an anti-analgesic effect when combined with pethidine), and
naloxone(an opioid antagonist) must always be available.
Respiratory depression in the newborn is not usually a prob-
lem with modern general anaesthetics currently in use in
Caesarean section. Several studies have shown an increased
incidence of spontaneous abortions in mothers who have had
general anaesthesia during pregnancy, although a causal rela-
tionship is not proven, and in most circumstances failure to
operate would have dramatically increased the risk to mother
and fetus.
ANTI-EMETICSNausea and vomiting are common in early pregnancy, but are
usually self-limiting, and ideally should be managed with
reassurance and non-drug strategies, such as small frequent
meals, avoiding large volumes of fluid and raising the head of
the bed. If symptoms are prolonged or severe, drug treatment
may be effective. An antihistamine, e.g. promethazineor
cyclizinemay be required. If ineffective, prochlorperazineis
an alternative. Metoclopramideis considered to be safe and
efficacious in labour and before anaesthesia in late pregnancy,
but its routine use in early pregnancy cannot be recommended
because of the lack of controlled data, and the significant inci-
dence of dystonic reactions in young women.
DYSPEPSIA AND CONSTIPATIONThe high incidence of dyspepsia due to gastro-oesophageal
reflux in the second and third trimesters is probably related to
the reduction in lower oesophageal sphincter pressure. Non-
drug treatment (reassurance, small frequent meals and advice
on posture) should be pursued in the first instance, particu-
larly in the first trimester. Fortunately, most cases occur later
in pregnancy when non-absorbable antacids, such as algi-
nates, should be used. In late pregnancy, metoclopromideis
particularly effective as it increases lower oesophageal sphinc-
ter pressure. H 2 -receptor blockers should not be used for non-
ulcer dyspepsia in this setting. Constipation should be managed
with dietary advice. Stimulant laxatives may be uterotonic
and should be avoided if possible.
PEPTIC ULCERATIONAntacids may relieve symptoms. Cimetidineandranitidine
have been widely prescribed in pregnancy without obvious
damage to the fetus. There are inadequate safety data on the
use of omeprazoleor other proton pump inhibitors in preg-
nancy. Sucralfatehas been recommended for use in preg-
nancy in the USA, and this is rational as it is not systemically
absorbed.Misoprostol, a prostaglandin which stimulates the
uterus, is contraindicated because it causes abortion.
ANTI-EPILEPTICSEpilepsy in pregnancy can lead to fetal and maternal morbid-
ity/mortality through convulsions, whilst all of the anticon-
vulsants used have been associated with teratogenic effects
(e.g.phenytoinis associated with cleft palate and congenital
heart disease). However, there is no doubt that the benefits of
good seizure control outweigh the drug-induced teratogenic
risk. Thorough explanation to the mother, ideally before a
planned pregnancy, is essential, and it must be emphasized
that the majority (90%) of epileptic mothers have normal
babies. (The usual risk of fetal malformation is 2–3% and in
epileptic mothers it is up to 10%.) In view of the association of
spina bifida with many anti-epileptics, e.g. sodium valproate
andcarbamazepinetherapy, it is often recommended that the
standard dose of folic acid should be increased to 5 mg daily.
Both of these anti-epileptics can also cause hypospadias. As
in non-pregnant epilepsy, single-drug therapy is preferable.
Plasma concentration monitoring is particularly relevant for
phenytoin, because the decrease in plasma protein binding and
the increase in hepatic metabolism may cause considerable
changes in the plasma concentration of free (active) drug. As
always, the guide to the correct dose is freedom from fits and
absence of toxicity. Owing to the changes in plasma protein
binding, it is generally recommended that the therapeutic
range is 5–15 mg/L, whereas in the non-pregnant state it is
10–20 mg/L. This is only a rough guide, as protein binding
varies.
The routine injection of vitamin K recommended at birth
counteracts the possible effect of some anti-epileptics on
vitamin K-dependent clotting factors.
Magnesium sulphate is the treatment of choice for the pre-
vention and control of eclamptic seizures.PRESCRIBING INPREGNANCY 49Key points- Epilepsy in pregnancy can lead to increased fetal
and maternal morbidity/mortality. - All anticonvulsants are teratogens.
- The benefits of good seizure control outweigh
drug-induced teratogenic risk. - Give a full explanation to the mother (preferably
before pregnancy): most epileptic mothers (90%)
have normal babies. - Advise an increase in the standard dose of folic acid up
to 12 weeks. - Make a referral to the neurologist and obstetrician.
- If epilepsy is well controlled, do not change
therapy. - Monitor plasma concentrations (levels tend to fall,
and note that the bound: unbound ratio changes); the
guide to the correct dose is freedom from fits and
absence of toxicity. - An early ultrasound scan at 12 weeks may detect gross
neural tube defects. - Detailed ultrasound scan and α-fetoprotein at 16–18
weeks should be considered.