Safety concerns for the use of calcium channel blockers in pregnancy for the treatment of spontaneous preterm labour and hypertension: a systematic review and meta-regression analysis.
BACKGROUND
Calcium channel blockers (CCBs) are not licensed for use in pregnancy but are used without robust surveillance to treat hypertension in pregnancy and preterm labour. The objective of this study was to evaluate the fetomaternal safety of CCB in pregnancy by a quantitative systematic review.


METHODS
Medline (1996-2005), EMBASE (1996-2003), BIOSIS (1993-2003), Current contents (1995-2003), DERWENT DRUGFILE (1983-2003) and Cochrane Library (2005: issue 3). The number of women reporting an adverse event was used to compute a percentage of the total number of women in whom the occurrence of that event or confirmation of its absence was reported. Meta-regression with generalised estimation equations modelling explored reasons for heterogeneity, seeking factors that increased the rates of the most commonly reported adverse events.


RESULTS
Of 269 relevant reports, including 5607 women, adverse fetomaternal events varied according to the total dose of nifedipine and study design. Adverse events were highest amongst women given more than 60 mg total dose of nifedipine [odds ratio (OR) 3.78, 95% confidence interval (CI) 1.27-11.2, p = 0.017] and in reports from case series compared to controlled studies (OR 2.45, 95% CI 1.17-5.15, p = 0.018).


CONCLUSIONS
Adverse event rates generated from this study provide an evidence base for clinical guidelines and informed patient consent for CCB use in pregnancy.
Khan
Khalid
K
University of Birmingham Women's Hospital, Birmingham UK.
Zamora
Javier
J
Lamont
Ronald F
RF
Van Geijn Hp
Herman
H
Svare
Jens
J
Santos-Jorge
Carlos
C
Jacquemyn
Yves
Y
Husslein
Peter
P
Helmer H
Hanns
H
Dudenhausen
Joachim
J
Di Renzo
Gian Carlo
GC
Roura
Luis Cabero
LC
Beattie
Bryan
B
D002121:Calcium Channel Blockers / Q000009:adverse effects* / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy* / Q000453:epidemiology; D007231:Infant, Newborn; D007752:Obstetric Labor, Premature / Q000188:drug therapy* / Q000453:epidemiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000453:epidemiology; D012044:Regression Analysis; D014481:United States / Q000453:epidemiology
D002121:Calcium Channel Blockers