Halting the Canadian STRIDER randomised controlled trial of sildenafil for severe, early-onset fetal growth restriction: ethical, methodological, and pragmatic considerations.

OBJECTIVES: To determine the efficacy and safety of sildenafil citrate to improve outcomes in pregnancies complicated by early-onset, dismal prognosis, fetal growth restriction (FGR). Eligibility: women ≥ 18 years, singleton, 18 + 0-27 + 6 weeks' gestation, estimated fetal weight < 700 g, low PLFG, and ≥ 1 of (i) abdominal circumference < 10th percentile for gestational age (GA); or (ii) reduced growth velocity and either abnormal uterine artery Doppler or prior early-onset FGR with adverse outcome. Ineligibility criteria included: planned termination or reversed umbilical artery end-diastolic flow. Eligibility confirmed by placental growth factor (PLGF) < 5 th percentile for GA measured post randomization. Women randomly received (1:1) either sildenafil 25 mg three times daily or matched placebo until either delivery or 31 + 6 weeks. PRIMARY OUTCOME: delivery GA. The trial stopped early when Dutch STRIDER signalled potential harm; despite distinct eligibility criteria and IRB and DSMB support to continue, because of futility. NCT02442492 [registered 13/05/2015]. RESULTS: Between May 2017 and June 2018, 21 (90 planned) women were randomised [10 sildenafil; 11 placebo (1 withdrawal)]. Baseline characteristics, PLGF levels, maternal and perinatal outcomes, and adverse events did not differ. Delivery GA: 26 + 6 weeks (sildenafil) vs 29 + 2 weeks (placebo); p = 0.200. Data will contribute to an individual participant data meta-analysis.

PIERS proteinuria: relationship with adverse maternal and perinatal outcome.

OBJECTIVE: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes. METHODS: We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women ("ALL measures") who had all three proteinuria assessments. RESULTS: More women were proteinuric by urinary dipstick (≥ 2+, 61.4%) than by spot urine Pr/Cr (≥ 30 g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome. CONCLUSION: The measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.

Acceptance of a rapid herpes test in labour: survey of attitudes of patients and health care providers.

OBJECTIVE: To determine the acceptability to pregnant women and their health care providers of a rapid test for genital herpes simplex virus (HSV) in labour. METHODS: A cross-sectional survey was conducted with outpatient pregnant women and their health care providers (obstetricians, family physicians and midwives) at BC Women's Hospital and Health Centre. RESULTS: Of pregnant women approached, 207 (92%) completed the survey; 90% reported no history of genital herpes. Rapid HSV testing in labour was acceptable to 85% of pregnant women. Among the 133 women who were planning a vaginal delivery, 63% were willing to consider delivery by Caesarean section and 53% were willing to consider intrapartum anti-viral medications if HSV was present in the genital tract. Of 51 health care providers surveyed, 98% indicated interest in knowing if their patient had a newly acquired HSV infection, while 84% indicated interest in knowing if the patient had a reactivation of infection. If HSV was detected in their patient's genital tract, 36% indicated they would recommend a Caesarean section, and 25% would consider antiviral medication as an investigational intrapartum treatment. Interestingly, both of these proportions increased if the patient had ruptured membranes for more than four hours. CONCLUSION: Most pregnant women and their health care providers are receptive to the use of a rapid polymerase chain reaction test to detect genital HSV shedding in labour. This supports the development of HSV rapid testing and antiviral therapy trials in the labour setting.

The evaluation of the fetal fibronectin test for prediction of preterm delivery in symptomatic patients.

OBJECTIVE: This study was conducted to evaluate the usefulness of testing for fetal fibronectin (fFN) to rule out the diagnosis of preterm labour in symptomatic patients in a Canadian setting. METHODS: This was a prospective, blinded clinical evaluation of fFN testing in women presenting with threatened preterm labour at between 24 and 34 weeks' gestation at two Canadian tertiary care centres. RESULTS: Of the 149 women tested, 32 had a positive fFN test. In the total patient population, 10.1% delivered within seven days of testing, and 18.2% delivered prior to 34 weeks. A negative fFN result was associated with a 97.4% likelihood of delivering more than seven days after testing and with a 91.4% chance of delivering after 34 weeks. CONCLUSION: The fFN test appears to provide useful information in the risk assessment of Canadian women presenting with symptoms compatible with preterm labour. A negative test has a high predictive value for delivering more than seven days after presentation.