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OBJECTIVE - To assess whether interpregnancy interval length after a pregnancy loss is associated with risk of repeat miscarriage.
METHODS - This analysis includes pregnant women participating in the Right From the Start (2000-2012) community-based prospective cohort study whose most recent pregnancy before enrollment ended in miscarriage. Interpregnancy interval was defined as the time between a prior miscarriage and the last menstrual period of the study pregnancy. Miscarriage was defined as pregnancy loss before 20 weeks of gestation. Cox proportional hazard models were used to estimate crude and adjusted hazard ratios and 95% CIs for the association between different interpregnancy interval lengths and miscarriage in the study pregnancy. Adjusted models included maternal age, race, parity, body mass index, and education.
RESULTS - Among the 514 study participants who reported miscarriage as their most recent pregnancy outcome, 15.7% had a repeat miscarriage in the study pregnancy (n=81). Median maternal age was 30 years (interquartile range 27-34) and 55.6% of participants had at least one previous livebirth (n=286). When compared with women with interpregnancy intervals of 6-18 months (n=136), women with intervals of less than 3 months (n=124) had the lowest risk of repeat miscarriage (7.3% compared with 22.1%; adjusted hazard ratio 0.33, 95% CI 0.16-0.71). Neither maternal race nor parity modified the association. Attempting to conceive immediately was not associated with increased risk of miscarriage in the next pregnancy.
CONCLUSION - An interpregnancy interval after pregnancy loss of less than 3 months is associated with the lowest risk of subsequent miscarriage. This implies counseling women to delay conception to reduce risk of miscarriage may not be warranted.
PURPOSE - The reproductive windows between age at menarche and age at first birth (standardized age at first birth) and from menarche to menopause (reproductive lifespan) may interact with genetic variants in association with breast cancer risk.
METHODS - We assessed this hypothesis in 6131 breast cancer cases and 7274 controls who participated in the population-based Collaborative Breast Cancer Study. Risk factor information was collected through telephone interviews, and DNA samples were collected on a subsample (N= 1484 cases, 1307 controls) to genotype for 13 genome-wide association study-identified loci. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and P values for the interaction between reproductive windows and genotypes were obtained by adding cross-product terms to statistical models.
RESULTS - For standardized age at first birth, the OR was 1.52 (CI, 1.36-1.71) comparing the highest quintile with the lowest quintile. Carrier status for rs10941679 (5p12) and rs10483813 (RAD51B) appeared to modify this relationship (P = .04 and P = .02, respectively). For reproductive lifespan, the OR comparing the highest quintile with the lowest quintiles was 1.62 (CI, 1.35-1.95). No interactions were detected between genotype and reproductive lifespan (all P > .05). All results were similar regardless of ductal versus lobular breast cancer subtype.
CONCLUSIONS - Our results suggest that the reproductive windows are associated with breast cancer risk and that associations may vary by genetic variants.
Copyright © 2014 Elsevier Inc. All rights reserved.
BACKGROUND - Late age at first full-term birth and nulliparity are known to increase breast cancer risk. The frequency of these risk factors has increased in recent decades.
METHODS - The purpose of this population-based case-control study was to examine associations between parity, age at first birth (AFB), and specific histological subtypes of breast cancer. Women with breast cancer were identified from cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control subjects were randomly selected from population lists. Interviews collected information on reproductive histories and other risk factors. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of ductal, lobular, and mixed ductal-lobular breast cancer diagnosis in association with AFB and nulliparity.
RESULTS - AFB ≥30 years was associated with a 2.4-fold increase in risk of lobular breast cancer compared with AFB <20 years (OR, 2.4; 95% CI, 1.9-2.9). The association was less pronounced for ductal breast cancer (OR, 1.3; 95% CI, 1.2-1.4). Nulliparity was associated with increased risk for all breast cancer subtypes, compared with women with AFB <20 years, but the association was stronger for lobular (OR, 1.7; 95% CI, 1.3-2.2) than for ductal (OR, 1.2; 95% CI, 1.1-1.3) subtypes (P = .004). The adverse effects of later AFB was stronger with obesity (P = .03) in lobular, but not ductal, breast cancer.
CONCLUSIONS - Stronger associations observed for late AFB and nulliparity suggest that these factors preferentially stimulate growth of lobular breast carcinomas. Recent temporal changes in reproductive patterns and rates of obesity may impact the histological presentation of breast cancer.
Copyright © 2010 American Cancer Society.
OBJECTIVE - The purpose of this study was to identify associations between maternal and fetal genetic variants in candidate genes and spontaneous preterm birth (PTB) in a Norwegian population and to determine the effect size of those associations that corroborate a previous study of PTB.
METHODS - DNA from 434 mother-baby dyads (214 cases and 220 controls) collected from the Norwegian Mother and Child Cohort (MoBa) was examined for association between 1,430 single nucleotide polymorphisms in 143 genes and PTB. These results were compared to a previous study on European Americans (EA) from Centennial Women's Hospital in Nashville, TN, USA. Odds ratios for SNPs that corroborated the Cenntennial study were determined on the combined MoBa and Centennial studies.
RESULTS - In maternal samples the strongest results that corroborated the Centennial study were in the prostaglandin E receptor 3 gene (PTGER3; rs977214) (combined genotype p = 3x10(-4)). The best model for rs977214 was the AG/GG genotypes relative to the AA genotype and resulted in an OR of 0.55 (95% CI = 0.37-0.82, p = 0.003), indicating a protective effect. In fetal samples the most significant association in the combined data was rs854552 in the paraoxonase 1 gene (PON1) (combined allele p = 8x10(-4)). The best model was the TT genotype relative to the CC/CT genotypes, and resulted in an OR of 1.32 (95% CI = 1.13-1.53, p = 4x10(-4)).
CONCLUSIONS - These studies identify single locus associations with preterm birth for both maternal and fetal genotypes in two populations of European ancestry.
Vaginal bleeding during pregnancy has been considered a marker of an at-risk pregnancy, but the accuracy of reported bleeding has not been assessed. We sought to evaluate the agreement in vaginal bleeding reports based on prospective daily diary and retrospective recall at first-trimester interview and to investigate predictors of reporting accuracy. Participants recruited prior to pregnancy for a community-based pregnancy cohort (n = 153) completed web-based daily diaries beginning before pregnancy until the end of the first trimester. A comprehensive first-trimester interview was conducted, and the bleeding data from diary and interview were compared. Kappa statistics were used to quantify agreement. Log-linear models were used to investigate maternal age, prior miscarriage, and current pregnancy outcome as potential predictors of agreement. We found that bleeding characteristics (number of bleeding episodes, bleeding heaviness, duration and gestational timing) from the diary and interview were reported with high levels of agreement. Kappas ranged from 0.77 to 0.84. Retrospective report of any bleeding had a sensitivity of 0.80 and specificity of 1.0; however, sensitivity was lower when examined within smaller time intervals. Important predictors of agreement were not identified in this analysis, but the sample was small. Overall, the presence of vaginal bleeding, a common and potentially alarming symptom of early pregnancy, may be assessed by interview later in pregnancy with reasonable accuracy.
BACKGROUND - Previous research has demonstrated that heavy prenatal alcohol exposure affects the size and shape of the corpus callosum (CC) and compromises interhemispheric transfer of information. The aim of this study was to confirm the previous reports of poorer performance on a finger localization test (FLT) of interhemispheric transfer in a cohort of heavily exposed children and to extend these findings to a cohort of moderately exposed young adults.
METHODS - In Study 1, the FLT was administered to 40 heavily exposed and 23 nonexposed children from the Cape Coloured community of Cape Town, South Africa, who were evaluated for fetal alcohol syndrome (FAS) dysmorphology and growth. Anatomical images of the CC were obtained using structural MRI on a subset of these children. In Study 2, the FLT was administered to a cohort of 85 moderate-to-heavily exposed young adults participating in a 19-year follow-up assessment of the Detroit Prenatal Alcohol Exposure cohort, whose alcohol exposure had been ascertained prospectively during gestation.
RESULTS - In Study 1, children with FAS showed more transfer-related errors than controls after adjustment for confounding, and increased transfer-related errors were associated with volume reductions in the isthmus and splenium of the CC. In Study 2, transfer-related errors were associated with quantity of alcohol consumed per occasion during pregnancy. More errors were made if the mother reported binge drinking (> or =5 standard drinks) during pregnancy than if she drank regularly (M > or = 1 drink/day) without binge drinking.
CONCLUSIONS - These findings confirm a previous report of impaired interhemispheric transfer of tactile information in children heavily exposed to alcohol in utero and extend these findings to show that these deficits are also seen in more moderately exposed individuals, particularly those exposed to binge-like pregnancy drinking.
OBJECTIVES - The goals were to estimate the year-round burden of health care visits attributable to bronchiolitis and to identify risk factors for bronchiolitis in term healthy infants.
METHODS - We conducted a population-based, retrospective cohort study of 103 670 term, non-low birth weight infants enrolled in Tennessee Medicaid in 1995-2003. We monitored infants through the first year of life. Risk factors for bronchiolitis during infancy and rates of inpatient, emergency department, and outpatient visits during the study period were calculated by using claims data.
RESULTS - Over the 9 study years, rates of bronchiolitis visits were 238 outpatient visits per 1000 infant-years, 77 emergency department visits per 1000 infant-years, and 71 hospitalizations per 1000 infant-years. Average annual rates of bronchiolitis visits increased 41%, from 188 visits per 1000 infant-years to 265 visits per 1000 infant-years, from 1996-1997 to 2002-2003. Analysis of the linear trend in 500-g increments demonstrated a negative association between increasing birth weight and bronchiolitis diagnosis. There was a significant negative trend between maternal age and infant bronchiolitis diagnosis. Compared with infants of mothers 20 to 29 years of age, infants of mothers 15 to 19 years of age had a small increase in risk of having a bronchiolitis visit, whereas infants of older mothers (30-39 or 40-44 years of age) were less likely to have a visit.
CONCLUSIONS - The disease burden of bronchiolitis is substantial, with increasing rates of all types of visits among term, otherwise-healthy infants enrolled in Tennessee Medicaid between 1995 and 2003. Protective factors in this cohort of term infants included higher birth weight and older maternal age.
Research has demonstrated that prolonged duration of breastfeeding promotes child survival. This study examines the impact of unintended--mistimed or unwanted--pregnancy on breastfeeding duration. We use data from the 1990 Paraguay and 1994 Bolivia Demographic and Health Surveys and restrict our analysis to last-born, surviving children younger than 36 months from singleton births. To assess the association, unintended and intended pregnancies are compared by calculating incidence rates and adjusted hazard ratios (aHR) using survival analysis. Most children (approximately 95 percent) were breastfed initially, but the median duration of breastfeeding in Bolivia was five months longer than that in Paraguay (19 versus 14 months). A greater proportion of pregnancies were described as intended in Paraguay than in Bolivia (74 percent versus 45 percent). In adjusted analyses, unwanted and mistimed pregnancies were associated with slightly longer duration of breastfeeding (aHR = 0.9) than were intended pregnancies, but the association was not statistically significant. In this study, therefore, pregnancy intention was not an important factor in duration of breastfeeding in Bolivia or Paraguay.
Inverse associations have been reported between birthweight and subsequent mortality from circulatory disease and diabetes among women. In the current study, we assessed whether perinatal factors were associated with mortality from breast cancer. This follow-up study consists of breast cancer cases who participated in two population-based case-control studies of breast cancer in women under age 45 years conducted between 1983 and 1992 in three western Washington counties. This analysis is restricted to the 1,024 cases or their proxies who completed a supplementary questionnaire on perinatal factors from 1994 to 1996. The mean and median length of follow-up among living cohort members were 153 and 148 months, respectively. Relative to women who were firstborn, women who were born second or higher in the birth order seemed to have lower mortality from breast cancer [hazard ratio (HR), 0.2; 95% confidence interval (95% CI), 0.2-0.3]. In contrast, maternal age of > or =35 years (HR, 1.7; 95% CI, 1.1-2.8) was associated with higher breast cancer mortality relative to a maternal age of <25 years. Birth order modified the effect of maternal age on mortality from breast cancer (P = 0.03). There was evidence of increased breast cancer mortality for birthweight of > or =4,000 g (HR, 1.8; 95% CI, 1.0-3.1) and twin membership (HR, 2.5; 95% CI, 1.0-6.2). The protective effect of being born second or higher in the birth order against breast cancer mortality regardless of maternal age is striking and needs to be confirmed in future studies.
Hormonally-linked adult reproductive and anthropometric risk factors have been well established in the etiology of postmenopausal breast cancer, though early life exposures have been evaluated only more recently. Here, we examine the evidence for associations between lifetime reproductive and anthropometric risk factors for postmenopausal breast cancer. The review finds some evidence for the hypothesis that breast cancer risk is determined by the number of susceptible stem cells, modified by the hormonal environment. The in utero experience of an infant may be associated with postmenopausal breast cancer; preeclampsia may decrease and greater birthweight increase risk, but more evidence is needed. Earlier and more rapid childhood growth appears to increase postmenopausal breast cancer risk and childhood obesity to decrease risk, but very few studies have yet examined these associations. Increased final height and earlier age at menarche are consistently associated with increased risk for postmenopausal breast cancer. Later age at first birth, decreased parity, later menopausal age, use of hormone replacement therapy (especially progestin containing), and increased postmenopausal adiposity are well-established risk factors for postmenopausal breast cancer. The effect of a woman's own pregnancy conditions and lactation are not established. Further investigation is needed to identify whether events occurring early in life modify later events or accumulate over the life course. Many aspects of this research can be conducted by examining the influence of early life events on intermediary events without the need for longitudinal data.