Does abortion increase breast cancer risk?

PIP: Abortion may increase the risk of breast cancer. Leon Bradlow, M.D., director of the Laboratory of Biochemical Endocrinology and the Strang-Cornell Cancer Research Laboratory in New York, believes that pregnancy protects against breast cancer through the differentiation of breast cells during the second half of pregnancy. Since estrogen, which increases breast cancer risk, is secreted during the first half of pregnancy in order to stimulate breast growth, abortion at that time will expose the mother to high concentrations of estrogen when cells are undifferentiated. Bradlow believes the public should be made aware of studies showing this. Louise Brinton, M.D., of the National Cancer Institute's Division of Cancer Etiology, disagrees because there are many studies that show no link between breast cancer and abortion. Malcolm Pike, M.D., who did the first study linking the two in 1981 (Women less than 33 years of age who had an abortion were 2.4 times more likely to get breast cancer.), declined comment because he had not studied recent data. Holly Howe, Ph.D., of the New York State Department of Health, examined data from fetal death certificates and breast cancer incidence records (1451 women between 1976 and 1980), to find that women (40 years of age) whose pregnancies had been terminated had a relative risk of breast cancer ranging from 1.5 to 1.9. An unpublished study by Janet Daling, M.D., of the Fred Hutchison Cancer Research Center in Seattle, shows a 50% to 90% increase in risk for women who had an abortion before the age of 18. Lynn Rosenberg, M.D., of the Slone Epidemiology Unit of the Boston University School of Medicine, based on a study of 3200 women with breast cancer and 4844 controls, found no relationship between abortion and risk. Brinton is currently conducting a study on breast cancer risk that includes abortion evaluation.^ieng

Risk of breast cancer after miscarriage or induced abortion: a Scottish record linkage case-control study.

STUDY OBJECTIVE: To assess the risk of breast cancer in patients with a previous history of miscarriage or induced abortion. DESIGN: Case-control study relating "exposure" to outcome by linkage of national hospital discharge and maternity records, the national cancer registry, and death records. SETTING: Scotland. PARTICIPANTS: Miscarriage analysis-2828 women with breast cancer and 9781 matched controls; induced abortion analysis-2833 women with breast cancer and 9888 matched controls. MAIN RESULTS: After stratification for age at diagnosis, parity, and age at first birth, the odds ratio (95% confidence intervals) of breast cancer was 1.02 (0.88 to 1.18) in women with a previous miscarriage, and 0.80 (0.72 to 0.89) in women with a previous induced abortion. Further adjustments for age at bilateral oophorectomy, socioeconomic status (based on small area of residence), and health board area of residence had only minor effects on these odds ratios. CONCLUSION: These data do not support the hypothesis that miscarriage or induced abortion represent substantive risk factors for the future development of breast cancer.

Perinatal transmission of HIV-1: lack of impact of maternal HIV infection on characteristics of livebirths and on neonatal mortality in Kigali, Rwanda.

We present the baseline results of a prospective cohort study on the perinatal transmission of HIV-1 in Kigali, Rwanda. HIV-1-antibody testing was offered to all women of urban origin delivering a live newborn at the maternity ward of the Centre Hospitalier de Kigali from November 1988 to June 1989; 218 newborns of 215 HIV-positive mothers were matched to 218 newborns of 216 HIV-negative mothers. The matching criteria were maternal age and parity. No differences in socioeconomic characteristics were observed between HIV-positive and HIV-negative women. HIV-positive mothers more frequently reported a history of at least one death of a previously born child (P less than 0.01) and a history of abortion (P less than 0.001). Most of the HIV-positive women were asymptomatic, but 72.4% of them had a CD4; CD8 ratio less than 1 versus 10.1% in the HIV-negative group (P less than 0.001). The frequency of signs and symptoms was not statistically different in the two groups, except for a history of herpes zoster or chronic cough, which was more frequent among HIV-positive women. The rates of prematurity, low birth weight, congenital malformations and neonatal mortality were comparable in the two groups. However, infants of HIV-positive mothers had a mean birth weight 130 g lower than the infants of HIV-negative mothers (P less than 0.01). The impact of maternal HIV-1 infection on the infant seems limited during the neonatal period.

Thyroiditis after pregnancy loss.

We present a case series evaluating the development and characteristics of thyroiditis following pregnancy loss. Five women were followed prospectively with measurement of thyroid function and antithyroid antibodies after pregnancy loss. Serum TSH concentrations were measured by immunoradiometric assay and antithyroid antibodies by RIA and hemagglutination techniques. All women had normal serum TSH concentrations before conception or at the time of pregnancy loss, and all but one had positive antithyroid antibodies. Pregnancy loss occurred between 5-20 weeks gestation because of ectopic pregnancy or either spontaneous or elective abortion. Two women had subclinical hypothyroidism with peak serum TSH values of 8.7 mU/L and 5.4 mU/L at 2 and 7 months after pregnancy loss, respectively. Three women had clinical hyperthyroidism with serum TSH values < or = 0.2 mU/L diagnosed between 3-11 months after pregnancy loss followed subsequently by a hypothyroid phase. Painless thyroiditis within 1 yr of pregnancy loss in these women suggests that the immunological changes of a short-term gestation may be sufficient to lead to thyroiditis.

Hashimoto's thyroiditis and insulin-dependent diabetes mellitus: differences among individuals with and without abnormal thyroid function.

Insulin-dependent diabetes mellitus probands from the Familial Autoimmune and Diabetes Study were evaluated for autoimmune thyroid disease (n = 265). The prevalence of Hashimoto's thyroiditis was 26.6%; 42.0% of these individuals were euthyroid, and 58.0% were hypothyroid. There was a female predominance among hypothyroid and euthyroid Hashimoto's cases compared to those with no thyroid disease (75% vs. 72.4% vs. 41.6%; P < 0.001). Insulin-dependent diabetes mellitus patients with hypothyroid Hashimoto's thyroiditis were more likely to report another autoimmune disease compared to euthyroid Hashimoto's patients or individuals with no thyroid disease (30.8% vs. 17.2% vs. 13.9%; P < 0.01). Sex-specific analysis revealed that this difference was significant for men but not for women. Both euthyroid and hypothyroid Hashimoto's cases were more likely to have a family history of the disease (66.7% vs. 69.2% vs. 47.7%; P < 0.05). No differences were observed in the prevalence of DQA1*0501-DQB1*0201 or DQA1*0301-DQB1*0302 across the three groups. Body mass index, lipid levels, glycemic control, and diabetes complications were also similar. However, euthyroid Hashimoto's women were more likely to report spontaneous abortions than those with hypothyroid Hashimoto's thyroiditis or no thyroid disease (23.8% vs. 61.5% vs. 29.1%; P < 0.05). These data suggest that gender-specific risk factors may be primary determinants of Hashimoto's thyroiditis and other autoimmune diseases among women. However, disease-specific determinants may also increase susceptibility to other autoimmune diseases.

Onset of obsessive-compulsive disorder in pregnancy.

OBJECTIVE: Although the role of pregnancy and childbirth in postpartum psychosis and depression has been studied, the association between pregnancy and obsessive-compulsive disorder has not been specifically addressed. The authors evaluated the role of pregnancy in the onset of obsessive-compulsive disorder. METHOD: Female patients with obsessive-compulsive disorder (N = 106) completed a questionnaire assessing age at onset of symptoms, marital status, number of children, age at each pregnancy, and life events associated with the onset of obsessive-compulsive disorder. RESULTS: Of the 106 women, 42 were childless and 59 had at least one child each; five others were also childless but had had abortions (N = 4) or a miscarriage (N = 1). Of the 42 women without children, 12 (28.6%) had first experienced obsessive-compulsive symptoms between the ages of 13 and 15 years, but there were two peaks of onset for the women with children: ages 22-24 and 29-32 years. Of the 59 patients with children, 23 (39.0%) had experienced symptom onset during pregnancy; this was the first pregnancy for 12, the second pregnancy for eight, and the third pregnancy for three. Four of the five women who had had abortions or a miscarriage had experienced the onset or an exacerbation of obsessive-compulsive symptoms during pregnancy. CONCLUSIONS: The association between pregnancy and the onset of obsessive-compulsive symptoms in these female patients highlights the need for further research on psychological and biological factors associated with pregnancy and obsessive-compulsive disorder.

Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients.

Five hundred consecutive patients with systemic lupus erythematosus (SLE) were entered into a prospective study of anticardiolipin antibodies (ACLA) in their 3 major immunoglobulin isotypes and followed thereafter with repeated testing for a mean period of nearly 8 months. Manifestations of SLE that were strongly associated with ACLA included venous thrombosis (particularly when recurrent), thrombocytopenia, hemolytic anemia, recurrent fetal loss, and leg ulcers. Other manifestations found to be associated with ACLA were arterial occlusions, transverse myelitis, and pulmonary hypertension. Conversely, we found no relationship between ACLA and migraine, convulsions, transient ischemic attacks, psychoses, or avascular necrosis of bone. No relationship was found between the presence of ACLA and that of anti-DNA antibodies studied in the same serum sample. Association with ACLA grew stronger and titers became higher in patients with several of the associated manifestations. Statistical analyses revealed the existence of a syndrome, the antiphospholipid syndrome, comprising 2 or more manifestations in conjunction with ACLA titers 5 standard deviations above the mean of normal control subjects, particularly if ACLA had been positive on at least 2 occasions. We propose that such criteria could be applied to the definition of the antiphospholipid syndrome. The presence and the titers of these antibodies related to disease activity and titer decreased by treatment, particularly when they were of the IgM isotype. Patients in whom a thrombotic episode occurred during the course of the study were observed to have a coincident decrease in ACLA titers, a finding that might indicate consumption of the antibody during the event. Treatment and the resulting inactivation of disease appear to have independent effects on ACLA titers. Physicians should therefore be cautious in prescribing high doses of corticosteroids or immunosuppressants to patients with SLE solely because they have high titers of ACLA.

Periventricular heterotopia and epilepsy.

We report a family with nodular subependymal masses of heterotopic gray matter occurring in six members in four generations. Only female members of the family are affected, and there is a high rate of spontaneous abortion, consistent with X-linked dominant inheritance, and lack of viability in affected males. Both in this family and in sporadic cases of subependymal heterotopias there is a high frequency of convulsive disorders, suggesting that epilepsy may be the major clinical manifestation of this developmental defect.

Adeno-associated virus DNA in human gestational trophoblastic disease.

Previous studies had shown a correlation between infection with the human adeno-associated virus (AAV) and spontaneous abortion in early pregnancy. Furthermore, AAV DNA had been detected in cells of the human trophoblast lines, Jeg-3, JAr, and BeWo, in cells of the human amnion line, FL, and in trophoblasts from amnion fluids. Infectious AAV virions could be isolated from amnion fluids. To further analyse AAV infection during pregnancy, we tested material from Gestational Trophoblastic Disease for the presence of AAV DNA. With 63 tissue samples from patients from Brazil, including 49 hydatiform moles and 14 choriocarcinomas, nested PCR was performed to detect the presence of AAV DNA. In addition, 15 samples from spontaneous abortions were analysed. AAV DNA was found in 43 samples (28/49 hydatiform moles, 4/14 choriocarcinomas, 11/15 miscarriage material). These findings confirm AAV infection of embryo-derived tissue in humans and further suggest a role of AAV in miscarriage and trophoblastic disease.

Anxiety disorders following miscarriage.

BACKGROUND: Several previous studies have established that miscarriage is a risk factor for depressive symptoms and disorder. By contrast, research on miscarriage as a possible risk factor for anxiety symptoms is inconclusive, and for anxiety disorders, sparse and uninformative. The current study examines the incidence of and relative risk for 3 DSM-III anxiety disorders (obsessive-compulsive disorder [OCD], panic disorder, and phobic disorders) within the 6 months following miscarriage. Adequate diagnostic data on other anxiety disorders were not available. METHOD: Using a cohort design, we tested whether women who miscarry are at increased risk for a first or recurrent episode of an anxiety disorder in the 6 months following loss. The miscarriage cohort consisted of women attending a medical center for spontaneous abortion (N = 229); the comparison group was a population-based cohort of women drawn from the community (N = 230). RESULTS: Among miscarrying women, 3.5% experienced a recurrent episode of OCD, compared with 0.4% of community women (relative risk [RR] = 8.0; 95% confidence interval [CI] = 1.0 to 63.7). The relative risk for noncomorbid panic disorder was substantial (RR = 3.6), albeit not statistically significant (95% CI = 0.8 to 17.2). There was no strong evidence for increased risk for phobic disorders or agoraphobia, combined or considered separately, in the 6 months following loss. Relative risk for all 3 disorders combined was 1.5 (95% CI = 0.9 to 2.3). CONCLUSION: In this first miscarriage cohort study using a concurrent frequency-matched comparison group, miscarriage was a substantial risk factor for an initial or recurrent episode of OCD. Given statistical power limitations of this investigation, the current findings do not preclude a possible contribution of miscarriage to risk for other anxiety disorders.

The influence of medical conditions associated with hormones on the risk of breast cancer.

Medical conditions related to hormonal abnormalities were investigated in a case-control study of breast cancer among women who attended a screening centre. Information was obtained by telephone interview regarding physician-diagnosed medical conditions such as thyroid or liver diseases, diabetes, and hypertension, as well as hirsutism, acne, galactorrhoea, and reproductive, menstrual, and gynaecological factors. Results are presented for 354 cases and 747 controls. Women with fertility problems who never succeeded in becoming pregnant were at significantly increased breast cancer risk (adjusted odds ratio [OR] = 3.5; 95% confidence interval [CI]:1.1-10.9). An elevated cancer risk was also associated with having excess body hair (OR = 1.5; 95% CI:1.0-2.3), or having excess body hair in addition to persistent adult acne (OR = 6.8; 95% CI:1.7-27.1). Recurrent amenorrhea (OR = 3.5; 95% CI:1.1-11.5), and a treated hyperthyroid condition (OR = 2.2; 95% CI:1.1-4.4) were significantly associated with risk. A non-significant elevation of risk was present for endometrial hyperplasia (OR = 1.8; 95% CI: 0.8-4.0). There was a suggestion of an association between a history of galactorrhoea and breast cancer risk (OR = 2.0; 95% CI:0.8-4.9) among premenopausal women. No associations were found with other medical or gynaecological factors. The possibility that some of these findings are due to chance cannot be excluded because of the problem of multiple comparisons.

Variation in spontaneous abortion rate relates to the indication for therapeutic donor insemination.

OBJECTIVE: To evaluate the relationship between indications for donor insemination and the rate of spontaneous abortion of these pregnancies. METHODS: All therapeutic donor insemination pregnancies from our clinic over a 15-year period were categorized according to the indications for insemination, recipient's age, cycle of conception, use of ovulation-inducing agents, use of fresh or frozen semen, and pregnancy outcome. Spontaneous abortion rates were compared between groups segregated according to the indication for donor insemination; differences in maternal age were taken into account. Statistical evaluation was done using chi 2 analysis. RESULTS: Women whose partners produced some sperm in their ejaculates had a spontaneous abortion rate of 21.8%, as compared to 15.4% for women whose partners were azoospermic (P < .05). When couples with oligospermia were segregated by degree of oligospermia, those with counts greater than 2 x 10(6)/mL had an abortion rate of 26.2%, as compared to 11.7% in those with counts less than 1 x 10(6)/mL (P < .025). CONCLUSIONS: The indication for performing therapeutic donor insemination has an influence on the resultant spontaneous abortion rate. Several possible reasons for this relationship may exist, but more data will be needed for verification. A better understanding of the influences that the indication for donor insemination has upon the outcome will facilitate more accurate counseling of candidate couples.

Placental previa in relation to induced and spontaneous abortion: a population-based study.

OBJECTIVE: To evaluate the impact of induced abortion and spontaneous abortion on the occurrence of placenta previa in later pregnancies. METHODS: A population-based, case-control study was conducted using 1984-1987 Washington state birth certificate data. The study population included 486 white women with a pregnancy complicated by placenta previa and 1598 randomly selected controls without placenta previa. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals (CIs). RESULTS: After adjustment for confounding variables, the odds ratio in association with one or more induced abortions was 1.28 (95% CI 1.00-1.63). For one or more spontaneous abortions, the odds ratio was 1.30 (95% CI 1.01-1.66). CONCLUSIONS: Women who report one or more induced or spontaneous abortions are 30% more likely to have a subsequent pregnancy complicated by placenta previa than women without such a history. The results should not be generalized to areas where suction curettage is not the preferred method of induced abortion.

Spontaneous resolution of ectopic pregnancy.

Fourteen patients with ampullary tubal pregnancy confirmed by laparoscopy were initially managed conservatively. Serum human chorionic gonadotropin (hCG) levels were measured daily and strict clinical monitoring performed. In nine patients (64%), the tubal pregnancy spontaneously resolved. In four cases (29%), surgery was ultimately necessary. One patient with a coexistent intra- and extrauterine pregnancy was also successfully managed conservatively. There was a high probability of spontaneous resolution of the pregnancy when the serum hCG level at diagnosis was less than 1000 mIU/mL. Hysterosalpingography was performed after the spontaneous resolution of the tubal pregnancies. Tubal patency was demonstrated in all six patients, and three are currently pregnant. We conclude that conservative therapy allows spontaneous resolution of certain types of ectopic pregnancy.

Post-miscarriage thyroid dysfunction.

BACKGROUND: Thyroid dysfunction is a common postpartum event affecting as many as 16.7% of women. The purpose of this paper was to report the first known case of post-miscarriage thyroid dysfunction. CASE: A 32-year-old woman with a 9-year history of infertility underwent in vitro fertilization. After two spontaneous miscarriages, she delivered a full-term healthy child. Spontaneous menses did not return following delivery, and hormonal evaluation revealed severe postpartum thyroid disease associated with hyperprolactinemia. Retrospective analysis of frozen sera revealed thyroid dysfunction and hyperprolactinemia after the first miscarriage, even though the gestation lasted only 47 days. CONCLUSION: The present case of thyroid dysfunction following a first-trimester miscarriage raises issues concerning the immunology of pregnancy and thyroid dysfunction after pregnancy. The incidence of post-miscarriage thyroid dysfunction and severe postpartum thyroid disease resulting in amenorrhea requires further study.

Maternal risk factors in infants with very low birth weight.

To determine whether maternal risk factors associated with the delivery of very low birth weight infants under 1501 g are different from those associated with low birth weight infants of 1501 to 2500 g, prenatal data on 12,247 deliveries were evaluated. The sample contained 302 very low birth weight infants. Maternal race, age, height, weight, gravidity, parity, past pregnancy performance, and pregnancy complications were analyzed. Factors related to very low birth weight but not to low birth weight infants were previous abortions, previous fetal deaths, and hypertensive vascular disease. Race, maternal height, and prepregnancy weight were not related to very low birth weight but were associated with an increase in low birth weight. There was no significant difference in the rate of very low birth weight or low birth weight by maternal age from 14 to 40 years. These results contradict the concept of a uniform set of predisposing factors for birth of all infants weighing 2500 g or less.

Unfavorable outcome in penultimate pregnancy and premature rupture of membranes in successive pregnancy.

OBJECTIVES: Previous adverse obstetric events are known to influence the outcome of the succeeding pregnancy. We tested the hypothesis that preterm premature rupture of membranes (PROM), full-term PROM, and preterm delivery without PROM relate independently to the outcome of the immediately preceding pregnancy. METHODS: In a case-control study, 345 women 15-45 years old with preterm PROM, full-term PROM, or preterm delivery without PROM were singly matched by age, race, and parity to women having full-term delivery. Information about the penultimate pregnancy, household smoking, and sociodemographic variables were obtained during face-to-face interviews. Obstetric history, infections during pregnancy, and pregnancy complications abstracted from medical records were cross-checked with patient interview data. Penultimate pregnancy outcomes included full-term delivery, premature delivery, fetal loss or miscarriage, and planned abortion. RESULTS: Women having preterm PROM or preterm delivery without PROM in the index pregnancy were, respectively, 6.34 and 21.28 times more likely than controls to have had preterm delivery in the preceding pregnancy. A preceding fetal loss or miscarriage also increased 4.39-fold the risk for preterm PROM. Exposure to cigarette smoke, urinary tract infections, and vaginal bleeding during the index pregnancy independently increased the risk for preterm PROM. Women with full-term PROM did not differ significantly from controls in the outcomes of the penultimate pregnancy. CONCLUSION: Preterm delivery in the preceding pregnancy is associated with an increased risk for preterm delivery with or without PROM.

Oral contraceptive use and risk of uterine fibroids.

The association between oral contraceptive (OC) use and the risk of uterine fibroids was analyzed in a case-control study conducted between 1986-1990. The subjects were 390 patients under 55 years of age with histologically confirmed fibroids and 1136 controls in hospitals for a spectrum of acute conditions (other than gynecologic, hormonal, or neoplastic) apparently unrelated to OC use. A total of 78 cases (20%) and 200 controls (18%) reported OC use. Compared with never-users, the multivariate relative risk for ever-users was 1.1 (95% confidence interval [CI] 0.8-1.5). No direct relationship emerged with duration of use, the estimated relative risk being 1.3 (95% CI 0.9-2.0) in users of OCs for less than 3 years and 0.8 (95% CI 0.5-1.3) in users for 3 years or more. The risk of fibroids was apparently (though not significantly) greater with longer recency of use: The estimated relative risks were 0.9 and 1.5, respectively, in women reporting last OC use less than 10 years before and 10 or more years before diagnosis of the disease. No relationship emerged with latency of use. There was no noteworthy interaction regarding risk of fibroids between OC use and potential covariates. These findings suggest that fibroids are unrelated to the use of OCs.

Cervical incompetence: diagnosis and outcome.

The results of 147 cervical cerclage procedures were reviewed in a retrospective study. Patient history and past reproductive performance were assessed to determine which factors were predictive of successful pregnancy outcome after cervical cerclage. A past history of spontaneous second trimester abortion or premature labor was associated with a better outcome than was a history classically associated with cervical incompetence. Morbidity immediately following the procedure was low, however significant morbidity related to cervical scarring occurred at the time of delivery. There was poor correlation between the clinical history, examination and adjunctive tests of cervical incompetence, and the pregnancy outcome following cerclage. These observations indicate the need for a prospective, randomized study of the efficacy of this procedure.

Postpartum and Postabortal Ovarian Vein Thrombophlebitis.

Six cases of ovarian vein thrombophlebitis are reported including one resulting in operative death, a case diagnosed by phlebography, a postabortal case, and a case followed by habitual abortion. An historic review of this disease is presented. It is suggested that the ovarian vein may be the most commonly involved vein in puerperal pelvic thrombophlebitis.