View source for Birth defect

{{Short description|Condition present at birth regardless of cause}}
{{About-distinguish|congenital disorders in humans|teratology|genetic disorder}}
{{Infobox medical condition
| name          = Birth defect
| synonyms      = Congenital disorder, congenital disease, congenital deformity, congenital anomaly<ref>{{cite book|author1=Ruth A. Hannon|title=Porth pathophysiology : concepts of altered health states|date=2010|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Philadelphia, PA|isbn=978-1-60547-781-7|page=128|edition=1st Canadian|url=https://books.google.com/books?id=2-MFXOEG0lcC&pg=PA128}}</ref>
| image         = Incomplete Cleft Lip.png
| caption       = Incomplete [[cleft lip]]
| field         = [[Medical genetics]], [[pediatrics]]
| symptoms      = [[Physical disability]], [[intellectual disability]], [[developmental disability]]<ref name=NIH2017Def/>
| complications =
| onset         = Present at birth<ref name=NIH2017Def/>
| duration      =
| types         = Structural, functional<ref name=NIH2017What/>
| causes        = [[Genetics|Genetic]]s, exposure to certain medications or chemicals, certain [[infection]]s during [[pregnancy]]<ref name=NIH2017Ca/>
| risks         = Insufficient [[folic acid]], drinking [[ethanol|alcohol]] or [[smoking]], poorly controlled [[diabetes]], mother over the age of 35<ref name=NIH2017Risk/><ref name=CDC2017Fact/>
| diagnosis     =
| differential  =
| prevention    =
| treatment     = [[Therapy]], medication, surgery, [[assistive technology]]<ref name=NIH2017Tx/>
| medication    =
| prognosis     =
| frequency     = 3% of newborns (US)<ref name=CDC2015Epi/>
| deaths        = 628,000 (2015)<ref name=GBD2015De/>
| alt           =
}}

<!-- Definition and symptoms -->
A '''birth defect'''{{efn|Also known as a '''congenital disorder''', '''congenital disease''', '''congenital deformity''', or '''congenital anomaly'''.}} is an abnormal condition that is present at [[childbirth|birth]], regardless of its cause.<ref name="NIH2017Def" /> Birth defects may result in [[disability|disabilities]] that may be [[physical disability|physical]], [[intellectual disability|intellectual]], or [[developmental disability|developmental]].<ref name=NIH2017Def>{{cite web|title=Birth Defects: Condition Information|url=https://www.nichd.nih.gov/health/topics/birthdefects/conditioninfo/Pages/default.aspx|website=www.nichd.nih.gov|date=September 2017 |access-date=8 December 2017|archive-date=22 December 2017|archive-url=https://web.archive.org/web/20171222005255/https://www.nichd.nih.gov/health/topics/birthdefects/conditioninfo/Pages/default.aspx|url-status=live}}</ref> The disabilities can range from mild to severe.<ref name="CDC2017Fact">{{cite web |date=7 September 2017 |title=What are Birth Defects? |url=https://www.cdc.gov/ncbddd/birthdefects/facts.html |access-date=14 April 2023 |website=Centers for Disease Control and Prevention |language=en-us |archive-date=15 June 2018 |archive-url=https://web.archive.org/web/20180615073401/https://www.cdc.gov/ncbddd/birthdefects/facts.html |url-status=live }}</ref> Birth defects are divided into two main types: structural disorders in which problems are seen with the shape of a body part and [[functional disorder]]s in which problems exist with how a body part works.<ref name=NIH2017What/> Functional disorders include [[metabolic disorder|metabolic]] and [[degenerative disease|degenerative disorders]].<ref name=NIH2017What/> Some birth defects include both structural and functional disorders.<ref name=NIH2017What>{{cite web|title=What are the types of birth defects?|url=https://www.nichd.nih.gov/health/topics/birthdefects/conditioninfo/pages/types.aspx|website=www.nichd.nih.gov|date=September 2017 |access-date=8 December 2017|archive-date=22 December 2017|archive-url=https://web.archive.org/web/20171222005918/https://www.nichd.nih.gov/health/topics/birthdefects/conditioninfo/pages/types.aspx|url-status=live}}</ref>

<!-- Cause and diagnosis -->
Birth defects may result from [[genetic disorder|genetic]] or [[chromosome abnormality|chromosomal disorders]], exposure to certain medications or chemicals, or certain [[vertically transmitted infection|infections during pregnancy]].<ref name=NIH2017Ca>{{cite web|title=What causes birth defects?|url=https://www.nichd.nih.gov/health/topics/birthdefects/conditioninfo/pages/causes.aspx|website=www.nichd.nih.gov|date=September 2017 |access-date=8 December 2017|archive-date=17 December 2017|archive-url=https://web.archive.org/web/20171217014359/https://www.nichd.nih.gov/health/topics/birthdefects/conditioninfo/Pages/causes.aspx|url-status=live}}</ref> Risk factors include [[folate deficiency]], [[alcohol drink|drinking alcohol]] or [[Smoking and pregnancy|smoking]] during pregnancy, poorly controlled [[gestational diabetes|diabetes]], and a mother over the age of 35 years old.<ref name=NIH2017Risk>{{cite web|title=How many people are affected by/at risk for birth defects?|url=https://www.nichd.nih.gov/health/topics/birthdefects/conditioninfo/pages/risk.aspx|website=www.nichd.nih.gov|access-date=8 December 2017|archive-date=17 December 2017|archive-url=https://web.archive.org/web/20171217014346/https://www.nichd.nih.gov/health/topics/birthdefects/conditioninfo/Pages/risk.aspx|url-status=live}}</ref><ref name=CDC2017Fact/> Many birth defects are believed to involve multiple factors.<ref name=CDC2017Fact/> Birth defects may be visible at birth or diagnosed by [[newborn screening|screening tests]].<ref name=NIH2017Diag/> A number of defects can be detected before birth by different [[prenatal testing|prenatal tests]].<ref name=NIH2017Diag>{{cite web|title=How do health care providers diagnose birth defects?|url=https://www.nichd.nih.gov/health/topics/birthdefects/conditioninfo/pages/diagnosed.aspx|website=www.nichd.nih.gov|date=September 2017 |access-date=8 December 2017|archive-date=22 December 2017|archive-url=https://web.archive.org/web/20171222005911/https://www.nichd.nih.gov/health/topics/birthdefects/conditioninfo/pages/diagnosed.aspx|url-status=live}}</ref>

<!-- Treatment and epidemiology -->
Treatment varies depending on the defect in question.<ref name=NIH2017Tx/> This may include [[therapy]], medication, surgery, or [[assistive technology]].<ref name=NIH2017Tx>{{cite web|title=What are the treatments for birth defects?|url=https://www.nichd.nih.gov/health/topics/birthdefects/conditioninfo/pages/treatment.aspx|website=www.nichd.nih.gov|date=September 2017 |access-date=8 December 2017|archive-date=20 December 2017|archive-url=https://web.archive.org/web/20171220090604/https://www.nichd.nih.gov/health/topics/birthdefects/conditioninfo/Pages/treatment.aspx|url-status=live}}</ref> Birth defects affected about 96 million people {{as of|2015|lc=y}}.<ref name="GBD2015Pre">{{Cite journal |date=8 October 2016 |title=Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. |journal=Lancet |volume=388 |issue=10053 |pages=1545–1602 |doi=10.1016/S0140-6736(16)31678-6 |pmc=5055577 |pmid=27733282 |last1=Vos |first1=Theo |last2=Allen |first2=Christine |last3=Arora |first3=Megha |last4=Barber |first4=Ryan M. |last5=Bhutta |first5=Zulfiqar A. |last6=Brown |first6=Alexandria |last7=Carter |first7=Austin |last8=Casey |first8=Daniel C. |last9=Charlson |first9=Fiona J. |last10=Chen |first10=Alan Z. |last11=Coggeshall |first11=Megan |last12=Cornaby |first12=Leslie |last13=Dandona |first13=Lalit |last14=Dicker |first14=Daniel J. |last15=Dilegge |first15=Tina |last16=Erskine |first16=Holly E. |last17=Ferrari |first17=Alize J. |last18=Fitzmaurice |first18=Christina |last19=Fleming |first19=Tom |last20=Forouzanfar |first20=Mohammad H. |last21=Fullman |first21=Nancy |last22=Gething |first22=Peter W. |last23=Goldberg |first23=Ellen M. |last24=Graetz |first24=Nicholas |last25=Haagsma |first25=Juanita A. |last26=Hay |first26=Simon I. |last27=Johnson |first27=Catherine O. |last28=Kassebaum |first28=Nicholas J. |last29=Kawashima |first29=Toana |last30=Kemmer |first30=Laura |display-authors=1 }}</ref> In the United States, they occur in about 3% of newborns.<ref name=CDC2015Epi>{{cite web|title=Birth Defects|url=https://www.cdc.gov/ncbddd/birthdefects/data.html|access-date=17 Jan 2016|date=Dec 15, 2015|archive-date=18 June 2018|archive-url=https://web.archive.org/web/20180618042145/https://www.cdc.gov/ncbddd/birthdefects/data.html|url-status=live}}</ref> They resulted in about 628,000 deaths in 2015, down from 751,000 in 1990.<ref name=GBD2015De/><ref name=GBD204>{{cite journal|title=Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013.|journal=Lancet|date=17 December 2014|pmid=25530442|doi=10.1016/S0140-6736(14)61682-2|volume=385|issue=9963|pages=117–71|pmc=4340604 |author=((GBD 2013 Mortality and Causes of Death Collaborators))}}</ref> The types with the greatest numbers of deaths are [[congenital heart disease]] (303,000), followed by [[neural tube defects]] (65,000).<ref name=GBD2015De>{{cite journal|title=Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015.|journal=Lancet|date=8 October 2016|volume=388|issue=10053|pages=1459–1544|pmid=27733281|doi=10.1016/s0140-6736(16)31012-1|pmc=5388903 |last1=Wang |first1=Haidong |last2=Naghavi |first2=Mohsen |last3=Allen |first3=Christine |last4=Barber |first4=Ryan M. |last5=Bhutta |first5=Zulfiqar A. |last6=Carter |first6=Austin |last7=Casey |first7=Daniel C. |last8=Charlson |first8=Fiona J. |last9=Chen |first9=Alan Zian |last10=Coates |first10=Matthew M. |last11=Coggeshall |first11=Megan |last12=Dandona |first12=Lalit |last13=Dicker |first13=Daniel J. |last14=Erskine |first14=Holly E. |last15=Ferrari |first15=Alize J. |last16=Fitzmaurice |first16=Christina |last17=Foreman |first17=Kyle |last18=Forouzanfar |first18=Mohammad H. |last19=Fraser |first19=Maya S. |last20=Fullman |first20=Nancy |last21=Gething |first21=Peter W. |last22=Goldberg |first22=Ellen M. |last23=Graetz |first23=Nicholas |last24=Haagsma |first24=Juanita A. |last25=Hay |first25=Simon I. |last26=Huynh |first26=Chantal |last27=Johnson |first27=Catherine O. |last28=Kassebaum |first28=Nicholas J. |last29=Kinfu |first29=Yohannes |last30=Kulikoff |first30=Xie Rachel |display-authors=1 }}</ref>
{{TOC limit|3}}

== Classification ==
Much of the language used for describing congenital conditions antedates [[gene mapping|genome mapping]], and structural conditions are often considered separately from other congenital conditions. Many metabolic conditions are now known to have subtle structural expression, and structural conditions often have genetic links. Still, congenital conditions are often classified on a structural basis, organized when possible by primary organ system affected.{{citation needed|date=August 2017}}

=== Primarily structural ===
Several terms are used to describe congenital abnormalities. (Some of these are also used to describe noncongenital conditions, and more than one term may apply in an individual condition.)

==== {{anchor|malformation|congenital malformation|malformation syndrome|congenital physical anomaly}}Terminology ====
* A '''congenital physical anomaly''' is an abnormality of the structure of a body part. It may or may not be perceived as a problem condition. Many, if not most, people have one or more [[minor physical anomalies]] if examined carefully. Examples of minor anomalies can include curvature of the fifth finger ([[clinodactyly]]), a third nipple, tiny indentations of the skin near the ears ([[Preauricular sinus and cyst|preauricular]] pits), shortness of the fourth [[metacarpal]] or [[metatarsal]] bones, or dimples over the lower spine ([[sacral dimple]]s). Some minor anomalies may be clues to more significant internal abnormalities.{{citation needed|date=December 2024}}
* '''Birth defect''' is a widely used term for a congenital malformation, ''i.e.'' a congenital, physical anomaly that is recognizable at [[Childbirth|birth]], and which is significant enough to be considered a problem. According to the [[Centers for Disease Control and Prevention]] (CDC), most birth defects are believed to be caused by a complex mix of factors including genetics, environment, and behaviors,<ref name="cdc">[https://www.cdc.gov/ncbddd/bd/research.htm Birth Defects Research] {{Webarchive|url=https://web.archive.org/web/20150924064625/http://www.cdc.gov/ncbddd/bd/research.htm |date=2015-09-24 }}. Centers for Disease Control and Prevention.</ref> though many birth defects have no known cause. An example of a birth defect is [[cleft palate]], which occurs during the fourth through seventh weeks of gestation.<ref name="cdc.gov">{{Cite web|url=https://www.cdc.gov/ncbddd/birthdefects/cleftlip.html|title=Facts about Cleft Lip and Cleft Palate {{!}} Birth Defects {{!}} NCBDDD {{!}} CDC|website=www.cdc.gov|access-date=2016-03-16|archive-date=2015-05-08|archive-url=https://web.archive.org/web/20150508162121/http://www.cdc.gov/ncbddd/birthdefects/CleftLip.html|url-status=live}}</ref> Body tissue and special cells from each side of the head grow toward the center of the face. They join to make the face.<ref name="cdc.gov" /> A cleft means a split or separation; the "roof" of the mouth is called the palate.<ref>{{Cite web|url=http://www.entnet.org/content/cleft-lip-and-cleft-palate|title=Cleft Lip and Cleft Palate|last=communications|website=American Academy of Otolaryngology–Head and Neck Surgery|access-date=2016-03-16|archive-date=2016-03-21|archive-url=https://web.archive.org/web/20160321210939/http://www.entnet.org/content/cleft-lip-and-cleft-palate|url-status=live}}</ref>
* A '''congenital malformation''' is a physical anomaly that is deleterious, ''i.e.'' a structural defect perceived as a problem. A typical combination of malformations affecting more than one body part is referred to as a '''malformation syndrome'''.{{citation needed|date=December 2024}}
* Some conditions are due to abnormal tissue development:
** A malformation is associated with a disorder of tissue development.<ref name="isbn0-7216-1489-2">{{cite book |author=Graham, John Whichello |title=Smith's Recognizable Patterns of Human Deformation, 3rd Edition |publisher=Saunders |location=Philadelphia |year=2007 |pages=3 |isbn=978-0-7216-1489-2 }}</ref> Malformations often occur in the first trimester.
** A [[dysplasia]] is a disorder at the organ level that is due to problems with tissue development.<ref name="isbn0-7216-1489-2" />
* Conditions also can arise after tissue is formed:
** A [[deformity|deformation]] is a condition arising from mechanical stress to normal tissue.<ref name="isbn0-7216-1489-2" /> Deformations often occur in the second or third trimester, and can be due to [[oligohydramnios]].{{citation needed|date=December 2024}}
** A disruption involves breakdown of normal tissues.<ref name="isbn0-7216-1489-2" />
* When multiple effects occur in a specified order, they are known as a [[sequence (medicine)|sequence]]. When the order is not known, it is a [[syndrome]].

==== Examples of primarily structural congenital disorders ====
A limb anomaly is called a [[dysmelia]]. These include all forms of limbs anomalies, such as [[amelia (birth defect)|amelia]], [[ectrodactyly]], [[phocomelia]], [[polymelia]], [[polydactyly]], [[syndactyly]], [[polysyndactyly]], [[oligodactyly]], [[brachydactyly]], [[dwarfism|achondroplasia]], congenital [[aplasia]] or [[hypoplasia]], [[amniotic band syndrome]], and [[cleidocranial dysostosis]].<ref>{{Cite journal |last1=Tayel |first1=SM |last2=Fawzia |first2=MM |last3=Al-Naqeeb |first3=Niran A |last4=Gouda |first4=Said |last5=Al Awadi |first5=SA |last6=Naguib |first6=KK |date=2005 |title=A morpho-etiological description of congenital limb anomalies |journal=Annals of Saudi Medicine |language=en |volume=25 |issue=3 |pages=219–227 |doi=10.5144/0256-4947.2005.219 |pmid=16119523 |pmc=6147980 |issn=0256-4947}}</ref>

[[Congenital heart defect]]s include [[patent ductus arteriosus]], [[atrial septal defect]], [[ventricular septal defect]], and [[tetralogy of Fallot]].

Congenital anomalies of the nervous system include neural tube defects such as [[spina bifida]], [[encephalocele]], and [[anencephaly]]. Other congenital anomalies of the nervous system include the [[Arnold–Chiari malformation]], the [[Dandy–Walker malformation]], [[hydrocephalus]], [[microencephaly]], [[megalencephaly]], [[lissencephaly]], [[polymicrogyria]], [[holoprosencephaly]], and [[agenesis of the corpus callosum]].<ref>{{Cite journal |last1=Gaitanis |first1=John |last2=Tarui |first2=Tomo |date=2018 |title=Nervous System Malformations |journal=CONTINUUM: Lifelong Learning in Neurology |language=en |volume=24 |issue=1 |pages=72–95 |doi=10.1212/CON.0000000000000561 |pmid=29432238 |pmc=6463295 |issn=1080-2371}}</ref>

Congenital anomalies of the [[gastrointestinal system]] include numerous forms of [[stenosis]] and [[atresia]], and perforation, such as [[gastroschisis]].<ref>{{Cite web |last=CDC |date=2021-03-31 |title=Congenital Anomalies of the Digestive System |url=https://www.cdc.gov/ncbddd/birthdefects/surveillancemanual/quick-reference-handbook/congenital-anomalies-of-digestive-system.html |access-date=2022-10-31 |website=Centers for Disease Control and Prevention |language=en-us |archive-date=2022-10-31 |archive-url=https://web.archive.org/web/20221031154232/https://www.cdc.gov/ncbddd/birthdefects/surveillancemanual/quick-reference-handbook/congenital-anomalies-of-digestive-system.html |url-status=live }}</ref>

Congenital anomalies of the kidney and urinary tract include renal parenchyma, kidneys, and urinary collecting system.<ref>{{cite web|title=Overview of congenital anomalies of the kidney and urinary tract (CAKUT)|url=http://www.uptodate.com/contents/overview-of-congenital-anomalies-of-the-kidney-and-urinary-tract-cakut|publisher=UpToDate – Wolters Kluer Health|access-date=29 October 2012|archive-date=27 June 2012|archive-url=https://web.archive.org/web/20120627062629/http://www.uptodate.com/contents/overview-of-congenital-anomalies-of-the-kidney-and-urinary-tract-cakut|url-status=live}}</ref>

Defects can be bilateral or unilateral, and different defects often coexist in an individual child.<ref>{{Cite journal |last1=Jain |first1=Sanjay |last2=Chen |first2=Feng |date=2018-12-01 |title=Developmental pathology of congenital kidney and urinary tract anomalies |journal=Clinical Kidney Journal |volume=12 |issue=3 |pages=382–399 |doi=10.1093/ckj/sfy112 |issn=2048-8505 |pmc=6543978 |pmid=31198539}}</ref>

=== Primarily metabolic ===
{{Main|Inborn error of metabolism}}
A '''congenital metabolic disease''' is also referred to as an [[inborn error of metabolism]]. Most of these are [[Genetic disorder#Single-gene|single-gene defects]], usually heritable. Many affect the structure of body parts, but some simply affect the function.<ref>{{Cite journal |last=Arnold |first=Georgianne L. |date=2018 |title=Inborn errors of metabolism in the 21st century: past to present |journal=Annals of Translational Medicine |volume=6 |issue=24 |pages=467 |doi=10.21037/atm.2018.11.36 |issn=2305-5839 |pmc=6331363 |pmid=30740398 |doi-access=free }}</ref>

=== Other ===
Other well-defined genetic conditions may affect the production of hormones, receptors, structural proteins, and ion channels.{{citation needed|date=December 2024}}

== Causes ==

=== Alcohol exposure ===
{{Main|Fetal alcohol spectrum disorder}}

The mother's consumption of alcohol during pregnancy can cause a continuum of various permanent birth defects: craniofacial abnormalities,<ref>{{cite journal |vauthors=Jones K, Smith D | year = 1975 | title = The fetal alcohol syndrome | journal = Teratology | volume = 12 | issue = 1| pages = 1–10 | doi = 10.1002/tera.1420120102 | pmid = 1162620 }}</ref> brain damage,<ref>{{cite journal |vauthors=Clarren S, Alvord E, Sumi S, Streissguth A, Smith D | year = 1978 | title = Brain malformations related to prenatal exposure to ethanol | journal = J Pediatr | volume = 92 | issue = 1| pages = 64–7 | doi = 10.1016/S0022-3476(78)80072-9 | pmid = 619080 }}</ref> intellectual disability,<ref>{{cite journal | pmid = 2877359 | volume=2 | issue=8517 | title=Fetal alcohol syndrome is now leading cause of mental retardation | date=November 1986 |vauthors=Abel EL, Sokol RJ | journal=Lancet | pages=1222 | doi=10.1016/s0140-6736(86)92234-8| s2cid=42708464 }}</ref> heart disease, kidney abnormality, skeletal anomalies, ocular abnormalities.<ref>{{cite journal |vauthors=Strömland K, Pinazo-Durán M | year = 2002 | title = Ophthalmic involvement in the fetal alcohol syndrome: clinical and animal model studies | journal = Alcohol Alcohol | volume = 37 | issue = 1| pages = 2–8 | doi = 10.1093/alcalc/37.1.2 | pmid = 11825849 | doi-access = free }}</ref> There is no known safe amount of alcohol to consume while pregnant.<ref>{{Cite web |last=CDC |date=2025-01-30 |title=About Alcohol Use During Pregnancy |url=https://www.cdc.gov/alcohol-pregnancy/about/index.html#:~:text=Alcohol%20use%20can%20be%20harmful,wine,%20beer,%20and%20liquor |access-date=2025-03-27 |website=Alcohol and Pregnancy |language=en-us}}</ref>

The prevalence of children affected is estimated at least 1% in U.S.<ref>{{cite journal |author1=May PA. |author2=Gossage JP. | year = 2001 | title = Estimating the prevalence of fetal alcohol syndrome. A summary | journal = Alcohol Res Health | volume = 25 | issue = 3| pages = 159–67 | pmid = 11810953 |pmc=6707173 }}</ref> as well in Canada.

Very few studies have investigated the links between paternal alcohol use and offspring health.<ref name="DeSantis">{{cite journal|last1=De Santis|first1=Marco|last2=Cesari|first2=Elena|last3=Cavaliere|first3=Annafranca|last4=Ligato|first4=Maria Serena|last5=Nobili|first5=Elena|last6=Visconti|first6=Daniela|last7=Caruso|first7=Alessandro|title=Paternal exposure and counselling: Experience of a Teratology Information Service|journal=Reproductive Toxicology|date=September 2008|volume=26|issue=1|pages=42–46|doi=10.1016/j.reprotox.2008.06.003|pmid=18598753}}</ref>

However, recent animal research has shown a correlation between paternal alcohol exposure and decreased offspring birth weight. Behavioral and cognitive disorders, including difficulties with learning and memory, hyperactivity, and lowered stress tolerance have been linked to paternal alcohol ingestion.<ref>{{Cite journal |last1=Hollander |first1=Jessica |last2=McNivens |first2=Megan |last3=Pautassi |first3=Ricardo M. |last4=Nizhnikov |first4=Michael E. |date=2019 |title=Offspring of male rats exposed to binge alcohol exhibit heightened ethanol intake at infancy and alterations in T-maze performance |journal=Alcohol |language=en |volume=76 |pages=65–71 |doi=10.1016/j.alcohol.2018.07.013 |pmid=30583252 |pmc=6368891 |issn=0741-8329}}</ref> The compromised stress management skills of animals whose male parent was exposed to alcohol are similar to the exaggerated responses to stress that children with [[fetal alcohol spectrum disorder|fetal alcohol syndrome]] display because of maternal alcohol use. These birth defects and behavioral disorders were found in cases of both long- and short-term paternal alcohol ingestion.<ref name="Trasler">{{cite journal|last1=Trasler|first1=Jacquetta M.|last2=Doerksen|first2=Tonia|title=Teratogen update: paternal exposures—reproductive risks|journal=Teratology|date=September 1999|volume=60|issue=3|pages=161–172|doi=10.1002/(SICI)1096-9926(199909)60:3<161::AID-TERA12>3.0.CO;2-A|pmid=10471901}}</ref><ref name="Abel">{{cite journal|last1=Abel|first1=E. L.|title=Paternal contribution to fetal alcohol syndrome|journal=Addiction Biology|date=2004|volume=9|issue=2|pages=127–133|doi=10.1080/13556210410001716980|pmid=15223537|s2cid=22202776}}</ref> In the same animal study, paternal alcohol exposure was correlated with a significant difference in organ size and the increased risk of the offspring displaying [[ventricular septal defect]]s at birth.<ref name=Abel />

=== Toxic substances ===
{{Further|Developmental toxicity|drugs in pregnancy|environmental toxicants and fetal development}}

Substances whose [[toxicity]] can cause congenital disorders are called [[teratology|teratogens]], and include certain pharmaceutical and recreational [[drugs in pregnancy]], as well as many [[environmental toxins in pregnancy]].<ref>{{Cite book|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK132140/|chapter=Teratogens/Prenatal Substance Abuse|title=Understanding Genetics: A District of Columbia Guide for Patients and Health Professionals|date=2010-02-17|publisher=Genetic Alliance; District of Columbia Department of Health|language=en|access-date=2018-11-07|archive-date=2019-12-20|archive-url=https://web.archive.org/web/20191220050245/https://www.ncbi.nlm.nih.gov/books/NBK132140/|url-status=live}}</ref>

A review published in 2010 identified six main teratogenic mechanisms associated with medication use: [[folate antagonism]], [[neural crest cell]] disruption, [[endocrine disruption]], [[oxidative stress]], [[blood vessel|vascular]] disruption, and specific receptor- or enzyme-mediated teratogenesis.<ref>{{cite journal |vauthors=van Gelder MM, van Rooij IA, Miller RK, Zielhuis GA, de Jong-van den Berg LT, Roeleveld N |title=Teratogenic mechanisms of medical drugs |journal=Hum Reprod Update |volume= 16|issue= 4|pages= 378–94|date=January 2010 |pmid=20061329 |doi=10.1093/humupd/dmp052 |doi-access=free |hdl=2066/89039 |hdl-access=free }}</ref>

An estimated 10% of all birth defects are caused by prenatal exposure to a teratogenic agent.<ref name="isbn0-471-38225-6" /> These exposures include medication or drug exposures, maternal infections and diseases, and environmental and occupational exposures. Paternal smoking has also been linked to an increased risk of birth defects and childhood cancer for the offspring, where the paternal germline undergoes oxidative damage due to cigarette use.<ref name="Zhu">{{cite journal|last1=Zhu|first1=J. L.|last2=Madsen|first2=K. M.|last3=Vestergaard|first3=M|last4=Olesen|first4=A. V.|last5=Basso|first5=O|last6=Olsen|first6=J|title=Paternal age and congenital malformations|journal=Human Reproduction|date=15 July 2005|volume=20|issue=11|pages=3173–3177|doi=10.1093/humrep/dei186|pmid=16006461|doi-access=free}}</ref><ref name="Ji">{{cite journal|last1=Ji|first1=B.-T.|last2=Shu|first2=X.-O.|last3=Zheng|first3=W.|last4=Ying|first4=D.-M.|last5=Linet|first5=M. S.|last6=Wacholder|first6=S.|last7=Gao|first7=Y.-T.|last8=Jin|first8=F.|title=Paternal Cigarette Smoking and the Risk of Childhood Cancer Among Offspring of Nonsmoking Mothers|journal=Journal of the National Cancer Institute|date=5 February 1997|volume=89|issue=3|pages=238–243|doi=10.1093/jnci/89.3.238|pmid=9017004|doi-access=free}}</ref> Teratogen-caused birth defects are potentially preventable. Nearly 50% of pregnant women have been exposed to at least one medication during gestation.<ref name="pmid7266953">{{cite journal |author=Bracken MB, Holford TR |title=Exposure to prescribed drugs in pregnancy and association with congenital malformations |journal=Obstetrics and Gynecology |volume=58 |issue=3 |pages=336–44 |year=1981 |pmid=7266953 |last2=Holford }}</ref> During pregnancy, a woman can also be exposed to teratogens from contaminated clothing or toxins within the seminal fluid of a partner.<ref name="anderson">{{cite journal|last1=Anderson|first1=Diana|last2=Schmid|first2=ThomasE|last3=Baumgartner|first3=Adolf|title=Male-mediated developmental toxicity|journal=Asian Journal of Andrology|date=2014|volume=16|issue=1|pages=81–8|doi=10.4103/1008-682X.122342|pmid=24369136|pmc=3901885 |doi-access=free }}</ref><ref name=Trasler /><ref name="chia">{{cite journal|last1=Chia|first1=S-E|last2=Shi|first2=L. M.|title=Review of recent epidemiological studies on paternal occupations and birth defects|journal=Occupational and Environmental Medicine|date=1 March 2002|volume=59|issue=3|pages=149–155|doi=10.1136/oem.59.3.149|pmid=11886946|pmc=1763633}}</ref> An additional study found that of 200 individuals referred for genetic counseling for a teratogenic exposure, 52% were exposed to more than one potential teratogen.<ref name="pmid3703408">{{cite journal |author=King CR |title=Genetic counseling for teratogen exposure |journal=Obstetrics and Gynecology |volume=67 |issue=6 |pages=843–6 |year=1986 |pmid=3703408 |doi=10.1097/00006250-198606000-00020}}</ref>

The [[United States Environmental Protection Agency]] studied 1,065 chemical and drug substances in their ToxCast program (part of the [[CompTox Chemicals Dashboard]]) using ''[[in silico]]'' modeling and a human [[pluripotent]] [[stem cell]]-based assay to predict [[in vivo]] developmental intoxicants based on changes in cellular [[metabolism]] following chemical exposure. Findings of the study published in 2020 were that 19% of the 1065 chemicals yielded a prediction of [[developmental toxicity]].<ref>{{cite journal|last1=Zurlinden|first1=TJ|last2=Saili|first2=KS|last3=Rush|first3=N|last4=Kothiya|first4=P|last5=Judson|first5=RS|last6=Houck|first6=KA|last7=Hunter|first7=ES|last8=Baker|first8=NC|last9=Palmer|first9=JA|last10=Thomas|first10=RS|last11=Knudson|first11=TB|title=Profiling the ToxCast Library With a Pluripotent Human (H9) Stem Cell Line-Based Biomarker Assay for Developmental Toxicity|journal=Toxicological Sciences|date=2020|volume=174|issue=2|pages=189–209|pmid=32073639|doi=10.1093/toxsci/kfaa014|pmc=8527599}}</ref>

==== Medications and supplements ====
Probably, the most well-known teratogenic drug is [[thalidomide]]. It was developed near the end of the 1950s by Chemie Grünenthal as a [[hypnotic|sleep-inducing aid]] and [[antiemetic]]. Because of its ability to prevent nausea, it was prescribed for pregnant women in almost 50 countries worldwide between 1956 and 1962.<ref name="isbn978-80-246-1780-0">{{cite book|first1=Miroslav|last1=Peterka|first2=Božena|last2=Novotná|title=Úvod do teratologie: příčiny a mechanizmy vzniku vrozených vad|date=2010|publisher= [[Karolinum Press]] |location=Praha|isbn=978-80-246-1780-0|edition=1. vyd.}}</ref> Until [[William McBride (doctor)|William McBride]] published the study leading to its withdrawal from the market in 1961, about 8,000 to 10,000 severely malformed children were born. The most typical disorders induced by thalidomide were reductional deformities of the long bones of the extremities. [[Phocomelia]], otherwise a rare deformity, therefore helped to recognise the teratogenic effect of the new drug. Among other malformations caused by thalidomide were those of ears, eyes, brain, kidney, heart, and digestive and respiratory tracts; 40% of the prenatally affected children died soon after birth.<ref name="isbn978-80-246-1780-0" /> As thalidomide is used today as a treatment for [[multiple myeloma]] and [[leprosy]], several births of affected children were described in spite of the strictly required use of contraception among female patients treated by it.{{citation needed|date=December 2024}}

[[Vitamin A]] is the sole vitamin that is embryotoxic even in a therapeutic dose, for example in [[multivitamin]]s, because its metabolite, [[retinoic acid]], plays an important role as a signal molecule in the development of several tissues and organs. Its natural precursor, [[β-carotene]], is considered safe, whereas the consumption of animal liver can lead to malformation, as the liver stores lipophilic vitamins, including retinol.<ref name="isbn978-80-246-1780-0" /> [[Isotretinoin]] (13-cis-retinoic-acid; brand name Roaccutane), vitamin A analog, which is often used to treat severe [[Acne vulgaris|acne]], is such a strong teratogen that just a single dose taken by a pregnant woman (even [[transdermal]]ly) may result in serious birth defects. Because of this effect, most countries have systems in place to ensure that it is not given to pregnant women and that the patient is aware of how important it is to prevent pregnancy during and at least one month after treatment. Medical guidelines also suggest that pregnant women should limit vitamin A intake to about 700 [[μg]]/day, as it has teratogenic potential when consumed in excess.<ref name="pmid8602195">{{cite journal |author=Hunt JR |title=Teratogenicity of high vitamin A intake |journal=N. Engl. J. Med. |volume=334 |issue=18 |pages=1197–1200 |year=1996 |pmid=8602195 |doi=10.1056/NEJM199605023341814}}</ref><ref name="pmid16028634">{{cite journal |vauthors=Hartmann S, Brørs O, Bock J |title=Exposure to retinoic acids in non-pregnant women following high vitamin A intake with a liver meal |journal=International Journal for Vitamin and Nutrition Research |volume=75 |issue=3 |pages=187–94 |year=2005 |pmid=16028634 |doi=10.1024/0300-9831.75.3.187 |display-authors=etal  }}</ref> Vitamin A and similar substances can induce spontaneous abortions, premature births, defects of eyes ([[microphthalmia]]), ears, thymus, face deformities, and neurological ([[hydrocephalus]], [[microcephalia]]) and cardiovascular defects, as well as [[intellectual disability]].<ref name="isbn978-80-246-1780-0" />

[[Tetracycline]], an [[antibiotic]], should never be prescribed to women of reproductive age or to children, because of its negative impact on [[bone]] mineralization and [[Human tooth development|teeth mineralization]]. The "tetracycline teeth" have brown or grey colour as a result of a defective development of both the [[dentine]] and the [[enamel of teeth]].<ref name="isbn978-80-246-1780-0" />

Several [[anticonvulsants]] are known to be highly teratogenic. [[Phenytoin]], also known as diphenylhydantoin, along with [[carbamazepine]], is responsible for the [[fetal hydantoin syndrome]], which may typically include broad nose base, cleft lip and/or palate, [[microcephalia]], nails and fingers [[hypoplasia]], [[Small for gestational age|intrauterine growth restriction]], and intellectual disability. [[Trimethadione]] taken during pregnancy is responsible for the [[fetal trimethadione syndrome]], characterized by craniofacial, cardiovascular, renal, and spine malformations, along with a delay in mental and physical development. [[Valproate]] has [[antifolate]] effects, leading to [[neural tube]] closure-related defects such as spina bifida. Lower [[IQ]] and [[autism]] have recently also been reported as a result of intrauterine valproate exposure.<ref name="isbn978-80-246-1780-0" />

[[Hormonal contraception]] is considered harmless for the embryo. Peterka and Novotná<ref name="isbn978-80-246-1780-0" /> do, however, state that synthetic [[progestin]]s used to prevent miscarriage in the past frequently caused masculinization of the outer reproductive organs of female newborns due to their [[androgen]]ic activity. [[Diethylstilbestrol]] is a synthetic [[estrogen]] used from the 1940s to 1971, when the prenatal exposition has been linked to the [[clear-cell adenocarcinoma of the vagina]]. Following studies showed elevated risks for other tumors and congenital malformations of the sex organs for both sexes.{{citation needed|date=December 2024}}

All [[Chemotherapy|cytostatics]] are strong teratogens; [[abortion]] is usually recommended when pregnancy is discovered during or before chemotherapy. [[Aminopterin]], a cytostatic drug with anti[[folate]] effect, was used during the 1950s and 1960s to induce [[therapeutic abortion]]s. In some cases, the abortion did not happen, but the newborns had a fetal aminopterin syndrome consisting of growth retardation, [[craniosynostosis]], hydrocephalus, facial dismorphities, intellectual disability, or leg deformities<ref name="isbn978-80-246-1780-0" /><ref name="Aminopterin syndrome">{{cite web|title=Search Jablonski's Syndromes Database|url=https://www.nlm.nih.gov/archive/20061212/mesh/jablonski/cgi/jablonski/syndrome_cgif026.html|website=United States National Library of Medicine|access-date=2016-04-07|archive-date=2017-05-04|archive-url=https://web.archive.org/web/20170504155825/https://www.nlm.nih.gov/archive/20061212/mesh/jablonski/cgi/jablonski/syndrome_cgif026.html|url-status=live}}</ref>

==== Toxic substances ====
[[Drinking water]] is often a medium through which harmful toxins travel. Heavy metals, elements, nitrates, nitrites, and fluoride can be carried through water and cause congenital disorders.<ref>{{Cite journal |last1=Manassaram |first1=Deana M. |last2=Backer |first2=Lorraine C. |last3=Moll |first3=Deborah M. |date=2006 |title=A Review of Nitrates in Drinking Water: Maternal Exposure and Adverse Reproductive and Developmental Outcomes |journal=Environmental Health Perspectives |language=en |volume=114 |issue=3 |pages=320–327 |doi=10.1289/ehp.8407 |pmid=16507452 |pmc=1392223 |issn=0091-6765}}</ref>

Nitrate, which is found mostly in drinking water from ground sources, is a powerful teratogen. A case-control study in rural Australia that was conducted following frequent reports of prenatal mortality and congenital malformations found that those who drank the nitrate-containing groundwater, as opposed to rain water, ran the risk of giving birth to children with central nervous system disorders, muscoskeletal defects, and cardiac defects.<ref>{{cite journal|last1=Croen|first1=Lisa|last2=Todoroff|first2=Karen|last3=Shaw|first3=Gary|title=Maternal Exposure to Nitrate from Drinking Water and Diet and Risk for Neural Tube Defects|journal=American Journal of Epidemiology|date=2001|volume=153|issue=4|pages=325–31|doi=10.1093/aje/153.4.325|pmid=11207149|doi-access=free}}</ref>

Chlorinated and aromatic solvents such as benzene and trichloroethylene sometimes enter the water supply due to oversights in waste disposal. A case-control study on the area found that by 1986, leukemia was occurring in the children of Woburn, Massachusetts, at a rate that was four times the expected rate of incidence. Further investigation revealed a connection between the high occurrence of leukemia and an error in water distribution that delivered water to the town with significant contamination with manufacturing waste containing trichloroethylene.<ref>{{cite journal|last1=Costas|first1=K.|last2=Knorr|first2=R.S.|last3=Condon|first3=S.K.|title=A case-control study of childhood leukemia in Woburn, Massachusetts: the relationship between leukemia incidence and exposure to public drinking water|journal=Science of the Total Environment|date=2002|volume=300|issue=1–3|pages=23–35|pmid=12685468|doi=10.1016/s0048-9697(02)00169-9|bibcode=2002ScTEn.300...23C}}</ref>
As an [[endocrine disruptor]], [[DDT]] was shown to induce [[miscarriage]]s, interfere with the development of the [[female reproductive system]], cause [[congenital hypothyroidism]], and suspectably [[childhood obesity]].<ref name="isbn978-80-246-1780-0" />

Fluoride, when transmitted through water at high levels, can also act as a teratogen. Two reports on fluoride exposure from China, which were controlled to account for the education level of parents, found that children born to parents who were exposed to 4.12 ppm fluoride grew to have IQs that were, on average, seven points lower than their counterparts whose parents consumed water that contained 0.91 ppm fluoride. In studies conducted on rats, higher fluoride in drinking water led to increased acetylcholinesterase levels, which can alter prenatal brain development. The most significant effects were noted at a level of 5 ppm.<ref>{{cite report|title=In Harm's Way: Toxic Threats to Child Development|date=May 2000|pages=90–2|url=http://www.slweb.org/psr.html|publisher=Greater Boston Physicians for Social Responsibility|access-date=7 December 2014|archive-date=24 September 2015|archive-url=https://web.archive.org/web/20150924102732/http://www.slweb.org/psr.html|url-status=live}}</ref>

The fetus is even more susceptible to damage from carbon monoxide intake, which can be harmful when inhaled during pregnancy, usually through first- or second-hand tobacco smoke. The concentration of carbon monoxide in the infant born to a nonsmoking mother is around 2%, and this concentration drastically increases to a range of 6%–9% if the mother smoked tobacco. Other possible sources of prenatal carbon monoxide intoxication are exhaust gas from combustion motors, use of dichloromethane (paint thinner, varnish removers) in enclosed areas, defective gas water heaters, indoor barbeques, open flames in poorly ventilated areas, and atmospheric exposure in highly polluted areas.<ref>{{Cite journal |last1=Delomenie |first1=Myriam |last2=Schneider |first2=Floriane |last3=Beaudet |first3=Joëlle |last4=Gabriel |first4=René |last5=Bednarek |first5=Nathalie |last6=Graesslin |first6=Olivier |date=2015 |title=Carbon Monoxide Poisoning during Pregnancy: Presentation of a Rare Severe Case with Fetal Bladder Complications |journal=Case Reports in Obstetrics and Gynecology |language=en |volume=2015 |page=687975 |doi=10.1155/2015/687975 |pmid=25834750 |pmc=4365372 |issn=2090-6684|doi-access=free }}</ref> Exposure to carbon monoxide at toxic levels during the first two trimesters of pregnancy can lead to intrauterine growth restriction, leading to a baby who has stunted growth and is born smaller than 90% of other babies at the same gestational age. The effect of chronic exposure to carbon monoxide can depend on the stage of pregnancy in which the mother is exposed. Exposure during the embryonic stage can have neurological consequences, such as telencephalic dysgenesis, behavioral difficulties during infancy, and reduction of cerebellum volume. Also, possible skeletal defects could result from exposure to carbon monoxide during the embryonic stage, such as hand and foot malformations, [[hip dysplasia]], hip subluxation, agenesis of a limb, and inferior maxillary atresia with [[glossoptosis]]. Also, carbon monoxide exposure between days 35 and 40 of embryonic development can lead to an increased risk of the child developing a cleft palate. Exposure to carbon monoxide or polluted ozone exposure can also lead to cardiac defects of the ventrical septal, pulmonary artery, and heart valves.<ref>{{cite journal|last1=Ritz|first1=B.|last2=Yu|first2=F.|last3=Fruin|first3=S.|last4=Chapa|first4=G.|last5=Shaw|first5=G.|last6=Harris|first6=J.|title=Ambient Air Pollution and Risk of Birth Defects in Southern California|journal=American Journal of Epidemiology|date=2002|volume=155|issue=1|pages=17–25|url=http://psr-la.org/files/Infant_Death_Syndrome_Ritz.pdf|access-date=7 December 2014|pmid=11772780|doi=10.1093/aje/155.1.17|doi-access=free|archive-date=30 April 2015|archive-url=https://web.archive.org/web/20150430124337/http://psr-la.org/files/Infant_Death_Syndrome_Ritz.pdf|url-status=dead}}</ref> The effects of carbon monoxide exposure are decreased later in fetal development during the fetal stage, but they may still lead to [[Hypoxia (medical)|anoxic]] [[encephalopathy]].<ref>{{cite journal|last1=Aubard|first1=Yves|last2=Magne|first2=Isabelle|title=Carbon monoxide poisoning in pregnancy|journal=British Journal of Obstetrics and Gynaecology|date=12 Aug 2005|volume=107|issue=7|pages=833–8|doi=10.1111/j.1471-0528.2000.tb11078.x|pmid=10901551|pmc=2146365}}</ref>

Industrial pollution can also lead to congenital defects.<ref>congenital defects</ref> Over a period of 37 years, the [[Chisso]] Corporation, a petrochemical and plastics company, contaminated the waters of [[Minamata Bay]] with an estimated 27 tons of [[methylmercury]], contaminating the local water supply. This led many people in the area to develop what became known as the "[[Minamata disease]]". Because methylmercury is a teratogen, the [[mercury poisoning]] of those residing by the bay resulted in neurological defects in the offspring. Infants exposed to mercury poisoning ''in utero'' showed predispositions to [[cerebral palsy]], [[ataxia]], inhibited psychomotor development, and intellectual disability.<ref>{{cite web|last1=Griesbauer|first1=Laura|title=Methylmercury Contamination in Fish and Shellfish|url=http://www.csa.com/discoveryguides/mercury/review5.php|website=CSA|publisher=CSA 2007|access-date=7 December 2014|archive-date=13 December 2014|archive-url=https://web.archive.org/web/20141213002717/http://www.csa.com/discoveryguides/mercury/review5.php|url-status=dead}}</ref>

Landfill sites have been shown to have adverse effects on fetal development. Extensive research has shown that landfills have several negative effects on babies born to mothers living near landfill sites: low birth weight, birth defects, spontaneous abortion, and fetal and infant mortality. Studies done around the [[Love Canal]] site near Niagara Falls and the [[Lipari Landfill]] in New Jersey have shown a higher proportion of low birth-weight babies than communities farther away from landfills. A study done in California showed a positive correlation between time and quantity of dumping and low birth weights and neonatal deaths. A study in the United Kingdom showed a correlation between pregnant women living near landfill sites and an increased risk of congenital disorders, such as neural tube defects, [[hypospadias]], [[epispadia]], and [[abdominal wall defects]], such as [[gastroschisis]] and exomphalos. A study conducted on a Welsh community also showed an increased incidence of gastroschisis. Another study on 21 European hazardous-waste sites showed that those living within 3&nbsp;km had an increased risk of giving birth to infants with birth defects and that as distance from the land increased, the risk decreased. These birth defects included neural tube defects, malformations of the cardiac septa, anomalies of arteries and veins, and chromosomal anomalies.<ref>{{cite journal|last1=Rushton|first1=Lesley|s2cid=1500545|title=Health hazards and waste management|journal=British Medical Bulletin|date=2003|volume=68|issue=1|pages=183–97|doi=10.1093/bmb/ldg034|pmid=14757717|doi-access=free}}</ref> Looking at communities that live near landfill sites brings up environmental justice. A vast majority of sites are located near poor, mostly black, communities. For example, between the early 1920s and 1978, about 25% of Houston's population was black. However, over 80% of landfills and incinerators during this time were located in these black communities.<ref>{{cite web|last1=Bullard|first1=Robert|title=Environmental Justice for All|url=http://nationalhumanitiescenter.org/tserve/nattrans/ntuseland/essays/envjust.htm|website=National Humanities Center|access-date=9 December 2014|archive-date=29 March 2015|archive-url=https://web.archive.org/web/20150329001037/http://nationalhumanitiescenter.org/tserve/nattrans/ntuseland/essays/envjust.htm|url-status=live}}</ref>

Another issue regarding [[environmental justice]] is [[lead poisoning]]. A fetus exposed to lead during the pregnancy can result in learning difficulties and slowed growth. Some paints (before 1978) and pipes contain lead. Therefore, pregnant women who live in homes with lead paint inhale the dust containing lead, leading to lead exposure in the fetus. When lead pipes are used for drinking water and cooking water, this water is ingested, along with the lead, exposing the fetus to this toxin. This issue is more prevalent in poorer communities because more well-off families are able to afford to have their homes repainted and pipes renovated.<ref>{{cite web|title=Lead Poisoning|url=http://www.mayoclinic.org/diseases-conditions/lead-poisoning/basics/definition/con-20035487|website=Mayo Clinic|access-date=9 December 2014|archive-date=21 December 2014|archive-url=https://web.archive.org/web/20141221122813/http://www.mayoclinic.org/diseases-conditions/lead-poisoning/basics/definition/con-20035487|url-status=live}}</ref>

=== Endometriosis ===
{{Main|Endometriosis}}

Endometriosis can impact a woman's [[fetus]], causing a 30% higher risk for congenital malformations and a 50% higher risk of [[neonates]] being under-sized for their gestational age.<ref name="PMID28181672">{{cite journal |last1=Berlac |first1=Janne Foss |last2=Hartwell |first2=Dorthe |last3=Skovlund |first3=Charlotte Wessel |last4=Langhoff-Roos |first4=Jens |last5=Lidegaard |first5=Øjvind |title=Endometriosis increases the risk of obstetrical and neonatal complications |journal=Acta Obstetricia et Gynecologica Scandinavica |date=June 2017 |volume=96 |issue=6 |pages=751–760 |doi=10.1111/aogs.13111 |pmid=28181672}}</ref>

=== Smoking ===
Paternal smoking prior to conception has been linked with the increased risk of congenital abnormalities in offspring.<ref name=DeSantis />

Smoking causes DNA mutations in the germline of the father, which can be inherited by the offspring. Cigarette smoke acts as a chemical mutagen on germ cell DNA. The germ cells suffer oxidative damage, and the effects can be seen in altered mRNA production, infertility issues, and side effects in the embryonic and fetal stages of development. This [[oxidative stress|oxidative damage]] may result in epigenetic or genetic modifications of the father's germline. Fetal [[lymphocyte]]s have been damaged as a result of a father's smoking habits prior to conception.<ref name=Ji /><ref name=anderson />

Correlations between paternal smoking and the increased risk of offspring developing childhood cancers (including acute [[leukemia]], [[brain tumors]], and [[lymphoma]]) before age five have been established. Little is currently known about how paternal smoking damages the fetus, and what window of time in which the father smokes is most harmful to offspring.<ref name=Ji />

=== Infections ===
{{Main|Vertically transmitted infection}}
A [[vertically transmitted infection]] is an [[infection]] caused by [[bacteria]], [[virus]]es, or in rare cases, [[parasite]]s [[Transmission (medicine)|transmitted]] directly from the mother to an [[embryo]], [[fetus]], or baby during pregnancy or childbirth.<ref>{{Cite journal |last1=Arora |first1=Nitin |last2=Sadovsky |first2=Yoel |last3=Dermody |first3=Terence S. |last4=Coyne |first4=Carolyn B. |date=2017 |title=Microbial Vertical Transmission during Human Pregnancy |journal=Cell Host & Microbe |language=en |volume=21 |issue=5 |pages=561–567 |doi=10.1016/j.chom.2017.04.007 |pmid=28494237 |pmc=6148370 |issn=1931-3128}}</ref>

Congenital disorders were initially believed to be the result of only hereditary factors. However, in the early 1940s, Australian pediatric ophthalmologist [[Norman Gregg]] began recognizing a pattern in which the infants arriving at his surgery were developing congenital cataracts at a higher rate than those who developed it from hereditary factors.<ref>{{Cite journal |last1=Mawson |first1=Anthony R. |last2=Croft |first2=Ashley M. |date=2019 |title=Rubella Virus Infection, the Congenital Rubella Syndrome, and the Link to Autism |journal=International Journal of Environmental Research and Public Health |language=en |volume=16 |issue=19 |pages=3543 |doi=10.3390/ijerph16193543 |pmid=31546693 |pmc=6801530 |issn=1660-4601|doi-access=free }}</ref> On October 15, 1941, Gregg delivered a paper that explained his findings-68 out of the 78 children with congenital cataracts had been exposed'' in utero'' to rubella due to an outbreak in Australian army camps. These findings confirmed, to Gregg, that, in fact, environmental causes for congenital disorders could exist.{{citation needed|date=December 2024}}

[[Rubella]] is known to cause abnormalities of the eye, internal ear, heart, and sometimes the teeth. More specifically, fetal exposure to rubella during weeks five to ten of development (the sixth week particularly) can cause [[cataracts]] and [[microphthalmia]] in the eyes. If the mother is infected with rubella during the ninth week, a crucial week for internal ear development, destruction of the [[organ of Corti]] can occur, causing deafness. In the heart, the [[ductus arteriosus]] can remain after birth, leading to hypertension. Rubella can also lead to atrial and ventricular septal defects in the heart. If exposed to rubella in the second trimester, the fetus can develop central nervous system malformations. However, because infections of rubella may remain undetected, misdiagnosed, or unrecognized in the mother, and/or some abnormalities are not evident until later in the child's life, precise incidence of birth defects due to rubella are not entirely known. The timing of the mother's infection during fetal development determines the risk and type of birth defect. As the embryo develops, the risk of abnormalities decreases. If exposed to the rubella virus during the first four weeks, the risk of malformations is 47%. Exposure during weeks five through eight creates a 22% chance, while weeks 9–12, a 7% chance exists, followed by 6% if the exposure is during the 13th-16th weeks. Exposure during the first eight weeks of development can also lead to premature birth and fetal death. These numbers are calculated from immediate inspection of the infant after birth. Therefore, mental defects are not accounted for in the percentages because they are not evident until later in the child's life. If they were to be included, these numbers would be much higher.<ref name="Langman's Medical Embryology">{{cite book|last1=Sadler|first1=T.W.|title=Langman's Medical Embryology|url=https://archive.org/details/langmansmedicale00lang_0|url-access=registration|date=1985|publisher=William & Wilkins|location=Baltimore|pages=[https://archive.org/details/langmansmedicale00lang_0/page/109 109–12]|isbn=9780683074901|edition=5th}}</ref>

Other infectious agents include [[cytomegalovirus]], the [[herpes simplex virus]], [[hyperthermia]], [[toxoplasmosis]], and [[syphilis]]. Maternal exposure to cytomegalovirus can cause [[microcephaly]], cerebral calcifications, blindness, [[chorioretinitis]] (which can cause blindness), [[hepatosplenomegaly]], and meningoencephalitis in fetuses.<ref name="Langman's Medical Embryology" /> Microcephaly is a disorder in which the fetus has an atypically small head,<ref>{{cite web|title=Microcephaly|url=http://www.mayoclinic.org/diseases-conditions/microcephaly/basics/complications/con-20034823|website=Mayo Clinic|access-date=7 December 2014|archive-date=21 December 2014|archive-url=https://web.archive.org/web/20141221132839/http://www.mayoclinic.org/diseases-conditions/microcephaly/basics/complications/con-20034823|url-status=live}}</ref> cerebral calcifications means certain areas of the brain have atypical calcium deposits,<ref>{{cite web|title=Cerebral calcification, nonarteriosclerotic|url=http://www.medicinenet.com/script/main/art.asp?articlekey=8490|website=MedicineNet.com|access-date=7 December 2014|archive-date=3 July 2015|archive-url=https://web.archive.org/web/20150703115307/http://www.medicinenet.com/script/main/art.asp?articlekey=8490|url-status=dead}}</ref> and meningoencephalitis is the enlargement of the brain. All three disorders cause abnormal brain function or intellectual disability. Hepatosplenomegaly is the enlargement of the liver and spleen which causes digestive problems.<ref>{{cite web|title=Hepatosplenomegaly-Symptoms, Causes, Treatment|url=http://symptomstreatment.org/hepatosplenomegaly-symptomscauses-treatment/|website=Symptoms and Treatment RSS|date=22 August 2011|access-date=7 December 2014|archive-date=10 November 2014|archive-url=https://web.archive.org/web/20141110130727/http://symptomstreatment.org/hepatosplenomegaly-symptomscauses-treatment/|url-status=live}}</ref> It can also cause some [[kernicterus]] and [[petechiae]]. Kernicterus causes yellow pigmentation of the skin, brain damage, and deafness.<ref>{{cite web|title=Kernicterus|url=https://www.nlm.nih.gov/medlineplus/ency/article/007309.htm|website=MedlinePlus Medical Encyclopedia|access-date=7 December 2014|archive-date=5 January 2015|archive-url=https://web.archive.org/web/20150105042120/http://www.nlm.nih.gov/medlineplus/ency/article/007309.htm|url-status=live}}</ref> Petechaie is when the capillaries bleed resulting in red/purple spots on the skin.<ref>{{cite web|title=Petechiae|url=http://www.mayoclinic.org/symptoms/petechiae/basics/causes/SYM-20050724|website=Mayo Clinic|access-date=7 December 2014|archive-date=22 April 2015|archive-url=https://web.archive.org/web/20150422162203/http://www.mayoclinic.org/symptoms/petechiae/basics/causes/sym-20050724|url-status=live}}</ref> However, cytomegalovirus is often fatal in the embryo. The [[Zika virus]] can also be transmitted from the pregnant mother to her baby and cause microcephaly.{{citation needed|date=December 2024}}

The herpes simplex virus can cause [[microcephaly]], microphthalmus (abnormally small eyeballs),<ref>{{cite web|title=Microphthalmus|url=http://www.tsbvi.edu/curriculum-a-publications/992-microphthalmus|website=Texas School for the Blind and Visually Impaired|access-date=7 December 2014|archive-date=17 November 2014|archive-url=https://web.archive.org/web/20141117040457/http://www.tsbvi.edu/curriculum-a-publications/992-microphthalmus|url-status=dead}}</ref> retinal dysplasia, [[hepatosplenomegaly]], and intellectual disability.<ref name="Langman's Medical Embryology" /> Both microphthalmus and retinal dysplasia can cause blindness. However, the most common symptom in infants is an inflammatory response that develops during the first three weeks of life.<ref name="Langman's Medical Embryology" /> Hyperthermia causes [[anencephaly]], which is when part of the brain and skull are absent in the infant.<ref name="Langman's Medical Embryology" /><ref>{{cite web|title=Facts about Anencephaly|url=https://www.cdc.gov/ncbddd/birthdefects/Anencephaly.html|website=Centers for Disease Control and Prevention|access-date=7 December 2014|archive-date=10 December 2014|archive-url=https://web.archive.org/web/20141210102844/http://www.cdc.gov/ncbddd/birthdefects/Anencephaly.html|url-status=live}}</ref> Mother exposure to toxoplasmosis can cause cerebral calcification, hydrocephalus (causes mental disabilities),<ref>{{cite web|title=Hydrocephalus|url=http://www.mayoclinic.org/diseases-conditions/hydrocephalus/basics/complications/con-20030706|website=Mayo Clinic|access-date=7 December 2014|archive-date=24 December 2014|archive-url=https://web.archive.org/web/20141224072018/http://www.mayoclinic.org/diseases-conditions/hydrocephalus/basics/complications/con-20030706|url-status=live}}</ref> and intellectual disability in infants. Other birth abnormalities have been reported as well, such as chorioretinitis, microphthalmus, and ocular defects. Syphilis causes congenital deafness, intellectual disability, and diffuse fibrosis in organs, such as the liver and lungs, if the embryo is exposed.<ref name="Langman's Medical Embryology" />

=== Malnutrition ===
{{Further|Nutrition and pregnancy|folate deficiency}}

For example, a lack of [[folic acid]], a B vitamin, in the diet of a mother can cause cellular [[neural tube]] deformities that result in spina bifida. Congenital disorders such as a neural tube deformity can be prevented by 72% if the mother consumes 4&nbsp;mg of folic acid before the conception and after twelve weeks of pregnancy.<ref name="example1">{{cite book|last1=Raats|first1=Monique|title=Changing Preconceptions|date=1998|publisher=Health Education Authority|location=London|isbn=978-0-7521-1231-2|page=11}}</ref> Folic acid, or vitamin B<sub>9</sub>, aids the development of the foetal nervous system.<ref name="example1" />

Studies with mice have found that food deprivation of the male mouse prior to conception leads to the offspring displaying significantly lower blood glucose levels.<ref name="anderson2">{{cite journal|last1=Anderson|first1=Lucy M.|last2=Riffle|first2=Lisa|last3=Wilson|first3=Ralph|last4=Travlos|first4=Gregory S.|last5=Lubomirski|first5=Mariusz S.|last6=Alvord|first6=W. Gregory|title=Preconceptional fasting of fathers alters serum glucose in offspring of mice|journal=Nutrition|date=March 2006|volume=22|issue=3|pages=327–331|doi=10.1016/j.nut.2005.09.006|pmid=16500559|url=https://zenodo.org/record/1259285|access-date=2019-09-12|archive-date=2020-07-27|archive-url=https://web.archive.org/web/20200727004018/https://zenodo.org/record/1259285|url-status=live}}</ref>

=== Physical restraint ===
External physical shocks or constraints due to growth in a restricted space may result in unintended deformation or separation of cellular structures resulting in an abnormal final shape or damaged structures unable to function as expected. An example is [[Potter syndrome]] due to [[oligohydramnios]]. This finding is important for future understanding of how genetics may predispose individuals for diseases such as obesity, diabetes, and cancer.<ref>{{Citation |last1=Bhandari |first1=Jenish |title=Potter Syndrome |date=2022 |url=http://www.ncbi.nlm.nih.gov/books/NBK560858/ |work=StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32809693 |access-date=2022-10-31 |last2=Thada |first2=Pawan K. |last3=Sergent |first3=Shane R. |archive-date=2023-03-16 |archive-url=https://web.archive.org/web/20230316123757/https://www.ncbi.nlm.nih.gov/books/NBK560858/ |url-status=live }}</ref>

For multicellular organisms that develop in a [[womb]], the physical interference or presence of other similarly developing organisms such as [[twins]] can result in the two cellular masses being integrated into a larger whole, with the combined cells attempting to continue to develop in a manner that satisfies the intended growth patterns of both cell masses.<ref>{{Cite journal |last1=Rahbaran |first1=Mohaddeseh |last2=Razeghian |first2=Ehsan |last3=Maashi |first3=Marwah Suliman |last4=Jalil |first4=Abduladheem Turki |last5=Widjaja |first5=Gunawan |last6=Thangavelu |first6=Lakshmi |last7=Kuznetsova |first7=Mariya Yurievna |last8=Nasirmoghadas |first8=Pourya |last9=Heidari |first9=Farid |last10=Marofi |first10=Faroogh |last11=Jarahian |first11=Mostafa |date=2021-11-30 |title=Cloning and Embryo Splitting in Mammalians: Brief History, Methods, and Achievements |journal=Stem Cells International |volume=2021 |pages=2347506 |doi=10.1155/2021/2347506 |issn=1687-966X |pmc=8651392 |pmid=34887927|doi-access=free }}</ref> The two cellular masses can compete with each other, and may either duplicate or merge various structures. This results in conditions such as [[conjoined twins]], and the resulting merged organism may die at birth when it must leave the life-sustaining environment of the womb and must attempt to sustain its biological processes independently.{{citation needed|date=December 2024}}

=== Genetics ===
{{Main|Genetic disorder}}
Genetic causes of birth defects include [[Heredity|inheritance]] of abnormal [[gene]]s from the mother or the father, as well as new [[mutation]]s in one of the [[germ cell]]s that gave rise to the fetus. Male germ cells mutate at a much faster rate than female germ cells, and as the father ages, the DNA of the germ cells mutates quickly.<ref name=Zhu /><ref name="Sartorius">{{cite journal|last1=Sartorius|first1=G. A.|last2=Nieschlag|first2=E.|title=Paternal age and reproduction|journal=Human Reproduction Update|date=20 August 2009|volume=16|issue=1|pages=65–79|doi=10.1093/humupd/dmp027|pmid=19696093|doi-access=free}}</ref> If an egg is fertilized with sperm that has damaged DNA, a possibility exists that the fetus could develop abnormally.<ref name=Sartorius /><ref name="Savitz">{{cite journal|last1=Savitz|first1=David A.|last2=Schwingl|first2=Pamela J.|last3=Keels|first3=Martha Ann|title=Influence of paternal age, smoking, and alcohol consumption on congenital anomalies|journal=Teratology|date=October 1991|volume=44|issue=4|pages=429–440|doi=10.1002/tera.1420440409|pmid=1962288}}</ref>

Genetic disorders are all congenital (present at birth), though they may not be expressed or recognized until later in life. Genetic disorders may be grouped into single-gene defects, multiple-gene disorders, or [[chromosome abnormality|chromosomal defects]]. Single-gene defects may arise from abnormalities of both copies of an [[autosome|autosomal]] gene (a [[dominance (genetics)#Recessive allele|recessive]] disorder) or of only one of the two copies (a [[dominance (genetics)#Dominant allele|dominant]] disorder). Some conditions result from deletions or abnormalities of a few genes located contiguously on a chromosome. Chromosomal disorders involve the loss or duplication of larger portions of a chromosome (or an entire chromosome) containing hundreds of genes. Large chromosomal abnormalities always produce effects on many different body parts and organ systems.{{citation needed|date=December 2024}}

===Defective sperm===
Non-genetic defects in sperm cells, such as deformed [[centriole]]s and other components in the tail and neck of the sperm which are important for the embryonic development, may result in defects.<ref>{{Cite journal|title=The Role of Sperm Centrioles in Human Reproduction – The Known and the Unknown - PMC|year=2019 |pmc=6781795 |last1=Avidor-Reiss |first1=T. |last2=Mazur |first2=M. |last3=Fishman |first3=E. L. |last4=Sindhwani |first4=P. |journal=Frontiers in Cell and Developmental Biology |volume=7 |page=188 |doi=10.3389/fcell.2019.00188 |pmid=31632960 |doi-access=free }}</ref><ref>{{Cite web|url=https://news.utoledo.edu/index.php/06_07_2018/men-may-contribute-to-infertility-through-newly-discovered-part-of-sperm|title=Men may contribute to infertility through newly discovered part of sperm &#124; UToledo News|date=June 7, 2018|access-date=January 8, 2023|archive-date=January 8, 2023|archive-url=https://web.archive.org/web/20230108065226/https://news.utoledo.edu/index.php/06_07_2018/men-may-contribute-to-infertility-through-newly-discovered-part-of-sperm|url-status=live}}</ref>

=== Socioeconomics ===
A low [[socioeconomic status]] in a deprived neighborhood may include exposure to "environmental stressors and risk factors".<ref name="Graaf">{{cite journal|last1=de Graaf|first1=Johanna P.|last2=Steegers|first2=Eric A.P.|last3=Bonsel|first3=Gouke J.|title=Inequalities in perinatal and maternal health|journal=Current Opinion in Obstetrics and Gynecology|date=April 2013|volume=25|issue=2|pages=98–108|doi=10.1097/GCO.0b013e32835ec9b0|pmid=23425665|s2cid=41767750}}</ref> Socioeconomic inequalities are commonly measured by the Cartairs-Morris score, Index of Multiple Deprivation, Townsend deprivation index, and the Jarman score.<ref name="Vos">{{cite journal|last1=Vos|first1=Amber A.|last2=Posthumus|first2=Anke G.|last3=Bonsel|first3=Gouke J.|last4=Steegers|first4=Eric A.P.|last5=Denktaş|first5=Semiha|title=Deprived neighborhoods and adverse perinatal outcome: a systematic review and meta-analysis|journal=Acta Obstetricia et Gynecologica Scandinavica|date=August 2014|volume=93|issue=8|pages=727–740|doi=10.1111/aogs.12430|pmid=24834960|s2cid=39860659|hdl=1765/68911|hdl-access=free}}</ref> The Jarman score, for example, considers "unemployment, overcrowding, single parents, under-fives, elderly living alone, ethnicity, low social class and residential mobility".<ref name=Vos /> In Vos' meta-analysis these indices are used to view the effect of low SES neighborhoods on maternal health. In the meta-analysis, data from individual studies were collected from 1985 up until 2008.<ref name=Vos /> Vos concludes that a correlation exists between prenatal adversities and deprived neighborhoods.<ref name=Vos /> Other studies have shown that low SES is closely associated with the development of the fetus in utero and growth retardation.<ref name="Bradley and Corwyn">{{cite journal|last1=Bradley|first1=Robert H.|last2=Corwyn|first2=Robert F.|s2cid=43766257|title=S S C D|journal=Annual Review of Psychology|date=February 2002|volume=53|issue=1|pages=371–399|doi=10.1146/annurev.psych.53.100901.135233|pmid=11752490}}</ref> Studies also suggest that children born in low SES families are "likely to be born prematurely, at low birth weight, or with asphyxia, a birth defect, a disability, fetal alcohol syndrome, or AIDS".<ref name="Bradley and Corwyn" /> Bradley and Corwyn also suggest that congenital disorders arise from the mother's lack of nutrition, a poor lifestyle, maternal substance abuse and "living in a neighborhood that contains hazards affecting fetal development (toxic waste dumps)".<ref name="Bradley and Corwyn" /> In a meta-analysis that viewed how inequalities influenced maternal health, it was suggested that deprived neighborhoods often promoted behaviors such as smoking, drug and alcohol use.<ref name=Graaf /> After controlling for socioeconomic factors and ethnicity, several individual studies demonstrated an association with outcomes such as perinatal mortality and preterm birth.<ref name=Graaf />

=== Radiation ===
For the survivors of the [[atomic bombing of Hiroshima]] and [[atomic bombing of Nagasaki|Nagasaki]], who are known as the ''[[Hibakusha]]'', no statistically demonstrable increase of birth defects/congenital malformations was found among their later conceived children, or found in the later conceived children of cancer survivors who had previously received [[radiotherapy]].<ref>{{cite book|url=http://apps.who.int/iris/bitstream/10665/78218/1/9789241505130_eng.pdf|publisher=[[World Health Organization]]|title=Health risk assessment from the nuclear accident after the 2011 Great East Japan Earthquake and Tsunami based on a preliminary dose estimation|year=2013|isbn=978-92-4-150513-0|pages=23–24|access-date=2013-11-21|archive-date=2017-12-15|archive-url=https://web.archive.org/web/20171215065509/http://apps.who.int/iris/bitstream/10665/78218/1/9789241505130_eng.pdf|url-status=live}}</ref><ref>{{cite journal|doi=10.1001/jama.1992.03490050109039|quote= No differences were found (in frequencies of birth defects, stillbirths, etc), thus allaying the immediate public concern that atomic radiation might spawn an epidemic of malformed children|title= The Children of Atomic Bomb Survivors: A Genetic Study|journal= JAMA: The Journal of the American Medical Association|volume= 268|issue= 5|pages= 633–634|year= 1992|last1= Heath|first1= Clark W.|pmc= 1682172|bibcode= 1992RadR..131..229A}}</ref><ref name="books.google.ie">{{cite book|url={{ google books|plainurl=y|id=DykKlVU0V-oC|page=21}}|page=21 |title=Teratology in the Twentieth Century Plus Ten|last=Kalter|first=Harold|publisher=[[Springer Netherlands]]|date=2010|isbn=978-90-481-8820-8|access-date=28 October 2014}}</ref><ref>{{cite journal|doi=10.1038/sj.bjc.6600748|pmid=12569380|title=Sex ratio among offspring of childhood cancer survivors treated with radiotherapy|journal=British Journal of Cancer|volume=88|issue=3|pages=382–7|year=2003|last1=Winther|first1=J F|last2=Boice|first2=J D|last3=Thomsen|first3=B L|last4=Schull|first4=W J|last5=Stovall|first5=M|last6=j h Olsen|pmc=2747537}}</ref>
The surviving women of Hiroshima and Nagasaki who were able to conceive, though exposed to substantial amounts of radiation, later had children with no higher incidence of abnormalities/birth defects than in the Japanese population as a whole.<ref>{{cite web |url=http://www.rerf.jp/radefx/genetics_e/birthdef.html |title=Birth defects among the children of atomic-bomb survivors (1948–1954) |website=RERF.jp |publisher=[[Radiation Effects Research Foundation]] |access-date=2013-11-21 |archive-date=2018-05-20 |archive-url=https://web.archive.org/web/20180520224831/http://www.rerf.jp/radefx/genetics_e/birthdef.html |url-status=live }}</ref><ref>{{cite web |url=http://www.eenews.net/public/Greenwire/2011/04/11/1 |title=Nuclear crisis: Hiroshima and Nagasaki cast long shadows over radiation science |date=11 April 2011 |first=Paul |last=Voosen |website=[[E&E News]] |access-date=28 October 2014 |archive-date=5 April 2012 |archive-url=https://web.archive.org/web/20120405235042/http://www.eenews.net/public/Greenwire/2011/04/11/1 |url-status=dead }}</ref>

Relatively few studies have researched the effects of paternal radiation exposure on offspring. Following the [[Chernobyl]] disaster, it was assumed in the 1990s that the germ line of irradiated fathers suffered [[minisatellite]] mutations in the DNA, which was inherited by descendants.<ref name=Trasler /><ref name="dubrova">{{cite journal|last1=Dubrova|first1=Yuri E.|last2=Nesterov|first2=Valeri N.|last3=Krouchinsky|first3=Nicolay G.|last4=Ostapenko|first4=Valdislav A.|last5=Neumann|first5=Rita|last6=Neil|first6=David L.|last7=Jeffreys|first7=Alec J.|title=Human minisatellite mutation rate after the Chernobyl accident|journal=Nature|date=25 April 1996|volume=380|issue=6576|pages=683–686|doi=10.1038/380683a0|pmid=8614461|bibcode=1996Natur.380..683D|s2cid=4303433}}</ref> More recently, however, the World Health Organization states, "children conceived before or after their father's exposure showed no statistically significant differences in mutation frequencies".<ref>{{Cite book | url = http://whqlibdoc.who.int/publications/2006/9241594179_eng.pdf | title = Health Effects of the Chernobyl Accident and Special Health Care Programmes: Report of the UN Chernobyl Forum, Expert Group "Health" | editor-first = Burton | editor-last = Bennett | editor2-first = Michael | editor2-last = Repacholi | editor3-first = Zhanat | editor3-last = Carr | year = 2006 | publisher = World Health Organization (WHO) | location = Geneva | isbn = 978-92-4-159417-2 | access-date = 20 August 2011 | page = 79 | archive-date = 12 August 2011 | archive-url = https://web.archive.org/web/20110812174332/http://whqlibdoc.who.int/publications/2006/9241594179_eng.pdf | url-status = live }}</ref> This [[statistically insignificant]] increase was also seen by independent researchers analyzing the children of the [[Chernobyl liquidators|liquidators]].<ref>{{cite journal| doi=10.1016/j.mrgentox.2004.11.002 | pmid=15725606 | volume=581 | issue=1–2 | title=Microsatellite mutations show no increases in the children of the Chernobyl liquidators | year=2005 | journal=Mutation Research/Genetic Toxicology and Environmental Mutagenesis | pages=69–82 | author=Furitsu Katsumi| bibcode=2005MRGTE.581...69F }}</ref> Animal studies have shown that incomparably ''massive'' doses of X-ray irradiation of male mice resulted in birth defects of the offspring.<ref name=anderson />

In the 1980s, a relatively high prevalence of pediatric leukemia cases in children living near a nuclear processing plant in West Cumbria, UK, led researchers to investigate whether the cancer was a result of paternal radiation exposure. A significant association between paternal irradiation and offspring cancer was found, but further research areas close to other nuclear processing plants did not produce the same results.<ref name=anderson /><ref name=Trasler /> Later this was determined to be the [[List of cancer clusters|Seascale cluster]] in which the leading hypothesis is the influx of foreign workers, who have a different rate of leukemia within their race than the British average, resulted in the observed cluster of 6 children more than expected around Cumbria.<ref>{{cite journal | author = Dickinson HO, Parker L | year = 1999 | title = Quantifying the effect of population mixing on childhood leukaemia risk: the Seascale cluster | journal = British Journal of Cancer | volume = 81 | issue = 1| pages = 144–151 [146, 149] | doi=10.1038/sj.bjc.6690664| pmid = 10487626 | pmc = 2374359 }}</ref>

=== Parent's age ===
{{Main|Advanced maternal age |Paternal age effect}}
Certain birth complications can occur more often in [[advanced maternal age]] (greater than 35 years). Complications include fetal growth restriction, preeclampsia, placental abruption, pre-mature births, and stillbirth. These complications not only may put the child at risk, but also the mother.<ref>{{Cite journal|last1=Lean|first1=Samantha C.|last2=Derricott|first2=Hayley|last3=Jones|first3=Rebecca L.|last4=Heazell|first4=Alexander E. P.|date=2017-10-17|title=Advanced maternal age and adverse pregnancy outcomes: A systematic review and meta-analysis|journal=PLOS ONE|language=en|volume=12|issue=10|pages=e0186287|doi=10.1371/journal.pone.0186287|pmid=29040334|pmc=5645107|issn=1932-6203|bibcode=2017PLoSO..1286287L|doi-access=free}}</ref>

The effects of the father's age on offspring are not yet well understood and are studied far less extensively than the effects of the mother's age.<ref name="olshan">{{cite journal|last1=Olshan|first1=Andrew F.|last2=Schnitzer|first2=Patricia G.|last3=Baird|first3=Patricia A.|title=Paternal age and the risk of congenital heart defects|journal=Teratology|date=July 1994|volume=50|issue=1|pages=80–84|doi=10.1002/tera.1420500111|pmid=7974258}}</ref> Fathers contribute proportionally more DNA mutations to their offspring via their germ cells than the mother, with the paternal age governing how many mutations are passed on. This is because, as humans age, male germ cells acquire mutations at a much faster rate than female germ cells.<ref name=Zhu /><ref name=anderson /><ref name=Sartorius />

Around a 5% increase in the incidence of [[Septal defect|ventricular septal defects]], atrial septal defects, and [[patent ductus arteriosus]] in offspring has been found to be correlated with advanced paternal age. Advanced paternal age has also been linked to increased risk of [[achondroplasia]] and [[Apert syndrome]]. Offspring born to fathers under the age of 20 show increased risk of being affected by patent ductus arteriosus, ventricular septal defects, and the [[tetralogy of Fallot]]. It is hypothesized that this may be due to environmental exposures or lifestyle choices.<ref name=olshan />

Research has found that there is a correlation between advanced paternal age and risk of birth defects such as [[Dysmelia|limb anomalies]], syndromes involving multiple systems, and [[Down syndrome]].<ref name=Sartorius /><ref name=Zhu /><ref name="yang">{{cite journal|last1=Yang|first1=Q.|last2=Wen|first2=S.W.|last3=Leader|first3=A.|last4=Chen|first4=X.K.|last5=Lipson|first5=J.|last6=Walker|first6=M.|title=Paternal age and birth defects: how strong is the association?|journal=Human Reproduction|date=7 December 2006|volume=22|issue=3|pages=696–701|doi=10.1093/humrep/del453|pmid=17164268|doi-access=}}</ref> Recent studies have concluded that 5–9% of Down syndrome cases are due to paternal effects, but these findings are controversial.<ref name=Sartorius /><ref name=Savitz /><ref name=Zhu /><ref name="wiener">{{cite journal|last1=Wiener-Megnazi|first1=Zofnat|last2=Auslender|first2=Ron|last3=Dirnfeld|first3=Martha|title=Advanced paternal age and reproductive outcome|journal=Asian Journal of Andrology|date=12 December 2011|volume=14|issue=1|pages=69–76|doi=10.1038/aja.2011.69|pmid=22157982|pmc=3735149}}</ref>

There is concrete evidence that advanced paternal age is associated with the increased likelihood that a mother will have a [[miscarriage]] or that [[Perinatal mortality|fetal death]] will occur.<ref name=Sartorius />

=== Unknown ===
Although significant progress has been made in identifying the etiology of some birth defects, approximately 65% have no known or identifiable cause.<ref name="isbn0-471-38225-6">{{cite book |author1=Ronan O'Rahilly |author2=Fabiola Müller |title=Human embryology & teratology |publisher=Wiley-Liss |location=New York |year=2001 |isbn=978-0-471-38225-6 }}</ref> These are referred to as sporadic, a term that implies an unknown cause, random occurrence regardless of maternal living conditions,<ref name="pmid10960809">{{cite journal |vauthors=Bezerra Guimarães MJ, Marques NM, Melo Filho DA |title=Taux de mortalité infantile et disparités sociales à Recife, métropole du Nord-Est du Brésil |trans-title=Infant mortality rate and social disparity at Recife, the metropolis of the North-East of Brazil |language=fr |journal=Santé |volume=10 |issue=2 |pages=117–21 |year=2000 |pmid=10960809 |url=http://www.john-libbey-eurotext.fr/medline.md?issn=1157-5999&vol=10&iss=2&page=117 |access-date=2013-11-10 |archive-date=2021-08-28 |archive-url=https://web.archive.org/web/20210828004048/https://www.jle.com/fr/revues/san/e-docs/taux_de_mortalite_infantile_et_disparites_sociales_a_recife_metropole_du_nord_est_du_bresil_220156/article.phtml |url-status=live }}</ref> and a low recurrence risk for future children. For 20–25% of anomalies there seems to be a "multifactorial" cause, meaning a complex interaction of multiple minor genetic anomalies with environmental risk factors. Another 10–13% of anomalies have a purely environmental cause (e.g. infections, illness, or drug abuse in the mother). Only 12–25% of anomalies have a purely genetic cause. Of these, the majority are [[chromosomal anomalies]].<ref name="KAF473">Kumar, Abbas and Fausto, eds., ''Robbins and Cotran's Pathologic Basis of Disease, 7th edition'', p.473.</ref>

Congenital disorders are not limited to humans and can be found in a variety of other species, including cattle. One such condition is called schistosomus reflexus and is defined by spinal inversion, exposure of abdominal viscera, and limb abnormalities.<ref>Miniard L., Nichols C., Smith J., Jarrin-Yepez P., Grzeskowiak R., & Newkirk K. (2023). Schistosomus reflexus with another fetus in a beef heifer. Clinical Theriogenology, 15. https://doi.org/10.58292/ct.v15.9609</ref>

== Prevention ==

Folate supplements decrease the risk of neural tube defects. Tentative evidence supports the role of [[L-arginine]] in decreasing the risk of [[intrauterine growth restriction]].<ref>{{cite journal |last1=Chen |first1=J |last2=Gong |first2=X |last3=Chen |first3=P |last4=Luo |first4=K |last5=Zhang |first5=X |title=Effect of L-arginine and sildenafil citrate on intrauterine growth restriction fetuses: a meta-analysis. |journal=BMC Pregnancy and Childbirth |date=16 August 2016 |volume=16 |pages=225 |doi=10.1186/s12884-016-1009-6 |pmid=27528012|pmc=4986189 |doi-access=free }}</ref>

==Screening==
{{Main|Newborn screening}}
[[Newborn screening|Newborn screening tests]] were introduced in the early 1960s and initially dealt with just two disorders. Since then [[tandem mass spectrometry]], [[gas chromatography–mass spectrometry]], and DNA analysis has made it possible for a much larger range of disorders to be screened. Newborn screening mostly measures metabolite and enzyme activity using a dried blood spot sample.<ref name="Simonsen">{{cite journal|last1=Simonsen|first1=H|title=[Screening of newborns for inborn errors of metabolism by tandem mass spectrometry].|journal=Ugeskrift for Laeger|date=25 November 2002|volume=164|issue=48|pages=5607–12|pmid=12523003}}</ref> Screening tests are carried out in order to detect serious disorders that may be treatable to some extent.<ref name="Wilcken">{{cite journal|last1=Wilcken|first1=B|last2=Wiley|first2=V|title=Newborn screening.|journal=Pathology|date=February 2008|volume=40|issue=2|pages=104–15|doi=10.1080/00313020701813743|pmid=18203033}}</ref> Early diagnosis makes possible the readiness of therapeutic dietary information, enzyme replacement therapy and organ transplants.<ref name="Ezgu">{{cite book|last1=Ezgu|first1=F|title=Inborn Errors of Metabolism.|journal=Advances in Clinical Chemistry|date=2016|volume=73|pages=195–250|doi=10.1016/bs.acc.2015.12.001|pmid=26975974|isbn=9780128046906}}</ref> Different countries support the screening for a number of metabolic disorders ([[inborn errors of metabolism]] (IEM)), and genetic disorders including [[cystic fibrosis]] and [[Duchenne muscular dystrophy]].<ref name="Wilcken"/><ref name=DMD>{{cite web|title=Newborn screening for DMD shows promise as an international model|url=http://www.nationwidechildrens.org/research-news-viewer/simplified-newborn-screening-for-duchenne-muscular-dystrophy-shows-promise-as-an-international-model?contentid=100432|publisher=Nationwide Children's Hospital|access-date=2018-04-02|date=2012-03-19|archive-date=2015-10-15|archive-url=https://web.archive.org/web/20151015051038/http://www.nationwidechildrens.org/research-news-viewer/simplified-newborn-screening-for-duchenne-muscular-dystrophy-shows-promise-as-an-international-model?contentId=100432|url-status=dead}}</ref>
Tandem mass spectroscopy can also be used for IEM, and investigation of sudden infant death, and shaken baby syndrome.<ref name="Wilcken"/>

Screening can also be carried out [[prenatal testing|prenatally]] and can include [[obstetric ultrasonography]] to give scans such as the [[nuchal scan]]. [[3D ultrasound]] scans can give detailed information of structural anomalies.{{citation needed|date=December 2024}}

== Epidemiology ==
[[File:Congenital anomalies world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.2|Congenital anomalies deaths per million persons in 2012: {{Div col|small=yes|colwidth=10em}}{{legend|#ffff20|0–26}}{{legend|#ffe820|27–34}}{{legend|#ffd820|35–46}}{{legend|#ffc020|47–72}}{{legend|#ffa020|73–91}}{{legend|#ff9a20|92–111}}{{legend|#f08015|112–134}}{{legend|#e06815|135–155}}{{legend|#d85010|156–176}}{{legend|#d02010|177–396}}{{div col end}}]]
[[File:Congenital anomalies world map - DALY - WHO2004.svg|thumb|upright=1.2|[[Disability-adjusted life year]] for congenital anomalies per 100,000 inhabitants in 2004:<ref>{{cite web |url=https://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |title=WHO Disease and injury country estimates |year=2009 |work=World Health Organization |access-date=Nov 11, 2009 |archive-date=November 11, 2009 |archive-url=https://web.archive.org/web/20091111101009/http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |url-status=live }}</ref>{{Div col|small=yes|colwidth=10em}}
{{legend|#b3b3b3|no data}}
{{legend|#ffff65|less than 160}}
{{legend|#fff200|160–240}}
{{legend|#ffdc00|240–320}}
{{legend|#ffc600|320–400}}
{{legend|#ffb000|400–480}}
{{legend|#ff9a00|480–560}}
{{legend|#ff8400|560–640}}
{{legend|#ff6e00|640–720}}
{{legend|#ff5800|720–800}}
{{legend|#ff4200|800–900}}
{{legend|#ff2c00|900–950}}
{{legend|#cb0000|more than 950}}
{{div col end}}]]

Congenital anomalies resulted in about 632,000 deaths per year in 2013 down from 751,000 in 1990.<ref name=GBD204 /> The types with the greatest death are [[congenital heart defect]]s (323,000), followed by [[neural tube defects]] (69,000).<ref name=GBD204 />

Many studies have found that the frequency of occurrence of certain congenital malformations depends on the sex of the child (table).<ref>{{Cite journal|pmc=1254713|pages= 286–294|year= 1964|last1= Gittelsohn|first1= A|title= Statistical Study of Twins—Methods|journal= American Journal of Public Health and the Nation's Health|volume= 54|issue= 2|last2= Milham|first2= S|doi=10.2105/ajph.54.2.286|pmid=14115496}}</ref><ref>{{Cite journal|pmid=717306|pages= 970–972|year= 1978|last1= Fernando|first1= J|title= Sex liability to single structural defects|journal= American Journal of Diseases of Children|volume= 132|issue= 10|last2= Arena|first2= P|last3= Smith|first3= D. W.|doi= 10.1001/archpedi.1978.02120350034004}}</ref><ref>{{Cite journal|pmid=9096746|pages= 225–228|year= 1997|last1= Lubinsky|first1= M. S.|title= Classifying sex biased congenital anomalies|journal= American Journal of Medical Genetics|volume= 69|issue= 3|doi= 10.1002/(SICI)1096-8628(19970331)69:3<225::AID-AJMG1>3.0.CO;2-K}}</ref><ref>{{cite journal|pmid=11745830|pages=237–251|year=2001|last1=Lary|first1=J. M.|title=Sex differences in the prevalence of human birth defects: A population-based study|journal=Teratology|volume=64|issue=5|last2=Paulozzi|first2=L. J.|doi=10.1002/tera.1070}}</ref><ref name="Cui">{{cite journal|pmid=16265641|pages= 876–880|year= 2005|last1= Cui|first1= W|title= Sex differences in birth defects: A study of opposite-sex twins|journal= Birth Defects Research Part A: Clinical and Molecular Teratology|volume= 73|issue= 11|last2= Ma|first2= C. X.|last3= Tang|first3= Y|last4= Chang|first4= V|last5= Rao|first5= P. V.|last6= Ariet|first6= M|last7= Resnick|first7= M. B.|last8= Roth|first8= J|doi= 10.1002/bdra.20196}}</ref> For example, pyloric stenosis occurs more often in males while congenital hip dislocation is four to five times more likely to occur in females. Among children with one kidney, there are approximately twice as many males, whereas among children with three kidneys there are approximately 2.5 times more females. The same pattern is observed among infants with excessive number of ribs, vertebrae, teeth and other organs which in a process of evolution have undergone reduction—among them there are more females. Contrarily, among the infants with their scarcity, there are more males. Anencephaly is shown to occur approximately twice as frequently in females.<ref name="WHO reports">World Health Organization reports. "Congenital malformations", Geneve, 1966, p. 128.</ref> The number of boys born with 6 fingers is two times higher than the number of girls.<ref>Darwin C. (1871) The descent of man and selection in relation to sex. London, John Murray, 1st ed.</ref> Now various techniques are available to detect congenital anomalies in fetus before birth.<ref>{{Cite news|url=https://www.cdc.gov/ncbddd/birthdefects/diagnosis.html|title=Diagnosis {{!}} Birth Defects {{!}} NCBDDD {{!}} CDC|date=2017-12-04|work=Centers for Disease Control and Prevention|access-date=2018-11-07|language=en-us|archive-date=2018-11-07|archive-url=https://web.archive.org/web/20181107224830/https://www.cdc.gov/ncbddd/birthdefects/diagnosis.html|url-status=live}}</ref>

About 3% of newborns have a "major physical anomaly", meaning a physical anomaly that has cosmetic or functional significance.<ref>Kumar, Abbas and Fausto, eds., ''Robbins and Cotran's Pathologic Basis of Disease, 7th edition'', p.470.</ref>
Physical congenital abnormalities are the leading cause of infant mortality in the United States, accounting for more than 20% of all infant deaths. Seven to ten percent of all children{{clarify|reason=Of literally "all" children or just "all" of the 3% above?|date=November 2014}} will require extensive medical care to diagnose or treat a birth defect.<ref name="pmid2468064">{{cite journal |author=Dicke JM |title=Teratology: principles and practice |journal=Med. Clin. North Am. |volume=73 |issue=3 |pages=567–82 |year=1989 |pmid=2468064 |doi=10.1016/S0025-7125(16)30658-7}}</ref>

:{| class="wikitable"
|+ '''The sex ratio of patients with congenital malformations'''
! Congenital anomaly !! Sex ratio, ♂♂:♀♀
|-
| '''Defects with female predominance''' ||
|-
| Congenital hip dislocation || 1 ''':''' 5.2;<ref name="Rajewski" /> 1 ''':''' 5;<ref name="Montagu">Montagu A. (1968) Natural Superiority of Women, The, Altamira Press, 1999.</ref> 1 ''':''' 8;<ref name="Cui" /> 1 ''':''' 3.7<ref name="Riley, Halliday">Riley M., Halliday J. (2002) Birth Defects in Victoria 1999–2000, Melbourne.</ref>
|-
| [[Cleft lip and palate|Cleft palate]] || 1 ''':''' 3<ref name="Montagu" />
|-
| [[Anencephaly]] || 1 ''':''' 1.9;<ref name="Rajewski" /> 1 ''':''' 2<ref name="WHO reports" />
|-
| Craniocele || 1 ''':''' 1.8<ref name="Rajewski" />
|-
| Aplasia of lung || 1 ''':''' 1.51<ref name="Rajewski" />
|-
| Spinal herniation || 1 ''':''' 1.4<ref name="Rajewski" />
|-
| Diverticulum of the esophagus || 1 ''':''' 1.4<ref name="Rajewski" />
|-
| Stomach || 1 ''':''' 1.4<ref name="Rajewski" />
|-
| '''Neutral defects''' ||
|-
| Hypoplasia of the tibia and femur || 1 ''':''' 1.2<ref name="Rajewski" />
|-
| [[Spina bifida]] || 1 ''':''' 1.2<ref name="Riley, Halliday" />
|-
| Atresia of small intestine || 1 ''':''' 1<ref name="Rajewski" />
|-
| [[Microcephaly]] || 1.2 ''':''' 1<ref name="Riley, Halliday" />
|-
| [[Esophageal atresia]] || 1.3 ''':''' 1;<ref name="Rajewski" /> 1.5 ''':''' 1<ref name="Riley, Halliday" />
|-
| [[Hydrocephalus]] || 1.3 ''':''' 1<ref name="Riley, Halliday" />
|-
| '''Defects with male predominance''' ||
|-
| Diverticula of the colon || 1.5 ''':''' 1<ref name="Rajewski" />
|-
| Atresia of the rectum || 1.5 ''':''' 1;<ref name="Rajewski" /> 2 ''':''' 1<ref name="Riley, Halliday" />
|-
| Unilateral [[renal agenesis]] || 2 ''':''' 1;<ref name="Rajewski" /> 2.1 ''':''' 1<ref name="Riley, Halliday" />
|-
| Schistocystis || 2 ''':''' 1<ref name="Rajewski" />
|-
| [[Cleft lip and palate]] || 2 ''':''' 1;<ref name="Montagu" /> 1.47 ''':''' 1<ref name="Riley, Halliday" />
|-
| Bilateral [[renal agenesis]] || 2.6 ''':''' 1<ref name="Rajewski" />
|-
| Congenital anomalies of the genitourinary system || 2.7 ''':''' 1<ref name="Cui" />
|-
| [[Pyloric stenosis]], congenital || 5 ''':''' 1;<ref name="Montagu" /> 5.4 ''':''' 1<ref name="Cui" />
|-
| [[Meckel's diverticulum]] || More common in boys<ref name="Rajewski" />
|-
| [[Congenital megacolon]] || More common in boys<ref name="Rajewski" />
|-
| '''All defects''' || 1.22 ''':''' 1;<ref>{{Cite journal|pmid=14745913|pages=953–958|year=2003|last1=Shaw|first1=G. M.|title=Differential risks to males and females for congenital malformations among 2.5 million California births, 1989–1997|journal=Birth Defects Research Part A: Clinical and Molecular Teratology|volume=67|issue=12|last2=Carmichael|first2=S. L.|last3=Kaidarova|first3=Z|last4=Harris|first4=J. A.|doi=10.1002/bdra.10129}}</ref> '''1.29 : 1'''<ref name="Cui" />
|}
* Data<ref name="Cui" /> obtained on opposite-sex twins. ** — Data<ref name="Riley, Halliday" /> were obtained in the period 1983–1994.

P. M. Rajewski and A. L. Sherman (1976) have analyzed the frequency of congenital anomalies in relation to the system of the organism. Prevalence of men was recorded for the anomalies of phylogenetically younger organs and systems.<ref name="Rajewski">Rajewski P. M., Sherman A. L. (1976) The importance of gender in the epidemiology of malignant tumors (systemic-evolutionary approach). In: Mathematical treatment of medical-biological information. M., Nauka, p. 170–181.</ref>

In respect of an etiology, sexual distinctions can be divided on appearing before and after differentiation of male's gonads during embryonic development, which begins from the eighteenth week. The testosterone level in male embryos thus raises considerably.<ref>{{cite journal|pmid=4856555|pages= 612–617|year= 1974|last1= Reyes|first1= F. I.|title= Studies on human sexual development. II. Fetal and maternal serum gonadotropin and sex steroid concentrations|journal= The Journal of Clinical Endocrinology & Metabolism|volume= 38|issue= 4|last2= Boroditsky|first2= R. S.|last3= Winter|first3= J. S.|last4= Faiman|first4= C|doi= 10.1210/jcem-38-4-612}}</ref> The subsequent hormonal and physiological distinctions of male and female embryos can explain some sexual differences in frequency of congenital defects.<ref>{{Cite web|date=2021-01-31|title=Birth Defects: Saving Pediatric Patients from Congenital Defects|url=https://mdforlives.blog/2021/01/31/birth-defects-preventable/|access-date=2021-02-09|website=MDforLives|language=en-US|archive-date=2021-02-13|archive-url=https://web.archive.org/web/20210213003823/https://mdforlives.blog/2021/01/31/birth-defects-preventable/|url-status=live}}</ref> It is difficult to explain the observed differences in the frequency of birth defects between the sexes by the details of the reproductive functions or the influence of environmental and social factors.{{citation needed|date=December 2024}}

=== United States ===
The CDC and National Birth Defect Project studied the incidence of birth defects in the US. Key findings include:{{citation needed|date=December 2024}}
* Down syndrome was the most common condition with an estimated prevalence of 14.47 per 10,000 live births, implying about 6,000 diagnoses each year.
* About 7,000 babies are born with a cleft palate, cleft lip or both.

{| class="wikitable"
|+Adjusted National Prevalence Estimates and Estimated Number of Cases in the United States, 2004–2006<ref>{{Cite web|url = https://www.cdc.gov/ncbddd/birthdefects/features/birthdefects-keyfindings.html|title = Key Findings: Updated National Birth Prevalence Estimates for Selected Birth Defects in the United States, 2004–2006|access-date = October 1, 2014|website = CDC|publisher = Centers for Disease Control and Prevention (CDC) and the National Birth Defects Prevention Network|archive-date = October 28, 2014|archive-url = https://web.archive.org/web/20141028181420/http://www.cdc.gov/ncbddd/birthdefects/features/birthdefects-keyfindings.html|url-status = live}}</ref>
!Birth Defects !! Cases per Births !! Estimated Annual Number of Cases !! Estimated National Prevalence per 10,000 Live Births (Adjusted for maternal race/ethnicity)
|-
| colspan="4" |'''Central nervous system defects'''
|-
| [[Anencephaly]]||1 in 4,859||859||2.06
|-
| [[Spina bifida]] without anencephaly||1 in 2,858||1460||3.50
|-
| [[Encephalocele]]||1 in 12,235||341||0.82
|-
| colspan="4" | '''Eye defects'''
|-
| [[Anophthalmia]]/ [[microphthalmia]]||1 in 5,349||780||1.87
|-
| colspan="4" |'''Cardiovascular defects'''
|-
| Common truncus||1 in 13,876||301||0.72
|-
| Transposition of great arteries||1 in 3,333||1252||3.00
|-
| [[Tetralogy of Fallot]]||1 in 2,518||1657||3.97
|-
| [[Atrioventricular septal defect]]||1 in 2,122||1966||4.71
|-
| [[Hypoplastic left heart syndrome]]||1 in 4,344||960||2.30
|-
| colspan="4" |'''Orofacial defects'''
|-
| [[Cleft palate]] without cleft lip||1 in 1,574||2651||6.35
|-
| [[Cleft lip]] with and without cleft palate||1 in 940||4437||10.63
|-
| colspan="4" |'''Gastrointestinal defects'''
|-
| [[Esophageal atresia]]/tracheoeophageal fistula||1 in 4,608||905||2.17
|-
| Rectal and large intestinalatresia/[[stenosis]]||1 in 2,138||1952||4.68
|-
| colspan="4" | '''Musculoskeletal defects'''
|-
| [[Clubfoot]], lower limbs||1 in 250 ~ 1000||...||...
|-
| Reduction deformity, upper limbs||1 in 2,869||1454||3.49
|-
| Reduction deformity, lower limbs||1 in 5,949||701||1.68
|-
| [[Gastroschisis]]||1 in 2,229||1871||4.49
|-
| [[Omphalocele]]||1 in 5,386||775||1.86
|-
| [[Diaphragmatic hernia]]||1 in 3,836||1088||2.61
|-
| colspan="4" |'''Chromosomal anomalies'''
|-
| [[Trisomy 13]]||1 in 7,906||528||1.26
|-
| [[Trisomy 21]] ([[Down syndrome]])||1 in 691||6037||14.47
|-
| [[Trisomy 18]]||1 in 3,762||1109||2.66
|}

== See also ==
* [[Idiopathic]]
* [[List of congenital disorders]]
* [[List of ICD-9 codes 740-759: Congenital anomalies]]
* [[Malformative syndrome]]
* [[March of Dimes]]
* [[Mitochondrial disease]]
* [[National Birth Defects Prevention Network]], founded 1997
* [[Supernumerary body part]]
{{clear}}

== Notes ==
{{Notelist}}

== References ==
{{Reflist|30em}}

== External links ==
{{Wikiquote}}
* [https://www.who.int/news-room/fact-sheets/detail/birth-defects WHO fact sheet on birth defects]
* [https://web.archive.org/web/20101020145505/http://www.cdc.gov/ncbddd/bd/facts.htm CDC's National Center on Birth Defects and Developmental Disabilities]
{{Medical resources
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|  eMedicineSubj  =
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|  MeshID         = D009358
}}

{{Chromosomal abnormalities |state=collapsed}}
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{{Infants and their care}}
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[[Category:Congenital disorders| ]]
[[Category:Animal developmental biology]]
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