Paeds · genetics-dysmorphology-and-metabolism
Prenatal diagnosis and reproductive genetics
Also known as Prenatal genetic diagnosis · Antenatal genetic testing · Chorionic villus sampling · Amniocentesis · Chromosomal microarray · Prenatal exome sequencing · Preimplantation genetic testing · Carrier screening · Non-invasive prenatal diagnosis · Reproductive genetic counselling
Fellowship guide to prenatal diagnosis and reproductive genetics: screening versus diagnostic genetic testing, first-trimester combined screening and cell-free DNA, chorionic villus sampling and amniocentesis with contemporary procedure-related risk, chromosomal microarray versus karyotype, prenatal exome and genome sequencing, variant interpretation, Mendelian and empirical recurrence risk, expanded carrier screening, preimplantation genetic testing, non-invasive prenatal diagnosis, multidisciplinary coordination, and regional programme differences.
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Target exams
Red flags
- A positive screening result treated as a confirmed genetic diagnosis without counselling or diagnostic testing
- A variant of uncertain significance over-interpreted as pathogenic, or dismissed as benign
- A confined placental mosaicism on CVS reported as true fetal genotype without amniocentesis confirmation
- Legacy (high) procedure-related miscarriage risks quoted to deter families from needed diagnostic testing
- A normal microarray treated as exclusion of all single-gene or structural genetic disease
- A no-call cell-free DNA result relabelled as low-risk
- An inconclusive, declined or incomplete genetic result discharged without a named owner and safety-net
- A confirmed fetal genetic condition with no multidisciplinary or neonatal-team planning before delivery
Life stages
Care settings
Clinical exam formats
Board mappings
- Genetics and metabolic medicine
- General and Community Paediatrics
- Neonatal medicine
- Current 2026 PREP curriculum — genetics and metabolism
- Current 2026 PREP curriculum — fetal and neonatal medicine
- Renewed curriculum for first-year trainees from 2027 — essential general paediatrics
- Renewed curriculum for first-year trainees from 2027 — communication with patients, families, and health professionals
- Clinical Applications
- Medical Sciences
- Long Cases
- Short Cases
- Patient management
- Communication
- Genetics: prenatal counselling and the newborn with a prenatally diagnosed genetic condition
- Foundation of Practice (FOP)
- Theory and Science (TAS)
- Applied Knowledge in Practice (AKP)
- Clinical
- History
- General Pediatrics Content Outline — Domain related to Genetics and Metabolism
- General Pediatrics Content Outline — Universal Task 2: Epidemiology and Risk Assessment
- General Pediatrics Content Outline — Universal Task 3: Diagnosis
- General Pediatrics Content Outline — Universal Task 4: Management and Treatment
- Patient Care: prenatal genetic diagnosis and neonatal transition planning
- Systems-Based Practice: coordination of care across genetics, maternal-fetal medicine and neonatology
- Interpersonal and Communication Skills: non-directive family-centred genetic counselling
- Medical Expert
- Communicator
- Collaborator
- Pediatrics EPAs related to genetics and prenatal consultation
Overview & Definition
Prenatal diagnosis and reproductive genetics is the set of tests and counselling conversations that allow families and clinical teams to know the genetic status of a fetus before or at birth. The field spans carrier screening before pregnancy, aneuploidy and structural screening during pregnancy, invasive diagnostic procedures, molecular genetic tests of escalating resolution, and reproductive technologies such as preimplantation genetic testing. The paediatrician's role is to participate in antenatal multidisciplinary discussion, translate a confirmed genetic result into a postnatal plan, and own the medical-home function through birth and beyond. [6] [9]
The single most important distinction in this topic is screening versus diagnosis. Screening estimates a probability. Diagnostic testing confirms or excludes a condition. Cell-free DNA screening, first-trimester combined screening and the mid-trimester scan are screens — they tell you whether the chance of a problem is raised. Chorionic villus sampling, amniocentesis and the downstream molecular tests on those samples are diagnostic — they tell you what the chromosomes or genes actually are. Blurring that line is the most common and most dangerous counselling error in reproductive genetics. [3] [7]
The second key distinction is the resolution ladder of genetic testing. A karyotype sees whole chromosomes under the microscope. A chromosomal microarray detects submicroscopic copy-number variants — deletions and duplications — down to the kilobase level, which is why it is first-tier for structurally abnormal fetuses. Exome sequencing interrogates the coding regions of nearly all genes and finds single-nucleotide variants responsible for Mendelian disease. Genome sequencing reads the entire genome. Each step up the ladder increases diagnostic yield but also increases the chance of finding a variant of uncertain significance, which is why the counselling complexity rises with the resolution. [1] [6] [11]
What you actually do across the reproductive genetics pathway
- 1
Assess pre-test probability
Maternal age, family history, consanguinity, prior affected child, parental carrier status, BMI — interpret every result against this baseline.
- 2
Offer screening
Aneuploidy screening (combined or cfDNA), structural survey, carrier screening — document the result state, never leave a blank.
- 3
Confirm diagnostically
CVS or amniocentesis for genuinely raised risk; choose microarray, exome or targeted testing by the clinical question.
- 4
Interpret honestly
Pathogenic, likely pathogenic, VUS, likely benign, benign — state what each means and does not mean.
- 5
Close the loop
Multidisciplinary planning, reproductive options counselling, neonatal alert, named owner, postnatal confirmation and surveillance.
References11ShowHide
- [1]Wapner RJ, Martin CL, Levy B, et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. The New England journal of medicine, 2012.PMID 23215555
- [2]Reddy UM, Page GP, Saade GR, et al. Karyotype versus microarray testing for genetic abnormalities after stillbirth. The New England journal of medicine, 2012.PMID 23215556
- [3]Norton ME, Jacobsson B, Swamy GK, et al. Cell-free DNA analysis for noninvasive examination of trisomy. The New England journal of medicine, 2015.PMID 25830321
- [4]Salomon LJ, Sotiriadis A, Wulff CB, et al. Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis. Ultrasound in obstetrics & gynecology, 2019.PMID 31124209
- [5]Beta J, Zhang W, Geris S, et al. Procedure-related risk of miscarriage following chorionic villus sampling and amniocentesis. Ultrasound in obstetrics & gynecology, 2019.PMID 30977213
- [6]Stosic M, Levy B, Wapner R. The use of chromosomal microarray analysis in prenatal diagnosis. Obstetrics and gynecology clinics of North America, 2018.PMID 29428286
- [7]American College of Obstetricians and Gynecologists. Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin Summary, Number 226. Obstetrics and gynecology, 2020.PMID 32976375
- [8]Spinella F, Bronet F, Carvalho F, et al. ESHRE PGT Consortium data collection XXI: PGT analyses in 2018. Human reproduction open, 2023.PMID 37091225
- [9]Salomon LJ, Alfirevic Z, Berghella V, et al. ISUOG Practice Guidelines (updated): performance of the routine mid-trimester fetal ultrasound scan. Ultrasound in obstetrics & gynecology, 2022.PMID 35592929
- [10]Vossaert L, Wang Q, Salman R, et al. Reliable detection of subchromosomal deletions and duplications using cell-based noninvasive prenatal testing. Prenatal diagnosis, 2018.PMID 30357877
- [11]Lord J, McMullan DJ, Eberhardt RY, et al. Congenital heart disease and the Diagnostic yield with Exome sequencing (CODE) study: prospective cohort study and systematic review. Ultrasound in obstetrics & gynecology, 2021.PMID 32388881