Study: Mifepristone pretreatment improves management of first-trimester pregnancy loss

June 19, 2018

A recent study compared pretreatment with mifepristone followed by treatment with misoprostol against treating with misoprostol alone for the management of  first-trimester pregnancy loss. Plus: Are patients less satisfied with MDs who reduce opioids? Also: Does infant exposure to hypertensive disorders or pregnancy affect neurodevelopment?

Pretreatment with mifepristone followed by treatment with misoprostol resulted in a higher likelihood of successful management of first-trimester pregnancy loss than treatment with misoprostol alone, according to a study published in The New England Journal of Medicine. First-trimester miscarriage is the most common pregnancy complication in the United States, and while misoprostol treatment is recommended by society guidelines, the standard dose of 800 µg has low efficacy in women with a closed cervical os. Mifepristone is a 19-nor steroid that acts as a competitive progesterone-receptor antagonist and glucocorticoid-receptor antagonist and helps prepare the myometrium and cervix for prostaglandin activity.

The study included 300 women with an anembryonic gestation or embryonic or fetal death who were randomized to either pretreatment with 200 mg of oral mifepristone, followed by 800 µg of vaginal misoprostol (pretreatment group) or 800 µg of vaginal misoprostol alone (misoprostol-alone group). Participants were eligible if they were at least 18 years old and had an ultrasound that showed a nonviable intrauterine pregnancy between 5 and 12 completed weeks’ gestation. Women were excluded if they had an incomplete or inevitable abortion, a contraindication to misoprostol or mifepristone, evidence of a viable or ectopic pregnancy, a hemoglobin level lower than 9.5 g/dL, a known clotting defect, or a pregnancy with an intrauterine device in place.

The primary outcome of the study was successful gestational sac expulsion by the first follow-up visit (at least 24 hours but not more than 4 days after misoprostol use) with one dose of misoprostol and no additional surgical or medical interventions within 30 days. Secondary outcomes included adverse events (AEs) measured by a Likert scale, acceptability of treatment based on responses to a 3-point Likert scale, and assessment of the clinical characteristics associated with gestational sac expulsion.

The misoprostol-alone group consisted of 151 randomly assigned women, while 149 women were assigned to the mifepristone-pretreatment group. During the study, three women were excluded from the results (2 lost to follow-up and 1 found to be clinically ineligible). The median number of days between misoprostol administration and first follow-up was 2.0 (range, 0.5-5.5) in the mifepristone-pretreatment group and 2.6 (range, 0.7-9.6) in the misoprostol-alone group (P = 0.04). In the mifepristone group, 124 of 148 women (83.8%; 95% CI, 76.8-89.3) had treatment success by the first follow-up visit with no further interventions necessary 30 days after treatment. In the misoprostol-alone group, 100 of 149 women (67.1%; 95% CI, 59.0-74.6) had treatment success. In the pretreatment group, 65 women did not wait the full 24 hours before administering misoprostol. In these women, the success rate was 79.7%.

In the pretreatment group, 24 women (16.2%) did not experience gestational sac expulsion by the first 24-hour follow-up and in the misoprostol-alone group, 49 women (32.9%) did not have expulsion. Among these 73 women, 41% chose expectant management, 27% chose a second dose of misoprostol, and 31% underwent uterine aspiration. Complete expulsion of the gestational sac with one dose of misoprostol by Day 8 occurred in 130 of 149 women. Thirty  days after treatment, the cumulative rate of gestational sac expulsion with up to two doses of misoprostol was 91.2% (95% CI, 85.4-95.2) in the pretreatment group and 75.8% (95% CI, 68.2-82.5) in the misoprostol-alone group.

Through subgroup analyses, the researchers found that rates of treatment success by the first follow-up visit among women who were at 9 weeks’ gestation or less were 84.8% (117 of 138 women) in the pretreatment group and 66.7% (94 of 141 women) in the misoprostol-alone group. There were also no reported significant AEs either arm of the study.

A few strengths and limitations were noted by the authors. Among the strengths mentioned were the high retention rate of the participants and the diverse population of participants. Among the limitations mentioned was the vaginal administration of misoprostol. In future studies, the authors suggested, might want be warranted to explore success rates with oral, rectal, buccal, or sublingual routes. They also noted that several participants in the pretreatment group did not wait the full 24 hours between mifepristone pretreatment and misoprostol, so the effect on treatment of shorter intervals between administration mifepristone and misoprostol might be another avenue for exploration. 

NEXT: Are patients less satisfied with MDs who reduce opioids?

Are patients less satisfied with MDs who reduce opioids?

US physicians are increasingly being called upon to curb opioid prescribing because the drugs have been so overused. Results of new research suggest that reducing dosages for chronic pain may not lead to patient dissatisfaction with care.

The findings, published in The American Journal of Managed Care, are from a retrospective cohort study by Kaiser Permanente Southern California. The authors looked at satisfaction scores for patients who had been prescribed opioids for chronic pain for at least 6 months between 2009 and 2014. Individuals younger than age 18 or who had a known cancer diagnosis were excluded.

Data were analyzed from two groups: patients who had a drop in morphine milligram equivalents (MME) to < 50 for ≥ 30 days following a clinical encounter and patients who continued using ≥ 50 MME for ≥ 30 days following an encounter. In keeping with Kaiser Permanente’s routine operations, satisfaction surveys were sent to patients after approximately 15% of randomly selected encounters.

The authors looked at the effect to reducing opioid dosage on satisfaction scores for encounters between patients and their assigned primary care provider (PCP) versus encounters between patients and an unassigned provider. Scores were derived from 10 questions about a patient’s satisfaction with the encounter, with responses on a scale of 1 to 10, from very dissatisfied to very satisfied.

A total of 2492 encounters were reflected in the data, 29% of which included a reduction in opioid prescribing, 86.4% resulted in favorable satisfaction scores. After adjustment, the odds of an unfavorable score in the dose reduction group were just marginally higher and not significant (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.00 to 1.73). Stratified by different encounter types, opioid dose reduction was not associated with unfavorable scores for visits with an assigned PCP (OR, 1.16; 95% CI, 0.79 to 1.70). The odds of an unfavorable score were higher, however, when a patient’s encounter was with an unassigned provider (OR, 1.50; 95% CI, 1.01 to 2.23).

The results, the authors said, “highlight the benefits of an assigned PCP managing chronic pain, as low satisfaction had a slight association with reductions in opioid dosing for encounters with an established provider.” They said noted that their data might be limited by unmeasured confounders, such as motivating factors associated with opioid dose reduction, and that Kaiser Permanente’s approximate 18% response rate also might introduce response bias. The researchers concluded, however, that the study results “are indicative of the actual satisfaction scores that are currently reported for comparisons of hospitals, health plans, and physicians and therefore representative of how satisfaction surveys are use din practice, as opposed to research settings.”


NEXT: Does infant exposure to hypertensive disorders or pregnancy affect neurodevelopment?

Does infant exposure to hypertensive disorders or pregnancy affect neurodevelopment?

A systematic review and meta-analysis of 61 journal articles, recently published in JAMA Psychiatry, found that increased risks of childhood autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) may be associated with infant exposure to hypertensive disorders of pregnancy (HDP). Hypertensive disorders are among the most common prenatal complications and the results of this study highlight the need for greater pediatric surveillance of children exposed to HDP, according to the authors.

The systematic review included studies with: a population of pregnant women and their children, exposure to HDP, a comparison group with no HDP, and a primary outcome of ASD or ADHD, with secondary outcomes of neurodevelopmental and other behavioral or cognitive outcomes. While no restrictions were placed on publication date, location of study, or age of participants, the included studies were limited to reports in English of studies with human participants. A total of 61 unique articles were included in the systematic review: 20 on ASD, 10 on ADHD and 31 on other neurodevelopmental outcomes. 

In the 20 HDP and ASD articles, prevalence of HDP among cohort studies of ASD ranged from 1.3% to 9.1% (mean, 6.2%; median 6.9%; interquartile range [IQR], 3.6% -8.9%). Crude and partial estimates produced a pooled odds ratio (OR) of 1.41 (95% CI, 1.22-1.64). The researchers performed subgroup analysis to examine the association between preeclampsia and ASD and other HDP and AASD separately resulted in ORs of 1.37 (95% CI, 1.07-1.75) and 1.43 (95% CI, 1.17-1.73), respectively. Adjusted estimates reduced the overall HDP-ASD estimate to 1.35 (95% CI, 1.11-1.64). Subgroup analysis of e the association between preeclampsia and ASD resulted in an OR of 1.50 (95% CI, 1.26-1.78) and subgroup analysis of ASD and other HDP returned a nonsignificant OR of 1.25 (95% CI, 0.90-1.73).

In the 10 HDP and ADHD articles, prevalence of HDP among cohort studies of ADHD ranged from 0.1% to 20.8% (mean, 7.8%; median, 5.5%; IQR, 2.4%-15.1%). Crude and partial estimates produced an OR of 1.32 (95% CI, 1.20-1.45) in subgroup analysis examining the association between preeclampsia and ADHD alone, the OR was 1.31 (95% CI, 1.19-1.44) and the OR for the association between other HDP and ADHD was 1.62 (95% CI, 1.07-2.47). Adjusted estimates remained relatively unchanged.

In the 31 studies examining the association between HDP and neurodevelopmental cognitive or behavioral outcomes, results were mostly inconsistent. However, 6 of 10 studies suggested a positive association between preeclampsia and cognitive impairment within specific populations. In addition, 4 of 5 studies suggested a potential association between HDP and intellectual disability.

The authors noted that there did not seem to be publication bias in the review (Egger test, P = .43; 95% CI, –1.8-4.0). Heterogeneity among the ASD studies was 0 when studies that adjusted for maternal age, maternal smoking and birth order were analyzed separately.

The authors believe that their findings reinforce the notion that maternal hypertension is linked to neurodevelopmental disorders. The adjusted pooled results indicated that exposure to HDP was associated with 35% increased odds of ASD compared to non-exposure. Adjusted pooled results also suggested that HDP-exposed offspring were 30% more likely to have ADHD compared with unexposed offspring. However, literature examining the association between HDP and other neurodevelopmental disorders remains inconsistent.

The authors brought up a few strengths and limitations of their review. Among the strengths were going through a pre-prepared protocol and following Meta-analysis of Observational studies in Epidemiology guidelines. Limitations included restriction to English-language studies, small sample sizes, and residual or unmeasured confounding. Ultimately, the authors believe their systematic review illustrates the need for increased developmental screening of HDP-exposed infants to allow for early intervention and improve neurodevelopmental outcomes, but more research is still necessary to address this review’s limitations.