Obstetric cholestasis has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood,
therapies have been empiric. The first version of this review, published in 2001, and including nine randomised controlled trials involving 227 women, concluded that there was insufficient evidence to recommend any of the interventions alone or in combination. This is the first update.
OBJECTIVES: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 February 2013) and reference lists of identified studies.
SELECTION CRITERIA: The review authors independently assessed trials for eligibility and risk of bias. We independently extracted data and checked these for accuracy.
MAIN RESULTS: We included 21 trials with a total of 1197 women. They were mostly at moderate to high risk of bias. They assessed 11 different interventions resulting in 15 different comparisons.Compared with placebo,
ursodeoxycholic acid (UDCA) showed improvement in
pruritus in five (228 women) out of seven trials. There were no significant differences in instances of
fetal distress in the UDCA groups compared with placebo (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.22 to 2.02; five trials, 304 women; random-effects analysis: T² = 0.74; I² = 48%). There were significantly fewer total
preterm births with UDCA (RR 0.46; 95% CI 0.28 to 0.73; two trials, 179 women). The difference for spontaneous
preterm births was not significant (RR 0.99; 95% CI 0.41 to 2.36, two trials, 109 women).Two trials (48 women) reported lower (better)
pruritus scores for
S-adenosylmethionine (SAMe) compared with placebo, while two other trials of 34 women reported no significant differences between groups.UDCA was more effective in improving
pruritus than either SAMe (four trials; 133 women) or
cholestyramine (one trial; 84 women), as was combined UDCA+SAMe when compared with placebo (one trial; 16 women) and SAMe alone (two trials; 68 women). However, combined UDCA+SAMe was no more effective than UDCA alone in regard to
pruritus improvement (one trial; 53 women) and two trials (80 women) reported data were insufficient to draw any conclusions from. In one trial comparing UDCA and
dexamethasone (83 women), a significant improvement with UDCA was seen only in a subgroup of women with severe
obstetric cholestasis (23 women).Danxiaoling significantly improved
pruritus in comparison to Yiganling. No significant differences were seen in
pruritus improvement with other interventions.Eight trials reported fetal or
neonatal deaths, with two deaths reported overall (both in the placebo groups).Women receiving UDCA and
cholestyramine experienced
nausea,
vomiting and diarrhoea.
Guar gum caused mild abdominal distress, diarrhoea and
flatulence during the first days of treatment. Women found
charcoal suspension unpleasant to swallow.
Dexamethasone caused
nausea,
dizziness and stomach
pain in one woman.One trial (62 women) looked at the timing of delivery intervention. There were no
stillbirths or
neonatal deaths in 'early delivery' or the 'await spontaneous labour' group. There were no significant differences in the rates of
caesarean section, meconium passage or admission to neonatal intensive care unit between the two groups.
AUTHORS' CONCLUSIONS: Different approaches to assessing and reporting
pruritus precluded pooling of trials comparing the effects of UDCA versus placebo on
pruritus, but examination of individual trials suggests that UDCA significantly improves
pruritus, albeit by a small amount. Fewer instances of
fetal distress/asphyxial events were seen in the UDCA groups when compared with placebo but the difference was not statistically significant. Large trials of UDCA to determine fetal benefits or risks are needed.A single trial was too small to rule in or out a clinically important effect of early term delivery on
caesarean section.There is insufficient evidence to indicate that SAMe,
guar gum,
activated charcoal,
dexamethasone,
cholestyramine, Salvia, Yinchenghao decoction (YCHD), Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with
cholestasis of pregnancy.