COVID-19 in Pregnancy and Outcomes Among Pregnant Women and Neonates: A Literature Review

Abstract

Limited data are available about the outcomes of COVID-19 during pregnancy and risk of vertical transmission in exposed neonates. We reviewed studies published February 1, 2020, through August 15, 2020, on outcomes in pregnant women with COVID-19 and neonates with perinatal exposure. Among pregnant women with COVID-19, 181 (11%) required ICU admission and 123 (8%) required mechanical ventilation. There were 22 maternal deaths. Most infections occurred in the third trimester. Among women who delivered, 28% had a preterm birth and 57% had a Caesarean section. Sixty-one (4%) of 1222 neonates with reported testing had at least one positive SARS-CoV-2 polymerase chain reaction (PCR) test. The most common symptom among neonates was respiratory distress (n=126, 21%). There were 14 neonatal deaths, one of which occurred in a neonate with positive testing. Further study of COVID-19 in pregnant women and neonates, including standardized reporting of outcomes, testing, and treatment protocols, are essential to optimize maternal and neonatal care.

Introduction

In December 2019, a cluster of pneumonia cases in Wuhan, China, led to the identification of the novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[1] On January 30, 2020, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) epidemic a Public Health Emergency of International Concern.[2] SARS-CoV-2 is a betacoronavirus that is genetically similar to the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), both known to cause severe respiratory illness in humans and associated with high case fatality rates (CFRs) among affected pregnant women.[3–5] Though the clinical presentation of COVID-19 appears to be less severe in children than adults, the pediatric spectrum of disease ranges from asymptomatic infection to acute respiratory failure.[6,7]

Neonates represent a unique at-risk population, with potential for exposure to infection in utero, intrapartum, and after delivery. Neonatal susceptibility to infection is amplified by an immature immune system and frequent contact with family caregivers and healthcare workers, especially among preterm or critically ill neonates. Understanding the epidemiology of COVID-19 is essential for infection prevention and management of neonatal patients, as well as for anticipatory guidance for pregnant women and families. This literature review summarizes the emerging data on outcomes among pregnant women with COVID-19 and neonates with perinatal COVID exposure.

Materials and Methods

We conducted a literature review to identify studies published from February 1, 2020, until August 15, 2020, on outcomes among pregnant women with laboratory confirmed SARS-CoV-2 (by polymerase chain reaction (PCR) or IgM) and neonates with perinatal COVID exposure. We searched Medline, Embase, and Google Scholar and only included peer-reviewed articles for which full text articles could be retrieved. After the initial search, snowball searches were conducted to identify additional articles of interest. Studies including previously published cases were excluded except in provision of additional detail in maternal and neonatal outcomes, where appropriate. Personal communication (J.J. and S.M.) with corresponding authors was used to confirm exclusion of cases previously reported or clarify reported data when possible. Individual patient data from case series and case reports was used to assess overlap. In larger studies without individual patient data, but with confirmed overlap of enrollment dates or location, studies published earlier were preferentially included.

Data were abstracted independently by two reviewers (either E.G.M. and J.J. or J.J. and S.M.); discrepancies were resolved by discussion and consensus of a third reviewer (M.M.G). Descriptive analysis was performed to summarize demographic and clinical characteristics among neonates born to mothers with confirmed COVID-19. Maternal outcomes of interest included clinical presentation, adverse pregnancy outcomes, intensive care unit (ICU) admission, respiratory support, and death. Neonatal outcomes of interest included gestational age, sex, mode of delivery, birthweight, APGAR scores at 1 and 5 minutes, neonatal ICU (NICU) admission, clinical course, laboratory parameters and chest imaging, SARS-CoV-2 testing results, and disposition. Neonates with positive SARS-CoV-2 PCR testing prior to hospital discharge and within the first 14 days of life were considered infected in the perinatal period. Statistical analyses were performed using Stata version 15.1 (Stata Corp., College Station, TX).

Results

We identified 233 studies describing outcomes among pregnant women with COVID-19 published from February 1, 2020, until August 15, 2020 (see Table, Supplemental Digital Content 1). After excluding 37 studies for overlap with previously published studies, 196 studies remained. Cumulatively, these studies reported 1922 women with COVID-19 during pregnancy and 1361 neonates with perinatal exposure; nine studies reported prevalence estimates without detailed pregnancy or neonatal outcomes. The greatest number of publications (n=55) and reported cases of COVID-19 in pregnancy (n=709) were from the United States. A significant number of publications (n=44) and cases (n=206) were from China.

Epidemiology of COVID-19 in pregnancy, maternal clinical course and adverse pregnancy outcomes

Population prevalence of COVID-19 among pregnant women is difficult to estimate given geographic and temporal variability in the prevalence of COVID-19 and differing thresholds for testing pregnant women. However, some studies provide local estimates. Data from New York City in late March to early April 2020 report the highest prevalence of COVID-19 in pregnant women undergoing universal screening at the time of delivery, with results ranging from 15.4% - 19.9% of all women admitted.[8–10] Outside of the endemic region of New York City, prevalence estimates in the United States were lower over the same month (April), ranging from 0.0% (in Los Angeles) to 3.9% (in Connecticut).[8,11–14] Campbell et al. highlight the temporal variability of COVID, with the prevalence among women admitted for delivery at the same three academic centers in Connecticut rising from 0.5% prevalence in the first two weeks of April 2020 to 5% in the second two weeks of April 2020.[11] In Europe, prevalence estimates (based on universal screening data) differed based on region and time period, ranging from 0.6% in the Lombardy region of Italy in early March to 7.0% in March in London.[15–17]

Maternal severity of SARS-CoV-2 infection ranged from asymptomatic to critical illness. The concern for asymptomatic or pre-symptomatic disease among pregnant women admitted to Labor and Delivery was first reported by Breslin et al. in a case series of seven women with COVID-19, two of whom were asymptomatic and admitted for obstetrically indicated induction of labor, with intra- and postpartum onset of symptomatic COVID-19 ultimately necessitating ICU admission.[18] Multiple studies on universal screening programs have confirmed high rates of asymptomatic or pre-symptomatic disease, ranging from 61.5% of women with a positive test in Belgium to 85–90% in areas of London and New York City.[9,10,15,17]

Critical maternal illness has been reported, with 181 (11%) women admitted to the ICU and 123 (8%) requiring mechanical ventilation (Table 1). Twenty-two maternal deaths due to COVID-19 have been reported. Two women were successfully resuscitated after cardiac arrest, one in the setting of COVID-19-associated cardiomyopathy.[19,20]

Table 1.

Outcomes among pregnant women with laboratory confirmed SARS-CoV-2 infection

	Total n=1922
Trimester (n=1539)
First trimester, n (%)	36 (2)
Second trimester, n (%)	140 (9)
Third trimester, n (%)	1363 (89)
Hospital course
ICU admission, n (%)	181 (11)
Mechanical ventilation, n (%)	123 (8)
Death, n (%)	22 (1)
Pregnancy outcome (n=1825)
Delivered, live birth, n (%)	1359 (74)
Delivered, stillbirth, n (%)	19 (1)
Delivered, neonatal outcome not reported, n (%)	74 (4)
Induced abortion, n (%)	8 (0)
Spontaneous abortion, n (%)	12 (1)
Ectopic pregnancy, n (%)	1 (0)
Remained pregnant, n (%)	352 (19)

notes. Maternal and pregnancy outcomes among women with laboratory confirmed SARS-CoV-2 infection. Pregnant women described as mild or asymptomatic were presumed to not have been admitted to an ICU or have required mechanical ventilation, even if not explicitly stated. Cases reported as critical were presumed to require ICU admission, even if not explicitly stated. ICU admission was not presumed for cases described as severe. N reported for individual pregnancy outcomes reflects number of pregnant women with each outcome, not number of fetuses or neonates; multiple gestation is not reflected. Live birth does not preclude later neonatal death; refer to Supplemental Tables 2 and 3 for neonatal outcomes. Percentages reported for each trimester reflect proportion of women for whom trimester could be assigned. Percentages reported for maternal ICU admission, mechanical ventilation, and death were calculating using denominator of women for whom outcomes were known (n=1613, n=1547, and n=1718, respectively). Abbreviations: ICU – intensive care unit; SARS-CoV-2 – severe acute respiratory syndrome coronavirus 2.

There was significant heterogeneity on reporting of maternal comorbidities. Multiple individual studies provided data on maternal comorbidities during pregnancy and their correlation with maternal SARS-CoV-2 infection and neonatal outcomes. In a retrospective cohort comparing 101 SARS-CoV-2 positive pregnant women to 1317 SARS-CoV-2 negative pregnant women at a US academic center, Sarkowitz et al. found no significant difference in rates of hypertension or gestational diabetes, but did note an increased association between obesity and COVID-19 infection.[21] Pierce-Williams et al. reported that, of 64 pregnant women with severe or critical disease, 17% had pre-existing cardiac comorbidities (including chronic hypertension), and two women (3%) developed gestational hypertension or preeclampsia.[20] Vivanti et al. reported on 100 SARS-CoV-2 positive women in France, of whom 52% required hospitalization.[22] While 9% of women in this study had asthma, 6% had chronic hypertension, and 7% had diabetes, the authors found no difference between pre-existing conditions and ICU admission. In a small cohort of women in the UK, Antoun et al. found a prevalence of 10.5% (2/19) of severe preeclampsia, one of whom developed hemolysis, elevated liver enzymes, low platelet count syndrome (HELLP) and disseminated intravascular coagulation (DIC).[23]

Most reported cases of COVID-19 in pregnancy to date have been third trimester infections; among women for whom trimester was reported, 89% had third trimester infections (Table 1). Among 1825 women with known pregnancy outcome, there were 1359 (74%) live births, 19 (1%) stillbirths, 20 (1%) abortions, and 1 ectopic pregnancy; 352 (19%) remained pregnant. There were 35 (2%) multiple pregnancies, resulting in 1428 liveborn neonates and 21 stillborn neonates.

Among 1274 women with reported mode of delivery, 725 (57%) were delivered via Cesarean delivery. Maternal COVID-19 was reported as the indication for Caesarean delivery in 176 (12%) women, though not all studies explicitly reported indication for Caesarean delivery. Ninety-one (6%) pregnancies were complicated by decreased fetal movement or abnormal fetal heart rate tracing. Among 1341 women with reported gestational age, 377 (28%) delivered preterm (<37 weeks gestation). Most studies did not report final delivery outcome among women who were infected in the first or second trimester and remained pregnant at the time of infection, though there have been a few case reports of uncomplicated deliveries at term in convalesced mothers.

Outcomes among neonates born to mothers with COVID-19

Among 1222 neonates with perinatal exposure for whom SARS-CoV-2 PCR results were reported, 61 (4%) tested positive within 14 days or prior to discharge, whichever came first (see Table, Supplemental Digital Content 2). Details regarding hospital course and testing results for neonates who had positive SARS-CoV-2 PCR testing are provided (see Table, Supplemental Digital Content 3).

Among neonates with positive SARS-CoV-2 PCR testing, seventeen (28%) did not have testing site specifically reported. Of the remaining 44, 42 (95%) had a positive upper respiratory sample (nasopharyngeal (NP) versus oropharyngeal (OP)). SARS-CoV-2 PCR testing was positive from tracheal/bronchial aspirates (n=4; 17%), anal/rectal swabs (n=7; 10%), stool (n=3; 14%), and blood (n=4; 21%). There were no positive tests from sputum, gastric aspirates, urine, or cerebrospinal fluid. One of 34 (3%) cord blood samples was positive. Positive neonatal serologic testing for SARS-CoV-2 was reported by Zeng et al. and Dong et al.[24,25] These two studies cumulatively reported three neonates in whom IgM was elevated; all three neonates had negative SARS-CoV-2 PCR testing.

SARS-CoV-2 testing of maternal samples was reported by 40 studies, though number and type of samples obtained were highly variable (see Table, Supplemental Digital Content 2). Among these studies, SARS-CoV-2 PCR testing was positive in samples from amniotic fluid (n=2, 5%), placental tissue or swab (n=4, 11%), vaginal swab (n=2, 18%), maternal anal/rectal swab (n=1, 25%), and stool (n=1, 25%). Three of 45 breast milk samples (7%) were positive. Bastug et al. report an asymptomatic infant with negative nasopharyngeal PCR testing at eight hours of life, who was isolated from his mother and other caregivers, and tested positive for SARS-CoV-2 from multiple sites (nasopharyngeal, stool, and blood) on day of life four after being fed breast milk with detectable virus.[26]

Sixty-eight percent of neonates with known disposition were separated from mother immediately after delivery and cared for in an isolation room in the nursery or NICU. Regarding infants who were not separated, while some studies report use of parental hand hygiene and masking to reduce transmission risk, others describe close contact (such as breastfeeding without a mask) in the early postpartum phase, prior to a maternal or neonatal diagnosis of COVID-19.[27–30] Suspected postnatal infection from close contact with caregivers was not only reported in full term, breastfeeding infants; Piersigilli et al. reported likely postnatal transmission from an infected parent in a 26 week preterm neonate admitted to the NICU.[31]

Respiratory distress was the most common symptom among neonates with perinatal COVID-19 exposure (n =126, 21%) (Table 3). The most common laboratory abnormalities included lymphopenia (n=12), thrombocytopenia (n=21), and elevated aminotransferases (n=92), though there was significant heterogeneity in reporting of neonatal laboratory studies. Among 65 neonates with reported chest imaging (X-ray or computed tomography (CT) scan), 43 (66%) had abnormal findings. Forty-four (5%) of 918 neonates required mechanical ventilation. Four neonates were reported as having DIC; one had positive testing. There were seventeen neonates with asphyxia. One neonate with confirmed SARS-CoV-2 infection presented with encephalitic symptoms.[32] Fourteen neonatal deaths have been described; thirteen of these neonates had negative SARS-CoV-2 PCR testing. One neonate who died shortly after birth had no reported testing.[33] Eight of these deaths occurred in the setting of maternal critical illness.[33–39]

Table 3.

Clinical and demographic characteristics of neonates born to mothers with SARS-CoV-2 infection

	Neonates with positive SARS-CoV-2 PCR testing n=61	Neonates without positive SARS-CoV-2 testing n=1269	All neonates n=1330
Maternal critical illness, n/total (%)	10/31 (32)	101/802 (13)	121/973 (12)
Gestational age in completed weeks, median (IQR)	35 (31-38) n=38	38 (36-39) n=554	38 (36-39) n=592
Preterm, n/total (%)	22/40 (55)	281/1056 (27)	339/1273 (27)
Birth weight in grams, median (IQR)	2520 (1808-3184) n=34	3110 (2675-3400) n=431	3110 (2600-3380) n=465
Male sex, n/total (%)	21/35 (60)	226/398 (57)	250/439 (57)
Caesarean delivery, n/total (%)	31/45 (69)	671/1164 (58)	714/1230 (58)
APGAR score at 1 minute, median (IQR)	8 (5-9) n=25	8 (8-9) n=365	8 (8-9) n=435
APGAR score at 5 minutes, median (IQR)	9 (8-9) n=26	9 (9-10) n=408	9 (9-10) n=479
Neonatal asphyxia, n (%)	2/46 (4)	15/1023 (1)	17/1070 (2)
Separation from mother after delivery, n/total (%)	34/40 (85)	375/559 (67)	415/611 (68)
Breastfed, n/total (%)	4/31 (13)	184/575 (32)	199/627 (32)
NICU admission, n/total (%)	39/43 (91)	296/932 (32)	343/997 (34)
Fever, n/total (%)	9/32 (28)	8/511 (2)	18/554 (32)
Respiratory distress, n/total (%)	35/51 (69)	91/535 (17)	126/590 (21)
Abnormal chest imaging, n (%)	21/26 (81)	22/39 (56)	43/65 (66)
Need for PPV, n/total (%)	11/38 (29)	34/837 (4)	45/885 (5)
Need for mechanical ventilation, n/total (%)	14/50 (28)	30/864 (3)	44/918 (5)
GI symptoms, n/total (%)	8/29 (28)	16/481 (3)	25/527 (5)
DIC, n/total (%)	1/44 (2)	3/836 (0)	4/888 (0)
Lymphopenia, n/total (%)	4/17 (24)	8/190 (4)	12/207 (6)
Thrombocytopenia, n/total (%)	5/17 (29)	16/170 (9)	21/187 (11)
Elevated aminotransferases, n/total (%)	8/16 (50)	84/160 (53)	92/176 (52)
Neonatal death, n (%)	1/55 (2)	13/1131 (1)	14/1167 (1)

notes. Clinical and demographic characteristics of neonatal with perinatal COVID exposure. Studies not reporting neonatal outcomes were excluded. Neonates without positive SARS-CoV-2 PCR testing include neonates with negative testing and neonates in whom testing was not performed or reported. Not all variables of interest were reported for all neonates; denominators reported for individual variables as appropriate. Breastfeeding was defined as direct breastfeeding; use of expressed breast milk only was not considered breastfeeding. Neonates described as asymptomatic were presumed to not have clinical symptoms (fever, respiratory distress, GI symptoms, asphyxia) or have required PPV or mechanical ventilation. PPV includes non-invasive modalities including CPAP, SiPAP, and NIPPV. GI symptoms include abdominal distention, feeding intolerance, vomiting, and diarrhea. Lymphopenia was defined as a lymphocyte count <1,500/mm³. Thrombocytopenia was defined as a platelet count <150,000/mm³. Aminotransferases were considered elevated if either aspartate aminotransferase or alanine aminotransferase was >40 U/L. Abbreviations: APGAR – Appearance, Pulse, Grimace, Activity, and Respiration score ; CPAP – continuous positive airway pressure; DIC – disseminated intravascular coagulation; GI – gastrointestinal; IQR – interquartile range; NICU – neonatal intensive care unit; NIPPV - noninvasive positive pressure ventilation; PCR – polymerase chain reaction; PPV – positive pressure ventilation; SARS-CoV-2 – severe acute respiratory syndrome coronavirus 2; SiPAP – synchronized intermittent positive airway pressure.

Neonatal length of stay was highly variable, with some case reports describing prolonged admission for isolation and observation despite lack of symptoms or positive testing. Ten studies reported follow-up via telephone or clinic visit, with good short-term neonatal outcomes.[27,40–45] Salvatore et al. prospectively followed 120 neonates born to SARS-CoV-2 positive mothers for up to 1 month of life.[45] In their study, no neonates were positive in the perinatal period, and, of the 82 who completed follow up, 72 were asymptomatic and tested negative at both 5–7 days and 14 days of life. No cases of readmission after hospital discharge were reported, though most studies did not include this as an outcome of interest.

Discussion

This literature review summarizes available data on outcomes among pregnant women with COVID-19 and neonates with perinatal exposure. Pregnancy complications in the setting of maternal COVID-19 include preterm delivery and fetal distress necessitating emergent delivery. The rates of Cesarean section (57%) and preterm delivery (28%) in pregnancies affected by COVID-19 in this study were higher than the general prevalence of Cesarean section and preterm birth as reported by the WHO (21% and 11%, respectively).[46,47] Limited data exist on the effects of maternal infection during early pregnancy, as most reported cases to date have occurred during the third trimester.

Data from the effects of SARS and MERS in pregnancy stand in stark contrast to available data from the COVID-19 pandemic, with significantly higher reported CFRs and pregnancy complications (including spontaneous abortion and preterm birth) reported among women affected by SARS and MERS.[48] There are no cases of confirmed vertical transmission of SARS; however, abnormal placental pathology with evidence of inflammation has been described.[49,50] Among preterm neonates with perinatal SARS exposure, respiratory distress syndrome (RDS) and gastrointestinal complications have been reported.[51] Only 11 cases of MERS in pregnancy have been reported in the literature; three were complicated by maternal death and three resulted in neonatal death or stillbirth.[52]

The majority of neonates (68%) who tested positive for SARS-CoV-2 were separated from mother immediately following delivery and placed in isolation, which raises the concern for vertical transmission. Some studies describe only a single swab obtained immediately after birth, potentially limiting yield of testing. Demirjian et al. report a full-term infant born via Caesarian section to an intubated, critically ill mother with documented viremia on day of delivery.[53] The infant, who had negative testing for SARS-CoV-2 at birth from the respiratory tract, blood, and stool samples, tested positive on day of life three, despite strict isolation, airborne, and droplet precautions. Oncel et al. reported four positive neonates, three of whom became positive over 48 hours after birth despite negative swabs at birth and isolation practices in the NICU.[39] Other studies reported neonates with early diagnosis (<24 hours of life) with persistent positive testing, making false positive or transient colonization at birth less likely.[39,54,55] Significant variability was noted in infection prevention practices, timing, number of tests, and sample sites of neonatal SARS-CoV-2 PCR tests, which makes differentiation of vertical transmission and postnatal infections difficult. Standardized testing of neonates born to mothers with COVID, as recommended by the American Academy of Pediatrics (AAP), may increase test sensitivity and also differentiate between vertical and horizontal transmission of SARS-CoV-2.

Several reports describe concerning clinical features among neonates with negative testing that, in some cases, mirror COVID, including respiratory distress requiring positive pressure, imaging consistent with pneumonia, and lymphopenia. It is unclear whether these neonates were infected and had false negative testing or whether maternal COVID-19 may be responsible for an inflammatory response in the neonate that accounts for these symptoms. These clinical features may also be due to other etiologies, such as respiratory distress syndrome associated with prematurity or early onset bacterial sepsis.

Two studies included in this review reported three neonates in whom SARS-CoV-2 IgM was elevated, raising concern for possible vertical transmission despite negative SARS-CoV-2 PCR testing.[24,25] As noted by an accompanying editorial article, serologic diagnosis of congenital viral infection is limited by high rates of false positive testing, and the rapid decline of IgM levels in these neonates suggests that true vertical transmission is unlikely.[56] Tang et al. reported positive IgG, but negative IgM and negative PCR testing in an asymptomatic premature infant born to a mother with positive IgM, but negative PCR testing.[57] Given lack of wide implementation, further study is warranted to assess the utility of SARS-CoV-2 serologic testing to assess presence of perinatally acquired neonatal COVID-19.

Although multiple studies reported likely postnatal transmission, the risk of neonatal COVID-19 acquired in the postnatal period is not easy to quantify given variability in infection prevention precautions. Case-control and prospective cohort studies are needed to understand risk of horizontal transmission to neonates not isolated from infected caregivers. Available data are limited in assessing the transmissibility of SARS-CoV-2 via expressed breast milk, with only three of 45 reported breast milk samples in this study testing positive for SARS-CoV-2.[36,58,59] The case reported by Bastug et al. raises the suspicion for transmission via breast milk, but highlights the difficulty of differentiating between various modes of likely postnatal transmission.[26]

Recommended infection control measures in the home after hospital discharge of mother and baby include physical distancing when possible and use of a mask and hand hygiene during breastfeeding and other newborn care.[60] Similarly, infection control measures must be implemented in healthcare facilities to reduce risk of postnatal acquisition from an infected caregiver, especially given high rates of asymptomatic infection.

Limitations of this literature review include availability of primarily case reports and case series, with variable reporting of detailed neonatal outcomes, including laboratory and imaging studies. Furthermore, we could not ascertain whether some of the studies included in this literature review reported overlapping cases of perinatal exposure. Several published studies appear to include cases from the same healthcare facilities and during similar time periods; we excluded studies with identified data overlap.

COVID-19 has presented significant novel challenges and medical risks to pregnant women. Vertical transmission from mother to infant does not seem common but remains possible based on available reporting. The significance of vertical transmission to the newborn is not clear. Most newborns who acquire COVID-19 have a self-limited illness with relatively good clinical outcomes. With the establishment of national and international COVID-19 registries, wide participation should be encouraged to standardize reporting. While the COVID-19 pandemic is rapidly evolving, we should strive to optimize maternal and neonatal outcomes, which can be best achieved by rigorous study and rapid dissemination of these data. For a full list of included studies, please Supplemental Digital Content 4.

Supplementary Material

SDC 1 table

Supplemental Digital Content 1. Table: Outcomes among pregnant women with laboratory-confirmed COVID-19 by study

SDC 2 table

Supplemental Digital Content 2. Table: Studies reporting SARS-CoV-2 testing and outcomes among neonates with perinatal COVID-19 exposure by country, author, and study type

SDC 3 table

Supplemental Digital Content 3. Table: Neonates with positive SARS-CoV-2 PCR testing after perinatal COVID exposure

SDC 4 Full References

Supplemental Digital Content 4. Full references

Table 2.

SARS-CoV-2 PCR test results among neonates with perinatal COVID-19 exposure

	Total n=1361
Neonatal samples	n positive/total samples (%)
NP/OP swab	42/820 (5)
Sputum	0/2
Gastric aspirate	0/15
Anal/rectal swab	7/68 (10)
Stool	3/22 (14)
Urine	0/20
Blood	4/19 (21)
CSF	0/3
Unspecified	17/400 (4)
No reported testing	139 (10)
Neonates with at least one positive SARS-CoV-2 sample	61/1361 (4) 61/1222 with reported testing (5)
Maternal/delivery samples
Cord blood	1/34 (3)
Amniotic fluid	2/40 (2)
Placenta	4/35 (11)
Vaginal	2/11 (18)
Cervical	0/1
Anal/rectal swab	1/4 (25)
Stool	1/4 (25)
Urine	0/4
Blood	2/8 (25)
Breast milk	3/45 (7)

>notes. SARS-CoV-2 PCR test results by sample type. Multiple samples of the same sample type/location collected from a neonate at multiple time intervals are only counted once. For detailed test results by study, please see Supplemental Table 2. Abbreviations: CSF – cerebrospinal fluid; NP – nasopharyngeal; OP – oropharyngeal; PCR – polymerase chain reaction.