A Textbook of Clinical Pharmacology and Therapeutics

PRESCRIBING IN PREGNANCY

The prescription of drugs to a pregnant woman is a balance
between possible adverse drug effects on the fetus and the risk
to mother and fetus of leaving maternal disease inadequately
treated. Effects on the human fetus cannot be reliably pre-
dicted from animal studies – hence one should prescribe drugs
for which there is experience of safety over many years in
preference to new or untried drugs. The smallest effective
dose should be used. The fetus is most sensitive to adverse
drug effects during the first trimester. It has been estimated
that nearly half of all pregnancies in the UK are unplanned,
and that most women do not present to a doctor until five to
seven weeks after conception. Thus, sexually active women of
childbearing potential should be assumed to be pregnant until
it has been proved otherwise.
Delayed toxicity is a sinister problem (e.g. diethylstilbestrol)
and if the teratogenic effect of thalidomidehad not produced
such an unusual congenital abnormality, namely phocomelia,
its detection might have been delayed further. If drugs (or envi-
ronmental toxins) have more subtle effects on the fetus (e.g. a
minor reduction in intelligence) or cause an increased incidence
of a common disease (e.g. atopy), these effects may never be
detected. Many publications demand careful prospective con-
trolled clinical trials, but the ethics and practicalities of such
studies often make their demands unrealistic. A more rational
approach is for drug regulatory bodies, the pharmaceutical
industry and drug information agencies to collaborate closely
and internationally to collate all information concerning drug
use in pregnancy (whether inadvertent or planned) and associ-
ate these with outcome. This will require significant investment
of time and money, as well as considerable encouragement to
doctors and midwives to complete the endless forms.

Guidance on the use of drugs for a selection of conditions is

summarized below. If in doubt, consult the British National

Formulary, appendix 4 (which is appropriately conservative).

Information for health professionals in the UK about the

safety of drugs in pregnancy can also be obtained from the

National Teratology Information Service (Tel. 0191 232 1525).

ANTIMICROBIAL DRUGS

Antimicrobial drugs are commonly prescribed during preg-

nancy. The safest antibiotics in pregnancy are the penicillins

and cephalosporins. Trimethoprimis a theoretical teratogen

as it is a folic acid antagonist. The aminoglycosides can

cause ototoxicity. There is minimal experience in pregnancy

with the fluoroquinolones (e.g. ciprofloxacin) and they should

be avoided. Erythromycinis probably safe. Metronidazoleis

a teratogen in animals, but there is no evidence of teratogenic-

ity in humans, and its benefit in serious anaerobic sepsis prob-

ably outweighs any risks. Unless there is a life-threatening

infection in the mother, antiviral agents should be avoided in

pregnancy. Falciparum malaria (Chapter 47) has an especially

high mortality rate in late pregnancy. Fortunately, the stan-

dard regimens of intravenous and oral quinine are safe in

pregnancy.

ANALGESICS

Opioids cross the placenta. This is particularly relevant in the

management of labour when the use of opioids, such as pethi-

dine, depresses the fetal respiratory centre and can inhibit

the start of normal respiration. If the mother is dependent on

opioids, the fetus can experience opioid withdrawal syn-

drome during and after delivery, which can be fatal. In

neonates, the chief withdrawal symptoms are tremor, irritabil-

ity, diarrhoea and vomiting. Chlorpromazineis commonly

used to treat this withdrawal state. Paracetamolis preferred to

aspirin when mild analgesia is required. In cases where a sys-

temic anti-inflammatory action is required (e.g. in rheumatoid

arthritis), ibuprofenis the drug of choice. Non-steroidal

anti-inflammatory drugs can cause constriction of the ductus

arteriosus. Occasionally, this may be used to therapeutic

benefit.

ANAESTHESIA

Anaesthesia in pregnancy is a very specialist area and should

only be undertaken by experienced anaesthetists. Local anaes-

thetics used for regional anaesthesia readily cross the pla-

centa. However, when used in epidural anaesthesia, the drug

remains largely confined to the epidural space. Pregnant

women are at increased risk of aspiration. Although com-

monly used, pethidinefrequently causes vomiting and may

also lead to neonatal respiratory depression. Metoclopramide

should be used in preference to prochlorperazine(which has

48 DRUGS IN PREGNANCY

Key points

Prescribing in pregnancy is a balance between the risk of

adverse drug effects on the fetus and the risk of leaving

maternal disease untreated. The effects on the human

fetus are not reliably predicted by animal experiments.

However, untreated maternal disease may cause morbidity

and/or mortality to mother and/or fetus.

Therefore,

• minimize prescribing;


• use ‘tried and tested’ drugs whenever possible in
  preference to new agents;


• use the smallest effective dose;


• remember that the fetus is most sensitive in the first
  trimester;


• consider pregnancy in all women of childbearing
  potential;


• discuss the potential risks of taking or withholding
  therapy with the patient;


• seek guidance on the use of drugs in pregnancy in the
  British National Formulary, Drug Information Services,
  National Teratology Information Service (NTIS);


• warn the patient about the risks of smoking, alcohol,
  over-the-counter drugs and drugs of abuse.