Teratogens: Drugs Materials And Other Factors That Can Disturb The Normal Development Of An Embryo Or Foetus

Arvind K. Singh Chandel, CSIR CSMCRI Bhavnagar

2018-02-24 10:51:16

Credit: pexels.com

Credit: pexels.com

Any agent and conditions that can impair prenatal development and lead to birth defects or even death, or interruptthe normal development embryo or foetus known as teratogens. These are able form a birth defect in the child or a teratogen may break the pregnancy complete. The teratogens include few drugs, viruses,radiation, maternal infections, chemicals, and some foods. Behavioural teratogens agents that tend to harm the prenatal brain, affecting the future child’s intellectual and emotional functioning. Although all teratogens increase the risk of harm to the developing child, none always cause damage; the ultimate impact be governed by on the complex interaction of many factors.

Teratology is the investigation of variations from the norm of physiological advancement. It is regularly thought of as the investigation of human innate anomalies, yet it is more extensive than that, considering other non-birth formative stages, including adolescence; and different living beings, including plants. The related term formative lethality incorporates all indications of unusual advancement that are caused by natural affront. These may incorporate development hindrance, postponed mental improvement or other inherent issue with no basic distortions

The kind of distortion relies upon the medication and also the phase of presentation to the teratogen. Foetal introduction relies upon the blood level and term for which the medication stays in maternal flow. The teratogenic capability of a medication is to be considered against the foundation of inherent variations from the norm happening suddenly,which is ~ 2% of all pregnancies.

Factors influencing the effect of teratogens

1. Timing:The effect of a teratogen on the developing embryo or foetus depends on what period in the pregnancy (in development) the child is exposed to the teratogen.Some teratogens cause damage only during specific days or weeks in early pregnancy other teratogens are harmful at any time during the pregnancy for example, for behavioural teratogens, there is no safe period the brain and nervous system can be harmed throughout the pregnancy.

Drugs can affect the foetus at 3 stages—

I. Fertilization and implantation: conception to 17 days—failure of pregnancy which often

goes unnoticed.

II Organogenesis—18 to 55 days of gestation—most vulnerable period, deformities are pro-

  1.  

III. Growth and development—56 days onwards— developmental and functional abnorma-

lities can occur, e.g. ACE inhibitors can cause hypoplasia of organs, specially lungs and

Kidneys; NSAIDs may induce premature closure of ductus arteriosus.

2. Critical period:In prenatal development, the time when a particular organ or other body part is most susceptible to teratogenic damage in developing embryo or foetus.

3.Exposure: The effect of a teratogen on the developing embryo or foetus also depends on the dose and/or frequency of exposure of/to the teratogen.

4.Threshold effect: The phenomenon in which a particular teratogen is relatively harmless in small doses but becomes harmful when exposure reaches a certain level.

5. Interaction effect: the phenomenon in which a particular teratogens potential for causing harm increases when it is combined with another teratogen or another risk factor

6.Genetic variability: another factor that determines whether a specific teratogen will be harmful is the genetic make-up of the developing organism.Possessing and not possessing certain genes may make the developing child more susceptible to the effect of a teratogen.

Drug teratogen

Sr no.

Drug

Effect

  1.  

Isotretinoin

Craniofacial, heart and CNS defects

  1.  

Thalidomide

Phocomelia, multiple defects

  1.  

Tetracyclines

Discoloured and deformed teeth, retarded bone growth

  1.  

Anticancer drugs

Cleft palate, hydrocephalus, multiple defects,foetal death

  1.  

Warfarin

Depressed nose; eye and hand defects, growth retardation

  1.  

Phenytoin

Hypoplasticphalanges, cleft lip/palate, microcephaly

  1.  

Progestins

Virilizationof female foetus

  1.  

Stilboestrol

Vaginal carcinoma in teenage female offspring

  1.  

Androgen

Virilization; limb, esophageal, cardiac defects

  1.  

Phenobarbitone

Various malformations

  1.  

Valproate sod.

Spina bifida and other neural tube defects

  1.  

Alcohol

Low IQ baby, growth retardation, foetal alcohol syndrome

  1.  

Carbamazepine

Neural tube defects, other abnormalities

  1.  

ACE inhibitors

Hypoplasia of organs, growth retardation, foetal loss

  1.  

Antithyroid drugs

Foetal goiter and hypothyroidism

  1.  

Lithium

Foetal goiter, cardiac and other abnormalities

  1.  

Indomethacin/aspirin

Premature closure of ductus arteriosus

  1.  

Selective serotonin reuptake inhibitors SSRls

 

Are capable of crossing the placenta and affecting the baby. Most of the effects in the baby are subtle, and include irritability, agitation, tremor, increased respiratory rate, nasal congestion, or diarrhoea. However, the SSRI paroxetine is thought to cause birth defects in early pregnancy.

 

Risk category of drugs during pregnancy

The US-FDA has evaluated the documentation of hazard for causing birth abandons into five classifications It is, in this way, insightful to stay away from all medications amid pregnancy unless convincing reasons exist for their utilization paying little mind to the appointed pregnancy class, or assumed security. Recurrence of unconstrained and in addition sedate actuated mutations, particularly neural tube abandons, might be diminished by folate treatment amid pregnancy.

Category

Explanation

  1.  

Sufficient examinations in pregnant ladies have neglected to illustrate

a risk to the foetus e.g.Inj. Magthyroxinesulfate,

 

  1.  

Satisfactory investigations in pregnant ladies have neglected to exhibit a hazard to the embryo, however creature thinks about have demonstrated an unfavorable impact on the foetus. e.g.paracetamol,erythromycin,Peniciline V,amoxiciline, lignocaine, Cefactor

  1.  

No adequate studies in pregnant women and animal studies are lacking or have shown and adverse effect on foetus, but potential benefit may warrant use of the drug in pregnant women despite potential riske.gMorphine,atropine, corticosteroids, adrenaline, thiopentone, bupivacainecodeine,

  1.  

There is evidence of human foetal risk, but the potential benefits from use

of the drug may be acceptable despite the potential risk e.g.Aspirin,phenytoin,

carbamazepine, valproate, lorazepam

  1.  

Studies in animals or humans have demonstrated foetal abnormalities, andpotential risk clearly outweighs possible benefit e.g. Estrogens, isotretinoin,ergometrin

Infections in the mother

Few dangerous infections may cause their teratogenic effect on the foetus:

  • Chickenpox and shingles
  • Hepatitis B, C, D, E
  • Enteroviruses, a group of viruses such as poliovirus
  • AIDS
  • Parvovirus B19,
  • Syphilis
  • Sexually transmitted such as gonorrhoea and chlamydia
  • Herpes simplex virus​
  • Cytomegalovirus, Rubella
  • Group B streptococcus, listeria, and candida

Alcohol and smoking

Alcohol utilize is a notable reason for inborn variations from the norm amid pregnancy. Indeed, even direct measures of liquor in pregnancy can cause formative issues in the unborn child. Variations from the norm caused by liquor in pregnancy incorporate disfigurements of the face, arms, and legs, heart conditions, scholarly inability and foetal development confinement.     Cigarette smoking is connected with foetal development confinement and untimely birth. Smoking may likewise cause issues with the advancement of the mind, cardiovascular framework, and respiratory framework. This is genuine whether the mother smokes herself or is presented to second-hand smoke. The utilization of weed in pregnancy can cause different issues in the infant, for example, poor encouraging, touchiness, and fast relaxing.

Amphetamines, likewise called "speed," empower the focal sensory system. Pre-birth utilization of these medications is related with untimely birth, low birth weight, or intracranial dying. The utilization of opioid drugs, for example, heroin or methadone, amid pregnancy can prompt foetal development limitation, untimely birth, and low birth weight.

            Cocaine utilize is known to cause various issues amid pregnancy. These incorporate unnatural birth cycle, foetal development limitation, and issues with the improvement of the urinary framework or genital tract. The utilization of cocaine can prompt microcephaly, where the mind is too little. Offspring of moms who utilized cocaine amid pregnancy are likewise more inclined to creating neurobehavioral issues. Cocaine use amid pregnancy has been related with a higher danger of a difficult issue with the placenta, called placental unexpectedness. Pre-birth utilization of cocaine may likewise cause expanded startling, jumpiness, and over the top sucking in the infant.

The utilization of these sorts of medications amid pregnancy can likewise prompt a condition called neonatal restraint disorder, where the infant encounters withdrawal. At the point when a lady is pregnant and takes one of these medications, her infant can wind up dependent

Other food and factors

Fish and Shellfish: Certain fish may contain high levels of mercury, which can affect the baby’s developing nervous system

Milk and Milk Products:Keep away from unpasteurized drain and cheddar. This incorporates delicate cheeses, for example, feta, brie, Camembert, blue cheeses, and goat cheddar. These sustenance may contain microscopic organisms called listeria, which are unsafe and can be fatal to unborn infants.

Certain Meats: Avoid meat pates, and all liver products because of the risk of listeria

  • Caffeine crosses the placental obstruction into the infant's blood when you are pregnant. Not exclusively is caffeine dangerous to your child's creating sensory system however it likewise meddles with press retention and the body's capacity to adequately utilize insulin.

Artificial Sweeteners: Aspartame, sucralose, and acesulfame-potassium are used in many foods such as soft drinks, desserts, yogurt, fruit spreads, salad dressings, chewing gum, and candy. These should be used sparingly.

Raw or Undercooked Meats, Poultry or Eggs: Undercooked meat, poultry, and eggs can contain microscopic organisms and parasites that can hurt an unborn child. Make sure to cook ground meat and pork to no less than 160°F, dishes and steaks to 145°F, entire poultry to 180°F, and eggs until the point that the yolk and white are firm, not runny. Purchase natural meat and eggs.

Environmental Toxins within Your Home: Purchase natural or privately developed create. Try not to utilize artistic dishes unless they are guaranteed sans lead. Abstain from microwaving in plastic compartments or wraps; utilize glass. Ventilate your home well by opening the windows every day, as the air in your home can frequently be more harmful than that outside because of diminished flow. Fix holes and dampness issues to control for form development. Appropriately introduce and keep up ignition machines.

Avoid over dose of Vitamins: do not take more than the recommended daily amount of Vitamins A, C and E.