Alphafetoprotein levels in amniotic fluid from 8 to 18 weeks of pregnancy.

OBJECTIVE: The aim of this study was to ascertain the normal range of amniotic fluid alphafetoprotein (AFP) levels from 8 to 18 weeks of pregnancy. DESIGN: Amniotic fluid samples obtained by amniocentesis were analysed by radioimmunoassay for AFP. From 8 to 12 weeks, fluid was obtained by transvaginal amniocentesis prior to termination of pregnancy. Samples from 13 to 18 weeks were obtained from amniotic fluid specimens submitted for cytogenetic analysis. SETTING: A tertiary referral prenatal diagnostic service. SUBJECTS: Two hundred thirty-seven women between 8 and 18 weeks gestation. RESULTS: High levels of AFP were present in amniotic fluid at 8 weeks (median 83.0 kU/ml), falling rapidly to 11 weeks (median 19.9 kU/ml) (P < 0.01). Levels then rose to a peak at 13 weeks (median 30.7 kU/ml), thereafter falling to 18 weeks. CONCLUSIONS: A single coherent view of the levels of AFP from 8 to 18 weeks of pregnancy is presented for the first time. The rapid changes and complex pattern of AFP levels in early pregnancy suggest that interpretation of amniotic fluid AFP levels in the diagnosis of neural tube defects may be more difficult between 8 and 13 weeks of pregnancy than in the second trimester.

Early amniocentesis: alphafetoprotein levels in amniotic fluid, extraembryonic coelomic fluid and maternal serum between 8 and 13 weeks.

OBJECTIVE: The aim was to establish a normal range of alphafetoprotein (AFP) concentrations in amniotic fluid from 8 to 12 weeks gestation, and to determine any difference between AFP levels in amniotic fluid and extraembryonic coelomic fluid. DESIGN AND SUBJECTS: 150 women had a transvaginal ultrasound guided amniocentesis before termination of an apparently normal first trimester pregnancy. Separately identified samples of amniotic fluid and extraembryonic coelomic fluid were obtained and assayed by radioimmunoassay for AFP. RESULTS: In amniotic fluid, very high levels of AFP were present at 8 weeks, levels falling rapidly up to 10 weeks after which there was a slight rise. Thus over the period 8 to 10 weeks, there was a significant inverse correlation between amniotic fluid AFP and gestational age (r = 0.67; P less than 0.001). In extraembryonic coelomic fluid, by contrast there was no trend in AFP relative to gestational age. CONCLUSIONS: The rapidly changing levels of AFP from 8 to 10 weeks as well as the small volume of the amniotic cavity makes the use of amniocentesis impracticable before 11 weeks gestation. The lack of any relation between AFP levels in amniotic fluid and extraembryonic coelomic fluid emphasises the importance of identifying the site of amniocentesis in the first trimester.

Human chorionic gonadotrophin and alpha-fetoprotein levels in matched samples of amniotic fluid, extraembryonic coelomic fluid, and maternal serum in the first trimester of pregnancy.

Separately identified samples of amniotic fluid and extraembryonic coelomic fluid obtained by high resolution transvaginal ultrasound-guided amniocentesis from 32 women between 7 and 12 weeks of pregnancy were analysed for human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP). There was a highly significant difference between the hCG levels in amniotic fluid (median level 6.3 U/ml; range 1.6-310.0 U/ml) and those in extraembryonic coelomic fluid (median level 400.0 U/ml; range 135.0-2250.0 U/ml) (p less than 0.001; Mann-Whitney U-test). The levels of AFP were very similar in amniotic fluid (median 26.0 kU/ml; range 10.0-116.5 kU/ml) and extraembryonic coelomic fluid (median level 24.1 kU/ml; range 12.4-94.4 kU/ml).

PIP: Physicians used transvaginal ultrasound to guide the aspiration needle into the amniotic fluid and extraembryonic celomic fluid from 32 women at 7-12 weeks gestation in St. Bartholomew's Hospital or Homerton Hospital in London, England. They also collected blood. Their intent was to determine the levels of alpha fetoprotein (AFP) [a fetal product] and human chorionic gonadotropin (hCG) [a placental product]. All of the these women had normal pregnancies, but were in the hospital to undergo a therapeutic abortion. Levels of hCG in the amniotic fluid stood significantly lower (median 6.3 U/ml) than those in the extraembryonic celomic fluid (400 U/ml; p.001). Serum levels of hCG were in between those in the fluids (75 U/ml). AFP levels in the amniotic fluid (26 U/ml) and extraembryonic celomic fluid ((24 U/ml) were not significantly different. No definitive trend in hCG or AFP levels with gestation in the 2 fluids occurred. A possible explanation for the higher levels of hCG levels in the extraembryonic celomic fluid may be that the extraembryonic celom is next to the chorion from where hCG originates. The amnion effectively separates the extraembryonic celom from the amniotic fluid. Perhaps the extraembryonic celomic fluid works as a sump for hCG. These results stress the importance of confirming the exact site of aspiration in the 1st trimester amniocentesis. Moreover, the transvaginal ultrasound is superior to the abdominal ultrasound in distinguishing between the 2 cavities since it has the necessary degree of resolution. It also is an effortless and precise method amniocentesis. These results also suggest that physicians can make and earlier diagnosis of neural tube defects since AFP leaks into its surroundings at a very early gestation.

Changes in circulating alphafetoprotein following administration of mifepristone in first trimester pregnancy.

The occurrence of fetomaternal haemorrhage was investigated in 30 women by measuring maternal serum alphafetoprotein (AFP) levels before and after the administration of mifepristone (RU 486) for termination of first trimester pregnancy. A significant rise in AFP levels was seen in 21 women (70%), the increase ranging from 6 to 660% of baseline levels. The apparent frequency of fetomaternal haemorrhage was similar to that reported previously for surgical termination of first trimester pregnancies.

PIP: Fetomaternal hemorrhage-induced rises in circulating alphafetoprotein (AFP) levels can occur as a result of invasive procedures in the 1st half of pregnancy, including amniocentesis and induced abortion. In this study, 30 women under 9 weeks of gestation were given a single oral dose of 600 mg of RU-486 followed 48 hours later be insertion of a vaginal pessary containing 1 mg of gemeprost. All 30 women aborted within 2-4 hours of gemeprost administration. There was moderate bleeding for 24 hours after the abortion in 2 women. In the 4-hour period following RU-486 administration, subjects did not show any change over baseline values in AFP levels. However, 2 days later, before gemeprost administration, 21 women showed a significant increase (median of 87%, range 6-660%) in AFP. This finding suggests that fetal blood can enter the maternal circulation during pregnancy termination, and the RU-486 is not able to counteract this process. The 70% rate of elevation of AFP with RU-486 is in fact higher than that recorded for surgical termination of 1st-trimester abortion (58%). Surprising was the finding that these changes in circulating AFP occurred before the administration of prostaglandin.

Maternal serum AFP levels in the first trimester of pregnancy.

Maternal serum alphafetoprotein was assayed in 436 women presenting for termination of pregnancy at 6 to 12 weeks. The normal range for each week is presented. There was a progressive rise of AFP levels from week 7 onwards, but a clear separation from non-pregnant values was only apparent after 8 weeks. The definition of a 'low normal' range for the identification of cases at risk of Down's syndrome will probably only be possible at 11 weeks or later.

Serum alphafetoprotein levels in subjects infected with hepatitis B virus.

Serum alphafetoprotein (AFP) levels were measured using a sensitive radioimmunoassay in 108 hepatitis B surface antigen (HBsAg)-positive subjects and 695 controls. The concentrations were significantly higher in the HBsAg-positives. Within this group, the highest levels were found in those with active HBV infection. In those without evidence of acute infection, the levels were higher in the high-risk than in the low-risk subjects. It is concluded: 1) that measurement of serum AFP might be a useful additional index of infectivity and prognosis in HBsAg-positive subjects; and 2) that in the light of the association between chronic HBV infection, hepatocellular carcinoma, and raised AFP in non-European populations, consideration should be given to regular monitoring of AFP levels in HBsAg-positive subjects in the United Kingdom.

The incidence of fetomaternal haemorrhage following elective termination of first-trimester pregnancy.

Alphafetoprotein (AFP) levels were determined in 62 patients undergoing termination of first-trimester pregnancy in order to ascertain the incidence of fetomaternal haemorrhage. The apparent frequency of this phenomenon (58%) was higher than that previously reported. There was no evidence of fetomaternal haemorrhage associated with simple bimanual examination.

PIP: As an indicator of the incidence of feto-maternal hemorrhage due to 1st trimester abortion by vacuum aspiration, alphafetoprotein (AFP) levels were determined in 62 women before and after the procedure. The 62 women were grouped as follows: 1) 42 sampled before and after abortion; 2) 8 sampled before, after, and 3 and 6 hours after abortion; and 3) 12 sampled before and after pelvic exam 2 days before. AFP levels rose in 58% of the women assayed immediately after termination, but did not rise further in those assayed 3 and 6 hours later. Pelvic examination had no detectable effect on AFP. The degree of feto-maternal hemorrhage associated with vacuum aspiration was considered sufficient to cause sensitization in rhesus-negative women.

Maternal serum alpha fetoprotein concentrations in mid trimester in hepatitis B surface antigen positive and negative subjects.

Maternal serum alpha fetoprotein (AFP) was measured as part of a routine antenatal screening programme in 48 patients positive for hepatitis B surface antigen (HBsAg). After exclusion of two cases with obvious obstetric abnormalities there was no difference in AFP concentrations between subjects who were positive or negative for HBsAg.

In vitro secretion of human chorionic gonadotrophin by bladder tumour cells.

Human chorionic gonadotrophin (hCG) and alphafetoprotein (AFP) were measured in culture media from a panel of 29 cell lines including 9 bladder carcinomas, 5 'normal' bladder epithelia, 10 germ cell tumours, and 5 miscellaneous tumours and 'normal' cell lines. In 7 of the 9 bladder carcinomas and 4 of the 5 'normal' bladder epithelia, the media contained hCG at levels ranging from between 34 and 3,600 IU l(-1). All other cell lines, including the 10 germ cell tumour lines gave negative results for hCG. These findings indicate that in vitro secretion of hCG is a common feature of normal and neoplastic bladder transitional epithelia, and support the hypothesis that parts of the genito-urinary epithelium have a potential for hCG production.

Mid-trimester levels of alphafetoprotein in the screening of low birthweight.

Elevated maternal levels of alphafetoprotein (AFP) in midtrimester are believed by some to be a useful screening test for premature labour, low birthweight and low birthweight for gestation. In a prospective study on 887 randomly selected pregnant women we found that although there was an association between low birthweight and elevated AFP, the test would miss five out of every six cases of low birthweight and there would be nine false-positives for every case correctly identified. The test is not therefore sufficiently predictive of low birthweight to be of value as a screening test for this condition.

Maternal and fetal alphafetoprotein (AFP) levels at term. Relation to sex, weight and gestation of the infant.

Serum alpha-fetoprotein (AFP) was measured in maternal, cord arterial and venous blood. Samples were collected at the time of vaginal delivery from 105 women at 36-42 weeks' gestation. There was a significant correlation between maternal, cord arterial and venous AFP. Umbilical cord arterial and venous AFP levels were considerably higher in male infants than in females. Umbilical AFP levels declined with lengthening gestation and increasing birthweight for both male and female infants and a similar pattern was seen in the mother. Fetal AFP levels were significantly higher in subjects giving birth at 40 weeks whose infants had a birthweight below the population mean vis-à-vis those above the mean. It is concluded that the absolute size of the fetus as well as gestational age may play a significant role in determining maternal and fetal AFP concentration.

Short-term variation in the level of alpha-fetoprotein in maternal serum.

Serial serum levels of alpha-fetoprotein (AFP) were examined over a 24-h period in six subjects. A short-term variation was demonstrated which was significantly greater than that due to the assay alone, but which showed no particular pattern. These findings may explain why an 'abnormal' AFP level frequently reverts to a 'normal' level on second sampling.

Maternal serum alpha-fetoprotein levels as an index of fetal risk.

In a prospective study on an obstetric population (1,059 cases) an association was found between elevated levels of maternal serum AFP at weeks 16 to 22 and the occurrence of premature labor or the need for emergency cesarean section in the third trimester. There was no association with other late fetal complications including perinatal death, perinatal asphyxia, and intrauterine growth retardation. The sensitivity of the test in respect of premature labor was 14 per cent but the high incidence of false-positive results reduces the practical value of the test.

The significance of raised maternal plasma alpha-fetoprotein in twin pregnancy.

A hundred twin pregnancies were examined before 27 weeks gestation. The level of maternal plasma alpha-fetoprotein (AFP) was correlated with outcome of the pregnancy. Forty per cent of all women had elevated plasma AFP levels. At birth the combined infant weights were greater in the women with elevated AFP; the gestational age at delivery was unrelated to the level of AFP in early pregnancy.

Fetal wastage as a result of an alpha-fetoprotein screening programme.

Amniocentesis was performed in 102 pregnancies in which maternal serum-alpha-fetoprotein (A.F.P.) concentrations were raised. 18 pregnancies were terminated. There were 15 neural-tube defects, 2 gastrointestinal abnormalities (1 of which could have been corrected by surgery), and 1 case of hydrocephaly. There was an association between raised maternal serum-A.F.P. and complications of late pregnancy including premature labour, perinatal death, and severe pre-eclampsia. After amniocentesis there was spontaneous abortion of 3 normal fetuses and 1 abnormal fetus.