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what an obstetrician
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KERALA FEDERATION OF
Content
OBSTETRICS & GYNECOLOGY
JOURNAL
Fetal medicine -
06 RELEVANCE OF GENETIC
TESTING IN PREGNANCY
Dr Anusmitha Andrews
what an obstetrician
07
should know INVERTING THE PYRAMID
OF ANTENATAL CARE-
President Academic IDENTIFICATION OF
Dr. Aswath kumar Dr. Reji Mohan PREGNANCIES WITH BAD
Secretary Adolescent
OBSTETRIC OUTCOME
Dr. Anitha Joseph
Dr. Venugopal M. Dr. Mini Balakrishnan
Vice President Reprod.Health
Dr Hariprasad
Joint Secretary
Dr.Shyjus P
Dr. Fessy Louis
Oncology
Dr. Jeena Baburaj
10 SCREENING FOR DOWN
SYNDROME - THE FACTS
Dr Pio James J, Dr. Asha Biju
Treasurer Research
13
Dr. Bindu M Dr. K.U. Kunjimoideen FIRST TRIMESTERS
Journal Editor Medicolegal Committee SCAN- A NECESSITY, NOT A
Dr. Parvathy Deth Dr. Subhash Mallaya FORMALITY
Liaison Officer PPMD / EMOCALS- D Dr Pio James J, Dr Sindhu P
Dr. V. Rajasekharan Nair Dr. Neetha George
15
EMOCALS- N DOPPLER IN FETAL
Dr. Deepthy M. GROWTH RESTRICTION
Committee Chairpersons Quality Standards Dr. Jyothi Mancheri
Mat. Fetal Med. Dr. Vasanthy Jayaraj
Dr. K. Ambujam O.R.R.T
CRMD
Dr. Paily V.P
Dr. Raji Raj
MDMNSR
Dr Lekshmi Ammal
18 INTERVENTIONS IN COMPLICATED
MONOCHORIONIC TWINS TO
IMPROVE OUTCOME
Dr.Rinshi Abid Elayedatt,
KFOG Head Quarters: Dr. Vivek Krishnan
TOGS Academia, East Sooryagramam,
Thrissur- 680 005, Kerala
Ph: 0487 2320233 | kfogsecretary@gmail.com
www. kfogkerala.com
Dear Colleagues,
Greetings from KFOG. Hope all of the enthusiasm and effort put into the
you and family are doing well. Every articles.
new editor brings new energy new I also wish to encourage members of
ideas and refreshing inputs into the KFOG to contribute in large numbers
KFOG JOURNAL. articles for the future editions of the
Congratulations to Dr Parvathy on journal.
taking up the new assignment with After a hiatus there will be print
great zeal and enthusiasm. version of the journal and I am
The theme of this journal focused sure it will be appreciated by many .
Dr Venugopal on Fetal medicine is very relevant Best wishes and happy reading.
Secretary, KFOG to day to day practice and I wish to Dr Venugopal
congratulate each contributor for
F
or many decades, prenatal genetic testing was
offered to pregnant women in certain specific These days, Next-generation sequencing has been
situations. Traditional karyotyping was used to identify causative genes in many Mendelian
offered to women at increased risk for chromosomal disorders. These include panel tests and Whole exome
abnormalities , based on aneuploidy screening sequencing ( WES ). WES in prenatal testing has the
using maternal age, serum marker testing, ultrasound potential to provide a more precise genetic diagnosis
or a combination of these. Chorionic villus sampling .However since the data is under validation for benefits
(CVS) with DNA analysis was offered to couples at / pitfalls , it is ideally not recommended for routine
high risk for a fetus with dominant or recessive genetic use for prenatal diagnosis .
condition. Another situation is karyotyping after the
Most forms of prenatal diagnosis require invasive
diagnosis of fetal structural anomalies on ultrasound
procedures for fetal-sample collection and therefore,
examination.
although considered safe, these procedures involve
Nowadays prenatal diagnosis plays an essential a small risk of fetal loss. The most widely used non
role in obstetrical care, and with proper planning, it invasive test or aneuploidy screening methods are
is a boon for obstetricians and prospective parents combined first trimester screening and second
.Prenatal testing has become more sophisticated with trimester quadruple test .The introduction of cell-
improved level of resolution . free fetal DNA has revolutionized prenatal diagnosis
and fetal medicine. It can be offered as a primary
FISH and Qf PCR are targeted tests which detect
first trimester screen , positive first trimester screen
aneuploidies of chromosomes 13,18 , 21 and sex
, presence of ultrasound markers of aneuploidy in
chromosomes with a turnaround time of 2 – 3 days
second trimester and in cases of previous child with
. Traditional Karyotype has been superceded by
T21 with a detection rate of 99.7 % for T21 .However ,
chromosomal microarray which identifies copy number
a proper pretest and posttest counseling is necessary.
variants . Karyotype may not identify chromosomal
imbalances of < 10 Mb whereas Microarray can detect The birth of a child with intellectual disability or a
submicroscopic deletions and duplications (20-200 genetic abnormality is traumatic to the family. Hence
Kb ). CMA identifies all abnormalities that Karyotype determining genetic diagnosis prenatally, helps us
can offer , except for low level mosaicism and balanced to counsel the family about possible fetal outcomes,
translocations . However , the result has to be management options and recurrence risks. Therefore,
interpreted carefully since some copy number variants it is important for the obstetrician to be aware of the
may be present in normal individuals also . Moreover genetic conditions, and to use appropriate testing
diagnosis of monogenic or single gene disorders is .Referrals to genetic healthcare providers may be done
beyond the scope of Karyotype and CMA . in order to obtain a specific diagnosis.
T
raditionally, , the third trimester has been This concept was inspired by the success of first
considered the most important of all trimesters trimester ultrasound screening for fetal aneuploidy
with recommendations that surveillance using nuchal translucency (NT) and the realisation
be more frequent and focussed on this trimester that increased NT can be a marker for other fetal
when most complications arise. The first trimester abnormalities. With time, more ammunition was
was deemed a period of helplessness. Then came added to the screening armamentarium. What
a seminal paper in 2011 by Kypros Nicolaides in seemed a dream in 2011 is more a reality now.
which he challenged this notion and proposed a Here’s a look at what has worked and at what the
radical different approach to antenatal care. He future might hold.
suggested that instead of waiting for complications First trimester estimation of gestational age
to occur, a more proactive and pre-emptive attitude
Determining the gestational age is one of the
be adopted; that 11-14 week of pregnancy be used
most early and vital steps in obstetric practice
as a window of opportunity for screening and early
which influences almost every obstetric decision.
diagnosis of major pregnancy complications.
Measurement of CRL in the first trimester yields
This would entail using a multi-pronged the most accurate assessment of gestational age
approach (history, maternal characteristics, particularly when the CRL falls between 30 and 84
ultrasound, and laboratory investigations) to assess mm.
the risk status of every pregnancy and use that
Screening for aneuploidies
information to plan further antenatal care i.e., high
risk pregnancies are directed towards specialist Fetal aneuploidies, trisomy 21 in particular, are
care while low risk pregnancies are followed up at major contributors to perinatal morbidity/ mortality
less frequent intervals. As illustrated below, the late and long-term disability. First trimester combined
first trimester thus becomes the base of the pyramid screening incorporating maternal age and history,
upon which the rest of pregnancy care is built. gestational age, NT measurement, PAPP-A and
KFOG Journal | April - June 2023 7
free beta-hCG has become the preferred screening
modality worldwide due to its high detection rate transvaginal assessment was a part of the protocol.
(90% for trisomy 21, about 95% for trisomies 13 and Conditions like acrania, alobar holoprosencephaly,
18), low false positive rate and cost-effectiveness. limb body wall complex can always be diagnosed
The performance can be improved further by adding at 11-14 weeks; other conditions like open neural
on ultrasound markers like nasal bone, ductus tube defects can be diagnosed with careful scrutiny;
venosus Doppler, tricuspid regurgitation and other others like agenesis of corpus callosum still evade
serum markers like PLGF and AFP. detection at this period of gestation.
In the past decade, NIPT has emerged as a challenger Early diagnosis of fetal aneuploidies/ anomalies
to the combined test because it offers a higher provides the opportunity for early termination of
detection rate (>99% for trisomy 21) for a much pregnancy which is preferable to midtrimester
lower false positive rate (0.1%). The one significant termination.
argument against it being used for universal
Assessment of multiple gestations
screening is the cost. Most centres prefer to use it in
special situations like advanced maternal age or in Multi-order pregnancies are at increased risk for
the intermediate risk group (contingent screening). perinatal morbidity and mortality; this risk is most
Many laboratories have also included screening for influenced by chorionicity. Monochorionic fetuses
common microdeletions in their portfolio, but these are at double the risk for perinatal mortality than
haven’t been validated satisfactorily. their dichorionic counterparts. First trimester is
the best time to determine the chorionicity based
It should be remembered that above mentioned
upon which, an appropriate plan to monitor and
tests are all screening tests; screen positive patients
manage these pregnancies can be chalked out. In
should undergo a diagnostic test like CVS or
addition, large differences in the NT of two fetuses
amniocentesis before concluding that the fetus is
or discrepancy in DV flow patten could be early
affected.
signs of TTTS and could serve as further tools to
Screening for structural anomalies triage multi-order pregnancies.
The understanding that increased NT is Screening for preeclampsia and FGR
also associated with structural defects (cardiac
anomalies, CDH, omphalocele etc.) led to an Recent years have seen a renewed interest
attempt to diagnose fetal structural anomalies in screening for conditions which arise out of
during the 11-14 weeks scan. Recent data suggest abnormal placentation. First trimester presents
that the detection rate for fetal anomlies is around a unique window of opportunity in this regard
50%. Higher detection rates can be achieved when as any intervention to prevent preeclampsia or
8 KFOG Journal | April - June 2023
FGR must be initiated before 16 weeks ie before birth before 34 weeks by 35-40%. In those with
the second wave of placentation is complete. history of preterm birth, early elective cerclage may
be planned if the 11-13 weeks scan demonstrates
Screening based on maternal characteristics
no major fetal abnormality. Alternatively, these
and history alone identifies <50 % of women at
patients may be placed on 2 weekly surveillance and
risk for preeclampsia which is unsatisfactorily.
cerclage may be placed when cervical length is <2.5
Throwing mean arterial pressure, mean uterine
mm. Both strategies reduce the risk of preterm birth
artery PI and serum PlGF into the mix predicts
before 34 weeks by 25%. Serial cervical assessment
about 90% of early PE (<34 weeks), 75% of
starting at 14 weeks is also recommended in women
preterm PE (<37 weeks) and 45% of term PE
with history of other risk factors like unicornuate
(≥37 weeks), at screen positive rate of 10%.
or septate uterus. In twin gestations with cervical
Treatment with low-dose aspirin (150mg length of <2.5mm, vaginal progesterone may reduce
at bedtime) from 12- 36 weeks of gestation the risk PTB at <34 weeks by up to 30%.
effectively reduced the incidence of preeclampsia
Other areas of interest
before 37 weeks by 60%. With good compliance,
reduction rates of 75% can be achieved. Screening for SGA without preeclampsia,
gestational diabetes mellitus and fetal macrosomia
Timely administration of low dose aspirin
have shown some promise and it is likely that
also reduces the incidence of FGR which
algorithms and protocols will be available for the
translates into lower healthcare cost related
prediction of these conditions too in the near future.
to prematurity and neurodevelopmental
disability. To conclude, while there may be disagreements
regarding the number of visits proposed by
Screening for preterm labour
Nicolaides, there is no denying that the late first
Prematurity is the leading cause of neonatal trimester gives us the opportunity to get many things
deaths globally. As most spontaneous preterm right early on and provides a foundation upon which
births occur in women without history of previous the right plan of management can be constructed.
preterm birth, screening based on history alone is However, the uptake and implementation of above-
not effective. Using a combination of cervical length mentioned screening programmes have been less
measured vaginally and obstetric history increases than satisfactory, particularly in the peripheries.
the sensitivity of screening. This in turn provides an This may be due to ignorance from both the patients’
opportunity to prevent or delay preterm birth. and the doctors’ side, non-availability of laboratory
Natural progesterone given vaginally and cerclage facilities, relatively expensive nature of the tests
are the two strategies currently proven to prevent and social/religious factors. But whatever be the
preterm births. In asymptomatic women with a obstacles, we should strive to give our patients the
cervical length of <2.5mm, natural progesterone best possible start on their obstetric journey. Well
200mg given vaginally reduces the risk of preterm begun is half done.
Introduction:
When we look at the prenatal prevalence of ultrasound. They live a life expectancy of 45 to 50
chromosomal abnormalities, approximately 75% years and survive with lots of medical morbidities
is contributed by Trisomy 21/13/18 of which like severe learning disability, congenital heart
50% is contributed by Trisomy 21 alone. 50% of disease, endocrinological problems, leukaemia,
Downs syndrome (DS) foetuses will look normal in Alzheimer’s disease etc.
AFP
βHCG
Micronised Estriol
Inhibin A
Table: 1
• Triple Test has a very poor sensitivity. It is obsolete and should not be offered to the patient in the current scenario
as Quadruple test with better sensitivity and similar cost is available in the second trimester
• Quadruple test is done after 15 weeks, preferably after 16 weeks or fetal BPD measures >33mm
3. Is it mandatory for all pregnant mothers • In a busy OPD, alternative methods like
to undergo Downs Syndrome screening group counselling by dedicated staff, video
in pregnancy? demonstration in the OPD or information
pamphlets should be provided.
FIRST
TRIMESTERS SCAN- Dr Pio James J
Consultant in ‘SRADHA’ -
F
irst trimester scan is done during the 11 – 13+6 pulmonary and skeletal disorders.
weeks period. For many of us, the 11-14 wks
3. Multiple pregnancy – the most important factor
Scan is for measuring Nuchal Translucency
for the management of multiple pregnancy is
(NT) and Aneuploidy screening. However it is is
the chorionicity. Best time to do it is before 14
beyond that. If appropriately done, it can detect most
wks with a sensitivity of 100% and a specificity of
of the major aneuploidies, major anomalies, and
99.8%. If we assign chorionicity at the anomaly
define patient specific risks for most complications.
scan, we could go wrong in 14% of the cases.
At present, First trimester screening is considered Labelling of twins is also extremely important
one of the most integral part of fetal care, not only in identifying them in subsequent follow ups,
because of the earlier point of examination but especially if the twins are discordant. Since the
also due to its diagnosing potential. In the current whole pregnancy management revolves around
medical practice, no fetal care is complete without the chorionicity and labelling, it is essential to
a good quality first trimester scan. This a strong document it in writing and in the form of image
statement, however the following aspects will help for future references.
in justifying this.
4. Screening for common aneuploidies during the
Scope of First trimester scan first trimester period is well established and well
1. Crown rump length (CRL) – one of the basic accepted. The high sensitivity and specificity
measurements during the first trimester scan. is majorly contributed by the ultrasound
Helps in accurate dating which is essential to parameters like CRL, NT and NB and also
identify growth disorders and prevent still births, biochemical markers like βhcg and PAPP A.
perinatal morbidity, iatrogenic prematurity etc The first trimester screening has a sensitivity of
around 85 – 90% with a 5% false positive rate.
2. Nuchal translucency (NT)– has evolved from The quality of the whole screening program
marker for Down syndrome to being a marker depends on the quality of the first trimester
for various conditions like other chromosomal scan.
abnormalities, genetic disorders, cardiac,
D
When there is placental damage, umbilical artery
oppler studies of the various vessels have
Doppler shows a definite, chronological change.
contributed enormously in the field of
When the placental involvement is 30% or more,
obstetrics. Fetal growth restriction (FGR)
there will be increased resistance in the umbilical
contributes to 40% of all intrauterine fetal demises
artery PI. When it is >50%, absent diastolic flow
and 25% of all perinatal morbidity. If we follow
and >70% reversal in the end diastolic flow.
the standard definition of estimated fetal weight
(EFW) less than 10 percentile as the criteria for FGR When there is placental dysfunction, there will be
diagnosis, more than 2/3rd will be constitutionally fetal hypoxia, leading on to compensatory changes
small. Doppler studies of various vessels are used in the foetus like preferential shunting of blood
to improve the detection and management of to brain, heart, adrenal and spleen. There will be
pathologically growth restricted fetuses. Major decrease in blood flow to organs like kidneys, liver,
vessels studied in relation to growth restriction muscle and bowel. It will manifest as decreased urine
are uterine artery, Umbilical artery (UA), Middle production and oligohydramnios, bowel ischemia,
cerebral artery (MCA), aortic isthmus and ductus cerebral vasodilatation and low resistance in middle
venosus (DV). Other parameters, which are widely cerebral artery etc. In extremely preterm fetuses as
studied but not part of the accepted guidelines as the tolerance to hypoxia is high the compensatory
of now, are umbilical vein and cardiac function changes and the changes in the umbilical artery will
evaluation. Use of Doppler has shown 38% reduction be seen in a chronological pattern.
in overall perinatal deaths (Neilson JP et al 2005)
In late onset FGR, this pattern is not seen as near
term fetuses have minimal tolerance to hypoxia.
Even before the placental damage is 30%, fetal
Umbilical Artery :
compromise may happen. Hence we cannot rely
Umbilical artery is the much-studied vessel in on the umbilical artery Doppler changes alone to
relation to FGR. For the diagnosis, prognosis and diagnose, prognosticate or manage late onset FGR.
management of early onset FGR umbilical artery
Middle Cerebral Artery Doppler :
Doppler changes is the most widely used Doppler
parameter. MCA Doppler is mainly used in the management
KFOG Journal | April - June 2023 15
of late onset FGR. MCA vascular resistance is almost Aortic Doppler:
constant throughout pregnancy. Placental resistance
This vessel reflects the balance between the
drops with gestation hence Cerebro placental ratio
impedance of the brain and systemic vascular
(CPR), the ratio of PI of MCA to UA, increases with
systems. In hypoxic fetus due to redistribution of
gestation. As previously mentioned, when there is
blood flow, there is increased vasoconstriction and
fetal hypoxia, the preferential blood flow to the fetal
peripheral resistance and rise in RI and PI values.
brain is reflected as the low resistance in middle
In the presence of severe hypoxia, diastolic flow
cerebral artery blood flow. This will be evident
reverses. This has strong association with both
as low pulsatility index in MCA. When there is
adverse perinatal and neurological outcome. AoI
placental dysfunction, MCA PI will start dropping
precedes Ductus Venosus abnormalities by 1 week
and the umbilical PI will start increasing. CPR will
be abnormal even before the individual parameters Ductus venosus Doppler:
are abnormal; hence it is a better predictor of fetal In early onset FGR the final stage of compensation
hypoxia. In general CPR of less than 1 is considered is fetal academia. This will be reflected as the
as abnormal. When hypoxia is severe, MCA PI tends changes in the ductus venosus flow. This is part of
to rise, which reflects development of brain edema. the cardiac compromise and the final warning before
MCA Doppler is used in the Barcelona staging of fetal demise. In about 50% of cases, abnormal DV
FGR as well as in timing of delivery of fetuses with precedes absent STV in cCTG. In about 90% of cases
late onset FGR. DV flow is abnormal 48– 72 h before the biophysical
Uterine Artery : profile is abnormal. Absent or reversed velocities
during atrial contraction are associated with very
Uterine artery blood flow indices have been
high perinatal mortality Hence DV abnormality is
used as a screening tool for FGR. Uterine artery
used as the cut off for timing the delivery
pulsatility Index (PI) along with maternal blood
pressure, Serum levels of PAPP-A, PLGF, and HCG
will predict 52 % of the early onset FGR and 20% of Application of Doppler
late onset FGR. (FMF UK)
Role of Doppler in diagnosing FGR- Delphi
Mean Uterine PI of more than 2.35 in the first consensus
trimester and 1.44 in the 2nd trimester is roughly
taken as cut off for categorizing patients in to high In order to distinguish between SGA and true
risk for FGR. Increased uterine PI along with SGA is FGR apart from severe
most likely related to placental or uterine cause for smallness and poor growth velocity, UA and MCA
FGR. 3rd trimester uterine artery Doppler resistance Doppler studies are included in Delphi consensus.
has been shown to be associated with abnormal
CPR. Uterine artery Doppler PI is incorporated in Role of Doppler in staging
the Barcelona staging protocol as one of the criteria and management of FGR
for distinguishing SGA from FGR As per the Barcelona protocol Doppler parameters
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