Fetal Anomalies in the First Trimester

Fetal
Anomalies in the First Trimester

         

• Whitlow
  B.J., Economides D.L 
  
  
  Screening for fetal anomalies in the first
  trimester.
  
  
  Progress in Obstetric &Gynaecology 14th
  vol.,edited by John Studd.
  
   
  
  
  One child in 55 will be born with a major structural
  abnormality. Such abnormalities can contribute up to
  15% of perinatal deaths and a similar number of
  deaths in the first year of life. The most common
  reasons for terminating a fetus with a serious
  anomaly are neural tube defects followed by
  chromosome abnormality.
  
   
  
  
  It is not just for terminating that prenatal
  diagnosis is useful. It has profound implications on
  antenatal and intrapartum management. Certain
  malformations can be treated in utero (e.g.
  diaphragmatic hernia) or postnatally (e.g. certain
  cardiac defects), so early diagnosis can facilitate
  decision making regarding mode and place of
  delivery, especially if neonatal resuscitation and
  immediate surgery are required.
  
   
  
  
  The Royal College of Obstetricians and
  Gynaecologists recommend an ultrasound examination
  at 18-20 weeks. Should fetal abnormalities be
  detected at this stage, a second trimester
  termination may be necessary and this is associated
  with marked psychological sequelae in around 25% of
  cases. It is assumed that if prenatal diagnosis is
  made earlier then a safer first trimester
  termination could be achieved.
  
   
  
  
  GENERAL USES OF SONOGRAPHY IN THE FIRST TRIMESTER
  
   
  
  
  It is important to accurately date a woman’s
  pregnancy. It is possible to accurately predict
  gestational age to within 7 days in the first
  trimester. Viability of a pregnancy can also be
  determined when the crown-rump length is 6mm or more
  and/or the mean gestational sack diameter is 20mm or
  more. If there is absence of cardiac activity in the
  presence of the aforementioned criteria, then the
  pregnancy can be diagnosed as being non-viable.
  Determination of chorionicity in multiple
  pregnancies can be more easily detected in the first
  trimester, as the lambda sign (suggesting
  dichorionicity) becomes obliterated at later
  gestations. Early ultrasound may re-assure those
  mothers with increased anxiety (especially those who
  have had a previous ectopic pregnancy or those that
  suffer from recurrent early miscarriages). Indeed
  the presence of a viable fetus at 12-13 weeks’
  gestation may be associated with a live birth in
  over 98% of cases.
  
   
  
  
  A significant proportion i.e.2.2% of pregnancies at
  11-14 weeks will have failed and the detection of
  such missed abortions will enable a planned
  evacuation of the uterus. The anomalies can be
  structural or chromosomal. The problem of diagnosing
  structural anomalies early is that pathological
  confirmation is technically more difficult, time
  consuming and impossible if suction termination is
  performed.
  
   
  
  
  Feasibility of examining fetal anatomy in the first
  trimester.
  
  Feasibility of TAS.
  
   
  
  
  Green and Hobbins observed that detailed fetal
  anatomy could be visualized with TAS in the first
  trimester.
  
   
  
  
  Advantages of TAS
  
  Probe manoeuvrability is superior with
  transabdominal sonography (TAS).
  
   
  
  
  Advantages of TVS
  
  TVS in general has superior resolution over TAS.
  Bladder filling for TAS was found to cause marked
  discomfort in 4.9%, whilst marked discomfort with
  TVS was found in only 0.7%. 
  
   
  
  
  TAS versus TVS
  
  Cullen concluded that TVS was better used to
  complete, not replace TAS examination for the
  visualization of the first trimester fetus. 
  
   
  
  
  TVS, however, took longer than TAS, with the mean
  scan time for a complete anatomical survey being
  11min for TAS and 16 min for TVS. Complete
  anatomical surveys were performed in 72% by TAS and
  82% by TAS, and in 95% using a combination of both
  scan modes.
  
   
  
  
  The unique appearance of fetal organs in the first
  trimester.
  
   
  
  
  The choroid plexi completely fill the lateral
  borders of the posterior and anterior ventricles,
  and this in turn occupies most of the hemisphere;
  thus hydrocephalus can be potentially difficult to
  diagnose in the first trimester. So also with
  anencephaly, a ‘Mickey Mouse’ appearance, is seen
  which is different from ‘frogs’ eye in the second
  trimester. An omphalocele should not be considered
  as abnormal unless the crown-rump length of the
  fetus is ³ 46mm, since the bowel is present in the
  umbilical cord in early embryonic development.
  
   
  
  
  The heart is difficult to visualize in detail in the
  first trimester. Dolkar et al assessed the 4
  chambers view including the major outlet vessels and
  found that by 12 weeks some 90%, and 13 weeks 100%,
  of cardiac views were satisfactory. The kidneys’
  appearance changes with gestation, being very
  echodense at 9-10 weeks and becoming more sonolucent
  at 11 weeks as excretory function begins.
  
   
  
  
  Since excretory function only occurs after 11 weeks,
  major renal tract anomalies are unlikely to be
  visualized before this time. The hands are often
  open in the first trimester, thus making it easier
  to count the digits and examine for polydactyly.
  
    
  
  
  NUCHAL TRANSLUCENCY MEASUREMENT
  
   
  
  
  Nuchal oedema, or nuchal translucency (NT) as it is
  now more commonly known, is measured from a sagittal
  view of the fetus and is the maximum thickness of
  subcutaneous translucency between the skin and soft
  tissues overlying the cervical spine.
  
   
  
  
  A sonographer is considered trained to measure NT,
  and this is usually achieved after 80-100 supervised
  scans.
  
   
  
  
  Standardising nuchal translucency measurement.
  
   
  
  
  Position
  
  Most studies examining NT in the first trimester
  will measure the NT in the midline sagittal plane
  and measure only the sonolucent (black) area between
  the fetal spine and skin at 28-83 mm crown-rump
  length. A NT will be different when the fetal neck
  is in neutral positions, flexed, or extended. They
  found that fetal umbilical cord can be positioned
  around the neck in 8.23% of fetuses at 10-14 weeks’
  gestation, and that this can add a mean of 0.8mm to
  the NT measurement.
  
   
  
  
  Charts were constructed to derive the probabilities
  of a fetus being affected by a chromosomal
  abnormality on the basis of maternal age combined
  with NT mesurement. Using this method, an 85%
  sensitivity for the detection of fetal chromosomal
  abnormality was predicted with a false positive rate
  of 5%. Investigators have since found that
  measurement of NT, increases with gestation to a
  peak at 13 weeks, after which it decreases.
  Consequently, the use of a single NT threshold value
  for all gestations (10-14 weeks) is incorrect.
  
   
  
  
  Nuchal translucency in unselected populations
  
   
  
  
  Without taking maternal age into consideration and
  using either the 99th centile for nuchal
  translucency or the presence of a structural
  abnormality as indications for karyotyping, were
  able to diagnose 18% of chromosomal abnormalities
  and 75% of cases of trisomy 21 at 11-14 weeks.
  
   
  
  
  This is the largest UK multicentre trial (96,127
  women) involving NT to date. They found that on
  average 30 invasive tests would be required to
  identify one affected fetus.
  
   
  
  
  Sonographic markers for chromosomal abnormalities in
  the first trimester.
  
   
  
  
  The significance of ‘soft’ ultrasound markers for
  the detection of chromosomal abnormalities in the
  first trimester is unknown. Fetuses with markers in
  the first trimester were not necessarily the same
  fetuses with markers in the second trimester. The
  presence of two or more such markers should
  stimulate the clinician to discuss invasive
  karyotyping with the patient in the first trimester.
  
   
  
  
  Outcome of fetuses with enlarged nuchal translucency
  and a normal karyotype.
  
   
  
  
  Souka et al in a study of over 4000 such cases,
  found that a live birth can be expected in 94.4%.
  Structural abnormalities can be expected in 10-17%
  of cases. Equally, genetic syndromes and single gene
  disorders can be expected in an additional 12% of
  fetuses. Thus the chances of taking home a normal
  baby in the presence of an increased NT is around
  34% (when chromosomal structural, genetic syndromes
  and miscarraiges are considered together).
  
   
  
  
  Nuchal translucency and cardiac abnormalities.
  
   
  
  
  Increased NT is also associated with cardiac system
  abnormalities; the greater the measurement of NT,
  the more severe the abnormality. Karyotypically
  normal fetuses with increased NT should have
  mid-trimester fetal echocardiography
  
   
  
  
  The benefits of first-trimester sonography for the
  detection of Down’s syndrome depend on its
  diagnostic accuracy, but it has the potential for
  annual savings of $22 million in the US.
  
   
  
  
  Maternal first trimester serum biochemical screening
  
   
  
  
  Wald et al measured free b-hCG and PAPP-A at 18-14
  weeks’ gestation and found that the respective
  multiple of the median values in those pregnancies
  affected by Down’s syndrome were on average 1.79 and
  0.43, respectively. The combination of these two
  markers were shown to be 63% sensitive and 94.5%
  specific. Other markers are not found to be useful.
  
   
  
  
  Nuchal translucency and first trimerster biochemical
  markers.
  
   
  
  
  It was reported that Down’s syndrome was detected by
  biochemistry in 61%, by nuchal translucency in 73%
  and in 87% by combining both methods for a 5%
  false-positive rate. Future maternal biochemical
  screening may invovle blood being taken at initial
  ultrasound visit (11-14 weeks) and results being
  available by the end of the scan, thus improving
  efficiency and giving the mother one single risk
  figure. 
  
   
  
  
  The optimal gestational age to perform the first
  trimester scan
  
   
  
  
  It was found that the optimal gestational age to
  examine fetal anatomy and measure nuchal
  translucency in the first trimester to be at 13
  weeks.
  
   
  
  
  Fetal trimester detection of fetal structural
  abnormalities
  
   
  
  
  It was found that performing the first ultrasound at
  a later gestational age would miss transient
  anomalies associated with chromosomally abnormal
  fetuses, and suggested that screening in the early
  mid-trimester be offered to everyone.
  
   
  
  
  Screening low-risk populations for structural
  anomalies
  
   
  
  
  A total of 5,616 patients have been studied so far.
  The abnormality rate was found to be 0.8% (47/5616).
  Thirty-two of these abnormalities were diagnosed in
  the first trimester (685 sensitivity), with a
  specificity of 99.9%.
  
   
  
  
  Fetal abnormalities from all the major systems have
  been diagnosed in the first trimester. Certain
  abnormalities are more easily detectable at 11-14
  weeks than others. First trimester sonography was
  found to be particularly good for diagnosing central
  nervous system defects, neck anomalies,
  gastrointestinal and renal defects. A lemon shaped
  skull in the first trimester has been described and
  this may prove to aid diagnosis of spina-bifida. The
  detection of cardiac abnormalities in the first
  trimester in this study was below what one might
  expect when compared to the second trimester scan
  i.e.38% vs 69%.
  
   
  
  
  Some 17% of abnormalities not detected at 13-16
  weeks were subsequently detected at the 18-20 week
  scan. The anomalies not diagnosed by the combination
  of first and second trimester scans are mainly heart
  and limb defects. Thus, in karyotypically normal
  fetuses with increased NT, there maybe a place for
  mid-trimester fetal echocardiography at 22-24 weeks’
  gestation when the cardiovascular system can be
  better visualised. 
  
   
  
  
  Some abnormalities, however, develop as a transitory
  finding in the first trimester and may not be
  present at later gestations (e.g. cystic hygromas
  and nuchal translucency). Thus the sonographer
  should be aware of the chronological order of
  development of specific malformations. Therefore, a
  single scan in pregnancy will not detect all fetal
  malformations.
  
   
  
  
  Thus, in the second trimester scan, there should be
  more emphasis on diagnosing the more difficult
  anomalies by concentrating on the heart, spine and
  limbs.
  
   
  
  
  The main reason for this physiological bowel
  herniation in to the cord that does occur up to 11
  weeks and can be mistaken for exomphalos.
  
   
  
  
  The psychological aspects first trimester scanning.
  
   
  
  
  It has been shown that the level of psychological
  morbidity following termination for fetal
  abnormality in the second trimester is similar to
  that following spontaneous perinatal loss and is of
  the order of 25%.
  
   
  
  
  Finanical implications of screening for fetal
  anomalies in the first trimester.
  
    
  
  
  They found that first trimester sonography at 11-14
  weeks could detect the majority of fetal structural
  defects (68%) and chromosomal defects (79%), at an
  estimated cost per abnormality of Pound 6885 for
  detecting fetal aneuploidy, Pound 5809 per case for
  structural defects and Pound 3955 per anomalous
  fetus.
  
   
  
  
  
  CONCLUSIONS:
  
  Nuchal translucency screening for Down’s syndrome
  has been given a grade B recommendation by the RCOG
  working party, as has serum screening at 9-13 weeks.