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Biomedical subjects

N C Wathen

Publications and source records attributed to N C Wathen.

At least 37 records · Page 2Linked to original sources
PubMed1994

Second trimester amniotic fluid placental alkaline phosphatase levels are low in Down's syndrome but not in other fetal abnormalities.

Second trimester amniotic fluid placental alkaline phosphatase (PLAP) immunoreactivity was measured in 756 normal pregnancies, 63 Down's syndrome pregnancies and 42 pregnancies associated with other chromosomal abnormalities. PLAP levels were significantly reduced in cases of Down's syndrome (MoM = 0.72, U = 17,565, P = 0.0002, 95% Cl = 0.63-0.88). However, there was no significant difference between other aneuploid conditions and the normals (MoM = 0.88, U = 13,289, P = 0.35, 95% CI = 0.77-1.08). PLAP is the carrier protein for immunoglobulin G. Neonates with Downs syndrome but not other chromosomal abnormalities are associated with a deficiency of IgG. These data therefore support the theory that the low IgG levels in Downs syndrome are a result of a defect in PLAP transport.

Alkaline Phosphatase↗
PubMed1994

Pregnancy-associated plasma protein A levels in maternal serum, extraembryonic coelomic and amniotic fluids in the first trimester.

First trimester maternal serum levels of pregnancy-associated plasma protein A(PAPP-P) are reduced in women with a Down's syndrome pregnancy. We have examined the concentration of this molecule in the amniotic (AF) and extra-embryonic coelomic (EECF) fluids surrounding the developing fetus. Maternal serum levels of PAPP-A were elevated in all samples and steadily rose from a median of 480 mIU/1 at 8 weeks to a median of 6375 mIU/1 at 14 weeks gestation. Levels of PAPP-A were low in EECF and undetectable in the AF until 14 weeks gestation. This pattern of distribution is in contrast to that of most other trophoblast-associated antigens. This may reflect PAPP-A physiology and its specific production by the syncytiotrophoblast.

Amniotic Fluid↗
PubMed1994

Low levels of amniotic fluid pregnancy specific beta-1-glycoprotein in Down's syndrome.

Amniotic fluid levels of beta-1-glycoprotein (SP1) were measured in 46 cases of Down's syndrome and compared with levels in 106 pregnancies of normal karyotype from 10 to 23 weeks of gestation. In normal pregnancies, levels rose from 87.5 iu/l at 10 weeks to a peak of 610.0 iu/l at 19 weeks of gestation. In cases of Down's syndrome, levels were reduced prior to 19 weeks of gestation (median multiple of the median, MoM = 0.75, P = 0.02). This effect was most marked prior to 16 weeks of gestation when the median multiple of the median (MoM) was 0.51 (P = 0.006). These data demonstrate that amniotic fluid levels of SP1 are low in Down's syndrome before 19 weeks of gestation.

Amniotic Fluid↗
PubMed1994

Concentrations of vitamins A and E in amniotic fluid, extraembryonic coelomic fluid, and maternal serum in the first trimester of pregnancy.

Paired samples of amniotic fluid and coelomic fluid were obtained by transvaginal ultrasound guided amniocentesis from 15 women with an ultrasonographically normal pregnancy between 8 and 12 weeks' gestation. Vitamins A and E were measured in the two pregnancy fluids and in maternal serum by high performance liquid chromatography with detection by ultraviolet absorption and fluorimetry respectively. Concentrations of vitamins A and E were higher in maternal serum than in coelomic fluid and were generally undetectable in amniotic fluid. All differences in concentration were significant. The vitamin E/cholesterol ratio was similar in maternal serum and coelomic fluid. No correlation was shown between the vitamin concentrations in the three fluids. These findings suggest that the coelomic cavity plays a part in the maternofetal exchange of these vitamins.

Amniotic Fluid↗
PubMed1994

Insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and proteolyzed IGFBP-3 in embryonic cavities in early human pregnancy: their potential relevance to maternal-embryonic and fetal interactions.

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are believed to be important in fetal growth and development. In the current study, the developmental changes in the IGF and IGFBP axis were examined in 23 paired samples of human amniotic fluid (AF), extraembryonic coelomic (EEC) fluid, and maternal serum (MS) between 9 and 12 weeks gestation. Levels of IGF-I were very low in AF (7 +/- 3 ng/mL) and EEC (10 +/- 3 ng/mL) compared to those in MS (237 +/- 42 ng/mL). In contrast, IGF-II concentrations were 210 +/- 36 and 174 +/- 22 ng/mL in AF and EEC, respectively, and were approximately 25% of MS serum levels (884 +/- 122 ng/mL). There was no dependence on gestational age for either peptide in AF or EEC during the period of gestation examined. IGFBP-1 levels in AF increased about 20-fold (1.6 +/- 0.3 to 33.0 +/- 0.1 ng/mL) between 9 and 12 weeks of pregnancy, and IGFBP-1 levels were nearly 2 orders of magnitude higher in EEC, increasing about 100-fold (365 +/- 119 to 3014 +/- 100.0 ng/mL) by the end of the first trimester. In contrast, IGFBP-1 levels were low in MS (24.9 +/- 3.5 ng/mL) and showed no gestational age dependence. Using RIA, high levels of IGFBP-3 were found in EEC (2062 +/- 177 ng/mL) and MS (6590 +/- 357 ng/mL) compared to those in AF (152 +/- 24 ng/mL). Levels of IGFBP-3 in MS and EEC did not change significantly with gestational age, whereas an increase in IGFBP-1 was observed in AF after the tenth week of pregnancy. In contrast to high levels of IGFBP-3 in MS and EEC, determined by RIA, the 37- to 43-kilodalton IGFBP-3 doublet was barely detectable by Western ligand blot analysis. This discrepancy suggested the presence of an IGFBP-3 protease in EEC, as has been found in MS, that decreases the affinity of this BP for IGF peptides and, therefore, renders it less readily detectable by Western ligand blot analysis. Using [125I]IGFBP-3 as substrate, lower levels of IGFBP-3 protease activity were detected in EEC compared to MS, and nearly undetectable levels were found in AF. By Western immunoblotting, a smaller (28-kilodalton) immunoreactive form of IGFBP-3 was detected only in MS and EEC, suggesting proteolyzed IGFBP-3 in MS and EEC, but not in AF, during this gestational period.(ABSTRACT TRUNCATED AT 400 WORDS)

Amniotic Fluid↗
PubMed1994

Levels of insulin-like growth factor-binding protein-2 and insulin-like growth factor-II in maternal serum, amniotic fluid and extraembryonic coelomic fluid at 9-20 weeks of pregnancy.

Insulin-like growth factor-II (IGF-II) and IGF-binding protein-2 (IGFBP-2) were measured in amniotic fluid, extraembryonic fluid and maternal serum from 20 women with apparently normal first trimester pregnancies prior to termination. A further 111 specimens of amniotic fluid were collected from women at 10-20 weeks of pregnancy. Levels of IGFBP-2 were similar in coelomic fluid and maternal serum. Levels in amniotic fluid were lower than those in serum and coelomic fluid (Mann-Whitney test; P = 0.0002 and P < 0.0001 respectively). The levels of IGF-II were much higher in maternal serum than in coelomic fluid, and higher in the latter than in amniotic fluid (Mann-Whitney test; P < 0.0001 for both situations). The levels of IGFBP-2 were relatively low at 10-11 weeks (medians 19.8 and 61.1 micrograms/l) but thereafter increased to 20 weeks (median 1400 micrograms/l). The levels of IGF-II showed a similar pattern. The findings suggest that the role of IGF-II and IGFBP-2 in the regulation of growth or differentiation of the fetus or of its surrounding membranes may change with advancing pregnancy.

Adult↗
PubMed1993

Dynamics of prolactin in amniotic fluid and extraembryonic coelomic fluid in early human pregnancy.

Concentrations of prolactin were measured by an immunoradiometric assay in 26 matched samples of amniotic fluid, extraembryonic coelomic fluid and maternal serum from 9 to 12 weeks of pregnancy and in a further 131 amniotic fluid samples from 9 to 20 weeks. Low levels of prolactin (median 40 MU/l) were present in amniotic fluid from 9 to 12 weeks. Levels in the coelomic fluid were higher (median level 371 MU/l; P < 0.0001) than in amniotic fluid. From 13 weeks, there was a rapid rise in amniotic fluid prolactin to reach a peak at 19 weeks (median level 99,850 MU/l). The pattern of increase of prolactin in amniotic fluid is similar to, but occurs 2 weeks later than that for insulin-like growth factor-binding protein-1, another major decidual product.

Amniotic Fluid↗
PubMed1993

Tumor necrosis factor, interleukin-1, and interleukin-6 in normal human pregnancy.

OBJECTIVE: Our purpose was to investigate the cytokines, tumor necrosis factor, interleukin-1, and interleukin-6 in normal human pregnancy and labor. STUDY DESIGN: Bioassays were used to measure these factors in extraembryonic coelomic fluid, amniotic fluid, placenta, and maternal and cord serum. RESULTS: Little or no tumor necrosis factor, interleukin-1, or interleukin-6 was found in coelomic fluid or amniotic fluid in the first trimester. Interleukin-6 appeared in second-trimester amniotic fluid. At term tumor necrosis factor was present (median 17 pg/ml) and increased with the onset of labor (median 58 pg/ml), as did interleukin-1 (median 188 to 680 pg/ml) and interleukin-6 (median 399 to 4800 pg/ml). Maternal serum interleukin-6 increased during pregnancy with a further increment with the onset of labor. Cord interleukin-6 also increased with labor but at a lower level. CONCLUSION: The cytokines tumor necrosis factor, interleukin-1, and interleukin-6 may play a role in the onset of normal labor.

Amniotic Fluid↗
PubMed1993

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.

Amniocentesis↗
PubMed1993

Low levels of amniotic fluid placental alkaline phosphatase in Down's syndrome.

OBJECTIVE: To investigate amniotic fluid placental alkaline phosphatase (PLAP) levels in normal and trisomy 21 pregnancies. DESIGN: Cross sectional study. SETTING: A tertiary referral prenatal diagnostic service. SUBJECTS: Three hundred and eleven women with singleton pregnancies of normal karyotype between 10 and 23 weeks gestation and 31 women with pregnancies associated with trisomy 21 Down's syndrome. OUTCOME MEASURES: PLAP levels were measured by immunoradiometric assay in amniotic fluid obtained by amniocentesis. RESULTS: Amniotic fluid PLAP was detectable from 12 weeks gestation and the median value rose to a peak of 4.57 iu/l at 18 weeks. Pregnancies associated with Down's syndrome had significantly lower levels with a median multiple of median (MoM) of 0.638, (U = 3374, P = 0.0016, 95% CI = 0.50, 0.89). For the 20 women with trisomy 21 pregnancies detected at 16 to 18 weeks, the median MoM was 0.482, (U = 3694, P = 0.0011, 95% CI = 0.37, 0.85). CONCLUSION: These data demonstrates that PLAP levels are reduced in the amniotic fluid of women carrying a fetus with trisomy 21.

Alkaline Phosphatase↗
PubMed1993

Levels of insulin-like growth factor-binding protein-1 increase rapidly in amniotic fluid from 11 to 16 weeks of pregnancy.

Concentrations of IGF-binding protein-1 (IGFBP-1) were measured by radioimmunoassay in 176 amniotic fluid samples from 9 to 20 and 36 to 42 weeks of pregnancy. Low levels of IGFBP-1 were present at 9 and 10 weeks (median values 35.0 and 45.0 micrograms/l respectively). After 10 weeks, the levels increased by four orders of magnitude to reach a peak at 16 weeks (median 145.2 mg/l). After 16 weeks levels fell. Near term, the levels (median 27.1 mg/l) were lower than in the second trimester. The rapid increase in IGFBP-1 shown by radioimmunoassay was confirmed by Western ligand blotting. The findings suggest that the regulatory role of IGFBP-1 in the growth or differentiation of the fetus or of its surrounding membranes may change as pregnancy advances.

Amniotic Fluid↗
PubMed1992

Alpha-fetoprotein levels and yolk sac size in the first trimester of pregnancy.

Transvaginal ultrasound measurement of the yolk sac and transvaginal amniocentesis were carried out on 94 women prior to first-trimester termination of pregnancy. Maternal serum and fluids from the amniotic cavity and extraembryonic coelom were analysed for alpha-fetoprotein (AFP). No correlation was found between the yolk sac size and the levels of AFP in any of these sites.

Amniocentesis↗
PubMed1992

Insulin-like growth factor-1 and insulin-like growth factor binding protein-1 in early human pregnancy.

Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-1 (IGFBP-1) were measured in amniotic fluid, extraembryonic coelomic fluid and maternal serum from 23 women with apparently normal first trimester pregnancies prior to termination. The levels of IGF-1 and IGFBP-1 were significantly higher in coelomic fluid than amniotic fluid (IGF-1, P = 0.006; IGFBP-1, P = 0.0008 (paired t-test)). The levels of IGFBP-1 were lower in amniotic fluid than in maternal serum (P = 0.017), a finding in sharp contrast to the situation in the second and third trimesters of pregnancy. There was a significant relation between levels of IGF-1 and IGFBP-1 in amniotic fluid (r = 0.43; P = 0.04) and in coelomic fluid (r = 0.81; P less than 0.001) but not in maternal serum. The finding that both the absolute levels of IGFBP-1 and the ratio to IGF-1 were low in amniotic fluid implies that there is a very high level of unbound, biologically active IGF-1 in this compartment in the first trimester. Thus, the regulatory role of IGFBP-1 may change as pregnancy advances.

Amniotic Fluid↗
PubMed1992

Human chorionic gonadotrophin and subunit composition of maternal serum and coelomic and amniotic fluids in the first trimester of pregnancy.

Sixteen matched samples of first trimester amniotic fluid (AF), extraembryonic coelomic fluid (EECF) and maternal serum (MS) were assayed for intact human chorionic gonadotrophin (hCG) and free subunits. Total beta-hCG (free beta-subunit and intact hCG) levels in the EECF (median 410 kIU/l) were 61 times greater than levels in AF (median 6.73 kIU/l) and 2.8 times greater than in MS (median 141.5 kIU/l). Levels of intact hCG in the EECF (median 245 kIU/l) were 142 times greater than in AF (median 1.73 kIU/l) and 1.6 times greater than in MS (median 157 kIU/l). Free alpha-subunit levels in EECF (median 17.3 mg/l) were 66 times greater than in AF (median 0.262 mg/l) and 12 times greater than in MS (median 1.3 mg/l). Virtually all of the total beta-hCG immunoreactivity in MS can be attributed to intact hCG, but only 60% of total beta-hCG in the EECF and 20% of that in AF can be accounted for by the intact hormone. In both EECF and AF the free alpha-subunit was a major constituent; on a molar basis the ratio of free alpha:free beta:intact hCG was 1:1.2:0.3 in AF, 1:0.6:0.5 in EECF and 1:0:5 in MS. Chromatography of MS, EECF and AF on Sephadex G-100 confirmed the hCG and subunit composition of the fluids. On the basis of these findings it seems likely that previous studies showing very high levels of hCG in AF during the first trimester may have incorrectly sampled the EECF. In reality, the levels of total hCG (and free subunits) are low in the AF, and only 20% is intact hCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗
PubMed1991

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).

Abortion, Therapeutic↗
PubMed1991

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.

Amniotic Fluid↗