Letter: G

Guselkumab is a recombinant human monoclonal antibody (mAb) which selectively binds to the cytokine interleukin-23 (IL-23) and is used in the treatment of plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis.

Published data relating to guselkumab use during pregnancy are limited and include at least 620 exposed pregnancies, derived from two disproportionalities analyses utilising the same WHO database, two pharmacovigilance database studies, and several small case series. Overall, these data do not suggest an increased risk of adverse pregnancy outcomes; however, owing to the relatively small number of exposed pregnancies, the available data is insufficient to exclude small increases in risk, particularly for rare outcomes.

Immunoglobulin G (IgG) mAbs do not actively cross the placenta in the first trimester. Therefore, use during this period is not expected to result in direct fetal exposure, and 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 later pregnancy could result in immunosuppression in the newborn and increase the risk of infection. Data specifically evaluating the effects of in utero guselkumab 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 guselkumab exposure.

Exposure to guselkumab 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.

Gamma-hydroxybutyrate (GHB) is acts as a nervous system depressant. Street names include liquid ecstasy, liquid X, Gamma-O, Blue Verve, Gobbe, Soap, Scoop, G, Gina, Geebs, and Juice.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are licensed as second-line treatment options for type 2 diabetes mellitus (where metformin is inappropriate), for use in combination with diet and exercise for weight management in people with obesity, or those who are overweight with at least one weight-related co-morbidity. Currently available GLP-1 RAs in the UK include dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide. Tirzepatide is a long-acting dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist.

Obesity is associated with increased risks of adverse pregnancy and fetal outcomes, and all women are encouraged to eat a balanced healthy diet and be physically active (moderate- intensity). Dieting through calorie deficit, and/or anti-obesity or weight loss medications are not recommended in pregnancy.

Maternal hyperglycaemia in pregnancy is associated with increased risks of adverse pregnancy and fetal outcomes. As such, it is important that the maternal blood glucose is tightly controlled around the time of conception and during pregnancy. National Institute for Health and Care Excellence (NICE) recommendations suggest metformin (alone or in combination with insulin) for the management of pre-existing or gestational diabetes. For more information, please see the metformin monograph.

Safety data relating to GLP-1 RAs includes more than 47,000 exposed pregnancies. However, many of the available studies are methodologically limited, and in most cases treatment was discontinued in early to mid-pregnancy. As such, limited conclusions can be drawn regarding the safety of longer-term GLP-1 RA use in pregnancy. Given their high molecular masses, placental transfer of GLP-1 RAs is not expected.

The available data do not indicate increased risks of miscarriage, malformation, intrauterine death/stillbirth, low infant birth weight, macrosomia, or preterm delivery following exposure to GLP-1 RAs in early to mid-pregnancy. Although uncontrolled case reports have described fetal macrosomia and neonatal complications, including jaundice, sepsis, hypoglycaemia, and respiratory distress syndrome, these outcomes are considered unlikely to be causally related to GLP-1 RA use. Furthermore, a small number of controlled studies do not demonstrate clear increased risks of jaundice, hypoglycaemia, or respiratory distress syndrome among GLP-1 RA-exposed neonates, a small number of whom were exposed in late pregnancy. Two case reports describe normal infant growth and development up to 12 and 14 months post-delivery. No studies have been located which have investigated the risk of neurodevelopmental impairment or childhood cancer following GLP-1 RA use in pregnancy.

Inadvertent exposure to GLP-1 RAs at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, where exposure occurs close to delivery, there is a theoretical risk of neonatal hypoglycaemia; therefore, neonatal monitoring recommended. Other risk factors which could independently increase the risk of adverse pregnancy outcomes may be present in individual cases. Such factors are important to consider when performing case-specific risk assessments.

Gabapentin is an antiseizure medication drug indicated as monotherapy or adjunctive therapy in the treatment of partial seizures with or without secondary generalisation, and for the treatment of peripheral neuropathic pain. It is also used off-licence for migraine prophylaxis, for the treatment of oscillopsia and spasticity in multiple sclerosis, and to ameliorate hot flushes in women receiving treatment for breast cancer.

Much of the available epidemiological data relate to gabapentin use in pregnancy for the treatment of epilepsy. A few case reports/series describe use of gabapentin in the treatment of neuropathic pain or hyperemesis gravidarum, but studies have not assessed fetal outcomes following use in pregnancy for these indications.

The available data do not provide robust evidence of an increased risk of congenital malformation, either overall or for specific anomalies, following first trimester gabapentin exposure in pregnancy. However, the evidence is conflicting, and therefore further studies are required. Data regarding risk of cardiac malformation are conflicting and likely confounded. However, the highest quality data do not indicate an increased risk.

Data regarding the risk of miscarriage are conflicting but do not provide reliable evidence of an increased risk following gabapentin exposure in early pregnancy. A single small study did not find an association with intrauterine death. Conflicting results regarding possible increased risks of preterm delivery and low birth weight have been described in a small number of studies but these data may be confounded. Data relating to neurodevelopment following in utero gabapentin exposure are limited and conflicting; further research is required before evidence-based conclusions can be drawn.

Exposed infants have seen an increase in NICU admissions, with documented indications including neonatal withdrawal, neonatal jaundice, bradycardia, hypotonia, hypoglycaemia, apnoea, respiratory distress, jitteriness, diarrhoea, fever and arrhythmia. Use of any centrally acting drug throughout pregnancy or near delivery may be associated with withdrawal symptoms in the neonate and/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 be planned in a unit with neonatal intensive care facilities.

Gabapentin may impact upon maternal folate status. UK guidelines state that women who take any anti-epileptic medication should be prescribed high-dose folic acid (5mg), although it is currently not known whether high-dose folic acid supplementation offers any additional benefit or protective effects over standard dose regimes when taking gabapentin pre-conceptually or during pregnancy.

More research is required to define the pregnancy safety profile of gabapentin. Pregnant women and women of childbearing potential should be made aware that data for most pregnancy outcomes are conflicting, and although the highest quality evidence does not indicate an association with adverse outcomes, further studies are still required. Gabapentin should only be used during pregnancy where benefits of treatment are considered to outweigh any potential risks. In view of the limited human pregnancy data, close monitoring of mother and fetus should be considered with use of gabapentin in pregnancy. 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.

Ginger (Zingiber officinale Roscoe) is one of the most commonly used non-medicinal remedies for pregnancy-related nausea, particularly during the first trimester when symptoms of nausea and vomiting are common.

Three cohort studies, one case-control study, and a number of small clinical trials which addressed the safety of ginger use during human pregnancy found no increased incidence of adverse pregnancy outcomes, including congenital malformations. As a commonly ingested food item, no adverse fetal effects are expected.  

Exposure to ginger at any stage in pregnancy would not be regarded as medical grounds for termination or for 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.

Glaucoma is an eye disorder characterised by loss of visual field and optic nerve damage. Usually, glaucoma is associated with raised intra-ocular pressure but in some cases intra-ocular pressure may be within normal limits. Primary open-angle glaucoma (chronic simple glaucoma), the most common form, is asymptomatic and the patient may present with gradual visual field loss. Primary angle-closure glaucoma (acute closed-angle glaucoma) is a medical emergency occurring when the flow of aqueous humour into the anterior chamber is interrupted.

Pharmacological treatments which reduce the intraocular pressure include ocular beta-adrenoceptor blocking drugs, prostaglandin analogues, miotics, sympathomimetics, and ocular and systemic carbonic anhydrase inhibitors.

There is very limited information on use of these medications during pregnancy, therefore an evidence-based assessment of fetal risk is not possible. However, poorly managed glaucoma can cause permanent vision loss, and the benefits of treatment are likely to outweigh any potential risk. Treatment, therefore, should not be withheld on the basis of pregnancy.

Exposure to medications for the treatment of glaucoma at any stage in pregnancy would not usually be regarded as medical grounds for termination. Due to the lack of data, reporting of exposure to UKTIS is advised. Additional fetal monitoring may be warranted in individual cases and where other risk factors which independently increase the risk of adverse pregnancy outcome are present. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.