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Notes for seminaires de lundi: Yves Ville - Maternité Necker- Institut de Puériculture et de Périnatalogie (IPP) Boulevard Brune
“Prima facie” = acronym for « prévention des risques maternels et foetaux par une action de conseil et information éclairée ».
Diagnosis of tri 21 as far as possible in first trimester, taking into account blood sera measurements (hCG, PAPPA), nuchal transparency (skin over back of neck to cervical vertebrae), and maternal age.
Don’t concentrate only on trisomy 21 but also take advantage of the information acquired between 11-14 weeks to address other pregnancy problems that are even more frequent than trisomy 21.
Affirms, prematurity and pre-eclamspia and hemorrhagia can be diagnosed already at this point in the pregnancy.
Ambition to create a “centre de depistage” at the “Brune” (hospital?)
Pregnancy has 12 consultations – recent progress – and 3 ultrasounds. Types of maternities I, II and III to orient women according to the risks of her pregnancy.
1/800 = tri 21; compare to 1% severe preeclampsia, 1% <28 sa prematurity, malformations graves 1% and others +2%; retard de croissance intrauterine 3%, others +10%, less premature 5%.
This first consultation about 20 minutes between 11-14 weeks. Depistage is voluntary, take blood pressure, measure cranial-caudal length, type if a multiple pregnancy. Check morphology, some things are already visible in first trimester if other signs are worrisome. Also transuterine Doppler to check uterine vascularization.
Calculate risk of chromosomal anomalies, check out any uterine scarring if ever the placenta is implanted on top of that scar (hemorrhagia), etc. A longer consultation = three doctors, 3 hours, including the delivery and explanation of the results.
90% accurate prediction of sex looking at orientation/angle of genital tubercule re pelvis.
Too many invasive samples taken to diagnose – risk 1/250 loss of the foetus, so risk of the disease needs to be greater than that to make it worthwhile. Morphological study at 20-22 weeks devt. But can actually diagnose 3% false positive, 90% correct diagnoses (as before), in the first trimester. Maternal age + bHCG need to take 60 samples for karyotyping to get a positive tri 21 - nuchal transparency only 1/200 will be positive. Here they can take only 12 to get a positive.
Medical interruption of pregnancy can then be, if chosen, at 14 weeks’ not 22 weeks’ development.
Now 20% of population is over the age where risk is relatively high (1/251-1/1000) whereas the desire to be reassured by an invasive gesture actually extends to more of the pregnant women population. Can narrow down those who really need it with careful ultrasound exam, rather early.
First trimester exam of spine (cf recent publication from King’s College, London) can show a spina bifida already – because 100% of a series of 60, get less 4th ventricle volume b/c start Arnold-Chiari malformation. Can also diagnose
Michel Zerat – 100 kids per year with spina bifida, none had prenatal diagnosis <1998; then big hole where prenatal diagnosis and essentially interruptions. Now last three years, prenatal diagnosis, as many kids being operated but the pregnancy was a choice to continue.
First trimester – can see congenital diaphragmatic hernia, larger heart defects. Gastroschisis, exomphalos, GIT obstruction, some renal defects (most severe). For limbs, can see skeletal dysplasias, arthrogryposis.
Nuchal transparency need to check if the measurement is confirmed. Can have nuchal transparency but with normal karyotype – often indicates other malformations, can have collagen diseases (CDH, megacystis, abdominal wall defect, chondrodysplasias and arthrogryposis) – all of these are compressive on the thorax. Or can be a problem with lymphatic connections – cystic hygroma, dilation of jugular sac, obstacle – hemodynamic failures such as aortic or great vessel-type cardiac defects, anemia or infection (generalized oedema)
Screening for major heart defects, 3.5 mm = 95% population less than this measurement, but at this point, chance of heart defect is 3x more than the rest of the population. Clearly at this measurement there is a much larger incidence of all sorts of congenital malformations. (eg 13% polycystic kidneys?)
Nuchal transparency also has been observed in association with Sotos syndrome, Noonan (PTPN11 for 50% of them). Need to be careful because there are more than 90% of the families where everything turns out just fine.
Nuchal transparency becomes a cystic hygroma = dilated jugular sacs (generalized oedema). 90% of these will disappear if the karyotype is normal. Followed a population of babies like that over 2 years, where transparency was wider than 99% of population. (>4.1 mm). 222 foetuses. ¼ had abnormal karyotype, followed the 139 remaining where 25 others had interruptions of pregnancy – spontaneous or medically indicated.
In this population of 139 children, 11 (8%) had a more long-term problem – epilepsy +IUGR, Wolf-Parkinson-White with tachycardia, hypospadias/uretral fistula, Stickler syndrome, ASD, CIV, CIV + neurological pbs, hydrocephaly, aortic coarctation, right cervical sinus…
Compare with national control population – odds ratio, prenatal risk is 2x for major problems in prenatal period, but in postnatal, not statistically different than the rest of the population. However, indication for postnatal followup. The more postnatal pathology goes up by odds-ratio of 3x per additional mm over 99th percentile.
Joscelyn – what about false-negatives? 20% at the end of first trimester. But isn’t that a reason to continue doing the amniocenteses? Answer – need to balance reasonable or not worry among pregnant women, with economic and medical cost of unnecessary karyotypes. The idea is not to be eugenic relative to trisomy 21, and 80% efficacity of diagnosis considered a good balance. Unless a woman absolutely insists on having the invasive gesture of amniocentesis.
Remi – would it be possible to propose this kind of detailed diagnosis to every pregnancy in France? Answer – have not yet experimented with centre de depistage – but tested with diffuse network of qualified ultrasound specialists, without a centralized location. There must be a qualification system to make sure the ultrasound measurements are as accurate as possible.
Jean-Paul – when receive women coming in, how many of the transparency measurements are actually confirmed? It’s not permanent and not a malformation. If discrepancy, need to have the original cursors and the original photo. Judge how acceptable the photo was. Take on the responsibility if the photo is not very good according to their standards, this happens more than they would like.
Martine - If major centers for screening in catchment areas – if normal, go back home. If not, how is followup ensured? Necker maternity – will only take fetal risk into account. If maternal, will contact obstetrician, and/or sent to Port-Royal. If fetal risk is high, the correspondent has a local network, or not (usually) eg a congenital heart defect, then local followup in the reference center. Eg here out of 15K patients, 150 need to actually follow per year.
Arnold – impact of Prima Facies on department of genetics? Probably as many questions, but the women did not have the genetic/familial indications. Many of the orphan diseases the women had no genetic consultation until the first birth, even if it’s a clearly genetically transmitted condition. Will there be genealogical trees established, and a genetic counseling? How manage 15K pregnancies per year?
Says try to orient with a pertinent questionnaire to do a kind of pre-information to see if proper genetic counseling necessary.
Mr. Feingold - Discussion in counseling takes at least an hour, usually done for 5 minutes, in Prima Facies about 20 minutes. Out of 800K women per year, at least that many hours for information. Most women don’t realize why the exams at birth for example eg phenylketonuria. Says at the PF center currently welcoming women who already know about a particular condition, sort of recruitment bias, they are not actually very naïve.
Jeanne – what about women with polymalformative syndrome with early 11-14 sa – IMG are by “voie basse” – in order to have proper diagnosis by the foetal pathologist.