Trisomy 21 Ebook

Teaching Down Syndrome

Although Home is Where the Smart Is is packed with information in its 104 pages, it is not an exhaustive work. It's a consideration of the basics of teaching your child with Down syndrome, starting from birth through the foundational elementary years. What's inside: Why Down syndrome is Not mental retardation .page 14 How you really can reat Down syndrome. . page 17 How you can save frustration and diapers with an old method of potty training . pg 49 How you can keep that tongue from sticking out . page 38, 69 The fastest way to teach your child to read . page 60 Developmental milestones, word lists, websites and resources . page 90 And, if you must be involved with the public school system, basic guidelines for Individual Educational Plans (Ieps) and 15 snippy questions to ask educators.

Teaching Down Syndrome Summary


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Author: Helen Middlebrooke

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Diagnostic Testing for Down Syndrome

The diagnosis of fetal trisomy is made by karyotyping fetal cells, typically obtained through amniocentesis. Midtrimester amniocentesis (MTA) is performed between the 15 th and 22nd wk of gestation and is by far the most common prenatal procedure leading to a diagnosis of fetal trisomy 21. The first karyotype analysis from human amniocytes was described in 1966 (77) and the first Down syndrome diagnosis following amniocentesis (78) was made in 1968. As an invasive procedure, MTA poses a risk to the pregnancy (79) with fetal loss rates generally accepted as being 1 in 200. For this reason, the diagnostic procedure is offered only to women who have been shown to have an equivalent or greater risk of carrying an affected pregnancy.

Maternal Age and Down Syndrome Screening

The goal of screening is to raise the prevalence of the targeted disorder in the screen-positive subpopulation, to the point where the risk of the disorder exceeds the risk associated with the diagnostic procedures. In 1933, Penrose first published the association between maternal age and the risk of Down syndrome (83), and women became aware of their biological clock. Nevertheless, true screening on the basis of maternal age could not be performed until a diagnostic test for fetal trisomy was developed, some 35 yr later (78). The simple act of asking a woman her age became a screening procedure, although it remains largely unrecognized as such, even today. Patients, and to some extent health care providers, view the association between maternal age and Down syndrome in a binary sense patients are deemed to be either at low risk or at increased risk, depending on whether the patient will be under or over the age of 35 at delivery. The reality is that maternal age is a continuous risk...

The Advent of Biochemical Screening for Down Syndrome

In the early 1980s, MSAFP screening for ONTD was becoming fairly common. In 1983, there was a fortuitous observation of a low concentration of MSAFP in a trisomy 18 (T18) pregnancy. This led to an investigation by Merkatz et al. of whether low MSAFP was predictive of fetal trisomies (92). Their study showed that low concentrations of second-trimester MSAFP were not only associated with T18, they were also predictive of trisomy 21, or Down syndrome. This was the first observation that a biochemical marker in a pregnant woman's serum was informative of a chromosomal defect in the fetus. In 1984, Cuckle et al. showed that MSAFP concentrations in Down syndrome Fig. 7. The association between maternal age at expected date of delivery and the risk of fetal Down syndrome at term. Six studies are shown (84-89) that differ only slightly at ages less than 45 yr. Inset represents full dataset up to 55 yr of age. Fig. 7. The association between maternal age at expected date of delivery and the...

Down syndrome screening in pregnancies with twins or more

For many years, the most common way of screening pregnancies for Down syndrome was by measuring different markers in the mother's blood at 16 weeks of pregnancy (see Chapter 8). The accuracy of this test with twins is fair, but with triplets or more, it doesn't help at all. The newer method of Down syndrome screening in the first trimester (nuchal translucency, see Chapter 8) appears particularly promising for moms with multiple gestations because your doctor can obtain a nuchal-translucency measurement for each fetus, thus determining each fetus's individual risk of having Down syndrome. Using the nuchal translucency and mom's blood markers, you can detect about 70 to 75 percent of all cases of Down syndrome in twins. This is a little lower than the detection rate in single fetuses, but still pretty good. With triplets or more, using the nuchal-translucency measurement alone tends to be the most helpful approach because it's difficult to determine how to use the mother's blood...

1 10 100 1000 10000 Actual Prevalence of Down syndrome 1 in n

Agreement between the observed prevalence of fetal Down syndrome and the calculated risk of Down syndrome based on maternal age and maternal serum concentrations of AFP, uE3, and total hCG (see ref. 169). Down Syndrome Screen Performance at a Risk Cutoff Equivalent to the Risk at Age 35,Using Past and Present Screening Algorithms Down Syndrome Screen Performance at a Risk Cutoff Equivalent to the Risk at Age 35,Using Past and Present Screening Algorithms

Urine Markers for Down Syndrome

Screening for fetal Down syndrome by measuring one or more markers in maternal urine would be less invasive than serum screening. Urine would require the additional step of correction for the varying dilution of the specimens, using creatinine or another dilution marker. The potential urine markers that have been examined include total and free p-hCG, and a degredation product of hCG sometimes called the P-core fragment. None of these has proved sufficient to displace serum marker screening (103,112,182).

Screening for Down Syndrome What Are the Choices

The advent of the new Down syndrome screening algorithms brings the promise of lower false positive rates and higher detection rates. Higher costs for screening can be recovered from the ensuing decrease in the number of patients requiring or requesting expensive follow-up services (see Table 6). Screening programs are constrained to offer only those algorithms for which there is published evidence of efficacy, but increasingly that leaves patients and programs with considerable choice. There are trade-offs between early detection and the small increase in miscarriage rate associated with the early diagnostic procedure, or between maximized detection and the need for two blood collections and holding of ultrasound results. The new algorithms add to the complexity of what patients need to know and choose. It will be necessary to provide information to patients about the choices they can have in their care. The diagram in Fig. 20 is an example of an educative instrument designed to...

Biology of Second Trimester Serum Biochemical Markers for Down Syndrome

Maternal Serum Median Ue3

The pathophysiological basis of Down syndrome is unknown, although the sequence of chromosome 21 has now been completed (120). Similarly, the reasons for altered second-trimester maternal serum analytes in Down syndrome pregnancy remain largely unexplained. A current hypothesis for the second trimester is that the serum analyte pattern is related to poorly functioning fetal tissue with compensatory placental hyper-function. The mechanisms leading to this phenomenon of increased placental and decreased fetal products in second-trimester maternal serum of Down syndrome pregnancy are actively being investigated (121-126). Placental-Derived Down Syndrome Markers hCG and DIA Placental secretory products, such as hCG and DIA are generally increased in the second trimester of Down syndrome pregnancy. None of the genes for these placental products resides on chromosome 21, thereby eliminating a simple higher-dose effect to explain their increased concentrations. Placental size and weight are...

Clinical Aspects of Trisomy 21 Down Syndrome

A congenital syndrome of mental retardation associated with specific facial and physical features was first described by J. Langdon Down in 1866 ( 72). Down syndrome is characterized by a moderate to severe learning disability (average IQ approx 40) and congenital heart defects affecting approx 50 of affected individuals. The birth prevalence of Down syndrome ranges from approx 1 in 800 up to 1 in 400, depending on the maternal age distribution of pregnant women in the region. Down syndrome is the most common fetal chromosome disorder compatible with life. Before the advent of antibiotics, the survival of Down syndrome infants was relatively poor. The life expectancy was only 12 yr in 1947 (73), but the current use of antibiotics and cardiac surgery to repair congenital cardiac anomalies has helped to increase life expectancy. Of those surviving the first 5 yr of life, 85 will have a life expectancy of at least 30 yr with many living to age 50 (74,75). There are medical problems...

Down Syndrome Tests

What is Down Syndrome Down Syndrome is the most common cause of significant mental retardation and learning disability in children. It is caused by a change in chromosomal number (genetic makeup) in the egg before it is fertilized by the sperm (at the time of conception). This usually occurs due to chance, and is more common in older mothers. As a result, the fertilized embryo contains an extra chromosome 21 making it three instead of the usual pair (hence the name trisomy 21).

Down Syndrome

Down syndrome is one of the most commonly occurring conditions associated with a chromosomal abnormality. Normally, there are 46 chromosomes 23 pairs with one of each pair inherited from each parent. Chromosomes contain all the genetic information needed for the cells in the body to function properly. Most children with Down syndrome have cells that contain not 46 but 47 chromosomes. About 95 percent of Down syndrome cases occur when an infant is born with three rather than two copies of chromosome 21. In most of the remaining 5 percent of people with Down syndrome, the genetic material from the extra chromosome 21 is attached to another chromosome. This extra genetic material disrupts the child's physical and mental development. Exactly why these chromosomal abnormalities occur is unknown. Women ages 35 and older have a higher risk of giving birth to a child with Down syndrome. The risk of a 25-year-old woman having a baby with Down syndrome is about 1 in 2,250. By age 45, the risk...

Musculoskeletal Disorders

Musculoskeletal Ribs

Chest radiograph showing 11 ribs. The presence of 11 ribs is not an uncommon finding in normal infants but occurs with greater frequency in infants with Down syndrome. Note the cardiac enlargement and enlarged thymus. Figure 1.1. Chest radiograph showing 11 ribs. The presence of 11 ribs is not an uncommon finding in normal infants but occurs with greater frequency in infants with Down syndrome. Note the cardiac enlargement and enlarged thymus.

If Theres a Problem at Birth

Some birth defects, genetic diseases, and chromosomal problems can be diagnosed prenatally, especially if the mother has had an ultrasound or amniocentesis performed. (See Chapter 1, Prenatal Care, for more information about these tests.) These conditions include spina bifida (in which the spinal cord doesn't close properly), Down syndrome, some heart malformations, and cleft lip or palate. Many of these conditions are described in Chapter 32, Health Problems in Early Childhood.

Risk Factors And Aetiology For Pregnancy Failure

The aetiology of pregnancy failure is complicated and could be the subject of an entire chapter. Suffice it to say that it can be associated with chromosomal abnormalities. Pregnancies associated with trisomy 21, 18 and 13 are the most likely to survive. All other trisomies end in early pregnancy failure. Congenital anomalies are also a source of pregnancy failure. Maternal endocrinopathies, especially diabetes, and haemoglobin A1C levels at conception correlate with risk of pregnancy failure. Other related conditions include uterine abnormalities (adhesions, septae and submucous fibroids). Acute or chronic maternal illness and or infection can result in early pregnancy failure. Thrombophilia as well as auto-immune disorders are controversial as to their role, if any, in early pregnancy failure and recurrent miscarriage in particular.

2118 Gout interval therapy

Apart from the nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofcn, colchicine is the classic medication for gout attacks. Colchicine is a mitotic spindle poison, and is by this action capable of blocking cell division. It has mutagenic and genotoxic properties and. in various animal studies, an embryotoxic action. Mutagenic effects on lymphocytes have been described in patients who are treated with colchicine. Colchicine is the only effective therapy to prevent attacks of Familial Mediterranean Fever (FMF) and to treat the renal amyloidosis that often accompanies FMF and which may itself cause several maternal and fetal complications (Ben-Chetrit 2003, Mordel 1993), However, to date, teratogenic damage or other adverse pregnancy outcomes in women with long-term colchicine treatment for FMF have not been observed in several reports. In one study, evaluating the outcome of 225 completed pregnancies in mothers with FMF, the authors also did not find an unusual frequency of...

Nuchal Translucency Scan Week 1114

In the recent years, ultrasound scans in the first trimester can be used to assess the risk of your baby being affected by Down Syndrome (Figure 14.3). This is done by a measurement of the skin fold thickness (nuchal trans-lucency) at the back of neck of the baby. If the neck fold is unusually thick, it may indicate that your baby may have Down syndrome (see Chapter 11). Other causes may include heart abnormalities or even other rarer genetic syndromes. This test is quite accurate to detect Down Syndrome as the detection rate is 80 in the hands of experienced doctors. So do consider this test, which is perfectly safe for your baby. If your baby is in an optimal position, ultrasound examination after 11 weeks may be able to visualize the baby's nose bone (known as nasal bone). The absence of the nose bone is a worrying sign, which increases the risk of Down Syndrome.

Screening Tests FTS or MSS

Baby Has Long Nasal Bone Down Syndrome

Screening tests do not tell you if your baby has Down Syndrome. Their purpose is to tell you if your fetus belongs to a low or high risk group. If the screening test shows that there is a high risk of your baby being affected, you will be offered a diagnostic test (see below) to confirm it. Screening tests are noninvasive hence, there is no risk of miscarriage to the baby. First trimester screening (FTS) This consists of a detailed ultrasound scan of your baby at 11-14 weeks gestation to measure the nuchal translucency (NT). NT is the skin at the back of your baby's neck (Figure 11.4). If this is increased above the normal range, most babies will still be normal although there is an increased risk of Down Syndrome, heart problem or rare genetic syndrome in some babies. Its accuracy is about 80 , and increases to 90 if maternal blood tests are done as well. This is known as integrated screening. A result of 1 in 300 means that 299 out of 300 women with this particular test result will...

2651 Albendazole and thiabendazole

Albendazole is a highly effective broad-spectrum anthelmintic, structurally related to mebendazole. It also kills the parasite through inhibition of the glucose uptake. It is the first-line drug for the treatment of alveolar forms of echinococcosis (Echinococcus multilocularis), and also for the advanced cystic forms (Echinococcus granulosus). During a mass drug administration for lymphatic filiriasis in Ghana, 50 women were inadvertently (because their pregnancy was not recognized) treated with ivermectin and albendazole their pregnancy outcomes were compared with those of 293 women with a recognized pregnancy who were not treated. Of the 39 children who were exposed during the first trimester, 1 congenital malformation (a hearing impairment), versus 5 of the untreated group, was reported. The authors concluded that there was no evidence of increased risk after exposure to ivermectin and albendazole (Gyapong 2003). One Down syndrome was observed in a small prospective study of...

Windsock Deformity Duodenum

Dilated Bowel Newborn

Duodenal atresia observed clinically in an infant at the age of 6 hours. Note the dilated stomach and dilated proximal duodenum giving rise to the double bubble appearance. At this early age, the infant also has a scaphoid lower abdomen. Thirty percent of infants with duodenal atresia will have other major anomalies, especially chromosomal abnormalities (e.g., Down syndrome).

Pregnant Teen Supermodels

Shortly after Alaska Governor Sarah Palin was tabbed as the Republican candidate for vice president, a blog appeared in the online Daily Kos speculating that Trig, the candidate's Down Syndrome infant, actually was the baby of her 17 year-old daughter, Bristol. That steaming, made-up crap diminished the left-wing blogosphere but it was rich crap. After all, Sarah Palin was a loud advocate of conservative family values, publicly parading her family at public events as a shining example. It was all shortly debunked. Trig was Sarah's kid. Bristol was pregnant by her then-18-year-old fiance, Levi Johnston. It was time for a new round of crap.

Indications For Prenatal Cytogenetic Diagnosis

Of requests for prenatal diagnosis, more than 90 are for the diagnosis of chromosome abnormalities in the fetus by cytogenetic techniques. The risk of having a child with trisomy 21, trisomy 18, trisomy 13, and sex chromosome aneuploidies such as 47,XXX or 47,XXY increases with maternal age as a result of the increased tendency toward meiotic nondisjunction in oogenesis (5.7,5.8 and 59). It was suggested by Hook and Cross that an association exists between maternal age and supernumerary marker chromosomes (60). Advanced maternal age is therefore the most common indication for cytogenetic prenatal diagnosis. The criteria for determining at what age to offer amniocentesis were derived largely from several surveys (61,62). Most centers in the United States now offer amniocentesis to women who will be over 35 at the time of delivery. However, this cutoff reflects the age at which the risks for the procedure are balanced by the risks of finding an abnormality. Increasing numbers of younger...

Full Ascertainment of Pregnancy Outcomes in Screening

Down syndrome detection should be assessed in accordance with the full outcome ascertainment protocol outlined by Palomaki (166). In addition to the Down syndrome outcomes in screen-positive patients (true positives TP ) and liveborn Down syndrome outcomes in screen-negative patients (false negatives FNLB ), there must be an allowance made for the screen-negative affected pregnancies that were spontaneously lost before term (FNSL). Otherwise, a substantially overestimated detection rate will be reported (167). The proper detection rate calculation is In addition, the expected total number of Down syndrome cases should be calculated from the known maternal age distribution of the study population (84-87), and this should be compared to the number actually ascertained. The calculated fetal loss rates should be similar to literature reports (84,90,91).

Validation of Reported Patient Risks

The risk of fetal Down syndrome calculated and reported to a patient cannot be validated in any individual patient a patient either has, or does not have, a Down syndrome pregnancy. However, it is possible to group patients with similar estimated risks into clusters and to compare the mean reported risk against the actual prevalence of Down syndrome in the cluster (see Fig. 12). Such an analysis requires close to complete pregnancy outcome ascertainment and a large screened population. At least three such validation studies have been reported for triple marker screening (168-170) and one report for first trimester (see below) screening with nuchal translucency (NT), pregnancy-associated plasma protein A (PAPP-A), and free p-hCG (171). Second-Trimester Down Syndrome Screening Performance In the 1970s, when Down syndrome screening based on maternal age commenced, the fraction of the pregnant population over the age of 35 (the FPR) was 5 , which is low compared to the present...

Psychological Impact of Prenatal Screening

Patients gain a better understanding of their risk when a numerical probability is provided (e.g., 1 200) compared to when only a verbal probability ( moderate risk ) is provided (176). In addition, verbal probability statements are more likely to invoke a framing effect that biases decisions (e.g., a discussion of the risk of the disorder vs the chance of an unaffected child ). Framing might occur in the phrasing used to describe the risk of an amniocentesis procedure compared to the description of a patient's risk of Down syndrome. Numerical probability statements are less susceptible to a framing effect (177).

Fetal Cells and DNA in Maternal Serum

Fetal nucleated red cells in the maternal circulation can be identified and concentrated, and such cells have been proposed as a noninvasive source for prenatal diagnosis of chromosome abnormalities and other genetic disorders (188-190). Although the technology has not yet permitted prenatal diagnosis, and may never, a separate finding of a larger number of fetal cells present in the maternal circulation in trisomy 21 and other chromosome abnormalities has raised the possibility of using the concentration of fetal cells as a screening marker (191). However, it is unlikely that such a test would be cost efficient and easy enough to be performed on a large scale basis. More recently, cell-free fetal DNA has been found in the maternal circulation and, like fetal cells in maternal blood, the concentration of fetal DNA in maternal plasma and serum is higher in Down syndrome pregnancies. Although fetal DNA has been discussed as having potential for noninvasive diagnostics (192,193), similar...

First Trimester Markers Biochemistry and Biometry

The focus on the second trimester as the timing for Down syndrome biochemical markers arose from the connection with NTD screening and the fact that the safest diagnostic procedures rely on second-trimester amniocentesis. However, there are perceived advantages and patient preferences for having information about the health of the developing baby earlier in the pregnancy. In addition to the simple preference for an earlier answer, there is increased patient privacy when screening is performed before the pregnancy is announced, and there are safer termination procedures should they be needed. There is also the potential of adding new markers that are informative only in the first trimester (197). PAPP-A is a glycoprotein derived from the placenta. Despite its name, PAPP-A is also present in serum and plasma in nonpregnant women and men, and recently it has been described as a marker of plaque instability in acute coronary syndromes (198). During pregnancy, PAPP-A circulates in a...

Potential Biases in First Trimester Screening

High rate of spontaneous loss of Down syndrome affected pregnancies (45 ) between the first trimester and term (91). The first source of bias arises because most, if not all, marker-negative Down syndrome pregnancies that are spontaneously lost are not counted (not ascertained) in prospective intervention studies. This was probably true in the NT study of Snijders et al. in 1998 (234). The effect of this ascertainment bias on marker performance can be explained as follows most unascertained cases have marker values that place them below the screen cutoff, and exclusion of these when calculating the Down syndrome population mean for that marker overestimates the mean and overestimates the detection rate (103,250,251). This source of bias can be approximated, and adjustments can be made (167,205,250,252).

Chromosomal Disorders

Chromosomal abnormalities are fairly common. They occur in about 1 in every 200 deliveries, although many of these infants are phenotypically normal. In addition, 50 of all spontaneous abortions involve a chromosomal abnormality. Nondisjunction, where an extra chromosome (or part of a chromosome) is present (e.g., trisomy 21), is the most common cause of chromosomal disorders. Translocation syndromes, where chromosomal material breaks off from one chromosome and translocates to another, may not have classic clinical findings and may be difficult to diagnose. Usually infants with balanced translocations are only carriers and do not demonstrate clinical manifestations, while unbalanced translocations result in clinical signs. A deletion occurs when chromosomal material is missing from either the upper (p) or lower (q) arms of a chromosome (e.g., cri du chat syndrome with deletion of the upper short arm of chromosome 5 5p-). An abnormal number of X or Y chromosomes can also result in...

Combined First Trimester Biochemical and Ultrasound Screening

The early reports of ultrasound screening in the first trimester were based on NT measurements, with and without maternal age. The debate that arose at the time, and that still persists in some locales, was whether the combination of NT and maternal age was sufficient by itself to support screening. Sometimes the discourse over the power of NT as a marker is confused as dismissing it altogether as a marker, but this is not the intent. NT is a powerful marker for fetal Down syndrome, and the more recent studies have been examining how best to utilize NT and maximize its performance consistency (255). Wald and Hackshaw took the approach of modeling a combined first-trimester screening algorithm using three separate datasets (233). These authors adjusted the NT dataset of Pandya et al. (218) to compensate for a probable ascertainment bias, and then combined it with a similar NT dataset from Schuchter et al. (231) in order to construct log10 MoM NT distributions for the Down syndrome and...

Sequential or Stepwise Screening With Ultrasound and Biochemistry

Because ultrasound examinations are performed on patients in real time, patients have an expectation of immediately receiving some form of report, even if only a brief verbal statement. However, to comment on an ultrasound examination that is only one of several components of a Down syndrome screening algorithm is to issue a partial or stepwise screening report a practice that diminishes the overall performance of the screen. The need to hold information, even briefly, is not always recognized and accepted by health care providers and patients (224). Favorable ultrasound reports can induce patients to forego subsequent blood tests, whereas removing high-risk patients by screening them positive on the basis of an increased NT measurement will alter the prevalence of the disorder in the patients who go on to have all components of the screen. Calculated second-trimester risks in these latter patients will be over-estimated if the first-trimester results for individual markers are not...

Other Conditions Identified By Serum

Although not the targets of any formal screening protocol, a number of deleterious conditions and disorders are adventitiously detected through Down syndrome and T18 screening algorithms. In order for this to occur, the conditions must have marker patterns that overlap with those of a targeted disorder, causing the conditions to cluster among the screen positives. Other chromosome abnormalities are not screened for specifically, but they may be detected with increased frequency through Down syndrome and T18 protocols and the subsequent karyotype studies. For example, women carrying a fetus affected with hydropic Turner syndrome (45,X) have a maternal serum triple-marker pattern very similar to that observed in cases of Down syndrome (274,283,284). DIA concentrations in Turner syndrome pregnancies are markedly elevated in the presence of fetal hydrops and low in the absence of hydrops (274). Therefore, inclusion of DIA in Down syndrome screening will increase the opportune detection of...

Summary And Perspective

Initially based on maternal age alone, and then linked through AFP to screening for ONTDs, the performance of prenatal screening tests for Down syndrome has improved rapidly during the past 25 yr. With the development of multiple screening markers (both in maternal serum and by using ultrasound) and with the ability to combine these markers into a rational screening algorithm, detection rates are becoming high enough to allow a focus on reducing the FPR. The goal in reducing the FPR is to improve safety in screening because a lower FPR leads to reduced use of invasive diagnostic testing, thus reducing the risk of losing a wanted pregnancy. The goal is a detection rate approaching 100 with an FPR approaching zero. At a point, perhaps not too far in the future, safe, noninvasive diagnostic testing for serious birth defects will have been achieved.

Nail Diseases And Disorders

Hypoplastic Toenails

There is marked webbing of the neck in this infant with Turner's syndrome. Note the low posterior hairline. Compare this with the webbing of the neck and high hairline in trisomy 21 (see Figure 4.47). The infant also had congenital heart disease (coarctation of the aorta). Figure 4.65. There is marked webbing of the neck in this infant with Turner's syndrome. Note the low posterior hairline. Compare this with the webbing of the neck and high hairline in trisomy 21 (see Figure 4.47). The infant also had congenital heart disease (coarctation of the aorta).

Brushfield Spots And Zellweger

Simian Crease

This infant with Zellweger syndrome had marked hypotonia and shows the typical appearance of the head and face, the single palmar creases, and clinodactyly. There is commonly ulnar deviation with simian creases of the hand. Brushfield's spots also occur in infants with Zellweger syndrome. Because of the hypotonia, craniofacial findings, Brushfield's spots, and simian creases, these infants often are mistaken for infants with trisomy 21. Figure 3.208. This infant with Zellweger syndrome had marked hypotonia and shows the typical appearance of the head and face, the single palmar creases, and clinodactyly. There is commonly ulnar deviation with simian creases of the hand. Brushfield's spots also occur in infants with Zellweger syndrome. Because of the hypotonia, craniofacial findings, Brushfield's spots, and simian creases, these infants often are mistaken for infants with trisomy 21.

Identification Of Fetal Structural Anomalies In The First Trimester

Omphalocele Weeks

Clearly, many anomalies will not be apparent in the first trimester and first trimester anomaly scanning will not replace the second trimester anatomy scan. However, the widespread introduction of Down syndrome screening, requiring accurate dating, with nuchal translucency and nasal bone assessment at the 10-14 week scan has resulted in many more anomalies being detectable in the first trimester.32 It must be kept in mind that a proportion of such anomalies will result in spontaneous miscarriage, before assessment is carried out, and the emotional and financial burden of 'routine' anatomy scanning in the first trimester have yet to be adequately assessed.

Screening Scan Week 1822

Finding of certain abnormalities during an ultrasound scan may also alert doctors to the possibility of Down Syndrome or other genetic abnormalities in the baby. Further testing can then be done to exclude these. Ultrasound screening for physical abnormalities is usually done during around the fifth month or 20th weeks of your pregnancy.

Antenatal screening tests

In a multicentre study at the Harris Birthright Centre and four district general hospitals 20,804 pregnancies were included in nuchal screening at 10-14 weeks' gestation (Snijders et al. 1996). It was demonstrated that 80 of affected fetuses with trisomy 21 could be identified through using this method with a false-positive rate of 5 .

Confounding Variables of Second Trimester Markers and Risk

Similar to prenatal screening for ONTD, there are a number of factors that modify the risk of Down syndrome from that derived from the maternal age and optimally measured marker concentrations. MSuE3 concentrations increase by approx 25 per wk through the early second trimester (Fig. 10), although this rate of rise diminishes slightly beyond week 18 (143). In contrast, maternal serum (MShCG) concentrations decrease from their 10-12 wk maximum, most rapidly during weeks 15-17, reaching relatively stable concentrations by weeks 19-20. DIA concentrations are relatively constant throughout the early second trimester, with a slight nadir at week 16 (144). Regressed median concentrations can be obtained for each week of gestation for each marker in a manner similar to MSAFP, such that all four markers are expressed in MoM units. The optimum gestational age for measuring MSAFP, uE3, hCG, and DIA in terms of the degree of separation between Down syndrome and unaffected pregnancies is between...

Pre Pregnancy Preparation

The prime of your fertility is when you are 20-24 years old, with a sharp decline from 35 years old onwards. On average, there is a drop of 3 in fertility with each increasing year of the woman's age (Figure 1.1). The chance of genetic abnormalities like Down syndrome as well as complications in pregnancy like miscarriages, high blood pressure and diabetes, increase as you grow older, particularly beyond 35 years of age. So, start young when you are in your prime

Combining Multiple Markers Into a Risk Based Screen

As a marker for risk of Down syndrome, MSAFP by itself measured solely for the purpose of estimating the risk of Down syndrome would not be powerful enough to be justified. However, because MSAFP is widely used for ONTD screening, use of its modest additional information about the risk of Down syndrome is easily justified. Screening for Down syndrome also benefited from screening for ONTD in that the concept of the MoM had already been developed for ONTD screening (see Using the MoM to Adjust for Gestational Age above). Like MSAFP, the concentrations of all the markers for fetal trisomy screening are expressed as MoMs. Being a ratio (the patient's concentration divided by the median concentration at that gestational age), the MoM has no units. The MoM compensates for the concentration changes that occur with gestational age and enables combinations of multiple markers on a common scale. Initially, MSAFP was used in Down syndrome screening in a binary fashion any value below a fixed...

Practical Problems In Prenatal Cytogenetic Diagnosis

Both amniotic fluid and chorionic villus samples may occasionally include maternal cells because of the way these samples are obtained. Maternal cell contamination (MCC) is usually identified when an admixture of male and female cells is observed in one culture. A European collaborative study gave an admixture detection incidence of 0.315 (95), and data from several North American laboratories suggest a detection rate of 0.23 (2,5,96). Because contamination of female cultures will usually go unnoticed, the actual frequency should be estimated as twice that observed with male fetuses alone. Amniotic fluid cultures affected by MCC may yield a variable proportion of maternal to fetal cells and are therefore a potential source of error in prenatal diagnosis. At least four cases of trisomy 21 were misdiagnosed and considered normal because of an overgrowth of maternal cells in culture, whereas in others the wrong fetal sex was determined (86).

Congenital Heart Disease

Sels that feed into it, or the vessels that carry blood out from it. The causes of most of these defects are unknown. Genetic factors play some role, and the risk of a child having a heart defect increases if a parent or sibling has one. In one large study, 12 percent of the cases of congenital heart malformations were related to a chromosomal defect such as Down syndrome (see Down Syndrome in this chapter), and 8 percent occurred in infants who had multiple congenital abnormalities (birth defects). Some children with congenital heart disease have an identifiable single gene defect, such as Marfan syndrome, a hereditary connective tissue disorder.

The Other Strep

Is higher. (The risk of Down syndrome rises with the mother's age. It is estimated to be 1 in 1,400 if the mother is 20, 1 in 250 if she is 35, 1 in 75 if she is 40, and 1 in 20 if she is 45.) Be sure to discuss any questions or concerns you might have about this test with your doctor.

No Guarantees

Although testing before and during pregnancy can rule out many problems, it cannot detect all possible problems or guarantee that your baby will be healthy. And although amniocentesis and chorionic villus sampling are highly accurate in detecting Down syndrome and some other chromosome problems, ultrasound results and fetal monitoring tests are often difficult to interpret. If you get a test result that concerns you, it's wise to get a second opinion if possible, from a maternal-fetal medicine specialist or another physician who is skilled and experienced at dealing with high-risk pregnancies. Getting an expert second opinion is especially important if you are considering terminating the pregnancy based on abnormal test results.

Amniotic Fluid

Because amniotic fluid is derived from substances of fetal origin, it is often sampled and tested in order to monitor fetal development or detect fetal disease. Amniotic fluid is sampled routinely to obtain fetal cells for chromosomal analysis and detection of Down syndrome, trisomy 18, and a variety of other chromosomal abnormalities and to measure a-fetoprotein and acetylcholinesterase to detect neural tube defects (see Chapters 5 and 6 for more detail). It is also sampled later in pregnancy for the analysis of fetal lung-

21815 Fluoride

Whether a fluoride supplement during pregnancy of about 1 mg day in tablet form (equivalent to about 2mg sodium fluoride), or ingested via fluoridated drinking water (about 1 mg l), actually reduces the incidence of caries in the baby is somewhat controversial. However, such fluoride prophylaxis does not appear to harm the fetus. Earlier suspicions regarding the possible toxic effect of regular fluoride on reproduction - for example, an increased rate of Down syndrome -is biologically implausible. Even high fluoride doses as a result of environmentally contaminated drinking water (above 10mg l) do not apparently cause any increase in birth defects, Prenatally induced fluorosis of the teeth and bones in the second half of pregnancy is theoretically possible, and has been described in individual cases after extreme continuous exposure, but would not be expected after (as has occasionally happened) accidental intake of an osteoporosis preparation containing about 25 mg of fluoride.

Assay Methodologies

A number of immunoassays exist for uE3, but not all of them achieve the expected degree of separation between the affected and unaffected populations in prenatal screening, either for Down syndrome (54,298) or for T18 (299). A validated assay should be used if the published distribution parameters are to be used in calculating risks. There have been no reports of differential performance of any intact or total P-hCG assays in Down syndrome screening. Free P-hCG has whole blood specimen stability issues that must be considered on standing, there is an increase in the apparent free p-hCG concentration caused by the temperature-dependent dissociation of the very large amount of intact hCG present (300). Prompt separation of the serum appears to minimize this problem (101,131). Most intact and total hCG assays are optimized for concentrations found in early pregnancy (up to approx 2000 IU L). Concentrations of intact and total hCG found in the late first and early second trimesters are...


Low Papp Pregnancy

Trisomy 18 (Edwards' syndrome T18 ) is less common and more lethal than trisomy 21. The prevalence of T18 during the first and second trimester is approx 1 in 3000 but spontaneous loss of T18 pregnancies reduces the birth prevalence to approx 1 in 8000. T18 pregnancies miscarry at a rate of 70 between midpregnancy and term (264,265). Like Down syndrome, the prevalence of T18 is correlated with increasing maternal age. The occurrence of a low MSAFP in a T18 pregnancy was the impetus for the first assessment of MSAFP as a marker for fetal trisomy risk (92). Although this earliest study resulted in screening for the more prevalent trisomy, Down syndrome, the correlation between low MSAFP and T18 was not forgotten. As new markers for Down syndrome were discovered and added to screening programs, the markers were assessed for their potential as T18 markers. Within a few years of the advent of triple-marker screening, it was known that T18 pregnancies had a relatively distinctive pattern of...

Mickey Mouse Pelvis

Musculoskeletal Disorders

The gap between the first and second toes ( sandal or thong sign) is a typical finding in trisomy 21. The feet are broad and short. The plantar surfaces are creased with a deep long furrow (ape-line) between the first and second toes. Figure 4.56. A close-up view of the broad short foot of an infant with trisomy 21 shows the marked separation of the first and second toes and the deep furrows on the sole. Figure 4.56. A close-up view of the broad short foot of an infant with trisomy 21 shows the marked separation of the first and second toes and the deep furrows on the sole. Figure 4.57. Total radiograph of an infant with trisomy 21 shows the long narrow chest cage with downslanting ribs due to hypotonia. Any infant who is hypotonic has this appearance of the chest cage. The finding of eleven pairs of ribs, as in this infant, is common in Down syndrome but also may occur as a finding in normal infants. The pelvis is a typical mongoloid pelvis. The infant also had...

Mild Microcephaly

Heart Defects Associated With Trisomy

The typical appearance of an infant with trisomy 21 (Down syndrome). Note die marked hypotonia, flat facies, single palmar crease and separation of the first and second toes. The abdominal surgery was for the common finding of duodenal atresia. There is a burn at the left knee which occurred during surgery. The incidence of trisomy 21 is 1 in 700 newborns. The typical findings in trisomy 21 include hypotonia, poor Moro's reflex, hyperflexibility of joints, excess skin at the back of the neck, a flat facial profile, slanted palpebral fissures, dysplasia of the pelvis, and hand and feet abnormalities. Figure 4.40. The typical appearance of an infant with trisomy 21 (Down syndrome). Note die marked hypotonia, flat facies, single palmar crease and separation of the first and second toes. The abdominal surgery was for the common finding of duodenal atresia. There is a burn at the left knee which occurred during surgery. The incidence of trisomy 21 is 1 in 700 newborns. The...

21512 Estrogens

Several studies have analyzed the relationship between oral contraceptives and Down syndrome, some of them with negative results (Kallen 1989, Harlap 1985B, Ericson 1983), but others have suggested that women who take oral contraceptives during the month just before conception (Mikkelsen 1991) or who fall pregnant following oral contraceptive failure (Harlap 1980) have an increased risk for Down syndrome. A more recent case-control study has demonstrated an increased risk of 2.8-fold for infants with Down syndrome in women younger than 35 years of age if the mother became pregnant while she was taking oral contraceptives (Martmez-Frias 2001).