thalidomide, retinoids, or vitamin A coegers)
Alcohol consumption
Vehicle exhaust components
By-products of disinfectants
Incinerators (proximity)
Agricultural pesticides
Solvents
Landfill sites
Heavy metalsMaternal exposure to carbon monoxide from smoke (e.g. from cigarettes) has been known for having the ability of quickly crossing the placenta into the fetus, which then attaches itself to fetal haemoglobin, leaving a shortage of nutrients and oxygen as a result. A relation between these events and congenital heart disease (including PAVSD) has been showed in 3 recent meta-analyses.Paternal smoking (that is, smoking by the father) has also been shown to be a contributing factor to congenital heart disease; while light smoking slightly increased the risk of the mans offspring having a (congenital) conotruncal heart defect, heavy smoking of more than 14 cigarettes a day doubled the risk for said man to have a child with congenital heart disease. Higher amounts than this were linked to a higher risk of having children with septal defects and/or obstruction of the left ventricular outflow tract.Other risk factors include maternal obesity, diabetes, rubella, indomethacin tocolysis, phenylketonuria, or elderly age. Multifactorial: involving genetic and environmental factors at the same time
A link between certain genes and maternal smoking has been shown to increase the chance of having children with congenital heart disease (including PAVSD): mothers who have a CC genotype at position 677 of the MTHFR gene have an increased chance of having a CHD-ridden child. Other genes that increase the chance of a child with CHD in smoker mothers who carry genetic variations in them include ERCC1, ERCC5, PARP2, and OSGEP.
The most severe variant involves the presence of severely hypoplastic main pulmonary arteries and branch pulmonary arteries, alongside agenesis of the patent ductus arteriosus. Blood flow to the lungs comes from various dysplastic (malformed) blood vessels from the thoracic aorta called major aortapulmonary collateral arteries, these blood vessels narrow down as time goes on. Causes
Although this birth defect is congenital, the exact cause is unknown, and it may vary between children with the condition, the following factors have been known to influence the risk of a baby being born with the condition:

Genetics
The molecular genetics of this condition isnt known in most people with PA(VSD), however, there have been candidate genes found to be possibly implicated in the pathogenesis of this condition:
DNAH10
DST
FAT1
HMCN1
HNRNPC
TEP1
TYK2
NDRG4
TBX5
NKX2.5
GATA4There have also been copy number variants described in the medical literature as associated with PA(VSD):
Deletion in chromosome 16p11.2
Deletion in chromosome 5q35.3
Deletion in chromosome 5p13.1
Deletion in chromosome 22q11.2
Deletion in chromosome 15q11.2
Deletion in chromosome 8p23.2
Deletion in chromosome 17p13.2
Duplication in chromosome 5q14.1
Duplication in chromosome 10p13A 1998 study done in Britain revealed that children with a mother who had a congenital heart defect (including PAVSD) had a higher risk of being born with a congenital heart defect themselves than those whose father had a congenital heart defect. Syndromes
Some cases of PA(VSD) have been associated with genetic syndromes such as VACTERL association, Alagille syndrome, CHARGE syndrome, trisomy 13, 18, and 21. Environmental
While congenital heart defects cant be acquired, they can also be caused by environmental factors the mother exposed herself to before and/or during pregnancy, these include:
Smoking
Certain medications (e.g.