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

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 (1.6%) 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.

Figure 1.. Conceptual Model of Relationships Between Maternal SARS-CoV-2 in Pregnancy, Birth Characteristics, and Neonatal Outcomes

Based on Etminan et al.

Figure 2.. Neonatal Outcomes (Resuscitation at Birth, Admission to Neonatal Unit, Admission Hypothermia, Neurologic Disorders, and Respiratory Disorders and Treatments) Among Infants Born in Sweden (March 11, 2020–January 31, 2021) by Maternal SARS-CoV-2 Test Status in Pregnancy (Assessed as of March 8, 2021)

Data are No. (%) unless otherwise indicated. CPAP indicates continuous positive airway pressure. ^aBetween infants of SARS-CoV-2–positive mothers vs matched infants of mothers without a positive test result. ^bAdmission to a unit with capacity to treat and care for ill or preterm infants. Very preterm indicates <32 weeks; preterm, <35 weeks; near-term, 35 to 36 weeks; term, 37 to 41 weeks; and postterm, ≥42 weeks. ^cDefined as <35.5 °C in infants <32 weeks of gestational age. ^dStage 2 to 3 is moderate to severe encephalopathy. ^eDefined as intraventricular hemorrhage grade 3 to 4 (grade 4 is most severe, with hemorrhage from the ventricles extending into the surrounding brain) or cystic periventricular leukomalacia (last stage of white-matter brain injury with cystic scaring) among infants <32 weeks of gestational age. ^fIn infants <32 weeks of gestational age. ^gRespiratory distress syndrome, transient tachypnea of the newborn, meconium aspiration, or pneumonia.

Figure 3.. Neonatal Outcomes (Infections; Circulatory, Metabolic, Hematologic, and Gastrointestinal Problems; In-Hospital Mortality; Length of Hospital Stay; Breastfeeding; and Infant SARS-CoV-2 Test Status) Among Infants Born in Sweden (March 11, 2020–January 31, 2021) by Maternal SARS-CoV-2 Test Status in Pregnancy

Data are No. (%) unless otherwise indicated. IQR indicates interquartile range. Neonatal outcomes were assessed as of March 8, 2021. ^aRisk differences or median differences between infants of SARS-CoV-2–positive mothers vs matched infants of mothers without a positive test result. ^bIn infants <32 weeks of gestational age.