Dr. Masami Yamamoto Clínica Universidad de los Andes€¦ · Ejemplo1: 10 millones de mujeres, 5% de >35 años Ejemplo 2: 10 millones de mujeres, 10% de >35 años Edad ≤35 >35

Dr. Masami Yamamoto Clínica Universidadde los Andes

Dr. Masami YamamotoMedicina FETAL

Clínica Universidad de los Andes

Screening de Aneuploidias


Control prenatal

PRENATAL DIAGNOSIS

Prenat Diagn 2011; 31: 3–6.Published online in Wiley Online Library

(wileyonlinelibrary.com) DOI: 10.1002/pd.2685

EDITORIAL

A model for a new pyramid of prenatal care basedon the 11 to 13 weeks’ assessment

Kypros H. Nicolaides1,2*

1Harris Birthright Research Centre of Fetal Medicine, King’sCollege Hospital, London, UK2Department of Fetal Medicine, University College Hospital, London, UK

One century ago it was recognized that with the methodsand material at our disposal we were not making allthe progress possible toward solving many problemsof prenatal diagnosis and treatment (Ballantyne, 1901,1921). In order to achieve these objectives it was urgedthat a new means of investigation should be undertakenwhich had not yet been tried, at least not yet attemptedon a large scale and in a systematic fashion. This ledto the introduction of prenatal care which constituted amajor advance in the care of pregnant women and playeda pivotal role in the substantial reduction in maternal andperinatal mortality achieved during the last century.

In 1929, the Ministry of Health in the UK issueda Memorandum on Antenatal Clinics recommendingthat women should first be seen at 16 weeks, then at24 and 28 weeks, fortnightly thereafter until 36 weeksand then weekly until delivery (Figure 1) (Ministry ofHealth Report, 1929). No explicit rationale was offeredfor either the timing or clinical content of visits, yetthese guidelines established the pattern of prenatal careto be followed throughout the world until now. Thehigh concentration of visits in the late third trimesterimplies that most complications occur toward the endof pregnancy and most adverse outcomes cannot bepredicted from the first trimester. However, is this reallythe case? Scientific advances in the last 20 years haveraised the hope that many pregnancy complications arepotentially detectable from at least as early as the 12thweek of gestation. It has become apparent that mostmajor aneuploidies can be identified at 11 to 13 weeks’gestation by a combination of maternal characteristics,ultrasound findings and biochemical testing of maternalblood. It is also becoming increasingly apparent thatan integrated first hospital visit at 11 to 13 weekscombining data from maternal characteristics and historywith findings of biophysical and biochemical tests candefine the patient-specific risk for a wide spectrumof pregnancy complications, including miscarriage andfetal death, preterm delivery, preeclampsia, gestationaldiabetes, fetal growth restriction and macrosomia.

*Correspondence to: Prof. Kypros H. Nicolaides, Harris BirthrightResearch Centre for Fetal Medicine, King’s College Hospital,Denmark Hill, London SE5 9RS, UK.E-mail: [email protected]

Figure 1—Pyramid of prenatal care: past (left) and future (right)

FETAL ANEUPLOIDIES

We have learnt that about 90% of fetuses with major ane-uploidies can be identified by a combination of maternalage, fetal nuchal translucency (NT) thickness and mater-nal serum-free ß-hCG and PAPP-A at 11 to 13 weeks(Nicolaides, 2011). Improvement in the performance offirst-trimester screening can be achieved by first carry-ing out the biochemical test at 9 to 10 weeks and theultrasound scan at 12 weeks and second, inclusion inthe ultrasound examination assessment of the nasal boneand flow in the ductus venosus, hepatic artery and acrossthe tricuspid valve. A similar performance of screeningcan be achieved by examining the additional ultrasoundmarkers in all cases and by a contingent policy in whichfirst-stage combined screening classifies the patients ashigh-, intermediate- and low-risk and the new markersare examined only in the intermediate-risk group whichis then reclassified as low- or high-risk.

FETAL STRUCTURAL ABNORMALITIES

We have learnt that at the 11 to 13 weeks’ scan itis possible to diagnose or suspect the presence ofmost major abnormalities, which are either lethal orassociated with severe handicap, so that the parentscan have the option of earlier and safer pregnancytermination. Major fetal abnormalities fall into essen-tially three groups in relation to whether they can bedetected at the 11 to 13 weeks’ scan (Syngelaki et al.,2011): first, those which are always detectable abnor-malities, including body stalk anomaly, anencephaly,

Copyright Ó 2011 John Wiley & Sons, Ltd. Received: 30 November 2010Revised: 5 December 2010

Accepted: 5 December 2010

antes ¿quizás?NICOLAIDES. PRENAT DIAGN . 2011

EVALUACIÓN PRECOZ RIESGO

INTERVENCION

11-14 sem

22-24 sem

28-32 semanas

Ecografias recomendadas

Translucencia nucal

Marcadores 1er TrimAnomalías fetales

Riesgo

Aborto Múltiples

&

Corionicidad

Pre-eclampsia /

RCF

ECOGRAFÍA 11-14 SEMANAS

Dr. Masami Yamamoto

Dr. Masami Yamamoto


Dr. Masami Yamamoto

Screening por Edad materna:

Criterio: >35 años

Ejemplo1: 10 millones de mujeres, 5% de >35 años

Ejemplo 2: 10 millones de mujeres, 10% de >35 años

Edad

≤35

>35

Población

9.500.000

500.000

Prob. T21

1/1000

1/200

Casos T21

9.500

2.500

Edad

≤35

>35

Población

9.000.000

1.000.000

Prob. T21

1/1000

1/200

Casos T21

9.000

5.000

Efecto de la mayor

Edad materna

Dr. Masami Yamamoto

http://images.google.cl/imgres?imgurl=http://www.mater-imaging.com.au/images/nuchal2.jpg&imgrefurl=http://www.mater-imaging.com.au/procedures/ultrasound_nuchal.html&h=217&w=265&sz=20&tbnid=Ky1AQuLyiksJ:&tbnh=88&tbnw=107&hl=es&start=2&prev=/images?q=Nuchal+translucency&hl=es&lr=&sa=G

Tamizaje Prenatal: Sd Down

• Ecografía 11-14 semanas

• Marcadores secundarios

• Doppler Tricuspídeo

• Doppler Ductus Venoso

• Hueso nasal

• Translucencia nucal: principal marcador

Dr. Masami Yamamoto

Definición de TN

aumentada:

> p95

Dr. Masami Yamamoto

+1/20






• Hueso nasal







• Hueso nasal


Tamizaje Prenatal: Sd Down• Ecografía 11-14

semanas• Marcadores secundarios



• Hueso nasal


Bioquimica Materna

o

Marcadores Sericos


Screening de aneuploidias

Bioquímica materna

PAPP-A

βHCG libre

LHR =4


Metodo Matemático

estimación del riesgoedad materna

*base X

Eco

LR

Marcardores

LRX

= Probabilidad Final


Ejemplo:

Mujer 36 años

1/196 X

Eco

1/98 (LR =2)

Marcardores

1/65 (LR =3)X

= Probabilidad Final

2 x 3 x 1/196


Mujer 36 años

1/196 X

Eco

1/98 (LR =2)

Marcardores

1/65 (LR =3)X

= 1/196 x 2 x 3Probabilidad Final

6/196=1/32


Método Tasa de

Detección

%

screening

positivo

Edad >35 años 30% 5%

Edad +

Marcadores séricos 2°T

60% 5%

Edad +

Translucencia nucal

80% 3%

Edad + TN + MS 1er T 85% 2%

Edad + TN + Hueso Nasal 90% 2%

Edad+TN+HN+MS1erT 95% 2%

Dr. YM Dennis Lo

• Presence of fetal DNA in maternal plasma and serum.

• The Lancet, Vol 350; 9076: 485-487

• August 1997

Procedimientos invasivos

Para confirmacion

Edad gestacional

AMNIOCENTESIS

BIOPSIA DE VELLOSIDADES

CORDOCENTESIS

11 16 20 40

AMNIOCENTESISBVC


Amniocentesis

N=4374

early:12 (11-13) late:15(15-17)N=2183 N=2185

Abortos 5.6% 2.9% p=0.012

Pies Bots 1.3% 0.1% p=0.0001

RPM 3.5% 1.7% p=0.0007

Dificultad TEC 10% 4 % p<0.001

2° Proced. 3% 0.4% p<0.001

CEMAT, Lancet 1998

AMNIOCENTESIS

12 vs 15 semanas

Cavidad Amniotica a 11 semanas

Amniocentesis precoz puede

no entrar, o desgarrar la membrana.

Biopsia de vellosidades coriales

(BVC)

Doble aguja

Photo aspi ++

Incidencia general 1 / 5000

BVC 1 / 200-1500

Amputation 8 wks

Terminal phalanges 10 wksFirth 1994

•hipoperfusion

• Embolizacion

•Vasoactivos

Reduccion de miembros

Apodia

Acheira

Amelia

Hemimelia

Reduccion luego de BVC

(n 130.839)L

RD

/10

.000

EG Jackson, 1993

5,834,8

4,2 4

0

2

4

6

8

< 10 10 11 > 11


Cordocentesis

amniocentesis

biopsia de

vellosidades

coriales

cordocentesis

Riesgo de aborto 0,5 a 1% 1 a 2% 2 a 25%

EG 15 semanas 11 a 14 semanas 24 o mas

Mosaicismo

placentarioRaro 1 a 2% 2%

muestra amniocitos vellosidades sangre fetal

RESUMEN

• Modelo de screening en base a eco y procedimientos

confirmatorios tiene riesgos.

• Ecografia y marcadores tienen falsos postivos 2 a 5% de pob.

• El proceso de screening require operadores expertos en

ecografia y conocimiento de valores diagnosticos, para reducir

desinformacion.

• La instauracion de un protocol de screening a larga escala

producira exceso de perdidas fetales.


Gracias por su atención

Y gracias por su atención

Documents

Dr. Masami Yamamoto Clínica Universidad de los Andes€¦ · Ejemplo1: 10 millones de mujeres, 5% de >35 años Ejemplo 2: 10 millones de mujeres, 10% de >35 años Edad ≤35 >35