Mid-trimester Genetic 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.

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.)

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.)

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).

A new screening protocol combining urine β-core fragment and ultrasonography for Down syndrome detection

OBJECTIVE: Our purpose was to ascertain the screening efficiency of a new midtrimester Down syndrome detection protocol that combines maternal urine testing and ultrasonographic examination. STUDY DESIGN: In a prospective study, β-core fragment, the stable end product of human chorionic gonadotropin metabolism, was measured in maternal urine. The results were standardized for urine creatinine levels. The study was performed in women undergoing midtrimester genetic amniocentesis (15 to 24 weeks' gestation). Urine β-core fragment values were expressed as multiples of the normal median for gestational age. The screening performance of a combination of ultrasonographic parameters and urine β-core values for Down syndrome detection was determined. RESULTS: A total of 511 singleton pregnancies in women undergoing amniocentesis were studied, 18 of the women (3.5%) had a Down syndrome fetus. A urine β-core fragment level ≥97th percentile had a sensitivity of 61.1% and a false-positive rate of 3.2%. An abnormal prenatal screen was defined as a urine β-core level ≥97th percentile, increased nuchal thickness (≥5 mm), or the presence of gross structural defects. Corresponding values for the screening efficiency of an abnormal prenatal screen were sensitivity of 77.8% and a false-positive rate of 4.1%. With an abnormal prenatal screen the odds ratio is 82.8 (95% confidence interval 22.6 to 364.9) for having a Down syndrome fetus. CONCLUSION: The presence of an abnormal maternal urine β-core level, a gross ultrasonographic anomaly, or increased nuchal thickness had a high detection rate and a low false-positive rate for Down syndrome. This novel screening algorithm is useful for further delineating the risk status in patients at high risk who are reluctant to undergo or decline genetic amniocentesis. (Am J Obstet Gynecol 1998;178:779-82.)

Septic Shock, Adult Respiratory Distress Syndrome, and Disseminated Intravascular Coagulopathy Following Midtrimester Genetic Amniocentesis

Background: Midtrimester genetic amniocentesis is a commonly performed procedure, with acknowledgment of some risk to mother and fetus. Case: We present an unusual case of midtrimester genetic amniocentesis with bowel injury and resulting septic shock, adult respiratory distress syndrome, and disseminated intravascular coagulation. A total abdominal hysterectomy and bilateral salpingoophorectomy were required for resolution of sepsis. The patient also required prolonged ventilatory support postoperatively. Conclusion: Although relatively safe, genetic amniocentesis can result in serious morbidity, and attention to technique should be maintained.

Septic shock, adult respiratory distress syndrome, and disseminated intravascular coagulopathy following midtrimester genetic amniocentesis

Background Midtrimester genetic amniocentesis is a commonly performed procedure, with acknowledgment of some risk to mother and fetus. Purpose We present an unusual case of midtrimester genetic amniocentesis with bowel injury and resulting septic shock, adult respiratory distress syndrome, and disseminated intravascular coagulation. A total abdominal hysterectomy and bilateral salpingoophorectomy were required for resolution of sepsis. The patient also required prolonged ventilatory support postoperatively. Conclusion Although relatively safe, genetic amniocentesis can result in serious morbidity, and attention to technique should be maintained. Infect. Dis. Obstet. Gynecol. 5:386–390, 1997. © 1998 Wiley-Liss, Inc.

Interleukin-1 alpha and interleukin-1 beta in preterm and term human parturition.

Interleukin-1 (IL-1) has been implicated in the mechanism of human parturition in the setting of infection. The purpose of this study was to determine the effect of labor (term and preterm) and microbial invasion of the amniotic cavity on amniotic fluid (AF) concentrations IL-1 alpha and IL-1 beta. AF was retrieved by transabdominal amniocentesis from the following groups of women: midtrimester genetic amniocentesis (16 to 18 wk) (N = 15), preterm labor with intact membranes (21 to 36 wk) with or without infection (N = 72), preterm premature rupture of membranes (PROM) (N = 88), and term not in labor or in active labor with or without infection (N = 58). AF was cultured for aerobic and anaerobic bacteria as well as Mycoplasmas. IL-1 was measured with a commercially available immunoassay validated for AF (sensitivity: IL-1 alpha, 157 pg/ml; IL-1 beta, 50 pg/ml). All women at midtrimester had undetectable AF IL-1 alpha and IL-1 beta. Among women in preterm labor with positive AF cultures, IL-1 alpha and IL-1 beta were detectable in the AF in 86.6% (13/15) and 100% (15/15), respectively. In contrast, all women with negative AF cultures without labor (N = 36) had undetectable AF IL-1 alpha concentrations and 52.7% (19/36) had undetectable AF IL-1 beta concentrations. Histopathological chorioamnionitis was present in 92.8% (13/14) of patients who had positive AF cultures and detectable IL-1 in the AF. IL-1 was significantly higher in patients with preterm PROM, labor, and positive AF cultures than in the other subgroups of patients with preterm PROM.(ABSTRACT TRUNCATED AT 250 WORDS)

Screening for Down's syndrome in older women based on maternal serum alpha-fetoprotein levels and age: Preliminary results

We report the results of screening for Down's syndrome (DS) in older women using published rate schedules based on maternal serum alpha-fetoprotein (MSAFP) and age. Five hundred and seventeen patients aged 35 years and older, who were referred for a mid-trimester genetic amniocentesis, were first tested for MSAFP and then underwent an amniocentesis. Individual risks for DS, combining MSAFP and age, were derived using three different published rate schedules. Theoretical selection for amniocentesis was made using the cut-off level of the average collective risk for a 35-year-old woman (1:380 at live birth or 1:270 at amniocentesis). Six affected pregnancies (five with DS and one with trisomy 18), which were diagnosed prenatally, were all found to be at a higher risk than the specified cut-off. These cases would have been diagnosed in any event, using any of the published rate schedules. According to these rate schedules, between 39 and 45 per cent of the patients would be in the lower risk group and therefore would have been counselled not to undergo amniocentesis. Further studies should be conducted in order to reach conclusive screening policies for DS in older women.

641 The significance of dark-stained amniotic fluid at mid-trimester genetic amniocentesis

641 The significance of dark-stained amniotic fluid at mid-trimester genetic amniocentesis

Rhesus sensitization after midtrimester genetic amniocentesis

In 944 Rh-negative patients who received rhesus immunoglobulin (anti-D) following genetic amniocentesis, not a single case of Rh sensitization occurred. Routine administration of a small dose (100 micrograms) of anti-D is effective in preventing Rh sensitization after midtrimester amniocentesis.

Midgestational Amniotic Fluid Human Atrial Natriuretic Polypeptide (HANP): Possible Predictor of Third-Trimester Pregnancy-Induced Hypertension

Atrial natriuretic polypeptide (ANP) comprises a group of potent diuretic and vasorelaxant substances synthesized and released by mammalian atrial cardiocytes. In late pregnancy, plasma ANP concentrations appear to be increased in gravidas with severe pregnancy-induced hypertension (PIH) versus normotensive parturients. Earlier gestational assessments of ANP in plasma and other fluid compartments are needed at various stages of gestation in gravidas who remain normotensive and those who become hypertensive. The present retrospective study was undertaken to determine if midgestational amniotic fluid concentrations of ANP in healthy controls and in gravidas destined to develop PIH would be significantly different and possibly predictive of later hypertensive disease. The findings in 14 gravidas who underwent midtrimester genetic amniocentesis and later developed PIH were compared with 44 matched control patients. Midgestational amniotic fluid ANP concentrations were determined to not be significantly differ...

Neonatal lung function following mid-trimester amniocentesis.

Three hundred and fifty-four women who underwent midtrimester genetic amniocentesis were matched for age, parity, indication, and smoking history, with an equivalent number of women who had declined the procedure, for the purpose of comparing the neonatal respiratory status of their offspring. There was no evidence that the infants exposed to genetic amniocentesis were compromised.

Infant development following midtrimester amniocentesis

The present study examined potential developmental and behavioral effects of midtrimester genetic amniocentesis. Comparisons between infants whose mothers had this diagnostic test and control infants yielded no differences in the neonatal period or at age 6 months. The continued need for longitudinal studies is discussed.

Midtrimester genetic amniocentesis in eastern Ontario: a review from 1970 to 1985.

Greater use of genetic amniocentesis in the Eastern Ontario region occurred once the results from the various national trials were published. Acceptance also paralleled an increase in the number of low parity older women having children and the centralisation and greater publicity given to our programme in the late 1970s. A centralised approach has had the positive effects of preventing unnecessary procedures, assuring appropriate patient counselling, follow up, and review, and of increasing obstetric and laboratory expertise. Advanced maternal age has been largely responsible for the increased demand for the service and accounted for an increasing proportion of tests performed, while the absolute number for several other diagnostic categories remained unchanged. We found no evidence that women with a history of previous miscarriage had a higher rate of pregnancy loss following the procedure, and comparison with a group of women who declined amniocentesis did not show that the test increased the risk of miscarriage.

The significance of meconium in midtrimester genetic amniocentesis

Since the advent in recent years of midtrimester amniocentesis for genetic testing, there has been an increasing number of reports of occasional instances of meconium-stained amniotic fluid of uncertain prognostic significance. Previous reports have suggested a fetal mortality of 30%. With larger series now available for study, more accurate information on the incidence of this occurrence and its significance is presented. The present series consists of 4709 consecutive amniocenteses performed from 1978 to 1983, at two genetic testing centers in Portland, Oregon. Meconium-stained amniotic fluid was found in 79 cases, for an incidence of 1.67%. Contrary to previously published reports, the fetal mortality was 5.06%. Thus the finding of meconium-stained amniotic fluid during midtrimester genetic amniocentesis may not carry the ominous prognosis that originally might have been predicted.

Midtrimester amniocentesis: Obstetric outcome and neonatal neurobehavioral status

The possible effects of midtrimester genetic amniocentesis on neurobehavioral status were studied in newborn infants of women who had had the procedure (N = 100) and in newborn infants of women who had declined the test (N = 56). Brazelton's Neonatal Behavioral Assessment Scale was administered to newborn infants born at term and did not reveal consequences of amniocentesis on neonatal orientation, range of state, motor ability, autonomic regulation, regulation of state, response decrement, or reflexes. Information on obstetric complications also was obtained. The findings raised questions regarding the temporal relationship between amniocentesis and fetal loss and focused attention on preterm birth as a potential risk that warrants further investigation. This study provides the foundation for our prospective longitudinal follow-up in which the cohort will be reassessed later in infancy and in childhood.

Fetal exsanguination and other vascular injuries from midtrimester genetic amniocentesis

A case of fetal exsanguination after midtrimester genetic amniocentesis is reported. Examination of the ratio of fetal-to-maternal red cells in the amniotic fluid obtained by amniocentesis for genetic study from 242 consecutive patients, including the reported case, suggests that fetal hemorrhage is relatively common and difficult to avoid during this procedure. It also appears that hemorrhage occurs significantly more often when the placenta is located anteriorly. Reasons as to why the accident is rarely fatal are considered, and some recommendations for patient counselling and management are discussed.