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Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes

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Question  What are the outcomes in newborn infants of mothers testing positive for SARS-CoV-2 in pregnancy?

Findings  In this nationwide, prospective cohort study that included 88 159 infants from Sweden, SARS-CoV-2 infection in pregnancy was significantly associated with higher risk of any neonatal respiratory disorder (2.8% vs 2.0%; odds ratio, 1.42) and some other neonatal morbidities, but not neonatal mortality (0.30% vs 0.12%; odds ratio, 2.55).

Meaning  Maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in the absolute risk of respiratory disorders and some other neonatal morbidities.

Abstract

Importance  The outcomes of newborn infants of women testing positive for SARS-CoV-2 in pregnancy is unclear.

Objective  To evaluate neonatal outcomes in relation to maternal SARS-CoV-2 test positivity in pregnancy.

Design, Setting, and Participants  Nationwide, prospective cohort study based on linkage of the Swedish Pregnancy Register, the Neonatal Quality Register, and the Register for Communicable Diseases. Ninety-two percent of all live births in Sweden between March 11, 2020, and January 31, 2021, were investigated for neonatal outcomes by March 8, 2021. Infants with malformations were excluded. Infants of women who tested positive for SARS-CoV-2 were matched, directly and using propensity scores, on maternal characteristics with up to 4 comparator infants.

Exposures  Maternal test positivity for SARS-CoV-2 in pregnancy.

Main Outcomes and Measures  In-hospital mortality; neonatal resuscitation; admission for neonatal care; respiratory, circulatory, neurologic, infectious, gastrointestinal, metabolic, and hematologic disorders and their treatments; length of hospital stay; breastfeeding; and infant test positivity for SARS-CoV-2.

Results  Of 88 159 infants (49.0% girls), 2323 (2.6%) were delivered by mothers who tested positive for SARS-CoV-2. The mean gestational age of infants of SARS-CoV-2–positive mothers was 39.2 (SD, 2.2) weeks vs 39.6 (SD, 1.8) weeks for comparator infants, and the proportions of preterm infants (gestational age <37 weeks) were 205/2323 (8.8%) among infants of SARS-CoV-2–positive mothers and 4719/85 836 (5.5%) among comparator infants. After matching on maternal characteristics, maternal SARS-CoV-2 test positivity was significantly associated with admission for neonatal care (11.7% vs 8.4%; odds ratio [OR], 1.47; 95% CI, 1.26-1.70) and with neonatal morbidities such as respiratory distress syndrome (1.2% vs 0.5%; OR, 2.40; 95% CI, 1.50-3.84), any neonatal respiratory disorder (2.8% vs 2.0%; OR, 1.42; 95% CI, 1.07-1.90), and hyperbilirubinemia (3.6% vs 2.5%; OR, 1.47; 95% CI, 1.13-1.90). Mortality (0.30% vs 0.12%; OR, 2.55; 95% CI, 0.99-6.57), breastfeeding rates at discharge (94.4% vs 95.1%; OR, 0.84; 95% CI, 0.67-1.05), and length of stay in neonatal care (median, 6 days in both groups; difference, 0 days; 95% CI, −2 to 7 days) did not differ significantly between the groups. Twenty-one infants (0.90%) of SARS-CoV-2–positive mothers tested positive for SARS-CoV-2 in the neonatal period; 12 did not have neonatal morbidity, 9 had diagnoses with unclear relation to SARS-CoV-2, and none had congenital pneumonia.

Conclusions and Relevance  In a nationwide cohort of infants in Sweden, maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in some neonatal morbidities. Given the small numbers of events for many of the outcomes and the large number of statistical comparisons, the findings should be interpreted as exploratory.

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Article Information

Corresponding Author: Mikael Norman, MD, Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Novum, Blickagången 6A, Karolinska Institutet, SE-141 57 Stockholm, Sweden (mikael.norman@ki.se).

Correction: This article was corrected September 14, 2021, to change 1.6% to 2.6% in the first sentence in the Results section of the abstract and in the second sentence in the Results section of the text.

Published Online: April 29, 2021. doi:10.1001/jama.2021.5775

Accepted for Publication: March 30, 2021.

Author Contributions: Dr Söderling had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Norman, Söderling, Hervius Askling, Aronsson, Byström, Jonsson, Sengpiel, Stephansson.

Acquisition, analysis, or interpretation of data: Norman, Navér, Söderling, Ahlberg, Hervius Askling, Aronsson, Byström, Ludvigsson, Håkansson, Stephansson.

Drafting of the manuscript: Norman.

Critical revision of the manuscript for important intellectual content: Navér, Söderling, Ahlberg, Hervius Askling, Aronsson, Byström, Jonsson, Sengpiel, Ludvigsson, Håkansson, Stephansson.

Statistical analysis: Norman, Söderling, Ahlberg.

Obtained funding: Norman, Stephansson.

Administrative, technical, or material support: Norman, Stephansson.

Supervision: Norman.

Conflict of Interest Disclosures: Dr Ludvigsson reported coordinating a study on behalf of the Swedish IBD Quality Register (SWIBREG), which has received funding from Janssen. No other disclosures were reported.

Funding/Support: This study was supported by grants from the Swedish Society of Medicine (2020-937944) and NordForsk (105545), by grants from a regional agreement on clinical research between Region Stockholm and Karolinska Institutet (ALF2020-0443), and by the Childhood Foundation of the Swedish Order of Freemasons. The Swedish Neonatal Quality Register and the Swedish Pregnancy Register are funded by the Swedish government (Ministry of Health and Social Affairs) and the body of Regional Health Care Providers (County Councils).

Role of the Funder/Sponsor: The funding bodies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Additional Contributions: We thank all obstetric and pediatric departments in Sweden for contributing and sharing data to the quality registers.

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