Letter: Q

Quetiapine is an atypical antipsychotic used in the treatment of schizophrenia, bipolar disorder, other psychoses, and major depressive disorder.

The considerable data regarding first trimester exposure to quetiapine do not suggest an overall increased risk of congenital malformation. More limited data do not support an association between quetiapine exposure and small for gestational age or preterm delivery. A large study of neurodevelopment in children exposed to quetiapine gestationally did not identify an increased risk of any clinical diagnosis of neurodevelopmental delay. A single study has suggested an increased risk of miscarriage, while no studies have investigated the risk of intrauterine death following in utero exposure to quetiapine specifically. Studies of antipsychotics as a class have presented conflicting findings for all of these outcomes.

Use of antipsychotics throughout pregnancy or near delivery has been associated with withdrawal symptoms in the neonate and/or poor neonatal adaptation syndrome (PNAS). These symptoms may vary in severity and duration but are likely to be more severe in infants exposed in utero to more than one CNS-acting drug. Three studies have reported higher rates of symptoms for quetiapine exposure in comparison to other antipsychotics. Delivery should be planned in a unit with facilities to monitor exposed neonates.

There is evidence that atypical antipsychotic use in pregnancy increases the risk of gestational diabetes mellitus. Studies have identified an increased risk of large for gestational age among antipsychotic-exposed infants; therefore, additional maternal, fetal and neonatal monitoring is recommended.

It is important to ensure that maternal mental health is treated appropriately. Where a patient is stabilised on quetiapine, 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 quetiapine use during pregnancy with the patient. Where the benefit of continued treatment is considered to outweigh any potential or known risks, quetiapine may be prescribed for use in pregnancy.

Quinine is an antimalarial drug which has rapid schizontocidal activity against the erythrocytic forms of all Plasmodium species. It is the treatment of choice for acute chloroquine-resistant falciparum malaria, but is not considered suitable for malaria prophylaxis. Quinine may also be used in the treatment of leg cramps where other treatments have been ineffective.

Concerns have been raised regarding the use of quinine during pregnancy as it has been shown to have oxytocic effects and to increase insulin secretion, resulting in iatrogenic hypoglycaemia which may be severe, particularly in late pregnancy.

Several case reports have described major adverse fetal outcomes following quinine overdose during pregnancy. These have included reports of stillbirth, congenital deafness, hypoplasia of the optic nerve, and anomalies of the CNS, limbs, face and heart. There is, however, no evidence that the use of therapeutic doses of quinine for the treatment of acute malaria during pregnancy is associated with an increased risk of congenital malformations or other adverse fetal outcomes.

Updated WHO guidelines (2023) recommend a combination of artemether and lumefantrine for the treatment of uncomplicated P. falciparum malaria infection in the first trimester, based on findings from a large meta-analysis. Quinine is recommended as a second-line therapy to artemisinin-based combination therapies in the second and third trimester, based on findings from a large meta-analysis. Untreated or inadequately treated maternal malaria infection poses a serious risk to both the mother and the fetus, and quinine treatment should not be withheld on account of pregnancy. There are no available data relating to the use of quinine in the treatment of nocturnal leg cramps during pregnancy.

Additional fetal monitoring may be recommended in cases of supratherapeutic exposure to quinine, especially following such exposure in the first trimester. 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. Discussion with UKTIS is recommended in all cases.

Important: Please ensure that the selected antimalarial will provide appropriate prophylaxis for the area of travel. Advice is available from a number of sources (e.g., UKHSA,^[1] WHO^[2], BNF,^[3] Fit For Travel,^[4] Travel Health Pro,^[5] RCOG^[6] and TRAVAX^[7]).

The quinolones (including ciprofloxacin, levofloxacin, moxifloxacin, nalidixic acid, norfloxacin and ofloxacin) are broad-spectrum synthetic antibiotics used in the treatment of a wide variety of infections including those of the urinary tract, respiratory-tract, gastro-intestinal system, bones and joints, as well as gonorrhoea, chlamydia and septicaemia. Ciprofloxacin is also used in the treatment or post-exposure prophylaxis of anthrax.

No increased risk of congenital malformations overall, low birth weight, preterm delivery, intrauterine death or neonatal complications have been found for in utero exposure to quinolone antibiotics when studied as a class. Data on offspring malformation risk for individual quinolones are generally limited. Single studies have suggested an association between in utero quinolone exposure and conotruncal defects and Tetralogy of Fallot, and in utero nalidixic acid exposure and infantile pyloric stenosis, however these findings were based on a small number of exposed infants with these anomalies. One study found an increased risk of spontaneous abortion for quinolones as a class and for ciprofloxacin, levofloxacin, norfloxacin, moxifloxacin and oflxacin specifically. Further studies are needed before these associations can be confirmed or refuted.

Neonatal exposure to quinolones have been shown to cause arthropathy in animal studies. Due to the theoretical risk of similar effects on the developing human fetus, the use of quinolones in pregnancy is not generally recommended, except for the treatment of serious or life-threatening conditions unresponsive to other antibiotic therapies considered suitable for use in pregnancy. Where possible, the results of culture and sensitivity tests should be available before making an antibiotic treatment choice in accordance with local prescribing guidelines.

Exposure to quinolones 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.