What Is the Risk of Having a Down Syndrome Baby After 35
Down Syndrome: Prenatal Risk Assessment and Diagnosis
A more than recent article on this topic is available.
Am Fam Physician. 2000 Aug 15;62(four):825-832.
See related patient information handout on Down syndrome, written by the writer of this commodity.
Related Editorial
Article Sections
- Abstruse
- Etiology and Clinical Manifestations
- Prenatal Risk Cess
- Prenatal Diagnosis
- Counseling Aspects
- References
Down's syndrome (trisomy 21) is the most ordinarily recognized genetic cause of mental retardation. The hazard of trisomy 21 is straight related to maternal historic period. All forms of prenatal testing for Downwards syndrome must exist voluntary. A nondirective approach should be used when presenting patients with options for prenatal screening and diagnostic testing. Patients who volition exist 35 years or older on their due appointment should be offered chorionic villus sampling or 2d-trimester amniocentesis. Women younger than 35 years should be offered maternal serum screening at 16 to eighteen weeks of gestation. The maternal serum markers used to screen for trisomy 21 are alpha-fetoprotein, unconjugated estriol and homo chorionic gonadotropin. The utilize of ultrasound to approximate gestational age improves the sensitivity and specificity of maternal serum screening.
Down's syndrome is a variable combination of congenital malformations acquired by trisomy 21. It is the well-nigh commonly recognized genetic cause of mental retardation, with an estimated prevalence of ix.2 cases per 10,000 live births in the The states.1,2 Because of the morbidity associated with Down syndrome, screening and diagnostic testing for this condition are offered equally optional components of prenatal care. Prenatal diagnosis of trisomy 21 allows parents the choice of continuing or terminating an afflicted pregnancy.
Etiology and Clinical Manifestations
- Abstract
- Etiology and Clinical Manifestations
- Prenatal Risk Assessment
- Prenatal Diagnosis
- Counseling Aspects
- References
Down syndrome is usually identified soon after birth by a feature pattern of dysmorphic features (Table 1).3,4 The diagnosis is confirmed by karyotype analysis. Trisomy 21 is present in 95 percent of persons with Down's syndrome. Mosaicism, a mixture of normal diploid and trisomy 21 cells, occurs in 2 pct. The remaining 3 percent have a Robertsonian translocation in which all or office of an extra chromosome 21 is fused with some other chromosome. Most chromosome-21 translocations are sporadic. Nonetheless, some are inherited from a parent who carries the translocation balanced by a chromosome deletion.1,3,4
Tabular array 1
Frequency of Dysmorphic Signs in Neonates with Trisomy 21
| Dysmorphic sign | Frequency (%) |
|---|---|
| Flat facial contour | 90 |
| Poor Moro reflex | 85 |
| Hypotonia | 80 |
| Hyperflexibility of large joints | eighty |
| Loose skin on back of neck | 80 |
| Slanted palpebral fissures | 80 |
| Dysmorphic pelvis on radiographs | seventy |
| Small round ears | threescore |
| Hypoplasia of small finger, middle phalanx | threescore |
| Single palmar crease | 45 |
Molecular genetic studies reveal that 95 percent of occurrences of trisomy 21 result from nondisjunction during meiotic division of the main oocyte.one The exact mechanism for this meiotic error remains unknown. Most trisomy 21 pregnancies prove to be nonviable. Only 1 quarter of fetuses with trisomy 21 survive to term.four
Persons with Down syndrome usually have mild to moderate mental retardation. In some, mental retardation can be astringent. Schoolhouse-aged children with Down syndrome often take difficulty with language, communication and problem-solving skills. Adults with Down's syndrome have a high prevalence of early Alzheimer'due south illness, farther impairing cognitive function.1
A number of built malformations and acquired diseases occur with increased frequency in persons with Down syndrome (Table 2).1,iii–half dozen Congenital heart disease and pneumonia are leading causes of mortality, especially in early on childhood.
Table 2
Incidence of Some Associated Medical Complications in Persons with Down Syndrome
| Disorder | Incidence (%) |
|---|---|
| Mental retardation | > 95 |
| Growth retardation | > 95 |
| Early on Alzheimer'due south disease | Affects 75% by age 60 |
| Congenital heart defects (atrioventricular culvert defect, ventricular septal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot) | 40 |
| Hearing loss (related to otitis media with effusion or sensorineural) | xl to 75 |
| Ophthalmic disorders (congenital cataracts, glaucoma, strabismus) | 60 |
| Epilepsy | 5 to 10 |
| Gastrointestinal malformations (duodenal atresia, Hirschsprung disease) | v |
| Hypothyroidism | v |
| Leukemia | 1 |
| Atlantoaxial subluxation with spinal string compression | < 1 |
| Increased susceptibility to infection (pneumonia, otitis media, sinusitis, pharyngitis, periodontal disease) | Unknown |
| Infertility | > 99% in men; anovulation in 30% of women |
Prenatal Risk Assessment
- Abstruse
- Etiology and Clinical Manifestations
- Prenatal Adventure Cess
- Prenatal Diagnosis
- Counseling Aspects
- References
ADVANCED MATERNAL AGE
The incidence of fetal trisomies is directly related to maternal age.7 The gamble of having a child with Down syndrome increases in a gradual, linear manner until about historic period 30 and increases exponentially thereafter (Figure one).8 The risk of having a child with Down syndrome is 1/1,300 for a 25-year-old woman; at age 35, the run a risk increases to 1/365. At age 45, the gamble of a having a child with Downward syndrome increases to ane/30. (By convention, maternal age refers to age at the estimated or actual commitment date.)
Effigy i.
Estimated risk of Downward syndrome according to maternal age. Data from reference 8.
Historically, maternal age can exist viewed as the start "screening examination" for fetal chromosome abnormalities. In the late 1970s, about v percent of pregnancies in the United States occurred in women who were 35 years or older.9 At age 35, the second-trimester prevalence of trisomy 21 (ane/270) approaches the estimated risk of fetal loss due to amniocentesis (1/200).10 Therefore, age 35 was called as the screening cutoff—the take a chance threshold at which diagnostic testing is offered.
MATERNAL SERUM SCREENING
If all pregnant women 35 years or older chose to take amniocentesis, nearly 30 per centum of trisomy 21 pregnancies would be detected.xi Women younger than 35 years give birth to about lxx per centum of infants with Down syndrome.12 Maternal serum screening (multiple-marker screening) tin let the detection of trisomy 21 pregnancies in women in this younger age grouping.
Blastoff-fetoprotein (AFP), unconjugated estriol and human chorionic gonadotropin (hCG) are the serum markers almost widely used to screen for Down's syndrome.13 This combination is known as the "triple exam" or "triple screen." AFP is produced in the yolk sac and fetal liver. Unconjugated estriol and hCG are produced by the placenta. The maternal serum levels of each of these proteins and of steroid hormones vary with the gestational age of the pregnancy. With trisomy 21, second-trimester maternal serum levels of AFP and unconjugated estriol are about 25 percent lower than normal levels and maternal serum hCG is approximately two times college than the normal hCG level.12
The triple examination is ordinarily performed at 15 to 18 weeks of gestation. The level of each serum marker is measured and reported as a multiple of the median (MoM) for women with pregnancies of the same gestational historic period as that of the patient's. The likelihood of trisomy 21 is calculated on the basis of each of the serum mark results and the patient's age. A composite guess of the risk of trisomy 21 is reported to the clinician. A standard risk cutoff is used to decide when the test is considered "positive." Most laboratories utilize a take chances cutoff of 1/270, which is equal to the second-trimester take a chance of trisomy 21 in a 35-year-old woman.13 A positive test is an indication for amniocentesis (Figure 2).
Screening for Down syndrome
FIGURE 2.
Algorithm for Down syndrome screening using the triple examination results and a risk of 1/270 or higher. (LMP = terminal menstrual period)
The triple test tin can find 60 percent of trisomy 21 pregnancies; it has a false-positive rate of 5 per centum.xi,fourteen The likelihood of a fetus having trisomy 21 in a patient with a positive test is near 2 percent. A normal result reduces the likelihood of trisomy 21 but does not exclude information technology. Test performance can exist slightly improved by adjusting for maternal weight, ethnic group and insulin-dependent diabetes mellitus.12 In 1995 in the United States, maternal serum screening for Down syndrome was ordered in 60 percent of pregnancies.thirteen
For women 35 years or older, maternal serum screening can provide an private guess of the likelihood of fetal trisomy 21.fifteen Still, the triple test fails to discover 10 to 15 percent of trisomy 21 pregnancies in women in this older age group.16 Therefore, electric current U.S. practice standards indicate that for women 35 years or older, maternal serum screening should non be offered as an equivalent alternative to amniocentesis or chorionic villus sampling.16–eighteen Guidelines published by the American College of Obstetricians and Gynecologists state that maternal serum screening may be offered "equally an selection for those women who practise non take the risk of amniocentesis or chorionic villus sampling or who wish to have this additional data prior to making a decision about having amniocentesis."18
ULTRASOUND Cess
An gauge of gestational age by ultrasound test improves the operation of the triple examination. In one study,19 the use of ultrasound was establish to raise the sensitivity of the triple test from 60 percent to 74 percent and to decrease the initial false-positive rate from 9 percentage to 5 percent. When available, an ultrasound estimate of gestational age should be provided to the laboratory instead of the due date based on the patient's final menstrual period. The biparietal bore provides the all-time gestational age estimate for this purpose. Femur length and composite estimates derived from it should not be used, because this parameter underestimates the gestational age of fetuses with trisomy 21.xix
2nd-trimester ultrasound cess may be helpful for predicting the likelihood of trisomy 21 in pregnancies at increased risk.20,21 This method of evaluation may be useful when amniocentesis is being considered in a patient with advanced maternal historic period or positive findings on the triple test. The nigh common ultrasonographic finding associated with trisomy 21 is increased nuchal fold thickness (nuchal translucency), which is caused by subcutaneous edema at the base of the occiput (Tabular array 3).20–22
TABLE 3
Ultrasonographic Findings Associated with Fetal Down syndrome
| Intrauterine growth restriction |
| Balmy cerebral ventriculomegaly |
| Choroid plexus cysts |
| Increased nuchal fold thickness |
| Cystic hygromas |
| Echogenic intracardiac foci |
| Congenital heart defects |
| Increased intestinal echogenicity |
| Duodenal atresia ("double-bubble sign") |
| Renal pelvis dilation |
| Shortened humerus and femur |
| Increased iliac wing angle |
| Incurving (clinodactyly) and hypoplasia of the fifth finger |
| Increased space between first and second toes |
| Two-vessel umbilical string |
FIRST-TRIMESTER SCREENING
Ultrasound measurement of nuchal translucency has been studied alone and in combination with new biochemical markers as a potentially useful starting time-trimester screening test for trisomy 21. Estimates are that first-trimester screening past means of maternal age and measurement of nuchal translucency could provide a trisomy 21 detection rate of 63 percentage, with a v percent false-positive rate.23 Combining this process with measurement of maternal serum complimentary beta-hCG subunit and pregnancy-associated protein A (PAP A) could increase the detection rate to lxxx per centum, at the same false-positive rate.23 Farther written report of the clinical utility and reliability of first-trimester screening is ongoing.
RECURRENCE Gamble AND Family HISTORY
If a patient has had a trisomy 21 pregnancy in the past, the risk of recurrence in a subsequent pregnancy increases to approximately one percent above the baseline risk determined by maternal age. Diagnosis of a chromosome-21 translocation in the fetus or newborn is an indication for karyotype analysis of both parents. If both parents have normal karyotypes, the recurrence risk is 2 to 3 percentage. If i parent carries a counterbalanced translocation, the recurrence risk depends on the sex of the carrier parent and the specific chromosomes that are fused.four
The significance of a family history of Down syndrome depends on the karyotype of the affected person (proband). If the proband has trisomy 21, the likelihood of a trisomy 21 pregnancy is minimally increased for family members other than the parents. If the proband has a chromosome-21 translocation or if the karyotype is unknown, family members should exist offered genetic counseling and karyotype analysis.iv
Prenatal Diagnosis
- Abstract
- Etiology and Clinical Manifestations
- Prenatal Chance Assessment
- Prenatal Diagnosis
- Counseling Aspects
- References
Definitive prenatal diagnosis of trisomy 21 requires cytogenetic analysis of cells obtained past one of three invasive procedures (Tabular array iv).10 Second-trimester amniocentesis has been used the most extensively, and the safety of this technique continues to improve as technical advances have occurred.24 Chorionic villus sampling offers the opportunity for first-trimester diagnosis, when elective pregnancy termination carries the lowest gamble of maternal morbidity, as compared with the hazard in the second and third trimesters. Early amniocentesis offers a similar advantage, but the fetal loss rate associated with this technique is college than that of chorionic villus sampling.ten
Karyotype assay commonly requires seven to ten days. A recently adult assay that uses fluorescent in situ hybridization (FISH) can allow rapid diagnosis of trisomy 21 after amniocentesis.25
TABLE iv
Procedures for Prenatal Genetic Diagnosis
| Diagnostic procedure | Gestational age when test is done (weeks) | Risk of fetal loss (%) |
|---|---|---|
| Chorionic villus sampling | 10 to 12 | 0.5 to one.5 |
| Early amniocentesis | 12 to 15 | ane.0 to ii.0 |
| Second-trimester amniocentesis | xv to 20 | 0.5 to 1.0 |
Counseling Aspects
- Abstract
- Etiology and Clinical Manifestations
- Prenatal Adventure Assessment
- Prenatal Diagnosis
- Counseling Aspects
- References
Cess of the risk of Down syndrome begins with the first prenatal visit. All forms of prenatal testing for Downwardly syndrome must be voluntary. A nondirective approach should be used when discussing the methods of prenatal screening and diagnostic testing.26 Informed consent to testing should exist documented in the patient'southward chart.
Consultation with a medical geneticist or a genetic advisor should be sought if there has been a previous pregnancy complicated by a chromosome aberration or if either parent is known to comport a balanced translocation.
Women who volition be 35 years or older on their due engagement should be offered chorionic villus sampling or second-trimester amniocentesis. These patients may be offered maternal serum screening and ultrasound evaluation before they brand a decision about having amniocentesis, provided that they are informed of the express sensitivity of noninvasive testing.18
Women younger than 35 years should exist offered maternal serum screening at fifteen to xviii weeks' gestation. They should exist counseled about the imperfect sensitivity of maternal serum screening and the possibility that a false-positive issue could lead to invasive testing. Test results should be reported to the patient promptly. Patients who receive news of aberrant results frequently experience considerable anxiety.27 These patients tin be reassured by the knowledge that the likelihood of Down's syndrome is small, even after a positive triple test.28 Ultrasound and amniocentesis should be offered. The risk of fetal loss from amniocentesis should be discussed.
If diagnostic testing reveals fetal trisomy 21, the parents should be provided with current, accurate information well-nigh Down's syndrome and assistance in deciding on a course of action. Their options include continuing the pregnancy and raising the child, standing the pregnancy and seeking adoption placement for the child or terminating the pregnancy. Consultation with a genetic advisor, a medical geneticist or a developmental pediatrician tin be helpful to accost the parents' concerns and facilitate their controlling process.29
Parents who decide to keep the pregnancy should be advised that there is an increased take chances of fetal demise in trisomy 21 pregnancies. A fetal echocardiogram should exist performed at 20 weeks of gestation to notice serious cardiac malformations. An ultrasound test should be performed at 28 to 32 weeks of gestation to monitor growth and detect duodenal atresia.29 The parents should be provided with referrals to support groups and organizations that abet for persons with Down syndrome and their families.5 A positive outlook should be encouraged, recognizing that improvements in medical care, early intervention, special education and vocational counseling have enabled persons with Down syndrome to live more normal lives.29
SOURCES OF Information FOR PATIENTS AND PHYSICIANS
In addition to the patient information handout that accompanies this article, a more than detailed brochure, "Facts About Downward Syndrome," has been produced by the National Constitute of Kid Health and Man Development (NIH Publication No. 97–3402). This brochure is available in English and Spanish from NICHD Clearinghouse, PO Box 3006, Rockville, Doctor 20847; telephone: 800-370-2943. In addition, the Genetic Counseling and Principal Care Web site (http://stork.cellb.bcm.tmc.edu/~genetics/) provides links to sources of additional information about Down syndrome and case-oriented tutorials on topics in genetics and genetic counseling.
To see the total article, log in or buy admission.
This piece of work was supported in function past a Faculty Development Grant from the Bureau of Health Professions, Health Resource and Services Assistants.
REFERENCES
show all references
1. Epstein CJ. Downward syndrome (Trisomy 21). In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill, 1995:749–94. ...
2. Down syndrome prevalence at birth—U.s.a., 1983–1990. MMWR Morb Mortal Wkly Rep. 1994;43:617–22.
3. Smith DW, Jones KL. Smith's Recognizable patterns of human malformation. quaternary ed. Philadelphia: Saunders, 1988:10–5.
4. Tolmie JL. Down syndrome and other autosomal trisomies. In: Rimoin DL, Connor JM, Pyeritz RE, eds. Emery and Rimoin'southward Principles and practice of medical genetics. 3rd ed. New York: Churchill Livingstone, 1996:925–71.
v. Saenz RB. Primary care of infants and young children with Down syndrome. Am Fam Md. 1999;59:381–90392395–six.
vi. American Academy of Pediatrics Committee on Sports Medicine and Fitness. Atlantoaxial instability in Down's syndrome: subject area review. Pediatrics. 1995;96:151–4.
7. Hook EB. Rates of chromosome abnormalities at different maternal ages. Obstet Gynecol. 1981;58:282–5.
8. Cuckle HS, Wald NJ, Thompson SG. Estimating a woman'southward risk of having a pregnancy associated with Downwards's syndrome using her age and serum alpha-fetoprotein level. Br J Obstet Gynaecol. 1987;94:387–402.
9. Merkatz IR, Nitowsky HM, Macri JN, Johnson WE. An association between low maternal serum alpha-fetoprotein and fetal chromosome abnormalities. Am J Obstet Gynecol. 1984;148:886–94.
ten. Kuller JA, Laifer SA. Contemporary approaches to prenatal diagnosis. Am Fam Doctor. 1995;52:2277–83.
11. Wald NJ, Cuckle HS, Densem JW, Nanchahal K, Royston P, Chard T, et al. Maternal serum screening for Downwards's syndrome in early pregnancy. BMJ. 1988;297:883–vii [Published erratum appears in BMJ 1988;297:1029]
12. Saller DN, Canick JA. Maternal serum screening for Down syndrome: clinical aspects. Clin Obstet Gynecol. 1996;39:783–92.
thirteen. Palomaki GE, Knight GJ, McCarthy JE, Haddow JE, Donhowe JM. Maternal serum screening for Downwardly syndrome in the Us: a 1995 survey. Am J Obstet Gynecol. 1997;176:1046–51.
14. Haddow JE, Palomaki GE, Knight GJ, Williams J, Pulkkinen A, Canick JA, et al. Prenatal screening for Down'southward syndrome with utilise of maternal serum markers. North Engl J Med. 1992;327:588–93.
fifteen. Haddow JE, Palomaki GE, Knight GJ, Cunningham GC, Lustig LS, Boyd PA. Reducing the need for amniocentesis in women 35 years of age or older with serum markers for screening. N Engl J Med. 1994;330:1114–eight.
xvi. American College of Medical Genetics Clinical Exercise Commission. ACMG position statement on multiple mark screening in women 35 and older. American College of Medical Genetics Higher Newsletter, January 1994;2.
17. American College of Medical Genetics Clinical Practice Committee. Argument on multiple mark screening in pregnant women. American College of Medical Genetics Higher Newsletter, January 1996;6.
18. American College of Obstetricians and Gynecologists. Maternal serum screening. ACOG Educational Bulletin, 1996; no. 228.
19. Benn PA, Borgida A, Horne D, Briganti Due south, Collins R, Rodis J. Downward syndrome and neural tube defect screening: the value of using gestational historic period by ultrasonography. Am J Obstet Gynecol. 1997;176:1056–61.
20. Benacerraf BR. Ultrasound of fetal syndromes. New York: Churchill Livingstone, 1998:328–38.
21. Vintzileos AM, Campbell WA, Rodis JF, Guzman ER, Smulian JC, Knuppel RA. The apply of second-trimester genetic sonogram in guiding clinical management of patients at increased risk for fetal trisomy 21. Obstet Gynecol. 1996;87:948–52.
22. Gross SJ, Bombard AT. Screening for the aneuploid fetus. Obstet Gynecol Clin Due north Am. 1998;25:573–95.
23. Chitty LS. Antenatal screening for aneuploidy. Curr Opin Obstet Gynecol. 1998;10:91–6.
24. U.South. Preventive Services Job Force. Guide to clinical preventive services: report of the U.S. Preventive Services Task Forcefulness. 2nd ed. Baltimore: Williams & Wilkins, 1996:449–65.
25. Jalal SM, Police ME, Carlson RO, Dewald GW. Prenatal detection of aneuploidy by directly labeled multicolored probes and interphase fluorescence in situ hybridization. Mayo Clin Proc. 1998;73:132–7.
26. Abramsky L. Counseling prior to prenatal testing. In: Abramsky L, Chapple J, eds. Prenatal diagnosis: the human side. New York: Chapman & Hall, 1994:seventy–85.
27. Dark-green JM. Women's experiences of prenatal screening and diagnosis. In: Abramsky L, Chapple J, eds. Prenatal diagnosis: the human side. New York: Chapman & Hall, 1994:37–53.
28. Reynolds TM, Goose egg AB, Dunstan FD, Dawson AJ. Age-specific detection and false-positive rates: an aid to counseling in Down's syndrome chance screening. Obstet Gynecol. 1993;81:447–50.
29. Stein MT, Scioscia A, Jones KL, Cohen WI, Glass CK, Drinking glass RF. Responding to parental concerns after a prenatal diagnosis of trisomy 21. J Dev Behav Pediatr. 1997;18:42–half dozen.
Copyright © 2000 by the American University of Family Physicians.
This content is endemic by the AAFP. A person viewing it online may make i printout of the material and may use that printout merely for his or her personal, non-commercial reference. This material may not otherwise exist downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or subsequently invented, except as authorized in writing past the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.
MOST RECENT ISSUE
Feb 2022
Access the latest consequence of American Family Physician
Read the Issue
Email Alerts
Don't miss a unmarried issue. Sign up for the free AFP e-mail tabular array of contents.
Sign Upwards Now
Source: https://www.aafp.org/afp/2000/0815/p825.html
0 Response to "What Is the Risk of Having a Down Syndrome Baby After 35"
Post a Comment