Congenital malformations - Edocr

36 PART I GENERAL CONSIDERATIONS
maternal serum screen results. 13 A detailed fetal
ultrasound can detect approximately 90–95% of
ONTDs and anencephaly and should be offered
in pregnancy following an elevated a-fetoprotein
level on the serum screen. Ultrasound cannot
be used to diagnose chromosome anomalies
but can be helpful in adjusting risk for fetal aneuploidy
by screening for features (choroids
plexus cysts, echogenic bowl, cystic hygroma,
and so on) known to be associated with an increased
risk. For genetic conditions associated
with multiple malformations in which direct
DNA testing is not available, fetal ultrasound can
be used as a method of screening for recurrence
in a subsequent pregnancy for conditions such
as the short-rib polydactyly syndromes, which
are associated with autosomal recessive inheritance
but for which the genetic defects are unknown.
A detailed or high resolution fetal ultrasound
can be performed by sonographers with expertise
in screening for skeletal abnormalities that are
visible by the mid-second trimester.
Congenital heart defects are among the
most common birth defects, with an incidence
of 8 per 1000 live births. 14 Fetal echocardiograms
with Doppler performed after 20 weeks gestation
can detect the majority of structural cardiovascular
defects and rhythm abnormalities. The
early detection of fetal cardiovascular defects allows
for better management during the pregnancy
and during the perinatal period, prompt
screening for potential chromosome abnormalities
and other structural anomalies in the fetus,
and better education and preparation of the parents.
According to the American Academy of
Pediatrics, Committee on Genetics, fetal echocardiography
should be considered when (1) a cardiac
defect is suspected on a routine ultrasound
exam; (2) an extracardiac structural defect has
been identified by ultrasound; (3) positive family
history of a cardiovascular or rhythm defect;
(4) chromosome abnormality or genetic disorder
associated with cardiac defects is suspected
in the fetus; (5) maternal disease associated with
increased risk for cardiac defects in the fetus,
such as maternal diabetes or phenylketonuria
(PKU); (6) known prenatal exposure to a teratogenic
agent; (7) fetal arrhythmia has been
detected on examination. 13
With advances in ultrafast MRI technology
overcoming distortion of images by fetal motion
artifact, MRI has become a more prevalent tool
for the detailed characterization of structural abnormalities
in pregnancy. Fetal MRI has been
most helpful in delineating central nervous system
abnormalities 15 allowing for a more accurate
diagnosis and prognosis of the infant. Fetal
MRI can also be used in the second trimester to
better characterize abnormalities in fetal vasculature,
thorax, abdomen, and pelvis. 15 MRI can
be helpful in visualizing fetal anatomy when
oligohydramnios is present, making ultrasound
difficult. Fetal MRI is not recommended in the
first trimester 13 and should be offered to couples
when a structural defect is suspected on ultrasound
that could be better characterized by MRI.
Lastly, preimplantation genetic diagnosis
(PGD) has become an important alternative to
traditional methods of prenatal diagnosis of genetic
disorders. PGD is defined as a method of
analyzing the chromosomal or genetic makeup
of an embryo obtained by in vitro fertilization
(IVF) techniques. 16 Once a diagnosis is established,
embryos can be transferred to the woman’s
uterus for a successful pregnancy. PGD was first
used to determine the sex of embryos for couples
at risk of having a child with an X-linked
condition. Since then, PGD has been used for
the diagnosis of chromosome aneuploidy and
translocations, over 100 single gene disorders,
and for HLA typing for a potential stem cell
donor match relative. 16 Currently there are three
methods of genetic testing of an embryo, early
embryo biopsy, polar body extraction, and
blastocyst-stage biopsy. 16 Early embryo biopsy
involves removing one or two blastomeres from
the embryo on the third day after IVF. The cells
can then be used for single cell FISH for certain
chromosome anomalies or polymerase chain
reaction (PCR)-based DNA analysis for single gene
disorders. The blastocyst-stage biopsy involves
the laser-guided removal of several cells from the