Almost two years have passed since the start of COVID-19 pandemic and despite so much progress and many achievements, unfortunately we are still far from tranquility.

In particular, public health agencies are now concerned about the population of pregnant women and their unborn children, given that currently dominant variant has determined many serious complications in several countries.

Article by Claudia Ravaldi and Alfredo Vannacci

We at CiaoLapo are dealing with perinatal health for 15 years and have been working both on the effects of COVID-19 on women’s health , and on the effects of restrictions on psychophysical well-being of women and babies: data collected by our COVID-ASSESS study showed a considerable concern of Italian women for the spread of the virus, with important changes in the perception of pregnancy and childbirth (read on Women and Birth ); the psychological impact of the spread of the virus was particularly important especially for those women who had already suffered in the past from anxiety or mood depression (read on Archives of Women’s Mental Health ).

In 2020 the international COCOON project was started together with our colleagues at CRE Stillbirth in Australia, with the aim of understanding the impact of pandemic on pregnancy care, particularlu in case of of perinatal loss.

When data on anti-COVID vaccinations in pregnancy have finally been available, we also started dealing with this issue: the availability of vaccinations has fortunately changed the perspective and, even if the problem is not completely solved, it has made it possible to greatly reduce hospitalization and general mortality from COVID-19.

Knowing that a vaccination with high safety margins is available is of great importance, especially in light of the very recent data published by the Center for Disease Control and Prevention (CDC) on the danger of the new Delta variant for mothers’ and babies’ health and life.

In this article we present a brief summary on the state of the art of SARS-CoV-2 infection in pregnancy and on the role of vaccines: an important European monitoring project is underway in which we are participating in order to reach the greatest amount of information possible on the efficacy and safety of vaccinations during pregnancy.

Risks of COVID-19 in Pregnancy

During the pandemic, publications on the risks associated with infection in pregnancy have increased dramatically from early 2020 until today: it started with individual case reports, with case series and then observational studies and systematic reviews were published.

At the beginning of the pandemic, pregnant women were not considered particularly susceptible to SARS-CoV-2, and this allowed us to breathe a sigh of relief (and to insist as a priority on maintaining all perinatal rights, both in case of physiological pregnancy and in case of miscarriage and perinatal death).

Unfortunately, since the variant B.1.617.2 (Delta) has become the predominant one (currently verging on 100% of cases in all of Europe), things for pregnant women and their babies have greatly changed . Although pregnant women do not appear to be at a higher risk of contracting COVID-19 than people who are not pregnant, however, it is now clear that once infected, pregnant women have a high risk of developing a severe form of the disease (hospitalization and ICU admission) as well as an increased risk of adverse pregnancy outcomes and maternal and neonatal complications .

Precisely the complications that we take care of, and that we would NEVER want to see increase, EVER.

In fact, in the course of 2021 various reports of miscarriage and stillbirth were published in the literature, as well as serious pathological findings: cases of placentitis and thrombosis of the placenta caused by viral infection.

In SARS-CoV-2-positive mothers, a greater number of preterm births (premature babies) were also recorded and infants were more likely to need hospitalization in NICU .

Unfortunately, a significant increase in cases of preeclampsia , gestational diabetes and low birth weight has also been detected in women affected by COVID-19 during pregnancy.

The latest report by the CDC (Center for Disease Control and Prevention) on 1,249,634 hospitalizations for childbirth in the period March 2020-September 2021 is extremely concerning : women with COVID-19 were found to be at increased risk of stillbirth compared to women without COVID-19 (adjusted relative risk [aRR] = 1.90; 95% CI = 1.69-2.15).

In simpler words, this means that if we consider 1 the risk of losing the baby of a woman not affected by COVID-19, women with the infection have a risk of 1.9, which is almost double .

The magnitude of the association is greater in the period of predominance of the Delta variant than in the pre-Delta period, with a risk of stillbirth increased by as much as 4 times (aRR = 4.04; 95% CI = 3.28–4.97) in the case of Delta variant (i.e. the one that is currently predominant).

Four times would mean going from 3 out of a thousand stillbirths to 12 in case of widespread infections. A number that fills us with worry and despair.

Some factors have also been identified that further increase the risk of stillbirth in pregnant women affected by COVID-19: these include chronic hypertension, twin pregnancy, heart problems, sepsis, shock, the need for mechanical ventilation and hospitalization in intensive care.

Vaccination in pregnancy

Given this recent and painful picture of increased danger to pregnant women, it is particularly important that this group can safely access COVID-19 vaccination.

COVID-19 vaccination has alredy been suggested during pregnancy and breastfeeding by the main international scientific societies, including American College of Obstetricians and Gynecologists (ACOG ), Royal College of Obstetricians and Gynaecologists (RCOG ), Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG ), Center for Disease Control and Prevention (CDC ) and the Italian Society of Gynecology and Obstetrics (SIGO ), because the studies carried out have brought to light the efficacy and safety of vaccination in this population of women.

To date , hundreds of thousands of pregnant or breastfeeding women have been vaccinated (initially the health workers, then those most at risk, then whoever wanted) and now we have a lot of data on efficacy and safety:

the measurement of antibody titers (amount of circulating antibodies after the vaccine) showed identical values in vaccinated pregnant or lactating women compared to the general population;
the efficacy of the vaccine in pregnancy is very high: 78% in the only clinical study published to date (other studies are currently ongoing);
adverse effects after vaccination are few, mild and very similar in pregnant women compared to non-pregnant women (effects such as pain at the injection site 84%, fatigue 62%, headache 52%, muscle aches 37%, fever 16%);
no increase in the most important complications (miscarriage and stillbirth, preterm birth, growth restriction, congenital defects etc …) was identified, all of them were extremely rare and exactly identical to those of healthy unvaccinated women (while as we said in women with COVID-19 the risks are very high);
antibodies against SARS-CoV-2 were found in umbilical cord blood as early as two weeks after the first dose in pregnancy and in breast milk 6 weeks after vaccination. This means that the antibodies produced by the mother’s vaccination can cross the placenta and are secreted into the milk, providing some protection to newborns , both during pregnancy and through breastfeeding.

As doctors we want to remind you that, even if the available data clearly indicate the safety of COVID-19 vaccination during pregnancy and breastfeeding , this does not (unfortunately) mean that the vaccine is effective in 100% of cases or that NEVER cause ANY problem (side effect). Medicine is not an exact and totally predictable science, dealing with living matter, as we are, but it is based on the most advanced knowledge and on a continuous and updated evaluation of the risk / benefit ratio .

As parents we have faced the experience of being part of a number considered very small, that of people affected by the stillbirth of their child for an unknown cause: an experience that is so devastating that it cannot stand, in our opinion, the comparison with any other risk very small present in a table of side effects.

This obviously remains our personal thought: this article wants to bring to the attention of women the latest scientific updates available on COVID-19, the Delta variant and perinatal health, then every expectant woman will make in total freedom the best choice for her and her baby. provided she has reasonable and realistic information, which allows her to properly assess risks and benefits .

Booster dose in pregnancy

Finally, one of the crucial points at this moment concerns the administration of the third dose during pregnancy or breastfeeding (so-called ” booster dose”) to women who had completed the two-dose cycle before becoming pregnant (in the case of the single-dose J&J vaccine the booster dose is obviously the second one).

Data currently available are clearly in favor of the booster dose during pregnancy or breastfeeding .

For example, the ACOG guidelines recommend that:

pregnant or lactating women should receive the booster dose of vaccine (third dose of mRNA, approximately 6 months after the second, or second J&J dose approximately 2 months after the first one).
pregnant or breastfeeding women can receive any type of booster vaccine they are offered, not necessarily the same brand they previously received (mix – & – match approach)

The Australian government guidelines follow the same approach and also point out that

there is no reason to delay vaccination during pregnancy; it could be given at any gestational age .
the anti-COVID-19 vaccine can be received together with the flu vaccine (remember, flushot is of FUNDAMENTAL importance in pregnancy) that is, in the same session.

Efficacy and safety of vaccines in pregnancy

CiaoLapo participates as stakeholder representative (sensitive population) in the activities of the Vac4EU European project on the safety of anti-COVID19 vaccines in pregnancy and breastfeeding ; you can get more detailed information on the project here: https://www.ciaolapo.it/2021/monitoraggio-dei-vaccini-covid-19-in-gravidanza/

If you are pregnant or are you breastfeeding (including in a pregnancy following a loss) and have received or are about to receive the first dose or booster dose (third dose) of the COVID-19 vaccine , you can participate in monitoring the side effects of COVID-19 vaccines by registering on the website covidvaccinemonitor for up to 48 hours after receiving the vaccine.

If you want ,you can watch this short introduction video (remember that it applies to both the first dose and the third dose ):

Conclusions

If you are looking for a pregnancy, if you are already pregnant or breastfeeding and you have doubts about whether or not to get the COVID-19 vaccine, this is the updated health information:

getting sick with COVID-19 during pregnancy is very dangerous for both you and your baby (stillbirth goes from 3 in a thousand to 12 in a thousand born with the latest variant);
the anti-COVID-19 vaccines are effective and safe during pregnancy and breastfeeding in all the studies done (unfortunately this does not mean zero risk, because there is no zero risk in medicine);
international scientific societies recommend vaccination , both the first dose and the booster (third dose) at any gestational age;
if you decide to get the vaccine, register within 48 hours on the website www.covidvaccinemonitor.eu/it (the ideal is to do it during the 15-min waiting after the shot) and answer the questionnaires that will be sent to you. You will be able to monitor the progress of your vaccination and help keep the safety profile of the vaccine continuously updated, for you and for all pregnant and breastfeeding women.

References

DeSisto CL, Wallace B, Simeone RM, et al. Risk for Stillbirth Among Women With and Without COVID-19 at Delivery Hospitalization – United States, March 2020 – September 2021. MMWR Morb Mortal Wkly Rep 2021; 70: 1640–1645. DOI: http://dx.doi.org/10.15585/mmwr.mm7047e1
Luxi, N., Giovanazzi, A., Capuano, A. et al. COVID-19 Vaccination in Pregnancy, Paediatrics, Immunocompromised Patients, and Persons with History of Allergy or Prior SARS-CoV-2 Infection: Overview of Current Recommendations and Pre- and Post-Marketing Evidence for Vaccine Efficacy and Safety. Drug Saf 44, 1247–1269 (2021). https://doi.org/10.1007/s40264-021-01131-6
Ravaldi, C., Ricca, V., Wilson, A. et al. Previous psychopathology predicted severe COVID-19 concern, anxiety, and PTSD symptoms in pregnant women during “lockdown” in Italy. Arch Womens Ment Health 23, 783–786 (2020). https://doi.org/10.1007/s00737-020-01086-0
Ravaldi C, Wilson A, Ricca V, Homer C, Vannacci A. Pregnant women voice their concerns and birth expectations during the COVID-19 pandemic in Italy. Women Birth. 2021 Jul; 34 (4): 335-343. doi: https: //10.1016/j.wombi.2020.07.002
Ravaldi C, Vannacci A. The COVID-ASSESS dataset – COVID19 related anxiety and stress in prEgnancy, poSt-partum and breaStfeeding during lockdown in Italy. Data Brief. 2020 Dec; 33: 106440. doi: https: //10.1016/j.dib.2020.106440