Coronavirus disease 2019 (COVID-19) quickly spread worldwide in 2020, causing over 6.2 million deaths and widespread economic crises. In most cases, the disease causes mild flu-like symptoms, but it can progress to a more serious disease, causing organ failure and long-terSevere acute respiratory symptom coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, primarily spreads between hosts through droplet transmission but can follow other routes also.
Researchers from the Hospital General Universitario Gregorio Marañón have been investigating the spread of the disease from pregnant women to newborns, and have published their results in The Paediatric Infectious Disease Journal.
Any pregnant woman with microbiologically confirmed SARS-CoV-2 infection during any trimester or delivery was eligible for inclusion in the study, which took place across thirteen different Spanish hospitals. Diagnosis must have been confirmed using reverse-transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. Demographic data and clinical history, including time of diagnosis, comorbidities, obstetric history, and clinical presentation of infection were gathered, as well as perinatal and delivery clinical data.
Samples were collected from pregnant women at the time of diagnosis and delivery, and nasopharyngeal swabs were collected from infants within 48 hours post-delivery. Breast milk samples were collected through hand or breast pumping. Biological samples were tested for the presence of SARS-CoV-2 RNA using a commercially available kit.
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To classify how an infection could pass from the mother to the infant, Blumberg's classification was used. This defines intrauterine transmission as requiring positive nasopharyngeal swabs, amniotic fluid or neonatal blood within 24 hours as well as a positive swab of the neonatal respiratory tract within 24 hours or positive IgM within the first week. Intrapartum/early postnatal transmission is defined as requiring a negative RT-PCR swab of the neonatal respiratory tract within 24 hours of delivery and a positive swab of the same respiratory tract after 24 hours. Superficial exposure/transient viremia was defined as positive PCR results from a nasopharyngeal swab, amniotic fluid, cord blood, or neonatal blood within 24 hours, but no evidence of persistence or immune response.
Statistical analysis consisted of the use of medians and interquartile ranges for continuous variables, and categorical variables presented as absolute frequencies and percentages. Categorical variables were compared using the X^2 or Fisher's exact test, and continuous variables were assessed with the Wilcoxon rank-sum test.
In total, the details of 174 women infected with SARS-CoV-2 during pregnancy were recorded, with 177 newborns detailed. At the time of delivery, 39% of women had an acute infection, 30% had a recent infection, and 31% had a past infection. 115 maternal blood samples and 81 placenta samples were collected for RT-PCR, revealing only one case of viral load in both blood sample and placenta, which originated from a woman with mild clinical symptoms beginning 48 hours prior to delivery. The newborn tested negative for SARS-CoV-2 and remained asymptomatic. No viral load was detected in any breast milk samples.
All RT-PCR results for cord blood and newborn blood samples were negative, but viral load was detected in three newborn urine samples and 3 meconium samples, and all of these newborns tested positive for SARS-CoV-2 infections by RT-PCR of nasopharyngeal swabs in their first 48 hours of age.
While all newborns were tested within the first forty-eight hours after delivery, only twelve infants showed positive test results. The researchers determined that three of the infants were infected through intrauterine transmission, five were infected through intrapartum or early postnatal transmission, and two were through secretal contamination or transient viremia. As expected, all were born to mothers who were acutely infected at the time of delivery. Only two of the infected newborns showed any symptoms, both of which resolved without any significant adverse events. When the statistical analysis was performed, no significant differences were found when comparing the development of symptoms and admission to the neonatal intensive care unit between infected newborns and noninfected newborns.
This study reveals that while intrauterine transmission of SARS-CoV-2 does appear very rare, it is possible - although early postnatal transmission through contact with infected individuals is far more frequent.
Healthy infants infected in this manner appear largely resistant to the disease, with most remaining asymptomatic or showing mild symptoms that resolved well. The presence of viremia remains difficult to determine, but the researchers have shown that it is extremely unlikely for the disease to pass in breast milk.
Overall, this study may help to inform healthcare workers and reassure infected pregnant women.
