Combined Screening for Early Diagnosis of Chromosomal Abnormalities during the First Trimester of Pregnancy

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; GLUJOVSKY, D.; ALCARAZ, A.; LOPEZ, A.; BARDACH, A.; CIAPPONI, A; VALANZASCA, P

Documento de Evaluación de tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

Chromosomal abnormalities increase with maternal age. Fifty percent of these chromosomal abnormalities result in Down syndrome (trisomy 21). The incidence of trisomy 21 is approximately 1:1000 at 30, 1:300 at 35 and 1:100 at 40 years old. In the last decades, the incidence of chromosomal abnormalities has increased, mainly because maternal age has increased. To diagnose fetal chromosomal abnormalities many algorithms may be used including non-invasive screening tests and invasive testing. Among the invasive diagnostic studies, the most commonly used are chorionic villus sampling and amniocentesis, with an associated miscarriage risk of about 0.5-1%. Ultrasound assessments and detection of certain blood markers may be mentioned as some the non invasive alternatives, both in the first and second trimesters. Combined screening in the first trimester is one of the most frequently used methods.TechnologyCombined prenatal screening is performed during the first trimester and is based on studies that include ultrasound (TN), biochemical (PAPP-A and free-β-hCG) parameters and maternal age. The post-test risk calculation is made using specific software. The assessment is performed between weeks 11 and 14 of pregnancy. The results report the post-test likelihood of having a fetus with trisomy 21, 18 and 13.PurposeTo assess the available evidence on the efficacy, safety and coverage related issues about the use of combined screening for early diagnosed chromosomal abnormalities during the first trimester of pregnancy.MethodsA bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems.ResultsIn this report one systematic review, 3 studies evaluating combined screening during the first trimester and one study on survival of children with Down syndrome before and after the screening program implementation were included, in addition to the results from 4 clinical practice guidelines, 3 health technology assessment documents and one study which evaluated coverage policies.In 2004 and 2005, two studies were published which evaluated a total of more than 80,000 pregnant women with a single fetus between 11 and 13.6 weeks of gestation. Sensitivity ranged between 85-87%, with a false positive rate of 4-5%. A better diagnostic performance was observed at week 11, compared to weeks 12 and 13.In 2011, one systematic review of the literature up to 2009 was published (which included the previously mentioned studies) with an 83% sensitivity and a 5% of false positives.In addition, in 2011, one retrospective study evaluated the performance of combined screening during the first trimester at different maternal age strata. Sensitivity did no change in women under or over 36 years old, although the false positive rate can be higher for the latter group, depending on the cut-off point.In 2009, one study was published which carried out a retrospective follow-up of trisomy 21 cases during a period where chromosomal abnormalities prenatal screening was not performed, and another where it was routine practice. A higher incidence of induced abortions in the second group (63% vs. 23%) was observed, but there were no differences in survival at 5 years among the Down syndrome children whose pregnancies were not interrupted.The different clinical practice guidelines found, recommend counselling on chromosomal abnormality screening for all pregnant women, independent from their age, concluding that combined screening during the first trimester of pregnancy is effective for the general population, and that the use of TN as well as maternal age as a unique evaluation, are less effective than their used in combination with serum markers. All the previous recommendations mention that this screening should be performed at specialized centers and that they should be standardized.In 2008, a study showed that in 10 out of 18 European countries evaluated there were national policies for Down syndrome screening in pregnant women in place, where 68% of cases were diagnosed prenatally and in 88% pregnancy was interrupted. Finally, more pregnancies with Down syndrome were diagnosed prenatally in those countries where national screening policies are in place and, mainly in those that prioritize first trimester screening (compared to those that do not make a difference between the first or second trimester screening).One study published in 2010, compared the health policies about this matter in the U.S. and United Kingdom. In the U.S. the screening strategy depends on the health plan and the invasive diagnostic tests are offered to every women; in the United Kingdom, although there are regional variations, their performance is suggested if the sensitivity is over 75% and the false positive rate is under 3% (year 2009) and invasive diagnostic tests are offered when the risk is over 1:250. In both countries, with some restrictions and variations, abortion is legal.Most of the cost-effectiveness studies found include induced abortion among the different alternatives. Since in most Latin-American countries induced abortion is not legal, the inclusion of data from these studies from these studies loses relevance. No cost-effectiveness studies were found in Latin-America.ConclusionsThe evidence reported in this document comes from studies of good methodological quality and statistical power. Combined screening in the first trimester has a Down syndrome detection rates ranging from 85% to 94%, with false positive rates under 5%. The clinical practice guidelines consulted suggest counselling to all pregnant women on the existence of these screening tests, regardless of their maternal age. These guidelines recommend this screening be performed at specialized centers with specific training and standardize quality controls.