Randomized trial to compare acceptability of magnesium sulphate administration for preeclampsia and eclampsia: Springfusor pump versus standard of care.

INTRODUCTION: In low-resource settings, magnesium sulphate (MgSO4) for preeclampsia is administered majorly through an injection into the gluteal muscles 4-hourly for 24 hours. The repeated injections are very painful and may lead to infection, abscess formation, and reduced compliance. OBJECTIVE: To determine the acceptability of Springfusor® pump for the administration of Magnesium Sulphate in preeclampsia and eclampsia. DESIGN: Randomized Open Label Clinical Trial. METHODS: The study was conducted at Kawempe National Referral Hospital. Eligible women had a systolic blood pressure of ≥140mmHg and or diastolic blood pressure >90mmHg, proteinuria ≥+1, and the physician's decision to start on MgSO4. Four-hundred-ninety-six participants were randomized to a Springfusor® pump group (n = 248) or control (standard of care) (n = 248) administration of MgSO4. Intervention group had a loading dose (4gm of 50% MgSO4 intravenously over 20 minutes) and maintenance therapy (1gm of 50% MgSO4 intravenously per hour for 24 hours) administered using the Springfusor®. The standard of care (SOC) group received a loading dose of 4gm of 20% MgSO4 IV over 15-20 minutes, followed by 10gm of 50% MgSO4 intramuscular (5gm in each buttock) and a maintenance dose of 5gm of 50% MgSO4 was administered IM every 4 hours for 24 hours. Both arms received the rest of the care for preeclampsia/eclampsia as per the hospital guidelines. Acceptability of the method of administration was assessed using a Likert scale (1-5; 1 and 2: acceptable and 3-5: unacceptable). Pain at the site of MgSO4 administration was assessed using a Visual Analogue Scale 1-7, (1 minimal pain and 7 worst pain). Comparisons were assessed with the Chi-square test, Mann Whitney-Wilcoxon test, and Students' t-test. RESULTS: Intervention arm; was more acceptable than the standard of care arm, (95.3% vs70.3%; p<0.001), had a lower median pain score, (2(CI: 2-2), vs 4(CI: 4-5) p<0.001), and fewer side effects. Maternal mortality was comparable between groups (0.8% in the intervention arm vs 1.2% in the IM arm). TRIAL REGISTRATION: Trial No PACTR201712002887266 (https://pactr.samrc.ac.za/).

Oral misoprostol alone, compared with oral misoprostol followed by oxytocin, in women induced for hypertension of pregnancy: A multicentre randomised trial.

OBJECTIVE: To assess whether, in those requiring continuing uterine stimulation after cervical ripening with oral misoprostol and membrane rupture, augmentation with low-dose oral misoprostol is superior to intravenous oxytocin. DESIGN: Open-label, superiority randomised trial. SETTING: Government hospitals in India. POPULATION: Women who were induced for hypertensive disease in pregnancy and had undergone cervical ripening with oral misoprostol, but required continuing stimulation after artificial membrane rupture. METHODS: Participants received misoprostol (25 micrograms, orally, 2-hourly) or titrated oxytocin through an infusion pump. All women had one-to-one care; fetal monitoring was conducted using a mixture of intermittent and continuous electronic fetal monitoring. MAIN OUTCOME MEASURES: Caesarean birth. RESULTS: A total of 520 women were randomised and the baseline characteristics were comparable between the groups. The caesarean section rate was not reduced with the use of misoprostol (misoprostol, 84/260, 32.3%, vs oxytocin, 71/260, 27.3%; aOR 1.23; 95% CI 0.81-1.85; P = 0.33). The interval from randomisation to birth was somewhat longer with misoprostol (225 min, 207-244 min, vs 194 min, 179-210 min; aOR 1.137; 95% CI 1.023-1.264; P = 0.017). There were no cases of hyperstimulation in either arm. The rates of fetal heart rate abnormalities and maternal side effects were similar. Fewer babies in the misoprostol arm were admitted to the special care unit (10 vs 21 in the oxytocin group; aOR 0.463; 95% CI 0.203-1.058; P = 0.068) and there were no neonatal deaths in the misoprostol group, compared with three neonatal deaths in the oxytocin arm. Women's acceptability ratings were high in both study groups. CONCLUSIONS: Following cervical preparation with oral misoprostol and membrane rupture, the use of continuing oral misoprostol for augmentation did not significantly reduce caesarean rates, compared with the use of oxytocin. There were no hyperstimulation or significant adverse events in either arm of the trial.

The Induction with Foley OR Misoprostol (INFORM) Study dataset. A dataset of 602 women with hypertensive disease in pregnancy, in India, randomised to either Foley catheter or oral misoprostol for induction of labour.

OBJECTIVES: Induction of labour (IOL), or starting labour artificially, can be a lifesaving intervention for pregnant women and their babies, and rates are rising significantly globally. As rates increase, it becomes increasingly important to fully evaluate all available data, especially that from low income settings where the potential benefits and harms are greater. The goal of this paper is to describe the datasets collected as part of the Induction with Foley OR Misoprostol (INFORM) Study, a randomised trial comparing two of the recommended methods of cervical ripening for labour induction, oral misoprostol and Foley catheter, in women being induced for hypertension in pregnancy, at two sites in India during 2013-15. DATA DESCRIPTION: This dataset includes comprehensive data on 602 women who underwent IOL for hypertensive disorders in pregnancy. Women were randomly assigned to cervical ripening with oral misoprostol or a transcervical Foley catheter in two government hospitals in India. The main dataset has 367 variables including monitoring during the induction of labour, medications administered, timing and mode of delivery, measures of neonatal morbidity and mortality, maternal mortality and morbidity, maternal satisfaction and health economic data. The dataset is anonymised and available on ReShare.

Oral Misoprostol alone versus oral misoprostol followed by oxytocin for labour induction in women with hypertension in pregnancy (MOLI): protocol for a randomised controlled trial.

BACKGROUND: Every year approximately 30,000 women die from hypertensive disease in pregnancy. Magnesium sulphate and anti-hypertensives reduce morbidity, but delivery is the only cure. Low dose oral misoprostol, a prostaglandin E1 analogue, is a highly effective method for labour induction. Usually, once active labour has commenced, the misoprostol is replaced with an intravenous oxytocin infusion if ongoing stimulation is required. However, some studies have shown that oral misoprostol can be continued into active labour, a simpler and potentially more acceptable protocol for women. To date, these two protocols have never been directly compared. METHODS: This pragmatic, open-label, randomised trial will compare a misoprostol alone labour induction protocol with the standard misoprostol plus oxytocin protocol in three Indian hospitals. The study will recruit 520 pregnant women being induced for hypertensive disease in pregnancy and requiring augmentation after membrane rupture. Participants will be randomised to receive either further oral misoprostol 25mcg every 2 h, or titrated intravenous oxytocin. The primary outcome will be caesarean birth. Secondary outcomes will assess the efficacy of the induction process, maternal and fetal/neonatal complications and patient acceptability. This protocol (version 1.04) adheres to the SPIRIT checklist. A cost-effectiveness analysis, situational analysis and formal qualitative assessment of women's experience are also planned. DISCUSSION: Avoiding oxytocin and continuing low dose misoprostol into active labour may have a number of benefits for both women and the health care system. Misoprostol is heat stable, oral medication and thus easy to store, transport and administer; qualities particularly desirable in low resource settings. An oral medication protocol requires less equipment (e.g. electronic infusion pumps) and may free up health care providers to assist with other aspects of the woman's care. The simplicity of the protocol may also help to reduce human errors associated with the delivery of intravenous infusions. Finally, women may prefer to be mobile during labour and not restricted by an intravenous infusion. There is a need, therefore, to assess whether augmentation using oral misoprostol is superior clinically and economically to the standard protocol of intravenous oxytocin. TRIAL REGISTRATION: Clinical Trials.gov, NCT03749902 , registered on 21st Nov 2018.

Congo red test for identification of preeclampsia: Results of a prospective diagnostic case-control study in Bangladesh and Mexico.

BACKGROUND: Misfolded proteins in the urine of women with preeclampsia bind to Congo Red dye (urine congophilia). We evaluated a beta prototype of a point-of-care test for the identification of urine congophilia in preeclamptic women. METHODS: Prospective diagnostic case-control study conducted in 409 pregnant women (n = 204 preeclampsia; n = 205 uncomplicated pregnancies) presenting for delivery in two tertiary level hospitals located in Bangladesh and Mexico. The GV-005, a beta prototype of a point-of-care test for detecting congophilia, was performed on fresh and refrigerated urine samples. The primary outcome was the prevalence of urine congophilia in each of the two groups. Secondary outcome was the likelihood of the GV-005 (index test) to confirm and rule-out preeclampsia based on an adjudicated diagnosis (reference standard). FINDINGS: The GV-005 was positive in 85% of clinical cases (83/98) and negative in 81% of clinical controls (79/98) in the Bangladesh cohort. In the Mexico cohort, the GV-005 test was positive in 48% of clinical cases (51/106) and negative in 77% of clinical controls (82/107). Adjudication confirmed preeclampsia in 92% of Bangladesh clinical cases (90/98) and 61% of Mexico clinical cases (65/106). The odds ratio of a urine congophilia in adjudicated cases versus controls in the Bangladesh cohort was 34.5 (14.7 - 81.1) (p<0.001) compared to 4.2 (2.1 - 8.4; p<0.001) in the Mexico cohort. INTERPRETATION: The GV-005, a beta prototype of a point-of-care test for detection of urine congophilia, is a promising tool for rapid identification of preeclampsia. FUNDING: Saving Lives at Birth.

Mifepristone pretreatment followed by misoprostol 200 mcg buccal for the medical management of intrauterine fetal death at 14-28 weeks: A randomized, placebo-controlled, double blind trial.

OBJECTIVE: To evaluate whether fetal and placental expulsion is more likely within 48 h if women receive mifepristone pre-treatment vs placebo pre-treatment followed by misoprostol 200 mcg buccally for treatment of fetal death at 14 weeks 0 days to 28 weeks and 6 days gestation. STUDY DESIGN: We randomized 176 women with a confirmed fetal death between 14 weeks and 0 days to 28 weeks and 6 days to mifepristone 200 mg or placebo; 24 h later all participants received misoprostol 200 mcg buccally every 3 h for up to 16 doses or 48 h. The trial took place in Hanoi, Vietnam and Mexico City in 2015-2018. RESULTS: Complete expulsion of the fetus and placenta within 48 h of misoprostol administration occurred in 74 of 90 women (82.2%, 95% confidence interval (CI), 72.7%-89.5%) in the mifepristone-misoprostol group and in 70 of 86 women (81.4%, 95% CI, 71.6%-89.0%) in the placebo-misoprostol group (Relative Risk (RR) 1.01, 95%CI 0.87-1.16, p = 0.887). The median time from the start of the misoprostol induction to fetal expulsion was shorter among women who received mifepristone-misoprostol compared to women assigned to placebo-misoprostol (7 h vs ±5 vs 12 ± 13 h; p < 0.001). Women in the mifepristone-misoprostol group were more likely to expel the fetus within 24 h of the start of misoprostol administration (96% vs 78%; RR 1.22 (1.09-1.39) p = 0.009). CONCLUSION(S): Mifepristone-misoprostol did not result in a higher rate of complete expulsion of the fetus and the placenta within 48 h of the start of misoprostol administration without any additional surgical intervention or medication (e.g. additional misoprostol doses or oxytocin) than placebo-misoprostol. However, treatment with mifepristone-misoprostol did result in a shorter time to expulsion than placebo misoprostol. IMPLICATIONS: Pretreatment with mifepristone followed by misoprostol bucally resulted in a shorter treatment time for medical management of fetal death than treatment with misoprostol alone. Pre-treatment with mifepristone may be more acceptable to women and providers by both reducing the length of hospital stay and the amount of misoprostol required.

Oral antihypertensive regimens (nifedipine retard, labetalol, and methyldopa) for management of severe hypertension in pregnancy: an open-label, randomised controlled trial.

BACKGROUND: Hypertension is the most common medical disorder in pregnancy, complicating one in ten pregnancies. Treatment of severely increased blood pressure is widely recommended to reduce the risk for maternal complications. Regimens for the acute treatment of severe hypertension typically include intravenous medications. Although effective, these drugs require venous access and careful fetal monitoring and might not be feasible in busy or low-resource environments. We therefore aimed to compare the efficacy and safety of three oral drugs, labetalol, nifedipine retard, and methyldopa for the management of severe hypertension in pregnancy. METHODS: In this multicentre, parallel-group, open-label, randomised controlled trial, we compared these oral antihypertensives in two public hospitals in Nagpur, India. Pregnant women were eligible for the trial if they were aged at least 18 years; they were pregnant with fetuses that had reached a gestational age of at least 28 weeks; they required pharmacological blood pressure control for severe hypertension (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg); and were able to swallow oral medications. Women were randomly assigned to receive 10 mg oral nifedipine, 200 mg oral labetalol (hourly, in both of which the dose could be escalated if hypertension was maintained), or 1000 mg methyldopa (a single dose, without dose escalation). Masking of participants, study investigators, and care providers to group allocation was not possible because of different escalation protocols in the study groups. The primary outcome was blood pressure control (defined as 120-150 mm Hg systolic blood pressure and 70-100 mm Hg diastolic blood pressure) within 6 h with no adverse outcomes. This study is registered with ClinicalTrials.gov, number NCT01912677, and the Clinical Trial Registry, India, number ctri/2013/08/003866. FINDINGS: Between April 1, 2015, and Aug 21, 2017, we screened 2307 women for their inclusion in the study. We excluded 1413 (61%) women who were ineligible, declined to participate, had impending eclampsia, were in active labour, or had a combination of these factors. 11 (4%) women in the nifedipine group, ten (3%) women in the labetalol group, and 11 (4%) women in the methyldopa group were ineligible for treatment (because they had only one qualifying blood pressure measurement) or had treatment stopped (because of delivery or transfer elsewhere). 894 (39%) women were randomly assigned to a treatment group and were included in the intention-to-treat analysis: 298 (33%) women were assigned to receive nifedipine, 295 (33%) women were assigned to receive labetalol, and 301 (33%) women were assigned to receive methyldopa. The primary outcome was significantly more common in women in the nifedipine group than in those in the methyldopa group (249 [84%] women vs 230 [76%] women; p=0·03). However, the primary outcome did not differ between the nifedipine and labetalol groups (249 [84%] women vs 228 [77%] women; p=0·05) or the labetalol and methyldopa groups (p=0·80). Seven serious adverse events (1% of births) were reported during the study: one (<1%) woman in the labetalol group had an intrapartum seizure and six (1%) neonates (one [<1%] neonate in the nifedipine group, two [1%] neonates in the labetalol group, and three [1%] neonates in the methyldopa group) were stillborn. No birth had more than one adverse event. INTERPRETATION: All oral antihypertensives reduced blood pressure to the reference range in most women. As single drugs, nifedipine retard use resulted in a greater frequency of primary outcome attainment than labetalol or methyldopa use. All three oral drugs-methyldopa, nifedipine, and labetalol-are viable initial options for treating severe hypertension in low-resource settings. FUNDING: PREEMPT (University of British Columbia, Vancouver, BC, Canada; grantee of Bill & Melinda Gates Foundation).

A randomized trial comparing the pharmacology of magnesium sulfate when used to treat severe preeclampsia with serial intravenous boluses versus a continuous intravenous infusion.

BACKGROUND: Magnesium sulfate is the preferred pharmacological intervention for the prevention and treatment of eclamptic seizures in pregnancy. Pain associated with intramuscular injections and the need for an electronic infusion pump for use intravenously represent significant barriers to broader utilization. We hypothesize that an alternative regimen based on serial intravenous (IV) boluses can produce serum concentrations comparable to those produced by a continuous infusion. METHODS: An open-label randomized trial was performed at two hospitals in Egypt. Women with severe preeclampsia were eligible and enrolled between January 2015 and February 2016. Two hundred subjects were randomized by random numbers generated centrally in distinct blocks and stratified by study site. They were assigned to a continuous infusion arm, (4 g loading dose with 1 g/hr. continuous infusion) or a serial IV bolus arm, (6 g loading dose with 2 g bolus every 2 h using a Springfusor® pump). Sparsely sampled magnesium serum concentrations were collected, nonlinear mixed effect modeling was conducted and Monte Carlo simulations were used to generate 200 simulated subjects in each treatment arm. The simulated populations were used to determine area under the concentration-time curve (AUC) as a measure of total drug exposure and compared. RESULTS: Simulated area under the magnesium serum concentration-time curve was significantly higher in the serial IV bolus arm than in the continuous infusion arm (1107 ± 461 mmol•min /L vs. 1010 ± 398 mmol•min /L, (P = 0.02)). Four percent of women in the serial bolus arm considered the treatment unacceptable or very unacceptable compared to 2% in the continuous infusion arm, (P = 0.68). CONCLUSIONS: Serial IV boluses achieve serum magnesium concentrations statistically significantly higher but clinically comparable to those achieved with a continuous infusion and offer a third option for the administration of MgSO4 to women with preeclampsia that may reduce barriers to utilization. TRIAL REGISTRATION: Trial no. NCT02091401, March 17, 2014.

Low-sensitivity urine pregnancy testing to assess medical abortion outcome: A systematic review.

OBJECTIVE: The objective was to summarize data on the accuracy and acceptability of a strategy for identifying ongoing pregnancy after medical abortion treatment using a low-sensitivity pregnancy test (LSPT). STUDY DESIGN: We searched PubMed to identify studies that evaluated the use of a single posttreatment LSPT for detection of ongoing pregnancy after treatment with mifepristone and misoprostol. We extracted, assessed and summarized data from each study. RESULTS: We found 10 studies that evaluated 6 LSPTs with human chorionic gonadotropin detection thresholds of 1000, 1500 or 2000 mIU/mL. The three earliest studies compared the pregnancy test strategy to standard assessment in the same women; the sensitivity of a positive or invalid LSPT result for detecting ongoing pregnancy ranged from 67% to 100%. Three randomized trials found no significant difference in detection of ongoing pregnancy between the LSPT strategy and routine in-person follow-up. Four noncomparative studies found that of the 12 women who had ongoing pregnancies diagnosed after performing an LSPT, 8 (67%) had positive or invalid LSPT results. Across the 10 studies, 30 of the 59 total ongoing pregnancies (51%) were identified based on symptoms without a positive or invalid LSPT result. Women expressed satisfaction with the LSPT strategy. Risk of bias in the seven later studies was high. CONCLUSIONS: Despite their limitations, most studies showed that the LSPT strategy had moderate sensitivity for identifying ongoing pregnancy and can enable the majority of medical abortion patients to assess treatment outcome at home. However, the LSPT itself had a limited role in the detection of treatment failures in the studies. IMPLICATIONS STATEMENT: The LSPT strategy shows promise for reducing the need for in-person follow-up after medical abortion. A range of home-based options should be validated to meet the varied needs of women and abortion providers in diverse settings.

Mifepristone-misoprostol for menstrual regulation in public sector facilities in Bangladesh.

OBJECTIVE: To examine the use of mifepristone and misoprostol for menstrual regulation among Bangladeshi women attending public sector facilities. METHODS: In a prospective study, women (aged ≥18 years) with up to 9 weeks of amenorrhea were enrolled at 24 government health facilities in Bangladesh from November 2012 to June 2015. Paramedics or female welfare visitors provided most menstrual regulation care. Participants took 200 mg mifepristone followed by 800 µg buccal misoprostol after 24 hours, and were asked to return to the clinic 10-14 days later for clinical assessment and an exit interview. The primary outcome was successful evacuation of the uterus without need for surgical intervention. Women who completed follow-up were included in analyses for the primary outcome. RESULTS: Among 1744 enrolled participants, 1738 completed follow-up. Most (1674, 96.3%) had a successful uterine evacuation without the need for surgical intervention. A successful outcome was significantly more common in primary (724/744, 97.3%) and secondary facilities (861/895, 96.2%) than in the specialty hospital (89/99, 89.9%; P<0.001 and P=0.004, respectively). CONCLUSION: Menstrual regulation with mifepristone and misoprostol can be provided effectively in public sector facilities in Bangladesh. CLINICALTRIALS.GOV: NCT01798017.

Foley catheterisation versus oral misoprostol for induction of labour in hypertensive women in India (INFORM): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Between 62 000 and 77 000 women die annually from pre-eclampsia and eclampsia. Prompt delivery, preferably by the vaginal route, is vital for good maternal and neonatal outcomes. Two low-cost interventions-low-dose oral misoprostol tablets and transcervical Foley catheterisation-are already used in low-resource settings. We aimed to compare the relative risks and benefits of these interventions. METHODS: We undertook this multicentre, open-label, randomised controlled trial in two public hospitals in Nagpur, India. Women (aged ≥18 years) who were at 20 weeks' gestation or later with a live fetus and required delivery as a result of pre-eclampsia or hypertension were randomly assigned (1:1), via computer-generated block randomisation (block sizes of four, six, and eight) with concealment by use of opaque, sequentially numbered, sealed envelopes, to receive labour induction with either oral misoprostol 25 µg every 2 h (maximum of 12 doses) or a transcervical Foley catheter (silicone, size 18 F with 30 mL balloon). Randomisation was stratified by study centre. The catheter remained in place until active labour started, the catheter fell out, or 12 h had elapsed. If the catheter did not fall out within 12 h, induction continued with artificial membrane rupture and oxytocin, administered through a micro-drip gravity infusion set. Fetal monitoring was by intermittent auscultation. The primary outcome was vaginal birth within 24 h. Due to the nature of the interventions, masking of participants, study investigators, and care providers to group allocation was not possible. We analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01801410. FINDINGS: Between Dec 20, 2013, and June 29, 2015, we randomly assigned 602 women to induction with misoprostol (n=302) or the Foley catheter (n=300; intention-to-treat population). Vaginal birth within 24 h was more common in women in the misoprostol group than in the Foley catheter group (172 [57·0%] vs 141 [47·0%] women; absolute risk difference 10·0%, 95% CI 2·0-17·9; p=0·0136). Rates of uterine hyperstimulation were low in both the misoprostol and Foley catheter groups (two [0·7%] vs one [0·3%] cases; absolute risk difference 0·3%, 95% CI -0·8 to 1·5; p=0·566) and neonatal deaths did not differ significantly between groups (six [2·0%] vs three [1·0%] neonatal deaths; 1·0, -1·04 to 2·97; p=0·322). 17 serious adverse events (3%) were reported during the study: one case of intrapartum convulsion and one case of disseminated intravascular coagulation (both in the Foley group); ten perinatal deaths, including two stillbirths (both in the Foley catheter group) and eight neonatal deaths (n=5 in the misoprostol group and n=3 in the Foley catheter group); and five of neonatal morbidity, comprising birth asphyxia (n=3), septicaemia (n=1), and neonatal convulsion (n=1). INTERPRETATION: Oral misoprostol was more effective than transcervical Foley catheterisation for induction of labour in women with pre-eclampsia or hypertension. Future studies are required to assess whether oxytocin augmentation following misoprostol can be replaced by regular doses of oral misoprostol tablets. FUNDING: Medical Research Council, Department for International Development, and Wellcome Trust Joint Global Health Trials Scheme.

Serial multilevel urine pregnancy testing to assess medical abortion outcome: a meta-analysis.

OBJECTIVES: To summarize data on the accuracy of a strategy designed to exclude ongoing pregnancy after medical abortion treatment by observing a decline in urine human chorionic gonadotropin (hCG) concentration as estimated by multilevel urine pregnancy tests (MLPTs) performed before and after treatment. STUDY DESIGN: We collated original data from seven studies performed by our organization that evaluated the accuracy of the MLPT strategy for assessment of outcome of medical abortion. Our first analysis included data from the five studies in which each participant was evaluated both with the MLPT strategy and with ultrasound or other clinical assessment. Our second analysis combined data from two randomized trials that compared the MLPT strategy to assessment by ultrasound. Both analyses included only participants treated at ≤63 days of gestation. RESULTS: In the first analysis, 1482 (93%) of 1599 participants had a decline in hCG concentration after treatment. Twenty-one (1.3%) had an ongoing pregnancy, none of whom had a decline (predictive value 100%, 95% CI 93.3%, 100%). The remaining 96 women (6.0%) had no decline without an ongoing pregnancy. The second analysis, which included 3762 participants with follow-up, found no significant difference in the rates of ongoing pregnancy ascertained in the randomized groups (RR 0.88; 95% CI 0.50, 1.54). Nearly all of the post-treatment MLPTs in the seven studies (3484/3535; 99%) were performed by the participants themselves. CONCLUSIONS: Serial multilevel urine pregnancy testing is a highly reliable and efficient strategy for excluding ongoing pregnancy after medical abortion at≤63 days of gestation. IMPLICATIONS STATEMENT: Serial urine testing using MLPTs can obviate the need for routine ultrasound or examination after medical abortion treatment and can allow most women to avoid an in-person follow-up visit to the abortion facility.

Early medical abortion without prior ultrasound.

OBJECTIVE: To explore the potential for using last menstrual period (LMP) rather than ultrasound to establish gestational age (GA) eligibility for medical abortion. STUDY DESIGN: We used the results of a recently published systematic review to identify studies with data on the number of abortion patients with GA more than 63 or 70 days by ultrasound but less than those or other specific limits by LMP. We analyzed data from these studies to estimate the proportion of women with GAs greater than 63 or 70 days by ultrasound in various subgroups of women defined by LMP. RESULTS: We found three studies with relevant data. One enrolled 4257 medical abortion patients of whom 4% had GAs of >70 days by ultrasound. Of the 2681 who were certain that their LMPs began no more than 56 days prior, only 16 (0.6%) were >70 days by ultrasound. In a second much smaller study of surgical abortion patients, of whom 19% were >70 days by ultrasound, 90 women were certain that their LMPs started more than 56 days prior, and of those, 7 (7.8%) had GAs of >70 days by ultrasound. In the third study, which included surgical abortion patients with a mean GA of 61 days, at least 12% of the 138 patients with LMPs <63 days prior were >70 days by ultrasound. CONCLUSION: The possibility that access to medical abortion can be enhanced for selected women by omitting the requirement for a screening ultrasound is promising and should be further investigated. IMPLICATIONS: Gestational dating using LMP rather than ultrasound may be reasonable for selected patients before medical abortion.

A prospective open-label study of home use of mifepristone for medical abortion in Nepal.

OBJECTIVE: To assess the uptake and acceptability of self-administration of mifepristone at home for medical abortion in Nepal. METHODS: A prospective, comparative, non-randomized, open-label study was conducted at two hospitals in Kathmandu, Nepal, between November 11, 2009, and January 15, 2011. All women in good health and aged 18 years or older who sought medical abortion after fewer than 64 days of pregnancy were enrolled. Participants were offered the choice of taking 200mg mifepristone orally in the clinic or at home; all participants self-administered 400 µg of sublingual misoprostol at home 24-72 hours later. All participants were scheduled to return to the clinic within 14 days of mifepristone administration for follow-up. RESULTS: Among 200 participants, 144 (72.0%) opted to take the mifepristone at home. Medical abortion was successful in 130 (95.6%) of 136 women in the home group who were followed up and 53 (94.6%) of 56 women in the clinic group. Only 4 (2.9%) women in the home group took the mifepristone after the scheduled time. Overall, 133 (97.8%) women in the home group stated that they would recommend home administration of mifepristone if a friend wanted a medical abortion. CONCLUSION: Self-administration of mifepristone outside the clinic should be offered to all women as part of routine medical abortion services in Nepal. Clinical trials.gov: NCT00994734.

Induction of labour in pre-eclamptic women: a randomised trial comparing the Foley balloon catheter with oral misoprostol.

BACKGROUND: Between 40,000 and 80,000 pregnant women die annually from pre-eclampsia and eclampsia. Although magnesium sulphate and anti-hypertensive therapies can reduce the morbidity and mortality associated with pre-eclampsia, the only cure comes with delivery. Prompt delivery of the baby, preferably by vaginal route, is vital in order to achieve good maternal and neonatal outcomes. Induction of labour is therefore a critical intervention in order to prevent morbidity to both mother and baby. Two low cost interventions - oral misoprostol tablets and transcervical Foley catheterization - are already used by some in low resource settings, but their relative risks and benefits are not known. The trial will compare the risks, benefits, and trade-offs in efficacy, safety, acceptability and cost of misoprostol and Foley catheter for induction in women with preeclampsia or uncontrolled hypertension. METHODS/DESIGN: A total of 602 women with an ongoing pregnancy with a live fetus requiring delivery because of pre-eclampsia or uncontrolled hypertension will be randomly assigned to labor induction with a transcervical Foley catheter or oral misoprostol 25 micrograms. Women will be recruited at two hospitals in Nagpur, India. The misoprostol group will receive oral misoprostol 25 microgram every 2 hours for a maximum of 12 doses or until active labor commences. The Foley group will undergo induction using a Foley catheter (silicone, size 18 F with 30 ml balloon) which will remain until active labor starts, the Foley catheter falls out, or 12 hours have elapsed. The primary outcome will be the attainment of vaginal delivery within 24 hours. Providers administering the treatment and those assessing the outcomes will not be blinded to group assignment. TRIAL REGISTRATION: NCT01801410 (ClinicalTrials.gov).

Calibrated delivery drape versus indirect gravimetric technique for the measurement of blood loss after delivery: a randomized trial.

BACKGROUND: Trials of interventions for PPH prevention and treatment rely on different measurement methods for the quantification of blood loss and identification of PPH. This study's objective was to compare measures of blood loss obtained from two different measurement protocols frequently used in studies. METHODS: Nine hundred women presenting for vaginal delivery were randomized to a direct method (a calibrated delivery drape) or an indirect method (a shallow bedpan placed below the buttocks and weighing the collected blood and blood-soaked gauze/pads). Blood loss was measured from immediately after delivery for at least one hour or until active bleeding stopped. RESULTS: Significantly greater mean blood loss was recorded by the direct than by the indirect measurement technique (253.9 mL and 195.3 mL, respectively; difference = 58.6 mL (95% CI: 31-86); p < 0.001). Almost twice as many women in the direct than in the indirect group measured blood loss > 500 mL (8.7% vs. 4.7%, p = 0.02). CONCLUSIONS: The study suggests a real and significant difference in blood loss measurement between these methods. Research using blood loss measurement as an endpoint needs to be interpreted taking measurement technique into consideration. TRIAL REGISTRATION: This study has been registered at clinicaltrials.gov as NCT01885845.

RU OK? The acceptability and feasibility of remote technologies for follow-up after early medical abortion.

OBJECTIVES: We tested the effectiveness and feasibility of remote communication technologies to increase follow-up after early medical abortion. STUDY DESIGN: Women (n=999) were randomized to 'remote' follow-up incorporating a low-sensitivity pregnancy test and standardized symptom questionnaire administered online, by text message or telephone by a non-clinical call center operator 2 weeks after treatment, or to 'clinic-based' follow-up with ultrasound at 1 week. Women in the clinic-based group who could not return performed a high-sensitivity pregnancy test at 3 weeks and had a telephone call with clinic staff. The primary outcome was completion of follow-up. Rates of complications, acceptability and preferences were compared. RESULTS: The overall follow-up rate did not differ by group {clinic-based, 73% vs. remote, 69%; risk ratio (RR) 1.0 [95% confidence interval (CI) 0.9-1.2]}. In the clinic-based group, 83% did not return for an ultrasound scan and were followed up by phone. In the remote group, follow-up by phone or text was more successful than online (text: 75.4%; phone: 73.7%; online: 46.5%, p<.001). The proportion of women receiving additional care was 9% in the clinic-based group and was 4% in the remote group [RR 1.8 (95% CI 1.1-3.1)]. Most women found their follow-up method acceptable but would prefer follow-up by phone or text message if needed in future. CONCLUSIONS: Follow-up after medical abortion using remote communication is feasible and, for most women, preferable to a clinic visit. IMPLICATIONS: Medical abortion protocols typically use follow-up visits to ensure early identification of complications. This study demonstrates that follow-up can be achieved using remote communication technologies. This model may reduce the burden of multiple clinic visits on patients and providers.

Buccal misoprostol for treatment of fetal death at 14-28 weeks of pregnancy: a double-blind randomized controlled trial.

OBJECTIVE: To assess whether buccal misoprostol is effective for the treatment of intrauterine fetal death. STUDY DESIGN: This double-blind randomized trial was conducted at five tertiary-level hospitals in the United States and Vietnam. One hundred fifty-three women with an intrauterine fetal death at 14-28 weeks of pregnancy received either 100 mcg buccal misoprostol or 200 mcg buccal misoprostol every 6 h for a maximum of 8 doses. The main outcome measure was the fetal-placental delivery rate within 48 hours of prostaglandin commencement without any additional intervention. RESULTS: Most of the women (140/153) were recruited at the study site in Vietnam. Expulsion of both fetus and placenta within 48 hours of prostaglandin commencement without any additional interventions occurred in 61.8% (47/76) of women receiving misoprostol 100 mcg and 77.9% (60/77) of women receiving misoprostol 200 mcg. The 200 mcg dose was significantly more effective than the 100 mcg dose at expelling the fetus and placenta within 48 h [RR 0.68 (95% CI: 0.50-0.92; p=.03)]. The mean time to expulsion was significantly shorter using the 200 mcg dose (18.5±11.9 h) than the 100 mcg dose (23.9±12.5 h) (p=.02). Most women in both groups found the procedure satisfactory or very satisfactory (100 mcg: 76.7% (56/73); 200 mcg: 89.5% (68/76) [RR 0.86 (95% CI: 0.74-1.00)]. CONCLUSION: Buccal misoprostol is an effective method for medical induction of labor after intrauterine fetal demise. A 200 mcg dose is significantly more effective than 100 mcg for evacuating the uterus within 48h. The treatment is highly acceptable to women. IMPLICATIONS: Administration of 200 mcg buccal misoprostol every six hours is an effective and acceptable method to effect the delivery of a demised fetus at 14-28 weeks that can be feasibly implemented in a wide variety of settings.

Acceptability and feasibility of phone follow-up after early medical abortion in Vietnam: a randomized controlled trial.

OBJECTIVE: To investigate phone follow-up with a semiquantitative urine pregnancy test and symptom checklist as a replacement for universal clinic follow-up after medical abortion. METHODS: One thousand four hundred thirty-three women seeking early medical abortion at four hospitals in Vietnam were randomized to clinic or phone follow-up. Women allocated to clinic follow-up returned to the hospital for confirmation of abortion outcome 2 weeks after mifepristone administration. Women assigned to phone follow-up completed a semiquantitative pregnancy test at initial visit to determine baseline human chorionic gonadotropin range and again at home 2 weeks later. Clinic staff called women to review the pregnancy test results and symptom checklist. Women who screened positive were referred to the clinic. Effectiveness, feasibility, and acceptability of the follow-up methods were assessed. RESULTS: The rate of ongoing pregnancy was not significantly different between the two groups (clinic: 2.7% phone, 2.5%, relative risk 0.9, 95% confidence interval 0.99-1.02). Eighty-five percent of women in the phone group did not need an additional clinic visit. Phone follow-up was highly effective in screening for ongoing pregnancy with a sensitivity and specificity of 92.8% and 90.6%, respectively. Specificity of the pregnancy test alone (eg, without the symptom checklist) was higher (95.7%). CONCLUSION: Phone follow-up offers a feasible and effective approach to identify women with ongoing pregnancy after early medical abortion. When used with the semiquantitative pregnancy test, the symptom checklist offered no additional benefit and decreased the specificity of the screening. Given its effectiveness and ease of use, the semiquantitative pregnancy test alone could replace routine clinic follow-up after early medical abortion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01150422. LEVEL OF EVIDENCE: I.

A two-pill sublingual misoprostol outpatient regimen following mifepristone for medical abortion through 70 days' LMP: a prospective comparative open-label trial.

OBJECTIVE: To test the effectiveness and acceptability of an outpatient medical abortion protocol with 200 mg mifepristone and 400 mcg sublingual misoprostol at 64-70 days' last menstrual period (LMP) and compare it to the already known efficacy of the 57-63 days' LMP gestational age range. STUDY DESIGN: We conducted a prospective, comparative open-label trial in six hospitals and clinics in Ukraine, Georgia, India and Tunisia. We enrolled 714 reproductive age women with pregnancies 57 to 70 days who presented requesting abortion. Medical abortions were managed with the current service delivery protocol (200 mg oral mifepristone followed in 24-48 h by 400 mcg sublingual misoprostol). Data on safety, efficacy and acceptability were collected. The main outcome measure was complete abortion without surgical intervention at any point. RESULTS: A total of 703 cases were analyzable for efficacy. Success rates did not differ significantly in the two groups [57-63-day group: 94·8%; 64-70-day group: 91.9%; Relative Risk (RR): 0.79 (0.61-1.04)]. Ongoing pregnancy rates also did not differ significantly (57-63 days: 1.8%; 64-70 days: 2.2%; RR: 1.10 (0.65-1.87)]. CONCLUSION: A medical abortion regimen of 200 mg mifepristone followed in 24-48 h by 400 mcg sublingual misoprostol is effective through 70 days' gestation and may be offered within existing outpatient abortion services. IMPLICATIONS: A regimen of 200 mg mifepristone followed in 24-48 h by 400 mcg sublingual misoprostol is effective up to 70 days' LMP. The findings have important implications for expanding access to outpatient medical abortion services in settings where the cost of misoprostol is of concern or a two-pill misoprostol regimen is the standard of care.