Letter: G

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.

Glibenclamide (glyburide) is an oral sulfonylurea hypoglycaemic agent indicated in the treatment of non-insulin-dependent diabetes in patients who fail to respond to dietary measures alone.

Data on the use of glibenclamide in pregnancy consist of >9,500 exposures; however, glibenclamide is used in the management of gestational diabetes, which most commonly occurs in the second or third trimester; therefore, first trimester exposure data are lacking and an increased risk of congenital malformation or miscarriage cannot be excluded. 

Data regarding risk of large for gestational age (LGA) or macrosomia in the infant and neonatal hypoglycaemia following glibenclamide treatment of gestational diabetes when compared to insulin and/or metformin are conflicting, possibly as a result of a lack of efficacy resulting in variation in maternal obesity and glycaemic control, both of which are known to significantly affect these outcomes. No increased risks were identified for intrauterine death, preterm delivery, neonatal jaundice/hyperbilirubinaemia or admission to a neonatal intensive care unit (NICU).

Current recommendations from The National Institute for Health and Care Excellence (NICE) suggest metformin (alone or in combination with insulin) for the management of pre-existing or gestational diabetes. For information on metformin please see the separate monograph.

Women with pre-existing diabetes who are planning to become pregnant should be advised to take high-dose folic acid (5mg daily) prior to conception and throughout the first trimester.

Exposure to glibenclamide at any stage of pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, women with diabetes may require additional monitoring of fetal growth and amniotic fluid volume irrespective of medication. 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.

Gabapentin is an antiepileptic 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 and to ameliorate hot flushes in women receiving treatment for breast cancer.

The majority of the available epidemiological data relate to gabapentin use in pregnancy for the treatment of maternal epilepsy. A few case reports/series describe use of gabapentin in the treatment of neuropathic pain or hyperemesis gravidarum, but no epidemiological studies have assessed fetal outcomes following use in pregnancy for these maternal indications.

The available data do not provide robust evidence of an increased risk of congenital malformation overall, or for cardiac malformation/hypospadias specifically, following gabapentin exposure in pregnancy. However, the evidence is also too limited to definitively exclude a risk. Studies which assessed rates of miscarriage or intrauterine death following gabapentin exposure in pregnancy do not currently identify an increased risk of these outcomes. Conflicting results regarding a possible increased risk 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 neurodevelopmental impairment are limited and conflicting, therefore further research on this subject is required before firm conclusions can be drawn.

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).

More research is required to define the pregnancy safety profile of gabapentin. Pregnant women and women of child bearing potential should be made aware of the lack of data for most pregnancy outcomes. 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.

Glaucoma is a disorder of the eye 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 where the flow of aqueous humour into the anterior chamber is blocked.

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 are little or no data on pregnancy outcomes following the use of these medications in pregnancy, therefore an evidence-based assessment of risk to the developing fetus with maternal exposure is not possible. However, untreated or under-treated glaucoma could potentially lead to maternal loss of vision, and as the potential benefits gained from treatment are likely to outweigh any unknown increase in risk to the fetus, optimum treatment of maternal glaucoma in pregnancy should be offered and this risk-benefit analysis discussed with the patient. 

Exposure to medications licensed in the UK 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.