Insulin-like growth factors (IGF) 1 and 2 in human foetal plasma and relationship to gestational age and foetal size during midpregnancy

IGF-1 and IGF-2 were measured by specific radioimmunoassay after acid-ethanol extraction of plasma obtained by foetoscopy from 20 normal foetuses aged 15-23 weeks. IGF-1 and IGF-2 levels were 36 +/- 11 and 162 +/- 55 ng/ml, respectively. In comparison, levels in cord blood were 84 +/- 58 and 264 +/- 176 ng/ml, respectively, and in adult plasma were 410 +/- 106 and 818 +/- 272 ng/ml. Both IGF-1 and IGF-2 were in the normal foetal range in a further three foetuses with anencephaly and two foetuses with spina bifida. No sex difference was observed. IGF-1 was positively correlated with foetal body weight (P less than 0.001), placenta weight (P less than 0.02) and with body length measured crown-rump (P less than 0.01) or crown-heel (P less than 0.02). No correlation between IGF-2 and body weight, length, placenta weight or gestational age was found. Both IGF-1 and IGF-2 are present in the human foetal circulation earlier in gestation than has previously been demonstrated, the levels being low throughout this period of gestation in comparison with adult plasma.     

Expression of pro-EPIL peptides encoded by the insulin-like 4 (INSL4) gene in chromosomally abnormal pregnancies

The recent development of a specific immunoassay based on monoclonal antibodies directed to chain C and chain A of early placenta insulin-like peptide (EPIL) encoded by the INSL4 gene, has made it possible to demonstrate pro-EPIL peptide expression during normal pregnancy. In the present study, we report on the expression of pro-EPIL peptides in chromosomally abnormal pregnancies, namely trisomy 21 and 18. EPIL peptide levels were measured in amniotic fluid (AF) and maternal serum (MS) from pregnancies with trisomy 21 (n=16) or 18 (n=14) and compared to levels detected in AF and MS from 33 chromosomally normal pregnancies between 12 and 32 weeks of gestation. Pro-EPIL peptide levels were significantly higher in amniotic fluids from T21 than in AF from chromosomally normal pregnancies (mean pro-EPIL levels +/- SEM, 449+/-129.2 ng/mL vs 137+/-29.6 ng/mL, P = 0.0195), whereas there was only a trend towards an increase in pro-EPIL peptide levels in maternal serum. In a limited matched gestational age range (15 to 17 weeks), it was confirmed that pro-EPIL peptide levels were significantly higher in AF from T21 pregnancies (644.0+/-155.9 ng/mL, n = 11) than in AF from normal pregnancies (177.8+/-39.0 ng/mL, n = 12; P < 0.0001). Interestingly, the expression patterns of pro-EPIL peptides, human chorionic gonadotropin (hCG) and its free subunits were parallel in T21 pregnancies as recently observed in normal pregnancies. These results are in line with previous observations suggesting that the biosynthesis of both hCG and EPIL follows common regulation pathways.     

Reliable prenatal diagnosis of Canavan disease (aspartoacylase deficiency): Comparison of enzymatic and metabolite analysis

Summary Prenatal diagnosis has been undertaken in 17 pregnancies in 15 families at risk for aspartoacylase deficiency. Amniocentesis was at 14–18 weeks gestation followed by measurement of amniotic fluidN-acetyl-l-aspartate (NAA) levels in all pregnancies and amniocyte aspartoacylase activity in most pregnancies. In one case amniocentesis was performed at 11 weeks gestation in conjunction with chorionic villus sampling. At 14–18 weeks of gestation, control levels of NAA were 0.30–2.55 µmol/L. The fetus was predicted to be affected in 8 of the pregnancies, 4 of which were confirmed by enzyme analysis on fetal tissue and 2 by the clinical and metabolic expression of Canavan disease in a newborn. In two cases there was no fetal tissue available for enzyme confirmation. One of these had the highest amniotic fluid NAA level (8.68 µmol/L) and in the other pregnancy there were two amniocenteses, both with markedly elevated levels. Of 9 fetuses predicted to be normal, 8 newborns were clinically and biochemically normal. A single case with amniotic fluid NAA in the normal range (1.56 µmol/L, measured in one laboratory only) resulted in an aborted fetus in whom aspartoacylase was deficient in cultured skin fibroblasts. We propose that amniotic fluid NAA levels remain the best predictor of an affected fetus and recommend that the assay be performed in multiple laboratories.     

Amniotic fluid propionylcarnitine in methylmalonic aciduria

Summary Amniotic fluid samples from pregnancies complicated by foetal methylmalonic aciduria and from metabolically normal pregnancies were obtained at 16–18 weeks of gestation and analysed for total, free and acylcarnitine and individual carnitine esters. The amniotic fluid concentrations of total acylcarnitine and propionylcarnitine were higher in pregnancies with methylmalonic aciduria than in normal pregnancies. The predominant carnitine ester was propionylcarnitine in the methylmalonic aciduria group and acetylcarnitine in the normal group. These findings suggest that in methylmalonic aciduria, abnormalities of carnitine metabolism already occur early in gestation. The amount of propionylcarnitine in amniotic fluid may be useful as an additional indicator of foetal methylmalonic aciduria     

Amniotic fluid concentrations of dimeric inhibins, activin A and follistatin in pregnancy

OBJECTIVE: The feto-placental unit is the major source of circulating concentrations of inhibin A and activin A in human pregnancy. The aim of this study was to measure the amniotic fluid concentrations of inhibin A, inhibin B, activin A and follistatin in pregnancies bearing male and female fetuses. DESIGN AND METHOD: Amniotic fluid samples collected by amniocentesis were stored at -20 degrees C. Dimeric inhibins, 'total' activin A and 'total' follistatin were measured using specific two-site enzyme immunoassays. Samples were assayed blindly and the information on fetal sex was obtained from the cytogenetics laboratory. RESULTS: Data show that amniotic fluid concentrations of inhibin A, inhibin B and activin A gradually increase with gestation whilst concentrations of follistatin are similar between weeks 15 and 20 of pregnancy. Mean amniotic fluid levels of inhibin A and inhibin B at 16 and 17 weeks gestation and mean activin A levels at 15 and 16 weeks gestation are considerably lower in pregnancies with male (n=24) compared with female (n=28) fetuses. Levels of follistatin are not different in the male and female fetal pregnancies at any studied gestation. CONCLUSIONS: The results indicate that amniotic fluid contains high concentrations of inhibins (A and B), activin A and follistatin in early pregnancy suggesting that these hormones are produced by the fetal membranes and may be involved in the development of the fetus.     

Fluctuations in levels of antiphospholipid antibodies and increased coagulation activation markers in normal and heparin-treated antiphospholipid syndrome pregnancies

Antiphospholipid antibodies (aPL) are associated with an increased risk of thrombosis and recurrent miscarriage. We assessed levels of coagulation activation markers and aPL during normal pregnancy and in women with the antiphospholipid syndrome (aPS). Fluctuations in aPL levels were observed in all patients with aPS. No particular pattern of antibody positivity, or fluctuation in aPL level, was associated with poor pregnancy outcome. A significant increase was observed in levels of factor Xlla (FXIIa; P < 0.001), factor VIIa (FVIIa, P < 0.001), thrombin antithrombin complexes (TAT; P < 0.001), prothrombin fragment F1.2 (F1.2; P < 0.001) and D-dimer (DD; P < 0.05) during normal pregnancy. Factor VIIa, TAT, F1.2 and DD increased significantly before 20 weeks gestation, while a statistically significant increase in FXIIa levels was first detected between weeks 20 and 30 of gestation. In pregnant women with aPS, increases in FXIIa were similar to those in normal pregnancy, but increased FVIIa levels were not observed until after 30 weeks gestation. Similar to normal pregnancy, increased levels of TAT and F1.2 were detected in aPS pregnancies before 20 weeks gestation, but increased DD were not observed until after week 20. Surprisingly, women with aPS receiving low molecular weight heparin prophylaxis had significantly higher (P = 0.02) levels of TAT (median 8.6; interquartile range (IQR) 6.5-20.8) between weeks 20 and 30 of gestation compared to the normal pregnant population (median 5.9; IQR 4.7-7.9), thus indicating increased thrombin generation in women with aPS in mid-pregnancy.     

Total homocyst(e)ine in plasma and amniotic fluid of pregnant women

Total homocyst(e)ine was determined by the quantitation of protein-bound homocyst(e)ine in the stored plasma and amniotic fluid from 25 pregnant women and in the stored plasma from 17 nonpregnant women. The mean +/- SE of plasma total homocyst(e)ine was 29.8 +/- 2.4 nmol/g protein in pregnant women and 52.4 +/- 3.8 nmol/g protein in nonpregnant women. In contrast, the mean +/- SE of total homocyst(e)ine in amniotic fluid obtained at 16 weeks of gestation was 36.3 +/- 2.9 nmol/g protein. There was a statistically significant difference in the plasma total homocyst(e)ine concentrations from pregnant and nonpregnant women (P less than 0.01). Similarly, there was also a statistically significant difference between plasma total homocyst(e)ine from nonpregnant women and amniotic fluid total homocyst(e)ine (P less than 0.01). These observations suggested that the metabolism of homocysteine to cysteine was more efficient in pregnant women. In addition, the concentrations of total homocyst(e)ine in amniotic fluids were within narrow limits in normal pregnancies. Hence, total homocyst(e)ine concentration might be very valuable as a rapid assessment of fetuses for congenital defects of homocysteine metabolism.     

Increased human placental growth hormone at midtrimester pregnancies may be an index of intrauterine growth retardation related to preeclampsia

OBJECTIVE: To evaluate the relationship between maternal serum and amniotic fluid levels of human Placental Growth Hormone (hPGH) with the fetal intrauterine growth retardation (IUGR) related to preeclampsia. DESIGN: We analyzed samples in pairs of serum and amniotic fluid retrospectively from 25 women, who manifested preeclampsia and IUGR in the late second or the third trimester of gestation. The samples were obtained at 16-22 weeks' gestation during amniocentesis for fetal karyotyping. At this time, there was no clinical or sonographic evidence of preeclampsia or IUGR, respectively. Sixty-two serum samples were used as controls which were obtained at 16-22 weeks' gestation from women with singleton, uncomplicated pregnancies, with normal outcome, and appropriate for gestational age neonatal birth weight. Forty-seven amniotic fluid samples were also used as controls which were obtained at 16-22 weeks' gestation from the women that were included in the control group who underwent an amniocentesis. hPGH levels were measured by a solid phase immunoradiometric assay. RESULTS: The mean hPGH values in the serum and the amniotic fluid of the IUGR related to preeclampsia affected pregnancies were significantly higher (P<0.05) than those of the normal pregnancies at 16-22 weeks' gestation: mean+/-SD in the serum was 13.16+/-10.52 ng/ml vs. 4.39+/-2.23 ng/ml; mean+/-SD in the amniotic fluid 2.49+/-1.6 ng/ml vs. 0.82+/-0.67 ng/ml. CONCLUSION: hPGH levels in maternal serum and amniotic fluid were found to be higher at 16-22 weeks' gestation in pregnancies that will be complicated subsequently by IUGR related to preeclampsia. Our findings suggest that the evaluation of the changes of hPGH levels at midtrimester should be further investigated for the possibility to provide a potential predictive index of IUGR and preeclampsia.     

Prenatal diagnosis of 11beta-hydroxylase deficiency congenital adrenal hyperplasia.

To predict 11beta-hydroxylase deficiency congenital adrenal hyperplasia antenatally, studies were performed in urines and amniotic fluids from 2 pregnant women who had previously given birth to affected infants and whose present pregnancies also resulted in infants with the disease. Urinary tetrahydro-11-deoxycortisol [pregnane-3alpha, 17alpha, 21-triol-20-one (THS)] was abnormally elevated in the first, second, and third trimesters (maximal values, 3.5 and 0.9 mg/24 h, respectively) but was undetectable after delivery in these mothers, in 15 normal pregnancies (10--40 weeks of gestation), and in 6 heterozygote parents. Amniotic fluid levels of THS, tetrahydrocortisol [pregnane-3alpha, 11beta, 17alpha, 21-tetra-o1-20-one (THF)], tetrahydrocortisone [pregnane-3alpha, 17alpha, 21-triol-11, 20-dione (THE)] measured by RIA at 18 weeks of gestation in the first mother and at 40 weeks in the second revealed 12.5- and 8.4-fold increases in THS, respectively, but normal THF and THE levels compared to mean levels in normal pregnancies. The THS to THF plus THE ratio, which was constant throughout pregnancy in 125 normal women (mean +/- SD, 0.63 +/- 0.34) despite the variable levels of these metabolites, was significantly elevated in both patients (4.4 and 3.8, respectively). These studies indicate that prenatal diagnosis of 11beta-hydroxylase deficiency congenital adrenal hyperplasia based on hormonal measurements is feasible.     

Amniotic fluid levels of dimeric inhibins, pro-αC inhibin, activin A and follistatin in Down''s syndrome

OBJECTIVE: In the second trimester of pregnancy, inhibin A is significantly increased in maternal serum and decreased in amniotic fluid in Down's syndrome pregnancies compared to normal. We wished to further evaluate the levels of inhibin A, inhibin B, pro-alpha C inhibin, activin A and the binding protein follistatin in amniotic fluid in Down's syndrome and control pregnancies. DESIGN: Case-matched control study. PATIENTS: 29 Down's syndrome and 290 chromosomally normal control pregnancies were identified from records and amniotic fluid, collected at second trimester amniocentesis, retrieved from routine storage for analysis. MEASUREMENTS: Inhibin A, inhibin B, pro-alpha C inhibin, total activin A and follistatin were measured using sensitive and specific enzyme linked immunosorbent assays. RESULTS: The median (10th-90th percentiles) amniotic fluid inhibin A level in the control pregnancies increased from 334 (122-553) ng/l at 14 weeks' to 695 (316-1475) ng/l at 19 weeks' gestation. The corresponding figures for inhibin B and the alpha-subunit precursor inhibin pro-alpha C were 632 (185-1354) and 2062 (1237-3381) ng/l, respectively at 14 weeks' and 2439 (748-5307) and 3115 (2021-6567) ng/l, respectively at 19 weeks' gestation. Total activin A increased from 3795 (1554-5296) at 14 weeks' to 5086 (3059-8224) at 18 weeks' gestation. Expressed as multiples of the median (MoM) the median (95% CI) amniotic fluid levels of inhibin A, inhibin B, pro-alpha C inhibin and acitivin A in the Down's syndrome samples were 0.77 (0.59-0.85), 0.94 (0.63-1.23), 0.77 (0.49-0.84) and 0.77 (0.53-0.87), respectively. Compared to controls the levels of inhibin A, pro-alpha C inhibin and activin A were significantly lower in Down's syndrome pregnancies (P < 0.01, Mann-Whitney U test). Follistatin levels in the controls declined slightly from 2106 (1421-3538) ng/l at 14 weeks' to 1600 (1281-2543) ng/l at 18 weeks' gestation. Levels in the Downs' syndrome pregnancies were similar to controls. CONCLUSIONS: The data suggest that the production, secretion or metabolism of the inhibin alpha- and beta A-subunits is altered in Down's syndrome pregnancies in the second trimester.     

Maternal side effects of prenatal dexamethasone therapy for fetal congenital adrenal hyperplasia.

Prenatal treatment of virilizing congenital adrenal hyperplasia in female fetuses via maternal dexamethasone (Dex) therapy (1-1.5 mg/day) from first trimester to birth was associated with excessive weight gain (47-56 pounds at 35-37 weeks gestation), Cushingoid facial features, severe striae resulting in permanent scarring, and hyperglycemic response (8-11.7 nmol/L) to oral glucose administration in all our experience (three cases). Other symptoms included hypertension, gastrointestinal intolerance, or extreme irritability. Previous pregnancies were uncomplicated by these problems. In each case, first or second trimester amniotic fluid 17-hydroxyprogesterone (17OHP, 17-41 nmol/L; normal less than 0.4 nmol/L), androstenedione (22-31 nmol/L, normal less than 5 nmol/L), and testosterone levels (0.54-0.7 nmol/L, normal less than 0.4 nmol/L) during Dex treatment were elevated regardless of the newborn genital outcome. Maternal serum estriol (E3) levels in one mother (normal newborn genitalia) were consistently low (less than 0.2 nmol/L) during the second and third trimester. In two mothers (partially virilized newborn genitalia) initial second trimester E3 levels were unsuppressed (11, 17.4 nmol/L) and suppressed (less than 1.4 nmol/L) following short-term increased dose. Conclusion: prenatal Dex treatment of virilizing congenital adrenal hyperplasia at a dose of 1-1.5 mg daily throughout gestation is associated with significant maternal side effects. Parents should be informed of these side effects before initiation of treatment. Careful monitoring for signs of side effects, medical intervention when necessary, and lowering of Dex dose during the second half of gestation would minimize the side effects. Maternal serum E3 levels appear useful for prediction of fetal outcome while amniotic fluid steroid levels may not.     

Antenatal management of severe feto-maternal alloimmune thrombocytopenia: HLA incompatibility may affect responses to fetal platelet transfusions

In feto-maternal alloimmune thrombocytopenia (FMAIT), severe hemorrhage, particularly intracranial haemorrhage (ICH), may occur before delivery. Management strategies to prevent ICH in high-risk pregnancies include maternal administration of intravenous Ig with or without steroids and fetal platelet transfusions. This report describes a patient who lost three fetuses with ICH because of FMAIT due to anti- HPA-1a. ICH occurred earlier in successive pregnancies (at 28, 19, and 16 weeks of gestation) despite maternal treatment with intravenous Ig and steroids from 14 weeks of gestation in the third pregnancy. The fourth pregnancy was managed by administering weekly intraperitoneal injections of Ig to the fetus from 12 to 18 weeks of gestation. At 18 weeks, there was no evidence of ICH, but the fetal platelet count was only 12 x 10(9)/L. Serial fetal platelet transfusions were started, but there were poor responses because of immune destruction of the transfused platelets by maternal HLA antibodies. There were improved responses to transfusions prepared from the mother and from HLA- compatible HPA-1a-negative donors. At 35 weeks of gestation, a normal infant was delivered by Caesarean section after 20 platelet transfusions. There was prolonged thrombocytopenia in the baby for 15 weeks after birth, probably due to transfer of HPA-1a antibodies in the transfusions of unwashed maternal platelets. The optimal management of pregnancies likely to be severely affected by FMAIT is still evolving. Intensive management was successful in this case, but a successful outcome cannot be guaranteed in severely affected cases. This is the first time that HLA incompatibility has been found to complicate fetal transfusion therapy.     

Mortality from neural tube defects in Mexico, 1980-1997

OBJECTIVE: To describe the mortality due to neural tube defects (NTD) in Mexico for the 1980-1997 period. MATERIAL AND METHODS: The annual NTD mortality rates per 10000 liveborn infants were calculated by state and for the country. The time trend was evaluated with the annual percent change (APC) obtained using a Poisson regression model. The NTD mortality ratio was calculated using the average national rate as reference. NTD mortality rates and ratios were graphically displayed on maps. RESULTS: During the 1980-1997 period the gross NTD mortality rate was 5.8 per 10000 live-born infants. Anencephaly (International Classification of Diseases ICD-9 740.0) was the most frequent type of NTD (37.7%), followed by spina bifida without hydrocephaly (CIE9 741.9) (31.6%). The national trend of NTD mortality increased between 1980 and 1990 (APC 7.5 95% CI 6.5, 8.6) and decreased between 1990 and 1997 (APC-2.3 95% CI-3.6, -0.9). CONCLUSIONS: The high NTD mortality rates were related to the high frequency of anencephaly. Also, the increase observed is not only attributable to diagnostic factors or to improved reporting. In Mexico, the influence of some NTD-associated factors such as specific genetic polymorphisms, folic acid deficit, maternal obesity, occupational exposure to pesticides, and poverty, should be assessed in specific studies.     

Spina bifida

Spina bifida results from failure of fusion of the caudal neural tube, and is one of the most common malformations of human structure. The causes of this disorder are heterogeneous and include chromosome abnormalities, single gene disorders, and teratogenic exposures. However, the cause is not known in most cases. Up to 70% of spina bifida cases can be prevented by maternal, periconceptional folic acid supplementation. The mechanism underlying this protective effect is unknown, but it is likely to include genes that regulate folate transport and metabolism. Individuals with spina bifida need both surgical and medical management. Although surgical closure of the malformation is generally done in the neonatal period, a randomised clinical trial to assess in utero closure of spina bifida has been initiated in the USA. Medical management is a lifelong necessity for individuals with spina bifida, and should be provided by a multidisciplinary team.     

Elevated first trimester maternal levels of soluble fibrin polymer are associated with lower birthweight in twin gestation.

We assessed soluble fibrin polymer longitudinally in normal pregnancy, thrombophilic pregnancy and twin gestation Thirty-three thrombophilic pregnancies, 34 uncomplicated multiple gestations and 23 singleton normal pregnancies were studied. Maternal plasma samples were collected in the first (6-12 weeks), 2nd (13-25 weeks) and 3rd trimesters of pregnancy (26-40 weeks) and were stored at -70 degrees C until assay. Soluble fibrin polymer was assayed by enzyme-linked immunosorbent assay (ABS, Copiague, New York, USA). Statistical analysis were made by Spearman test and Levine's test for equality of variance (P < 0.05). First soluble fibrin polymer maternal levels in twin gestation were significantly higher than in normal pregnancy and thrombophilic pregnancy, (23.8 +/- 4.5 mug/ml versus 9.2 +/- 3.1 and 10.0 +/- 2.0 mug/ml respectively, P < 0.005). Second and third trimester maternal levels of SFP in twins were also significantly higher than in normal pregnancy. First trimester soluble fibrin polymer was highly correlated with birthweight in twin gestation (r = -1, P < 0.01). In the third trimester, maternal soluble fibrin polymer correlated with placental weight in twin gestation (r = 0.639, P < 0.01). Overall, soluble fibrin polymer was correlated with placental weight and birthweight in the three groups but this did not reach statistical significance. Elevated maternal plasma levels of soluble fibrin polymer in twin gestation may derive from an accelerated coagulation process due to extensive vascular remodelling. Current studies are underway to determine the utility of soluble fibrin polymer in assessing fetal growth abnormalities.     

Cortisol production and inactivation by the human lung during gestation and infancy.

The enzyme which interconverts the active hormone cortisol (F) and its biologically inactive analog cortisone (E), viz. 11 beta-hydroxysteroid dehydrogenase, is known to be present in many tissues. In this study, its possible role as a regulator of cortisol concentration in the human lung was investigated. Small amounts of minced tissue were incubated for 2 h at 37 C in the presence of tracer F or E. After extraction, the steroids were chromatographed using Sephadex LH-20 column chromatography. From 11-21 weeks of gestation, inactivation of F to E occurred (54.7 +/- 8.0%), while in 11 premature infants there was no conversion in either direction and in 9 infants (4 months to 2 yr of age) there was slight conversion of E to F (7.0 +/- 3.4%). Activity in children was negligible. Lung tissue from 4 anencephalics (35-40 + weeks) retained the ability to inactivate F to E (21.3 +/- 4.3%), though to a lesser extent (P less than 0.01) than fetuses up to 21 weeks. The validity of these in vitro studies was borne out by assays of the endogenous steroids in lung tissue and serum. These results suggest that there is an alteration from rapid inactivation of F to E in early fetal life to slight F production in infancy and that this change is advanced by pituitary or other factors which are decreased in anencephaly. This decreasing inactivation by the lung during late gestation results in higher intracellular F levels which probably act to promote lung maturation in preparation for birth.     

AMNIOTIC FLUID CONCENTRATIONS OF 3,3'',5''-TRI-IODOTHYRONINE (REVERSE T3), 3,3''-DI-IODOTHYRONINE, 3,5,3''-TRI-IODOTHYRONINE (T3) AND THYROXINE (T4) IN NORMAL AND COMPLICATED PREGNANCY

Amniotic fluid concentrations of 3,3',5'-tri-iodothyronine (rT3), 3,3'-Di-iodothyronine (3,3'-T2), 3,5,3'-tri-iodothyronine (T3) and T4 were studied in 384 women during normal and complicated pregnancy. An inverse correlation was observed between decreasing rT3 and increasing 3,3'-T2 concentrations in amniotic fluid with gestational age. The mean rT3 level in normal pregnancy was 2.81 nmol/1 at 12-20 weeks and decreased significantly to 1.06 nmol/1 at 36-42 weeks of gestation. The mean 3,3'-T2 concentration was 49.1 pmol/1 at12-20 weeks increasing to 119 pmol/1 at 36-42 weeks. The mean T4 value of 3.83 nmol/1 at 12-20 weeks was about half that of later periods. The T3 concentration in a random sample of 45 amniotic fluids ranged from less than 28 to 370 pmol/1 (mean 102 pmol/1). The mean rT3, 3,3'-T2 and T4 values measured in patients with intra-uterine malnutrition, gestation diabetes, tocolysis, placental insufficiency and rhesus incompatibility at 31-40 weeks of gestation were not significantly different from those in uncomplicated pregnancy. Significantly decreased rT3 and T4 concentrations were found in toxaemia. From the results obtained in complicated pregnancy it may be concluded that measurements of iodothyronines, especially rT3, in amniotic fluid have insignificant diagnostic value in the recognition of intra-uterine lesions with the probable exception of fetal hypothyroidism. The analysis of the dependence of iodothyronine concentrations on the gestational age showed a maximum of rT3 and T4 levels between 20 and 30 weeks of pregnancy. This marked rise of iodothyronine concentrations in amniotic fluid at mid-gestation may be due to the onsetting maturation of the hypothalamic-pituitary-thyroid control system of the fetus.     

Feasibility of DNA diagnosis of haemoglobinopathies on coelocentesis

At 5–12 weeks of gestation the amniotic sac is surrounded by celomic fluid, which contains cells of fetal origin. This fluid can be sampled by celocentesis, which involves the ultrasound‐guided insertion of a needle through the vagina. The aim of this study was to examine the feasibility of prenatal diagnosis of haemoglobinopathies from the celomic fluid using a specific protocol. Celocentesis was performed at 7–9 weeks gestation in 26 singleton pregnancies at risk for haemoglobinopathies. In 25 cases more than 30 fetal cells were recovered from the celomic fluid and in all these cases molecular analysis for haemoglobinopathies was possible and the results were confirmed by subsequent chorionic villus sampling or amniocentesis. The results of this study suggest that reliable diagnosis of thalassemia syndromes can be performed from 7 weeks gestation by celocentesis. Further work is necessary to demonstrate the safety of celocentesis before widespread use.     

The steroid hormonal milieu of the undisturbed human fetus and mother at 16-20 weeks gestation

The interrelations of steroid hormone levels in plasma and amniotic fluid from mothers and their undisturbed fetuses at early midgestation of human pregnancy have not been defined previously. We, therefore, studied 12 healthy mothers and their fetuses undergoing termination of pregnancy for social reasons at 16-20 weeks gestation. Fetal arterial and venous blood was obtained by direct vessel puncture through a fetoscope in the conscious sedated mothers immediately before termination of pregnancy. Simultaneously, maternal peripheral venous blood and amniotic fluid were collected. Aldosterone (Aldo), corticosterone (B), 11-deoxycorticosterone, progesterone (P), 17-hydroxyprogesterone (17OHP), 11-deoxycortisol, cortisol (F), and cortisone were simultaneously determined by specific RIA after extraction and chromatography. Positive fetal arterio-venous differences were found for F, B, and Aldo, whereas arteriovenous differences were negative for P and 17OHP. In amniotic fluid, six of the eight corticosteroids showed significantly lower levels during fetoscopy than during routine amniocentesis, as reported previously using the same analytical methods. The present study demonstrates that the undisturbed human fetus at 16-20 weeks gestation actively secretes the most important gluco- and mineralocorticoids, F, B, and Aldo, independent of the mother. P and 17OHP were shown to be primarily derived from placental production and supplied to the fetus as a source of F and Aldo biosynthesis. The fetoscopy procedure with premedication seemed to give rise to less stress to the fetus than routine amniocentesis without sedation. Fetoscopy is, therefore, an ideal method to study feto-maternal steroid interrelations in human pregnancy.     

Studies on human sexual development. VI. Concentrations of unconjugated dehydroepiandrosterone, estradiol, and estriol in amniotic fluid throughout gestation.

Concentrations of unconjugated dehydroepiandrosterone, estradiol, and estriol were measured in samples of amniotic fluid from uneventful pregnancies of 9-40 weeks conceptual age. There was no apparent influence of fetal sex upon the levels of these steroids. Dehydroepiandrosterone concentrations rose slightly from 9-20 weeks, and then showed little further change. Estradiol concentrations declined slightly from 9-20 weeks; after 32 weeks gestation, there was a 2-fold rise to term. Estriol levels rose in almost exponential fashion throughout gestation.