Trisomy 18 and maternal serum and amniotic fluid alpha-fetoprotein

Maternal serum and amniotic fluid alpha-fetoprotein levels were studied retrospectively in a total of 58 pregnancies with trisomy 18. In those pregnancies uncomplicated by either fetal exomphalos or neural tube defect the midtrimester maternal serum alpha-fetoprotein (MSAFP) levels were markedly reduced, the median value for 38 such pregnancies being 0.6 multiples of the median (MoM). Trisomy 18 with exomphalos was associated with a higher median MSAFP, but still within the normal range: 1.1 MoM, (nine pregnancies); trisomy 18 with exomphalos and neural tube defect (NTD) was associated with grossly raised levels: median MSAFP was 4.5 MoM (three pregnancies). Amniotic fluid alpha-fetoprotein (AFAFP) levels were normal in uncomplicated trisomy 18 pregnancies: median AFAFP, for 19 pregnancies, was 1.1 MoM. Exomphalos alone, or together with neural tube defect, was associated with greatly elevated levels of AFAFP; for exomphalos alone median AFAFP was 9.59 MoM (four pregnancies), and for exomphalos with neural tube defect the median AFAFP was 23.95 Mom (three pregnancies). Screening with low and high MSAFP, routine ultrasound, and amniocentesis on all women aged 35 years or over, together might identify over 50 per cent of pregnancies with trisomy 18.     

Amniotic fluid alpha-fetoprotein levels and the prenatal diagnosis of neural tube defects: a collaborative study of 2180 pregnancies in the Netherlands.

Amniotic fluid alpha-fetoprotein (AFP) concentrations were measured in 2180 patients at risk of fetal abnormality because of previous history, family history, advanced maternal age, suspected fetal growth retardation and hydramnios. In 12 patients investigated before 20 weeks gestation, pregnancy was terminated because of a raised amniotic fluid AFP-level: 11 fetuses had neural tube defects (NTDs) and one had a congenital nephrosis. There were no false negative results in the 1927 patients tested before 20 weeks and with a pregnancy of known outcome. In patients tested after 20 weeks, the amniotic fluid AFP concentration was raised in 20 cases of anencephaly, in 9 fetuses with severe congenital malformations without NTD and in one apparently normal fetus. Of 428 patients with a previous offspring who had a NTD, only 8(1.9 per cent) again had a fetus with a NTD.     

Elevated maternal serum alpha-fetoprotein concentration and fetal chromosomal abnormalities.

Amniocentesis was performed in 1038 patients with elevated maternal serum alpha-fetoprotein (MSAFP) concentrations. Patients were divided into two groups based upon the amniotic fluid AFP concentration. Group 1 (N = 964) had a normal amniotic fluid AFP concentration and group 2 (N = 74) had elevated amniotic fluid AFP. Fetal chromosomal results were reviewed from the study population, with the finding of eight major fetal chromosomal abnormalities. Of the eight fetal chromosomal abnormalities, five were associated with elevated amniotic fluid AFP and three were associated with normal amniotic fluid AFP. The sensitivity and specificity of elevated amniotic fluid AFP concentrations in screening for a fetal chromosomal abnormality were 62.5 and 93.3%, respectively. In women with elevated MSAFP but normal amniotic fluid AFP concentrations, the probability of a major fetal chromosomal abnormality is extremely small.     

Prenatal diagnosis of neural tube defects. I. Problems and pitfalls: analysis of 2495 cases using the alpha-fetoprotein assay.

The alpha-fetoprotein (AFP) assay is now an established tool for the prenatal diagnosis of neural tube defects (NTDs). About 90% of these defects are diagnosable prenatally early in the second trimester, the other 10% consisting of closed lesions that are not amenable to this approach. From the analysis of our 2495 consecutive cases, 49 NTDs were diagnosed with AFP levels 3 SD above the mean. One closed NTD sample, as expected, did not have an elevated AFP level. Various other fetal disorders or conditions were also associated with elevated AFP levels. AFP assays on amniotic fluids from 1858 patients without a family history of NTD and studied primarily for fetal karyotyping yielded a frequency of 1 NTD in 310 cases. Any amniotic fluid study in the second trimester of pregnancy should include an assay for AFP.     

Folate and vitamin B12 concentrations in maternal and fetal blood, and amniotic fluid in second trimester pregnancies complicated by neural tube defects.

OBJECTIVE: To investigate maternal and fetal folate and vitamin B12 concentrations in pregnancies affected by neural tube defects (NTD). DESIGN: Measurement of folate and vitamin B12 concentrations in amniotic fluid, fetal blood and maternal blood samples in midgestation. SUBJECTS: 32 women undergoing termination of pregnancy at 14-21 weeks gestation for social reasons (n = 24) or for fetuses with neural tube defects (n = 8). INTERVENTIONS: Fetoscopy before intra-amniotic injection of prostaglandins. RESULTS: In normal pregnancies there was a positive correlation between maternal and fetal serum folate, and the fetal serum and red blood cell folate concentrations were higher than the maternal. There were no differences in amniotic fluid, maternal blood or fetal blood folate concentrations between pregnancies with NTD and normal pregnancies. Although amniotic fluid vitamin B12 was lower in pregnancies with NTD, maternal serum vitamin B12 concentration was not reduced. CONCLUSION: In this small group of pregnancies with NTD at mid-gestation there is no evidence to suggest folate or vitamin B12 deficiency.     

Maternal plasma alpha-fetoprotein screening for fetal neural tube defects.

Maternal plasma alpha-fetoprotein (AFP) screening for fetal neural tube defects (NTD) was used as a part of routine antenatal care in three hospitals over a 26 month period. Blood samples were obtained for plasma AFP measurement at 15 to 20 weeks gestation from 6377 women, representing 79 per cent of antenatal bookings. The outcome of pregnancy was ascertained in 96 per cent of patients: 13 cases of anencephaly and 7 of open spina bifida were detected by plasma screening and a further 3 cases of open NTD through the mother's previous medical history and amniotic fluid determination. Four fetuses with open NTDs and four with closed NTDS were not detected by plasma AFP measurement and the detection efficiency for open NTDs was thus 83 per cent. Integration of screening into the existing pattern of antenatal care required only minor alterations in clinic schedules. Some extra time was needed for explanation of the objectives of the study, for ultrasound examination and for amniocentesis. Eight patients declined the offer of a plasma test, while only one refused an amniocentesis.     

Amniotic fluid alpha-fetoprotein levels and prenatal diagnosis of autosomal trisomies

Pregnancies with fetal trisomy 21 have been associated with low amniotic fluid alpha-fetoprotein levels (AFAFP). This observation led to the suggestion that low AFAFP levels be used as a criterion for completion of a chromosomal analysis in patients who are not otherwise at increased risk for a fetal chromosome abnormality and in whom karyotyping might not have been completed for economic reasons. In order to assess the usefulness of such criteria, we reviewed the AFAFP levels of 90 cases of fetal trisomy 21, 23 cases of trisomy 18, and 10 cases of trisomy 13. These were compared with 2400 control samples with normal chromosome constitution. AFAFP levels were generally lower in pregnancies with trisomy 21, showing a median value of 0.72 MoM. However, 40 per cent of the trisomy 21 samples had AFAFP values greater than 0.8 MoM and 20 per cent were over 1.0 MoM. These data imply that over 50 per cent of Down syndrome cases might have been missed using a cut-off level of 0.70 MoM for completion of chromosome analysis. Using a higher cut-off level will leave only a small percentage of samples unkaryotyped. The distribution of AFP levels in trisomy 13 and 18 is no different from controls; we therefore believe that fetal karyotyping should be completed in every amniotic fluid sample obtained.     

Prenatal diagnosis, fetal surgery, recurrence risk and differential diagnosis of neural tube defects

Prenatal screening with alpha-fetoprotein (AFP) and ultrasonography have allowed the prenatal diagnosis of neural tube defects (NTDs) in current obstetric care, and open spina bifida has been considered a potential candidate for in utero treatment in modern pediatric surgery. This article provides an overview of maternal serum AFP screening, amniotic fluid AFP assays, amniotic fluid acetylcholinesterase immunoassays and level II ultrasound for NTDs, prenatal repair of fetal myelomeningocele, recurrence risk of NTDs, and differential diagnosis of NTDs on prenatal ultrasound.     

Maternal serum alpha-fetoprotein screening: promise not yet fulfilled.

Measurement of alpha fetoprotein (AFP) levels in amniotic fluid has been used as a diagnostic tool for detection of neural tube defects (NTDs) in the fetus. AFP measurement in conjunction with ultrasonography yields a 90% NTD detection rate. The technique is recommended for use in pregnancies known to be at risk of NTDs and as a screening technique for use with 2nd-trimester amniocentesis. In recent years, maternal serum AFP assays have been used for NTD detection. The technique has promise as a diagnostic tool but is not recommended for routine maternal screening. Problems with maternal AFP screening are: 1) the large number of false positive results; 2) lack of general patient and physician education on the screening technique; 3) technical problems related to the assay; 4) inconsistency of assay results from 1 laboratory to another; and 5) the lack of established normal standards for the test.     

Are amniotic fluid alpha-fetoprotein levels influenced by the gender in twin pairs?

OBJECTIVES: To examine the assumption that amniotic fluid alpha-fetoprotein (AFAFP) levels are different in female and male twin fetuses. DESIGN: Amniotic fluid levels of AFP in pregnancies with female and male fetuses in gender-concordant and gender-discordant twins were compared. A t test of p < 0.05 was considered significant. MATERIAL AND METHODS: Between 1995 and 1999, 332 genetic amniocenteses on twin pregnancies were performed at Meir Hospital, Kfar Saba, and Rambam Hospital, Haifa, Israel. One hundred and sixty-six were concordant for gender (84 females and 82 males) while 166 pairs differed in their gender. The amniotic fluid AFP levels of each sac were measured using fluorescent immunoassay methods by an AutoDELFIA machine. RESULTS: The mean levels of AFAFP were lower in female twins compared to their male counterparts in same-gender twins (p = 0.07), although the difference was quite small. Nevertheless, there was no such difference between AFAFP of male versus female fetuses in gender-discordant twins. CONCLUSIONS: The levels of AFAFP were higher in the male twins of gender-concordant twins in comparison to female twins. No such difference was found between female versus male fetuses in gender-disconcordant twins.     

Fetal death: A condition with a dissociation in the concentrations of soluble vascular endothelial growth factor receptor-2 between the maternal and fetal compartments

Objective.?An anti-angiogenic state has been implicated in the pathophysiology of preeclampsia, fetal growth restriction and fetal death. Vascular endothelial growth factor (VEGF), an indispensible angiogenic factor for embryonic and placental development exerts its angiogenic properties through the VEGF receptor (VEGFR)-2. A soluble form of this protein (sVEGFR-2) has been recently detected in maternal blood. The aim of this study was to determine if fetal death was associated with changes in the concentrations of sVEGFR-2 in maternal plasma and amniotic fluid.

Study Design.?Maternal plasma was obtained from patients with fetal death (n?=?59) and normal pregnant women (n?=?134). Amniotic fluid was collected from 36 patients with fetal death and the control group consisting of patients who had an amniocentesis and delivered at term (n?=?160). Patients with fetal death were classified according to the clinical circumstances into the following groups: (1) unexplained; (2) preeclampsia and/or placental abruption; (3) chromosomal and/or congenital anomalies. Plasma and amniotic fluid concentrations of sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied.

Results.?(1) Patients with a fetal death had a significantly lower median plasma concentration of sVEGFR-2 than normal pregnant women (p?<?0.001). The median plasma concentration of sVEGFR-2 in patients with unexplained fetal death and in those with preeclampsia/abruption, but not that of those with congenital anomalies, was lower than that of normal pregnant women (p?=?0.006, p?<?0.001 and p?=?0.2, respectively); (2) the association between plasma sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 3.2; 95% CI: 1.4–7.3 per each quartile decrease in plasma sVEGFR-2 concentrations); (3) each subgroup of fetal death had a higher median amniotic fluid concentration of sVEGFR-2 than the control group (p?<?0.001 for each); (4) the association between amniotic fluid sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 15.6; 95% CI: 1.5–164.2 per each quartile increase in amniotic fluid sVEGFR-2 concentrations); (5) among women with fetal death, there was no relationship between maternal plasma and amniotic fluid concentrations of sVEGFR-2 (Spearman Rho: 0.02; p?=?0.9).

Conclusion.?Pregnancies with a fetal death, at the time of diagnosis, are characterized by a decrease in the maternal plasma concentration of sVEGFR-2, but an increase in the amniotic fluid concentration of this protein. Although a decrease in sVEGFR-2 concentration in maternal circulation depends upon the clinical circumstances of fetal death, an increase in sVEGFR-2 concentration in amniotic fluid seems to be a common feature of fetal death. It remains to be determined if the perturbation in sVEGFR-2 concentrations in maternal and fetal compartments observed herein preceded the death of a fetus.     

Participation of the novel cytokine interleukin 18 in the host response to intra-amniotic infection

OBJECTIVE: Interleukin 18 is a proinflammatory pleiotropic cytokine that has been implicated in the host defense against infection. This study was undertaken to determine whether interleukin 18 concentrations change in the maternal, fetal, and amniotic fluid compartments with labor (term and preterm) and microbial invasion of the amniotic cavity. STUDY DESIGN: Amniotic fluid was assayed for interleukin 18 in samples obtained from 285 patients in the following groups: (1) term not in labor (n = 22), in labor (n = 19), and with microbial invasion of the amniotic cavity (n = 16); (2) preterm labor who delivered at term (n = 38), who delivered preterm but without microbial invasion of the amniotic cavity (n = 41), and preterm labor with microbial invasion of the amniotic cavity (n = 24); (3) preterm premature rupture of membranes without microbial invasion of the amniotic cavity (n = 30) and with microbial invasion of the amniotic cavity (n = 34); (4) term premature rupture of membranes not in labor (n = 20) and term premature rupture of membranes in labor (n = 19); and (5) midtrimester (n = 22). In addition, cord and maternal plasma samples from women at term not in labor (n = 20) and in labor (n = 20) were assayed for interleukin 18. RESULTS: (1) Interleukin 18 was detectable in all amniotic fluid samples and maternal and umbilical cord blood samples. (2) Interleukin 18 concentrations increased with advancing gestational age (r = 0.47; P <.0001). (3) Microbial invasion of the amniotic cavity in either preterm or term parturition was associated with a significant increase in the amniotic fluid concentration of interleukin 18 (preterm labor without microbial invasion of the amniotic cavity: median, 14.95 pg/mL; range, 3.9-277.0 pg/mL; vs preterm labor with microbial invasion of the amniotic cavity: median, 20.75 pg/mL; range, 5.53-160.21 pg/mL; P <.02; term labor without microbial invasion of the amniotic cavity: median, 18.73 pg/mL; range, 5.09-95.44 pg/mL; vs term labor with microbial invasion of the amniotic cavity: median, 24.35 pg/mL; range, 10.07-144.42 pg/mL; P<.004). (4) Both term and preterm parturition were associated with a modest increase in amniotic fluid interleukin 18 concentrations, although this trend did not reach statistical significance. (5) Rupture of membranes at term was associated with a significant decrease in amniotic fluid interleukin 18 concentrations (intact membranes: median, 14.96 pg/mL; range, <3.89-26.07 pg/mL; vs rupture of membranes: median, 10.1 pg/mL; range, 4.29-21.44 pg/mL; P <.001). CONCLUSION: (1) Interleukin 18 is increased in cases of microbial invasion of the amniotic cavity. (2) Interleukin 18 is detectable in the amniotic, maternal, and fetal compartments. (3) We propose that this novel cytokine plays a role in the host defense against infection.     

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.     

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.     

Prenatal Characteristics of Congenital Nephrosis

The purpose of this study was to evaluate the prenatal characteristics of congenital nephrosis of the Finnish type (CNF). Patients presenting with elevated maternal serum and/or amniotic fluid α-fetoprotein levels, normal ultrasound examinations and normal fetal karyotypes were included.

A retrospective cohort study was conducted using questionnaires sent to all board certified clinical geneticists. Perinatal outcome, including histologic verification of CNF, was obtained.

Forty index cases met the above criteria. Ten cases ultimately did not have the diagnosis of CNF, with a median MSAFP level of 7.59 MoM (range 2.7–27.64 MoM) and a median AFAFP level of 10.99 MoM (range 1.47–128.6 MoM). In the affected cohort of index pregnancies, the initial median MSAFP level was 14.49 MoM (range 3.1–38.0 MoM); the median AFAFP level was 40.0 MoM (range 2.4–80.9).

MSAFP and AFAFP levels may be lower than previously recognized in patients carrying fetuses with CNF. There is significant overlap between the affected and unaffected patients.     

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.     

Human beta-defensin-2: a natural antimicrobial peptide present in amniotic fluid participates in the host response to microbial invasion of the amniotic cavity.

OBJECTIVE: Human beta-defensin-2 (HBD-2) is a potent antimicrobial peptide that is part of the innate immune response. The purpose of this study was to determine whether HBD-2 is present in amniotic fluid and if its concentration changes with microbial invasion of the amniotic cavity (MIAC) and labor. STUDY DESIGN: Amniotic fluid was retrieved by amniocentesis from 318 patients in the following groups: (1) mid-trimester (n=75); (2) term not in labor (n=28) and in labor (n=51); (3) preterm labor and intact membranes without MIAC who delivered at term (n=36), who delivered preterm without MIAC (n=52), and preterm labor with MIAC who delivered preterm (n=25); and (4) preterm premature rupture of membranes (preterm PROM) with (n=25) and without MIAC (n=26). MIAC was defined as a positive amniotic fluid culture for microorganisms. Amniotic fluid HBD-2 concentrations were determined using a sensitive and specific ELISA. Non-parametric statistics were used for analysis. RESULTS: (1) HBD-2 was detected in all amniotic fluid samples; (2) the concentration of HBD-2 did not change with gestational age from mid-trimester to term (p=0.8); (3) intra-amniotic infection was associated with a significant increase in amniotic fluid concentrations of HBD-2 in both women with preterm labor and intact membranes, and women with preterm PROM (p<0.05 for each comparison); (4) patients with preterm labor and a negative amniotic fluid culture who delivered preterm had a higher median amniotic fluid HBD-2 concentration than those with preterm labor who delivered at term (p=0.001); and (5) among patients with preterm labor without MIAC, those who had intra-amniotic inflammation (amniotic fluid white blood cell count>100 cells per mL) had a higher median amniotic fluid concentration of HBD-2 than those without this condition (p<0.002). CONCLUSION: (1) Amniotic fluid contains HBD-2, a natural antimicrobial peptide, and this may account for some of the antimicrobial activity of amniotic fluid; (2) amniotic fluid HBD-2 concentrations are increased in women with MIAC, regardless of the membrane status (intact membranes or PROM); and (3) we propose that amniotic fluid HBD-2 is part of the innate immune system within the amniotic cavity.     

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.     

Evidence of maternal platelet activation,excessive thrombin generation,and high amniotic fluid tissue factor immunoreactivity and functional activity in patients with fetal death

Objective. Fetal death can lead to disseminated intravascular coagulation or fetal death syndrome. However, currently it is not clear what are the changes in the coagulation system in patients with a fetal death without the fetal death syndrome. This study was undertaken to determine: (1) whether fetal death in the absence of fetal death syndrome is associated with changes in hemostatic markers in maternal plasma and amniotic fluid; and (2) whether maternal hypertension or placental abruption are associated with further changes in the hemostatic profile of these patients.

Methods. A cross-sectional study included the following: (1) determination of changes in markers of coagulation and platelet activation in patients with a normal pregnancy (n = 71) and patients with fetal demise (FD) without disseminated intravascular coagulation (n = 65); (2) determination of the amniotic fluid (AF)–tissue factor concentration and activity, as well as the concentrations of thrombin–antithrombin III (TAT) complexes in patients with a normal pregnancy (n = 25) and those with a FD (n = 36) who underwent amniocentesis. Plasma and AF concentrations of TAT complexes and TF (an index of thrombin generation), as well as maternal plasma concentrations of sCD40L (a marker of platelet activation), tissue factor pathway inhibitor (TFPI) and prothrombin fragments (PF) 1 + 2 (also an indicator of in vivo thrombin generation) were measured by ELISA. TF and TFPI activity were measured using chromogenic assays.

Results. (1) patients with FD without hypertension had a higher median maternal plasma sCD40L concentration than normal pregnant women (P < 0.001); (2) patients with FD had a higher median maternal plasma TAT III complexes than women with a normal pregnancy (P < 0.001); (3) the median AF–TF concentration and activity were higher in the FD group than in the normal pregnancy group (P < 0.001 for both); (4) patients with preeclampsia and FD had a higher median maternal plasma immunoreactive TF concentration than both normotensive patients with FD and women with normal pregnancies (P < 0.001 and P = 0.001, respectively); (5) the median plasma TF activity was higher in patients with preeclampsia and FD than that of women with normal pregnancies (P = 0.003); (6) among patients with a FD, those with placental abruption had a higher median AF–TAT complexes concentration than those without abruption (P = 0.0004).

Conclusions. Our findings indicate that: (1) mothers with a FD have evidence of increased in vivo thrombin generation and platelet activation than women with normal pregnancies; (2) patients with a FD and hypertension had a higher degree of TF activation than those with fetal death but without hypertension; (3) the AF of women with a FD had a higher median TF concentration and activity than that of normal pregnant women. AF can be a potential source for tissue factor and it participates in the development of fetal death syndrome in patients with a retained dead fetus.