Polypharmacy in pregnancy

What is polypharmacy?

Polypharmacy refers to people taking two or more different prescription medications at the same time. It has been increasing over the last 30 years, partly due to more health conditions being diagnosed, and also to more drugs being available.

Side effects are a possible problem for anyone taking prescription medicine, and it is a bigger issue for people who are taking two or more medicines. They may also have problems caused by the interaction between different medications.  We are studying the impact of polypharmacy on people with a variety of health conditions, to help us develop ways to combat the problems of taking so much medication.  

Why focus on polypharmacy in pregnancy?

Doctors, midwives and researchers don’t have a good understanding of how much polypharmacy affects pregnant women and birthing people and their babies.  This is mainly because new medication is rarely tested on pregnant women due to concerns about the possible impact on the unborn baby. We do know that the changes that occur in the body during pregnancy mean that medications may not have the same effect as they do in someone who is not pregnant. Conversely, due to the evidence gap, it can also be harmful for pregnant women with long term health conditions to stop their regular medications.

MuM-PreDiCT is working to address this gap in knowledge, with a particular focus on pregnant women with two or more long term health conditions.

What have we discovered so far?

We have reviewed earlier research studies looking at polypharmacy in pregnancy. We found that overall, one in five pregnancies were reported to be affected by polypharmacy.

We then analysed GP electronic health records of over 800,000 pregnancies that occurred in the UK between 2000 and 2019. We found that the number of medications prescribed during pregnancy has increased over the last 20 years. About a quarter of all pregnant women were prescribed two or more medications.  And of the women who had two or more long term conditions, more than half were prescribed two or more medications during pregnancy.

The most commonly prescribed medications in pregnancy are:

  • antibiotics
  • antidepressants
  • painkillers
  • iron
  • laxatives
  • inhalers
  • anti-inflammatory creams/gels/ointments

When we looked at the patterns of polypharmacy, we found two main groups:

  • Inhalers are commonly prescribed with antidepressants, antihistamines, anti-inflammatory creams/gels/ointments, emollients and steroids.
  • Antidepressants are commonly prescribed with medications for heartburn and acid reflux, and thyroid disorders.

What’s next?

We will look more closely at how polypharmacy affects the health of pregnant women and their babies, both during and after pregnancy. We will conduct further studies to look at whether certain combinations of medications increase or decrease the risk of pregnancy complications such as pre-eclampsia, gestational diabetes, and premature delivery or health conditions in the baby, such as birth defects.

Knowing the potential benefits and harms of consuming medications during pregnancy will help pregnant women and their health care professionals to make informed decisions about whether to continue or start medications in pregnancy.

Take home points

Multiple medications are commonly prescribed in pregnancy, and more so among those women with multiple health conditions. Women contemplating pregnancy, and the health professionals caring for them, have to weigh up the possible benefits and harms to both the mother and her baby of continuing with or stopping pre-pregnancy medications, and of starting new medication during pregnancy. Further research is needed to understand the potential effects of medications that are commonly prescribed together.

Compiled by Anuradhaa Subramanian, Ngawai Moss, Katherine Phillips, Rachel Plachcinski, Siang Ing Lee.

Christmas Quiz

Here at MuM-PreDiCT HQ, we do like a friendly quiz for Christmas.

Socialising (and sharing answers over a few drinks) may be limited this year, so here is our offering to while away the lazy afternoons whilst you digest turkey, roast potatoes, and sprouts. We’ve even included links to places you can find the answers.

Here’s to a COVID-19 free Christmas and a happy new year.

Quiz

1) Name two of the three top research questions from our patient & public (PPI) advisory group.

2) MuM-PreDiCT is studying 79 long term health conditions – can you name 10 of them?

3) Why do we study both mild and serious health conditions?

4) Which 3 groups of individuals will we be speaking with to establish how care can be improved for women with 2 or more long-term physical or mental health conditions during pregnancy?(answer is on page 3 of the document)

5) What is a core outcome set?

 6) Who should be involved in the development of a core outcome set?

7) Among the several definitions for polypharmacy, how many medications are concurrently prescribed as a minimum?

8) What medication is prescribed the most among pregnant women?

9) MuM-PreDiCT is building risk prediction models to estimate the risk of developing 6 health conditions. Can you name 3 of these health conditions? (Answer at the end of the list)

10) What is the next MuM-PreDiCT study that I can get involved in?

Concept for this blog post: Rachel Plachcinski (women representative lead). Questions prepared by the MuM-PreDiCT team.

Focus group: What should researchers measure?

Are you…

Planning a pregnancy / pregnant in the last 5 years?
– Living with 2 or more long-term physical or mental health conditions 
(eg hypertension, diabetes, asthma, eczema, depression, anxiety, etc)?  

We would like to invite you to join an online Focus Group. We want to hear your views on what researchers should measure in studies of pregnant women & birthing people with multiple health conditions.

This is part of a bigger study to develop a Core Outcome Set.

What is a Core Outcome Set?

Researchers measure outcomes to understand what impact a health condition or an intervention has on a person.

Core Outcome Set is a list of outcomes that should be reported in all research studies for a specific health condition. It is agreed by people with the health condition, their health care professionals and researchers. If all studies for a health condition report the same types of outcomes, the results can be compared and combined.

Watch this short video on Core Outcome Set: http://www.comet-initiative.org/Patients

Why is it important?

We would like to find out what outcomes are important to you, that should be reported in all future studies of pregnant women and birthing people with multiple health conditions. Having the Core Outcome Set ready will make it easier and encourage researchers to do studies in this area. 

What is involved?

You will be invited to take part in an online Focus Group hosted on Zoom lasting for 1.5 to 2 hours. You will be reimbursed with a £25 voucher. Each focus group will have 6-8 participants and 2-3 facilitators. You can bring along your partner / carer / a family member so they can join the discussion too (and they will also be reimbursed £25).

When will the Focus Group take place?

There are two dates:

Thursday, 10th February 20222000pm to 2200pmWomen or birthing people with multiple long-term conditions only
Tuesday, 8th March 20222000pm to 2200pmWomen / birthing people with multiple long-term conditions  

with their partner / a family member / carer

How do I get involved?

If you would like to take part, please email the research team at s.i.lee@bham.ac.uk  

We’ll be in touch with next steps soon after that!

We can provide a separate session to talk through how to use Zoom if you have never used it before.

More information

COMET study registration: https://cometinitiative.org/Studies/Details/1724

Protocol published in BMJ Open: https://pubmed.ncbi.nlm.nih.gov/34716152/

Participant information sheet:  https://tinyurl.com/2p3v6536

Researching a wide range of long-term health conditions and how these interact with pregnancy

This blog post was written by our parent and public representatives Rachel Plachcinski, Ngawai Moss and our PPI Advisory Group. The infographic was designed by Ngawai Moss.

MuM-PreDiCT’s chief investigator, Professor Krish Nirantharakumar, outlines why it is important to include a wide range of long-term health conditions when studying how these interact with pregnancy. The research will also explore how multiple health conditions develop over time, from hay fever to heart disease.

In consultation with our parent representatives and the senior clinicians on our research team, we have developed a list of conditions to include in our research.1  These vary in how widespread they are within the population but also from seemingly mild to more serious conditions.

Why include both mild and serious conditions?

By analysing all the long-term health conditions affecting anyone who has been pregnant, regardless of their impact on day-to-day life, we can get an idea of how different conditions cluster together. We can then watch how the clusters develop over time and whether they are likely to lead to more serious conditions later in life.

For example, does having a few seemingly minor allergies predispose someone to developing a more severe autoimmune condition, such as lupus, later in life?2

Does the order in which the allergies develop, plus pregnancy, influence this?

Is a particular cluster, which includes both serious and relatively mild conditions, in the mother likely to result in health problems for her baby?

And does a particular combination of prescription medication play a part in any of this?

The MuM-PreDiCT research aims to answer some of these questions.

Serious conditions – common and uncommon

It’s also important to study serious health conditions as many of them are under-researched. Often there is little or no guidance for health professionals on how to care for women with these conditions during pregnancy.

Some serious conditions are relatively common, for example diabetes affects about 5% of pregnant women in the UK. These more common serious conditions are easier to study because researchers have enough cases to work out what was likely to have caused them (and potential issues for an individual’s future health). There is also likely to be a care pathway in place, such as the NICE guidance for caring for women with diabetes in pregnancy.3 All these things give us a great starting point for working out what further research is needed and how we can improve maternity care for the women affected.

Other serious conditions are much less common, especially in women who are of an age to fall pregnant, such as stroke, congenital heart disease, cancer and kidney disease. Uncommon serious conditions are much harder to study as the small number of people affected means it is harder to draw general conclusions about that condition and make predictions. Add in the pregnancy requirement and the numbers get even smaller.

Many midwives and doctors will never encounter a pregnant woman with uncommon health conditions, so producing research and guidance about how to care for women with each separate condition would be a very expensive way to improve care.

MuM-PreDiCT is going to look in more detail at one or two uncommon conditions as part of our cluster analysis. We want to identify what clusters these women form and then study their pregnancy outcomes. We don’t have the funding to look at more of the uncommon serious conditions in this way, but we hope the way we run the project will become established as a framework to help other researchers in the future. 

A care pathway for all women with two or more long-term health conditions

Women and birthing people experiencing pregnancy along with two or more long-term health conditions face particular challenges in navigating day-to-day life and health care. The MuM-PreDiCT team believes it is important to improve maternity knowledge and care for all of them.

Part of our project is to interview these women, and the doctors and midwives caring for them. We will then combine these findings with our research looking at health records, so we can make recommendations about general care pathways for more complex pregnancies.

It is important to include a wide range of long-term health conditions within our research, so we have a holistic understanding of how long-term health conditions interact with pregnancy. We hope that the learning from our 3-year research project will lead to measurable and long-lasting changes in maternity care which will benefit women and their families.

References

1.           MuM-PreDiCT. 79 health conditions defining 2 or more long-term health conditions inpregnancy. 2021. https://mumpredict.org/79-health-conditions-defining-2-or-more-long-term-health-conditions-in-pregnancy/.

2.           Krishna MT, Subramanian A, Adderley NJ, Zemedikun DT, Gkoutos GV, Nirantharakumar K. Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis. European Respiratory Journal 2019; 54(5): 1900476.

3.           National Institute for Health and Care Excellence. NICE guideline [NG3]: Diabetes in pregnancy: management from preconception to the postnatal period. 16 December 2020. https://www.nice.org.uk/guidance/ng3.

Focus group: Health / social care professionals (Core Outcome Set)

Are you…

  • A health or social care professionals in maternity services (e.g. midwife, doctor, nurse, health visitor, etc)?
  • Do you look after pregnant women & birthing people with 2 or more long-term physical or mental health conditions (eg hypertension, diabetes, eczema, depression, anxiety, etc)?

We would like to invite you to join a Focus Group to discuss what research outcomes are important to you.

This is part of a bigger study to develop a Core Outcome Set.

What is a Core Outcome Set?

An outcome is how a treatment affects a health condition. If all studies for a health condition report the same outcomes, they can be compared so we get a better idea of whether a new treatment works. A Core Outcome Set is a list of outcomes that should ideally be reported in research studies. It is agreed by people with the health condition, their health care professionals and researchers. We will have focus groups for pregnant women and birthing people with multiple long-term health conditions next Spring – stay tune for updates!

Why is it important?

We would like to find out what research outcomes are important to you, that should be reported in future studies on pregnant women and birthing people with 2 or more long-term health or mental health conditions. Having the Core Outcome Set ready will make it easier and encourage researchers to do studies in this area. Watch a short video on Core Outcome Set: http://www.comet-initiative.org/Patients

What is involved?

One Focus Group hosted on Zoom lasting for 45 to 60 minutes.

How do I get involved?

If you would like to take part, please email the research team at s.i.lee@bham.ac.uk  

We’ll be in touch with next steps soon after that!

More information

COMET study registration: https://cometinitiative.org/Studies/Details/1724

Protocol published in BMJ Open: https://pubmed.ncbi.nlm.nih.gov/34716152/

Participant information sheet: https://tinyurl.com/372jhzkc

We are expanding our Patient & Public Advisory Group

Are you interested in finding out more about health research?

Do you have two or more long term health conditions, and recent experience of pregnancy and birth?

We’re expanding the MuM-PreDiCT patient and public involvement advisory group and are looking for people who can help us shape this exciting research project.

Six amazing women – Sara, Jennifer, Charis, Siddequah, Nicola and Mary – joined the group last year and their insights and priorities were an important part of our successful bid for funding for the research.

Now we want to expand the group to make sure we cover pregnant women and birthing people’s experiences of maternity care and having two or more long term health conditions in all four countries of the UK, and from a variety of backgrounds. We particularly want to hear from people who:

  • Live in Northern Ireland, Wales or Scotland
  • Were born in another country, such as Poland or Pakistan
  • Live in very rural areas, with a significant distance to travel to see medical specialists
  • Are of Black or Mixed ethnic group
  • Have experienced health issues such as cancer, deafness, heart disease, skin conditions, blood disorders such as sickle cell disease, being HIV positive or having an organ transplant

The group meets (virtually online) 3 or 4 times per year to find out how the research is progressing and discuss issues arising from this. All members are paid £25 per hour for attending. We also have a WhatsApp group where we keep in touch between meetings.

To find out more about the group, or to express an interest in joining, email r.plachcinski@bham.ac.uk.

To see the full list of health conditions we are studying see this blog post https://mumpredict.org/79-health-conditions-defining-2-or-more-long-term-health-conditions-in-pregnancy/

MuM-PreDiCT gets funded!

We are very pleased to announce that MuM-PreDiCT has been successful in the funding call from the Strategic Priorities Fund (SPF): Tackling multimorbidity at scale: Understanding disease clusters, determinants & biological pathways (grant number MR/W014432/1).

The Strategic Priority Fund “Tackling multimorbidity at scale” programme is delivered by the Medical Research Council (MRC) and the National Institute for Health Research (NIHR) in partnership with the Economic and Social Research Council and in collaboration with the Engineering and Physical Sciences Research Council.

We would like to extend our heartfelt gratitude to our amazing patient and public involvement (PPI) advisory group and PPI co-investigators, and every research team member for all the hardwork.

We look forward to embarking on this exciting journey!


Links:

Multimorbidity / multiple long-term conditions (MLTC) – Research – Medical Research Council (ukri.org)

New study aims to improve healthcare for pregnant women with multiple health conditions (birmingham.ac.uk)

Funding to support key research into multimorbidity – School of Medicine News (st-andrews.ac.uk)

New study aims to improve healthcare for pregnant women with multiple health conditions – Keele University

News in Brief – new Life Sciences Chair, anti-racism campaign launched, medical director update – Leading Healthcare

79 health conditions: defining 2 or more long-term health conditions in pregnancy

Definition of multimorbidity

Multimorbidity was defined by the presence of two or more pre-existing long-term physical or mental health conditions prior to the index pregnancy. Pregnancy related conditions (e.g. gestational diabetes) were not included.

An exhaustive list of long-term health conditions was first identified from existing literature, in particular based on the work commissioned by Health Data Research UK on multimorbidity conceptualisation [1], and a recent publication on prevalence of different conditions in the UK [2]. This list and phenome definitions were refined and harmonised through workshops with our research advisory group, consisting of women representatives, clinicians from general practice, obstetrics, maternal medicine, psychiatry, public health, and data scientists. Health conditions were selected on the following basis: (i) prevalence; (ii) impact on pregnancy outcomes; (iii) considered important by women; and (iv) recorded in the study datasets.

LIST OF 79 CONDITIONS:

Cancers

  1. All cancers
    • Solid cancers
    • Haematological cancers
    • Metastatic cancers
    • Exclude basal cell carcinoma

Cardiovascular disease

  1. Hypertension
  2. Ischemic heart disease & Myocardial infarction
    • Myocardial infarction (thrombosis)
    • Myocardial infarction (dissection)
  3. Heart failure
  4. Stroke
    • Transient ischemic attack
    • Ischemic stroke
    • Haemorrhagic stroke
    • Unspecified stroke
  5. Atrial fibrillation
  6. Congenital heart disease
  7. Valvular heart disease (mitral, aortic, mixed)
    • Congenital
    • Acquired (e.g Rheumatic valvular disease)
  8.  Cardiomyopathy
    • Congenital
    • Acquired

Dermatology

  1. Eczema
  2. Psoriasis
  3. Autoimmune skin disease
    • Vitiligo
    • Alopecia areata
  4. Other dermatological conditions
    • Seborrheic dermatitis
    • Rosacea
    • Hidradenitis suppurativa
    • Lichen planus

Ear, Nose, Throat

  1. Profound deafness
  2. Allergic rhinitis & allergic conjunctivitis

Eye

  1. Inflammatory eye disease
    • Scleritis & episcleritis
    • Anterior uveitis
    • Posterior uveitis
  2. Cataract
  3. Diabetic eye disease
  4. Severe blindness
  5. Retinal detachment

Gastroenterology

  1. Irritable bowel syndrome
  2. Inflammatory bowel disease
    • Ulcerative colitis
    • Crohn’s disease
  3. Coeliac disease 
  4. Chronic liver disease
    • Chronic hepatitis B & C
    • Alcoholic liver disease
    • Autoimmune liver disease
    • Cirrhosis
    • Non-alcoholic fatty liver disease
  5. Peptic ulcer
  6. Gall stones (cholelithiasis)

Gynaecology

  1. Polycystic ovarian syndrome
  2. Endometriosis
  3. Leiomyoma (fibroids)
  4. Infertility

Haematology

  1. History of venous thromboembolism (VTE)
    • Deep vein thrombosis
    • Pulmonary embolism
    • Other VTE
  2. Primary thrombocytopenia
  3. Haemophilia 
  4. Sickle cell anaemia
  5. Pernicious anaemia

Mental health

  1. Depression
  2. Anxiety
    • Anxiety
    • Panic disorder
    • Phobia disorder
    • Post traumatic stress disorder
  3. Serious mental illness 
  • bipolar affective disorder
  • schizophrenia
  • psychosis
  1. Eating disorder
  2. History of alcohol use disorder (misuse / dependence)
  3. History of substance misuse 
  4. Neurodevelopmental disorder
    • Learning disability
    • Attention deficit hyperactivity disorder
    • Autistic spectrum disorder
  5. Others
    • Obsessive compulsive disorder (OCD)
    • Self-harm
    • Personality disorder
    • Dissociative disorder 

Rheumatology

  1. Systemic lupus erythematosus
  2. Spondyloarthritis
    • Psoriatic arthritis
    • Ankylosing spondylitis
  3. Inflammatory arthritis
    • Rheumatoid arthritis
    • Sjogern’s syndrome
    • Raynaud’s syndrome
    • Systemic sclerosis
    • Primary systemic vasculitis
  4. Ehler’s Danlos Syndrome (EDS) Type 3 (Hypermobile EDS)

Orthopaedic

  1. Scoliosis
  2. Vertebral disorder
    • Intervertebral disc disorder
    • Spondylosis
    • Spondylolisthesis
    • Collapsed vertebrae
    • Spinal stenosis
  3. Chronic back pain
  4. Osteoporosis 
  5. Osteoarthritis

Neurology

  1. Migraine
  2. Other chronic headache (including cluster headache, tension headache, other chronic headache)
  3. Epilepsy
  4. Multiple sclerosis
  5. Spina bifida
  6. Idiopathic intracranial hypertension
  7. Peripheral neuropathy
  8. Somatoform disorder 
    • chronic fatigue syndrome / myalgic encephalomyelitis
    • fibromyalgia
    • chronic pain syndrome (includes chronic regional pain syndrome, myofascial pain syndrome)

Respiratory

  1. Asthma
  2. Chronic obstructive pulmonary disease
  3. Obstructive sleep apnoea
  4. Pulmonary fibrosis, interstitial lung disease
  5. Pulmonary hypertension
  6. Bronchiectasis
  7. Cystic fibrosis
  8. Sarcoidosis

Renal

  1. Chronic kidney disease 
  2. Urinary tract stones

Endocrine

  1. Diabetes mellitus
  2. Thyroid disorder
  3. Pituitary disorder
  4. Adrenal benign tumour
  5. Hyperparathyroidism

Other

  1. Human immunodeficiency viral (HIV) infection / AIDS
  2. Turner’s syndrome
  3. Marfan’s syndrome
  4. Solid organ transplant 

References

[1] Ho IS, Azcoaga-Lorenzo A, Akbari A, Black C, Davies J, Hodgins P, Khunti K, Kadam U, Lyons RA, McCowan C, Mercer S, Nirantharakumar K, Guthrie B. Examining variation in the measurement of multimorbidity in research: a systematic review of 566 studies. Lancet Public Health. 2021 Aug;6(8):e587-e597. doi: 10.1016/S2468-2667(21)00107-9. Epub 2021 Jun 22. PMID: 34166630.

[2] Kuan V, Denaxas S, Gonzalez-Izquierdo A, Direk K, Bhatti O, Husain S, et al. A chronological map of 308 physical and mental health conditions from 4 million individuals in the English National Health Service. The Lancet Digital health. 2019;1(2):e63-e77. Epub 2019/10/28. doi: 10.1016/s2589-7500(19)30012-3. PubMed PMID: 31650125; PubMed Central PMCID: PMCPMC6798263.

Phenome definitions (physical and mental health conditions, active multimorbidity)

Github: For Read codes, ICD-10 codes and phenome definitions