Neville C. Wathen

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.

Maternal and fetal levels of methionine and homocysteine in early human pregnancy

Objective To investigate methionine metabolism during normal human embryonic development by measuring levels of methionine and total homocysteine in samples of maternal serum, extra‐embryonic coelomic fluid, and amniotic fluid.

Biochemical composition of amniotic fluid and extraembryonic coelomic fluid in the first trimester of pregnancy

Objective To determine the biochemical composition of amniotic fluid and extra‐embryonic coelomic fluid between 8 and 12 weeks gestation.

Soluble tumor necrosis factor receptors and soluble interleukin-6 receptor in fetal and maternal sera, coelomic and amniotic fluids in normal and pre-eclamptic pregnancies

The aim of this study was (a) to measure soluble tumor necrosis factor receptors (sTNF-Rs) and soluble interleukin-6 receptor (sIL-6-R) in coelomic and amniotic fluids, cord and maternal sera in pregnancy and labor, (b) to examine whether the changes in concentrations of biologically active TNF and IL-6 are related to changes in their soluble receptors, and (c) to determine if levels of soluble receptors in pre-eclamptic disorders differ from normal pregnancies at delivery. Materials collected from 206 women during pregnancy and at delivery were analyzed for soluble receptors by enzyme-linked immunosorbent assay (ELISA). All receptors were present in higher concentrations in coelomic than in the corresponding amniotic fluid. Concentrations increased in amniotic fluid from first to second trimester. The level of sIL-6-R then remained unchanged to term, but there was a decrease in the sTNF-Rs which might account for the simultaneous appearance of bioactive TNF. Labor did not affect the concentration of any receptor in amniotic fluid. In maternal serum, sTNF-Rs increased with gestational age and labor in parallel with IL-6. The origin and physiological importance of these soluble receptors are still unknown. In pre-eclamptic disorders p55 sTNF-R was elevated in maternal serum before initiation of labor compared to normal pregnancy.

A relationship between sex hormone binding globulin and dehydroepiandrosterone sulfate in normally menstruating females.

Blood samples were collected from 120 normally menstruating women throughout the menstrual cycle. Serum was assayed for sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), estradiol (E2) and testosterone (T). There was an inverse relationship between SHBG and DHEAS, but no relationship between T or E2 and SHBG levels. There is at present no model which readily explains this inverse relationship between SHBG and DHEAS in normal subjects.

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.

Erythropoietin levels in amniotic fluid and extraembryonic coelomic fluid in the first trimester of pregnancy

Objective The aim was to measure erythropoietin levels in amniotic fluid and extraembryonic coelomic fluid from 7–12 weeks’ gestation.

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.

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.

The coelomic cavity — A reservoir for metals

OBJECTIVE The concentrations of metals in fluids surrounding the first-trimester fetus were measured. STUDY DESIGN Atomic absorption spectrometry was used to measure concentrations of metals in matched samples of amniotic and extraembryonic coelomic fluids in 17 women between 9 and 12 weeks of pregnancy. RESULTS Concentrations of calcium, magnesium, iron, copper, and manganese (but not zinc, cadmium, or lead) were significantly higher in coelomic than in amniotic fluid. There was no significant difference between levels of iron, manganese, and lead in controls and amniotic fluid or between concentrations of manganese, cadmium, and lead in controls and coelomic fluid. There was no relationship between the concentrations of each metal in amniotic and coelomic fluid. CONCLUSION The extraembryonic coelom is an important site of concentration of metals in early pregnancy. This might represent a store of metals essential for normal embryonic and fetal development or constitute a defense mechanism against environmental conditions adverse to the fetus.