Risk factors for ectopic pregnancy: a case-control study in France, with special focus on infectious factors

A case-control study was conducted in 1988 in seven Paris area maternity hospitals to evaluate the role of several risk factors, particularly infectious factors, in ectopic pregnancy. A total of 279 cases and 279 controls were compared for sociodemographic characteristics, cigarette smoking, sexual, reproductive and surgical histories, and conditions of conception. Pelvic inflammatory disease confirmed by celioscopy (odds ratio (OR) = 5.5, 95% confidence interval (CI) 2.1-13.9) and Chlamydia trachomatis seropositivity (OR = 3.9, 95% CI 2.3-6.7) appeared to be important risk factors for ectopic pregnancy. Other risk factors found to be associated with an increased risk of ectopic pregnancy were dose-related cigarette smoking at the time of conception (ORs 1.3 to 2.5), appendectomy (OR = 1.6, 95% CI 1.1-2.5), prior tubal surgery (OR = 5.1, 95% CI 1.7-15.4), induced conception cycle (OR = 3.2, 95% CI 1.1-9.3), and prior ectopic pregnancy (OR = 13.3, 95% CI 4.5-39.2). However, some of the latter risk factors, i.e., prior tubal surgery, prior ectopic pregnancy, and perhaps appendectomy, may be considered to be the results of pelvic inflammatory disease and sexually transmitted diseases. Maternal age, parity, prior induced abortion, and prior spontaneous abortion were not associated with ectopic pregnancy. Use of intrauterine device, progestagen micropill, and also combined estroprogestative pill at the time of conception were associated with a better prevention of intrauterine pregnancy than of ectopic pregnancy. These findings confirm the importance of several previously reported risk factors of ectopic pregnancy: sexually transmitted diseases, cigarette smoking, and prior ectopic pregnancy. They also identified new risk factors, appendectomy and induced conception cycle, and revealed that the combined estroprogestative pill does not prevent ectopic pregnancy as effectively as it does intrauterine pregnancy.     

The use of electric bed heaters and the risk of clinically recognized spontaneous abortion

We conducted a prospective cohort study to evaluate the relation of spontaneous abortion and electric bed heater use during the first trimester of pregnancy. Compared with non-users, rates of spontaneous abortion were lower for women who used electric bed heaters. The adjusted odds ratio and 95% confidence interval (CI) for the two major devices used, electric blankets (N = 524) and waterbeds (N = 796), were, respectively, 0.8 (95% CI = 0.5-1.1) and 0.9 (95% CI = 0.7-1.2). An increase of risk with increasing intensity (setting-duration combination) of use was not observed. Users of electric blankets at low settings for most of the night (N = 171) had lower risks of spontaneous abortion than non-users (adjusted odds ratio = 0.5; 95% CI = 0.3-1.0). Twenty women who used electric blankets at a high setting for 1 hour or less had an adjusted odds ratio of 3.0 (95% CI = 1.1-8.3), but we found no spontaneous abortions among the few women (N = 13) who used a high setting for 2 or more hours. We found that exposure rankings of the magnetic field time-weighted average and a rate of change metric did not correspond monotonically to the pattern of spontaneous abortion risks and that electric blankets contribute less to overnight time-weighted average magnetic fields than has been thought.     

Preconception B-vitamin and homocysteine status, conception, and early pregnancy loss

Maternal vitamin status contributes to clinical spontaneous abortion, but the role of B-vitamin and homocysteine status in subclinical early pregnancy loss is unknown. Three-hundred sixty-four textile workers from Anqing, China, who conceived at least once during prospective observation (1996-1998), provided daily urine specimens for up to 1 year, and urinary human chorionic gonadotropin was assayed to detect conception and early pregnancy loss. Homocysteine, folate, and vitamins B6 and B12 were measured in preconception plasma. Relative to women in the lowest quartile of vitamin B6, those in the third and fourth quartiles had higher adjusted proportional hazard ratios of conception (hazard ratio (HR)=2.2, 95% confidence interval (CI): 1.3, 3.4; HR=1.6, 95% CI: 1.1, 2.3, respectively), and the adjusted odds ratio for early pregnancy loss in conceptive cycles was lower in the fourth quartile (odds ratio=0.5, 95% CI: 0.3, 1.0). Women with sufficient vitamin B6 had a higher adjusted hazard ratio of conception (HR=1.4, 95% CI: 1.1, 1.9) and a lower adjusted odds ratio of early pregnancy loss in conceptive cycles (odds ratio=0.7, 95% CI: 0.4, 1.1) than did women with vitamin B6 deficiency. Poor vitamin B6 status appears to decrease the probability of conception and to contribute to the risk of early pregnancy loss in this population.     

Relations of gestational length and timing and type of incomplete pregnancy to ovarian cancer risk

While the protective nature of parity with respect to ovarian cancer has been well documented, whether a history of incomplete pregnancy affects ovarian cancer risk is uncertain. Data collected from 739 epithelial ovarian cancer cases and 1,313 community controls in the Delaware Valley from 1994 to 1998 were used to evaluate the relation between gestational length and timing of first induced or spontaneous abortion and ovarian cancer risk. Incomplete pregnancy was not associated with ovarian cancer among nulliparous women or among ever-pregnant women either before or after adjustment for relevant confounders (for nulliparous women, odds ratio (OR) = 1.12, 95% confidence interval (CI): 0.66, 1.89; for ever-pregnant women, OR = 0.95, 95% CI: 0.76, 1.18). Among unigravid women, one full-term pregnancy was more protective than an incomplete pregnancy (adjusted OR = 0.29, 95% CI: 0.15, 0.57). These results were independent of the type of pregnancy loss. Among ever-pregnant women, a spontaneous abortion before a first birth provided significant protection (adjusted OR = 0.47, 95% CI: 0.30, 0.75), while no significant effect was found for an induced abortion prior to a first birth (adjusted OR = 0.80, 95% CI: 0.44, 1.47). These data do not support an independent association between incomplete pregnancies, either spontaneous or induced, and ovarian cancer risk.     

Exposure to phenoxy herbicides and the risk of spontaneous abortion.

The Ontario Farm Family Health Study was designed to assess retrospectively the potential adverse effects of exposure to pesticides on pregnancy. Information on the health and life style of approximately 2,000 farm couples, as well as a history of use of pesticides on the farm, was collected by questionnaire. This analysis focuses on pre- and postconception exposure to phenoxy herbicides and the risk of spontaneous abortion using the complete (to date) pregnancy history for each woman. Preconception exposure (from 3 months before conception to the month of conception) was weakly associated with the risk of spontaneous abortion at <20 weeks' gestation [adjusted odds ratio (OR) = 1.1; 95% confidence interval (CI) = 0.6-1.9]. When the analyses were restricted to spontaneous abortions of <12 weeks, the risk was more than doubled (adjusted OR = 2.5; 95% CI = 1.0-6.4), but the results were sensitive to the cutpoint used. If the husband did not normally wear protective equipment during application, the crude OR for early spontaneous abortions was 5.0 (95% CI = 0.7-36.2). Exposure to phenoxy herbicides during the first trimester was generally not associated with increased risk of spontaneous abortion. The results suggest a possible role of preconception (possibly paternal) exposures to phenoxy herbicides in the risk of early spontaneous abortions.     

Caffeine consumption during pregnancy and spontaneous abortion

We conducted a case-control study of spontaneous abortion in Santa Clara County, California between 1986 and 1987. We analyzed data on 607 cases and 1,284 controls to evaluate the potential association between caffeine consumption during the first trimester of pregnancy and spontaneous abortion. About 70% of the women consumed caffeinated coffee, tea, and/or soda; 7% of the women consumed more than an average of 300 mg of caffeine daily. The crude odds ratio (OR) for heavy caffeine consumption (greater than 300 mg/day) was 1.55 (95% CI: 1.04-2.31), which decreased to 1.22 (95% CI: 0.80-1.87) after controlling for confounding factors. For these heavy users, nausea modified the association of spontaneous abortion and caffeine; heavy caffeine consumers reporting nausea had a doubled risk for spontaneous abortion (adjusted OR = 2.10, 95% CI: 1.20-3.70), in contrast to those who did not report nausea (adjusted OR = 0.53, 95% CI: 0.27-1.04). Heavy caffeine consumers who decreased their caffeine intake early in pregnancy had a risk of spontaneous abortion similar to that of nonconsumers.     

Paternal and Maternal Smoking Habits before Conception and During the First Trimester: Relation to Spontaneous Abortion

PURPOSE: This study examined the association between maternal smoking before and during the first trimester of pregnancy and spontaneous abortion.

METHODS: We have been conducting a hospital-based case-control study on risk factors for spontaneous abortion in the greater Milan area. We collected information from 782 cases of spontaneous abortions and 1543 controls (women who delivered at term healthy infants).

RESULTS: With respect to never smokers, the odds ratio (OR) were 0.7 (95%, confidence interval (CI), 0.5–1.0) for women who quit smoking and 1.3 (95% CI, 1.0–1.6) for those who continued during pregnancy. Women who smoked more than 10 cigarettes/day in the first trimester were at increased risk of miscarriage, with an OR of 1.4 (95% CI, 1.0–2.1). No relationship was evident between the number of cigarettes smoked before conception and the risk of abortion. Likewise, no association emerged between paternal smoking and miscarriage. Moreover, no significant interaction or modification effect was obtained when strata of age and other major characteristics were investigated.

CONCLUSIONS: The risk of abortion associated with cigarette smoking during the first trimester of pregnancy was measurable and noticeable in this population, and accounted for 9% (95% CI, 6–13%) of all cases. The increased risk of spontaneous abortion in women smoking during pregnancy is a further reason to encourage pregnant women to quit.     

Risk of ectopic pregnancy and previous induced abortion.

OBJECTIVES: This study investigated the role of prior history of induced abortion in subsequent ectopic pregnancies. METHODS: Data from two French case-control studies were used to examine the effect of induced abortion on ectopic pregnancy risk. Case patients (n = 570) were women admitted for ectopic pregnancy during the study period; controls (n = 1385) were women who delivered in the same center. RESULTS: The analysis among women with no previous ectopic pregnancy showed that, after control for the main ectopic pregnancy risk factors, prior induced abortion was associated with an increased risk of ectopic pregnancy (odds ratio [OR] = 1.5, 95% confidence interval [CI] = 1.0, 2.0); there was a significant trend between number of previous induced abortions and ectopic pregnancy risk (ORs = 1.4 for 1 previous induced abortion and 1.9 for 2 or more). CONCLUSIONS: This study suggests that induced abortion may be a risk factor for ectopic pregnancy for women with no previous ectopic pregnancy, particularly in the case of women who have had several induced abortions.     

Influence of maternal smoking on placental abruption in successive pregnancies: a population-based prospective cohort study in Sweden

The authors examined associations between cumulative smoking during a woman's first and second pregnancies and risk of placental abruption in the second pregnancy. They performed a population-based prospective cohort study of 526,690 women who delivered their first two consecutive singletons in Sweden in 1983-2001. Using logistic regression models, the authors found that, among women without placental abruption in the first pregnancy, smoking was associated with increased risk of abruption in the second pregnancy; however, this effect was confined to exposure occurring during the second pregnancy (adjusted odds ratio (OR)=1.8, 95% confidence interval (CI): 1.4, 2.3) but not the first (adjusted OR=1.1, 95% CI: 0.9, 1.3). Among women with a prior abruption, the risk of repeating abruption was increased irrespective of smoking habits. When women smoked during both pregnancies, there was an almost 11-fold increase in risk (adjusted OR=10.9, 95% CI: 7.3, 16.3). These findings suggest that women who quit smoking before pregnancy may benefit from reduced risk of abruption. The observation that the recurrence of abruption is substantially increased regardless of changes in smoking habits suggests that factors other than smoking may influence the recurrence of placental abruption.     

Paternal smoking and pregnancy loss: a prospective study using a biomarker of pregnancy

Results of studies on paternal smoking and spontaneous abortions have been inconsistent. The authors examined the effect of paternal smoking on the risk of pregnancy loss in a prospective cohort of 526 newly married, nonsmoking, female textile workers in China between 1996 and 1998. Upon stopping contraception, subjects provided daily urine specimens and records of vaginal bleeding for up to 1 year or until clinical pregnancy. Daily urinary human chorionic gonadotropin was assayed to detect conception and early pregnancy losses, and pregnancies were followed to detect clinical spontaneous abortions. Subjects were grouped by the number of cigarettes that husbands reported smoking daily: nonsmokers (group 1, n = 216), fewer than 20 cigarettes (group 2, n = 239), and 20 or more cigarettes (group 3, n = 71). Compared with that for group 1, the adjusted odds ratio of early pregnancy loss of any conception for group 2 was 1.04 (95% confidence interval (CI): 0.67, 1.63) and for group 3 was 1.81 (95% CI: 1.00, 3.29). The adjusted hazard ratio of conception for group 2 was 0.90 (95% CI: 0.70, 1.18) and for group 3 was 0.96 (95% CI: 0.66, 1.39), while the adjusted hazard ratio of clinical pregnancy for group 2 was 0.93 (95% CI: 0.72, 1.20) and for group 3 was 0.78 (95% CI: 0.55, 1.12). The authors conclude that heavy paternal smoking increased the risk of early pregnancy loss through maternal and/or paternal exposure.     

Risk of spontaneous abortion among women exposed to polybrominated biphenyls

Accidental contamination of livestock in Michigan in 1973 with polybrominated biphenyls (PBBs) led to the establishment of a registry of exposed individuals in 1976. At the time of enrollment, serum was collected and analyzed for PBBs and polychlorinated biphenyls (PCBs). In 1997, women aged 18 years or older and active in the registry were invited to participate in a telephone interview about their health. Using generalized estimating equations to account for correlated outcomes within the same woman, we assessed the risk of spontaneous abortion among 529 women with 1344 potentially exposed pregnancies. PBB and PCB exposure were not associated with risk of spontaneous abortion after adjusting for maternal age at conception, age at menarche, and prior infertility. Compared to pregnancies with PBB exposure below the limit of detection, those with levels above 2.9 ppb had a non-significant reduced odds of spontaneous abortion (adjusted OR=0.73; 95% CI=0.47-1.13). Compared to pregnancies with PCB exposure below the limit of detection, those with levels above 6.5 ppb had little difference in risk (adjusted OR=0.91; 95% CI=0.59-1.41). Maternal age at conception above 34 years was significantly associated with elevated risk of spontaneous abortion (OR=2.46; 95% CI=1.10-5.49). The effect of prior infertility was of borderline significance (OR=1.52; 95% CI=0.98-2.38). Older age at menarche was associated with decreased risk of spontaneous abortion (adjusted OR=0.58; 95% CI: 0.38-0.89, comparing menarche at 12-13 with menarche <12). Our results do not support an association between exposure to PBBs or PCBs and risk of spontaneous abortion.     

南方女性复发性流产环境因素分析

目的:探讨南方女性不明原因复发性流产(undentifiedrecurrentspontaneousabortion,URSA)流行病学因素。方法:对326例URSA及400例正常对照育龄妇女进行健康问卷调查,用Logistic回归模型,纳入体重指数(BMI)、自然流产家族史、吸烟史、被动吸烟史、饮酒史、饮咖啡史,找出有独立意义的环境危险因素,并对自然流产次数3次及≥4次者进行分层分析。结果:吸烟史、饮酒史和饮咖啡史不是URSA的危险因素,短时间被动吸烟(1h/天)及长时间被动吸烟(≥1h/天)是URSA的危险因素,OR及95%CI分别是2.30,1.50～3.52及4.76,3.24～6.99。家族史及BMI≥24.0kg/m2是URSA危险因素,OR及95%CI分别是2.12,1.28～3.49及1.55,1.12～2.14。结论:被动吸烟史、BMI≥24.0kg/m2、自然流产家族史是中国南方女性URSA独立危险因素。     

Infertility among women exposed prenatally to diethylstilbestrol

Although it is well established that women exposed to diethylstilbestrol in utero have an increased risk of spontaneous abortion, ectopic pregnancy, and preterm delivery, it is not known whether they also have an increased risk of infertility. The authors assessed this question in data from a collaborative follow-up study of the offspring of women who took diethylstilbestrol during pregnancy. In 1994, 1,753 diethylstilbestrol-exposed and 1,050 unexposed women from an ongoing cohort study (National Cooperative Diethylstilbestrol Adenosis Study and Dieckmann cohorts) provided data on difficulties in conceiving and reasons for the difficulty. Age-adjusted relative risks were computed for the association of diethylstilbestrol exposure with specific types of infertility. A greater proportion of exposed than unexposed women were nulligravid (relative risk (RR) = 1.3, 95% confidence interval (CI): 1.1, 1.5), and a greater proportion had tried to become pregnant for at least 12 months without success (RR = 1.8, 95% CI: 1.6, 2.1). Diethylstilbestrol exposure was significantly associated with infertility due to uterine and tubal problems, with relative risks of 7.7 (95% CI: 2.3, 25) and 2.4 (95% CI: 1.2, 4.6), respectively. The present findings indicate that diethylstilbestrol-exposed women have a higher risk of infertility than do unexposed women and that the increased risk of infertility is primarily due to uterine or tubal problems.     

Association of perforation of the appendix with female tubal infertility

Although perforation of the appendix is considered a risk factor for female tubal infertility, the epidemiologic evidence supporting this relation is inconsistent. Risk factors for tubal infertility were compared for 121 women with documented primary tubal infertility attending in vitro fertilization clinics in Toronto, Canada, from July to December 1998 and 490 controls who were pregnant during the same time period. Self-administered questionnaires and review of medical records were used to assess exposures. The authors found that neither history of acute appendicitis nor perforation of the appendix was a statistically significant risk factor for tubal infertility. The crude odds ratio for perforated appendicitis was 3.4 (95% confidence interval (CI): 0.9, 12.9), and the adjusted odds ratio was 1.4 (95% CI: 0.3, 6.2). In addition to increased age and annual income, cigarette smoking (odds ratio (OR) = 2.0, 95% CI: 1.2, 3.2), history of endometriosis (OR = 6.0, 95% CI: 2.8,12.8), and history of pelvic inflammatory disease (OR = 6.0, 95% CI: 2.8, 12.8) were significantly associated with tubal infertility in multivariate analysis. These data do not provide substantial evidence that perforation of the appendix is an important risk factor for female tubal infertility.     

Prior spontaneous abortion, prior elective termination, interpregnancy interval, and risk of neural tube defects

A woman with a history of spontaneous abortion in her immediately prior pregnancy may be at increased risk for a pregnancy affected by a neural tube defect (NTD). A short interpregnancy interval may further increase this risk. Using data from a population-based case-control study (1989-1991), the authors investigated NTD risk resulting from a prior spontaneous abortion or elective termination and a short interpregnancy interval. Of 538 interviewed case mothers and 539 interviewed control mothers, 408 case mothers and 433 control mothers reported having a prior pregnancy. Analysis showed a slightly decreased NTD risk among mothers whose immediately prior pregnancy had ended in a spontaneous abortion or elective termination in comparison with a live birth (odds ratio (OR) = 0.82; 95% confidence interval (CI): 0.61, 1.1). This decreased risk was consistent across strata of short or long interpregnancy intervals. Additional analysis revealed an increased NTD risk for mothers with an interpregnancy interval of < or =6 months compared with >12-< or =24 months (OR = 1.5; 95% CI: 0.93, 2.4). This latter risk was greatest among mothers whose immediately prior pregnancy had resulted in a live birth (OR = 2.0; 95% CI: 1.0, 3.8) rather than a spontaneous abortion or elective termination (OR = 0.96; 95% CI: 0.44, 2.1). Adjustment for potential covariates did not substantially alter observed risk estimates.     

Spontaneous abortions among Finnish flight attendants.

We conducted a retrospective cohort study to investigate whether work as a cabin attendant is related to an increased risk for spontaneous abortion. Data on female cabin crew members were linked to medical records on pregnancies. There were 1751 eligible pregnancies for the final analysis. Flight attendants who worked during early pregnancy had a slightly elevated risk of spontaneous abortion, as compared with attendants who were pregnant outside a time span of active flying (odds ratio [OR] = 1.3; 95% confidence interval [CI], 0.9 to 1.8). During the earliest years of the study period (1973 through 1977), the risk seemed to be decreased (OR = 0.4; 95% CI, 0.2 to 1.1), whereas during the later years (1978 through 1994) the risk was increased (OR = 1.6; 95% CI, 1.1 to 2.4). The results are in agreement with earlier studies, showing suggestive evidence of a slightly increased risk of spontaneous abortion among female cabin crew members.     

Reproductive outcomes among women exposed to a brominated flame retardant in utero

The authors studied 194 women exposed to polybrominated biphenyls (PBB) in utero when their mothers consumed products accidentally contaminated in Michigan in 1973. Generalized estimating equations were used to examine the effect of in utero PBB exposure on adult pregnancy-related outcomes. Compared to those with the lowest exposure (≤1 ppb), those with mid-range (>1-3.16 ppb) and high (≥3.17 ppb) PBB exposure had increased odds of spontaneous abortion with wide confidence intervals (odds ratio [OR] = 2.75, 95% confidence interval [CI] = 0.64-11.79, OR = 4.08, 95% CI = 0.94-17.70; respectively; p for trend = .05). Exposure during infancy to PBB-contaminated breast milk further increased this risk. Time to pregnancy and infertility were not associated with in utero exposure to PBB. Future studies should examine the suggested relationship between spontaneous abortion and other brominated flame retardants.     

Moderate maternal and paternal alcohol consumption and the risk of spontaneous abortion.

Maternal alcoholism can lead to the fetal alcohol syndrome in offspring, but the effect of more moderate alcohol consumption during pregnancy remains an issue of concern. Therefore, we analyzed data from a large case-control study of spontaneous abortion (626 cases, 1,300 controls) that ascertained maternal alcohol consumption before and during pregnancy, as well as paternal consumption. Asking when in pregnancy alcohol consumption changed allowed us to calculate a weighted average of the amount consumed weekly during the first trimester. The odds ratio for consumption of seven or more drinks per week was 1.9 [95% confidence interval (CI) = 1.1-3.4] when adjusted for maternal smoking, passive smoking, and maternal age. Data were too sparse to examine higher consumption levels. There was some evidence that cases may have had less opportunity than controls to decrease consumption during their shorter pregnancies, potentially biasing the odds ratio upward. The adjusted odds ratio for any paternal alcohol consumption was 1.2 (CI = 0.93-1.5), with no dose-response effect seen. Among pregnancies in which the mother did not drink, there was no association with paternal drinking.     

Subfertility and risk of spontaneous abortion

OBJECTIVES: The purpose of this study was to assess the association between subfertility and spontaneous abortion. METHODS: A total of 1572 women in New York and Vermont reported 3269 pregnancies between 1980 and 1990 and were able to provide an estimate of the waiting time to conception for 2967. Subfertility was defined as a delay of 1 year or more before a recognized conception was achieved. Rates of spontaneous abortion were determined among women with and without subfertility, and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated via multiple logistic regression. RESULTS: Spontaneous abortion rates were 23.0% in pregnancies preceded by subfertility and 14.0% in pregnancies without impaired fertility (adjusted OR = 1.71, 95% CI = 1.26, 2.94). The attributable risk of spontaneous abortion associated with subfertility was 6.2%. CONCLUSIONS: Subfertile women evidence an increased number of spontaneous abortions.