4 Research recommendations

The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future. The Guideline Development Group's full set of research recommendations is detailed in the full guideline (see section 5).

4.1 Reducing the risk of hypertensive disorders in pregnancy

How clinically and cost effective is calcium supplementation (compared with placebo) for the prevention of pre-eclampsia in women at both moderate and high risk of pre-eclampsia?

Why this is important

Pre-eclampsia and gestational hypertension represent common pregnancy complications. Although large studies on the use of calcium supplementation to prevent hypertensive disorders during pregnancy have been carried out, the variation in populations and calcium status at entry to the studies has made it impossible to reach a conclusion on the value of such treatment in any setting. Calcium supplementation as a treatment is cheap, likely to be well tolerated, and likely to be safe for both the woman and the fetus, although this needs to be confirmed. Even a modest effect would be potentially important given the simplicity of the treatment. A new meta-analysis, using the technique of meta-analysis regression, is needed to clarify the roles of dietary calcium intake and underlying pre-eclampsia risk, taking advantage of subgroup data and seeking additional information from the authors of published trials where possible. Further randomised controlled trials could also be conducted to examine risk reduction in women at moderate and high risk of pre-eclampsia, and to re-examine risk reduction in women at low risk of pre-eclampsia. These trials should consider maternal diet and calcium status and they should evaluate both maternal outcomes (incidence of hypertensive diseases during pregnancy, including severe disease) and neonatal or infant outcomes (neonatal morbidity, infant growth and development).

4.2 Assessment of proteinuria in hypertensive disorders of pregnancy

How should significant proteinuria be defined in women with hypertension during pregnancy?

Why this is important

Most adverse outcomes in new-onset hypertensive disorders during pregnancy arise in women with proteinuria. However, the quality of evidence for the diagnosis of significant proteinuria is poor and the prognostic value of different quantities of urinary protein is unclear. There is a need for large, high-quality prospective studies comparing the various methods of measuring proteinuria (automated reagent-strip reading devices, urinary protein:creatinine ratio, urinary albumin:creatinine ratio, and 24-hour urine collection) in women with new-onset hypertensive disorders during pregnancy. The studies should aim to determine which method of measurement, and which diagnostic thresholds, are most accurate in predicting clinically important outcomes. Such studies would inform decisions regarding clinical management of new-onset hypertensive disorders during pregnancy. If predictive parameters were identified then interventions based on these and aimed at improving outcomes could be evaluated in randomised clinical trials.

4.3 Haematological and biochemical monitoring in women with gestational hypertension

What is the role of assessing haematological or biochemical parameters at diagnosis of gestational hypertension and during surveillance of gestational hypertension?

Why this is important

Pre-eclampsia is a multisystem disorder, but it is not clear whether routine assessment of a range of haematological or biochemical parameters in women with gestational hypertension helps clinical care or is sufficiently discriminatory to allow better targeted care. Information on which assessments might be useful is incomplete and there are confusing data on whether clinical outcomes are changed.

Large prospective studies should be carried out to examine a range of parameters singly and serially (kidney function, liver function, coagulation, measurement of proteinuria) in women with gestational hypertension. These studies should use properly validated pregnancy values and examine the prediction of clinically important outcomes (severe pre-eclampsia and its maternal and fetal complications).

If parameters with sufficient prediction are identified, randomised controlled trials should be used to compare the effect of knowledge of these compared with no knowledge on clinical maternal and perinatal outcomes. Trial results should be incorporated in health economic models to assess cost effectiveness.

4.4 Timing of birth in women with pre-eclampsia

When should women who have pre-eclampsia with mild or moderate hypertension give birth?

Why this is important

There is a 'grey' zone for women who have pre-eclampsia with mild or moderate hypertension between 34 and 37 weeks when the optimal timing of birth is not clear.

Women who have pre-eclampsia with mild or moderate hypertension may progress to severe disease with its risks, but it is not clear whether these risks outweigh or should outweigh the risks of planned late preterm birth for the baby. Neonatal services are under constant pressure and planned preterm birth without clear benefit to either woman or baby would have costs.

Randomised controlled trials should be carried out that compare policies of immediate planned birth between 34+0 and 36+6 weeks in women who have pre-eclampsia with mild or moderate hypertension with expectant management and birth for clinical progression. Outcomes should include severe pre-eclampsia and its complications, need for critical care, maternal satisfaction, neonatal morbidity and mortality, and health economics. Trials need to be large enough to examine less common complications in the woman.

4.5 Antihypertensive agents and breastfeeding

How safe are commonly used antihypertensive agents when used by women who are breastfeeding?

Why this is important

With the increasing incidence of hypertensive disorders during pregnancy, more pregnant and breastfeeding women will potentially be exposed to antihypertensive medication. Most of the relevant drugs are not licensed for use in pregnancy. For most drugs there is no information on their presence in human breast milk, or if such a presence has any clinical effect. As a result, women may either be denied effective treatment in the postnatal period or advised against breastfeeding. Studies should measure the concentration of relevant drugs and their metabolites in breast milk, taking account of drug pharmacokinetics (peak levels and elimination) and comparing neonatal behaviour and physiological variables in women using each drug with those in women who choose not to breastfeed. Studies should follow women and their babies for long enough to exclude cumulative effects and they should be large enough to provide reassurance to licensing and drug regulating authorities.

  • National Institute for Health and Care Excellence (NICE)