Drugs in pregnancy

Drugs used during pregnancy can have temporary or permanent effects on the fetus. Any drug that acts during embryonic or fetal development to produce a permanent alteration of form or function is known as a teratogen.

Prescribing for the pregnant woman

Many physicians would prefer not to prescribe for pregnant women, the major concern being over teratogenicity of the drugs. The apprehension is not necessarily data driven and is mostly due to lack of clinical studies in pregnant women. This can result in inappropriate treatment of pregnant women and fetus. Use of drugs in pregnancy is not always wrong. For example, high fever is harmful for the fetus in the early months, thus the use of paracetamol (acetaminophen) is generally associated with lower risk than the fever itself. Similarly, diabetes mellitus during pregnancy may need intensive therapy with insulin to prevent complications to mother and baby.

Period of drug use

Pregnancy and development of fetus progresses through various changes. The period of one week from fertilisation to implantation of the fertilized egg is called preimplantation period. This is an 'all or none' period, .i.e an insult can either cause death or complete recovery. The period from the 8th day to the end of 8th week (2nd month) is the period of organogenesis during which the organs are formed in the fetus. This is the most crucial time with regard to 'structural malformations' and concern over teratogenicity of drugs. From the 3rd month week to the end of 9 months is the period of fetal maturation. Intake of drugs during this period may modify the 'function' of the fetal organs rather than causing gross structural malformations in the fetus, for example, aminoglycosides can affect the functioning of kidneys and also the hearing mechanism.

Categories of drugs

The Food and Drug Administration (FDA) has developed a rating system to provide therapeutic guidance based on potential benefits and fetal risks. Drugs have been classified into categories A, B, C, D and X based on this system of classification. Drugs like multivitamins that have demonstrated no fetal risks after controlled studies in humans are classified as Category A. On the other hand drugs like thalidomide with proven fetal risks that outweigh all benefits are classified as Category X.

Classification of a few important drugs/vaccines

Antibacterial agents

• Category B : Penicillin, metronidazole, nitrofurantoin, cephalosporins, clindamycin, terbinafine, some macrolides e.g. azithromycin, erythromycin

• Category C : Some aminoglycosides, chloroquine, quinolones, mebendazole, fluconazole

• Category D : Tetracyclines, gentamicin, tobramycin

Cardiovascular drugs

• Category B : Heparin (LMW)

• Category C : Heparin (conventional), beta-blockers, (dihydropyridine) calcium antagonists, furosemide, digoxin, methyldopa

• Category D : ACE inhibitors, ARBs, coumarins, thiazides, diltiazem

Central nervous system drugs

• Category B : Acetaminophen, caffeine

• Category C : Aspirin, clonidine, rofecoxib

• Category D : Carbamezapine, valproic acid, diazepam, lithium

Vaccines

• Category C : Tetanus toxoid, polio vaccine , BCG vaccine, hepatitis A vaccine, hepatitis B vaccine and rabies vaccine.