OBSTETRICS

OBSTETRICS

Nuchal Translucency Thresholds in Prenatal

Screening for Down Syndrome and Trisomy 18
Pierre Miron, MD,1,2 Yvan P. Côté, PhD,3 Jean Lambert, PhD4
1
Department of Obstetrics and Gynaecology, Hôpital Maisonneuve-Rosemont, University of Montreal, Montreal QC
2
Prenagen Inc., Laval QC
3
Warnex Medical Laboratories, Laval QC
4
Department of Social and Preventive Medicine, Faculty of Medicine, University of Montreal, Montreal QC

Abstract négatifs (faible risque) ont été signalés par un test de dépistage
prénatal du premier trimestre combinant la PAPP-A, la b-hCG
Objective: To determine if nuchal translucency (NT) can be used as
libre et la CN.
a first trimester triage marker in prenatal screening for Down
syndrome and trisomy 18. Résultats : Le dépistage prénatal combiné était toujours positif en ce
qui concerne le syndrome de Down lorsque l’épaisseur de la CN
Methods: Data from first trimester prenatal screening in 77 443
dépassait 4,0 mm. Au fur et à mesure du vieillissement chez les
women were stratified by maternal and gestational ages. They
femmes, ce seuil supérieur de la CN a évolué en fonction de l’âge
were then analyzed to identify NT thresholds above or below
gestationnel. Chez les femmes âgées de 35 à 37 ans, le
which only positive (high-risk) or negative (low-risk) results were
dépistage prénatal combiné était toujours positif lorsque la CN
reported by a first trimester prenatal screening test combining e e
dépassait 2,8 mm, 3,0 mm et 3,4 mm à la 11 , à la 12 et à la
PAPP-A, free b-hCG and NT. e
13 semaine de gestation, respectivement. Chez les femmes de
Results: Combined prenatal screening was always positive for Down plus de 42 ans, le seuil supérieur de la CN était de 1,8 mm, de
e e e
syndrome when NT thickness exceeded 4.0 mm. As women aged, 2,4 mm et de 2,7 mm à la 11 , à la 12 et à la 13 semaine de
this upper NT threshold value changed according to gestational gestation, respectivement. Chez les femmes de moins de 35 ans,
age. In women aged 35 to 37 years, combined prenatal screening nous avons identifié des seuils inférieurs en deçà desquels le
was always positive when NT exceeded 2.8 mm, 3.0 mm, and dépistage prénatal combiné était toujours négatif.
3.4 mm at 11, 12, and 13 weeks of gestation, respectively. In
Conclusion : Dans le cadre du dépistage prénatal du syndrome de
women over 42 years of age, the upper threshold value for NT
Down et de la trisomie 18, il est possible d’identifier des seuils de
was 1.8 mm, 2.4 mm, and 2.7 mm at 11, 12, and 13 weeks of
CN au-dessus desquels le dépistage biochimique n’offre aucun
gestation, respectively. In women less than 35 years of age, we
avantage additionnel. En ce qui concerne les grossesses dans le
identified lower threshold values below which combined prenatal
cadre desquelles la CN se situe au-delà des seuils supérieurs
screening for Down syndrome was always negative.
établis, un dépistage prénatal effractif peut être offert sans délai.
Conclusion: In prenatal screening for Down syndrome and trisomy
J Obstet Gynaecol Can 2009;31(3):227–235
18, it is possible to identify NT threshold values above which
biochemical screening provides no additional benefit. In
pregnancies in which NT is above the established upper cut-offs, INTRODUCTION
invasive prenatal screening can be offered without delay.
ltrasound measurement of fetal nuchal translucency
Résumé U was proposed for the first time in 1992 to detect fetal
Objectif : Déterminer si la clarté nucale (CN) peut être utilisée à titre chromosomal anomalies in the first trimester of pregnancy.1
de marqueur de triage du premier trimestre dans le cadre du Since then, use of NT has gained in popularity, and it is now
dépistage prénatal du syndrome de Down et de la trisomie 18.
the most widely used ultrasound marker for aneuploidy.
Méthodes : Les données issues du dépistage prénatal du premier
trimestre mené chez 77 443 femmes ont été stratifiées en fonction Because of its highly associated false-positive rate, its use as
des âges maternel et gestationnel. Elles ont par la suite été a stand-alone screening test to identify aneuploidy in single
analysées en vue d’identifier les seuils de CN au-dessus ou en
deçà desquels seuls des résultats positifs (risque élevé) ou pregnancies was considered by many to be inappropriate.2
In fact, only a few studies have suggested that first trimester
Key Words: Nuchal translucency measurement, maternal blood screening provides no additional benefit
pregnancy-associated plasma protein-A, chorionic gonadotropin, when the NT measurement is above 4.0 mm.3,4
beta subunit, human, Down syndrome, trisomy
To improve the accuracy of prenatal screening in the first
Competing Interests: see Acknowledgements.
trimester, combining NT with biochemical markers such as
Received on May 7, 2008
pregnancy-associated plasma protein-A and free b-subunit
Accepted on August 6, 2008
of human chorionic gonadotropin was successfully

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proposed in the 1990s.5–7 This approach has been prospec- Table 1. Demographic and clinical characteristics of
tively validated in more than 200 000 screens, with a the studied population (n = 77 443)
detection rate of 88% for Down syndrome at a fixed
false-positive rate of 5%.8 In order to study more precisely A. Quantitative variables N Mean ± SD
the NT levels that, when combined with serum levels of Women’s age (years) 77 443 31.2 ± 3.9
PAPP-A and free b-hCG, would mark the threshold Gestational age at time of 77 443 12.4 ± 0.6
between positive or negative screening results, we analyzed sonography (weeks)
fetal NT measurements in a large cohort of patients in the Weight (kg) 77 424 65.1 ± 12.6
context of maternal and gestational ages. The main objec- Crown–rump length (mm) 77 443 63.8 ± 8.3
tive of this analysis was to determine if NT could, in some Nuchal thickness (mm) 77 443 1.60 ± 0.48
instances, be used alone as a first trimester triage marker in Nasal bone (mm) 16 918 1.88 ± 0.42
screening for Down syndrome and trisomy 18. B. Qualitative variables %

MATERIALS AND METHODS Ethnic origin 77 443

Caucasian 74 561 96.3
Data were extracted from a historical cohort of 77 443
Asian 1 453 1.9
women in Quebec who underwent prenatal screening for
Afro-Caribbean 633 0.8
Down syndrome and trisomy 18 in their first trimester of
Native 60 0.1
pregnancy (i.e., between the 11th and 14th weeks) between
Other 736 0.9
1999 and 2007. These women had given consent for their
Smoking 4995 6.4
results to be used anonymously for research purposes.
Since pregnancy outcomes could not be obtained from all Active vaginal bleeding 7044 9.1

women, this information was not included in the analysis.

Fetal crown–rump length and nuchal translucency mea-
surements were performed by ultrasonographers who were Laboratories (New York, NY). Individual risk was deter-
instructed to follow the Fetal Medicine Foundation guide- mined by multiplying the likelihood ratio by the woman’s
line.9 Fetal nasal bone assessments (n = 16 918) were risk of having a fetus with Down syndrome and trisomy 18
initiated in 2003 but were not included in the calculation of before screening, based on maternal age, gestational age and
risks. prior history of trisomy. Women with a risk greater than
Overall risk assessments for Down syndrome and trisomy that of a 35-year-old at the same gestational age were con-
18 were produced by combining NT with maternal blood sidered to be at an increased risk of having a fetus with
levels of PAPP-A and free b-hCG (referred to as combined Down syndrome.11 Cut-off levels used for positive results
first trimester prenatal screening). In all subjects, blood were set at 1:210 to 1:266 for Down syndrome (depending
samples were collected and transported to the laboratory on gestational age) and at 1:150 for trisomy 18.
using dried blood filter paper. Maternal blood levels of Only women with no missing data related to maternal age,
PAPP-A and free b-hCG were determined using in-house gestational age (as defined by crown–rump length) and
enzyme-linked immunosorbant assays, as described previ- combined prenatal screening results were included (N = 77 443).
ously.10 The software program used for risk assessment of
Gestational age was categorized as follows:
Down syndrome and trisomy 18 was provided by NTD
CRL 45 mm to < 55 mm = 11+1 to 11+6 weeks for GA
CRL 55 mm to < 69 mm = 12 to 12+6 weeks for GA
CRL from 69 mm to 84 mm = 13 to 13+6 weeks for GA
ABBREVIATIONS Overall positive (high-risk) and negative (low-risk) prenatal
screening results for Down syndrome and trisomy 18 were
AFP alpha fetoprotein
stratified by categorized maternal and gestational ages. For
CRL crown–rump length
each combination, minimum and maximum NT values
CVS chorionic villus sampling
were compared between positive and negative overall
GA gestational age
results to find NT levels above or below which only positive
hCG human chorionic gonadotropin
or negative values were observed in a given combination.
NT nuchal translucency
Finally, NT and maternal age cut-offs were chosen to iden-
PAPP-A pregnancy-associated plasma protein-A tify women for whom CVS or amniocentesis would have

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 Nuchal Translucency Thresholds in Prenatal Screening for Down Syndrome and Trisomy 18

Table 2. Nuchal translucency distribution stratified by categorized maternal age, categorized crown–rump
length, and overall results for Down syndrome

Nuchal translucency (mm)

Maternal age (years) CRL (mm) Screen results n Mean ± SD Minimum Maximum

< 23 45–54 – 134 1.32 ± 0.37 0.7 2.8

+ 2 1.95 ± 1.06 1.2 2.7
55–68 – 419 1.57 ± 0.37 0.4 3.4
+ 11 3.26 ± 1.23 1.4 6.1
69–84 – 219 1.74 ± 0.44 0.8 3.4
+ 2 3.10 ± 1.27 2.2 4.0
23–26 45–54 – 1268 1.28 ± 0.35 0.5 3.3
+ 26 3.54 ± 2.06 1.0 8.8
55–68 – 4487 1.54 ± 0.37 0.3 3.8
+ 60 3.11 ± 2.05 1.0 11.4
69–84 – 2138 1.74 ± 0.40 0.6 4.0
+ 32 2.92 ± 1.47 1.0 9.0
27–34 45–54 – 7500 1.28 ± 0.33 0.4 3.2
+ 202 2.59 ± 1.51 0.6 10.0
55–68 – 29 477 1.55 ± 0.36 0.2 3.8
+ 624 2.61 ± 1.48 0.8 10.0
69–84 – 15039 1.75 ± 0.39 0.5 3.9
+ 399 2.58 ± 1.02 0.9 10.0
35–37 45–54 – 1363 1.29 ± 0.33 0.6 2.8
+ 80 2.11 ± 1.52 0.6 9.1
55–68 – 5759 1.57 ± 0.36 0.5 3.0
+ 345 2.11 ± 1.04 0.9 10.0
69–84 – 3126 1.77 ± 0.38 0.6 3.4
+ 248 2.25 ± 0.71 0.7 5.1
38–41 45–54 – 454 1.28 ± 0.29 0.4 2.3
+ 65 2.04 ± 1,49 0.7 8.6
55–68 – 1983 1.56 ± 0.35 0.6 2.8
+ 316 2.06 ± 1.16 0.6 14.0
69–84 – 1014 1.76 ± 0.37 0.7 3.0
+ 219 2.21 ± 1.02 0.9 10.0
³ 42 45–54 – 28 1.35 ± 0.27 0.8 1.8
+ 19 1.56 ± 0.42 0.8 2.4
55–68 – 136 1.55 ± 0.32 0.8 2.4
+ 100 1.89 ± 0.79 0.8 8.0
69–84 – 99 1.80 ± 0.32 1.0 2.7
+ 50 2.07 ± 0.79 0.8 5.7

been offered with or without the biochemical analysis, or significantly older than the Quebec population of pregnant
for whom no further testing was required because of women at the time of screening (29.1 years; P <
perceived low risk. 0.001).12 The average gestational age on ultrasound was
12.4 ± 0.6 weeks. Most of the women included in this study
RESULTS were of Caucasian origin (96%), followed by Asian (1.9%),
and Afro-Caribbean (0.8%) (Table 1).
A total of 77 443 prenatal screenings performed in the first
trimester of pregnancy (i.e., with fetal CRL from 45 to 84 mm) For the whole cohort, 3.6% of women screened positive for
were analyzed. Mean maternal age was 31.2 ± 3.9 years, the combined test (n = 2800). As shown in Figure 1, this

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Table 3. Cut-off levels of nuchal translucency in relation to gestational and maternal age above which
there are N combined first trimester prenatal screenings always positive for Down syndrome

n/Positive screen NT
Gestational age CRL, (mm) n/total pop. (%) population (%) Cut-off (mm)

A. All women
11+1 to 11+6 weeks 45–54 77/11 141 (0.7) 77/394 (20) > 3.3
12 to 12+6 weeks 55–68 115/43 717 (0.3) 115/1456 (8) > 3.8
13 to 13+6 weeks 69–84 43/22 585 (0.2) 43/950 (5) > 4.0
B. Women < 35 years old
11+1 to 11+6 weeks 45–54 61/9132 (0.7) 61/230 (27) > 3.3
12 to 12+6 weeks 55–68 86/35 078 (0.2) 86/695 (12) > 3.8
13 to 13+6 weeks 69–84 29/17 829 (0.2) 29/433 (7) > 4.0
C. Women 35–37 years old
11+1 to 11+6 weeks 45–54 14/1443 (1) 14/80 (18) > 2.8
12 to 12+6 weeks 55–68 31/6104 (0.5) 31/345 (9) > 3.0
13 to 13+6 weeks 69–84 16/3374 (0.5) 16/248 (6) > 3.4
C. Women 38–41 years old
11+1 to 11+6 weeks 45–54 11/519 (2) 11/65 (15) > 2.3
12 to 12+6 weeks 55–68 34/2299 (1) 34/316 (11) > 2.8
13 to 13+6 weeks 69–84 17/1233 (1) 17/219 (8) > 3.0
Women ³ 42 years old
11+1 to 11+6 weeks 45–54 5/47 (11) 5/19 (26) > 1.8
12 to 12+6 weeks 55–68 12/236 (5) 12/100 (12) > 2.4
13 to 13+6 weeks 69–84 7/149 (5) 7/50 (14) > 2.7

percentage increased progressively with maternal age. No increased number of women (n = 323) had an NT above
women under 19 years of age had a positive screening which combined prenatal screening was always positive,
(n = 21), while almost all women over 43 years of age representing 11.5% of the total screen positive population.
screened positive (86/90 or 96%). For each category of maternal and gestational ages, the
same upper cut-off values of NT set for Down syndrome
The distribution of NT (mean ± SD, minimum and maxi- could also be used for trisomy 18.
mum values), stratified by categorized maternal age, catego-
rized CRL, and overall screen results for Down syndrome, The NT cut-off levels below which combined first trimester
with upper and lower cut-off levels, is summarized in prenatal screening for Down syndrome was always negative
Tables 2, 3, and 4. varied from less than 0.6 mm to 2.2 mm, depending on
maternal and gestational ages (Table 4). For women less
Combined prenatal screening was always positive when NT than 23 years of age, lower NT cut-off levels were found to
was found to be above 4.0 mm (n = 197), representing 7.0% be 1.2 mm, 1.4 mm, and 2.2 mm at 11, 12, and 13 weeks of
of the total positive screen population. Nevertheless, this gestation, respectively. The NT lower threshold values also
NT cut-off level, above which combined prenatal screening progressively decreased with maternal aging, reaching
was always positive, could vary from 1.8 mm to 4.0 mm or 1.0 mm in women aged 23 to 26, and 0.6 mm, 0.8 mm, and
more, depending on categorized maternal and gestational 0.9 mm in women aged 27 to 34 at 11, 12, and 13 weeks of
ages. For women less than 35 years of age, upper NT gestation, respectively. Women with NT values below their
cut-off levels were 3.3 mm, 3.8 mm, and 4.0 mm at 11, 12, specific lower cut-off levels represented only a very small
and 13 weeks of gestation, respectively. NT upper threshold proportion of the total screen population (0.08%). No use-
values progressively decreased with maternal aging, reach- ful lower NT cut-off levels for combined negative screen
ing 2.8 mm, 3.0 mm, and 3.4 mm in women aged 35 to 37, could be found in women older than 34 years of age.
and 1.8 mm, 2.4 mm, and 2.7 mm in women over 42 years
of age at 11, 12, and 13 weeks of gestation, respectively. The same cut-off levels of NT thickness below which com-
With stratification by maternal and gestational ages, an bined first trimester prenatal screening for Down syndrome

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 Nuchal Translucency Thresholds in Prenatal Screening for Down Syndrome and Trisomy 18

Table 4. Cut-off levels of NT thickness in relation to gestational and maternal ages below which
there are N combined first trimester prenatal screenings always negative for Down syndrome

n/Negative screen NT.

Gestational age CRL (mm) n/Total pop. (%) population (%) Cut-off (mm)

A. All women
11+1 to 11+6 weeks 45–54 22/11 141 (0.2) 22/10 747 (0.2) < 0.6
12 to 12+6 weeks 55–68 20/43 717 (0.05) 20/42 261 (0.05) < 0.6
13 to 13+6 weeks 69–84 9/22 585 (0.04) 9/21 635 (0.04) < 0.7
B. Women < 23 years old
11+1 to 11+6 weeks 45–54 45/136 (33) 45/134 (34) < 1.2
12 to 12+6 weeks 55–68 109/430 (25) 109/419 (26) < 1.4
13 to 13+6 weeks 69–84 185/221 (84) 185/219 (84) < 2.2
C. Women 23–26 years old
11+1 to 11+6 weeks 45–54 168/1294 (13) 168/1268 (13) < 1.0
12 to 12+6 weeks* 55–68 136/4547 (3) 136/4487 (3) < 1.0
13 to 13+6 weeks 69–84 15/2170 (0.7) 15/2138 (0.7) < 1.0
D. Women 27–34 years old
11+1 to 11+6 weeks 45–54 18/7702 (0.2) 18/7500 (0.2) < 0.6
12 to 12+6 weeks 55–68 126/30 101 (0.4) 126/29 477 (0.4) < 0.8
13 to 13+6 weeks 69–84 59/15 438 (0.4) 59/15 039 (0.4) < 0.9

*One positive outlier screen test for T18 at 0.8 mm.

was always negative could also be applied for trisomy 18 confirmed by (a) women’s preference for first trimester
results, with the exception of one woman aged 23 with a screening of pregnancy,18,19 (b) ethical principles of
fetal CRL of 59 mm. In this individual’s case, PAPP-A and informed consent and respect for patient autonomy, benefi-
free-bhCG multiples of the median were found to be very cence, and justice,20 and (c) the recent joint statement of the
low at 0.07 and 0.10, respectively. An increased risk for National Institute of Child Health and Human Develop-
trisomy 18 or 13 was initially suggested. Several major struc- ment, the Society for Maternal-Fetal Medicine, and the
tural abnormalities were found on ultrasound in the second American College of Obstetricians and Gynecologists.21
trimester (club hands, cardiac defect, cerebral
ventriculomegaly, and asymmetrical intrauterine growth
restriction) and a triploidy (69,XXX) was finally diagnosed In 1992, the first-trimester NT was reported to be increased
by fetal karyotyping. in 35% of aneuploid fetuses, compared with only 1% of
euploid fetuses.1 Since then, several large studies have
DISCUSSION confirmed that NT screening, which takes into account
Several, often complex, strategies have been proposed to maternal and gestational ages, has a detection rate for Down
screen for Down syndrome and other common syndrome ranging from 69% to 75% with a false positive
aneuploidies.13,14 Over the last decade, the popularity of rate of 5% to 8.1%.22–24 The Society of Obstetricians and
second trimester prenatal screening (AFP, estriol, AFP ± Gynaecologists of Canada and the Canadian College of
inhibin A) has declined and first trimester screening using a Medical Geneticists jointly stated in 2007 that any prenatal
combination of maternal blood biochemical markers (free screen for Down syndrome should, as a minimum standard,
b-hCG and PAPP-A) with fetal nuchal translucency measure- have a detection rate of at least 75%, with a false positive
ment has increased. Although more recent approaches rate of no more than 5%. Their recommendation was that
combining first and second trimester markers have been NT alone without biochemical markers should never be
proposed, such as integrated, sequential, and contingent offered, except in the context of multiple pregnancy.2 We
screenings, there is a clear trend towards early disclosure of believe this is not entirely true and that there are some
results to a maximum number of patients.15–17 This trend is exceptions to this guideline.

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Figure 1. Combined prenatal screening positive according to maternal age

With our analysis of the findings in 77 443 women in the chromosomal abnormalities, specifically in women £ 35
first trimester, we confirmed that with a NT value greater years old at 12 or 13 weeks of pregnancy, a combination of
than 4.0 mm there is no added value in delaying offering our strategy with that of the Fetal Medicine Foundation
immediate invasive diagnostic testing. On the basis of cate- could also be used (i.e., to offer fetal karyotyping by CVS in
gorized gestational and maternal ages, our study also dem- this specific group when the NT value is above 3.5 mm).25
onstrated that better and lower NT cut-offs values can be
used by clinicians at the time of NT sonography to disclose
positive screening to their patients immediately. Prenatal screening is based on respect for a patient’s auton-
omy. It could therefore be argued that communicating a
The FASTER Research Consortium has recommended result as being “at risk” or “not at risk” is inappropriate and
that, in the presence of a NT value ³ 3.0 mm, immediate that communicating a result as a probability is more suit-
invasive testing should be offered to all patients without able. In order to fully respect an informed consent process,
obtaining serum markers.4 With this strategy, 31.1% of the we believe that, in the presence of a NT value above the
women in our study with a NT value ³ 3.0 mm would have suggested thresholds, all of the following options are
been needlessly offered invasive testing because their final ethically acceptable and should be thoroughly discussed
result in combined screening was actually negative. As with the patient: (1) no further screening or diagnostic test-
demonstrated in Figure 2, we believe that upper cut-off NT ing; (2) immediate disclosure of a probability, using NT
limits for screen positivity should be adapted instead to with maternal and gestational ages; (3) completion of the
maternal and gestational ages at the time of screening. In screening process with biochemical markers; (4) proceeding
women older than 37 years of age, this upper cut-off limit of directly with diagnostic testing such as a transabdominal
3.0 mm can be further decreased, while in younger women CVS or an amniocentesis after 15 weeks. Additional assess-
it most often needs to be raised. With this new strategy, all ment of fetal nasal bone, frontomaxillary facial angle and
women with NT values greater than the suggested upper other early soft markers of aneuploidy could also be used
cut-off levels would screen positive with or without bio- eventually to refine the probability of aneuploidy at the time
chemical markers. To decrease further the risk of missing of first trimester ultrasound.26–28

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 Nuchal Translucency Thresholds in Prenatal Screening for Down Syndrome and Trisomy 18

Figure 2. Proposed NT threshold levels above which prenatal diagnosis should be offered,
regardless of biochemical results (polynomial curves), compared to FMF strategy in grey
area25

The NT threshold level of 3.0 mm for the (35–37 y.o.) x (55–68 mm CRL) combination given in Table 3 was set to 3.2 mm in
Figure 2 to better agree with other functions which seem logarithmic or quadratic. This modification introduces a more conservative
threshold value.

NT threshold values below which no further screening is free b-hCG and PAPP-A within 30 minutes of obtaining
required, because of negative results regardless of biochem- the blood sample with concomitant ultrasound assessment
ical markers, are presented in Figure 3. In this case, how- of CRL and NT, allowing rapid production of a combined
ever, prediction by NT of a negative screen result pertains risk report.33 However, to be successful and financially via-
to a very limited proportion of women and to very thin NT. ble, the one-stop clinics for risk assessment usually require a
We therefore recommend that if such cut-off levels are ever large volume of patients and are therefore limited to a very
used, they should be restricted mainly to women younger few busy ultrasound clinics. This approach does not pre-
than 27 years of age. With this strategy, one case of triploidy clude use of NT alone in selected cases, as proposed by our
in 74 643 negative screenings would have been missed. results. Taking blood at 8 to 9 weeks of gestation, prior to
However, a high proportion of fetuses with triploidy have the NT scan, has also been suggested, but this remains a
major structural abnormalities often detectable by second limited option, particularly in Canada where early access to a
trimester ultrasound, and almost all of these affected fetuses first obstetrical consultation has become a matter of concern.34,35
will die in utero or within the first year of life.29–31
Until recently, the recommended maternal age for directly
Official reports of first trimester risk assessment, combin- offering amniocentesis or CVS varied from 35 years of age
ing biochemical and ultrasound markers, are usually pro- to 38 years of age and over in most developed countries.36,37
duced by routine diagnostic laboratories within 7 to 10 days In the context of enhanced prenatal non-invasive screening,
after the medical visit. In an attempt to accelerate early dis- this approach is now considered by many to be obsolete.
closure, another concept of point of care service has been The American College of Obstetricians and Gynecologists
suggested, by which combined first trimester results can be recommended in its recent Practice Bulletin that all women
provided to the patient within one hour.32 With the advent regardless of age should have the option of invasive testing.
of rapid immunoassays, this service provided by one-stop In Canada, the low risk of fetal loss following mid-trimester
clinics for risk assessment involves serum measurements of amniocentesis recently reported by a secondary analysis of

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Figure 3. Proposed NT threshold levels below which no further screening would be

required (polynomial curves)

data from the FASTER trial (1/1600) was questioned and CONCLUSION
quoted as misleading, with an estimate of procedural fetal
In this study we have defined NT threshold levels above
loss of 0.6% to 1.0% (1/175–1/100) seen as more realis- and below which women will always have high- or low-risk
tic.38,39 Regardless, in Canada it has now been recom- results for Down syndrome screening regardless of bio-
mended to raise the maternal age for offering CVS or chemical findings in maternal blood. Prenatal screening for
amniocentesis directly from 35 years of age to 40 years of aneuploidy can be offered as a first step to all pregnant
age or over at the time of delivery.2,39 However, in our women up to the age of 43, rather than CVS or amnio-
cohort, women aged 43 years had a probability of at least centesis. Newer approaches to facilitate rapid results to the
69% of having a negative prenatal screening result. In youn- patient in the first trimester of pregnancy need to be
ger women, this proportion of negative screening results explored. Specific cut-off NT values can sometimes be used
increased rapidly. Given that the vast majority of younger alone in a selected population without increasing false
women in our study had a negative combined first trimester positive rates.
prenatal screening, and if our results can be confirmed by
studies with pregnancy outcomes, it will be reasonable to ACKNOWLEDGEMENTS
consider raising the maternal age for directly offering Dr Miron is the owner of Prenagen Inc. and is a consultant
invasive testing to 44 years of age or over (Figure 1). through this corporation for Warnex Inc.

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