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'''Understanding congentital disorders in [[Ayurveda]] and contemporary research'''  

'''Understanding congentital disorders in [[Ayurveda]] and contemporary research'''  

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Congenital disorders are disabilities or malformations present at or before birth.  These are identified in prenatal life or at birth, or many years later. As per the World Health Organization, congenital anomalies are a leading cause of neonatal deaths. Every year an estimated 295 000 newborns die within 28 days of birth due to congenital anomalies. These can contribute to long-term disability, with significant impacts on individuals, families, healthcare systems, and societies.  

Congenital disorders are disabilities or malformations present at or before birth.  These are identified in prenatal life or at birth, or many years later. As per the World Health Organization, congenital anomalies are a leading cause of neonatal deaths. Every year an estimated 295 000 newborns die within 28 days of birth due to congenital anomalies. These can contribute to long-term disability, with significant impacts on individuals, families, healthcare systems, and societies. <ref>Available from https://www.who.int/news-room/fact-sheets/detail/congenital-anomalies accessed on 15/06/2021</ref>

    

    

Human genetics studies individual genes, their role and function in disease, and their mode of inheritance.  Genomics refers to an organism's entire genetic information，the genome，and the function and interaction of DNA within the genome， as well as with environmental or nongenetic factors，such as a person's lifestyle.  Characterization of the human genome in genomic studies has supported genetics to elucidate the etiology, pathogenesis of the disease, and improve therapeutic interventions and outcomes.The impressive advances in genetics，genomics， and health care information technology have significantly increased the wealth of knowledge.It is helpful in medical practice and play a prominent role in the diagnosis， prevention，and treatment of disease.   

Human genetics studies individual genes, their role and function in disease, and their mode of inheritance.  Genomics refers to an organism's entire genetic information，the genome，and the function and interaction of DNA within the genome， as well as with environmental or nongenetic factors，such as a person's lifestyle.  Characterization of the human genome in genomic studies has supported genetics to elucidate the etiology, pathogenesis of the disease, and improve therapeutic interventions and outcomes.The impressive advances in genetics，genomics， and health care information technology have significantly increased the wealth of knowledge.It is helpful in medical practice and play a prominent role in the diagnosis， prevention，and treatment of disease.<ref>J. Larry Ja meson， Peter Kopp. Principles of Human Genetics. In Harrison’s principles of internal medicine. 19th edition. Pg. 425. </ref>    

The ancient rishis of [[Ayurveda]] had recognized the genetic basis of diseases. They have documented the knowledge in various contexts. The current medical system focuses on the identification of genes responsible for diseases. At the same time, the references found in [[Ayurveda]] texts indicate the causes of genetic disorders and their role in health and diseases. A proper study to bridge the gaps and connect these two pools of information can reveal significant insights for a comprehensive understanding of why and what of congenital and genetic disorders.  The present article describes congenital disorders in [[Ayurveda]] texts and contemporary research.

The ancient rishis of [[Ayurveda]] had recognized the genetic basis of diseases. They have documented the knowledge in various contexts. The current medical system focuses on the identification of genes responsible for diseases. At the same time, the references found in [[Ayurveda]] texts indicate the causes of genetic disorders and their role in health and diseases. A proper study to bridge the gaps and connect these two pools of information can reveal significant insights for a comprehensive understanding of why and what of congenital and genetic disorders.  The present article describes congenital disorders in [[Ayurveda]] texts and contemporary research.

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Age of the parents at the time of conception is important. In Ayurvedic texts, the minimum age for normal and healthy conception is described as twenty five years for male and sixteen years for female. At this age, the individual attains complete psycho-sexual maturity to become responsible parents. [Su. Sa. Sutra Sthana 35/13] Young girls and  old women are not advised for conception. [Cha. Sa. [[Sharira Sthana]] 8/6] If the recommended age is not followed for conception, it can lead to intrauterine death of fetus, neonatal death, ill health and deformed body parts of  the child.[A. S. Sharira Sthana 1/5]

Age of the parents at the time of conception is important. In Ayurvedic texts, the minimum age for normal and healthy conception is described as twenty five years for male and sixteen years for female. At this age, the individual attains complete psycho-sexual maturity to become responsible parents. [Su. Sa. Sutra Sthana 35/13] Young girls and  old women are not advised for conception. [Cha. Sa. [[Sharira Sthana]] 8/6] If the recommended age is not followed for conception, it can lead to intrauterine death of fetus, neonatal death, ill health and deformed body parts of  the child.[A. S. Sharira Sthana 1/5]

Pregnancy at a very young age causes premature births. Aneuploidy (abnormal chromosome number) is the principal hereditary abnormality associated with age of either parent.  Advanced maternal age is associated with increased risks for miscarriage, chromosomal abnormalities, stillbirth, foetal growth restriction and preterm birth.Recent research shows that younger paternal age(< 20 years) could increase the risks of urogenital abnormalities and chromosome disorders in fetus. Advanced paternal age (≥ 40 years) could increase the risks of cardiovascular abnormalities, facial deformities, urogenital abnormalities, and chromosome disorders in their offspring. Growing evidences also indicate that the offspring of older fathers are prone to reduced fertility and an increased risk of birth defects, some cancers, and schizophrenia.  

Pregnancy at a very young age causes premature births. Aneuploidy (abnormal chromosome number) is the principal hereditary abnormality associated with age of either parent.  Advanced maternal age is associated with increased risks for miscarriage, chromosomal abnormalities, stillbirth, foetal growth restriction and preterm birth.<ref>Frick AP. Advanced maternal age and adverse pregnancy outcomes. Best Pract Res Clin Obstet Gynaecol. 2021 Jan;70:92-100. doi: 10.1016/j.bpobgyn.2020.07.005. Epub 2020 Jul 15. PMID: 32741623.</ref>Recent research shows that younger paternal age(< 20 years) could increase the risks of urogenital abnormalities and chromosome disorders in fetus. Advanced paternal age (≥ 40 years) could increase the risks of cardiovascular abnormalities, facial deformities, urogenital abnormalities, and chromosome disorders in their offspring.<ref>Fang Y, Wang Y, Peng M, et al. Effect of paternal age on offspring birth defects: a systematic review and meta-analysis. Aging (Albany NY). 2020;12(24):25373-25394. doi:10.18632/aging.104141</ref> Growing evidences also indicate that the offspring of older fathers are prone to reduced fertility and an increased risk of birth defects, some cancers, and schizophrenia.<ref>Bray I, Gunnell D, Davey Smith G. Advanced paternal age: how old is too old?. J Epidemiol Community Health. 2006;60(10):851-853. doi:10.1136/jech.2005.045179</ref>

===Psychological and behavioral factors===

===Psychological and behavioral factors===

A pleasant state of mind is the prime requirement for conception. [Cha. Sa. [[Sutra Sthana]] 25/40] The mental status of parents during coitus and conception is important. Coitus shall be avoided, when either of the partners is hungry, thirsty, or frightened, averse, sorrow-stricken, angry, distressed with relationship, or not desiring for sex. These states during coitus adversely affect conception and health of progeny.  [Cha. Sa. [[Sharira Sthana]] 8/17] Studies show that preconception stress alters offspring development in a parental and fetal sex-specific manner. This is reflected in the metabolic and immune-related genes in the placenta as well as brain transcriptome.  

A pleasant state of mind is the prime requirement for conception. [Cha. Sa. [[Sutra Sthana]] 25/40] The mental status of parents during coitus and conception is important. Coitus shall be avoided, when either of the partners is hungry, thirsty, or frightened, averse, sorrow-stricken, angry, distressed with relationship, or not desiring for sex. These states during coitus adversely affect conception and health of progeny.  [Cha. Sa. [[Sharira Sthana]] 8/17] Studies show that preconception stress alters offspring development in a parental and fetal sex-specific manner. This is reflected in the metabolic and immune-related genes in the placenta as well as brain transcriptome.<ref>Yasmine M.Cissé et al, Brain and placental transcriptional responses as a readout of maternal and paternal preconception stress are fetal sex specific, Placenta, Volume 100, October 2020, Pages 164-170.</ref>

===Spiritual factors ===

===Spiritual factors ===

Sinful acts and atheistic attitude of parents [Su. Sa. Sharira Sthana 2/50-52], deeds of previous life ([[atma]] –karma dosha) [Cha. Sa. [[Sharira Sthana]] 2/29] and unrighteousness(adharma) [Su. Sa. Sharira Sthana 3/36] can cause congenital disorders.  These factors are commonly considered as of ‘unknown origin’ in current medical practices.  

Sinful acts and atheistic attitude of parents [Su. Sa. Sharira Sthana 2/50-52], deeds of previous life ([[atma]] –karma dosha) [Cha. Sa. [[Sharira Sthana]] 2/29] and unrighteousness(adharma) [Su. Sa. Sharira Sthana 3/36] can cause congenital disorders.  These factors are commonly considered as of ‘unknown origin’ in current medical practices.  

The effect of diet taken by the mother vitiating particular [[dosha]] is described. [A. S. Sharira Sthana 2/54-56]

The effect of diet taken by the mother vitiating particular [[dosha]] is described. [A. S. Sharira Sthana 2/54-56]

A systematic review shows that parental alcohol exposures are significantly associated with the risk of congenital heart diseases in offspring. This highlights the necessity of improving health awareness to prevent alcohol exposure during preconception and conception periods.  

A systematic review shows that parental alcohol exposures are significantly associated with the risk of congenital heart diseases in offspring. This highlights the necessity of improving health awareness to prevent alcohol exposure during preconception and conception periods.<ref>Zhang S, Wang L, Yang T, Chen L, Zhao L, Wang T, Chen L, Ye Z, Zheng Z, Qin J. Parental alcohol consumption and the risk of congenital heart diseases in offspring: An updated systematic review and meta-analysis. Eur J Prev Cardiol. 2020 Mar;27(4):410-421. doi: 10.1177/2047487319874530. Epub 2019 Oct 2. PMID: 31578093.</ref>

===Effect of maternal diseases upon the fetus===

===Effect of maternal diseases upon the fetus===

The affliction of the body part of the pregnant woman, either by vitiation of [[dosha ]] or trauma, leads to the affliction of the identical part of the fetal body. [ Su. Sa. Sharira Sthana 3/17] Maternal autoantibodies can cross the placenta and cause fetal damage. For example, fetal thyroid goiter can be developed in response to maternal Graves' disease.  

The affliction of the body part of the pregnant woman, either by vitiation of [[dosha ]] or trauma, leads to the affliction of the identical part of the fetal body. [ Su. Sa. Sharira Sthana 3/17] Maternal autoantibodies can cross the placenta and cause fetal damage. For example, fetal thyroid goiter can be developed in response to maternal Graves' disease.<ref>Panaitescu AM, Nicolaides K. Maternal autoimmune disorders and fetal defects. J Matern Fetal Neonatal Med. 2018;31(13):1798‐1806. doi:10.1080/14767058.2017.1326904</ref>

===Effect of non-fulfillment of longings/desires of the mother during pregnancy (dauhruda vimanana):===

===Effect of non-fulfillment of longings/desires of the mother during pregnancy (dauhruda vimanana):===

The fetus expresses desires through mother. Hence the desires of the pregnant woman (dauhruda) should always be fulfilled. Any negligence or non-fulfillment can cause abnormalities or even death of the fetus. Suppression of desires vitiates [[vayu]], and produces various diseases, abnormalities in the fetus, or even death. [Cha. Sa. [[Sharira Sthana]] 4/25]

The fetus expresses desires through mother. Hence the desires of the pregnant woman (dauhruda) should always be fulfilled. Any negligence or non-fulfillment can cause abnormalities or even death of the fetus. Suppression of desires vitiates [[vayu]], and produces various diseases, abnormalities in the fetus, or even death. [Cha. Sa. [[Sharira Sthana]] 4/25]

Various studies indicate that mental illness and neurocognitive decline are prevalent co-morbidities in the adolescent and adult population with congenital heart diseases (CHD).   

Various studies indicate that mental illness and neurocognitive decline are prevalent co-morbidities in the adolescent and adult population with congenital heart diseases (CHD).<ref>Khanna AD, Duca LM, Kay JD, Shore J, Kelly SL, Crume T. Prevalence of Mental Illness in Adolescents and Adults With Congenital Heart Disease from the Colorado Congenital Heart Defect Surveillance System. Am J Cardiol. 2019;124(4):618‐626. doi:10.1016/j.amjcard.2019.05.023</ref> <ref>Keir M, Ebert P, Kovacs AH, et al. Neurocognition in Adult Congenital Heart Disease: How to Monitor and Prevent Progressive Decline. Can J Cardiol. 2019;35(12):1675‐1685. doi:10.1016/j.cjca.2019.06.020 </ref>  

=== Environmental factors===   

=== Environmental factors===   

Environmental conditions can play a role in fetal development. A retrospective cohort study reported a significant positive association between soil cadmium and air pollution evaluated by air quality index (AQI) and level of screening serum TSH in congenital hypothyroidism patients. It is inferred that the interaction of genetic, autoimmune, familial, and environmental factors with each other could have an influence on neonatal thyroid function.  

Environmental conditions can play a role in fetal development. A retrospective cohort study reported a significant positive association between soil cadmium and air pollution evaluated by air quality index (AQI) and level of screening serum TSH in congenital hypothyroidism patients. It is inferred that the interaction of genetic, autoimmune, familial, and environmental factors with each other could have an influence on neonatal thyroid function.<ref>Hashemipour, M., Kelishadi, R., Amin, M.M. et al. The association between familial and environmental factors and prevalence of congenital hypothyroidism in center of Iran. Environ Sci Pollut Res (2020). https://doi.org/10.1007/s11356-020-10959-x</ref>

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==Factors related to intra partum period==

==Factors related to intra partum period==

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Many health conditions are caused by the combined effects of multiple genes which are known as polygenic. It may be by the interactions between genes and the environment also.  For example, heart disease, type 2 diabetes, schizophrenia, certain types of cancer etc.

Many health conditions are caused by the combined effects of multiple genes which are known as polygenic. It may be by the interactions between genes and the environment also.  For example, heart disease, type 2 diabetes, schizophrenia, certain types of cancer etc.<ref>https://ghr.nlm.nih.gov/primer/inheritance/inheritancepatterns</ref>

==Diagnosis of Congenital disorders==

==Diagnosis of Congenital disorders==

===History of parents:===

===History of parents:===

A careful history of either several spontaneous abortions or offspring with multiple anomalies is an indication for chromosome analyses on both parents. Among known genetic disorders, the severity of X-linked disorders differs in males and females. Genetic mutations originate more frequently among males, and the frequency increases with advancing paternal age. This is seen in Marfan syndrome, achondroplasia, hemophilia A, and the Lesch-Nyhan syndrome.  

A careful history of either several spontaneous abortions or offspring with multiple anomalies is an indication for chromosome analyses on both parents. Among known genetic disorders, the severity of X-linked disorders differs in males and females. Genetic mutations originate more frequently among males, and the frequency increases with advancing paternal age. This is seen in Marfan syndrome, achondroplasia, hemophilia A, and the Lesch-Nyhan syndrome.<ref>Congenital deformities and chromosomal disorders: maternal versus paternal age. Fertil Steril. 1977;28(8):888. doi:10.1016/s0015-0282(16)42748-2</ref>

The genetic analyses in such cases can diagnose probable genetic disorders in progeny.  

The genetic analyses in such cases can diagnose probable genetic disorders in progeny.  

'''Check up before pregnancy:'''  

'''Check up before pregnancy:'''  

The genetic diseases like cystic fibrosis, fragile X syndrome, sickle cell disease, Tay-Sachs disease, Spinal muscular atrophy can be identified in carrier parents before pregnancy.  It can also be done in high-risk category parents who are susceptible to disorders due to ethnicity. Common susceptible groups that may be carriers include non-Hispanic whites (cystic fibrosis), people of Eastern European Jewish descent (Tay-Sachs disease, cystic fibrosis, and others), and those of African, Mediterranean, and Southeast Asian backgrounds (sickle cell disease).  

The genetic diseases like cystic fibrosis, fragile X syndrome, sickle cell disease, Tay-Sachs disease, Spinal muscular atrophy can be identified in carrier parents before pregnancy.  It can also be done in high-risk category parents who are susceptible to disorders due to ethnicity. Common susceptible groups that may be carriers include non-Hispanic whites (cystic fibrosis), people of Eastern European Jewish descent (Tay-Sachs disease, cystic fibrosis, and others), and those of African, Mediterranean, and Southeast Asian backgrounds (sickle cell disease). <ref>Available from https://www.webmd.com/baby/pregnant-genetic-testing cited on 17/06/2021</ref> 

'''During pregnancy:'''  

'''During pregnancy:'''  

'''Antenatal anomaly scan:'''

'''Antenatal anomaly scan:'''

An anomaly scan or mid-pregnancy scan is done to detect significant physical abnormalities in the growing baby. It is an ultrasound scan done between the 18th and 21st week of pregnancy. It helps detect congenital disorders like anencephaly, diaphragmatic hernia, gastroschisis, exomphalos, open spina bifida, bilateral renal agenesis, lethal skeletal dysplasia, Edwards’ syndrome or T18, Patau’s syndrome or T13, cleft lip and serious cardiac abnormalities.  

An anomaly scan or mid-pregnancy scan is done to detect significant physical abnormalities in the growing baby. It is an ultrasound scan done between the 18th and 21st week of pregnancy. It helps detect congenital disorders like anencephaly, diaphragmatic hernia, gastroschisis, exomphalos, open spina bifida, bilateral renal agenesis, lethal skeletal dysplasia, Edwards’ syndrome or T18, Patau’s syndrome or T13, cleft lip and serious cardiac abnormalities.<ref>Available from https://www.motherhoodindia.com/specialities-pregnancy-care/pregnancy-scans/anomaly-scan-detail/ cited on 17/06/2021 </ref>

   

   

===Clinical examination:===

===Clinical examination:===

As per modern embryology, susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this genetic composition interacts with the environment. The maternal genome is also important with respect to drug metabolism, resistance to infection, and other biochemical and molecular processes that affect the conceptus. Susceptibility to teratogens varies with the developmental stage at the time of exposure.  

As per modern embryology, susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this genetic composition interacts with the environment. The maternal genome is also important with respect to drug metabolism, resistance to infection, and other biochemical and molecular processes that affect the conceptus. Susceptibility to teratogens varies with the developmental stage at the time of exposure.  

The most sensitive period for inducing congenital disabilities is the third to eight weeks of gestation, the period of embryogenesis.   

The most sensitive period for inducing congenital disabilities is the third to eight weeks of gestation, the period of embryogenesis.<ref>Prof.Hari Hirdya Awasthi,Dr.Mohd.Ashraf Khan, Garbha sarira, Chaukhambha Orientalia. Varanasi; 1996. First edition.pg.136</ref>  

There are three phases of intrauterine growth. Zygote, embryo, and fetus.  

There are three phases of intrauterine growth. Zygote, embryo, and fetus.  

'''3. The fetal phase / Period III''' (weeks 9 – 38): In this phase, further growth and elaboration of the organ systems take place. During this phase, various factors can result in minor or not-so-severe defects.

'''3. The fetal phase / Period III''' (weeks 9 – 38): In this phase, further growth and elaboration of the organ systems take place. During this phase, various factors can result in minor or not-so-severe defects.

Congenital disabilities occur due to three main reasons i.e.abnormal formation of tissues, abnormal forces on normal tissues, or destruction of normal tissues. Some of these defects may have a cascade effect and result in related anomalies or multiple anomalies (syndromes).  

Congenital disabilities occur due to three main reasons i.e.abnormal formation of tissues, abnormal forces on normal tissues, or destruction of normal tissues. Some of these defects may have a cascade effect and result in related anomalies or multiple anomalies (syndromes).<ref>Dhiman K, Kumar A, Dhiman KS. Shad Garbhakara Bhavas vis-a-vis congenital and genetic disorders. Ayu. 2010;31(2):175‐184. doi:10.4103/0974-8520.72384</ref>

Nowadays, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is emerging as a treatment of choice for various congenital disorders.

 

Nowadays, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is emerging as a treatment of choice for various congenital disorders.<ref>Faraci M, Giardino S, Bagnasco F, et al. Allogeneic hematopoietic stem cell transplantation in congenital disorders: A single-center experience. Pediatr Transplant. 2017;21(6):10.1111/petr.12997. doi:10.1111/petr.12997</ref>

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