Objective To compare the efficacy of S-adenosyl-L-methionine and ursodeoxycholic acid in improving serum biochemical abnormalities in gestational cholestasis. Design Randomised clinical trial.Setting University hospital.Population All women at <36 weeks of gestation with severe gestational cholestasis during June 1996 to December 2001. Methods Enrolled women were randomly assigned oral S-adenosyl-L-methionine 500 mg twice daily or oral ursodeoxycholic acid 300 mg twice daily until delivery. Main outcome measures Reduction in the concentration of serum bile acids. Other variables considered included obstetric and neonatal outcome, clinical symptoms and other laboratory measurements (serum levels of transaminases and bilirubin). The two groups were compared using Student's t test, Wilcoxon's signed rank sum test and Fisher's exact test, with a two-tailed P < 0.05 being considered significant. Results Of the 46 women enrolled, 24 received ursodeoxycholic acid and 22 S-adenosyl-L-methionine. At enrolment, gestational age, duration of therapy, rate of nulliparity, pruritus score and biochemical characteristics were similar between the groups. Both therapies significantly and equally improved pruritus. Women receiving ursodeoxycholic acid had a significantly greater improvement in the concentration of serum bile acids ( P ¼ 0.001), aspartate aminotransferase ( P ¼ 0.01), alanine aminotransferase (<0.001) and bilirubin ( P ¼ 0.002) compared with those receiving S-adenosyl-L-methionine. Duration of therapy was significantly greater in women receiving ursodeoxycholic acid compared with S-adenosyl-Lmethionine ( P ¼ 0.04), whereas gestational age at delivery and rate of prematurity were similar in the two groups. Conclusions In women with intrahepatic cholestasis of pregnancy, ursodeoxycholic acid is more effective than S-adenosyl-L-methionine at improving the concentration of serum bile acids and other tests of liver function, whereas both therapies are equally effective at improving pruritus.

Objective To estimate whether prenatal treatment with neuroprotective peptides prevent the developmental delay and the glial deficit in the Ts65Dn mouse model for Down syndrome, and to explore the peptides effects on achievement of normal development. Methods Pregnant Ts65Dn females were randomly assigned to NAPVSIPQ+ SALLRSIPA or control and were treated by investigators blinded to treatment and genotype on gestational days 8–12. Offspring were tested from postnatal day (P) 5 to 21 for motor and sensory milestones with standardized tests by operators blinded to the pup’s treatment and genotype. The pup’s genotype was determined after completion of all tests. Activity-dependent-neurotrophic-factor, glial fibrillary acidic protein, and vasoactive intestinal peptide expression were determined using real time polymerase chain reaction. Results Trisomic (Ts) mice achieved milestones with a significant delay in 4 of 5 motor and sensory milestones. Ts mice that were prenatally exposed to NAPVSIPQ+SALLRSIPA achieved developmental milestones at the same time as the controls in 3 of 4 motor and 1 of 4 sensory milestones (p<0.01). Euploid pups prenatally treated with NAPVSIPQ+SALLRSIPA achieved developmental milestones significantly earlier than the euploid pups prenatally treated with placebo. Activity-dependent-neurotrophic-factor, expression was significantly downregulated in the Ts65Dn brains versus the controls, prenatal treatment with NAPVSIPQ+SALLRSIPA prevented the activity-dependent-neurotrophic-factor, decrease in the Ts65Dn brains, and the expression was not different from the controls. The glial marker glial fibrillary acidic protein demonstrated the known glial deficit in the Ts65Dn mice, and treatment with NAPVSIPQ+SALLRSIPA prevented its downregulation. Lastly, vasoactive intestinal peptide levels were increased in the Ts brains, while treatment with NAPVSIPQ+SALLRSIPA did not prevent its upregulation. Conclusions Prenatal treatment with NAPVSIPQ and SALLRSIPA prevented developmental delay and the glial deficit in Down syndrome. These findings highlight a possibility for the prevention of developmental sequelae in Down syndrome and suggest a potential intervention during pregnancy that may improve the outcome.

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The later in pregnancy the abnormal UtA Doppler findings are observed, the greater the risk of preeclampsia. Normalization of UtA Doppler after 25 weeks reduces the risk of preeclampsia to 8%.