How specific delivery management interventions are associated with early neonatal SARS-CoV-2 infection and neonatal death

By Neha MathurReviewed by Danielle Ellis, B.Sc.Feb 17 2023

In a recent study posted to the medRxiv* server, researchers reviewed the association between specific delivery management interventions (DMI) and neonatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (ENI) and neonatal death (ND) in less than 28 days of life.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

They confirmed the SARS-CoV-2-positivity of a neonate by reverse transcription-polymerase chain reaction (RT-PCR) test, done on a neonatal sample taken between 12 hours and ten days of birth. Likewise, for mothers, they relied on RT-PCR test results confirming coronavirus disease 2019 (COVID-19) 10 days before delivery or within 48 hours post-delivery.

Background

SARS-CoV-2 infections in pregnant women dramatically increase the risk of maternal death and maternal and neonatal morbidities. Despite evidence that COVID-19 vaccines reduce the risk of transmission to the fetus, infected pregnant females are hesitant to take COVID-19 vaccines, and there is a shortage of vaccines in many countries.

Notably, infants remain surrounded by multiple caregivers who might be infectious. Thus, it also remains challenging to locate the SARS-CoV-2 infection source of a neonate. Also, the presentation of COVID-19 symptoms and its discourse in neonates is subtle and hard to diagnose.

Finally, data from available case reports show how tedious it is to collect all delivery material (e.g., placenta, colostrum, amniotic fluid, etc.) for RT-PCR assessments. In addition, it is challenging to sample the infant and all caregivers for serial RT-PCRs. Together, these factors make it difficult for clinicians to determine the exact time or route of SARS-CoV-2 transmission in neonates.

Most importantly, despite recommendations for several DMIs for women with active SARS-CoV-2 infection, there is a lack of support for the same in real-world settings, which continues to be a major risk factor for early COVID-19-related neonatal deaths.

About the study

In the present study, researchers extensively searched published articles specifying DMI, ENI, and ND in three international databases, MEDLINE, Cochrane review, and Google Scholar, between 1 January 2020 and 31 December 2021.

The two review authors screened all articles independently and then resolved differences, if any, through a discussion. They recorded the flow of information through the different phases of review in a PRISMA flow diagram and entered all data on a Microsoft Excel spreadsheet.

The current systematic review covered quasi-randomized trials, randomized controlled trials/RCTs, cross-sectional, case-control, cohort studies, and case reports/series. Other study inclusion criteria for articles were they describe a delivery method and RT-PCR results for the infant.

The studies covered in this review had two primary outcomes - ND and ENI. They also described types of DMI. For instance, article(s) mentioned whether the delivery room had negative pressure, aerosolization, and droplet-managed environment, distance from the mother during resuscitation (≥ six feet or not), mother used a face mask vs. not during delivery, and what measures were adopted to minimize contact with maternal fluids.

Moreover, they described whether obstetricians performed cesarean section (C-section) for infection prevention and used a separate room from the delivery room to place the newborn. In addition, all the included studies mentioned infant care practices in detail.

The researchers treated ENI and ND as binary variables for all patient-level analyses. They pooled all maternal and infant characteristics by DerSimonian-Laird inverse variance method and expressed results as percentages (%) with a 95% confidence interval (CI). Furthermore, they used I₂ statistics to assess the heterogeneity of included studies, with a value of less than 25% indicating low and over 75% indicating high heterogeneity.

Study findings

The researchers screened 11,075 publications in total; however, they included barely 117 publications comprising data on 243, and 231 infants and mothers, respectively. Regarding their clinical characteristics, the average maternal age was 31.2 years, with 31.3% of these women having moderate SARS-CoV-2 illness.

Of 231 mothers, 79% underwent C-section delivery. Of 243 infants with an average birthweight of approximately 2.56kg, 58% were male. ENI description was available for 23.4% of cases, and ND in less than 28 days was documented in 2.1% of cases.

With these results, the contribution of DMI to neonatal outcomes remains uncertain. However, they showed that maternal COVID-19 severity before delivery might have influenced ENI and ND. Likewise, the viral load of mothers during the pregnancy and cohorts of moderately symptomatic mothers with their infants impacted ENI and ND.

Conclusions

According to the authors, this is the first systematic review comparing DMI combinations with routine care and the risk of ENI or ND. The researchers observed substantial publication biases during the active phases of the COVID-19 pandemic. Indeed, there was the preferential publication of cases involving ENI and ND but reports not specifying routine delivery management practices. Notably, these publications described altered management of deliveries but without mentioning similar descriptions of delivery outcomes when conducted routinely.

Other limitations that introduced biases in the included publications were the lack of randomization and data on postpartum infant care practices. This hindered providing evidence for best practice DMIs for reducing ENI and ND. In addition, reviewers' opinions varied on expert consensus guidelines. Since it is crucial to minimize ENI and ND while ensuring safety and optimal care to both mother and infant, the researchers advocated shared decision-making between healthcare professionals and patients to ensure mother and infant safety.

Nevertheless, efforts should continue to accrue more data via multinational studies on the best practice guidelines for DMI. Possibly, these efforts would lead to a prospective database addressing the question of optimal delivery management to help prevent airborne SARS-CoV-2 transmission from mother to newborn.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.