European Journal of Obstetrics and Gynecology 298 (2024) 158–164

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European Journal of Obstetrics & Gynecology and

Reproductive Biology
journal homepage: www.journals.elsevier.com/european-journal-of-obstetrics-and-gynecology-and-
reproductive-biology

Full length article

Abnormal maternal apolipoprotein levels during pregnancy are risk factors

for preterm birth in women with dichorionic twin pregnancies: A
retrospective study
Pingping Su , Yao Su , Xinrui Jia , Huan Han , Wenjiao Li *, Hao Ying
Department of Obstetrics, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China

A R T I C L E I N F O A B S T R A C T

Keywords: Objective: In singleton-pregnant women, abnormal maternal apolipoprotein levels have been confirmed as a risk
Apolipoprotein factor for preterm birth. However, there are currently no studies on the relationship of the related research in
Preterm birth twin-pregnant women.
Dichorionic
Methods: This single-center retrospective study included 743 dichorionic twin-pregnant women who delivered
Twin pregnancy
between January 2019 and December 2020. Twins delivered before 37 weeks gestation were categorized as the
preterm group, while those delivered at or after 37 weeks gestation were classified as the term group. Maternal
serum apolipoprotein A1 (ApoA1) levels, apolipoprotein B (ApoB) levels, and the ApoB/ApoA1 ratio were
measured in the first trimester(6–14 weeks), the second trimester(18–28 weeks) and the third trimester(after 28
weeks). We conducted SPSS analysis to evaluate the correlation between ApoA1 levels, ApoB levels, the ApoB/
ApoA1 ratio and preterm birth.
Results: Among the 743 included dichorionic twin-pregnant women, 53.57 % (398/743) delivered preterm.
Compared with the term group, the ApoA1 levels in the third trimester were lower (p < 0.001), while the Apo B/
ApoA1 ratio was higher in the second (p = 0.01) and third trimesters in the preterm group (p = 0.001). When
preterm birth was categorized as iatrogenic and spontaneous preterm birth, the results were similar. In the
analysis stratified by prepregnancy BMI, a higher risk of preterm birth was associated with low ApoA1 levels and
a high Apo B/ApoA1 ratio in the second and third trimesters only among the subgroup of overweight/obese
dichorionic twin-pregnant women.
Conclusions: Low ApoA1 levels and a high Apo B/ApoA1 ratio during the second and third trimesters were
associated with a high incidence of preterm birth for overweight/obese dichorionic twin-pregnant women.

Introduction metabolomics, which not only helps to understand the mechanisms of

Due to the rapid development of assisted reproductive technology,
the incidence of twin pregnancies has increased dramatically in the past
few decades [1,2]. The incidence of twin pregnancies in the United
States was 32.6 per 1000 pregnancies in 2018[3]. Twin-pregnant
women have 10 times the risk of preterm birth and 5 times the risk of
serious complications compared with singleton-pregnant women [4].
The health needs of preterm infants are a heavy burden for families and
society, and reducing the preterm birth rate has become a major public
health issue [5]. Therefore, early identification of potentially modifiable
risk factors to reduce the incidence of preterm birth is critical. In recent
years, the focus on preterm birth has shifted to the field of
preterm birth but also helps to screen people at high risk of preterm
birth. Studies have shown that preterm birth may be associated with
maternal dyslipidemia during pregnancy [6–10].
Apolipoproteins (Apos) are key components in lipid metabolism and
transport. ApoA1 is the main structural protein of high-density lipo­
protein (HDL) and has anti-atherosclerotic effects. ApoB is the major
protein molecule associated with atherogenic lipoprotein particles[11].
The Apo B/ApoA1 ratio reflects the balance between atherogenic and
anti-atherogenic lipoprotein particles and is associated with cardiovas­
cular disease, insulin resistance, and metabolic syndrome in nonpreg­
nant populations[12–14]. Previous studies found that ApoB, ApoA1, and
the Apo B/ApoA1 ratio are associated with preterm birth in singleton-

* Corresponding author.
E-mail address: liwenjiao2006@163.com (W. Li).

https://doi.org/10.1016/j.ejogrb.2024.05.013
Received 26 November 2023; Received in revised form 10 May 2024; Accepted 12 May 2024
Available online 13 May 2024
0301-2115/© 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
P. Su et al.
pregnant women [15–17]. However, the relationship between APOs and
preterm birth in twin-pregnant women has not been studied. Because of
the more severe adverse outcomes of twin preterm infants, it is partic­
ularly important to clarify the relationship between APOs and preterm
birth in twin-pregnant women. In addition, it is not clear whether pre­
pregnancy BMI and APOs are associated with preterm birth in twin-
pregnant women.
Therefore, we conducted a retrospective study of twin pregnancies to
measure maternal ApoA1 and ApoB concentrations longitudinally and
the Apo B/ApoA1 ratio, explore their trends during pregnancy, and
investigate the association between APO levels and preterm birth in
twin-pregnant women stratified by prepregnancy BMI.
Methods
Study population
Participants were 1309 twin-pregnant women who underwent
formal prenatal examination and delivered in Shanghai First Maternity
and Infant Hospital Affiliated to Tongji University from January 2019 to
December 2020. The exclusion criteria were as follows: 1) women
without lipid screening data; 2) women diagnosed with hypertension,
diabetes, or thyroid diseases before pregnancy; 3) stillbirth or infant
deformity; 4) maternal age < 18 or > 45 years; 6) gestational age < 28
weeks or > 42 weeks; or 7) monochorionic twin pregnancy. Finally, 743
dichorionic twin-pregnant women were included in this study.
Data collection and measures
At the first prenatal visit before 14 weeks of gestation, data on
maternal characteristics were recorded, including age, height, pre­
pregnancy weight, gestational week, parity, medical history, reproduc­
tive and prenatal history, and mode of conception. Maternal blood
pressure and pregnancy complications were recorded at each examina­
tion. All participants were followed until postpartum.
Blood samples were collected from peripheral venous blood after 10
to 12 h of fasting. Serial lipid assessments were performed in all three
trimesters: in the first trimester (6–14 weeks gestation), the second
trimester (18–28 weeks gestation), and the third trimester (after 28
weeks gestation). Serum ApoA1 and ApoB concentrations were
measured using latex agglutination immunoturbidimetry by a fully
automatic instrument (Labospect 008; Hitachi, Japan), and the intra­
batch and interbatch coefficients of variation (CV) were determined to
be 5.3 % and 9.2 %, respectively.
Operational definitions
BMI was calculated as the weight divided by the square of the height,
and the unit was kg/m2. The low-weight group included patients with a
BMI < 18.5 kg/m2. The normal-weight group included patients with a
BMI between 18.5 and 25 kg/m2. The overweight and obese group
(OWO) included patients with a BMI ≥ 25 kg/m2. Weight gain was
defined as weight gain from the time of pregnancy confirmation to the
time of delivery. Gestational age was calculated according to the date of
the last menstrual period and corrected using ultrasound measurements.
Chorionicity was determined by ultrasonography in the first trimester
according to the ISUOG practice guidelines published in 2016 [18].
Preterm birth was defined as a delivery with a gestational age of less
than 37 weeks. Iatrogenic preterm birth was defined as preterm birth
following labor induction or cesarean delivery due to maternal com­
plications or fetal indications. Spontaneous preterm birth was defined as
preterm birth that followed spontaneous labor and preterm prelabor
rupture of membranes [19].
Hypertensive disorders of pregnancy (HDP) included gestational
hypertension and preeclampsia, defined as the first onset of hyperten­
sion after 20 weeks of gestation, with a systolic blood pressure ≥ 140
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European Journal of Obstetrics & Gynecology and Reproductive Biology 298 (2024) 158–164
mmHg or a diastolic blood pressure ≥ 90 mmHg, with or without a
positive urinary protein test. The diagnosis of gestational diabetes
mellitus (GDM) depended on the oral glucose tolerance test (OGTT) at
24–28 weeks gestation. The normal range of blood glucose values at the
three time points was < 5.1, <10.0, and < 8.5 mmol/L. If the blood
glucose value exceeded the above standards at any time, GDM was
diagnosed. Intrahepatic cholestasis of pregnancy (ICP) was defined as
unexplained pruritus and elevated serum bile acids(≥10 μmol/L) that
completely normalizes after delivery in the absence of other causes of
liver dysfunction or itching.
Statistical analysis
Continuous variables are presented as the means (standard de­
viations [SDs]), and between-group differences were analyzed using
independent Student’s t test. Categorical variables are reported as fre­
quencies and proportions and were tested using the chi-square (χ2) or
Fisher’s exact test, as appropriate. To analyze the relationship between
lipid levels and the risk of preterm birth, a logistic regression model was
employed. As there are no standard reference ranges of lipid profiles for
pregnant women thus far, maternal serum ApoA1, Apo B and Apo B/
ApoA1 ratio were categorized into three groups according to the
quantile of each parameter: low group (<10 %), optimal group (10
%-90 %) and high group (>90 %). The median group was set as the
reference in all analyses. Several variables, including maternal age,
parity, prepregnancy BMI and weight gain, were suspected to be con­
founders prior to or according to the univariate analyses.
All statistical analyses were performed in SPSS version 16.0, and p <
0.05 was considered statistically significant.
Results
The clinical characteristics of the study group
Among the 1309 enrolled pregnant women, 743 patients with
dichorionic twin pregnancies met the inclusion criteria (Fig. 1). The
preterm birth rate in this cohort study was 53.57 % (398/743), and the
average gestational age was 34.94 ± 1.90 weeks. Twins delivered before
37 weeks gestation were categorized into the preterm group, while those
delivered at or after 37 weeks gestation were classified into the term
group. There were no significant differences in maternal age, parity, or
IVF-ET use between the two groups. The proportion of underweight
participants was 11.56 % in the preterm group and 6.38 % in the term
group. The weight gain from prepregnancy until delivery in the preterm
group was significantly lower than that in the term group (14.48 vs.
15.99, p < 0.001). The incidence of HDP and ICP was also higher in the
preterm group than in the term group (HDP: 119 vs. 39, p < 0.001; ICP:
68 vs. 9, p < 0.001). The incidence of GDM between the two groups was
similar. Gestational age for blood draw in the third trimester was higher
in the term group than in the preterm group (36.17 vs. 34.25 weeks, p <
0.001) (Table 1).
Maternal ApoA1 and Apo B levels and the Apo B/ApoA1 ratio during
pregnancy
Maternal apolipoprotein levels during pregnancy are presented in
Fig. 2 and Table S1. Our results showed that the ApoA1 concentration
increased from the first to the second trimester, with a decrease in the
third trimester. In contrast, Apo B levels and the Apo B/ApoA1 ratio
increased progressively throughout pregnancy. Meanwhile, there were
similar trends in the term and preterm birth groups. Moreover,
compared with the term birth group, the preterm birth group had lower
ApoA1 levels in the third trimester (1.89 vs. 1.78 g/L, p < 0.001) and
higher Apo B/ApoA1 ratios in the second and third trimesters (second:
0.66 vs. 0.70 g/L, p = 0.01; third: 0.78 vs. 0.83 g/L, p = 0.001) (Fig. 3
and Table S2). In addition, no significant difference in Apo B levels was
P. Su et al. European Journal of Obstetrics & Gynecology and Reproductive Biology 298 (2024) 158–164

Fig. 1. Study flow diagram.

observed between the two groups during pregnancy.

Table 1
The demographic and clinical characteristics of study participants.
Maternal ApoA1 levels, Apo B/ApoA1 ratio and risks of preterm birth
Characteristics Overall (n Preterm birth Term birth p
= 743) (n = 398) (n = 345)
The association between maternal apolipoprotein levels and the risk
Maternal age(years) 32.51(3.60) 32.52(3.71) 32.51(3.49) 0.98 of preterm birth is shown in Table 2. Compared with women with
Pre-pregnancy(kg/ 0.02
normal levels (10-90th percentile), women with low ApoA1 levels
m2)
≤18.4 68(9.15) 46(11.56) 22(6.38) (<10th percentile) and a high Apo B/ApoA1 ratio (>90th percentile)
18.5–24.9 537(72.27) 287(72.11) 250(72.45) had an increased risk of preterm birth in the second trimester and third
≥25 138(18.57) 65(16.33) 73(21.16) trimester. After adjusting for potential confounders including maternal
Weight gain(kg） 15.18(4.88) 14.48(5.00) 15.99(4.62) <0.001
age, parity, prepregnancy BMI, weight gain and gestational age of lipid
Nulliparous-n(%) 659(88.69) 352(88.44) 307(88.99) 0.91
In vitro fertilization-n 526(70.79) 280(70.35) 246(71.30) 0.84
measurement, low ApoA1 levels were associated with 111 % (aOR =
(%) 2.11, 95 % CI: 1.19–3.75) and 158 % (aOR = 2.58, 95 % CI: 1.29–5.17)
Gestational age at 35.98(1.79) 34.94(1.90) 37.18(0.23) <0.001 higher risks of preterm birth during the second and third trimesters,
delivery(w) respectively. A high Apo B/ApoA1 ratio was also associated with an
HDP-n(%) 158(21.26) 119(29.90) 39(11.30)
increased risk of preterm birth in the second trimester and third
<0.001
ICP-n(%) 77(10.36) 68(17.09) 9(2.61) <0.001
GDM-n(%) 138(18.57) 78(19.60) 60(17.39) 0.40 trimester (aOR = 2.18, 95 % CI: 1.28–3.69 and aOR = 2.79, 95 % CI:
Mean twin 2471.65 2275.78 2697.62 <0.001 1.41–5.52, respectively). There was no association of Apo B levels with
birthweight(g) (403.95) (410.78) (248.27) the risk of preterm birth during pregnancy.

Gestational age for The relationship between the rate of preterm birth and maternal ApoA1
blood draw(w) levels and the Apo B/ApoA1 ratio stratified by spontaneous vs. Iatrogenic
First trimester 11.09(1.89) 11.14(1.82) 11.03(1.97) 0.43
preterm birth
Second trimester 25.42(1.17) 25.39(1.14) 25.44(1.21) 0.55
Third trimester 35.14(1.82) 34.25(2.00) 36.17(0.75) <0.001
The relationship between preterm birth and maternal apolipoprotein
Continuous variables were expressed as mean(SD), and categorical variables
levels was further stratified by causes of preterm birth: spontaneous vs.
were represented as frequencies with proportions(%).
iatrogenic preterm birth (Tables 3 and 4). The main finding was an
increased risk of spontaneous and iatrogenic preterm birth in individuals
with low ApoA1 levels and a high Apo B/ApoA1 ratio in the second and
third trimesters before and after adjusting for potential confounders. In

Fig. 2. The levels of apolipoprotein protein in different trimesters.

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Fig. 3. The levels of apolipoprotein profile of term and preterm birth in different trimesters.

Table 2 Table 3
Maternal apolipoprotein profile in the second and third trimesters and risk of Maternal apolipoprotein profile in the second trimester and risks of spontaneous
preterm birth. and iatrogenic preterm birth.
Apolipoprotein OR (95 % CI) OR (95 % CI) Apolipoprotein Spontaneous preterm birth(n Iatrogenic preterm birth(n =
second trimester third trimester = 152) 246)
OR(95 % CI) OR(95 % CI)
Model A Model B Model A Model B
Model A Model B Model A Model B
ApoA1
10th 2.45 2.11 2.04 2.58 ApoA1
(1.39–4.32) (1.19–3.75) (1.16–3.59) (1.29–5.17) 10th 3.11 2.57 2.07 1.99
10th-90th ref ref ref ref (1.61–6.01) (1.28–5.15) (1.10–3.89) (1.05–3.77)
90th 1.06 1.01 0.86 0.85 10th-90th ref ref ref ref
(0.67–1.71) (0.63–1.63) (0.53–1.38) (0.48–1.52) 90th 1.10 1.00 1.05 1.00
(0.59–2.06) (0.52–1.94) (0.61–1.78) (0.58–1.71)

ApoB
10th 0.90 0.96 1.38 1.52 ApoB
(0.53–1.54) (0.55–1.66) (0.81–2.37) (0.77–2.99) 10th 0.80 0.92 0.96 1.01
10th-90th ref ref ref ref (0.38–1.69) (0.42–2.04) (0.53–1.71) (0.55–1.86)
90th 1.58 1.34 1.08 0.93 10th-90th ref ref ref ref
(0.96–2.57) (0.81–2.20) (0.67–1.73) (0.52–1.68) 90th 1.49 1.19 1.63 1.45
(0.80–2.80) (0.61–2.30) (0.95–2.80) (0.83–2.52)

ApoB/ApoA1
10th 1.43 1.50 0.88 0.68 ApoB/ApoA1
(0.90–2.24) (0.95–2.39) (0.55–1.41) (0.36–1.27) 10th 1.33 1.55 1.48 1.54
10th-90th ref ref ref ref (0.72–2.44) (0.81–2.97) (0.90–2.45) (0.92–2.55)
90th 2.47 2.18 3.05 2.79 10th-90th ref ref ref ref
(1.47–4.15) (1.28–3.69) (1.76–5.31) (1.41–5.52) 90th 3.14 2.70 2.07 1.91
(1.71–5.78) (1.41–5.16) (1.15–3.71) (1.06–3.44)
Model A was unadjusted. Model B was adjusted for maternal age, parity, pre-
pregnancy BMI, gestational age of lipid measurement and weight-gain Model A was unadjusted. Model B was adjusted for maternal age, parity, pre-
pregnancy BMI, gestational age of lipid measurement and weight-gain
contrast, Apo B levels were not associated with the rate of spontaneous
or iatrogenic preterm birth during pregnancy. low ApoA1 levels and a high Apo B/ApoA1 ratio in the second and third
trimesters were associated with an increased risk of preterm birth.
Further analysis showed that abnormal apolipoprotein levels only
The ApoA1 levels and Apo B/ApoA1 ratio in the OWO group were increased the risk of preterm birth in OWO dichorionic twin-pregnant
correlated with preterm birth women but not in dichorionic twin-pregnant women with low weight
or normal weight. It is suggested that controlling prepregnancy body
After stratifying by prepregnancy BMI, we further analyzed apoli­ weight and screening apolipoprotein levels during pregnancy are
poprotein levels and the risk of preterm birth. The results showed that a important to reduce the risk of preterm birth in dichorionic twin-
high risk of preterm birth was associated with low ApoA1 levels and a pregnant women.
high Apo B/ApoA1 ratio only in OWO women but not in underweight or Fat accumulation and hyperlipidemia are characteristic features of
normal-weight women (Tables 5 and 6). In the adjusted model, low maternal lipid metabolism during pregnancy. The changes are essential
ApoA1 levels and a high Apo B/ApoA1 ratio increased the risk of pre­ for nutrient supply to fetal growth and development [20,21]. In the
term birth among women with OWO in the second trimester (aOR = present study, we found that Apo B levels increased gradually during
2.36, 95 % CI: 1.21–4.60 and aOR = 2.60, 95 % CI: 1.39–4.86, respec­ pregnancy, while ApoA1 levels increased from the first to second
tively) and third trimester (aOR = 5.16, 95 % CI: 2.06–12.94 and aOR = trimester only and slightly decreased from the second to the third
4.20, 95 % CI: 1.76–10.06, respectively). trimester. Previous studies found that the HDL concentration signifi­
cantly increased in the second trimester and slightly decreased in the
Discussion third trimester, while the LDL concentration increased progressively
throughout pregnancy [22,23]. Our findings regarding the apolipopro­
This is the first study to date to investigate the effect of maternal tein profile were consistent with changes in HDL and LDL levels during
apoprotein levels during pregnancy on the risk of preterm birth in pregnancy and aligned with the clinical significance of apolipoproteins.
dichorionic twin-pregnant women. This retrospective study found that

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Table 4 Apo B/ApoA1 ratio and preterm birth. ApoA1 can manifest antioxidant
Maternal apolipoprotein profile in the third trimester and risks of spontaneous and anti-inflammatory effects and stimulate both endothelial produc­
and iatrogenic preterm birth. tion of nitric oxide and release of prostacyclin from the endothelium
Apolipoprotein Spontaneous preterm birth(n = Iatrogenic preterm birth(n = [27–29]. The Apo B/ApoA1 ratio could represent the balance between
152) 246) atherogenic and antiatherogenic lipoprotein particles. The higher the
OR(95 % CI) OR(95 % CI) level of the Apo B/ApoA1 ratio is, the more likely cholesterol is to be
Model A Model B Model A Model B deposited in the arterial wall, thereby provoking atherogenesis [30].
ApoA1 Therefore, low ApoA1 and a high Apo B/ApoA1 ratio are related to
10th 2.05 3.08 2.04 2.56 increased levels of inflammation and oxidative stress and higher
(1.03–4.08) (1.13–8.38) (1.10–3.78) (1.20–5.50) atherogenic lipoproteins, which are known contributors to preterm birth
10th-90th ref ref ref ref [8,31–33]. In our study, Apo B levels during pregnancy were not
90th 0.59 0.60 1.03 0.99
(0.29–1.22) (0.21–1.74) (0.61–1.74) (0.54–1.82)
significantly different between the term and preterm groups, which was
inconsistent with the result of a previous study in singleton-pregnant
women [17]. Further studies are needed to elucidate this issue.
ApoB
10th 1.62 1.85 1.23 1.42 Preterm births can be categorized as spontaneous or iatrogenic based
(0.84–3.12) (0.75–4.53) (0.66–2.29) (0.66–3.06) on their causes. Distinguishing spontaneous from iatrogenic preterm
10th-90th ref ref ref ref births is crucial [34]. A recent study showed an increase in preterm birth
90th 0.65 0.48 1.35 1.15 rates among women with dichorionic twin pregnancies over a ten-year
(0.31–1.36) (0.17–1.34) (0.81–2.25) (0.62–2.15)
period between 2007 and 2017, driven by an increase in iatrogenic
preterm births [35]. Therefore, it is necessary to verify the effect of
ApoB/ApoA1
atherogenic lipoproteins on the risk of preterm birth by fully considering
10th 0.91 0.83 0.86 0.71
(0.47–1.73) (0.33–2.10) (0.50–1.48) (0.36–1.40)
the causes of preterm birth. In our study, the incidence of iatrogenic
10th-90th ref ref ref ref preterm birth was 33.11 %, which was consistent with that in a retro­
90th 3.88 3.97 2.57 2.58 spective cohort study in which the incidence of iatrogenic preterm birth
(2.06–7.32) (1.54–10.24) (1.40–4.73) (1.22–5.44) among 4045 dichorionic twin pregnancies was 39.5 % [35]. Moreover,
Model A was unadjusted. Model B was adjusted for maternal age, parity, pre- our results showed that low ApoA1 levels and a high Apo B/ApoA1 ratio
pregnancy BMI, gestational age of lipid measurement and weight-gain predisposed the pregnancy not only to iatrogenic preterm birth may due
to an increased risk of maternal or fetal complications but also to
In addition, our study showed that the Apo B/ApoA1 ratio increased spontaneous preterm birth may due to the pathological effects of deviant
gradually during gestation, which had not been reported in previous apolipoproteins. Recent studies found that low ApoA1 levels and a high
research. Apo B/ApoA1 ratio were related to an elevated risk of preeclampsia
Data on the relationship between maternal apolipoprotein levels and [15,36], which may be one of the reasons why deviant apolipoproteins
preterm birth are limited. Some studies have reported an association increase the risk of iatrogenic preterm birth. Additional studies should
between ApoA1 levels during pregnancy and preterm birth, while others be performed to elucidate the underlying mechanisms between low
found no such association.The results are controversial and mainly ApoA1 and a high Apo B/ApoA1 ratio and both subgroups of preterm
focused on singleton-pregnant women [17,24–26]. Moreover, only one birth.
study indicated that high levels of serum Apo B and the Apo B/ApoA1 Our study found that low ApoA1 levels and a high Apo B/ApoA1
ratio during mid-pregnancy were associated with an increased risk of ratio in the second and third trimesters contribute to a significantly
preterm birth in singletons. However, the relationship between maternal increased risk of preterm birth only among the OWO group. This sug­
apolipoprotein levels and preterm birth in dichorionic twin-pregnant gests that lower ApoA1 levels and a higher Apo B/ApoA1 ratio are more
women is still unknown. In this study, we found that low ApoA1 crucial factors in predicting preterm birth in the OWO group.A previous
levels and a high Apo B/ApoA1 ratio in the second and third trimesters study showed that overweight nonpregnant participants had a higher
were associated with an increased risk of preterm birth in dichorionic Apo B/ApoA1 ratio and lower ApoA1 levels than normal-weight
twin pregnancies. Oxidative stress and inflammation might be involved nonpregnant participants [37]. Therefore, it can be seen that the
in the mechanisms of association between low ApoA1 levels and a high higher the BMI of pregnant women is, the more prone they are to

Table 5
Maternal apolipoprotein profile in the second trimester and risk of preterm birth stratified by pre-pregnancy BMI.
Apolipoprotein BMI ≤ 18.4 BMI18.5–24.9 BMI ≥ 25.0
OR(95 % CI) OR(95 % CI) OR(95 % CI)

Model A Model B Model A Model B Model A Model B

ApoA1
10th 2.06(0.21–19.91) 1.95(0.19–19.65) 1.84(0.49–6.86) 1.18(0.29–4.81) 2.66(1.37–5.13) 2.36(1.21–4.60)
10th-90th ref ref ref ref ref ref
90th 1.16(0.31–4.32) 0.95(0.24–3.74) 1.84(0.49–6.86) 1.86(0.46–7.45) 0.87(0.50–1.52) 0.84(0.48–1.47)

ApoB
10th 0.51(0.03–8.64) 0.44(0.03–7.72) 1.22(0.40–3.69) 1.23(0.38–4.02) 0.90(0.48–1.69) 0.91(0.48–1.73)
10th-90th ref ref ref ref ref ref
90th 3.08(0.35–27.34) 3.13(0.34–28.70) 2.13(0.59–7.68) 1.93(0.51–7.37) 1.40(0.80–2.44) 1.23(0.70–2.19)

ApoB/ApoA1
10th 1.80(0.34–9.57) 1.42(0.25–8.00) 1.60(0.58–4.36) 1.50(0.51–4.37) 1.35(0.78–2.32) 1.41(0.81–2.44)
10th-90th ref ref ref ref ref ref
90th 1.03(0.17–6.16) 1.00(0.16–6.21) 2.04(0.63–6.65) 1.71(0.50–5.92) 2.87(1.55–5.32) 2.60(1.39–4.86)

Model A was unadjusted. Model B was adjusted for maternal age, parity, pre-pregnancy BMI, gestational age of lipid measurement and weight-gain

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Table 6
Maternal apolipoprotein profile in the third trimester and risk of preterm birth stratified by prepregnancy BMI.
Apolipoprotein BMI ≤ 18.4 BMI18.5–24.9 BMI ≥ 25.0
OR(95 % CI) OR(95 % CI) OR(95 % CI)

Model A Model B Model A Model B Model A Model B

ApoA1
10th 0.08(0.01–1.79) 0.23(0.02–3.14) 0.80(0.24–2.67) 0.68(0.13–3.57) 4.42(2.01–9.71) 5.16(2.06–12.94)
10th-90th ref ref ref ref ref ref
90th 0.33(0.08–1.30) 0.20(0.03–1.29) 1.12(0.41–3.03) 1.17(0.31–4.36) 0.88(0.49–1.60) 0.95(0.47–1.92)

ApoB
10th 0.71(0.11–4.63) 0.59(0.06–5.53) 1.71(0.56–5.27) 2.29(0.57–9.21) 1.44(0.75–2.75) 1.37(0.60–3.16)
10th-90th ref ref ref ref ref ref
90th 1.18(0.21–6.70) 3.40(0.46–25.10) 2.57(0.73–9.31) 0.73(0.13–4.05) 0.88(0.51–1.53) 0.84(0.42–1.65)

ApoB/ApoA1
10th 0.67(0.17–2.69) 0.43(0.06–3.02) 1.05(0.39–2.80) 1.42(0.39–5.11) 0.83(0.46–1.51) 0.52(0.23–1.15)
10th-90th ref ref ref ref ref ref
90th 0.90(0.15–5.36) 0.46(0.03–7.12) 1.33(0.45–3.95) 1.56(0.39–6.32) 5.02(2.40–10.50) 4.20(1.76–10.06)

Model A was unadjusted. Model B was adjusted for maternal age, parity, prepregnancy BMI, gestational age of lipid measurement and weight-gain.

increased atherogenic lipoprotein levels during pregnancy. Moreover, Foundation of China (82171684) and the National Key Research and
obesity, persistent inflammation and oxidative stress are all tightly Development Program (2022YFC2704600).
associated [38]. As a result, we speculated that high BMI strengthened
the effects of low ApoA1 levels and a high Apo B/ApoA1 ratio on pre­ CRediT authorship contribution statement
term birth.However, no such association with preterm birth was found
in the normal and underweight groups. A possible explanation is that Pingping Su: Writing – original draft, Data curation. Yao Su:
lipid metabolism in low-and normal-weight individuals differ from that Investigation, Formal analysis. Xinrui Jia: Investigation, Formal anal­
in OWO individuals, leading to different effects of lipid metabolism on ysis. Huan Han: Investigation, Formal analysis. Wenjiao Li: Writing –
preterm birth among three groups. It may be beneficial to conduct review & editing, Funding acquisition, Conceptualization. Hao Ying:
additional prospective studies in order to provide further confirmation Conceptualization, Project administration.
of our findings.
Our study has several strengths. This was the first study on maternal
Declaration of competing interest
apolipoprotein levels in dichorionic twin-pregnant women with preterm
birth with a relatively large sample size. Furthermore, we tracked the
The authors declare that they have no known competing financial
trajectory of apolipoprotein levels throughout pregnancy and separately
interests or personal relationships that could have appeared to influence
discussed in detail the relationship between maternal apolipoprotein
the work reported in this paper.
levels and the risks of spontaneous and iatrogenic preterm birth. How­
ever, some limitations should be discussed. First, chorionicity is one of
Acknowledgments
the most important factors contributing to the development of preterm
birth in twin pregnancies. The inclusion of only dichorionic twins in this
We thank Xiujuan Su for her contributions to the data analysis.
study narrowed its generalizability to monochorionic twins. Second,
apolipoprotein levels vary according to ethnicity [39,40]. In this study,
Appendix A. Supplementary data
we did not document ethnicity. Third, this was a retrospective study in a
single center, which means that the use of samples obtained from only
Supplementary data to this article can be found online at https://doi.
one hospital may affect the validity of the conclusions.
org/10.1016/j.ejogrb.2024.05.013.

Conclusions
References

For OWO dichorionic twin-pregnant women, low APOA1 levels and a
high Apo B/APOA1 ratio in the second and third trimesters increase the
incidence of preterm birth. This suggests that controlling prepregnancy
weight and monitoring apolipoprotein levels during pregnancy may
help to reduce the incidence of preterm birth in dichorionic twin-
pregnant women.
Ethical approval statement
This study received ethical approval(KS23245).
Consent for publication
Not applicable.
Availability of data and materials.
The datasets used and analyzed during the current study are avail­
able from the corresponding author upon reasonable request.
Funding
This study was supported by a project of the National Natural Science
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