Birth defect -Why and who is responsive ? What embryonic period is dangerous for abnormal foetus?

 

The placenta allows for the transfer of many drugs and dietary substances. Lipid- soluble compounds readily cross the placenta and water soluble substances pass less well the greater their molecular weight. The degree to which a drug is bound to plasma protein also influences the amount of drug that is free to cross the placenta. Virtually all  drugs cross the placenta to some degree with the exception of large molecules such as heparin and insulin.

What is the etiology of foetal abnormality???

Ans : Developmental defects in humans may result from genetic environmental or unknown causes. About 25% are unequivocally genetic in origin .  However drug exposure accounts for only 2% to 3 % of birth defects . About 65% of defects are of unknown etiology but may be from combinations of genetic and environmental factors.

What  is the prevalence of BD(Birth Defects) ?  The incidence of major malformations in the general population is 2 % to 3 % . A major malformation is defined as one that is incompatible with survival such as anencephaly one requiring major surgery for correction such as cleft palate or congenital heart disease or one producing major dysfunction such as mental retardation.

 If minor malformations are also included such as ear tags or extra digits the rate may be as high as 7 % to 10%  . The risk for malformation after exposure to a drug must be compared with this background rate.

Species specific teratogenecity:--There is marked species specificity in drug teratogenesis. For example thalidomide was not found to be teratogenic in rats and mice but is a potent human teratogen. Thus extrapolating from animal studies to humans is hazardous and of limited applicability clinically.

What is the risk period?? The classic teratogenic period is from day 31 after the last menstrual period in a 28 day cycle to 71 days from the last period. During this critical period organs are forming and teratogens may cause malformations that are usually overt at birth. Timing of exposure is important .Administration of drugs early in the period of organogenesis affects the organs developing at that time such as the heart or neural tube. Closer to the end of the classic teratogenic period the ear and palate are forming and may be affected by a teratogen.

Before day 31 exposure to teratogen produces an all or-none effect  . If any defect the embryo will immediately repair!!!! With exposure around conception the conceptus usually either does not survive or survives without anomalies. Because so few cells exist in the early stages irreparable damage to some may be lethal to the entire organism. . If the organism remains viable however organ specific anomalies are not manifested because either repair or replacement will occur to permit normal development . A similar insult at a later stage may produce organ-specific defects.