Letter: S

Secukinumab is a recombinant human monoclonal antibody that selectively binds to the cytokine interleukin-17A (IL-17A) and is used in the treatment of several chronic autoimmune and inflammatory conditions, including plaque psoriasis, psoriatic arthritis, axial spondyloarthritis, and hidradenitis suppurativa.

Published data relating to secukinumab use during pregnancy are limited and consist of case reports/series and a small cohort study collectively describing 190 unique secukinumab-exposed pregnancies. In addition, two analyses of adverse event reporting data include over 1,700 reported exposures. Overall, these data do not suggest an increased risk of adverse pregnancy outcomes; however, due to the small number of exposed pregnancies, they are insufficient to exclude small increased risks or risks of rare outcomes.

IgG monoclonal antibodies (mAbs) do not actively cross the placenta in the first trimester and use at this stage is not expected to result in direct fetal exposure; therefore, direct teratogenic or embryotoxic effects are not anticipated.

Although inflammatory autoimmune conditions may improve during pregnancy, active or poorly controlled disease is associated with an increased risk of adverse pregnancy outcomes. The risks and benefits of continuing treatment during pregnancy should therefore be considered on an individual basis and through a shared decision-making process.

Use of immunosuppressant antibodies that actively cross the placenta during pregnancy could result in immunosuppression in the newborn and increase the risk of infection. Data specifically evaluating the effects of in utero secukinumab exposure on infant immune function are very limited.

Guidance from the UK Health Security Agency (UKHSA), issued in 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. Please contact UKTIS for an individualised risk assessment where BCG vaccination is indicated in an infant under 6 months of age with prenatal secukinumab exposure.

Exposure to secukinumab 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.

Urinary incontinence, defined as the involuntary leakage of urine, has multiple causes which may require different management strategies. Stress incontinence is common during pregnancy, caused by the hormonal changes of pregnancy and pressure on the bladder from the expanding uterus. Pharmacological treatment is not routinely indicated for urinary stress incontinence that has occurred due to pregnancy.

Women with pre-existing conditions that cause urinary frequency, enuresis and incontinence may require ongoing treatment during pregnancy under specialist supervision. Human pregnancy safety data is limited or lacking for most of the drug options, and the risks and benefits should therefore be considered on a case-by-case basis, taking into account the severity of the woman’s condition and likely effects on her health and quality of life if an established medication regimen is altered.

Oxybutynin is the best studied treatment for urinary frequency during pregnancy, although data are still very limited. Neither of two studies nor a handful of case reports raise concern that oxybutynin exposure is associated with infant congenital malformation. Increased risks of preterm delivery and low infant birth weight were noted in one of the studies but may be related to the underlying maternal condition. These findings require confirmation.

There are no further published human pregnancy exposure data for drugs to treat urinary frequency, enuresis and/or incontinence. A small number of pregnancy outcomes have been reported to UKTIS following prenatal exposure to oxybutynin, solifenacin, tolterodine, fesoterodine, mirabegron, propantheline, and trospium, with no major congenital malformations described. Data are absent for darifenacin, flavoxate, and propiverine.

Adverse fetal effects have been observed in preclinical (animal) studies of darifenacin, propiverine, fesoterodine, mirabegron, oxybutynin, and tolterodine; however, some exposures were at maternally toxic doses.

Exposure to drugs used to reduce symptoms of urinary frequency, enuresis and incontinence at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy; however, due to the lack of data, additional fetal monitoring may be warranted. Other risk factors may also 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.

Spiramycin is a macrolide antibiotic that is not licensed in the United Kingdom. It is used to treat toxoplasmosis and may reduce the risk of transmission of maternal infection to the fetus.

Only two studies have investigated the risk of malformation following exposure to spiramycin in pregnancy. The limited available data do not show an increased risk of congenital malformation overall and there is no compelling evidence for specific anomalies, and although one study has shown an increased risk of hydrocephaly and spina bifida, this does not provide compelling evidence of a causal association; further research is required.

The limited available data do not suggest an increased risk of miscarriage following gestational exposure to spiramycin; however, further studies are required to confirm this finding. There are no studies investigating the risk of intrauterine death, low birth weight, preterm delivery, neonatal complications, or neurodevelopmental impairment following the use of spiramycin 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 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 spiramycin 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.

Sotrovimab is an IgG1 monoclonal antibody which binds to a conserved epitope on the spike protein receptor binding domain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thereby inhibiting viral fusion to the cell membrane. It is licensed for the treatment of symptomatic acute coronavirus disease 2019 (COVID-19) infection in people who do not require oxygen supplementation but are at increased risk of severe COVID-19. The National Institute for Health and Care Excellence (NICE) guidelines recommend that sotrovimab can be considered where nirmatrelvir/ritonavir is contraindicated or unsuitable.

Although pregnant women without comorbidities do not appear to be more likely to contract SARS-CoV-2 than the general population, increased risks have been described for those with pre-existing diabetes, gestational diabetes requiring insulin treatment, and in those who are overweight or obese. However, pregnant women are at increased risk of developing severe COVID-19, particularly in late pregnancy. Increased risks of adverse pregnancy outcomes, including growth restriction, preterm delivery and stillbirth have also been described. Where indicated, treatments for COVID-19 should not be withheld on account of pregnancy.

Published data regarding sotrovimab exposure in pregnancy are limited, and although there is no compelling evidence indicating increased risks of adverse pregnancy, fetal or neonatal outcomes, additional studies are required before more definitive conclusions can be provided. Where nirmatrelvir/ritonavir is contraindicated or unsuitable and the benefits of treatment are expected to outweigh the risks, sotrovimab can be considered for use in pregnant women with COVID-19.

Exposure to sotrovimab 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.

Sulpiride is an atypical antipsychotic (AAP) used in the treatment of schizophrenic disorders.

There are no studies which specifically investigate the use of sulpiride during pregnancy. Although sulpiride exposures are included in a small number of studies which report on the fetal outcomes of women exposed to antipsychotics (APs) as a group, sulpiride exposures represented only a very small proportion of the total study cohort and the outcomes have not been analysed separately. There has been one small controlled prospective study which specifically examined the outcomes of 162 pregnancies following gestational exposure to the s-enantiomer of sulpiride, levosulpiride. This study found no significantly increased risk of miscarriage, major malformation, stillbirth or specific neonatal complications in exposed pregnancies compared to age-matched non-exposed controls. However, this study is statistically underpowered and mainly reports outcomes following short inadvertent exposures early in the first trimester. While data do not currently raise concern of increased risks of adverse pregnancy outcomes, they are currently too limited to exclude such associations.

Studies of APs/AAPs as therapeutic classes describe a collective total of >50,000 exposures. Although the available data are largely reassuring for most outcomes, data relating to stillbirth risks are conflicting. Similarly, although associations have been described for first generation AP exposure with preterm delivery and small for gestational age (SGA), and preterm delivery and AAP exposure, these data are also conflicting and likely confounded. These data do not provide compelling evidence of causal associations, and further research is required to confirm or refute the findings. Data regarding neurodevelopmental outcomes are conflicting, and studies have provided demonstrations of data confounding due to the underlying maternal condition and factors associated with it.

In the non-pregnant population, use of AAPs (particularly olanzapine and clozapine) is a risk factor for impaired glucose homeostasis and type 2 diabetes. Concerns regarding an increased risk of maternal gestational diabetes mellitus (GDM) and its sequelae therefore exist following gestational AP. There are no data that investigate risk of GDM with use of sulpiride specifically.

Use of APs throughout pregnancy or near delivery has been associated with withdrawal symptoms in the neonate or poor neonatal adaptation syndrome (PNAS). These symptoms are likely to be more severe in infants exposed in utero to more than one CNS-acting drug. Delivery should therefore be planned in a unit with neonatal intensive care facilities.

It is important to ensure that maternal mental health conditions are treated appropriately. Where a woman’s illness is stabilised on sulpiride, either prior to conception or during pregnancy, the risk of discontinuing or changing medication, or reducing the dose, should be carefully weighed against the risk of relapse of the maternal condition. Where clinically appropriate, clinicians are encouraged to discuss the advantages and disadvantages of continued sulpiride use during pregnancy with the patient. Where the benefit of continued treatment is considered to outweigh any potential or known risks, sulpiride use in pregnancy may be the best option for both mother and baby.

Exposure to sulpiride 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. Owing to the lack of data regarding malformation risks, women who have been exposed to sulpiride in the first trimester are particularly encouraged to attend their routine detailed fetal anomaly scan, which is generally conducted at around 18 to 20 weeks of pregnancy.

Sulfasalazine (sulphasalazine) is a sulphonamide aminosalicylic acid compound licensed for the induction and maintenance of remission of ulcerative colitis, and for treating active Crohn’s disease and rheumatoid arthritis.

Most of the data relating to sulfasalazine exposure during pregnancy derive from studies of women undergoing treatment for inflammatory bowel disease (IBD). Active (uncontrolled) IBD has been associated with increased risks of adverse pregnancy outcomes, including congenital malformations, preterm delivery, and small for gestational age infants. Control of the maternal condition throughout pregnancy may therefore prove beneficial to both mother and fetus.

Guidelines from the British Society of Gastroenterology and the British Society for Rheumatology state that sulfasalazine can be used in pregnancy if clinically appropriate. The available human data do not suggest that sulfasalazine use during pregnancy is associated with an increased overall risk of congenital malformation or of a number of specific malformations. Risk of miscarriage is currently undetermined, although a single study of 5-acetylsalicylic acid (5-ASA) medications as a class did not identify a significant increased risk. No robust evidence of increased risks of stillbirth, low birth weight, or preterm delivery has been provided from a small number of studies, though additional data are ideally required.

There are theoretical concerns regarding an increased risk of neonatal hyperbilirubinaemia following in utero sulfasalazine exposure, although there is no good evidence confirming this association.

Sulfasalazine has been shown to actively inhibit the absorption and metabolism of folic acid, which may result in folic acid deficiency. Pregnant women undergoing treatment with sulfasalazine are advised to supplement with high dose folic acid (5mg/day) for three months prior to conception and during the first 12 weeks of pregnancy.

Exposure to sulfasalazine 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.

Statins (atorvastatin, fluvastatin, pravastatin, rosuvastatin and simvastatin) are a class of HMG-CoA reductase inhibitors used to lower cholesterol. They are indicated as an adjunct to diet for the treatment of primary hypercholesterolaemia or mixed dyslipidaemia when non-pharmacological treatments (e.g., diet, exercise, weight reduction) are inadequate, or for reduction of cardiovascular morbidity and mortality.

Cholesterol is required for normal development of the placenta and fetus; therefore, theoretical concerns of teratogenic effects exist for any drug that inhibits endogenous cholesterol production. A high proportion of pregnant women taking statins will have pre-existing diabetes, and/or obesity, both of which carry independent risks for fetal malformation and other adverse pregnancy outcomes.

Although the available data are limited for some pregnancy outcomes, they do not suggest that in utero statin exposure increases the risks of overall malformation, stillbirth, preterm delivery, fetal growth impairment or neonatal complications.

Evidence relating to the risk of cardiac malformation is conflicting and possibly confounded; however, a small increased risk cannot be excluded. An absolute risk of approximately 1.5 to 2%, relative to a background risk of approximately 1%, may be suggested by the available data.

Several studies have described small increased risks of miscarriage following maternal statin use in pregnancy; however, these data may be influenced by data confounding and methodological limitations.

Offspring neurodevelopment following gestational statin exposure has not been studied. As neurodevelopmental impairment is a key feature of several genetic cholesterol synthesis disorders, an effect cannot be ruled out and ongoing data collection is required.

Current guidelines on diseases for which statins are frequently prescribed recommend that statins are discontinued three months prior to attempting to conceive, or as soon as pregnancy is confirmed. Where statins are prescribed for conditions associated with high cholesterol, temporary suspension of therapy for the duration of pregnancy is thought unlikely to compromise maternal health. However, there may be some conditions, such as familial hypercholesterolaemia, where continued statin use in pregnancy may be considered. Discussion with UKTIS is recommended in all such cases.

Exposure to statins at any stage of pregnancy would not usually be regarded as medical grounds for termination of pregnancy. However, other risk factors for adverse pregnancy outcome are likely to be present in women exposed to statins, such as obesity and diabetes. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.

Sotalol is a non-selective beta blocker with antiarrhythmic effects and is licensed in the UK for the treatment and prophylaxis of cardiac arrhythmias, including ventricular and supraventricular tachyarrhythmias. It is not used in the treatment of hypertension. Sotalol is sometimes used off-licence in the transplacental treatment of fetal tachyarrhythmias.

There are no studies of rates of specific pregnancy outcomes following gestational exposure to sotalol. While a handful of case reports do not raise concern of adverse effects following exposure mainly in the third trimester, there are no data on the absolute risks of congenital malformation, miscarriage, stillbirth, intrauterine growth restriction (IUGR), preterm delivery and adverse neurodevelopmental effects following in utero exposure.

Studies of beta blockers as a class do not show that use during pregnancy is associated with fetal structural malformation. Use of beta blockers in pregnancy has been associated with adverse effects on fetal growth, although because maternal hypertension is linked to IUGR, the relative contribution of beta blocker exposure to this outcome remains unquantified. Overall, data do not suggest that gestational beta blocker exposure increases the risk of preterm delivery. Data on rates of miscarriage, stillbirth and neurodevelopmental outcomes are too limited to permit a risk assessment.

Use of beta blockers near term may result in neonatal beta-adrenoceptor blockade, leading to neonatal bradycardia, hypotension and hypoglycaemia. Respiratory distress has also been reported. Assessment of the neonate for these effects is advised.

Exposure to sotalol at any stage in pregnancy would not be regarded as medical grounds for termination of pregnancy. Additional fetal monitoring is generally indicated in pregnancies complicated by maternal cardiac disease, regardless of pharmacotherapy. Additional growth scans should be offered following gestational exposure to beta blockers. 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.

Sodium thiosulfate is an inorganic reducing agent used in commercial/industrial processes and as an antidote for cyanide poisoning.

There are no human pregnancy exposure data regarding the fetal effects of sodium thiosulfate exposure. The available animal data, although limited, have not demonstrated teratogenic effects for sodium thiosulfate. Improved maternal and fetal outcomes have been demonstrated when sodium thiosulfate was administered in the treatment of cyanogenic compound exposure in pregnant ewes.

If sodium thiosulfate is required in the management of cyanide poisoning during pregnancy, treatment should not be withheld on account of pregnancy.

As with all chemicals, unnecessary exposure to sodium thiosulfate should be avoided. Where occupational exposure is unavoidable, precautions should be taken to ensure that exposure is well within the recommended exposure limits and not associated with toxic symptoms.

Exposure to sodium thiosulfate 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.

Where exposure to cyanide has occurred in pregnancy, enhanced antenatal monitoring may be warranted and discussion with UKTIS is recommended in all cases.

Please note – This monograph has received an interim update. Selected figures have been amended; the published data remains current to December 2025 and the guidance is unchanged.

Sodium valproate is an antiseizure medication used either as sole or adjunctive treatment for all forms of epilepsy. Sodium valproate and the related compounds valproate semisodium and valproic acid are also used in the treatment of acute manic episodes in bipolar disorder, and off-licence for migraine prophylaxis.

Sodium valproate (referred to hereafter as valproate or VPA) is an established human teratogen and should therefore only be used in women of childbearing potential when there is no safer effective alternative to treat epilepsy and following a discussion of the risks and benefits. Valproate should not be used to treat bipolar disorder in pregnancy. All healthcare providers should refer to the MHRA guidance documents before prescribing valproate (as a new or repeat therapy) to girls, pregnant women, or women of childbearing potential. The fetal risks associated with use of valproate in pregnancy are assumed to apply to all valproate-containing compounds. Where use of valproate during pregnancy or in women of childbearing potential is clinically necessary, use of the lowest effective dose is advised.

Valproate monotherapy in the first trimester is generally associated with an absolute risk of infant congenital malformation (CM) of up to 11% (i.e. more than three times increased above background rates). Malformations caused by in utero valproate exposure include neural tube defects (NTD), particularly spina bifida, cardiac defects, orofacial clefts and hypospadias. Malformations of the skull, limb and digits have also been documented. Although there is no ‘safe’ threshold dose, a dose-response relationship has been observed, with a number of studies identifying 1,000mg/day as the dose above which CM risk significantly increases. CM risk of up to 62.1% has been reported with valproate doses of 3,000mg/day.

Only one study has assessed the CM risk associated with dosing regimens that may avoid high peak plasma levels, such as divided dosing or use of modified release preparations. No significant difference in risk was observed compared to once daily dosing. Use of divided doses or slow-release preparations is, however, advised where possible, based on a theoretical benefit.

Overall, there is no strong evidence that valproate use in polytherapy is associated with a risk of congenital anomaly higher than that observed at the same dose used in monotherapy but data are limited and require confirmation.

Valproate impairs the production of the active metabolite of folate. It is therefore recommended that women who take valproate also take high dose folic acid (5mg daily) prior to conception and throughout the first trimester. Women should, however, be counselled that while folic acid reduces the overall risk of NTDs in the general population, there is no strong evidence that it protects against NTDs and other adverse outcomes specifically caused by valproate.

Valproate is also a neurobehavioural teratogen that has adverse effects on features, including offspring IQ and motor skills. Data suggest that the likelihood of autism spectrum disorder may be up to three-fold increased following prenatal valproate exposure, compared to the ~1% incidence in the background population. Studies have noted that between 19% and 62% of valproate-exposed children require additional educational support. Individuals with neurodevelopmental disorders caused by prenatal valproate exposure may not exhibit overt structural anomalies.

The relationship between maternal valproate dose and offspring neurodevelopment is not fully established. A 2014 Cochrane systematic review identified a potential association between poorer cognitive outcome and daily valproate doses in excess of 800 to 1,000mg.

Data relating to miscarriage are limited but high doses of valproate (>750mg/day) have been associated with a possible increased risk. There is weak evidence that folate supplementation may offer a protective effect with doses of valproate <1,000mg/day.

The available data suggest that valproate exposure may be associated with low infant birth weight and additional fetal growth monitoring in the third trimester may therefore be indicated. There is no evidence of an increased risk of preterm delivery. Data relating to stillbirth are limited, and although two large studies have suggested a crude likelihood of ~1% (compared to expected background risk of ~0.5%), lack of statistical analysis means that this outcome requires further assessment before conclusions regarding causality can be drawn.

Use of any centrally acting drug throughout pregnancy or near delivery may lead to poor neonatal adaptation syndrome (PNAS). There are reports of adverse neonatal symptoms following in utero exposure to valproate, although the absolute risk is unquantified. Withdrawal symptoms are likely to be more severe following exposure to more than one CNS acting drug. Delivery should be planned in a unit with facilities for neonatal care.

Regular clinical review is indicated for pregnant women who continue treatment with valproate as plasma concentrations may change as pregnancy progresses and dose adjustment may be required to maintain therapeutic levels.

Periconceptual paternal valproate use is not linked to offspring congenital anomaly. Valproate exposure has been associated with impaired male fertility that may be reversible on cessation of treatment. A single study indicated a potential association with neurodevelopmental impairment in the children of periconceptually exposed men, but this finding was not replicated when part of the original dataset was systematically reanalysed, including comprehensive sub-analyses designed to account for residual confounding. As a precautionary measure, the UK Medicines and Healthcare products Regulatory Agency (MHRA) advises that men should avoid fathering a pregnancy while using valproate and for three months following treatment. UKTIS pragmatically advises that, as the initial signal suggesting altered neurodevelopment in the offspring of exposed fathers has not been reproduced, prescribers should consider the potential risks of valproate discontinuation and the likelihood that an alternative treatment will be effective when carrying out a medication review for a man planning to father a pregnancy. For further information, or patient specific risk assessments, please contact UKTIS.

Women exposed to valproate during early pregnancy should be offered detailed anomaly scans from 16 weeks gestational age, although some anomalies linked to valproate will not be detected by ultrasound. Patients should also be counselled about the increased risk of adverse neurodevelopmental outcomes, which are often not noted at least until after infancy. Other risk factors may also 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.