Best Genetic Counselling in Delhi — Expert Prenatal & Hereditary Condition Guidance

Genetic counselling is one of the most consequential conversations a family can have — and the quality of that conversation depends entirely on the qualifications and experience of the specialist delivering it. At the Fetal & Genetic Clinic in Chittaranjan Park, New Delhi, Dr. Ashutosh Gupta provides the best genetic counselling in Delhi backed by a DM in Medical Genetics from SGPGIMS, Lucknow — the highest academic super-specialisation qualification in this field in India — combined with over 15 years of dedicated fetal medicine practice and more than 3,000 invasive prenatal procedures.

Whether you need genetic counselling because of recurrent pregnancy loss, an abnormal prenatal scan, a chromosomal finding, a family history of hereditary disease, or a positive NIPT result that needs expert interpretation, this page explains what genetic counselling involves, which situations require it, and why choosing a DM-qualified Medical Geneticist delivers a fundamentally different level of care than a gynaecologist offering counselling as part of a general practice.

What Is Genetic Counselling?

Genetic counselling is a specialist medical consultation that focuses on understanding the genetic and chromosomal aspects of a clinical finding, a family history, or a reproductive concern. It is not a test in itself — it is the process of expert interpretation, risk explanation, and informed decision support that happens around testing.

A consultation with Dr. Gupta involves reviewing your personal and family medical history, interpreting any existing scan or laboratory results in their full clinical context, explaining the nature and inheritance pattern of any identified condition in plain language, walking through the available testing options with their benefits, limitations and associated risks, and providing the time and space for questions without any pressure toward a particular decision.

Who Needs Genetic Counselling?

Genetic counselling is not only for families already dealing with a diagnosed genetic condition. It is relevant across a broad range of clinical situations — many of which arise during routine pregnancy care. You should consider a genetic counselling consultation if any of the following apply to you or your partner:

• You have had two or more unexplained pregnancy losses: Recurrent pregnancy loss has a chromosomal cause in approximately 3 to 5 percent of cases — a balanced translocation in one parent that goes undetected without specific genetic testing.
• Your NT scan result is elevated or your serum screening returned a high-risk figure: Both require specialist interpretation to understand the precise risk and advise on the most appropriate next step — NIPT, CVS, or amniocentesis.
• Your NIPT result has come back as high risk: NIPT is a screening test — a high-risk result does not mean a confirmed diagnosis. Expert counselling is essential to understand the positive predictive value and the confirmatory pathway.
• You or your partner are thalassaemia carriers: If both partners are carriers, there is a 25 percent chance in each pregnancy of having a baby with thalassaemia major. Counselling guides prenatal testing options.
• A family member has a diagnosed genetic condition: Including thalassaemia, Down syndrome, DMD, spinal muscular atrophy, cystic fibrosis, hereditary cancer, inherited heart disease, or any other heritable condition.
• You are 35 or older and pregnant or planning pregnancy: Age-related chromosomal risk increases progressively from 35 and warrants formal risk assessment.
• You have had a previous pregnancy or child affected by a chromosomal condition: Recurrence risk counselling, parental karyotyping, and prenatal testing planning for future pregnancies.
• You and your partner are related (consanguineous couple): Elevated risk of autosomal recessive conditions that may not be evident until a child is born affected.
• An anomaly scan has identified a structural finding: A structural abnormality — cardiac, renal, neural tube, or skeletal — may have chromosomal or genetic implications requiring specialist interpretation.
• You are seeking pre-conception guidance: Before starting a family, a genetic counselling consultation can identify risk factors, guide carrier testing, and optimise the safety of your pregnancy from the start.

Dr. Ashutosh Gupta holds a DM in Medical Genetics from SGPGIMS — a programme that admits only a handful of candidates each year from across India. This is the foundational credential that makes his genetic counselling service qualitatively different from what is available at most Delhi clinics and hospitals.

Genetic Counselling for Recurrent Pregnancy Loss in Delhi

Recurrent pregnancy loss — defined as two or more consecutive pregnancy losses before 24 weeks — affects approximately one percent of couples and carries a profound emotional burden alongside the clinical one. Many couples who experience repeated losses are told 'it is just bad luck' and are not offered a structured investigation. This is changing — and genetic counselling is central to that change.

A comprehensive genetic counselling evaluation for recurrent pregnancy loss at the Fetal & Genetic Clinic covers seven evidence-based causal categories:

• Chromosomal translocation in either parent: Responsible for 3 to 5 percent of RPL cases. A balanced translocation carrier has a normal phenotype — the condition is only identified on specific karyotyping. Once identified, prenatal diagnosis by CVS or amniocentesis in future pregnancies can confirm whether the fetus has an unbalanced chromosomal arrangement.
• Uterine structural abnormalities: Uterine septa, submucous fibroids, and intrauterine adhesions are identified in 2 to 8 percent of women with RPL and are potentially correctable.
• Antiphospholipid Syndrome (APS): Present in 15 percent of women with RPL. APS-related pregnancy loss is highly treatable with aspirin and low molecular weight heparin — raising live birth rates from approximately 10 percent to 70 percent.
• Thyroid disease and endocrine factors: Uncontrolled thyroid disease, PCOS (present in 41 percent of RPL cases vs 22 percent in controls), and diabetes all contribute to pregnancy loss and are amenable to management.
• Inherited thrombophilias: Factor V Leiden mutation, prothrombin gene mutation, and protein C/S deficiencies can cause thrombosis of uteroplacental vessels, contributing to recurrent loss.
• Cervical incompetence: Mid-trimester losses with painless cervical dilatation — managed with cervical cerclage.
• Unexplained RPL: Even without an identified cause, approximately 75 percent of couples go on to have a successful subsequent pregnancy with supportive care and monitoring. Understanding this is itself a clinically important counselling outcome.

Down Syndrome Screening, Diagnosis & Counselling in Delhi

Down syndrome (Trisomy 21) is the most common chromosomal condition in live births, occurring in approximately 1 in 660 pregnancies. Genetic counselling for Down syndrome is relevant in three distinct scenarios: when first-trimester screening has returned a high-risk result; when a prenatal or postnatal diagnosis has been made; and when a couple has had a previous pregnancy affected by Trisomy 21 and needs to understand their recurrence risk.

Dr. Gupta provides genetic counselling covering the full range of Down syndrome-related situations — including interpretation of NT scan results and combined first-trimester screening, NIPT results and their positive predictive value, chromosomal karyotyping results from CVS or amniocentesis, and recurrence risk based on the type of Trisomy 21 identified (free trisomy vs Robertsonian translocation vs mosaic).

A critical point that many patients are not told: the recurrence risk for Down syndrome depends entirely on which type of chromosomal abnormality caused the condition. For free Trisomy 21 (the most common form, arising from non-disjunction), the recurrence risk is low — approximately 1 percent above age-related risk. For translocation Down syndrome, recurrence risk can range from less than 1 percent to 100 percent depending on which parent carries the translocation and its specific type. This distinction is only possible to make after specialist genetic analysis — and it changes clinical management entirely.

Thalassaemia, Sickle Cell & Duchenne Muscular Dystrophy — Carrier Counselling in Delhi

Thalassaemia Carrier Counselling

Beta thalassaemia is among the most prevalent genetic disorders in India, with approximately 1 in 550 to 600 individuals being a carrier. When both parents carry the thalassaemia gene, each pregnancy has a 25 percent chance of resulting in a baby with thalassaemia major — a condition requiring monthly blood transfusions from infancy and, without bone marrow transplantation, a significantly shortened life expectancy.

Carrier status is identified through a simple blood test — complete blood count and haemoglobin electrophoresis. If only one partner is a carrier, the baby cannot have thalassaemia major. If both are carriers, prenatal diagnosis by CVS at 12 weeks or amniocentesis at 16 weeks determines whether the fetus is affected, a carrier, or unaffected. Dr. Gupta advises on the full pathway from carrier identification through to prenatal diagnosis and result interpretation.

Sickle Cell Anaemia

Sickle cell anaemia follows the same autosomal recessive inheritance pattern as thalassaemia — when both parents carry the sickle cell trait, there is a 25 percent chance of an affected baby in each pregnancy. Prenatal diagnosis is available by CVS or amniocentesis. Carrier testing is a simple blood test.

Duchenne Muscular Dystrophy (DMD)

DMD is an X-linked recessive condition affecting approximately 1 in 3,600 boys. Female carriers are typically unaffected but have a 50 percent chance of passing the mutation to each son. Genetic testing identifies affected male fetuses and female carriers, enabling informed reproductive decisions.

Hereditary Cancer, Cardiac & Medical Genetics Counselling in Delhi

Genetic counselling extends beyond pregnancy. Dr. Gupta's DM in Medical Genetics positions him to provide comprehensive counselling for hereditary conditions across all life stages — not just in the prenatal context.

• Hereditary Cancer Genetics: Families with a history of early-onset breast, ovarian, colorectal, pancreatic, or other cancers may carry pathogenic variants in genes such as BRCA1, BRCA2, or the Lynch syndrome genes. Genetic counselling determines who should be tested, interprets results, advises on risk reduction strategies, and guides surveillance planning for carriers.
• Cardiac Genetics: Hypertrophic cardiomyopathy, dilated cardiomyopathy, long QT syndrome, and familial hypercholesterolaemia are heritable conditions that can cause sudden cardiac death in young people. Genetic counselling identifies at-risk family members before they develop symptoms — enabling preventive monitoring and treatment.
• Pharmacogenomics: Your genetic profile determines how your body metabolises specific medications. Pharmacogenomic counselling identifies variants in drug-metabolising genes that affect your response to common medications — enabling safer, more personalised prescribing.
• Genetic Diabetes (MODY): Maturity-onset diabetes of the young is frequently misdiagnosed as type 1 or type 2 diabetes. The correct genetic diagnosis changes management decisively — some MODY subtypes require no medication at all; others respond specifically to sulphonylureas. Genetic counselling identifies families who may benefit from molecular testing.
• Hereditary Kidney Disease: Polycystic kidney disease, Alport syndrome, and other hereditary nephropathies can be identified by genetic testing before overt renal failure develops — enabling early surveillance and management.

When Should You See a Genetic Counsellor? — Quick Reference Table

The table below provides a clinical quick reference for the most common situations in which a genetic counselling consultation is indicated, the reason it helps, and the typical next steps. Use it to identify whether your specific situation warrants a consultation.

What Happens in a Genetic Counselling Session at Our Delhi Clinic?

Many patients are uncertain about what to expect from a genetic counselling appointment. Unlike a routine consultation, a genetic counselling session at the Fetal & Genetic Clinic is structured around your specific clinical situation — not a standard script. Here is what a typical consultation involves:

• Step 1 — History review: Dr. Gupta reviews your personal and family medical history in detail, including pregnancy history, previous test results, medications, and any known diagnoses on both sides of the family. For prenatal counselling, all previous scan reports and blood test results should be brought to the appointment.
• Step 2 — Family tree analysis: A three-generation pedigree is constructed where relevant — mapping the pattern of inheritance in the family. This is often the first time a patient has seen their family history laid out visually, and it frequently reveals inheritance patterns that change the clinical assessment.
• Step 3 — Risk assessment: Dr. Gupta calculates or reviews the risk of the condition in question — taking into account the specific type of chromosomal or genetic finding, the inheritance pattern, and the patient's specific clinical details. Risk figures are communicated clearly, in terms of both probability and what that probability means in practice.
• Step 4 — Testing options: All available testing options are explained with their benefits, limitations, costs, and risks — whether that is NIPT, CVS, amniocentesis, carrier screening, karyotyping, or molecular genetic testing. The decision about which test to proceed with is yours — Dr. Gupta provides the information and recommendation; the choice remains with you.
• Step 5 — Decision support: There is no pressure toward a particular decision. The goal of the session is to ensure you fully understand your situation and your options. Questions are encouraged throughout. A written summary of the consultation, including the risk figure and the recommended next steps, is provided.
• Step 6 — Follow-up: Where results are pending, Dr. Gupta reviews them with you directly — in person or by phone — and advises on the appropriate next step based on what the result shows.

Why Dr. Ashutosh Gupta Offers the Best Genetic Counselling in Delhi

Genetic counselling is available from many gynaecologists and clinics across Delhi — but not all genetic counselling is equal. Here is what makes a consultation with Dr. Ashutosh Gupta specifically the best genetic counselling in Delhi:

• DM in Medical Genetics from SGPGIMS — India's highest specialist qualification in this field: SGPGIMS, Lucknow is one of India's premier postgraduate medical institutions. The DM in Medical Genetics is a three-year super-specialisation degree admitted by competitive examination — held by very few practicing clinicians in Delhi. A gynaecologist offering genetic counselling as part of an obstetric practice simply cannot match this depth of specialisation.
• Dual expertise in fetal medicine AND medical genetics — in one consultation: Dr. Gupta's unique combination of clinical fetal medicine and DM Medical Genetics means that the full clinical picture — what a scan shows, what it means genetically, and what testing or intervention is appropriate — is addressed in a single, integrated consultation. No referral to a separate specialist required.
• 3,000+ invasive fetal procedures performed: For patients where counselling leads to a recommendation for CVS or amniocentesis, Dr. Gupta performs both procedures himself at the same clinic. His procedural volume of over 3,000 cases directly translates into a lower complication risk for each patient.
• Plain-language communication without pressure: Dr. Gupta is consistently described by patients as clear, honest, and unhurried. In a specialty where families frequently receive frightening or unexpected findings, the quality of communication is not a soft consideration — it is a clinical one.
• All counselling conditions covered in one clinic: From recurrent pregnancy loss and Down syndrome to NIPT interpretation, thalassaemia, hereditary cancer genetics, cardiac genetics, and pharmacogenomics — Dr. Gupta's DM qualification covers the full spectrum of conditions that require genetic counselling.
• South Delhi clinic — accessible without hospital complexity: E-874, Basement, Chittaranjan Park, New Delhi — accessible from Greater Kailash, Kalkaji, Saket, Lajpat Nagar, Nehru Place, and parts of Noida and Gurugram. Appointments are focused and confidential.

Book the Best Genetic Counselling in Delhi

Whether you have received an unexpected scan or test result, are managing a high-risk pregnancy, carry a family history of a genetic condition, or need expert guidance on NIPT, thalassaemia, recurrent pregnancy loss, or hereditary disease, a consultation with Dr. Ashutosh Gupta delivers specialist genetic counselling backed by India's highest qualification in this field.

Recurrent Pregnancy Loss (Abortions); Thalassemia, Duchenne muscular dystrophy (DMD), Sickle Cell Anaemia
Recurring Pregnancy Loss (RPL)
Recurrent miscarriage - ≥ 3 pregnancy loss; affects about 1% of all women.
It is a heterogeneous condition with multifactorial aetiology
Advanced Maternal age and previous miscarriages are two independent risk factors for a further miscarriage.

1. Genetic factor:
3–5% of couples with RPL; anyone may be a balanced chromosomal translocation carrier; 5–10% chance of a pregnancy with an unbalanced translocation in subsequent pregnancy.

2. Anatomical factors
Uterine anomalies in RPL is in range of 2% and 8%.

3. Cervical weaknesses
Mid-trimester miscarriage; history of mid trimester miscarriage with spontaneous rupture of membranes and painless cervical dilatation.

4. Endocrine factors
Routine screening for occult diabetes and thyroid disease may be helpful. Polycystic ovarian syndrome (PCOS) has been linked to miscarriage; significantly common among women with recurrent miscarriage (41%) when compared with the general population (22%).

5. Immune factors
Antiphospholipid syndrome (APS): Adverse pregnancy outcomes include (a) ≥ 3 consecutive miscarriages < 10 weeks of gestation, (b) ≥ 1 normal foetal deaths > 10 week of gestation (c) ≥ 1 preterm births ; < 34 week of gestation due to severe pre-eclampsia, eclampsia or placental insufficiency.

APS with chronic inflammatory disorders; Systemic lupus erythematosus
It inhibits trophoblastic function, differentiation, might lead to thrombosis of the uteroplacental vasculature.
Antiphospholipid antibodies are present in 15% of women with RPL as compared to < 2% of controls. In women with RPL associated with aPL, the live birth rate of pregnancies with no pharmacological intervention is in the range of 10%.

Live birth rate with RPL - 40% with aspirin only; significantly increases to 70% with aspirin & low molecular weight heparin (LMWH). Aspirin & LMWH significantly reduces the pregnancy losses by 50%.

Alloimmune factors
Immunotherapy (paternal cell immunisation), third-party donor leucocytes and intravenous immunoglobulin (IVIG), in women with RPL does not improve the live birth rate.

Infective agents
TORCH screening

6. Inherited thrombophilic defects
Factor V Leiden mutation; deficiencies of protein C/S and antithrombin III, hyperhomocysteinaemia and prothrombin gene mutation are established factors for thrombosis of uteroplacental circulation.

7. Unexplained recurrent miscarriage
A significant proportion of cases of recurrent miscarriage remain unexplained, despite detailed investigation. The prognosis for a successful future pregnancy with supportive care alone is in the region of 75%.

Thalassemia
One of the commonest genetic disease
1 in 550-600 induvial is beta thalassemia carrier around 250 million people (4.5% of world population) is affected by Thalassemia.
Thalassemia Major - Requires life-long repeated blood transfusions, on monthly basis.
Thalassemia can be corrected by Bone Marrow Transplantation.
If both parents are thalassemia carrier; there is 25% (1 in 4) chance to have thalassemia major foetus
Prenatal testing
Chorionic villus sampling (CVS)

Duchenne muscular dystrophy (DMD)
X-linked recessive; affects around 1 in 3,600 boys
Mutation in dystrophin gene; located on X chromosome.
Males are affected while the females are usually carriers and asymptomatic.
Genetic testing
To identify affected male & Carrier (Female partner)

Sickle Cell Anaemia
Sickle-cell anaemia; also known as “HbSS” disease.
Autosomal recessive in nature; both partners are heterozygous (HbAS) or “sickle cell trait”.
Rare forms of sickle-cell disease can be compound heterozygous; sickle-haemoglobin C disease (HbSC), sickle beta-plus-thalassaemia (HbS/β+) and sickle beta-zero-thalassaemia (HbS/β0).

In SCD; the body makes sickle-shaped red blood cells (RBCs are crescent shaped). Normally the RBCs are disc-shaped and move easily through the blood vessels, carrying oxygen from the lungs to the tissues. Sickle cells are sickle / crescent shaped which are stiff, sticky and tend to block blood flow in the blood vessels of the limbs and organs causing pain and organ damage.

Down’s Syndrome and Recurrence
Down Syndrome: Down syndrome (DS) or trisomy 21 is the most common genetic disorder with a prevalence of 1 in 660 live births

DS is of 3 types
Free trisomy 21 - Characterized by the presence of three complete copies of chromosome 21; occurring in about 90-95% of DS cases; > 90% of the cases of chromosomal meiotic nondisjunction are maternal in origin, about 5% due to an additional paternal extra chromosome and 2% is due to post-zygotic mitotic non-disjunction.


Translocations: Attribute to 1-7% of DS cases; Robertsonian translocation involving chromosomes 14 and 21 being the most common type.

Mosaicism - Characterized by 2 or more cell lines, some cells containing 46 chromosomes and others with 47 chromosomes (with an extra chromosome 1), is reported in 1-7% of DS cases.

DS phenotype is complex and variable
It present a combination of dysmorphic features and developmental delay. Intellectual disability is universal, muscular hypotonia (99%), upslanted palpebral fissures (90%), microcephaly (85%), flat occipital (80%), joint hyperextension (80%), broad hands with short fingers (70%), short stature (60%), clinodactyly of fifth finger (50%), epicanthal fold (40%), low-set ears (50%), single palmar crease (40%), atlantoaxial instability (15%) and on average, 50-70% have congenital heart defects, such as ventricular septal defect, atrial septal defect, tetralogy of Fallot, patent ductus arteriosus and atrioventricular septal defect.

For DS, a well-established risk factor is advanced maternal age at conception. The estimated risk for foetal trisomy 21 for 20 years women at 12 weeks of gestation is about 1/1000 & delivering an affected baby at term is 1/1500. The risk for this aneuploidy for a woman aged 35 years at 12 weeks of gestation is about 1/250 and delivering an affected baby at term is 1/350.

Risk of recurrence
Women < 35 years of age at previous trisomy 21, the revised risk is the age-related risk times 3.5.
Women ≥35 years of age at previous trisomy 21, the revised risk is the age-related risk times 1.7
Robertsonian translocations involving chromosome 13, 14, 15 or 22 and the chromosome 21, the recurrence risk is upto17% when the mother is the carrier and upto 1.4% father is the carrier of this balanced translocation.

If one of the parents is the carrier of a balanced translocation involving two chromosomes 21, the recurrence risk of DS is 100% Individual with DS; theoretical risk to have a child with DS is 50% to 66%. However, Rate of fetal demise between 11 weeks and term is about 43% for trisomy 21; chances of birth of a child with DS decreases. Individuals with mosaicism, the maximum theoretical recurrence risk is as high as 50% (dependent upon the proportion of trisomic gonadal cells)

Serum screening
Elevated β-hCG (produced from placenta), elevated NH-A (corpus luteum and placenta) and low levels of AFP (produced from yolk sac and fetal liver) and uE3 (placenta); may be suggestive of the presence of DS fetus. The quadruple test has expected detection rate and false-positivity of 79-82% & 6.5-7.8%, respectively.

Ultrasound screening for DS
Genetic Sonogram
Objective is the detection of major and soft markers of aneuploidy. Increased nuchal translucency in the first trimester; Second trimester of gestation - lack of visualization of the nasal bone, reduced femur and humerus length, mild pyelectasis, hyperechoic bowel and echogenic intracardiac focus.

Prenatal invasive methods
Chorionic villus sampling (CVS)
Aspiration of trophoblastic tissue under continuous ultrasound guidance, performed via trans-abdominal route; done in first trimester of pregnancy (12-13 weeks of pregnancy). Risk miscarriage associated to this procedure is about 1/300.

Amniocentesis
Done at 16 weeks of gestation; a small sample of amniotic fluid aspirated transabdominally under ultrasound guidance. The procedure-related foetal loss rate is about 1/500

After obtaining foetal cells
Fluorescence in situ hybridization (FISH) has allowed the prenatal diagnosis of most frequent trisomies (21, 13, 18) and aneuploidy of sex chromosomes quickly and accurately, obtaining result from one to two days.

Polymerase chain reaction quantitative fluorescent (QF-PCR) are also be used for a rapid diagnosis of aneuploidies. Conventional karyotype analysis is the gold standard for the prenatal diagnosis of numerical and major structural chromosomal abnormalities; is labour intensive and requires an average reporting time of 14 days.

QF-PCR technique presents 95.4% sensitivity, 100% specificity, 99.5% efficiency for diagnosis of DS.

Importance of the prenatal diagnosis of DS is to provide the needed healthcare for the child, to prepare the family emotional and psychologically and to plan early intervention therapies.

Genetic causes of Down syndrome and associated recurrence risks

Absent or Hypoplastic Nasal Bones
3 distinct lines
The first 2 lines; are horizontal and parallel to each other, resembling an ‘‘equal sign.’’ The top line represents the skin and the bottom line, which is thicker and more echogenic than the overlying skin, represents the nasal bone.

A third line, represents the tip of the nose.

When the nasal bone line appears as a thin line, less echogenic than the overlying skin, it suggests that the nasal bone is not yet ossified and is classified therefore as being absent.

In chromosomally normal foetus; Absent nasal bone is < 1% in white populations & 10% in Afro-Caribbean populations
Trisomy 21 is associated with abnormal flow in ductus venosus and maxillary hypoplasia.
NOT visible in I trimester or < 2.5 mm in the mid-sagittal section of the foetal profile in II trimester
Nasal bone was absent in 65 % of foetuses with trisomy 21 but only in 0.8 % of chromosomally normal foetuses
In the second trimester, this marker becomes less predictive with absent NB seen in 30–40 % of foetuses with trisomy 21 and 0.3–0.7 % of chromosomally normal foetuses

Nasal hypoplasia of the NB include an absolute cutoff of < 2.5 mm; gestational age-related cutoff of <2.5th or <5th percentile, a ratio of BPD/NB length or multiples of the median for gestational age with <0.75 MoM being the cutoff for abnormal NB measurement

Considering NB hypoplasia or absent nasal bone as a single category, the finding was seen in 50–60 % of foetuses with trisomy 21 and 6–7 % of chromosomally normal foetuses

There is natural variation in the appearance of the NB.
Absence of the NB at or before 13 weeks gestation can be a result of delayed ossification instead of absence or hypoplasia.
Similarly, ethnic variations exist in the presence and size of the nasal bone

Increased Foetal Nuchal Translucency
Increased Foetal Nuchal Translucency thickness

> 95th centile for CRL
maximum thickness of the subcutaneous translucency between the skin and soft tissue overlying the cervical spine Sensitivity & false-positive rate of foetal NT in screening for trisomy 21 is similar in both singleton and DADC pregnancies DAMC twins; increased NT (> 95th centile) at the 11–14-week scan – 4 fold increase in risk for TTTS syndrome Increased NT in recipient foetus may be due to heart failure due to hypervolemic congestion but with advancing gestation; diuresis tends to correct the hypervolemia and reduce heart strain, resolving both congestive heart failure and increased NT.

1. 1/3 (28.7%) have chromosomal abnormalities; 75% of these are trisomy 21 or 18
2. Foetal cardiovascular, pulmonary defects, skeletal dysplasias, congenital infection, metabolic and hematologic disorders
3. Cardiac defects (abnormalities of heart and great arteries) 4.8 to 32.1%
4. Venous congestion in the head and neck,
a. Superior mediastinal compression (diaphragmatic hernia or narrow chest in skeletal dysplasia),
5. Altered composition of the extracellular matrix (altered gene dosage effects),
6. Abnormal or delayed development of the lymphatic system,
7. Foetal anemia or hypoproteinemia,
8. Congenital infection.

Approximately 30% of affected foetuses die between 12 weeks of gestation and term NO significant association between foetal NT & maternal serum free b-hCG or PAPP-A in either trisomy 21 or chromosomally normal pregnancies Trisomy 21 is associated with nasal hypoplasia, increased nuchal fold thickness, cardiac defects, intracardiac echogenic foci, duodenal atresia and echogenic bowel, mild hydronephrosis, shortening of the femur and humerus, sandal gap, and clinodactyly or mid-phalanx hypoplasia of the fifth finger.

In DADC twins; chance that at least 1 foetus is affected by a chromosomal defect is twice as high as in singleton pregnancies In monozygotic twins, the risk for chromosomal abnormalities is the same as in singleton pregnancies Relative proportion of DADC to DAMC twins is approximately 2-to-1; thus the prevalence of chromosomal abnormalities in twin pregnancies is expected to be approximately 1.6 times that in singleton pregnancies Increased NT is found in 4.4% of chromosomally normal foetuses, which are at a significant risk of foetal malformations, skeletal dysplasia, genetic syndromes and delayed brain development

Heart defects, ranging from 4.8 to 32.1%
0.8/1000 NT < 95th centile; 63.5/1000 NT > 99th centile; 56% NT > 95th centile Translucent area disappears after 14 weeks gestational age, when the subcutaneous tissue becomes more echogenic. NT is therefore a transient phenomenon

Hyperextension foetal neck can increase the NT measurement artificially by 0.6 mm, and flexion can decrease the measurement by 0.4 mm

Umbilical cord in neck in 5–10%; falsely increased NT; adding about 0.8 mm to the measurement; appropriate to use the smaller measurement.

Chromosomally normal foetuses; with NT > 95th centile and normal foetal morphological examination at 20 weeks; a favourable pregnancy outcome increases remarkably.

Caution is recommended when the NT is ≥ 6.5 mm.

Pathophysiology of Increased NT
In normal foetuses, collagen VI was only sparsely present in the dermis; which increased tremendously in trisomy-21 foetuses
Triplication of the genes encoding for collagen VI; the genes are located on chromosome 21 (COL6A1 and COL6A2).
Overexpression of genes of mRNA of the a1 chain of collagen VI which binds hyaluronan
Lymphatic and blood vessels are neither dilated nor hyperplastic
NT as an interstitial oedema, due to the presence of large amounts of hyaluronan
Overexpression of superoxide dismutase gene; also on chromosome 21; it stabilizes hyaluronan against free radicals.

Altered composition of the extracellular matrix - collagen metabolism (achondrogenesis type II), abnormalities FGFR (achondroplasia, thanatophoric dysplasia) or peroxisomal disorder (Zellweger syndrome).

Lymphatic abnormalities
Malformations of both the main jugular lymphatic trunk & peripheral lymphatic system; impaired lymphatic drainage; lack of connection with the venous system in these monosomy-X

Enlargement of these lymphatic sacs due to aortic arch malformations
Monosomy-X foetuses; peripheral lymphatic vessels are either absent or hypoplastic;

In trisomic and euploid foetuses with nuchal oedema these vessels were numerous and dilated
Using TVS (transvaginal ultrasound) in I -trimester foetuses with increased NT; enlarged lymphatic sacs could be visualized as Translucent cystic areas in foetal neck in the majority of cases, assumed to be the jugular lymphatic sacs

Enlargement of the jugular lymphatic sacs is due to delay in reconnection with the venous system or due to increased overall expression of the hyaluronic acid receptor With continued development, the lymphatic sacs are remodelled into lymph nodes and are reconnected to the venous system where upon the excess fluid drains away, which explains the TRANSIENT nature of the increased NT.

At 14 weeks of gestation; drop in placental & peripheral resistance leads to draining of excess fluid.
In Turner's syndrome, increased NT - Abnormal development of the jugular lymphatic sacs.
Enlarged lymphatic jugular sacs become only partly re-organized and do not get proper reconnection into the jugular veins, leading to large amount of fluid in the posterior neck region, which is PERSISTENT & not transient and is called `hygroma colli'; delay in this process explains local accumulation of in the nuchal region and not in other areas of the foetal body

In normal embryos; main lymphatics develop from the venous walls & subsequently lose their connections with the veins to form a separate lymphatic system, except for jugulo-axillary sacs, which drain the lymph to the venous system.

Impaired foetal movements, foetal akinesia deformation sequence

Venous congestion
Congenital diaphragmatic hernia, oesophageal atresia causes mediastinal compression and increased impedance to venous return leading to venous congestion of the head and neck

In skeletal dysplasia; increased intrathoracic pressure occurs due to impaired thoracic growth

Foetal infection
First-trimester increased NT is NOT associated with foetal infection; in contrast to foetuses in II / III trimester hydrops.
Screen for maternal infections when increased translucency evolves into second- or third-trimester oedema or generalized hydrops.
Foetal hydrops at 12 weeks, due to a parvovirus infection, is due of cardiac failure is due to (a temporary) myocarditis rather than anaemia

Cardiac failure
Absent or reverse flow a wave DV
90% of chromosomally abnormal; in chromosomally normal foetuses with cardiac defects
Increased levels of atrial and brain natriuretic peptide mRNA in foetal hearts indicating heart strain

Triploidy
Additional chromosome complement - paternal (diandric) - partially molar placenta; b-hCG is greatly increased, PAPP-A is mildly decreased.
Maternal - Digynic triploidy - small normal-looking placenta and severe asymmetrical foetal growth restriction, markedly decreased maternal serum free b-hCG and PAPP-A.

COMBINED I trimester NT and PAPP-A with II trimester free b-hCG, estriol and inhibin A, claiming a potential sensitivity of 94% for a 5% false-positive rate.

In the mid-trimester scan minor foetal defects or markers are common and they are not usually associated with any handicap, unless there is an associated chromosomal abnormality.

Hyperechogenic bowel (intra-amniotic bleeding) and relative shortening of the femur (placental insufficiency) may well be related to serum biochemistry (high free b-hCG, high inhibin-A, low estriol - placental damage) and should be considered together in estimating the risk for trisomy 21.

Increased Nuchal fold thickness
A thickened NF- ≥ 6 mm at 15–20 weeks
Nuchal index is the mean nuchal fold/mean biparietal diameter (BPD) X 100. A value of 11 or greater has a sensitivity of 50% and a specificity of 96%

Noonan syndrome
Craniofacial abnormalities, brachicephaly, hypertelorism, low set ears, broad nose, full lips, cardiac anomalies (pulmonic stenosis, atrial septal defects, obstructive cardiomyopathy), hydrops foetalis and pleural effusion

If isolated:
a. Women with no prior screening, regardless of age - amniocentesis
b. Women with prior first, second-trimester screening - readjust the risk based on previous testing
c. Women with negative CVS, amniocentesis or NIPT for Down syndrome: no further assessment
d. Women with normal karyotype but a thickened NT that persisted as thickened NF into the second trimester: Noonan syndrome and specific diagnostic testing.


Pregnancy Pre-Eclampsia Screening – 12 weeks
I trimester & Pre-eclampsia

Preeclampsia is a major reason for maternal and perinatal morbidity and mortality; consequent of impaired placentation. Risk is higher when the disease is severe and of early onset requiring delivery before 34 weeks Challenge is for early identification & undertaking the measures to improve placentation and reduce the prevalence of the disease. Combination of maternal medical and obstetric history, uterine artery pulsatility index (PI), mean arterial pressure (MAP) and maternal serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at 11–13 weeks’ gestation.

Maternal age > 35 years, increasing weight, Afro-Caribbean / South Asian origin, previous pregnancy with PE, IVF conception and a medical history of chronic hypertension, pre-existing diabetes mellitus and systemic lupus erythematosus or antiphospholipid syndrome, increase the risk for development of PE.

Aetiology impaired placentation due to inadequate trophoblastic invasion of the maternal spiral arteries; reduced placental perfusion leading to placental ischaemia and release of inflammatory factors, platelet activation, endothelial dysfunction, maternal renal dysfunction or abnormal oxidative stress.

Pregnancy-associated plasma protein A (PAPPA) is a syncytiotrophoblast derived metalloproteinase; it enhances the mitogenic function of the insulin-like growth factors; important for placental growth and development significant relationship between PAPP-A levels < 5th centile and IUGR, preterm delivery, PE, and stillbirth

Combination of I Tri PAPP-A and II Tri sFlt-1/PlGF ratio (DR 87.5% ; FPR 5%)

Angiogenic Factors
Pro-Angiogenic Markers
Vascular Endothelial Growth Factor (VEGF) and Placental Growth Factor (PlGF)
Placental growth factor (PIGF)
It is a glycosylated dimeric glycoprotein; member of vascular endothelial growth factor sub-family. PlGF has both vasculogenetic and angiogenetic functions; controlling the expansion of the capillary network.

Curvilinear relationship with gestational age; increase in I/II trimesters; peak at 30 weeks & subsequently decrease Maternal serum levels of PlGF at 11–13 weeks’ gestation are decreased in pregnancies with foetal aneuploidies and those with impaired placentation, resulting in PE and delivery of small-for-gestational-age neonates.

First-trimester maternal serum concentrations of PAPP-A and PlGF Mom are affected by gestational age at screening, maternal weight, racial origin, cigarette smoking, conception by IVF, nulliparity and pre-existing diabetes mellitus.

Serum PlGF is also affected by maternal age
• PlGF decreases with gestational age and maternal weight
• It is higher in Afro-Caribbean and South Asian race than in Caucasians
• Higher in parous than nulliparous women
• Higher in smokers than non-smokers.
• PAPP-A & PlGF MoM are significantly reduced at 11–13 weeks’ gestation in women who subsequently develop PE.

Anti-Angiogenic Markers
Serum sFlt-1
Circulates freely in the serum; binds and neutralizes VEGF and PlGF
Excessive placental production of sFlt-1 (antagonist of VEGF and PlGF) contributes to the pathogenesis of PE
Defective early placentation with impaired trophoblast invasion and restricted remodeling; early-onset PE, resulting in reduced uteroplacental perfusion.

II/III trimester sFlt-1/PlGF ratios - detection rate of 87.5% , FPR 10% for early PE in a low-risk population
• It increases with gestational age and maternal age
• decreases with maternal weight
• Increased Afro-Caribbean race
• Increased in pregnancies conceived by IVF
• Lower in parous than nulliparous women
• Pregnancies complicated by PE; have decreased serum PlGF MoM; increased sFlt-1 MoM.

Soluble Endoglin (sEng)
Truncated form of receptor for transforming growth factor (TGF)-β1 and TGF-β2; anti-angiogenic factor; interferes with production of nitric oxide, vasodilation, and capillary formation.

sEng along with sFlt-1 to induce a severe PE-like disease

Inhibin-A and Activin-A
Members of TGF-β family; Inhibin-A - negative feedback of gonadotropins
Concentrations of inhibin-A and activin-A; are increased in women who will have PE
Inhibin-A and activin-A have been shown to be increased prior to 14 weeks in PE pregnancies

Fetal Hemoglobin
Upregulation of HbF genes; accumulation of extracellular HbF in the vascular lumen in PE placentas
With unexplained placental hypoxia - upregulation of placental HbF genes and proteins - induce formation of ROS, oxidative damage and leakage of the feto-maternal barrier in PE.

Leak of feto-maternal barrier results in endothelial dysfunction, hypertension, and proteinuria.
Significantly elevated levels of HbF and antioxidant alpha(1)-microglobulin (A1M) in the PE group

Cell-Free DNA
Human fetal DNA triggers in vitro activation of NF-κB, with resultant increased IL-6 production in both pregnant and nonpregnant donors

There is graded response between the quantity of fetal DNA and the risk of developing PE; highest levels HELLP syndrome. Increase in shed DNA in PE reflects the increased hypoxic cell death

Foetal Echogenic Bowel
Seen in 0.4% to 1.8% of normal foetuses, resolves spontaneously in 19.7% of cases
Chromosomal (Down syndrome), Cystic fibrosis, Congenital intrauterine infections (cytomegalovirus, parvovirus, rubella, varicella and toxoplasmosis), Intrauterine growth restriction (IUGR), Intrauterine foetal demise (IUFD).

Risk of IUGR is increases with raised MSAFP
Relative risk - 1.6 for IUGR & 8.6 for intrauterine foetal demise
Dilated hyperechogenic bowel - higher risk for gastrointestinal bowel obstruction and meconium peritonitis
Swallowing of amniotic fluid contaminated by intraamniotic blood
IUGR: 9.9–23%, IUFD: 7.3–10%, cystic fibrosis: 2.3–7.6% and congenital infection: 1–10%
Incidence of aneuploidy in foetuses with isolated hyperechogenic bowel is 3.3 to 16% (Trisomy 21)



Foetal Echogenic Bowel
Pyelectasis; dilatation exclusively involving the foetal renal pelvis, is a common ultrasonographic finding
Prevalence among normal foetuses - 0.6 - 4.5%
Isolated pyelectasis is seen in 0.7% of foetuses at 16 to 26 weeks gestation; 2% in Down syndrome

Mild renal pyelectasis has an increased risk of aneuploidy, particularly trisomy 21 when another risk factor such as advanced maternal age (≥ 36 years) or associated anomalies are involved

Renal pelvic anteroposterior diameter is ≥ 4mm in < 20 weeks of gestation; ≥ 7 mm in < 28 weeks of gestation and ≥ 10 mm at any gestational age.

In Euploid foetuses

Mild renal pyelectasis resolves antenatally in 80% of cases; postnatally in 17% and 3% of the foetuses might require postnatal work up.

From Grade III upwards, when the renal pelvis along with both major and minor calyceal dilation; postnatal referral and examination of the infant by paediatric urologist is warranted to minimize renal injury and scarring.

Foetal Echogenic Bowel
Bone length < 5th centile for gestational age, observed in 0.4 to 3.9% of normal foetus

Foetuses of Asian descent - shorter mean FL & foetuses of African American descent - longer mean FL when compared to foetuses from Caucasian mothers.

Shortening for HL is more sensitive and specific than FL Associated deformity, demineralization, bowing or fracture of the long bones to be looked for Early sign of placental dysfunction and warrant increased antenatal surveillance for growth assessment Short long bones may be observed in skeletal dysplasias, genetic syndromes, fetuses with growth restriction, chromosomal abnormalities and also in constitutionally small babies.

In majority; Serial growth scans, Uterine artery Doppler screening, foetal karyotyping, genetic testing may be performed to differentiate constitutionally small babies from those with skeletal dysplasias and chromosomally abnormal babies.

This helps in counselling regarding the exact nature; likelihood course of the disease; prognosis and also assess the recurrence risks.