Difference between revisions of "Human Abnormal Development"

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{{Header}}
 
[[File:Amniocentesis.jpg|300px|right]]
 
[[File:Amniocentesis.jpg|300px|right]]
 
==Introduction==
 
==Introduction==
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'''How and why do things go wrong in development?'''
  
How and why do things go wrong in development?
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[[File:child smallpox.jpg|thumb|Mother with child, face and body showing smallpox scars.]]
  
These notes cover abnormalities that can occur during development often described as congenital defects or birth defects. There are many different ways that developmental abnormalities can occur the 3 major types are '''Genetic''' (inherited), '''Environmental''' (maternal) and '''Unknown''' (not determined) derived abnormalities. The environmental factors that cause or lead to any of these abnormalities are described as Teratogens.
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These notes cover abnormalities that can occur during development ({{abnormal development}}) often described as {{congenital abnormalities}} or {{birth defects}}. There are many different ways that developmental abnormalities can occur the 3 major types are '''Genetic''' (inherited), '''Environmental''' (maternal) and '''Idiopathic''' (unknown, not determined) derived abnormalities. The environmental factors that cause or lead to any of these abnormalities are described as teratogens. Congenital abnormalities are classified under the system called the [[International Classification of Diseases]] ({{ICD-11}}) that version updated in 2018.
  
While genetic abnormalites will have well-defined impacts upon development, environmentally derived effects can be harder to define and often variable depending on many different factors (timing, exposure level, and the combination effects with other factors). This combination effect can also be seen between genetic and environmental interacting to give an even broader spectrum of both major and minor abnormalities.
 
  
It is the group now classified as "unknown causes" that require further research to place them in one of the two other real categories.
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Note that genetic and environmental effects can also interact and it is this and the group, now classified as idiopathic or "unknown causes", that require further research to place them in either or both of the two real categories. Furthermore developmental organizer genes, for example Hedgehog{{#pmid:31557471|PMID31557471}}, have been recently implicated in adult carcinogenesis.
  
:{{Template:Abnormality Links}}
 
  
'''Prenatal diagnosis''' are the clinical tools used to determine both normal and abnormal development. There are a growing number of new diagnostic techniques that are being applied to human embryonic development.
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''Please note that abnormal development pages may contain clinical images not suitable for children.''
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 +
 
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{{Abnormality Links}}
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==Prenatal Diagnosis==
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'''Prenatal diagnosis''' are the clinical tools used to determine both normal and abnormal development. There are a growing number of new diagnostic techniques that are being applied to human embryonic development. Tests that occur after birth are described in [[Neonatal Diagnosis]].
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 +
 
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{{Prenatal diagnosis}} | [[BGD_Tutorial_-_Applied_Embryology_and_Teratology|BGD Tutorial - Applied Embryology and Teratology]]
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==Neonatal Diagnosis==
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{{Neonatal Diagnosis links}}
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 +
==Genetic==
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{{Genetic}} | {{Meiosis}} |  {{Mitosis}}
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==Environmental==
 +
 
 +
While genetic abnormalities will have well-defined impacts upon development, environmentally derived effects can be harder to define and often variable depending on many different factors (timing, exposure level, and the combination effects with other factors). This combination effect can also be seen between genetic and environmental interacting to give an even broader spectrum of both major and minor abnormalities.
 +
 
 +
 
 +
{{Environmental}}
  
:{{Template:Prenatal diagnosis}} | [[2010_BGD_Tutorial_-_Applied_Embryology_and_Teratology|2010 BGD Phase 2 Tutorial - Applied Embryology and Teratology]]
 
  
 
Often not considered, is that pregnancy itself can also expose abnormalities in the mother (congenital heart disease, diabetes, reproductive disorders) that until then had gone undetected. This section of notes also includes links to prenatal diagnosis techniques, twinning and statistical information relating to abnormalities at birth from several different countries.
 
Often not considered, is that pregnancy itself can also expose abnormalities in the mother (congenital heart disease, diabetes, reproductive disorders) that until then had gone undetected. This section of notes also includes links to prenatal diagnosis techniques, twinning and statistical information relating to abnormalities at birth from several different countries.
  
== Statistics - Top Ten ==
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==Undergraduate Science Projects==
[[Image:Abnormal AusData81-92Graph.png|thumb|Australian Data 1981-92]]
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The ten most frequently reported birth defects in Victoria between 2003-2004 (More? [http://embryology.med.unsw.edu.au/Defect/page3c.htm Australian Statistics - Victoria])
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The links below are to Science student group projects prepared on the topics of prenatal diagnosis (2010) and abnormal development (2011).
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 +
 
 +
:'''2011 Student Projects:''' [[2011_Group_Project_1|Turner Syndrome]] | [[2011_Group_Project_2|DiGeorge Syndrome]] | [[2011_Group_Project_3|Klinefelter's Syndrome]] | [[2011_Group_Project_4|Huntington's Disease]] | [[2011_Group_Project_5|Fragile X Syndrome]] | [[2011_Group_Project_6|Tetralogy of Fallot]] | [[2011_Group_Project_7|Angelman Syndrome]] | [[2011_Group_Project_8|Friedreich's Ataxia]] | [[2011_Group_Project_9|Williams-Beuren Syndrome]] | [[2011_Group_Project_10|Duchenne Muscular Dystrolphy]] | [[2011_Group_Project_11|Cleft Palate and Lip]]
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 +
 
 +
 
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:'''2010 Student Projects:''' [[2010_Group_Project_1|Ultrasound]] | [[2010_Group_Project_2|Chorionic villus sampling]] | [[2010_Group_Project_3|Amniocentesis]] |  [[2010_Group_Project_4|Percutaneous Umbilical Cord Blood Sampling]] |  [[2010_Group_Project_5|Fetal Fibronectin]] | [[2010_Group_Project_6|Maternal serum alpha-fetoprotein]]
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 +
== Statistics==
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===Sex Bias===
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Some developmental abnormalities show a difference in distribution related to embryo sex, {{male}} and {{female}}. While other genetic abnormalities are related to maternal mitochondrial inheritance sex chromosomes {{ChrX)} and {{ChrY).
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Some examples of some abnormalities sex related statistics are shown below.
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{{USA 1997-2009 Abnormalities Sex Ratio table}}
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Some {{neural abnormalities}}, such as autism and intellectual disability, have a {{male}} sex bias. This can be affected by the presence of specific comorbidities, specific copy number variants, mutational burden, and pre-existing family history of neurodevelopmental phenotypes.{{#pmid:26307204|PMID26307204}}
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More than 80% of auto{{immune}} disease predominantly affects {{female}}s.{{#pmid:26713507|PMID26713507}}
  
# Hypospadias
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[[File:Thyroid pyramidal lobe.jpg|thumb|150px|alt=Thyroid pyramidal lobe|Thyroid pyramidal lobe]]
# [[O#obstructive renal pelvis defect|Obstructive Defects of the Renal Pelvis]] or [[O#Obstructive Genitourinary Defects|Obstructive Genitourinary Defects]]
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Other abnormalities of development are considered "anatomical variations" as they do not have any serious impacts. For example, the {{thyroid}} has a common anatomical variation of a pyramidal lobe seen more frequently in {{male}} than in {{female}}.{{#pmid:17146601|PMID17146601}}
# [[V#ventricular septal defect|Ventricular Septal Defect]]
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# [[C#congenital dislocated hip|Congenital Dislocated Hip]]
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===Australia - Top 10===
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[[File:Abnormal AusData81-92Graph.png|thumb|alt=Congenital Anomalies Australian Data 1981-92|Australian Data 1981-92]]
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{{Congenital Anomalies Australia 2002-2003 table}}
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The ten most frequently reported birth defects in Victoria between 2003-2004.
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# [[Genital_Abnormality_-_Hypospadia|Hypospadias]]
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# [[Renal_System_-_Abnormalities#Obstructive_Renal_Pelvis_Defect|Obstructive Defects of the Renal Pelvis]] or [[Renal_System_-_Abnormalities|Obstructive Genitourinary Defects]]
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# [[Cardiovascular_System_-_Ventricular_Septal_Defects|Ventricular Septal Defect]]
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# [[Musculoskeletal_System_-_Abnormalities#Developmental_Dysplasia_of_the_Hip |Congenital Dislocated Hip]]
 
# [[Trisomy 21]] or Down syndrome
 
# [[Trisomy 21]] or Down syndrome
# [[H#hydrocephalus|Hydrocephalus]]
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# [[Abnormal_Development_-_Congenital_Hydrocephalus |Hydrocephalus]]
# [[C#cleft palate|Cleft Palate]]
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# [[Palate Development|Cleft Palate]]
 
# [[Trisomy 18]] or Edward Syndrome - multiple abnormalities of the heart, diaphragm, lungs, kidneys, ureters and palate 86% discontinued.
 
# [[Trisomy 18]] or Edward Syndrome - multiple abnormalities of the heart, diaphragm, lungs, kidneys, ureters and palate 86% discontinued.
# Renal Agenesis/Dysgenesis - reduction in neonatal death and stillbirth since 1993 may be due to the more severe cases being identified in utero and being represented amongst the increased proportion of terminations (approximately 31%).
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# [[Renal_System_-_Abnormalities#Renal_Agenesis_or_Dysgenesis|Renal Agenesis/Dysgenesis]] - reduction in neonatal death and stillbirth since 1993 may be due to the more severe cases being identified in utero and being represented amongst the increased proportion of terminations (approximately 31%).
# [[C#cleft lip|Cleft Lip]] and Palate - occur with another defect in 33.7% of cases.
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# [[Palate Development|Cleft Lip]] and Palate - occur with another defect in 33.7% of cases.
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:'''Links:''' [[#Australian Congenital Anomalies Monitoring System|ACAMS]] | [[Australian Statistics]]
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===USA - Selected===
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{| class="wikitable mw-collapsible mw-collapsed"
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! USA Statistics  
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|-
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|
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{{USA_Selected_defect_table_2006}}
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|}
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===Birth Defects Sex Ratios===
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{{USA}} National Birth Defects Prevention Study (1997-2009){{#pmid:25711982|PMID25711982}}
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This study presents estimates of sex ratio for both isolated cases and those with multiple congenital anomalies, as well as by race/ethnicity. Male-female sex ratios and their 95% confidence intervals were calculated for 25,952 clinically reviewed case infants included in the National Birth Defects Prevention Study (1997-2009), a large population-based case-control study of birth defects.
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{{USA 1997-2009 Abnormalities Sex Ratio table}}
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Differences were observed by race/ethnicity for some but not for most types of birth defects. The sex differences we observed for specific defects, between those with isolated versus multiple defects, as well as by race/ethnicity, demonstrate patterns that may suggest etiology and improve classification.
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:'''Links:''' [[#USA Monitoring Programmes|USA Monitoring Programmes]] | [[USA Statistics]]
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===Nigeria===
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Congenital malformations among newborns admitted in the neonatal unit of a tertiary hospital in Enugu, South-East Nigeria{{#pmid:22472067|PMID22472067}}
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:"The results of this study show that congenital abnormal- ities occur in 2.8% of newborns admitted in the neonatal unit of the University Of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu and that the commonest forms seen are cleft lip/cleft palate and neural tube defects. The prevalence rate obtained in this study, however, may not reflect the true situation in the general population for reasons adduced in the discussion above but gives a clue to the existence of the problem and could serve as a stimulus for further studies on the subject."
  
 
==Neural Tube Defects==
 
==Neural Tube Defects==
 
Neural tube defects that were just outside the top ten most common birth defects but are widely known.
 
Neural tube defects that were just outside the top ten most common birth defects but are widely known.
  
:'''Spina Bifida''' - (73%) of parents choose to discontinue a pregnancy affected by spina bifida.
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:'''{{Spina bifida}}''' - (73%) of parents choose to discontinue a pregnancy affected by spina bifida.
  
:'''Anencephaly''' - (94%) of parents choose to discontinue a pregnancy affected by anencephaly.
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:'''{{anencephaly}}''' - (94%) of parents choose to discontinue a pregnancy affected by anencephaly.
  
(Data from the Victorian Perinatal Data Collection Unit)
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::Data: from the [http://www.health.vic.gov.au/ccopmm/vpdc/index.htm Victorian Perinatal Data Collection Unit]
  
== Australian Birth Anomalies System ==
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'''Links:''' {{folate}} | {{anencephaly}} | [[Neural System - Abnormalities]]
  
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==Genetic (inherited)==
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{{Genetic}}
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==Environmental (maternal)==
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{{Environmental}}
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===Critical Periods===
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During prenatal development there are "windows of time" or "critical periods", that following exposure to teratogens can lead to developmental abnormalities (anomalies, congenital). In general, the effects for each system are more severe (major anomalies) in the earlier embryonic period during organogenesis in the first trimester. Later teratogen exposure are less severe (minor anomalies) in the fetal period during continued growth and differentiation in the second and third trimester.
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{{Critical Periods table}}
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===Cardiac Critical Periods===
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As an example, the table below shows the "critical periods" of {{cardiac}} development.
 +
 +
{{Anderson2016 table2}}
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== Teratology ==
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 +
Now consider how different environmental effects during pregnancy may influence developmental outcomes. The terms listed below are often used to describe these environmental effects
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* [[T#teratogen|Teratogen]] (Greek, teraton = monster) any agent that causes a structural abnormality (congenital abnormalities) following fetal exposure during pregnancy. The overall effect depends on dosage and time of exposure. (More? Critical Periods of Development)
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* [[A#absolute_risk|Absolute risk]] the rate of occurrence of an abnormal phenotype among individuals exposed to the agent. (e.g. fetal alcohol syndrome)
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* [[R#relative_risk|Relative risk]] the ratio of the rate of the condition among the exposed and the nonexposed. (e.g. smokers risk of having a low birth weight baby compared to non-smokers) A high relative risk may indicate a low absolute risk if the condition is rare.
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* [[M#mutagen|Mutagen]] a chemical or agent that can cause permanent damage to the deoxyribonucleic acid (DNA) in a cell. DNA damage in the human egg or sperm may lead to reduced fertility, spontaneous abortion (miscarriage), birth defects and heritable diseases.
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* [[F#fetotoxicant|Fetotoxicant]] is a chemical that adversely affects the developing fetus, resulting in low birth weight, symptoms of poisoning at birth or stillbirth (fetus dies before it is born).
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* '''Synergism''' when the combined effect of exposure to more than one chemical at one time, or to a chemical in combination with other hazards (heat, radiation, infection) results in effects of such exposure to be greater than the sum of the individual effects of each hazard by itself.
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* [[T#toxicogenomics|Toxicogenomics]] the interaction between the genome, chemicals in the environment, and disease. Cells exposed to a stress, drug or toxicant respond by altering the pattern of expression of genes within their chromosomes. Based on new genetic and microarray technologies.
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 +
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==Australian Congenital Anomalies Monitoring System==
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{{Congenital Anomalies Australia 2002-2003 table}}
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 +
The following text is from AIHW National Perinatal Epidemiology and Statistics Unit [http://www.npesu.unsw.edu.au/data-collection/australian-congenital-anomalies-monitoring-system-acams Australian Congenital Anomalies Monitoring System (ACAMS)]
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:"The Australian Congenital Anomalies Monitoring System (ACAMS) contains data based on notifications of major congenital anomalies to birth defects registers in New South Wales, Victoria, Western Australia and South Australia and on data collected on congenital anomalies in Queensland, Tasmania and the Australian Capital Territory. The Northern Territory is currently unable to provide data in a format enabling it to be compiled with data from the other states and territories. Some summary data have been provided by the Northern Territory for inclusion in the ACAS. Congenital anomalies are mainly notified from data collected as part of perinatal collections. Other sources of data include perinatal death certificates, cytogenetic or pathology reports, admitted patient data, maternal and child health nurses and medical officers.
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:Information is included on live births and stillbirths of 20 weeks gestational age or more or 400 grams birthweight or more (including induced abortions) with a congenital anomaly for all states and the Australian Capital Territory. Information on induced abortions of less than 20 weeks gestational age and less than 400 grams weight with a congenital anomaly is only available for four states and is included for: New South Wales, Victoria, Western Australia and South Australia. Births included in the ACAS are also included in the National Perinatal Data Collection.
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:The period of notification varies among the state and territory collections and ranges from prenatal diagnosis to notification up to 15 years of age. For New South Wales, the data include births with congenital anomalies notified up to 1 year of age. The data for Victoria, Western Australia and South Australia include births with congenital anomalies notified up to 15 years, 6 years and 5 years of age respectively. The data for Queensland, Tasmania, and the Australia Capital Territory include births with congenital anomalies notified in the perinatal period.
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:Data items relating to the woman, including demographic characteristics and factors relating to the birth, and data items relating to the baby, including, birthweight, gestational age and sex, are included. Congenital anomalies are coded using the British Paediatric Association Classification of Diseases (ICD-9-BPA), which is based on the International Classification of Diseases, 9th Revision (ICD-9).
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:ACAS supersedes the National Congenital Malformations and Birth Defects Data Collection (NCM&BD), which commenced in 1981 in response to claims of increased incidence of congenital anomalies in small areas of Australia. Data were provided by four jurisdictions in 1998–1985 and all states and territories provided data from 1986. Data are included up to and including the 1997 birth cohort. The NCM&BD data collection was reviewed in 2004 and the development of the ACAS was a recommendation of the review."
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{| class="wikitable mw-collapsible mw-collapsed"
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! Previous - Australian Birth Anomalies System
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|-
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|
 
:"The national collation and reporting of birth anomalies data has been suspended in recent years due to concerns about data quality and comparability."
 
:"The national collation and reporting of birth anomalies data has been suspended in recent years due to concerns about data quality and comparability."
  
Line 60: Line 204:
  
 
(Modified from [http://www.aihw.gov.au/ Australian Institute of Health and Welfare (AIHW)])
 
(Modified from [http://www.aihw.gov.au/ Australian Institute of Health and Welfare (AIHW)])
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|}
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[http://www.preru.unsw.edu.au/PRERUWeb.nsf/page/ba3 Congenital Anomalies in Australia 2002-2003]
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:'''Links:''' [http://www.npesu.unsw.edu.au/data-collection/australian-congenital-anomalies-monitoring-system-acams Australian Congenital Anomalies Monitoring System (ACAMS)] | [http://www.aihw.gov.au/ Australian Institute of Health and Welfare (AIHW)]
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==New Zealand==
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New Zealand Birth Defects Monitoring Programme ([http://publichealth.massey.ac.nz/research/CPHRBased/Current/New%20Zealand%20Birth%20Defects%20Monitoring%20Programme%20(NZBDMP).htm NZBDMP])
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* monitoring the occurrence of birth defects among livebirths and fetal deaths in New Zealand.
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* provide data on the prevalence of birth defects for ad hoc.
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* provide annual data to the Ministry of Health and International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR)
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* investigate clusters of birth defects
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* provide expert technical assistance and advice on the epidemiology of birth defects
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==USA Monitoring Programmes==
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Centers for Disease Control (CDC) conducted two birth defects surveillance systems<ref><pubmed>7287285</pubmed></ref> and each state also maintain their own programs (see [[#External Links|External Links]]).
  
:'''Links:''' [http://www.npsu.unsw.edu.au/PRERUWeb.nsf/page/CADC Australian Congenital Anomalies Monitoring System (ACAMS)] | [http://www.aihw.gov.au/ Australian Institute of Health and Welfare (AIHW)]
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* Metropolitan Atlanta Congenital Defects Programme (MACDP)
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** established in 1967
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** an intensive surveillance system using several methods to identify infants born with birth defects in the Atlanta area.
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** [http://onlinelibrary.wiley.com/doi/10.1002/bdra.v79:2/issuetoc  40th Edition Surveillance Report February 2007]
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* Birth Defects Monitoring Programme (BDMP)
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** a nationwide surveillance system that monitors 1 million births per year.
  
==Genetic (inherited)==
 
{{Template:Genetic}}
 
  
==Environmental (maternal)==
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{{USA Selected defect table 2006}}
{{Template:Environmental}}
 
  
===Critical Periods===
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==International Classification of Diseases==
The table below identifies approximate windows of time, "critical periods", that following exposure to teratogens can lead to developmental abnormalities (anomalies, congenital). In general, the effects for each system are more severe (major anomalies) in the embryonic period during organogenesis in the first trimester. Later teratogen exposure are less severe (minor anomalies) in the fetal period during continued growth and differentiation in the second and third trimester.
 
  
{| class="prettytable"
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The [[International Classification of Diseases]] version 11 ({{ICD-11}}) is the standard diagnostic tool for epidemiology, health management and clinical purposes. This includes the analysis of the general health situation of population groups. It is used to monitor the incidence and prevalence of diseases and other health problems.
| bgcolor= "LightCyan" colspan="2" | '''Conceptus'''
 
| bgcolor= "LightBlue" colspan="13" | '''Embryonic development''' (weeks)
 
| bgcolor= "LightSkyBlue" colspan="5" | '''Fetal period''' (weeks)
 
  
|-
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{{ICD-11 Developmental anomalies table}}
| bgcolor= "LightCyan" width="50px" |<center>'''1'''</center>
 
| bgcolor= "LightCyan" width="50px" |<center>'''2'''</center>
 
| bgcolor= "LightBlue" width="50px" colspan="2" |<center>'''3'''</center>
 
| bgcolor= "LightBlue" width="50px" colspan="3" |<center>'''4'''</center>
 
| bgcolor= "LightBlue" width="50px" | <center>'''5'''</center>
 
| bgcolor= "LightBlue" width="50px" colspan="2" | <center>'''6'''</center>
 
| bgcolor= "LightBlue" width="50px" colspan="2" | <center>'''7'''</center>
 
| bgcolor= "LightBlue" width="50px" colspan="3" | <center>'''8'''</center>
 
| bgcolor= "LightSkyBlue" width="50px" colspan="2" | <center>'''9'''</center>
 
| bgcolor= "LightSkyBlue" width="50px" | <center>'''16'''</center>
 
| bgcolor= "LightSkyBlue" width="50px" | <center>'''20-36'''</center>
 
| bgcolor= "LightSkyBlue" width="50px" | <center>'''38'''</center>
 
  
|-
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:'''Links:''' [[International Classification of Diseases]]
| bgcolor= "LightCyan" width="50px" | [[File:Early_zygote.jpg|50px]]
 
| bgcolor= "LightCyan" width="50px" | [[File:Week2_001 icon.jpg|50px]]
 
| bgcolor= "LightBlue" width="50px" colspan="2" |[[File:Stage9_sem4c.jpg|50px]]
 
| bgcolor= "LightBlue" width="50px" colspan="3" |[[File:Stage13_sem1c.jpg|50px]]
 
| bgcolor= "LightBlue" width="50px" |[[File:Stage15_bf1c.jpg|50px]]
 
| bgcolor= "LightBlue" width="50px" colspan="2" |[[File:Stage17_bf1c.jpg|50px]]
 
| bgcolor= "LightBlue" width="50px" colspan="2" |[[File:Stage19_bf1c.jpg|50px]]
 
| bgcolor= "LightBlue" width="50px" colspan="3" |[[File:Stage23_bf1c.jpg|50px]]
 
| bgcolor= "LightSkyBlue" width="50px" colspan="2" |
 
| bgcolor= "LightSkyBlue" width="50px" |
 
| bgcolor= "LightSkyBlue" width="50px" |
 
| bgcolor= "LightSkyBlue" width="50px" |
 
  
|-
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==Germline Gene Editing==
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Technology development in germline gene editing has allowed the development of many animal models of human congenital defects. More recently there has been debate around the ethics of using similar methods in "correcting" these abnormalities using similar techniques in humans. In 2018 the European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a background document and recommendations to inform and stimulate ongoing societal debates.{{#pmid:29326428|PMID29326428}}{{#pmid:29326429|PMID29326429}} The European Society of Human Genetics and the European Society for Human Reproduction and Embryology have developed a similar consensus covering this topic and other {{ART}}-related topics.{{#pmid:29199274|PMID29199274}}
|
 
| bgcolor= "Salmon" colspan="16" | '''Neural'''
 
| bgcolor= "LightSalmon" colspan="2" |  
 
  
|-
 
| [[File:Stage2.jpg|50px]]
 
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| bgcolor= "Salmon" colspan="6" | '''Heart'''
 
| bgcolor= "LightSalmon" colspan="6" |
 
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| bgcolor= "Salmon" colspan="6" | '''Upper limbs'''
 
| bgcolor= "LightSalmon" colspan="5" |
 
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:'''Links:''' {{ART}} | {{molecular}}
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| bgcolor= "Salmon" colspan="6" | '''Lower limbs'''
 
| bgcolor= "LightSalmon" colspan="4" |
 
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==References==
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| bgcolor= "Salmon" colspan="9" | '''Ear'''
 
| bgcolor= "LightSalmon" colspan="4" |
 
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<references/>
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| bgcolor= "Salmon" colspan="7" | '''Eye'''
 
| bgcolor= "LightSalmon" colspan="7" |
 
  
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==Terms==
| [[File:CSt3.jpg|50px]]
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* '''abnormal''' - term describing development that is different from normal or not typical, usual, or regular.
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| bgcolor= "Salmon" colspan="7" | '''Palate'''
 
| bgcolor= "LightSalmon" |
 
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* '''agenesis''' congenital abnormality of complete failure of organ or tissue development during embryonic growth.
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| bgcolor= "Salmon" colspan="6" | '''Teeth'''
 
| bgcolor= "LightSalmon" colspan="5" |
 
  
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* '''association''' - term referring to a nonrandom occurrence in two or more individuals of multiple defects not known to be a polytopic field defect, sequence, or syndrome.
| [[File:Week2_001 icon.jpg|50px]]
 
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| bgcolor= "Salmon" colspan="5" | '''External genitalia'''
 
| bgcolor= "LightSalmon" colspan="4" |
 
  
|-
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* '''Australian Congenital Anomalies Monitoring System''' - (ACAMS) contains data based on notifications of major congenital anomalies to birth defects registers in Australian states and territories, except the Northern Territory. Information is included on live births and stillbirths of 20 weeks gestational age or more or 400 grams birthweight or more (including induced abortions) with a congenital anomaly. ACAMS replaces the National Congenital Malformations and Birth Defects Data Collection that began in 1981. (More? [[Australian Statistics]] | [http://www.npsu.unsw.edu.au/PRERUWeb.nsf/page/CADC AIHW National Perinatal Epidemiology and Statistics Unit])
| bgcolor= "LightCyan" colspan="2" | '''Loss'''
 
| bgcolor= "Salmon" colspan="10" | '''Major abnormalities'''
 
| bgcolor= "LightSalmon" colspan="8" | '''Functional and Minor abnormalities'''
 
  
|}
+
* '''congenital''' - (Latin, ''congenitus'' = born together) refers to developmental disorder that is present at birth (or during the neonatal period) due to genetic, environmental or a combination of known and unknown factors.
  
== Teratology ==
+
* '''dysmorphology''' - term referring to the study of birth defects.
  
Now consider how different environmental effects during pregnancy may influence developmental outcomes. The terms listed below are often used to describe these environmental effects
+
* '''environmental''' -  term used to describe effects due to the physical and biological factors resulting in abnormal development.
  
* [[T#teratogen|Teratogen]] (Greek, teraton = monster) any agent that causes a structural abnormality (congenital abnormalities) following fetal exposure during pregnancy. The overall effect depends on dosage and time of exposure. (More? Critical Periods of Development)
+
* '''expanded carrier screening''' - (ECS) term related to additional genetic testing for carrier status.
  
* [[A#absolute_risk|Absolute risk]] the rate of occurrence of an abnormal phenotype among individuals exposed to the agent. (e.g. fetal alcohol syndrome)
+
* '''genetic''' - term used to describe effects due to embryo genes, their mutation, altered expression or epigenetic effects resulting in abnormal development.
  
* [[R#relative_risk|Relative risk]] the ratio of the rate of the condition among the exposed and the nonexposed. (e.g. smokers risk of having a low birth weight baby compared to non-smokers) A high relative risk may indicate a low absolute risk if the condition is rare.
+
* '''hypogenesis''' - congenital abnormality of an under-development of either parts or organs of the body.
  
* [[M#mutagen|Mutagen]] a chemical or agent that can cause permanent damage to the deoxyribonucleic acid (DNA) in a cell. DNA damage in the human egg or sperm may lead to reduced fertility, spontaneous abortion (miscarriage), birth defects and heritable diseases.
+
* '''International Classification of Diseases''' - (ICD) is the standard diagnostic tool for epidemiology, health management and clinical purposes. This classification has been developed by the World Health Organization (WHO). ICD-10 came into use in 1994, ICD-11 revision has begun and will continue until 2015. (More? [[International Classification of Diseases]] | [http://www.who.int/classifications/icd/en/ WHO - ICD])
  
* [[F#fetotoxicant|Fetotoxicant]] is a chemical that adversely affects the developing fetus, resulting in low birth weight, symptoms of poisoning at birth or stillbirth (fetus dies before it is born).
+
* '''polytopic field defect''' - term describing developmental defects that are all concentrated in one particular area of the body (developmental field).
  
* '''Synergism''' when the combined effect of exposure to more than one chemical at one time, or to a chemical in combination with other hazards (heat, radiation, infection) results in effects of such exposure to be greater than the sum of the individual effects of each hazard by itself.
+
* '''sequence''' - clinical term for a pattern of multiple defects derived from a single known or presumed structural defect or mechanical factor.
  
* [[T#toxicogenomics|Toxicogenomics]] the interaction between the genome, chemicals in the environment, and disease. Cells exposed to a stress, drug or toxicant respond by altering the pattern of expression of genes within their chromosomes. Based on new genetic and microarray technologies.
+
* '''syndrome''' - clinical term for a pattern of multiple defects related pathogenetically though not known to represent a single sequence or a polytopic field defect.
  
== UNSW Embryology Links ==
+
* '''unknown''' - term used to describe abnormal development due to single or multiple genetic and or environmental effects that have not yet been completely identified or described.
* [http://embryology.med.unsw.edu.au/Defect/page1.htm Abnormal Development]
 
* [http://embryology.med.unsw.edu.au/Defect/page3.htm Abnormal Development- Australian Statistics] | [http://embryology.med.unsw.edu.au/Defect/page4.htm Abnormalities by Systems]
 
* [http://embryology.med.unsw.edu.au/Defect/page7.htm Prenatal Diagnosis]
 
* [http://embryology.med.unsw.edu.au/Defect/genetic.htm Genetic Abnormalities] | [http://embryology.med.unsw.edu.au/Defect/page21.htm Down Syndrome] | [http://embryology.med.unsw.edu.au/Defect/page18.htm Edwards Syndrome] | [http://embryology.med.unsw.edu.au/Defect/fragilex.htm Fragile X] | [http://embryology.med.unsw.edu.au/Defect/leschnyhan.htm Lesch-Nyhan Syndrome]
 
* [http://embryology.med.unsw.edu.au/Defect/maternal.htm Maternal Factors] | [http://embryology.med.unsw.edu.au/Defect/maternaldiabetes.htm Maternal Diabetes] | [http://embryology.med.unsw.edu.au/Defect/hyperthermia.htm Maternal Hyperthermia] | [http://embryology.med.unsw.edu.au/Defect/page5e.htm Neural Tube Defects] | [http://embryology.med.unsw.edu.au/Defect/page5a.htm Fetal Alcohol Syndrome] | [http://embryology.med.unsw.edu.au/Defect/smoking.htm Smoking] | [http://embryology.med.unsw.edu.au/Defect/chemical.htm Chemical] | [http://embryology.med.unsw.edu.au/Defect/drugs.htm Drugs] | [http://embryology.med.unsw.edu.au/Defect/drugs2.htm Illegal Drugs] | [http://embryology.med.unsw.edu.au/Defect/radiation.htm Radiation] | [http://embryology.med.unsw.edu.au/Defect/metal.htm Heavy Metal] | [http://embryology.med.unsw.edu.au/Defect/page11.htm Iodine Deficiency] | [http://embryology.med.unsw.edu.au/Defect/virus.htm Viral Infection] | [http://embryology.med.unsw.edu.au/Defect/rubella.htm Rubella] | [http://embryology.med.unsw.edu.au/Defect/polio.htm Polio] | [http://embryology.med.unsw.edu.au/Defect/parvovirus.htm Parvovirus] | [http://embryology.med.unsw.edu.au/Defect/varicella.htm Varicella] | [http://embryology.med.unsw.edu.au/Defect/bacteria.htm Bacterial Infection] | [http://embryology.med.unsw.edu.au/Defect/malaria.htm Malaria] | [http://embryology.med.unsw.edu.au/Defect/toxoplasmosis.htm Toxoplasmosis] | [http://embryology.med.unsw.edu.au/Defect/autism.htm Autism]
 
* [http://embryology.med.unsw.edu.au/Defect/page10.htm Fetal Origins Hypothesis]
 
* [http://embryology.med.unsw.edu.au/Defect/IUGR.htm Intrauterine Growth Retardation]
 
* [http://embryology.med.unsw.edu.au/Defect/twin.htm Twinning]
 
  
 
== External Links ==
 
== External Links ==
* [http://www.aihw.gov.au/ Australian Institute of Health and Welfare (AIHW)]
+
{{External Links}}
 +
 
 +
* '''Australia'''
 +
** [http://www.aihw.gov.au/ Australian Institute of Health and Welfare (AIHW)]
 +
** [http://www.npesu.unsw.edu.au/data-collection/australian-congenital-anomalies-monitoring-system-acams Australian Congenital Anomalies Monitoring System] (ACAMS)
 +
* '''USA''' [http://www.cdc.gov/ncbddd/index.html National Center on Birth Defects and Developmental Disabilities]
 +
** Arizona Birth Defects Monitoring Program ([http://www.azdhs.gov/phs/phstats/bdr/index.htm ABDMP])
 +
** California Birth Defects Monitoring Program ([http://www.cdph.ca.gov/programs/cbdmp/Pages/default.aspx CBDMP])
 +
** North Carolina Birth Defects Monitoring Program ([http://www.schs.state.nc.us/SCHS/bdmp/ NCBDMP])
 +
** Louisiana Birth Defects Monitoring Network (http://new.dhh.louisiana.gov/index.cfm/page/771 LBDMN)
 +
 
 +
* CDC [http://www.cdc.gov/ncbddd/birthdefects/data.html Birth Defects - Data & Statistics]
 +
 
 +
 
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{{Glossary}}
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{{Template:Glossary}}
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{{Footer}}
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[[Category:Prenatal Diagnosis]] [[Category:Abnormal Development]] [[Category:Genetic Abnormalities]] [[Category:Environmental Abnormalities]] [[Category:Human Embryo]] [[Category:Human Fetus]] [[Category:Statistics]]
 
[[Category:Prenatal Diagnosis]] [[Category:Abnormal Development]] [[Category:Genetic Abnormalities]] [[Category:Environmental Abnormalities]] [[Category:Human Embryo]] [[Category:Human Fetus]] [[Category:Statistics]]

Revision as of 11:38, 14 November 2019

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Amniocentesis.jpg

Introduction

How and why do things go wrong in development?

Mother with child, face and body showing smallpox scars.

These notes cover abnormalities that can occur during development (abnormal development) often described as congenital abnormalities or birth defects. There are many different ways that developmental abnormalities can occur the 3 major types are Genetic (inherited), Environmental (maternal) and Idiopathic (unknown, not determined) derived abnormalities. The environmental factors that cause or lead to any of these abnormalities are described as teratogens. Congenital abnormalities are classified under the system called the International Classification of DiseasesICD-11) that version updated in 2018.


Note that genetic and environmental effects can also interact and it is this and the group, now classified as idiopathic or "unknown causes", that require further research to place them in either or both of the two real categories. Furthermore developmental organizer genes, for example Hedgehog[1], have been recently implicated in adult carcinogenesis.


Please note that abnormal development pages may contain clinical images not suitable for children.


Abnormality Links: abnormal development | abnormal genetic | abnormal environmental | Unknown | teratogens | ectopic pregnancy | cardiovascular abnormalities | coelom abnormalities | endocrine abnormalities | gastrointestinal abnormalities | genital abnormalities | head abnormalities | integumentary abnormalities | musculoskeletal abnormalities | limb abnormalities | neural abnormalities | neural crest abnormalities | placenta abnormalities | renal abnormalities | respiratory abnormalities | hearing abnormalities | vision abnormalities | twinning | Developmental Origins of Health and Disease |  ICD-11
Historic Embryology  
1915 Congenital Cardiac Disease | 1917 Frequency of Anomalies in Human Embryos | 1920 Hydatiform Degeneration Tubal Pregnancy | 1921 Anencephalic Embryo | 1921 Rat and Man | 1966 Congenital Malformations

Prenatal Diagnosis

Prenatal diagnosis are the clinical tools used to determine both normal and abnormal development. There are a growing number of new diagnostic techniques that are being applied to human embryonic development. Tests that occur after birth are described in Neonatal Diagnosis.


Diagnosis Links: Prenatal Diagnosis | pregnancy test | amniocentesis | chorionic villus sampling | ultrasound | Alpha-Fetoprotein | Pregnancy-associated plasma protein-A | Fetal Blood Sampling | Magnetic Resonance Imaging | Computed Tomography | Non-Invasive Prenatal Testing | Fetal Cells in Maternal Blood | Preimplantation Genetic Screening | Comparative Genomic Hybridization | Genome Sequencing | Neonatal Diagnosis | Category:Prenatal Diagnosis | Fetal Surgery | Classification of Diseases | Category:Neonatal Diagnosis

| BGD Tutorial - Applied Embryology and Teratology

Neonatal Diagnosis

Neonatal Diagnosis Links: neonatal diagnosis | Apgar test | Guthrie test | hearing test | Electrocardiogram (ECG/EKG) | X-ray | Tandem mass spectrometry | Classification of Diseases

Genetic

Genetic Links: genetic abnormalities | maternal age | Trisomy 21 | Trisomy 18 | Trisomy 13 | Trisomy X | trisomy mosaicism | Monosomy | Fragile X | Williams | Alagille | Philadelphia chromosome | mitochondria | VACTERL | hydatidiform mole | epigenetics | Prenatal Diagnosis | Neonatal Diagnosis | meiosis | mitosis | International Classification of Diseases | genetics

| meiosis | mitosis


Environmental

While genetic abnormalities will have well-defined impacts upon development, environmentally derived effects can be harder to define and often variable depending on many different factors (timing, exposure level, and the combination effects with other factors). This combination effect can also be seen between genetic and environmental interacting to give an even broader spectrum of both major and minor abnormalities.


Environmental Links: Introduction | low folic acid | iodine deficiency | Nutrition | Drugs | Australian Drug Categories | USA Drug Categories | thalidomide | herbal drugs | Illegal Drugs | smoking | Fetal Alcohol Syndrome | TORCH | viral infection | bacterial infection | fungal infection | zoonotic infection | toxoplasmosis | Malaria | maternal diabetes | maternal hypertension | maternal hyperthermia | Maternal Inflammation | Maternal Obesity | hypoxia | biological toxins | chemicals | heavy metals | air pollution | radiation | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Fetal Origins Hypothesis


Often not considered, is that pregnancy itself can also expose abnormalities in the mother (congenital heart disease, diabetes, reproductive disorders) that until then had gone undetected. This section of notes also includes links to prenatal diagnosis techniques, twinning and statistical information relating to abnormalities at birth from several different countries.

Undergraduate Science Projects

The links below are to Science student group projects prepared on the topics of prenatal diagnosis (2010) and abnormal development (2011).


2011 Student Projects: Turner Syndrome | DiGeorge Syndrome | Klinefelter's Syndrome | Huntington's Disease | Fragile X Syndrome | Tetralogy of Fallot | Angelman Syndrome | Friedreich's Ataxia | Williams-Beuren Syndrome | Duchenne Muscular Dystrolphy | Cleft Palate and Lip


2010 Student Projects: Ultrasound | Chorionic villus sampling | Amniocentesis | Percutaneous Umbilical Cord Blood Sampling | Fetal Fibronectin | Maternal serum alpha-fetoprotein

Statistics

Sex Bias

Some developmental abnormalities show a difference in distribution related to embryo sex, Male and Female. While other genetic abnormalities are related to maternal mitochondrial inheritance sex chromosomes {{ChrX)} and {{ChrY).

Some examples of some abnormalities sex related statistics are shown below.

USA Abnormalities Sex Ratio (1997-2009)
Male preponderance Female preponderance
Cardiac defects
Table data[2]   Links: abnormal development | cardiovascular abnormalities | USA | Male | Female | cleft lip and palate


Some neural abnormalities, such as autism and intellectual disability, have a Male sex bias. This can be affected by the presence of specific comorbidities, specific copy number variants, mutational burden, and pre-existing family history of neurodevelopmental phenotypes.[3]

More than 80% of autoimmune disease predominantly affects Females.[4]

Thyroid pyramidal lobe
Thyroid pyramidal lobe

Other abnormalities of development are considered "anatomical variations" as they do not have any serious impacts. For example, the thyroid has a common anatomical variation of a pyramidal lobe seen more frequently in Male than in Female.[5]


Australia - Top 10

Congenital Anomalies Australian Data 1981-92
Australian Data 1981-92
Congenital Anomalies in Australia 2002-2003  
Congenital anomalies in Australia 2002-2003[6] was published in 2008 as part a new revised series on 33 selected congenital anomalies also monitored internationally by the International Clearinghouse of Birth Defects Surveillance and Research.
  • Hypospadia is the most commonly reported condition at birth, but severity of the condition is not reported to the national data collection.
  • Trisomy 21 (Down’s syndrome) is the next most commonly reported condition at birth (11.1 per 10,000 births), but many affected pregnancies are detected early and managed by early termination. An estimated 63.6% of the fetuses diagnosed with trisomy 21 were managed by terminations of pregnancy or were fetal deaths. When terminations of pregnancy were included, the estimated rate for trisomy 21 was 26.3 per 10,000 pregnancies. Trisomy 21 was more common with advancing maternal age.
    • Other chromosomal abnormalities such as trisomy 13 and trisomy 18 also had a large proportion of fetal deaths or terminations of pregnancy and were more common in women aged 40 years or older.
  • Neural tube defects were diagnosed in about 4.2 per 10,000 births.
  • More males than females diagnosed with congenital anomalies for many of the reported conditions (e.g. hydrocephalus, most of the reported congenital heart diseases, oesophageal atresia and polycystic kidneys).
  • Anencephaly - younger women had a higher rate compared with older women, most of the women who gave birth to a baby with anencephaly (77.2%) were in the 20–34 years age group.
Links: Human Abnormal Development | Hypospadia | Trisomy 21 | Trisomy 13 Trisomy 18 | Neural Tube Defects | Folic Acid and Neural Tube Defects | Hydrocephalus | Cardiovascular Abnormalities | Polycystic Kidney Disease | Anencephaly | Australian Statistics | Reports
External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.
External Links: AIHW Report Page | NPESU Report Page | International Clearinghouse of Birth Defects Surveillance and Research

The ten most frequently reported birth defects in Victoria between 2003-2004.

  1. Hypospadias
  2. Obstructive Defects of the Renal Pelvis or Obstructive Genitourinary Defects
  3. Ventricular Septal Defect
  4. Congenital Dislocated Hip
  5. Trisomy 21 or Down syndrome
  6. Hydrocephalus
  7. Cleft Palate
  8. Trisomy 18 or Edward Syndrome - multiple abnormalities of the heart, diaphragm, lungs, kidneys, ureters and palate 86% discontinued.
  9. Renal Agenesis/Dysgenesis - reduction in neonatal death and stillbirth since 1993 may be due to the more severe cases being identified in utero and being represented amongst the increased proportion of terminations (approximately 31%).
  10. Cleft Lip and Palate - occur with another defect in 33.7% of cases.


Links: ACAMS | Australian Statistics

USA - Selected

USA Statistics  
USA Selected Abnormalities (CDC National estimates for 21 selected major birth defects 2004–2006)  
Birth Defects Cases per Births (1 in ...) Estimated Annual Number of Cases
anencephaly 4,859 859
spina bifida without anencephaly 2,858 1,460
encephalocele 12,235 341
Anophthalmia/microphthalmia 5,349 780
patent ductus arteriosus‎/common truncus 13,876 301
transposition of the great vessels 3,333 1,252
Tetralogy of Fallot 2,518 1,657
atrial septal defects/ventricular septal defects 2,122 1,966
hypoplastic left heart 4,344 960
cleft palate without cleft lip 1,574 2,651
cleft lip with and without cleft palate 940 4,437
Esophageal atresia/tracheoesophageal fistula 4,608 905
Rectal and large intestinal atresia/stenosis 2,138 1,952
Reduction deformity, upper limbs 2,869 1,454
Reduction deformity, lower limbs 5,949 701
gastroschisis 2,229 1,871
omphalocele 5,386 775
Diaphragmatic hernia 3,836 1,088
Trisomy 13 7,906 528
Trisomy 21 (Down syndrome) 691 6,037
Trisomy 18 3,762 1,109
Links: Human Abnormal Development | CDC Birth Defects - Data & Statistics | USA Statistics | Victoria 2004 | USA 2006 | Europe 2010

Birth Defects Sex Ratios

USA National Birth Defects Prevention Study (1997-2009)[2]

This study presents estimates of sex ratio for both isolated cases and those with multiple congenital anomalies, as well as by race/ethnicity. Male-female sex ratios and their 95% confidence intervals were calculated for 25,952 clinically reviewed case infants included in the National Birth Defects Prevention Study (1997-2009), a large population-based case-control study of birth defects.

USA Abnormalities Sex Ratio (1997-2009)
Male preponderance Female preponderance
Cardiac defects
Table data[2]   Links: abnormal development | cardiovascular abnormalities | USA | Male | Female | cleft lip and palate


Differences were observed by race/ethnicity for some but not for most types of birth defects. The sex differences we observed for specific defects, between those with isolated versus multiple defects, as well as by race/ethnicity, demonstrate patterns that may suggest etiology and improve classification.


Links: USA Monitoring Programmes | USA Statistics

Nigeria

Congenital malformations among newborns admitted in the neonatal unit of a tertiary hospital in Enugu, South-East Nigeria[7]

"The results of this study show that congenital abnormal- ities occur in 2.8% of newborns admitted in the neonatal unit of the University Of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu and that the commonest forms seen are cleft lip/cleft palate and neural tube defects. The prevalence rate obtained in this study, however, may not reflect the true situation in the general population for reasons adduced in the discussion above but gives a clue to the existence of the problem and could serve as a stimulus for further studies on the subject."

Neural Tube Defects

Neural tube defects that were just outside the top ten most common birth defects but are widely known.

spina bifida - (73%) of parents choose to discontinue a pregnancy affected by spina bifida.
anencephaly - (94%) of parents choose to discontinue a pregnancy affected by anencephaly.
Data: from the Victorian Perinatal Data Collection Unit

Links: folate | anencephaly | Neural System - Abnormalities

Genetic (inherited)

Genetic Links: genetic abnormalities | maternal age | Trisomy 21 | Trisomy 18 | Trisomy 13 | Trisomy X | trisomy mosaicism | Monosomy | Fragile X | Williams | Alagille | Philadelphia chromosome | mitochondria | VACTERL | hydatidiform mole | epigenetics | Prenatal Diagnosis | Neonatal Diagnosis | meiosis | mitosis | International Classification of Diseases | genetics


Environmental (maternal)

Environmental Links: Introduction | low folic acid | iodine deficiency | Nutrition | Drugs | Australian Drug Categories | USA Drug Categories | thalidomide | herbal drugs | Illegal Drugs | smoking | Fetal Alcohol Syndrome | TORCH | viral infection | bacterial infection | fungal infection | zoonotic infection | toxoplasmosis | Malaria | maternal diabetes | maternal hypertension | maternal hyperthermia | Maternal Inflammation | Maternal Obesity | hypoxia | biological toxins | chemicals | heavy metals | air pollution | radiation | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Fetal Origins Hypothesis


Critical Periods

During prenatal development there are "windows of time" or "critical periods", that following exposure to teratogens can lead to developmental abnormalities (anomalies, congenital). In general, the effects for each system are more severe (major anomalies) in the earlier embryonic period during organogenesis in the first trimester. Later teratogen exposure are less severe (minor anomalies) in the fetal period during continued growth and differentiation in the second and third trimester.

Critical Periods of Human Development
Conceptus Embryonic development (weeks) Fetal period (weeks)
1
2
3
4
5
6
7
8
9
16
20-36
38
Early zygote.jpg Week2 001 icon.jpg Stage9 sem4c.jpg Stage13 sem1c.jpg Stage15 bf1c.jpg Stage17 bf1c.jpg Stage19 bf1c.jpg Stage23 bf1c.jpg
Neural
Stage2.jpg Heart
Upper limbs
Lower limbs
Ear
Eye
CSt3.jpg Palate
Teeth
Week2 001 icon.jpg External genitalia
Loss Major abnormalities Functional and Minor abnormalities
  Critical Period Links: critical period | abnormal development | Critical Periods table | Image - Critical Periods table | Genital | Opioids | Neural | Thalidomide | Environmental

Cardiac Critical Periods

As an example, the table below shows the "critical periods" of cardiac development.

Table 2. Summary of Timing (Post Fertilization) of Susceptibility to a Drug-Induced Malformation
Lesion Start of Susceptibility
to Malformation
End of Susceptibility
to Malformation
Interatrial communications
Oval fossa defect 6 weeks (E13.5) Term
Sinus venosus defect 8 weeks 12 weeks
Coronary sinus defect 8 weeks Term
Vestibular defect 7 weeks 8 weeks
Ventricular Septal Defect
Muscular 8 weeks Difficult to predict
Perimembranous 6 weeks 8 weeks
Doubly committed 7 weeks 8 weeks
Atrioventricular Septal Defect
Ostium primum 5 weeks 6 weeks
“Complete” 5 weeks 6 weeks
Aortic coarctation
With VSD 5 weeks 8 weeks
With intact ventricular septum 8 weeks Term
Double Outlet Right Ventricle 6 weeks 8 weeks
Transposition of Great Arteries 6 weeks 8 weeks
Ebstein’s malformation 6 weeks 8 weeks
Hypoplastic left heart syndrome
With mitral atresia 5 weeks 8 weeks
With mitral stenosis 8 weeks Term
Pulmonary atresia
With VSD 6 weeks 8 weeks
With intact ventricular septum 8 weeks Term
Other
Functionally single ventricle 5 weeks 6 weeks
Tetralogy of Fallot 7 weeks 8 weeks
Totally anomalous pulmonary venous return 8 weeks 12 weeks
Tricuspid atresia 5 weeks 6 weeks
Common arterial trunk 5 weeks 7 weeks
Bicuspid aortic valve 6 weeks Term
Notes
For approximate clinical Gestational Age GA add 2 weeks; number in brackets is mouse equivalent. Data Reference[8] Links: heart | abnormal development | timeline | Category:Timeline
Table 2. Summary of Timing (Post Fertilization) of Cardiac Susceptibility to a Drug-Induced Malformation  
Lesion Start of Susceptibility
to Malformation
End of Susceptibility
to Malformation
Interatrial communications
Oval fossa defect 6 weeks (E13.5) Term
Sinus venosus defect 8 weeks 12 weeks
Coronary sinus defect 8 weeks Term
Vestibular defect 7 weeks 8 weeks
Ventricular Septal Defect
Muscular 8 weeks Difficult to predict
Perimembranous 6 weeks 8 weeks
Doubly committed 7 weeks 8 weeks
Atrioventricular Septal Defect
Ostium primum 5 weeks 6 weeks
“Complete” 5 weeks 6 weeks
Aortic coarctation
With VSD 5 weeks 8 weeks
With intact ventricular septum 8 weeks Term
Double Outlet Right Ventricle 6 weeks 8 weeks
Transposition of Great Arteries 6 weeks 8 weeks
Ebstein’s malformation 6 weeks 8 weeks
Hypoplastic left heart syndrome
With mitral atresia 5 weeks 8 weeks
With mitral stenosis 8 weeks Term
Pulmonary atresia
With VSD 6 weeks 8 weeks
With intact ventricular septum 8 weeks Term
Other
Functionally single ventricle 5 weeks 6 weeks
Tetralogy of Fallot 7 weeks 8 weeks
Totally anomalous pulmonary venous return 8 weeks 12 weeks
Tricuspid atresia 5 weeks 6 weeks
Common arterial trunk 5 weeks 7 weeks
Bicuspid aortic valve 6 weeks Term

Notes: For approximate clinical Gestational Age GA add 2 weeks; number in brackets is mouse equivalent.

Reference: Anderson RH. Teratogenecity in the setting of cardiac development and maldevelopment. (2016)

Teratology

Now consider how different environmental effects during pregnancy may influence developmental outcomes. The terms listed below are often used to describe these environmental effects

  • Teratogen (Greek, teraton = monster) any agent that causes a structural abnormality (congenital abnormalities) following fetal exposure during pregnancy. The overall effect depends on dosage and time of exposure. (More? Critical Periods of Development)
  • Absolute risk the rate of occurrence of an abnormal phenotype among individuals exposed to the agent. (e.g. fetal alcohol syndrome)
  • Relative risk the ratio of the rate of the condition among the exposed and the nonexposed. (e.g. smokers risk of having a low birth weight baby compared to non-smokers) A high relative risk may indicate a low absolute risk if the condition is rare.
  • Mutagen a chemical or agent that can cause permanent damage to the deoxyribonucleic acid (DNA) in a cell. DNA damage in the human egg or sperm may lead to reduced fertility, spontaneous abortion (miscarriage), birth defects and heritable diseases.
  • Fetotoxicant is a chemical that adversely affects the developing fetus, resulting in low birth weight, symptoms of poisoning at birth or stillbirth (fetus dies before it is born).
  • Synergism when the combined effect of exposure to more than one chemical at one time, or to a chemical in combination with other hazards (heat, radiation, infection) results in effects of such exposure to be greater than the sum of the individual effects of each hazard by itself.
  • Toxicogenomics the interaction between the genome, chemicals in the environment, and disease. Cells exposed to a stress, drug or toxicant respond by altering the pattern of expression of genes within their chromosomes. Based on new genetic and microarray technologies.


Australian Congenital Anomalies Monitoring System

Congenital Anomalies in Australia 2002-2003  
Congenital anomalies in Australia 2002-2003[9] was published in 2008 as part a new revised series on 33 selected congenital anomalies also monitored internationally by the International Clearinghouse of Birth Defects Surveillance and Research.
  • Hypospadia is the most commonly reported condition at birth, but severity of the condition is not reported to the national data collection.
  • Trisomy 21 (Down’s syndrome) is the next most commonly reported condition at birth (11.1 per 10,000 births), but many affected pregnancies are detected early and managed by early termination. An estimated 63.6% of the fetuses diagnosed with trisomy 21 were managed by terminations of pregnancy or were fetal deaths. When terminations of pregnancy were included, the estimated rate for trisomy 21 was 26.3 per 10,000 pregnancies. Trisomy 21 was more common with advancing maternal age.
    • Other chromosomal abnormalities such as trisomy 13 and trisomy 18 also had a large proportion of fetal deaths or terminations of pregnancy and were more common in women aged 40 years or older.
  • Neural tube defects were diagnosed in about 4.2 per 10,000 births.
  • More males than females diagnosed with congenital anomalies for many of the reported conditions (e.g. hydrocephalus, most of the reported congenital heart diseases, oesophageal atresia and polycystic kidneys).
  • Anencephaly - younger women had a higher rate compared with older women, most of the women who gave birth to a baby with anencephaly (77.2%) were in the 20–34 years age group.
Links: Human Abnormal Development | Hypospadia | Trisomy 21 | Trisomy 13 Trisomy 18 | Neural Tube Defects | Folic Acid and Neural Tube Defects | Hydrocephalus | Cardiovascular Abnormalities | Polycystic Kidney Disease | Anencephaly | Australian Statistics | Reports
External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.
External Links: AIHW Report Page | NPESU Report Page | International Clearinghouse of Birth Defects Surveillance and Research

The following text is from AIHW National Perinatal Epidemiology and Statistics Unit Australian Congenital Anomalies Monitoring System (ACAMS)

"The Australian Congenital Anomalies Monitoring System (ACAMS) contains data based on notifications of major congenital anomalies to birth defects registers in New South Wales, Victoria, Western Australia and South Australia and on data collected on congenital anomalies in Queensland, Tasmania and the Australian Capital Territory. The Northern Territory is currently unable to provide data in a format enabling it to be compiled with data from the other states and territories. Some summary data have been provided by the Northern Territory for inclusion in the ACAS. Congenital anomalies are mainly notified from data collected as part of perinatal collections. Other sources of data include perinatal death certificates, cytogenetic or pathology reports, admitted patient data, maternal and child health nurses and medical officers.
Information is included on live births and stillbirths of 20 weeks gestational age or more or 400 grams birthweight or more (including induced abortions) with a congenital anomaly for all states and the Australian Capital Territory. Information on induced abortions of less than 20 weeks gestational age and less than 400 grams weight with a congenital anomaly is only available for four states and is included for: New South Wales, Victoria, Western Australia and South Australia. Births included in the ACAS are also included in the National Perinatal Data Collection.
The period of notification varies among the state and territory collections and ranges from prenatal diagnosis to notification up to 15 years of age. For New South Wales, the data include births with congenital anomalies notified up to 1 year of age. The data for Victoria, Western Australia and South Australia include births with congenital anomalies notified up to 15 years, 6 years and 5 years of age respectively. The data for Queensland, Tasmania, and the Australia Capital Territory include births with congenital anomalies notified in the perinatal period.
Data items relating to the woman, including demographic characteristics and factors relating to the birth, and data items relating to the baby, including, birthweight, gestational age and sex, are included. Congenital anomalies are coded using the British Paediatric Association Classification of Diseases (ICD-9-BPA), which is based on the International Classification of Diseases, 9th Revision (ICD-9).
ACAS supersedes the National Congenital Malformations and Birth Defects Data Collection (NCM&BD), which commenced in 1981 in response to claims of increased incidence of congenital anomalies in small areas of Australia. Data were provided by four jurisdictions in 1998–1985 and all states and territories provided data from 1986. Data are included up to and including the 1997 birth cohort. The NCM&BD data collection was reviewed in 2004 and the development of the ACAS was a recommendation of the review."


Previous - Australian Birth Anomalies System
"The national collation and reporting of birth anomalies data has been suspended in recent years due to concerns about data quality and comparability."
  • Variability among states and territories in scope of birth anomalies data collections
    • sources of birth anomalies notifications
    • definitions and classifications used
    • method of data collection
    • available resources
  • Variability among the states and territories in the timing and method of the provision of birth anomalies data to the AIHW National Perinatal Statistics Unit (NPSU) for national collation and reporting.
  • New Australian Birth Anomalies System should be data for birth anomalies detected up to 1 year of age
    • including data on terminations of pregnancies with birth anomalies
    • regardless of gestational age (i.e. including less than 20 weeks gestation)
  • System will initially be based on data from the states able to detect birth anomalies at least up to 1 year of age
    • NSW, VIC, WA and SA
    • further extending the period of detection in the future

(Modified from Australian Institute of Health and Welfare (AIHW))

Congenital Anomalies in Australia 2002-2003


Links: Australian Congenital Anomalies Monitoring System (ACAMS) | Australian Institute of Health and Welfare (AIHW)

New Zealand

New Zealand Birth Defects Monitoring Programme (NZBDMP)

  • monitoring the occurrence of birth defects among livebirths and fetal deaths in New Zealand.
  • provide data on the prevalence of birth defects for ad hoc.
  • provide annual data to the Ministry of Health and International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR)
  • investigate clusters of birth defects
  • provide expert technical assistance and advice on the epidemiology of birth defects

USA Monitoring Programmes

Centers for Disease Control (CDC) conducted two birth defects surveillance systems[10] and each state also maintain their own programs (see External Links).

  • Metropolitan Atlanta Congenital Defects Programme (MACDP)
  • Birth Defects Monitoring Programme (BDMP)
    • a nationwide surveillance system that monitors 1 million births per year.


USA Selected Abnormalities (CDC National estimates for 21 selected major birth defects 2004–2006)  
Birth Defects Cases per Births (1 in ...) Estimated Annual Number of Cases
anencephaly 4,859 859
spina bifida without anencephaly 2,858 1,460
encephalocele 12,235 341
Anophthalmia/microphthalmia 5,349 780
patent ductus arteriosus‎/common truncus 13,876 301
transposition of the great vessels 3,333 1,252
Tetralogy of Fallot 2,518 1,657
atrial septal defects/ventricular septal defects 2,122 1,966
hypoplastic left heart 4,344 960
cleft palate without cleft lip 1,574 2,651
cleft lip with and without cleft palate 940 4,437
Esophageal atresia/tracheoesophageal fistula 4,608 905
Rectal and large intestinal atresia/stenosis 2,138 1,952
Reduction deformity, upper limbs 2,869 1,454
Reduction deformity, lower limbs 5,949 701
gastroschisis 2,229 1,871
omphalocele 5,386 775
Diaphragmatic hernia 3,836 1,088
Trisomy 13 7,906 528
Trisomy 21 (Down syndrome) 691 6,037
Trisomy 18 3,762 1,109
Links: Human Abnormal Development | CDC Birth Defects - Data & Statistics | USA Statistics | Victoria 2004 | USA 2006 | Europe 2010

International Classification of Diseases

The International Classification of Diseases version 11 ( ICD-11) is the standard diagnostic tool for epidemiology, health management and clinical purposes. This includes the analysis of the general health situation of population groups. It is used to monitor the incidence and prevalence of diseases and other health problems.

 ICD-11 20 Developmental anomalies - Structural developmental anomalies primarily affecting one body system
System  ICD-11 Embryology page link
nervous system neural abnormalities
eye, eyelid or lacrimal apparatus vision abnormalities
ear hearing abnormalities
face, mouth or teeth tooth abnormalities
neck head abnormalities
respiratory system respiratory abnormalities
circulatory system cardiovascular abnormalities
diaphragm, abdominal wall or umbilical cord diaphragm abnormalities | placenta abnormalities
digestive tract gastrointestinal abnormalities
liver, biliary tract, pancreas or spleen liver abnormalities | gall bladder abnormalities | pancreas abnormalities
urinary system renal abnormalities
female genital system genital abnormalities
male genital system genital abnormalities
breast mammary abnormalities
skeleton musculoskeletal abnormalities
skin integumentary abnormalities
adrenal glands adrenal abnormalities
 ICD-11 abnormal development | prenatal diagnosis | neonatal diagnosis
Links: International Classification of Diseases

Germline Gene Editing

Technology development in germline gene editing has allowed the development of many animal models of human congenital defects. More recently there has been debate around the ethics of using similar methods in "correcting" these abnormalities using similar techniques in humans. In 2018 the European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a background document and recommendations to inform and stimulate ongoing societal debates.[11][12] The European Society of Human Genetics and the European Society for Human Reproduction and Embryology have developed a similar consensus covering this topic and other ART-related topics.[13]


Links: ART | molecular

References

  1. Bajpai A & Sinha P. (2019). Hh signaling from de novo organizers drive lgl neoplasia in Drosophila epithelium. Dev. Biol. , , . PMID: 31557471 DOI.
  2. 2.0 2.1 2.2 Michalski AM, Richardson SD, Browne ML, Carmichael SL, Canfield MA, VanZutphen AR, Anderka MT, Marshall EG & Druschel CM. (2015). Sex ratios among infants with birth defects, National Birth Defects Prevention Study, 1997-2009. Am. J. Med. Genet. A , 167A, 1071-81. PMID: 25711982 DOI.
  3. Polyak A, Rosenfeld JA & Girirajan S. (2015). An assessment of sex bias in neurodevelopmental disorders. Genome Med , 7, 94. PMID: 26307204 DOI.
  4. Liu K, Kurien BT, Zimmerman SL, Kaufman KM, Taft DH, Kottyan LC, Lazaro S, Weaver CA, Ice JA, Adler AJ, Chodosh J, Radfar L, Rasmussen A, Stone DU, Lewis DM, Li S, Koelsch KA, Igoe A, Talsania M, Kumar J, Maier-Moore JS, Harris VM, Gopalakrishnan R, Jonsson R, Lessard JA, Lu X, Gottenberg JE, Anaya JM, Cunninghame-Graham DS, Huang AJW, Brennan MT, Hughes P, Illei GG, Miceli-Richard C, Keystone EC, Bykerk VP, Hirschfield G, Xie G, Ng WF, Nordmark G, Eriksson P, Omdal R, Rhodus NL, Rischmueller M, Rohrer M, Segal BM, Vyse TJ, Wahren-Herlenius M, Witte T, Pons-Estel B, Alarcon-Riquelme ME, Guthridge JM, James JA, Lessard CJ, Kelly JA, Thompson SD, Gaffney PM, Montgomery CG, Edberg JC, Kimberly RP, Alarcón GS, Langefeld CL, Gilkeson GS, Kamen DL, Tsao BP, McCune WJ, Salmon JE, Merrill JT, Weisman MH, Wallace DJ, Utset TO, Bottinger EP, Amos CI, Siminovitch KA, Mariette X, Sivils KL, Harley JB & Scofield RH. (2016). X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome. , 68, 1290-1300. PMID: 26713507 DOI.
  5. Braun EM, Windisch G, Wolf G, Hausleitner L & Anderhuber F. (2007). The pyramidal lobe: clinical anatomy and its importance in thyroid surgery. Surg Radiol Anat , 29, 21-7. PMID: 17146601 DOI.
  6. Abeywardana S & Sullivan EA 2008. Congenital anomalies in Australia 2002–2003. Birth anomalies series no. 3 Cat. no. PER 41. Sydney: AIHW National Perinatal Statistics Unit.
  7. Obu HA, Chinawa JM, Uleanya ND, Adimora GN & Obi IE. (2012). Congenital malformations among newborns admitted in the neonatal unit of a tertiary hospital in Enugu, South-East Nigeria--a retrospective study. BMC Res Notes , 5, 177. PMID: 22472067 DOI.
  8. Anderson RH. Teratogenecity in the setting of cardiac development and maldevelopment. (2016)
  9. Abeywardana S & Sullivan EA 2008. Congenital anomalies in Australia 2002–2003. Birth anomalies series no. 3 Cat. no. PER 41. Sydney: AIHW National Perinatal Statistics Unit.
  10. <pubmed>7287285</pubmed>
  11. de Wert G, Pennings G, Clarke A, Eichenlaub-Ritter U, van El CG, Forzano F, Goddijn M, Heindryckx B, Howard HC, Radojkovic D, Rial-Sebbag E, Tarlatzis BC & Cornel MC. (2018). Human germline gene editing: Recommendations of ESHG and ESHRE. Eur. J. Hum. Genet. , 26, 445-449. PMID: 29326428 DOI.
  12. De Wert G, Heindryckx B, Pennings G, Clarke A, Eichenlaub-Ritter U, van El CG, Forzano F, Goddijn M, Howard HC, Radojkovic D, Rial-Sebbag E, Dondorp W, Tarlatzis BC & Cornel MC. (2018). Responsible innovation in human germline gene editing: Background document to the recommendations of ESHG and ESHRE. Eur. J. Hum. Genet. , , . PMID: 29326429 DOI.
  13. Harper JC, Aittomäki K, Borry P, Cornel MC, de Wert G, Dondorp W, Geraedts J, Gianaroli L, Ketterson K, Liebaers I, Lundin K, Mertes H, Morris M, Pennings G, Sermon K, Spits C, Soini S, van Montfoort APA, Veiga A, Vermeesch JR, Viville S & Macek M. (2018). Recent developments in genetics and medically assisted reproduction: from research to clinical applications. Eur. J. Hum. Genet. , 26, 12-33. PMID: 29199274 DOI.

Terms

  • abnormal - term describing development that is different from normal or not typical, usual, or regular.
  • agenesis congenital abnormality of complete failure of organ or tissue development during embryonic growth.
  • association - term referring to a nonrandom occurrence in two or more individuals of multiple defects not known to be a polytopic field defect, sequence, or syndrome.
  • Australian Congenital Anomalies Monitoring System - (ACAMS) contains data based on notifications of major congenital anomalies to birth defects registers in Australian states and territories, except the Northern Territory. Information is included on live births and stillbirths of 20 weeks gestational age or more or 400 grams birthweight or more (including induced abortions) with a congenital anomaly. ACAMS replaces the National Congenital Malformations and Birth Defects Data Collection that began in 1981. (More? Australian Statistics | AIHW National Perinatal Epidemiology and Statistics Unit)
  • congenital - (Latin, congenitus = born together) refers to developmental disorder that is present at birth (or during the neonatal period) due to genetic, environmental or a combination of known and unknown factors.
  • dysmorphology - term referring to the study of birth defects.
  • environmental - term used to describe effects due to the physical and biological factors resulting in abnormal development.
  • expanded carrier screening - (ECS) term related to additional genetic testing for carrier status.
  • genetic - term used to describe effects due to embryo genes, their mutation, altered expression or epigenetic effects resulting in abnormal development.
  • hypogenesis - congenital abnormality of an under-development of either parts or organs of the body.
  • International Classification of Diseases - (ICD) is the standard diagnostic tool for epidemiology, health management and clinical purposes. This classification has been developed by the World Health Organization (WHO). ICD-10 came into use in 1994, ICD-11 revision has begun and will continue until 2015. (More? International Classification of Diseases | WHO - ICD)
  • polytopic field defect - term describing developmental defects that are all concentrated in one particular area of the body (developmental field).
  • sequence - clinical term for a pattern of multiple defects derived from a single known or presumed structural defect or mechanical factor.
  • syndrome - clinical term for a pattern of multiple defects related pathogenetically though not known to represent a single sequence or a polytopic field defect.
  • unknown - term used to describe abnormal development due to single or multiple genetic and or environmental effects that have not yet been completely identified or described.

External Links

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Cite this page: Hill, M.A. (2019, December 11) Embryology Human Abnormal Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Human_Abnormal_Development

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G