Frequently Asked Questions

1)     What are the inclusion criteria for WILL?

Women must meet ALL of the following criteria:

• Maternal age ≥16 years
• Diagnosis of chronic or gestational hypertension (as per NICE guidance)
• Singleton pregnancy
• Live fetus: Please note that at the time of consent, the presence of a fetal heartbeat should be documented in the medical notes.
• Gestational age of 36+0 to 37+6 weeks
• Able to give documented informed consent to participate

2)     What are the exclusion criteria for WILL?

Women must meet NONE of the following criteria:

• Contraindication to either one of the trial arms (e.g. evidence of pre-eclampsia)
• Severe hypertension (i.e. blood pressure [BP] ≥160mmHg systolic or ≥110mmHg diastolic) until BP is controlled below this level
• Major fetal anomaly anticipated to require neonatal unit admission
• Participation in another timing of delivery trial

Please NOTE that neither maternal co-morbidities (e.g. diabetes) nor fetal size are exclusion criteria.

3)     What are the exclusion criteria related to fetal anomalies?

A woman should not be included in WILL if the baby has a known (major) congenital anomaly that is likely to require admission to a neonatal care unit after birth.

3b) Which types of fetal anomalies would make women ineligible for WILL?

Examples include: diaphragmatic hernia, gastroschisis, omphalocoele, neural tube defects, hydrocephalus, microcephaly, chromosomal abnormalities, cleft lip or palate, and cyanotic congenital heart disease.

If you are unsure whether a fetal anomaly would make a woman ineligible for WILL, please contact the WILL trial team either by email at will@trials.bham.ac.uk or by phone on 0121 415 9109. We are always happy to help you.

 3c) Which types of fetal anomalies would still allow women to be eligible for WILL?

Examples include: hypospadias, unilateral renal disease, solitary kidney, isolated talipes (club foot), isolated choroid plexus cysts, mild ventriculomegaly, and mild cardiac abnormalities (such as a ventriculoseptal defect).

If you are unsure whether a fetal anomaly would still allow a woman to be eligible for WILL, please contact the WILL trial team  either by email at will@trials.bham.ac.uk or by phone on 0121 415 9109. We are always happy to help you.

 4)     Can a site that is participating in the Big Baby trial take part in the WILL trial?

Yes, indeed! Sites can take part in both trials. However, as Big Baby and WILL are both timing of delivery trials women can only consent to take part in one. Each site should work out how they will screen for eligibility to each trial. Most sites will screen for Big Baby at ultrasound and diabetes clinics, and for WILL at hypertension clinics and maternity assessment units. The WILL and Big Baby teams are working together to make the research experience a positive one for all concerned, and to maximise recruitment of women to research.

5)     If a woman has diabetes or another co-morbidity, does this exclude her from participating in the WILL trial?

No, neither maternal co-morbidities nor fetal size will be exclusion criteria. We are keen to be as inclusive as possible, so that the results of the trial would apply to women who we all see in the NHS.

If you are unsure whether a woman is eligible for WILL, please contact the WILL trial team, as we are always happy to help you.

6)     The inclusion criteria for gestational hypertension state that women must not have ‘new’ proteinuria. Are women who have a history of renal disease with proteinuria eligible?

Yes, women with pre-existing renal disease are eligible for inclusion in WILL, as long as they have no evidence of superimposed pre-eclampsia and meet other inclusion/exclusion criteria. If women present with proteinuria after 20 weeks’ gestation, but it persists and the clinician comes to believe that this is due to renal disease and not pre-eclampsia, the woman is eligible.

These cases can be quite confusing, so please do not hesitate to contact the WILL trial team to discuss.

7)     What blood pressure ranges are required for a woman to be eligible for WILL?

To be eligible for WILL, a woman must have a diagnosis of chronic hypertension or gestational hypertension. The diagnosis must have been made by a doctor or midwife, according to current NICE guidance (now NG133, June 2019, https://www.nice.org.uk/guidance/ng133). It is important to note that the woman does not need to have elevated blood pressure at the time of consent or randomisation.

If a woman’s blood pressure is ≥160/110mmHg, she would be ineligible for WILL until her BP were ‘controlled’ (i.e. falls below this level). However, she could be reassessed for eligibility thereafter.

8)     Do women with gestational hypertension need to have this diagnosis written in their notes prior to consent?

Yes, although similar terms can be used, such as “pregnancy-induced hypertension (PIH)”. However, the woman must not have evidence of pre-eclampsia.

You may see the term, “suspected pre-eclampsia” written in the notes. It is used when women present with either a rise in their chronic hypertension or new gestational hypertension, without new proteinuria (that confirms a diagnosis of pre-eclampsia), but instead with other manifestations, such as new headache or fetal growth restriction.  At 36+0 weeks onward, women are not offered placental growth factor (PlGF)-based testing, so the diagnosis of pre-eclampsia will be based on an assessment of maternal and fetal well-being using clinical, laboratory, and ultrasonographic criteria. The clinician should be able to make a decision about whether or not pre-eclampsia is present within 24-48 hr of presentation.

9)     If a woman is planning delivery at a certain time (such as 39 weeks), is she eligible for WILL?

 Yes, if she is willing to potentially change that timing to one of the two trial arms. 

1) At what gestation can women be consented and randomised?

Eligible women can be consented for the trial at 36+0 - 37+6 weeks gestation.

Consented women can be randomised from 37+0 - 37+6 weeks gestation.

Please note that eligible women who are at 37+0-37+6 weeks can be consented and randomised at the same visit.

2) Why are consent and randomisation performed at different times in some women?

Taking consent for WILL requires a face-to-face interaction; as women are routinely seen at 36 weeks, taking consent thereafter would require women to return to the hospital. This could be a barrier to recruitment.

If women are enrolled too close to 38+0-38+3 weeks, there will be less time to book their inductions/elective caesareans.

We have tried to strike a compromise in WILL. Women can be consented at their 36 week routine antenatal care visit, and then re-contacted at 37+0 to 37+6 weeks, by phone, by the research midwife in order to reconfirm eligibility (done verbally) and willingness to be randomised, and then to perform randomisation.

Remember: If a woman is consented between 37+0-37+6 weeks, then she can be randomised on the same day. At your site, if women with hypertension are seen weekly, this may be the easier approach.

3) If a woman reports symptoms of pre-eclampsia when completing the Reconfirmation of Eligibility form, is she still eligible for WILL?

Maybe. However, she will need to be reassessed. Please advise her to contact her midwife, hospital doctor or maternity assessment unit for review. Please then arrange to recontact the woman after this and reassess for eligibility again on the Reconfirmation of Eligibility Form (Form 2). If she is assessed to be well and without pre-eclampsia, she will remain eligible and can be randomised.

4)     What if a woman is randomised to the early term delivery group and the IOL or ELCS cannot be commenced within the study arm time frame?

Women in the planned early term delivery group (at 38+0-38+3 weeks) may have their induction or caesarean commenced after 38+3 weeks due to reasons that are out of the local team’s control. These include busy labour induction or theatre schedules. The reason(s) for the delay will be documented on the Delivery form of the database, and these will be monitored by site throughout the trial. If the timing of delivery is based on personal preference by the participant or clinician preference (without a medical reason), then we ask that a Protocol Deviation Form be completed so that we can understand as well as possible when led to this decision.

5)     Can clinicians/doctors intervene in the usual care arm if there is a clinical need for delivery, such as reduced fetal movements etc.?

Yes. The WILL intervention is planned timing of delivery. We anticipate that, given their underlying hypertensive disease, some women in each of the trial arms may be delivered earlier for clinical need. It is very important that all women and babies in the trial receive the best possible care.

If the team has any questions, please do not hesitate to contact the WILL trial team to discuss.

6)     Can women be offered membrane sweeps before 40 weeks if they are in the usual care arm?

No. This practice should NOT be offered to women in the planned usual care arm of the trial. Also, women who are enrolled in WILL should understand that they will not be offered membrane sweeping. If however, women are inadvertently offered membrane sweeps, women should stay in the trial and the information should be documented on the Delivery Page of the database under the labour induction section.

Membrane sweeps are a form of labour induction, although their effectiveness compared with other methods (that would be used in the planned early term delivery arm) has not been demonstrated.

Sweeping of the membranes, performed as a general policy for women at term (including those without hypertension), shortens the duration of pregnancy by an average of 3 days. Fewer women in these studies continued beyond 41 weeks (RR 0.59, 95% CI 0.46 to 0.74) or 42 weeks (RR 0.28, 95% CI 0.15 to 0.50). These conclusions were based on a 2005 Cochrane review of 20 trials (2797 women) of sweeping of membranes versus no treatment. The risk of caesarean delivery was similar. Importantly, discomfort during vaginal examination and other adverse effects (bleeding, irregular contractions) were more frequently reported by women allocated to sweeping; at least 70% of women who undergo membrane sweeping suffer significant discomfort and about 30% suffer significant pain. The authors concluded that the routine use of sweeping of membranes from 38 weeks of pregnancy onwards does not seem to produce clinically important benefits.

Reference: Boulvain M, Stan C, Irion O. Membrane sweeping for induction of labour. Cochrane Database Syst Rev.2005;(1):CD000451. PMID: 15674873

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD000451.pub2/full

 7)     How do we document weekly contact with the participant if the notes are handheld and the contact is by telephone?

There is usually a place on electronic systems for telephone consults. If it is all paper, then we would suggest writing a note to be filed later. This aspect of the trial is to maintain contact and a good relationship with the woman.

8)     Do we need a paediatric doctor to assess the baby at 28 days?

No, it would just be part of the outcomes that we capture from the routine medical document. Please note that the primary outcome for the baby is measured until primary discharge home 28 days of life, whichever is earlier; only in rare circumstances do we expect that babies will still be in hospital at 28 days after birth. 

1)     Who can sign off maternal outcomes on Maternal Outcome Form?

The PI or delegate (who can be a midwife, nurse, or other member of the research team who is assigned this duty on the site signature and delegation Log) can sign-off the primary maternal outcome components, detailed in the ‘Maternal complications’ and ‘Maternal Management’ sections of the Maternal outcome form.

2)     If the PI or delegate has been involved in the care of the woman, can they still do the sign off?

No, this needs to be someone who wasn’t involved in the care of the woman.

Please contact BCTU or the WILL research midwives if there are any difficulties with this.

3)     How can we make sure that the sign off reviewer is masked to allocation?

When reviewing the notes and entering data, please photocopy only the relevant sections (or print out if using electronic notes) and redact the sections showing the allocated arm of the trial before giving to the person doing the sign-off.

Each site will find a different solution to adjudication, and we will provide you with all the support that you need.             

4)     Why does the allocated arm need to be blinded for the sign-off?

The masking is being done to eliminate any bias, conscious or unconscious. Thank you for your help with this. 

1)     Do we need to capture transitional care on the neonatal form?

No. Neonatal care unit admission refers to care that takes the baby away from his/her mother.

2)     Can an interpreter be used to call the woman to complete the Childbirth Experience Questionnaire and six-week Questionnaire?

Yes. This is entirely acceptable.

CEQ: A family member could be used to help with the CEQ after birth and before discharge home, given that these are personal questions and some even involve the partner.

Six-week questionnaire: The team would need to contact the woman at 6 weeks postpartum to complete this questionnaire with her over the phone with the support of an interpreter.

3)     What forms need to be completed for women who are consented and not randomised?

The WILL database will automatically select the required forms that need to be completed for all women.

If the woman consented and was eligible for randomisation when re-contacted, but declined, then please complete:

• Trial withdrawal form

If the woman consented, but was not eligible to be randomised, then please complete:

• Reconfirmation of Eligibility
• Additional Baseline Information
• Delivery
• Maternal outcome and postpartum management
• Neonatal

1)     How can the team prevent the six-week postpartum questionnaire being sent to a woman who has died or whose baby has died?

Prompt submission of outcome data to the BCTU will prevent this from happening. Please let us know as soon as you become aware of the death of a woman and/or baby in WILL. (Also, an SAE form will need to be completed for all deaths.) BCTU will then ensure that Textlocal does not contact the woman by sending out a text message and link to the questionnaire.

In the unfortunate situation that despite these efforts, a link to the questionnaire is sent out, the woman/family has the option of not responding or declining to participate. Please let us know immediately should such a situation arise. 

2)     What is the time frame for reporting SAEs?

The Investigator should document in the source data, all SAEs experienced by the trial participant, from randomisation until 6 weeks postpartum. All SAEs must be followed to their resolution, even if this extends the time frame beyond 6 weeks postpartum.