Transcript Screening for NTDs

Spinabifida – Prenatal Aspects
Dr R B Beattie
Consultant in Fetal Medicine
UHS Cardiff
Overview of Presentation
•Spina Bifida
•Maternal Serum AFP
•Amniotic Fluid AFP and Ach
•Anomaly Scan (18-22 weeks)
•3D Scan and MRI
•First Trimester Scan (11-13 weeks)
•Fetal Surgery
Anatomy of Spinabifida
AC Malformation
Myelomeningocoele
Anatomy of Spinabifida
Meningocoele
Myelomeningocoele
Anatomy of Spinabifida
Myelomeningocoele
Types of Spinabifida
Ventriculomgaly / Hydrocephalus
Risk factors for NTD
Risk Factor
Incidence
General incidence
1.4–1.6
Amniocentesis for advanced maternal age
1.5–3.0
Diabetes mellitus
20
Valproic acid in first trimester
10–20
One sibling with NTD
15–30
Two siblings with NTD*
57
Parent with NTD
11
Half sibling with NTD
8
First cousin (mother's sister's child)
10
Other first cousins
3
Sibling with severe scoliosis secondary to multiple vertebral defects
15–30
Sibling with occult spinal dysraphism
15–30
Sibling with sacrococcygeal teratoma or hamartoma
15–30
NTD, neural tube defect. *Risk is higher in UK studies. Risk increases further for three or more siblings or combinations of other close relatives.
Main DM, Mennuti MT: Neural tube defects: Issues in prenatal diagnosis and counseling. Obstet Gynecology 67:1–15, 1986.
Causes of NTD
Multifactorial inheritance
Single-gene (autosomal recessive) disorders
Meckel syndrome (most common)
Robert syndrome
Jarcho-Levin syndrome
Median facial cleft syndrome
HARDE (Walker-Warburg) syndrome
Oculo-auriculo-vertebral (Goldenhar) syndrome
Teratogens
Valproic acid
Carbamazepine
Aminopterin
Thalidomide
Oral isotretinoin
Chromosomal aneuploidy
Trisomy 18
Trisomy 13
Trisomy 21
Triploidy
Unbalanced translocations, markers, ring chromosomes
Amniotic band sequence
Cloacal extrophy
Sacrococcygeal teratoma
Maternal IDDM
MSAFP and Spinabifida
Fetal, Amniotic & Maternal AFP
Fetal
(mg)
Amniotic Fluid
(ug)
Maternal
(ng)
•Fig. 4. Alpha-fetoprotein values in different compartments. A. Fetal serum. B. Amniotic fluid. C. Maternal serum.
•Notice the various laboratory units for each graph.
• (Habib A: Maternal serum alpha-fetoprotein: Its value in antenatal diagnosis of genetic disease and obstreticical-gynecologic care.
•Acta Obstet Gynecol Scand 6(Suppl): 14, 1977.)
MSFAP Screening Programme
Fig. 5. Anticipated results for MSAFP screening of 10,000 prenatal patients.
(Adapted from Haddow JE: Screening for spinal defects. Hosp Pract 17:128–138, 1982.)
MSAFP Limitations
False-Positive Levels
Inaccurate gestational dating (patient > gestation than estimated)
Multiple gestation
Race (black patients have higher levels than white patients)
Underweight patients (less than 90 pounds)
Spontaneous fetal to maternal bleeding
False-Negative Levels
Inaccurate gestational dating (patient < gestation than estimated)
Maternal insulin-dependent diabetes mellitus
Obesity
Amniotic Acetylchoinesterase
•
If AAFP is high then check AChe
•
AChE found in red blood cells, muscle, and neural tissue.
•
Concentrations of AChE are much higher in fetal cerebrospinal fluid than in fetal serum.
•
If the fetus has an open NTD, amniotic fluid AFP and AChE are usually both elevated and the high
concentration of AChE in cerebrospinal fluid transudates across the defect into the amniotic fluid.
•
AChE is a sensitive test for confirming an open NTD.
Fetal blood contamination is the most common source of falsely elevated AFP levels in amniotic
fluid, and the amniocentesis performed to obtain the sample is the most common cause of fetal
blood in the fluid.
•
In such cases, amniotic fluid AFP is usually in the 3–5 standard deviation range. AChE is not
detected in 90% of cases because of the relatively low AChE concentrations in the fetal blood.
•
In congenital (Finnish) nephrosis, a rare autosomal recessive disorder, amniotic fluid AFP levels
may be very high, and AChE is not identified.
High MSAFP but no NTD
•Ventral wall defects
Omphalocele
Gastroschisis
•Triploidy
•Trisomies: 18, 13, 21
•Unbalanced translocations
•Amniotic band sequence
•Pentalogy of Cantrell: omphalocele, lower sternal defect, deficiency of diaphragmatic pericardium, intracardiac
abnormality, anterior diaphragm defect
•Renal agenesis
•Fetal demise
•Multiple gestation
•Congenital nephrosis (Finnish type)
•Sacrococcygeal teratoma
•Dermatologic disorders
•Epidermolysis bullosa
•Congenital icthyosiform erythroderma
•Chorioangioma
•Maternal hepatoma
•Maternal ovarian teratoma
Anomaly Scan – Normal Brain
Anomaly Scan – Normal Spine
3D Scan – Normal Spine
2D Scan - Spinabifida
Lemon Sign
Banana
Spinabifida
Spinabifida
Spinabifida
2D Scan - Myelomeningocoele
•http://www.sonoworld.com/fetus/page.aspx?id=2504
3D Scan - Myelomeningocoele
•http://www.sonoworld.com/fetus/page.aspx?id=2504
3D Scan & MRI - Myelomeningocoele
A
C
3D Scan shows accurate
vertebral level of spina
bifida (A)
MRI shows chiari type II
malformation and spinal
cord inside the spinal
canal (C)
D
B
In late pregnancy
MRI better than 3D scan as
cerebrospinal region and
intravertebral structure not
seen well due to because of
cranial/vertebral ossification
(D)
2D Scan -11 to 13 weeks
Normal
NB
P
MB
1.5 to 2.5mm
NT
Mid-sagittal plane of the fetal face showing the nasal bone, palate,
mandible, nuchal translucency (NT), thalamus (T), midbrain (MB), brain
stem (B) and medulla oblongata (MO). Fourth ventricle 1.5 to 2.5mm
2D Scan -11 to 13 weeks
Spinabifida
NB
P
MB
NT
Mid-sagittal plane of the fetal face showing the nasal bone, palate,
mandible, nuchal translucency (NT), thalamus (T), midbrain (MB), brain
stem (B) and medulla oblongata (MO). Fourth ventricle is compressed.
2D Scan – Spinafida
Mid-sagittal plane of the fetal face in a case of open spina bifida demonstrating
compression of the fourth ventricle with no visible translucency.
2D Scan – Spinabifida video
Mid-sagittal plane of the fetal faces in spina bifida.
The arrows point to the brain stem with absence of the fourth ventricle
2D Scan – Spinabifida video
Early BPD and Spinabifida
Screening for fetal spina bifida by ultrasound examination in the first trimester of pregnancy
using fetal biparietal diameter.
OBJECTIVE:
We assessed screening potential of simple and reproducible fetal biometry at 11-14 weeks
STUDY DESIGN:
34,951 unselected consecutive pregnancies included 18 with spina bifida.
Another 28 cases were referred for assessment.
Biometric measurements were expressed in multiples of the median for crown-rump length.
RESULTS:
Biparietal diameter (BPD) <5th centile in spina bifida (P < .0001).
In all, 22 of 44 (50%) cases with spina bifida aperta had a BPD <5th centile.
CONCLUSION:
BPD simple and reproducible
5% had BPD < 5th centile identifying 50% cases of open spina bifida
Am J Obstet Gynecol. 2012 Oct;207(4):306.e1-5. doi: 10.1016/j.ajog.2012.05.014. Epub 2012 May 18.
Fetal Surgery – MOMS Study
• MOMS began 2003.
• 200 women 18+ years
• Enroll before 25 weeks
• RCT – Postnatal versus fetal surgery
• Fetal surgery 19-25 weeks
•Fetal surgery group stay local until delivery
• Delivery by CS around 37 weeks
?Reduced AC Malformation
?Reduced Shunting
?Improved ambulation
Fetal Surgery - video