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BSC SEM 4 UNIT 2 PATHOLOGY 2 & GENETICS.

UNIT 2 Maternal, prenatal and genetic influences on development of defects and diseases.

Maternal, Prenatal, and Genetic Influences on Development of Defects and Diseases

1. Maternal Influences

These refer to the mother’s health, habits, and environment during pregnancy that can directly affect fetal development.

a. Maternal Nutrition

  • Deficiency of folic acid – Can lead to neural tube defects like spina bifida.
  • Lack of iodine – May result in cretinism or intellectual disability.
  • Protein-energy malnutrition – Causes intrauterine growth retardation (IUGR), low birth weight.
  • Excessive vitamin A – Can be teratogenic (cause congenital malformations).

b. Maternal Infections (TORCH)

  • Toxoplasmosis
  • Other (Syphilis, Varicella, Zika)
  • Rubella – Can cause congenital rubella syndrome (CRS): deafness, heart defects, cataracts.
  • Cytomegalovirus (CMV) – Leads to microcephaly, hearing loss.
  • Herpes simplex virus (HSV) – May cause brain damage or death.

c. Chronic Maternal Illnesses

  • Diabetes mellitus – Associated with congenital heart defects, macrosomia.
  • Hypertension – Increases risk of placental abruption, IUGR.
  • Hypothyroidism – Affects brain development.

d. Substance Use and Lifestyle Factors

  • Smoking – Causes low birth weight, prematurity, increased SIDS risk.
  • Alcohol use – Leads to fetal alcohol spectrum disorders (FASD): growth problems, facial anomalies, intellectual disability.
  • Illicit drugs – Cocaine, heroin use may result in placental abruption, neonatal withdrawal.

e. Environmental Exposures

  • Radiation, pesticides, lead, or mercury exposure can cause developmental delays or physical defects.

2. Prenatal Influences

These involve conditions affecting the fetus during intrauterine life, including both maternal factors and others.

a. Placental Insufficiency

  • Results in inadequate nutrient and oxygen supply → IUGR, hypoxia, stillbirth.

b. Amniotic Fluid Abnormalities

  • Oligohydramnios – Can cause limb contractures, pulmonary hypoplasia.
  • Polyhydramnios – May be linked to gastrointestinal or neurological malformations.

c. Birth Injuries

  • From prolonged or obstructed labor, may cause cerebral palsy, brachial plexus injury.

d. Multiple Pregnancies

  • Higher risk of preterm birth, twin-to-twin transfusion syndrome (TTTS), growth discordance.

3. Genetic Influences

Genetic defects may be inherited or arise from mutations during gamete formation or early development.

a. Chromosomal Abnormalities

  • Numerical:
    • Down syndrome (Trisomy 21) – Intellectual disability, facial features, congenital heart defects.
    • Turner syndrome (XO) – Short stature, infertility, webbed neck.
  • Structural:
    • Deletion or translocation of genetic material (e.g., Cri-du-chat syndrome).

b. Single-Gene Disorders

  • Autosomal dominant – Marfan syndrome, neurofibromatosis.
  • Autosomal recessive – Cystic fibrosis, sickle cell anemia, thalassemia.
  • X-linked – Hemophilia, Duchenne muscular dystrophy.

c. Multifactorial Inheritance

  • Defects influenced by both genes and environment:
    • Cleft lip/palate, congenital heart defects, neural tube defects.

d. Mitochondrial Inheritance

  • Passed from mother only; can affect energy production, leading to neuromuscular diseases.

4. Interactions Between Genetics and Environment

  • A genetically susceptible fetus may develop disease only when exposed to environmental triggers.
    • Example: A fetus with a genetic predisposition to diabetes might express the disease if exposed to poor maternal glucose control.

🧬 Genetic Conditions Affecting the Mother and Their Impact on Fetal Development

Maternal genetic disorders can impact fetal development either directly through inheritance or indirectly by affecting the uterine environment, maternal health, or metabolism.


1. Single-Gene Disorders in the Mother

a. Phenylketonuria (PKU)

  • Cause: Autosomal recessive disorder affecting the breakdown of phenylalanine.
  • Impact: Even if the fetus does not inherit PKU, high maternal phenylalanine levels during pregnancy are teratogenic.
  • Fetal risks: Microcephaly, intellectual disability, congenital heart defects.
  • Management: Strict maternal dietary control before and during pregnancy.

b. Cystic Fibrosis (CF)

  • Carrier risk: If the mother is a carrier and the father is also a carrier, the child has a 25% chance of inheriting CF.
  • Impact on pregnancy: Severe maternal CF may affect nutrition and lung function, increasing the risk of preterm labor or low birth weight.

2. Chromosomal Abnormalities in the Mother

a. Balanced Translocations

  • A mother may carry a balanced chromosomal translocation (no symptoms herself), but it can lead to unbalanced chromosomes in the fetus → causing miscarriage or congenital abnormalities.

b. Turner Syndrome (Mosaic Forms)

  • Some women with mosaic Turner syndrome may conceive but have increased risk of pregnancy complications or miscarriage.

3. Multifactorial or Polygenic Conditions

a. Epilepsy with Genetic Basis

  • Some types of epilepsy have genetic links.
  • Risk: Antiepileptic drugs (AEDs) like valproic acid can be teratogenic, especially if not managed carefully.
  • Fetal risks: Neural tube defects, developmental delay.

b. Diabetes Mellitus (Type 1 or MODY)

  • Genetic predisposition in the mother can increase diabetes risk in offspring.
  • Poorly controlled maternal diabetes during pregnancy can cause:
    • Macrosomia (large baby)
    • Birth injuries
    • Congenital heart defects
    • Neonatal hypoglycemia

4. Mitochondrial Disorders

  • Mitochondrial DNA is maternally inherited.
  • If the mother has a mitochondrial disorder (e.g., MELAS syndrome), the fetus is at risk for neuromuscular or metabolic conditions.
  • Severity varies depending on the proportion of mutated mitochondria passed on.

5. Inherited Clotting Disorders

a. Factor V Leiden Mutation

  • Increases risk of thrombosis during pregnancy → can cause placental insufficiency, miscarriage, stillbirth.

b. Antiphospholipid Syndrome (autoimmune but with genetic susceptibility)

  • Associated with recurrent miscarriage, fetal growth restriction, or preeclampsia.

6. Family History or Carrier State

  • Even if the mother is asymptomatic, being a carrier of genetic disorders (e.g., thalassemia, sickle cell anemia, Tay-Sachs) poses a risk if the partner is also a carrier.
  • Genetic counseling and prenatal testing (e.g., amniocentesis, chorionic villus sampling) are important.

🦠 Conditions Affecting the Mother: Infections

Maternal infections can cross the placenta or affect the intrauterine environment, causing congenital anomalies, growth retardation, preterm labor, or fetal death. Some of the most critical infections are grouped under the TORCH complex, but other infections are also important.


🌟 1. TORCH Infections

These are a group of perinatal infections known for causing congenital defects:

InfectionEffects on FetusNotes
ToxoplasmosisHydrocephalus, intracranial calcifications, chorioretinitis, seizuresFrom undercooked meat or cat feces
Other (Syphilis, Varicella, Zika)Stillbirth, skeletal abnormalities (syphilis), limb hypoplasia (varicella), microcephaly (Zika)Syphilis and Zika can cross the placenta
Rubella (German measles)Congenital Rubella Syndrome – deafness, heart defects, cataracts, microcephalyMost dangerous in 1st trimester
Cytomegalovirus (CMV)Microcephaly, sensorineural deafness, hepatosplenomegaly, developmental delaysMost common congenital infection
Herpes Simplex Virus (HSV)Skin lesions, eye damage, encephalitis, deathUsually transmitted during vaginal delivery

🦠 2. Other Significant Maternal Infections

a. HIV/AIDS

  • Transmitted transplacentally, during delivery, or through breastfeeding.
  • Without treatment, risk of transmission is 25–40%.
  • ART during pregnancy and C-section delivery reduce risk.

b. Hepatitis B & C

  • HBV can be transmitted during delivery.
  • Newborn needs HBV vaccine + immunoglobulin (HBIG) within 12 hours.
  • HCV risk of transmission is lower but possible; no vaccine available.

c. Group B Streptococcus (GBS)

  • Found in maternal vaginal flora.
  • Can cause neonatal sepsis, pneumonia, or meningitis.
  • Mothers are screened at 35–37 weeks; treated with intrapartum antibiotics if positive.

d. Zika Virus

  • Causes severe microcephaly, brain anomalies, eye defects.
  • Transmitted by mosquito bites or sexual contact.

e. COVID-19

  • May increase risk of preterm birth, preeclampsia, and fetal distress.
  • Vertical transmission is rare, but maternal illness can affect fetal outcomes.

f. Listeriosis

  • Caused by Listeria monocytogenes from unpasteurized milk or soft cheeses.
  • Can result in miscarriage, stillbirth, or neonatal meningitis.

⚠️ Fetal Effects of Maternal Infections

  • Structural defects: brain, heart, eye anomalies.
  • Functional disorders: hearing loss, intellectual disability.
  • Growth issues: IUGR, low birth weight.
  • Neurological damage: seizures, developmental delay.
  • Fetal death or miscarriage.

💉 Prevention Strategies

  • Vaccination (Rubella, Hepatitis B, Influenza)
  • Prenatal screening for TORCH, HIV, GBS
  • Hygiene practices: avoid raw meat, wash hands, avoid cat litter
  • Safe sex practices
  • Avoidance of high-risk travel zones (e.g., Zika-endemic areas)

🌱 Maternal, Prenatal, and Genetic Influences on Development of Defects and Diseases


🧬 1. Genetic Influences

These are inherited or spontaneous abnormalities in the genetic material (DNA) that affect fetal development.

a. Chromosomal Abnormalities

  • Numerical: Extra or missing chromosomes
    • Example: Trisomy 21 (Down syndrome) – causes intellectual disability, heart defects.
  • Structural: Deletions, duplications, or translocations
    • Example: Cri-du-chat syndrome, Turner syndrome.

b. Single-Gene Disorders

  • Autosomal Dominant: Marfan syndrome, neurofibromatosis.
  • Autosomal Recessive: Thalassemia, cystic fibrosis.
  • X-linked: Hemophilia, Duchenne muscular dystrophy.

c. Multifactorial Inheritance

  • Interaction of multiple genes and environmental triggers.
    • Examples: Cleft lip/palate, neural tube defects, congenital heart disease.

d. Consanguinity

  • Refers to marriage or union between blood relatives (e.g., first cousins).
  • Increases the risk of autosomal recessive disorders because both parents may carry the same faulty gene.
    • Common conditions: Thalassemia, congenital deafness, metabolic disorders.

👩‍⚕️ 2. Maternal Influences

These are conditions or behaviors of the mother during pregnancy that affect fetal health.

a. Maternal Infections (TORCH)

  • Toxoplasmosis, Rubella, Cytomegalovirus, Herpes, Syphilis
    → Cause blindness, deafness, brain damage, congenital heart disease.

b. Chronic Illnesses

  • Diabetes → Risk of macrosomia, heart defects.
  • Hypertension → IUGR, preeclampsia.
  • Epilepsy (especially with teratogenic drugs like valproate) → Neural tube defects.

c. Nutrition

  • Folic acid deficiency → Neural tube defects.
  • Iodine deficiency → Cretinism (intellectual disability, stunted growth).
  • Malnutrition → Low birth weight, poor brain development.

d. Substance Use

  • Alcohol → Fetal Alcohol Syndrome.
  • Tobacco → Low birth weight, placental complications.
  • Drugs → Withdrawal symptoms, prematurity.

e. Atopy (Allergic Tendency)

  • A mother with atopy (genetic tendency to develop allergies like asthma, eczema, allergic rhinitis) can pass this predisposition to her child.
  • Not a structural defect but increases risk for allergic diseases in childhood.

🤰 3. Prenatal Influences

These include factors acting on the fetus during intrauterine life.

a. Placental Problems

  • Placental insufficiency → Reduced oxygen/nutrient supply → IUGR, stillbirth.

b. Amniotic Fluid Abnormalities

  • Oligohydramnios → Limb deformities, lung underdevelopment.
  • Polyhydramnios → Linked to GI or neurological anomalies.

c. Multiple Pregnancies

  • Higher risk of twin-to-twin transfusion syndrome, preterm birth, growth restriction.

d. Exposure to Teratogens

  • Radiation, chemicals (e.g., pesticides), certain medications → May cause birth defects depending on timing and dose.

🔍 Summary Table

CategoryExamplesPotential Effects
GeneticConsanguinity, chromosomal or single-gene disordersCongenital anomalies, inherited diseases
MaternalDiabetes, infections, atopy, malnutritionGrowth retardation, organ malformations, allergic risk
PrenatalAmniotic fluid imbalance, placental issues, teratogensPhysical deformities, developmental delay, prematurity

🧬 Consanguinity and Atopy: Their Influence on Child Development


1. Consanguinity (Blood Relationship)

Definition:
Consanguinity refers to a marriage or union between individuals who are closely related biologically, such as first cousins.

🔬 Why It Matters:

  • Close relatives share a significant percentage of genes.
  • If both parents carry the same recessive gene mutation, the risk of a child inheriting two copies of that faulty gene increases.
  • This raises the chances of genetic disorders in the child.

⚠️ Common Outcomes of Consanguineous Marriages:

  • Autosomal recessive disorders:
    • Thalassemia
    • Cystic fibrosis
    • Phenylketonuria (PKU)
    • Congenital deafness or blindness
    • Metabolic disorders (e.g., maple syrup urine disease)
  • Increased risk of:
    • Stillbirths
    • Intellectual disability
    • Congenital malformations
    • Infant mortality

💡 Prevention:

  • Genetic counseling before marriage or conception
  • Carrier screening for common inherited disorders (especially in high-risk communities)

2. Atopy (Allergic Tendency)

Definition:
Atopy is a genetic predisposition to develop allergic hypersensitivity reactions to common environmental substances.

🌿 Common Atopic Conditions:

  • Asthma
  • Eczema (Atopic dermatitis)
  • Allergic rhinitis (hay fever)
  • Food allergies

👶 Impact on the Child:

  • If one parent is atopic, the child has a 30–50% chance of developing allergies.
  • If both parents are atopic, the risk increases to 50–80%.
  • May cause chronic respiratory problems, skin issues, or food intolerances in childhood.

🧬 Difference from Genetic Defects:

  • Atopy does not usually cause structural birth defects.
  • It increases the risk of functional immune hypersensitivity.

🧾 Summary Table

FactorDefinitionEffect on Child
ConsanguinityMarriage between blood relativesHigher risk of inherited genetic disorders, birth defects
AtopyGenetic tendency to develop allergiesHigher risk of asthma, eczema, food allergies

🥗 Prenatal Nutrition and Food Allergies


🧠 1. Importance of Prenatal Nutrition

Prenatal nutrition refers to the mother’s diet during pregnancy, which plays a crucial role in:

  • Fetal growth and development
  • Organ formation
  • Immune system programming
  • Prevention of congenital defects

Key Nutrients Required During Pregnancy:

NutrientRoleDeficiency Effects
Folic acidPrevents neural tube defectsSpina bifida, anencephaly
IronSupports oxygen transportAnemia in mother, low birth weight
CalciumBone developmentWeak bones, muscle spasms
IodineBrain and thyroid functionCretinism, developmental delay
Omega-3 fatty acids (DHA)Brain and eye developmentPoor neurodevelopment
ProteinCell growth and repairIUGR, low muscle mass

🌾 2. Prenatal Nutrition and Food Allergies in the Child

Food allergies are abnormal immune responses to specific foods (e.g., milk, eggs, peanuts, soy, wheat, shellfish) that may appear early in childhood.

👶 How Maternal Diet Affects Fetal Allergy Risk:

a. Immune Programming
  • The fetus’s immune system begins developing in the womb.
  • What the mother eats can expose the fetus to food proteins, influencing whether the immune system tolerates or reacts to them.
b. Maternal Allergen Exposure
  • Current research suggests that eating common allergens during pregnancy (in moderation) may reduce the risk of allergies in the baby.
  • Early exposure helps the fetus develop tolerance rather than hypersensitivity.
c. Maternal Gut Health & Microbiota
  • A healthy maternal gut microbiome supports fetal immune development.
  • Probiotic and prebiotic foods during pregnancy may reduce risk of eczema and food allergy.
d. Vitamin D Deficiency
  • Low levels of Vitamin D in pregnancy are associated with increased asthma and allergy risk in the child.

⚠️ Dietary Recommendations (Based on Latest Guidelines)

DoAvoid
Eat a balanced diet including fruits, vegetables, whole grains, and proteinAvoid excessive restriction of allergenic foods unless medically indicated
Include probiotics (e.g., yogurt, fermented foods)Avoid processed and junk foods
Ensure adequate Vitamin D and Omega-3 intakeAvoid alcohol, raw meats, and unpasteurized foods

📌 Note on Food Avoidance

Earlier guidelines advised avoiding common allergenic foods during pregnancy. However, recent evidence suggests that avoiding allergens (like peanuts or eggs) may actually increase the child’s risk of food allergy.

👉 Unless the mother herself has a food allergy or medical reason to avoid certain foods, a varied and balanced diet is encouraged.


🧾 Summary Points

  • Prenatal nutrition is crucial for brain, immune, and organ development.
  • Maternal diet may influence whether the child develops tolerance or allergy to certain foods.
  • Balanced intake, especially of vitamins, omega-3s, and diverse foods, supports a healthy fetal immune system.
  • Unnecessary food restrictions may do more harm than good in allergy prevention.

👩‍🍼 Maternal Age and Its Impact on Fetal Development


🧬 1. What Is Maternal Age?

Maternal age refers to the age of the woman at the time of conception or delivery. It is an important factor that can affect:

  • Fertility
  • Pregnancy outcomes
  • Risk of birth defects and diseases in the baby

Both young mothers (under 18) and older mothers (over 35) face increased risks.


🔻 2. Risks Associated with Advanced Maternal Age (≥ 35 years)

a. Genetic and Chromosomal Disorders

  • Increased risk of meiotic errors in the egg.
  • Leads to chromosomal abnormalities like:
    • Down syndrome (Trisomy 21)
    • Edward syndrome (Trisomy 18)
    • Patau syndrome (Trisomy 13)

b. Pregnancy Complications

  • Gestational diabetes
  • Preeclampsia (high blood pressure)
  • Placenta previa or placental abruption
  • Higher chance of C-section

c. Infertility and Miscarriage

  • Reduced egg quality with age.
  • Increased risk of spontaneous abortion in the first trimester.

d. Low Birth Weight and Preterm Delivery

  • Age-related uterine or placental insufficiency can affect fetal growth.

🔺 3. Risks Associated with Teenage Pregnancy (< 18 years)

a. Physical Immaturity

  • Pelvis may be underdeveloped → Complications in labor.

b. Nutritional Deficiency

  • Young mothers may compete with the fetus for nutrients (like calcium, iron) → Fetal growth retardation.

c. Poor Prenatal Care

  • Late or inadequate antenatal visits.
  • Higher risk of preterm birth, low birth weight, and neonatal mortality.

d. Social and Emotional Stress

  • Can affect mental health, bonding, and child-rearing capacity.

📊 Comparison Table

Age GroupRisks to BabyRisks to Mother
< 18 yearsPreterm birth, low birth weight, IUGRAnemia, eclampsia, obstructed labor
19–34 years (optimal)Lowest risk of birth defectsHealthy pregnancy outcomes
≥ 35 yearsDown syndrome, miscarriage, stillbirthHypertension, diabetes, C-section

🧾 Key Takeaways

  • Optimal maternal age for pregnancy: 20–34 years.
  • Advanced maternal age (35+) increases risk of chromosomal defects, infertility, and complications.
  • Teenage pregnancies carry high risk due to biological immaturity and poor nutrition.
  • Regardless of age, proper prenatal care, nutrition, and lifestyle management can reduce risks.

💊 Maternal Drug Therapy and Its Impact on Fetal Development


🧬 1. What is Maternal Drug Therapy?

Maternal drug therapy refers to any medications, supplements, or substances taken by the mother before or during pregnancy.
These drugs can cross the placenta and affect the developing fetus, especially during critical periods of organ development (first trimester).


⚠️ 2. Teratogenic Effects of Drugs

Teratogens are agents (drugs, chemicals, infections) that can cause structural or functional defects in the fetus.

🕒 Critical Period:

  • First trimester (weeks 3–12) is the most sensitive period for structural abnormalities.
  • Later trimesters may affect growth, brain development, or organ function.

🔍 3. Examples of Harmful (Teratogenic) Drugs

Drug/ClassPotential Fetal Effect
ThalidomideLimb deformities (phocomelia)
Isotretinoin (for acne)Severe birth defects (brain, heart, face)
ACE inhibitors (for BP)Renal failure, skull defects
Tetracycline antibioticsTooth discoloration, inhibited bone growth
Valproic acid (antiepileptic)Neural tube defects
Warfarin (anticoagulant)Nasal hypoplasia, bleeding
Cytotoxic drugs (e.g., methotrexate)Miscarriage, malformations
AlcoholFetal Alcohol Syndrome: facial defects, intellectual disability
High doses of Vitamin AHeart and cranial defects

🟢 4. Safe Drug Use in Pregnancy

  • Not all drugs are harmful. Some are essential for the mother and must be continued with caution.
  • Always assess risk vs. benefit before prescribing or continuing any drug.

Examples of Safer Drugs (under medical supervision):

  • Paracetamol (for pain/fever)
  • Folic acid (prevents neural tube defects)
  • Iron supplements (prevents anemia)
  • Prenatal multivitamins
  • Insulin (for gestational diabetes)
  • Certain antibiotics (e.g., amoxicillin)

📌 FDA Pregnancy Risk Categories (Now Replaced with Narrative Labels)

Old system (still commonly referred to):

CategoryMeaning
ANo risk in controlled studies
BNo evidence of risk in humans
CRisk cannot be ruled out
DEvidence of human fetal risk
XContraindicated in pregnancy (high risk)

🤰 5. Special Considerations in Maternal Drug Therapy

  • Dose, duration, timing, and route of administration affect fetal exposure.
  • Use lowest effective dose for the shortest duration.
  • Avoid self-medication during pregnancy.
  • Preconception counseling is important for women with chronic illnesses (e.g., epilepsy, diabetes, hypertension) who require medications.

🧾 Summary

AspectDetails
DefinitionDrug use by a mother during pregnancy
Risk PeriodHighest in first trimester (organogenesis)
Harmful DrugsValproate, isotretinoin, thalidomide, warfarin
Safe Drugs (under medical advice)Folic acid, paracetamol, insulin, certain antibiotics
PreventionCareful prescribing, prenatal counseling, avoid self-medication

🧪🤰 Prenatal Testing and Diagnosis


🧬 1. What is Prenatal Testing?

Prenatal testing refers to the medical tests done during pregnancy to:

  • Assess the health and development of the fetus
  • Detect any congenital abnormalities or genetic disorders
  • Monitor maternal-fetal well-being

There are two main categories:

  1. Screening tests – estimate the risk of a condition
  2. Diagnostic tests – confirm whether a fetus has a specific condition

📋 2. Types of Prenatal Tests


🧪 A. Screening Tests (Non-invasive, low risk)

TestTimingPurpose
Ultrasound (NT scan)11–13 weeksMeasures nuchal translucency → risk of Down syndrome
First Trimester Screening11–14 weeksCombines NT scan + blood tests (hCG, PAPP-A)
Second Trimester Quadruple Test15–20 weeksDetects risk of Down syndrome, Trisomy 18, neural tube defects
Non-Invasive Prenatal Testing (NIPT)From 10 weeksAnalyzes fetal DNA in maternal blood for chromosomal disorders

Screening tests do not confirm a disorder but help identify high-risk pregnancies for further testing.


🧬 B. Diagnostic Tests (More accurate but invasive)

TestTimingMethodWhat It Detects
Chorionic Villus Sampling (CVS)10–13 weeksPlacental tissue sampleGenetic/chromosomal conditions like Down syndrome, Tay-Sachs
Amniocentesis15–20 weeksAmniotic fluid sampleChromosomal disorders, neural tube defects
Fetal Blood Sampling (Cordocentesis)After 18 weeksFetal blood from umbilical cordBlood disorders, infections

These tests carry a small risk of miscarriage and are usually offered if the mother is high-risk.


📌 3. Indications for Prenatal Testing

  • Maternal age ≥ 35 years
  • Abnormal screening test results
  • Previous child with a genetic disorder
  • Family history of inherited diseases
  • Known carrier status (e.g., thalassemia)
  • Maternal infections (e.g., TORCH)
  • Exposure to teratogens

👶 4. Conditions Commonly Detected

TypeExamples
Chromosomal abnormalitiesDown syndrome (Trisomy 21), Edward syndrome (Trisomy 18), Patau syndrome (Trisomy 13)
Neural tube defectsSpina bifida, anencephaly
Genetic disordersCystic fibrosis, sickle cell anemia, thalassemia
Structural anomaliesHeart defects, cleft lip/palate (via ultrasound)

🧾 5. Benefits and Ethical Considerations

Benefits

  • Informed decision-making for parents
  • Early preparation for special needs care
  • Option for medical or surgical interventions (in some cases)

⚠️ Ethical Concerns

  • Decision about pregnancy continuation
  • Risk of anxiety, stress
  • Cultural and religious beliefs may affect choices

🧠 Summary

TypePurposeExamples
ScreeningEstimate riskNT scan, NIPT, blood tests
DiagnosticConfirm conditionAmniocentesis, CVS
UltrasoundStructural assessmentDetect physical abnormalities

🧬👶 Prenatal Testing and Diagnosis.


1. What is Prenatal Testing and Diagnosis?

Prenatal Testing involves medical evaluations during pregnancy to assess:

  • Fetal growth and development
  • Risk or presence of congenital defects
  • Maternal-fetal health

Tests are classified into:

TypePurposeExample
Screening testsEstimate the risk of a conditionNT scan, NIPT, Quad test
Diagnostic testsConfirm the presence of a conditionAmniocentesis, CVS

These tests help identify problems arising from genetic, maternal, or prenatal (environmental) factors.


🔍 2. Maternal, Prenatal, and Genetic Influences on Development of Defects and Diseases


👩‍⚕️ A. Maternal Influences

These are conditions or exposures in the mother that affect the fetus:

FactorEffect on Fetus
Maternal age ≥ 35 yearsHigher risk of Down syndrome
Poor nutrition (e.g. folic acid deficiency)Neural tube defects
Maternal infections (TORCH)Brain damage, blindness, deafness
Chronic illness (diabetes, epilepsy)Congenital heart disease, neural tube defects
Drug or alcohol useFetal Alcohol Syndrome, malformations
SmokingLow birth weight, premature birth
Atopy (allergic tendency)Increased risk of allergies, eczema, asthma
ConsanguinityIncreases chance of autosomal recessive genetic disorders

Prenatal testing (like ultrasound, blood tests, NIPT) helps detect abnormalities early in at-risk mothers.


🤰 B. Prenatal (Environmental) Influences

These are influences during pregnancy that affect fetal growth and organ development:

FactorEffect on Fetus
Placental insufficiencyIUGR, stillbirth
Amniotic fluid abnormalitiesSkeletal or lung defects
Teratogen exposure (radiation, chemicals)Physical malformations, brain defects
Multiple gestationTwin-to-twin transfusion, prematurity
Stress or traumaPremature labor, fetal distress

Ultrasound, Doppler studies, and fetal monitoring can assess these prenatal risks.


🧬 C. Genetic Influences

These are inherited or spontaneous mutations affecting fetal health:

TypeExamplesEffect
Chromosomal disordersDown syndrome (Trisomy 21), Turner syndromeIntellectual disability, heart defects
Single-gene disordersThalassemia, cystic fibrosis, PKUInherited metabolic/blood disorders
Multifactorial inheritanceCleft lip, neural tube defectsCombined genetic + environmental factors
Mitochondrial disordersMELASEnergy metabolism issues

Genetic screening, carrier testing, NIPT, CVS, and amniocentesis help identify such conditions early.


🧪 3. Common Prenatal Tests and What They Detect

TestTimingWhat It Detects
Nuchal Translucency (NT) Scan11–14 weeksDown syndrome risk
Non-Invasive Prenatal Testing (NIPT)From 10 weeksTrisomies 21, 18, 13
Quadruple Marker Test15–20 weeksNeural tube defects, Down syndrome
Chorionic Villus Sampling (CVS)10–13 weeksChromosomal/genetic disorders
Amniocentesis15–20 weeksChromosomal abnormalities, neural tube defects
Anomaly Scan (Level 2)18–22 weeksStructural defects (brain, heart, limbs)

📌 Summary Chart

Influence TypeExamplesFetal RiskDetection Method
MaternalInfections, drugs, age, nutritionMalformations, IUGR, syndromesBlood tests, ultrasound, history
PrenatalPlacenta, fluid, teratogensOrgan damage, prematurityUltrasound, Doppler, monitoring
GeneticTrisomies, inherited disordersCongenital syndromesCVS, amniocentesis, NIPT

☢️💊🧪 Effect of Radiation, Drugs, and Chemicals on Fetal Development.


🔬 I. Effects of Radiation, Drugs, and Chemicals

These are teratogens—agents that cause structural or functional defects in the developing fetus, especially during the first trimester (organogenesis period).


☢️ A. Radiation

  • Ionizing radiation (e.g., X-rays, nuclear exposure) can damage dividing cells of the embryo.
  • Critical exposure in early pregnancy (2–8 weeks) can lead to:
    • Microcephaly
    • Intellectual disability
    • Growth restriction
    • Eye abnormalities
    • Increased childhood cancer risk (e.g., leukemia)

🔎 Risk increases with high doses (> 10 rads); diagnostic X-rays are usually safe but should be avoided unless essential.


💊 B. Drugs

❌ Harmful (Teratogenic) Drugs:

DrugEffect on Fetus
ThalidomideLimb deformities (phocomelia)
Isotretinoin (Vitamin A derivative)Craniofacial, brain, and heart defects
Valproic acidNeural tube defects
ACE inhibitorsKidney failure, skull defects
TetracyclineTooth discoloration, bone growth issues
WarfarinNasal hypoplasia, brain hemorrhage
Cytotoxic drugs (e.g., methotrexate)Miscarriage, birth defects
AlcoholFetal Alcohol Syndrome: facial deformity, mental retardation
Recreational drugsGrowth delay, behavior issues, withdrawal in newborn

Safe drugs include folic acid, iron, paracetamol, and insulin—when used appropriately under medical advice.


🧪 C. Chemicals and Pesticides

  • Exposure to lead, mercury, arsenic, industrial solvents, pesticides can result in:
    • Miscarriage
    • Stillbirth
    • Brain damage (e.g., Minamata disease from mercury)
    • Limb and organ malformations
    • Cancer risk later in life

🚫 High-risk occupations (factories, agriculture) require protective measures during pregnancy.


🧬👩‍⚕️ II. Maternal, Prenatal, and Genetic Influences on Defects and Diseases

These three categories represent internal and external risk factors for abnormal fetal development.


👩‍⚕️ A. Maternal Influences

Maternal FactorEffect on Baby
Maternal age ≥ 35 yearsDown syndrome, miscarriage
Malnutrition (folic acid/iodine deficiency)Neural tube defects, cretinism
Infections (TORCH)Microcephaly, blindness, deafness
Substance abuse (alcohol, tobacco)FASD, low birth weight, developmental delay
Chronic illness (diabetes, epilepsy)Heart defects, neural tube defects
ConsanguinityIncreased risk of genetic defects
AtopyIncreases allergic disease risk in child

🤰 B. Prenatal Influences (Environmental)

FactorEffect on Fetus
Placental insufficiencyIUGR, preterm birth, stillbirth
Abnormal amniotic fluidSkeletal or lung anomalies
Multiple gestationGrowth restriction, prematurity
Exposure to teratogens (radiation, drugs, chemicals)Malformations, miscarriage
Maternal trauma or stressPreterm labor, fetal distress

🧬 C. Genetic Influences

TypeExamplesEffect on Child
ChromosomalTrisomy 21 (Down syndrome), Turner syndromeIntellectual disability, physical defects
Single-gene disordersThalassemia, cystic fibrosis, PKUMetabolic/blood disorders
Mitochondrial inheritanceMELAS syndromeNeurological or energy metabolism issues
Multifactorial inheritanceCleft lip, neural tube defectsGenetic + environmental impact

📌 Summary Chart

InfluenceExamplesRisk/Outcome
RadiationX-rays, nuclear exposureMicrocephaly, growth retardation
DrugsValproic acid, thalidomideMalformations, fetal death
ChemicalsLead, mercury, pesticidesBrain damage, birth defects
MaternalAge, illness, infection, malnutritionSyndromes, IUGR, miscarriage
PrenatalPlacental issues, environmentPreterm birth, organ defects
GeneticDown syndrome, thalassemiaCongenital diseases, intellectual disability

🚫🤰 Infertility.


I. What is Infertility?

Infertility is defined as the inability to conceive after 12 months of regular, unprotected sexual intercourse.

  • Primary infertility: Never conceived
  • Secondary infertility: Conceived before but unable to again

It affects both men and women, but here we focus on maternal infertility and its consequences on pregnancy outcomes and fetal health.


🔬 II. Causes of Maternal Infertility

CauseExamples
Hormonal disordersPCOS, thyroid disease, hyperprolactinemia
Structural issuesBlocked fallopian tubes, uterine fibroids, adhesions
Ovulation problemsIrregular periods, anovulation
Age-related declineOvarian reserve decreases after 35
EndometriosisInflammatory damage to reproductive organs
Lifestyle factorsSmoking, stress, obesity, underweight
Genetic disordersTurner syndrome, Fragile X premutation

⚠️ III. Infertility and Assisted Reproductive Technology (ART)

When natural conception fails, many couples undergo ART, such as:

  • IVF (In vitro fertilization)
  • ICSI (Intracytoplasmic sperm injection)
  • Hormonal stimulation therapies

However, these can come with increased risks to fetal development.


🧬👶 IV. Maternal, Prenatal, and Genetic Influences on Fetal Defects and Diseases (in the Context of Infertility)


👩‍⚕️ A. Maternal Influences (in Infertile Women or ART pregnancies)

FactorEffect on Baby
Advanced maternal age (common in infertility)Increased risk of Down syndrome, miscarriage
Ovarian hyperstimulationMay cause preterm birth, low birth weight
Underlying disorders (e.g., PCOS, endometriosis)Placental dysfunction, gestational diabetes
Multiple embryo transfer (in IVF)High chance of twins/triplets → prematurity, IUGR
Medications used in ARTMay affect early development if not closely monitored

🤰 B. Prenatal Influences (Post-Conception in Infertility Cases)

FactorImpact on Fetus
Multiple gestation (common in IVF)Twin-to-twin transfusion, growth discordance
Placental issuesPre-eclampsia, IUGR, stillbirth
Amniotic fluid abnormalitiesCommon in ART pregnancies; risk of malformations
Preterm deliveryMore likely in ART or older mothers

🧬 C. Genetic Influences

Genetic IssueEffect
Parental chromosomal abnormalities (e.g., balanced translocation)Can cause infertility and miscarriage
Gene mutations in mother or egg donorCan be passed to child (e.g., cystic fibrosis if both are carriers)
Mitochondrial DNA disordersMay be inherited maternally, especially with egg aging

Prenatal genetic testing (NIPT, amniocentesis) is often recommended in ART pregnancies due to these increased risks.


📌 Summary Table

AspectExamplesFetal Impact
Infertility causesPCOS, blocked tubes, ageDifficulty conceiving; higher-risk pregnancies
Maternal influenceAdvanced age, hormone therapyMiscarriage, genetic syndromes, low birth weight
Prenatal influenceIVF, multiple embryosPrematurity, IUGR, complications
Genetic influenceChromosomal defects, inherited disordersDown syndrome, thalassemia, metabolic defects

🧪💡 Special Note: Role of Prenatal Testing in Infertility Pregnancies

  • Screening: NT scan, NIPT, triple test
  • Diagnostic: Amniocentesis, chorionic villus sampling (CVS)
  • Used more frequently in infertility/ART pregnancies to detect:
    • Chromosomal defects
    • Structural abnormalities
    • Genetic diseases

🩸🤰 Spontaneous Abortion (Miscarriage).


I. What is Spontaneous Abortion?

Spontaneous abortion is the natural loss of a pregnancy before 20 weeks of gestation, without any medical or surgical intervention.

  • Occurs in 10–20% of clinically recognized pregnancies
  • Can be symptomatic (bleeding, cramping) or missed (fetus dies but is not expelled immediately)

📚 II. Types of Spontaneous Abortion

TypeDescription
ThreatenedVaginal bleeding, cervix closed, pregnancy may continue
InevitableBleeding + dilated cervix, miscarriage will occur
IncompleteSome products of conception expelled; others remain inside
CompleteAll products expelled; uterus empty
MissedFetal death without expulsion; no bleeding
SepticInfection in the uterus after miscarriage

🧬👩‍🍼 III. Maternal, Prenatal, and Genetic Influences on Spontaneous Abortion and Fetal Defects


👩‍⚕️ A. Maternal Influences

FactorRisk/Effect
Advanced maternal age (> 35 years)Higher risk of miscarriage and chromosomal defects
Uncontrolled diabetes or thyroid disordersIncreased miscarriage risk
Maternal infections (TORCH, syphilis)Can cause fetal death or malformations
Substance abuse (alcohol, tobacco, drugs)Spontaneous abortion, low birth weight
Uterine anomalies (fibroids, septum)Implantation failure or miscarriage
Immunological causesAntiphospholipid syndrome, autoimmune disorders
Malnutrition (e.g., folate deficiency)Neural tube defects, placental problems

🤰 B. Prenatal Influences

FactorEffect
Radiation exposureFetal cell damage → miscarriage or malformations
Exposure to teratogenic drugs/chemicalsEmbryotoxicity → spontaneous abortion
Infections during early pregnancyIntrauterine infection → fetal loss
Trauma or high stressLinked to hormonal imbalance and fetal loss
Hormonal imbalanceInadequate progesterone → implantation failure or early miscarriage

🧬 C. Genetic Influences

CauseEffect
Chromosomal abnormalities (in embryo)Cause of ~50–60% of first-trimester miscarriages
Trisomy, monosomy (e.g., Turner’s syndrome)Incompatible with life → spontaneous abortion
Inherited gene mutationsMay cause lethal malformations
ConsanguinityIncreases risk of autosomal recessive disorders and miscarriage

Genetic testing (e.g., karyotyping of products of conception) is often recommended after recurrent miscarriage.


🔬 IV. Diagnosis and Management

📋 Diagnosis

  • Ultrasound: To check fetal heartbeat and growth
  • hCG levels: Falling levels may indicate pregnancy loss
  • Pelvic exam: To assess cervix and bleeding

🛠️ Management

TypeTreatment
ThreatenedRest, close monitoring
Inevitable/IncompleteSurgical (D&C), medical (misoprostol)
MissedSurgical evacuation or expectant management
SepticAntibiotics + uterine evacuation

📌 Summary Table

Influence TypeExamplesEffect on Pregnancy
MaternalAge, illness, infection, uterine anomalyMiscarriage, IUGR, malformations
PrenatalRadiation, drugs, trauma, infectionMiscarriage, structural defects
GeneticTrisomy, monosomy, inherited disordersLethal anomalies → miscarriage

🧠 Key Takeaways

  • Spontaneous abortion is a common but distressing event that can result from a wide range of genetic, maternal, or environmental factors.
  • Proper prenatal care, screening, and counseling can help prevent or prepare for risks.
  • In cases of recurrent miscarriage, further genetic and hormonal investigations are essential.

🧠🔻 Neural Tube Defects (NTDs) and the Role of Folic Acid in Lowering the Risks


🧬 I. What Are Neural Tube Defects (NTDs)?

Neural Tube Defects (NTDs) are serious birth defects of the brain, spine, or spinal cord that occur when the neural tube fails to close properly during early fetal development.

🗓️ Timing: The neural tube closes between day 21 and day 28 of pregnancy (often before the woman even knows she’s pregnant).


🔍 II. Types of Neural Tube Defects

NTD TypeDescriptionOutcome
Spina BifidaIncomplete closure of the spine and spinal cordPhysical disability, paralysis, bowel/bladder problems
AnencephalyAbsence of major parts of the brain and skullUsually fatal within hours/days after birth
EncephaloceleBrain tissue protrudes through an opening in the skullCan cause seizures, intellectual disability

⚠️ III. Risk Factors for Neural Tube Defects

CategoryExamples
NutritionalFolic acid deficiency
GeneticFamily history of NTDs
Maternal conditionsDiabetes, obesity
Drug exposureAntiepileptic drugs (valproic acid)
EnvironmentalExposure to high heat (fever, hot tubs) during early pregnancy

🍀 IV. Role of Folic Acid in Preventing NTDs

✅ What is Folic Acid?

  • A B-complex vitamin (Vitamin B9) that helps in DNA synthesis, cell division, and neural tissue development.

🛡️ How Does It Prevent NTDs?

  • Folic acid supports normal neural tube closure during the first few weeks of pregnancy.
  • It reduces the risk of NTDs by 50–70% when taken adequately before conception and in early pregnancy.

💊 V. Folic Acid Supplementation Guidelines

GroupRecommended Dose
All women of reproductive age400 mcg/day (even if not planning pregnancy)
Women planning pregnancy or pregnant400–600 mcg/day
High-risk women (e.g., previous NTD baby, on antiepileptic drugs)4 mg/day (4,000 mcg), under medical supervision

Should be taken at least 1 month before conception and continued through the first trimester.


🧾 VI. Food Sources of Folate

Natural FolateFolic Acid (Fortified)
Green leafy vegetables (spinach, kale)Fortified cereals
Legumes (lentils, beans)Enriched flour and rice
Citrus fruitsMultivitamin tablets
Eggs, nutsPrenatal supplements

📌 Summary Table

AspectDetails
NTDsBirth defects of brain/spine due to neural tube closure failure
TypesSpina bifida, anencephaly, encephalocele
Risk PeriodDay 21–28 of gestation (very early!)
PreventionFolic acid 400–600 mcg/day
High-Risk Dose4 mg/day (with prior NTDs or medications)

🧠 Key Takeaways

  • NTDs are largely preventable with adequate folic acid intake.
  • Folic acid must be taken before conception and during early pregnancy for full protective effect.
  • It’s a low-cost, safe, and effective public health measure.

🧬👶 Down Syndrome (Trisomy 21)


📚 I. What is Down Syndrome?

Down Syndrome is a genetic disorder caused by the presence of an extra copy of chromosome 21 (i.e., Trisomy 21).

  • Normal humans have 46 chromosomes (23 pairs).
  • In Down syndrome, there are 47 chromosomes due to an extra 21st chromosome.
  • This extra genetic material causes developmental delays, intellectual disability, and physical features characteristic of the condition.

🔬 II. Types of Down Syndrome

TypeDescriptionFrequency
Trisomy 21 (95%)Every cell has 3 copies of chromosome 21Most common
Translocation (4%)Extra chromosome 21 is attached to another chromosomeCan be inherited
Mosaicism (1%)Some cells have Trisomy 21, others are normalMilder symptoms

🔎 III. Causes and Risk Factors

👩‍⚕️ Maternal Influence

  • Advanced maternal age is the most significant risk factor:
    • Age 25: 1 in 1,300 chance
    • Age 35: 1 in 350
    • Age 40: 1 in 100
    • Age 45: 1 in 30

🧬 Genetic Influence

  • Mostly due to random errors in cell division (nondisjunction)
  • Translocation Down syndrome can be inherited (especially if a parent is a balanced carrier)

🧠 IV. Clinical Features of Down Syndrome

SystemFeatures
FacialFlat facial profile, small nose, upward slanting eyes, epicanthal folds
Head and HandsSmall head, short neck, single palmar crease, short fingers
DevelopmentalIntellectual disability (mild to moderate), delayed speech/motor skills
CardiacCongenital heart defects (AV canal, VSD, ASD) in ~50%
GI TractDuodenal atresia, Hirschsprung disease
OtherHypotonia (low muscle tone), increased risk of leukemia, thyroid disorders, early-onset Alzheimer’s disease

🧪 V. Diagnosis and Prenatal Detection

A. Screening Tests (Non-invasive)

  • First trimester: NT scan + serum markers (PAPP-A, hCG)
  • Second trimester: Triple or quadruple marker test
  • NIPT (Non-Invasive Prenatal Testing): Cell-free fetal DNA from maternal blood (high accuracy)

B. Diagnostic Tests (Invasive)

TestTimingSampleConfirmatory
Chorionic Villus Sampling (CVS)10–13 weeksPlacental tissueYes
Amniocentesis15–20 weeksAmniotic fluidYes
CordocentesisAfter 18 weeksFetal bloodYes

❤️ VI. Management and Support

Down syndrome cannot be cured, but early intervention and supportive care can greatly improve quality of life.

🌱 Care Focus:

  • Cardiac surgery (if heart defects)
  • Speech, occupational, and physical therapy
  • Special education programs
  • Regular health check-ups (vision, hearing, thyroid, etc.)
  • Family counseling and support groups

📌 VII. Summary Table

AspectDescription
CauseExtra copy of chromosome 21 (Trisomy 21)
Risk FactorAdvanced maternal age, genetic translocation
FeaturesIntellectual disability, facial features, heart/GI defects
DiagnosisNIPT, NT scan, amniocentesis
TreatmentSupportive: therapies, surgeries, education

🧠 Key Points

  • Down syndrome is a common genetic disorder with a wide range of developmental and physical impacts.
  • Risk increases with maternal age, but it can occur at any age.
  • Prenatal screening and diagnosis are important for early detection.
  • With proper care, individuals with Down syndrome can live healthy and fulfilling lives.
Published
Categorized as BSC SEM 4 PATHOLOGY 2 & GENETICS, Uncategorised