Mid-trimester Amniocentesis Research Articles

A new guidance system for freehand, obstetric ultrasound-guided procedures.

To assess the performance of the UltraGuide 1000 system, and to compare ultrasound-guided freehand mid-trimester amniocentesis with and without the new guidance system. One hundred and sixty-nine women referred for mid-trimester genetic amniocentesis were divided into two groups: a control group of 99 women who underwent the procedure by the freehand technique with scored needles and 70 patients who had the procedure carried out with the aid of a guidance system (UltraGuide 1000) with non-scored needles. The procedures were compared for duration, number of punctures and repositionings of the needle, the visibility of the needle during the puncture and the number of bloody taps. The study group had significantly lower rates of reinsertion (none vs. 7.1%), repositioning (7.1% vs. 17.7%), bloody taps (none vs. 6.1%), touching the fetus (5.7% vs. 22.2%) and prolonged duration of the procedure (4.3% vs. 14.4%) compared with the control group. There was one fetal loss in the control group. Non-visibility of the needle before reaching the amniotic sac occurred in 18.6% of cases in the study group and in 38.4% of cases in the control group. The new guidance system combines the benefits of an attached guide with the flexibility of the 'freehand' technique. Use of the new guidance system for mid-trimester genetic amniocentesis increases needle visibility and lowers the incidence of common complications.

Alpha-Fetoprotein Values in Amniotic Fluid Obtained during Early Amniocentesis (11–13 Weeks)

Objectives: To determine the normal values of α-fetoprotein (AFP) in amniotic fluid between the gestational ages of 11 and 13 weeks and compare these with previously published values. Methods: Amniotic fluid AFP was analyzed in 149 patients who had undergone amniocentesis between 11 ± 0 and 13 ± 6 weeks gestation as part of the pilot study of the Canadian Early and Mid-Trimester Amniocentesis Trial. Analysis was done using the Abbott IMX System (Abbott Laboratories Diagnostic Division, Abbott Park, Ill.). These values were then compared with previously published values. Results: There is a progressive and linear rise in the amniotic fluid AFP concentration from 11 to 13 weeks gestation. The differences between each of the three gestational ages were statistically significant at the 0.05 level. The values differed significantly from those obtained by Crandall et al. [Am J Obstet Gynecol 1989;160:1204–1206], which were also consistently higher. Conclusion: Although reference points for 11, 12 and 13 weeks have been established, there are limitations to their clinical application.

Elevated monocyte chemotactic protein-1 in amniotic fluid is a risk factor for pregnancy loss

Objective: Pregnancy loss after mid-trimester amniocentesis occurs in 0.5–1% of cases and is frequently attributed to the procedure. Accumulating evidence implicates a pre-existing, but clinicallysilent, intra-amniotic inflammation in the etiology of adverse pregnancy outcome after mid-trimester amniocentesis. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine produced by a wide varietyof cells during the course of an inflammatory response. This study was designed to assess if the amniotic fluid concentration of this chemokine identifies patients at risk for spontaneous abortion and/orfetal death.Method: A retrospective case–control study of women who had a mid-trimester amniocentesis was designed. Cases (n = 10) consisted of patients who had a spontaneous pregnancyloss after the procedure, while the control group (n = 84) consisted of patients who had a normal pregnancy outcome after mid-trimester amniocentesis. MCP-1 was measured by a specific enzyme immunoassay(sensitivity, 18.3 pg/ml). The Kolmogorov–Smirnov test was utilized to assess normal distribution of the data. Logarithmic transformation was applied to achieve normality. Statistical analysis wasperformed using Student's t test. A receiver operating characteristic (ROC) curve analysis was used to select a cut-off to dichotomize amniotic fluid concentrations of MCP-1.Results:MCP-1 was detectable in all amniotic fluid samples. Patients who had a mid-trimester amniocentesis and a subsequent pregnancy loss had a higher mean amniotic fluid log MCP-1 concentration than those witha normal pregnancy outcome (pregnancy loss, mean 2.95 ± 0.19 pg/ml vs. normal outcome, mean 2.78 ± 0.19 pg/ml; p = 0.01). A cut-off of > 765 pg/ml was selected by ROC curve analysis(area under the curve, 0.74; p = 0.01). An amniotic fluid concentration of MCP-1 above this level was strongly associated with pregnancy loss (odds ratio, 7.35; 95% confidence interval, 1.7–31.1),a sensitivity of 70%, and a specificity of 76%.Conclusion: A subset of women who had a pregnancy loss after a mid-trimester amniocentesis had higher concentrations of the chemokine MCP-1 thanthose who had a normal pregnancy outcome. Subclinical intra-amniotic inflammation is a risk factor for pregnancy loss after mid-trimester amniocentesis. This observation may have medicolegal and clinicalimplications. An elevated MCP-1 concentration in amniotic fluid of patients with a pregnancy loss after a mid-trimester amniocentesis indicates that a pathological condition was present at the time of theprocedure.

Elevated amniotic fluid ferritin levels are associated with inflammation-related pregnancy loss following mid-trimester amniocentesis

Objective: Occult infection accounts for up to 12% of pregnancy losses following genetic amniocentesis. Elevated serum and cervical fluid levels of ferritin, an acute-phase reactant, have been associatedwith spontaneous preterm delivery. We determined the association between amniotic fluid (AF) ferritin levels and post-amniocentesis pregnancy loss.Methods: We performed a case-control studyinvolving 66 women with a non-anomalous fetus who had a spontaneous pregnancy loss within 30 days following genetic amniocentesis and 66 term controls matched for maternal age, gestational age, time oftest and indication for amniocentesis. Amniotic fluid ferritin and interleukin-6 (IL-6) levels were measured using commercially available kits.Results: Mean (± SD) AF ferritin levelswere similar between the cases (19.3 ± 21.4 ng/ml) and the controls (19.8 ± 22.7 ng/ml) (p = 0.9). Mean (± SD) AF IL-6 levels were significantly higher in the women with post-amniocentesispregnancy loss (4.0 ± 13.1 ng/ml) than in controls (0.5 ± 0.7 ng/ml) (p = 0.04). A significant proportion (12.1%, 8/66) of the women with postamniocentesis pregnancy loss had elevatedamniotic fluid IL-6 levels (> 3 SD, 2.5 ng/ml) indicating inflammation, as compared to none in the control group (p = 0.01). In this subgroup of women with pregnancy loss and elevated IL-6 levels,AF ferritin levels were significantly elevated (52.0 ± 45.5 ng/ml) compared to the level in women who had a term delivery (19.8 ± 22.7 ng/ml) (p = 0.002), and were strongly correlatedwith IL-6 levels among the cases (r = 0.67, p < 0.001).Conclusion: The strong correlation of AF ferritin with IL-6 levels, along with the high ferritin values in cases withhigh AF IL-6, indicates that ferritin is a marker of inflammation in asymptomatic women destined to have an early pregnancy loss.

Lipopolysaccharide-binding protein in microbial invasion of the amniotic cavity and human parturition

Objective: Lipopolysaccharide-binding protein (LBP) is an acute-phase protein of predominantly hepatic origin, capable of binding the lipid A fraction of bacterial lipopolysaccharide (LPS). The complexLBP-LPS binds to CD14, and has been implicated in the host response to Gram-negative infection. The purpose of this study was to determine whether microbial invasion of the amniotic cavity (MIAC) and parturition(term and preterm) are associated with changes in the amniotic fluid concentration of LBP.Study design: Amniotic fluid was retrieved by amniocentesis from 343 patients in the following groups:(1) those in mid-trimester with a subsequent normal pregnancy outcome (n = 84); (2) those in mid-trimester with a fetal loss after the procedure (n = 10); (3) those with preterm labor andintact membranes without MIAC who delivered at term (n = 36) or prematurely (n = 52), and those with preterm labor with MIAC (n = 26); (4) those with preterm premature rupture of membranes(PROM) with (n = 26) and without (n = 26) MIAC; and (5) those delivering at term with intact membranes in the absence of MIAC, in labor (n = 52) and not in labor (n = 31). Theconcentration of LBP in amniotic fluid was determined with a specific and sensitive immunoassay. Non-parametric statistics were used. A p value of < 0.05 was considered significant.Results:LBP was detected in 98% (335/343) of the amniotic fluid samples. MIAC was associated with a significant increase in amniotic fluid concentration of LBP in women with preterm labor and intact membranes,but not in preterm PROM. Spontaneous preterm parturition was associated with a significant increase in amniotic fluid concentration of LBP. Patients who had a spontaneous fetal loss after a mid-trimesteramniocentesis had a significantly higher median amniotic fluid LBP concentration than those who had a mid-trimester amniocentesis and a normal perinatal outcome.Conclusion: Preterm labor withMIAC and preterm parturition are associated with higher amniotic fluid concentrations of LBP than those with sterile amniotic fluid.

A randomised trial of progesterone prophylaxis after midtrimester amniocentesis

Background: Midtrimester amniocentesis to investigate fetal karyotype carries a small risk of fetal loss. Aim: To test the hypothesis that progesterone prophylaxis may reduce this. Study design: A randomised controlled trial comparing a short prophylactic treatment with progesterone after amniocentesis with untreated controls. Results: There were no differences in frequency of miscarriage, preterm delivery or neonatal outcome. Conclusion: Prophylactic progesterone treatment after amniocentesis does not improve obstetric outcome.

Association between congenital foot anomalies and gestational age at amniocentesis.

Our objectives were to confirm the reported association between early amniocentesis and congenital foot anomalies as well as to report, for the first time, on the outcome of amniocenteses performed during the 13th and 14th weeks of gestation. We conducted a triple cohort retrospective study of 4457 amniocenteses. Cohort definitions: early amniocentesis (EA), 11 weeks and 0/7 days to 12 weeks to 6/7 days; early midtrimester amniocentesis (EMA), 13 weeks and 0/7 days to 14 weeks and 6/7 days; and midtrimester amniocentesis (MA), 15 weeks and 0/7 days to 19 weeks and 6/7 days. Outcome measures were obtained by searching the Alberta Congenital Anomalies Surveillance System (ACASS) database for children born with foot anomalies represented by International Classification of Diseases version 9 (ICD-9) codes 754.5, 754.6 and 754.7. Incidences of congenital foot anomalies were: EA 11/980 (1.1%), EMA 11/2515 (0.4%), and MA 1/962 (0.1%). There is a significant difference between the EA and EMA cohorts (p=0.019) and between the EA and MA cohorts (p=0.003); however, these data suggest there is no difference between EMA and MA cohorts (p=0.11). Our incidence of congenital foot anomalies of 1.1% for women who underwent EA is similar to previously reported data, which further validates this association; however, our data also suggest that the foot anomaly risk may be limited to amniocenteses performed before the 13th week of gestation.

An elevated amniotic fluid matrix metalloproteinase-8 level at the time of mid-trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery

Objective: Strong evidence implicates chronic intra-amniotic inflammation in the etiology of mid-trimester abortion and spontaneous preterm delivery. The purpose of this study was to determine if concentrations of amniotic fluid matrix metalloproteinase-8, and cytokines such as interleukin-6 and angiogenin can identify patients at risk for spontaneous preterm delivery in patients undergoing mid-trimester amniocentesis. Study Design: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin in patients who delivered at term and in those who delivered before term. The study included 19 cases with spontaneous preterm delivery and 95 matched controls with normal outcomes. Patients with abnormal fetal karyotypes or major anomalies were excluded. Matrix metalloproteinase-8, interleukin-6, and angiogenin were measured by using specific immunoassays. Mann-Whitney U tests, Fisher exact tests, and receiver-operating characteristic curves were used for statistical analysis. Results: The median amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin concentrations of patients with spontaneous preterm delivery were significantly higher than those of control cases (matrix metalloproteinase-8: median, 3.1 ng/mL [range, 0.3-1954.9 ng/mL] vs median, 1.3 ng/mL [range, <0.3-45.2 ng/mL], P <.01; interleukin-6: median, 0.32 ng/mL [range, 0.04-2.52 ng/mL] vs median, 0.18 ng/mL [range, 0.01-1.81 ng/mL], P <.01; angiogenin: median, 11.1 ng/mL [range, 4.5-30.7 ng/mL] vs median, 6.7 ng/mL [range, 1.3-21.9 ng/mL], P <.001). Amniotic fluid matrix metalloproteinase-8 concentrations higher than 23 ng/mL had the highest specificity and odds ratio (sensitivity, 42% [8/19]; specificity, 99% [94/95]; OR, 68.4 [95% CI, 7.8-599.1]) in the identification of the patients with preterm delivery after genetic amniocentesis. Conclusions: Elevated mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin are a risk factor for early spontaneous preterm delivery (<32 weeks). An elevated matrix metalloproteinase-8 level of >23 ng/mL is a powerful predictor of spontaneous preterm delivery (<32 weeks) with an odds ratio of 68.4. Amniotic fluid studies can be used to improve the risk assessment for preterm delivery in women who undergo mid-trimester amniocentesis for genetic indications. (Am J Obstet Gynecol 2001;185:1162-7.)

Review of the Effect of Early Amniocentesis on Foot Deformity in the Neonate

A recent publication by the Canadian Early and Mid-Trimester Amniocentesis Trial Group reported an increase in orthopaedic foot deformities in infants whose mothers underwent an amniocentesis from 11 to 12 + 6 gestational weeks versus a group sampled between 15 to 16 + 6 gestational weeks. Because the sampling of the former group was at the time of maximum foot growth and maximum acquisition of amniotic fluid, the authors hypothesize that the foot deformities are secondary to decreased fetal movement during a key phase in foot and ankle development.

Optimization of cytokine stability in stored amniotic fluid

Objective: Many studies use stored amniotic fluid samples to assay cytokines and other proteins for outcome-based research; however, there is little information on the optimal methods of storage. The objective of our study was to evaluate cytokine stability in amniotic fluid stored at different temperatures both with and without a proteolytic enzyme inhibitor. Study Design: Patients undergoing midtrimester genetic amniocentesis for routine indications gave consent for the study. After the sample was centrifuged, the acellular portion of the sample was mixed to homogeneity and aliquoted in 0.5-mL increments and stored for 1 year at 4°C, –20°C, and –80°C with and without the protease inhibitor aprotinin. Enzyme-linked immunoassays for angiogenin, interleukin-6, and vascular endothelial growth factor were performed simultaneously on each aliquot. Results: Thirty samples were assayed for each storage condition. Results were calculated as the percentage of its own sister aliquot stored at -80°C without aprotinin. In all samples, there was a significant relation between storage temperature and cytokine levels, with the lowest levels found at 4°C and the highest at –80°C (angiogenin, P =.004; interleukin-6, P <.001; vascular endothelial growth factor, P =.02). The addition of aprotinin improved stability only for angiogenin at all temperatures (all P <.05). Conclusions: Degradation of cytokines occurs when amniotic fluid samples are stored for prolonged periods at temperatures greater than –80°C. The addition of a protease inhibitor helps stem the degradation of some cytokines. (Am J Obstet Gynecol 2001;185:459-62.)

Obstetrician-gynecologists performing genetic amniocentesis may be misleading themselves and their patients

Objective: Our purpose was to compare midtrimester amniocentesis-related fetal loss rates between obstetrician-gynecologists and perinatologists. Study Design: This cohort study analyzes 1384 midtrimester amniocenteses from January 1, 1996, to December 31, 1999. Obstetrician-gynecologists who split their practices between two or more hospitals and explained fetal losses (eg, fetal anomalies, aneuploidy) were excluded from analysis. Eight obstetriciangynecologists performed 138 procedures; 3 perinatologists performed 1246 procedures. Three experienced obstetrician-gynecologists accounted for 113 procedures. Analysis was by χ 2. Results: Within 30 days of midtrimester amniocentesis, there were 3 fetal losses for obstetriciangynecologists and 4 for perinatologists ( P = .02, χ 2 = 5.19, degrees of freedom = 1). Obstetriciangynecologist loss rates were 1 in 46 procedures versus 1 in 312 procedures for perinatologists. Losses were clustered among the 3 experienced obstetrician-gynecologists ( P < .01, χ 2 = 6.93, degrees of freedom = 1). The experienced obstetrician-gynecologist fetal loss rate was 1 in 38 amniocenteses, and the perinatologist fetal loss rate was 1 in 312. Conclusion: The risk of fetal loss from midtrimester amniocentesis appears to be higher when performed by an obstetrician-gynecologist compared with a perinatologist. (Am J Obstet Gynecol 2001;184:1340-4.)

Ratio of nuchal thickness to humerus length for Down syndrome detection

Objective: Ultrasonographic biometry markers are now being used clinically to adjust Down syndrome risk. The limitations are that the definitions of “abnormal” measurements used are arbitrary, thus reducing screening performance, and also that patient-specific Down syndrome risks cannot be calculated. We report a new ultrasonographic algorithm that is sensitive for Down syndrome detection and that estimates individual risk. Study Design: Overall in fetal populations with Down syndrome the humerus length is decreased, whereas the nuchal thickness is increased relative to that of a normal population. The nuchal thickness/humerus length ratio therefore shows an even greater increase and magnifies the separation between Down syndrome and healthy groups. Prospective data were collected in midtrimester amniocentesis cases. A regression equation for the median nuchal thickness/humerus length ratio based on biparietal partial diameter was generated. The Down syndrome likelihood ratio, or the odds on the basis of the nuchal thickness/humerus length ratio (multiples of the median), was multiplied by the age-related risk to give the posterior Down syndrome risk. Charts for rapid estimation of individual Down syndrome risk on the basis of maternal age and the nuchal thickness/humerus length ratio were constructed. Results: There were 94 cases of Down syndrome and 4700 cases in which the karyotype was normal. The mean (±SD) gestational age of the study population was 16.1 ± 1.6 weeks. Thirty-three fetuses with Down syndrome and 68 karyotypically normal fetuses had gross anomalies. The equation for the expected median nuchal thickness/humerus length ratio was as follows: 10e(1.7163 – 0.0292) × BPD + 0.0003 × BPD2, where BPD is the biparietal diameter. In the overall study population the nuchal thickness/humerus length ratio and maternal age had a 79.8% detection rate at a 22.1% false-positive rate, compared with maternal age plus humerus length (sensitivity, 55.1%) or maternal age plus nuchal thickness (sensitivity, 66.7%) at the same false-positive rate. For women ≥35 years old the values were 80% and 22.0%, respectively. Conclusions: We report an ultrasonographic biometry algorithm that, in combination with maternal age, detects 79.6% of Down syndrome cases in a high-risk group. Individual Down syndrome risk can be quickly calculated at the bedside and made available to women who desire this information before making a decision on amniocentesis. On the basis of published standards, ultrasonographic biometry as described would be a cost-effective alternative to amniocentesis in this high-risk group. (Am J Obstet Gynecol 2001;184:1284-8.)

WS13‐06Multiple pregnancy‐considerations of antenatal diagnostics

The aim of this study is to retrospectively evaluate the complications, safety and accuracy of midtrimester amniocentesis (MTAcz) in multiple pregnancy (MP). The indications and complications of MTAcz are the same for singleton pregnancies (SP) and MP, but what's different is the technique of the procedure and frequency of complications. Various techniques are here quoted, the purpose of which is to prove that samples have been taken from separate sacs. In general, the efficacy in amniotic fluid collection is 92–98%, and 95.6% in autors' cases. The number of insertion needles may have the influence on the abortion rate, but the opposite opinion also exists. The rate of spontaneous abortions has been analysed retrospectively in a group of SP with and without amniocentesis. The same parameters were also evaluated for MP. The risk of spontaneous abortions following MTAcz is nearly 2.5 times higher in MP (1.7% vs. 3.89%) than in SP, but is still within the range of normally elevated biological risk (4.5%) of this group of subjects.

What invasive procedure to use in early pregnancy?

As scientific knowledge and medicine advance so do the expectations of the general public. Advances in molecular biology, ultrasonography, access to the early gestational sac and prenatal diagnosis have helped both drive and meet these expectations. We discuss the use, advantages, potential risks and complications of invasive prenatal diagnostic procedures in early pregnancy. All invasive procedures should be performed under continuous ultrasound guidance by experienced operators. Within this context, mid-trimester amniocentesis remains the safest invasive procedure. Chorionic villus sampling (CVS) and early amniocentesis (EA) are associated with a higher risk of subsequent pregnancy loss. There is also a 10-fold increase in the risk of mosaicism with CVS compared to amniocentesis. Both CVS and EA can induce fetal structural defects and should be abandoned as routine invasive tests. Patient counselling should include an evaluation of the risk associated with each individual procedure but also the operator's personal complication rate.

First-trimester transcervical chorionic villus sampling by biopsy forceps versus mid-trimester amniocentesis: a randomized controlled trial project

Up to now, no data are available comparing amniocentesis and chorionic villus sampling (CVS) using biopsy forceps. A series of 1313 consecutive women referred to our unit before 12 weeks of pregnancy for fetal cytogenetic analysis because of advanced maternal age, were randomized into CVS with the use of transcervical biopsy forceps or mid-trimester amniocentesis. The diagnostic success rates of the two groups were 98 per cent and 100 per cent, and a second procedure was needed in 4.1 per cent (13/314) and in 0. 3 per cent (1/358), respectively. Follow-up was achieved in 98.7 per cent of the pregnancies. Postprocedure spontaneous fetal losses, until the first week after birth, in the 672 pregnancies that completed the trial accounted for 2.2 per cent (7/314) in the CVS group and 2.8 per cent (10/358) in the amniocentesis group. Although the trial was prematurely discontinued, and therefore the sample size was smaller than initially planned, the results indicate that transcervical CVS was as safe as mid-trimester amniocentesis.

First‐trimester transcervical chorionic villus sampling by biopsy forceps versus mid‐trimester amniocentesis: a randomized controlled trial project

Up to now, no data are available comparing amniocentesis and chorionic villus sampling (CVS) using biopsy forceps. A series of 1313 consecutive women referred to our unit before 12 weeks of pregnancy for fetal cytogenetic analysis because of advanced maternal age, were randomized into CVS with the use of transcervical biopsy forceps or mid-trimester amniocentesis. The diagnostic success rates of the two groups were 98 per cent and 100 per cent, and a second procedure was needed in 4.1 per cent (13/314) and in 0.3 per cent (1/358), respectively. Follow-up was achieved in 98.7 per cent of the pregnancies. Postprocedure spontaneous fetal losses, until the first week after birth, in the 672 pregnancies that completed the trial accounted for 2.2 per cent (7/314) in the CVS group and 2.8 per cent (10/358) in the amniocentesis group. Although the trial was prematurely discontinued, and therefore the sample size was smaller than initially planned, the results indicate that transcervical CVS was as safe as mid-trimester amniocentesis. Copyright © 1999 John Wiley & Sons, Ltd.

Club foot, an adverse outcome of early amniocentesis: disruption or deformation?

An association between the occurrence of club foot and early amniocentesis has been reported. The largest of these randomised studies was the Canadian Early and Mid-Trimester Amniocentesis Trial. Data describing...

First trimester prenatal diagnosis: Amniocentesis

Twenty years after midtrimester genetic amniocentesis was first used, first trimester invasive prenatal procedures were introduced. Chorionic villous sampling presents some disadvantages that entitled many centers to look into an alternative for first trimester diagnosis. Early amniocentesis (EA) can be performed effectively, as shown over the years in many observational studies and partially randomized and randomized trials. Recently, a multicenter randomized trial (Canadian Early and Midtrimester Amniocentesis Trial) reported a higher total pregnancy loss, a significant increased incidence of musculoskeletal foot deformities, a significant increased culture failure rate, and an increased postamniocentesis rate of leakage in the EA group compared with midtrimester amniocentesis. These results concerning EA procedures from 11w(+0) to 12w(+6) should be included in any pre-EA counseling. However, further trials have started to evaluate EA procedures between 13w(+0) to 14w(+6).

Increased midtrimester amniotic fluid activin A: A risk factor for subsequent fetal death

Objective: The objective of this study was to determine whether concentrations of activin A and corticotropin-releasing factor in amniotic fluid can identify patients at risk of fetal death. Study Design: A retrospective case-control study of women who have had a midtrimester amniocentesis was designed. Case subjects consisted of patients who had a spontaneous fetal death after the procedure, whereas the control group consisted of patients who had a normal pregnancy outcome after midtrimester amniocentesis. Dimeric activin A was measured by a specific 2-site enzyme immunoassay, and corticotropin-releasing factor was measured by a specific and sensitive radioimmunoassay after acidic extraction. Statistical analysis was performed with Mann-Whitney U test, Fisher's exact test, and χ 2 tests and regression analysis. Results: First, activin A was detectable in all amniotic fluid samples. Second, the concentration of activin A in amniotic fluid increased with advancing gestational age. Third, patients who subsequently had a fetal death had a higher median concentration of activin A than those with a normal pregnancy outcome ( P < .01). Fourth, an amniotic fluid concentration of activin A greater than the 95th confidence interval for gestational age was found in 40% of patients who subsequently had a fetal death (odds ratio: 21.6; P < .005). Finally, the median concentration of corticotropin-releasing factor in amniotic fluid was not different in case subjects and control subjects. Conclusions: An elevated concentration of activin A in amniotic fluid identifies women at risk of fetal death. (Am J Obstet Gynecol 1999;180:194-7.)

Maternal serum screening for trisomy 18 in the first trimester of pregnancy.

The aim of this study was to evaluate the feasibility of first-trimester biochemical screening for trisomy 18, by using pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (hCG) in combination with maternal age. Maternal serum levels of PAPP-A and free beta-hCG were assayed retrospectively in stored sera from 323 singleton pregnancies at 8-13 weeks' gestation. These samples included 23 trisomy 18 pregnancies and 300 unaffected controls, diagnosed either at chorionic villus sampling or at mid-trimester amniocentesis. The median MOM in affected pregnancies was 0.25 for PAPP-A and 0.34 for free beta-hCG. Statistically significant reductions were found in the mean levels of both PAPP-A (t test: P < 0.000001) and free beta-hCG (p < 0.000001) in trisomy 18 affected pregnancies when compared with the unaffected samples. Screening for trisomy 18 using a combination of maternal age, PAPP-A and free beta-hCG would achieve a detection rate of 76.6 per cent for a false-positive rate of 0.5 per cent. These results suggest that first-trimester biochemical screening for trisomy 18 might be possible. Further investigations in a general population are needed before introducing such screening into clinical practice.