Edited by: Marianne Vidler, University of British Columbia, Canada
Reviewed by: Veronique Demers-Mathieu, Medolac Laboratories, United States; Lorraine Toner, Mount Sinai Hospital, United States
This article was submitted to Maternal Health, a section of the journal Frontiers in Global Women's Health
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Amidst the COVID-19 pandemic, there is a need for further research on its manifestation in pregnant women, since they are particularly prone to respiratory pathogens, like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), due to physiological changes during pregnancy. Its effects on infants born to mothers with COVID-19 are also not well-studied, and more evidence is needed on vertical transmission of the disease from mother to infant and on the transmission of IgG/IgM antibodies between mother and infant. We aim to systematically review and evaluate the effects of COVID-19 among SARS-CoV-2-positive pregnant women in late pregnancy and neonates with SARS-CoV-2-positive pregnant mothers using blood assays to find indicators of maternal and neonatal complications. We searched for original published articles in Google Scholar, Medline (PubMed), and Embase databases to identify articles in the English language from December 2019 to July 20, 2020. Duplicate entries were searched by their titles, authors, date of publication, and Digital Object Identifier. The selected studies were included based on patient pregnancy on admission, pregnant mothers with laboratory-confirmed COVID-19 virus, maternal/neonatal complications, and blood test results. We excluded duplicate studies, articles where full text was not available, other languages than English, opinions, and perspectives. The meta-analysis using the Generalized Linear Mixed model was conducted using the “meta” and “metaprop” packages in R code. Of the 1,642 studies assessed for eligibility, 29 studies (375 mothers and neonates) were included. Preterm birth rate was 34.2%, and cesarean section rate was 82.7%. Maternal laboratory findings found elevated neutrophils (71.4%; 95% CI: 38.5–90.9), elevated CRP (67.7%; 95%: 50.6–81.1), and low hemoglobin (57.3%; 95% CI: 26.0–87.8). We found platelet count, lactate dehydrogenase, and procalcitonin to be less strongly correlated with preterm birth than between high neutrophil counts (
A global pandemic due to the outbreak of a novel coronavirus was first reported in Wuhan, China in December 2019. This novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes the disease COVID-19. While the name of SARS-CoV-2 suggests that COVID-19 is primarily a respiratory illness presenting with symptoms including fever, cough, and shortness of breath, which may progress to respiratory failure, COVID-19 can present with a wide spectrum of symptoms including sore throat, headache, loss of taste or smell, nausea, vomiting, and diarrhea (
Pregnant women are particularly prone to respiratory pathogens, like SARS-CoV-2, due to physiological changes during pregnancy; increased oxygen intake and diaphragm elevation make pregnant women susceptible to hypoxia (
Reported laboratory abnormalities seen in pregnant patients with COVID-19 include lower white blood cell counts (lymphopenia and thrombocytopenia) and increased C-reactive (CRP) protein levels, elevated lactate dehydrogenase, and prolonged prothrombin time (
This systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reviews of analytical observational studies.
We searched for original published articles in Google Scholar, Medline (PubMed), and Embase databases to identify articles reporting maternal and neonatal complications in pregnant women with COVID-19 in accordance with the PRISMA guidelines (
PRISMA flow diagram.
Two authors (C.Z. and J.Z.) searched the literature, compiled all articles identified through the literature search, and extracted the data. The primary eligibility for inclusion of studies were published studies, with patient pregnancy on admission and COVID-19 infection confirmed by laboratory diagnosis, which investigated maternal/neonatal complications, and recorded blood assay results. The following information was extracted from each eligible study: authors, publication date, type of study, study size, maternal characteristics (age, gestation, preterm birth, vaginal/cesarean birth, symptom severity, and maternal death), infant characteristics (birth weight, Apgar score, and neonatal death), maternal and neonatal blood assays, and laboratory-confirmed vertical transmission of COVID-19. We excluded duplicate studies, articles where full text was not available, other languages than English, opinions, and perspectives. After assessment for duplicates, titles, and abstracts, and full texts of articles, the individual patient characteristics and summary estimates from each selected article were extracted to an Excel spreadsheet (see section Data Availability Statement).
The meta-analysis included all studies. Pooled means on age, gestational age, blood assay values, antibody levels, and pooled prevalence on preterm birth, C-section delivery, vertical transmission, abnormal blood assay values, and elevated antibody levels were assessed using the Generalized Linear Mixed model; the meta-analysis was performed using the “meta” (
A total of 1,673 literatures were initially retrieved from searching online databases and citations. Among these, 695 duplicate literatures were identified and removed. Remaining literatures were screened according to their titles and abstracts. Twenty-nine articles were selected to be analyzed (
Baseline characteristics of included studies.
Zeng et al. ( |
January to February 2020 | Cohort | 3 | NA | 37 |
Dong et al. ( |
February 2020 | Case Study | 1 | 29 | 34 |
Chen et al. ( |
January 2020 | Retrospective | 9 | 29.89 | 37.11 |
Zhu et al. ( |
January to February 2020 | Retrospective | 9 | 30.89 | 35.11 |
Khan et al. ( |
January to February 2020 | Case Series | 17 | 29.29 | 37.82 |
Yin et al. ( |
January to February 2020 | Cohort | 17 | 31 | 37 |
Liu et al. ( |
January to February 2020 | Retrospective | 18 | 31 | 38.6 |
Chen et al. ( |
March 2020 | Case Series | 4 | 29 | 37.75 |
Alzamora et al. ( |
March 2020 | Case Study | 1 | 41 | 33 |
Xiong et al. ( |
January 2020 | Case Study | 1 | 25 | 33 |
Yang et al. ( |
January to March 2020 | Cohort | 13 | 30.2 | 38.2 |
Hantouchzadeh et al. ( |
March 2020 | Retrospective | 9 | 34.86 | 30 |
Qiancheng et al. ( |
January to March 2020 | Cohort | 22 | 30 | 38 |
Hu et al. ( |
January to February 2020 | Case Series | 7 | 32.71 | 38.71 |
Lu et al. ( |
February 2020 | Case Study | 1 | 22 | 38 |
Yan et al. ( |
January to March 2020 | Retrospective | 99 | 30.8 | 38 |
Ferrazzi et al. ( |
March 2020 | Retrospective | 24 | 30.9 | NA |
Zeng et al. ( |
March 2020 | Retrospective | 6 | NA | NA |
Iqbal et al. ( |
April 2020 | Case Study | 1 | 34 | NA |
Yang et al. ( |
January 2020 | Case Series | 7 | NA | 36.71 |
Wu et al. ( |
December 2019 to March 2020 | Retrospective | 20 | 33.35 | 31.87 |
Zhang et al. ( |
January to March 2020 | Observational | 18 | 29.11 | 38.4 |
Liu et al. ( |
March 2020 | Retrospective | 21 | 31 | NA |
Lee et al. ( |
January 2020 | Case Study | 1 | 28 | 37 |
Li et al. ( |
January to February 2020 | Retrospective | 16 | 30.9 | 38 |
Ibrahim ( |
February 2020 | Retrospective | 6 | NA | NA |
Semeshkin et al. ( |
May 2020 | Observational | 20 | NA | NA |
Liu et al. ( |
January to February 2020 | Case Series | 3 | 32.67 | 39 |
Adhdam et al. ( |
March 2020 | Case Study | 1 | NA | NA |
The general characteristics of pregnant patients with COVID-19 are summarized in
Meta-analysis of general maternal and neonatal characteristics.
Maternal Age (years) | 23 | 30.86 | 30.16 | 31.55 | 66.3 | <0.01 | 0.63 | 0.76 | 0.68 | |
Gestational Age (weeks) | 22 | 38–42 | 37.20 | 36.52 | 37.88 | 77.8 | <0.01 | 0.09 | 0.02 | 0.03 |
Preterm Birth | 21 | 10% | 34.19% | 28.29% | 40.61% | 6.3 | 0.06 | 0.30 | 0.95 | 0.68 |
Vaginal Birth | 20 | 68.1% | 15.33% | 8.49% | 26.11% | 60.9 | <0.01 | 0.21 | 0.31 | 0.02 |
Cesarean Birth | 20 | 31.9% | 82.69% | 70.48% | 90.53% | 66.5 | <0.01 | 0.36 | 0.41 | 0.07 |
Severe Symptoms | 11 | 9.28% | 2.83% | 26.44% | 75.0 | <0.01 | 0.37 | 0.99 | 0.14 | |
Maternal Death | 26 | 0% | 0% | 100% | 98.9% | 0.01 | 0.00 | 0.01 | 0.00 | |
Birth Weight (g) | 23 | 2,500–4,000 | 3,040 | 2,910 | 3,170 | 74.8 | <0.01 | 0.26 | 0.43 | 0.00 |
Low Birth Weight | 18 | 8.2% | 13.32% | 5.92% | 27.31% | 57.4 | <0.01 | 0.29 | 0.32 | 0.02 |
Prevalence of maternal and neonatal abnormalities.
Meta-analysis of correlations between maternal and neonatal characteristics.
Mat. IgG | Neo. IgG | 3 | 0.85 | 0.67 | 0.93 | <0.01 | 0% | 0.41 | 0.16 | 0.00 | 0.00 |
Mat. IgM | Neo. IgM | 3 | 0.43 | 0.06 | 0.70 | 0.03 | 0% | 0.97 | 0.22 | 0.03 | 0.02 |
Maternal age | Gestation | 20 | 0.15 | −0.50 | 0.08 | 0.15 | 95% | <0.01 | 0.02 | 0.00 | 0.00 |
Weight | 20 | −33.71 | −87.24 | 19.82 | 0.22 | 80% | <0.01 | 0.30 | 0.54 | 0.27 | |
WBC | 16 | −0.12 | −0.55 | 0.31 | 0.58 | 73% | 0.00 | 0.65 | 0.43 | 0.76 | |
Neutrophil | 11 | 0.55 | −0.08 | 1.18 | 0.08 | 98% | <0.01 | 0.04 | 0.11 | 0.09 | |
Lymphocytes | 13 | 0.05 | −0.11 | 0.10 | 0.96 | 69% | 0.00 | 0.67 | 0.56 | 0.90 | |
Platelets | 9 | −2.57 | −9.66 | 4.53 | 0.48 | 79% | <0.01 | 0.75 | 0.04 | 0.24 | |
Hemoglobin | 9 | −0.18 | −2.17 | 1.81 | 0.86 | 82% | 0.00 | 0.02 | 0.00 | 0.05 | |
C-reactive | 17 | −1.22 | −4.20 | 1.77 | 0.42 | 99% | <0.01 | 0.58 | 0.04 | 0.00 | |
Creatine-Kin. | 6 | −0.98 | −5.64 | 3.69 | 0.68 | 99% | <0.01 | 0.70 | 0.05 | 0.23 | |
PCT | 8 | 0.01 | −0.08 | 0.11 | 0.26 | 96% | <0.01 | 0.70 | 0.57 | 0.12 | |
AST | 14 | 0.51 | −5.18 | 6.21 | 0.86 | 99% | <0.01 | 0.54 | 0.77 | 0.00 | |
ALT | 15 | 0.09 | −7.83 | 8.02 | 0.98 | 100% | <0.01 | 0.27 | 0.74 | 0.00 | |
Bilirubin | 4 | −1.01 | −4.03 | 2.00 | 0.51 | 83% | 0.00 | 0.72 | 0.63 | 0.62 | |
Lact Dehydro | 4 | 10.82 | 47.63 | 69.26 | 0.72 | 98% | <0.01 | 0.75 | 0.83 | 0.96 | |
Albumin | 6 | −1.02 | −3.48 | 1.43 | 0.41 | 100% | <0.01 | 0.42 | 0.46 | 0.51 | |
BUN | 7 | −0.03 | 0.23 | 0.17 | 0.78 | 97% | <0.01 | 1.00 | 0.43 | 0.68 | |
D-dimer | 7 | −0.08 | −0.38 | 0.23 | 0.63 | 95% | <0.01 | 0.36 | 0.66 | 0.59 | |
Gestational age | Weight | 21 | 111.26 | 56.04 | 166.4 | <0.01 | 56% | 0.00 | 0.18 | 0.09 | 0.14 |
WBC | 15 | −0.26 | −0.81 | 0.30 | 0.37 | 75% | 0.00 | 0.52 | 0.51 | 0.60 | |
Neutrophil | 10 | −1.17 | −1.84 | -0.49 | 0.00 | 95% | <0.01 | 0.05 | 0.03 | 0.14 | |
Lymphocytes | 12 | 0.06 | −0.14 | 0.26 | 0.58 | 73% | 0.00 | 0.54 | 0.11 | 0.81 | |
Platelets | 8 | −1.04 | −12.80 | 10.73 | 0.86 | 83% | <0.01 | 0.71 | 0.00 | 0.24 | |
Hemoglobin | 8 | 3.25 | 0.54 | 5.97 | 0.02 | 58% | 0.04 | 0.03 | 0.09 | 0.10 | |
C-reactive | 16 | −1.30 | −6.02 | 3.43 | 0.59 | 99% | <0.01 | 0.52 | 0.03 | 0.00 | |
Creatine-Kin. | 6 | 7.56 | −4.63 | 19.74 | 0.22 | 99% | <0.01 | 0.70 | 0.14 | 0.23 | |
PCT | 8 | 0.02 | −0.15 | 0.18 | 0.83 | 98% | <0.01 | 0.70 | 0.03 | 0.12 | |
AST | 13 | −1.56 | −11.27 | 8.15 | 0.75 | 99% | <0.01 | 0.39 | 0.77 | 0.01 | |
ALT | 14 | −0.82 | −14.29 | 12.66 | 0.91 | 100% | <0.01 | 0.18 | 0.58 | 0.00 | |
Albumin | 5 | 0.87 | −0.33 | 2.08 | 0.16 | 92% | <0.01 | 0.80 | 0.45 | 0.67 | |
BUN | 6 | 0.26 | 0.01 | 0.51 | 0.04 | 67% | 0.03 | 0.44 | 0.68 | 0.90 | |
D-dimer | 6 | −0.18 | −0.61 | 0.25 | 0.41 | 95% | <0.01 | 0.72 | 0.38 | 0.66 | |
Gestational age |
WBC | 9 | 0.48 | −0.35 | 1.31 | 0.26 | 14% | 0.35 | 0.75 | 0.05 | 0.46 |
Neutrophil | 5 | −0.44 | −1.75 | 0.87 | 0.51 | 26% | 0.21 | 0.48 | 0.35 | 0.50 | |
Lymphocytes | 6 | −0.03 | −0.91 | 0.85 | 0.95 | 92% | <0.01 | 1.00 | 0.07 | 0.81 | |
Platelets | 6 | 3.71 | −19.28 | 26.70 | 0.75 | 79% | 0.01 | 1.00 | 0.19 | 0.69 | |
Hemoglobin | 4 | 3.20 | −5.40 | 11.81 | 4.66 | 42% | 0.19 | 0.75 | 0.56 | 0.65 | |
C-reactive | 8 | −0.33 | −1.00 | 0.35 | 0.34 | 98% | <0.01 | 105.00 | 0.79 | 0.60 | |
Creatine-Kin. | 5 | −139.9 | −277.3 | -2.48 | 0.05 | 100% | <0.01 | 0.48 | 0.36 | 0.70 | |
PCT | 6 | −0.16 | −1.31 | 0.99 | 0.79 | 100% | <0.01 | 0.44 | 0.06 | 0.54 | |
AST | 9 | 3.75 | −2.21 | 9.70 | 0.22 | 0% | 0.68 | 0.75 | 0.80 | 0.91 | |
ALT | 9 | 2.03 | −0.83 | 4.89 | 0.16 | 0% | 0.93 | 0.46 | 0.22 | 0.29 | |
Apgar 1 min | 17 | 0.24 | −0.09 | 0.57 | 0.15 | 99% | <0.01 | 0.45 | 0.43 | 0.10 | |
Apgar 5 min | 17 | 0.17 | −0.15 | 0.49 | 0.31 | 99% | <0.01 | 0.41 | 0.87 | 0.00 | |
Vertical | 22 | 1.06 | 2.95 | 0.82 | 0.26 | 96% | 1.00 | 0.72 | 0.30 | 0.31 | |
Birth weight |
WBC | 10 | 0.00 | 0.00 | 0.01 | 0.12 | 11% | 0.14 | 0.86 | 0.94 | 0.59 |
Neutrophil | 5 | −0.01 | −0.03 | 0.01 | 0.27 | 0% | 0.03 | 0.46 | 0.45 | 0.50 | |
Lymphocytes | 6 | 0.00 | −0.01 | 0.01 | 0.82 | 92% | <0.01 | 1.00 | 0.30 | 0.81 | |
Platelets | 7 | 0.03 | −0.05 | 0.12 | 0.44 | 81% | 0.00 | 0.77 | 0.65 | 0.73 | |
Hemoglobin | 5 | 0.02 | −0.01 | 0.04 | 0.30 | 23% | 0.21 | 0.23 | 0.14 | 0.20 | |
C-reactive | 9 | 0.00 | −0.01 | 0.00 | 0.15 | 97% | <0.01 | 0.11 | 0.90 | 0.46 | |
Creatine-Kin. | 5 | 0.15 | −0.95 | 1.26 | 0.78 | 100% | <0.01 | 0.48 | 0.04 | 0.70 | |
PCT | 6 | −0.01 | −0.01 | −0.01 | <0.01 | 90% | <0.01 | 0.44 | 0.06 | 0.53 | |
AST | 9 | 0.02 | 0.00 | 0.05 | 0.09 | 0% | 0.83 | 0.75 | 0.84 | 0.91 | |
ALT | 9 | 0.01 | −0.01 | 0.03 | 0.21 | 0% | 0.90 | 0.46 | 0.31 | 0.29 | |
Apgar 1 min | 17 | 0.00 | 0.00 | 0.00 | 0.04 | 98% | <0.01 | 0.45 | 0.10 | 0.10 | |
Apgar 5 min | 17 | 0.00 | 0.00 | 0.00 | 0.05 | 99% | <0.01 | 0.41 | 0.58 | 0.00 | |
Vertical | 23 | 0.00 | −0.01 | 0.00 | 0.25 | 89% | 0.00 | 0.56 | 0.87 | 0.47 |
Frequency of severe symptoms/admission to intensive care units (ICUs) was estimated at 9.28% (95% CI: 2.83–26.44%), which is not significantly different from the normal. There were seven cases of maternal death in this review; the prevalence of maternal death was not significantly different from zero (95% CI: 0.0–100.0%) and had significant publication bias (Begg's Test
The maternal laboratory findings are summarized in
Meta-analysis of maternal laboratory tests and antibodies.
WBC (109/L) | 15 | 4.5–11 | 8.50 | 7.60 | 9.43 | 61.2 | <0.01 | 0.63 | 0.76 | 0.68 |
Normal WBC | 16 | 60.32% | 47.28% | 72.04% | 59.2 | <0.01 | 0.09 | 0.02 | 0.03 | |
Neutrophil (109/L) | 11 | 1.5–8.0 | 7.08 | 5.07 | 9.10 | 99.7 | 0.00 | 0.30 | 0.95 | 0.68 |
High neutrophil | 6 | 71.39% | 38.49% | 90.87% | 60.9 | 0.02 | 0.21 | 0.31 | 0.02 | |
Neutrophil percent | 5 | 45–75% | 78.47 | 71.69 | 85.24 | 90.0 | <0.01 | 0.36 | 0.41 | 0.07 |
Lymphocytes (109/L) | 13 | 1.0–5.0 | 1.26 | 1.14 | 1.39 | 62.7 | <0.01 | 0.37 | 0.99 | 0.14 |
Low lymphocytes | 15 | 31.99% | 21.64% | 44.49% | 59.4 | <0.01 | 0.00 | 0.01 | 0.00 | |
Lymphocytes percent | 6 | 18%−45% | 25.55 | 4.67 | 46.43 | 100 | 0.00 | 0.65 | 0.51 | 0.18 |
Platelets (103/μl) | 9 | 150–450 | 177.92 | 151.02 | 204.82 | 77.3 | <0.01 | 0.85 | 0.05 | 0.09 |
Low platelets | 8 | 15.07% | 3.95% | 43.37% | 68.1 | <0.01 | 0.04 | 0.01 | 0.15 | |
Hemoglobin (g/L) | 9 | 120–155 | 112.4 | 13.70 | 121.1 | 70.2 | <0.01 | 0.44 | 0.21 | 0.68 |
Low hemoglobin | 7 | 57.30% | 26.00% | 86.76% | 57.3 | <0.01 | 0.41 | 0.99 | 0.91 | |
CRP (mg/L) | 17 | <10 | 24.88 | 13.80 | 35.96 | 97.1 | <0.01 | 0.67 | 0.49 | 0.06 |
Elevated CRP | 13 | 67.70% | 50.59% | 81.09% | 70.0 | <0.01 | 0.58 | 0.26 | 0.93 | |
Creatine-kinase (U/L) | 6 | 22–198 | 49.56 | 26.34 | 72.79 | 99.2 | <0.01 | 1.00 | 0.26 | 0.46 |
High creatine-kinase | 5 | 2.17% | 0.31% | 13.88% | 0.0 | 0.8267 | 0.75 | 0.12 | 0.40 | |
PCT (ng/ml) | 8 | <0.5 | 0.27 | 0.00 | 0.59 | 80.3 | <0.01 | 0.88 | 0.59 | 0.53 |
High PCT | 8 | 3.76% | 0.06% | 72.79% | 70.5 | 0.04 | 0.02 | 0.02 | 0.94 | |
AST (U/L) | 14 | <36 | 41.11 | 18.24 | 63.98 | 96.6 | <0.01 | 0.19 | 0.10 | 0.09 |
ALT (U/L) | 15 | <36 | 40.39 | 9.00 | 71.78 | 98.9 | <0.01 | 0.58 | 0.01 | 0.01 |
Elevated AST/ALT | 13 | 18.81% | 8.21% | 37.49% | 68.0 | <0.01 | 0.29 | 0.04 | 0.00 | |
Total bilirubin (μmol/L) | 4 | 1–12 | 14.37 | 2.98 | 25.76 | 77.5 | <0.01 | 0.70 | 0.09 | 0.61 |
Lactate dehydro. (U/L) | 4 | <225 | 236.9 | 148.3 | 325.5 | 97.4 | <0.01 | 0.07 | 0.20 | 0.02 |
Albumin (g/L) | 6 | 35–50 | 26.73 | 16.85 | 36.07 | 99.3 | <0.01 | 0.70 | 0.19 | 0.12 |
BUN (mmol/L) | 7 | 2.5–7.1 | 3.22 | 2.28 | 4.14 | 88.5 | <0.01 | 1.00 | 0.31 | 0.01 |
PT (s) | 3 | 8.7–11.5 | 12.11 | 11.72 | 12.50 | 0.0 | <0.01 | 0.54 | 0.08 | <0.01 |
APTT (s) | 3 | 30–40 | 3.10 | 29.93 | 44.27 | 90.9 | <0.01 | 0.27 | 0.10 | 0.00 |
D-dimer (mg/L) | 7 | <0.5 | 2.27 | 1.30 | 3.23 | 95.5 | <0.01 | 0.62 | 0.95 | 0.15 |
IgG (AU/ml) | 15 | <10 | 76.90 | 43.02 | 110.79 | 61.2 | <0.01 | 0.72 | 0.86 | 0.50 |
High IgG | 16 | 72.73% | 55.35% | 85.16% | 59.2 | <0.01 | 0.50 | 0.52 | 0.17 | |
IgM (AU/ml) | 11 | <10 | 96.89 | 0.00 | 212.81 | 99.7 | 0.00 | 0.42 | 0.34 | 0.48 |
High IgM | 6 | 48.94% | 14.35% | 84.58% | 60.9 | 0.02 | 1.00 | 0.85 | 0.66 |
The following outcomes were from a meta-analysis with <10 studies. The pooled mean of lactate dehydrogenase has been estimated as 236.91 U/L (95% CI: 148.28–325.54), which is not significantly different from the normal. The results of the meta-regression showed that blood urea nitrogen (BUN) levels have a significant relationship with gestational age (coefficient: 0.26,
The general characteristics of infants born to mothers with COVID-19 are summarized in
The neonatal laboratory findings are summarized in
Meta-analysis of neonatal laboratory tests and antibodies.
WBC (109/L) | 10 | 4.5–11 | 3,040 | 2,910 | 3,170 | 41.9% | 0.08 | 0.26 | 0.43 | 0.00 |
Normal WBC | 10 | 13.32% | 5.92% | 27.31% | 22.6% | 0.17 | 0.29 | 0.32 | 0.02 | |
Neutrophil (109/L) | 5 | 1.5–8.0 | 14.73 | 13.05 | 16.42 | 17.2% | 0.31 | 0.86 | 0.94 | 0.60 |
High neutrophil | 5 | 9.85% | 3.13% | 26.96% | 0.0% | 0.21 | 0.12 | 0.69 | 0.02 | |
Neutrophil (%) | 3 | 45%−75% | 10.18 | 8.90 | 11.46 | 96.7% | <0.01 | 0.33 | 0.32 | 1.00 |
Lymphocytes (109/L) | 6 | 1.0–5.0 | 66.67% | 47.33% | 81.66% | 94.5% | <0.01 | 0.45 | 0.85 | 0.93 |
Low lymphocytes | 8 | 60.09 | 40.45 | 79.73 | 75.9% | <0.01 | 1.00 | 0.86 | 0.98 | |
Lymphocytes (%) | 4 | 18%−45% | 2.87 | 1.57 | 4.16 | 89.7% | <0.01 | 0.85 | 0.15 | 0.00 |
Platelets (103/μl) | 7 | 150–450 | 4.75% | 0.35% | 41.35% | 72.5% | <0.01 | 1.00 | 0.03 | 0.01 |
Low platelets | 7 | 28.85 | 15.26 | 42.45 | 21.2% | 0.22 | 0.28 | 0.49 | 0.96 | |
Hemoglobin (g/L) | 5 | 120–155 | 250.8 | 219.4 | 282.2 | 34.7% | 0.19 | 0.65 | 0.84 | 0.81 |
Low hemoglobin | 5 | 23.37% | 11.27% | 42.26% | 0.0% | 0.73 | 0.36 | 0.31 | 0.66 | |
CRP (mg/L) | 9 | <10 | 168.9 | 158.1 | 179.7 | 96.8% | <0.01 | 0.14 | 0.14 | 0.73 |
Elevated CRP | 9 | 4.17% | 0.58% | 24.35% | 0.0% | 0.98 | 0.14 | 0.66 | 0.01 | |
Creatine-kinase (U/L) | 5 | 22–198 | 1.86 | 0.56 | 3.15 | 99.6% | <0.01 | 0.11 | 0.24 | 0.37 |
High creatine-kinase | 5 | 1.96% | 0.28% | 12.65% | 69.4% | 0.02 | 0.00 | 0.04 | 0.00 | |
PCT (ng/ml) | 6 | <0.5 | 64.84 | 61.03 | 68.65 | 50.6% | 0.09 | 0.33 | 0.27 | 0.56 |
High PCT | 6 | 10.65% | 1.30% | 51.92% | 23.0% | 0.21 | 0.62 | 0.92 | 0.88 | |
AST (U/L) | 9 | <36 | 0.29 | 0.22 | 0.35 | 0.0% | 0.60 | 0.44 | 0.18 | 0.14 |
ALT (U/L) | 9 | <36 | 23.17% | 8.40% | 49.78% | 0.0% | 0.82 | 1.00 | 0.20 | 0.02 |
Elevated AST/ALT | 8 | 59.34 | 49.81 | 68.86 | 0.0% | 0.80 | 0.75 | 0.79 | 0.05 | |
Albumin (g/L) | 3 | 35–50 | 14.65 | 11.93 | 17.37 | 44.7% | 0.16 | 0.46 | 0.16 | 0.00 |
IL-6 (pg/ml) | 3 | 62.00% | 47.96% | 74.28% | 35.6% | 0.21 | 0.71 | 0.72 | 0.23 | |
High IL-6 | 3 | 32.94 | 28.67 | 37.21 | 86.1% | <0.01 | 0.60 | 0.71 | 0.81 | |
IgG (AU/ml) | 4 | <10 | 23.22 | 16.94 | 29.49 | 89.2% | <0.01 | 0.60 | 0.47 | 0.33 |
High IgG | 4 | 91.10% | 32.38% | 99.97% | 2.0% | 0.30 | 0.60 | 0.27 | 0.17 | |
IgM (AU/ml) | 4 | <10 | 72.47 | 26.41 | 118.5 | 91.6% | <0.01 | 0.04 | 0.00 | 0.99 |
High IgM | 4 | 67.16% | 37.87% | 87.27% | 72.5% | <0.01 | 0.70 | 0.12 | 0.00 | |
Apgar, 1 min | 20 | 7–10 | 15.86 | 0.00 | 34.65 | 96.0% | <0.01 | 0.17 | 0.16 | 0.84 |
Apgar, 5 min | 20 | 7–10 | 20.65% | 2.75% | 70.54% | 97.6% | <0.01 | 0.70 | 0.85 | 0.83 |
Vertical transmission | 27 | 7.94 | 7.26 | 8.62 | 88.6% | <0.01 | 0.87 | 0.75 | 0.01 |
Frequency of high PCT was less common and has been estimated as 23.17% (95% CI: 8.4–49.785%). The results of the meta-regression showed that PCT levels have a relationship with birth weight (coefficient: −0.01,
The pooled mean of 1-min Apgar has been estimated as 7.94 (95% CI: 7.26–8.62). The results of the meta-regression showed that 1-min Apgar scores have a relationship with birth weight (coefficient: 0.002,
The pooled prevalence of vertical transmission has been estimated as 0.18%, but it was not significantly different from zero (95% CI: 0.0%−8.95%;
High IgG in mothers was highly prevalent and has been estimated as 72.73% (95% CI: 55.35–85.16%). The pooled mean of maternal IgG was estimated as 76.90 AU/ml (95% CI: 43.02–110.79), which is significantly higher than the normal. The pooled prevalence of high IgM in mothers was less than high IgG and was estimated as 48.94% (95% CI: 14.35–84.58). The pooled mean of maternal IgM was estimated as 96.89 AU/ml (95% CI: 0.00–212.81).
High IgG in neonates born to mother with COVID-19 was highly prevalent and was estimated as 67.16% (95% CI: 37.87–87.27%). The pooled mean of neonatal IgG was estimated as 72.47 AU/ml (95% CI: 26.41–118.54). The pooled prevalence of high IgM in neonates was estimated as 20.65% (95% CI: 2.75–70.54%). The pooled mean of neonatal IgM was estimated as 15.86 AU/ml (95% CI: 0.00–34.65).
The results of the meta-regression showed that infant IgG levels have a relationship with their mother's IgG level (coefficient: 0.85,
The global proportion of cesarean section was ~21.1% in 2017 (
Results from our study suggest that severe symptoms or the need for intensive care appeared to be higher than that that for non-pregnant women of similar age (30.56 years). We found the proportion to be 9.3%, which was higher than previous estimates of 4.2–7.0% (
The most common abnormalities found in the pooled blood assay were high neutrophil count, increased C-reactive protein (CRP), and low hemoglobin (71.9, 67.7, and 57.3%, respectively). Compared to abnormalities found in previous reviews, the only abnormalities shared by our review was increased CRPs among mothers with COVID-19 (
Thrombocytopenia was previously identified as a symptom of infection. In this current study, the prevalence of low platelet counts was estimated at 15.1%, and its pooled mean was not significantly different from the normal range (150–450 103/L). Platelet counts generally decrease during pregnancy, particularly during the third trimester, termed “gestational thrombocytopenia.” In order to adjust for this, we used a lower limit for platelet count of 115 103/μl (
Similarly, while elevated lactate dehydrogenase was identified in COVID-19 patients in previous studies and is associated with worse clinical outcome (
Interestingly, we did not find elevated PCT to be a prevalent symptom of infection. Its prevalence was estimated at 3.8%, and its pooled mean, 0.29 ng/ml, was not significantly different from the normal range (<0.15 ng/ml). Furthermore, there was significant publication bias (Lin and Chu
In this study, we present other noteworthy values from the blood assays: neutrophils count, D-dimer, hemoglobin, and BUN. The most prevalent abnormality was high neutrophil count, or neutrophilia, with 71.4% of the women having this condition. Neutrophilia is its associated increased risk of small-for-gestational-age (SGA) birth, which reflects a cycle of inflammation and placental insufficiency (
The pooled mean of D-dimer was estimated as 2.27 mg/L, which is much greater than the normal range (<0.5 mg/L) for non-pregnant patients. D-dimer is generally elevated during pregnancy; therefore, using this upper limit of 0.5 mg/L would result in false positives if using an upper limit of 0.5 mg/L. Studies have suggested increasing this threshold to 1.0 or 2.0 mg/L (
Low hemoglobin levels were the second most prevalent abnormality in the present study, with 57.3% patients presenting this abnormality. In general, pregnancy-induced anemia is common, so the normal hemoglobin range for pregnant women in the third trimester is 95–150 g/L (
The pooled mean of BUN was estimated as 3.22 mmol/L, which falls within the normal range (2.5–7.1). We found that BUN had a significant positive correlation (
The most common abnormality found in the pooled blood assay was elevated IL-6, abnormal white blood cell count (WBC), elevated neutrophil count, and elevated AST/ALT. The pooled mean of IL-6, 23.22 pg/ml, is significantly above the normal range for IL-6 (5–15 pg/ml) (
Abnormal WBC and elevated neutrophils are well recognized within neonates (
The pooled mean for PCT has been estimated at 0.23 ng/ml and is significantly higher than the normal value for children older than 72 h (0.15 ng/ml). The results of the meta-regression found a significant negative relationship (
The pooled 1 and 5 min Apgar scores, 7.94 and 8.97, respectively, were not significantly different from the normal range (
The pooled prevalence of vertical transmission was estimated to be 0.18%, which is not significantly different from 0%. Therefore, we found that the risk of vertical transmission is very low. Due to the significant publication bias, this suggests that the prevalence of vertical transmission is even lower than 0.18%. Recent studies into vertical transmission of SARS-CoV-2 via the placenta have also concluded that the virus very rarely infects the placenta and can only do so with very high maternal viral loads (
High levels of IgM antibodies were indicated as the first line of defense to SARS-CoV-2 when the disease is still active, whereas detection of SARS-CoV-2 virus IgG indicates recovery or past exposure to the virus (
Interestingly, 67.1% of infants born to mothers with COVID-19 had elevated IgG levels. The pooled mean for neonatal IgG was significantly different from the normal range, estimated at 72.47 AU/ml. This indicates that infants with mothers with COVID-19 may gain natural passive immunity through IgG crossing the placenta during late pregnancy (
The major limitations of this systematic review are the retrospective design in almost all of the included studies, the lack of universal testing for COVID-19, the lack of standardized management and timing of women with COVID-19 and the inconsistent treatment and reporting for their newborns, and the lack of standardized blood testing. A significant proportion of the pregnancies were affected by COVID-19 during the third trimester, so we cannot meaningfully comment on early exposure. While common outcomes in blood assay, such as WBC and CRP, are commonly reported, other factors such as lactate dehydrogenase, BUN, D-dimer, and all neonatal outcomes should be tested more often so we can better verify if they are good tools to predicting the symptoms of COVID-19. Lastly, our review did not include studies that were recently published in the literature, particularly in languages other than English.
This systematic review and meta-analysis corroborated with previous studies that pregnant women with COVID-19 are at higher risk of preterm birth, are more likely to undergo cesarean section, and have elevated CRP levels and prolonged PT. In contrast to previously published reviews, we did not find an association between COVID-19 and thrombocytopenia, elevated lactate dehydrogenase, and elevated PCT to be prevalent symptoms for COVID-19. We report additional findings associated with COVID-19-infected mothers, including high neutrophil counts, low hemoglobin, and risk of preterm birth. Consistent with other reports, we found little evidence for vertical transmission. In neonates, we observed that infants born to mothers with COVID-19 are more likely to have elevated PCT levels and NS, but also may gain passive immunity to COVID-19 through antibody transfer via placenta. More testing and laboratory data are needed to clarify the relationships we found between D-dimer and thromboembolism, and between BUN and gestational age. Since the evidence is still increasing, this review provides information that can guide future systematic reviews for more meaningful results and can guide current health care during the current SARS-CoV-2 pandemic.
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: Mendeley Data:
CZ and HC conceived the study. CZ and JZ searched the literature and extracted the data. CZ performed the statistical analysis and drafted the manuscript. YV and HC helped to edit the manuscript. All authors contributed to the article and approved the submitted version.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The Supplementary Material for this article can be found online at: