COVID: probs in pregnancy, recs on pregnancy and lactation

 A large healthcare database documented significant maternal (and likely fetal) problems associated with Covid-19 infection during pregnancy (see covid pregnancy outcomes jamaintmed2021 in dropbox, or https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2775396 )

 

Details:

-- data from the Premium Healthcare Database, an all-payer database including 20% of US hospitalizations, from April 1 to November 23, 2020

-- mean age 29 (25% <25yo, 55% 25-34yo, 18% 35-44yo)

-- 6380 (1.6%) of women had Covid-19 versus 400,066 women who did not

    -- the biggest differences between these groups: those with Covid were more often Black (18% versus 15%), Hispanic (43% versus 18%), less often white (28% versus 57%); more often from the Northeast (25% versus 15%), less often from the Midwest (15% versus 23% or West 12% versus 16%)

    -- comorbidities: more often obesity 17% versus 15% and gestational diabetes 11% versus 10%, and less often gestational hypertension 6% vs 7%

-- race and ethnicity were self-reported; Covid-19 status, comorbidities, and in-hospital outcomes were identified by diagnostic and billing codes

-- discharge disposition and in-hospital deaths were reported for all patients

 

Results: 

-- there were a lot of highly statistically significant differences in outcomes, almost all with p<0.001, but many of them involved very small percentage differences, as happens in such large studies

-- major differences:

    -- preterm labor 5% versus 4%, preterm birth 7% versus 6%, preeclampsia 9% versus 7%, MI 0.1% versus 0%, stroke 0.2% versus 0.1%, intensive care 3% versus 0.4%

    -- deaths: 9 women (0.1%) versus 20 (0%), translating to 141 versus 5 deaths/100,000 women

        -- though, as a reference, the overall US maternal mortality rate in 2018 was 17.4/100K women, far worse than other industrialized countries (eg New Zealand was 1.7/100K, Canada 8.6/100K): https://www.commonwealthfund.org/publications/issue-briefs/2020/nov/maternal-mortality-maternity-care-us-compared-10-countries

-- though stillbirth was 23% higher, this was not statistically significant

--specific factors associated with need for mechanical ventilation in those with Covid-19 infection:

    --age: OR 1.91 (1.31-2.77), per 10 years

    --morbid obesity: OR 3.85 (2.05-7.21)

    --diabetes: OR 4.51 (2.10-9.70)

    --kidney disease: OR 21.57 (7.73-60.10)

    --eclampsia: OR 116.1 (22.91-588.50)

    --thrombotic events: OR 45.10 (17.13-118.8)

    --stillbirth: OR 7.88 (2.39-25.98)

 

Commentary: 

--from this huge database, it is pretty clear that there are more adverse maternal outcomes in those with Covid-19

--the absolute increases in adverse pregnancy effects associated with Covid were small (though the relative risks were often quite high: eg, MI was found in 8 women with Covid (0.1%) vs 18 without (0.0%), a quite small absolute difference of 0.1%, but the adjusted relative risk was 30.89-fold. These low absolute risks overall are not unexpected in this cohort of young women (though would be nice to know the breakdown of these specific events by their age groupings)

    --other relative risks for more common outcomes, such as pre-eclampsia and preterm birth, which were 20% higher in the covid-positive group

--prior studies have suggested very low potential transmission rate from mothers to kids by breast-feeding: see http://gmodestmedblogs.blogspot.com/2021/01/covid-breastfeeding-and-rooming-in-seem.html 

Limitations:

-- this was a large data-mining study, without lots of granular data. Many factors were not included, especially psychosocial, or socioeconomic factors: for example, quality nutrition, exercise, number of people living in a house/crowding, stressors, …

    --were those women with covid infections in living/social situations that, in and of themselves, place women at higher risk of Covid infection as well as adverse pregnancy or neonatal adverse events?? And it was the living situation that was more determinant of bad outcomes than the covid infection?

--some of the demographic differences (race/ethnicity, residency location) also likely reflect differences in testing frequency as well as important differences in socioeconomic factors/access to care/quality of care, etc

-- Especially in light of this lack of important data, I focused on the major differences in outcomes in those with and without Covid. there were highly significant ones which showed lesser absolute effect in the article (eg, <2-fold); in these cases there is a pretty high likelihood that a more detailed and all-inclusive study (preferably a prospective one with more granular data) might have found very different results. Some of the major results may then prove to be nonsignificant as well... But typically in these large studies, a relative risk of <2 often turns out not to be significant in a more detailed prospective study

-- this Premium Healthcare Database also did not have granular data on the reason why Covid-19 was diagnosed in these women. was there selective screening done? what inspired the clinicians to do the screenings? was there an inherent bias in this decision, which might have led to different treatments/outcomes? though at least for part of the observation period of this study, there was likely some routine screening of all pregnant women

    -- a New York study found that pregnant women tested routinely during the height of covid there found that lots of women had asymptomatic infection: see http://gmodestmedblogs.blogspot.com/2020/04/covid-asymptomatic-ob-patients.html . we do not know how these asymptomatic infections might affect mother/child. and the number of these infections will likely track with the pretest probability: in times of more infections overall, there will be lots more asymptomatic ones

    -- also, any asymptomatic women identified, perhaps by universal screening or contact tracing, might have been treated differently at the time of childbirth, and this could have affected their outcomes, and limit study generalizability

    -- after this New York study, several hospitals did begin universal screening, starting in late April (this was not a systematic effort, however)

-- however, in this study the ICD-10 code used to identify Covid-19 (U07.1) in this study seems to include only symptomatic infections, and explicitly excludes “coronavirus infection, unspecified”. so, unlikely that asymptomatic infections were included. we really do need more data on the effect of asymptomatic infections on mothers and kids

-- there are no granular data assessing the timing of the Covid infection and outcomes: was it infection in the 1^st trimester? Near the time of delivery????

So, there is an association between covid infection in pregnant women and adverse outcomes, based on this data-mining study (though limited by the lack of important data). So, what makes sense???

--the background is that there seem to be an array of bad outcomes that are more common if a pregnant woman gets covid. but, still, the absolute risk increase is pretty small for the vast majority of pregnant women, who have several factors decreasing their risk of adverse outcomes: they are women, young, and basically healthy (in general)

--I would still strongly suggest vaccination for pregnant women, though this is a data-free suggestion, but:

    --based on the mechanics of the mRNA vaccines available in the US, and the actual adverse effects of the vaccine (no significant long-term ones found so far, with data stretching back almost 1 year since the beginning of the vaccine trials): it is very likely very safe

    --it is likely that the baby will be protected after birth, through placental transfer of IgG antibodies post maternal vaccination (at least this happens with other vaccines)

    --Covid is likely to become more prevalent with more variants developing, with some being more transmissible. And, potentially with more adverse outcomes for mother and child (eg see http://gmodestmedblogs.blogspot.com/2021/02/covid-b117-variant-update-more-deadly.html ).

--and, by secondary analysis, it seems that some women are more likely to have worse pregnancy outcomes if they develop covid (eg, older, underlying diabetes, kidney disease, morbid obesity, etc). and these women are even more likely to get more benefit by vaccination

 

--though, of course, this question of vaccination is a really, really difficult one for mothers/families to deal with.  There will, as always, be some adverse pregnancy outcomes no matter what. When that happens, was the bad outcome related to the decision to have the vaccine? (a setting for long-term guilt and myriad of other self-blamings.) Though the same may well be true (or truer) for those not getting the vaccine and having bad outcomes.

    --for some women, it may well be as good a decision to be aggressively prudent at home (if one has the ability to do that) and have other household members vaccinated (though, again, would be important to have the currently unavailable data on asymptomatic SARS-CoV-2 carriage, effects on kids/mothers, and transmissibility)

 

So, certainly a gamble given lack of data, but my guess is that for most women, vaccination benefits outweigh potential risks

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Here are society recommendations:

 

A JAMA article reviewed the data (not much actual data are available, leading to some differences in the recommendations) and recommendations for mRNA vaccines in pregnant and lactating women (see covid pregnant women recs jama2021 in dropbox, or https://jamanetwork.com/journals/jama/fullarticle/2776447 )

here is their table:

geoff

 

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