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Lactation in relation to postmenopausal breast cancer.

A modest inverse association between lactation and breast cancer risk has most consistently been observed in premenopausal women, and certain breastfeeding patterns, such as prolonged duration and early age at first lactation, may be important determinants of risk. However, these associations have not generally been observed in relation to postmenopausal breast cancer. As part of a multicenter population-based case-control study, the authors examined postmenopausal breast cancer risk according to breastfeeding characteristics. Breast cancer patients aged 50-79 years were identified from statewide tumor registries in Massachusetts, New Hampshire, and Wisconsin from July 1992 through July 1995. Similarly aged control women were randomly selected from population lists. Information regarding lactation history and breast cancer risk factors was obtained through telephone interviews. This analysis included only data on parous postmenopausal women (3,633 cases and 3,790 controls). After adjustment for age, parity, age at first birth, and other breast cancer risk factors, breastfeeding for at least 2 weeks was associated with a slightly reduced risk of breast cancer in comparison with women who had never lactated (relative risk = 0.87, 95% confidence interval 0.78-0.96). There was only a modest suggestion that increasing cumulative duration of lactation was inversely associated with breast cancer risk; the relative risk for women who had breastfed for > or =24 months was 0.73 (95% confidence interval 0.56-0.94) (p-trend for duration = 0.10). Age at first lactation was not consistently associated with risk. Modest inverse associations appeared to persist even up to 50 years since first lactation. Use of hormones to suppress lactation was not associated with postmenopausal breast cancer, nor was inability to breastfeed related to risk. These results suggest that lactation may have a slight and perhaps long-lasting protective effect on postmenopausal breast cancer risk.

Age Factors↗

Migration, fertility, and state policy in Hubei Province, China.

Despite China's one-child family planning policy, the nation experienced a slight rise in the birth rate in the mid-1980s. Many observers attributed this rise to the heightened fertility of those rural-to-urban migrants who moved without a change in registration (temporary migrants), presumably to avoid the surveillance of family planning programs at origin and destination. Using a sequential logit analysis with life-history data from a 1988 survey of Hubei Province, we test this possibility by comparing nonmigrants, permanent migrants, and temporary migrants. While changing family planning policies have a strong impact on timing of first birth and on the likelihood of higher-order births, migrants generally do not have more children than nonmigrants. In fact, migration tends to lower the propensity to have a child. More specifically, the fertility of temporary migrants does not differ significantly from that of other women.

Adolescent↗

Risk factors for brain tumors in children.

An exploratory case-control study was conducted in 15 hospitals in the Baltimore, MD, SMSA of possible etiologic factors associated with brain tumors in children. Eighty-four children with brain tumors were compared to normal children and to children with other malignancies. Parents of these children were interviewed about a variety of possible etiologic factors. The findings included: 1) children with brain tumors as well as children with other cancers had a greater tendency than normal children to have been first births and to have had higher birth weights; 2) more children with brain tumors had a sibling with epilepsy or seizures than did normal children, and several of the mothers of children with brain tumors had themselves had epilepsy or a stroke at a relatively young age; 3) there were no significant differences between the groups with regard to several maternal characteristics, including smoking during pregnancy and prior radiation exposure; 4) more children with brain tumors and children with other cancers were found to have had exposures to insecticides than had normal children; 5) fewer children with brain tumors or with other cancers were reported to have had tonsillectomies than normal children; and 6) more of the children with brain tumors as well as the children with other malignancies were reported to have been exposed to farm animals and to sick pets. This exploratory study is one of the first case-control studies of the epidemiology of brain tumors in children, and the results suggest directions for future epidemiologic studies in this relatively uncharted field.

Adolescent↗

Early-age body size, adult weight gain and endometrial cancer risk.

To further characterize the association of obesity and endometrial cancer, in particular with regard to the role of early-age obesity and adult weight gain, the authors assembled by computer linkage a population-based historical cohort of 30,266 women born between 1913 and 1932, for whom weight and height had been recorded in 1942-43 and 1972. Linkage of this cohort to the Hawaii Tumor Registry resulted in the identification of 214 (mainly post-menopausal) incident cases of endometrial cancer for 1972-1986. An average of 37 cancer-free controls were matched to each case on month and year of birth and ethnicity. A case-control analysis, conducted in each 5-year birth cohort, revealed no clear association of endometrial cancer with weight, height or body mass at ages 10 to 29 years. However, positive associations with adult body weight and gain in body mass since 1942 were observed for women diagnosed at age 60 or older. This association with obesity was strongest in women whose body mass was below the median in 1942 and equal to or above the median in 1972. No association with body size was detected in women diagnosed before age 60. Parity, age at first birth and socioeconomic indicators for 1942 and 1972 did not confound the analysis. These findings suggest that obesity affects the late stages of endometrial carcinogenesis, and the possibility that one or more determinants of weight gain may be independently associated with endometrial cancer risk.

Aged↗

Reproductive risk factors for breast cancer by receptor status, histology, laterality and location.

It is well established that a woman's reproductive history influences her risk of breast cancer. We examined whether the effect of reproductive history was similar for different sub-types of breast cancer. The study was based on a population-based cohort of 1.5 million Danish women born between 1935 and 1978, with individual information on births. Between 1978 and 1994, 10,790 incident cases of breast cancer were identified in a nationwide cancer registry, including detailed information on receptor status, histology, laterality and location of the tumour. Overall, the incidence of breast cancer was 13% lower in parous compared with nulliparous women. This reduction was significantly stronger for mucinous than for ductal carcinomas and for tumours located centrally than for those non-central in the breast. Overall, the incidence in parous women increased by 10% by each 5-year postponement of their first birth. For the incidence of lobular carcinomas this increase was significantly stronger, and for mucinous carcinomas it tended to be stronger than for ductal carcinomas. For the incidence of centrally located tumours the increase was stronger than for non-centrally located tumours. On average, there was a 10% decrease in breast-cancer risk by each additional birth. This decrease was seen in most sub-types, but not for lobular carcinomas of for centrally located tumours. According to our findings, lobular and mucinous carcinomas and centrally located tumours may have risk-factor profiles that differ from other types of breast cancer.

Adolescent↗

Risk factors for the recurrence of premature rupture of the membranes.

Premature rupture of the amniotic membranes (PROM) occurs in up to 20% of all births. Although many studies have examined risk factors for PROM and, in particular, preterm PROM (PPROM, if less than 37 weeks' gestation), the aetiology of PROM recurrence has not been examined as closely. This study investigated factors that may increase the risk of PROM among women who have already experienced one PROM birth. Maternally linked Washington State birth certificates from 1984 to 1993 identified 208 women with consecutive PROM births. Controls were a random sample (n = 848) of women who had one birth on record complicated by PROM, but whose subsequent birth was not. Among women with a prior term PROM, increased risk for PROM recurrence (term PROM or PPROM) was associated with an intervening fetal death at less than 20 weeks' gestation (OR = 2.4, 1.3-4.5) and with parity of two or more (OR = 2.0, 1.3-3.4). None of the factors assessed significantly increased the risk of recurrence of PROM (term PROM or PPROM) among women with a prior PPROM. Other potential risk factors for PROM recurrence were evaluated within the two PROM groups (PPROM or term PROM at first birth) by stratifying among the cases according to gestational length at subsequent birth.

Case-Control Studies↗

Body size at different periods of life and breast cancer risk.

The inconclusive findings of past analytic epidemiologic studies on diet and breast cancer may have resulted from the inability of these studies to assess early dietary exposures. The role of macronutrient intake during early life can be indirectly studied, however, by examining past and present body size. The authors identified by computer linkage a population-based historical cohort of 38,084 women born between 1918 and 1943, on whom information about weight and height had been recorded in Hawaii in both 1942-1943 and 1972. Linkage of this cohort to the Hawaii Tumor Registry resulted in the identification of 607 incident cases of breast cancer for 1972-1983. An average of 4.4 cancer-free controls were matched to each case on year and month of birth and race of the parents. A matched case-control analysis, conducted in each five-year birth cohort, revealed a negative association of adolescent body mass to premenopausal breast cancer. This negative association was statistically significant in girls aged 10-14 years in 1942 (p for trend, 0.004), was present in all ethnic groups, and was strongest among overweight young women who remained overweight in adulthood. Early-age weight, height, and body surface area were not associated with either pre- or postmenopausal breast cancer. Adult weight and gain in body mass since 1942 were positively associated with postmenopausal breast cancer risk. Adjustment for age at first birth, parity and socioeconomic indicators for 1942 and 1972 did not modify the results. This study provides evidence for a protective role of adolescent obesity against premenopausal breast cancer, and for an enhancing role of a positive energy balance during adult life on postmenopausal breast cancer.

Adolescent↗

A sub-site-specific analysis of the relationship between colorectal cancer and parity in complete male and female Norwegian birth cohorts.

Register and census data for complete cohorts of Norwegian men and women born between 1935 and 1969 have been used to examine the relationship between reproductive factors and the incidence of colorectal cancer. Among 1.1 million men and 1.1 million women under observation, 491 male and 859 female cases of colorectal cancer were diagnosed during the period of follow-up. Our hazard model estimates clearly show that in these young cohorts, women with 2 or more children run a lower risk of having a malignant tumor in the cecum or ascending colon than do other women of the same age and in the same birth cohort. No association with parity is found with respect to cancer in the transverse or descending colon, whereas a downward trend in the effect estimates, followed by an upturn, appears for the rectum, sigmoid colon and rectosigmoid junction. Such correlations, which also hold when we control for education and place of residence, are not found for men. The observed relationship between parity and cancer incidence is not likely to be exclusively explained by life-style differentials. Presumably, there is a biological effect of the number of pregnancies and deliveries, net of age at first birth and other reproductive factors, on the development of colorectal cancer.

Age Factors↗

Molecular and ionic basis of congenital complete heart block.

Congenital heart block (CHB), detected at or before birth in a structurally normal heart, is strongly associated with autoantibodies reactive with the intracellular soluble ribonucleoproteins 48kD SSB/La, 52kD SSA/Ro, and 60kD SSA/Ro. CHB is presumed to be due to the transplacental passage of autoantibodies from the mother into the fetal circulation. Varying degrees of heart block have been reported. Although second degree block has, on rare occasion, reverted to normal sinus rhythm, complete atrio-ventricular (AV) block is irreversible. CHB carries substantial mortality and morbidity, with > 60% of affected children requiring lifelong pacemakers. The recurrence rate exceeds, by at least twofold, that of the first birth and is likely to influence the decision to have more children. Curiously, the mother's heart is almost never affected (with complete heart block) despite exposure to identical circulating autoantibodies. As part of our continuing effort to understand the complex factors contributing to the pathogenesis of CHB, we have established an animal model of CHB by immunizing female mice with recombinant proteins/antigens, reproduced the human complete AV block in an isolated Langendorff perfused fetal heart, and correlated these findings with L-type Ca channel inhibition by maternal antibodies from mothers of children with CHB. In addition, we established a passive animal model by directly injecting maternal antibodies into pregnant mice and reported significant sinus bradycardia, indicating that the spectrum of conduction abnormalities may extend beyond the AV node. All together, the data provided strong evidence supporting an etiologic role of antibody/Ca channel involvement in the pathogenesis of CHB. However, other yet unknown factors seem necessary to explain the full expression of CHB.

Animals↗

Preterm delivery and risk of breast cancer.

To explore the risk of breast cancer in relation to the length of a pregnancy we tested whether a preterm delivery carries a higher risk of breast cancer than does a full-term delivery. Based on information from the Civil Registration System, and the National Birth Registry in Denmark, we established a population-based cohort of 474 156 women born since April 1935, with vital status and detailed parity information, including the gestational age of liveborn children and stillbirths. Information on spontaneous and induced abortions was obtained from the National Hospital Discharge Registry and the National Registry of Induced Abortions. Incident cases of breast cancer in the cohort (n = 1363) were identified through linkage with the Danish Cancer Registry. The period at risk started in 1978 and continued until a breast cancer diagnosis, death, emigration, or 31 December, 1992, whichever occurred first. After adjusting for attained age, parity, age at first birth and calendar period, we observed the following relative risks of breast cancer for different lengths of the pregnancy: < 29 gestational weeks = 2.11 (95% confidence interval 1.00-4.45); 29-31 weeks = 2.08 (1.20-3.60); 32-33 weeks = 1.12 (0.62-2.04); 34-35 weeks = 1.08 (0.71-1.66); 36-37 weeks = 1.04 (0.83-1.32); 38-39 weeks = 1.02 (0.89-1.17); 40 weeks = 1 (reference). Parous women who had a preterm delivery below 32 weeks gestation had a 1.72-fold (1.14-2.59) increased risk of breast cancer compared with other parous women. In conclusion, a preterm delivery of 32+ weeks gestation did not significantly increase a woman's risk of contracting breast cancer. Only for the very small group of women with preterm deliveries of less than 32 weeks gestation did we observe an increased risk.

Adult↗

Hospital level of care and neonatal mortality in low- and high-risk deliveries: reassessing the question in Sweden by multilevel analysis.

BACKGROUND: In high-risk births, the availability and concentration of neonatal resources in larger regional hospitals increases the chance of survival. The advantages of regionalization for low-risk deliveries are still unclear, but some studies have suggested that regionalization also is beneficial for low risk deliveries. The aim of the present study was to investigate both the relevance of regionalization and the concentration of neonatal resources as determinants of mortality in low- and high-risk deliveries in Sweden. METHODS: Interhospital differences in 28-day neonatal mortality were analyzed distinguishing maternal and delivery factors from institutional ones. Using information from the Swedish Birth Register (1990-1995), we performed risk-stratified multilevel logistic regression analysis to study 691,742 births (first level) nested within the 66 Swedish hospitals with maternity wards (second level). RESULTS: In low-risk deliveries, mortality decreased with improved access to neonatal resources. Mortality was lowest in larger regional hospitals with full access to neonatal care. This association remained unchanged after adjusting for patient mix. With regard to high-risk deliveries, mortality was higher in large county and regional hospitals than in small hospitals without access to neonatal care but, as expected, this increased risk disappeared after adjustment for patient mix. CONCLUSIONS: Increased regionalization and concentration of neonatal resources for low-risk births is justified from a strictly medical point of view. From a public health perspective, closing small obstetrics units may prevent an appreciable number of deaths, but it would have only a very small impact on the risk of mortality from the individual's point of view. The cost-effectiveness of such a step remains to be analyzed from a health economics perspective.

Adult↗

Determinants of adolescent fertility and its consequences for maternal health, with special reference to rural Bangladesh.

The second section of this paper set forth a theoretical model relating adolescent growth and development to family formation patterns and their implications for maternal and child health. Subsequent sections of the paper examine the evidence to support specific relationships hypothesized in the model, focusing on longitudinal data from Matlab, Bangladesh. Despite the emphasis on developing country populations, literature from developed countries was also reviewed. The weight of the evidence suggests that in the developed countries, while there is a positive relationship between reproductive maturation and subsequent reproductive behavior, the negative effects of young maternal age on pregnancy outcome is confounded with socioeconomic factors. Teenage pregnancy, or at least teenage birth, occurs disproportionately among the socially and economically disadvantaged. Moreover, teenage childbearing in the U.S., especially when it occurs outside of marriage, violates social norms, at least in the white population. Poor diet may be a problem in the U.S. but it does not appear to result in notable delays in physical growth and development, delayed or compromised adolescent growth, or late age at menarche. Limited evidence suggests that early menarche may be associated with more rapid onset of mature menstrual cycle activity but these findings have not been replicated elsewhere. In developing countries the situation is quite different. First, early marriage and childbearing are desired and common across most segments of society. Second, malnutrition is widespread, and is sufficiently severe to delay the adolescent growth spurt and raise average age at menarche by two to three years compared with developed country populations. This is certainly the case in Bangladesh. In this setting, several observations regarding the relationship of nutritional status, adolescent development and reproduction have been made. First, undernutrition delays growth and reproductive maturation, and women who mature early (i.e., women with young age at menarche) marry at younger ages than later maturers. In addition, body weight appears to have an independent effect on age at marriage, net of age at menarche, such that relatively heavy women marry at younger ages than their lighter counterparts. Explanations for this finding include correlation between body weight and development of secondary sex characteristics, and perhaps a cultural perception that heavier (i.e., normal body weight) women are more attractive, or healthier, mates. The effect of menarche and nutritional status on marriage gives rise to concern that an improvement in nutritional status, and an increase in the age at menarche, would lead to younger marriage and first birth, and higher lifetime fertility.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Treatment-seeking practices for malaria in pregnancy among rural women in Mukono district, Uganda.

Understanding treatment-seeking practices for malaria in pregnancy is necessary in designing effective programmes to address the high malaria morbidity in pregnancy. This study assessed women's perceptions on malaria in pregnancy, recognition of early signs of pregnancy and of malaria, and the cultural context in which treatment seeking takes place in Mukono District. Focus group discussions (FGD) and key informant interviews were conducted among pregnant women, non-pregnant women, adolescents and men. The results showed that malaria, locally known as omusujja, was perceived as the most common cause of ill health among pregnant women. Although malaria commonly presents with fever, some pregnant women feel hot in the womb with or without signs of fever and this illness, locally known as nabuguma, may lead to progressive weakness and occasionally to miscarriage and few respondents associated it with malaria. Primigravidae, adolescents and men were not considered at risk of omusujja or nabuguma. Similarly anaemia and low birth weight were not associated with malaria; in fact paleness was described as a normal sign of pregnancy. There are cultural and social pressures on married women to get pregnant and this forces them to conceal symptoms like feeling feverishness, backache, nausea, general weakness, loss of appetite and vomiting until they are sure these are due to pregnancy. Most women, however, could not differentiate symptoms of malaria from those of early pregnancy. There is a belief that omusujja is a normal sign of pregnancy and this is coupled with a strong cultural practice of using herbs and clays as a first resort to treat pregnancy ailments including malaria. The cultural beliefs and practices regarding delivery of twin and first births, coupled with the high cost of care, prevent women from delivering and using other services at health units.

Adult↗

Induced abortion and breast cancer risk.

Results from case-control studies suggest that induced abortion may be associated with a small increase in risk of breast cancer. While risk estimates from cohort studies have generally not observed such an association, these studies have had limited information regarding abortion and possible confounding variables. Therefore, we conducted a study among a cohort of post-menopausal women from whom detailed information regarding pregnancy outcomes as well as risk factors for breast cancer had been collected. The study sample included 37,247 Iowa Women's Health Study participants, 55-64 years of age at baseline in 1986, who reported no history of breast, or other, cancer (except non-melanoma skin cancer), and for whom information regarding pregnancy outcomes (that is, live birth, stillbirth, spontaneous abortion, ectopic pregnancy or induced abortion) was available. We used linkage with records of the State Health Registry of Iowa, part of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, to estimate the incidence of breast cancer among cohort members through 1995. We calculated age-adjusted relative risks and 95% confidence intervals using Cox proportional hazards regression. Only 653 women (1.8%) reported an induced abortion. The age-adjusted relative risk of breast cancer among women with prior induced abortion compared with those without was 1.1 (95% CI = 0.8-1.6). Relative risks were higher among women whose age at first abortion was less than 20 or at least 30 years, for those whose abortion took place after their first birth or who never gave birth, and for those with early termination (0-2 months). These estimates varied from 1.3-1.7, but the confidence intervals around each were wide. Since most women in this cohort were beyond their reproductive years when abortion became legal in 1973, the low prevalence of induced abortion argues for a cautious interpretation.

Abortion, Induced↗

Substance use and prenatal care during pregnancy among young women.

Data on a cohort of young mothers from the National Longitudinal Survey of Youth were examined for use of alcohol, cigarettes and marijuana during pregnancies leading to first births. A substantial proportion of women (45 percent) were found to have used at least one of these substances. White women were more likely to use a substance during pregnancy than were Hispanic or black women; women with the prospective father present in the household were less likely than other women to use a substance. Compared with well-educated and older women, less-educated and younger women were more likely to smoke cigarettes or marijuana during pregnancy, but were less likely to drink alcohol. Only about 13 percent of women used more than one substance. Nineteen percent of the women received no prenatal care in the first trimester of pregnancy. Less-educated and younger women were least likely to receive early prenatal care. Multivariate analysis found no association between neglect of prenatal care and substance use. Rather, the analysis revealed that the two behaviors shared likely antecedents, such as whether the prospective father was in the home prior to the pregnancy.

Adult↗

Italian randomized trial among women with hysterectomy: tamoxifen and hormone-dependent breast cancer in high-risk women.

Tamoxifen improves outcome in women with breast cancer and reduces the incidence of estrogen receptor-positive (ER+) breast tumors in prevention trials. Tamoxifen use is associated with an increased risk of potentially serious adverse events, principally endometrial cancer and venous thromboembolic events and, therefore, detailed knowledge of the effects of tamoxifen is important. With more cases of breast cancer being found as the follow-up time increases, it is now possible to perform more detailed analysis of the Italian Randomized Trial of Tamoxifen. Women with hysterectomy (N = 5408) were randomly assigned to receive 20 mg tamoxifen per day (N = 2700) or placebo (N = 2708). After a median of 81.2 months of follow-up, 79 case subjects (34 in the tamoxifen arm and 45 in the placebo arm) were diagnosed with breast cancer. We were able to identify a group of women at increased risk of ER+ breast cancers (high-risk group) on the basis of baseline as well as reproductive and hormonal characteristics (height, age at menarche, parity, age at first birth, and oophorectomy). Tamoxifen administered to women in the high-risk group showed statistically significantly reduced incidence of breast cancer (tamoxifen, 3 and placebo, 15; P =.003), but no such effect was seen in the low-risk group (tamoxifen, 31 and placebo, 30; P =.89). The positive effect of tamoxifen on breast cancer among high-risk women is most marked for ER+ tumors (tamoxifen, 1 and placebo, 11; P =.002). Chemoprevention of breast cancer with tamoxifen appears to be effective in women at high risk of ER+ tumors but not among women at low risk, who may well be protected naturally by late age at menarche or early first pregnancy, or artificially by removal of the ovaries. Tamoxifen could be offered as a preventive agent to women identified at high-risk of breast cancer because of hormone-related risk factors. Such a strategy would greatly reduce the numbers of women who would need to take tamoxifen to obtain the same absolute reduction in breast cancer. These findings are exploratory and need to be confirmed in other randomized trials.

Antineoplastic Agents, Hormonal↗

Breastfeeding history, pregnancy experience and risk of breast cancer.

Epidemiological evidence suggests that breastfeeding protects against breast cancer. Whether an effect of age at first breastfeeding is independent of an effect of age at first birth is unclear. We hypothesized that nausea and vomiting in pregnancy, which are associated with elevated serum oestradiol levels during pregnancy, may increase risk. Cases were 452 parous, premenopausal women, 40 years or younger, diagnosed with breast cancer in Los Angeles County from July 1983 to December 1988. Control subjects were matched to cases on age, race, parity and neighbourhood. Pregnancy and breastfeeding histories were obtained from in-person interviews. Odds of breast cancer among women who breastfed for at least 16 months relative to those among women who did not breastfeed was 0.66 [95% confidence interval (CI) 0.41-1.05]. Number of children breastfed was not associated with risk. Risk was lower in women who first breastfed at older ages. Having ever been treated for nausea or vomiting during pregnancy was associated with an increased risk, especially in women experiencing recent pregnancies (OR = 2.03, 95% CI 1.05-3.92). These results support a protective role of breastfeeding and an adverse role of nausea or vomiting during pregnancy in the development of premenopausal breast cancer, especially in the years immediately following pregnancy.

Adult↗

Elderly nulliparae in midwifery care in Amsterdam.

OBJECTIVE: to compare labour complications, after an uncomplicated pregnancy, of first births in women 35 years and older with women 20-30 years old. DESIGN: an explorative prospective cohort study. SETTING: four independent midwives' practices in Amsterdam. PARTICIPANTS: a group of 49 elderly nulliparae was compared with a group of 99 younger nulliparae. MEASUREMENTS AND FINDINGS: percentage of referrals and reasons for referral during pregnancy and labour, mode of delivery and obstetric outcome. KEY CONCLUSIONS: no significant differences in referrals were found between the two compared groups. Obstetric-outcome was not different between the groups, except for a lower birthweight in the elderly group. A trend is seen for a raised percentage of referrals during labour in the older group. This is almost completely explained by a failure to progress during first and second stages of labour. Related to this was a trend for an increased incidence of caesarean section in the older group of women. IMPLICATIONS FOR PRACTICE: after selection, the elderly nullipara, under the care of a midwife, does not have an increased risk of fetal distress or other emergency factors compared to the younger nullipara. However, the referral rates during labour, both of younger and older women, are high.

Adult↗