First trimester prenatal diagnosis: Amniocentesis

First Trimester Prenatal Diagnosis: Amniocentesis Marie-France Delisle and R. Douglas Wilson

Twenty years after midtrimester genetic amniocentesis was first used, first trimester invasive prenatal p r o c e d u r e s were introduced. Chorionic villous sampling presents some disadvantages that entitled many centers to look into an alternative for first trimester diagnosis. Early amniocentesis (EA) can be p e r f o r m e d effectively, as shown over the years in many observational studies and partially randomized and r a n d o m i z e d trials. Recently, a multicenter r a n d o m i z e d trial (Canadian Early and Midtrimester Amniocentesis Trial) r e p o r t e d a higher total pregnancy loss, a significant increased incidence o f musculoskeletal foot deformities, a significant increased culture failure rate, and an increased postamniocentesis rate o f leakage in the EA group c o m p a r e d with midtrimester amniocentesis. T h e s e results concerning EA procedures f r o m 11w +~ to 12w +6 should be included in any pre-EA counseling. However, further trials have started to evaluate EA p r o c e d u r e s between 13w +~ to 14w +6. Copyright 9 1999 by W.B. Saunders

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T prenatal diagnosis dates back to the mid1950s. Riis and Fuchs I showed that amniocytes could be used for fetal sex determination. In 1966, Steele and Berg 2 were able to culture and karyotype amniotic fluid cells, which led to the first prenatal r e p o r t o f a chromosomal abnormality by Jacobson and Barter 3 in 1967. Since then, genetic amniocentesis p e r f o r m e d in the 15th to 16th week has b e c o m e the gold standard for routine invasive prenatal diagnosis. With the addition of ultrasonographic guidance and the i m p r o v e m e n t of the laboratory techniques, o t h e r options have b e e n progressively introduced: chorionic villous sampling (CVS), cordocentesis, fetal tissue biopsy, fetoscopy, and embryoscopy. 4 T h e introduction o f earlier prenatal diagnosis by CVS in the mid-1980s examined the advantages and risks o f first trimester testing. It offers patients, with abnormal results, the option for an earlier and safer termination o f pregnancy with possible r e d u c e d social and psychological trauma. 5,6 CVS provides an advantage when prenatal molecular testing is r e q u i r e d / T h i s technique, however, has several disadvantages, which From the Division of Maternal-Fetal Medicine, Departments of Obstetrics, Gynecology and Medical Genetics, University of British Columbia, BC Women's Hospital, Vancouver, British Columbia. Address reprint requests to R. Douglas Wilson, MD, MSC, FRCSC, BC Women's Hospital, 4500 Oak St, Vancouver, British Columbia, V6H 3N1 Canada. Copyright 9 1999 by W.B. Saunders Company 0146-0005/99/2305-0007510. 00/0

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include the absence of alpha-fetoprotein (AFP) determination, the i n h e r e n t biological problem o f placental mosaicism, and the higher incidence o f maternal-cell contamination. 4,6,8 Debate continues about the risk of limb r e d u c t i o n / vascular disruption sequence and facial abnormalities associated with CVS. 4,7 T h i s risk appears to be related to gestational age (less than 9 weeks of gestation) and the experience of the operator. Because o f these concerns, plus the economic cost o f CVS and the lack of physician expertise, many centers have looked into an alternative for first trimester invasive prenatal testing. 9 Early amniocentesis (EA) has b e e n proposed as an option as this familiar technique may allow earlier diagnosis with the same safety and accuracy as the standard amniocentesis. 4,5 As Assel et al 1~ indicated, the advantages of early amniocentesis would include: (1) the use of a familiar technique that is widely available; (2) the diminution of inaccuracy by reduction of maternal-cell contamination and placental mosaicism, which complicate CVS; (3) the availability of cytogenetic information and amniotic fluid AFP measurement; and (4) the option o f an early secondtrimester pregnancy interruption by dilatation and evacuation if required. 1~ However, before EA can be o f f e r e d as an alternative to CVS, specific differences in diagnostic results, pregnancy outcome, and evaluation of fetal and neonatal effects must be considered, l~ These issues have b e e n reviewed in recent large series, partially randomized and randomized trials, so

Seminars in Perinatology, Vol 23, No 5 (October), 1999: pp 414-423

First Trimester Amniocentesis

EA can now be analyzed in-depth and with better critical appraisal.

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tion), the a m n i o n is now in direct contact with the chorion, obliterating the chorionic cavity. 4,13 T h e yolk sac has shrunk and disappeared.

Definition Early amniocentesis is defined as a first trimester p r o c e d u r e p e r f o r m e d before 14 weeks of gestation (from 11 +0 to 13+6). 4,5 Some series have included procedures as early as 9 +0 weeks. Traditional amniocentesis is usually p e r f o r m e d after 15 +0 weeks of gestation; invasive procedures between 14 +0 and 14 +6 are usually considered early and have been included in some series (Table 1).

Embryology As implantation of the blastocyst progresses, a small cavity called the p r i m o r d i u m of the amniotic cavity appears in the inner cell mass at a r o u n d 7 to 8 days postfertilization. ~2 Amnioblasts separate from the epiblast and form a thin m e m b r a n e called the amnion, which encloses the amniotic cavity. T h e epiblast, 1 of the 2 layers of the embryonic disk, forms the floor of the amniotic cavity. T h e other layer o f the embryonic disk, the hypoblast, forms the r o o f o f the exocoelomic cavity and is continuous with the thin exocoelomic membrane, a2 This m e m b r a n e and its cavity b e c o m e the primary yolk sac. T h e embryonic disk lies then between the amniotic cavity and primary yolk sac. T h e extraembryonic coelom is f o r m e d by the fusion of isolated spaces within the extraembryonic mesoderm.~2 As the extraembryonic coelom forms, the primary yolk sac decreases in size and a smaller secondary yolk sac forms. T h e extraembryonic mesoderm and the 2 layers o f trophoblast constitute the chorion. T h e chorion forms the wall o f the chorionic sac (gestational sac), within which the embryo and its amniotic and yolk sacs are suspended by the connecting stalk (future umbilical cord). ~3 By development day 13 (postfertilization), the future amniotic cavity is approximately one third the size o f the secondary yolk sac. 13 T h e amniotic cavity has s u r r o u n d e d the embryo as well as the connecting stalk by day 28 (posffertilization). ~3 At 10 weeks of gestation, the embryo is still c o n n e c t e d to the yolk sac by the vitelline duct. T h e yolk sac is located between the two gestational sac membranes (amnion, chorion). By the e n d o f the 12th postfertilization week (14th week of gesta-

Amuiotic Fluid Sampling and Results Technique T h e EA technique is similar to amniocentesis p e r f o r m e d at later gestational ages. A spinal needle (length 9 or 14 cm) is inserted through the maternal a b d o m e n wall and uterine wall into a pocket of amniotic fluid within the amniotic sac. Continuous ultrasonographic guidance is advised to visualize the needle tip and e n h a n c e success and safety. T h e amniotic fluid is aspirated usually into a 10 to 20 m L syringe or through a filtration system. 14 A 22-gauge needle is most often used (Table 1) and approximately 1 m L o f amniotic fluid per week o f gestation is aspirated. Recent laboratory techniques allow smaller volumes o f amniotic fluid to be aspirated, because higher postprocedural fetal loss rates have been associated with larger extracted volumes at earlier gestational ages. 15 T h e physiology and the anatomy o f the fetal membranes differ at 16 weeks of gestation compared with the late first trimester (11 +0 to 13 +6 weeks of gestation).9 T h e amniotic membranes have 5 layers of a m n i o n and 3 layers of chorion. 12 At gestational ages o f 14 to 15 weeks, the a m n i o n has not completely e x p a n d e d to bec o m e adjacent and occluding the extraembryonic coelom. 16 "Tenting" o f the amniotic membranes may occur in front of the spinal needle preventing access to the amniotic cavity and the amniotic fluid. 5 This p r o c e d u r e complication has been reported in up to 5% of the amniocentesisA 7 T h e approach, unique to this EA technique, may require the use o f a m o r e vigorous m o v e m e n t o f the needle through the a m n i o n membrane. ~ T h e sampling failure rate associated with EA r e p o r t e d has ranged between 0.2% and 2.7% (Table 1). T h e Canadian Early and Midtrimester Amniocentesis Trial (CEMAT),ls through a secondary analysis focusing o n p r o c e d u r a l / t e c h n i cal variables, showed that failed or unsuccessful procedures (not a t t e m p t e d or not completed) were significantly m o r e c o m m o n with the EA technique than the traditional mid-trimester amniocentesis (1.6 v 0.4; P < .01). 19 This technical difficulty did not directly correlate with an in-

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Table 1. Randomized, Partially Randomized, and Observational Studies on Early Amniocentesis Gestational Age (wk)

R a n d o m i z e d studies C E M A T is (1998) S u n d b e r g 14 (1997) J o h n s o n 66 (1996)

No.