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To evaluate whether hyperemesis gravidarum (HG) affects first-trimester maternal serum PAPP-A and free β-hCG levels.An observational study was conducted in 115 cases of HG and 110 control pregnancies who attended the first-trimester prenatal screening program between January 2006 and July 2010.Maternal serum TSH levels were lower and free T4, and transaminases (ALT, AST) levels were higher in pregnancies complicated with HG compared with controls (p < 0.05 for all). In HG cases, median values of maternal serum PAPP-A were significantly higher with respect to normal pregnancies (1.2 vs 1.0 MoM; p = 0.009). Similarly, median values of free β-hCG were 1.3 MoM in HG pregnancies and 1.0 MoM in controls (p = 0.006). Multivariate analysis revealed that PAPP-A and hCG were independently associated with HG after controlling for TSH, free T4, AST, and ALT.HG is associated with elevated levels of PAPP-A and free β-hCG, and such changes are independent of serum indicators of thyroid and liver function. Copyright © 2011 John Wiley & Sons, Ltd.