Human beta-endorphin and beta-lipotropin levels in maternal and fetal plasma and amniotic fluid

We measured beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) levels in human maternal and fetal plasma and amniotic fluid, simultaneously. It appeared evident that maternal circulating levels of beta-EP (n = 11, 163.9 +/- 12.9 pg/ml, mean +/- S.E.) and beta-LPH (n = 11, 413.0 +/- 25.9 pg/ml) at delivery were significantly (p less than 0.01) higher than those of maternal plasma at term (beta-EP; n = 4, 18.3 +/- 2.1 pg/ml, beta-LPH; 213.4 +/- 24.3 pg/ml) and those of amniotic fluid (beta-EP; n = 5, 8.5 +/- 1.2 pg/ml, beta-LPH; 215.1 +/- 44.9 pg/ml). Fetal beta-EP levels (n = 11, 79.1 +/- 5.8 pg/ml) were significantly (p less than 0.01) higher than those of amniotic fluid. These data suggest that the origin of amniotic fluid beta-EP may be an increased synthesis in the maternal and fetal pituitary gland but not in the placenta.     

Plasma somatostatin 28 increases in response to feeding in man.

Tissue somatostatin-like immunoreactivity (SLI) consists of a number of molecular species including the cyclic tetradecapeptide or SRIF, an N-terminally extended form of SRIF termed somatostatin-28, as well as larger precursor peptides. The function and nature of circulating SLI is not well understood. In this report, we describe techniques for the definition of the components of plasma SLI in normal human plasma. Plasma SLI measured after gel filtration on Bio-gel P-6 columns was found to consist of from 1-3 peaks. The void volume peak was present in greatest concentration (34.2 +/- 8.9 pg/ml) and did not increase in response to a mixed meal. Very low levels of two additional peaks of SLI activity were found. To further characterize these peaks, 10-ml plasma samples were extracted and concentrated on octadecylsilyl silica (C-18) cartridges with subsequent fractionation on Bio-gel P-6 columns. The two peaks that coeluted with synthetic SRIF and S-28 markers, respectively, were present in concentrations of 5.4 +/- 1.4 and 4.8 +/- 1.9 pg/ml in fasting plasma. In response to a mixed meal, the SLI14 peak doubled (12.9 +/- 2.4 pg/ml) while the SLI28 peak increased to 29.9 +/- 7.2 pg/ml at 120 min. These results provide evidence that S-28 circulates in human plasma and its increase after feeding is consistent with a possible biological role for this peptide.     

Arginine vasotocin in ovine fetal blood, urine, and amniotic fluid.

Arginine vasotocin ([8-arginine]-oxytocin) (AVT), the primary antidiuretic principle in submammalian vertebrates, has been reported to be present in mammalian pituitary and pineal glands. Although the most phyletically ubiquitous of the known neurohypophysial peptides, AVT is still not recognized as a mammalian hormone. We examined plasma, urine, and amniotic fluid from fetal lambs by radioimmunoassay (RIA) for evidence of AVT to assess the possibility of its being such a hormone. Measureable quantities of AVT-like immunoreactivity (irAVT) were observed in fetal plasma (2.4 +/- 0.2 pg/ml), urine (1.4 +/- 0.2 pg/ml), and amniotic fluid (1.9 +/- 0.2 pg/ml). Since the AVT antiserum shows minimal cross-reactivity with arginine vasopressin (AVP) and oxytocin (OT), measurements of AVP and OT concentrations in the same biological fluids also were conducted with specific antisera. The results suggest that the irAVT was not accountable on the basis of cross-reaction. To further verify the identity of the irAVT, a high pressure liquid chromatography system using RIA as a means of detection was developed. This system is sufficiently sensitive to allow the separation and quantitation of picogram quantities of the synthetic peptides AVT, AVP, and OT. In this system, the irAVT in fetal plasma, urine, and amniotic fluid appeared as a single peak coeluting with synthetic AVT. These results indicate that AVT is present in ovine fetal plasma and support the view that the fetus secretes this peptide. The physiological significance of circulating AVT remains to be defined.     

Immunoassay for the determination of surfactant apoprotein (SP-A) in human amniotic fluid: comparison with other indices of assessing foetal lung maturity.

The concentration of the major surfactant-associated protein SP-A (28-36 kDa) was determined in 73 amniotic fluid samples obtained from normal (n = 40) and complicated (n = 33) pregnancies. Lecithin/sphingomyelin (L/S) ratio and phosphatidylglycerol (PG) levels were also determined in all the samples by one-dimensional step-wise thin-layer chromatography. An enzyme-linked immunosorbent assay was used to determine human lung surfactant apoprotein SP-A. The amount of SP-A in human amniotic fluid increased as a function of gestational age from 8 mg l-1 at 36 weeks to 11.75 mg l-1 at 40-41 weeks of gestation. There was a significant difference (p less than 0.01) in amniotic fluid SP-A concentration from female (9.93 +/- 0.60 micrograms ml-1) compared to male (9.10 +/- 0.52 micrograms ml-1) foetuses. In amniotic fluid samples obtained from a group of complicated pregnancies, SP-A levels were significantly lower than in the normal group when adjusted for gestational age and sex of the foetus (p less than 0.05).     

Early oxidative stress in amniotic fluid of pregnancies with Down syndrome

OBJECTIVE: Some evidence suggests that oxidative stress, due to an imbalance between oxidants and antioxidants, occurs in babies with Down syndrome (DS). This study tests the hypothesis that oxidative stress occurs early in DS pregnancies. DESIGN AND METHODS: Isoprostanes (IPs), a new marker of free radical-catalyzed lipid peroxidation, were measured in amniotic fluid from pregnancies with normal, growth restricted and DS fetuses, diagnosed by karyotype analysis of amniotic cells cultured. RESULTS: A nine-fold increase in IP concentrations was found in amniotic fluid of pregnancies with DS fetuses. This increase (595.15; 542.96-631.64 pg/ml, median; 95% CI), was greater than in pregnancies with fetal growth-restricted fetuses (155; 130.57-172.23 pg/ml, median; 95% CI) and normal fetuses (67; 49.82-98.38 pg/ml, median; 95% CI; p<0.0001). CONCLUSIONS: The study reveals that oxidative stress occurs early in pregnancy and supports the idea of testing whether prenatal antioxidant therapy may prevent or delay the onset of oxidative stress diseases in the DS population.     

Contribution of the pancreas to circulating somatostatin-like immunoreactivity in the normal dog.

These studies were performed to assess the contribution of the pancreas to the somatostatin-like immunoreactivity (SLI) circulating in arterial and portal venous plasma. Basal SLI concentrations in arterial, pancreatic venous, and portal venous plasma were 95 +/- 9, 277 +/- 32, and 130 +/- 12 pg/ml, (means +/- SEM), respectively. Measurement of pancreatic and portal venous blood flow (5 +/- 1 vs. 365 +/- 46 ml/min) and hematocrit allowed calculation of net, base-line SLI output from the right lobe of the pancreas (521 +/- 104 pg/min) and from the gastrointestinal tract (8,088 +/- 1,487 pg/min), which suggested that the contribution of the pancreas to circulating SLI was minor when the D cells were not stimulated. To stimulate the secretion of SLI from both pancreatic and nonpancreatic sources, isoproterenol, a beta-adrenergic agonist, was infused intravenously for 1 h into six anesthetized dogs. Arterial SLI increased by 52 +/- 9 pg/ml; superior pancreatico-duodenal venous SLI increased by 380 +/- 95 pg/ml; portal venous SLI increased by 134 +/- 14 pg/ml. Pancreatic venous blood flow remained unchanged at 5 +/- 1 ml/min, but portal venous blood flow increased to 522 +/- 62 ml/min. SLI output from the right lobe of the pancreas increased by 684 +/- 227 pg/min and that from the gastrointestinal tract increased by 23,911 +/- 3,197 pg/min, again suggesting that the pancreas was a minor source of circulating SLI even when the D cells were stimulated. We conclude that the measurement of arterial-venous SLI concentrations, in the absence of measurements of organ blood flow, can give a false impression of the organ's contributions of circulating SLI. To verify that the contribution of the pancreas was negligible, six dogs received an acute pancreatectomy and then an intravenous infusion of isoproterenol at the same rate. In these dogs, both the base-line level of SLI in arterial plasma (109 +/- 12 pg/ml) and the increment during isoproterenol (56 +/- 8 pg/ml) were similar to those of normal dogs. Likewise, in pancreatectomized dogs both the base-line level of SLI in portal venous plasma (129 +/- 16 pg/ml) and the increment during isoproterenol (174 +/- 34 pg/ml) were similar to those of normal dogs. We conclude that, in normal dogs, the pancreas makes a negligible contribution to the basal and stimulated level of SLI in arterial and portal venous plasma and therefore that these levels should not be used as an index of secretory activity of the pancreatic D cells.     

Stable isotope dilution analysis of very long chain fatty acids in plasma, urine and amniotic fluid by electron capture negative ion mass fragmentography.

A sensitive and selective stable isotope dilution electron capture negative ion chemical ionization mass fragmentography method applying pentafluorobenzyl derivatives was developed for the accurate quantitation of very long chain fatty acids. This technique allowed detection of 1-5 pg of each compound and was applied to plasma (100 microliters), amniotic fluid (1 ml) and urine (1 ml). Normal concentrations were established and the concentrations in samples of selected patients with classified peroxisomal disorders were determined. In plasma samples of all patients the C26:0/C22:0 ratios were elevated (range 0.03-0.43), compared to the control ratios (range 0.003-0.021). The ratio C26:0/C22:0 was elevated in four of five amniotic fluid samples from fetuses with peroxisomal disorders (range 0.18-0.54) when compared with controls (range 0.05-0.25). An elevation of the ratio C26:1/C22:0 was observed in all five amniotic fluid samples (range 0.22-0.60 vs. 0-0.08 in controls). Urinary C26:0 concentrations were lower than in plasma and amniotic fluid and diagnostic ratios were not elevated in patients with peroxisomal disorders.     

Concanavalin A binding of alpha-fetoprotein in amniotic fluid as an aid in the diagnosis of neural tube defects

Concanavalin A nonreactive alpha-fetoprotein was determined in samples of amniotic fluid from 16 abnormal pregnancies complicated by anencephaly (7), open spina bifida (6), intra-uterine death (1), anencephaly with exomphalos (1), or open spina bifida with exomphalos (1), and in amniotic fluid from 50 normal pregnancies with gestational age between 13 and 24 weeks. In all 16 cases with fetal malformations, the proportion of nonreactive alpha-fetoprotein was significantly decreased (median 5.3%) as compared with amniotic fluid from pregnancies with a normal outcome (median 39.7%). The results confirm that this measurement is useful in the diagnosis of neural tube defects, especially when the concentration of alpha-fetoprotein in amniotic fluid is normal or only slightly above normal and gestational age is uncertain.     

The use of fetal echocardiography for predicting intrapartum fetal heart rate patterns in the post-term pregnancy.

One of the shortcomings of antepartum testing in the post-term pregnancy is that it does not identify the majority of fetuses who develop abnormal intrapartum fetal heart rate changes. The purpose of this study was to determine whether antenatal cardiovascular evaluation could aid in the identification of post-term fetuses at risk for intrapartum heart rate abnormalities. Seventy-five patients with a gestational age greater than 41 weeks underwent a non-stress test, amniotic fluid index and real-time assessment of the heart for the presence or absence of a pericardial effusion. M-mode measurements of the right ventricular inner dimension (RVID), left ventricular inner dimension (LVID), biventricular outer dimension (BVOD) and Doppler velocimetry of the umbilical artery (S/D) were performed. Group I (n = 32) had normal intrapartum heart rate tracings. Group II (n = 20) had abnormal intrapartum fetal heart rate tracings but did not undergo emergency delivery. Group III (n = 23) had abnormal intrapartum fetal heart rate tracings but underwent emergency delivery. When comparing Group I with Group II, the latter had significant differences for abnormal RVID, RVID/LVID ratio, and pericardial effusion. When comparing Groups I and III, there were significant differences for RVID, RVID/LVID ratio, pericardial effusion, BVOD, LVID and amniotic fluid index. Neither the non-stress test nor S/D predicted abnormal intrapartum fetal heart rate patterns. For prediction of abnormal intrapartum heart rate patterns, the sensitivities of the RVID (0.79), LVID (0.33), RVID/LVID ratio (0.72) and BVOD (0.63) were 1.7-4 times greater than the non-stress test (0.19) and the sensitivities of the RVID, RVID/LVID ratio and BVOD were 2 times greater than the amniotic fluid index (0.28). The positive (0.50-0.86) and negative (0.42-0.68) predictive values were similar for all groups. To predict emergency delivery associated with abnormal heart rate tracings, the sensitivities of the RVID (0.83), RVID/LVID ratio (0.70) and BVOD (0.65) were 2.5-3 times greater than the non-stress test (0.26) and 1.5 times greater than the amniotic fluid index (0.39). The positive (0.36-0.56) and negative (0.70-0.86) predictive values were similar. The presence of pericardial effusion had a higher sensitivity than the non-stress test and amniotic fluid index for predicting abnormal intrapartum heart rate patterns but not emergency delivery. Doppler velocimetry of the umbilical artery had a lower sensitivity than the non-stress test and amniotic fluid index for predicting intrapartum heart rate patterns as well as identifying the fetus needing emergency delivery. The results of this study would suggest that there is initially dilatation of the right ventricle which may be associated with abnormal intrapartum fetal heart rate patterns. However, when the left ventricle dilates, leading to cardiomegaly, there is a greater incidence of abnormal intrapartum fetal heart rate changes and associated emergency delivery. The amniotic fluid index appears to be a later finding for predicting abnormal intrapartum fetal heart rate changes.     

羊水样本卵磷脂和鞘磷脂检测超高效液相色谱串联质谱方法的建立及应用

目的建立检测羊水中卵磷脂和鞘磷脂(L/S)的超高效液相色谱串联质谱(UPLC-MS/MS)方法,以便准确、高效地预测胎儿肺成熟度。方法收集孕32~39周孕妇分娩时的羊水样本23份。依据新生儿Apgar评分标准,有3例胎儿胎肺未成熟、20例胎儿胎肺成熟。另收集孕18周孕妇羊水样本7份作为基线对照,建立检测羊水中卵磷脂和鞘磷脂水平的UPLC-MS/MS方法,计算卵磷脂/鞘磷脂(L/S)比值,同时采用板层小体计数(LBC)法检测板层小体(LB),评价2种方法在预测胎肺成熟度中的价值。结果建立的检测羊水中卵磷脂和鞘磷脂的UPLC-MS/MS方法精密度良好,离子峰强度和保留时间均在可检测范围内,主成分分析(PCA)显示6个质控样本聚类良好。以L/S比值=10作为判断胎肺成熟度与不成熟的临界值,UPLC-MS/MS的敏感性和特异性均为100%。以LB=50×10^9/L作为判断胎肺成熟度与不成熟的临界值,LBC法的敏感性和特异性分别为80%和95%。结论建立了检测羊水中卵磷脂和鞘磷脂水平的UPLC-MS/MS方法,其结果可靠,可以准确、高效地预测胎肺成熟度。     

Correlation between fetal gastric size and amniotic fluid volume

PURPOSE: Since abnormal conditions of the fetal digestive tract may alter both amniotic fluid volume and fetal gastric volume, we sought to determine whether amniotic fluid volume is correlated with fetal gastric volume in normal pregnancy. METHODS: A total of 280 fetal gastric size measurements were made prospectively from routine sonographic examinations of women with normal singleton pregnancies between 16 and 42 weeks of gestation. The fetal stomach was defined as the largest area including the pyloric site on transverse or oblique real-time sonographic scans. Gastric volume was calculated according to the formula for a prolate ellipsoid. The amniotic fluid index (AFI) was used for the evaluation of amniotic fluid volume. RESULTS: Both fetal gastric volume and AFI were significantly correlated with gestational age (R2= 0.422 and R2= 0.128, respectively). Only a weak correlation was found between gastric volume and AFI (R2= 0.036, p <0.001). On multivariate linear regression analysis adjusting for gestational age and fetal biometric measurements, gastric volume was not an independent and significant predictor of AFI. CONCLUSIONS: Although sonographically determined fetal gastric volume measurements appear to be useful in the assessment of fetal digestive tract anomalies, fetal gastric volume has no clinically significant effect on the amniotic fluid volume in normal pregnancy.     

Evidence for a Role of Free Fatty Acids in the Regulation of Somatostatin Secretion in Normal and Alloxan Diabetic Dogs

To investigate the effect of acute elevation of plasma free fatty acids (FFA) on the secretion of splanchnic somatostatin-like immunoreactivity (SLI), the peripheral venous, pancreatic, and gastric venous effluent levels of SLI were measured in normal and chronic alloxan diabetic dogs before and after the infusion of a fat emulsion supplemented with heparin. In normal conscious dogs heparin injected during the infusion of a fat emulsion elevated FFA levels from a mean (+/-SE) base-line level of 0.7+/-0.1 meq/liter to a peak value of 1.5+/-0.1 meq/liter (P < 0.001) and plasma SLI rose from a mean (+/-SE) base-line value of 145+/-7 pg/ml to a peak of 253+/-44 pg/ml (P < 0.05). Neither the infusion of glycerol, of fat emulsion without heparin, of heparin alone nor of saline itself had an effect on either the plasma level of FFA or SLI. In another group of anesthetized dogs with surgically implanted catheters the administration of fat emulsion plus heparin was accompanied by more than a two-fold rise in the concentration of SLI in the venous effluent of the pancreas and of the gastric fundus and antrum in association with an elevation of FFA levels. In a group of conscious diabetic dogs fat emulsion plus heparin raised FFA from a mean base-line level of 1.2+/-0.2 to 1.6+/-0.3 meq/liter (P < 0.05) and SLI rose from a mean base-line level of 185+/-9 pg/ml to a peak value of 310+/-44 pg/ml (P < 0.01). Although SLI levels were significantly greater than in normal dogs at several time points after the rise in FFA, the magnitude of the increment in diabetic dogs did not differ from normal. These results demonstrate that a rise in FFA levels is a potent stimulus for SLI secretion from the pancreas and stomach and raise the possibility that FFA is an important physiological regulator of SLI secretion.     

Somatostatin molecular variants in the vitreous fluid: a comparative study between diabetic patients with proliferative diabetic retinopathy and nondiabetic control subjects

OBJECTIVE: There is growing evidence to indicate that somatostatin could be added to the list of natural antiangiogenic factors that exist in the vitreous fluid. In addition, a deficit of intravitreous somatostatin-like immunoreactivity (SLI) has been found in diabetic patients with proliferative diabetic retinopathy (PDR). In the present study, we have determined the main molecular variants of somatostatin (somatostatin-14 and somatostatin-28) in the vitreous fluid and plasma of nondiabetic control subjects and diabetic patients with PDR. In addition, the contribution of cortistatin, a neuropeptide with strong structural similarities to somatostatin, to SLI and its levels in vitreous and plasma in both nondiabetic and diabetic patients has also been measured. RESERCH DESIGN AND METHODS: Plasma and vitreous fluid from 22 diabetic patients with PDR and 22 nondiabetic control subjects were analyzed. Somatostatin-14, somatostatin-28 and cortistatin were measured by radioimmunoassay but separation by high-performance liquid chromatography was required to measure somatostatin-14. RESULTS: The predominant molecular form of somatostatin within the vitreous fluid was somatostatin-28 (fivefold higher than somatostatin-14 in control subjects and threefold higher in patients with PDR). Cortistatin significantly contributed to SLI and its intravitreous levels were higher than those detected in plasma (nondiabetic control subjects: 147 [102-837] vs. 78 [24-32] pg/ml; patients with PDR: 187 [87-998] vs. 62 [24-472] pg/ml; P = 0.01 for both). Intravitreous somatostatin-14 was similar in both subjects with PDR and the control group (P = 0.87). By contrast, somatostatin-28 concentration was lower in patients with PDR than in nondiabetic control subjects (350 +/- 32 vs. 595 +/- 66 pg/ml; P = 0.004). CONCLUSIONS: Somatostatin-28 is the main molecular variant in the vitreous fluid. The intravitreous SLI deficit detected in patients with PDR is mainly due to somatostatin-28. Cortistatin is abundant in the vitreous fluid and significantly contributes to SLI. These findings could open up new strategies for PDR treatment.     

Deficit of somatostatin-like immunoreactivity in the vitreous fluid of diabetic patients: possible role in the development of proliferative diabetic retinopathy

OBJECTIVE: To evaluate the vitreous levels of somatostatin-like immunoreactivity (SLI) in patients with proliferative diabetic retinopathy (PDR). RESEARCH DESIGN AND METHODS: A total of 14 diabetic patients with PDR, in whom a vitrectomy was performed, were included in the study. Sixteen nondiabetic patients, with other conditions requiring vitrectomy, served as a control group. Both venous blood and vitreous samples were collected at the time of vitreoretinal surgery. Patients in whom intravitreous hemoglobin was detectable were excluded. In addition, a correction for plasma levels of SLI and intravitreal proteins was performed. SLI was measured by radioimmunoassay and vitreous hemoglobin by spectrophotometry. RESULTS: SLI in the vitreous fluid was significantly lower in diabetic patients than in the control group (68 +/- 18.7 vs. 193.6 +/- 30.8 pg/ml, P < 0.01). The vitreous SLI-to-plasma SLI ratio was strikingly higher in nondiabetic subjects than in diabetic patients with PDR (5.3 [1.2-71.1] vs. 0.6 [0.03-4.1], P < 0.01). After correcting for total vitreous protein concentration, SLI (pg/mg of proteins) remained significantly higher in nondiabetic control subjects than in diabetic patients with PDR (186 [51-463] vs. 7.5 [0.8-82], P < 0.0001). Remarkably, intravitreous levels of SLI were higher than those obtained in plasma in nondiabetic control subjects (193.6 +/- 30.8 vs. 43.5 +/- 10.7 pg/ml, P < 0.0001). Finally, a lack of relationship between plasma and vitreous levels of SLI was observed in both diabetic patients with PDR and nondiabetic control subjects. CONCLUSIONS: The significantly higher SLI in the vitreous fluid than in plasma detected in nondiabetic control subjects supports the concept that somatostatin plays a relevant role in retinal homeostasis. In addition, the intravitreous deficit of SLI observed in diabetic patients with PDR suggests that it might contribute to the process of retinal neovascularization.     

三维超声测量正常中晚期单胎妊娠胎儿产尿率

目的 应用三维超声测量正常中晚期单胎妊娠胎儿的膀胱容量以估算不同孕期胎儿的产尿率,并探讨胎儿产尿率与孕周及羊水指数之间的关系.方法 对138例正常中晚期单胎妊娠胎儿进行三维超声检查,采用三维超声体积自动测量技术,间隔5～15 min,重复2～3次测量胎儿膀胱容量并计算产尿率.结果 胎儿的产尿率随孕周增加而增加,自孕24周的12.84 ml/h升至孕42周的64.70 ml/h,二者之间有明显相关关系(r=0.900,P<0.05).胎儿的产尿率与羊水指数无明显相关关系(r=-0.199,P>0.05).结论 运用三维超声体积自动测量技术测量正常中晚期单胎妊娠胎儿的膀胱容量变化可估算胎儿的产尿率,并可了解胎儿肾功能状态及宫内安危情况.     

Changes in alpha 1-acid glycoprotein serum concentrations and glycoforms in the developing human fetus.

alpha 1-Acid glycoprotein concentrations and reactivity to concanavalin A were measured in maternal and fetal serum and amniotic fluid obtained from 24 women undergoing diagnostic cordocentesis at 20 to 33 wk gestation and in 30 additional fetal sera (19 to 34 weeks gestation). Maternal alpha 1-acid glycoprotein serum levels were five to ten times higher than fetal and amniotic levels. Fetal alpha 1-acid glycoprotein levels were found to increase with advancing gestational age. Using crossed immunoaffino electrophoresis with concanavalin A, alpha 1-acid glycoprotein patterns were identical in maternal serum and amniotic fluid but totally different in fetal serum. The fetal concanavalin A pattern changed progressively during fetal life towards that of the newborn. These data confirm earlier assumptions of fetal synthesis of alpha 1-acid glycoprotein and provide normal reference values for alpha 1-acid glycoprotein in fetal serum. In addition, the specific fetal concanavalin A pattern indicates that the alpha 1-acid glycoprotein glycosylation process during fetal life differs from that in post-natal life.     

Early fetal megacystis between 11 and 15 weeks of gestation.

OBJECTIVE: The purpose of this study was to evaluate the prognostic criteria of early fetal megacystis. DESIGN: A prospective, transvaginal ultrasound, cross-sectional study at 11-15 weeks of gestation at a tertiary referral fetal medicine unit. SUBJECTS AND METHODS: Sixteen pregnancies out of a total of 5240 were identified with early fetal megacystis. Fetal biometry, morphology, amniotic fluid, bladder size and volume were also evaluated. The karyotype was available in 15 cases. Vesicocentesis was performed in six fetuses and three had concomitant cystoscopies. RESULTS: In six fetuses, the megacystis was isolated. In the remaining ten, we detected associated hygroma (n = 5), nuchal translucency (n = 3), omphalocele (n = 1), mild pyelectasis (n = 1) and bilateral talipes (n = 1). In three cases the fetuses demonstrated renal hyperechogenicity with cysts, and in two cases oligohydramnios was found; four cases (25%) had chromosomal abnormalities; 47, XY + 13 (two cases), 47, XY + 18 and 47, XY + 21. Only one fetus from this study survived. In the remaining 13 cases, termination was proposed after counselling of the patients on the poor prognosis. The mean gestational age at termination was 15.5 +/- 2.4 weeks (range 12-20). Three fetal transabdominal cystoscopies did not allow us to view the valves; one urethral atresia was suspected, and confirmed postnatally. CONCLUSIONS: We found a high rate of associated malformations, especially intestinal malformations. The systematic evaluation of the intestinal enzymes in the amniotic fluid and urine samples might be an important aid in the diagnosis of multiple malformations, such as cloacal dysgenesis.     

The Ontogenesis of Human Fetal Hormones: I. GROWTH HORMONE AND INSULIN

The content and concentration of immunoreactive growth hormone (GH) were measured in 117 human fetal pituitary glands from 68 days of gestation to term and in the pituitary glands of 20 children 1 month to 9 yr of age. Physicochemical and immunochemical properties of GH of fetal pituitary glands and GH from adult pituitary glands were indistinguishable by disc gel electrophoresis, immunoelectrophoresis, starch gel electrophoresis, and radioimmunoassay techniques. In the fetal pituitary gland, the GH content rose from mean levels of 0.44+/-0.2 mug at 10-14 wk of gestation, to 9.21+/-2.31 mug at 15-19 wk, to 59.38+/-11.08 mug at 20-24 wk, to 225.93+/-40.49 mug at 25-29 wk, to 577.67+/-90 mug at 30-34 wk, and to 675.17+/-112.33 mug at 35-40 wk. There was a significant positive correlation between growth hormone content of the pituitary and gestational age, crown-rump length, and the weight of the pituitary gland.The content and concentration (micrograms/milligram) of human growth hormone (HGH) in the fetal pituitary showed significant increments (P < 0.001) for each 4 wk period of gestation until 35 wk. Further increases in the HGH content were noted in pituitaries of children aged 1-9 yr (range of 832 to 11.211 mug).Immunoreactive GH was detected in fetal serum at a concentration of 14.5 ng/ml as early as 70 days gestation, the youngest fetus assayed. At 10-14 wk, the mean concentration of serum growth hormone was 65.2+/-7.6 ng/ml; at 15-19 wk 114.9+/-12.5 ng/ml; at 20-24 wk 119.3+/-19.8 ng/ml; at 25-29 wk 72.0+/-11.5 ng/ml; and 33.5+/-4.2 ng/ml at term. A significant negative correlation of serum growth hormone with advancing gestational age after 20-24 wk was observed (P < 0.001). In 17 fetuses paired serum and pituitary samples were assayed; no significant correlation between the concentration of serum GH and the pituitary content or concentration of GH was demonstrable.The serum concentration of chorionic somatomammotropin (HCS) in the fetus was unrelated to gestational age. Insulin (1-30 muU/ml) was detected in 42 of 46 fetal sera assayed.These data suggest that the appearance and development of the secretory capacity for GH by the human fetal pituitary gland coincides with developmental changes in the portal system and hypothalamus. Maturation of inhibitory central nervous system control mechanisms for secretion of GH may not occur until infancy.     

Maternal and fetal atrial natriuretic peptide levels, maternal plasma renin activity, angiotensin II, prostacyclin and thromboxane A2 levels in normal and preeclamptic pregnancies.

To clarify the possible role of elevated atrial natriuretic peptide (ANP) in the pathophysiology of preeclampsia, we measured ANP, renin activity (PRA), angiotensin II (Ang II), TXB2 (a stable metabolite of TXA2) and 6-keto-PGF1 alpha (a stable end product of PGI2) concentrations in the plasma of 19 normal pregnant women and 35 severe preeclamptic patients at term. Plasma ANP levels in the preeclamptic patients (n = 35, 71.5 +/- 3.8 pg/ml, mean +/- S.E.) and also umbilical plasma ANP (n = 35, 83.0 +/- 4.2 pg/ml) were significantly (p less than 0.01) higher than those of normal pregnant women plasma (n = 19, 58.7 +/- 3.7 pg/ml) and umbilical plasma (n = 19, 47.6 +/- 4.7 pg/ml). There was a significant (p less than 0.01) positive correlation between maternal ANP levels and fetal ANP levels (n = 54, r = 0.44). Plasma PRA and 6-keto-PGF1 alpha levels in preeclampsia were significantly (p less than 0.05) lower than those of normal pregnancy. The ratio of 6-keto-PGF1 alpha/TXB2 in preeclampsia was significantly (p less than 0.01) lower than that of normal pregnancy as we reported previously. There was no significant correlation between plasma ANP level and plasma PRA, Ang II, plasma TXB2 and 6-keto-PGF1 alpha concentrations. Moreover there was no significant correlation between plasma ANP level and the severity of preeclampsia. These data suggest the possibility of a transplacental crossing of ANP secreted by feto-placental unit, which might be, at least in part, responsible for the high ANP levels observed in preeclampsia. The ANP in preeclampsia is not related directly to hypertension, but it may play a substantial role in the regulation or normalization of blood volume and vascular reactivity.     

Observations on the maturation of thyroid function in early fetal life

Serum samples were obtained from 21 normal human fetuses after therapeutic abortion for psychiatric indications. Fetal crown-rump length ranged from 5.2 to 22.5 cm, corresponding to the gestational age of 65-168 days.Serum thyroxine, assayed by a modification of the Murphy-Pattee method, was identified in the second smallest fetus examined at 78 days gestation. Thereafter it increased rapidly, maintaining a significant linear correlation with crown-rump length until term (r = 0.800, P < 0.001). Free thyroxine (FT4) also increased in a linear relation to gestational age (r = 0.908, P < 0.001), but reached term levels by 18-20 wk. Radioimmunoassayable thyroid-stimulating hormone (TSH) was detected at 78 days gestation. Levels increased rapidly with advancing gestation, so that by 16 wk almost all were within the range of term infants. After 16 wk gestation, levels were usually greater than 4.0 muU/cc, higher than that seen in normal children.No correlation was demonstrated between the serum TSH levels and total thyroxine. TSH and FT4, however, increased in a parallel manner with a significant positive correlation. This suggested that fetal TSH secretion was responsive to FT4 levels from very early in gestation, possibly as early as 11 wk.Thyroxine-binding globulin (TBG) was detected in a fetus of 78 days gestation (1.4 mug/100 ml). Levels increased rapidly, paralleling the rise in serum thyroxine and maintaining a linear correlation with crownrump length (r = 0.864, P < 0.001). Thyroxine-binding prealbumin binding capacity (TBPA) in fetuses 14-24 wk gestation was comparable with that seen at term.When examining the distribution of tracer amounts of thyroxine-(131)I (T4-(131)I) between the thyroxine-binding proteins, it was found that a major fraction was bound to TBPA and albumin during the early part of gestation. This decreased linearly with maturation of the fetus as the fraction bound to TBG increased. By 20 wk gestation fetal TBG was able to bind 78% of tracer despite a TBG capacity of only 7.7 mug/100 ml. This appeared to be the result of relatively low concentrations of TBPA and albumin during this period of gestation. The theoretical association constant calculated for fetal and newborn TBG was found to be similar to that estimated for normal adult males and females.