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Editorials

Long term implications of covid-19 in pregnancy

BMJ 2022; 377 doi: https://doi.org/10.1136/bmj-2022-071296 (Published 31 May 2022) Cite this as: BMJ 2022;377:e071296
  1. Allyah Abbas-Hanif, honorary clinical senior lecturer12,
  2. Neena Modi, professor of neonatal medicine3,
  3. Azeem Majeed, professor of primary care and public health1
  1. 1Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK
  2. 2Faculty of Pharmaceutical Medicine, Royal College of Physicians, London, UK
  3. 3Section of Neonatal Medicine, Faculty of Medicine, Imperial College London, UK
  1. Correspondence to: A Abbas-Hanif: allyah.abbas{at}imperial.ac.uk

We must characterise the risks and take urgent steps to reduce harm

Complications in pregnancy, including maternal and perinatal deaths, increased with each wave of the covid-19 pandemic. By contrast, serious illness fell in other high risk groups because of vaccines and approved treatments.1 More than a year after the UK’s Joint Committee on Vaccination and Immunisation (JVCI) opened up covid-19 vaccination to pregnant women, 40% of women giving birth have still not received a first dose.2 This is despite a positive benefit-risk profile, endorsement in guidelines, and public health campaigns. Worryingly, 69.5% of black women giving birth have not received any covid-19 vaccine.2

Meanwhile the JCVI has chosen not to include pregnant women in its interim autumn booster plans.3 Strategies for treating covid-19 in pregnancy and potential long term complications are also underused.1 A large portion of the diffidence for both vaccination and treatment in pregnancy stems from the continued exclusion of pregnant women from much of the pre-approval drug development process. This results in delayed or even absent data on benefit-risk profiles and a dangerous spiral of indecision.4

The public health implications for postpartum women are unclear, but some key considerations are increased cardiovascular risk, including in future pregnancies; the impact of long covid; and the effect of ethnic and socioeconomic inequalities that widened during the pandemic.4 The downstream amplification of cardiovascular risk for women who have covid-19 in pregnancy must not be overlooked. Covid-19 during pregnancy substantially increases the risk of pre-eclampsia,5 which could increase cardiovascular disease later in life.6 In addition, acute covid-19 significantly increases the risks and one year burden of cardiovascular disease in the general population.7

The UK is ideally placed to define these risks more precisely, taking a life course approach and using NHS data in either anonymised or consented cohorts. Observational studies to understand covid-19’s long term effect in babies have begun, but a deeper understanding of the biological mechanisms at play and effects on whole populations are needed.8

Unprepared

Global preparedness frameworks continue to overlook risks to pregnant women and babies during epidemics. Beyond covid-19, this neglect had tragic consequences for women affected by the Zika and Ebola outbreaks. Intrauterine exposures to maternal covid-19 could reach 20 million a year globally, according to recent estimates.9 This, coupled with lessons from previous antenatal viral infections, means the possibility of long term neurological or neurodevelopmental harms from covid-19 warrant close attention.

A recent case-control study reports that maternal SARS-CoV-2 infection is associated with an increased incidence of neurodevelopmental disorders in babies, particularly disorders of motor function or speech and language in the first 12 months after delivery, even after the higher risk of preterm delivery associated with covid-19 is taken into account.10 Babies born to women vaccinated during pregnancy, particularly during the third trimester, benefit from transplacental transfer of maternal antibodies and are 61% less likely to be admitted to hospital with covid-19 in the first six months.11 Despite this, infants under 1 year made up a larger proportions of covid-19 hospital admissions during the omicron wave than at any other time during the pandemic.12

Keeping ahead of covid-19

The increase in SARS-CoV-2 variants risks undermining the effectiveness of current covid-19 treatments.13 The UK’s Recovery trial enrolled pregnant women receiving hospital treatment, providing critical data to inform guidelines.14 To keep pace with the omicron sublineages BA.2, BA.4, and BA.5 and other emerging variants, Recovery now needs to move beyond repurposed drugs and evaluate newer monoclonal antibody treatments. Monoclonal antibodies are strong therapeutic candidates in pregnancy because of their high efficacy, minimal off-target activity, and limited placental transfer.4 The summary of product characteristics for recently approved prophylactic Evusheld (tixagevimab and cilgavimab) cautiously allows use in pregnancy and is a welcome addition to protective options for pregnant women.

The pandemic has spurred several stakeholder groups to tackle the data vacuum in maternal drug development.151617 A recent UK policy report describes reproduction and childbirth as the ‘Cinderella’ area of research, accounting for only 2% of national research funding.18 Investment, advocacy, and a collaborative regulatory landscape are crucial to meaningful change.

We previously outlined possible approaches to improving the availability of safe and effective drugs in pregnancy.4 Using the extensive post-marketing pharmacovigilance data already available in pregnancy to update information on labels and in summaries of product characteristics of currently used drugs, including covid-19 vaccines and treatments, could be a swift and powerful step towards improved prescribing in pregnancy. Updating the globally endorsed International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines19 to ensure safe, effective, and high quality medicines are developed and that the process appropriately includes pregnant and breastfeeding women would fundamentally transform this area.

Covid-19 in pregnancy increases the risk of severe complications for both mother and baby. The long term implications are unknown, but emerging signals warn of substantial public health threats. To counter high vaccine hesitancy in pregnancy we must end the default exclusion of pregnant women from the rigorous regulated drug development process and implement systematic, long term, population-wide surveillance of infected and non-infected people.

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References

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