Prenatal diagnosis is the science of identifying structural or functional abnormalities - birth by defects in the fetus

Etiology of Birth Defects

1.      Malformation- it is most common type of structural fetal abnormality. It is an intrinsic abnormality programmed in development regardless of whether a precise genetic etiology is known. e.g. Spina bifida

2.      Deformation- when a genetically normal fetus develops abnormally because of mechanical forces imposed by the uterine environment. e.g. an otherwise normal  limb  that  develops  contractures  because  of  prolonged oligohydraminos.

3.      Disruption- it is more severe change in form or function that occurs when genetically normal tissue is modified as the result of specific insult.e.g. Damage from an amniotic band causing a cephalocele or limb reduction abnormality.

4.      Syndrome - a cluster of several abnormalities of defects with having same cause. e.g. Trisomy 18

5.      Sequence - all anomalies developed sequentially as a result of one initial insult.

e.g. Oligohydraminos leading to pulmonary hypoplasa, limb contractures and facial deformities.

6.      Association - in which particular anomalies occur together frequently but do not seem to be linked etiologically. E.g. VATER association of vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, and radial dysplasia.

Risk involved

Baseline risk for having a child with a serious birth defect is 2-3%

Purpose of prenatal diagnosis:

·        To diagnose fetal anomalies and termination of pregnancy.

·        Provide a range of informed choice to the couple who are at high risk of having child with congenital abnormality

·        Reassurance and reduce anxiety, especially among high risk groups

·        Allow the high risk couples to know that the presence or absence of the disorder could be confirmed by testing

·        Allow the couples the option of appropriate management (psychological, pregnancy I delivery and postnatal)

·        To enable prenatal treatment of the affected fetus

Indications for Prenatal Diagnosis:

·        Singleton pregnancy and Advanced maternal age > 35 yrs (most important) - 1 in 385 risk of down syndrome and 1 in 178 risks of chromosomal abnormalities at term.

·        Previous pregnancy with chromosomal abnormality.

·        Chromosomal abnormality in either parent.

·        Family H/O chromosomal abnormality.

·        Bad obstetric history (H/O recurrent abortions).

·        Family H/O NTD.

·        Previous child birth having multiple malformations.

·        Couples at risk of inborn error of metabolism or NTD or sickle cell anemia.

·        One or both parents' carrier of sex linked or autosomal trait.

·        A mentally retarded child present.

·        Mother with H/O viral infections like rubella orcytomegalovirus.

·        Fetal sex determination in pregnancies at risk of a serious X linked recessive disorders. Parental consanguinity leading to hereditary or congenital abnormalities.

·        Maternal illnesses like poorly controlled diabetes mellitus and maternal epilepsy treated with antiepileptic drugs.

·        When mother have been exposed to high grade radiations.

·        Dizygotic twin pregnancy and maternal age older than 31 at delivery.

Role of Obstetrician in Prenatal Diagnosis:

·        Screening of all the pregnant women during the first or second trimester of pregnancy for chromosomal abnormalities and refer all the patients with positive screening to adequate facilities for counselling and further testing. (* Refer patient to higher centre for further management)

·        Screening of all pregnant women for fetal anomalies by ultrasound examination at 18- 20 weeks of gestation and refer all women with positive findings to adequate facilities for counselling and further testing.

Methods of Prenatal Diagnosis:

Non invasive                                                                                                           Invasive methods

•                          Maternal serum markers                                           •          Chronic villous sampling

•                          Double screen: Free β- hCG, PAPP-A, 11-14wks.               •                                                                                               Amniocentetis

•                          Triple screen: MSAFP + Free β-hCG+                  •          Fetal sampling unconjugated estriol 15-18 weeks.              •          Fetal biopsy

•                          Quadriple screen: MSAFP + Free β-hCG +                                                                                              •       Fetoscopy unconjugated estriol + inhibin A, 15_20 weeks

First Trimester Screening of Fetal Abnormalities

The 11 to 14 week window of gestational age is the best period to assess gestational age, to screen for fetal aneuploidy based on nuchal translucency (NT) and, to obtain a potentially detailed anatomic survey. Increased NT >3.5mm may be seen in trisomy 21, 18, 13, cardiac defects, diaphragmatic hernia, exomphalos and Noonan syndrome. Early termination of pregnancy has proven its medical and psychological benefits for women than with late termination.

Down syndrome is the most common chromosomal abnormality in liveborn children. It is caused by nondisjunction during meiosis, translocation, and inversion. A woman's risk of having fetus with Down syndrome depends on her age, the gestational age and her history of chromosomal defects. A 33yr old female at 10wks GA has 1 in 352 risk of having such fetus and it decreases with advancing gestation because of spontaneous death of fetuses with chromosomal anomalies, the risk decreases to 1 in 547 at 40wks.

Neural Tube Defects:

•                          Second most common major congenital defect (1-2/1000)

•                          Not a chromosomal anomaly

•                          Routinely tested and screened for in pregnancy

•                          Failure of neural tube to close at 28 days of gestation

•                          20% are closed lesions and difficult to detect prenatally

Risk Factors of NTDs

•                          Family history

•                          MTHFR - methylene tetrahyd rofolate reductase gene mutation.

•                          Aneuploidy – T13, 18, triploidy

•                          Diabetes

•                          Hyperthermia - hot tub, fever (controversial)

•                          Medications-valproic      acid,      carbamazepine, coumarin, aminopterin, thalidomide, efavirenz

•                          UK, India, China, Egypt, Mexico

•                          Syndromes associated like - Meckel Gubler syndrome, Roberts, HARDE

*Most common structural defects diagnosed prenatally during screening at 11 -1 4wks

•                          Atrioventricular defects and hypoplastic left heart syndrome

•                          Acrania

•                          Holoprosencephaly

•                          Omphalocoele and gastroschisis

•                          Megacystitis

•                          Lethal skeletal defects