COVID: mRNA vaccines safe in pregnancy

 A new preliminary assessment suggested that the mRNA vaccines were safe for pregnant women and their subsequent infants (see covid pregnancy mRNA vax safe in dropbox, or DOI: 10.1056/NEJMoa2104983)

 

Details:

-- results were derived from 3 databases, from December 14, 2020 to February 28, 2021:

    -- the V-safe Surveillance System and Pregnancy Registry, a new CDC smartphone-based active surveillance system developed for the Covid-19 vaccination program. Voluntary enrollment. Text messages were sent to participants to assess adverse reactions and health status postvaccination. For the 1^st week after vaccination participants were prompted to report local and systemic signs and symptoms during daily surveys and rank them as mild, moderate, or severe. Eligible patients were vaccinated when pregnant or in the perconception period

        -- 35,691 v-safe participants 16-54yo were identified as pregnant

    -- VAERS, national passive surveillance system established in 1990 and administered by the CDC and FDA, for spontaneous reporting of vaccine adverse events

    -- historic pre-Covid data on pregnancy and neonatal outcomes from the year prior to the pandemic

-- 54% received the Pfizer vaccine and 46% the Moderna one, with similar age distributions/demographics for both

    -- 61% were 25-34-year-old, 31% were 35-44 years old, 76% non-Hispanic white and 87% were pregnant at the time of vaccination

-- 3719 (94%) identified themselves as health care personnel (and many of them received early vaccination because of their profession)

-- timing of 1^st dose during pregnancy:

    -- Periconception: 2%

    -- 1^st trimester: 29%

    -- 2^nd trimester: 43%

    -- 3^rd trimester: 26%

-- 98% did not have a Covid-19 infection during pregnancy

-- outcomes assessed: local and systemic reactogenicity, maternal and neonatal outcomes compared with prior year

 

Results:

-- pregnancy outcome: 827 had a completed pregnancy by the time of this report (mostly from those vaccinated in the 3^rd trimester, too early to see outcomes for those earlier in pregnancy), 115 (14%) had a pregnancy loss/86% had a live birth

-- adverse neonatal outcomes, as compared to historical pregnancy and neonatal outcomes prior to Covid-19: preterm birth (9.4% vs 8-15%), small-for-gestational age (3.2% vs 3.5%), neonatal deaths (0 vs <1%)

    -- ie, similar incidences for pregnancy and neonatal outcomes from data before Covid-19 to these currently vaccinated women

-- VAERS: 221 pregnancy related adverse events reported: most frequent was spontaneous abortion (46 cases)

-- adverse events from vaccine: solicited reports found the most common to be injection-site pain (about 90%), fatigue (about 50%, much more after 2^nd injection), headache (about 30% much more after 2^nd injection), and myalgia (about 30%, much more after 2^nd injection)

    -- of note, there were very small differences in reporting frequency in these adverse events between pregnant and nonpregnant women

 

Commentary:

-- pregnant women are at increased risk of severe Covid-19 illness (including ICU care, mechanical ventilation, ECMO) and death, as compared to age-matched nonpregnant women (see http://gmodestmedblogs.blogspot.com/2021/03/covid-probs-in-pregnancy-recs-on.html for a large database review of Covid-related problems in the US during pregnancy, as well as vaccine recommendations for pregnancy and lactation by the major US medical societies)

-- adverse neonatal outcomes post-vaccination however have had inconsistent results in prior reports

-- there is evidence that there is placental transfer of the SARS-CoV-2 antibodies after vaccination during the 3^rd trimester, suggesting there may be some level of neonatal protection by maternal vaccination

    -- there is evidence of SARS-CoV-2 vertical transmission from mothers to neonates (see http://gmodestmedblogs.blogspot.com/2020/03/sars-cov-2-vertical-maternalneonatal.html ), suggesting this neonatal protection may be useful 

 

Limitations:

-- this was a voluntary reporting system and therefore might not represent the general population: it was largely of healthcare workers, people who were tech savvy, and those likely more educated than the general population

    -- this was also not a randomized controlled trial of vaccinated vs not vaccinated women, so there may be inherent biases as in any observational study, reflecting potential unmeasured confounders in such a study (eg perhaps clinicians were more emphatic about vaccination in some particular women over others, and some women might have been more inclined to want the vaccine: these differences may all reflect differences in psycho-socio-demographics-prior medical history of the pregnant women, and these unmeasured differences themselves might affect outcomes (more so than the vaccine)

-- there is likely inherent bias in self-reported outcomes. Different patients may be more inclined to report problems; they may well grade them very differently from each other (mild vs moderate vs severe) and their own assessment of the severity of the problems might change significantly over time (initially mild symptoms might later be graded as moderate as they seem more long-term and bothersome/concerning)

-- comparing outcomes of the vaccinated women the study to pre-Covid control populations is a bit fraught: things change over time, especially now when Covid has so dramatically affected people physically and psychologically, which also could affect perceptions and reporting of problems

-- their results basically reflect people getting the vaccine during the 3^rd trimester, limiting its validity earlier in pregnancy (to be reported later). Issues around neonatal outcomes and congenital anomalies in particular are typically related to 1^st trimester insults

-- only 15% of people who identified themselves for pregnant participated in the v-safe surveillance system. And the VAERS system of voluntary reporting is often underutilized

so, this study reinforces a few things:

-- we know pretty well that Covid-19 can be bad in pregnancy and can be vertically transmitted to neonates

-- we pretty likely know from the above that the vaccine is safe in pregnant women and neonates, esp if given in the third trimester: the data from the 1st 2 trimesters is pending (and info should be available on earlier pregnancy in the next several months)

so at this point and with the absence of better data to the contrary, it certainly seems reasonable to proceed with vaccination of pregnant women, as per the medical society guidelines...

geoff

 

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