Drugs are now used in over half of all pregnancies and the prevalence of their use is steadily increasing. Some of the most commonly prescribed drugs include analgesics, antiemetics, antimicrobials and antihistamines. In addition to this the use of social and illicit drugs is also commonplace and rising.

Firm evidence-based guidelines for drug use during pregnancy is lacking for many drugs. If the potential benefit of the drug use outweighs the known risk, then the drug may be considered for use to treat certain disorders.

The effect that the drug will have on the fetus is largely determined by the fetal age at time of exposure, the dosage of the drug, and the potency of the drug.

Broadly speaking the fetal age at time of exposure effects the type of drug effect as follows:

  • Before the 20th day after fertilization: the effect is generally all-or-nothing, killing the embryo or having no affect at all.
  • Remainder of the 1st trimester: this is time during which organogenesis occurs and teratogenesis is most likely during this stage.
  • 2nd and 3rd trimesters: teratogenesis is unlikely during this stage but the growth and function of normally formed fetal organs and tissues may be altered.

 

A solid understanding of the drugs that are contraindicated and most commonly cause fetal abnormalities is vital knowledge for any practitioner that prescribes during pregnancy. For this reason, it is a very common exam topic and is frequently tested in most medical examinations.

The following table outlines the most commonly encountered drugs that have adverse effects during pregnancy:

 

DrugAdverse effects
ACE inhibitors
e.g. ramipril
If given in 2nd and 3rd trimester can cause hypoperfusion, renal failure and the oligohydramnios sequence.
Aminoglycosides
e.g. gentamicin
Ototoxicity
Deafness
AspirinHigh doses can cause 1st trimester abortions, delayed onset labour, premature closure of the fetal ductus arteriosus and fetal kernicterus.
Low doses (e.g. 75 mg) have no significant associated risk.
Benzodiazepines
e.g. diazepam
When given late in pregnancy respiratory depression and a neonatal withdrawal syndrome can occur.
Calcium-channel blockersIf given in 1st trimester can cause phalangeal abnormalities.
If given in the 2nd and 3rd trimester can cause fetal growth retardation.
CarbemazepineHaemorrhagic disease of the newborn
Neural tube defects
ChloramphenicolGrey baby syndrome
CorticosteroidsIf given in the 1st trimester may cause orofacial clefts
DanazolIf given in the 1st trimester can cause masculinisation of female fetus’s genitals
FinasterideFinasteride should not be even handled by a pregnant woman. Crushed or broken tablets can be absorbed through the skin and can affect male sex organ development.
HaloperidolIf given in the 1st trimester may cause limb malformations.
If given in the 3rd trimester increased risk of extrapyramidal symptoms in neonate.
HeparinMaternal bleeding
Thrombocytopaenia
IsoniazidMaternal liver damage.
Neuropathy and seizures in the neonate.
IsotretinoinHigh risk of teratogenicity (e.g. multiple congenital malformations, spontaneous abortion, and intellectual disability.
LithiumIf given in 1st trimester risk of fetal cardiac malformations.
If given in 2nd and 3rd trimesters risk of hypotonia, lethargy, feeding problems, hypothyroidism, goitre and nephrogenic diabetes insipidus in neonate.
MetforminRisk of neonatal hypoglycaemia.
MethadoneRisk of neonatal opioid withdrawal syndrome.
MethotrexateRisk of numerous congenital malformations e.g. fetal growth retardation, mandibular hypoplasia, cleft palate, spinal defects, ear defects and club foot.
Misoprostol Can cause miscarriage.
NSAIDS
e.g. ibuprofen
If given in 1st trimester can cause miscarriage, delayed onset labour, premature closure of the fetal ductos arteriosus and fetal kernicterus.
OestrodialLink with urogenital abnormalities in offspring that manifest in later life, most notably cancer of cervix and uterus.
PhenobarbitoneHaemorrhagic disease of the newborn
Some risk of congenital malformation
PhenytoinHaemorrhagic disease of the newborn
Risk of congenital malformations e.g. cleft lip, hypospadias and cardiovascular defects.
Sodium valproateRisk of major congenital malformations e.g. neural tube, cardiac, craniofacial and limb defects.
SSRIs
e.g. sertraline, fluoxetine
If given in 3rd trimester is associated with discontinuation syndrome and persistent pulmonary hypertension of the newborn.
Statins
e.g. simvastatin, atorvastatin
Cholesterol is required for fetal growth and its reduction by statins may affect fetal development.
TetracyclineSlowed bone growth, enamel hypoplasia, permanent yellowing of teeth and increased susceptibility to cavities in offspring.
Occasionally causes liver failure in pregnant women.
TrimethoprimIf given in 1st trimester increased risk of neural tube defects due to folate antagonism.
WarfarinIf given in 1st trimester may cause fetal warfarin syndrome (nasal hypoplasia, bone stippling, bilateral optic atrophy and intellectual disability)
If given in 2nd or 3rd trimester can cause optic atrophy, cataracts, microcephaly, microphthalmia, intellectual disability and fetal and/or maternal haemorrhage.

 


Thank you to the joint editorial team of www.plabprep.co.uk for this article.

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