Amniocentesis and placental sampling for pre-birth diagnosis

What is the issue?

Many women want to be reassured that their unborn baby is healthy. Second trimester amniocentesis performed around 16 weeks' gestation is the test most often used. A needle is inserted through the abdomen into the uterus to remove a sample of amniotic fluid. Early amniocentesis can be done before 15 weeks. With chorionic villus sampling, a needle is used to withdraw a sample of placental tissue. The needle can be inserted through the abdomen (transabdominal), or vaginally through the cervix (transcervical).

Why is this important?

It is important that tests used to indicate high-risk (screening tests), and tests used to make a diagnosis (diagnostic tests) are safe and accurate. It is also important that diagnostic tests can be done early enough to allow parents the choice of early termination of pregnancy.

What evidence did we find?

We searched for evidence on 3 March 2017; we included 16 randomised controlled trials in the review, with a total of 33,555 women. The overall risk of bias was low, with very low to high-quality evidence supporting the outcomes studied. One study of 4606 women found that a second trimester amniocentesis increased spontaneous miscarriages and pregnancy losses, but the estimate remains quite imprecise, ranging from 0 to 2%.

Early amniocentesis was not as safe as second trimester amniocentesis because of increased pregnancy loss and spontaneous miscarriages, and higher occurrences of anomalies, particularly deformed or clubfeet (talipes).

Low-quality evidence found no clear differences in pregnancy loss or spontaneous miscarriages after transabdominal chorionic villus sampling or second trimester amniocentesis. Transcervical chorionic villus sampling may increase the total risk of pregnancy loss compared with a second trimester amniocentesis, mostly because of increased spontaneous miscarriages. Healthcare staff may have found transcervical chorionic villus sampling more difficult to perform than transabdominal chorionic villus sampling, because there were more failures to obtain a sample, and more repeat testing.

What does this mean?

High-quality evidence supported second trimester amniocentesis as the procedure of first choice for testing from 15 weeks' gestation or later. When a test is required earlier than 15 weeks' gestation, low-quality to moderate-quality evidence suggested that transabdominal chorionic villus sampling could be considered the procedure of first choice, depending on the outcome of interest.

Authors' conclusions: 

Second trimester amniocentesis increased the risk of pregnancy loss, but it was not possible to quantify this increase precisely from only one study, carried out more than 30 years ago.

Early amniocentesis was not as safe as second trimester amniocentesis, illustrated by increased pregnancy loss and congenital anomalies (talipes). Transcervical chorionic villus sampling compared with second trimester amniocentesis may be associated with a higher risk of pregnancy loss, but results were quite heterogeneous.

Diagnostic accuracy of different methods could not be assessed adequately because of incomplete karyotype data in most studies.

Read the full abstract...
Background: 

During pregnancy, fetal cells suitable for genetic testing can be obtained from amniotic fluid by amniocentesis (AC), placental tissue by chorionic villus sampling (CVS), or fetal blood. A major disadvantage of second trimester amniocentesis is that the results are available relatively late in pregnancy (after 16 weeks' gestation). Earlier alternatives are chorionic villus sampling (CVS) and early amniocentesis, which can be performed in the first trimester of pregnancy.

Objectives: 

The objective of this review was to compare the safety and accuracy of all types of AC (i.e. early and late) and CVS (e.g. transabdominal, transcervical) for prenatal diagnosis.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (3 March 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP; 3 March 2017), and reference lists of retrieved studies.

Selection criteria: 

All randomised trials comparing AC and CVS by either transabdominal or transcervical route.

Data collection and analysis: 

Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach.

Main results: 

We included a total of 16 randomised studies, with a total of 33,555 women, 14 of which were deemed to be at low risk of bias. The number of women included in the trials ranged from 223 to 4606.

Studies were categorized into six comparisons: 1. second trimester AC versus control; 2. early versus second trimester AC; 3. CVS versus second trimester AC; 4. CVS methods; 5. Early AC versus CVS; and 6. AC with or without ultrasound.

One study compared second trimester AC with no AC (control) in a low risk population (women = 4606). Background pregnancy loss was around 2%. Second trimester AC compared to no testing increased total pregnancy loss by another 1%. The confidence intervals (CI) around this excess risk were relatively large (3.2% versus 2.3 %, average risk ratio (RR) 1.41, 95% CI 0.99 to 2.00; moderate-quality evidence). In the same study, spontaneous miscarriages were also higher (2.1% versus 1.3%; average RR 1.60, 95% CI 1.02 to 2.52; high-quality evidence). The number of congenital anomalies was similar in both groups (2.0% versus 2.2%, average RR 0.93, 95% CI 0.62 to 1.39; moderate-quality evidence).

One study (women = 4334) found that early amniocentesis was not a safe early alternative compared to second trimester amniocentesis because of increased total pregnancy losses (7.6% versus 5.9%; average RR 1.29, 95% CI 1.03 to 1.61; high-quality evidence), spontaneous miscarriages (3.6% versus 2.5%, average RR 1.41, 95% CI 1.00 to 1.98; moderate-quality evidence), and a higher incidence of congential anomalies, including talipes (4.7% versus 2.7%; average RR 1.73, 95% CI 1.26 to 2.38; high-quality evidence).

When pregnancy loss after CVS was compared with second trimester AC, there was a clinically significant heterogeneity in the size and direction of the effect depending on the technique used (transabdominal or transcervical), therefore, the results were not pooled. Only one study compared transabdominal CVS with second trimester AC (women = 2234). They found no clear difference between the two procedures in the total pregnancy loss (6.3% versus 7%; average RR 0.90, 95% CI 0.66 to 1.23, low-quality evidence), spontaneous miscarriages (3.0% versus 3.9%; average RR 0.77, 95% CI 0.49 to 1.21; low-quality evidence), and perinatal deaths (0.7% versus 0.6%; average RR 1.18, 95% CI 0.40 to 3.51; low-quality evidence). Transcervical CVS may carry a higher risk of pregnancy loss (14.5% versus 11.5%; average RR 1.40, 95% CI 1.09 to 1.81), but the results were quite heterogeneous.

Five studies compared transabdominal and transcervical CVS (women = 7978). There were no clear differences between the two methods in pregnancy losses (average RR 1.16, 95% CI 0.81 to 1.65; very low-quality evidence), spontaneous miscarriages (average RR 1.68, 95% CI 0.79 to 3.58; very low-quality evidence), or anomalies (average RR 0.68, 95% CI 0.41 to 1.12; low-quality evidence). We downgraded the quality of the evidence to low due to heterogeneity between studies. Transcervical CVS may be more technically demanding than transabdominal CVS, with more failures to obtain sample (2.0% versus 1.1%; average RR 1.79, 95% CI 1.13 to 2.82, moderate-quality evidence).

Overall, we found low-quality evidence for outcomes when early amniocentesis was compared to transabdominal CVS. Spontaneous miscarriage was the only outcome supported by moderate-quality evidence, resulting in more miscarriages after early AC compared with transabdominal CVS (2.3% versus 1.3%; average RR 1.73, 95% CI 1.15 to 2.60). There were no clear differences in pregnancy losses (average RR 1.15, 95% CI 0.86 to 1.54; low-quality evidence), or anomalies (average RR 1.14, 95% CI 0.57 to 2.30; very low-quality evidence).

We found one study that examined AC with or without ultrasound, which evaluated a type of ultrasound-assisted procedure that is now considered obsolete.

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