Elizabeth G. Raymond

Trial of calcium to prevent preeclampsia

Background Previous trials have suggested that calcium supplementation during pregnancy may reduce the risk of preeclampsia. However, differences in study design and a low dietary calcium intake in the populations studied limit acceptance of the data. Methods We randomly assigned 4589 healthy nulliparous women who were 13 to 21 weeks pregnant to receive daily treatment with either 2 g of elemental calcium or placebo for the remainder of their pregnancies. Surveillance for preeclampsia was conducted by personnel unaware of treatment-group assignments, using standardized measurements of blood pressure and urinary protein excretion at uniformly scheduled prenatal visits, protocols for monitoring these measurements during the hospitalization for delivery, and reviews of medical records of unscheduled outpatient visits and all hospitalizations. Results Calcium supplementation did not significantly reduce the incidence or severity of preeclampsia or delay its onset. Preeclampsia occurred in 158 of the 2295 wome...

Population effect of increased access to emergency contraceptive pills: a systematic review.

OBJECTIVE: We systematically reviewed data on effects of increased access to emergency contraceptive pills on pregnancy rates and use of the pills. DATA SOURCES: We searched MEDLINE, POPLINE, EMBASE, and LILACS, and we consulted with experts. METHODS OF STUDY SELECTION: We included studies that compared the effect of different levels of access to emergency contraceptive pills on pregnancy rates, use of the pills, and other outcomes. TABULATION, INTEGRATION, AND RESULTS: Of the 717 articles identified, we selected 23 for review. The studies included randomized trials, cohort studies, and evaluations of community interventions. The quality of these studies varied. In all but one study, increased access to emergency contraceptive pills was associated with greater use. However, no study found an effect on pregnancy or abortion rates. CONCLUSION: Increased access to emergency contraceptive pills enhances use but has not been shown to reduce unintended pregnancy rates. Further research is needed to explain this finding and to define the best ways to use emergency contraception to produce a public health benefit.

On the mechanisms of action of short-term levonorgestrel administration in emergency contraception

The effects of short-term administration of levonorgestrel (LNG) at different stages of the ovarian cycle on the pituitary-ovarian axis, corpus luteum function, and endometrium were investigated. Forty-five surgically sterilized women were studied during two menstrual cycles. In the second cycle, each women received two doses of 0.75 mg LNG taken 12 h apart on day 10 of the cycle (Group A), at the time of serum luteinizing hormone (LH) surge (Group B), 48 h after positive detection of urinary LH (Group C), or late follicular phase (Group D). In both cycles, transvaginal ultrasound and serum LH were performed from the detection of urinary LH until ovulation. Serum estradiol (E2) and progesterone (P(4)) were measured during the complete luteal phase. In addition, an endometrial biopsy was taken at day LH + 9. Eighty percent of participants in Group A were anovulatory, the remaining (three participants) presented significant shortness of the luteal phase with notably lower luteal P4 serum concentrations. In Groups B and C, no significant differences on either cycle length or luteal P4 and E2 serum concentrations were observed between the untreated and treated cycles. Participants in Group D had normal cycle length but significantly lower luteal P4 serum concentrations. Endometrial histology was normal in all ovulatory-treated cycles. It is suggested that interference of LNG with the mechanisms initiating the LH preovulatory surge depends on the stage of follicle development. Thus, anovulation results from disrupting the normal development and/or the hormonal activity of the growing follicle only when LNG is given preovulatory. In addition, peri- and post-ovulatory administration of LNG did not impair corpus luteum function or endometrial morphology.

Effects of maternal age, parity, and smoking on the risk of stillbirth

Objective To examine the effects of advanced maternal age, nulliparity, and smoking on risk of stillbirth as gestation advances, and to explore possible clinical mediators of these effects.

The comparative safety of legal induced abortion and childbirth in the United States.

OBJECTIVE: To assess the safety of abortion compared with childbirth. METHODS: We estimated mortality rates associated with live births and legal induced abortions in the United States in 1998–2005. We used data from the Centers for Disease Control and Preventions Pregnancy Mortality Surveillance System, birth certificates, and Guttmacher Institute surveys. In addition, we searched for population-based data comparing the morbidity of abortion and childbirth. RESULTS: The pregnancy-associated mortality rate among women who delivered live neonates was 8.8 deaths per 100,000 live births. The mortality rate related to induced abortion was 0.6 deaths per 100,000 abortions. In the one recent comparative study of pregnancy morbidity in the United States, pregnancy-related complications were more common with childbirth than with abortion. CONCLUSION: Legal induced abortion is markedly safer than childbirth. The risk of death associated with childbirth is approximately 14 times higher than that with abortion. Similarly, the overall morbidity associated with childbirth exceeds that with abortion. LEVEL OF EVIDENCE: II

Placental abruption: Maternal risk factors and associated fetal conditions

Objective. To investigate maternal risk factors and fetal conditions associated with abruption.

Impact of increased access to emergency contraceptive pills: A randomized controlled trial

OBJECTIVE: To assess how a strategy to maximize access to emergency contraceptive pills would affect rates of pregnancy and sexually transmitted infections. METHODS: Sexually active women, 14–24 years old, were randomly assigned to two methods of access to emergency contraceptive pills: increased access (two packages of pills dispensed in advance with unlimited resupply at no charge) or standard access (pills dispensed when needed at usual charges). Participants were followed for 1 year to assess incidence of pregnancy, gonorrhea, chlamydia, and trichomonas. RESULTS: The numbers of women enrolled in the increased and standard access groups were 746 and 744, respectively. More than 93% of participants completed a full year of follow-up. The incidence of pregnancy was similar in both groups (increased access group: 9.9/100 woman years, 95% confidence interval [CI] 7.7–12.6; standard access group: 10.5/100 woman years, 95% CI 8.2–13.2). Aggregate rates of gonorrhea, chlamydia, and trichomonas were also similar in the two groups (increased access group: 6.9/100 woman years, 95% CI 5.1–9.1; standard access group: 7.6/100 woman years, 95% CI 5.7–9.9). The increased access group used emergency contraceptive pills substantially more often and sooner after coitus than the standard access group. No other differences were noted between groups in self-reported measures of sexual behavior and contraceptive use. CONCLUSION: This intensive strategy to enhance access to emergency contraceptive pills substantially increased use of the method and had no adverse impact on risk of sexually transmitted infections. However, it did not show benefit in decreasing pregnancy rates. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00060463 LEVEL OF EVIDENCE: II-1

Emergency contraception over-the-counter: the medical and legal imperatives.

Requiring a physicians prescription for hormonal emergency contraceptive pills makes no sense. Unintended pregnancies remain endemic in the United States, and wider use of emergency contraceptive pills could substantially help. However, the prescription requirement poses an unnecessary barrier to prompt, effective use of this preventive therapy. According to the Durham-Humphrey Amendment of 1951, the default option for all new drugs is, in principle, over-the-counter, unless a drug is addictive or dangerous when self-administered. Clearly, hormonal emergency contraception is neither of these. Emergency contraceptive pills meet all the customary criteria for over-the-counter use: low toxicity, no potential for overdose or addiction, no teratogenicity, no need for medical screening, self-identification of the need, uniform dosage, and no important drug interactions. The Food and Drug Administration is authorized, and, by its own regulations, should be required to switch hormonal emergency contraception to over-the-counter status without delay. The current prescription requirement is not only gratuitous but also harmful to womens health because it impedes access to this important therapy.

Trial of calcium for preeclampsia prevention (CPEP): Rationale, design, and methods

The results of ten clinical trials suggest that supplemental calcium may prevent preeclampsia. However, methodologic problems and differences in study design limit the acceptance of the results and their relevance to other patient populations. Many of the trials were conducted in countries where, unlike the United States, the usual daily diet contained little calcium. Moreover, none of the trials has reported the outcome of systematic surveillance for urolithiasis, a potential complication of calcium supplementation. In response to the need for a thorough evaluation of the effects of calcium supplementation for the prevention of preeclampsia in the United States, the trial of Calcium for Preeclampsia Prevention (CPEP) was undertaken at five university medical centers. Healthy nulliparous patients were randomly assigned to receive either 2 g supplemental calcium daily (n = 2295) or placebo (n = 2294) in a double-blind study. Study tablets were administered beginning from 13 to 21 completed weeks of gestation and continued until the termination of pregnancy. CPEP employed detailed diagnostic criteria, standardized techniques of measurement, and systematic surveillance for the major study endpoints and for urolithiasis. The nutrient intake of each patient was assessed at randomization and at 32-33 weeks gestation. This report describes the study rationale, design, and methods.

Ectopic pregnancy and emergency contraceptive pills: a systematic review.

OBJECTIVE: To evaluate the existing data to estimate the rate of ectopic pregnancy among emergency contraceptive pill treatment failures. DATA SOURCES: Our initial reference list was generated from a 2008 Cochrane review of emergency contraception. In August 2009, we searched Biosys Previews, the Cochrane Database of Systematic Reviews, Medline, Global Health Database, Health Source: Popline, and Wanfang Data (a Chinese database). METHODS: This study included data from 136 studies, which followed a defined population of women treated one time with emergency contraceptive pills (either mifepristone or levonorgestrel) and in which the number and location of pregnancies were ascertained. RESULTS: Data from each article were abstracted independently by two reviewers. In the studies of mifepristone, 3 of 494 (0.6%) pregnancies were ectopic; in the levonorgestrel studies, 3 of 307 (1%) were ectopic. CONCLUSION: The rate of ectopic pregnancy when treatment with emergency contraceptive pills fails does not exceed the rate observed in the general population. Because emergency contraceptive pills are effective in lowering the risk of pregnancy, their use will reduce the chance that an act of intercourse will result in ectopic pregnancy. LEVEL OF EVIDENCE: III