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Birth defect

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This article is about congenital disorders in humans. Not to be confused withteratologyorgenetic disorder.
Birth defect
Other namesCongenital disorder, congenital disease, congenital deformity, congenital anomaly[1]
Incompletecleft lip
SpecialtyMedical genetics,pediatrics
SymptomsPhysical disability,intellectual disability,developmental disability[2]
Usual onsetPresent at birth[2]
TypesStructural, functional[3]
CausesGenetics,exposure to certain medications or chemicals, certaininfectionsduringpregnancy[4]
Risk factorsInsufficientfolic acid,drinkingalcoholorsmoking,poorly controlleddiabetes,mother over the age of 35[5][6]
TreatmentTherapy,medication, surgery,assistive technology[7]
Frequency3% of newborns (US)[8]
Deaths628,000 (2015)[9]

Abirth defect[a]is an abnormal condition that is present atbirth,regardless of its cause.[2]Birth defects may result indisabilitiesthat may bephysical,intellectual,ordevelopmental.[2]The disabilities can range from mild to severe.[6]Birth defects are divided into two main types: structural disorders in which problems are seen with the shape of a body part andfunctional disordersin which problems exist with how a body part works.[3]Functional disorders includemetabolicanddegenerative disorders.[3]Some birth defects include both structural and functional disorders.[3]

Birth defects may result fromgeneticorchromosomal disorders,exposure to certain medications or chemicals, or certaininfections during pregnancy.[4]Risk factors includefolate deficiency,drinking alcoholorsmokingduring pregnancy, poorly controlleddiabetes,and a mother over the age of 35 years old.[5][6]Many are believed to involve multiple factors.[6]Birth defects may be visible at birth or diagnosed byscreening tests.[10]A number of defects can be detected before birth by differentprenatal tests.[10]

Treatment varies depending on the defect in question.[7]This may includetherapy,medication, surgery, orassistive technology.[7]Birth defects affected about 96 million people as of 2015.[11]In the United States, they occur in about 3% of newborns.[8]They resulted in about 628,000 deaths in 2015, down from 751,000 in 1990.[9][12]The types with the greatest numbers of deaths arecongenital heart disease(303,000), followed byneural tube defects(65,000).[9]

Classification

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Much of the language used for describing congenital conditions antedatesgenome 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]

Primarily structural

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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.)

Terminology

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  • Acongenital physical anomalyis 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 moreminor physical anomaliesif 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 (preauricularpits), shortness of the fourthmetacarpalormetatarsalbones, or dimples over the lower spine (sacral dimples). Some minor anomalies may be clues to more significant internal abnormalities.
  • Birth defectis a widely used term for a congenital malformation,i.e.a congenital, physical anomaly that is recognizable atbirth,and which is significant enough to be considered a problem. According to theCenters 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,[13]though many birth defects have no known cause. An example of a birth defect iscleft palate,which occurs during the fourth through seventh weeks of gestation.[14]Body tissue and special cells from each side of the head grow toward the center of the face. They join to make the face.[14]A cleft means a split or separation; the "roof" of the mouth is called the palate.[15]
  • Acongenital malformationis 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 amalformation syndrome.
  • Some conditions are due to abnormal tissue development:
    • A malformation is associated with a disorder of tissue development.[16]Malformations often occur in the first trimester.
    • Adysplasiais a disorder at the organ level that is due to problems with tissue development.[16]
  • Conditions also can arise after tissue is formed:
    • Adeformationis a condition arising from mechanical stress to normal tissue.[16]Deformations often occur in the second or third trimester, and can be due tooligohydramnios.
    • A disruption involves breakdown of normal tissues.[16]
  • When multiple effects occur in a specified order, they are known as asequence.When the order is not known, it is asyndrome.

Examples of primarily structural congenital disorders

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A limb anomaly is called adysmelia.These include all forms of limbs anomalies, such asamelia,ectrodactyly,phocomelia,polymelia,polydactyly,syndactyly,polysyndactyly,oligodactyly,brachydactyly,achondroplasia,congenitalaplasiaorhypoplasia,amniotic band syndrome,andcleidocranial dysostosis.[17]

Congenital heart defectsincludepatent ductus arteriosus,atrial septal defect,ventricular septal defect,andtetralogy of Fallot.

Congenital anomalies of the nervous system include neural tube defects such asspina bifida,encephalocele,andanencephaly.Other congenital anomalies of the nervous system include theArnold–Chiari malformation,theDandy–Walker malformation,hydrocephalus,microencephaly,megalencephaly,lissencephaly,polymicrogyria,holoprosencephaly,andagenesis of the corpus callosum.[18]

Congenital anomalies of thegastrointestinal systeminclude numerous forms ofstenosisandatresia,and perforation, such asgastroschisis.[19]

Congenital anomalies of the kidney and urinary tract include renal parenchyma, kidneys, and urinary collecting system.[20]

Defects can be bilateral or unilateral, and different defects often coexist in an individual child.[21]

Primarily metabolic

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Main article:Inborn error of metabolism

Acongenital metabolic diseaseis also referred to as aninborn error of metabolism.Most of these aresingle-gene defects,usually heritable. Many affect the structure of body parts, but some simply affect the function.[22]

Other

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Other well-defined genetic conditions may affect the production of hormones, receptors, structural proteins, and ion channels.

Causes

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Alcohol exposure

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Main article:Fetal alcohol spectrum disorder

The mother's consumption of alcohol during pregnancy can cause a continuum of various permanent birth defects: craniofacial abnormalities,[23]brain damage,[24]intellectual disability,[25]heart disease, kidney abnormality, skeletal anomalies, ocular abnormalities.[26]

The prevalence of children affected is estimated at least 1% in U.S.[27]as well in Canada.

Very few studies have investigated the links between paternal alcohol use and offspring health.[28]

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.[29]The compromised stress management skills of animals whose male parent was exposed to alcohol are similar to the exaggerated responses to stress that children withfetal alcohol syndromedisplay because of maternal alcohol use. These birth defects and behavioral disorders were found in cases of both long- and short-term paternal alcohol ingestion.[30][31]In the same animal study, paternal alcohol exposure was correlated with a significant difference in organ size and the increased risk of the offspring displayingventricular septal defectsat birth.[31]

Toxic substances

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Further information:Developmental toxicity,drugs in pregnancy,andenvironmental toxicants and fetal development

Substances whosetoxicitycan cause congenital disorders are calledteratogens,and include certain pharmaceutical and recreationaldrugs in pregnancy,as well as manyenvironmental toxins in pregnancy.[32]

A review published in 2010 identified six main teratogenic mechanisms associated with medication use:folate antagonism,neural crest celldisruption,endocrine disruption,oxidative stress,vasculardisruption, and specific receptor- or enzyme-mediated teratogenesis.[33]

An estimated 10% of all birth defects are caused by prenatal exposure to a teratogenic agent.[34]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.[35][36]Teratogen-caused birth defects are potentially preventable. Nearly 50% of pregnant women have been exposed to at least one medication during gestation.[37]During pregnancy, a woman can also be exposed to teratogens from contaminated clothing or toxins within the seminal fluid of a partner.[38][30][39]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.[40]

TheUnited States Environmental Protection Agencystudied 1,065 chemical and drug substances in their ToxCast program (part of theCompTox Chemicals Dashboard) usingin silicomodeling and a humanpluripotentstem cell-based assay to predictin vivodevelopmental intoxicants based on changes in cellularmetabolismfollowing chemical exposure. Findings of the study published in 2020 were that 19% of the 1065 chemicals yielded a prediction ofdevelopmental toxicity.[41]

Medications and supplements

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Probably, the most well-known teratogenic drug isthalidomide.It was developed near the end of the 1950s by Chemie Grünenthal as asleep-inducing aidandantiemetic.Because of its ability to prevent nausea, it was prescribed for pregnant women in almost 50 countries worldwide between 1956 and 1962.[42]UntilWilliam McBridepublished 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.[42]As thalidomide is used today as a treatment formultiple myelomaandleprosy,several births of affected children were described in spite of the strictly required use of contraception among female patients treated by it.

Vitamin Ais the sole vitamin that is embryotoxic even in a therapeutic dose, for example inmultivitamins,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.[42]Isotretinoin(13-cis-retinoic-acid; brand name Roaccutane), vitamin A analog, which is often used to treat severeacne,is such a strong teratogen that just a single dose taken by a pregnant woman (eventransdermally) 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 700μg/day, as it has teratogenic potential when consumed in excess.[43][44]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 asintellectual disability.[42]

Tetracycline,anantibiotic,should never be prescribed to women of reproductive age or to children, because of its negative impact onbonemineralization andteeth mineralization.The "tetracycline teeth" have brown or grey colour as a result of a defective development of both thedentineand theenamel of teeth.[42]

Severalanticonvulsantsare known to be highly teratogenic.Phenytoin,also known as diphenylhydantoin, along withcarbamazepine,is responsible for thefetal hydantoin syndrome,which may typically include broad nose base, cleft lip and/or palate,microcephalia,nails and fingershypoplasia,intrauterine growth restriction,and intellectual disability.Trimethadionetaken during pregnancy is responsible for thefetal trimethadione syndrome,characterized by craniofacial, cardiovascular, renal, and spine malformations, along with a delay in mental and physical development.Valproatehasantifolateeffects, leading toneural tubeclosure-related defects such as spina bifida. LowerIQandautismhave recently also been reported as a result of intrauterine valproate exposure.[42]

Hormonal contraceptionis considered harmless for the embryo. Peterka and Novotná[42]do, however, state that syntheticprogestinsused to prevent miscarriage in the past frequently caused masculinization of the outer reproductive organs of female newborns due to theirandrogenicactivity.Diethylstilbestrolis a syntheticestrogenused from the 1940s to 1971, when the prenatal exposition has been linked to theclear-cell adenocarcinoma of the vagina.Following studies showed elevated risks for other tumors and congenital malformations of the sex organs for both sexes.

Allcytostaticsare strong teratogens;abortionis usually recommended when pregnancy is discovered during or before chemotherapy.Aminopterin,a cytostatic drug with antifolateeffect, was used during the 1950s and 1960s to inducetherapeutic abortions.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[42][45]

Toxic substances

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Drinking wateris often a medium through which harmful toxins travel. Heavy metals, elements, nitrates, nitrites, and fluoride can be carried through water and cause congenital disorders.[46]

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.[47]

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.[48] As anendocrine disruptor,DDTwas shown to inducemiscarriages,interfere with the development of thefemale reproductive system,cause thecongenital hypothyroidism,and suspectablychildhood obesity.[42]

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.[49]

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.[50]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 withglossoptosis.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.[51]The effects of carbon monoxide exposure are decreased later in fetal development during the fetal stage, but they may still lead toanoxicencephalopathy.[52]

Industrial pollution can also lead to congenital defects.[53]Over a period of 37 years, theChissoCorporation, a petrochemical and plastics company, contaminated the waters ofMinamata Baywith an estimated 27 tons ofmethylmercury,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, themercury poisoningof those residing by the bay resulted in neurological defects in the offspring. Infants exposed to mercury poisoningin uteroshowed predispositions tocerebral palsy,ataxia,inhibited psychomotor development, and intellectual disability.[54]

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 theLove Canalsite near Niagara Falls and theLipari Landfillin 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,andabdominal wall defects,such asgastroschisisand 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 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.[55]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.[56]

Another issue regardingenvironmental justiceislead 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.[57]

Endometriosis

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Main article:Endometriosis

Endometriosis can impact a woman'sfetus,causing a 30% higher risk for congenital malformations and a 50% higher risk ofneonatesbeing under-sized for their gestational age.[58]

Smoking

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Paternal smoking prior to conception has been linked with the increased risk of congenital abnormalities in offspring.[28]

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. Thisoxidative damagemay result in epigenetic or genetic modifications of the father's germline. Fetallymphocyteshave been damaged as a result of a father's smoking habits prior to conception.[36][38]

Correlations between paternal smoking and the increased risk of offspring developing childhood cancers (including acuteleukemia,brain tumors,andlymphoma) 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.[36]

Infections

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Main article:Vertically transmitted infection

Avertically transmitted infectionis aninfectioncaused bybacteria,viruses,or in rare cases,parasitestransmitteddirectly from the mother to anembryo,fetus,or baby during pregnancy or childbirth.[59]

Congenital disorders were initially believed to be the result of only hereditary factors. However, in the early 1940s, Australian pediatric ophthalmologistNorman Greggbegan 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.[60]On October 15, 1941, Gregg delivered a paper that explained his findings-68 out of the 78 children with congenital cataracts had been exposedin uteroto rubella due to an outbreak in Australian army camps. These findings confirmed, to Gregg, that, in fact, environmental causes for congenital disorders could exist.

Rubellais 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 causecataractsandmicrophthalmiain the eyes. If the mother is infected with rubella during the ninth week, a crucial week for internal ear development, destruction of theorgan of Cortican occur, causing deafness. In the heart, theductus arteriosuscan 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.[61]

Other infectious agents includecyt Omega lovirus,theherpes simplex virus,hyperthermia,toxoplasmosis,andsyphilis.Maternal exposure to cyt Omega lovirus can causemicrocephaly,cerebral calcifications, blindness,chorioretinitis(which can cause blindness),hepatosplen Omega ly,and meningoencephalitis in fetuses.[61]Microcephaly is a disorder in which the fetus has an atypically small head,[62]cerebral calcifications means certain areas of the brain have atypical calcium deposits,[63]and meningoencephalitis is the enlargement of the brain. All three disorders cause abnormal brain function or intellectual disability. Hepatosplen Omega ly is the enlargement of the liver and spleen which causes digestive problems.[64]It can also cause somekernicterusandpetechiae.Kernicterus causes yellow pigmentation of the skin, brain damage, and deafness.[65]Petechaie is when the capillaries bleed resulting in red/purple spots on the skin.[66]However, cyt Omega lovirus is often fatal in the embryo. TheZika viruscan also be transmitted from the pregnant mother to her baby and cause microcephaly.

The herpes simplex virus can causemicrocephaly,microphthalmus (abnormally small eyeballs),[67]retinal dysplasia,hepatosplen Omega ly,and intellectual disability.[61]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.[61]Hyperthermia causesanencephaly,which is when part of the brain and skull are absent in the infant.[61][68]Mother exposure to toxoplasmosis can cause cerebral calcification, hydrocephalus (causes mental disabilities),[69]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.[61]

Malnutrition

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Further information:Nutrition and pregnancyandfolate deficiency

For example, a lack offolic acid,a B vitamin, in the diet of a mother can cause cellularneural tubedeformities that result in spina bifida. Congenital disorders such as a neural tube deformity can be prevented by 72% if the mother consumes 4 mg of folic acid before the conception and after twelve weeks of pregnancy.[70]Folic acid, or vitamin B9,aids the development of the foetal nervous system.[70]

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.[71]

Physical restraint

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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 isPotter syndromedue tooligohydramnios.This finding is important for future understanding of how genetics may predispose individuals for diseases such as obesity, diabetes, and cancer.[72]

For multicellular organisms that develop in awomb,the physical interference or presence of other similarly developing organisms such astwinscan 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.[73]The two cellular masses can compete with each other, and may either duplicate or merge various structures. This results in conditions such asconjoined 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.

Genetics

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Main article:Genetic disorder

Genetic causes of birth defects includeinheritanceof abnormalgenesfrom the mother or the father, as well as newmutationsin one of thegerm cellsthat 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.[35][74]If an egg is fertilized with sperm that has damaged DNA, a possibility exists that the fetus could develop abnormally.[74][75]

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, orchromosomal defects.Single-gene defects may arise from abnormalities of both copies of anautosomalgene (arecessivedisorder) or of only one of the two copies (adominantdisorder). 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.

Defective sperm

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Non-genetic defects in sperm cells, such as deformedcentriolesand other components in the tail and neck of the sperm which are important for the embryonic development, may result in defects.[76][77]

Socioeconomics

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A lowsocioeconomic statusin a deprived neighborhood may include exposure to "environmental stressors and risk factors".[78]Socioeconomic inequalities are commonly measured by the Cartairs-Morris score, Index of Multiple Deprivation, Townsend deprivation index, and the Jarman score.[79]The Jarman score, for example, considers "unemployment, overcrowding, single parents, under-fives, elderly living alone, ethnicity, low social class and residential mobility".[79]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.[79]Vos concludes that a correlation exists between prenatal adversities and deprived neighborhoods.[79]Other studies have shown that low SES is closely associated with the development of the fetus in utero and growth retardation.[80]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".[80]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)".[80]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.[78]After controlling for socioeconomic factors and ethnicity, several individual studies demonstrated an association with outcomes such as perinatal mortality and preterm birth.[78]

Radiation

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For the survivors of theatomic bombing of HiroshimaandNagasaki,who are known as theHibakusha,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 receivedradiotherapy.[81][82][83][84] 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.[85][86]

Relatively few studies have researched the effects of paternal radiation exposure on offspring. Following theChernobyldisaster, it was assumed in the 1990s that the germ line of irradiated fathers sufferedminisatellitemutations in the DNA, which was inherited by descendants.[30][87]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".[88]Thisstatistically insignificantincrease was also seen by independent researchers analyzing the children of theliquidators.[89]Animal studies have shown that incomparablymassivedoses of X-ray irradiation of male mice resulted in birth defects of the offspring.[38]

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.[38][30]Later this was determined to be theSeascale clusterin 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.[90]

Parent's age

[edit]
Main articles:Advanced maternal ageandPaternal age effect

Certain birth complications can occur more often inadvanced 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.[91]

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.[92]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.[35][38][74]

Around a 5% increase in the incidence ofventricular septal defects,atrial septal defects, andpatent ductus arteriosusin offspring has been found to be correlated with advanced paternal age. Advanced paternal age has also been linked to increased risk ofachondroplasiaandApert syndrome.Offspring born to fathers under the age of 20 show increased risk of being affected by patent ductus arteriosus, ventricular septal defects, and thetetralogy of Fallot.It is hypothesized that this may be due to environmental exposures or lifestyle choices.[92]

Research has found that there is a correlation between advanced paternal age and risk of birth defects such aslimb anomalies,syndromes involving multiple systems, andDown syndrome.[74][35][93]Recent studies have concluded that 5-9% of Down syndrome cases are due to paternal effects, but these findings are controversial.[74][75][35][94]

There is concrete evidence that advanced paternal age is associated with the increased likelihood that a mother will have amiscarriageor thatfetal deathwill occur.[74]

Unknown

[edit]

Although significant progress has been made in identifying the etiology of some birth defects, approximately 65% have no known or identifiable cause.[34]These are referred to as sporadic, a term that implies an unknown cause, random occurrence regardless of maternal living conditions,[95]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 arechromosomal anomalies.[96]

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.[97]

Prevention

[edit]

Folate supplements decrease the risk of neural tube defects. Tentative evidence supports the role ofL-argininein decreasing the risk ofintrauterine growth restriction.[98]

Screening

[edit]
Main article:Newborn screening

Newborn screening testswere introduced in the early 1960s and initially dealt with just two disorders. Since thentandem 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.[99]Screening tests are carried out in order to detect serious disorders that may be treatable to some extent.[100]Early diagnosis makes possible the readiness of therapeutic dietary information, enzyme replacement therapy and organ transplants.[101]Different countries support the screening for a number of metabolic disorders (inborn errors of metabolism(IEM)), and genetic disorders includingcystic fibrosisandDuchenne muscular dystrophy.[100][102] Tandem mass spectroscopy can also be used for IEM, and investigation of sudden infant death, and shaken baby syndrome.[100]

Screening can also be carried outprenatallyand can includeobstetric ultrasonographyto give scans such as thenuchal scan.3D ultrasoundscans can give detailed information of structural anomalies.

Epidemiology

[edit]
Congenital anomalies deaths per million persons in 2012:
0–26
27–34
35–46
47–72
73–91
92–111
112–134
135–155
156–176
177–396
Disability-adjusted life yearfor congenital anomalies per 100,000 inhabitants in 2004:[103]
no data
less than 160
160–240
240–320
320–400
400–480
480–560
560–640
640–720
720–800
800–900
900–950
more than 950

Congenital anomalies resulted in about 632,000 deaths per year in 2013 down from 751,000 in 1990.[12]The types with the greatest death arecongenital heart defects(323,000), followed byneural tube defects(69,000).[12]

Many studies have found that the frequency of occurrence of certain congenital malformations depends on the sex of the child (table).[104][105][106][107][108]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.[109]The number of boys born with 6 fingers is two times higher than the number of girls.[110]Now various techniques are available to detect congenital anomalies in fetus before birth.[111]

About 3% of newborns have a "major physical anomaly", meaning a physical anomaly that has cosmetic or functional significance.[112] 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[clarification needed]will require extensive medical care to diagnose or treat a birth defect.[113]

The sex ratio of patients with congenital malformations
Congenital anomaly Sex ratio, ♂♂:♀♀
Defects with female predominance
Congenital hip dislocation 1:5.2;[114]1:5;[115]1:8;[108]1:3.7[116]
Cleft palate 1:3[115]
Anencephaly 1:1.9;[114]1:2[109]
Craniocele 1:1.8[114]
Aplasia of lung 1:1.51[114]
Spinal herniation 1:1.4[114]
Diverticulum of the esophagus 1:1.4[114]
Stomach 1:1.4[114]
Neutral defects
Hypoplasia of the tibia and femur 1:1.2[114]
Spina bifida 1:1.2[116]
Atresia of small intestine 1:1[114]
Microcephaly 1.2:1[116]
Esophageal atresia 1.3:1;[114]1.5:1[116]
Hydrocephalus 1.3:1[116]
Defects with male predominance
Diverticula of the colon 1.5:1[114]
Atresia of the rectum 1.5:1;[114]2:1[116]
Unilateralrenal agenesis 2:1;[114]2.1:1[116]
Schistocystis 2:1[114]
Cleft lip and palate 2:1;[115]1.47:1[116]
Bilateralrenal agenesis 2.6:1[114]
Congenital anomalies of the genitourinary system 2.7:1[108]
Pyloric stenosis,congenital 5:1;[115]5.4:1[108]
Meckel's diverticulum More common in boys[114]
Congenital megacolon More common in boys[114]
All defects 1.22:1;[117]1.29: 1[108]
  • Data[108]obtained on opposite-sex twins. ** — Data[116]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.[114]

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.[118]The subsequent hormonal and physiological distinctions of male and female embryos can explain some sexual differences in frequency of congenital defects.[119]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.

United States

[edit]

The CDC and National Birth Defect Project studied the incidence of birth defects in the US. Key findings include:

  • 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.
Adjusted National Prevalence Estimates and Estimated Number of Cases in the United States, 2004–2006[120]
Birth Defects Cases per Births Estimated Annual Number of Cases Estimated National Prevalence per 10,000 Live Births (Adjusted for maternal race/ethnicity)
Central nervous system defects
Anencephaly 1 in 4,859 859 2.06
Spina bifidawithout anencephaly 1 in 2,858 1460 3.50
Encephalocele 1 in 12,235 341 0.82
Eye defects
Anophthalmia/microphthalmia 1 in 5,349 780 1.87
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
Orofacial defects
Cleft palatewithout cleft lip 1 in 1,574 2651 6.35
Cleft lipwith and without cleft palate 1 in 940 4437 10.63
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
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
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

[edit]

Notes

[edit]
  1. ^Also known as acongenital disorder,congenital disease,congenital deformity,orcongenital anomaly.

References

[edit]
  1. ^Ruth A. Hannon (2010).Porth pathophysiology: concepts of altered health states(1st Canadian ed.). Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 128.ISBN978-1-60547-781-7.
  2. ^abcd"Birth Defects: Condition Information".nichd.nih.gov.September 2017.Archivedfrom the original on 22 December 2017.Retrieved8 December2017.
  3. ^abcd"What are the types of birth defects?".nichd.nih.gov.September 2017.Archivedfrom the original on 22 December 2017.Retrieved8 December2017.
  4. ^ab"What causes birth defects?".nichd.nih.gov.September 2017.Archivedfrom the original on 17 December 2017.Retrieved8 December2017.
  5. ^ab"How many people are affected by/at risk for birth defects?".nichd.nih.gov.Archivedfrom the original on 17 December 2017.Retrieved8 December2017.
  6. ^abcd"What are Birth Defects?".Centers for Disease Control and Prevention.7 September 2017.Archivedfrom the original on 15 June 2018.Retrieved14 April2023.
  7. ^abc"What are the treatments for birth defects?".nichd.nih.gov.September 2017.Archivedfrom the original on 20 December 2017.Retrieved8 December2017.
  8. ^ab"Birth Defects".Dec 15, 2015.Archivedfrom the original on 18 June 2018.Retrieved17 Jan2016.
  9. ^abcWang, Haidong; et al. (8 October 2016)."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".Lancet.388(10053): 1459–1544.doi:10.1016/s0140-6736(16)31012-1.PMC5388903.PMID27733281.
  10. ^ab"How do health care providers diagnose birth defects?".nichd.nih.gov.September 2017.Archivedfrom the original on 22 December 2017.Retrieved8 December2017.
  11. ^Vos, Theo; et al. (8 October 2016)."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".Lancet.388(10053): 1545–1602.doi:10.1016/S0140-6736(16)31678-6.PMC5055577.PMID27733282.
  12. ^abc"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".Lancet.385(9963): 117–71. 17 December 2014.doi:10.1016/S0140-6736(14)61682-2.PMC4340604.PMID25530442.
  13. ^Birth Defects ResearchArchived2015-09-24 at theWayback Machine.Centers for Disease Control and Prevention.
  14. ^ab"Facts about Cleft Lip and Cleft Palate | Birth Defects | NCBDDD | CDC".cdc.gov.Archivedfrom the original on 2015-05-08.Retrieved2016-03-16.
  15. ^communications."Cleft Lip and Cleft Palate".American Academy of Otolaryngology–Head and Neck Surgery.Archivedfrom the original on 2016-03-21.Retrieved2016-03-16.
  16. ^abcdGraham, John Whichello (2007).Smith's Recognizable Patterns of Human Deformation, 3rd Edition.Philadelphia: Saunders. p. 3.ISBN978-0-7216-1489-2.
  17. ^Tayel, SM; Fawzia, MM; Al-Naqeeb, Niran A; Gouda, Said; Al Awadi, SA; Naguib, KK (2005)."A morpho-etiological description of congenital limb anomalies".Annals of Saudi Medicine.25(3): 219–227.doi:10.5144/0256-4947.2005.219.ISSN0256-4947.PMC6147980.PMID16119523.
  18. ^Gaitanis, John; Tarui, Tomo (2018)."Nervous System Malformations".CONTINUUM: Lifelong Learning in Neurology.24(1): 72–95.doi:10.1212/CON.0000000000000561.ISSN1080-2371.PMC6463295.PMID29432238.
  19. ^CDC (2021-03-31)."Congenital Anomalies of the Digestive System".Centers for Disease Control and Prevention.Archivedfrom the original on 2022-10-31.Retrieved2022-10-31.
  20. ^"Overview of congenital anomalies of the kidney and urinary tract (CAKUT)".UpToDate – Wolters Kluer Health.Archivedfrom the original on 27 June 2012.Retrieved29 October2012.
  21. ^Jain, Sanjay; Chen, Feng (2018-12-01)."Developmental pathology of congenital kidney and urinary tract anomalies".Clinical Kidney Journal.12(3): 382–399.doi:10.1093/ckj/sfy112.ISSN2048-8505.PMC6543978.PMID31198539.
  22. ^Arnold, Georgianne L. (2018)."Inborn errors of metabolism in the 21st century: past to present".Annals of Translational Medicine.6(24): 467.doi:10.21037/atm.2018.11.36.ISSN2305-5839.PMC6331363.PMID30740398.
  23. ^Jones K, Smith D (1975). "The fetal alcohol syndrome".Teratology.12(1): 1–10.doi:10.1002/tera.1420120102.PMID1162620.
  24. ^Clarren S, Alvord E, Sumi S, Streissguth A, Smith D (1978). "Brain malformations related to prenatal exposure to ethanol".J Pediatr.92(1): 64–7.doi:10.1016/S0022-3476(78)80072-9.PMID619080.
  25. ^Abel EL, Sokol RJ (November 1986). "Fetal alcohol syndrome is now leading cause of mental retardation".Lancet.2(8517): 1222.doi:10.1016/s0140-6736(86)92234-8.PMID2877359.S2CID42708464.
  26. ^Strömland K, Pinazo-Durán M (2002)."Ophthalmic involvement in the fetal alcohol syndrome: clinical and animal model studies".Alcohol Alcohol.37(1): 2–8.doi:10.1093/alcalc/37.1.2.PMID11825849.
  27. ^May PA.; Gossage JP. (2001)."Estimating the prevalence of fetal alcohol syndrome. A summary".Alcohol Res Health.25(3): 159–67.PMC6707173.PMID11810953.
  28. ^abDe Santis, Marco; Cesari, Elena; Cavaliere, Annafranca; Ligato, Maria Serena; Nobili, Elena; Visconti, Daniela; Caruso, Alessandro (September 2008). "Paternal exposure and counselling: Experience of a Teratology Information Service".Reproductive Toxicology.26(1): 42–46.doi:10.1016/j.reprotox.2008.06.003.PMID18598753.
  29. ^Hollander, Jessica; McNivens, Megan; Pautassi, Ricardo M.; Nizhnikov, Michael E. (2019)."Offspring of male rats exposed to binge alcohol exhibit heightened ethanol intake at infancy and alterations in T-maze performance".Alcohol.76:65–71.doi:10.1016/j.alcohol.2018.07.013.ISSN0741-8329.PMC6368891.PMID30583252.
  30. ^abcdTrasler, Jacquetta M.; Doerksen, Tonia (September 1999). "Teratogen update: paternal exposures—reproductive risks".Teratology.60(3): 161–172.doi:10.1002/(SICI)1096-9926(199909)60:3<161::AID-TERA12>3.0.CO;2-A.PMID10471901.
  31. ^abAbel, E. L. (2004). "Paternal contribution to fetal alcohol syndrome".Addiction Biology.9(2): 127–133.doi:10.1080/13556210410001716980.PMID15223537.S2CID22202776.
  32. ^"Teratogens/Prenatal Substance Abuse".Understanding Genetics: A District of Columbia Guide for Patients and Health Professionals.Genetic Alliance; District of Columbia Department of Health. 2010-02-17.Archivedfrom the original on 2019-12-20.Retrieved2018-11-07.
  33. ^van Gelder MM, van Rooij IA, Miller RK, Zielhuis GA, de Jong-van den Berg LT, Roeleveld N (January 2010)."Teratogenic mechanisms of medical drugs".Hum Reprod Update.16(4): 378–94.doi:10.1093/humupd/dmp052.hdl:2066/89039.PMID20061329.
  34. ^abRonan O'Rahilly; Fabiola Müller (2001).Human embryology & teratology.New York: Wiley-Liss.ISBN978-0-471-38225-6.
  35. ^abcdeZhu, J. L.; Madsen, K. M.; Vestergaard, M; Olesen, A. V.; Basso, O; Olsen, J (15 July 2005)."Paternal age and congenital malformations".Human Reproduction.20(11): 3173–3177.doi:10.1093/humrep/dei186.PMID16006461.
  36. ^abcJi, B.-T.; Shu, X.-O.; Zheng, W.; Ying, D.-M.; Linet, M. S.; Wacholder, S.; Gao, Y.-T.; Jin, F. (5 February 1997)."Paternal Cigarette Smoking and the Risk of Childhood Cancer Among Offspring of Nonsmoking Mothers".JNCI Journal of the National Cancer Institute.89(3): 238–243.doi:10.1093/jnci/89.3.238.PMID9017004.
  37. ^Bracken MB, Holford TR; Holford (1981). "Exposure to prescribed drugs in pregnancy and association with congenital malformations".Obstetrics and Gynecology.58(3): 336–44.PMID7266953.
  38. ^abcdeAnderson, Diana; Schmid, ThomasE; Baumgartner, Adolf (2014)."Male-mediated developmental toxicity".Asian Journal of Andrology.16(1): 81–8.doi:10.4103/1008-682X.122342.PMC3901885.PMID24369136.
  39. ^Chia, S-E; Shi, L. M. (1 March 2002)."Review of recent epidemiological studies on paternal occupations and birth defects".Occupational and Environmental Medicine.59(3): 149–155.doi:10.1136/oem.59.3.149.PMC1763633.PMID11886946.
  40. ^King CR (1986). "Genetic counseling for teratogen exposure".Obstetrics and Gynecology.67(6): 843–6.doi:10.1097/00006250-198606000-00020.PMID3703408.
  41. ^Zurlinden, TJ; Saili, KS; Rush, N; Kothiya, P; Judson, RS; Houck, KA; Hunter, ES; Baker, NC; Palmer, JA; Thomas, RS; Knudson, TB (2020)."Profiling the ToxCast Library With a Pluripotent Human (H9) Stem Cell Line-Based Biomarker Assay for Developmental Toxicity".Toxicological Sciences.174(2): 189–209.doi:10.1093/toxsci/kfaa014.PMC8527599.PMID32073639.
  42. ^abcdefghiPeterka, Miroslav; Novotná, Božena (2010).Úvod do teratologie: příčiny a mechanizmy vzniku vrozených vad(1. vyd. ed.). Praha:Karolinum Press.ISBN978-80-246-1780-0.
  43. ^Hunt JR (1996). "Teratogenicity of high vitamin A intake".N. Engl. J. Med.334(18): 1197–1200.doi:10.1056/NEJM199605023341814.PMID8602195.
  44. ^Hartmann S, Brørs O, Bock J, et al. (2005). "Exposure to retinoic acids in non-pregnant women following high vitamin A intake with a liver meal".International Journal for Vitamin and Nutrition Research.75(3): 187–94.doi:10.1024/0300-9831.75.3.187.PMID16028634.
  45. ^"Search Jablonski's Syndromes Database".United States National Library of Medicine.Archivedfrom the original on 2017-05-04.Retrieved2016-04-07.
  46. ^Manassaram, Deana M.; Backer, Lorraine C.; Moll, Deborah M. (2006)."A Review of Nitrates in Drinking Water: Maternal Exposure and Adverse Reproductive and Developmental Outcomes".Environmental Health Perspectives.114(3): 320–327.doi:10.1289/ehp.8407.ISSN0091-6765.PMC1392223.PMID16507452.
  47. ^Croen, Lisa; Todoroff, Karen; Shaw, Gary (2001)."Maternal Exposure to Nitrate from Drinking Water and Diet and Risk for Neural Tube Defects".American Journal of Epidemiology.153(4): 325–31.doi:10.1093/aje/153.4.325.PMID11207149.
  48. ^Costas, K.; Knorr, R.S.; Condon, S.K. (2002). "A case-control study of childhood leukemia in Woburn, Massachusetts: the relationship between leukemia incidence and exposure to public drinking water".Science of the Total Environment.300(1–3): 23–35.Bibcode:2002ScTEn.300...23C.doi:10.1016/s0048-9697(02)00169-9.PMID12685468.
  49. ^In Harm's Way: Toxic Threats to Child Development(Report). Greater Boston Physicians for Social Responsibility. May 2000. pp. 90–2.Archivedfrom the original on 24 September 2015.Retrieved7 December2014.
  50. ^Delomenie, Myriam; Schneider, Floriane; Beaudet, Joëlle; Gabriel, René; Bednarek, Nathalie; Graesslin, Olivier (2015)."Carbon Monoxide Poisoning during Pregnancy: Presentation of a Rare Severe Case with Fetal Bladder Complications".Case Reports in Obstetrics and Gynecology.2015:687975.doi:10.1155/2015/687975.ISSN2090-6684.PMC4365372.PMID25834750.
  51. ^Ritz, B.; Yu, F.; Fruin, S.; Chapa, G.; Shaw, G.; Harris, J. (2002)."Ambient Air Pollution and Risk of Birth Defects in Southern California"(PDF).American Journal of Epidemiology.155(1): 17–25.doi:10.1093/aje/155.1.17.PMID11772780.Archived fromthe original(PDF)on 30 April 2015.Retrieved7 December2014.
  52. ^Aubard, Yves; Magne, Isabelle (12 Aug 2005)."Carbon monoxide poisoning in pregnancy".British Journal of Obstetrics and Gynaecology.107(7): 833–8.doi:10.1111/j.1471-0528.2000.tb11078.x.PMC2146365.PMID10901551.
  53. ^congenital defects
  54. ^Griesbauer, Laura."Methylmercury Contamination in Fish and Shellfish".CSA.CSA 2007. Archived fromthe originalon 13 December 2014.Retrieved7 December2014.
  55. ^Rushton, Lesley (2003)."Health hazards and waste management".British Medical Bulletin.68(1): 183–97.doi:10.1093/bmb/ldg034.PMID14757717.S2CID1500545.
  56. ^Bullard, Robert."Environmental Justice for All".National Humanities Center.Archivedfrom the original on 29 March 2015.Retrieved9 December2014.
  57. ^"Lead Poisoning".Mayo Clinic.Archivedfrom the original on 21 December 2014.Retrieved9 December2014.
  58. ^Berlac, Janne Foss; Hartwell, Dorthe; Skovlund, Charlotte Wessel; Langhoff-Roos, Jens; Lidegaard, Øjvind (June 2017). "Endometriosis increases the risk of obstetrical and neonatal complications".Acta Obstetricia et Gynecologica Scandinavica.96(6): 751–760.doi:10.1111/aogs.13111.PMID28181672.
  59. ^Arora, Nitin; Sadovsky, Yoel; Dermody, Terence S.; Coyne, Carolyn B. (2017)."Microbial Vertical Transmission during Human Pregnancy".Cell Host & Microbe.21(5): 561–567.doi:10.1016/j.chom.2017.04.007.ISSN1931-3128.PMC6148370.PMID28494237.
  60. ^Mawson, Anthony R.; Croft, Ashley M. (2019)."Rubella Virus Infection, the Congenital Rubella Syndrome, and the Link to Autism".International Journal of Environmental Research and Public Health.16(19): 3543.doi:10.3390/ijerph16193543.ISSN1660-4601.PMC6801530.PMID31546693.
  61. ^abcdefSadler, T.W. (1985).Langman's Medical Embryology(5th ed.). Baltimore: William & Wilkins. pp.109–12.ISBN9780683074901.
  62. ^"Microcephaly".Mayo Clinic.Archivedfrom the original on 21 December 2014.Retrieved7 December2014.
  63. ^"Cerebral calcification, nonarteriosclerotic".MedicineNet.Archived fromthe originalon 3 July 2015.Retrieved7 December2014.
  64. ^"Hepatosplen Omega ly-Symptoms, Causes, Treatment".Symptoms and Treatment RSS.22 August 2011.Archivedfrom the original on 10 November 2014.Retrieved7 December2014.
  65. ^"Kernicterus".MedlinePlus Medical Encyclopedia.Archivedfrom the original on 5 January 2015.Retrieved7 December2014.
  66. ^"Petechiae".Mayo Clinic.Archivedfrom the original on 22 April 2015.Retrieved7 December2014.
  67. ^"Microphthalmus".Texas School for the Blind and Visually Impaired.Archived fromthe originalon 17 November 2014.Retrieved7 December2014.
  68. ^"Facts about Anencephaly".Centers for Disease Control and Prevention.Archivedfrom the original on 10 December 2014.Retrieved7 December2014.
  69. ^"Hydrocephalus".Mayo Clinic.Archivedfrom the original on 24 December 2014.Retrieved7 December2014.
  70. ^abRaats, Monique (1998).Changing Preconceptions.London: Health Education Authority. p. 11.ISBN978-0-7521-1231-2.
  71. ^Anderson, Lucy M.; Riffle, Lisa; Wilson, Ralph; Travlos, Gregory S.; Lubomirski, Mariusz S.; Alvord, W. Gregory (March 2006)."Preconceptional fasting of fathers alters serum glucose in offspring of mice".Nutrition.22(3): 327–331.doi:10.1016/j.nut.2005.09.006.PMID16500559.Archivedfrom the original on 2020-07-27.Retrieved2019-09-12.
  72. ^Bhandari, Jenish; Thada, Pawan K.; Sergent, Shane R. (2022),"Potter Syndrome",StatPearls,Treasure Island (FL): StatPearls Publishing,PMID32809693,archivedfrom the original on 2023-03-16,retrieved2022-10-31
  73. ^Rahbaran, Mohaddeseh; Razeghian, Ehsan; Maashi, Marwah Suliman; Jalil, Abduladheem Turki; Widjaja, Gunawan; Thangavelu, Lakshmi; Kuznetsova, Mariya Yurievna; Nasirmoghadas, Pourya; Heidari, Farid; Marofi, Faroogh; Jarahian, Mostafa (2021-11-30)."Cloning and Embryo Splitting in Mammalians: Brief History, Methods, and Achievements".Stem Cells International.2021:2347506.doi:10.1155/2021/2347506.ISSN1687-966X.PMC8651392.PMID34887927.
  74. ^abcdefSartorius, G. A.; Nieschlag, E. (20 August 2009)."Paternal age and reproduction".Human Reproduction Update.16(1): 65–79.doi:10.1093/humupd/dmp027.PMID19696093.
  75. ^abSavitz, David A.; Schwingl, Pamela J.; Keels, Martha Ann (October 1991). "Influence of paternal age, smoking, and alcohol consumption on congenital anomalies".Teratology.44(4): 429–440.doi:10.1002/tera.1420440409.PMID1962288.
  76. ^Avidor-Reiss, T.; Mazur, M.; Fishman, E. L.; Sindhwani, P. (2019)."The Role of Sperm Centrioles in Human Reproduction – The Known and the Unknown - PMC".Frontiers in Cell and Developmental Biology.7:188.doi:10.3389/fcell.2019.00188.PMC6781795.PMID31632960.
  77. ^"Men may contribute to infertility through newly discovered part of sperm | UToledo News".June 7, 2018.Archivedfrom the original on January 8, 2023.RetrievedJanuary 8,2023.
  78. ^abcde Graaf, Johanna P.; Steegers, Eric A.P.; Bonsel, Gouke J. (April 2013). "Inequalities in perinatal and maternal health".Current Opinion in Obstetrics and Gynecology.25(2): 98–108.doi:10.1097/GCO.0b013e32835ec9b0.PMID23425665.S2CID41767750.
  79. ^abcdVos, Amber A.; Posthumus, Anke G.; Bonsel, Gouke J.; Steegers, Eric A.P.; Denktaş, Semiha (August 2014). "Deprived neighborhoods and adverse perinatal outcome: a systematic review and meta-analysis".Acta Obstetricia et Gynecologica Scandinavica.93(8): 727–740.doi:10.1111/aogs.12430.PMID24834960.S2CID39860659.
  80. ^abcBradley, Robert H.; Corwyn, Robert F. (February 2002). "S S C D".Annual Review of Psychology.53(1): 371–399.doi:10.1146/annurev.psych.53.100901.135233.PMID11752490.S2CID43766257.
  81. ^Health risk assessment from the nuclear accident after the 2011 Great East Japan Earthquake and Tsunami based on a preliminary dose estimation(PDF).World Health Organization.2013. pp. 23–24.ISBN978-92-4-150513-0.Archived(PDF)from the original on 2017-12-15.Retrieved2013-11-21.
  82. ^Heath, Clark W. (1992)."The Children of Atomic Bomb Survivors: A Genetic Study".JAMA: The Journal of the American Medical Association.268(5): 633–634.Bibcode:1992RadR..131..229A.doi:10.1001/jama.1992.03490050109039.PMC1682172.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
  83. ^Kalter, Harold (2010).Teratology in the Twentieth Century Plus Ten.Springer Netherlands.p. 21.ISBN978-90-481-8820-8.Retrieved28 October2014.
  84. ^Winther, J F; Boice, J D; Thomsen, B L; Schull, W J; Stovall, M; j h Olsen (2003)."Sex ratio among offspring of childhood cancer survivors treated with radiotherapy".British Journal of Cancer.88(3): 382–7.doi:10.1038/sj.bjc.6600748.PMC2747537.PMID12569380.
  85. ^"Birth defects among the children of atomic-bomb survivors (1948–1954)".RERF.jp.Radiation Effects Research Foundation.Archivedfrom the original on 2018-05-20.Retrieved2013-11-21.
  86. ^Voosen, Paul (11 April 2011)."Nuclear crisis: Hiroshima and Nagasaki cast long shadows over radiation science".E&E News.Archived fromthe originalon 5 April 2012.Retrieved28 October2014.
  87. ^Dubrova, Yuri E.; Nesterov, Valeri N.; Krouchinsky, Nicolay G.; Ostapenko, Valdislav A.; Neumann, Rita; Neil, David L.; Jeffreys, Alec J. (25 April 1996). "Human minisatellite mutation rate after the Chernobyl accident".Nature.380(6576): 683–686.Bibcode:1996Natur.380..683D.doi:10.1038/380683a0.PMID8614461.S2CID4303433.
  88. ^Bennett, Burton; Repacholi, Michael; Carr, Zhanat, eds. (2006).Health Effects of the Chernobyl Accident and Special Health Care Programmes: Report of the UN Chernobyl Forum, Expert Group "Health"(PDF).Geneva: World Health Organization (WHO). p. 79.ISBN978-92-4-159417-2.Archived(PDF)from the original on 12 August 2011.Retrieved20 August2011.
  89. ^Furitsu Katsumi (2005). "Microsatellite mutations show no increases in the children of the Chernobyl liquidators".Mutation Research/Genetic Toxicology and Environmental Mutagenesis.581(1–2): 69–82.Bibcode:2005MRGTE.581...69F.doi:10.1016/j.mrgentox.2004.11.002.PMID15725606.
  90. ^Dickinson HO, Parker L (1999)."Quantifying the effect of population mi xing on childhood leukaemia risk: the Seascale cluster".British Journal of Cancer.81(1): 144–151 [146, 149].doi:10.1038/sj.bjc.6690664.PMC2374359.PMID10487626.
  91. ^Lean, Samantha C.; Derricott, Hayley; Jones, Rebecca L.; Heazell, Alexander E. P. (2017-10-17)."Advanced maternal age and adverse pregnancy outcomes: A systematic review and meta-analysis".PLOS ONE.12(10): e0186287.Bibcode:2017PLoSO..1286287L.doi:10.1371/journal.pone.0186287.ISSN1932-6203.PMC5645107.PMID29040334.
  92. ^abOlshan, Andrew F.; Schnitzer, Patricia G.; Baird, Patricia A. (July 1994). "Paternal age and the risk of congenital heart defects".Teratology.50(1): 80–84.doi:10.1002/tera.1420500111.PMID7974258.
  93. ^Yang, Q.; Wen, S.W.; Leader, A.; Chen, X.K.; Lipson, J.; Walker, M. (7 December 2006). "Paternal age and birth defects: how strong is the association?".Human Reproduction.22(3): 696–701.doi:10.1093/humrep/del453.PMID17164268.
  94. ^Wiener-Megnazi, Zofnat; Auslender, Ron; Dirnfeld, Martha (12 December 2011)."Advanced paternal age and reproductive outcome".Asian Journal of Andrology.14(1): 69–76.doi:10.1038/aja.2011.69.PMC3735149.PMID22157982.
  95. ^Bezerra Guimarães MJ, Marques NM, Melo Filho DA (2000)."Taux de mortalité infantile et disparités sociales à Recife, métropole du Nord-Est du Brésil"[Infant mortality rate and social disparity at Recife, the metropolis of the North-East of Brazil].Santé(in French).10(2): 117–21.PMID10960809.Archivedfrom the original on 2021-08-28.Retrieved2013-11-10.
  96. ^Kumar, Abbas and Fausto, eds.,Robbins and Cotran's Pathologic Basis of Disease, 7th edition,p.473.
  97. ^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
  98. ^Chen, J; Gong, X; Chen, P; Luo, K; Zhang, X (16 August 2016)."Effect of L-arginine and sildenafil citrate on intrauterine growth restriction fetuses: a meta-analysis".BMC Pregnancy and Childbirth.16:225.doi:10.1186/s12884-016-1009-6.PMC4986189.PMID27528012.
  99. ^Simonsen, H (25 November 2002). "[Screening of newborns for inborn errors of metabolism by tandem mass spectrometry]".Ugeskrift for Laeger.164(48): 5607–12.PMID12523003.
  100. ^abcWilcken, B; Wiley, V (February 2008). "Newborn screening".Pathology.40(2): 104–15.doi:10.1080/00313020701813743.PMID18203033.
  101. ^Ezgu, F (2016).Inborn Errors of Metabolism.Vol. 73. pp. 195–250.doi:10.1016/bs.acc.2015.12.001.ISBN9780128046906.PMID26975974.{{cite book}}:|journal=ignored (help)
  102. ^"Newborn screening for DMD shows promise as an international model".Nationwide Children's Hospital. 2012-03-19. Archived fromthe originalon 2015-10-15.Retrieved2018-04-02.
  103. ^"WHO Disease and injury country estimates".World Health Organization.2009.Archivedfrom the original on November 11, 2009.RetrievedNov 11,2009.
  104. ^Gittelsohn, A; Milham, S (1964)."Statistical Study of Twins—Methods".American Journal of Public Health and the Nation's Health.54(2): 286–294.doi:10.2105/ajph.54.2.286.PMC1254713.PMID14115496.
  105. ^Fernando, J; Arena, P; Smith, D. W. (1978). "Sex liability to single structural defects".American Journal of Diseases of Children.132(10): 970–972.doi:10.1001/archpedi.1978.02120350034004.PMID717306.
  106. ^Lubinsky, M. S. (1997). "Classifying sex biased congenital anomalies".American Journal of Medical Genetics.69(3): 225–228.doi:10.1002/(SICI)1096-8628(19970331)69:3<225::AID-AJMG1>3.0.CO;2-K.PMID9096746.
  107. ^Lary, J. M.; Paulozzi, L. J. (2001). "Sex differences in the prevalence of human birth defects: A population-based study".Teratology.64(5): 237–251.doi:10.1002/tera.1070.PMID11745830.
  108. ^abcdefCui, W; Ma, C. X.; Tang, Y; Chang, V; Rao, P. V.; Ariet, M; Resnick, M. B.; Roth, J (2005). "Sex differences in birth defects: A study of opposite-sex twins".Birth Defects Research Part A: Clinical and Molecular Teratology.73(11): 876–880.doi:10.1002/bdra.20196.PMID16265641.
  109. ^abWorld Health Organization reports. "Congenital malformations", Geneve, 1966, p. 128.
  110. ^Darwin C. (1871) The descent of man and selection in relation to sex. London, John Murray, 1st ed.
  111. ^"Diagnosis | Birth Defects | NCBDDD | CDC".Centers for Disease Control and Prevention.2017-12-04.Archivedfrom the original on 2018-11-07.Retrieved2018-11-07.
  112. ^Kumar, Abbas and Fausto, eds.,Robbins and Cotran's Pathologic Basis of Disease, 7th edition,p.470.
  113. ^Dicke JM (1989). "Teratology: principles and practice".Med. Clin. North Am.73(3): 567–82.doi:10.1016/S0025-7125(16)30658-7.PMID2468064.
  114. ^abcdefghijklmnopqrRajewski 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.
  115. ^abcdMontagu A. (1968) Natural Superiority of Women, The, Altamira Press, 1999.
  116. ^abcdefghiRiley M., Halliday J. (2002) Birth Defects in Victoria 1999–2000, Melbourne.
  117. ^Shaw, G. M.; Carmichael, S. L.; Kaidarova, Z; Harris, J. A. (2003). "Differential risks to males and females for congenital malformations among 2.5 million California births, 1989–1997".Birth Defects Research Part A: Clinical and Molecular Teratology.67(12): 953–958.doi:10.1002/bdra.10129.PMID14745913.
  118. ^Reyes, F. I.; Boroditsky, R. S.; Winter, J. S.; Faiman, C (1974). "Studies on human sexual development. II. Fetal and maternal serum gonadotropin and sex steroid concentrations".The Journal of Clinical Endocrinology & Metabolism.38(4): 612–617.doi:10.1210/jcem-38-4-612.PMID4856555.
  119. ^"Birth Defects: Saving Pediatric Patients from Congenital Defects".MDforLives.2021-01-31.Archivedfrom the original on 2021-02-13.Retrieved2021-02-09.
  120. ^"Key Findings: Updated National Birth Prevalence Estimates for Selected Birth Defects in the United States, 2004–2006".CDC.Centers for Disease Control and Prevention (CDC) and the National Birth Defects Prevention Network.Archivedfrom the original on October 28, 2014.RetrievedOctober 1,2014.
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