Professor Lucy Chappell PhD FRCOG
NIHR Research Professor in Obstetrics
King’s College London
As we make progress on so many fronts in pregnancy hypertension, including important reductions in maternal mortality from the disease in high-income settings and globally, it is useful to reflect on some of the challenges that remain, particularly those that seem scientifically intractable despite best efforts. What makes a problem seemingly so hard to crack? There are perhaps three main possibilities.
The first is that the research question underpinning the problem is difficult to nail down for reasons of scientific uncertainty. This may be because we are at a relatively early stage of the pathway in unpicking mechanisms of disease, or we are still developing knowledge needed to produce a coherent model. Initial research that supported the concept of pre-eclampsia as more than pregnancy-induced hypertension has been followed by an appreciation that different phenotypes of pre-eclampsia (characterised by varying maternal and fetal manifestations) may require tailored preventative strategies. Initial optimism for prophylactic treatments based on amelioration of common pathophysiological pathways has been tempered by results of clinical trials which question whether we are treating the right group of women with the best prophylaxis from the optimal gestation.
The second possibility is that the infrastructure conspires against addressing a clinical need or a research gap. For maternal mortality from hypertensive disorders of pregnancy in low income settings, this may relate to policy, or financial imperatives beyond the scope of the usual researcher. Research questions in ‘Cinderella’ areas (i.e. those historically neglected by funders, policy-makers or academics), may be lacking strong advocacy for research effort due to political, gender-based, racial or other reasons. An example may be the challenge of finding effective preventative strategies for stillbirth, which remained uncounted in health surveys for many decades. More recently, investment into unpicking the various pathophysiological pathways of this heterogeneous problem suggest that prevention is not truly elusive but will be incrementally tackled. But collaboration between researchers in high-income countries with easier access to funds and those in settings where the greatest burden of disease exists, can focus on translation of interventions adapted appropriately. Successful examples of subsequent reverse translation may help such collaborative models flourish and grow. In all settings, research governance can act as an appropriate brake on unethical and fraudulent practice, but also as a barrier if not appropriately risk-proportionate. Lean, fit-for-purpose research governance must be the goal of every system, but is challenging in the pregnancy field where effects of interventions may sometimes only become apparent decades or generations later. Sometimes clinicians themselves may be part of the block, if they are slow to acknowledge research uncertainties and reluctant to engage with research that tackles such questions, acting as selective gatekeepers to women’s participation. Rarely are women not engaged with a research need – they are usually only too willing to accept such uncertainties and participate in research.
The third option is that the research required to address the challenge needs cross-disciplinary efforts with an approach out of the usual box found in academic institutions. The current disjointed model of research in most high-income countries rewards single discipline researchers as lead investigators, and does not always facilitate multiple sectors providing smaller contributions to an overall problem. For example, in many countries, short and long-term postnatal management of women after pregnancy hypertension is fragmented across specialties, and addressing the problem is labelled as being ‘too difficult’ to tackle. Further work is needed across a spectrum of research gaps ranging from establishing the safety of antihypertensive drugs in breastfeeding women through to finding effective interventions tailored to postnatal women to reduce long term increased risks of cardiovascular disease. These require collaboration across disciplines as diverse as clinical pharmacology to behaviour change psychology to epidemiology with much more in between.
What could be done to address these challenges labelled as intractable? The ISSHP is an organisation that harnesses clinicians and researchers across all sectors into improving care and outcomes for women with pregnancy hypertension and the seven-point plan put forward by the recent President suggests many ways to address the barriers above. Funders such as the UK Global Challenges Research Fund (GCRF) have recently launched calls specifically for Interdisciplinary Research Hubs to address ‘intractable challenges faced by developing countries’ which calls for transformative approaches to engender a step change in addressing the challenges of the UN’s Sustainable Development Goals (SDGs). This needs to be matched by investment in training the next (and the current) generation in methodology suitable to tackle these problems. These incentives, or pulls, are essential as multiple barriers – historical, political, medical amongst others – need to be overcome. The final word rests with pregnant women, as the key will be harnessing their active involvement and participation at all stages of the research to really make it count.
