SARS-CoV-2 infection during pregnancy could cause COVID-19 pneumonia, that could condition an alteration during the pregnancy. In our series, pregnant women with COVID-19 pneumonia had a higher risk of caesarean sections (p = 0.007; OR = 4.20, IC95%: 1.47–11.99) and premature newborns (p = 0.002; OR = 6.97, IC95% 2.34–22.75) than those not developing pneumonia.
COVID-19 pneumonia has been associated with gestational age at diagnosis, the older gestational age, the lower risk of pneumonia, for each week that increases gestational age, there is a 21% lower risk of pneumonia. It has also been associated with lymphopenia, having lymphopenia is 11 times more risk of pneumonia than not having it. The rate of severe pneumonia in pregnant women with SARS-CoV-2 infection in our study was 33%, increasing the rate reported in a review from Juan et al.7 (0–14%). The high rate of pneumonia diagnosed in this cohort could be explained because only patients with the moderate-severe disease were diagnosed and asymptomatic pregnant women delivering during the first month were not included at the beginning of the pandemic. Laboratory findings were consistent with values reported in non-pregnant adults with SARS-CoV-2 infection including elevated inflammatory index such as C-reactive protein and fibrinogen.
We report a high rate of caesarean sections with a higher risk in pregnant women with pneumonia (4 times more risk). In our results, we find a 36.2% of caesarean section deliveries, close to 41.5% reported by Khoury et al. [32], which is increased compared with the latest upload of caesarean sections data in Spain (26.6%) during 2015 (Instituto Nacional de Estadística, INE base, 2015). The rate of preterm births has been 20.6%, increased compared to 14.6% reported by Khoury et al. [32] and definitively increased compared with the Spanish rate in 2015 (8.18%) (Instituto Nacional de Estadística, INE base, 2015). This data supports Sentilhes et al. [10] and Li N et al. [33] reporting a higher rate of preterm delivery in infected women compared with non-infected women. In our study women developing pneumonia had 7 times more risk of preterm birth than women not developing pneumonia.
Elevated liver enzymes and D-dimer results have been found in women with pneumonia, as it was described before in other Spanish hospitals [11] but in our series, it has not been associated with pneumonia. Treatments used were safe for pregnant women and their newborns. All pregnant women diagnosed with SARS-CoV-2 received heparin for ten to fourteen days by protocol and there were no thromboembolic complications.
Vertical transmission has not been objective and a horizontal transmission case was detected in this study. Even positivity on RT-PCR testing, the newborn did not present any symptomatology at the diagnosis nor during the follow-up. As Buonsenso et al. [19] have reported previously, we report a case of late onset infection in a 15 days old baby born from a woman infected during pregnancy. Maternal breastfeeding has been discarded as a source of transmission because the mother was admitted at the ICU with severe pneumonia, so it has been speculated an intra-family transmission. SARS-CoV-2 could be transmitted to newborns by close contact when not using appropriate hygiene measures [34]. Our study reinforces the national and international recommendations based on not modifying the type of delivery, not separating the mother from the newborn at birth and promoting breastfeeding as well as recommending to maximize hygiene by performing isolation of the contact in the environment.
Our results suggest that gestational age at diagnosis is associated with developing pneumonia, so it could be recommended to implement SARS-CoV-2 infection screening during pregnancy.
All treatment options received by infected women were safe for both women and newborns. Remdesivir has not been used during pregnancy in our cohort, both women receiving remdesivir was after delivery.
Maternal breastfeeding was indicated to infected women in our cohort following national recommendations and we have not detected breastfeeding transmission. The case of the newborn infected horizontally at home highlight the need to follow hygienically measures with newborns at home to avoid intrafamiliar infection. Additional research is required about clinical implications of SARS-CoV-2 infection during pregnancy.
There is a high research gap in SARS-CoV-2 infection during pregnancy. It would be interesting to elucidate if there are potential long-term effects in women infected during pregnancy or possible consequences in newborns exposed to the virus during gestation. There is controversial data regarding the severity of SARS-CoV-2 infection during pregnancy; in our cohort, there is no mortality. Some studies have reported similar outcomes in infected pregnant women compared to non-pregnant adults with COVID-19 [35], but others have reported an increase in morbidity [36].
There are still unanswered questions, for example, what are the implications for women infected during the first trimester? Is there any consequence for newborns exposed to SARS-CoV-2 in a long term? These are important issues to clarify.
The most relevant limitation of our study is that at the beginning of the pandemic, the criteria for testing in Spain, and later by the neighbouring countries, only included patients with significant disease, which implicated the loss of asymptomatic infected women at delivery during the first month. All this, taking into account this is the largest multicentre study analysing both mother and newborn exposed to SARS-CoV-2 infection characteristics and outcomes and following newborns after birth.