Mortality 20x higher in pregnant women with COVID but SAHPRA says no to vaccination

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US authorities this week advised pregnant women be inoculated — based on a study of the Moderna/Pfizer vaccines — at the same time that the South African regulator recommended against their receiving the Johnson & Johnson vaccination “at this stage”, writes MedicalBrief. Separately, a large study found that women who contracted COVID-19 during pregnancy were 20 times more likely to die than those who did not contract the virus.

The Sisonke study’s J&J vaccinations resumed on Wednesday (28 April),  following a precautionary pause to assess thrombolytic risk.

SAHPRA’s decision is already under challenge. Health Minister Dr Zweli Mkhize said that SAHPRA “may have elected to err on the side of caution” in excluding pregnant and lactating women. He said that the SA Medical Research Council and other scientific bodies will engage SAHPRA on its recommendation and scientists would be able to make the case for pregnant women to receive the COVID-19 vaccine.

The chair of the Ministerial Advisory Committee on COVID-19 vaccines, Prof Barry Schoub, said scientists had recommended pregnant women be encouraged to get vaccinated from 14 weeks of pregnancy, in line with guidance from the College of Obstetricians and Gynaecologists of SA (COGSA). Pregnant women are at increased risk of severe illness and death from COVID-19, and no adverse events have so far been reported in pregnant women who received COVID-19 vaccines, he said.

The MRC said international expert groups, including the World Health Organization, and the International Federation of Obstetrics and Gynaecologists, were strongly united in recommending vaccination for pregnant and breastfeeding women because there were large amounts of safety data for similar “non-live” vaccines.

President of COGSA, Dr Priya Soma-Pillay, said all pregnant women should be offered a COVID-19 a vaccination, with a discussion with their healthcare provider about the risks and benefits. “These discussions should include the lack of safety data for pregnant women, the strong immune response conferred to women after vaccination, the benefits of immune transfer to the (baby), and that there are no known health risks associated with other non-live vaccines given in pregnancy.”

The MRC statement acknowledged that safety data for COVID-19 vaccines in pregnancy and breastfeeding are limited and still accumulating but went on to list the international consensus in favour of vaccination:

“International and local experts and groups such as COGSA, the WHO, the International Federation of Obstetrics and Gynaecologists, the US CDC, the United Kingdom’s Joint Committee on Vaccination and Immunisation, the American College of Obstetrics and Gynaecology and the Royal College of Obstetricians and Gynaecologists have remained united in strongly recommending vaccination for pregnant and breastfeeding women given large amounts of safety data for similar ‘non-live’ vaccines.

“Pregnancy exposure safety data for >100,000 exposed pregnancies for other ‘non-live’ vaccines including seasonal influenza and tetanus, diphtheria, pertussis and poliomyelitis polyvalent vaccines show no safety concerns. Animal studies for mRNA and the J&J vaccine showed no concerns, and the Ebola vaccine, which uses the same adenovirus vector as the J&J vaccine, has been used widely including pregnant women with no concerns.

“It is therefore considered highly unlikely that such vaccines would be harmful if administered in pregnancy or breastfeeding. We welcome last week the publication of the preliminary safety data on the safety profile of m-RNA vaccines in pregnant women in the United States showing no safety concerns and note the recommendation that pregnant women be offered a m-RNA vaccine.

“To health workers who have already received the vaccine while breastfeeding, please do not be concerned. COVID-19 vaccines are not able to replicate in the human body, disintegrate within 2-3 days of vaccination, and do not pass into breastmilk. Breastfeeding women have been included in all trials of the J&J vaccine thus far, with no safety concerns reported in mothers or their infants.”

SAHPRA CEO Boitumelo Semete-Makokotlela told BusinessLIVE that the regulator is reviewing “all the available data” on both the J&J and Pfizer vaccines, and would issue a statement before the end of the week. She did not elaborate.

Sisonke study co-principal investigator Ameena Goga is quoted on BusinessLIVE as saying that SAHPRA had told researchers there is insufficient data to justify the inclusion of pregnant and breast-feeding women. But Goga said in her view all the data worldwide suggests the vaccine is safe.

Goga said there was growing concern among healthcare professionals about the implications of SAHPRA’s decision for the national vaccination programme, due to begin on May 17. “We all want to understand what will happen with the rollout.” No other country has excluded pregnant and breastfeeding women from Covid-19 vaccination, she said.

The US Centers for Disease Control (CDC) recommendation is based on preliminary findings published this week in The New England Journal of Medicine, which evaluated data from more than 35,000 pregnant individuals who received the mRNA vaccines and found no obvious safety concerns. Early clinical trials of the two-dose shots did not include pregnant individuals, limiting data and creating a sense of uncertainty for many.

COVID-19 vaccines made by Moderna and Pfizer/BioNTech appear to be safe for people who are pregnant, according to research from the CDC. Preliminary findings evaluated data from more than 35,000 pregnant individuals who received the mRNA vaccines, and found no obvious safety concerns. This study did not look at the J&J vaccine, which was first authorised for use in the US in late February.

CDC Director Rochelle Walensky said: “Importantly, no safety concerns were observed for people vaccinated in the third trimester, or safety concerns for their babies.”  The CDC, American College of Obstetricians and Gynecologists and American Academy of Pediatrics have all previously issued guidance “indicating that COVID-19 vaccines should not be withheld from pregnant persons”.

Researchers looked at data between 14 December and 28 February from three federal databases and registries through which vaccine recipients nationwide can report side effects and provide information about their health. Pregnant individuals reported pain at the injection site more frequently than their non-pregnant counterparts but fewer follow-up symptoms such as headache, chills, muscle pain and fever.

Researchers said that the rates of pre-term births and miscarriages among the vaccinated people who completed their pregnancies during the study period were similar to those of the general pregnant population.

“Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA COVID-19 vaccines,” they wrote. “However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.”

The CDC’s Walensky acknowledged the decision to get vaccinated while pregnant is a “deeply personal” one and encouraged those who are deliberating to talk to their doctors or primary care providers.

The INTERCOVID Multinational Cohort Study of 2,100 pregnant women, published this week in JAMA Pediatrics, found that those who contracted COVID-19 during pregnancy were 20 times more likely to die than those who did not contract the virus. University of Washington Medicine and University of Oxford doctors led the first-of-its-kind study, whcih involved more than 100 researchers and pregnant women from 43 maternity hospitals in 18 low-, middle- and high-income nations. The research was conducted between April and August of 2020.

The study is unique because each woman affected by COVID-19 was compared with two uninfected pregnant women who gave birth during the same span in the same hospital. Aside from an increased risk of death, women and their newborns were also more likely to experience preterm birth, preeclampsia and admission to the ICU and/or intubation. Of the mothers who tested positive for the disease, 11.5% of their babies also tested positive, the study found.

Although other studies have looked at COVID-19’s effects on pregnant women, this is among the first study to have a concurrent control group with which to compare outcomes, said Dr Michael Gravett, one of the study’s lead authors.

“The No 1 takeaway from the research is that pregnant women are no more likely to get COVID-19, but if they get it, they are more likely to become very ill and more likely to require ICU care, ventilation, or experience preterm birth and preeclampsia,” he said.

One caveat, Gravett noted, was that women whose COVID-19 was asymptomatic or mild were not found to be at increased risk for ICU care, preterm birth or preeclampsia. About 40% of the women in this study were asymptomatic. Pregnant women who were obese or had hypertension or diabetes were at the greatest risk for severe disease, the findings showed.

Babies of the women infected with COVID-19 were more likely to be born preterm; but their infections were usually mild, the study found. Breastfeeding seemed not to be related to transmitting the disease. Delivery by Caesarean section, however, might be associated with an increased risk of having an infected new-born, the study found.

Gravett suggested that these and parallel research findings compelled US states’ decisions to open vaccine eligibility to pregnant women – who were initially considered a population at low risk for severe COVID-19.

“I would highly recommend that all pregnant women receive the COVID-19 vaccines,” based on this research, he said.

 

First Study details
Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons

Tom T Shimabukuro, Shin Y Kim, Tanya R Myers, Pedro L Moro, Titilope Oduyebo, Lakshmi Panagiotakopoulos, Paige L Marquez, Christine K Olson, Ruiling Liu, Karen T Chang, Sascha R Ellington, Veronica K Burkel, Ashley N Smoots, Caitlin J Green, Charles Licata, Bicheng C Zhang, Meghna Alimchandani, Adamma Mba-Jonas, Stacey W Martin,
Julianne M Gee, Dana M. Meaney-Delman for the CDC v-safe COVID-19 Pregnancy Registry Team

Published in the New England Journal of Medicine on 21 April 2021

Abstract
Background
Many pregnant persons in the United States are receiving messenger RNA (mRNA) coronavirus disease 2019 (Covid-19) vaccines, but data are limited on their safety in pregnancy.
Methods
From December 14, 2020, to February 28, 2021, we used data from the “v-safe after vaccination health checker” surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS) to characterize the initial safety of mRNA Covid-19 vaccines in pregnant persons.
Results
A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases).
Conclusions
Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.

 

Second Study details
Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection – INTERCOVID Multinational Cohort Study

José Villar, Shabina Ariff, Robert B. Gunier, Ramachandran Thiruvengadam, Stephen Rauch, Alexey Kholin, Paola Roggero, Federico Prefumo, Marynéa Silva do Vale, Jorge Arturo Cardona-Perez, Nerea Maiz, Irene Cetin, Valeria Savasi, Philippe Deruelle, Sarah Rae Easter, Joanna Sichitiu, Constanza P. Soto Conti, Ernawati Ernawati, Mohak Mhatre, Jagjit Singh Teji, Becky Liu, Carola Capelli, Manuela Oberto, Laura Salazar, Michael G. Gravett, Paolo Ivo Cavoretto, Vincent Bizor Nachinab, Hadiza Galadanci, Daniel Oros, Adejumoke Idowu Ayede, Loïc Sentilhes, Babagana Bako, Mónica Savorani, Hellas Cena, Perla K. García-May, Saturday Etuk, Roberto Casale, Sherief Abd-Elsalam, Satoru Ikenoue, Muhammad Baffah Aminu, Carmen Vecciarelli, Eduardo A. Duro, Mustapha Ado Usman, Yetunde John-Akinola, Ricardo Nieto, Enrico Ferrazi, Zulfiqar A. Bhutta, Ana Langer, Stephen H. Kennedy, Aris T. Papageorghiou

Published in JAMA Pediatrics on 22 April 2021

Abstract
Importance
Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed.
Objective
To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals.
Design, Setting, and Participants
In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge.
Exposures
COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms.
Main Outcomes and Measures
The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity.
Results
A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity.
Conclusions and Relevance
In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.

 

New England Journal of Medicine study (Open access)

JAMA Pediatrics study (Open access)

Full BusinessLIVE report (Restricted access)

 

See also MedicalBrief archives:

COVID may increase blood clot risk in women who are pregnant or taking oestrogen


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