Frezza 1984.

Methods	Randomised controlled trial.
Participants	18 women randomised. Setting: Milan, Italy. Recruitment: between 1979 to 1982. Inclusion criteria: women between 28 and 32 weeks of pregnancy with history of gestational pruritus starting after 19th week of gestation and elevated serum bile acids, bilirubin and transaminases. Normalisation of biochemical parameters and resolution of itching after birth. Exclusion criteria: acute hepatitis A, hepatitis B, dermatological diseases.
Interventions	SAMe (n = 6). Daily IV dose of 200 mg of SAMe (as disulphate‐p‐toluenesulfonate stable salt) dissolved in 500 mL of saline solution over 4 hours beginning at 8 am for 20 days. SAMe (n = 6). Daily IV dose of 800 mg of SAMe (as disulphate‐p‐toluenesulfonate stable salt) dissolved in 500 mL of saline solution over 4 hours beginning at 8 am for 20 days. Placebo (n = 6). Daily IV dose of 500 mL of saline solution over 4 hours beginning at 8 am for 20 days. Pruritus was assessed before randomisation and were repeated 10 and 20 days after treatment. It was graded as: 0, no pruritus; Grade 1+, rare; Grade 2+, occasional; Grade 3+, frequent; Grade 4+, almost continuous. Fasting blood samples were obtained for ALT, AST, ALP, bilirubin and total bile acid levels before randomisation and at 10‐day intervals.
Outcomes	Maternal: status of pruritus; assays of liver function and bile acids, maternal adverse events. Fetal/neonatal: Apgar scores.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described.
Allocation concealment (selection bias)	Unclear risk	Quote ‐ "Women were randomly allocated to three groups of six". No other details provided.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Single blinded. Participants were blinded. The medical staff were not blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	There were no losses to follow‐up.
Selective reporting (reporting bias)	High risk	Fetal outcomes, mean length of gestation, preterm birth rates, mode of birth and blood loss at birth were not reported. Some outcomes were only presented as graphs.
Other bias	Low risk	No other additional bias noted.