Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial.
OBJECTIVE
To compare pregnancy outcomes, accounting for allocated group, between methyldopa-treated and labetalol-treated women in the CHIPS Trial (ISRCTN 71416914) of 'less tight' versus 'tight' control of pregnancy hypertension.


METHODS
Secondary analysis of CHIPS Trial cohort.


METHODS
International randomised controlled trial (94 sites, 15 countries).


METHODS
Of 987 CHIPS recruits, 481/566 (85.0%) women treated with antihypertensive therapy at randomisation. Of 981 (99.4%) women followed to delivery, 656/745 (88.1%) treated postrandomisation.


METHODS
Logistic regression to compare outcomes among women who took methyldopa or labetalol, adjusted for the influence of baseline factors.


METHODS
CHIPS primary (perinatal loss or high level neonatal care for >48 hours) and secondary (serious maternal complications) outcomes, birthweight <10th centile, severe maternal hypertension, pre-eclampsia and delivery at <34 or <37 weeks.


RESULTS
Methyldopa and labetalol were used commonly at randomisation (243/987, 24.6% and 238/987, 24.6%, respectively) and post-randomisation (224/981, 22.8% and 433/981, 44.1%, respectively). Following adjusted analyses, methyldopa (versus labetalol) at randomisation was associated with fewer babies with birthweight <10th centile [adjusted odds ratio (aOR) 0.48; 95% CI 0.20-0.87]. Methyldopa (versus labetalol) postrandomisation was associated with fewer CHIPS primary outcomes (aOR 0.64; 95% CI 0.40-1.00), birthweight <10th centile (aOR 0.54; 95% CI 0.32-0.92), severe hypertension (aOR 0.51; 95% CI 0.31-0.83), pre-eclampsia (aOR 0.55; 95% CI 0.36-0.85), and delivery at <34 weeks (aOR 0.53; 95% CI 0.29-0.96) or <37 weeks (aOR 0.55; 95% CI 0.35-0.85).


CONCLUSIONS
These nonrandomised comparisons are subject to residual confounding, but women treated with methyldopa (versus labetalol), particularly those with pre-existing hypertension, may have had better outcomes.


CONCLUSIONS
There was no evidence that women treated with methyldopa versus labetalol had worse outcomes.
Medicine, University of British Columbia, Vancouver, BC, Canada.|Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada.|School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
L A
LA
Magee
Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada.|School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
P
P
von Dadelszen
School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.|Centre for Health Evaluation and Outcome Sciences (CHÉOS), Providence Health Care Research Institute, UBC, Vancouver, BC, Canada.
J
J
Singer
Centre for Health Evaluation and Outcome Sciences (CHÉOS), Providence Health Care Research Institute, UBC, Vancouver, BC, Canada.
T
T
Lee
Medicine and Obstetrics and Gynaecology, University of Montreal, Montreal, QC, Canada.
E
E
Rey
Obstetrics and Gynaecology, University of Alberta, Edmonton, AB, Canada.
S
S
Ross
Paediatrics, University of Toronto, Toronto, ON, Canada.|Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada.|The Centre for Mother, Infant and Child Research, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
E
E
Asztalos
Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada.|The Centre for Mother, Infant and Child Research, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
K E
KE
Murphy
Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada.
J
J
Menzies
The Centre for Mother, Infant and Child Research, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
J
J
Sanchez
Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
A
A
Gafni
Obstetrics and Gynaecology, University of Ottawa, Ottawa, ON, Canada.
A
A
Gruslin
Obstetrics and Gynaecology, University of Manitoba, Winnipeg, MB, Canada.
M
M
Helewa
Obstetrics and Gynaecology, McMaster University, Hamilton, ON, Canada.
E
E
Hutton
Paediatrics, University of Toronto, Toronto, ON, Canada.
G
G
Koren
Paediatrics, University of Toronto, Toronto, ON, Canada.
S K
SK
Lee
Medicine, University of Toronto, Toronto, ON, Canada.
A G
AG
Logan
Obstetrics and Gynaecology, University of Amsterdam, Amsterdam, the Netherlands.
J W
JW
Ganzevoort
Obstetrics and Gynaecology, Derriford Hospital, Devon, UK.
R
R
Welch
Obstetrics and Gynaecology, University of Nottingham, Nottingham, UK.
J G
JG
Thornton
Obstetrics and Gynaecology, Universite de Sherbrooke, Sherbrooke, QC, Canada.
J-M
JM
Moutquin
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology / Q000517:prevention & control; D046110:Hypertension, Pregnancy-Induced / Q000503:physiopathology / Q000517:prevention & control*; D007230:Infant, Low Birth Weight; D007741:Labetalol / Q000627:therapeutic use*; D008750:Methyldopa / Q000627:therapeutic use*; D011225:Pre-Eclampsia / Q000209:etiology / Q000503:physiopathology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology / Q000517:prevention & control; D011256:Pregnancy Outcome
D000959:Antihypertensive Agents; D008750:Methyldopa; D007741:Labetalol
CHIPS trial; hypertension; labetalol; methyldopa; pregnancy