Alphafetoprotein in midtrimester Down's syndrome

Serum alphafetoprotein was estimated in fetuses with and without Down's syndrome or with other chromosome abnormalities from the 17th to the 28th week of pregnancy. In normal fetuses, the AFP level declines steadily during this period. Before 20 weeks, there was no difference in the serum AFP levels of the three groups of fetuses. After 20 weeks, the serum AFP level in cases of Down's syndrome declined more rapidly than normal. This was not observed in fetuses with other chromosome abnormalities. This suggests that low maternal serum alphafetoprotein levels used for prenatal screening for Down's syndrome in the early second trimester cannot be explained by low levels in the Down's fetuses themselves. It is now well established that midtrimester maternal serum alphafetoprotein (MSAFP) levels tend to be lower than normal when the fetus has Down's syndrome. 1-6 Some workers have found that the amniotic fluid alphafetoprotein (AFAFP) levels are below the normal median in such cases too,2 58 while others have found them to be normally distributed. '4 The mechanism for these low AFP levels in the maternal serum, and possibly the amniotic fluid, is not yet known, but one suggestion has been that Down's syndrome fetuses produce less AFP than normal fetuses.9 My previous studyl' suggested that this is not so; consequently, I have examined this point further by determining the serum AFP levels in midtrimester fetuses with and without Down's syndrome. Materials and methods Fetal blood samples were obtained from two sources and the results were analysed separately. In one case, Division of Medical and Molecular Genetics, United Medical and Dental Schools of Guy's and St Thomas's Hospitals, Guy's Campus, London SEI 9RT. M J Seller Received for publication 12 April 1989. Revised version accepted for publication I November 1989. fresh fetal blood was obtained by percutaneous umbilical cord sampling (cordocentesis) from the 18th to 28th week of pregnancy for diagnostic fetal karyotyping. In the other, postmortem blood samples were obtained by cardiac puncture from fetuses received for postmortem examination after prostaglandin termination of pregnancy, or after a midtrimester spontaneous abortion, between 17 and 26 weeks of gestation. After either means of collection, the blood samples were spun at 6000 rpm for 10 minutes. The serum was diluted 1 in 200, 1 in 100, or 1 in 50 with distilled water according to gestational age, and the AFP level was quantified by one dimensional crossed antigenantibody electrophoresis (the rocket technique)." Cordocentesis samples from fetuses without Down's syndrome were divided into two groups and their results were also analysed separately. Group 1 (41 samples) comprised fetuses which were completely normal, both chromosomally and developmentally. These were derived from patients undergoing the procedure for raised maternal age who presented too late for amniocentesis, or where the amniotic cell culture had failed, or where the fetus was at risk for a blood disorder. Group 2 (49 samples) consisted of fetuses who were chromosomally normal but who had a developmental defect, such as diaphragmatic hernia, hydrocephalus, congenital heart defect, or exomphalos, or there was an obstructive uropathy or Rhesus incompatibility. Samples were also received from fetuses with renal agenesis, ascites, hydrops, and intrauterine growth retardation, but they were excluded from the study. All postmortem specimens of fetuses with Down's syndrome were derived from termination of pregnancy after prenatal diagnosis. Seven fetuses without Down's syndrome also came from terminations: five had a neural tube defect and two were normal. Serum AFP results from these were pooled with those obtained from 16 spontaneous abortions of an apparently normal fetus (group 3). Only those abortuses that were fresh, showing no sign of early maceration, were selected for study, in an attempt to obtain a comparable group to those from terminations, where the fetuses were presumably alive up to the time of the induction. Unfortunately, because of departmental policy not to perform chromosome 240 group.bmj.com on November 6, 2017 Published by http://jmg.bmj.com/ Downloaded from