Maternal and Reproductive Health

Our researchers strive to improve the health and wellbeing of mothers and fathers-to-be, their children and their support networks across the globe. Our patient-focused approach ensures science evidence is used for real world impact, reducing unnecessary risks and highlighting health inequality to save lives and healthcare resources.

Theme LeadProfessor Shakila Thangaratinam

Professor Shakila Thangaratinam

Professor of Maternal and Perinatal Health

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Conception and Early Pregnancy

About our research

Miscarriage affects 1 in 6 pregnancies and causes untold emotional and physical pain to couples across the world. We are conducting a broad Programme of work to better understand the causes of miscarriage and testing new treatments to prevent miscarriage, underpinned by the National Tommy’s Centre for Miscarriage Research, led by Coomarasamy and spanning across UoB, University of Warwick and Imperial College London.

Through a series of large multi-centre trials, Coomarasamy & team have achieved major breakthroughs, resulting in 3 NEJM publications in 2019 alone, and 5 NEJM papers in the last 3 years. This includes the PRISM trial, the largest ever miscarriage trial recruiting >4100 patients from 48 UK hospitals, which found that progesterone treatment increases live birth rate in women with early pregnancy bleeding and a history of previous miscarriages, with huge implications for practice.

The TABLET trial (Coomarasamy, Dhillon-Smith) aimed to test whether levothyroxine reduces the risk of miscarriage in women who have thyroid antibodies. The study found no benefit from this treatment, an important finding that should stop the unnecessary use of this treatment, a common practice in infertility clinics. We also explore the role of cell-free fetal DNA sequencing to investigate for chromosomal problems in the fetus (Kilby), the role of sperm DNA fragmentation in miscarriage risk (Kirkman-Brown), and the association between immune markers, placentation and miscarriage (Tamblyn, Hewison, Kilby).

Publications

A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy. Coomarasamy A, Devall AJ, Cheed V, Harb H, Middleton LJ, Gallos ID, Williams H, Eapen AK, Roberts T, Ogwulu CC, Goranitis I, Daniels JP, Ahmed A, Bender-Atik R, Bhatia K, Bottomley C, Brewin J, Choudhary M, Crosfill F, Deb S, Duncan WC, Ewer A, Hinshaw K, Holland T, Izzat F, Johns J, Kriedt K, Lumsden MA, Manda P, Norman JE, Nunes N, Overton CE, Quenby S, Rao S, Ross J, Shahid A, Underwood M, Vaithilingam N, Watkins L, Wykes C, Horne A, Jurkovic D. N Engl J Med. 2019 May 9;380(19):1815-1824.

Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception. Dhillon-Smith RK, Middleton LJ, Sunner KK, Cheed V, Baker K, Farrell-Carver S, Bender-Atik R, Agrawal R, Bhatia K, Edi-Osagie E, Ghobara T, Gupta P, Jurkovic D, Khalaf Y, MacLean M, McCabe C, Mulbagal K, Nunes N, Overton C, Quenby S, Rai R, Raine-Fenning N, Robinson L, Ross J, Sizer A, Small R, Tan A, Underwood M, Kilby MD, Boelaert K, Daniels J, Thangaratinam S, Chan SY, Coomarasamy A. N Engl J Med. 2019 Apr 4;380(14):1316-1325. 18 citations (Web of Science, Dec 2019)

Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study. Lord J, McMullan DJ, Eberhardt RY, Rinck G, Hamilton SJ, Quinlan-Jones E, Prigmore E, Keelagher R, Best SK, Carey GK, Mellis R, Robart S, Berry IR, Chandler KE, Cilliers D, Cresswell L, Edwards SL, Gardiner C, Henderson A, Holden ST, Homfray T, Lester T, Lewis RA, Newbury-Ecob R, Prescott K, Quarrell OW, Ramsden SC, Roberts E, Tapon D, Tooley MJ, Vasudevan PC, Weber AP, Wellesley DG, Westwood P, White H, Parker M, Williams D, Jenkins L, Scott RH, Kilby MD, Chitty LS, Hurles ME, Maher ER; Prenatal Assessment of Genomes and Exomes Consortium. Lancet. 2019 Feb 23;393(10173):747-757.

Late Pregnancy – Maternal and Fetal Health

About our research

A major research focus in on metabolic disorders and its impact on maternal and fetal health, including global maternal and perinatal medicine. Thangaratinam leads the prediction of pre-eclampsia IPPIC (International Prediction of Complications in Pregnancy) IPD meta-analysis project funded by NIHR HTA, and supported by the WHO. The IPPIC collaborative network consists of 73 collaborators from 21 countries and is the largest global repository of standardised IPD of over three million pregnancies (15 UK, 66 international datasets). She also leads the International Weight Management in Pregnancy (i-WIP) collaborative group (40 researchers, 16 countries), with the largest live repository of individual data of over 25,000 participants to undertake NIHR- and WHO-funded aggregate and IPD meta-analysis to determine the effects of diet and physical activity in pregnancy.

The overall aim is the prediction and prevention of complications in pregnancy and beyond. Another focus in late pregnancy is the fetal therapy in the management of the ‘sick baby’ in-utero (Kilby, Morris):  Particularly, the management of complex monochorionic twins (including complications of twin to twin transfusion syndrome). A work programme led by Ewer (in collaboration with Thangaratinam) drives the impact and implementation of the PulseOx Trial, which has provided a new diagnostic test for detection of congenital heart disorders in the neonatal period, which is currently being rolled out globally.

Publications

Risks of stillbirth and neonatal death with advancing gestation at term: A systematic review and meta-analysis of cohort studies of 15 million pregnancies. Muglu J, Rather H, Arroyo-Manzano D, Bhattacharya S, Balchin I, Khalil A, Thilaganathan B, Khan KS, Zamora J, Thangaratinam S. PLoS Med. 2019 Jul 2;16(7):e1002838.

Pregnancy Outcomes in Women With Transposition of the Great Arteries After an Arterial Switch Operation. Stoll VM, Drury NE, Thorne S, Selman T, Clift P, Chong H, Thompson PJ, Morris RK, Hudsmith LE. JAMA Cardiol. 2018 Nov 1;3(11):1119-1122.

Pulse oximetry screening for critical congenital heart defects. Plana MN, Zamora J, Suresh G, Fernandez-Pineda L, Thangaratinam S, Ewer AK. Cochrane Database Syst Rev. 2018 Mar 1;3:CD011912.  

Global Maternal Health

About our research

In low income countries, 1 in 8 women will suffer from excessive bleeding after birth (postpartum haemorrhage, PPH). Oxytocin is the standard medicine for the prevention of PPH, but it is often of poor quality as it requires cold storage and transport, which are not available in many countries. IMSR researchers (Gallos, Coomarasamy) found that other medicines, including a novel drug called carbetocin, were more effective than oxytocin. Carbetocin is heat-stable, and thus does not require refrigeration, with major impact on policy and practice.

The World Health Organisation (WHO) updated their guidance, with Gallos leading the evidence synthesis for effectiveness and safety. PPH is often detected late; a sequential approach to administering life-saving interventions could mean more time – and lives – are lost. We, along with WHO, have developed a “first-response PPH treatment bundle”. This includes formative research, evidence synthesis, policy formulation, stakeholder engagement, and a cluster randomised trial to assess the effectiveness of our approach.

The Bill and Melinda Gates Foundation is accelerating our work with an $11 million grant. Thangaratinam has been closely working with WHO and published key papers highlighting the risks of caesarean sections performed in low- and middle-income countries (LMIC). She is currently leading a joint Programme of work with WHO on gender disparities in LMIC for metabolic complications, role of nutritional supplementation and lifestyle interventions to improve health of mother and baby in LMIC.

Publications

Antibiotic prophylaxis in the surgical management of miscarriage in low-income countries: a cost-effectiveness analysis of the AIMS trial. Goranitis I, Lissauer DM, Coomarasamy A, Wilson A, Daniels J, Middleton L, Bishop J, Hewitt CA, Weeks AD, Mhango C, Mataya R, Ahmed I, Oladapo OT, Zamora J, Roberts TE. Lancet Glob Health. 2019 Sep;7(9):e1280-e1286.

Maternal and perinatal mortality and complications associated with caesarean section in low-income and middle-income countries: a systematic review and meta-analysis. Sobhy S, Arroyo-Manzano D, Murugesu N, Karthikeyan G, Kumar V, Kaur I, Fernandez E, Gundabattula SR, Betran AP, Khan K, Zamora J, Thangaratinam S. Lancet. 2019 May 11;393(10184):1973-1982.

A Randomized Trial of Prophylactic Antibiotics for Miscarriage Surgery. Lissauer D, Wilson A, Hewitt CA, Middleton L, Bishop JRB, Daniels J, Merriel A, Weeks A, Mhango C, Mataya R, Taulo F, Ngalawesa T, Chirwa A, Mphasa C, Tambala T, Chiudzu G, Mwalwanda C, Mboma A, Qureshi R, Ahmed I, Ismail H, Oladapo OT, Mbaruku G, Chibwana J, Watts G, Simon B, Ditai J, Otim Tom C, Acam J, Ekunait J, Unzia H, Iyaku M, Makiika JJ, Zamora J, Roberts T, Goranitis I, Bar-Zeev S, Desmond N, Arulkumaran S, Bhutta ZA, Gulmezoglu AM, Coomarasamy A. N Engl J Med. 2019 Mar 14;380(11):1012-1021.