Letter: O

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.

Omalizumab is a monoclonal humanised IgG1 antibody which binds to IgE and is used in the treatment of moderate-to-severe allergic asthma and chronic spontaneous urticaria (CSU).

The published data specific to omalizumab during pregnancy consist of case reports and small cohort studies collectively describing at least 300 unique omalizumab-exposed pregnancies. While a pharmacovigilance disproportionality analysis includes over 3,000 reports of omalizumab exposure, the study design limits the conclusions that can be drawn, and data from this source do not permit assessment of absolute risks of adverse pregnancy outcomes. Monoclonal antibodies (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 important to ensure that maternal asthma is well-controlled in pregnancy. Where asthma is well-controlled with omalizumab, 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. Effective control of CSU is also important to protect maternal health and wellbeing, including reducing the risk of poor sleep and associated mental health problems.

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 omalizumab is 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 omalizumab exposure.

Exposure to omalizumab 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.

Opioids used recreationally include heroin (brown sugar, China white, dope, H, horse, junk, skag, skunk, smack, white horse), codeine (captain cody, cody, lean, schoolboy, sizzurp, purple drank), fentanyl (Apache, China girl, China white, dance fever, friend, goodfella, jackpot, murder 8, tango and cash, TNT), methadone (amidone, fizzies), morphine (M, Miss Emma, monkey, white stuff), and oxycodone (O.C., oxycet, oxycotton, oxy, hillbilly heroin, percs).

Oropouche virus (Oropouche orthobunyavirus – OROV) is an arbovirus of the Peribunyaviridae family, endemic in many South and Central American countries, spread through the bites of infected midges and mosquitoes.

Clinical features of OROV disease are similar to those observed in people with other arboviruses (such as dengue, West Nile, yellow fever and Zika), and include abrupt onset fever with headache (often severe), rigors, myalgia, arthralgia, photophobia, dizziness, retroorbital or eye pain, nausea and vomiting, and maculopapular rash. Neuroinvasive disease such as meningitis and encephalitis may occur in severe cases. Symptoms typically start 3 to 10 days post-infection, and mostly resolve within 7 days, usually without long-term effects.

Retrospective serum sample investigations and case reports provide evidence of possible vertical transmission of OROV (from mother to fetus). Pregnancy outcomes in these reports include three cases of miscarriage, one intrauterine fetal death, and four live-born infants with microcephaly. Due to data limitations, it is not possible to establish OROV vertical transmission as the cause of these outcomes.

It is recommended that people travelling to affected areas should undertake standard bite prevention approaches during both day and night. There is currently no specific treatment recommended for OROV disease in pregnancy. Supportive care with rest, fluids, analgesics and antipyretics are generally recommended for most people with OROV disease (avoiding aspirin or NSAIDs in cases where dengue cannot be excluded due to a risk of bleeding). NSAIDs should also be avoided after 20 weeks of pregnancy. Further information on risks and prevention measures for travellers and health professionals is available from the National Travel Health Network and Centre (NaTHNaC).

Cases of suspected OROV disease in pregnant women from the UK who have travelled to regions where the virus is endemic should be reported to UKTIS for surveillance purposes, and should also be reported to the local UKHSA Health Protection Team to enable a public health response. Fetal medicine referral is recommended for those with proven infection or exposure to screen for microcephaly and to monitor fetal growth and wellbeing. Based on evidence acquired from congenital Zika syndrome surveillance, where congenital infection related microcephaly is observed, a severe impact on long-term neurodevelopmental and health outcomes is predicted. Discussion with UKTIS is recommended in all such cases.

Ocular antineovascularisation agents used in the UK include verteporfin and the intravitreal biologic vascular endothelial growth factor inhibitors (anti-VEGF) aflibercept, bevacizumab, brolucizumab, faricimab and ranibizumab.

Ocular antineovascularisation agents, including those administered intravitreally, are expected to reach the systemic circulation. However, their physical properties and/or factors related to the method of administration mean that a minimal direct fetal exposure could be expected. As adverse fetal effects could still occur following indirect exposure, data on the safety of antineovascularisation agents in pregnancy are still required.

There are limited data regarding the safety of ocular antineovascularisation agents in pregnancy. Data are mainly provided from uncontrolled case reports describing cases of single intravitreal administrations of anti-VEGF biologic in early pregnancy.

Although most uncontrolled reports of ocular antineovascularisation agent-exposed pregnancies describe healthy live-born infants, adverse pregnancy outcomes, including miscarriage, intrauterine fetal death, preterm delivery and fetal growth abnormalities have also been reported. A single study has suggested a possible association between intravitreal anti-VEGF biologic (aflibercept, bevacizumab and ranibizumab) exposure in pregnancy and miscarriage. However, these data are considered inconclusive as the study methodology is prone to bias and false positive findings. Further data are required to inform on the safety of ocular antineovascularisation agents in pregnancy.

Given the mechanism of action of ocular antineovascularisation agents, a cautious approach towards planned use in pregnancy is recommended until higher quality safety studies are available to better inform on the fetal risks. The impact of a period of untreated ocular disease on vision should also be taken into consideration when deciding treatment options during pregnancy. In cases of inadvertent exposure, discussion with UKTIS is recommended.

Exposure to ocular antineovascularisation agents at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. 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.

Oseltamivir is an oral neuraminidase inhibitor (NI) used in the treatment of influenza infection (licensed for use within 48 hours of the first symptoms), for post-exposure prophylaxis in at-risk groups when influenza is circulating in the community, and to prevent influenza in exceptional circumstances, such as during a pandemic. Oseltamivir is not currently recommended for routine prophylaxis against seasonal influenza.

Evidence from the H1N1 pandemic demonstrated that prompt treatment of influenza in pregnancy with NIs improves maternal outcomes. Oseltamivir is the NI for which there is the most experience of use in pregnancy. In the UK, oseltamivir is therefore currently recommended over zanamivir for treatment/prophylaxis in pregnant women, except in cases of known or suspected oseltamivir resistance. UK guidelines may, however, change and readers are advised to consult UK Health Security Agency (UKHSA) guidance directly or to contact UKTIS for current recommendations.

Human data relating to oseltamivir use in pregnancy are reassuring and there is currently no signal of a teratogenic effect, or increased risk of any other adverse fetal effects. However, data are limited or lacking for some specific outcomes. Due to the established maternal and fetal risks of influenza infection in pregnancy, the benefits of treatment with oseltamivir likely outweigh any theoretical risks to the fetus.

Exposure to oseltamivir 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.

Oxycodone is a semisynthetic opioid analgesic administered orally, intramuscularly or intravenously for the treatment of postoperative or severe pain.

The available data relating to the fetal effects of oxycodone use in pregnancy are limited. Malformation risks have been assessed in >500 pregnancies exposed in the first trimester (the majority therapeutically), with no overall increased risk identified. One small study assessed the risk of miscarriage and found no evidence of an association.

Frequencies of small for gestational age (SGA) infants and stillbirth were not found to be elevated in a study that included at least 2,000 therapeutically exposed pregnancies. 

Two studies have shown associations between oxycodone use in pregnancy and preterm or very preterm delivery. Critical appraisal of these data does not demonstrate a clearly causative effect of maternal oxycodone use. 

No studies have assessed neurodevelopmental outcomes or rates of childhood cancer in the offspring following use of oxycodone.

Use of any opioid during pregnancy, particularly around the time of delivery, confers a risk of neonatal respiratory depression and neonatal withdrawal, both of which have been described following in utero oxycodone exposure. Exposed infants should be delivered in a hospital setting and monitored for these effects.

Where oxycodone poisoning occurs in pregnancy, maternal toxicity is likely to be a major factor in determining any risk to the fetus. However, due to a lack of sufficient poisoning in pregnancy exposure data, an increased risk of adverse outcomes in the absence of maternal toxicity cannot be excluded. If use of an antidote (e.g. naloxone) is required in the management of maternal toxicity it should not be withheld on account of pregnancy.

Exposure to oxycodone at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy. 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. Enhanced fetal monitoring may be warranted during instances of maternal toxicity.

Oxprenolol is a cardioselective beta-blocker used to treat hypertension, angina pectoris, cardiac arrhythmias, and anxiety.

Readers should note that there are no oxprenolol-containing products currently available in the UK and this document is therefore for reference only.

There are no published data on overall rates of congenital malformation following oxprenolol use in pregnancy. A single case-control study found a possible association between first trimester oxprenolol exposure and cleft lip and/or palate. A further case-control study found no association between gestational oxprenolol use and neural tube defects. Both of these findings require ongoing research for confirmation. Limited data do not suggest that exposure to oxprenolol in utero adversely affects fetal growth or gestational length; however, further studies are required as reduced fetal growth has been observed following gestational exposure to other beta-blockers. Data are too limited to permit an evidence-based assessment of the risks of miscarriage, stillbirth, preterm delivery and adverse neurodevelopmental effects following gestational oxprenolol exposure.

Use of beta-blockers near term may result in beta-adrenoceptor blockade, leading to neonatal bradycardia, hypotension and hypoglycaemia. However, there are no data on rates of these neonatal complications in oxprenolol-exposed infants and the absolute risk therefore remains unquantified. Assessment of the neonate for these effects is advised until more robust data become available.

Exposure to oxprenolol at any stage of pregnancy would not usually be regarded as medical grounds for termination. In pregnancies complicated by maternal hypertension and/or where oxprenolol has been administered, careful monitoring of fetal growth is advised. 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 considering such factors when performing case-specific risk assessments.

Related document: Use of beta blockers in pregnancy

Orlistat is an orally administered gastric and pancreatic lipase inhibitor which reduces the absorption of dietary fat. It is used in conjunction with dietary measures to enhance weight loss in adults who are overweight (BMI ≥25). Systemic absorption of orlistat is expected to be negligible.

Maternal obesity has been associated with increased risks of adverse maternal and fetal outcomes, including congenital malformations. Weight loss prior to pregnancy is therefore strongly encouraged for women with obesity who are planning a pregnancy. However, the National Institute of Health and Care Excellence (NICE) states that intentional weight loss during pregnancy is not recommended. Orlistat should therefore be discontinued upon recognition of pregnancy.

The available data regarding orlistat use in pregnancy, although too limited to form definitive conclusions, do not indicate increased risks of fetal malformations or miscarriage. Other outcomes (preterm delivery, low birth weight, stillbirth and neonatal complication risks) have been studied in women with preconceptual exposure to orlistat, with no concern of increased risks. While orlistat is minimally absorbed from the gastrointestinal tract, it may impair the absorption of fat-soluble vitamins (A, D, E, and K); therefore, there are theoretical concerns that its use during pregnancy may restrict nutrient availability to the fetus.

 As data relating to orlistat use in pregnancy are limited, an earlier fetal anomaly scan (from 16 weeks of pregnancy) could be considered following exposure in the first trimester. Other risk factors which independently increase the risk of adverse pregnancy outcome may be present in individual cases. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.