To determine if first-trimester exposure to sex hormones, and oral contraceptives (OCs) specifically, is associated with an increased risk of external fetal genital malformations.
DATA SOURCES: MEDLINE and Science Citation Index data bases were searched for the years 1966-1992 for relevant English-language articles on first-trimester sex-hormone exposure and fetal genital changes.
METHODS OF STUDY SELECTION: One hundred eighty-six articles were identified initially. Inclusion criteria were cohort or case-control studies, first-trimester sex-hormone exposure, and live infants or full-term stillborn infants with external genital malformations. Exclusion criteria were diethylstilbestrol exposure, spontaneous abortions, and teratogen exposure.
DATA EXTRACTION AND SYNTHESIS: The Methods section of each study was reviewed independently by two authors and two outside reviewers, using the above criteria. Fourteen studies, seven cohort and seven case-control, involving 65,567 women, met the criteria for meta-analysis. Extracted data were entered into 2 x 2 tables. The overall summary odds ratio (OR) was 1.09 (95% confidence interval [CI] 0.90-1.32); subanalysis of OC exposure identified an OR of 0.98 (95% CI 0.24-3.94).
Conclusion
There was no association between first-trimester exposure to sex hormones generally (or to OCs specifically) and external genital malformations. Thus, women exposed to sex hormones after conception may be assured there is no increased risk of fetal sexual malformation.
first trimester sex hormone exposure fetal genital malformation, oral contraceptive exposure pregnancy birth defects meta-analysis, fetal genital effects hormonal contraceptive first trimester, inadvertent oral contraceptive use early pregnancy safety, sex hormone teratogenicity genital malformation risk, Raman-Wilms meta-analysis oral contraceptives fetal effects, first trimester progestin exposure external genital anomalies, contraceptive pill pregnancy exposure birth defects risk, hormonal exposure conception fetal safety meta-analysis, oral contraceptive failure pregnancy genital malformation odds ratio
PMID 7800312 7800312 DOI 10.1016/0029-7844(94)00341-a 10.1016/0029-7844(94)00341-a Raman-Wilms et al. 1995, Raman-Wilms 1995
Cite this article
Raman-Wilms, L., Tseng, A. L., Wighardt, S., Einarson, T. R., & Koren, G. (1995). Fetal genital effects of first-trimester sex hormone exposure: a meta-analysis. Obstetrics and gynecology, 85(1), 141-149. https://doi.org/10.1016/0029-7844(94)00341-a
Raman-Wilms L, Tseng AL, Wighardt S, Einarson TR, Koren G. Fetal genital effects of first-trimester sex hormone exposure: a meta-analysis. Obstet Gynecol. 1995;85(1):141-149. doi:10.1016/0029-7844(94)00341-a
Raman-Wilms, Lalitha, et al. "Fetal genital effects of first-trimester sex hormone exposure: a meta-analysis." Obstetrics and gynecology, vol. 85, no. 1, 1995, pp. 141-149.
To assess the cervicovaginal fetal fibronectin test to predict preterm delivery. We searched MEDLINE, Current Contents, Index Medicus, and proceedings of meetings for studies published between 1991 and June 1997. Inclusion criteria were prospective cohort study; test performed between 20 and 36 weeks' gestation; fetal fibronectin measured by a previously described assay, with a cutoff level set at 50 ng/mL; test results not disclosed to women or physicians; and fewer than 20% of study participants excluded from the analysis. TABULATION, INTEGRATION, Twenty-nine relevant studies were stratified according to the prevalence of preterm delivery, the number of tests performed, and delivery before 34, 35, or 37 weeks. Sensitivities, specificities, and likelihood ratios were calculated in each study. The summary estimates of the likelihood ratio for tests yielding positive results or tests yielding negative results along with their 95% confidence intervals (CIs) were computed in each stratum according to a random-effects model. All summary likelihood ratios for a test yielding positive results indicated a significant association with preterm delivery. The strongest association was found between a single test with positive results and delivery before 37 weeks in a low-risk population (likelihood ratio 7.5; 95% CI 4.6, 12.3). This association also was found in high-risk women (likelihood ratio 3.5; 95% CI 2.6, 4.6). In high-risk women, a test yielding negative results was associated with a reduction in risk of preterm delivery (likelihood ratio 0.4; 95% CI 0.3, 0.5). Fetal fibronectin in cervicovaginal secretions is associated with preterm delivery in both high-risk and low-risk women.
To evaluate whether preterm-birth prevention educational programs are effective at reducing neonatal mortality, low birth weight (LBW), and preterm delivery. A MEDLINE literature search of English-language studies was performed, supplemented by a bibliography search of original research and review articles to locate studies assessing preterm-birth prevention programs. We identified 31 studies that reported results from trials evaluating preterm-birth prevention programs. From this group, only the six randomized controlled trials evaluating preterm-birth prevention education programs satisfied criteria of homogeneity to be included in a meta-analysis. One of these six studies was a subset of another study and was excluded except when reporting outcomes that were not included in the larger report. Two independent reviewers assessed study methodology and identified the following outcomes: LBW frequency, preterm birth frequency, neonatal survival, birth weight, gestational age at delivery, and preterm labor diagnosis rates. When data were combined using meta-analytic techniques, no significant benefits were found for preterm-birth education programs in preventing neonatal death (cumulative relative risk [RR] 1.00, 95% confidence interval [CI] 0.99-1.01), LBW rates (RR 0.99, 95% CI 0.88-1.11), or preterm delivery rates (RR 1.08, 95% CI 0.92-1.27). The only statistically significant effect of preterm birth education programs appears to be an increase in the frequency at which preterm labor is diagnosed (RR 1.71, 95% CI 1.41-2.08). Preterm-birth prevention educational programs appear to have little benefit in reducing preterm birth and may result in an increased rate of diagnosis of preterm labor.
The relationship between asymptomatic bacteriuria and prematurity/low birth weight (LBW) is still a controversial issue, despite many studies. Meta-analysis, a research tool designed to analyze and combine the results of previous studies, may resolve this discrepancy among contradictory results of clinical trials. The purpose of this study was to examine the relationship between asymptomatic bacteriuria and preterm delivery/LBW using meta-analysis. Reports from the literature were classified according to study design into cohort or randomized-treatment control trials. Meta-analysis of cohort studies showed that untreated asymptomatic bacteriuria during pregnancy significantly increased rates of LBW and preterm delivery. Nonbacteriuric patients had only about two-thirds the risk (typical relative risk = 0.65; 95% confidence interval 0.57, 0.74) of LBW and half the risk (typical relative risk = 0.50; 95% confidence interval 0.36, 0.70) of preterm delivery of those with untreated asymptomatic bacteriuria. These reduced risks correspond to a 3.4 (confidence interval 1.8, 5.0) percentage-point difference in LBW and a 3.8 (1.1, 6.4) percentage-point difference in preterm delivery. The analysis of randomized clinical trials showed that antibiotic treatment significantly reduced the risk of LBW (typical relative risk = 0.56; 95% confidence interval 0.43, 0.73), with a substantial reduction of 6.4 (confidence interval 3.3, 9.5) percentage points in the rate of LBW. We conclude that clinical and epidemiologic evidence indicates a strong association between untreated asymptomatic bacteriuria and LBW/preterm delivery and that antibiotic treatment is effective in reducing the occurrence of LBW.
Adolescent heavy menstrual bleeding(HMB), menorrhagia or abnormal uterine bleeding commonly occur in adolescent women. The differential diagnosis can be challenging. The pneumonic: PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified), is commonly used but it does not stratify as to the likelihood of a disorder. We have sought to develop a probability-based differential diagnosis for Adolescent HMB, menorrhagia or abnormal uterine bleeding. A comprehensive literature search was conducted using PubMed, EMBASE, and SCOPUS databases. Case series describing adolescents from 10-19 years of age with HMB, menorrhagia or abnormal uterine bleeding was acceptable if: more than 10 patients were included; editorials, case reports, and secondary sources such as review articles, or book chapters were excluded. No language filter was used, but an English abstract was required. The etiology of HMB, menorrhagia or abnormal uterine bleeding, and the country of origin was extracted from articles that met inclusion criteria. Cumulative rate estimates were determined by Bayesian probability modeling. Seventeen full text articles were reviewed in detail; 2,770 patients were included. The most frequent causes of HMB were Ovarian Uterine Disorders (23.7%; 95% CredI 22-25.5%), Coagulation Disorders (19.4%; 95% CredI 17.8-21.1%), and Platelet Disorders (6.23%; 95% CredI 5.27-7.27%) with 45.9% (95% CredI 43.8-47.%9) of the cases of indeterminate origin. The leading causes of HMB in healthy adolescent females were varied. The sub-analysis identified distinct etiologies, suggesting that multiple factors must be considered in the evaluation of HMB. While PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified) provides us with a comprehensive picture of the possible causes of HMB in females, this systematic review assigns probabilities to the etiologies of HMB in adolescent females, providing physicians with a more focused and efficient pathway to diagnosis.