More than 2.5 million women are currently pregnant in the United States, and many are worried about the impact a COVID-19 infection might have on mothers and the development of their unborn children. A large literature surrounding the foetal origins hypothesis has shown that pregnancy conditions not only impact the mother but can also impair the offspring (Almond and Currie 2011). Maternal influenza infections during pregnancy may induce premature birth (Currie and Schwandt 2013) and strong cases may even impair foetal development to the point where repercussions throughout adulthood are observed (Schwandt 2019). In his seminal paper, Almond (2006) documented lower incomes and higher adult disability rates among the entire cohort of infants that was in-utero during the Spanish Flu pandemic.
What about children born during the COVID-19 pandemic?
While at this moment it is still unclear whether maternal COVID-19 infections impair foetal development, the existing evidence allows for cautious optimism. The rate of reported COVID-19 deaths among pregnant mothers is low (Hantoushzadeh et al. 2020) and while infections occur in pregnant mothers, most are mild or remain asymptomatic (Sutton et al. 2020, Luo and Yin 2020). Children of mothers infected with COVID-19 during pregnancy are born without detectable impairments and typically test negative for the virus (Chen et al. 2020; Yu et al. 2020).
However, it is too early to know whether in-utero exposure to COVID-19 has negative long-term consequences that are not immediately visible at birth. A potential reference point is the Spanish Flu pandemic (Aassve et al. 2020, Benmelech and Frydman 2020). However, it is important to keep in mind that the 1918 influenza virus had a very different, more devastating impact – particularly for pregnant mothers. Figure 1 compares the age profile of COVID-19 mortality in New York City with Spanish Flu mortality in Philadelphia, one of the hardest hit cities during the Spanish Flu pandemic (Markel et al. 2007). Both mortality rates are shown per 100,000 people, but are plotted on different y-axes since COVID-19 deaths rates are likely to continue increasing in the ongoing pandemic.
Figure 1 COVID-19 mortality (in NYC) and Spanish Flu mortality (in Philadelphia) by age and gender
Notes: Data on COVID-19 death counts for New York City, 1 February 2020-20 May 2020 (CDC 2020), combined with population estimates for 2017 (NYSDH 2017). Data on Spanish Flu mortality from Rogers (1920).
COVID-19 mortality increases exponentially with age, with extremely low death rates among infants, children, and young adults (these numbers include recent cases of multi-system inflammatory syndrome, Schroeder 2020). Mortality is particularly low for young women. Among a total of 16,493 COVID-19 deaths in New York City (between 1 February 2020 and 20 May 2020), not a single female fatality occurred below age 25. For women between the ages of 25 and 34, only five out of every 100,000 have died —and this figure is far lower than the rate for women 65 or older, where the data show more than 740 deaths per 100,000.
For the Spanish Flu, the age profile of deaths looked dramatically different. Fatalities were highly concentrated among infants and young adults. Among women, the majority of deaths occurred in the fertile age range and mortality was especially high among pregnant women (Almond 2006). For every death, there were many cases of severe illness, with recorded stillbirths more than doubling during the pandemic (Rogers 1920).
In other words, pregnant mothers who survived the Spanish Flu experienced extreme levels of sickness in response to influenza infections during the pandemic. This strong impact could not be more different from the current experience with COVID-19 infections, which often go largely unnoticed in pregnant mothers. This brings us to the last question in assessing the relative risks between the two pandemics for a developing fetus:
Are mothers’ mild responses to COVID-19 infections good or bad for an infant in utero?
Strong maternal reactions observed for influenza infections may drain the mother’s body, but they could be an efficient response, e.g. to protect the fetus from contracting the virus itself.
However, it turns out that the fetus does not usually get infected if the pregnant mother contracts an influenza virus or the COVID-19 virus (i.e. the virus does not pass the placenta). Hence, it is the strong maternal response to the influenza virus that impairs foetal development. A strong immune system response of the mother can lead to broad inflammations in the pregnant body (McDade 2012) which fight not only the virus but also damage healthy tissue such as the placenta. Pregnant womens’ mild immune system response to COVID-19 is, therefore, a hopeful sign.
Strong inflammations are also hypothesized to turn the mother’s immune system itself against the fetus. The father’s genes in the fetus are foreign to the mother’s body and are only tolerated due to the mediation of helper cells surrounding the placenta (Trowsdale and Betz 2006). A strong inflammatory response can compromise the functionality of these helper cells. As a result, the fetus might not only suffer from the inflammation itself, but an inflammation can actually cause the mother’s immune system to harm the fetus. It remains unclear why pregnancy makes women respond so strongly to the influenza virus (Kay et al. 2014), but it has been observed both for pandemics and seasonal influenza. Further, the resulting infections have similar negative impacts on the offspring – both at birth as well as into adulthood (Almond 2006, Creanga et al. 2009, Currie and Schwandt 2013, Schwandt 2019).
Cautious hope and stress relief
It is important to emphasize that our understanding of the threats of COVID-19 is still far from complete. We are learning from new research findings on a daily basis. But there is room for cautious optimism from what we know so far: COVID-19 seems to impact pregnant women less than influenza does. While immune system responses triggered by maternal influenza have been shown to impair foetal development, COVID-19 does not seem to cause such strong responses in mothers’ immune systems. Of course, it is still possible that other impairments in the offspring may appear later, even if they are not observable at birth. And only time will tell whether infants exposed to COVID-19 during the first or second trimester will show signs of impairment at birth. But, so far, the existing evidence allows for cautious hope that pregnant mothers and their offspring will fare much better during COVID-19 than they did during the last devastating global pandemic at the turn of the 20th century.
This is not to say that pregnant mothers and young children are entirely unaffected by the current pandemic. Food insecurity is on the rise (Schanzenbach and Pitts 2020), and many young families face financial stress as unemployment is soaring to unprecedented levels (Conti 2020). Nutritional, economic, and psychological stress during pregnancy is detrimental for the fetus as it increases the risk of poor health at birth which may in turn lead to negative long-term consequences (Aizer et al. 2016 Almond et al. 2011, Persson and Rossin-Slater 2018). Hence, we do not want to add unfounded anxieties about COVID-19 infections to mothers’ list of worries—as fewer worries might help their developing infants most.
This column first appeared at the American Society of Health Economics (reproduced with permission).
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