Chromosomal anomalies are a cause of still birth, neonatal death and also require special care in those who survive. This has implications for the care givers, society and health economics. Thus it is a major public health problem requiring intervention. The diagnostic tests and intervention in the form of termination is also available. Thus fulfilling some of the WHO criteria.
The screening is done on basis of age, past history, ultrasound scan and the combined test in the first trimester. The ultrasound screening in the first trimester offers an opportunity to confirm an intrauterine viable pregnancy. The dating done by the CRL measurement is most accurate in the first trimester. Multiple gestations may also be confirmed and chorionicity determined.
First trimester screening offers a chance for earlier termination of pregnancy. This may be a choice of surgical and medical termination. Early termination has fewer medical complications i.e. less cervical trauma and haemorrhage. Psychological benefit in the mother has not been confirmed though.
The disadvantage of early screening involves the large number of patients that would be needed to be scanned to detect gross structural anomalies. Resource allocation and staffing may be a problem. Training of staff to provide a high degree of accuracy also needs to be considered.
The diagnostic test for the first trimester is the chorionic villous sampling, which needs a higher degree of skill than amniocentesis and may need referral to a tertiary feto maternal medicine centre. Miscarriage rate is 1 to 2% and placental mosaicism may lead to erroneous diagnosis.
First trimester anomalies may be difficult to confirm. It may be possible to obtain tissue for chromosomal anomalies at surgical termination, however structural malformations may not be as easy to confirm. After a medical termination, it may be difficult to obtain any tissue at all.
Nearly 50 % of fetuses with chromosomal anomalies will miscarry by the second trimester, thus first trimester screening will need to unnecessary diagnosis and terminations. Terminations compared to a miscarriage may have more of a psychologically damaging effect.
The alternative is second trimester screening. The detection of structural anomalies is by transabdominal scanning which is more acceptable to patients. Presently an anomaly scan is done in all patients and hence no extra allocation of resources is needed. The diagnostic test is amniocentesis, which is performed in most centres with a miscarriage rate of 0.5%. With the availability of FISH, the provisional results are obtained within 48 hours.
The disadvantage is that most centres will offer only medical termination of pregnancy. The process is prolonged compared to first trimester termination. The need for inpatient stay is also greater. The perception of movements may have been there, and this may contribute to the grief of the mother.
Some patients would like to hold and feel their child and form them this may be more appropriate.
In conclusion, the first trimester screening has its advantages, but cannot be recommended for all the patients in the present scenario.
Posted by manjula C.
The screening tests for the detection of chromosomal anomalies depends on the trimester when it is performed..he first trimester tests are nuchal translucency and combinedtest.The second trimester tests are Triple test and Quadruple test.
For a given predictive value of 85% NT alone gives a false positive rate of about 20%,which is unacceptably high.That means more women undergo invasive procedures to detect one case of Trisomy which is not cost effective and also related with high procedure related fetal loss(cvs 2 % ,early amniocentesis also being almost the same) and associated defects.More over NT
needs an expert sonologist ( not available everywhere) and the measurements could be subjective.
To improve the false poisitive rate a Combined test is devised which along with NT includes serum markers like PAPPAand HCG. This has a false positive rate of 6% for a predictive value of 85% .
Many chromosomally abnormal babies abort before they complete first trimester,making first trimester test alone unnecessary,and moreover many women come for their first antenatal check up late.
However NT is found to be suitable in case of multiple pregnancy in which serum markers loose their value.First trimester detection of chromosomal defects can be offered termination of pregnancy which is much easier and less likely to cause psychological morbidity and grief .
In comparision second trimester tests like Triple tests and Double test have a high false positive rate and are superseded by Quadruple test(hcg estriol,afp,inhibina).This test has a false positive value of 6% for a detection rate of 85%.The second trimester is also a suitable time for fetal anomaly detection by ultrasonography(3d ultrasonography is found to be more effective). The serum tests can be correlated with usg markers and the dicision taken for invasive tests like amniocentesis.Second trimester amniocentesis also carries a low fetel loss rate of 1% which is half that of first trimester cvs and amnio.It also avoids the problems associated with cvs like mosaicism and maternal tissue contamination whish confuse the picture.However second trimester terminations are difficult and cause more maternal morbidity and psychological upset.
Both th e first and second trimester serum markers are affected by certain variables( like obesity,wrong dates, diabetes),hence used alone are not effective in detecting trisomies
Hence to improve the efficacy , tests which combine the benefits of both trimester tests have been developed depending on when the women attends for antenatal care.INTEGRATEDtest (NT,PAPPA,HCG,AFP,estriol,InhibinA) has a very low false positive value of 1.2% for a detection rate of 85% and is the most suitable test if the women attends for antenatal check up in first trimester.However if ultrasonographic expertise is not available then SERUM INTEGRATED test which excludes NT can be offered which has a false positivity of 2.7%.
If the woman attends in second trimester then Quadruple test is advisable.If the women requests for the first trimester test then Combined test is suitable. At a constant detection rate these tests
are advisable as the costeffectiveness is almost the same for all thre four.
Thus keeping all these drawbacks in view first trimester tests should be done only if the woman requests ,as they have a high false positivity.
Posted by Rani M.
Screening is not a diagnostic test. It helps in predicting which pregnancies are at high or low risk of chromosomal anamolies so that diagnostic tests( which are invasive,expensive and associated with fetal loss risks) can be done to detect such fetuses, thus helping women to choose between termination of pregnancy and continuing pregnancy.
Various screening methods used are history, ultrasound and biochemical test. Maternal age,a positive history in family or in the previous babies , exposure to drugs, infections and certain teratogens such as radiation, presence of medical illnesses such as diabetes, epilepsy and connective tissue diseases helps in identifying at risk population. This should ideally be done either in prepregnancy or early in pregnancy so that counselling can be offered to minimise risk.
Measurement of nuchal thickness is the screening test via ultrasound. Taking a cut off of 2.5 mm or more at 10 weeks detects 77% of chromosomal anamolies with a false positivity of 5 %. This is better than triple test done in second trimester. Another advantage of first trimester scan are dating, confirming intrauterine viable pregnancy( which is reassuring), chorionicity in multiple pregnancy which can be done with almost 100 % accuracy at this time.Ultasound is a simple , noninvasive test. It is also useful in detecting other structural malformations and genetic syndromes. But is is limited by operator\'s skills and resolution of the machine. Many organs will be too small at this gestation and some are still forming. So, T.V.S may be required( which some women nay consider uncomfortable) and second trimester repeat scan is still required for neural tube defects and for cardiac and urinary anamolies
Biochemical parameters used in first trimester are PAPP-A and beta hCG. This if combined with maternal age and Nuchal thickness ( NT) gives a detection rate of 89 % at a false positive rate of 5 %. This Combined test is the best available first trimester screening method .
Points in favour of first trimester screening are: early detection of anamoly reduces anxiety and psychological morbidity of waiting and uncertainity, especially in at risk population. Moreover, early termination of pregnancies is technically easier, is associated with lower complications and may be with less psychological morbidity.
It can be argued against that many of these pregnancy with anamolous babies are naturally destined to spontaneous miscarriage. Thus, early detection and termination leads to unnecessary intervention with its cost implications and exposing women to unnecessary physical and psychological complications. Termination in comparision with spontaneous miscarriage may be associatted with more guilt, anxiety and psychological morbidity.
First trimester daignostic test i.e. C.V.S ( chorionic villous sampling ) is associated with higher fetal loss rate 1-2% versus 0.5-1% for amniocentesis .There is 1-2 % risk of confined placental mosiacism leading to false positives.
First trimester screening by combined test will lead to about 44 diagnostic procedure related unaffected fetal loss rate for every 1 lakh women screened . This can be compared with 9 diagnostic procedure related unaffected fetal losses per 1 lakh women screened by integrated test. Integrated test which combines first trimester NT and PAPP_A with second trimester AFP, u estriol, beta hCG and Inhibin A detects 85 % of chromosomal anamolies at a false positive rate of only 1.2%.
Thus it can be concluded that screening should achieve maximum accuracy ( high detection rate) and minimum harm ( low false positive rate). This is best met by integrated test and not by first trimester or second trimester screening alone.Also best and most widely available diagnostic test i.e. amniocentesis is done in second trimester. Both medical and surgical methods of termination are available in both trimester now. most women will prefer one or the other.
Posted by Rani M.
DEar Paul,
Thanks for marking my answer. I had some query. Is it so that Nuchal thickness if done at 13 weeks as in SURUSS give detection rate of 85% at a false positivity of 19%.
But if done at 10 weeks taking 2.5mm cut off it detects 77% at a false positivity of 5 %. Please clear, does it mean differently or same?. I thought as it is first trimester screening I should talk for screening prior to 12 weeks.
Anyway as far as answer is concerned I know i forgot to write regarding maternal wishes, local resources and less cost effectiveness of first trimester screening as compared to integrated test,. But advantage of one point testing which integrated test lacks.
Why is it so that we tend to forget to write important points while writing essay and remember it later. Then the boat would have left already in the exam.
Posted by Rani M.
Dear Paul,
Thanks for clearing my doubts , it will be really very useful.
Posted by Rani M.
Dear Paul,
Thanks for clearing my doubts , it will be really very useful.
Posted by Rani M.
Dear Paul,
Thanks for clearing my doubts , it will be really very useful.
