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© Translational Pediatrics. All rights reserved. Transl Pediatr 2021;10(9):2347-2354 | http://dx.doi.org/10.21037/tp-21-400
Original Article
Multiple regression analysis of perinatal conditions, physical
development, and complications in assisted reproduction
singletons
Junfeng Li1, Xiuhong Fu1, Jingshang Lv2, Lina Cui2, Rongxiang Li1, Aihong Bai1, Haoran Wang3,
Xian Tang4
1Department of Reproductive Medicine, Luohe Central Hospital of Henan Province, Luohe, China; 2Department of Obstetrics and Gynecology,
Luohe Central Hospital of Henan Province, Luohe, China; 3Department of Cardiology, Luohe Central Hospital of Henan Province, Luohe, China;
4Department of Reproductive Medicine, Loudi Central Hospital of Hunan Province, Loudi, China
Contributions: (I) Conception and design: J Li, X Fu; (II) Administrative support: J Lv, L Cui; (III) Provision of study materials or patients: J Li, X
Fu, J Lv; (IV) Collection and assembly of data: R Li, A Bai; (V) Data analysis and interpretation: J Li, H Wang, X Tang; (VI) Manuscript writing: All
authors; (VII) Final approval of the manuscript: All authors.
Correspondence to: Xian Tang. Department of Reproductive Medicine, Loudi Central Hospital of Hunan Province, No. 51 Changqing Road, Loudi,
China. Email: ljijunfeng2021@163.com.
Background: There is no clear clinical conclusion on whether assisted reproductive technology (ART)
increases maternal and child risk and affects infant birth and development. This study aimed to perform
a multiple regression analysis of the perinatal maternal and infant conditions in an assisted reproductive
singleton pregnancy and the physical development and complications of such infants at 6 months old.
Methods: This study enrolled 145 singleton pregnant women who were admitted to Luohe Central
Hospital between December 2017 and December 2019 to undergo in vitro fertilization and embryo transfer
as a research group, and 160 singleton pregnant women who were naturally conceived at the same time and
delivered at our hospital were selected as the control group. The relevant data of the patients were collected,
and the perinatal conditions, neonatal complications, physical development and NBN score of infants aged
6 months were compared between the two groups. Multivariate logistic regression was used to analyze risk
factors for perinatal complications in assisted reproduction singleton pregnancy.
Results: The incidence of complications in the perinatal period in the study group was signicantly higher
than that in the control group (P<0.05). However, there was no signicant difference in the incidence of
complications such as very low birth weight, respiratory distress, neonatal hemolysis, hyperbilirubinemia,
hypoglycemia, infectious pneumonia and neonatal asphyxia between the two groups (P>0.05). Likewise,
at 6 months of age, the infants in the research group showed no significant difference to the control
group in physical development indicators, including weight, head circumference, body mass index,
height and NBN score (P>0.05). The analysis of the unconditional multivariate logistic regression model
revealed hypertension during pregnancy, placental previa, premature membrane rupture, gestational age
<32 weeks, and very low birth weight as risk factors that affect perinatal complications in patients with
assisted reproductive singleton pregnancy (P<0.05).
Conclusions: The incidence of complications in perinatal patients with assisted reproductive singleton
pregnancy is higher than that of natural singleton pregnancy, but there is no signicant difference in physical
development, NBN score and complications of 6 months old infants.
Keywords: Assisted reproduction; perinatal period; infant physical development; complications
Submitted Jul 12, 2021. Accepted for publication Sep 15, 2021.
doi: 10.21037/tp-21-400
View this article at: http://dx.doi.org/10.21037/tp-21-400
2354
2348 Li et al. Study of assisted reproduction singleton pregnancy
© Translational Pediatrics. All rights reserved. Transl Pediatr 2021;10(9):2347-2354 | http://dx.doi.org/10.21037/tp-21-400
Introduction
According to World Health Organization (WHO) statistics,
one in seven couples in the world encounters reproductive
health issues (1). A recent infertility research survey in
China has found that infertility affects about 10% of married
couples, and there is an upward trend year by year (2).
Assisted reproductive technology (ART) is a clinically
assisted medical approach for people facing infertility
which includes artificial insemination (AI) and in vitro
fertilization and embryo transfer (IVF-ET). IVF-ET
technology is widely used and can achieve certain clinical
effects (3). Studies have shown that individuals who become
pregnant through ART can experience complications,
such as placenta previa and placental adhesions, which can
affect maternal and infant outcomes and adversely affect
the growth and development of the baby after birth (4).
However, at present, there is no clear conclusion on
whether ART elevates the risk for mothers and their
children or affects the birth and development of infants (5).
Therefore, we conducted a study to compare the
perinatal maternal and infant conditions between 145 cases
of ART singleton pregnancy and 160 cases of naturally
conceived singleton pregnancy who were admitted to
our hospital, and observed physical development and
complications in both groups of infants at 6 months, to
provide a reference for clinical diagnosis and treatment.
We present the following article in accordance with the
STROBE reporting checklist (available at https://dx.doi.
org/10.21037/tp-21-400).
Methods
General information
The clinical treatment data of 145 singleton pregnant
women who received IVF-ET and were admitted to our
hospital between December 2017 and December 2019 were
selected. These patients (the study group) had an average
age of 30.41±5.18 years, the average number of pregnancies
was 1.41±0.52 times, the average number of births was
1.16±0.41 times, and the gestational week at delivery was
38.41±1.42 weeks. The inclusion criteria were as follows:
(I) infertility due to tubal blockage or male semen-related
factors; (II) diagnosed as intrauterine singleton pregnancy
by imaging examination; (III) no endocrine disease; and
(IV) complete clinical data. The exclusion criteria were as
follows: (I) patients with underlying diseases such as chronic
heart disease, diabetes, and hypertension; (II) immune,
chromosomal, or genetic diseases in one or both of the
parents; and (III) withdrawal from the study during the
research or poor intervention compliance. Additionally,
160 singleton pregnant women who conceived naturally
and gave birth in our hospital were selected as the control
group. These patients (the control group) had an average
age of 30.51±5.12 years, the average number of pregnancies
was 1.37±0.44, the average number of births was 1.21±0.34,
and the gestational week at delivery was 38.52±1.16 weeks.
There was no significant difference in general
information between the two groups of patients (P>0.05),
and they were comparable.
The study was approved by medical ethics committee
of Luohe Central Hospital (No. 20170526). The patients’
family members were aware of and agreed to this study,
and signed the relevant informed consent. The study was
conducted in accordance with the Declaration of Helsinki (as
revised in 2013).
Study methods
The maternity examination, delivery status, and newborn
data of the two groups were collected. The infants were
followed up for 6 months, and their physical development
and neurobehavioral development was monitored. Neonatal
behavioral neurological assessment (NBNA) was used
to evaluate neurobehavioral development of the infants.
Observation items included 6 items of behavioral ability,
4 items of passive muscle tension, 4 items of active muscle
tension, 3 items of primitive reex and 3 items of general
state, a total of 20 items. Each score has three points (0, 1, 2).
Full score 40, <35 score abnormal (6).
Perinatal conditions and complications
Maternal pregnancy/delivery, including gestational age,
mode of delivery, premature rupture of membranes,
placental abruption, premature birth, fetal distress,
threatened abortion, preeclampsia, threatened premature
birth, poly or oligohydramnios, restricted fetal growth,
stillbirth, severe fetal malformations, etc.
Neonatal complications
Neonatal complications included very low birth weight,
respiratory distress, neonatal hemolysis, hyperbilirubinemia,
hypoglycemia, infectious pneumonia and neonatal asphyxia.
Follow-up
The infants were followed up to the age of 6 months via
2349Translational Pediatrics, Vol 10, No 9 September 2021
© Translational Pediatrics. All rights reserved. Transl Pediatr 2021;10(9):2347-2354 | http://dx.doi.org/10.21037/tp-21-400
WeChat, telephone, or home visit. The nal follow-up was
on August 30, 2020. The content of the follow-up included
weight, length, head circumference, and body mass index
(BMI).
Statistical methods
The data in this study were statistically analyzed using
SPSS22.0 software (SPSS, Chicago, Illinois, USA). The
measurement data were described as the mean ± standard
deviation (x±s) and compared by t-test. Count data
were described as the pass rate or composition ratio and
compared by the χ2 test. Multivariate logistic regression was
used to analyze the risk factors for perinatal complications
in ART singleton pregnancy. The difference was considered
statistically signicant with P<0.05.
Results
Comparison of the perinatal conditions of the two groups
As shown in Table 1, the incidence of perinatal complications
was statistically signicantly higher in the study group than
in the control group (P<0.05).
Comparison of neonatal complications between the two
groups
As shown in Table 2, there was no significant difference
in the incidence of neonatal complications, such as very
low birth weight, respiratory distress, neonatal hemolysis,
hyperbilirubinemia, hypoglycemia, infectious pneumonia
and neonatal asphyxia between the study group and the
control group (P>0.05).
Table 1 Comparison of perinatal conditions between the study and control groups (n, %)
Perinatal conditions Study group Control group χ2P
N 145 160 – –
Normal delivery 51 (35.17) 82 (51.25) 7.996 0.005
Complications
Maternal entry into ICU 6 (4.14) 2 (1.25)
Premature delivery 19 (13.10) 8 (5.00)
Cesarean section 62 (42.76) 65 (40.63)
Other complications 7 (4.83) 3 (1.87)
Total 94 (64.83) 78 (48.75)
Table 2 Comparison of neonatal complications between the study and control groups (n, %)
Neonatal complications Study group Control group χ2P
N 145 160 – –
Very low birth weight 12 (8.26) 7 (4.38) 1.981 0.159
Respiratory distress 2 (1.38) 2 (1.25) 0.01 0.921
Neonatal hemolysis 1 (0.69) 3 (1.88) 0.826 0.364
Hyperbilirubinemia 9 (6.21) 11 (6.88) 0.055 0.814
Hypoglycemia 1 (0.69) 2 (1.25) 0.245 0.62
Infectious pneumonia 7 (4.83) 10 (6.25) 0.292 0.360
Neonatal asphyxia 6 (4.14) 9 (5.63) 0.589 0.549
2350 Li et al. Study of assisted reproduction singleton pregnancy
© Translational Pediatrics. All rights reserved. Transl Pediatr 2021;10(9):2347-2354 | http://dx.doi.org/10.21037/tp-21-400
Comparison of the physical development and NBN score of
6-month-old infants between the two groups
As shown in Table 3, the infants in the study group
showed no signicant differences in physical development
indicators, such as weight, head circumference, BMI, height
and NBN score, compared to those in the control group
(P>0.05).
Single-factor analysis of perinatal complications in assisted
reproduction singleton pregnancy
According to the above results, the majority of women in
both groups experienced perinatal complications. According
to the perinatal conditions described in Table 1, the study
participants were divided into groups; those who had a
normal delivery were dened as the no complications group,
and the rest were regarded as the complications group.
The results of the univariate analysis showed that
hypertension during pregnancy, gestational diabetes,
placental previa, premature rupture of membranes,
gestational age <32 weeks, and very low birth weight were
factors affecting the risk of perinatal complications in an
assisted reproduction singleton pregnancy (P<0.05) (Table 4).
Analysis of multiple factors affecting perinatal
complications in assisted reproduction singleton pregnancy
After unconditional multivariate logistic regression
model analysis, hypertension during pregnancy, placental
previa, premature rupture of membranes, gestational age
<32 weeks, and very low birth weight were found to be
independent risk factors for perinatal complications in an
assisted reproduction singleton pregnancy (P<0.05) (Table 5).
Discussion
With the continuous development of ART, IVF-
ET has become an effective treatment for individuals
with infertility. However, the safety of ART and the
health risks faced by children born through ART have
gradually received clinical attention. Although most
children conceived using ART are healthy, individual
differences still exist, which has resulted in concern
about ART and the health of mothers and babies (7).
Therefore, exploration of the factors affecting perinatal
and infant health after ART has important clinical value
in paving the way for targeted intervention measures and
reducing the impact of ART on mothers and infants (8).
To date, a clear conclusion on the impact of ART on
perinatal complications and neonatal short- and long-term
outcomes has not been reached (9). Studies have shown
that after IVF-ET treatment, the risk of complications
such as postpartum hemorrhage, placental abruption, and
premature rupture of membranes during the perinatal
period is higher than that with naturally conceived
pregnancies (10). However, it has also been reported that
IVF-ET treatment does not increase the risk of perinatal
complications but is associated with a higher cesarean
section rate (11). Therefore, the present study selected
145 women who underwent IVF-ET treatment in Luohe
Central Hospital and 160 women who conceived naturally
during the perinatal period. The incidence of complications
in the study group was observed to be significantly higher
than that in the control group. Logistic regression model
analysis showed that hypertension during pregnancy, placental
previa, and premature rupture of membranes gestational age
<32 weeks, and very low birth weight were risk factors for
perinatal complications in ART singleton pregnancy. These
Table 3 Comparison of the physical development and NBN score of 6-month-old infants between the study and control groups (x±s)
Physical development indicators Study group Control group t P
N 145 160 – –
Weight (kg) 7.15±1.14 7.21±1.05 0.478 0.632
Head circumference (cm) 40.09±2.51 40.12±2.61 0.102 0.918
BMI (kg/m2) 17.42±1.42 17.33±1.55 0.526 0.598
Height (cm) 64.85±3.16 64.71±3.23 0.381 0.702
NBN score 39.31±0.69 39.22±0.65 1.173 0.242
2351Translational Pediatrics, Vol 10, No 9 September 2021
© Translational Pediatrics. All rights reserved. Transl Pediatr 2021;10(9):2347-2354 | http://dx.doi.org/10.21037/tp-21-400
Table 4 Single-factor analysis of perinatal complications in assisted reproduction singleton pregnancy
Influencing factors No complications group
(n=51)
Complications group
(n=94) χ2P
Age (years) 0.055 0.814
≥30 25 48
<30 26 46
BMI (kg/m2) 0.091 0.763
≥24 29 51
<24 22 43
History of miscarriage 0.087 0.768
Yes 28 54
No 23 40
Hypertension in pregnancy 18.657 <0.001
Yes 20 71
No 31 23
Parity (time) 0.009 0.925
0 24 45
≥1 27 49
Gestational diabetes 18.110 <0.001
Yes 19 69
No 32 25
Placenta anterior 6.881 0.009
Yes 21 60
No 30 34
Premature rupture of membranes 23.955 <0.001
Yes 18 72
No 33 22
Polyhydramnios 0.298 0.585
Yes 29 49
No 22 45
Oligohydramnios 2.393 0.122
Yes 28 39
No 23 55
Gestational age <32 weeks 14.918 <0.001
Yes 16 61
No 35 33
Very low birth weight 4.133 0.042
Yes 1 11
No 50 83
Mother education degree 2.363 0.124
Junior high school and below 27 62
High school and above 24 32
2352 Li et al. Study of assisted reproduction singleton pregnancy
© Translational Pediatrics. All rights reserved. Transl Pediatr 2021;10(9):2347-2354 | http://dx.doi.org/10.21037/tp-21-400
Table 5 Analysis of multiple factors affecting perinatal complications in assisted reproduction singleton pregnancy
Influencing factors Regression
coefficients Standard error Wald χ2P OR (95% CI)
Hypertension in pregnancy (yes vs. no) 0.915 0.205 7.459 0.025 2.49 (1.670–3.731)
Gestational diabetes (yes vs. no) 0.506 0.316 5.184 0.201 1.65 (0.892–3.081)
Placenta anterior (yes vs. no) 0.987 0.147 9.157 <0.001 2.68 (2.011–3.579)
Premature rupture of membranes (yes vs. no) 0.946 0.152 8.595 0.011 2.57 (1.911–3.469)
Gestational age <32 weeks (yes vs. no) 0.977 0.231 7.112 0.032 2.656 (1.689–4.178)
Very low birth weight (yes vs. no) 0.922 0.342 8.670 0.007 2.514 (1.286–4.915)
ndings are similar to those of previous reports.
The research has indicated that hypertension in pregnancy
is related to factors such as age, parity, obesity, multiple
pregnancies, diabetes, and chronic immune diseases.
Ovulation induction and human chorionic gonadotropin
treatment in ART patients during pregnancy may activate
the renin-angiotensin-aldosterone system, which is related to
the occurrence of pregnancy-induced hypertension (12,13).
Furthermore, some studies have shown that high levels of
chorionic gonadotropin can damage the blood vessels of the
placenta in early pregnancy, leading to placental hypoxia
and pregnancy complications (14). However, ART patients
may have a history of frequent abortion or intrauterine
operations, which can damage the endometrium and cause
inflammation, causing endometrial vascular defects. After
ART implantation, due to the insufficient blood supply
caused by such endometrial vascular defects, the fertilized egg
stretches the lower part of the uterus and increases the area of
the placenta, resulting in placenta previa (15). Furthermore,
Nakamura et al. (16) stated that when some ART patients
undergo placental decompression therapy, the fetal reduction
can cause amnionitis and fetal membrane inflammation,
resulting in fetal membrane dysplasia and leaving them prone
to premature rupture of membranes and premature delivery.
Therefore, it is necessary to closely monitor the perinatal
condition of ART patients, detect potential pregnancy
complications as early as possible, and give early intervention
and treatment to reduce the risk of perinatal complications in
patients and obtain a good pregnancy outcome (17).
Additionally, in this study, neonatal complications among
women with ART and natural pregnancies and their infants
at 6 months were observed, and no signicant difference was
found between the two groups. Although previous foreign
studies have suggested that ART singleton babies have a
higher risk of respiratory distress than non-ART singleton
babies, this has yet to be conrmed (18). Scholars such as
Lledo et al. (19) have reported that IVF-ET technology
affects infants' development. Another study found that
children born with the help of IVF-ET experience similar
growth and development to children born through natural
pregnancy (20). Therefore, in the future, it is necessary to
expand the sample size and conduct multi-center, long-
term, targeted research to establish whether there is a
difference between children conceived with IVF-ET and
those conceived naturally. Follow-up of children, both those
conceived naturally and with IVF-ET, until adulthood or
even beyond is also needed to ensure the authenticity and
accuracy of experimental results.
Conclusions
In summary, complications in the perinatal period are
higher in women with ART singleton pregnancies than
in natural singleton pregnancies. However, there is no
significant difference in the physical development, NBN
score and complications of their infants at 6 months of age.
Early interventions for complications during the perinatal
period in women with ART singleton pregnancies can
maximize protection for the mother and child and reduce
the occurrence of adverse events.
Acknowledgments
Funding: None.
Footnote
Reporting Checklist: The authors have completed the
STROBE reporting checklist. Available at https://dx.doi.
org/10.21037/tp-21-400
2353Translational Pediatrics, Vol 10, No 9 September 2021
© Translational Pediatrics. All rights reserved. Transl Pediatr 2021;10(9):2347-2354 | http://dx.doi.org/10.21037/tp-21-400
Data Sharing Statement: Available at https://dx.doi.
org/10.21037/tp-21-400
Conicts of Interest: All authors have completed the ICMJE
uniform disclosure form (available at https://dx.doi.
org/10.21037/tp-21-400). The authors have no conflicts of
interest to declare.
Ethical Statement: The authors are accountable for all
aspects of the work in ensuring that questions related to the
accuracy or integrity of any part of the work are appropriately
investigated and resolved. The study was approved by
medical ethics committee of Luohe Central Hospital (No.
20170526). The patients’ family members were aware of
and agreed to this study, and signed the relevant informed
consent. The study was conducted in accordance with the
Declaration of Helsinki (as revised in 2013).
Open Access Statement: This is an Open Access article
distributed in accordance with the Creative Commons
Attribution-NonCommercial-NoDerivs 4.0 International
License (CC BY-NC-ND 4.0), which permits the non-
commercial replication and distribution of the article
with the strict proviso that no changes or edits are made
and the original work is properly cited (including links
to both the formal publication through the relevant
DOI and the license). See: https://creativecommons.org/
licenses/by-nc-nd/4.0/.
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Cite this article as: Li J, Fu X, Lv J, Cui L, Li R, Bai A,
Wang H, Tang X. Multiple regression analysis of perinatal
conditions, physical development, and complications in assisted
reproduction singletons. Transl Pediatr 2021;10(9):2347-2354.
doi: 10.21037/tp-21-400