts to reduce prepregnancy BMI by promoting physical activity and healthy eating among women of reproductive age should be intensified.

Cigarette smoking and epithelial ovarian cancer by histologic type

Objective To examine cigarette smoking as a risk factor for different types of epithelial ovarian cancer. Methods We used data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case control investigation. Cases were 447 women aged 20–54 years with diagnoses of epithelial ovarian cancer. Controls were 3868 women selected by random-digit dialing. Conditional logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) as estimators of the relative risk of ovarian cancer. With age and study site as conditioning variables, OR point estimates were additionally adjusted for parity and use of oral contraceptives. Results The OR of mucinous epithelial ovarian cancer for women who had ever smoked was 2.3 (95% CI 1.4, 3.9) and for current smokers was 2.9 (95% CI 1.7, 4.9). The OR of mucinous tumors for current smokers was significantly elevated regardless of years since first cigarette or age at which women first smoked. The OR of mucinous tumors for current smokers increased slightly as cumulative pack-years of smoking increased, although the trend was not significant. Similar patterns of elevated risk were not observed among serous, endometrioid, or other histologic types. Odds ratio point estimates for former smokers were not significantly elevated for any histologic type. Conclusion Current cigarette smoking was a risk factor for mucinous epithelial ovarian cancer, but not other histologic types.

Association of maternal body mass index, excessive weight gain, and gestational diabetes mellitus with large-for-gestational-age births.

OBJECTIVE: To estimate the percentage of large-for-gestational age (LGA) neonates associated with maternal overweight and obesity, excessive gestational weight gain, and gestational diabetes mellitus (GDM)—both individually and in combination—by race or ethnicity. METHODS: We analyzed 2004–2008 linked birth certificate and maternal hospital discharge data of live, singleton deliveries in Florida. We used multivariable logistic regression to assess the independent contributions of mothers prepregnancy body mass index (BMI), gestational weight gain, and GDM status on LGA (birth weight-for-gestational age 90th percentile or greater) risk by race and ethnicity while controlling for maternal age, nativity, and parity. We then calculated the adjusted population-attributable fraction of LGA neonates to each of these exposures. RESULTS: Large-for-gestational age prevalence was 5.7% among normal-weight women with adequate gestational weight gain and no GDM and 12.6%, 13.5% and 17.3% among women with BMIs of 25 or higher, excess gestational weight gain, and GDM, respectively. A reduction ranging between 46.8% in Asian and Pacific Islanders and 61.0% in non-Hispanic black women in LGA prevalence might result if women had none of the three exposures. For all race or ethnic groups, GDM contributed the least (2.0–8.0%), whereas excessive gestational weight gain contributed the most (33.3–37.7%) to LGA. CONCLUSION: Overweight and obesity, excessive gestational weight gain, and GDM all are associated with LGA; however, preventing excessive gestational weight gain has the greatest potential to reduce LGA risk. LEVEL OF EVIDENCE: III

Maternal mortality among Afghan refugees in Pakistan, 1999-2000

BACKGROUND Estimated at 3.6 million, Afghans are the largest population of refugees in the world. Information on the magnitude, causes, and preventable factors of maternal deaths among Afghan refugees may yield valuable information for prevention. METHODS Deaths were recorded between Jan 20, 1999, and Aug 31, 2000, during a census carried out in 12 Afghan refugee settlements in Pakistan. Deaths among women of reproductive age (15-49 years) were further investigated by verbal autopsy interviews to determine their cause, risk factors, and preventability, and to ascertain the barriers faced to obtaining health care. FINDINGS The census identified 134406 Afghan refugees and 1197 deaths; a crude mortality rate of 5.5 (95% CI 5.2-5.8) per thousand population. Among the 66 deaths among women of reproductive age, deaths due to maternal causes (n=27) exceeded any other cause (41% [95% CI 29-53]). 16 liveborn and nine stillborn infants were born to women who died of maternal causes; six of the liveborn infants died after birth. Therefore, 60% (15 of 24) of infants born to these women were either born dead or died after birth. Compared with women who died of non-maternal causes, women who died of maternal causes had a greater number of barriers to health care (p=0.001), and their deaths were more likely to be preventable (p<0.05). INTERPRETATION Maternal deaths account for a substantial burden of mortality among Afghan refugee women of reproductive age in Pakistan. The high prevalence of barriers to health care access indicates opportunities for reducing maternal deaths in refugee women and their children.

Fraction of Gestational Diabetes Mellitus Attributable to Overweight and Obesity by Race/Ethnicity, California, 2007–2009

OBJECTIVES We calculated the racial/ethnic-specific percentages of gestational diabetes mellitus (GDM) attributable to overweight and obesity. METHODS We analyzed 1 228 265 records of women aged 20 years or older with a live, singleton birth in California during 2007 to 2009. Using logistic regression, we estimated the magnitude of the association between prepregnancy body mass index and GDM and calculated the percentages of GDM attributable to overweight and obesity overall and by race/ethnicity. RESULTS The overall estimated GDM prevalence ranged from 5.4% among White women to 11.9% among Asian/Pacific Islander women. The adjusted percentages of GDM deliveries attributable to overweight and obesity were 17.8% among Asians/Pacific Islander, 41.2% among White, 44.2% among Hispanic, 51.2% among Black, and 57.8% among American Indian women. Select Asian subgroups, such as Vietnamese (13.0%), Asian Indian (14.0%), and Filipino (14.2%), had the highest GDM prevalence, but the lowest percentage attributable to obesity. CONCLUSIONS Elevated prepregnancy body mass index contributed to GDM in all racial/ethnic groups, which suggests that decreasing overweight and obesity among women of reproductive age could reduce GDM, associated delivery complications, and future risk of diabetes in both the mother and offspring.

Oral contraceptive formulation and risk of breast cancer

BACKGROUND While evidence on the association between oral contraceptive (OC) use and breast cancer generally suggests little or no increased risk, the question of whether breast cancer risk varies by OC formulation remains controversial. Few studies have examined this issue because large samples and extensive OC histories are required. STUDY DESIGN We used data from a multicenter, population-based, case-control investigation. Women aged 35-64 years were interviewed. To explore the association between OC formulation and breast cancer risk, we used conditional logistic regression to derive adjusted odds ratios, and we used likelihood ratio tests for heterogeneity to assess whether breast cancer risk varied by OC formulation. Key OC exposure variables were ever use, current or former use, duration of use and time since last use. To strengthen inferences about specific formulations, we restricted most analyses to the 2282 women with breast cancer and the 2424 women without breast cancer who reported no OC use or exclusive use of one OC. RESULTS Thirty-eight formulations were reported by the 2674 women who used one OC; most OC formulations were used by only a few women. We conducted multivariable analyses on the 10 formulations that were each used by at least 50 women and conducted supplemental analyses on selected formulations of interest based on recent research. Breast cancer risk did not vary significantly by OC formulation, and no formulation was associated with a significantly increased breast cancer risk. CONCLUSIONS These results add to the small body of literature on the relationship between OC formulation and breast cancer. Our data are reassuring in that, among women 35-64 years of age, we found no evidence that specific OC formulations increase breast cancer risk.

Maternal smokeless tobacco use in Alaska Native women and singleton infant birth size

Objective. To examine the effects of maternal prenatal smokeless tobacco use on infant birth size. Design. A retrospective medical record review of 502 randomly selected deliveries. Population and Setting. Singleton deliveries to Alaska Native women residing in a defined geographical region in western Alaska, 1997–2005. Methods. A regional medical centers electronic records were used to identify singleton deliveries. Data on maternal tobacco exposure and pregnancy outcomes were abstracted from medical records. Logistic models were used to estimate adjusted mean birthweight, length and head circumference for deliveries to women who used no tobacco (n=121), used smokeless tobacco (n=237) or smoked cigarettes (n=59). Differences in mean birthweight, length and head circumference, 95% confidence intervals and p‐values were calculated using non‐users as the reference group. Main Outcome Measures. Infant birthweight, crown–heel length and head circumference. Results. After adjustment for gestational age and other potential confounders, the mean birthweight of infants of smokeless tobacco users was reduced by 78g compared with that of infants of non‐users (p=0.18) and by 331g in infants of smokers (p<0.01). No association was found between maternal smokeless tobacco use and infant length or infant head circumference. Conclusions. We found a modest but non‐significant reduction in the birthweight of infants of smokeless tobacco users compared with infants of tobacco non‐users. Because smokeless tobacco contains many toxic compounds that could affect other pregnancy outcomes, results of this study should not be construed to mean that smokeless tobacco use is safe during pregnancy.

Racial/ethnic differences in the prevalence of gestational diabetes mellitus and maternal overweight and obesity, by Nativity, Florida, 2004-2007

We examined the risk of gestational diabetes mellitus (GDM) among foreign‐born and U.S.‐born mothers by race/ethnicity and BMI category.

Patterns of prenatal care initiation in Georgia, 1980-1992.

Objective To determine whether characteristics in a womans first pregnancy were associated with the trimester in which she initiated prenatal care in her second pregnancy. Methods Data for white and black women whose first and second pregnancies resulted in singleton live births between 1980 and 1992 were obtained from Georgia birth certificates (n = 177,041). Adjusted relative risks (RRs) for early prenatal care in the second pregnancy were computed by logistic regression models that included trimester of prenatal care initiation, infant outcomes, or maternal conditions in the womans first pregnancy as the exposure and controlled for maternal age, education, childs year of birth, interval between first and second pregnancy, presence of fathers name on the birth certificate, and the interaction between prenatal care and education. Models were stratified by race. Results Women of both races who initiated prenatal care in the first trimester of their first pregnancies were more likely than those with delayed care to initiate prenatal care in the first trimester of their second pregnancies (RR = 1.25 and 1.63 for white and black women educated beyond high school, respectively). Both white and black women who delivered a baby with very low birth weight (RR = 1.06 and 1.15, respectively) or who suffered an infant death (RR = 1.09 and 1.31, respectively) in their first pregnancies were more likely than those who did not experience these events to begin prenatal care in the first trimester of their second pregnancies. Conclusion Women with some potentially preventable adverse infant outcomes tend to obtain earlier care in their next pregnancy. Unfortunately, women who delayed prenatal care in their first pregnancy frequently delay prenatal care in their next.