Invasive Interventions in Pregnancy
In general, the frequency of anomalies encountered in pregnancies is around 2-4%. These may be chromosomal anomalies, single gene diseases, or structural anomalies. There is no cure for anomalies in infants. If the diagnosis can be made at the appropriate time, the family may be given the right to terminate pregnancy in diseases and anomalies that are incompatible with life or that may cause severe life problems. Although this decision is not made, the family should be given the right to know how the baby will be born. When it comes to the possibility of anomaly, what are the possibilities and expectations are clearly explained to the family, and the decision whether to perform an invasive intervention should be completely of the family. What method can be chosen in invasive procedures and the risks of the methods are explained. After the family learns the details of the current situation and invasive interventions, they will make their decision with their own truths in line with their own expectations.
Conditions that may require invasive intervention during pregnancy are listed below:
- Advanced maternal age: In the definition of advanced maternal age, there are discussions about which age will be accepted as the limit, but in general, it seems reasonable to accept 37 as the limit. Advanced maternal age is not an absolute reason for invasive intervention, but the possibilities should be discussed very well with the prospective mother and family. Over 35 years of age, the probability of anomaly can be reduced with screening tests and detailed ultrasonography, and this may be enough for the family. However, if absolute diagnosis is desired instead of probability calculations, many single genes with trisomy 13 and 18 and sex chromosome anomalies with Down Syndrome for 99% of Down Syndrome. Free fetal DNA test can be done in the blood which has a very high scanning capacity for the disease. However, absolute diagnosis can only be made by producing the material obtained by amniocentesis cordocentesis or chorion villus biopsy in cell culture.
- Detection of risk in screening tests: The detection of high risk in double, quadruple, integrated test or free fetal DNA tests, which we now use and have high screening capacity, shows an increased risk and suggests invasive intervention. In general, the probability of screening tests to suggest amniocentesis is around 5%. This rate is defined as the ‘amniocentesis rate’ of screening tests.
- Previous pregnancy history with anomaly: Down Syndrome in previous pregnancies, chromosome number anomalies, genetic diseases such as cystic fibrosis, structural diseases such as neural tube defect, history of disease with enzyme deficiency (such as Tay Sachs Syndrome). mostly will be required. Genetic diseases, which are completely random, as well as situations where there is a high risk of recurrence, will be discussed with the family and assisted by the family to make the appropriate decision for them. Invasive diagnostic methods are also frequently required in pregnancies with an anomaly but without chromosome testing.
- In the family history of chromosome anomaly, metabolic disease or single gene disease, if the family defines the problem well, tests can be programmed to diagnose the problem in the womb. In addition, if the mother or father has clear hereditary diseases or carriage as well as translocation carriage, invasive intervention will be required to evaluate the baby during pregnancy.
Even if consanguineous marriages are decreasing in our country, they still exist. If there is a carrier for any disease, the probability of disease is high due to the possibility of genetic similarity in the couple. If autosomal recessive (recessive) diseases are present at the mother and father candidate at the same time, 25% of the disease will occur or 50% will be the carrier. However, if there is no clear definition, invasive intervention is not recommended only because of consanguineous marriage. Screening tests and detailed ultrasonography are often sufficient.
- Bearing a baby with a neural tube defect earlier is also associated with an increased risk in subsequent pregnancies and requires invasive diagnosis. The fluid (AFP) (alphafetoprotein) obtained by amniocentesis from the mother’s womb can be examined and the conditions that are high can be determined by looking at the ACE (Acetylcholinesterase) level.
- In women with recurrent pregnancy loss, invasive intervention may be required if an abnormality has been previously detected in the abortion material or if a carrier has been detected in the prospective parent. In women who have recurrent miscarriages, if there is no genetic diagnosis in lost pregnancies, but if there is a suspicion of anomaly, the decision of invasive intervention may come up again.
- Determining markers of chromosome anomalies or structural anomalies in routine ultrasonography or detailed ultrasonography is also an indication for invasive intervention. Chromosome anomalies are found in approximately 0 of pregnancies with marker.
- In X chromosome linked diseases , baby boy with diseased baby girls are carriers. In such cases, invasive intervention can be made to determine gender. In these cases, termination of pregnancy in the baby boy may be considered. Diseases such as Hemophilia and Duchenne Muscular Dystrophy are also possible with special methods.
- In case of congenital infection, invasive intervention may be required to find out whether the infection has passed on to the baby. Normal chromosome analysis; does not rule out enzyme deficiency diseases, single gene anomalies and neural tube defects. It only shows that the chromosomes are structurally and numerically normal. For single gene diseases, enzyme deficiency and diseases such as neural tube defect, microduplication, microdeletion, fragile X syndrome, the disease will need to be pre-defined, preparing the genetic laboratory for the targeted disease, and using special methods.
Babies live in a pouch called amniotic sac in the uterus, and amniotic fluid is found around the baby in the amniotic sac. Amniotic fluid is not a stable fluid. It is in a continuous production and absorption movement. It provides the development of the baby’s respiratory system, the comfortable development of the arms and legs without pressure, the development of the digestive system, and the cords to travel comfortably in the uterus without being under pressure.
Amniocentesis is a prenatal (prenatal) diagnostic method applied between 16-19 weeks of pregnancy. Cells from the baby’s skin, respiratory tract, digestive system and urinary excretory system are poured into the amniotic fluid, which is the fluid that the baby lives in. These cells are equivalent to the baby’s genetics, and when produced through cell culture, the baby’s:
* Cytogenetic analysis (chromosome number and structure)
* DNA analysis
* Enzyme analysis
* It can be used for AFP and acetyl cholinesterase (ACE) analysis.
It is due to the need to calculate the waiting time for the genetic laboratory to report the result after amniocentesis in weeks 16-19. Genetic laboratories can now give results for up to 2 weeks. However, it may take up to 4 weeks to get results most of the time because the laboratory and service conditions are not homogeneous in our country. If the result is to be decided to terminate the pregnancy, it should not exceed medically and legally as much as 24 weeks.
Detailed ultrasonography of the patient is performed before amniocentesis. Detailed evaluation of the baby’s organs, its position in the uterus, the placenta’s location in the uterus, and the cord’s placement in the placenta, the amount of amniotic fluid are determined. The position of the baby and the placental structure are thus mapped.
Technically, the amniocentesis can be performed in an office or hospital, but it does not require an operating room environment. The procedure is always accompanied by ultrasonography. First, the baby is mapped in the womb and the comfortable area of amniotic fluid in a remote area is targeted. It is tried not to cross the placenta as much as possible. In the womb, the area to be inserted with the needle and its surroundings are wiped several times with antiseptic solution and disinfected. A vacant amniotic fluid space is determined as far as possible to the baby. Again, avoiding passing through the placenta as much as possible, it is entered into the uterus by seeing the passage of the needle under ultrasonography with special needles. First, the skin of the abdomen and the layers of the abdomen, and then the entrance into the uterine muscle. When the amniotic fluid is entered into the cavity, it is inserted into an injector behind the needle and the first 1-2 milliliters are discarded (in order to rule out the cells belonging to the mother). Then, an average of 20 cc amniotic fluid required for examination is drawn and sent to the genetics laboratory. During these weeks, 200-300 cc amniotic fluid is normally found around the baby and 10% will be withdrawn during amniocentesis. This amount is reproduced by the liquid baby within 1-2 hours and the required amount is provided. Amniotic fluid should not be bloody. When the procedure is completed, the needle is pulled rapidly while still under the guidance of ultrasonography.
Risks related to amniocentesis
The biggest problem encountered during the procedure is that the amniotic membrane can be tented together with the needle immediately after entering the uterine muscle and prevents entry into the amniotic fluid field. If the amniotic membrane is separated from the uterine muscle over a large area, it will be appropriate to stop the procedure and postpone it for a few weeks. Fast entry can reduce the risk of tenting.
No more than two attempts should be done in the same session.
It is not possible to injure the baby with a needle during the procedure, since the procedure is performed under ultrasonography. Small touches occur with the needle, but they are harmless.
Maternal death due to amniocentesis is very rare and there are only a few case reports in the world.
Vaginal leakage of amniotic fluid is observed in 1-2% of cases after the procedure. Most pregnancies will continue in normal conditions without harming this. Miscarriage may develop in 10% of cases with fluid leakage. From time to time, it can continue its pregnancy path with decreased amniotic fluid. In this case, babies may experience problems with lung development.
During the procedure, some of the baby’s blood cells pass into the mother’s circulation. In normal conditions, this transition does not make sense. However, if the mother is Rh negative and the father is Rh positive, the mother’s circulation will develop antibodies against Rh positive blood cells that have not been previously recognized. These antibodies are likely to result in severe fetal anemia, with the woman trying to destroy the Rh positive cells belonging to the baby with antibodies, and more likely in the current pregnancy, and more likely in the subsequent pregnancies. In case of Rh incompatibility, anti-D (Rh immunoglobulin) should be applied after the procedure. Cell passage is higher when the placenta has to be crossed during amniocentesis.
The risk of infection due to the procedure may arise from the environment in which it is performed and insufficient disinfection. However, it is most often affected by the natural flora or infections on the woman’s skin. The risk of infection is extremely low when proper conditions are provided and the woman’s skin is sufficiently disinfected. However, the doctor should be informed when there is pain, fever and foul-smelling discharge. If the infection is proven, it is a very serious condition and pregnancy should be terminated.
Amniotic fluid embolism, the transition of amniotic fluid to maternal blood and occlusion of vital organs, especially lung and brain, may occur and is extremely rare.
The most important condition in this discussion is pregnancy loss due to amniocentesis. This rate is given as 1/200 (0.5%). The most common cause is amniotic fluid leakage through the vaginal route. For amniocentesis, it may cause vaginal leakage from the pierced part of the amniotic membrane and not stopping. Bleeding from the cervix and infection can also be the cause of the miscarriage. It should also be noted that the natural loss rate present in these weeks in pregnancies without amniocentesis. The loss of pregnancy with the procedure is of course very relevant to the experience of the physician.
After the procedure, there may be moderate pain and a single dose of paracetamol can be used.
Bleeding is very rare and usually stops spontaneously and in a short time.
There may be blood accumulation in the mother’s abdominal wall called hematoma and it has no medical significance. It does not require treatment and will heal on its own.
In polyhydramnios, where amniotic fluid is excessively increased, amniosynthesis can be reduced by reducing amniocentesis (amnioreksis) and the procedure can be repeated if necessary. This procedure is independent of the gestational week. It is usually required during pregnancy weeks that are much larger than the time of genetic examination.
After amniocentesis, hospitalization or absolute bed rest is not recommended. 3 days activity restriction and home life are recommended. It would be appropriate to get an opinion from the doctor who performed amniocentesis for sexuality and travel. It is generally recommended to stay away from sexuality and travel for 1-2 weeks.
It is an invasive prenatal diagnosis method generally applied after the 18th week of pregnancy.
* Prenatal diagnosis method failure such as amniocentesis previously applied,
* Doubtful results,
* Family late application,
* Anomaly marker that appeared there late in ultrasonography
* It is applied in cases such as hereditary blood or suspicion of metabolic disease.
The chromosome numerical and structural disorders can be studied from the blood obtained by entering the cord of the baby. In order to learn the chromosome result, results can be obtained within 7-10 days from standard laboratories. It can be reported much faster according to the quality and density of the laboratory. DNA screening can be done by preparing for metabolic tests, enzyme levels, determination of antibody in terms of Rh incompatibility, level of infection, infection screening, and single gene diseases.
Another application area is to reduce the consequences of severe anemia in the fetus and the possibility of loss of the fetus by performing blood transfusion from the umbilical cord vessels to the fetus in pregnancies affected by Rh incompatibility. If necessary, fetal blood transfusion can be repeated by performing cordocentesis again.
In the cordocentesis application
The place and conditions of its intervention can be hospital or office environment as stated in amniocentesis. There is no need for operating room conditions. Before the fetus is evaluated by ultrasonography. Fetus and placenta are mapped by determining the place of placenta and cord entry into the placenta. The procedure is performed under the guidance of ultrasonography. The entrance area of the mother’s abdomen is cleaned using disinfectant. The balls in the umbilical cord are entered using a 9-15 mm needle, accompanied by ultrasonography. In the umbilical cord, there are two arteries and a vein. Balls are more suitable for entry because the vein is larger in diameter and the wall is thinner. More frequent fetal bradycardia (slowing of the heart beat) in the arterial entrances is one of the reasons for preferring the vein entrance. If possible, it is possible to enter the placenta from the document where the cord enters, if not possible from the free cord sections.
No more than two entries should be attempted in one session.
If the couple has Rh incompatibility, anti-D should be applied after the procedure. Since the blood cell is transferred from the baby to the mother’s circulation during the procedure, the mother will try to destroy the Rh (+) cell by counting it outside its own nature and develop antibodies. This situation, which puts the current pregnancy or mostly the next pregnancy at risk, can be resolved with anti-D application.
When compared to the application of amniocentesis, the cordocentesis may progress with more serious complications. It is more difficult and more physician experience and team work than amniocentesis. The probability of pregnancy loss is given as 1%. Amniotic fluid may leak or bleed after the procedure and disappear spontaneously. However, the probability of pregnancy loss or preterm birth may increase if it continues. In the umbilical cord during and after the application, hematoma (blood accumulation) may occur at the entry point of the needle and bradycardia (slowing of the heart beat) and fetal loss may occur in the fetus. As stated in amniocentesis, the risk of procedure-related infection is very rare. However, if infection is proven in case of severe pain, foul-smelling discharge and fever, pregnancy should be terminated.
1-2 days after the procedure, activity restriction and home life are recommended. Absolute bed rest is not required. For travel and sexuality, it is generally appropriate to avoid 1-2 weeks. However, opinions can be obtained from the doctor who applied the intervention.
Chorion Villus Biopsy
The cells of the fetus and the chorionic villus cells, which make up the content of the placenta, originate from the same progenitor cells. Therefore, their genetic structure is completely common. Due to this feature, it can be applied very early in determining the number and structure of chorion villus material chromosome taken from the placenta and diagnosing diseases such as cystic fibrosis, median anemia and single gene diseases known in the family and effective results can be obtained.
It can be applied from the 11th week of pregnancy. Since it facilitates early diagnosis, it provides great comfort in terms of timing.
Technical application; It can be performed in the hospital or office environment as stated in amniocentesis and cordocentesis, but does not require operating room conditions. First of all, a detailed ultrasonography is performed on the woman. Details of the fetus that can be seen this week are evaluated. Amniotic fluid amount and placement of the placenta are determined. Before the procedure, the abdominal area of the woman to be invasive will be cleaned with disinfectant. Accompanied by ultrasonography, 10-30 mg of chorion villus sample is taken from the abdomen by entering the placenta. The procedure takes 30-60 seconds and does not require anesthesia.
Absolute bed rest or hospitalization is not required after the procedure. Low-paced home life is sufficient for up to 3 days. It would be appropriate to avoid sexuality and travel for 1-2 weeks.
After chorion vills biopsy, cordocentesis may be required with 1% probability of obtaining fetal cells with amniocentesis or needing a blood sample from the fetus.
The probability of pregnancy loss is 1%. It should always be kept in mind that there is a possibility of spontaneous (spontaneous) pregnancy loss during early pregnancy weeks due to natural selection or other reasons. Bleeding to the back of the placenta or the uterine wall during the procedure and infection can be the cause of miscarriage.
There may be a short term amniotic fluid leak (water coming) after the procedure. It will most likely regress spontaneously. Bleeding is also very rare and usually stops spontaneously. The pain is also usually mild and stops with a single dose of paracetamol. However, in case of severe pain, the physician must be informed.
If infection develops after chorionic villus biopsy, pregnancy should be terminated. However, this situation is extremely rare.
Blood accumulation (hematoma) in the mother’s abdominal wall may rarely develop. However, it resolves spontaneously and has no clinical significance.
Maternal death is very rare and rare cases have been reported worldwide.
If the couple has Rh incompatibility, anti-D should be applied after the procedure. If the mother’s blood group is Rh negative and the fetus is Rh positive, the mother will be able to pass Rh positive blood cell to the mother, and the mother will develop an antibody, and the clinical consequences of Rh incompatibility will be encountered in the fetus in the current pregnancy, more likely in the subsequent pregnancies. With Anti-D application, this risk is eliminated.