The occurrence of coronavirus disease 2019 (COVID-19) in pregnancy has been thought to trigger several complications in the mother and fetus, and affect neonatal outcomes. The disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a wide spectrum of symptoms and signs, from mild to critical.
A new preprint on the medRxiv* server describes the protocol written for a study that aims to perform a systematic analysis of all the data available on the effect of this syndrome on pregnancy.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Changes in pregnancy
Pregnancy is a time of physiological adaptation to the process of growing and sustaining a new life within the human body. This involves multiple changes in the body systems, including the heart and the lungs. Some of these are increased heart rate and systolic volume, oxygen consumption, a reduction in lung capacity with advancing pregnancy.
There are also changes in immune tolerance and in the coagulation system, associated with increased coagulability and intravascular inflammation.
These are reflected in the response of a pregnant body to acute respiratory and infectious diseases, especially with complications like respiratory insufficiency and thromboembolic phenomena, these being commonly reported with COVID-19.
For this reason, pregnancy in earlier pathogenic coronavirus outbreaks, including the SARS and MERS (Middle East Respiratory Syndrome) pandemics, was associated with multiple adverse outcomes such as preterm births, growth restriction, miscarriages and abortions.
Lack of adequate data
An earlier study reports that half the pregnant women with SARS required intensive care unit (ICU) admission because of falling oxygen saturation. With a third being put on mechanical ventilation, the eventual death toll in this group was a shocking 25%.
Prior studies show that most women with SARS-CoV-2 infection had mild to moderate disease, with poor evidence for vertical transmission. However, the data has not been accurately recorded in many cases, making it difficult to agree on a standard of care, the relative risk posed by SARS-CoV-2 in pregnancy and the postpartum period.
Study protocol
The current study hoped to provide insights into these areas, thus advancing the management of this patient group.
The protocol was designed according to standard recommendations and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) guidelines.
The researchers aim to include all fully-reported case-control and cohort studies on pregnant women if fetal, neonatal and maternal mortality is reported. Other inclusion criteria include the reporting of the need for ICU admission, the mode of delivery, preterm birth, birth weight, Apgar score, growth restriction, and altered amniotic fluid. All studies should include controls in the form of pregnant women without COVID-19.
Only English, Spanish or Portuguese studies were included, and all studies had to provide outcome data at the level of individual patients.
The researchers aimed to use the prominent sites such as MEDLINE/PubMed, LILACS/BIREME, Web of science, bioRxiv, medRxiv, and Embase, using appropriate search terms. All the retrieved studies would be screened by title and abstract, followed by the full text.
Three independent reviews of the material would be carried out from this screening up to the stage of data extraction. After comparing the data, accounting for missing data by direct inquiry, and arriving at a consensus about the results, the data would be recorded for further analysis.
The data collected would include all patient characteristics, from age, body mass index, gestational age, and other illnesses, as well as the number of patients and the statistical outcomes.
Study outcomes
The aim is to understand the effect of COVID-19 on mortality in the mother-child unit, as well as the need for ICU admission, the mode of delivery, preterm delivery, birth weight below 2,500 g and 1,000 g for low birth weight and very low birth weight. Apgar scores, reflecting the baby’s health at birth, and changes in amniotic fluid, and growth restriction, are also assessed.
To assess the risk of bias (RoB) in these studies, the researchers decided to use the “Quality in Prognosis Studies” (QUIPS), with six categories including items like study participation, attrition, prognostic factor measurement and outcome measurement. Items in each domain are judged to be at low, moderate or high risk of bias.
With low RoB in all domains, the paper is considered to have low RoB, and also if only one domain has a moderate RoB with all others being at low RoB.
If three or more domains are at moderate RoB, or if one or more domains have high RoB, the study is considered to have high RoB. All in between are considered to have moderate RoB.
The data will then be extracted and analyzed. The researchers aim to estimate effect sizes and find pooled estimates by both fixed- and random-effect models. Assessments of heterogeneous quality or quantity, and sensitivity analyses, are also envisaged.
If any outcome has ten or more studies, subgroup analyses and meta-regression will be performed for each feature singly. Both types of analyses are built around hypotheses to avoid spurious associations.
Quality of evidence
The quality of evidence will be assessed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, which accounts for differences that affect the outcomes, based on study design, RoB, inconsistencies in the results, type of evidence, publication bias, effect size, dose-response profiles, and the effects of all confounding factors together provided that they will only decrease the demonstrated effect.
Conclusion
This systematic review will provide a meta-analysis to explore how COVID-19 affects pregnancy outcomes and the newborn. This will help establish evidence-based guidelines for the management of COVID-19 in pregnancy to improve outcomes in this patient group worldwide.
*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.
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