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Abstract

CORONAVIRUS DISEASE 2019: THE PREGNANT WOMAN, NEWBORN, AND RISK OF VERTICAL TRANSMISSION Coronavirus disease 2019 (COVID-19) is caused by the betacoronavirus, SARS-CoV-2, and is a member of the Coronavirus family. Other members of the Coronavirus family include MERS-CoV, responsible for Middle East respiratory syndrome, and SARS-CoV, responsible for severe acute respiratory syndrome. Corona viruses occur in both humans and animal species including camels, cattle, cats, and bats.1 Animal coronaviruses can infect people with subsequent person-to-person transmission.1 Person-to-person contact occurs through close contact with infected individuals (within 6 ft) and through respiratory droplets from sneezing or coughing.1 Although not believed to be the main route of exposure, spread from contact with infected surfaces may be possible.1 It is not known how long the virus can live without a host. Symptoms of COVID-19 may appear between 2 and 14 days after exposure and can include fever, cough, and shortness of breath.1 Symptoms can range from mild to severe illness and death.1 The current COVID-19 outbreak began in Wuhan, Hubei Province, China, with a link to a seafood and live animal market (suggesting animal-to-person spread).1 Person-to-person spread has since occurred in other countries, including the United States.1 On March 11, 2020, the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) declared COVID-19 a pandemic.2,3 A pandemic is a global outbreak with rapid spread due to no preexisting immunity to the virus.3 The number of cases and deaths from COVID-19 is not reported here as the numbers are changing rapidly. The WHO and the CDC update the number of cases and deaths from COVID-19 daily and can be accessed via https://www.who.int/docs/default-source/coronaviruse/20200312-sitrep-52-covid-19.pdf?sfvrsn=e2bfc9c0_2 and https://www.cdc.gov/coronavirus/2019-ncov/cases-in-us.html, respectively.4,5 Currently, there is a paucity of literature on the effects of COVID-19 on pregnant women and neonates and the risk for vertical transmission (via placenta or human milk). It is not currently known whether pregnant women are more susceptible to COVID-19 than other adults. The relative immunologic deficiencies that occur during pregnancy may make pregnant women more susceptible to COVID-19, but this has not been confirmed at this time. In the past, pregnant women were at a higher risk for severe illness, morbidity, and mortality with other similar coronaviruses, including SARS-CoV and MERS-CoV, and with both the influenza and H1N1 viruses.6 A retrospective review of medical records of 9 pregnant women who developed COVID-19 pneumonia during the third trimester in Wuhan, China, showed similar symptomatology with nonpregnant adult patients, including fever (n = 7), cough (n = 4), myalgia (n = 3), sore throat (n = 2), and malaise (n = 2).7 Five of the women had lymphocytopenia and 3 had increased aminotransferase concentrations. None of the 9 women developed severe disease or died. These findings must be interpreted with caution, as the possibility remains that COVID-19 could follow a similar, more severe disease progression as SARS and MERS in pregnant women. In the same review, fetal distress was noted in 2 cases. The 9 neonates were born via cesarean section (for rationales other than COVID-19 infection), with all exhibiting 1-minute Apgar scores of 8 to 9 and 5-minute Apgar scores of 9 to 10. No neonatal asphyxia was observed. All samples from amniotic fluid, cord blood, neonatal throat swabs, and human milk were negative for SARS-CoV-2, indicating no evidence of vertical transmission in women who developed COVID-19 pneumonia in the third trimester.7 Liu et al8 and Zhu et al9 also showed no evidence for vertical transmission in their retrospective reviews on 3 and 9 pregnant women, respectively, with COVID-19 pneumonia. Liu et al8 found all negative results for SARS-CoV-2 in neonatal oropharyngeal swabs, umbilical cord blood, and neonatal serum (n = 3). Zhu et al9 tested 9 neonates via nasopharyngeal swab, and all were negative for SARS-CoV-2. However, we must remain vigilant due to the small sample size of these studies. All 3 of the aforementioned studies involved pregnant women who became infected with COVID-19 in the third trimester. Questions remain as to the possibility of vertical transmission or fetal harm with maternal infection in the first or second trimester. In contrast to the aforementioned studies, there is a case report of a neonate with a positive nucleic acid test for COVID-19 at 30 hours of life, making vertical transmission a possibility.10 The mother of the neonate presented with COVID-19 pneumonia. The neonate exhibited shortness of breath, evidence of pulmonary infection, and slightly abnormal liver function tests. The neonate did not exhibit fever or cough and vital signs were stable.10 Of note, this information was obtained from a news brief, was not peer-reviewed and had to be translated from Chinese to English via Google Translate. A second report of a newborn who tested positive for COVID-19 has surfaced from London; the source a British tabloid.11 More recently, Zeng et al12 reviewed the medical records of 33 neonates born to COVID-19 positive mothers. Three of the neonates tested positive for COVID-19 via reverse transcriptase-polymerase chain reaction (RT-PCR) on day of life (DOL) #2. Vertical transmission may have occurred in these cases but it is difficult to interpret because the neonates were not tested until DOL#2. The aforementioned studies utilized RT-PCR for SARS-CoV-2 testing in all samples. In February of this year Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibody testing for SARS-CoV-2 became available. One case study and one retrospective analysis have since described the use of IgG and IgM antibody testing and have raised the possibility of in-utero transmission of COVID-19.13,14 Dong et al13 describe a case study of an infected pregnant woman with positive RT-PCR of nasopharyngeal swab at 34 weeks and 2 days gestation. At 37 weeks 5 days she had elevated serum IgG and IgM antibodies, however, PT-PCR of vaginal secretions was negative. She delivered via cesarean section at 37 weeks 6 days with an N95 mask on. The neonate was isolated in the NICU immediately after birth. The neonate was asymptomatic with Apgars of 9 and 10. At 2 hours of life the neonate had elevated SARS-CoV-2 IgG and IgM antibodies, elevated cytokines and an elevated WBC. The RT-PCR of nasopharyngeal swab was negative for a total of 5 tests performed at 2 hours of life through DOL #16. Limitations of this study include that it is a single case study and there was no testing of amniotic fluid or the placenta. Zeng et al14 performed a retrospective analysis of 6 pregnant women with symptomatic COVID-19 pneumonia and positive RT-PCR testing. All of the women delivered via cesarean section, wearing a mask, in a negative pressure room. The neonates were all isolated immediately after birth. All 6 neonates had Apgar scores of 8 to 9 and 9 to 10 at 1 and 5 minutes respectively. All 6 neonates had negative RT-PCR (via nasopharyngeal swab) results but evidence of both IgG and IgM antibodies in their serum. Two of the neonates had elevated levels of both IgG and IgM antibodies. IgM antibodies are not transferred to the fetus from the placenta; therefore, the presence of IgM by 2 hours of life in some of these infants suggests in utero infection.13,14 Additionally, IgM usually does not appear until 3 to 7 days after infection; making infection after delivery unlikely.13 The clinical significance of this is unknown. The three neonates with elevated IgM antibodies presented by Dong et al13 and Zeng et al14 were all asymptomatic. Currently, more data is available to describe the epidemiology in older infants and children than in neonates. Wei et al15 showed no severe illness in a small retrospective study with 9 infants (aged 28 days to 1 year) diagnosed with COVID-19 infection. Two of the infants presented with mild URI, 4 with fever, 1 had no symptoms, and no information was available on the remaining 2 infants. None of the infants required mechanical ventilation or intensive care, and there were no reported deaths. All 9 infants had an infected family member. Seven of the infants lived in Wuhan or had contact with someone who had been there recently, one had no direct linkage to Wuhan, and there was no information available for the remaining infant. This study is promising for good infant prognosis with COVID-19 infection but is too small to officially determine overall expected prognosis for infants, especially infants with comorbidities such as prematurity or congenital heart disease. Other non–COVID-19 viral infections are known to have more severe effects on younger children, those with pulmonary comorbidities, and those who are immunocompromised.16 In addition, the overall numbers for infant COVID-19 infection may be underestimated because of underdiagnosis with milder symptomatology.15 A retrospective, epidemiological analysis of 2143 pediatric patients with either laboratory-confirmed COVID-19 infection or suspected cases in mainland China found infants to be at a higher risk for severe or critical illness than older children.17 In total, 10.6% of infants (aged 0-1 year) developed severe or critical illness compared with 7.3%, 4.2%, 4.1%, and 3% of children aged 1 to 5 years, 6 to 10 years, 11 to 15 years, and older than 15 years, respectively. A limitation of this study is that some of the suspected cases could have been caused by a different respiratory virus. Other non–COVID-19 infections are associated with more severe outcomes in younger children as well.16 Breast milk provides the best immunologic protection for neonates. Although there is currently no evidence to support the transmission of COVID-19 through breast milk, the available evidence is limited. Recognizing that breast milk provides the best source of nutrition, the WHO, CDC, American Academy of Pediatrics (AAP) and Academy of Breastfeeding Medicine provide guidelines for women with confirmed COVID-19 infection who wish to breast feed.18,19,20,21 These guidelines include taking precautions to decrease the risk of transmission through strict handwashing before touching the baby, breast pump or bottles and wearing a face mask during breast feeding. Breast pumps and bottles should be cleaned thoroughly using manufacturer's instructions. The AAP recommends considering temporary separation of COVID-19 positive mothers and their neonates.20 In this case, expressed breast milk can be fed by another healthy individual.19,20 A priority must be placed on handwashing, cough etiquette, and effective infection control practices to stop the spread of COVID-19. Infection control measures outlined by the CDC include strategies for minimizing the chance for exposures, adhering to standard, contact and airborne precautions, managing visitor access, implementing engineering controls, monitoring and managing exposed healthcare personnel, training and education of healthcare personnel, implementing environmental infection control, and reporting within healthcare facilities and to public health authorities. This report can be accessed at https://www.cdc.gov/coronavirus/2019-ncov/infection-control/control-recommendations.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fhcp%2Finfection-control.html.22 Many questions remain due to the relative newness of the COVID-19 epidemic. It remains unclear as to whether pregnant women and neonates are at an increased risk for negative sequelae due to COVID-19 infection. The risk for vertical transmission remains unclear but may be possible. Children may exhibit a milder disease course and progression than adults, however; neonates may be more vulnerable, especially those with comorbidities such as prematurity. This is not well-defined, due to small numbers of neonates affected to date. As nursing professionals, we must educate parents and visitors in the neonatal intensive care unit and remain vigilant in our infection control practices.