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Pre-conceptional & Antepartum screening and counselling

  1. Preconceptional screening and counseling offer an opportunity to identify and mitigate maternal risk factors before pregnancy begins.
  2. The preconceptional visit is the single most important health care visit when viewed in the context of its effect on pregnancy.
  3. The Barker hypothesis states that the intra-uterine fetal environmental has a tremendous impact on the health and well-being of the adult that fetus will become. (IUGR babies are more prone to develop coronary artery disease in future.)

Neural Tube Defects

  1. The incidence of these defects is 1-2 per 1000 live births, and they are second only to cardiac anomalies, which are the most frequent structural fetal malformation.
  2. Some NTDs are associated with a specific mutation in the methylene tetrahydrofolate reductase gene, the adverse effects of which can be largely overcome by periconceptional folic acid supplementation.
  3. More than half of NTDs could be prevented with daily intake of 400 μg of folic acid throughout the periconceptional period.
  4. A woman with a prior pregnancy complicated by a neural tube defect can reduce the 23% recurrence risk by more than 70% if she takes 4 mg of folic acid for the month before conception and for the first trimester of pregnancy.

Risk Factors for NTD

  1. Family history of NTD
  2. Past history of NTD
  3. Diabetes mellitus
  4. Hyperthermia
  5. Drugs and medications (refer Teratogens)
  6. Genetic factors
  7. Production of antifolate receptor antibodies


  1. Anencephaly is a lethal NTD characterized by absence of the brain and cranium above the base of the skull and orbits. It can be diagnosed as early as the first trimester on USG.
  2. 70% of fetuses are female.
  3. Face presentation is the most common presentation.
  4. Recurrence risk is 5% after one affected fetus and 13% after two affected fetuses.
  5. Frog eyes are seen.
    Polyhydramnios is commonly seen due to the following reasons:
    1. Transudation of fluid across the membranes
    2. Absence of swallowing
    3. Absent fetal pituitary (absence of ADH hormone implies that the baby passes more urine)
  6. Postdatism is seen as fetal pituitary plays an important role in initiation of labor.
  7. However pre-term labor can also be there due to polyhydramnios.
  8. Pseudo shoulder dystocia is seen as the soft head/ face can slip through incompletely dilated cervix. Classically, fetuses with spina bifida have one or more of the following cranial signs on USG:
    • Small biparietal diameter
    • Ventriculomegaly
    • Frontal bone scalloping or the so-called lemon sign.
    • Elongation and downward displacement of the cerebellum, the so-called banana sign.
    • Effacement or obliteration of the cisterna magna.
      • The lateral ventricle is commonly measured at its atrium, which is the confluence of the temporal and occipital horns. The measurement is relatively constant at 7 mm, with standard deviation of 1 mm from 15 weeks onward.
      • Mild ventriculomegaly is diagnosed when the atrial width measures 10-15 mm and overt ventriculomegaly when it exceeds 15 mm. A dangling choroid plexus characteristically is found in severe cases.


Maternal serum alpha-fetoprotein (MSAFP) estimation is commonly done between 15 and 20 weeks of gestation.


Conditions Associated with Abnormal Maternal Serum Alpha-Fetoprotein Concentrations


Elevated Levels

  1. Neural tube defects
  2. Pilonidal cysts
  3. Esophageal or intestinal obstruction
  4. Liver necrosis
  5. Cystic hygroma
  6. Sacrococcygeal teratoma
  7. Abdominal wall defects-omphalocele, gastroschisis
  8. Urinary obstruction
  9. Renal anomalies-polycystic or absent kidneys
  10. Congenital nephrosis
  11. Osteogenesis imperfecta
  12. Congenital skin defects
  13. Cloacal exstrophy
  14. Chorioangioma of placenta
  15. Placenta accreta
  16. Oligohydramnios
  17. Preeclampsia
  18. Multifetal gestation
  19. Low birth weight
  20. Fetal death
  21. Underestimated gestational age, decreased maternal weight
  22. Maternal hepatoma or teratoma

Low Levels

  1. Chromosomal trisomies
  2. Gestational trophoblastic disease
  3. Increased maternal weight
  4. Overestimated gestational age
    • NTD is suspected if the maternal serum AFP is elevated, and if the ultrasonographic examination is nondiagnosed tic, then amniotic fluid AFP levels are measured.
    • An elevated amniotic fluid AFP level prompts assay of the same sample for acetylcholinesterase.
    • The presence of this enzyme 100% confirms that exposed neural tissue or another open fetal defect is present.

Down Syndrome

A trisomy 21 karyotype is found in 1 in 800 to 1000 newborns. It is the most common nonlethal trisomy. At the maternal age of 35 years, the risk of having a baby with Down syndrome is 1:365.

Recurrent Risk of Down Syndrome


Chromosome Constitution


Risk of the Offspring

Affected child





Trisomy 21



Mother < 30 yr in present pregnancy





Mother> 30 yr; had Down baby





before 30 yr of age

Risk at mothers age + 1 %




Mother >30 yr; had Down baby after

Risk at mother's age




30 yr age

















I Translocations 21/21





I Mosaic










C = Carrier; N = Normal

Triple Marker Test

This is a screening test done between 16 and 18 weeks of gestation, mainly to identify a mother who is at a high risk of having a fetus with trisomy 21. It involves estimation of 3 hormones: hCG, AFP, and unconjugated estriol (UE3).







Down syndrome (T 21)




Edward syndrome (T 18)





In Patau syndrome (T 13): AFP and UE3 are decreased but hCG values remain controversial. This test can detect up to 70% cases of Down syndrome.

Screening Tests

Detection of Down Syndrome (%)

Double test (hCG + PAPP A) (done in first trimester)


Triple test


Quadruple test (hCG, AFP, UE3, INHIBIN A)


Sr Integrated test (hCG, AFP, UE3, INHIBIN A, PAPP A)


Integrated test (hCG, AFP, UE3, INHIBIN A, PAPP A + NT on USG



PAPP A = pregnancy-associated plasma protein A; NT = nuchal translucency.

  1. PAPP A is decreased while INHIBIN A is increased in maternal serum if the fetus has Down syndrome.
  2. The only 100% confirmatory test for Down syndrome is karyotyping, the sample for which can be obtained by chorionic villus sampling or amniocentesis. Hence, in a patient who has a past history of fetus with Down syndrome, fetal karyotyping has to be done in the next pregnancy.
  3. Fetal nuchal translucency is the maximum thickness of the subcutaneous translucent area between the skin and soft tissue that overlies the fetal spine in the sagittal plane. It is measured between 11 and 13 weeks of gestation.
  4. Up to 3 mm is considered normal. NT > 3 mm is a marker for Down syndrome.

Causes of increased NT:

  1. Chromosomal anomalies
  2. Cardiac defects
  3. Pulmonary malformations
  4. Skeletal dysplasias
  5. Congenital intra-uterine infections
  6. Metabolic disorders
  7. Hematological disorders

USG Features of Down Syndrome (Soft Tissue Markers)

  1. Echogenic bowel
  2. Echogenic intracardiac foci
  3. Duodenal atresia
  4. Absent nasal bone
  5. Single umbilical artery
  6. Renal pyelectasis
  7. Exomphalos
  8. Choroid plexus cyst
  9. Short femur /humerus
  10. Cystic hygroma
  11. ASD/VSD
  12. Ventriculomegaly
  13. Annular pancreas
  14. Increased nuchal fold thickness, increased NT
  15. Congenital diaphragmatic hernia
  16. Sandal gap
  17. Fifth finger middle phalanx hypoplasia

Common causes of echogenic bowel include swallowed intra-amnionic blood, malformation, infection, and aneuploidy. Cystic fibrosis and trisomy 21 also have been associated with echogenic bowel.

Duodenal atresia occurs in about 1 in 10,000 live births. The lesion may be diagnosed prenatally by the demonstration of the so-called double bubble sign, which represents distention of the stomach and the first part of the duodenum. About 30% of fetuses with duodenal atresia diagnosed antenatally have trisomy 21 and more than half have other anomalies.

Indications for chorionic villus sampling/amniocentesis (acog guidelines)

  1. Singleton pregnancy at age over 35 years at delivery
  2. Dizygotic twin pregnancy at age over 31 years at delivery
  3. Previous autosomal trisomy birth
  4. Previous 47, XXX or 47, XXY birth or triploidy birth
  5. Patient or partner is carrier of chromosomal translocation/ inversion
  6. Some cases with repetitive early pregnancy losses
  7. Patient or partner has aneuploidy
  8. Major fetal structural defect identified by ultrasound


  1. Traditionally done between 16 and 20 weeks of gestation
  2. Early amniocentesis is done between 12 and 14 weeks of gestation
  3. It is done under use guidance
  4. Risk of gestational loss (abortion) is 0.3-0.5%
  5. Other complications include chorioamnionitis, PROM, fetal trauma

Chorionic Villus Sampling

  1. Can be done through transabdominal or transcervical route
  2. As per ACOG guidelines, CVS should be done only after 10 completed weeks (after 70 days)
  3. Complications a/w early CVS are limb reduction defects and oro-mandibular defects
  4. Risk of gestational loss with CVS is 0.8-1 %

Cordocentesis (Percutaneous Umbilical Blood Sampling)


It is done after 18 weeks of gestation. Risk of gestational loss is 1-5%.



  1. Rapid karyotyping in fetuses with structural anomalies on USG.
  2. Fetal hemolytic disease (diagnosis as well as management by intra-uterine transfusion)
  3. Suspected fetal thrombocytopenia/hemoglobinopathy
  4. Suspected fetal viral infection
  5. Diagnosis of twin-to-twin transfusion syndrome

Features of Trisomy 18 (Edward Syndrome)

  1. IUGR
  2. Prominent occiput
  3. Rotated and malformed auricles, short palpebral fissures, small mouth
  4. Cardiac defects (VSD/ ASD/PDA)
  5. Horseshoe kidney
  6. Radial aplasia, hemivertebrae
  7. Clenched hands and overlapping fingers, syndactyly
  8. Hernias, imperforate anus
  9. Severe MR
  10. Rocker bottom feet

Features of Trisomy 13 (Patau Syndrome)

  1. Cardiac defects
  2. Holoprosencephaly, moderate microcephaly, microphthalmia
  3. Cleft lip/palate, abnormal ears
  4. Omphalocele
  5. Polycystic kidneys
  6. Radial aplasia
  7. Cutis aplasia
  8. Polydactyly

Features of Turner Syndrome (45XO)

  1. Short stature
  2. Broad chest, widely spaced nipples
  3. Congenital lymphedema
  4. Cubitus valgus
  5. Webbed posterior neck
  6. High arched palate
  7. Ovarian dysgenesis and infertility (90%)
  8. Aortic coarctation or bicuspid aortic valves
  9. Normal intelligence
  10. Hypoplastic uterus (due to lack of estrogen)

Aneuploidy Risk Associated with Major Structural Fetal Malformations


Aneuploidy risk (%)

Cystic hygroma








Cardiac defects


Diaphragmatic hernia






Duodenal atresia


Facial cleft




Limb reduction



  1. A teratogen is any agent that acts during embryonic or fetal development to produce a permanent alteration of form or function.
  2. The word teratogen is derived from the Greek "teratos," meaning monster. Because this derivation implies obvious visible defects, a teratogen is most properly defined as an agent that produces structural abnormalities.
  3. A hadegen-after Hades, (the god who possessed a helmet conferring invisibility)-is an agent that interferes with normal maturation and function of an organ.
  4. Identical defects with different etiologies are called phenocopies.
  5. Exposures within the first 8 weeks result in an embryopathy and after 8 weeks in a fetopathy.
  6. The preimplantation period is 2 weeks from fertilization to implantation and has traditionally been called the "all or none" period. The zygote undergoes cleavage and cells divide into an outer and inner cell mass. An insult damaging a large number of cells usually causes death of the embryo. If only a few cells are injured, compensation is usually possible with continued normal development.

Proven Human Teratogens



Adverse Effect on Fetus

1. Phenytoin

Fetal hydantoin syndrome (craniofacial defects, limb defects, MR)

2. Valproic acids

Spina bifida (1-2% lumbosacral type)

3. Warfarin

Nasal hypoplasia, stippled vertebral and femoral epiphyses, agenesis of corpus callosum, Dandy Walker malformation, midline cerebellar atrophy, microphthalmia, optic atrophy, blindness, MR (Conradi's syndrome)

4. ACE inhibitors

Oligohydramnios, renal anomalies, neonatal renal failure, pulmonary hypoplasia, hypocalvaria, growth restriction, death.

5. Isotretinoin

Craniofacial defects, cleft palate, cardiac defects, hydrocephalus, thymic defects

6. DES

Clear cell adenocarcinoma of cervix/vagina, ectropion and adenosis, hypoplastic T-shaped uterus, cervical collars, hoods, septa, withered fallopian tubes; in male fetuses epididymal cysts, microphallus, cryptorchidism, testicular hypoplasia, hypospadias.

7. Cyclophosphamide

Missing/hypoplastic digits, cleft palate, single coronary artery, imperforate anus, IUGR microcephaly

8. Methotrexate

IUGR failure of calvarial ossification, craniosynostosis, hypoplastic supraorbital ridges, small posteriorly rotated ears, micrognathia, severe limb abnormalities

9. Tetracyclines

Yellowish brown discoloration of deciduous teeth

10. Streptomycin

VIII cranial nerve damage (i.e., ototoxicity)

11. Griseofulvin

Conjoint twins

12. Tobacco

IUGR, subfertility, spontaneous abortion, abruption and preterm delivery, cleft lip and palate, Poland sequence

13. Cocaine

Placental abruption, abortions, stillbirth, skull defects, cutis aplasia, porencephaly, ileal atresia, cardiac anomalies and visceral infarcts, urinary defects, periventricular leukomalacia, prune-belly syndrome

14. Thalidomide


15. Misoprostol

Moebius syndrome


Features of Fetal Alcohol Syndrome


Growth restriction

Behavioral disturbances

Brain defects

Cardiac defects

Spinal defects


Short nose

Short palpebral tissues

Craniofacial anomalies

Absence of hypoplastic philtrum

Broad upper lip

Flattened nasal bridge

Hypoplastic upper lip vermillion


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