Prescribing in Pregnancy: Safe Choices, Teratogens and Risk Communication

[HOST] Welcome to ClinicaliQ Clinical Essentials. I'm Emma, and with me is Dr Anzal Qurbain, pharmaceutical physician. Today we are covering prescribing in pregnancy — what is ok to use, what is not, and how to navigate a topic where the evidence is often incomplete. Dr Qurbain, this feels like an area where clinicians can become very risk-averse.

[EXPERT] And that risk aversion itself becomes a clinical hazard. Stopping a medicine in pregnancy because of vague concerns about safety — without weighing what happens to the mother if her condition deteriorates — can cause more harm than continuing. Untreated epilepsy, uncontrolled asthma, severe depression — these all carry serious risks for both mother and baby. The decision is always a risk-benefit judgement, not a blanket avoidance.

[HOST] Why is the evidence so patchy in this area?

[EXPERT] Because pregnant women are almost universally excluded from clinical trials for ethical reasons. So most of what we know about drug safety in pregnancy comes from pharmacovigilance data, registries, case series, and observational studies. That means the evidence base is retrospective and often based on inadvertent exposures rather than controlled studies. It's incomplete by design, which makes the uncertainty unavoidable.

[HOST] Let's start with folate. This feels like one of the clearest recommendations.

[EXPERT] Folate is one of the clearest and most important. All women planning pregnancy, or who could become pregnant, should take 400 micrograms of folic acid daily, ideally starting before conception and continuing through the first trimester. This reduces the risk of neural tube defects, including spina bifida. For women at higher risk — those on antiepileptic drugs like valproate or carbamazepine, those with a previous neural tube defect, those with diabetes, or those with obesity — the dose is 5 milligrams daily. The same higher dose is recommended for women on methotrexate, though methotrexate itself should ideally be stopped before conception.

[HOST] Let's talk about what's generally considered safe in pregnancy.

[EXPERT] Paracetamol remains the analgesic of first choice throughout pregnancy. There was a signal in some observational studies linking paracetamol exposure to ADHD and autism, but the MHRA reviewed this and the conclusion is that occasional use at the lowest effective dose for the shortest duration remains appropriate. Penicillins are well tolerated — amoxicillin, co-amoxiclav, flucloxacillin — as are most cephalosporins. For blood pressure, labetalol is the first-line antihypertensive in pregnancy, and methyldopa has a long safety record and is commonly used. Nifedipine is also used. For asthma, all the standard inhalers — short-acting beta agonists, inhaled corticosteroids — should be continued. The evidence is consistent that uncontrolled asthma is more dangerous than any of the inhalers used to treat it.

[HOST] What about antidepressants? This must come up frequently.

[EXPERT] Frequently and with a lot of anxiety on both sides. Untreated depression and anxiety in pregnancy carries real risks — poor nutrition, self-harm, disrupted ante-natal care, and significant post-partum complications. If a woman is already stable on an antidepressant when she conceives, the decision to continue needs careful weighing. Sertraline has the most data and is generally considered the safer SSRI in pregnancy. There are some signals for neonatal adaptation syndrome with SSRIs used close to delivery — the baby can have transient jitteriness, feeding difficulties, irritability — but this usually resolves within days and is not a reason to automatically stop in the third trimester.

[HOST] Are there antidepressants to specifically avoid?

[EXPERT] Paroxetine has a signal for cardiac defects in some registries, so it's generally avoided as first choice in pregnancy. Venlafaxine at high doses has a signal for raised blood pressure in the neonate. These are relative rather than absolute concerns, but they influence the choice when starting de novo.

[HOST] Let's move to the clear avoidances. NSAIDs?

[EXPERT] NSAIDs are problematic, particularly in the third trimester. They can cause premature closure of the ductus arteriosus — a critical foetal vessel — which is a serious cardiac problem. They also reduce amniotic fluid volume. From 30 weeks gestation, NSAIDs should be avoided. In the first and second trimesters, they're generally avoided too, especially from 20 weeks when some guidelines flag oligohydramnios risk. Ibuprofen is the most common NSAID and it's worth making sure women in later pregnancy know not to reach for it.

[HOST] ACE inhibitors and ARBs?

[EXPERT] These are contraindicated in the second and third trimesters. They cause foetal renal impairment, leading to oligohydramnios, limb contractures, skull ossification problems, and renal agenesis in severe cases. The effect in the first trimester is less clear, but most guidelines advise switching to a pregnancy-safe antihypertensive as soon as pregnancy is confirmed if the woman is on an ACE inhibitor or ARB. Labetalol or methyldopa are the usual alternatives.

[HOST] Statins?

[EXPERT] Statins are contraindicated in pregnancy. Cholesterol is essential for foetal development and statins inhibit its synthesis. There's limited human data, but animal studies show foetal abnormalities and the mechanistic concern is real. Statins should be stopped at least three months before planned conception where possible, or immediately if pregnancy is confirmed unexpectedly.

[HOST] Valproate. This is a topic that's received a lot of attention.

[EXPERT] Rightly so. Sodium valproate is associated with neural tube defects in around 1 to 2 percent of exposures, and with a broader pattern of congenital malformations in up to 10 percent. There's also a well-documented risk of neurodevelopmental effects — reduced IQ, autism spectrum disorder, ADHD — in children exposed in utero. The MHRA's PREVENT programme requires that valproate is not prescribed to women of childbearing potential unless they are enrolled in the Pregnancy Prevention Programme, which includes annual acknowledgement of risks, effective contraception, and specialist review. It's one of the most tightly regulated prescribing restrictions in UK medicine.

[HOST] What if a woman with epilepsy is already stable on valproate and becomes pregnant?

[EXPERT] This is a situation for urgent specialist review — ideally with neurology or epilepsy specialist involvement. Stopping valproate abruptly can precipitate seizures, which also carry foetal risk. It's a genuinely difficult situation and the conversation needs to happen with the woman fully informed of both risks — continuing valproate and stopping it. The goal whenever possible is to address this before pregnancy through pre-conception counselling.

[HOST] What about Warfarin?

[EXPERT] Warfarin crosses the placenta and causes warfarin embryopathy in the first trimester — nasal hypoplasia, limb abnormalities, and CNS effects. Women with mechanical heart valves who need anticoagulation during pregnancy are usually managed with low molecular weight heparin, which does not cross the placenta. This is a high-risk specialist situation requiring close multidisciplinary management.

[HOST] What resources should clinicians use when a specific drug comes up in pregnancy?

[EXPERT] UKTIS — the UK Teratology Information Service — is the definitive resource. It's at uktis.org and provides evidence-based information on specific drug exposures in pregnancy. The BNF appendix on prescribing in pregnancy is a good starting point but UKTIS is more detailed. For complex situations, clinicians can phone the UKTIS consultation service for specialist advice. It's underused and highly valuable.

[HOST] What's your clinical pearl for this topic?

[EXPERT] Don't stop essential medicines during pregnancy based on vague or theoretical concerns without specialist input. The instinct to "play it safe" by stopping a drug can lead to deteriorating maternal health, which itself carries foetal risk. The conversation should always be: what is the risk of continuing this medicine, and what is the risk of stopping or switching it? Both risks need to be on the table. Pre-conception counselling — reviewing all regular medicines before a woman tries to conceive — is the best opportunity to optimise this, and it's hugely valuable when it happens.

[HOST] Really important framing. To summarise: folate 400 micrograms for all, 5milligrams if higher risk; well tolerated medicines include paracetamol, penicillins, labetalol, methyldopa, and all standard inhalers; avoid NSAIDs particularly from 20 weeks, ACEi and ARBs in second and third trimesters, statins, tetracyclines, and warfarin in the first trimester; valproate has the PREVENT programme; and UKTIS is your go-to resource. And the clinical pearl — don't stop essential medicines based on vague concern. The harm from stopping can outweigh the harm from continuing. Thank you, Dr Qurbain.

[EXPERT] Thanks, Emma. Pre-conception planning really is where a lot of this gets done properly — it's worth encouraging every time.

[HOST] That's all for this episode of ClinicaliQ Clinical Essentials. Join us next time for more practical prescribing guidance.