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Pregnancy and Down Syndrome Joseph Mohan University of Manchester MedicalEducation Society Oogenesis Process bywhich matureova (egg cells) areproduced in theovary. Primordial germ cells multiplyto form oogonia. Fusion of thespermatozoa and Fertilization theovum.Zygote formation Cleavage • Cleavage – process of repeated cell division of the fertilised egg to form a ball of cells that becomes the blastocyst. The cells (blastomeres) do not grow between Blastulation divisions and so they decrease in size. Blastocyst Bilaminar and Trilaminar Embryo Layers 1. BlastocystImplantation: Theinner cell mass of the blastocystdifferentiates into two layers: Epiblastand Hypoblast 2. Formation of theAmnioticand Yolk SacCavities:epiblastforms theamniotic cavity, hypoblast forms theliningof theprimitive yolksac 3. Bilaminar Disc: Theepiblastandhypoblasttogether form the bilaminarembryonic disc. • which givesrise to all future tissuesandorgans. the bilaminar disc into atrilaminarstructure, 1. Primitive Streak Formation:forms on surface ofepiblast.Cranial endformsprimitive node. 2. CellMigration andFormation of Germ Layers: o Cells fromthe epiblastmigrate toward the primitive streak andinvaginate,forming endoderm o Otherepiblast cells movebetween theepiblast andthenewly formedendoderm to form themesoderm. o The remaining epiblastcellsbecometheectoderm. • Ectoderm: Givesriseto thenervous system,skin,andsome sense organs. • Mesoderm:Forms muscles, bones,thecardiovascularsystem,andconnective tissues. • Endoderm: Formsthelining of thedigestivetract,respiratory tract, andotherinternalorgans. Major Morphogenetic Events up to Gastrulation rd • Notochordformation occurs during 3 week afterthe trilaminar disc.Itestablishes thebody’s axial skeleton,servingassignalling centrefor developmentincluding the neural tube. 1. Primitive Streak andNodeFormation: 2. Migration of EpiblastCells: 3. Formation of theNotochordal Process: 4. Formation of theNotochordal Plate: 5. Formation of theDefinitive Notochord: • Role of the Notochord: o Axial Structure: o InductiveSignals: o Vertebral Column Formation • In summary, the notochordformsduring thethirdweekof embryogenesis frommigrating epiblast cells,anditis crucial forthe patterningof thesurrounding tissues,includingthe nervoussystem andvertebral column.Physiological Changes in Expectant Mothers Cardiovascular: Respiratory:Elevated Increased blood tidal volume volume, cardiac output Endocrine:Hormonal Renal: Increased GFR, shifts (progesterone, fluid retention estrogen) Events that Initiate Labour Hormonal Uterine changes: Increase contractions, in oxytocin, cervical prostaglandins effacementRole of Human Chorionic Gonadotropin (hCG) Maintenance of corpus luteum and progesterone productionDetection of Early Pregnancy • Combined Oral Contraceptive (COC) or progesterone-only pill (POP). • Progesterone prevents pregnancy by stopping ovulation, decreases GRH release which decreases FSH Hormonal and LH preventing follicular development and release. Thickens Contraception: cervical mucus Comparison • Oestrogen similar but less significant inhibitory function • Efficacy: Pills, patches, IUDs, injections • Side effects: Thrombosis, mood changes • All pregnant women should be informed of the availability and benefit to aneuploidy screening and follow-up diagnostic testing • Type of screening is limited to Antenatal previous pregnancies, family Screening history, gestational age, desire to termination in case of abnormal Influences test. • The cffDNA can be reliably detected after 10 weeks of gestation. Key Genetic Terms Genotype – the genetic constitution of an individual or group, as determined by the particular set of genes it possesses. Phenotype - the observable characteristics of an individual, resulting from the interaction between its genotype and the environment. Allele – one of two or more alternative forms of the same gene, only one of which can be present in a chromosome. Inheritance Patterns and Recurrence Risk • Autosomal dominant e.g. Huntington’s, Marfan’s, PCKD • Only one parent needs to be a carrier to pass trait onto offspring Inheritance Patterns and Recurrence Risk • Autosomal recessive e.g. Cystic Fibrosis Sickle cell anaemia • Both parents must be carriers to be able to pass on trait to offspring Inheritance Patterns and Recurrence Risk • X-linked dominant/recessive e.g.red-green colour blindness, haemophilia A& BGenetic Screening and Down Syndrome • Combinedtest –10-14 weekspregnancyultra-soundandblood test. Detectsnuchaltranslucencyinultrasound. • Quadrupletest-14-20 weekspregnancy,detectsfoetus at riskofdowns syndrome • Ifincreased risk is detectedintests othertestsare warranted: • Non-invasive prenatal testing (NIPT)–a blood testaiming todetect chromosomaldisorders inthe cfDNA, looking foraneuploidyin trisomy21, trisomy18,trisomy13,extra sexchromosomes. • Amniocentesis removes amniotic fluid fromthe uterine cavityusinga andtherapeutic purposes,includingfordiagnosticevaluationin the form ofchromosomal,biochemical,histopathological,andmicrobial assessments. • ChorionicVillus Sampling-invasive procedure doneunderultrasound needle intothechorionfrondosum.Itis doneinthefirsttrimesterforor prenatal diagnosis between10 to14weeks. Down Syndrome • RFs – increasing gestational age • Presents with physical, cognitiveand behavioral symptoms. Chromosomal Abnormalities • Aneuploidy is the presence of an incorrect number of chromosomes in a cell. Chromosome segregation errors during either mitosis or meiosis lead to aneuploid cells containing a number of chromosomes that differs fromthe exact haploid number.Mitosis, Meiosis, and Aging • Aging affects female fertility resultinginreduced oocytequality andimplantationrates,andincreased spontaneousabortions • Theoccurrenceoffoetalmiscarriage gradually increasesfrom 5.3% inwomenaged ≤30 yearsto7.6%inwomenaged 31–34 years,12.8%in womenaged35–39 years and22.2% inwomen aged≥40years.Therefore,maternal ageisa significantinducer offemalegermcell aneuploidy butthe aetiology is stillnot well understood. • Womenof advancedmaternal age(≥35 years)havean increasedriskofchromosomesegregation errorsduring meiosis.Errorsthat affect chromosome segregationcanoccur atanystageduring oocytedevelopment. Antenatal care: NHS framework 2 pregnancy ultrasound scans: • Early pregnancy (dating or booking scan) at 11-14 weeks • Mid-pregnancy (anomaly) scan at 18-21 weeks Bloods: • FBC • Blood group and Rhesus • Sickle cell and thalassaemia • Hepatitis B, syphilis and HIV • Down’s/Edward’s/Patau’s syndromeFeedback Form https://docs.google.com/forms/d/1qokB4I9ne7I- fmsjRjQz4oQNdfNKGi_RwaEmurAumgg/editAnyquestions? Thank you