DOHAD Flashcards
What is a birth defect defined as?
Structural or functional anomaly which is present at conception or occurs before the end of pregnancy and is either diagnosed in pregnancy or before 6 years of age.
What structural developmental anomalies can affect young foetuses?
Spina bifida
Congenital cardiac defects
Congenital dislocation of the hips
What functional developmental anomalies can affect young foetuses?
Cystic fibrosis
Haemophilia
What is the incidence of developmental anomalies in WA?
5% (1:20)
What is the job of the WARDA?
WARDA is the Western Australian Register for Developmental Anomalies. They collect data on developmental anomalies and cerebral palsy in WA.
WARDA collects data to guide research and investigation into causes, prevention, and management of developmental anomalies.
Notifications to WARDA are mandatory since 2011.
Each individual defect is coded according to the 5-digit British paediatric association ICD-9 system.
What are birth defects associated with?
Major cause of death.
Birth defect is present in 12.4% of still births and 28.9% of neonatal deaths.
Who are birth defects more common in?
Males and multiple pregnancies.
What are WARDAs diagnostic categories of birth defects? Which is most common?
Most common are musculoskeletal defects (in 2014)
Nervous system defects (4.2/1000 births annually)
Urogenital defects
Congenital abnormalities of the eye, ear, face, and neck
Congenital anomalies of the inegument
Cardiovascular defects (common)
Chromosome defects (common)
Respiratory system defects
GI defects
Other
What are the most common nervous system defects?
Neural tube defects (1.2/1000 births):
Anencephaly
Spina bifida
Encephalocele
Other nervous system defects:
Microcephaly (10 per year)
Congenital hydrocephalus (0.5/1000 births)
Congenital deafness (0.8/1000 births)
How does the neural tube close? What happens if there is a failure in this?
Begins in cervical area and spreads from there in the cranial and caudal directions.
Cranial end closes by day 24 and caudal end by day 26.
If the posterior neuropore does not close spina bifida occurs and if anterior neuropore closure fails to take place anencephaly results.
How are neural tube defects detected early on?
They can be seen via ultrasound.
What are the risk factors for neural tube defects?
Most cases of NTDs are multifactorial in origin
2 - 5% recurrence in subsequent pregnancies
Genetic influences (known genetic syndromes, familial clustering)
Multiple pregnancies
Environmental agents (hyperthermia)
Nutritional deficiencies (folate deficiency in particular)
What is folate important for?
It is a group B vitamin that is necessary for production and maintenance of new cells.
Folate is a coenzyme in one-carbon transfer during methylation cycle which form part of DNA and the neurotransmitters.
Methylation of homocysteine to produce methionine uses 5-MTHF as the methyl donor
What happens in folate deficiency?
Accumulation of homocysteine which results in associated cardiovascular disease risk.
How can folate and neural tube defects be prevented?
MTHFR gene mutation affects 8 - 35% of the population depending on ethnicity.
Reduced folate carrier gene (RFC1)
How does genetic influence folate metabolism?
Several gene polymorphisms affect folate metabolism.
These are associated with reduced folate absorption and therefore increased folate needs
How are folate related issues prevented during pregnancy?
Periconceptional folic acid is administered because it reduces the prevalence of NTD.
How much periconceptional folic acid is given to women daily?
Women with no risk factors for NTDs: 400 - 800 mcg folic acid preconception until 12 weeks gestation.
Women with risk factors: 5 mg folic acid
What alternative to folic acid supplementation has been proposed?
5-methyl-tetrahydrofolate
What risk factor is most commonly associated with chromosomal defects?
Age of the mother
How common is trisomy 21?
3.2/1000 in WA (100/year)
It accounts for 50% of chromosomal abnormalities.
What causes trisomy 21?
Non-disjunction (95% of cases)
Unbalanced translocation (4%)
Mosaicism (1%)
What are the phenotypic features of trisomy 21?
CNS: intellectual disability (IQ50), alzheimer’s disease, and hypotonia.
Conductive hearing loss
Cardiac defects AVSD
GI: duodenal atresia, imperforate anus
Short stature
Facies: Flat facial profile, macroglossia, epicanthal folds, small ears
Short broad fingers, clinodactyly, single palmar crease
Excessive neck skin
Joint laxity.
How can trisomy 21 be diagnosed prenatally?
Main techniques used are:
Prenatal diagnosis based on maternal age (amniocentesis/CVS)
Combined first trimester screening (80 - 90% detection rate)
Second trimester screening (60 - 70% detection rate)
Non-invasive prenatal testing (99.5% detection rate)
