Vitamin A concentration in amniotic fluid and maternal serum related to neural-tube defects

The vitamin A concentration of amniotic fluid and maternal serum was measured during the second trimester of pregnancy in 106 women, 12 of whom had a baby with a neural-tube defect. In these 12 pregnancies the amniotic fluid vitamin A concentration was significantly higher than in 94 normal pregnancies. There was a highly significant correlation between amniotic fluid vitamin A and both zinc and alpha-fetoprotein (AFP) levels. The maternal serum vitamin A levels were also significantly related to serum zinc levels. Women with a raised serum AFP level, but a normal baby, had significantly higher amniotic fluid vitamin A levels and significantly lower serum vitamin A levels compared with those in women with normal serum AFP levels.     

Vitamin A concentration in amniotic fluid and maternal serum related to neural-tube defects

Summary. The vitamin A concentration of amniotic fluid and maternal serum was measured during the second trimester of pregnancy in 106 women, 12 of whom had a baby with a neural-tube defect. In these 12 pregnancies the amniotic fluid vitamin A concentration was significantly higher than in 94 normal pregnancies. There was a highly significant correlation between amniotic fluid vitamin A and both zinc and α-fetoprotein (AFP) levels. The maternal serum vitamin A levels were also significantly related to serum zinc levels. Women with a raised serum AFP level, but a normal baby, had significantly higher amniotic fluid vitamin A levels and significantly lower serum vitamin A levels compared with those in women with normal serum AFP levels.     

Maternal serum alpha-fetoprotein levels and fetal outcome in early second-trimester oligohydramnios.

Early second-trimester oligohydramnios was associated with normal maternal serum alpha-fetoprotein (MSAFP) levels in nine out of 26 cases (35 per cent). Congenital malformations of the fetal urinary tract resulting in fetal anuria were present in nine cases; in seven of them, normal MSAFP levels were measured. In contrast, normal MSAFP levels were established in only 2 out of the 17 cases without fetal malformations. These data suggest that fetal urine is the major source of elevated AFP in the maternal compartment in early second-trimester oligohydramnios. This is further supported by the lack of any relationship between concentrations of MSAFP non-reactive with Concanavalin A, originating mainly from the yolk sac-derived amniotic fluid AFP pool, and the presence of fetal diuresis. Three out of 26 women had experienced early second-trimester oligohydramnios in a previous pregnancy, suggesting the existence of a recurrence risk for this condition.     

AFP transport across the fetal membranes in the human

In this investigation the original observation of a correlation between the concentration of amniotic fluid albumin and maternal serum alpha fetoprotein (AFP), as a proof for amniotic fluid-derived AFP in the maternal compartment is confirmed at 15 and 16 weeks of gestation. In contrast to the earlier reported highly significant relation in this study the correlation is only weak, especially at 15 weeks. This might be in agreement with a more frequent absence of raised maternal serum AFP levels in cases of raised amniotic fluid AFP levels prior to 16 weeks of gestation. Transamniotic AFP transport contributes a minor part of the AFP present in the maternal compartment, as also indicated by the lack of correlation between AFP concentrations in amniotic fluid and maternal serum.     

P-type inositol phosphoglycans in serum and amniotic fluid in active pre-eclampsia

OBJECTIVES: Abnormal secretion of P-type inositol phosphoglycans (IPG-P) has been described in maternal urine of pre-eclamptic women. The aim of this study was to determine the origin of production of IPG-P. We examined the IPG-P content of maternal and fetal serum, maternal urine and amniotic fluid in both normal pregnancy and pre-eclampsia. DESIGN: Established extraction and bioactivity assay techniques were used to compare total IPG-P levels in serum samples, and a polyclonal-antibody-based ELISA to assay the amniotic fluid and urine samples in matched pairs of women. SUBJECTS: Eleven women with pre-eclampsia requiring caesarean section (subjects), 11 pregnant women requiring elective caesarean section for reasons other than pre-eclampsia (controls). RESULTS: Our data confirm the abnormal level of IPG-P in maternal urine during pre-eclampsia. Moreover, IPG-P levels were higher in umbilical sera than in maternal sera samples. Amniotic fluid as well as urine ELISA results were significantly higher in the pre-eclamptic group compared with normal controls. Total IPG-P bioactivity in serum did not vary between serum compartments in normal pregnancy. Uterine vein IPG-P levels were lower in pre-eclampsia when compared with normal pregnancy. A possible correlation was observed between urine and amniotic fluid levels in normal women. No correlation was observed between measured blood levels and those in urine and amniotic fluid. CONCLUSIONS: It is hypothesized that steady state equilibrium of IPG-P in serum in normal pregnancy is disrupted in pre-eclampsia. Additionally, an abnormal IPG-P sub-fraction, detectable in urine and amniotic fluid, may be present and involved in the pathophysiology of the syndrome, although sites of production of this abnormal form remain unclear.     

Amniotic fluid and maternal serum leptin levels in pregnant women who subsequently develop preeclampsia

OBJECTIVES: To study the correlation between amniotic fluid leptin levels and maternal serum leptin levels during the early second trimester, and to determine whether the ratios of amniotic fluid leptin levels to maternal serum leptin levels are elevated in pregnant women who subsequently develop preeclampsia. STUDY DESIGN: Samples from 120 pregnant women were included in this prospective study, of which 20 were from pregnant women who subsequently developed preeclampsia and 100 were from normal pregnant women. Both the amniotic fluid and the maternal serum leptin levels were ascertained by radioimmunoassay (RIA). RESULTS: A strong correlation between amniotic fluid leptin levels and maternal serum leptin levels was observed in both preeclamptic and normal pregnant women. In addition, the ratios of amniotic fluid leptin levels to maternal serum leptin levels were positively correlated to amniotic fluid leptin levels, but negatively correlated to maternal serum leptin levels. Furthermore, the ratios of amniotic fluid leptin levels to maternal serum leptin levels in preeclamptic women were significantly higher than those in normal pregnant women. CONCLUSIONS: Amniotic fluid leptin levels correlated with maternal serum leptin levels during the early second trimester. The ratios of amniotic fluid leptin levels to maternal serum leptin levels were elevated in preeclamptic women. However, the maternal serum leptin levels themselves showed no such elevation. Therefore, this elevated ratio may be a marker at the early stage of pregnancy in preeclamptic women.     

The significance of raised maternal serum alpha-fetoprotein levels.

A radioimmunoassay for alpha-fetoprotein (AFP) is described and normal ranges for both maternal serum and in amniotic fluid throughout pregnancy are defined. Maternal serum AFP levels in at risk pregnancies were found to be no different from those in normal pregnancies. AFP levels in pregnancies complicated by neural tube and other congenital defects, fetal death or maternal hypertension are documented. Eight patients with a fetus deformed by anencephaly or an open spina bifida were tested before 22 weeks; seven of them had raised serum AFP levels. Other causes of raised serum AFP levels are described and the significance of a raised serum AFP level is discussed with particular reference to screening programmes.     

Prenatal diagnosis of spina bifida aperta after first-trimester valproate exposure.

In the context of a prospective study on the adverse effects of anti-epileptic drugs on fetal outcome, we evaluated our experience with prenatal diagnosis by ultrasonography and alpha-fetoprotein (AFP) determination in amniotic fluid. We compared these results with AFP values in maternal serum obtained prior to amniocentesis. From November 1985 to July 1990, amniocentesis at 16-18 weeks of gestation was performed in 267 pregnancies of 237 different women using anti-epileptic drugs. Among 92 pregnancies with maternal valproic acid use, five (including one concordantly affected monozygotic twin-pair) were terminated because of a spina bifida aperta, all prenatally diagnosed by AFP determination and acetylcholinesterase electrophoresis in amniotic fluid. The maternal serum AFP level was raised (> or = 2.5 multiples of the median (MOM) for singleton pregnancies and > or = 4.5 MOM for twin pregnancies) in only two of these five affected pregnancies. We emphasize that maternal serum AFP levels may be unreliable for prenatal screening for fetal neural tube defects in women taking valproate and recommend that amniocentesis and fetal ultrasound examination should be offered directly.     

Changes in alpha-fetoprotein levels in a case with multiple congenital anomalies.

A chromosomally normal women, who previously lost an infant with meningomyelocele and hydrocephalus, with a chromosomally normal husband, had normal alpha fetoprotein (AFP) levels in both amniotic fluid and maternal serum at about 19 weeks gestation. At 34 weeks, suspected hydramnios was confirmed clinically and radiographically; the latter showed no evidence of hydrocephalus. AFP levels at 36 weeks showed 224 ng/ml in maternal serum and 1249 ng/ml in amniotic fluid. Maternal serum rose from the 25th-19th percentile, and amniotic level was 5-fold greater than normal (200 ng/ml). At 39 weeks, abnormal AFP values of 258 and 1500 ng/ml for maternal serum and amniotic fluid, respectively, were measured. Though AFP patterns did not suggest an open neural tube defect (higher 19-week values were expected), spontaneous labor at 39 weeks resulted in a 1930-gm female with multiple congenital abnormalities. These AFP assays suggest: 1) that signaling of abnormalites other than neural tube defects is a valid use of AFP assays; 2) that the slope rather than single point values should be used in interpreting AFP results; 3) that assays in both amniotic fluid and maternal serum should be obtained and interpreted simultaneously in screening for birth defects; and 4) that sequential assays should be performed even in the presence of initially normal findings.     

Total alpha-fetoprotein and Lens culinaris agglutinin-reactive alpha-fetoprotein in fetal chromosomal abnormalities

Objective To examine the differences in multiples of the median (MoM) of total alpha-fetoprotein, and the proportion of Lens culinaris agglutinin reactive alpha-fetoprotein (% alpha-fetoprotein-L2+L3) in the maternal serum and amniotic fluid of pregnant women whose fetuses were diagnosed with autosomal or sex chromosomal abnormalities.
Design Prospective consecutive series.
Setting University hospital.
Sample Maternal sera and amniotic fluids from 46 pregnant women with trisomy 21 fetuses, 10 pregnant women with trisomy 18 fetuses, one pregnant woman with a trisomy 13 fetus, six pregnant women with fetal sex chromosomal abnormalities, and 100 pregnant women for whom the fetal karyotype was diagnosed as normal following a genetic amniocentesis.
Results The proportion of alpha-fetoprotein-L2+L3 in maternal serum for trisomy 21 (40.3%, P <0.0001) and trisomy 18 (39.8%,   P <0.05  ) showed a significantly higher value compared with normal (32.6%). The proportion of alpha-fetoprotein-L2+L3 in amniotic fluid was significantly higher (   P <0.0001  ) for trisomy 21 (46.6%) than for a normal karyotype (41.5%). Only for the trisomy 21 group was there a strong correlation in the % alpha-fetoprotein-L2+L3 between maternal serum and amniotic fluid (r=0.840, P <0.0001). For all groups, there was no correlation between alpha-fetoprotein MoM and % alpha-fetoprotein-L2+L3 in maternal serum and amniotic fluid.
Conclusion The proportion of alpha-fetoprotein-L2+L3 in maternal serum is an appropriate choice for a trisomy 21 biochemical marker, and it is possible that combining alpha-fetoprotein-L2+L3 analysis with assays of alpha-fetoprotein in maternal serum could further improve the sensitivity and specificity of multiple marker screening.     

Study of interleukin-6 and tumor necrosis factor-alpha levels in maternal serum and amniotic fluid of patients with premature rupture of membranes

To study the change and clinical significance of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels in the maternal serum and amniotic fluid of pregnant women with chorioamnionitis and with premature rupture of membranes. Twenty-six normal-term pregnant women formed the control group, and forty-six pregnant women with premature rupture of membranes were enrolled for the study. Maternal serum and amniotic fluid IL-6 and TNF-alpha levels were measured using a sensitive radioimmunoassay and enzyme-linked immunosorbent assay (ELISA); chorioamnionitis was diagnosed by fetal membrane pathology. The maternal serum IL-6 levels and amniotic fluid IL-6 and TNF-alpha levels were higher than those of the control (P < 0.01). There was a significant relationship between maternal serum IL-6 and maternal serum and amniotic fluid IL-6 and TNF-alpha with the time of the premature rupture of membranes, i.e. the longer the time, the higher the maternal serum and amniotic fluid IL-6 and TNF-alpha. There were 12 patients with chorioamnionitis in premature rupture of membranes and their maternal serum and amniotic fluid IL-6 and TNF-alpha levels were higher than that of non-chorioamnionitis patients (P < 0.01-0.05). IL-6 and TNF-alpha levels in maternal and amniotic fluids are a valuable index in identification of the chorioamnionitis in patients with premature rupture of membranes.     

Correlation of elevated leptin levels in amniotic fluid and maternal serum in neural tube defects

OBJECTIVE: To measure maternal serum and amniotic fluid leptin concentrations in pregnant women diagnosed antenatally as having fetuses with a neural tube defect in the second trimester. METHODS: Twenty pregnant women who had fetuses with a neural tube defect detected on ultrasonography (neural tube defect group) in the second trimester and 20 women who had abnormal triple screens indicating an increased risk for Down syndrome but had healthy fetuses (control group) were enrolled in the study. Amniotic fluid was obtained by amniocentesis, and maternal serum samples were taken simultaneously. RESULTS: The mean leptin levels in amniotic fluid (P <.001) and maternal serum (P <.05) of patients who had fetuses with a neural tube defect were found to be significantly higher than control group levels. The mean leptin levels in maternal serum of both groups were also higher than leptin levels in amniotic fluid (P <.05 for the neural tube defect group and P <.001 for the control group). Although there were significant correlations between maternal weight, weight gain, body mass index at the time of amniocentesis, and maternal serum leptin concentrations in both groups, a significant correlation between leptin concentrations in maternal serum and amniotic fluid was found only in the neural tube defect group (P <.05). CONCLUSIONS: We found significantly higher leptin levels in both amniotic fluid and maternal serum of patients who had fetuses with a neural tube defect. We suggest that the main source of leptin in amniotic fluid of pregnant women who had fetuses with a neural tube defect is the leakage into amniotic fluid from cerebrospinal fluid. The increase of maternal serum leptin concentrations has been attributed to the transportation of amniotic fluid leptin to the maternal circulation.     

alpha-Fetoprotein levels in pregnancies complicated by gastrointestinal abnormalities of the fetus.

alpha-Fetoprotein (AFP) levels have been measured in maternal serum and amniotic fluid in a variety of gastrointestinal abnormalities of the fetus. Maternal serum AFP levels were consistently elevated in abdominal wall defects of the fetus after 15 weeks gestation and the amniotic fluid levels were raised in 3 of the 4 patients measured. In atresia of the gastrointestinal tract and diaphragmatic hernia, serum AFP levels were usually normal unless there was an associated neural tube defect or multiple pregnancy, although the majority were not measured between 15 and 26 weeks gestation. If elevated amniotic fluid levels of AFP are used in the decision to terminate pregnancy on the assumption of a probable neural tube defect of the fetus, a proportion of terminations will be performed because of abdominal wall defects of the fetus.     

The association of birthweight with maternal and cord serum and amniotic fluid growth hormone and insulin levels, and with neonatal and maternal factors in pregnant women who delivered at term

AIM: To investigate the influence of maternal and cord serum and amniotic fluid growth hormone (GH) and insulin and other neonatal and maternal factors on birthweight. METHODS: A total of 160 pregnant women at 38-42 weeks' gestation were studied. All infants were categorized as small for gestational age (SGA) (n = 50), large for gestational age (LGA) (n = 50) or average for gestational age (AGA) (n = 60). GH and insulin levels were measured in maternal and cord serum and amniotic fluid at birth. RESULTS: GH levels in maternal and cord serum and amniotic fluid showed no differences among the three weight groups (P > 0.05). The cord insulin level was significantly lower in SGA (P < 0.01). The insulin level in venous cord blood correlated with birth and placental weights and neonatal height, whereas maternal serum and amniotic fluid insulin levels, and maternal and cord serum and amniotic fluid GH levels did not show any correlation with birthweight. The cord GH level at birth was correlated with GH levels after 4 postnatal weeks in the SGA group (P < 0.01). In addition, birthweight showed a correlation with prepartum maternal weight, maternal weight gain, maternal height, neonatal length and placental weight in all three weight groups. CONCLUSIONS: Cord GH, maternal serum and amniotic fluid GH and insulin levels did not correlate with birthweight in all three weight groups. The lack of correlation for GH levels in maternal and cord serum and amniotic fluid suggests that these compartments may be non-communicating separate units.     

Raised maternal serum alpha-fetoprotein in the absence of fetal abnormality--placental findings. A quantitative morphometric study

Ten placentae from pregnancies proceeding to term from mothers who on routine screening at 16-18 weeks gestation were found to have raised serum AFP but no increase in amniotic fluid AFP and no fetal abnormality, were studied using morphometric techniques. The results were compared with 20 placentae from normal term pregnancies where the maternal serum AFP level was not elevated. The mean total placental volume, volume of parenchyma and villous surface area were increased in the placentae associated with a raised maternal serum AFP. More of these placentae were infarcted and the fetal-placental weight ratio was significantly lower. The hypothesis that elevation of maternal serum AFP level is related to the increase in placental size is addressed.     

Is routine fetal karyotyping necessary for patients undergoing amniocentesis for elevated maternal serum alpha-fetoprotein?

OBJECTIVE: The object of the study was to determine the necessity of routine fetal karyotyping in patients undergoing amniocentesis for elevated maternal serum alpha-fetoprotein (AFP). METHODS: Data were collected retrospectively on patients under age 35 who underwent amniocentesis for elevated maternal serum AFP at the University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey, between 1 January 1986 and 31 March 1995. A total of 537 patients with maternal serum AFP values greater than 2.5 multiples of the median were included in the study. RESULTS: Of 509 patients in the group with normal amniotic fluid AFP, 505 had a normal karyotype (specificity 94.9%, negative predictive value 99.2%). One of 28 patients in the group with an elevated amniotic fluid AFP demonstrated an abnormal karyotype (sensitivity 20%, positive predictive value 3.6%). CONCLUSIONS: Routine fetal chromosomal analysis of amniotic fluid amniocytes may not be necessary in patients with a normal level of amniotic fluid AFP. A fetal karyotype is recommended in those patients with an elevated amniotic fluid AFP.     

Risk of fetal chromosomal anomalies in patients with elevated maternal serum alpha-fetoprotein.

When elevated maternal serum alpha-fetoprotein (MSAFP) results lead to diagnostic amniocentesis, a decision of whether to karyotype fetal cells must be made. We examined our experience with MSAFP screening in 71,563 unselected pregnancies in which karyotyping was performed when amniocentesis was done because of MSAFP elevations. A total of 727 women (1.0%) underwent amniocentesis because of elevated MSAFP values and among this group, seven chromosomal anomalies (incidence one in 104) were detected. Of the 727 women, 658 (91%) had normal amniotic fluid AFP. In this group, there were six (one in 109) chromosomally abnormal fetuses: three with triploidy, two with 47,XXX, and one with 46,XX,1q-. Among the 69 pregnancies with elevated amniotic fluid AFP, one fetal chromosomal anomaly (trisomy 13) was diagnosed. The incidence of all chromosomal anomalies observed in women undergoing amniocentesis because of elevated MSAFP is comparable to that reported in women 36 years of age undergoing testing because of advanced maternal age. We believe that chromosome analysis should be performed on amniotic fluid samples obtained because of elevated MSAFP unless there are compelling financial circumstances that preclude this. Even in such cases, cell cultures should be established until the amniotic fluid AFP result is available. Chromosome analysis is essential when the amniotic fluid AFP is elevated because of the known association between open fetal defects (spina bifida, omphalocele, and scalp defects) and trisomies 13 and 18.     

gamma-Glutamyl transpeptidase of human amniotic fluid

gamma-Glutamyl transpeptidase (GGTP) activity in normal amniotic fluids and corresponding maternal sera obtained at various gestational periods was measured. The ontogenic pattern of enzyme activity in amniotic fluid is very similar to alpha fetoprotein (AFP). However, the levels of these two proteins behaved differently in corresponding maternal sera. Also, in amniotic fluids obtained from pregnancies with neural tube defects (NTD), only AFP concentration was abnormally high whereas GGTP activity was normal.     

Amniotic fluid human chorionic gonadotrophin and alpha-fetoprotein levels in pregnancies conceived after assisted reproduction

OBJECTIVES: To study the alteration in the second-trimester maternal serum levels of human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) in pregnancies conceived after assisted reproduction. METHODS: We compared the amniotic fluid hCG and AFP concentrations of 45 pregnancies with fresh embryo transfer and 25 pregnancies with frozen-thawed embryo transfer with 269 spontaneous pregnancies. Wilcoxon rank-sum test was used for analysis. RESULTS: The median amniotic fluid hCG MoM in pregnancies conceived after frozen-thawed embryo transfer was significantly increased to 1.41 compared to 1.00 (p = 0.01) in naturally occurring pregnancies and 0.96 (p = 0.049) in pregnancies after fresh embryo transfer. Further analysis showed that this was only observed in frozen embryos fertilized by conventional insemination with MoM of 1.59. The AFP MoMs were similar among the groups. CONCLUSIONS: The observed raised amniotic fluid hCG level in IVF-FET pregnancies may reflect the elevated maternal serum level in these pregnancies. Further studies should be directed towards exploring the underlying pathophysiology.     

Oral hypoglycemic agents in pregnancy: their time has come

Objective: The object of the study was to determine the necessity of routine fetal karyotyping in patients undergoing amniocentesis for elevated maternal serum &#102 -fetoprotein (AFP). Methods: Data were collected retrospectively on patients under age 35 who underwent amniocentesis for elevated maternal serum AFP at the University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey, between 1 January 1986 and 31 March 1995. A total of 537 patients with maternal serum AFP values greater than 2.5 multiples of the median were included in the study. Results: Of 509 patients in the group with normal amniotic fluid AFP, 505 had a normal karyotype (specificity 94.9%, negative predictive value 99.2%). One of 28 patients in the group with an elevated amniotic fluid AFP demonstrated an abnormal karyotype (sensitivity 20%, positive predictive value 3.6%). Conclusions: Routine fetal chromosomal analysis of amniotic fluid amniocytes may not be necessary in patients with a normal level of amniotic fluid AFP. A fetal karyotype is recommended in those patients with an elevated amniotic fluid AFP.