British Journal of Obstetrics and Gynaecology
Randomised, double-blind, placebo-controlled trial of corticosteroids for the treatment of hyperemesis gravidarum
Introduction
Nausea and vomiting in pregnancy are common, affecting 60%-70% of all pregnancies. Hyperemesis, defined as persistent nausea and vomiting of such severity that the woman is unable to maintain adequate hydration, electrolyte balance or nutritional status, affects about 1% of pregnancies1. Severe hyperemesis, refractory to conventional management with intravenous fluids and antiemetics is a rare and disabling condition, associated with multiple hospital admissions, time away from work and the family, and psychological morbidity2. In extreme cases, women may request, or their obstetricians recommend, termination of the pregnancy. If inadequately or inappropriately treated, hyperemesis may cause Wernicke's encephalopathy3, central pontine myelinolysis3, and maternal death4. Infants of mothers with severe hyperemesis have significantly lower birthweights and birthweight centiles5, 6, 7. We have previously reported a case series of four women with severe hyperemesis who all showed dramatic improvement following the use of steroids8. Following this, some workers reported similar success9, 10, 11, 12 although others did not13. A definitive, randomised, double-blind, placebo-controlled trial was therefore needed to determine whether corticosteroids should be a therapeutic option for this miserable and disabling condition. Severe hyperemesis is not common and therefore a multicentre study was required. Based on our pilot studies8, 9, we hypothesised that corticosteroids would lead to rapid and complete remission of the symptoms of nausea and vomiting in cases of severe hyperemesis gravidarum.
Section snippets
Methods
The study population included pregnant women with severe or prolonged hyperemesis gravidarum, drawn from inpatient gynaecology wards in the eight collaborating centres. To be eligible the women met the following inclusion criteria: onset of nausea and vomiting before 12 weeks of gestation, dependent on intravenous fluids for at least one week (first admission for hyperemesis) or 24 hours (second or subsequent admission for hyperemesis), receiving regular treatment with at least one anti-emetic,
Results
A trial profile is given in Fig. 1. We did not collect data on the total number of eligible patients in each centre over the time period of the study. Between April 1995 and December 1996, 25 women were recruited. The numbers of patients allocated to each arm in each centre was similar.
Entry of patients ceased abruptly after December 1996, prior to the planned recruitment of the 45 subjects required. Results of the interim analysis and meeting of the data monitoring committee were not disclosed
Discussion
Hyperemesis is a heart-sink problem for gynaecologists, possibly because of the frustration at not being able to cure such distressed women, and also because prolonged or repeated admissions lead to blocking of cold surgery gynaecology beds. In its severe, but fortunately rare, form substantial maternal morbidity and occasionally mortality may result. Since corticosteroids are effective in the treatment of vomiting induced by chemotherapy, it was thought that they might also be of use in other
Conclusion
Our experience highlights the difficulties recruiting subjects to therapeutic trials in obstetrics. This multicentre randomised double-blind placebo-controlled study did not have the power to support or refute the hypothesis that steroids lead to a rapid and complete remission of the symptoms of nausea and vomiting in cases of severe hyperemesis gravidarum refractory to conventional management. Nevertheless, we believe that the results are important for comparison with previous and future
Acknowledgements
The authors would like to thank all the women who agreed to enter the study and the collaborators in the participating centres, including Dr C. Bottomley, Dr K. Harding, Professor P. Rubin, Dr K. Brackley, Dr J. Rutherford, Dr S. Crawshaw, Professor J. Walker, Dr J. Shillitto, Professor R. Taylor, Ms S. Jones, Dr J. Haley and Dr A. Mc Elligott. The collaborating centres included Queen's Medical Centre, Nottingham; Princess Mary Maternity Hospital, Newcastle-upon-Tyne; Bradford Hospital; Queen
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