Malformation

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X-ray image of a hand with six fingers

In medicine, a malformation , deformity , malformation , deformity or a birth defect is understood to be a malformation of an organ that developed or created before birth ( prenatally ) . Several organs can also be affected, whereby one speaks of malformation syndromes with different characteristic combinations . Malformations with little clinical impact are also called anomalies .

Malformations can occur spontaneously without any identifiable cause, be genetic or triggered by environmental ( teratogenic ) influences.

It is a change in shape and size or even the non-existence of one or more organs or organ systems as a result of peculiarities in early childhood development in the womb.

The cause of malformations can be mutations (changes in the genetic material) or external influences. Usually, however, a cause cannot be proven and one assumes mutations of unclear genesis . Malformations that go back to characteristics of ancestors and are regarded as classical evidence of evolution are called atavisms . The type and severity of peculiarities caused by exogenous factors depend on the point in time of the effect. Factors that have an effect on the embryo after the determination phase for an organ can no longer prevent its formation, but can be responsible for a more or less severe malformation.

For some peculiarities, such as the presence of a tail or additional fingers or toes ( polydactyly ), amputation treatment is widespread for aesthetic reasons, but is usually not medically necessary. Hermaphroditism is also medically treated in most countries , whereas those affected have joined together in protest movements. Obsolete, mainly used in the 18th century, but today mostly disparagingly, a born living being with severe visible malformations is also called a freak (from Old High German missa : alternately, bad, failed, failed).

Double-headed calf in the Weinheim local history museum
Common fire bug with a deformed hemielytre
Classification according to ICD-10
O35.- Care of the mother if the abnormality or damage to the fetus is identified or suspected
ICD-10 online (WHO version 2019)

Exposure to exogenous factors

Micronutrient deficiency

A deficiency of micronutrients in the mother can lead to malformations and even miscarriages. Iodine , folic acid and cobalamin deficiencies should be mentioned in particular .

Infectious diseases of the mother

Infectious diseases that are potentially harmful to the embryo or fetus are e.g. B. rubella and chickenpox ( varicella syndrome ). Depending on the time of infestation, the virus causes malformations in various organs such as the heart , eye or ear with different frequency and severity .

Further malformations can be caused by the toxoplasmosis pathogen . It can cause brain and eye damage. Sources of infection are eating raw meat, unwashed fruit or vegetables, or having close contact with pets, especially cats.

X-rays or rays of radioactive elements

Radiation can damage the developing and growing organism. The gonads are particularly at risk , as the long-lived early stages of the germ cells are mainly affected in them.

Medication

At the end of the 1950s, a noticeably higher number of children were born in the Federal Republic of Germany with malformations in which limbs were mainly shortened. 1961 could a causal connection between the peculiarities and thalidomide (= Contergan ). getting produced. Damage occurred only in those newborns whose mothers had taken medication containing thalidomide in an early stage of pregnancy . Also of antibiotics and neuroleptics are known teratogenic effects. The thalidomide scandal gave the topic a major role in the public eye.

The highest risk of malformations due to the effects of harmful substances (and thus also drugs) lies within the first three months of pregnancy (1st trimester ). At the beginning of the first trimester, however, the pregnancy is often not yet known. This is why around 80% of pregnant women take drugs in the 1st trimester, around 30% of which are prescribed by a doctor. On the other hand, a clear connection with malformations has only been proven for very few drugs (e.g. cytostatics , sex hormones , certain antibiotics, etc.). In addition, there is the fact that numerous factors must come together for the occurrence of a malformation, including not only the drug consumption, but also the duration of intake, time of intake, dosage, genotype of the fetus / embryo , metabolic situation , accompanying medication, existing underlying disease, etc. This gives rise to some important principles for drug therapy in pregnancy.

Cytostatics, antineoplastics

Antineoplastic drugs with a highly teratogenic effect are thalidomide (see also Contergan scandal ) and because of the structural relationship also lenalidomide . They are only used therapeutically under the strictest safety precautions within special programs for women of childbearing age.

A teratogenic effect, especially in the case of antimetabolites, is known among cytostatic agents . The now obsolete aminopterin was previously used to terminate pregnancy because of its embryotoxicity; In unsuccessful cases, a high proportion of children had deformities such as missing or delayed ossification of the skull, "open back" ( meningocele ), absence of the brain ( anencephaly ), water head ( hydrocephalus ), anomalies in the jaw, the ears, the position of the Eyes ( hypertelorism ) and others. Methotrexate has a similar effect; the risk of embryopathy is dose-dependent.

Retinoids

Vitamin A derivatives ( retinoids ) such as tretinoin and isotretinoin are, after thalidomide, the drugs with the strongest teratogenic effect in humans. They can cause severe malformations in the fetus, which mainly affect the central nervous system, the heart and large vessels (hydrocephalus, malformations of the cerebellum, conotruncal malformations such as Fallot's tetralogy , transposition of the large arteries ). Cleft lip and palate, malformations of the external auditory canal and eyes ( microphthalmia ) and malformations of the thymus and parathyroid glands were also observed. Systemic therapy is only allowed for women of childbearing potential if there is a strict indication that pregnancy has been excluded and if there is adequate contraception, which must be continued for at least one month after the medication has been discontinued, and for two years under therapy with acitretin . Even extremely high doses of vitamin A cause malformations in the same way as its synthetic derivatives.

Benzodiazepines

Benzodiazepines cause malformations in the heart of the fetus in the womb.

drug consumption

Due to multiple drug abuse during pregnancy results in congenital malformations of the child. The use of cocaine during pregnancy leads to malformations in the following organs: heart, brain, urinary and sexual organs.

Anticoagulants

If warfarin is used during pregnancy, there is a potential risk of childhood malformations (fetal warfarin syndrome ). In addition, after exposure in the 1st trimester as well as in the 2nd and / or 3rd trimester, more defects of the central nervous system can occur (e.g. Dandy Walker malformation with absence of the corpus callosum , microencephaly and atrophy of the optic nerve). Due to its chemical relationship with warfarin, a teratogenic risk cannot be excluded for phenprocoumon either. While in older literature the malformation risk is given as 15 to 30 percent, according to more recent studies the risk is 4 to 6 percent.

Anti-epileptic drugs, anticonvulsants

Classic representatives of this group of substances such as phenobarbital , primidone , phenytoin , carbamazepine and especially valproic acid have been shown to have a teratogenic potential in humans. Malformations of the heart, urinary tract, skeleton, cleft lip and palate as well as neural tube defects can occur. Phenobarbital is often viewed as of little concern; The daily dose should ideally be administered in several small doses over the day, especially during the sensitive phase of embryonic development between the 20th and 40th day of pregnancy. Newer drugs such as felbamate , gabapentin , lamotrigine and levetiracetam do not provide any clear indications of teratogenicity in animal experiments.

Sex hormones

High doses of synthetic progestins can masculinize female fetuses. In particular, high doses of ethisterone or norethisterone can cause the clitoris to enlarge and the labia to fuse . Low-dose preparations for hormonal contraception (including the morning-after pill ) and for treating the absence of menstrual bleeding ( amenorrhea ), according to current knowledge, do not present any significant risk with regard to gender differentiation disorders when used inadvertently into early pregnancy.

The estrogen-progestogen combination Duogynon ( solution for injection: estradiol benzoate and progesterone ; dragee form: ethinyl estradiol and norethisterone acetate ; marketed in other countries under the names Cumorit and Primodos ) by the manufacturer Schering was used since the 1950s to 1980 for the treatment of menstrual disorders and as a pregnancy test first associated in the 1960s with various malformations that occurred in newborns ( neural tube defects , cardiovascular malformations, VACTERL association ). The studies published in this context were of different quality and the results were inconsistent, so that neither a causal effect nor a statistically reliable correlation could be demonstrated. A case against Schering by the Berlin public prosecutor's office was closed in 1980.

alcohol

Every year, many children are born worldwide who were harmed by their mothers' alcohol consumption during pregnancy. Alcohol consumption during pregnancy is a common cause of non-genetic disability and one of the few harms that can be completely avoided by correct mother behavior. Symptoms of such an alcohol-related, embryo-damaging effect are u. a. Short stature , underweight, brain and heart damage , which are summarized under the Fetal Alcohol Syndrome (FAS).

Chemicals

A Vietnamese woman with her 14-year-old son who is mentally and physically severely disabled. In 2002 there were around 100,000 disabled children in Vietnam whose congenital malformations are attributed to their parents' exposure to dioxin . This was contained in Agent Orange , a defoliant used extensively by the US during the Vietnam War .

These include For example, the genetically altering environmental toxins known as the Dirty Dozen (e.g. DDT or PCB ), which are now banned worldwide, and many other organochlorine compounds , especially dioxins . There are also a number of (potential) endocrine disruptors , e.g. B. in the birth control pill . (See Teratogen and Category: Substance Toxic to Reproduction )

Peculiarities of the situation in the womb

An unusual position in the uterus can lead to a lack of oxygen ( hypoxia ) in the child. Hypoxia produced malformations in laboratory animals. Also umbilical cord complications can lead to deformities.

Classification of the particularities

Cleft lip and jaw on a calf's head

frequency

Around two percent of all newborns have genetic characteristics or physical malformations. In Germany, for example, around one in 500 babies is born with a cleft lip and palate , and around 0.5 to 0.7% of all children born alive are born with a heart defect . A clubfoot occurs in about one in 1,000 children in front, where boys are affected twice as often as girls.

Data collection

There is no national malformation register in Germany (as of 2019). In the mandatory perinatal survey , which was developed in the 1970s, doctors can note a malformation as the reason for a transfer, but the type of malformation is not specified. The hospital diagnosis statistics of the Federal Statistical Office show the number of inpatient treatment cases with specific diagnoses, but only allow limited conclusions to be drawn about the number of those affected: Children without inpatient treatment do not appear, whereas children who have been inpatient several times are counted several times. At the regional level, malformations have been recorded in the Saxony-Anhalt malformation monitoring system since 1980; In addition, there is the “Mainz Model” birth register. According to the Federal Ministry of Health, these regional data are reported to the European register EUROCAT .

See also

literature

  • Jürgen Beyer: freak. In: Encyclopedia of Fairy Tales. Concise dictionary for historical and comparative narrative research. Volume 9, Walter de Gruyter, Berlin / New York 1999, ISBN 3-11-015453-6 , Sp. 702-707.
  • Wolfgang Miram, Karl-Heinz Scharf: Biology Today SII . Schroedel Verlag, 1997, ISBN 3-507-10590-X . (School book)
  • R. Witkowski, O. Prokop, E. Ullrich, G. Thiel: Lexicon of the syndromes and malformations. 7th edition. Springer, 2003, ISBN 3-540-44305-3 .
  • Urs Zürcher : Monster or the whims of nature. Medicine and the study of malformations 1780–1914 . Campus, Frankfurt am Main et al. 2004, ISBN 3-593-37631-8 . (also dissertation, University of Zurich 2003)
  • Dieter Teichert : Distortion as an aesthetic concept. In: U. Hoyningen-Süess, C. Amrein (Hrsg.): Disfigurement and ugliness - contributions from a philosophical, medical, literary and art-historical perspective as well as from a special educational perspective. Haupt, Bern 1995, ISBN 3-258-05125-9 , pp. 15-29.

Web links

Commons : Birth Defects and Malformations  - Collection of Images, Videos and Audio Files

Individual evidence

  1. ↑ Ulrike Enke: freak. In: Werner E. Gerabek , Bernhard D. Haage, Gundolf Keil , Wolfgang Wegner (eds.): Enzyklopädie Medizingeschichte. De Gruyter, Berlin / New York 2005, ISBN 3-11-015714-4 , p. 997 f.
  2. ^ Duden online , accessed on March 22, 2010.
  3. ↑ a b Klaus Friese et al.: Medicines in pregnancy and breastfeeding. 6th edition. Stuttgart 2006, ISBN 3-8304-5434-1 .
  4. ↑ Martin Smollich, Alexander C. Jansen: Medicines in pregnancy and lactation. Advice quickly and safely. 1st edition. Stuttgart 2009, ISBN 978-3-8304-5434-2 .
  5. ↑ a b J. Kleinebrecht, J. Fränz, A. Windorfer: Medicines in pregnancy and lactation. 2nd Edition. WVG, Stuttgart 1986, p. 89.
  6. ↑ Pharmacovigilance and Advice Center for Embryonic Toxicology, Berlin: Methotrexate ( Memento of September 24, 2010 in the Internet Archive )
  7. ↑ Product information Isotretinoin ratiopharm soft capsules 10 mg / 20 mg. As of June 2008.
  8. ↑ Product information Neotigason ® 10 mg / 25 mg hard capsules. As of March 2008.
  9. ^ Ruthard Stachowske  ( page no longer available , search in web archives ). Retrieved May 29, 2014.@1@ 2Template: Toter Link / www.caritas-mannheim.de
  10. ↑ Specialist information Coumadin ® 5 mg, as of March 2008.
  11. ↑ Technical information Marcumar ® 3 mg tablets, as of September 2009.
  12. ↑ a b c C. Schaefer, C. Weber-Schöndorfer: Certified medical training: drug therapy in pregnancy. In: Deutsches Ärzteblatt. 102 (37), 2005, pp. A-2480 / B-2087 / C-1977.
  13. ↑ a b K. Moore, TVN Persaud, C. Viebahn: Embryology: stages of development - early development - organogenesis - clinic. 5th edition. Elsevier, Munich 2007, p. 195.
  14. ↑ Technical information Luminal ® injection solution / tablets, as of December 2008.
  15. ↑ Pharmacovigilance and Advisory Center for Embryonic Toxicology, Berlin: Oral Contraceptives ( Memento from September 24, 2010 in the Internet Archive )
  16. ↑ apotheke adhoc: Government strengthens Bayer at Duogynon. August 10, 2010.
  17. ↑ Vietnam Red Cross urges more aid for Agent Orange casualties. International Committee of the Red Cross, March 14, 2002.
  18. ↑ J. Langmann: Medical Embryology. 8th edition. Thieme Verlag, 1989, p. 114.
  19. ↑ a b c After cases in Gelsenkirchen: Ministry wants to query all NRW clinics about babies with malformations. In: FAZ. September 14, 2019, accessed September 15, 2019 .
  20. ↑ Philipp J. Meckert: "Nobody could tell us why". Parents of babies without hands describe their experiences. In: www.focus.de. September 14, 2019, accessed September 15, 2019 .
  21. ↑ Sarah Majorczyk: Physicians on the malformations These three steps bring more security. In: www.bild.de. September 16, 2019, accessed September 16, 2019 .
  22. ↑ In NRW. Babies are born with malformed hands: More cases surfaced. In: www.focus.de. September 14, 2019, accessed September 15, 2019 .