A new study conducted by researchers at Yonsei University College of Medicine, Korea, suggests that while having coronavirus disease 2019 (COVID-19) during pregnancy has little effect on fetal or neonatal mortality, it can be associated with premature birth and sometimes severe outcomes for mother and baby, including death.
The systematic literature review found that the majority of neonates born to mothers with COVID-19 did not test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and among four who did test positive, no evidence of vertical (mother to infant) transmission was observed.
However, the study did find that premature birth was common and that complications included small size for gestational age, low birth weight, and asphyxia.
Most infants born to mothers with COVID-19 were asymptomatic. Still, among those who did have symptoms, the most common clinical manifestations were shortness of breath, gastrointestinal problems, respiratory distress syndrome, and fever. In one case, a newborn died due to gastric bleeding.
Among mothers, common symptoms included shortness of breath, cough, fever, and myalgia, and the majority had pneumonia. Adverse pregnancy outcomes included premature rupture of membrane, pre-term labor, fetal distress, post-partum fever, and stillbirth.
S.H. Yoon and colleagues recommend that pregnant women with COVID-19 and their newborns are carefully monitored, and that infected mothers are quarantined to prevent passing SARS-CoV-2 onto their babies.
Concerns about infection during pregnancy and vertical transmission
The rapidly spreading COVID-19 pandemic has caused particular concern about pregnant women and newborns since the 2003 SARS-CoV-1 and 2012 the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreaks caused severe maternal and fetal complications, as well as high mortality rates.
Another crucial question is whether the virus can be vertically transmitted.
“However, knowledge of neonatal outcomes when mothers are infected with coronavirus disease (COVID-19) during pregnancy is still limited to several case reports and case series,” said Yoon and team.
To evaluate the maternal and neonatal outcomes and incidence of vertical transmission among women who have COVID-19 during pregnancy, the team conducted a systematic review of the literature available in PubMed and Embase up to April 15th, 2020.
The researchers included 16 case series and 12 case reports covering 223 pregnant women and 201 births.
Most newborns were not infected
As reported in the European Review for Medical and Pharmacological Sciences, the majority of newborns were not positive for SARS-CoV-2. Only four were reported to have laboratory-confirmed SARS-CoV-2 infection within 48 hours of birth.
All four babies were male. One had fetal distress and was delivered prematurely with low birth weight. All four had pneumonia, and the most common symptoms were fever, lethargy, and vomiting. All infected babies recovered well, and three tested negative for infection by reverse transcriptase-polymerase chain reaction (RT-PCR) within a week following birth.
Breast milk, cord blood, amniotic fluid, and the placenta all tested negative for SARS-CoV-2 by RT-PCR, suggesting that vertical transmission is not common in cases of maternal SARS-CoV-2 during pregnancy, say the researchers
However, “we recommend that further serologic studies with validation should be done, with repeated data on RT-PCR test results immediately after birth,” they write. “In addition, follow-up of neonates is needed to determine whether the disease occurs in the newborn.”
Premature birth was common
Fetal death was reported in two cases, and among 185 neonates for whom the mode of delivery was available, 163 (88.1%) were delivered by Cesarean section, and 22 (11.9%) were delivered vaginally.
Forty-eight (25.9%) were born prematurely. Infants born small for gestational age accounted for 8.3% of cases, and those with a low birth weight accounted for 15.6%. Birth asphyxia was reported in 1.8% of cases and respiratory distress syndrome in 6.4%.
Among 73 cases, 68 (93.2%) were asymptomatic. Of those who did have symptoms, the most common clinical manifestations were shortness of breath (9.6%), gastrointestinal symptoms such as feeding intolerance and vomiting (7.2%), respiratory distress syndrome (6.4%), and fever (4.0%).
Eighteen (26.5%) of 68 newborns also had pneumonia, with bacterial pneumonia reported in three cases.
Neonatal death was reported in one (0.6%) of 177 cases and was caused by intractable gastric bleeding.
Mothers were often symptomatic
Mothers often presented with clinical manifestations. Eighty-five (42.3%) of 201 cases had a fever; 64 (31.8%) of 201 cases had a cough; 12 (21.4%) of 56 cases had myalgia, and 16 (11.3%) of 142 cases had shortness of breath. Of 200 cases, 185 (92.5%) had pneumonia confirmed by a computed tomography (CT) scan.
Regarding pregnancy outcomes, mothers had premature rupture of the membrane in 16 (12.7%) of 126 cases and pre-term labor in 22 (22.7%) of 97 cases. Fetal distress was reported in 15 (10.6%) of 141 cases, and post-partum fever was reported in 34 (34.3%) of 99 cases.
Five women received mechanical ventilation and intensive care unit care, two of whom developed acute respiratory distress syndrome and delivered stillbirths.
What do the authors advise?
“The evidence from our systematic review of these studies suggests that the effect of COVID-19 during pregnancy on fetal and neonatal mortality is low but can be associated with adverse neonatal outcomes,” said Yoon and team.
“COVID-19 during pregnancy might cause severe neonatal and maternal morbidity, even death. Therefore, careful monitoring of mothers with COVID-19 and their neonates for possible complications and quarantine of infected mothers to prevent neonatal infection, are warranted,” they conclude.
- Yoon SH, et al. Clinical outcomes of 201 neonates born to mothers with COVID-19: a systematic review. European Review for Medical and Pharmacological Sciences 2020; 24 (14): 7804-7815. DOI: 10.26355/eurrev_202007_22285. https://www.europeanreview.org/article/22285