Novel coronavirus disease 2019 (COVID-19), sustained by the causative agent called
severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is highly contagious.[1]
[2] At present, above 2 million confirmed cases and over 170,000 deaths of COVID-19
have occurred in the world according to the World Health Organization.[3] Pregnant women, because of their special physiological conditions, are susceptible
to the virus and put themselves at greater risk.[4] Timely control and treatment of pregnant women with COVID-19 infection are a major
concern.[5] Moreover, laboratory medicine plays a vital role in this process.[6] Therefore, the purpose of this article is to identify the most common laboratory
abnormalities in pregnant women with COVID-19.
PubMed, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were
reviewed by two independent authors, using the keywords “coronavirus” OR “Wuhan coronavirus”
OR “SARS-CoV-2” OR “2019 novel coronavirus” OR “2019-nCoV” OR “COVID-19” AND “pregnancy”
OR “pregnant woman” OR “pregnant women” OR “vertical transmission” (up to April 20,
2020). There were no country, race, or language restrictions. We included articles
reporting laboratory data in pregnant women with confirmed COVID-19 by reading titles,
abstracts, and full texts. Besides, the lists of references for all articles were
also screened to identify potentially additional articles. A descriptive statistical
analysis was applied to summarize their findings. A random-effects model meta-analysis
was then carried out to calculate the pooled prevalence and 95%confidence interval
(95% CI) to assess the prevalence of laboratory abnormalities in pregnant women with
COVID-19. Double arcsine method was implemented to make original data conform to normal
distribution, and then we analyzed them in software Stata version 11.2 to obtain initial
results. Final results were restored by the formula (P = [sin(tp/2)]2).[7] Begg's test and Egger's test were utilized to evaluate publication bias.
A total of 244 articles were reviewed, among which 223 were removed due to a lack
of laboratory data about pregnant women. Although eight articles reported laboratory
data in pregnant women with COVID-19, they were eliminated because of duplicated data.
In addition, two articles that did not clearly report laboratory abnormalities were
also excluded. Overall, a total of 11 articles with 173 pregnant patients were included,[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18] among which 11 women had severe disease, and 2 women had critical disease. Most
of the patients came from China, and one each came from Korea, the United States,
Sweden, Iran, Peru, and Canada. The stages of pregnancy ranged from the first trimester
to the third trimester. The characteristics of these patients are indicated in [Table 1].
Table 1
Characteristics of the included studies
|
Characteristics
|
Wang et al[17]
|
Li et al[14]
|
Lee et al[13]
|
Iqbal et al[12]
|
Gidlöf et al[11]
|
Zamaniyan et al[18]
|
Alzamora et al[8]
|
Vlachodimitropoulou Koumoutsea et al[16]
|
Chen et al[10]
|
Liu et al[15]
|
Chen et al[9]
|
|
Location
|
China
|
China
|
Korea
|
USA
|
Sweden
|
Iran
|
Peru
|
Canada
|
China
|
China
|
China
|
|
Number of cases
|
1 (severe)
|
1
|
1
|
1
|
1
|
1 (critical)
|
1 (severe)
|
2
|
5
|
41
|
118 (9 severe and 1 critical)
|
|
Age (y)
|
28
|
30
|
28
|
34
|
34
|
22
|
41
|
40/23
|
29 (median)
|
30 (median)
|
31 (median)
|
|
Gestational age (wk)
|
30
|
35
|
37
|
39
|
36
|
32
|
33
|
35/35
|
38–41
|
22–40
|
N/R
|
|
Laboratory data
|
|
|
|
|
|
|
|
|
|
|
|
|
Leukocytes
|
↑100%
|
↔
|
N/R
|
↔
|
N/R
|
↔
|
↓100%
|
N/R
|
↑60%
|
↑41%
|
↑15%[a] ↓5%[a]
|
|
Neutrophils
|
↑100%
|
↑100%
|
N/R
|
↔
|
N/R
|
↑100%
|
N/R
|
N/R
|
↑80%
|
↑83%
|
N/R
|
|
Lymphocytes
|
↓100%
|
↔
|
N/R
|
↓100%
|
N/R
|
↓100%
|
↓100%
|
↓100%
|
↓80%
|
↓61%
|
↓44%[a]
|
|
CRP
|
↑100%
|
N/R
|
↔
|
N/R
|
N/R
|
↑100%
|
↑100%
|
N/R
|
↑100%[a]
|
↑66%
|
↑67%[a]
|
|
Platelets
|
N/R
|
↓100%
|
N/R
|
↔
|
N/R
|
N/R
|
↓100%
|
↓100%
|
↔
|
N/R
|
↓3%[a]
|
|
Hemoglobin
|
N/R
|
↔
|
↓100%
|
↓100%
|
N/R
|
N/R
|
↓100%
|
N/R
|
↓40%
|
N/R
|
N/R
|
|
Procalcitonin
|
↔
|
N/R
|
N/R
|
N/R
|
N/R
|
N/R
|
↔
|
N/R
|
↔
|
N/R
|
↑26%[a]
|
|
ESR
|
N/R
|
N/R
|
↑100%
|
N/R
|
N/R
|
N/R
|
N/R
|
N/R
|
N/R
|
N/R
|
N/R
|
|
Albumin
|
↓100%
|
N/R
|
N/R
|
↓100%
|
N/R
|
N/R
|
N/R
|
N/R
|
↓100%
|
N/R
|
N/R
|
|
ALT
|
↔
|
N/R
|
N/R
|
↔
|
N/R
|
N/R
|
↔
|
↑100%
|
↔
|
N/R
|
↑23%[a]
|
|
AST
|
↔
|
N/R
|
N/R
|
↔
|
N/R
|
N/R
|
↔
|
↑100%
|
↔
|
N/R
|
↑21%[a]
|
|
ALP
|
N/R
|
N/R
|
N/R
|
N/R
|
N/R
|
N/R
|
N/R
|
N/R
|
↑80%
|
N/R
|
N/R
|
|
Bilirubin
|
N/R
|
N/R
|
N/R
|
↔
|
N/R
|
N/R
|
↔
|
N/R
|
↔
|
N/R
|
N/R
|
|
Creatinine
|
↔
|
N/R
|
N/R
|
↓100%
|
↔
|
N/R
|
↓100%
|
N/R
|
↓20%
|
N/R
|
N/R
|
|
Creatine kinase
|
N/R
|
N/R
|
N/R
|
N/R
|
N/R
|
N/R
|
↓100%
|
N/R
|
↑20% ↓20%
|
N/R
|
N/R
|
|
LDH
|
↑100%
|
N/R
|
N/R
|
N/R
|
N/R
|
↔
|
N/R
|
N/R
|
↑20%
|
N/R
|
↑29%[a]
|
|
D-dimer
|
↑100%
|
↑100%
|
N/R
|
N/R
|
N/R
|
N/R
|
↑100%
|
↑100%
|
↑100%[a]
|
N/R
|
↑82%[a]
|
|
PT
|
N/R
|
↔
|
N/R
|
N/R
|
N/R
|
N/R
|
N/R
|
N/R
|
↔
|
N/R
|
N/R
|
Abbreviations: ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate
transaminase; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; ; LDH,
lactate dehydrogenase; N/R, not (clearly) reported; PT, prothrombin time.
a Data missing for patients; ↔Data within the normal reference range.
Note: laboratory data are presented as percent of patients with abnormalities defined
by local reference ranges.
Four articles were included in the meta-analysis.[9]
[10]
[15]
[16] Our results indicated that among all laboratory parameters of pregnant women with
COVID-19, the incidence of elevated D-dimer was 82% (95% CI: 75–89%), elevated neutrophil
count was 81% (95% CI: 69–91%), elevated C-reactive protein was 69% (95% CI: 58–79%),
and decreased lymphocyte count was 59% (95% CI: 41–75%). Begg's test and Egger's test
showed that no publication bias existed ([Table 2]). No other laboratory parameters showed apparently consistent changes due to the
limitation of available data.
Table 2
Meta-analysis results for assessing the prevalence of laboratory abnormalities in
pregnant women with COVID-19 (random-effects model)
|
Laboratory data
|
Studies
|
Case number
|
Initial results[a]
|
Final results[b]
|
Heterogeneity
|
Begg's test (p-Value)
|
Egger's test (p-Value)
|
|
I
2 (%)
|
p-Value
|
|
Elevated D-dimer
|
3
|
109
|
2.27 (2.09, 2.46)
|
0.82 (0.75, 0.89)
|
0.0
|
0.697
|
1
|
0.148
|
|
Elevated neutrophil count
|
2
|
46
|
2.25 (1.97, 2.53)
|
0.81 (0.69, 0.91)
|
0.0
|
0.707
|
1
|
–
|
|
Elevated CRP
|
3
|
151
|
1.95 (1.73, 2.18)
|
0.69 (0.58, 0.79)
|
31.2
|
0.234
|
1
|
0.317
|
|
Decreased lymphocyte count
|
4
|
164
|
1.75 (1.39, 2.10)
|
0.59 (0.41, 0.75)
|
62.9
|
0.044
|
0.308
|
0.082
|
|
Elevated leukocyte count
|
3
|
162
|
1.23 (0.69, 1.78)
|
0.33 (0.11, 0.60)
|
86.7
|
0.001
|
1
|
0.392
|
|
Elevated LDH
|
2
|
84
|
1.14 (0.93, 1.35)
|
0.29 (0.20, 0.39)
|
0.0
|
0.796
|
1
|
–
|
Abbreviations: COVID-19, coronavirus disease 2019; CRP, C-reactive protein; LDH, lactate
dehydrogenase.
a The pooled prevalence and 95%confidence interval obtained by meta-analysis after
adjusting the original data with the double arcsine method.
b The pooled prevalence and 95%confidence interval obtained after restoring the initial
results with the formula (P = [sin(tp/2)][2]).
Considering the relatively high-sequence identity of SARS-CoV-2 and SARS-CoV and the
effects of SARS-CoV on pregnant women, we must pay great attention to the group of
pregnant women infected with COVID-19.[19]
[20] Our review suggests that the most frequent abnormalities are elevated D-dimer (82%),
elevated neutrophil count (81%), elevated C-reactive protein (69%), and decreased
lymphocyte count (59%). However, a meta-analysis of adult COVID-19 infection reported
that decreased albumin (75.8%), high C-reactive protein (58.3%), high lactate dehydrogenase
(LDH; 57.0%), lymphopenia (43.1%), and high erythrocyte sedimentation rate (ESR; 41.8%)
were the most prevalent laboratory abnormalities.[21] Our study found that the incidence of increased LDH in pregnant women with COVID-19
was only 29%. A total of seven cases reported by Wang et al,[17] Iqbal et al,[12] and Chen et al[10] showed decreased albumin levels. Similarly, only Lee et al[13] described that ESR increased in the pregnant woman with COVID-19. Due to the limitation
of the data, we did not further conduct a meta-analysis on these laboratory parameters.
Thus, more studies with large sample size are needed to discuss this in the future.
In addition, Zhang et al[22] reported that among five pregnant women with SARS-CoV infection, two cases had decreased
lymphocytes. Recent studies also reported elevated D-dimer levels, elevated neutrophil
count, elevated C-reactive protein levels, and decreased lymphocyte count as indicators
of poor outcomes in nonpregnant individuals with COVID-19.[23] We should pay careful attention to these laboratory indicators of pregnant women
with COVID-19. However, D-dimer was typically elevated during pregnancy,[24] and a comparative cross-sectional study revealed that pregnant women had significantly
higher white blood cell count, neutrophil count, and lymphocyte count compared with
nonpregnant women.[25] Therefore, pregnancy factors should also be considered when dynamically monitoring
changes of laboratory indicators in pregnant women with COVID-19.
Of course, our review has some limitations. We included only 11 articles, including
case reports and case series, and most of them were from China. Again, reference ranges
for laboratory values differed between reports and several data elements were not
clearly reported. In addition, most of the pregnant women with COVID-19 included in
our review were mild and moderate, with only 11 cases being severe and 2 cases being
critical. We were unable to compare laboratory abnormalities between pregnant women
with mild and severe. So, more data from other regions are needed to better define
laboratory abnormalities in pregnant women with COVID-19 infection. In our meta-analysis,
elevated D-dimer levels, elevated neutrophil count, elevated C-reactive protein levels,
and decreased lymphocyte count are the most prevalent laboratory abnormalities in
pregnant women with COVID-19, which is slightly different from the characteristics
in nonpregnant patients. We should consider pregnancy factors when monitoring changes
in pregnant women.
