Letter: A

Direct oral anticoagulants (DOACs) include Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) and the direct thrombin inhibitor (dabigatran). These drugs act on specific components of the coagulation cascade, resulting in reduced thrombin generation and inhibition of fibrin clot formation. They are widely used for stroke prevention in atrial fibrillation, and the treatment and prevention of venous thromboembolism.

Small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists, also known as gepants, are used in the prevention and acute treatment of migraine.

Ampicillin is a broad-spectrum penicillin antibiotic indicated for the treatment of bronchitis, urinary tract infections, otitis media, sinusitis, uncomplicated community-acquired pneumonia, salmonellosis, endocarditis, and listeria meningitis.

The limited data available do not suggest an increased overall risk of congenital malformations and, although data for cardiac malformations are conflicting, they are likely highly confounded. Available data provide no convincing evidence of an increased risk of miscarriage, intrauterine death, low infant birth weight, preterm delivery, or neonatal complications following exposure to ampicillin. Where possible associations with adverse outcomes have been suggested, findings are considered likely influenced by the effects of maternal infection during pregnancy.

The extensive body of data relating to maternal use of penicillin antibiotics as a class does not indicate an increased risk of adverse fetal outcomes, although not all pregnancy outcomes have been studied in sufficient detail to fully exclude an increased risk. However, due to the potential adverse consequences of untreated maternal infection during pregnancy, the use of penicillin antibiotics, including those with limited or no pregnancy safety data, may be considered where clinically necessary.

Where possible, the results of culture and sensitivity tests should be available before making a treatment choice in accordance with local prescribing guidelines. It is important to ensure adequate treatment of infections in order to avoid adverse maternal and fetal effects from uncontrolled infection or pyrexia.

The Royal College of Obstetricians and Gynaecologists (RCOG) advise routine intrapartum antibiotic prophylaxis (IAP) for all women in preterm labour, with or without pre-labour rupture of membranes (PROM). Benzylpenicillin should be used preferentially, but a cephalosporin should be used in women with a non-severe penicillin allergy, or vancomycin where the allergy is severe. The National Institute for Health and Care Excellence (NICE) guidelines also state that women with pre-labour PROM should be offered oral erythromycin (250mg, 4 times a day) for a maximum of 10 days or until the woman is in established labour (whichever is sooner), with oral penicillin offered to women who cannot tolerate erythromycin.

Exposure to ampicillin at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.

Amoxicillin is a broad-spectrum penicillin antibiotic indicated for the treatment of sinusitis, otitis media, streptococcal tonsillitis and pharyngitis, pneumonia, cystitis, asymptomatic bacteriuria in pregnancy, acute pyelonephritis, typhoid and paratyphoid fever, dental abscess with spreading cellulitis, Helicobacter pylori eradication, and Lyme disease. It is available in combination with clavulanic acid to prevent inactivation by beta-lactamase enzymes such as co-amoxiclav.

A large body of data indicates no increased risk of congenital malformations, miscarriage, intrauterine death, low birth weight (LBW), preterm delivery, or neonatal complications following maternal exposure to amoxicillin or co-amoxiclav. Where possible associations with adverse outcomes have been suggested, findings are considered likely influenced by the effects of infection during pregnancy.

Where possible, the results of culture and sensitivity tests should be available before making a treatment choice in accordance with local prescribing guidelines. It is important to ensure adequate treatment of infection in order to avoid adverse maternal and fetal effects resulting from uncontrolled infection or pyrexia.

The Royal College of Obstetricians and Gynaecologists (RCOG) advises routine intrapartum antibiotic prophylaxis (IAP) for all women in preterm labour, with or without pre-labour rupture of membranes (PROM). Benzylpenicillin should be used preferentially, but a cephalosporin should be used in women with a non-severe penicillin allergy, or vancomycin where the allergy is severe. The National Institute for Health and Care Excellence (NICE) guidelines also state that women with pre-labour PROM should be offered oral erythromycin (250mg, 4 times a day) for a maximum of 10 days or until the woman is in established labour (whichever is sooner), with oral penicillin offered to women who cannot tolerate erythromycin.

Co-amoxiclav should not be used in women with pre-labour PROM owing to a possible increased risk of necrotising enterocolitis (NEC) in the neonate.

Exposure to amoxicillin/co-amoxiclav at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.

Summary: Asthma is one of the most common chronic conditions affecting pregnant women, and poorly controlled disease has been associated with increased risks of pre eclampsia, preterm birth, low birth weight, and perinatal mortality. Maternal hypoxia resulting from uncontrolled asthma can directly impair fetal oxygenation, highlighting the importance of maintaining stable respiratory function. Effective control of asthma during pregnancy is therefore essential to optimise both maternal and fetal outcomes.

The hormonal and physiological changes of pregnancy can affect asthma severity. Regular monitoring and tailored management are therefore crucial to minimise exacerbations. Appropriate use of asthma medications has been shown to be safe and effective, reducing the likelihood of acute attacks and improving overall pregnancy outcomes. Pregnant women with asthma should generally be managed as per the non-pregnant patient.

Guidance from NICE/BTS/SIGN on the general management of asthma recommends that the following pharmacological treatments (in various combinations and doses) can be used:

• An inhaled corticosteroid (ICS) plus a short-acting beta-2 agonist (SABA – usually salbutamol, with terbutaline used occasionally)
• An ICS/long-acting beta-2 agonist (LABA) combination inhaler (usually ICS/formoterol combination)
• A leukotriene receptor antagonist (LTRA) – montelukast
• A long-acting muscarinic receptor antagonist (LAMA) – tiotropium
• Theophylline
• Oral corticosteroids – most commonly prednisolone
• Biologics

Data on many asthma medications are limited, although they are widely used and not known to cause harm. Consensus expert opinion is that the risk of inadequately treated asthma during pregnancy outweighs any theoretical risk of asthma medication use.

Routine exposure to asthma medications is not an indication for additional fetal monitoring. Women with severe asthma exacerbations in pregnancy require careful management which may include additional monitoring of fetal growth and wellbeing. Other risk factors which could independently increase the risk of adverse pregnancy outcome may also be present in individual cases. Such factors are important to consider when performing case-specific risk assessments.

Six biologic monoclonal antibody (mAb) therapies are licensed for the management of severe asthma: mepolizumab, reslizumab, benralizumab, omalizumab, dupilumab, and tezepelumab. This monograph summarises the available data for mepolizumab, benralizumab, tezepelumab, and reslizumab. For further information on omalizumab and dupilumab, please see the separate UKTIS monographs.

There are limited published human pregnancy data relating to mepolizumab and benralizumab. Data regarding reslizumab are very limited. No published human pregnancy exposures to tezepelumab have been identified. Data are derived from case reports (mepolizumab-exposed n=3; benralizumab-exposed n=6) and a pharmacovigilance analysis including 154 mepolizumab exposed, 774 benralizumab exposed, and 25 reslizumab-exposed pregnancies. The nature and size of these datasets limit the assessment of the risk of adverse pregnancy outcomes. mAbs do not actively cross the placenta in the first trimester and are therefore not expected to result in direct fetal exposure; this may lead to a lower risk of teratogenic/embryotoxic effects.

It is critically important to ensure that maternal asthma is well-controlled in pregnancy. Where a woman’s asthma is well-controlled with a mAb, particularly when conventional treatments have been ineffective, the risks and benefits of continuing treatment during pregnancy should be assessed on a case-by-case basis and discussed with the patient as part of a shared decision-making process.

Guidance from the UK Health Security Agency (UKHSA) [issued 2017] advises that live vaccines should be avoided until the infant is at least 6 months of age following in utero exposure to biologic immunosuppressant therapies. While mAbs used to treat asthma are not broadly immunosuppressant, the effects of in utero exposure on the neonatal or infant immune system are largely unknown. Please contact UKTIS for an individualised risk assessment where BCG vaccination is indicated in an infant under 6 months of age with prenatal asthma mAb exposure.

Exposure to asthma mAbs at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors which could independently increase the risk of adverse pregnancy outcome may be present in individual cases. Such factors are important to consider when performing case-specific risk assessments.

Apremilast is indicated for the treatment of active psoriatic arthritis, moderate-to-severe chronic plaque psoriasis, and oral ulcers associated with Behçet’s disease.

There are no published human data on the use of apremilast during pregnancy; therefore, no definitive conclusions regarding its safety can be drawn. Although adverse effects have been reported in animal studies, these findings do not signal that apremilast use at therapeutic doses would be expected to result in teratogenic effects in humans.

It is important to ensure psoriatic arthritis is well controlled in pregnancy to decrease the risk of adverse outcomes for both mother and fetus. Where a woman’s condition is well controlled, particularly if first-line treatments have been ineffective, the risks and benefits of continuing apremilast during pregnancy should be assessed on a case-by-case basis and discussed with the patient as part of the shared decision-making process.

Behçet’s disease is not usually associated with a detrimental effect on pregnancy outcome, and many pregnant women report spontaneous improvement. In cases where the condition does not improve, treatment with more well-established pregnancy data should be considered in the first instance, for example, corticosteroids, azathioprine, or colchicine. Discussion with UKTIS is recommended.

Exposure to apremilast at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy. Due to the unknown fetal risks, women with first trimester exposure could be offered their anomaly scan from 16 weeks of pregnancy. Other risk factors which could independently increase the risk of adverse pregnancy outcome may also be present in individual cases. Such factors are important to consider when performing case-specific risk assessments.

Azelastine is a non-sedating antihistamine used for the symptomatic relief of allergic conditions.

Amfetamines are substituted phenethylamines with sympathomimetic properties. Common names include A, Aimies (also used for amyl nitrite), Amphet, Amphetamine, Bennies, Billy Whiz, Black Beauties, Bumblebees, Clear Rocks, Co-pilots, Crank, Croke, Glass, Ice (also used for cocaine), LA Turnarounds, Mollies, Oranges, Pep Pills, Pink Champagne, Pink Speed Bombs, Rippers, Rocks, Speed, Splash, Sulph, Sulphate, Wake Ups, and Whizz.

Azithromycin is a macrolide antibiotic, indications include sinusitis, otitis media, pharyngitis, tonsillitis, bronchitis, pneumonia, skin and soft tissue infections, chlamydia, and gonorrhoea.

Most studies investigating malformation risk following azithromycin use in pregnancy do not provide evidence of an association. A single study has described increased risks of specific malformations, including atrioventricular septal defects and syndactyly; however, further investigation is required as these findings may have been impacted by methodological biases and/or confounding by indication and therefore do not provide compelling evidence of a causal association.

The available data relating to miscarriage and preterm delivery do not suggest increased risks following gestational exposure to azithromycin. There are no studies investigating the risk of intrauterine death, low birth weight, neonatal complications, or neurodevelopmental impairment following the use of azithromycin during pregnancy; however, data do not suggest increased risks of these outcomes following gestational exposure to macrolide antibiotics as a class.

At the time of writing, the Royal College of Obstetricians and Gynaecologists (RCOG) advise routine intrapartum antibiotic prophylaxis for all women in preterm labour, with or without premature rupture of membranes (PROM). Benzylpenicillin should be used preferentially but substituted for a cephalosporin in patients with a non-severe penicillin allergy, or vancomycin where the allergy is severe. The National Institute for Health and Care Excellence (NICE) guidelines also state that women with pre-labour PROM should be offered oral erythromycin (250mg, 4 times a day) for a maximum of 10 days or until the woman is in established labour (whichever is sooner), with oral penicillin offered to patients who cannot tolerate erythromycin.

It is important to effectively treat infections in pregnancy as adverse maternal and fetal effects may result from uncontrolled infection or pyrexia.

Where possible, the results of culture and sensitivity tests should guide treatment choice in accordance with local prescribing guidelines. If a macrolide is indicated, erythromycin has historically been preferred during pregnancy because there is more documented experience of its use than for other macrolides. However, treatment choices should be made on a case-by-case basis accounting for likely efficacy and tolerability, as well as possible fetal effects.

Exposure to azithromycin at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.