Association between ABO blood groups and preeclampsia

Hypertension in Pregnancy
ISSN: (Print) (Online) Journal homepage: www.tandfonline.com/journals/ihip20
Association between ABO blood groups and
preeclampsia
Hid Felizardo Cordero-Franco, Ana María Salinas-Martínez, Luis Ángel Garza-
de Hoyos, Sofía Denisse González-Rueda, Joaquín Darío Treviño Báez &
Francisco Javier Guzmán-de la Garza
To cite this article: Hid Felizardo Cordero-Franco, Ana María Salinas-Martínez, Luis Ángel
Garza-de Hoyos, Sofía Denisse González-Rueda, Joaquín Darío Treviño Báez & Francisco
Javier Guzmán-de la Garza (2023) Association between ABO blood groups and preeclampsia,
Hypertension in Pregnancy, 42:1, 2209640, DOI: 10.1080/10641955.2023.2209640
To link to this article: https://doi.org/10.1080/10641955.2023.2209640
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ARTICLE
Association between ABO blood groups and preeclampsia
Hid Felizardo Cordero-Franco
a
, Ana María Salinas-Martínez
a,b
, Luis Ángel Garza-de Hoyos
c,d
,
Sofía Denisse González-Rueda
a
, Joaquín Darío Treviño Báez
e
, and Francisco Javier Guzmán-de la Garza
a,f
a
Unidad de Investigación Epidemiológica y en Servicios de Salud/CIBIN, Delegación Nuevo León, Instituto Mexicano del Seguro Social
Conjunto Lincoln (Contiguo Servicio de Urgencias Hospital No. 34), Monterrey, Mexico;
b
Universidad Autónoma de Nuevo León, Facultad de
Salud Pública y Nutrición, Monterrey, Mexico;
c
Unidad de Medicina Familiar No. 31, Instituto Mexicano del Seguro Social, San Nicolás de los
Garza, Mexico;
d
Vicerrectoría de Ciencias de la Salud, Universidad de Monterrey, San Pedro Garza García, Mexico;
e
Hospital de Ginecología
y Obstetricia No. 23, Instituto Mexicano del Seguro Social, Monterrey, Mexico;
f
Universidad Autónoma de Nuevo León, Facultad de Medicina,
Monterrey, Mexico
ABSTRACT
Objective: To determine the association between the ABO blood group and preeclampsia.
Methods: This is a case-control study that included patients with (n = 253) and without (n = 457)
preeclampsia/eclampsia in Northeastern Mexico. Data were obtained from electronic medical
records. Binary multiple logistic regression analysis was used for analyzing the association
between the ABO blood group and preeclampsia according to parity status while adjusting for
potential confounders.
Results: Blood groups A, B, and AB showed adjusted odds ratios of 0.6 (95%CI 0.3-1.0), 1.1 (95%CI
0.6-2.2), and 0.3 (95%CI 0.1-1.1) in multiparous women, respectively. No association was found in
nulliparous women either.
Conclusions: ABO blood groups were not associated with preeclampsia in Mexican women.
ARTICLE HISTORY
Received 20 September 2021
Accepted 27 April 2023
KEYWORDS
Preeclampsia; ABO blood-
group system; risk factors;
association
Introduction
Preeclampsia is diagnosed by the presence of de novo
hypertension after the 20th week of gestation accom-
panied by proteinuria and/or evidence of maternal
acute kidney injury, liver dysfunction, neurological
features, hemolysis, thrombocytopenia, or fetal growth
restriction (1). It is a public health problem that com-
plicates 5%-7% of pregnancies worldwide (2) and
causes 16% and 25% of maternal deaths in the United
States (3) and Latin America (4), respectively.
CONTACT Hid Felizardo Cordero-Franco [email protected] Unidad de Investigación Epidemiológica y en Servicios de Salud/CIBIN, Instituto
Mexicano del Seguro Social Conjunto Lincoln (Contiguo Servicio de Urgencias Hospital No. 34), María de Jesús Candia and Ave Lincoln s/n, Monterrey 64730,
Mexico
Supplemental data for this article can be accessed online at https://doi.org/10.1080/10641955.2023.2209640
HYPERTENSION IN PREGNANCY
2023, VOL. 42, NO. 1, 2209640
https://doi.org/10.1080/10641955.2023.2209640
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which
permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been
published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

Preeclampsia is associated with an increased rate of
very low neonatal birth weight, as high as 50%, and
the risk of neonatal death is up to 11 times greater than
that of patients without preeclampsia (5). Several risk
factors for preeclampsia have been described, some of
which are present before the index pregnancy (chronic
hypertension, diabetes, obesity, and previous pree-
clampsia), while others are linked to it (multiple gesta-
tion, assisted reproduction therapies, antiphospholipid
syndrome, and male fetal sex) (1,2–9). In recent years,
blood A and B antigens (blood groups A and B) have
been implicated in the pathophysiology of preeclamp-
sia. The various pathological mechanisms include the
following: a) an increase in von Willebrand factor,
whose prothrombotic activity triggers or exacerbates
pathophysiological events related to the disease (10),
b) a reduction in the placental protein PP13 (11–13),
and c) an increase in E-selectin, tumor necrosis factor-
alpha, and intercellular adhesion molecule-1 bioavail-
ability (12). The pathological mechanism of preeclamp-
sia in blood group O is unclear. Despite this biological
linkage, relevant studies have shown contradictory
results. Some studies have shown an increased risk in
patients of blood groups AB (11,12-14–18), A (14),
B (19), and O (20,21), while others did not find any
association (22–24). A consistent association would
make it possible to easily categorize those women at
risk since the determination of ABO groups is part of
the routine clinical practice of primary pregnancy care.
This study aimed to determine the association
between ABO blood groups and preeclampsia in
a Mexican population. This information may contri-
bute to the identification of patients at a high risk of
preeclampsia during the planning stage of pregnancy or
at the first antenatal visit to allow for the implementa-
tion of preventive and treatment interventions against
preeclampsia.
Methods
Design, patients, and procedures
This case-control study was conducted between 2017 and
2020 in mestizo patients from northeastern Mexico. Cases
comprised patients diagnosed with preeclampsia/eclampsia
by certified gynecologists who followed national and inter-
national guidelines: hypertension after the 20th week of
gestation and proteinuria. In the absence of the latter, they
considered signs of systemic severity such as thrombocyto-
penia and liver, kidney, or neurological dysfunction (n =
253) (25,26). The control group included patients who did
not meet the diagnostic criteria for preeclampsia (n = 457).
Cases and controls who visited our institution for the first
antenatal visit before the 20th week of pregnancy were
consecutively enrolled. Six eligible cases and 49 eligible
controls were excluded because information on blood
group type and other variables was unavailable. An initial
sample size of 186 cases and 372 controls was calculated
based on an odds ratio of 2.42 (for group AB) (15),
a percentage of exposure in cases of 12.9%, and statistical
power of 80%. The final sample was composed of 253 cases
and 457 controls, increasing the statistical power to 87.3%.
The protocol adhered to the institutional, national, and
international standards and regulations on research ethics
and was authorized by the Local Ethics and Research
Committee No. 1912 of the Mexican Institute of Social
Security (approval number R-2018-1912-021). All data
were recorded anonymously, respecting the confidentiality
of the patients. Since the information necessary for the
study was collected only from electronic medical records,
informed consent was not required from patients.
Study variables
The following clinical data were collected: systolic and
diastolic blood pressure at the first antenatal visit (first
trimester), history of gestational diabetes, and gestational
weight gain (weight difference between the last and first
antenatal visit). Obstetrical data included the number of
pregnancies, inter-pregnancy interval in multiparous
women, current multiple pregnancy, number of antenatal
visits, fetal sex, and gestational age at the last antenatal visit.
Medical history data included a history of preeclampsia/
eclampsia, hypertension, type 2 diabetes, pre-pregnancy
overweight/obesity (body mass index≥25 kg/m
2
), and
aspirin use during pregnancy. Sociodemographic data
included information on maternal age, education, and
occupation. Neonatal data included the gestational age,
birth weight, and one- and five-minute Apgar scores.
Laboratory data included the blood group type and Rh
factor. Blood groups were determined using the hemagglu-
tination technique. All data were collected from electronic
medical records. The mean arterial pressure was calculated
from the systolic and diastolic blood pressures using the
following formula: ([systolic blood pressure - diastolic
blood pressure/3] + diastolic blood pressure).
Data analysis
Measures of central tendency and dispersion were esti-
mated for quantitative variables and proportions for
categorical variables. Cases and controls were com-
pared using the Mann-Whitney U test, Kruskal-Wallis
test, or chi-square test, depending on the scale of the
variable. Univariate and multivariate odds ratios (OR)
2H. F. CORDERO-FRANCO ET AL.

with 95% confidence intervals (CIs) were determined
using binary multiple logistic regression. Two models
were run separately, one for nulliparous patients and
the other for multiparous patients. The blood group
was used as an independent variable after classifying
patients according to blood type (A, B, AB, and O; type
O was used as the reference group). Preeclampsia/
eclampsia was the dependent variable (1 = yes), and
confounding variables varied according to nulliparity
status (the model for multiparous patients included
a medical history of preeclampsia (27) and inter-
pregnancy interval (28). Statistical significance was set
at p < 0.05.
Results
Cases and controls had similar maternal (27.8 ± 5.8
vs 28.2 ± 5.7 years, p = 0.23) and gestational ages at
the first antenatal visit (13.2 ± 5.6 vs 13.6 ± 7.5 weeks,
p = 0.30), and an equivalent number of antenatal
visits (8.2 ± 3.5 vs 8.5 ± 4.3, p = 0.85). Preeclampsia
was of early onset (before the 34
th
week of gestation)
in thirteen (5.1%) cases. The proportion of patients
with an educational level of junior high or less, and
medical history of preeclampsia/eclampsia, hyperten-
sion, pre-pregnancy overweight/obesity, and male
fetal sex was higher among cases, while the econom-
ically active occupation was more common among
controls (Table 1). Compared to controls, cases had
higher systolic blood pressure, diastolic blood pres-
sure, and mean arterial pressure at the first antenatal
visit, more weight gain, and a higher proportion of
patients with a history of gestational diabetes; they
had lower gestational age at birth, birth weight, and
Apgar at 1 and 5 minutes (Table 2). The mean birth
weight in the early-onset preeclampsia group was
1563.01 g ±575.05 g, in the late preeclampsia group
was 2755.3 g ±477.8 g, and in controls was 3218.2
grams ±364.3 g (p < 0.001).
ABO blood groups and preeclampsia
Blood group O was the most frequent type (60.6%),
followed by A (22%), B (12.4%), and AB (5.1%). In
addition, a positive Rh factor was the most common
Table 1. Comparison of sociodemographic, medical, and obstetric characteristics between preg-
nant women with and without preeclampsia/eclampsia.
Variable
Cases Controls
(n = 253) (n = 457)
Sociodemographic
Education, junior high or less 133 (52.6%) * 156 (34.1%)
Occupation, economically active 103 (43.5%) 268 (58.9%) *
Medical history
Preeclampsia/eclampsia 52 (20.6%) * 23 (5.0%)
Hypertension 28 (11.1%) * 8 (1.8%)
Type 2 diabetes 5 (2.0%) 8 (1.8%)
Pre-pregnancy overweight/obesity 196 (77.5%) * 272 (59.5%)
Obstetric
Parity, nulliparous 85 (33.6%) 169 (37.0%)
Inter-pregnancy interval≥10 years in women with≥1 pregnancy 15 (8.9%) 19 (6.6%)
Multiple gestation 6 (2.4%) 8 (1.8%)
Gestational age at the last antenatal visit (weeks) 34.2 ± 4.2 33.1 ± 6.4
Aspirin use during pregnancy 10 (4.0%) 24 (5.3%)
Fetal sex (male) 151 (59.7%) * 201 (44.0)
*p < 0.0001.
Table 2. Comparison of blood group and factor type between pregnant women with and without
preeclampsia/eclampsia (cases, n = 253; controls, n = 457).
Variable
Cases
(n = 253)
Controls
(n = 457)
Clinical
Systolic blood pressure at first antenatal visit (mm Hg) 107.5 ± 13.4 ** 101.2 ± 8.9
Diastolic blood pressure at first antenatal visit (mm Hg) 67.8 ± 9.9 ** 64.0 ± 6.3
Mean arterial pressure at the first antenatal visit (mm Hg) 81.2 ± 10.8 ** 76.3 ± 6.3
Gestational diabetes 29 (11.6%) * 28 (6.2%)
Weight gain (kg) 8.7 ± 5.8 ** 7.3 ± 5.0
Perinatal outcome
Gestational age at delivery (weeks) 36.2 ± 3.3 ** 39.0 ± 1.8
Birth weight (g) 2,689.0 ± 745.1 ** 3,214.8 ± 500.0
Apgar score in 1st minute 7.5 ± 1.6 * 8.0 ± 0.7
Apgar score at 5th minute 8.5 ± 1.5 ** 9.0 ± 0.4
*p < 0.01, ** p < 0.001.
HYPERTENSION IN PREGNANCY 3

(97.7%). There was no difference in the frequency of
ABO blood groups and Rh factor between cases and
controls in multiparous (p = 0.152) or nulliparous
women (p = 0.223; Table 3). The unadjusted odds ratios
in multiparous women were as follows: A group = 0.7
(95% CI 0.4-1.1); B group = 1.1 (95% CI 0.6-1.9); and
AB group = 0.4 (95% CI 0.1-1.1). In nulliparous
women, they were as follows: A group = 1.5 (95% CI
0.8-2.8); B group = 1.5 (95% CI 0.5-2.5); and AB group
= 2.0 (95% CI 0.7-5.9). The lack of association contin-
ued even after adjusting for confounding variables
(Tables 4 and 5). Additionally, we identified previous
preeclampsia, chronic hypertension, obesity, higher
mean blood pressure at the first prenatal visit, and
male fetal sex increased the risk of preeclampsia in
multiparous women. The last two also increased the
risk of preeclampsia in nulliparous women (Table S1
and S2, respectively).
Discussion
This study examined the association between ABO
blood groups and preeclampsia in Mexican women,
adjusting for multiple confounding factors. Before dis-
cussing the main results, it is pertinent to mention that
women with preeclampsia had clinical and obstetric
characteristics that were consistent with prior knowl-
edge (27,29), that is, they were more exposed than
controls to previous preeclampsia, chronic hyperten-
sion, higher mean arterial pressure at the first prenatal
visit, and preexisting overweight/obesity. In addition,
the distribution of the ABO blood groups of the study
sample was similar to that reported in the Mexican
population (30).
Regarding our research question, we found no asso-
ciation between ABO blood groups and preeclampsia in
a Mexican population, which was similar to other stu-
dies (22–24), but opposite to others (11,12-14–17-19–
21-31). The discrepancy may be due to differences in
controlling confounding factors that could favor or
vanish the association. Only one of three studies with
results of no association (22–24) controlled for mater-
nal age and parity (23). In studies reporting an associa-
tion, there is also a lot of heterogeneity in terms of
adjustment for confounders. Mital et al. (12),
Manjunatha et al. (16), and Avci et al. (17) did not
adjust for confounding factors. Others did for age
(11,14,18,20,21) body mass index (11,14,18,20,21), par-
ity (14,18,20), and residence (11,20). Hiltunen et al.
(18) included Factor V Leiden (a genetic disorder char-
acterized by a poor anticoagulant response to activated
Protein C and an increased risk for venous throm-
boembolism) (32). Parity is an important confounding
variable because nulliparity is a well-known risk factor
for preeclampsia (2,4,26,33,34). Additionally, medical
history of preeclampsia (2,4,27) and inter-pregnancy
interval (28) only concerns women with two or more
pregnancies. So, the association analysis must consider
parity status. We did not find an association in nulli-
parous or multiparous women. Aghasadeghi et al. (23)
also found no association after controlling for parity.
Table 3. Comparison of blood group and factor type between pregnant women with and without preeclampsia/eclampsia
(cases, n = 253; controls, n = 457).
Multiparous Nulliparous
ABO blood groups
Cases
(n = 168)
Controls
(n = 288) p-value
Cases
(n = 85)
Controls
(n = 169) p-value
Type O 111 (66.1%) 170 (59.0%) 0.152 45 (52.9%) 104 (61.5%) 0.223
Type A 31 (18.5%) 69 (24.0%) 22 (25.9%) 34 (20.1%)
Type B 22 (13.1%) 32 (11.1%) 11 (12.9%) 23 (13.6%)
Type AB 4 (2.4%) 17 (5.9%) 7 (8.2%) 8 (13.6%)
Rh + blood group 164 (97.6%) 282 (97.9%) 1.000 84 (98.8%) 164 (97.0%) 0.667
Table 5. Crude and adjusted odds ratios between ABO blood
group and preeclampsia. Multivariate logistic regression model
among nulliparous pregnant women (cases, n = 85; controls, n
= 169).
Odds ratio (95% confidence interval)
Blood group Crude Adjusted
a
Type O 1.0 1.0
Type A 1.5 (0.8-2.8) 1.3 (0.6-2.7)
Type B 1.1 (0.5-2.5) 0.9 (0.4-2.3)
Type AB 2.0 (0.7-5.9) 2.2 (0.6-7.2)
a
By maternal age, chronic hypertension, pre-pregnancy overweight/obesity,
mean blood pressure at the first antenatal visit (first trimester), multiple
gestation, aspirin use during pregnancy, and fetal sex.
Table 4. Crude and adjusted odds ratios between ABO blood
group and preeclampsia. Multivariate logistic regression model
among multiparous pregnant women (cases, n = 168; controls,
n = 288).
Odds ratio (95% confidence interval)
Blood group Crude Adjusted
a
Type O 1.0 1.0
Type A 0.7 (0.4-1.1) 0.6 (0.3-1.0)
Type B 1.1 (0.6-1.9) 1.1 (0.6-2.2)
Type AB 0.4 (0.1-1.1) 0.3 (0.1-1.1)
a By maternal age, inter-pregnancy interval, medical history of preeclamp-
sia/eclampsia, chronic hypertension, type 2 diabetes, pre-pregnancy over-
weight/obesity, mean blood pressure at the first antenatal visit (first
trimester), multiple gestation, aspirin use during pregnancy, and fetal sex.
4H. F. CORDERO-FRANCO ET AL.