Second Trimester Screening Test for Down Syndrome

A Quad Screen is a maternal blood screening test that is similar to the Triple Screen Test (also know as AFP Plus and the Multiple Marker Screening). However, the Quad Screen looks for not only the three specific substances evaluated in those tests (AFP, hCG, and Estriol) but also a fourth substance known as Inhibin-A. It is done mainly to determine the risk of the pregnant mother carrying a child with Down syndrome. This blood analysis is usually performed between the 16th and 18th week of pregnancy. A high-risk mother is then advised to have further testing which will analyze cells from the fetus for the presence of structural chromosomal problems.

First Trimester Screening Test for Down Syndrome

Nuchal translucency ultrasound is a diagnostic tool used to evaluate the fetus for Down syndrome. It is performed between 11 to 13 weeks of pregnancy, and is usually combined with a plasma protein-A analysis. Lower levels of plasma protein-A from the 8th to the 14th week of gestation can indicate increased risk for Down syndrome and other gestational problems such as intrauterine growth restriction and premature delivery.

Other Tests Performed After a Tubal Reversal Pregnancy

Aside from the Quad Screen test, there are other tests which can be done following a tubal reversal pregnancy.

— Determination of inhibin A (IH-A)

— Amniocentesis

— Chorionic villus sampling (CVS)

— Percutaneous umbilical cord blood sampling (PUBS)

— Preimplantation genetic diagnosis (PGD)

What is meant by a positive Quad Screen?

A positive test means having a high risk of chromosomal abnormalities or neural tube defects. The Quad Screen can be implicated as an early precursor with an extensive deal of ensuing scientific improvements to deal the underlying problems. Patients with a positive screening are then further recommenced for more insightful and specific procedures. Most tubal reversal patients will elect to undergo invasive procedures such as an amniocentesis.

Sensitivity adjustments of the Quad Screen:

Although 78% sensitivity and 5% false-positive rate of the test makes it widely available in most countries as a common option to classify risk, the estimated sensitivity of the risk is calculated and attuned on certain factors including:

o the expectant mother’s age

o diabetic condition of the mother

o twins or other multiple gestation

o the gestational age

o weight of the mother

o ethnicity may also be adjusted in markers

These factors influence the markers, and thus interpretation is indicated for the increased risk.

Integrated Screening

This involves combined first-trimester nuchal translucency and PAPP –A, plus second-trimester Quad Screening, and improves sensitivity to 90%. As most tubal reversal pregnancies occur in older patients, many will opt for the Integrated Screen.

Limitations of the Quad Screen:

1. The test is not for a definite diagnosis

2. The test is only a precursor for more predictive amniocentesis.

3. The age of the mother is indicative for amniocentesis.

Due to the fact that Trisomy 13 has a distinctive set of physical characteristics, a doctor may be able make a diagnoses simply by performing a physical examination. The risk of Trisomy 13 does not increase as a result of a tubal reversal, but the risk does increase with age. To either rule out or verify this disorder, a small blood test can be performed. This blood test, a chromosomal analysis, allows doctors to ultimately verify the existence of an extra #13 chromosome.

Babies with Trisomy 13 generally have low birth weights and look premature even when they are at full-term. Babies with Trisomy 13 often have a small head with an inclined, or prone, forehead. This abnormality is due to structural malformations in the scull and in the brain. In babies with this particular genetic disorder, these characteristics can be identified after birth. Genetic disorders are not increased by a tubal reversal surgery.

Holoprosencephaly (a disorder that causes the front of the brain to be divided improperly) is also common in babies with Trisomy 13. Holoprosencephaly leads to structural problems in the growth of the baby’s face. These babies tend to have close-set eyes, cleft lips, and cleft palates. Their nostrils are not fully grown and their ears are low-set with abnormal shapes. In many cases, skin problems such as cutis aplasia (a scalp abnormality that looks like ulcers on the scalp), birthmarks (purplish-red in color), or hemangiomas (abnormal blood vessels) are also present.

Other major problems for Trisomy 13 babies include:

• Extra fingers and toes (polydactyly)
• Heart defects
• Kidney problems
• Abdominal wall disorders (omphalocele or gastroschisis)
• Malformations of the uterus

Diagnosis before birth

Any chromosomal abnormality, such as Trisomy 13, can be diagnosed before birth. The cells from the amniotic fluid or from the placenta can show defects. A fetal ultrasound (performed during a pregnancy) is not always 100 percent accurate, but can predict whether or not the fetus is at risk. To confirm the physical findings, a blood test can be taken and chromosomes can be analyzed to determine the presence of an extra #13 chromosome. As most tubal ligation reversal patients are older, and maternal age is a predictor for Trisomy 13, many tubal reversal patients will opt for definitive diagnosis prior to birth.

Correlation between Trisomy 13 and tubal ligation reversal

As a woman’s age increases, her chances of having a baby with a chromosomal abnormality also increases. Most women who desire a tubal reversal are older than the average woman trying to get pregnant. In general, the woman who opts for tubal reversal has previously had at least a couple of children before she decided to have her tubal ligation performed. Since these women are older, they are at increased risk for chromosomal abnormalities due to their age, and not due to the actual tubal reversal surgery. A tubal ligation reversal has no affect whatsoever on the risk of a Trisomy 13 or any other chromosomal abnormality.

Possible Risks of a Tubal Ligation

The possibility of tubal ligation failure has the greatest risk for ectopic pregnancy. It is debatable and questionable that Post Tubal Ligation Syndrome consists of only a few medical symptoms or that it is possibly a direct side effect and/or another risk of tubal ligation. In most studies, those who do have symptoms after having a tubal ligation consider these symptoms Post Tubal Ligation Syndrome.

What is considered the major cause of these symptoms?

Several of the symptoms of PTLS (Post Tubal Ligation Syndrome) are linked with having estrogen or progesterone imbalance. There are many research and case studies leading to controversies about these hormone imbalances. It is assumed that imbalance may be the direct result of capillary damage and decreased blood supply to the ovaries during the surgery. The damage to the veins and capillaries is quite varied and slight damage may possibly result in a slight estrogen progesterone imbalance.

For a woman who has both of her ovaries still functioning, if blood supply was not damaged to the uterus and ovaries, then she may experience PTLS due to estrogen/progesterone imbalance by some change in her hormonal message relay system.

Hormonal message relay system destruction is questionable

The assumption behind this is destruction of “target” or “receptor” cells that are significant in the relay of hormonal messages for the female reproductive system. It is unspecified that these cells might be injured, damaged, and or detached during the tubal ligation surgery. Having assumed that these target or receptor cells are positioned within the fallopian tube, many people consider a tubal ligation to be the cause of the destruction of some of these cells. For patients who believe this hypothesis, a tubal reversal would not be an option to reverse symptoms of PTLS. Tubal reversal should only be performed for patients who therefore have a strong belief that the symptoms are related to blockage of their fallopian tubes.

The average rate of Patau Syndrome is about one in 10,000 live births. Patau Syndrome can be detected during a prenatal ultrasound by your obstetrician noticing abnormalities in your baby’s appearance. Again, although women who have undergone tubal reversal are not more likely to experience this disorder, tubal reversal patients are typically older than the average mom and as a result of their age tubal reversal patients are at an increased risk. If you have concerns about your babies health and the affects that tubal ligation reversal can have on your pregnancy be sure to discuss your concerns with your obstetrician or gynecologist.

Signs and symptoms of babies born with trisomy 13 (three copies instead of two):

• Impaired motor coordination
• Mental retardation
• An abnormally small (microcephaly) or large head (macrocephaly)
• Low-set abnormally shaped ears
• Extra fingers (polydactyly)
• Abnormal palm creases
• Brain abnormalities
• Heart defects
• Deformed feet that may have a “rocker-bottom” appearance
• Prominent heels
• Eye defects
• Cleft palate
• Spinal defects
• Intestinal defects with an incompletely formed abdomen
• Abnormal genitalia
• Overlapping of fingers over thumb
• Kidney defects

Because the abnormalities associated with Patau Syndrome are severe, most babies surviving until delivery will die soon thereafter. Eighty percent of affected infants die within the first month of life and only 5 percent survive to be six months. When babies do survive they are likely to have severe intellectual disability, seizures, and difficulty growing and learning new skills.

Most cases of Patau Syndrome are not inherited from a mom or dad directly, like eye color, rather Patau Syndrome occurs randomly as a result of incorrect division of genetic material from either the mom’s egg or the dad’s sperm prior to fertilization. Because there is no inherited cause, the disease is said to be sporadic and is not more likely to occur in another child should the mom become pregnant in the future – regardless of whether she has undergone tubal ligation reversal. Rarely, one parent can be a carrier of this extra genetic material and have just a very mild disease. In those instances, recurrence is higher than the general population as the genetic defect can be directly passed on to the infant. It is also possible that only some of the cells in an infant’s body will have the extra genes in a form called mosaicism. Mosaicism is very rare. The chance of having another trisomy 13 affected child is less than 0.01%.

If a child is diagnosed with trisomy 13 it is important that the parents trust their obstetrician or gynecologist and have open conversation about their concerns and wishes for their child. In situations where the obstetrician or gynecologist and patient have developed a relationship, such as with a prior child or in cases where the mother has undergone a tubal reversal prior to becoming pregnant, any discussion about the decisions facing the family can be comforting. For infants with Patau Syndrome, care is decided based on the specific medical situation and the family’s wishes. Generally, treatment is aimed at providing comfort to the baby and to the family during this difficult time. Although long-term survival is not expected, psychological, physical, medical, occupational, and speech therapy can help families and infants cope and reach their full developmental potential.

A chromosomal abnormality like Down syndrome is associated with advancing maternal age.  A number of diagnostic tests are currently available which may detect Down syndrome during pregnancy.  These include the nuchal translucency ultrasound and Quad marker screening, among others.

What is a Nuchal Translucency Ultrasound?

A nuchal translucency ultrasound is a sonographic prenatal test which can identify a high risk pregnancy during the first trimester.  It is performed between the 11th and 14th  week of gestation.  Aside from Down syndrome, the test can also detect an increased risk for major heart efects and other chromosomal anomalies in the fetus. Because it is performed during the first trimester, compared to the Quad marker test performed during the second trimester, parents are able to know their risk much earlier in the pregnancy.

The test however does not provide a final diagnosis.  If a mother is in the high risk category, she is often advised to undergo an amniocentesis or a chorionic villus sampling.  These procedures are invasive and entail a small risk for miscarriage.  Findings from these two procedures will generally give the parents a definite diagnosis.

How is the Nuchal Translucency Ultrasound performed?

Nuchal translucency ultrasound is performed either by placing an ultrasound probe over the lower abdomen or by gently inserting a thin ultrasound probe into the vagina.  Ultrasound will measure the thickness of the fold located at the back of the fetal neck. Other information needed during the test includes the age of the mother, the gestational age of the fetus, and additional bloodwork.

What are the factors that influence the test results?

The following are important factors that influence the findings from the nuchal translucency ultrasound:

- Age of gestation (should be between the 11th and 14th week

- The scan is obtained with the fetus in the sagittal position

- Hyperflexed or extended position of the fetus may affect results

- The fetal image is enlarged to 75 percent within the screen

- The nuchal lucency should be distinguished from the underlying amniotic membrane

Is a history of tubal ligation reversal a risk factor for a chromosomal disorder?

Tubal ligation reversal has absolutely no adverse affect on the fetus. The correlation between a tubal reversal and any chromosomal disorder is strictly due to the fact that most patients who undergo a tubal reversal are older, and that older patients are inherently at increased risk for a chromosomal disorder in the fetus.

Many women who have had their fallopian tubes ligated are choosing to undergo tubal reversal procedures in order to have one or more children again.  Tubal reversal is a surgical operation that restores a woman’s ligated tubes back to normal and allows pregnancy to occur.  There are some concerns, however, that a woman above the age of 40 who had a tubal reversal has an increased risk of conceiving a child with trisomy 21 or Down syndrome.

Definition of Trisomy 21:

Every cell in the human body contains 23 pairs of chromosomes.  In trisomy 21 individuals an extra chromosome 21 is present. Most cases are due to random mutations occurring during egg or sperm cell formation.   Children with trisomy 21 have common physical features.  They usually have weak muscles, small and flat heads, wide nasal bridges, and a single crease on their palms.  They also have delayed mental growth.  Some affected children have heart defects and gastrointestinal problems as well.

Genetic Epidemiology In the General Population:

Trisomy 21 occurs in one newborn out of every 800 live births.  According to a study from the Center for Disease Control and Prevention, in the US

approximately 95% of all chromosomal abnormalities are due to trisomy 21.  Downs syndrome appears in all ethnic groups and in all economic classes of human race.

Maternal age influence:

Maternal age is an important contributing factor in conceiving a baby with Down syndrome.  At the ages between 20 and 24, the probability of having an affected child is one out of 1,562 live births.  Between the ages of 35 and 39, it is one in 214 live births.  Above the age of 45, this risk increases to 1 in every 19 live births.   Recent studies have also found that paternal age above 42 years could be another risk factor for the development of Downs syndrome.

Severity of Downs syndrome:

Manifestations of Downs syndrome range from mild to moderate to severe forms.  Most affected children present with moderate mental retardations as well as delayed physical and social developments.  Although there is no known therapy to cure the condition, children with Downs syndrome usually live well into their adulthood.

Tubal Reversal and Down Syndrome:

Women who choose to undergo tubal ligation reversal at an older age (40 and above) must explore their options before making a decision. Advanced age increases the risk of conceiving a child with chromosomal abnormalities such as Downs syndrome. Pregnancy at an advanced age, whether by tubal ligation reversal surgery or not, always puts on at increased risk of having a child with a chromosomal abnormality.

Trisomy 13, also known as Patau’s syndrome, and Trisomy 18, also known as Edwards’ syndrome, are conditions where the presence of chromosomal abnormalities generally result in severe mental retardation and physical disfigurement.  Children born with either condition usually

die within the first year of life.  Parents of these children often

undergo a tubal ligation surgery for fear that their next child would be

affected with the same disorder.

Some of these parents, after much consideration and consultation with

experts, recognize that this condition may not occur in future

pregnancies.  A tubal reversal is an option that will help these couples

bear children again.  Woman who are interested in a tubal reversal should be very aware of all the possible problems which may arise, especially if they are over the age of 40 . Although a tubal reversal may be the best option, these women should also explore other alternatives such as adoption. While the main concern will be the related risk of a trisomy 13 or trisomy 18, the fact is that the risk is the same for patients who undergo a tubal reversal as for those in the general population.

What is the possibility that parents with a child with trisomy 13 or trisomy 18 will have another baby with the same problem?

There is very little possibility that the parents of a child with trisomy 13 or trisomy 18 will have another baby with the same problem.  The likelihood of this occurrence is only 1% or less, as the majority of these cases are not inherited.  Trisomy 13 and trisomy 18 mostly occur secondary to random events occurring during sperm and egg cell formation.  The risk is different, however, in cases of translocation and mosaic trisomies of chromosomes 13 and 18. The chromosomal abnormalities present in these conditions have varied genetic implantation risks.

The risk of having children affected with these conditions is higher among mothers of advanced age. The average age of a mother who has a baby with trisomy 13 is 32 years old. For trisomy 18 the average age is 31.  The risk increases with each added year.

The physician will perform a karyotype to analyze the chromosomes of an infant suspected of having trisomy 13 or 18. A Karyotype is performed by extracting blood fromthe newborn.  Results give significant information to parents about their risk in future pregnancies.  The physician may also refer parents for genetic testing to determine if the condition was a translocation or a mosaic type. This determination will help predict the risk of recurrence in future pregnancies.

Is there a therapy which can cure or prevent trisomy 13 or trisomy 18?

Gene therapy has done immensely well over the past few decades in many fields, but there are still no specific therapies available to avert the

erratic chromosomal events that cause trisomy 13 or trisomy 18.

If I have a child with trisomy 13 or 18, will IVF be a better choice for me than a Tubal Reversal?

The major advantage of IVF over Tubal Reversal is the ability for Pre-implantation Genetic Determination. With IVF, the embyo can be Karyotyped prior to implantation to ensure that the child will not have trisomy 13 or 18. A patient who has a Tubal Reversal will not have this same luxury as the embryo produced from a Tubal Reversal pregnancy will not be selected out for either of these abnormalities.

Under normal circumstances, follicles grow, mature, and rise to the surface of the ovary, where they burst and release an egg to the fallopian tube. Pituitary hormones control this process. The remnants of the follicle then start to produce progesterone, which supports the lining of the uterus (endometrium) in case a fertilized egg finds it’s way into the uterine cavity. An increase in progesterone production will signal to the pituitary gland to stop stimulating the ovary for the development of eggs.

In polycystic ovaries, the follicles rise to just under the outer lining of the ovary, and are formed over and over because the pituitary has not been signaled to stop.  The ovaries become filled with these tiny cysts and can become enlarged.

These polycystic-appearing ovaries may be diagnosed based on their enlarged size.  Ovaries may get twice the normal size with small cysts present around the boundary and outside wall of the ovary.  These can be found in women who feel completely normal and have no symptoms, and also in women symptoms and significant endocrine disorders. Having polycystic-appearing ovaries do not necessarily mean that you have PCOS. PCOS requires that other criteria are met and includes other symptoms besides the presence of ovarian cysts.

PCOS increases your risk for metabolic and cardiovascular disease linked to insulin resistance, and endometrial cancer related to the prolonged exposure to persistant levels of Estrogen without Progesterone.

Risks of PCOS include:

• Increased glucose intolerance
• Type 2 diabetes
• Infertility; Polycystic ovarian syndrome is associated with anovulatory infertility
• High blood pressure
• An increased risk for endometrial cancer
• Abnormal periods and vaginal bleeding
• Increased risk of infertility
• Pregnancy-related complications

Although ultrasound is used to view the ovary as a diagnostic step in diagnosing the condition of polycystic ovaries, additional tests are required to diagnose PCOS. Since this condition is so common, many patients who undergo tubal ligation reversal will be affected by PCOS. A thorough evaluation by your primary gynecologist should rule out PCOS before you consider tubal reversal. Tubal reversal will not affect your PCOS condition, but in order to have success after a tubal ligation reversal, your risk of infertility from PCOS must be minimized.

To evaluate the risk of infertility from other causes beyond tubal disease, gynecologists will consider many additional tests. Having your tubal reversal performed by a skilled tubal reversal surgeon significantly improves your chance of getting pregnant. With an ideal tubal ligation reversal, your chance of achieving a pregnancy will be mostly affected by these other factors such as PCOS. Several medicines may be used after tubal reversal to cause increased ovarian stimulation for better follicle production to treat the underlying infertility caused by PCOS.

HSG is the best method to determine the tubal patency (if the tubes are open).  It is not recommended to have a HSG too soon after a tubal reversal surgery.  Most will recommended at least 4 to 6 months after a tubal ligation reversal because an HSG relies on increased pressure in the tube, and it the tube is still weak where the tubal ligation reversal occurred, the tube could be damaged. Also, the risk of infection is present whenever a HSG is performed.  It is recommended that patients try for a pregnancy first before going straight to an HSG.  A good number of patients conceive within this early period and will then not need or desire to have a HSG performed.

Get ready for an HSG:

• An HSG is optimally performed after menstruation and before ovulation.  If a HSG is performed after the time of ovulation it may interfere with a pregnancy.
• To diminish the risk of infection, antibiotics and sterile technique are used.
• Gynecologists will mostly recommend a prophylactic pain prescription of 800 mg of ibuprofen one hour before the HSG to minimize discomfort.

What happens in an HSG?

You will be positioned just as if you were having a pap smear performed. The speculum will be placed, and the cervix will be grasped and retracted.  A thin tube will be inserted into the uterus and this may cause some cramping. Dye is then injected through this tube and into the uterus. At the start the dye will fill up the uterine cavity.  It is necessary that the dye in fact enters the fallopian tubes up to the end where the anastomosis was done.  Once past the tubal ligation reversal point, the dye should continue to the end of the tube and be discharged from the end of the tube into the pelvic cavity. Flow through the entire tube may not occur due to a spasm of the muscle at the base of the tubes or a spasm in the tubal segments. As such, some patients who have had a tubal reversal may in fact have a HSG that looks like the tubes are not open. This is very rare.

If the dye passes through the portion of tube that was put back together during the tubal reversal, the fallopian tubes are considered repaired. If the dye spills into the abdominal cavity, the diagnosis of tubal patency is decisive.

Note: Care is taken to note that if in the x-rays show that the dye has passed through the tubal ligation reversal site, but has not yet spilled into the abdominal cavity, this may be due to an inadequate quantity of dye being injected.  The radiologist may incorrectly consider that the tube is blocked when it is in fact open. This also is very rare as the gynecologist performing the HSG should be careful to inject a proper amount of dye.