Learning Issue 5

Drugs in Pregnancy
FIRST TRIMESTER : congenital malformations (teratogenesis) SECOND & THIRD TRIMESTER : affect growth & fetal development or

toxic effects on fetal tissues

NEAR TERM : adverse effects on Labour or

neonate after delivery

Early development

Main embryonic period (weeks)

Fetal period (weeks)

16

32

38

Neural tube defects TA, ASD, and VSD

Mental retardation HEART LIMBS UPPER LIP EARS EYES TEETH PALATE

CNS

Amelia/Meromeli
a

Cleft lip

Low-set malformed ears and deafness Microphthalmia, cataracts,glaucoma Enamel hypoplasia Cleft palate Masculinsation Embryo Death Common site(s) of action Major congenital anomalies Highly sensitive period

GENITALIA Functional & minor anomalies Less sensitive period

The intra-uterine period between 2 weeks 3 months is when the most serious abnormalities of fetal development can be caused by drugs. Its during this period that the major organs are being formed. In animal studies, even one dose of a drug administered at the critical time has been shown to have a major effect. The mechanisms of damage are not yet known, but the molecular basis of differentiation of embryonic cells is an intense area of basic research and is likely to provide new insights in the near future. Ampicillin and Cephalosporins are considered one of the safest drugs which can be used during pregnancy.

During T2 & T3 of pregnancy, adverse effects on fetus of drugs administered to the mother are generally an exaggeration of the effects seen in the adult. Exceptions to this rule are the damage to tissues which are still developing e.g. teeth & bones by Tetracycline, and the impairment of brain development by Coumarin anticoagulant. Particular care must be taken with drugs given shortly before delivery. Analgesics, e.g. Meperidine (Pethidine), and tranquillizers e.g. (Benzodiazepines) may severely impair neonatal respiration. In addition, the newborn lacks many enzymes necessary for the efficient metabolism of drugs.

 Poorly

understood Probably multifactorial : - maternal tissue - differentiation process in the fetal tissue * vit. A (retinol) - deficiency of critical substance * folic acid deff. spina bifida - chronic consumption of high dose of ethanol fetal alcohol syndrome