S100B content and SOD activity in amniotic fluid of pregnancies with Down syndrome

Objectives: We measured S100B levels and superoxide dismutase (SOD) activity retrospectively in amniotic fluid samples from pregnancies with normal and Down syndrome (DS) fetuses.Design and methods: Samples from 26 normal and 71 Down syndrome fetuses were studied. S100B protein levels were determined using LIA-mat Sangtec kit, and SOD activity was measured with the RANSOD kit.Results: We observed significantly higher levels of S100B in the Down group (median of 1.24 μg/l) than in the control group (median 0.69 μg/l). S100B concentration in DS samples increased from the 13th to the 18th week of gestation and was positively correlated with gestational age. The amniotic fluid SOD activity in the DS group (16.60 U/mg/prot) was significantly higher than in the normal one (10.78 U/mg/prot).Conclusions: This study indicates that S100B and SOD in amniotic fluid could be used as additional parameters for prenatal screening of trissomy 21 and that S100B values are associated with the gestational age.     

High perinatal survival in monoamniotic twins managed by prophylactic sulindac, intensive ultrasound surveillance, and Cesarean delivery at 32 weeks' gestation.

OBJECTIVES: Increased perinatal mortality in monoamniotic twin pregnancies is attributed to cord accidents in utero and at delivery. We evaluated the following parameters in monoamniotic pregnancies: (1) the incidence of cord entanglement; (2) the effect of sulindac on amniotic fluid volume and stability of fetal lie; and (3) the perinatal outcome with our current management paradigm. METHODS: This is a retrospective review of monoamniotic pregnancies of >or=20 weeks' gestation managed with serial ultrasound surveillance, medical amnioreduction and elective Cesarean delivery at 32 weeks' gestation. Mean amniotic fluid index (AFI) and change in AFI in monoamniotic pregnancies managed with oral sulindac was compared with 40 gestation-matched monochorionic-diamniotic controls. RESULTS: Among 44 monoamniotic pregnancies, 20 with two live structurally normal twins at 20 weeks' gestation satisfied the inclusion criteria. All fetuses survived to 28 days postnatally despite early prenatal cord entanglement in all but one case. Whereas AFI remained stable throughout gestation in the controls, the AFI fell in those patients on sulindac from a mean value of 21.0 cm (95% CI, 18.5-23.6 cm) at 20 weeks to a mean of 12.4 cm (95% CI, 10.1-14.6 cm) at 32 weeks (ANOVA P across gestation = 0.001) but mainly remained within normal limits. Fetal lie was stabilized in 11/20 cases in the monoamniotic group compared with 13/40 in the control group (P < 0.0001). CONCLUSIONS: Cord entanglement appears unpreventable, as it typically occurs in early pregnancy. Sulindac therapy reduces AFI, leads to more stable fetal lie, and may prevent intrauterine death by diminishing the risk of constricting cords that are already entangled. Perinatal survival in monoamniotic pregnancies managed by a regime of sulindac from 20 weeks' gestation, close ultrasound surveillance and elective abdominal delivery at 32 weeks' gestation seems empirically higher than that in the literature.     

Association between oxidative stress in pregnancy and preterm premature rupture of membranes

BACKGROUND: Premature rupture of membranes (PROM) is caused by collagen damage in the chorioamniotic sac leading to tearing. Reactive oxygen species (ROS) may be the cause of collagen damage. Isoprostanes (F(2)-IP) are produced by ROS attack on polyunsaturated fatty acids and are sensitive and specific biomarkers of lipid-peroxidation in vivo. AIM: To verify whether oxidative stress occurs in pregnancies associated with preterm PROM. METHODS: F(2)-IPs were measured in amniotic fluid of 16 pregnancies with preterm PROM (Group II) and 97 without PROM (Group I). RESULTS: F(2)-IP concentrations (pg/mL) were significantly higher in group II than group I (p<0.0001). The ROC curve showed a sensitivity of 100% and a specificity of 84.5% at a cut-off of 124.4 pg/mL. CONCLUSIONS: An association exists between oxidative stress in pregnancy and preterm PROM. The detection of amniotic fluid F(2)-IP concentrations seems to be a reliable predictive index of risk of preterm PROM.     

Measurement, Characterization, and Source of Somatostatin-like Immunoreactivity in Human Amniotic Fluid

Somatostatin-like immunoreactivity (SLI) is widely distributed in tissues and biological fluids. To determine whether SLI is also present in amniotic fluid, samples obtained by amniocentesis from 30 normal and 27 abnormal pregnancies were studied by radioimmunoassay. Direct incubation of [(125)I-Tyr(1)]tetradecapeptide somatostatin (SRIF) with amniotic fluid resulted in 89% tracer degradation. Damage was reduced to <5% when samples were acidified and boiled before the assay. With this technique, SLI was detectable in all normal amniotic fluid samples; the mean level at 15-20 wk of gestation (320+/-55 pg/ml, n = 15) being 4.5 times higher than the mean at 32-43 wk (70+/-12 pg/ml, n = 15) (P < 0.001). In cases of preeclampsia (n = 6), gestational diabetes (n = 5), anencephaly (n = 1), and meningomyelocele (n = 1), SLI values were in the normal range, but in one juvenile diabetic and one patient with chronic renal failure, SLI was undetectable (<10 pg/ml). In a pair of monochorionic diamniotic twins, SLI levels were very different (33 and 197 pg/ml), which suggests that fetal factors are more important than materno-placental ones in determining amniotic fluid SLI. Serial dilutions of amniotic fluid showed parallelism with standard SRIF. When concentrates of pooled amniotic fluid were chromatographed on Sephadex G-25 columns, all SLI eluted in the void volume ahead of SRIF even after treatment with 8 M urea and dithiothreitol. This "big" SLI incubated in amniotic fluid showed 100% stability over 24 h at 37 degrees C, whereas SRIF was rapidly inactivated (t((1/2)) congruent with 7 min). Extracts of placenta and fetal membranes contained no SLI, but small amounts (6-20% of total amniotic fluid SLI) were found in cells from fresh fluid. Radioimmunoassay of SLI in extracts of seven paired cord arterial and venous plasma samples showed no arteriovenous gradient consistent with fetal origin of cord blood SLI. It is concluded that (a) amniotic fluid contains SLI which is of fetal origin and (b) normal levels vary with gestational age. The SLI has a higher molecular weight (>/=5,000) and is more stable in amniotic fluid than SRIF.     

Perinatal outcome in monochorionic twin pregnancies complicated by amniotic fluid discordance without severe twin-twin transfusion syndrome.

OBJECTIVES: To assess the natural history and perinatal outcome in monochorionic diamniotic twin pregnancies with discordant amniotic fluid volume without signs of severe twin-twin transfusion syndrome (TTTS). METHODS: This was an observational study of 84 consecutive monochorionic twin pregnancies which did not meet the criteria for severe TTTS and endoscopic laser coagulation of placental anastomoses at initial presentation. The population was subdivided into two groups. Group 1 consisted of 64 pregnancies (median gestational age, 20.1 (range, 15.6-24.7) weeks) with amniotic fluid discordance and no signs of congestive heart failure in the twin with the larger amniotic fluid volume (Twin 1) and positive end-diastolic flow in the umbilical artery of the twin with the smaller amniotic fluid volume (Twin 2). Group 2 (median gestational age, 19.1 (range, 16.0-24.4) weeks) consisted of 20 pregnancies with amniotic fluid discordance and intrauterine growth restriction (IUGR) (abdominal circumference < 5th percentile) in combination with absent or reversed end-diastolic (ARED) flow in the umbilical artery of Twin 2. After exclusion of one patient from Group 1, who opted for termination of pregnancy, nine patients in Group 1 and one in Group 2 developed severe TTTS, and laser coagulation was offered. The remaining 54 pregnancies of Group 1 were compared with the remaining 19 pregnancies of Group 2. RESULTS: Fetuses in Group 1 showed significantly higher survival rates (overall survival, 100/108 (92.6%) vs. 23/38 (60%), P < 0.0001; survival of both fetuses, 49/54 (90.7%) vs. 9/19 (47.4%), P = 0.0002) and median gestational age at delivery (33.6, (range, 27.6-37.8) weeks vs. 32.0 (range, 26.9-36.3) weeks, P = 0.0457). Overall, there was a significantly higher incidence of complications, defined as necessity for intrauterine intervention, fetal or neonatal death or delivery prior to 32 weeks, in Group 2 (Group 1: 30/63 (47.6%); Group 2: 16/20 (80%), P = 0.0188). CONCLUSIONS: Our data suggest that amniotic fluid discordance in monochorionic diamniotic twin pregnancies in combination with IUGR and umbilical artery ARED flow in one fetus represents an extremely high-risk constellation for adverse pregnancy outcome.     

Accuracy of ultrasonography in evaluating amniotic fluid volume at less than 24 weeks' gestation.

The purpose of this investigation was to evaluate the accuracy of common sonographic techniques in assessing the amniotic fluid volume in pregnancies of less than 24 weeks' gestation. Patients at less than 24 weeks' gestation undergoing an amniocentesis for the placement of prostaglandin F2 alpha for termination (because of genetic or fetal anomalies, or both) were assessed for amniotic fluid volume. All fetuses were alive at the time of prostaglandin instillation. The amniotic fluid index and two-diameter pocket were used to determine the amniotic fluid volume. Prior to the prostaglandin instillation, the amniotic fluid volume was determined with para-aminohippurate using a diazo dye reaction with spectrophotometric analysis. The amniotic fluid volume was determined in 21 pregnancies between 15 and 24 weeks' gestation, yielding volumes ranging from 189 to 1840 ml. Using published standards for amniotic fluid volume in singleton pregnancies, oligohydramnios was present in three gestations, the volume was found to be normal in 15, and hydramnios complicated three pregnancies. The two-diameter pocket identified the amniotic fluid volumes correctly more often (18 of 21 [85.7%]) than the amniotic fluid index (10 of 21 [47.6%]) (P = 0.02). Normal amniotic fluid volume was identified in nine of 15 (60%) pregnancies by the amniotic fluid index and in 14 of 15 (93.3%) by the two-diameter pocket (P = not significant). Abnormal amniotic fluid volumes, oligohydramnios, and hydramnios were recognized more often by the two-diameter pocket (66.7%) than by the amniotic fluid index (1 of 6 [16.7%], P = not significant).     

Total pregnancy-associated plasma protein A--a first trimester maternal serum marker for Down's syndrome: clinical and technical assessment of a poly-monoclonal enzyme immunoassay

Pregnancy-associated plasma protein A (PAPP-A) is a maternal serum marker of fetal chromosomal disease and a risk marker for adverse outcome. PAPP-A in the circulation exists both as a 2:2 complex (PAPP-A/proMBP) with the proform of eosinophil major basic protein (proMBP) and as dimeric PAPP-A. Non-PAPP-A containing proMBP complexes constitute the bulk of proMBP in maternal serum. We developed and characterized a sandwich enzyme immunoassay for PAPP-A using a polyclonal rabbit anti-PAPP-A/proMBP antibody (SSI 6823) and a monoclonal murine anti-PAPP-A/proMBP antibody (HYB 234-3), reactive with the PAPP-A part of PAPP-A/proMBP. The assay range was 2 mIU/L-500 mIU/L, intra- and inter-assay coefficients of variation <10%. The immunoreactivity eluted ahead of thyroglobulin, Mr 669 kDa, in gel filtration and bound to a heparin column. Serum concentrations of PAPP-A were determined in gestational weeks 5-13 in 167 pregnant women with normal fetuses and 39 women with Down's syndrome (DS) fetuses. The median PAPP-A MoM (multiples of the median in normal controls) in DS pregnancies was 0.30 (quartile range: 0.17-0.54). The PAPP-A logMoMs in DS pregnancies were normally distributed with a mean of -0.5927 and SD of 0.3639. When simulating the performance of PAPP-A and age as markers for DS in population screening a detection rate (DR) of 62% was found for a screen positive rate (SPR) of 5%. Together with beta-HCG and nuchal translucency, two other first trimester markers for fetal DS, a DR 90% could be obtained for an SPR of 5%.     

Alpha-fetoprotein microheterogeneity: a potential biochemical marker for Down's syndrome

Our purpose was to examine the utility of analyzing alpha-fetoprotein (AFP) microheterogeneity assessed by lectin affinity in Down's syndrome (DS) screening. Maternal sera and amniotic fluids were collected from 18 women who were carrying DS fetuses and 70 unaffected pregnancies around 16 weeks of gestation. The percentages of AFP which reacted with Lens culinaris agglutinin (AFP-L2,3) were determined by lectin affinity electrophoresis. AFP-L2,3 levels were significantly increased (P<0.0001) in both maternal serum and amniotic fluid from DS-affected versus unaffected pregnancies. The fractional areas under the receiver operating characteristic curves were 0.835 and 0.700 (P=0.106) for AFP-L3 and AFP MoM (multiples of the median) in maternal serum. No correlation was found between AFP-L3 and AFP MoM in maternal serum (r=0.006). Our data suggest that the measurement of AFP-L3 in maternal serum is a potential biochemical marker for DS.     

Triggering receptors expressed on myeloid cells in pulmonary aspiration syndromes

OBJECTIVE: To investigate the potential role of serum and alveolar soluble triggering receptor expressed on myeloid cells (sTREM-1) as a biological marker of pulmonary aspiration syndromes. DESIGN: Prospective cohort study. SETTING: University-affiliated intensive care unit. PATIENTS: Seventy-five patients with pulmonary aspiration and 13 controls receiving mechanical ventilation. INTERVENTIONS: Blood and bronchoalveolar lavage (BAL) fluid samples were collected on enrollment. Soluble TREM-1 levels were measured by an enzyme-linked immunosorbent assay. MEASUREMENTS AND RESULTS: Thirty-eight of 75 participants had documented BAL culture-positive pulmonary aspiration. While circulating levels of sTREM-1 were comparable between those with aspiration syndromes (19.81 +/- 12.09 pg/ml) and controls (15.96 +/- 11.16 pg/ml) (p=0.27), the alveolar levels of sTREM-1 were higher in patients with culture-positive pulmonary aspiration (344.41 +/- 152.82 pg/ml) compared with those culture-negative pulmonary aspiration (142.76 +/- 89.88 pg/ml; p < 0.001). A cut-off value of 250 pg/ml for alveolar sTREM-1 achieved a sensitivity of 65.8% (95% CI 48.6-80.4) and a specificity of 91.9% (95% CI 78.1-98.2) with an area under the curve of 0.87 (95% CI 0.78-0.94). CONCLUSIONS: Alveolar sTREM-1 levels can be a potential biomarker for distinguishing BAL culture-positive from BAL culture-negative pulmonary aspiration.     

Nasal bone hypoplasia in trisomy 21 at 15-22 weeks' gestation.

OBJECTIVE: To investigate the potential value of ultrasound examination of the fetal profile for present/hypoplastic fetal nasal bone at 15-22 weeks' gestation as a marker for trisomy 21. METHODS: This was an observational ultrasound study in 1046 singleton pregnancies undergoing amniocentesis for fetal karyotyping at 15-22 (median, 17) weeks' gestation. Immediately before amniocentesis the fetal profile was examined to determine if the nasal bone was present or hypoplastic (absent or shorter than 2.5 mm). The incidence of nasal hypoplasia in the trisomy 21 and the chromosomally normal fetuses was determined and the likelihood ratio for trisomy 21 for nasal hypoplasia was calculated. RESULTS: All fetuses were successfully examined for the presence of the nasal bone. The nasal bone was hypoplastic in 21/34 (61.8%) fetuses with trisomy 21, in 12/982 (1.2%) chromosomally normal fetuses and in 1/30 (3.3%) fetuses with other chromosomal defects. In 3/21 (14.3%) trisomy 21 fetuses with nasal hypoplasia there were no other abnormal ultrasound findings. In the chromosomally normal group hypoplastic nasal bone was found in 0.5% of Caucasians and in 8.8% of Afro-Caribbeans. The likelihood ratio for trisomy 21 for hypoplastic nasal bone was 50.5 (95% CI 27.1-92.7) and for present nasal bone it was 0.38 (95% CI 0.24-0.56). CONCLUSION: Nasal bone hypoplasia at the 15-22-week scan is associated with a high risk for trisomy 21 and it is a highly sensitive and specific marker for this chromosomal abnormality.     

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.     

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.     

Reactivity of amniotic fluid alpha-fetoprotein with concanavalin A in relation to gestational age: clinical implications

We used concanavalin A crossed-line affinity immunoelectrophoresis to determine the percentage of concanavalin A nonreactive alpha-fetoprotein in amniotic fluid samples from pregnancies with normal and abnormal fetuses. In 167 samples from pregnancies with a normal outcome and normal values for total alpha-fetoprotein concentration in amniotic fluid the percentage decreased from a median value of 27.4% in the 13th week to 8.5% in the 21st week of gestation, and a statistically significant (p < 0.001) average decrease of 1.7% per week was found from the 14th to the 19th week. A similar average decrease (2.2%) was found in 22 pregnancies from which two or more samples were obtained. The clinical significance of this decrease is discussed. Of 108 samples from patients with above-normal values for total alpha-fetoprotein and a normal outcome, seven had a total alpha-fetoprotein above recommended cut-off values, and only one of these had a low percentage of concanavalin A nonreactive alpha-fetoprotein. In contrast, for all 27 samples from pregnancies with a severe fetal malformation this percentage was low, even in one case where the total alpha-fetoprotein concentration was below the recommended cut-off value.     

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.     

Prolactin in amniotic fluid: its correlation with maternal plasma prolactin.

Prolactin concentrations in amniotic fluid from 319 women with normal pregnancies and 29 women with complicated pregnancies were determined by radioimmunoassay. Prolactin levels varied from 36 ng/ml to 1800 ng/ml mean +/- S.D. = 408 +/- 297) in the normal pregnancy group but showed no definite pattern of rise or fall during pregnancy. No difference in levels was found in complicated pregnancies. Prolactin concentrations in the plasma from 203 of these women were also assayed. The levels in the amniotic fluid were about 9 fold higher than those in the plasma. There was no significant correlation between amniotic fluid and plasma levels of prolactin.     

The natural history of oligohydramnios/polyhydramnios sequence in monochorionic diamniotic twins.

Twelve patients with monochorionic diamniotic twin pregnancies complicated by oligohydramnios/polyhydramnios sequence were evaluated to determine the natural history of this syndrome. Nine patients elected to continue their pregnancies and three underwent elective termination. Six of the nine continuing pregnancies delivered viable fetuses. Four of the nine continuing pregnancies had evidence of a 'stuck' twin at less than 20 weeks' gestation, and only one yielded live newborns (25%). Three patients diagnosed with a mild case of oligohydramnios/polyhydramnios sequence underwent worsening of the syndrome with a 'stuck' twin seen only after 26 weeks: all neonates survived. Five pregnancies initially diagnosed as having a 'stuck' twin showed improvement in amniotic fluid volume, with one actually reversing, so that the previously 'stuck' twin developed polyhydramnios and the co-twin became 'stuck'.In summary, among the nine non-aborted pregnancies managed conservatively, 12 of 18 fetuses (67%) survived. When the diagnosis of 'stuck' twin was made at 相似文献   

Amniotic fluid γ-glutarnyl transf erase activity in trisomy 21 and neural tube defects

The amniotic fluid γ-glutamyl transferase (γGT) has been measured in normal pregnancies (n = 128), six pregnancies associated with trisomy 21 and 12 pregnancies involving a foetus with a neural tube defect. In normal pregnancies, the amniotic fluid γGT activity falls during the second trimester, the level at 20 wk being 60% of that at 14 wk. In the six cases of trisomy 21 and 8 of the 12 cases with neural tube defects, the γGT levels were below the 95% confidence limit.     

Longitudinal thrombopoietin plasma concentrations in fetuses with alloimmune thrombocytopenia treated with intrauterine PLT transfusions

BACKGROUND: The purpose of this study was to describe longitudinal thrombopoietin (TPO) plasma concentrations in fetuses with fetomaternal alloimmune thrombocytopenia (FMAIT). STUDY DESIGN AND METHODS: Group 1 was the control group, 8 fetuses with normal hematopoiesis. Group 2 consisted of 4 nonthrombocytopenic fetuses with fetomaternal human PLT antigen incompatibility. Group 3 consisted of 14 fetuses with prenatal-diagnosed severe FMAIT owing to human PLT antigen-1a incompatibility. Fetal PLT counts, MoAb-specific immobilization of PLT antigen score, and TPO plasma concentrations were measured in a total number of 94 serial samples taken by cordocentesis before intrauterine PLT transfusion. RESULTS: Normal fetal TPO plasma concentrations ranged between 15 and 119 pg per mL (Group 1 median, 67 pg/mL). In fetuses with risk of FMAIT but normal PLT counts, TPO concentrations were normal (Group 2 median, 72 pg/mL; range, <15-158 pg/mL). In FMAIT with thrombocytopenia, the median TPO concentration was significantly higher than in Groups 1 and 2 (Group 3 median, 172 pg/mL; range, 15-623 pg/mL; p < 0.001). In the longitudinal analysis, TPO concentrations remained constant (n = 8), peaked only transiently (n = 3), or increased at the end of gestation (n = 3). Elevated TPO concentrations (592 and 623 pg/mL) were detected in one patient, who already had intracranial hemorrhage in utero. CONCLUSION: TPO concentrations are normal or slightly elevated in FMAIT. Further clinical information can be provided by the longitudinal analysis of TPO concentrations in severe FMAIT.     

Total pregnancy‐associated plasma protein A—a first trimester maternal serum marker for Down's syndrome: clinical and technical assessment of a poly‐monoclonal enzyme immunoassay

Pregnancy‐associated plasma protein A (PAPP‐A) is a maternal serum marker of fetal chromosomal disease and a risk marker for adverse outcome. PAPP‐A in the circulation exists both as a 2:2 complex (PAPP‐A/proMBP) with the proform of eosinophil major basic protein (proMBP) and as dimeric PAPP‐A. Non‐PAPP‐A containing proMBP complexes constitute the bulk of proMBP in maternal serum. We developed and characterized a sandwich enzyme immunoassay for PAPP‐A using a polyclonal rabbit anti‐PAPP‐A/proMBP antibody (SSI 6823) and a monoclonal murine anti‐PAPP‐A/proMBP antibody (HYB 234‐3), reactive with the PAPP‐A part of PAPP‐A/proMBP. The assay range was 2?mIU/L–500?mIU/L, intra‐ and inter‐assay coefficients of variation <10%. The immunoreactivity eluted ahead of thyroglobulin, M_r 669?kDa, in gel filtration and bound to a heparin column. Serum concentrations of PAPP‐A were determined in gestational weeks 5–13 in 167 pregnant women with normal fetuses and 39 women with Down's syndrome (DS) fetuses. The median PAPP‐A MoM (multiples of the median in normal controls) in DS pregnancies was 0.30 (quartile range: 0.17–0.54). The PAPP‐A logMoMs in DS pregnancies were normally distributed with a mean of ?0.5927 and SD of 0.3639. When simulating the performance of PAPP‐A and age as markers for DS in population screening a detection rate (DR) of 62% was found for a screen positive rate (SPR) of 5%. Together with β‐HCG and nuchal translucency, two other first trimester markers for fetal DS, a DR 90% could be obtained for an SPR of 5%.     

Nuchal translucency measurement and pregnancy outcome in karyotypically normal fetuses.

OBJECTIVE: The aim of the study was to evaluate the use of nuchal translucency measurement as a marker of adverse pregnancy outcome in karyotypically normal fetuses. METHODS: During the years 1995-99, nuchal translucency (NT) measurement was routinely offered to all women who had their dating scan in our unit. From the data collected, we calculated the 95th and 99th centiles of the NT for a given crown-rump length using regression analysis. The NT measurements were analyzed in relation to pregnancy outcome, especially with regards to miscarriage, intrauterine death and diagnosis of fetal structural abnormalities, after excluding chromosomal abnormalities. RESULTS: The pregnancy outcome was available in 6650 (89%) of the 7500 pregnancies. In fetuses with an NT over the 99th centile, 17.8% (relative risk 12.2, 95% CI 7.2-20.8) had an adverse pregnancy outcome (miscarriage, intrauterine death, or termination for fetal abnormality) versus 1.5% for those with a normal measurement. The incidence of structural abnormalities, especially heart defects, was significantly increased in the high-NT groups. Three out of 11 fetuses with major cardiac abnormalities had an NT measurement over the 99th centile. The calculated relative risk for major heart defects in fetuses with increased NT was 33.5 (95% CI 9-123). CONCLUSION: In the setting of routine antenatal screening, an increased NT measurement is a marker of a high-risk pregnancy even in karyotypically normal fetuses. In addition, the increased incidence of structural abnormalities makes the close follow-up of these pregnancies imperative and should include specialized fetal echocardiography.