Cordocentesis-associated fetal loss and risk factors: single-center experience with 6650 cases.

OBJECTIVES: To identify procedural risk factors associated with fetal loss following cordocentesis and to determine the rate of cordocentesis-related fetal loss associated with the current cordocentesis protocol used in our institution. METHODS: This was a retrospective cohort study of pregnancies that underwent midpregnancy cordocentesis in a single center (a tertiary hospital, teaching school), between 1992 and 2018, based on data retrieved from our prospective database. All consecutive cases were validated to retrieve those meeting the eligibility criteria, which included: singleton pregnancy without underlying maternal disease, normal fetus (no structural or chromosomal abnormality or severe disorder), gestational age between 16 and 24 weeks at the time of the procedure and availability of pregnancy outcome. Cases that resulted in termination of pregnancy were excluded. We assessed the effect of prior cordocentesis model training on the fetal-loss rate and procedure-related complications, and evaluated potential risk factors of fetal loss secondary to cordocentesis, including procedure difficulty, placenta penetration, prolonged bleeding, fetal bradycardia, puncture site and early gestational age at procedure. Pregnancy outcomes were compared between the study group and a control group of women, who did not undergo cordocentesis, selected randomly at a 1:1 ratio from our obstetric database. RESULTS: A total of 10 343 procedures were performed during the study period, of which 6650 met the eligibility criteria and were included in the analysis. The fetal-loss rate in the first 60 procedures (early practice) of six operators (n = 360 procedures), who did not have prior model training, was significantly higher than that during the early practice of 18 operators (n = 1080 procedures) with prior model training (6.9% vs 1.6%; P < 0.001); whereas the fetal-loss rate in the next 60 procedures of practice was comparable between the two groups. After excluding the first 360 procedures of the groups without prior model training, the overall fetal-loss rate in pregnancies that underwent cordocentesis was significantly higher than that in the control group (1.6% vs 1.0%; P < 0.001). Considering the fetal-loss rate in the normal controls as background loss, the incremental cordocentesis-associated fetal-loss rate was 0.6%. Penetration of the placenta (odds ratio (OR), 2.65 (95% CI, 1.71-4.10)), prolonged bleeding from the puncture site (OR, 10.85 (95% CI, 5.27-22.36)) and presence of fetal bradycardia (OR, 3.32 (95% CI, 1.83-6.04)) during cordocentesis were independent risk factors associated with fetal loss. CONCLUSIONS: Cordocentesis model training markedly reduces fetal loss during the early learning curve of practice. Thus, cordocentesis practice without prior model training should not be acceptable. Significant procedural risk factors for fetal loss secondary to cordocentesis are placental penetration, prolonged bleeding and fetal bradycardia. Cordocentesis-related fetal loss may be only 0.6%, much lower than the rate reported previously. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Associations between maternal serum free beta human chorionic gonadotropin (ß-hCG) levels and adverse pregnancy outcomes.

The objective was to determine the strength of relationship between maternal free beta human chorionic gonadotropin (ß-hCG) concentrations and rates of adverse pregnancy outcomes. Consecutive records of the database of our Down screening project were assessed for free ß-hCG levels and pregnancy outcomes. Pregnancies with foetal chromosomal or structural anomalies and those with underlying disease were excluded. Free ß-hCG levels of < 0.5, > 0.5 and < 2.0, and ≥ 2.0 MoM were categorised as low, normal and high, respectively. Of 17,082 screened women, 13,620 were available for analysis. In the first trimester (n = 8150), low ß-hCG levels significantly increased risk for intrauterine growth restriction (IUGR), preterm birth, low birth weight (LBW) and low Apgar score with relative risk of 1.66, 1.43, 1.83 and 2.89; whereas high ß-hCG group had a significant decreased risk of preterm birth and GDM with relative risk of 0.73 and 0.62. In the second trimester (n = 5470), both low and high ß-hCG groups had significant increased risks of the most common adverse outcomes, i.e. spontaneous abortion, IUGR and preterm birth. In conclusion, abnormally low (< 0.5MoM) or high (> 2.0 MoM) free ß-hCG levels are generally associated with an increased risk of adverse pregnancy outcomes. Nevertheless, high free ß-hCG levels in the first trimester may possibly decrease risk of preterm delivery and GDM.

Prenatal diagnosis of homozygous alpha-thalassemia-1 by cell-free fetal DNA in maternal plasma.

OBJECTIVE: To investigate the use of cell-free fetal DNA (cff-DNA) to determine fetal status in pregnant women who were risk for having Hb Bart's. METHODS: Plasma DNA was extracted from 10 mL of maternal blood from couples who both were alpha-thalassemia-1 carriers (SEA deletion). Real time quantitative PCR was performed using fluorescence-labeled probes to monitor wild type (wt) and SEA allele. The quantity of each allele was determined by cycle threshold (Ct). ΔCt (Ct of wt- Ct of SEA) was calculated from each sample. Prenatal diagnosis was performed to determine fetal status. RESULT: There were 62 Hb Bart's, 62 alpha-trait and 34 normal fetuses in this study. Mean ΔCt was 1.04 ± 0.38, 0.21 ± 0.37 and 0.14 ± 0.55 in Hb Bart's, alpha-trait and normal fetuses, respectively. Based on ROC, the best cut-off of ΔCt for predicting Hb Bart's was 0.51, giving 98.4% sensitivity and 20.8% false-positive rate. All but one Hb Bart's (98.4%) had ΔCt above 0.51, whereas 74.2% of alpha-trait and 88.2% of normal fetuses had ΔCt below 0.51. CONCLUSION: There is a positive trend to use cff-DNA in maternal plasma for prenatal diagnosis of homozygous alpha-thalassemia-1. With this technique, invasive prenatal testing and complications can be avoided in 79.2% of unaffected fetuses.

Fetal structural anomaly screening at 11-14 weeks of gestation at Maharaj Nakorn Chiang Mai Hospital.

OBJECTIVE: To determine the detection rate by ultrasound scanning of fetal anomaly by first trimester (11-14 weeks of gestation). MATERIAL AND METHOD: A prospective descriptive study of 597 pregnant women undergoing Nuchal Translucency (NT) measurement at 11-14 weeks of gestation at Maharaj Nakorn Chiang Mai Hospital. The sonographic examinations focused on NT thickness and fetal structural survey. The final diagnoses were based on neonatal outcomes assessed by the pediatricians and abortuses evaluated by the pathologists. The main outcome measure was the detection rate of fetal anomaly using ultrasonographic examination. RESULTS: Of 597 pregnant women recruited into the present study, the mean age was 29.41 +/- 5.8 years, the incidence of fetal anomaly was about 4% (24 from 597 cases). The detection rate by first ultrasound scans was 58% (14 from 24 cases) and the most common detected structural anomaly was cystic hygroma and exencephaly. The rate of undetected fetal anomalies was 42% (10 from 24 cases). Abnormal NT was found in 16 from a total of 597 cases (2.7%), most of them, however, had normal karyotype and no gross anomaly at birth. CONCLUSION: First trimester (11-14 weeks) ultrasound scan is probably a useful method for detection of fetal structural anomalies with a relatively high detection rate, and may be a good adjunct to the conventional examination.

Erythrocyte osmotic fragility test for screening of alpha-thalassemia-1 and beta-thalassemia trait in pregnancy.

OBJECTIVES: To evaluate the sensitivity and specificity of osmotic fragility test (OFT) as a screening test in predicting the severe thalassemia trait (alpha-thalassemia-1 & beta-thalassemia). METHODS: A descriptive analysis and diagnostic test of non-anemic pregnant women attending antenatal care clinic, Maharaj Nakorn Chiang Mai, during April, and July 2002 was made. Blood samples were collected from 446 singleton pregnancies with no obvious medical complication such as iron deficiency anemia. OFT was performed in the same day, using 0.45% glycerin saline solution and the cut-off value of less than 60% was used for an abnormal test. Quantitative HbA2 test and PCR (SEA type) were done as a gold standard to confirm the diagnosis of beta-thalassemia trait and alpha-thalassemia-1 trait, respectively. RESULTS: The main outcome measures were sensitivity, specificity, positive and negative predictive value of OFT. If the OFT cut-off value of less than 60% was considered positive, the test had a sensitivity, specificity, positive and negative predictive value of 97.6%, 72.9%, 33.6%, and 99.5%, respectively. CONCLUSION: OFT has high sensitivity in detection of alpha-thalassemia-1 trait or beta-thalassemia trait and due to its simplicity with very low cost it may, therefore, be considered as a screening test in a wide population.

Sonographic features of trisomy 13 at midpregnancy.

OBJECTIVES: To evaluate the sonographic characteristics, at 16-22 weeks of gestation, of fetuses later diagnosed with trisomy 13. METHODS: This descriptive analysis of a case series was conducted from June 1989 to May 2001 at the Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Thailand. Women with abnormal sonographic findings at midpregnancy (16-22 weeks of gestation) underwent amniocentesis or cordocentesis for karyotyping, and the inclusion criterion was proven trisomy 13. RESULTS: Indications for sonographic examination at midpregnancy were a genetic risk, large- or small-for-date fetus, and other suspected anomalies. Fifteen fetuses were later diagnosed with trisomy 13. In all of these cases there was at least one abnormal sonographic finding. In only one case did the fetus show no structural abnormality (at 17 weeks), but polyhydramnios and fetal growth restriction were observed. Common sonographic findings included holoprosencephaly with associated facial anomalies, and abnormal feet and/or hands, especially polydactyly. Non-structural abnormal findings such as polyhydramnios or fetal growth restriction were seen in less than one third of the fetuses. CONCLUSIONS: Nearly all the fetuses with trisomy 13 had sonographic characteristics of abnormalities at midpregnancy although common findings had often not yet appeared or the findings were low-sensitive. Detailed ultrasound at midpregnancy could effectively screen for further genetic testing pregnancies at risk for trisomy 13.

Sulfogalactosylglycerolipid is involved in human gamete interaction.

Recent results from our laboratory have revealed the role of sulfogalactosylglycerolipid (SGG) in mouse sperm-zona pellucida (ZP) binding. In this report, we demonstrated the presence of SGG in Percoll-gradient centrifuged (PGC) human sperm by high performance thin layer chromatography with orcinol and Azure A staining, specific for glycolipids and sulfolipids, respectively. SGG in human PGC sperm was quantified by its affinity to Azure A to be 12-15 mol% of sperm lipids. Indirect immunofluorescence revealed that SGG existed on both live and aldehyde fixed human sperm in the head region. Pretreatment of human PGC sperm with affinity purified antiSGG Fab markedly inhibited sperm binding to the ZP in a concentration dependent manner, without any changes in the spontaneous acrosome rate or sperm motility parameters. Fluorescently labeled SGG liposomes also bound uniformly to isolated human ZP, while fluorescently labeled galactosylglycerolipid (GG, SGG's parental lipid) or phosphatidylserine (PS, negatively charged like SGG) liposomes did not. All of these results suggested the role of human sperm SGG in ZP binding.

Prenatal diagnosis of hemoglobin Bart's hydrops fetalis by HPLC analysis of hemoglobin in fetal blood samples.

Since HbF and HbA are not found in fetuses with Hb Bart's hydrops fetalis the feasibility of prenatal diagnosis of homozygous alpha-thalassemia 1 by fetal hemoglobin typing was examined. Blood samples were obtained from fetuses at 18 to 22 weeks of gestation by cordocentesis in 32 pregnant women at risk of having a child with homozygous alpha-thalassemia 1 (alpha-thal-1). The samples were analyzed by a PCR-based method for the diagnosis of alpha-thal-1 (SEA type) and the proportion of hemoglobin fractions were determined by automated HPLC. DNA analysis showed that 8 of the 32 fetuses were homozygotes for alpha-thal-1, 17 were heterozygous for alpha-thal-1 (alpha-thal-1 trait), and a normal complement of four a-globin genes was found in 7 cases. The Hb typing in fetuses with homozygous alpha-thal-1 showed a peak of unbound Hb (Hb Bart's and Hb Portland) and no HbF, HbA and HbA The alpha-thal-1 trait chromatograms showed unbound Hb, pre HbF, HbF and HbA peaks. The chromatogram of normal fetuses showed HbF and HbA peaks without HbA2. In these cases the HbA proportion is between 3% and 10% with no apparent differences between the 18h and 22nd week of gestation. As the analysis of fetal Hb types by HPLC is facile and speedy and the results correspond with those obtained by DNA analysis, fetal Hb typing by automated HPLC is a convenient prenatal diagnostic method for homozygous alpha-thal-1. The method is recommended for prenatal diagnosis in populations with a high frequency of alpha-thal-1.

Prenatal sonographic markers of trisomy 21.

OBJECTIVE: To describe the sonographic characteristics of fetuses with trisomy 21. DESIGN: A prospective descriptive analysis. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University. SUBJECTS: Pregnancies at risk of trisomy 21 between 14-27 weeks' gestation. RESULTS: Thirty-six fetuses with subsequently proven trisomy 21 were prenatally evaluated by ultrasound in the second trimester. The main indications for detailed ultrasound examinations were advanced maternal age and abnormal findings on routine ultrasound. All of them had chromosome analysis by amniocentesis or cordocentesis. Nineteen (52.78%) had one or more abnormal findings. The common sonographic findings included thickened nuchal fold (33.33%), short femur (19.44%), and mild pyelectasis (22.22%). The other uncommon abnormalities included major anomalies (cardiac malformations, ventriculomegaly, duodenal atresia, esophageal atresia), hyperechoic bowel, echogenic intracardiac foci, abnormalities of extremities. In this study, rare minor markers but more specific markers including sandal gap, clinodactyly and mid-phalanx hypoplasia of the fifth finger were demonstrated. CONCLUSION: About half of the fetuses with trisomy 21 had abnormal sonographic findings in the second trimester. The most common marker was thickened nuchal fold. Although prenatal ultrasound can not permit a definite diagnosis of trisomy 21, about half of them have sonographic markers, warranting cytogenetic testing.

Prenatal diagnosis of beta-thalassemia major by high-performance liquid chromatography analysis of hemoglobins in fetal blood samples.

In Thailand and adjacent countries, most of the beta-thalassemia genes are beta(0)-thalassemia mutations that prevent the production of Hb A. We propose the quantitation of the Hb A fraction in fetal blood in the mid-trimester of pregnancy by automated high performance liquid chromatography as a reasonable prenatal diagnostic method to be applied in areas with limited laboratory facilities. Forty pregnant women at risk of delivering a child with beta-thalassemia major were identified using an erythrocyte osmotic fragility test and quantitation of Hb A2. Cordocentesis was performed at the gestational age of 18-22 weeks and fetal blood was analyzed for hemoglobin fractions by automated high performance liquid chromatography. The beta-globin gene mutations were characterized by beta-globin gene sequencing. The 4 bp deletion at codons 41/42 (-TTCT) was the most frequent of the 40 beta-thalassemia mutations observed (20/40 = 50%), followed by the splice site mutation IVS-I-1 (G-->T) (7/40 = 17.5%), the nonsense mutation at codon 17 (A-->T) (7/40 = 17.5%), the nonsense mutation at codon 35 (C-->A) (3/40 = 7.5%), and the beta(+)-thalassemia promoter mutation at -28 (A-->G) (3/40 = 7.5%). High performance liquid chromatography revealed nine fetuses which had only Hb F and no Hb A. All were homozygotes or compound heterozygotes for beta(0)-thalassemia mutations. In the remaining 31 fetuses, a Hb A peak was present in the chromatograms. One fetus with 0.5% Hb A was a compound heterozygote for the -28 (A-->G) and codons 41/42 (-TTCT) mutations. In the remaining 30 fetuses, the Hb A values ranged between 0.8 and 7.4%. Twenty of these, with a Hb A concentration of 1.82 +/- 0.49% (range 0.8-2.8%), were beta-thalassemia heterozygotes. The remaining 10 fetuses had Hb A values of 4.89 +/- 1.47% (range 2.9-7.4%) and normal beta-globin genes. The absence of Hb A in homozygotes or compound heterozygotes for beta(0)-thalassemia mutations and the presence of measurable amounts of Hb A in heterozygotes and normal homozygotes, permits the diagnosis of fetuses expected to develop postnatal beta-thalassemia major.

Prenatal eradication of Hb Bart's hydrops fetalis.

OBJECTIVE: To evaluate the effectiveness of prenatal prevention of Hb Bart's hydrops fetalis. STUDY DESIGN: The study was a prospective descriptive analysis of pregnant women attending an antenatal clinic between June 1990 and June 1998. The study consisted of two periods, the first half with no prenatal diagnosis (PND) (1990-1994) and the second half with PND. During the study period, all cases of Hb Bart's hydrops fetalis were prospectively collected and postnatally confirmed. In the second period, prenatal strategy to control severe thalassemia was introduced. The strategy included (1) carrier identification by retrospective (history review for known risk) and prospective screening (simple erythrocyte osmotic fragility test) in women without known risks, (2) the couples at risk were offered genetic counseling and cordocentesis, (3) analysis of fetal blood for diagnosis, and (4) counseling for termination of pregnancy. RESULTS: During the first half of the study, the prevalence of Hb Bart's hydrops fetalis was 0.305 (89 in 29,399 deliveries). There were no fetuses with Hb Bart's hydrops fetalis among 16,360 screened pregnancies in the second half. However, of 6,856 pregnancies in the second half not screened due to a late first visit, 10 (0.15%) fetuses had Hb Bart's hydrops fetalis. Among the screened group, cordocentesis was performed in 361 pregnancies at risk, 170 and 191 from retrospective and prospective screening, respectively; and 75 (20.8%) were proven to have Hb Bart's disease, which was diagnosed before hydropic changes occurred. CONCLUSION: The strategy proved effective in preventing Hb Bart's hydrops fetalis, and extensive experience with it suggests that it be considered an effective way to control severe thalassemia.

Prenatal diagnosis of thrombocytopenia-absent-radius (TAR) syndrome.

The prenatal diagnosis of thrombocytopenia-absent-radius (TAR) syndrome using ultrasound and cordocentesis in the 16th week of gestation is established. The sonographic findings detected in this case included bilateral absence of the radius and club hands with normal thumbs and metacarpals. Because of a high index of suspicion for the syndrome, cordocentesis for fetal blood analysis was performed. Thrombocytopenia, with a platelet count of 14,000/mm3, was identified. The pregnancy was electively terminated and subsequent findings confirmed the sonographic diagnosis. This report, to our knowledge, is one of a very limited number of cases published in the literature, in which the prenatal diagnosis of TAR syndrome was made.

Prenatal control of severe thalassaemia: Chiang Mai strategy.

Prenatal diagnosis of severe thalassaemia is conventionally diagnosed by fetal DNA analysis but it can not be widely used due to its drawbacks of high cost and technical effort. This prospective study describes a new prenatal strategy in preventing severe thalassaemia by a more simple and inexpensive way. The strategy included: (1) genetic counselling; (2) identification of pregnancies at risk by retrospective screening (history of known risk) and prospective screening for asymptomatic women; (3) cordocentesis at 16-22 weeks' gestation; (4) fetal blood analysis with high performance liquid chromatography (HPLC); (5) termination of affected pregnancy. The prospective screening consisted of 2 min osmotic fragility (OF) and HbE screening test in women with no risk, and testing the husbands of the women with a positive result. If both of the couple had a positive result, the diagnostic test (HbA(2) level and PCR alpha-thal 1) for the carrier was needed. A pregnancy in which both of the couple were carriers was considered at risk. This strategy identified 181 and 108 couples at risk by prospective (from 7954 pregnancies) and retrospective screening, respectively. Two hundred and forty-two underwent cordocentesis, 108 from retrospective screening and 134 from prospective screening, and 62 were proven to have severe thalassaemia (29 and 33 in retrospective and prospective screening, respectively). The strategy identified nearly all, if not all, fetuses with severe thalassaemia without false positives among the screened couples. In conclusion, the strategy proves to be highly effective in the control of severe thalassaemia.

Prenatal diagnosis: 10-year experience.

To evaluate the indications and results of prenatal diagnosis of the high risk pregnant women attending the antenatal care clinic at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University during 1988-1998, we analysed 2,315 amniocenteses, 1,000 cordocenteses, and 11,895 obstetric ultrasound examinations. Among the amniocentesis group, 2,017 cases (87%) were done with the indication of advanced maternal age. The prevalence of major abnormal fetal chromosomes among high risk pregnancies was 1:58. Of 1,000 cases with cordocentesis, the most common indication was fetal risk of severe thalassemia (658 cases; 65.8%) and followed by fetal risk of chromosome abnormalities (272 cases; 27.2%). In the group of cordocentesis for diagnosis of thalassemia, 99 and 49 pregnancies were affected with Hb Bart's disease and homozygous beta-thalassemia, respectively. Thirty three cases with indication of chromosome analysis had fetuses with abnormal chromosomes. The major indications of ultrasonography included suspicion of intrauterine growth restriction (IUGR), determination of gestational age and screening anomalies, respectively. In conclusion, our extensive experience has enabled us to prenatally detect most fetuses with severe thalassemia, and fetuses with abnormal chromosomes as well as anomalies in a significant number, contributing a great deal to our population. Therefore, we recommend that systematic prenatal diagnosis, either amniocentesis, cordocentesis or ultrasound should be provided to every high risk pregnant woman for a healthy newborn.

Fetal sonographic cardiothoracic ratio at midpregnancy as a predictor of Hb Bart disease.

The objective of this study is to evaluate the efficacy of sonographic cardiothoracic ratio at midpregnancy in predicting fetal hemoglobin Bart disease. Among 17,254 pregnant women screened for severe thalassemia between June 1994 and November 1998, 345 pregnant women at risk for having a fetus with hemoglobin Bart disease underwent ultrasonographic examination and cordocentesis at 18 to 21 weeks' gestation. Before cordocentesis, the cardiothoracic ratio was determined and recorded. The definite fetal diagnosis was based on fetal blood analysis with high performance liquid chromatography. Among 345 pregnancies in which sonographic examination and cordocentesis were performed, 70 fetuses were affected by hemoglobin Bart disease. The mean cardiothoracic ratio was significantly higher than that of unaffected fetuses (0.55 versus 0.45, Student's t-test, P<0.001). The sensitivity and specificity of the cardiothoracic ratio in prediction were calculated for various cutoff values. On the basis of the receiver operating characteristic curve, the best cutoff value was 0.50 (greater than 0.50 considered abnormal), giving the sensitivity of 98.6% and a specificity of 98.9%. In conclusion, the cardiothoracic ratio has very high accuracy in predicting hemoglobin Bart disease in pregnancies at risk. This finding suggests that invasive diagnostic method should be reserved for only the fetuses who have a cardiothoracic ratio of 0.5 or more; however, further studies are needed to confirm this observation.

Placental thickness at mid-pregnancy as a predictor of Hb Bart's disease.

The measurement of placental thickness can effectively differentiate normal pregnancies from affected pregnancies requiring invasive work-up. The objective was to evaluate the efficacy of placental thickness at mid-pregnancy in predicting fetal Hb Bart's disease in pregnancies at risk. Among 17 254 pregnant women screened for severe thalassaemia between June 1994 and December 1998, 345 pregnancies at risk for having a fetus with Hb Bart's disease underwent ultrasound examinations and cordocentesis at 18-21 gestational weeks. Before cordocentesis, the placental thickness was measured and recorded. The definite fetal diagnosis was performed with high performance liquid chromatography. The efficacy of placental thickness in predicting Hb Bart's disease was evaluated by sensitivity and specificity. Various cut-off values of the placental thickness were used for calculation and the best cut-off value was determined by a receiver-operating characteristic (ROC) curve. Of 345 pregnancies at risk, 70 fetuses with Hb Bart's disease were finally diagnosed. The mean placental thickness (+/-SD) of the normal pregnancies and pregnancies with Hb Bart's fetuses were significantly different, 24.6+/-5.2 mm and 34. 5+/-6.7 mm, respectively (Student's t-test, p<0.001). The sensitivity and specificity of placental thickness in prediction were calculated for various cut-off values. Based on the ROC curve, the best cut-off value was 30 mm (>30 mm considered abnormal), giving a sensitivity of 88.57 per cent, specificity of 90.18 per cent, positive-predictive value of 78.48 per cent and negative-predictive value of 96.87 per cent. For couples at risk, when sonographic placental thickness is normal, the risk of having an Hb Bart's fetus is markedly decreased. The measurement of placental thickness can effectively, though not absolutely, differentiate the normal pregnancies from affected ones requiring invasive work-up.

Amniocentesis-related fetal loss: a cohort study.

OBJECTIVE: To assess the risk of fetal loss attributable to second-trimester amniocentesis. METHODS: A cohort study was undertaken among singleton pregnant women undergoing genetic amniocentesis and controls matched prospectively on a one-to-one basis, matched strictly for maternal age, parity, and socioeconomic status. Both groups were recruited at 15-24 weeks' gestation and observed until delivery. The fetal loss rates of the groups were compared. RESULTS: A total of 2256 pairs were recruited to the study. After excluding those pairs lost to follow-up, those with fetal malformation, and those later proven to have major chromosomal abnormalities, 2045 matched pairs were compared by pregnancy outcomes. There were no significant differences in fetal loss rates, premature deliveries, or placental abruptions between the study and control groups (P > .05). However, this study did not have enough statistical power to identify differences of less than 1%. CONCLUSION: Second-trimester amniocentesis is probably not associated with a greater fetal loss rate than that of matched controls.