TYPE Original Research

PUBLISHED 23 February 2023

DOI 10.3389/fmed.2023.1056064

The interaction between age and

OPEN ACCESS parity on adverse pregnancy and
EDITED BY
Doron Kabiri,
Hadassah Medical Center,
neonatal outcomes
Israel

REVIEWED BY
Jiayang Dai1,2†, Ya Shi1,3†, Yinshuang Wu4, Lu Guo1, Dan Lu2,5,6,
Hongbiao Yu, Ying Chen7, Yuanyuan Wang1, Hanpeng Lai1 and Xiang Kong2,5,6*
Nanchong Central Hospital,
China 1
School of Nursing and School of Public Health, Yangzhou University, Yangzhou, China, 2Department of
Ling Li, Obstetrics and Gynecology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China,
Southeast University, 3
School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester,
China Manchester, United Kingdom, 4Graduate School of Dalian Medical University, Dalian, China, 5Institute of
Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China, 6Jiangsu Key
*CORRESPONDENCE
Laboratory of Experimental & Translational Non-Coding RNA Research, Yangzhou, Jiangsu Province, China,
Xiang Kong 7
Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
kongxiang123123@163.com
†
These authors have contributed equally to this work
and share first authorship

SPECIALTY SECTION Background: Although age and parity are recognized as associated factors for
This article was submitted to adverse pregnancy outcomes, there are no studies exploring the interaction between the
Obstetrics and Gynecology, a
section of the journal Frontiers two during pregnancy. This study aimed to investigate the impact of the interaction
in Medicine between age and parity on adverse pregnancy outcomes.
RECEIVED 24 October 2022 Methods: This was a retrospective cohort study with 15,861 women aged
ACCEPTED 06 February 2023
PUBLISHED 23 February 2023
≥20years. All women were grouped according to age, parity, and a mix of the two. The
data were analyzed using multivariate logistic regression analysis.
CITATION
Dai J, Shi Y, Wu Y, Guo L, Lu D, Chen Y, Wang Y, Results: Age, parity, and interaction between the two were related with the risk of
Lai H and Kong X (2023) The interaction between gestational hypertension, eclampsia/pre-eclampsia, placenta previa, placental
age and parity on adverse pregnancy and neonatal
outcomes. implantation, postpartum hemorrhage, preterm birth, cesarean section, and Apgar score <7
Front. Med. 10:1056064. within 5min of birth. The risk of gestational diabetes mellitus and transfer to the neonatal
doi: 10.3389/fmed.2023.1056064 unit was linked with age and the interaction between age and parity, but the impact of
COPYRIGHT parity was not statistically significant. The risk of anemia, placental abruption,
© 2023 Dai, Shi, Wu, Guo, Lu, Chen, Wang, Lai and premature rupture of the membrane, oligohydramnios, and macrosomia was only
Kong. This is an open-access article distributed
under the terms of the Creative Commons associated with parity; the risk of fetal distress was only associated with age.
Attribution License (CC BY). The use, distribution Conclusion: The interaction between advanced age and parity might results in more
or reproduction in other forums is permitted,
provided the original author(s) and the copyright adverse outcomes for both puerpera and infants, necessitating additional prenatal
owner(s) are credited and that the original screening and health education throughout pregnancy.
publication in this journal is cited, in accordance
with accepted academic practice. No use,
distribution or reproduction is permitted which KEYWORDS
does not comply with these terms.
retrospective cohort study, advanced maternal age, parity, pregnancy outcome,
neonatal outcome

Introduction
The International Federation of Gynaecology and Obstetrics (FIGO) defines advanced
maternal age (AMA) as age ≥35 years at the time of expected delivery (1). At present, the
definition of very advanced maternal age (vAMA) is rather debatable, with some
researchers defining ≥40 years at the time of expected delivery as very advanced maternal age
(vAMA) (2, 3).

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 Dai et 10.3389/fmed.2023.1056064

Currently, international research indicated that the proportion criteria

of AMA and vAMA increased with year (4, 5). In China, studies
have shown that the proportion of AMA increased from 7.4% in
2013 to 15.9% in 2018 (6). In addition, as assisted reproductive
technology becomes more prevalent, the proportion of AMA is
expected to increase in the coming years (7). There is a gradual
increase in the number of AMA in numerous countries. According
to a survey conducted by the World Health Organization (WHO)
of 308,149 mothers and newborns covering 29 countries in Africa,
Asia, Latin America, and the Middle East indicated that the
proportion of AMA reached 12.3% (8). The Centers for Disease
Control and Prevention (CDC) reported that the fertility rate for
women aged 35–44 years increased from 19.8‰ in 1980 to 52.6‰
in 2018 (9).
There are several risk factors for adverse pregnancy outcomes,
with advanced age and parity being the most significant (1, 10). Many
studies have been conducted to investigate the relationship
between advanced age or parity and adverse pregnancy outcomes
(1, 11). It has been demonstrated that advanced maternal age is
associated with numerous adverse pregnancy outcomes.
Vandekerckhove discovered that the risk of maternal and fetal
complications increased steadily with age and was particularly high
after 35 years (12). Guarga Montori also discovered that women >35
years had worse perinatal outcomes than younger women, with the
disparity being more pronounced in patients >40 (13). It is
debatable if parity is a risk factor for adverse pregnancy outcomes.
Shechter-Maor G indicated that pregnancy complications were
much more likely in nulliparous women of advanced maternal age
than multiparous women of the same age (14), and Schimmel MS
also found similar conclusions (15). Muniro Z, on the other hand,
discovered that grand multiparity was associated with increased
risks of adverse pregnancy outcomes, such as postpartum
hemorrhage, gestational hypertension, gestational diabetes
mellitus, and high perinatal mortality (16). Therefore, the
relationship between parity and adverse pregnancy outcomes remains
to be studied. Advanced age and parity have been studied more
frequently in relation to adverse pregnancy outcomes;
nevertheless, to our knowledge, there has been no investigation
into the impact of the interaction between advanced age and parity
on adverse pregnancy outcomes and neonatal outcomes, which
requires further investigation.
Overall, this study conducted retrospective analyzes on the
interaction between age and parity on adverse pregnancy and neonatal
outcomes to fill the gap in this area. We will identify trends in the
risk of pregnancy outcomes and neonatal outcomes across age and
parity, which will give obstetric healthcare professionals with more
detailed clinical evidence for more informed clinical consultation
and decision-making.

Materials and methods

Study population and design

The study population was women aged ≥20 years who had a
singleton birth at the Northern Jiangsu People’s Hospital in
Yangzhou City, Jiangsu Province, China, between January 2016
and December 2020.
The inclusion criteria were ≥28 weeks gestational week of
delivery, age ≥20 years, and singleton live birth. The exclusion

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were induction of labor, intrauterine fetal death, viral
myocarditis, congenital heart disease, liver, kidney, lung, and
other important organ pathologies, serious primary diseases,
combined with serious infectious diseases, mental disorders, or
cognitive dysfunction. Fifteen thousand eight hundred and
sixty-one mothers met the criteria.

Study methods

Data collection
The Northern Jiangsu People’s Hospital’s electronic information
system was used to collect the data for this investigation. Two
researchers independently collected case information of all
participants (Collecting time: May 2022–July 2022), including
age at delivery, height, pre-pregnancy body mass, education,
residence, mode of conception, parity, mode of previous
deliveries, and captured data on maternal pregnancy outcomes
and neonatal outcomes via the electronic information system.
They then checked each other’s work, and if a discrepancy was
discovered, a third person reviewed the data.

Diagnostic criteria
All women were grouped according to three bases: age, parity,
and a mixture of age and parity. According to age, pregnant
women were divided into five groups: the first appropriate age
group (20–24 years, A1 group), the second appropriate age group
(25–29 years, A2 group), the third appropriate age group (30–34
years, A3 group), the advanced maternal age group (35–39 years
old, AMA group), and the very advanced maternal age group
(≥40 years, vAMA group). For parity, pregnant women were
divided into two groups: a nulliparous group (parity = 1) and a
multiparous group (parity ≥ 2). With regard to the mixture of age
and parity, pregnant women were divided into 10 groups,
combining the two previous groupings. Education was
categorized into bachelor’s degree or above and no bachelor’s
degree. Residence was divided into urban and rural areas. Marital
status was divided into married and unmarried. Smoking was
divided into Yes and No. Pre-pregnancy BMI was calculated by
dividing pre-pregnancy weight (kg) by the square of height (m2).
BMI was divided into four categories using Asian-specific cut-offs
(17): <18.5, 18.5–23, 23–27.5, and ≥27.5 kg/m2. Gestational
weight gain (GWG) was classified following the 2009 Institute
of Medicine (IOM) guidelines, the standard divides GWG into
Inadequate, Adequate, and Excessive according to different
prenatal weight standards for pregnant women (18). Pregnancy
was divided into two categories: assisted reproduction and natural
conception. Gestational weeks were separated into three
categories: 28–31, 32–36, and 37 weeks and above, with deliveries
at less than 37 weeks being considered as preterm births. For
multiparas, the form of the previous birth was classified into
cesarean section and vaginal delivery.
The outcome indicators were maternal pregnancy outcomes
and neonatal outcomes. Maternal pregnancy outcomes included
gestational hypertension, eclampsia/pre-eclampsia, gestational
diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy
(ICP), anemia, placenta previa, placental abruption, placental
implantation, premature rupture of membranes, postpartum
hemorrhage, oligohydramnios, preterm birth, and cesarean
section. Neonatal outcomes included macrosomia, fetal
distress,

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transfer to the neonatal unit, neonatal jaundice, and an Apgar score Incidence of pregnancy outcomes and neonatal
<7 within 5 min of birth. All outcome indicators were diagnosed outcomes in women of different ages and
according to the International Classification of Diseases 10th parities
edition (ICD-10).
The incidence of adverse pregnancy outcomes ranged from
1.07 to 22.91%, with gestational diabetes mellitus (22.91%),
Statistical analysis premature rupture of membranes (17.92%), and transfer to the
neonatal unit (14.48%) being the three most prevalent diseases.
Microsoft Excel 2007 was used to record and organize the The incidence of adverse pregnancy and neonatal outcomes
data. The SPSS 26.0 statistical program was utilized for data for single age groups is shown in Table 2. In terms of a single age
collection and analysis. Quantitative data were described as x  s, group, the difference in the following outcomes among the five
and qualitative data were expressed as frequencies (percentage). The age groups was statistically significant, including the prevalence
χ2 test was used for comparisons among groups. Single-factor of gestational hypertension, eclampsia/pre-eclampsia, gestational
analysis was used to compare the prevalence of adverse pregnancy diabetes mellitus, placenta previa, placental implantation,
outcomes and adverse neonatal outcomes of pregnant women in the postpartum hemorrhage, preterm birth, cesarean section, vaginal
single age group, single parity group, and mixed group. Significant delivery, fetal distress, transfer to neonatal unit, and Apgar score
factors identified by the single-factor analysis were incorporated <7 within 5 min of birth, while the difference in the remaining
into a multivariate logistic regression analysis. After adjusting for indices was not statistically significant.
possible confounding factors, the adjusted OR (aOR) and 95% The incidence of adverse pregnancy outcomes and neonatal
confidence interval (95% CI) were used to show the risk of outcomes for single parity group are shown in Table 3. In terms of
pregnancy and neonatal adverse outcomes in the single age group, the single parity group, the difference in the following outcomes
single parity group, and combination group. All p values were among the two parity groups was statistically significant,
two-sided tests, with p < 0.05 indicating statistical significance. including the prevalence of gestational hypertension,
eclampsia/pre-eclampsia, gestational diabetes mellitus, anemia,
placenta previa, placental abruption, placental implantation,
Ethical considerations premature rupture of membranes, postpartum hemorrhage,
oligohydramnios, preterm birth, cesarean section, macrosomia,
Due to the absence of an ethical statement component in our fetal distress, transfer to the neonatal unit, and Apgar score <7
research, an ethics application is unnecessary. This data collection points within 5 min of birth, whereas the difference in the incidence
was approved by the Obstetrics and Gynecology Department of of intrahepatic cholestasis of pregnancy and neonatal jaundice was
the Northern Jiangsu People’s Hospital. not statistically significant.
The incidence of pregnancy outcomes and neonatal outcomes
for 10 groups of mixed age and parity are shown in Table 4. The
Results difference in the following outcomes among these 10 groups was
statistically significant: prevalence of gestational hypertension,
Sociodemographic data and pre- eclampsia/ pre-eclampsia, gestational diabetes mellitus, placenta
pregnancy characteristics previa, placental implantation, postpartum hemorrhage, preterm
birth, cesarean section, transfer to neonatal unit, and Apgar score
A total of 15,861, women were included in this study. Of <7 points within 5 min of birth, while the difference in the
these, 2,586 (16.3%) women were aged 20–24 years, 8,057 remaining indices was not statistically significant.
(50.80%) women were aged 25–29 years, 3,636 (22.92%) women
were aged 30–34 years, 1,314 (8.28%) women were aged 35–39
years, and 268 (1.69%) women were aged ≥40 years. There were Logistic regression analysis of adverse pregnancy
12,002 nulliparous women (75.67%) and 3,859 multiparous women outcomes and neonatal outcomes at different
(24.33%). 50.11% of these women have a bachelor’s degree or ages and parities
above, 60.38% of women living in urban areas. 96.65% of women
are married, and 1.08% of women have a bad habit of smoking. The risk of adverse pregnancy outcomes and neonatal
34.81% of women had a pre-pregnancy BMI in the normal range, outcomes for the single age group is shown in Figure 1. After
3.35% of women weighed less than the normal range, and 61.85% of correcting for confounding factors such as education, place of
pregnant women weighed more than the normal range. 69.97% of residence, pre-pregnancy BMI, assisted reproduction, and week of
women GWG at an appropriate level, 9.95% of women gained pregnancy, with increasing age, the risk of gestational
less gestational weight, and 20.08% of women gained more during hypertension, eclampsia/ pre-eclampsia, gestational diabetes
pregnancy. In terms of mode of conception, 5.43% of women mellitus, placenta previa, placental implantation, postpartum
using assisted reproductive technologies. In terms of the hemorrhage, preterm birth, cesarean section, transfer to the
gestational week of delivery, 88.21% of women gave birth at full neonatal unit, and Apgar score <7 within 5 min of birth showed an
term and 11.79% of women gave birth prematurely. 68.26% of upward trend, while only the A3 group of women (30–34 years)
women had a cesarean section at their previous birth, and 31.74% had a reduced incidence of fetal distress.
of women had a vaginal delivery (Table 1). The risk of adverse pregnancy outcomes and neonatal
outcomes for the single parity group is shown in Figure 2. After
correcting for

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TABLE 1 Sociodemographic and pre-pregnancy characteristics of study participants.

Variables Total Nulliparas p Multiparas p

A1 A2 A3 AM vAM A1 A2 A3 AM vAM
(%) (%) (%) A A (%) (%) (%) A A
(%) (%) (%) (%)
n 15,861 2,541 7,821 1,374 230 36 45 236 2,262 1,084 232

Education 0.00*** 0.00***

Bachelor’s degree or above 7,948 1,240 4,536 721 70 10 7 32 898 375 59

(50.11) (48.80) (58.00) (52.47) (30.43) (27.78) (15.56) (13.56) (39.7) (34.59) (25.43)

Undergraduate 7,913 1,301 3,285 653 160 26 38 204 1,364 709 173
(49.89) (51.20) (42.00) (47.53) (69.57) (72.22) (84.44) (86.44) (60.3) (65.41) (74.57)

Place of residence 0.00*** 0.00***

Urban 9,577 1,321 5,005 901 132 22 18 95 1,359 605 119

(60.38) (51.99) (63.99) (65.57) (57.39) (61.11) (40.00) (40.25) (60.01) (55.81) (51.29)

Rural 6,284 1,220 2,816 473 98 14 27 141 903 479 113

(39.62) (48.01) (36.01) (34.43) (42.61) (38.89) (60.00) (59.75) (39.92) (44.19) (48.71)

Marital status 0.92 0.85

Married 15,329 2,454 7,563 1,326 220 35 44 231 2,184 1,048 224
(96.65) (96.58) (96.70) (96.51) (95.65) (97.22) (97.78) (97.88) (96.55) (96.68) (96.55)

Unmarried 532 87 258 48 10 1 (2.78) 1 5 78 36 8 (3.45)

(3.35) (3.42) (3.30) (3.49) (4.35) (2.22) (2.12) (3.45) (3.32)

Smoking 0.89 0.95

Yes 172 28 82 15 2 1 (2.78) 1 3 26 12 2 (0.86)

(1.08) (1.10) (1.05) (1.09) (0.87) (2.22) (1.27) (1.15) (1.11)

No 15,689 2,513 7,739 1,359 228 35 44 233 2,236 1,072 230

(98.92) (98.90) (98.95) (98.91) (99.13) (97.22) (97.78) (98.73) (98.85) (98.89) (99.14)

Pre-pregnancy BMI (kg/m2) 0.07 0.72

<18.5 531 126 274 49 7 1 (2.78) 1 4 42 23 4 (1.72)

(3.35) (4.96) (3.50) (3.57) (3.04) (2.22) (1.69) (2.92) (1.20)

18.5–23 5,521 890 2,660 470 89 14 18 (40) 92 823 398 67

(34.81) (35.03) (34.01) (34.21) (38.70) (38.89) (38.98) (36.38) (36.72) (28.88)

23–27.5 6,320 1,017 3,128 549 87 14 18 (40) 92 899 418 98

(39.85) (40.02) (39.99) (39.96) (37.83) (38.89) (38.98) (39.74) (38.56) (42.24)

≥27.5 3,489 508 1,759 306 47 7 8 48 498 245 63

(22.00) (19.99) (22.49) (22.27) (20.43) (19.44) (17.78) (20.34) (22.02) (22.60) (27.16)

Gestational weight gain 0.54 0.98

(GWG)

Inadequate 1,578 240 780 140 33 2 (5.56) 3 25 218 112 25

(9.95) (9.45) (9.97) (10.19) (14.35) (6.67) (10.59) (9.64) (10.33) (10.78)

Adequate 11,098 1,796 5,483 957 151 27 33 163 1,584 742 162
(69.97) (70.68) (70.11) (69.65) (65.65) (75.00) (73.33) (69.07) (70.03) (68.45) (69.83)

Excessive 3,185 505 1,558 277 46 7 9 48 460 230 45

(20.08) (19.87) (19.92) (20.16) (20.00) (19.44) (20.00) (20.34) (20.34) (21.22) (19.40)

Assisted reproduction 0.00*** 0.00***

Yes 862 5 385 273 79 16 0 5 25 58 16

(5.43) (0.20) (4.92) (19.87) (34.35) (44.44) (2.12) (1.11) (5.35) (6.90)

No 14,999 2,536 7,436 1,101 151 20 45 231 2,237 1,026 216

(94.57) (99.80) (95.08) (80.13) (65.65) (55.56) (100) (97.88) (98.89) (94.65) (93.10)

Week of pregnancy (weeks) 0.31 0.11

28–31 weeks 199 31 94 15 3 1 (2.78) 1 3 32 15 4 (1.72)

(1.25) (1.22) (1.20) (1.09) (1.30) (2.22) (1.27) (1.41) (1.38)

(Continued)

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TABLE 1 Continued

Variables Total Nulliparas p Multiparas p

A1 A2 A3 AM vAM A1 A2 A3 AM vAM
(%) (%) (%) A A (%) (%) (%) A A
(%) (%) (%) (%)
32–36 weeks 1,671 255 780 122 34 5 6 30 244 159 36
(10.54) (10.04) (9.97) (8.88) (14.78) (13.89) (13.33) (12.71) (10.79) (14.67) (15.52)

≥37 weeks 13,991 2,255 6,947 1,237 193 30 38 203 1,986 910 192
(88.21) (88.74) (88.82) (90.03) (83.91) (83.33) (84.44) (86.02) (87.8) (83.95) (82.76)

Previous delivery 0.23

Cesarean section 2,634 —— —— —— —— —— 28 170 1,526 759 151

(68.26) (62.22) (72.03) (67.46) (70.02) (65.09)

Vaginal delivery 1,225 —— —— —— —— —— 17 66 736 325 81

(31.74) (37.78) (27.97) (32.54) (29.98) (34.91)
*p < 0.05, statistically difference, **p < 0.01, statistically significant difference, and ***p < 0.001, highly statistically significant difference. A1: 20–24 years old women, A2: 25–29 years old
women, A3: 30–34 years old women, AMA: 35–39 years old women, and vAMA: ≥40 years old women.

TABLE 2 Incidences of adverse pregnancy outcomes and neonatal outcomes for the single age group.

Variables Total A1 (%) A2 (%) A3 (%) AMA (%) vAMA (%) p

n 15,861 2,586 8,057 3,636 1,314 268

Gestational hypertension 740 (4.67) 68 (2.63) 317 (3.93) 177 (4.87) 136 (10.35) 42 (15.67) 0.00***

Eclampsia/pre-eclampsia 537 (3.39) 31 (1.20) 230 (2.85) 146 (4.02) 97 (7.38) 33 (12.31) 0.00***

Gestational diabetes mellitus 3,633 (22.91) 481 (18.60) 1,736 (21.55) 883 (24.28) 436 (33.18) 97 (36.19) 0.00***

Intrahepatic cholestasis of pregnancy 374 (2.36) 59 (2.28) 201 (2.49) 77 (2.12) 29 (2.21) 8 (2.99) 0.70

Anemia 262 (1.65) 36 (1.39) 118 (1.46) 74 (2.04) 27 (2.05) 7 (2.61) 0.06

Placenta previa 279 (1.76) 20 (0.77) 81 (1.01) 80 (2.20) 77 (5.86) 21 (7.84) 0.00***

Placental abruption 174 (1.10) 27 (1.04) 83 (1.03) 43 (1.18) 17 (1.29) 4 (1.49) 0.83

Placental implantation 170 (1.07) 28 (1.08) 71 (0.88) 33 (0.91) 29 (2.21) 9 (3.36) 0.00***

Premature rupture of membrane 2,843 (17.92) 478 (18.48) 1,492 (18.52) 618 (17.00) 211 (16.06) 44 (16.42) 0.09

Postpartum hemorrhage 665 (4.19) 82 (3.17) 304 (3.77) 164 (4.51) 89 (6.77) 26 (9.70) 0.00***

Oligohydramnios 741 (4.67) 116 (4.49) 371 (4.60) 168 (4.62) 64 (4.87) 22 (8.21) 0.09

Preterm birth 1,870 (11.79) 293 (11.33) 907 (11.26) 413 (11.36) 211 (16.06) 46 (17.16) 0.00***

Cesarean section 8,878 (55.97) 1,123 (43.43) 4,133 (51.30) 2,338 (64.30) 1,063 (80.90) 221 (82.46) 0.00***

Macrosomia 549 (3.46) 90 (3.48) 258 (3.20) 137 (3.77) 55 (4.19) 9 (3.36) 0.32

Fetal distress 120 (0.76) 33 (1.28) 65 (0.81) 15 (0.41) 6 (0.46) 1 (0.37) 0.002**

Transfer to neonatal unit 2,296 (14.48) 309 (11.95) 1,120 (13.90) 540 (14.85) 256 (19.48) 71 (26.49) 0.00***

Neonatal jaundice 778 (4.91) 119 (4.60) 394 (4.89) 171 (4.70) 73 (5.56) 21 (7.84) 0.14

Apgar score <7 within 5 min of birth 278 (1.75) 33 (1.28) 127 (1.58) 72 (1.98) 36 (2.74) 10 (3.73) 0.00***
*p < 0.05, statistically difference, **p < 0.01, statistically significant difference, and ***p < 0.001, highly statistically significant difference. A1: 20–24 years old women, A2: 25–29 years old
women, A3: 30–34 years old women, AMA: 35–39 years old women, and vAMA: ≥40 years old women.

confounding factors, such as education, place of residence, pre-

Table 5 and Figure 3. The 20–24-year-old nulliparous women
pregnancy BMI, assisted reproduction, and week of pregnancy,
were taken as the control group, after correcting for confounding
multiparous women showed a higher risk of gestational hypertension,
factors such as education, place of residence, and assisted
eclampsia/pre-eclampsia, anemia, placenta previa, placental
reproduction. Regarding age, mothers with increasing age showed an
abruption, placental implantation, postpartum hemorrhage,
increased risk of gestational hypertension, eclampsia/pre-
preterm birth, cesarean section, macrosomia, and Apgar score <7
eclampsia, gestational diabetes, placenta previa, placenta
within 5 min of birth than nulliparous women, whereas only the
implantation, postpartum hemorrhage, cesarean section, transfer to
probability of premature rupture of membranes and
the neonatal unit, and Apgar score <7 within 5 min of birth. From
oligohydramnios was less than that of nulliparous women.
the perspective of parity, multiparous women showed a higher risk
The risk of adverse pregnancy outcomes and neonatal
of placental previa, postpartum hemorrhage, transfer to the
outcomes for the combination group with mixed age and parity
neonatal unit, and Apgar score <7 within 5 min of birth than
is shown in
nulliparous women of the same

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TABLE 3 Incidences of pregnancy outcomes and neonatal outcomes for

the single parity group.
the risk of gestational hypertension, eclampsia/pre-eclampsia,
placenta previa, placental implantation, postpartum hemorrhage,
Variables Nulliparas (%) Multiparas (%) p preterm birth, cesarean section, and Apgar score <7 within 5 min
n 12,002 3,859 of birth was associated with age, parity, and the interaction between
Gestational 487 (4.06) 253 (6.56) 0.00***
the two. The risk of gestational diabetes mellitus and transfer to
hypertension
the neonatal unit was associated with age and the interaction
between age and parity, but the impact of parity was not
Eclampsia/pre- 349 (2.91) 188 (4.87) 0.00***
statistically significant; the risk of anemia, placental abruption,
eclampsia
premature rupture of membranes, oligohydramnios, and
Gestational diabetes 2,627 (21.89) 1,006 (26.07) 0.00*** macrosomia was only associated with parity; the risk of fetal
mellitus distress was only associated with age.
Intrahepatic 296 (2.47) 78 (2.02) 0.11 We discovered that the risk of placenta previa, placental
cholestasis of implantation, postpartum hemorrhage, and Apgar score <7 within
pregnancy 5 min of birth increased with age and parity, and that the
Anemia 176 (1.47) 86 (2.23) 0.00*** interaction between age and parity enhanced the risk of these
adverse outcomes even further. Both placenta previa and placental
Placenta previa 133 (1.11) 146 (3.78) 0.00***
implantation are frequent placental abnormalities in mothers. A
Placental abruption 128 (1.07) 70 (1.81) 0.00***
previous meta-analysis showed that AMA were 3.16 times more
Placental 114 (0.95) 56 (1.45) 0.01* likely to have placenta previa than women of normal age (19).
implantation According to Ozdemirci’s study, parity increased the chance of
Premature rupture of 2,226 (18.55) 418 (10.83) 0.00*** placenta previa (20). Consistent with our findings, another study
membrane found that women with a history of numerous cesarean procedures
Postpartum 452 (3.77) 213 (5.52) 0.00***
had a higher likelihood of placental implantation (21). Our study
hemorrhage
further proved that the interaction between age and parity had a
negative influence placental disease, possibly due to the reduced
Oligohydramnios 946 (7.88) 103 (2.67) 0.00***
physiological function of the placenta in women who are older and
Preterm birth 1,340 (11.16) 530 (13.73) 0.00*** have more parities and due to the history of poor childbirth in
Cesarean section 6,056 (50.46) 2,822 (73.13) 0.00*** some women, such as multiple miscarriages and short intervals
Macrosomia 393 (3.27) 156 (4.04) 0.02* between cesarean sections, which can lead to adverse outcomes
such as placenta previa and placental implantation. Placental
Fetal distress 107 (0.89) 13 (0.34) 0.00***
problems predispose women to postpartum hemorrhage. Guarga
Transfer to neonatal 1,688 (14.06) 608 (15.76) 0.00*** demonstrated that AMA and vAMA were 1.13 times and 1.85
unit
times more likely to have postpartum hemorrhage than those at an
Neonatal jaundice 573 (4.77) 205 (5.31) 0.18 appropriate age (13). According to Ozdemirci’s study, parity
Apgar score <7 182 (1.52) 96 (2.49) 0.00*** increases the likelihood of placenta previa, which, in turn,
within 5 min of birth increases the risk of postpartum hemorrhage (20). Our study also
*p < 0.05, statistically difference, **p < 0.01, statistically significant difference, ***p < 0.001,
confirmed that the interaction between age and parity further
highly statistically significant difference. A1: 20–24 years old women, A2: 25–29 years old increased the risk of postpartum hemorrhage, probably due to a
women, A3: 30–34 years old women, AMA: 35–39 years old women, and vAMA: ≥40 years prolonged third stage of labor or incomplete delivery of the
old women.
placenta as a result of decreased placental function, which
predisposes patients to postpartum hemorrhage. An Apgar score
age. Only the risk of nulliparous women with AMA suffering <7 within 5 min of birth is a common adverse neonatal outcome.
from gestational hypertension, eclampsia/pre-eclampsia, The study by Mehari MA revealed that the risk of an Apgar score
gestational diabetes mellitus, and cesarean section and the risk of <7 within 5 min of birth was 7.51 times higher in older mothers
nulliparous women with vAMA suffering from gestational diabetes than in those of appropriate age (22). There are few articles
and cesarean section were greater than those of multiparous examining the relationship between an Apgar score <7 within
women of the same age; however, the risk of preterm birth did not 5 min of birth and parity, but our analysis revealed that either age
vary regularly with age and parity. or parity was a risk factor, and that the interaction between age
and parity also increased its risk.
The interaction between age and parity further increased the
Discussion risk of partial pregnancy outcomes; however, it was not very
regular on some pregnancy outcomes. Gestational hypertension
Our study discovered that advanced age and multiple parities led (HDP) is a leading global cause of maternal morbidity and
to adverse pregnancy outcomes, while the interaction between mortality (23). Gestational hypertension includes gestational
advanced age and multiple parities further increased the risk of these hypertension, pre-eclampsia, eclampsia, and chronic hypertension
outcomes. The relationship between different pregnancy outcomes in pregnancy and chronic hypertension complicated by pre-
and the three categories of age, parity, and the interaction between eclampsia, which predispose mothers to increased vascular
age and parity are not entirely consistent. According to our endothelial damage with age, inflammatory immune
findings,

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TABLE 4 Incidences of adverse pregnancy outcomes and neonatal outcomes for the mixture group with different ages and parities.

Variables Total Nulliparas Multiparas p

(%)
A1 A2 A3 AM vAM A1 A2 A3 AM vAM
(%) (%) (%) A A (%) (%) (%) A A
(%) (%) (%) (%)
n 15,861 2,541 7,821 1,374 230 36 45 236 2,262 1,084 232

Gestational hypertension 740 66 308 77 30 6 (16.67) 2 9 (3.81) 100 106 36 0.00***

(4.67) (2.60) (3.94) (5.60) (13.04) (4.44) (4.42) (9.78) (15.52)

Eclampsia/pre-eclampsia 537 30 223 72 20 4 (11.11) 1 7 (2.97) 74 77 (7.10) 29 0.00***

(3.39) (1.18) (2.85) (5.24) (8.70) (2.22) (3.27) (12.50)

Gestational diabetes 3,633 474 1,689 362 88 14 7 47 521 348 83 0.00***

mellitus (22.91) (18.65) (21.60) (26.35) (38.26) (38.89) (15.56) (19.92) (23.03) (32.10) (35.78)

Intrahepatic cholestasis of 374 58 196 35 5 2 (5.56) 1 5 (2.12) 42 24 (2.21) 6 (2.59) 0.80

pregnancy (2.36) (2.28) (2.51) (2.55) (2.17) (2.22) (1.86)

Anemia 262 35 112 22 5 2 (5.56) 1 6 (2.54) 52 22 (2.03) 5 (2.16) 0.07

(1.65) (1.38) (1.43) (1.60) (2.17) (2.22) (2.30)

Placenta previa 279 20 77 23 10 3 (8.33) 0 4 (1.69) 57 67 (6.18) 18 (7.76) 0.00***

(1.76) (0.79) (0.98) (1.67) (4.35) (2.52)

Placental abruption 174 26 80 14 3 1 (2.78) 1 3 (1.27) 29 14 (1.29) 3 (1.29) 0.95

(1.10) (1.02) (1.02) (1.02) (1.30) (2.22) (1.28)

Placental implantation 170 28 70 12 3 1 (2.78) 0 1 (0.42) 21 26 (2.40) 8 (3.45) 0.00***

(1.07) (1.10) (0.90) (0.87) (1.30) (0.93)

Premature rupture of 2,845 473 1,454 253 42 6 (16.67) 7 38 365 169 38 0.14
membrane (17.94) (18.61) (18.59) (18.41) (18.26) (15.56) (16.10) (16.14) (15.59) (16.38)

Postpartum hemorrhage 665 80 296 60 12 4 (11.11) 2 8 (3.39) 104 77 (7.10) 22 (9.48) 0.00***
(4.19) (3.15) (3.78) (4.37) (5.22) (4.44) (4.60)

Oligohydramnios 741 114 360 62 11 2 (5.56) 2 11 106 53 (4.89) 20 (8.62) 0.79

(4.67) (4.49) (4.60) (4.51) (4.78) (4.44) (4.66) (4.69)

Preterm birth 1,870 286 874 137 37 6 (16.67) 7 33 276 174 40 0.00***
(11.79) (11.26) (11.18) (9.97) (16.09) (15.56) (13.98) (12.20) (16.05) (17.24)

Cesarean section 8,878 1,102 3,980 749 194 31 21 153 1,589 869 190 0.00***
(55.97) (43.37) (50.89) (54.51) (84.35) (86.11) (46.67) (64.83) (70.25) (80.17) (81.90)

Macrosomia 549 88 250 48 7 0 2 8 (3.39) 89 48 (4.43) 9 (3.88) 0.55

(3.46) (3.46) (3.20) (3.49) (3.04) (4.44) (3.93)

Fetal distress 206 32 99 18 3 1 (2.78) 1 3 (1.27) 30 15 (1.38) 4 (1.72) 0.1

(1.30) (1.26) (1.270) (1.31) (1.30) (2.22) (1.33)

Transfer to neonatal unit 2,296 305 1,095 227 48 13 4 25 313 208 58 0.00***
(14.48) (12.00) (14.00) (16.52) (20.87) (36.11) (8.89) (10.59) (13.84) (19.19) (25.00)

Neonatal jaundice 778 117 382 62 11 1 (2.78) 2 12 109 62 (5.72) 20 (8.62) 0.37
(4.91) (4.60) (4.88) (4.51) (4.78) (4.44) (5.08) (4.82)

Apgar score <7 278 32 123 22 4 1 (2.78) 1 4 (1.69) 50 32 (2.95) 9 (3.88) 0.01*
within 5 min of birth (1.75) (1.26) (1.57) (1.60) (1.74) (2.22) (2.21)
*p < 0.05, statistically difference, **p < 0.01, statistically significant difference, ***p < 0.001, highly statistically significant difference. A1: 20–24 years old women, A2: 25–29 years old women,
A3: 30–34 years old women, AMA: 35–39 years old women, and vAMA: ≥ 40 years old women.

hyperactivation, and uteroplacental, resulting in an increase in

compared to the normal age group, respectively. In terms of the
blood pressure, systemic small artery spasm, a decrease in blood
relationship between gestational hypertension and age or parity,
flow to the uterus and placenta, placental imbalance, and even
our findings are consistent with previous studies indicating that
placental abruption. Kahveci B observed that the prevalence of
either age or parity was a risk factor for gestational hypertension.
gestational hypertension in AMA was 1.55 times higher than that
However, in terms of the interaction between age and parity, our
in women of normal age and that the prevalence increased with
result showed that the prevalence of nulliparous women in the
age, with the prevalence in vAMA being 1.68 times higher than
AMA group was greater than that of multiparous women, which
that in women of normal age (2). The prevalence of eclampsia and
was inconsistent with previous studies and may be due to weak
pre-eclampsia was 2.39 and 9.92 times greater in the vAMA group
awareness of blood pressure control in nulliparous women of

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AMA. The cesarean section is a negative pregnancy outcome that

pathophysiology is still poorly known and may involve infection,
has received increased attention in recent years. Our study
hemorrhage, and maternal-fetal stress. Previous studies have
identified age and parity as risk factors for cesarean section.
demonstrated that the relationship between preterm birth and age
However, in terms of the interaction between age and parity on
follows a U-shaped curve, with the lowest risk at 30–34 years and
cesarean section, the risk of cesarean section was higher in
increased risk at both younger than 24 years and older than
multiparous women of appropriate age than in nulliparous women
40 years (25). In the single age group of our study, we found a
of appropriate age, but it was higher in nulliparous women in the
greater risk of preterm birth in advanced and very advanced
AMA and vAMA groups than in multiparous women. The risk of
maternal age than in appropriate age women, and in the single
cesarean section was significantly elevated in nulliparous women
parity group, we found a greater risk of preterm birth in
of AMA; recent research suggests that this is likely attributable to
multiparous women than in nulliparous women, which is
faster changes in the risk of adverse outcomes in nulliparous
consistent with previous findings, but in the mixture of age and
women of AMA and an increased proportion of elective maternal
parity group, we found no regular relationship between the risk of
cesarean section (24). Regarding preterm birth, the
preterm birth and changes in age and parity, possibly due to the

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TABLE 5 Multivariable adjusted odds ratios (aOR) for adverse pregnancy outcomes and neonatal outcomes by group with different ages and parities.

Variables
FIGURE 1 Parity A1 A2 A3 AMA vAMA
Forest plot for risk of adverse pregnancy outcomes and neonatal outcomes by single age group. *p<0.05, statistically difference, **p<0.01, statistically significant difference, and ***p<0.001,
Gestational hypertension Nulliparas 1 1.25 (0.95–1.64) 1.67 (1.17–2.37)** 5.52 (3.36–9.09)*** 8.17 (3.07–
21.76)***

Multiparas 3.86 (0.89–16.84) 2.54 (1.22–5.29)* 4.47 (3.18–6.27)*** 4.53 (3.26–6.29)*** 9.86 (6.22–
15.62)***

Eclampsia/pre-eclampsia Nulliparas 1 2.02 (1.37–2.97)*** 3.48 (2.22–5.45)*** 7.75 (4.16– 11.30 (3.54–
14.44)*** 36.08)***

Multiparas 4.41 (0.58–33.80) 4.59 (1.95– 6.66 (4.25– 7.20 (4.64– 17.43 (10.02–
10.78)*** 10.44)*** 11.15)*** 30.33)***

Gestational diabetes Nulliparas 1 1.13 (1.00–1.26)* 1.47 (1.25–1.73)*** 2.76 (2.06–3.71)*** 2.84 (1.43–5.65)**
mellitus Multiparas 0.92(0.41–2.08) 1.21 (0.87–1.70) 1.60 (1.38–1.85)*** 2.10 (1.78–2.47)*** 2.56 (1.92–3.43)***

Placenta previa Nulliparas 1 1.08 (0.66–1.78) 1.88 (1.01–3.50)* 6.60 (2.94– 14.60 (3.95–
14.82)*** 54.04)***

Multiparas 0.00 3.71 (1.24–11.11)* 5.73 (3.34–9.84)*** 9.71 (5.81– 14.60 (7.49–
16.24)*** 28.48)***

Placental implantation Nulliparas 0.68 (0.43–1.06) 0.67 (0.33–1.36) 1.47 (0.43–5.09) 3.82 (0.47–30.78) 0.68 (0.43–1.06)

Multiparas 0.00 0.89 (0.12–6.67) 1.72 (0.90–3.26) 2.77 (1.59–4.80)*** 5.24 (2.31–
11.91)***

Postpartum hemorrhage Nulliparas 1 1.41 (1.08–1.83)* 1.84 (1.33–2.56)*** 2.78 (1.66–4.65)*** 4.50 (1.73–11.75)**

Multiparas 1.85 (0.43–8.02) 2.33 (1.27–4.29)** 3.22 (2.34–4.43)*** 3.52 (2.56–4.83)*** 4.55 (2.83–7.33)***

Preterm birth Nulliparas 1 0.81 (0.70–0.94)** 0.73 (0.57–0.92)** 2.23 (1.46–3.40)*** 2.74 (1.03–7.31)*

Multiparas 5.07 (2.13–12.06)*** 3.87 (2.50–5.99)*** 2.16 (1.74–2.69)*** 2.15 (1.72–2.69)*** 3.25 (2.16–4.88)***

Cesarean section Nulliparas 1 1.14 (1.03–1.26)* 1.39 (1.20–1.61)*** 10.05 (6.83– 11.95 (4.42–
14.79)*** 32.27)***

Multiparas 1.74 (0.91–3.30) 3.87 (2.86–5.23)*** 6.94 (6.05–7.96)*** 7.06 (5.88–8.48)*** 8.94 (6.21–
12.89)***

Transfer to neonatal unit Nulliparas 1 0.89 (0.77–1.03) 0.92 (0.74–1.14) 1.94 (1.28–2.92)** 4.09 (1.65–10.13)**

Multiparas 1.34 (0.30–5.89) 2.25 (1.37–3.69)** 3.14 (2.49–3.97)*** 3.41 (2.74–4.24)*** 5.35 (3.62–7.93)***

Apgar score <7 Nulliparas 1 1.08 (0.73–1.61) 1.15 (0.65–2.04) 1.78 (0.61–5.24)* 3.25 (0.42–25.42)
within 5 min of birth Multiparas 4.21 (0.55–32.13) 2.78 (0.96–8.09) 2.83 (1.71–4.68)* 2.96 (1.79–4.91)* 4.82 (2.24–10.40)*
*p < 0.05, statistically difference, **p < 0.01, statistically significant difference, ***p < 0.001, highly statistically significant difference. A1: 20–24 years old women, A2: 25–29 years old women,
A3: 30–34 years old women, AMA: 35–39 years old women, and vAMA: ≥40 years old women.

interference of additional confounding factors. Therefore, the

of gestational diabetes mellitus was 1.57 times higher in women
impact of the interaction between age and parity on the risk of with
preterm birth remains inconclusive. ≥4 parities than in nulliparous women (28). In terms of neonatal
Moreover, the risk of gestational diabetes mellitus and transfer outcomes, transferring to the neonatal unit is an adverse neonatal
to the neonatal unit was associated with age and the interaction outcome that has been less well studied. Similar to our findings,
between age and parity, according to our study. Gestational Vandekerckhove’s study revealed an increased risk of fetal transfer
diabetes mellitus was the most prevalent condition among AMA to the neonatal unit in older women (12). Our study also revealed that
in this study, and multiple investigations indicate the independent the interaction between age and parity resulted in a higher rate of
relationship between AMA and gestational diabetes mellitus (7, transfer to the neonatal unit in multiparous women than in
26). Regarding the interaction between age and parity, our results nulliparous women. In addition, the risk of certain pregnancy
showed that the prevalence of gestational diabetes mellitus outcomes in this study was solely connected with a single factor.
increased with age, with a greater prevalence of multiparous women We found that the risk of anemia, placenta abruption, premature
in the age-appropriate group than in the nulliparous age group. rupture of membrane, oligohydramnios, and macrosomia was
However, nulliparous women in the AMA group and vAMA group exclusively connected with parity, while the risk of fetal distress was
showed a higher risk of gestational diabetes mellitus than only associated with age. More research on anemia in pregnancy has
multiparous women in the AMA group and vAMA group, similar been conducted in developing nations, likely because the majority of
with the findings of Kahveci B and possibly attributable to anemia in pregnancy is connected with maternal malnutrition. Lebso’s
abnormal glucose and lipid metabolism in advanced maternal age study showed that parity was a risk factor for anemia in pregnancy
(27). Our study found no correlation between gestational diabetes (29), and our study came to a similar conclusion. Lin’s study
mellitus and parity. Casagrande SS demonstrated that the risk indicated that the risk of anemia in AMA is 1.386 times higher than
that of women of appropriate age (30), but our study

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did not find a relationship between anemia and age or anemia and
placental function in multiparous women. Maternal hyperglycemia
the interaction between age and parity, likely because our study
stimulates the secretion of insulin in large quantities, resulting in
population involved women who gave birth in tertiary care hospitals
faster fetal growth and the formation of macrosomia (33). Lei showed
in a developed province in China. Future research should focus on
that the risk of macrosomia in multiparous women was 1.26 times
anemic women residing in different locations and hospital levels.
that of nulliparous women (34), which is similar to our findings. A
Placenta abruption and premature rupture of the membrane are
Brazilian study showed that the odds of macrosomia in AMA were
common placental problems during pregnancy. Numerous studies
1.22 times higher than in the appropriate age group (35), but our
have shown the relationship between placental abruption and
study did not find a relationship between macrosomia and age, and
parity, especially in women with previous cesarean sections, and a
we did not find influence of the interaction between age and parity
previous meta-analysis confirmed that advanced age was also a
on macrosomia, which may be due to the low prevalence of
risk factor for placental abruption (19). Our study merely confirmed
macrosomia in our cohort. Fetal distress is a common adverse
the link between placental abruption and parity, while the etiology
neonatal outcome. A Chinese study showed that the incidence of
of placental abruption is still poorly known. Premature rupture of
fetal distress increased in pregnant women
membranes was one of the few pregnancy outcomes in our study,
>45 years old (36). The combination of gestational hypertensive
for which the risk was higher in nulliparous women than in
disease in AMA results in changes in the small systemic vascular
multiparous women. It emerges from intricate, multiple pathways
arteries and impaired circulation to the uterus and placenta, which
and predisposes women to premature births (31). Claramonte
leads to an inadequate supply of oxygen and nutrients to the fetus,
Nieto et al. found that the risk of premature rupture of membranes
thereby adversely affecting normal fetal development and even
was 1.25 times higher in AMA than in women of appropriate age
stillbirth. This leads to a lack of oxygen and nutrient supply to the
(32). However, neither age nor the interaction between age and
FIGURE 2 fetus, thus adversely leading to fetal distress. Currently, the
parity were found to be related to premature membrane rupture. In
Forest plot for risk of adverse pregnancy outcomes and neonatal outcomes by single parity group. *p<0.05,
connection statistically
between difference,
fetal *p<0.01,
distress andstatistically
advanced significant
age difference,
is still and ***p<0.001
addition, few studies have verified the relationship between
controversial. Our study found that the incidence of fetal distress at
oligohydramnios and age or parity; our study only verified that
30–34 years old was reduced, and the incidence of other ages and
parity was a risk factor for oligohydramnios, possibly due to
parities was not statistically significant. This may be due to the low
decreased

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incidence of fetal distress in the cohort, and future cohort

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studies with bigger samples could be performed to determine the

of the interaction between age and parity on adverse pregnancy
association between fetal distress and age and parity.
outcomes and neonatal outcomes; comprehensive adverse
outcomes, including neonatal jaundice, transfer to neonatal unit, and
other adverse outcomes investigated less frequently in the past;
Conclusion comprehensive confounding factors include pre-pregnancy BMI,
gestational weight gain and assisted reproduction, etc. The limitations
This study focused on exploring the impact of the interaction
are that the data were only from one tertiary care hospital in
between age and parity on adverse pregnancy and neonatal outcomes,
Yangzhou, China, which may be subject to selection bias and not
which may fill the current gap in the mixed role of advanced age
representative of all advanced maternal age in China due to
and parity on pregnancy outcomes. The following are the paper’s
geographical differences, economic level differences, etc. In addition,
strengths: large sample size, 15,861 maternal cases collected from
due to the limitations of data administration in Chinese hospitals
tertiary care hospitals over 5 years; wide distribution of maternal age,
and the secrecy of certain topics, such as personal income, certain
maternal age ≥20 years, including very advanced maternal age ≥40
confounding factors, such as a family history of illness,
years; detailed grouping based on three levels (age, parity, age, and
medications taken during pregnancy, etc., may be excluded. There is
parity); comprehensive comparison
still an increasing trend of advanced maternal age and very advanced

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maternal

FIGURE 3
Forest plot for risk of adverse pregnancy outcomes and neonatal outcomes by group with different ages and parities.

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age, so a multicenter large sample study could be designed to

conducted some data analysis. JD, YS, XK, and DL revised the article
further investigate the current status of pregnancy and the risk of
and provided final approval of the manuscript. All authors contributed
adverse pregnancy outcomes among women with different ages and
to the article and approved the submitted version.
parities. In our study, the interaction between age and parity on
adverse pregnancy outcomes such as intrahepatic cholestasis of
pregnancy, preterm birth, and anemia was not clear, and further
studies should be conducted to investigate these pregnancy outcomes.
Acknowledgments
On the whole, all these results will provide clinicians, midwives, and
The authors thank the midwives and physicians at the Department
obstetric nurses with more detailed information on the risk of
of Obstetrics and Gynecology, the Northern Jiangsu People’s
adverse maternal outcomes and how to safeguard the health of the
Hospital, Yangzhou City, Jiangsu Province, China, for their help
mother and fetus.
with study design and data collection.

Data availability statement Conflict of interest

The data analyzed in this study are subject to the following
The authors declare that the research was conducted in the
licenses/restrictions: Our data are derived from the obstetrics and
absence of any commercial or financial relationships that could
gynecology system of Northern Jiangsu People’s Hospital in
be construed as a potential conflict of interest.
Yangzhou, China, and cannot be disclosed to the public due to the
confidentiality of personal data. Requests to access these datasets
should be directed to Jiayang Dai, DjyYzu@163.com.
Publisher’s note
All claims expressed in this article are solely those of the
Author contributions authors and do not necessarily represent those of their affiliated
organizations, or those of the publisher, the editors and the
JD and YS contributed to the conception or design of the
reviewers. Any product that may be evaluated in this article, or
study, and drafted the manuscript. JD, YiW, YC, and LG collected
claim that may be made by its manufacturer, is not guaranteed or
data and conducted data analysis. DL, YuW, and HL reviewed the
endorsed by the publisher.
literature and

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