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Reliability of self-reports: data from the Canadian Multi-Centre Osteoporosis Study (CaMos).

Reliable questions enhance study design. We assessed the reliability of questions that gather demographic, sun exposure, reproductive history, and physical activity information. Subjects were participants in the Canadian Multicentre Osteoporosis Study (CaMos), a cohort study of Canadian adults recruited January 1996 to September 1997 in nine cities, stratified by sex, age, and location. Following personal interviews, 367 subjects were re-administered part of the questionnaire by telephone. Reliability was assessed using kappa and intra-class correlation. Reliability was excellent for employment status, reproductive history, weight and height (0.91 to 0.97), not differing greatly when stratified by age group or sex. Physical activity and sun exposure were reported with fair to good reliability (0.44 to 0.58), except for moderate activity (kappa = 0.30, 95% confidence interval 0.23, 0.37). Stratification by body mass index did not show significant differences. Many items can be reported reliably, especially those of height, weight, employment status and reproductive history, and, to a lesser extent, physical activity and sun exposure. Similar questions might be used reliably in future studies.

Aged↗

Reproductive risk factors for epilepsy among ten-year-old children in metropolitan Atlanta.

The elements of a woman's reproductive history that may be associated with her risk of having a child who develops epilepsy have not been well described. To examine these possible associations, we used a multiple-source case ascertainment method to identify ten-year-old children with epilepsy who were living in the metropolitan Atlanta area in 1985-87; same-age control children were selected from public schools. To obtain reproductive history and other information, we interviewed 107 mothers of children with epilepsy and 408 mothers of control children. Twenty-nine children with a known intrauterine or postnatal aetiology were excluded from the analysis. We computed adjusted odds ratios for reproductive history characteristics, controlling for the race of the child, maternal education, census block group income, maternal pregnancy history and family history of a developmental disability. Our analyses indicated that mothers of children with epilepsy not only had more previous live births, but more previous adverse reproductive outcomes including spontaneous abortions, very low birthweight infants and infants with birth defects. The risk was especially strong for maternal history of a child with a birth defect. The specific types of birth defects reported in excess include central nervous system defects (specifically spina bifida) and Down's syndrome.

Case-Control Studies↗

Infertility and subfertility in Norwegian women aged 40-42. Prevalence and risk factors.

BACKGROUND: There are few population estimates of the prevalence of infertility that also include some information about medical conditions and social classification of study objects. This is a study of 4034 out of a total of 5139 (78% of all invited) women in one county of Norway. METHODS: All female inhabitants born 1950 to 1952 living in the county were invited to participate in a health screening. The screening comprised a clinical screening and two questionnaires; one about reproductive history and infertility. RESULTS: This survey found permanent primary infertility in 2.6% of the women. Subfertility, as at least one year's delay of pregnancy, was reported by 7.7%. A history of different reproductive problems was associated with impaired fertility. Thirty-two percent of primary infertile women had a history of PID, 13% had experienced amenorrhea and almost 40% reported premenstrual tension, compared with lower frequencies in women with normal fertility (11.0%, 3.3% and 29.4% respectively). CONCLUSIONS: Up to 10% of the female population may experience infertility at one stage in their reproductive career. Clinicians should pay special attention to women presenting any genital or reproductive disorder regarding risks for future fertility impairment.

Adult↗

Combined effect of family history and reproductive factors on breast cancer risk.

This study evaluated the combined effect of a family history of breast cancer and each of three reproductive factors on breast cancer risk in the sisters of 404 breast cancer patients. The patients had a family history of breast cancer in a sister and mother or in two sisters. Risks were highest in sisters who had menarche at an early age or who first gave birth at a late age whether the patient had unilateral or bilateral disease, and with low parity only when the patient had bilateral disease. The bilateral group may have included a higher fraction of hereditary forms of breast cancer than the unilateral group. Because similar findings have been reported previously for breast cancer patients in general, the current results suggest that these reproductive factors have an effect on breast cancer risk independent of a family history of the disease. It is important, therefore, that the combined effects of these risk factors be taken into account when counseling women about their breast cancer risks.

Adult↗

Can men be trusted? A comparison of pregnancy histories reported by husbands and wives.

Agreement between pregnancies and pregnancy outcomes reported by husbands and wives was assessed in a sample of 857 couples interviewed between June 1989 and July 1990. The respondents were men employed in a semiconductor manufacturing plant in Burlington, Vermont, and their wives. The wives' reports were used as the standard against which the husbands' reproductive histories were evaluated. Measures included sensitivity, specificity, and percentage of agreement. Reports were considered to be congruent if an outcome reported by the husband agreed with the outcome reported by the wife within a period of +/- 6 months. Although men and women reported similar numbers of livebirths (1,478 and 1,500, respectively), men tended to misreport the timing of events; therefore, complete agreement on the numbers and dates of births was only 88.5%. Men also misreported the prevalence of low birth weight (sensitivity, 74%). Specificity was poorer for the younger (< 35 years) and less educated (< or = 12 years) respondents. Husbands' reports of spontaneous abortions had lower sensitivity (71.2%) than their reports of livebirths, particularly among the better educated (66.9%). Induced abortions were frequently omitted by the husbands (sensitivity, 35.1%), and events such as stillbirths or tubal pregnancies were too few in number to permit meaningful analysis. It is concluded that husbands' misreporting of their wives' reproductive histories may be substantial and sufficient to compromise the validity of epidemiologic studies. It would, therefore, be prudent to avoid the use of husbands as proxy informants of their wives' reproductive histories.

Adult↗

Evaluation of serum-associated embryotoxicity/mutagenicity in females with reproductive dysfunctions using preimplantation mouse embryos in vitro.

Reproductive failures may be caused by chromosomal anomalies, complex interactions of maternal/fetal genotype and environmental factors. Some of them have also been attributed to undefined maternal serum factor(s). We have developed an assay to evaluate maternal-serum associated embryotoxicity/mutagenicity using the preimplantation mouse embryo. It is based on in vitro culture of 8-cell mouse embryos for 48 h in the presence of 10% sera from females with reproductive dysfunction along with suitable controls. The human sera were obtained from three groups of females: (i) with normal reproductive histories (negative controls), (ii) undergoing cancer chemotherapy (positive controls), and (iii) with a history of failing to achieve or maintain pregnancy (test group). The preimplantation mouse embryos were cultured in the three types of human sera and female rat serum (as an internal control for each experiment) and evaluated for toxicity (embryo survival) and mutagenicity (as measured by SCE). Embryos cultured in serum from women with normal reproductive histories and female rats had survival rates of 70.8 +/- 4.3 and 78.9 +/- 0.9%, respectively. The SCE frequencies for these two sera types were similar: 15.7 +/- 0.2 SCEs/cell (rat) and 16.3 +/- 0.3 SCEs/cell (human). Mouse embryos cultured in medium supplemented with serum from females undergoing chemotherapy had significantly (P less than 0.01) reduced survival (33.7 +/- 5.2%) and significantly (P less than 0.01) increased SCEs/cell (26.5 +/- 0.6). The effect of sera from women with histories of reproductive failures on preimplantation mouse embryos was variable and individual specific. Approximately 40% of the test group female sera yielded survival and SCEs/cell comparable to the sera from patients undergoing chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗

Cleft lip with or without cleft palate: effect of family history on reproductive planning, surgical timing, and parental stress.

OBJECTIVE: This study tested whether the presence of a family history of nonsyndromic cleft lip with or without cleft palate (NSCLP) lessens the negative impact on reproductive planning, decreases treatment anxiety, and relieves parental stress when there is a recurrent cleft. DESIGN: Sixty-one participating families, retrospectively ascertained through their children with NSCLP, were divided into two groups: those with a family history of clefting and those in which only the proband was affected. SETTING: Each family completed a questionnaire either at their home or during a clinic visit. PARTICIPANTS: Questionnaires were distributed to 117 families with an NSCLP child. Of these 117, 49 (42%) had another family member with NSCLP and 68 (58%) had no prior history of clefting. Sixty-one (52%) families returned the questionnaire and were categorized by family history. MAIN OUTCOME MEASURES: The Parenting Stress Index and the Hollingshead Index of Social Position were included with family and medical history questions in the 137-item questionnaire. RESULTS: The reproductive plans of the two groups were quite similar and were not dependent on the families' actual or perceived recurrence risks of NSCLP. The majority (85%) of the children with NSCLP underwent surgical closure at the recommended age. The two groups did not significantly differ on any score on the Parenting Stress Index, indicating a similar parental stress level between the groups. CONCLUSIONS: These findings suggest that family history does not significantly influence reproductive plans, timing of cleft repair, or stress of parents of a child with NSCLP. Further, these results indicate a need for additional psychosocial study of this population.

Adolescent↗

Should women be advised against pregnancy after breast-cancer treatment?

BACKGROUND: Oestrogen is an established growth factor in breast cancer. There has, therefore, been much discussion about whether women should be advised against becoming pregnant after breast-cancer treatment because of a possible negative prognostic effect from the high oestrogen concentrations associated with pregnancy. METHODS: We studied 5725 women with primary breast cancer. Information on these women was obtained from the Danish Breast Cancer Cooperative Group. Since 1977 this group has collected population-based data on tumour characteristics, treatment regimens, and follow-up status of Danish women with breast cancer. Details of reproductive history were obtained from The Danish Civil Registration System, the National Birth Registry, and the National induced Abortion registry. We estimated the relative risk of death among women who became pregnant after breast-cancer treatment compared with women who had not become pregnant. FINDINGS: 5725 women with primary breast cancer aged 45 years of younger at the time of diagnosis were followed up for 35,067 patient-years. Among these, 173 women became pregnant after treatment of breast cancer. Women who had a full-term pregnancy after breast-cancer treatment had a non-significantly reduced risk of death (relative risk 0.55 [95% CI 0.28-1.06]) compared with women who had had no full-term pregnancy after adjustment for age at diagnosis, stage of disease (tumour size, axillary nodal status, and histological grading), and reproductive history before diagnosis. The effect was also not significantly modified by age at diagnosis, tumour size, nodal status, or reproductive history before diagnosis of breast cancer. Neither miscarriages nor induced abortions after breast-cancer treatment influenced the prognosis. INTERPRETATION: We found no evidence that a pregnancy after breast-cancer treatment increased the risk of a poor outcome.

Abortion, Induced↗

Cell-mediated immunity to trophoblast antigens in women with recurrent spontaneous abortion.

OBJECTIVES: The purpose of this study was to determine whether trophoblast antigens activate cell-mediated immune responses in women with recurrent abortion of unknown cause by inducing lymphocyte proliferation and to correlate this with embryotoxic factor production. STUDY DESIGN: Mononuclear cells were isolated from 57 nonpregnant women with recurrent abortion of unknown cause and from 10 fertile controls with normal reproductive histories. Lymphocyte proliferation assays were performed with trophoblast antigen extracts from the human choriocarcinoma cell lines Jeg-3 and JAR, fractionated trophoblast antigens, and for control, red blood cell membrane antigens. A stimulation index > 3 was considered significant stimulation. Trophoblast-stimulated culture supernatants were also tested for embryotoxic activity. RESULTS: Thirty (52.6%) women with recurrent abortion of unknown cause responded to trophoblast antigen stimulation with a stimulation index > 3, whereas none of the control group responded. Neither patients with recurrent abortion nor women with normal reproductive histories responded to red blood cell membrane antigen. The mean stimulation index in the trophoblast antigen lymphocyte proliferation assay was significantly higher in women with recurrent abortion than in women with normal reproductive histories (3.99 +/- 2.82 vs 1.64 +/- 0.34, p < 0.01). Antigen extracts from the cytosol and membrane fractions of Jeg-3 provided the strongest stimulation. Lymphocyte proliferation correlated with embryotoxic factor production; 90.0% of women with a stimulation index > 3 and none of the controls produced embryotoxic factors after stimulation with trophoblast antigens. CONCLUSION: In this study 52.6% of women with recurrent abortion of unknown cause compared with none in controls exhibited in vitro evidence of T-cell immunity to trophoblast antigen stimulation. Further work is needed to determine whether T-cell immunity to trophoblast is involved in the pathogenesis of recurrent spontaneous abortion.

Abortion, Habitual↗

Prevalence of HIV antibody and pregnancy in Tayside, 1984-9: background to screening.

OBJECTIVE: To determine age specific prevalence of HIV antibody, incidence of pregnancy, and likelihood of detection and correct assignment to risk category by antenatal screening of women known to be positive for HIV antibody, from 1984 to 1989. DESIGN: Retrospective analysis of reproductive history and risk behaviour of women positive for HIV antibody and prediction of detection by screening on the basis of blood group samples, Guthrie tests, and rubella tests. SETTING: City of Dundee, where the prevalence of HIV is high, since the appearance of HIV in 1984, predominantly among heterosexual intravenous drug users. PATIENTS: All (61) women known to be positive for HIV antibody who had had clinically indicated tests, for whom case notes were available for 60. MAIN OUTCOME MEASURES: Risk assessment according to case notes and reported to the laboratory, incidence of infection, geographical location, age, date of positive test result, and reproductive history. RESULTS: With 61 infected women the overall minimum prevalence among women within the city of Dundee was 0.67/1000 and 2.9/1000 among women in their third decade. Of the 60 women whose reproductive history was available, 35 had 57 pregnancies, 36 of which occurred after seroconversion was known to have taken place, representing 8.7% of the total number of affected pregnancies reported for the United Kingdom. If antenatal screening for HIV had been performed between 1984 and 1989 it could not have detected positivity for HIV antibody in 25 (42%) women who had no pregnancies during this time. Among the remaining 35 women, screening samples taken for blood grouping could have identified a maximum of 34 (57%), samples taken to check rubella susceptibility a maximum of 22 (37%), and blood spots on Guthrie cards a maximum of 19 (32%). Retesting would have occurred in 14 women 33 times with samples taken for blood grouping, but three and four women would have been tested twice using samples taken for rubella testing and Guthrie cards respectively. Anonymous screening would have been unable to determine risk category as a history of intravenous drug use was known in 47 (79%) women before testing but this was increased by a further 5 (8%) who admitted to it after the test result was known. CONCLUSION: Interpreting the results of antenatal screening programmes will be complex and will underestimate overall prevalence of HIV antibody among women; this will be exaggerated by strategies based on anonymous testing with Guthrie cards or on samples taken for rubella testing, which do not include women who have had an earlier loss of pregnancy. Only open testing with consent will permit satisfactory attribution to

Acquired Immunodeficiency Syndrome↗

Imminent ovarian failure in childhood cancer survivors.

The aim of this study was to investigate reproductive history and the prevalence of imminent ovarian failure (IOF) in female childhood cancer survivors. Reproductive history and ovarian function were evaluated by questionnaires (n=124) and by measurement of follicle stimulating hormone (FSH) and oestradiol (E2) levels (n=93). IOF was defined as FSH>10 IU/l or E2>0.28 nmol/l on day 3 of the menstrual cycle, or FSH>12.4 IU/l on day 7 of the pill-free interval. IOF was demonstrated in 22.6% of the participants and correlated with age at diagnosis (P<0.005) and age at study (P=0.036). IOF correlated inversely with methotrexate (P=0.046). The incidence of miscarriages (22.7%) and recurrent miscarriages (7.3%) was increased. The male/female (M/F) ratio of the offspring was decreased. In conclusion, female childhood cancer survivors are at risk for IOF. If pregnant, the risk of (recurrent) miscarriages is increased. The M/F ratio in the offspring is decreased.

Abortion, Spontaneous↗

Determinants of obesity in relation to socioeconomic status among middle-aged Swedish women.

BACKGROUND: It has been previously demonstrated that obesity is common among women with low socioeconomic status (SES), but the factors accounting for this association are not well known. According to our hypothesis, low SES is associated with psychosocial stress, an unhealthy lifestyle, and reproductive history, which may increase the likelihood of women with low SES to be overweight or obese. METHODS: We examined overweight and obesity in relation to SES among 300 healthy women ages 30-65 years, who constitute the control group of the Stockholm Female Coronary Risk Study, a population-based case-control study of women with coronary heart disease. This control group was compared with a large population-based sample and found to be representative of healthy Swedish women ages 30-65 years. We used an aggregate of education and occupation as a measure of SES and defined overweight as body mass index (BMI) between 23.8 and 28.6 kg/m2 and obesity as BMI > 28.6 kg/m2. RESULTS: Low SES was a strong determinant of overweight and obesity among middle-aged healthy Swedish women. The odds of being overweight or obese increased with lower social position. After adjustment for age, the odds ratios for overweight and obesity among women in a low vs high position were 2.2 [95% confidence interval (CI) 1.1 to 4.4) and 2.7 (95% CI 1.1 to 6.7), respectively. Both low social position and obesity were related to reproductive history (higher parity and earlier age at menarche), unhealthy dietary habits, and unfavorable psychosocial factors (poor quality of life, low self-esteem, and job strain). These factors together explained 53% of the low-SES-obesity association. CONCLUSIONS: Reproductive history, unhealthy dietary habits, and psychosocial stress accounted for a large part of the association between low SES and obesity. Dietary habits and psychosocial stress are potentially modifiable factors, which should be taken into account in intervention programs among women with low SES.

Adult↗

A comparison of reproductive risk factors for CIS lesions and invasive breast cancer.

A differential effect of reproductive factors on the incidence of carcinoma in situ of the breast (CIS) and invasive cancer may indicate that hormonal factors related to reproductive history not only influence the initial steps towards breast cancer but also preinvasive malignant lesions. A comparison of reproductive factors was performed using a population-based cohort of 1.5 million Danish women born between 1935 and 1978. Between 1983 and 1998, 15,590 cases of invasive breast cancer and 871 cases of CIS were identified using a database with extensive clinical information. Number of births and age at first birth were similarly associated with the risk of being diagnosed with ductal carcinoma in situ (DCIS) compared to invasive breast cancer [RR(DCIS)(per birth)/RR(invasive)(per birth) = 1.03(0.93-1.14), RR(DCIS)(per 5yr) /RR(invasive)(per 5yr) = 1.06(0.96-1.17)]. Also, the short-term risk the first 10 years after birth was similar for DCIS and invasive cancer [RR(DCIS) /RR(invasive) = 0.90 (0.74-1.09)]. Additional analyses were performed according to characteristics of the DCIS lesion (size, malignancy grade, noncomedo or comedo type). In conclusion, our observations do not support the theory that reproductive history is associated with progression from noninvasive to invasive breast cancer.

Adolescent↗

Alcohol consumption and breast cancer.

The association between alcohol consumption and breast cancer was investigated in a case-control study involving 1,524 cases and 1,896 controls identified through a nationwide screening program. Ever drinking alcohol was not associated with any substantial increase in risk [odds ratio (OR) = 1.1; 95% confidence interval (Cl) = 1.0-1.3], but there was a significant trend in risk with increasing average weekly intake (P less than .04). Women who had one or fewer drinks daily (83% of all drinkers) did not experience any excess risk compared to nondrinkers, but significant excess risks were observed among those who drank from 1 to 2 (OR = 1.3; 95% Cl = 1.0-1.7) or more than 2 (OR = 1.7; 95% Cl = 1.2-2.4) drinks a day. An increased risk associated with alcohol consumption was evident only for those who drank at younger ages (less than 30 yr), regardless of current consumption. Alcohol effects were adjusted for a variety of factors, including reproductive history, were adjusted for a variety of factors, including reproductive history, socioeconomic indicators, and obesity, but none exerted any appreciable confounding influence. The results support an association between moderate alcohol consumption in early life and subsequent breast cancer risk, although interpretation should be cautious in the absence of dietary information.

Adult↗

Increased incidence of spontaneous abortion and infertility in women with scleroderma before disease onset: a controlled study.

A postal questionnaire was used in a nationwide case control study of women with scleroderma to investigate whether there was an increased rate of spontaneous abortion before the onset of the disease. The results from 155 case control pairs studied showed that the women with scleroderma had twice the rate of spontaneous abortion and three times the rate of fertility problems (no successful pregnancy by the age of 35) of the control women. Previous uncontrolled studies have suggested that established scleroderma is associated with an adverse reproductive history. The results from this investigation suggest that the adverse reproductive history may antedate the clinical diagnosis of scleroderma by many years and may possibly have an aetiological role. Such a hypothesis is consistent with the, as yet unexplained, marked female excess in incidence of the disease, with the peak age of onset occurring shortly after the reproductive period.

Abortion, Habitual↗

The importance of employing stringent methods to recruit fertile male controls.

Two methods of recruiting fertile male controls were evaluated and compared. The first group was recruited from the partners of women attending an antenatal clinic without obtaining details of their reproductive history. The second group was recruited after obtaining a detailed reproductive history from the couple and employing stringent entry criteria. Entry criteria for the second group included a length of exposure to the risk of pregnancy of not more than 12 months and no previous episode of involuntary infertility for either partner. There were significant differences between the distributions of semen parameters obtained from the two groups, indicating that the selection criteria for "fertile" men significantly influence results obtained and therefore that it is important to employ stringent criteria for the recruitment of fertile male controls. The group which was recruited by stringent criteria (mean length of exposure to the risk of pregnancy of 3 months) was characterised by a significantly higher median concentration of spermatozoa which exhibited slow linear or nonlinear motility. This confirms the findings of a previous study which suggested that slow linear or nonlinear motility are superior forms of spermatozoal motion.

Adult↗

Lifetime reproductive success, longevity, and reproductive life history of female yellow baboons (Papio cynocephalus) of Mikumi National Park, Tanzania.

The relationship between longevity and lifetime reproductive success (LRS) was studied in free-ranging female baboons of Mikumi National Park, Tanzania. A severe population decline occurred between the 12th and 20th years of the study. The total sample consisted of 72 females born and reaching adulthood before the start of the population decline. There were 27 females who were adult at the start of the study and 45 who became adult within the 12 years prior to the decline. The subjects were studied until all 72 were dead and all of their offspring were either dead or at least six years old; this took 24 years. The relationship of longevity to LRS was statistically significant for the total sample and for both sub-samples, with 70% of the total variance in LRS accounted for by longevity. Longevity was linked to LRS via a chain of statistically significant relationships: The longer the life span, the longer the reproductive life; the longer the reproductive life, the more offspring produced; the more offspring produced, the higher the LRS. Mean LRS, life span, and reproductive longevity all differed between the two sub-samples. Since the sub-samples were time-linked to a population decline affecting longevity, either sub-sample separately would fail to reflect the broader picture. This illustrates the importance of appreciable sample sizes from long-term studies in helping understand the dynamics between life history estimates and ecological conditions in variable environments.

Animals↗

Maternal age and fetal loss: population based register linkage study.

OBJECTIVE: To estimate the association between maternal age and fetal death (spontaneous abortion, ectopic pregnancy, stillbirth), taking into account a woman's reproductive history. DESIGN: Prospective register linkage study. SUBJECTS: All women with a reproductive outcome (live birth, stillbirth, spontaneous abortion leading to admission to hospital, induced abortion, ectopic pregnancy, or hydatidiform mole) in Denmark from 1978 to 1992; a total of 634 272 women and 1 221 546 pregnancy outcomes. MAIN OUTCOME MEASURES: Age related risk of fetal loss, ectopic pregnancy, and stillbirth, and age related risk of spontaneous abortion stratified according to parity and previous spontaneous abortions. RESULTS: Overall, 13.5% of the pregnancies intended to be carried to term ended with fetal loss. At age 42 years, more than half of such pregnancies resulted in fetal loss. The risk of a spontaneous abortion was 8.9% in women aged 20-24 years and 74.7% in those aged 45 years or more. High maternal age was a significant risk factor for spontaneous abortion irrespective of the number of previous miscarriages, parity, or calendar period. The risk of an ectopic pregnancy and stillbirth also increased with increasing maternal age. CONCLUSIONS: Fetal loss is high in women in their late 30s or older, irrespective of reproductive history. This should be taken into consideration in pregnancy planning and counselling.

Abortion, Spontaneous↗