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Effect of advanced maternal age on pregnancy outcomes: a single-centre data

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Effect of advanced maternal age on pregnancy

outcomes: a single-centre data from a tertiary
healthcare hospital

Ahkam Göksel Kanmaz, Abdurrahman Hamdi İnan, Emrah Beyan, Suriye

Ögür & Adnan Budak

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JOURNAL OF OBSTETRICS AND GYNAECOLOGY
https://doi.org/10.1080/01443615.2019.1606172

ORIGINAL ARTICLE

Effect of advanced maternal age on pregnancy outcomes: a single-centre data

from a tertiary healthcare hospital
€ksel Kanmaza, Abdurrahman Hamdi _Inana, Emrah Beyana
Ahkam Go € u
, Suriye Og €rb and Adnan Budakb
a
Department of Obstetrics and Gynecology, Tepecik Training and Research Hospital, Izmir, Turkey; bIzmir provincial health directorate,
Izmir, Turkey

ABSTRACT KEYWORDS
The aim of this study was to assess the effect of advanced maternal age on pregnancy and neonatal Maternal age; neonate;
outcomes in patients attending a tertiary centre hospital. Between January 2013 and December 2016, obstetric labour; parity;
the records of all patients who were referred for pregnancy follow-ups and delivery were retrospect- pregnancy complications
ively reviewed and were divided according to their parity and age. Patients over 35 years old were cat-
egorised as advanced maternal age; (1) 35–40 years old. (2) 40–45 years old. (3) 45 years and over.
Most of the prenatal complications were found to increase in the advanced maternal age group. The
caesarian section rate was found to be higher in all advanced maternal age groups. There was no sig-
nificant relationship between 5 Minute Apgar scores of <7 and perinatal mortality and post-term preg-
nancy and parity. Globally, advanced maternal age pregnancy shows an increase as a result pregnancy
complication will increase. It is important to make a appropriate follow-up for pregnancies of advance
maternal age mothers.

IMPACT STATEMENT

What is already known on this subject? Advanced maternal age is a poor prognostic factor for
pregnancy outcomes. But there remains no consensus opinion or a plan for the management of
pregnancy in this particular risk group.

What do the results of this study add? This clinical study makes a contribution to the literature
for advanced maternal age and pregnancy complications. This study is one of the few studies
emphasising the importance of parity in advanced maternal age and the relationship between first
trimester pregnancy complications and advanced maternal age.

What are the implications of these findings for clinical practice and/or further research? After
the ART pregnancies increasing all around the world not only advanced age but the parity become
an important role. Due to an increase in advanced maternal age pregnancies in all around the
world, we think that better understanding and management of the complications to be encoun-
tered in advanced maternal age and parity pregnancies will be appropriate.

Introduction
Women working in the industry wait until the 4th decade of
their lives to give their birth; this trend has resulted in an
increased rate of pregnancy in the advanced maternal age
(35 years) (Benzies et al. 2006) (‘Turkey Statistical Institute,
Birth Statistics, 2016’ n.d.). In the United States, the number
of births among women aged 35–39 and 40–45 years has
increased (Martin et al. 2013). According to the Turkish
Statistical Institute (TSI) data in 2016, the birth rate among
women aged 45–49 years in Turkey was 0.1%, whereas it was
0.12% at the age of 40–45 years and 0.51% at the age of
35–40 years. Over the last 3 years, the average number of
women giving birth at the age of 35–40 years has increased,
whereas the average number of women giving birth at the
age of 40–45 and 45–49 years has decreased (‘Turkey
Statistical Institute, Birth Statistics, 2016’ n.d.).
The following factors have significantly contributed to
increased maternal age in pregnancy: changes in social and
economic life, increased education levels, developments
related to reproductive health, and easy access to these
developments by patients (Chan and Lao 2008; Balasch and
Grataco s 2012; Khalil et al. 2013; Fuchs et al. 2018). In add-
ition, the widespread application of assisted reproductive
techniques (ART) also plays an important role in the increase
of maternal age to the mid-forties (Gill et al. 2012; Schimmel
et al. 2015).
Although there are many studies that have investigated
the effects of advanced maternal age on prenatal and post-
natal outcomes, the results are contradictory. Advanced
maternal age causes an increase in birth rates associated
with preeclampsia, gestational diabetes mellitus (GDM), pla-
cental anomalies, and caesarean section (Chan and Lao 2008;

CONTACT Ahkam G€oksel Kanmaz drgokselkanmaz@gmail.com Department of Obstetrics and Gynecology, Tepecik Training and Research Hospital, Izmir,
35170, Turkey
ß 2019 Informa UK Limited, trading as Taylor & Francis Group
2 A. G. KANMAZ ET AL.
Ludford et al. 2012; Fuchs et al. 2018; Wang et al. 2011).
Advanced maternal age is also a risk factor for foetal chromo-
somal anomalies and ectopic pregnancy; however, previous
studies have also reported that maternal age is not a risk fac-
tor for pregnancy complications such as gestational hyper-
tension, preterm delivery, and large for gestational age (LGA)
(Balasch and Grataco s 2012; Gill et al. 2012; Nilsen et al.
2012; Khalil et al. 2013). Furthermore, the significance of par-
ity has been emphasised in studies examining the relation-
ship between advanced maternal age and pregnancy
complications (Lisonkova et al. 2010; Schimmel et al. 2015).
The present study aimed to report the effects of age and par-
ity on prenatal and postnatal outcomes in advanced maternal
age pregnancies in our clinic.
Materials and methods
This study retrospectively screened the pregnancy outcomes
of cases for which all pregnancy follow-ups were performed
in accordance with the Republic of Turkey Ministry of Health
guidelines (Ministry of Health 2014) based on current infor-
mation in the literature and deliveries, newborn examina-
tions, and (if necessary) newborn admissions were performed
at the Tepecik Training and Research Hospital Obstetrics and
Gynaecology Clinic between January 2013 and December
2016. Screening was performed using the hospital informa-
tion system, and the pregnancies with missing data were
excluded from the study. The inclusion criteria’s were; (1)
Patients over 25 years of age, (2) Giving birth after 20 weeks
of gestation or (3) Giving birth to a baby weighing >500 g.
The exclusion criteria were; (1) Foetal malformations, (2)
_Intrauterine foetal demise, (3) Pregnancy loss before 20 weeks
of gestation, (4) Patients lower than 25 years old.
Patients aged 35 years were designated as the advanced
maternal age group, which was further divided into three sub-
groups: 35–39 years as advanced maternal age, 40–44 years as
very advanced maternal age, and 45 years as very late mater-
nal age. For this study, the control group included all pregnan-
cies between 25 and 34 years of age for which follow-ups,
deliveries, and postnatal cares were performed at our hospital.
In addition to maternal age, the patients included in the study
were divided into two groups according to their parity: nul-
liparous and multiparous. The differences between the groups
were examined in terms of pregnancy and delivery outcomes
and neonatal complications.
Gestational age was calculated both using by the
first day of the last menstrual period (LMP) and the first tri-
mester or early second-trimester ultrasonography. Pregnant
women with no previous history of birth after gestational
week 20 or giving birth to a baby weighing >500 g were
considered as nulliparous, and the remaining women were
considered as multiparous. The ACOG 2013 (American
College of Obstetricians and Gynaecologists and Task Force
on Hypertension in Pregnancy 2013) recommendations are
utilised in our clinic for the diagnosis of preeclampsia, and
the ADA 2012 (American Diabetes Association 2012) and
2014 (American Diabetes Association 2014) recommendations
are utilised for the diagnosis of GDM. Delivery before
gestational week 37 was considered as preterm birth, and
these pregnancies were subgrouped among themselves as
preterm pregnancy (34–37 weeks and 32–34 weeks),
advanced preterm (28–32 weeks) and very advanced preterm
(<28 weeks). Delivery types were classified as vaginal deliv-
ery, instrumental delivery (vacuum, forceps) and caesarean
delivery, and the primary caesarean delivery rates were pro-
vided as sub-analyses of births by caesarean delivery. The
abnormally invasive placenta is diagnosed in our clinic by
radiological methods (ultrasonography, magnetic resonance
imaging) and any suspected abnormal location of chorionic
villi after radiological imaging methods is defined as abnor-
mally invasive placenta. Diagnoses was confirmed after deliv-
ery. Placenta abruption was diagnosed with examination and
finding of some signs like vaginally bleeding, uterine tender-
ness, abnormal foetal heart rate and uterine tachysystole.
Birth weight was divided into two groups: <2500 g and
>2500 g. Low birth weight was further subdivided as
extremely low birth weight (ELBW) for <1000 g, very low
birth weight (VLBW) for <1500 g, and low birth weight (LBW)
for <2500 g. Stillbirth was determined by retrospectively
screening 5 minute Apgar scores and the need for newborn
intensive care based on the delivery room and newborn
intensive care unit records. Ethics committee approval for
this study was obtained from the Tepecik Education and
Research Hospital Ethics Committee with 2017-9-1
approval number.
Statistical analysis
The results were presented as frequency and percentage.
Kolmogorow–Smirnov and Shapiro–Wilk tests were selected
in accordance with the number of pregnancies for normality
tests, and a normal distribution pattern was accepted if
p > .05. The results were presented as mean±standard devi-
ation (SD) for normally distributed data and median (min,
max) for non-normally distributed data. The chi-square test
or Fisher’s exact test was used for intergroup differences of
categorical variables based on the number of data. For
numeric univariate analyses, analysis of variance was used
for parametric variables, and the Kruskal–Wallis test was used
for non-parametric variables. A generalised mixed model was
planned for determine the relative risk (95% CI) (crude and
adjusted) between advanced maternal age and prenatal–-
postnatal complications. p < .05 was considered statistically
significant. Statistical analyses were performed using SPSS
22.0 for Windows (SPSS Inc., Chicago, IL) and SAS (version 9,
SAS Institute Inc, Cary, NC).
Results
In total, 45,234 pregnant women who applied to our clinic
between January 2013 and December 2016 and for whom all
prenatal and postnatal follow-ups were conducted in our
clinic were retrospectively screened. Figure 1 demonstrates
the flow chart of the study population. When the results
were presented, parity was also taken into consideration, and
all patients were grouped as nulliparous and multiparous.
 JOURNAL OF OBSTETRICS AND GYNAECOLOGY 3

42008 women
100 (100%)

15,071 (35.9%)
were excluded ≤25
years

20,622 (76.6%) 4,908 (18.2%) 1,331 (4.9%)

76 (0.3%) women
women 25–35 women 35–40 women 40–45
>45 years
years years years

Figure 1. Flowchart of the study population.

Table 1. Demographic information according to maternal age groups.

Aged 25–35 years Aged 35–40 years Aged 40–45 years Aged 45 years
Demographic information 20,622 (76.6%) 4908 (18.2%) 1331 (4.9%) 76 (0.3%) p value
Age (years) median
(min-max)
Nulliparous 28 (25–34) 36 (35–59) 41 (40–44) 45 (45–48) <.001
Multiparous 29 (25–34) 36 (35–39) 41(40–44) 46 (45–51) <.001
Gestational Week median
(min-max)
Nulliparous 39 (20–43) 39 (25–42) 39 (20–42) 38 (23–41) .020
Multiparous 38 (20–43) 38 (20–43) 38 (22,42) 38 (23–42) <.001
Parity
Nulliparous (n,%) 4835 (23.4%) 662 (13.5%) 186 (14%) 11 (14.5%) <.001
Multiparous (n,%) 15787 (76.6%) 4246 (86.5%) 1145 (86%) 65 (85.5%) <.001
Parity Nulliparous (n,%)
Singleton 4713 (97.5%) 650 (98.2%) 186 (100%) 11 (100%) .109
Multiple 122 (7.5%) 12 (1.8%) 0 (%0) 0 (%0)
Multiparous (n,%)
Singleton 15064 (95.4%) 4041 (95.2%) 1102 (96.2%) 61 (93.8%) .434
Multiple 723 (4.6%) 205 (4.8%) 43 (3.8%) 4 (6.2%)
Pre-Pregnancy
BMI (mean ± SD)
Nulliparous 23.1±4.2 24.2±4.1 24.6±5.2 23.9±5.4 .097
Multiparous 24.1±3.4 23.9±5.1 25.1±4.9 24.3±5.1 .102
Assisted reproduct-
ive techniques
Nulliparous 145 (3.1%) 47 (7.3%) 17 (9.2%) 7 (63.6%) .001
Multiparous 473 (3.3%) 297 (7.1%) 81 (7.3%) 9 (13.8%) .027
SD: standard deviation.
Bold values are p < .05.

The demographic information of women included in
the study is summarised in Table 1. As the maternal age
increased, the multiparous pregnancy rate was found to be
higher than the nulliparous pregnancy rate (p < .001, respect-
ively). There was no statistically significant were detected
with multiple pregnancy and pre-pregnancy body mass index
(BMI) between neither the nulliparous nor the multiparous
advanced maternal age groups. It was found that the rate of
ART significantly increased due to increased maternal age,
regardless of parity (p ¼ .001 and p ¼ .027) (Table 1).
The relationship between advanced maternal age and
pregnancy and delivery outcomes is summarised in Table 2.
A significant relationship was found only between advanced
maternal age and abortus imminence in nulliparous pregnan-
cies (p < .001), whereas no significant relationship was found
between advanced maternal age and abortus imminence in
multiparous pregnancies. The incidence of hyperemesis gravi-
darum was not associated with advanced maternal age in
nulliparous pregnancies, but it was more common in preg-
nancies among women aged 45 years than in the control
group and less common in pregnancies among women aged
35–40 and 40–45 years than in the control group (p ¼ .002).
There was a statistically significant increase in the incidence
of GDM in nulliparous and multiparous women in the
advanced maternal age group in comparison to the control
group (p < .001 and p < .001, respectively). The incidence of
preeclampsia was similar to that of GDM, and it was found to
be significantly higher in the advanced maternal age group
than in the control group, regardless of parity (p < .001 and
p < .001, respectively). In multiparous pregnancies with
advanced maternal age, the rate of placenta previa showed a
statistically significant increase with maternal age (p ¼ .002).
There was no significant relationship between abnormally
invasive placenta and all advanced maternal age group and
also in nulliparous pregnancy group there was no significant
relationship between placenta previa and advanced maternal
age. Similarly, in nulliparous and multiparous pregnancies, a
significant increase in caesarean rates and a significant
decrease in the rate of normal spontaneous vaginal and
instrumental deliveries were found in the advanced maternal
4 A. G. KANMAZ ET AL.

Table 2. Comparison of pregnancy and delivery outcomes according to maternal age groups.
Aged 25–35 years Aged 35–40 years Aged 40–45 years Aged 45 years
Results 20622 (76.6%) 4908 (18.2%) 1331 (4.9%) 76 (0.3%) p value
Abortus imminens
Nulliparous (n,%) 217 (4.5%) 57 (8.6%) 14 (7.5%) 1 (9.09%) <.001
Multiparous (n,%) 611 (3.9%) 199 (4.7%) 47 (4.1%) 4 (6.2%) .090
Hyperemesis gravidarum
Nulliparous (n,%) 129 (2.7%) 10 (1.5%) 5 (2.7%) 0 (0%) .332
Multiparous (n,%) 359 (2.3%) 65 (1.5%) 19 (1.7%) 4 (6.2%) .002
Gestational diabetes mellitus
Nulliparous (n,%) 308 (6.4%) 102 (15.4%) 36 (19.4%) 2 (18.2%) <.001
Multiparous (n,%) 968 (6.1%) 503 (11.8%) 185 (16.2%) 13 (20%) <.001
Preeclampsia
Nulliparous (n,%) 260 (5.4%) 58 (8.8%) 21 (11.3%) 1 (9.09%) <.001
Multiparous (n,%) 537 (3.4%) 243 (5.7%) 117 (10.2%) 8 (12.3%) <.001
Abnormally invasive placenta
Nulliparous (n,%) 14 (0.22%) 2 (0.30%) 0 (0%) 0 (0%) .325
Multiparous (n,%) 44 (0.27%) 14 (0.32%) 2 (0.17%) 0 (0%) .546
Placenta previa
Nulliparous (n,%) 27 (0.55%) 7 (1.05%) 2 (1.07%) 0 (0%) .1
Multiparous (n,%) 101 (0.63%) 40 (0.94%) 15 (1.3%) 1 (1.5%) .002
Delivery method Vaginal
Nulliparous (n,%) 1718 (35.5%) 140 (21.1%) 16 (8.6%) 3 (27.2%) <.001
Multiparous (n,%) 6596 (41.8%) 1471 (34.6%) 364 (31.8%) 19 (28.2%) <.001
Instrumental
Nulliparous (n,%) 16 (0.3%) 4 (0.6%) 0 (0%) 0 (0%)
Multiparous (n,%) 16 (0.1%) 7 (0.2%) 3 (0.3%) 0 (0%)
Caesarean
Nulliparous (n,%) 3101 (64.1%) 518 (78.2%) 170 (91.4%) 8 (72.7%) <.001
Multiparous (n,%) 9175 (58.1%) 2786 (65.2%) 778 (67.9%) 46 (71.8%) <.001
Primary Caesarean
Nulliparous (n,%) 3101 (64.1%) 518 (78.2%) 170 (91.3%) 8 (72.7%) <.001
Multiparous (n,%) 3160 (20%) 1138 (26.08%) 405 (35.3%) 29 (43.2%) <.001
Foetal presentation in vaginal birth Vertex
Nulliparous (n,%) 4591 (95%) 614 (92.7%) 175 (94.1%) 11 (100%) <.001
Multiparous (n,%) 15171 (96.1%) 4044 (95.2%) 1073 (93.7%) 58 (89.2%) <.001
Breech presentation
Nulliparous (n,%) 211 (4.4%) 39 (5.9%) 7 (3.8%) 0 (0%) .056
Multiparous (n,%) 561 (3.6%) 183 (4.3%) 64 (5.6%) 4 (6.2%) .002
Other
Nulliparous (n,%) 33 (0.6%) 9 (1.4%) 4 (2.2%) 0 (0%) <.001
Multiparous (n,%) 55 (0.3%) 19 (0.4%) 8 (0.7%) 3 (4.6%) <.001
Preterm delivery 28 weeks or earlier
Nulliparous (n,%) 67 (1.3%) 2 (0.3%) 1(0.5%) 0 (0%) .02
Multiparous (n,%) 277(1.8%) 86 (2%) 33 (2.9%) 3 (4.4%) <.001
28–32 weeks
Nulliparous (n,%) 89 (1.8%) 15 (2.2%) 3 (1.6%) 1 (9.09%) .005
Multiparous (n,%) 348 (2.2%) 148 (3.5%) 29 (2.5%) 3(4.4%) .03
32–34 weeks
Nulliparous (n,%) 112 (2.3%) 12 (1.8%) 6 (3.2%) 0 (0%) .05
Multiparous (n,%) 402 (2.5%) 125 (3%) 25 (2.2%) 0 (0%) .03
34–37 weeks
Nulliparous (n,%) 427 (8.8%) 74 (11.1%) 16 (8.6%) 4 (36.3%) <.001
Multiparous (n,%) 1821 (11.5%) 561 (13.2%) 177 (15.5%) 10 (14.9%) <.001
Bold values are p < .05.

age group (p < .001 and p < .001, respectively). A statistically
significant increase in non-vertex foetal presentation and
advanced maternal age was found in all pregnancies
(p < .001 and p < .001, respectively), and this increase was
more prominent in multiparous pregnancies. There was a
statistically significant correlation between the primary cae-
sarean rate and advanced maternal age in both nulliparous
and multiparous women who delivered by caesarean section
(p < .001 and p < .001, respectively).
As the maternal age is increased, there was a significant
preterm birth in nulliparous and multiparous women (Table
2). However, the frequency of delivery before gestational
week 28 significantly decreased as the maternal age
increased only in nulliparous women (p ¼ .02). The effect of
advanced maternal age on neonatal outcomes is summarised
in Table 3. There was a statistically significant increase in the
birth weight in nulliparous pregnancies as maternal age
increased (p ¼ .035), whereas a decrease was observed in the
birth weight in multiparous pregnancies as the maternal age
increased; however, this difference was not significant
(p ¼ .056). There was no significant relationship between
maternal age and LBW (<2500 g, 1000–1500 g, and <1000 g)
in nulliparous pregnancies, but there was a statistically sig-
nificant relationship between advanced maternal age and
LBW in multiparous pregnancies (p ¼ .005, p ¼ .004 and
p ¼ .005, respectively). The incidence of macrosomic foetuses
significantly increased with advanced maternal age, regard-
less of parity (p < .001 and p < .001, respectively). There was
 JOURNAL OF OBSTETRICS AND GYNAECOLOGY 5

Table 3. Evaluation of neonatal outcomes according to maternal age groups.

Aged 25–35 years Aged 35–40 years Aged 40–45 years Aged 45 years
Results 20622 (76.6%) 4908 (18.2%) 1331 (4.9%) 76 (0.3%) p value
Birth weight in gestation (g) (median, min-max)
Nulliparous 3200 (500–5750) 3197 (580–5340) 3325 (600–4530) 3280 (1095–3910) .035
Multiparous 3220 (500–5550) 3200 (500–5480) 3200 (500–5550) 3100 (515–4360) .056
Low birth weight 1500–2500 g
Nulliparous (n,%) 498 (10.2%) 80 (12%) 18 (9.6%) 0 (0%) .071
Multiparous (n,%) 1575 (9.9%) 492 (11.5%) 138 (12%) 6 (54.5%) .005
1000–1500 g
Nulliparous (n,%) 95 (1.96%) 10 (1.51%) 2 (1%) 1 (9.09%) .089
Multiparous (n,%) 252 (1.5%) 125 (2.9%) 28 (15%) 1 (9.09%) .004
1000 g or less
Nulliparous (n,%) 76 (1.5%) 5 (0.7%) 3 (1.6%) 0 (0%) .086
Multiparous (n,%) 284 (1.8%) 97(2.2%) 37 (3.2%) 3 (27.2%) .005
Macrosomic foetus
Nulliparous (n,%) 313 (6.4%) 95 (9.3%) 17 (9.1%) 0 (0%) <.001
Multiparous (n,%) 969 (6.1%) 336 (7.1%) 115 (10%) 5 (7.7%) <.001
5 Minute Apgar score <7
Nulliparous (n,%) 97 (2%) 13 (1.98%) 4 (2.3%) 0 (0%) .465
Multiparous (n,%) 315 (1.9%) 100 (2.3%) 23 (2.1%) 2 (3.2%) .068
Newborn intensive care needs
Nulliparous (n,%) 463 (9.6%) 75 (11.3%) 24 (12.9%) 2 (18.2%) .139
Multiparous (n,%) 1460 (9.2%) 534 (12.6%) 161 (14.1%) 13 (20%) <.001
Stillbirth
Nulliparous (n,%) 57 (1.2%) 5 (0.8%) 1 (0.5%) 0 (0%) .653
Multiparous (n,%) 270 (1.7%) 67 (1.6%) 27 (2.4%) 1 (1.5%) .349
Bold values are p < .05.

Table 4. Effect of advanced maternal age on pregnancy and neonatal complications.

Aged 35–40 years 4908 (18.2%) Aged 40–45 years 1331 (4.9%) Aged 45 years 76 (0.3%)
Crude RR Adjusted RR Crude RR Adjusted RR Crude RR Adjusted RR
(95 % CI) (95 % CI) (95 % CI) (95 % CI) (95 % CI) (95 % CI)
Abortus imminence
Nulliparous 1.16 (1.03–1.32) 0.91 (0.69–1.19) 1.09 (0.08–1.48) 0.96 (.61–1.51) 0 (0%) 0 (0%)
Multiparous 0.88 (0.74–1.05) 0.89 (0.69–1.06) 0.74 (050–1.11) 0.74 (0.49–1.13) 2.67 (1.06–6.07) 2.42 (0.94–6.42)
Hyperemesis gravidarum
Nulliparous 0.71 (0.57–0.90) 0.85 (0.60–1.22) 1.34 (0.92–1.92) 0.67 (0.34–1.32) 0.85 (0.11–6.10) 1.64 (0.22–12.2)
Multiparous 0.67 (0.52–0.88) 0.77 (0.57–1.04) 0.93 (0.57–1.50) 0.94 (0.57–1.57) 1.91 (0.46–7.81) 1.79 (0.43–7.48)
Gestational diabetes mellitus
Nulliparous 1.69 (1.57–1.83) 1.07 (0.82–1.39) 0.81 (0.61–1.09) 1.25 (0.82–1.89) 0.90 (0.28–2.82) 0.90 (0.12–6.74)
Multiparous 0.80 (0.62–1.04) 0.93 (0.80–1.09) 0.98 (0.74–1.30) 0.99 (0.74–1.33) 0.96 (0.30–3.07) 0.88 (0.27–2.87)
Preeclampsia
Nulliparous 1.49 (1.34–1.66) 0.91 (0.69–1.19) 0.76 (0.52–1.11) 0.92 (0.62–1.49) 0.48 (0.06–3.41) 0.69 (0.09–5.31)
Multiparous 1.08 (0.93–1.27) 1.12 (0.92–1.37) 1.11 (0.79–1.55) 1.14 (0.64–1,64) 1.63 (0.51–5.23) 1.17 (0.35–3.91)
C section
Nulliparous 1.12 (1.04–1.24) 1.15 (0.98–1.44) 1.22 (1.09–1.36) 1.09 (0.99–1.46) 1.07 (0.63–1.82) 1.02 (0.59–1.72)
Multiparous 1.07 (1.04–1.17) 1.12 (0.84–1.16) 1.10 (1.04–1.16) 0.98 (0.86–1.10) 1.12 (0.90–1.41) 1.07 (0.85–1.29)
Preterm delivery
Nulliparous 1.19 (1.12–1.27) 0.90 (0.74–1.09) 1.03 (0.88–1.20) 0.83 (0.59–1.17) 1.92 (1.07–3.44) 1.07 (0.27–4.25)
Multiparous 0.97 (0.89–1.05) 0.91 (0.86–1.1) 0.98 (0.63–1.60) 0.96 (0.73–1.27) 2.23 (1.25–3.95) 1.36 (0.59–3.14)
NICU need
Nulliparous 1.30 (1.20–1.40) 0.77 (0.61–0.96) 0.94 (0.76–1.19) 1.15 (0.81–1.61) 0.37 (0.09–1.54) 0.83 (0.17–4.09)
Multiparous 1.09 (0.98–1.20) 1.17 (1.02–1.34) 1.02 (0.82–1.27) 1.05 (0.80–1.37) 2.56 (1.31–4.98) 1.78 (0.78–4.04)
Stillbirth
Nulliparous 1.06 (0.86–1.32) 1.29 (0.71–2.32) 1.01 (0.62–1.63) 0.60 (0.26–1.36) 0.93 (0.13–6.70) 0.23 (0.02–2.18)
Multiparous 0.92 (0.70–.120) 0.75 (0.56–1.01) 1.18 (0.67–2.06) 1.16 (0.62–2.14) 0.86 (01.2–6.31) 1.13 (0.14–3.14)
Adjusted for maternal prepregnancy BMI, birthweight, ART pregnancy.
Bold values are p < .05.
Data compared with the 25–35 years group variable for calculate relative risk.

no significant relationship between 5 Minute Apgar scores of
<7 and perinatal mortality and advanced gestational week
and parity. Although there was no significant difference in
the need for newborn intensive care in advanced maternal
age nulliparous pregnancies, the need for newborn intensive
care in multiparous pregnancies was found to be significantly
higher in the advanced maternal age group than in the con-
trol group (p < .001).
The relative risks of pregnancy and neonatal complications
in advanced maternal age for nulliparity and multiparity were
calculated and summarised in Table 4. Only the risk of HEG
(hyperemesis gravidarum) (RR 0.71, 95% CI 0.57-0.90, p < .05)
was significantly decreased in the 35–40 years nulliparous
group. However, no statistically significant difference was
found in the relative risks of pregnancy complications except
caesarean section (C section) in multiparous pregnancies in
6 A. G. KANMAZ ET AL.
the 35–40 years group. When relative risk was adjusted for
maternal prepregnancy BMI, birthweight, ART pregnancy;
only gestational diabetes in nulliparous group (aRR 1.07, 95%
CI 0.82–1.39, p < .05), and need for NICU in both nulliparous
(aRR 0.77, 95% CI 0.61–0.96, p < .05) and multiparous group
(aRR 1.17, 95% CI 1.02–1.34, p < .005) to be found statistically
significance. Regarding the relationship between 35–40 years
group and pregnancy and neonatal outcomes; in the
40–45 years group only C section risk ratio was slightly
increased. Like crude risk ratio adjusted risk ratio was only
statistically significance between C section rate and
40–45 years nulliparous pregnancy. While abortus imminence
(RR 2.67, 95% CI 1.06–6.07, p < .05), preterm delivery (RR 2.23,
95% CI 1.25–3.95, p < .05) and need for NICU (RR 2.56, 95%
CI 1.31–4.98, p < .05) relative risks were significantly increased
in above 45 years multiparous group, there was a significant
increase only in the relative risk of preterm delivery (RR 1.92,
95% CI 1.07–3.44, p < .05) in nulliparous pregnants. Despite
of crude relative risks there was no statistically significance
adjusted relative risk increase in above 45 years group.
Discussion
There has been a worldwide increase in advanced maternal
age pregnancies, which are likely to further increase in the
following years. As a result, it is expected that the complica-
tion rates will increase in mothers with their first pregnancy
at an advanced age and their children.
In our study, the incidence of GDM and preeclampsia was
found to significantly increase with increase in maternal age
during pregnancy. In our study, a highly significant increase
in the incidence of preeclampsia was observed particularly in
the multiparous advanced maternal age group above
45 years (aRR 5.31 95% CI). Furthermore, the risk of GDM
increased by 6.74 in nulliparous pregnancies in maternal age
above 45 years and by 2.87 in multiparous pregnancies with
a 95%. Our results are consistent with those of other
reported studies (Ludford et al. 2012; Kenny et al. 2013;
Marozio et al. 2017). The incidence of preeclampsia in
advanced maternal age pregnancies may increase due to
increased oxidative stress with age and endothelial dysfunc-
tion that may occur in the vascular wall (Bruno et al. 2018).
The incidence of GDM may increase due to the changes in
carbohydrate metabolism that occur with increasing age
(Lohse et al. 2018). However, previous studies have also
reported that there is no relationship between preeclampsia
and advanced maternal age and parity and there is no rela-
tionship between GDM and advanced maternal age (Balasch
and Grataco s 2012; Ludford et al. 2012; Nilsen et al. 2012;
Khalil et al. 2013; Fuchs et al. 2018; Wang et al. 2011).
In our study, it was determined that the significant
increased relative risk of first trimester bleeding was in
45 years and above multiparous group. One of the possible
mechanism may be affected progesterone levels at first tri-
mester because of lack of corpus gravidarum due to
increased rates of ART pregnancies at advanced maternal age
(De Sutter et al. 2006) and the other possible mechanism is
the aging of endometrium and ovarian follicle (Yang J et al.
2005). Likewise, hyperemesis gravidarum risk increase more
in multiparous advanced maternal age pregnancies. Our
results about hyperemesis gravidarum was contrary to the lit-
erature (Bolin et al. 2013; Petry et al. 2018). Social demo-
graphic differs may have a role for the different results about
hyperemesis gravidarum in our study.
In our study, an increase relative risk in caesarean delivery
were found in all advanced maternal age groups independ-
ently of parity. Higher rates of ART, increased uterine surgery
rates, and pregnancy complications being more frequent in
advanced maternal age pregnancies played a major role in
this outcome. Many studies have also found an increase in
caesarean delivery rates in advanced maternal age pregnancies
(Yogev et al. 2010; Khalil et al. 2013; Marozio et al. 2017; Wang
et al. 2011). In subanalyses, women giving birth by caesarean
section were subdivided into two groups as primary caesarean
and recurrent caesarean, and the caesarean delivery rates were
found to be higher in advanced maternal age pregnancies,
particularly in nulliparous women. The most important reason
for the higher rate of primary caesarean section in nulliparous
women is ART pregnancies, and in a study evaluating ART
pregnancies, the ratio of primary caesarean section was shown
to be higher than spontaneous pregnancy (Jackson et al.
2015) . Although the relationship between instrumental deliv-
ery and advanced maternal age in our study is similar to that
reported in the literature, we believe that the instrumental
delivery rate obtained in our study was lower than that
reported in similar studies primarily due to medicolegal con-
siderations. Similar to other studies, as maternal age increased,
it was found that non-vertex foetal position is increased in
both nulliparous and multiparous women (Yogev et al. 2010;
Laopaiboon et al. 2014; Jackson et al. 2015).
In our study, a significant increase was found in the pre-
term delivery in advanced maternal age pregnancies inde-
pendently of parity and the highest significant relative risk
was determined in 45 years and above multiparous group
(aRR 2.23, 95% CI 1.25 and 3.95, p < .05). Although there are
studies in agreement with our results, the study by Schimmel
et al. in 2015 found no significant relationship between pre-
term pregnancies before gestational week 34 and advanced
maternal age (Yogev et al. 2010; Schimmel et al. 2015;
Marozio et al. 2017). These different results may be attributed
to the fact that the age range of the control group was lower
than that in our study. In our study, the rate of delivery
before gestational week 28 decreased in nulliparous pregnan-
cies with advanced maternal age, and this could have been
due to advanced maternal age nulliparous pregnancies being
mostly ART pregnancies (De Sutter et al. 2006) and increased
rate of working mother may have a reason for increased early
PTB (Goldenberg et al. 2008).
In our study, there was no significant difference between
LBW and advanced maternal age in nulliparous pregnancies.
However, there was a significant relationship between LBW
and advanced maternal age in multiparous pregnancies,
which is similar to results reported in the literature (Yogev
et al. 2010; Khalil et al. 2013; Marozio et al. 2017). Consistent
with the literature, the incidence of macrosomic foetuses in
advanced maternal age pregnancies was higher in both nul-
liparous and multiparous pregnancies (Kenny et al. 2013).

However, Lisonkova et al. found no significant relationship
between small for gestational age (SGA) and advanced
maternal age in multiparous pregnancies in 2010, and
Schimmel et al. and Wang et al. found no relationship
between primiparous and multiparaous advanced maternal
age pregnancies and LBW (Lisonkova et al. 2010; Schimmel
et al. 2015; Wang et al. 2011). Moreover, previous studies
have conduced that there is no relationship between macro-
somia and advanced maternal age (Yogev et al. 2010;
Marozio et al. 2017). Patient selection criteria, different geo-
graphical locations, and different genetic backgrounds may
play a role in these different outcomes.
Consistent with many studies in the literature, we found
no significant relationship between 5 minute Apgar scores of
<7, perinatal mortality, and advanced maternal age and par-
ity (Schimmel et al. 2015; Marozio et al. 2017; Wang et al.
2011). In our study, it was found that the need for newborn
intensive care was significantly higher except above 45 years
nulliparous group in infants of multiparous advanced mater-
nal age pregnancies. Our results were consistent with those
of Yogev et al. 2010 and Laopaiboon et al. 2014.
Our study has various limitations. This study was a retro-
spective study and our data were not countywide like some
of the biggest studies. Despite of our limitations, there are
only a few single-centred studies in the literature evaluating
a high number of pregnancies and an advanced maternal
age of 45 years. In most studies in the literature on
advanced maternal age and pregnancy outcomes, parity was
not taken into consideration in the results. In order to avoid
possible biases related to parity, our results were organised
into two groups: nulliparous and multiparous pregnancies.
Our study also differs from other studies in the literature in
that it also includes first trimester pregnancy complications.
In conclusion, our findings indicate that the incidence of
many pregnancy complications, particularly GDM and pree-
clampsia and also first trimester pregnancy complications, is
increased in advanced maternal age pregnancies and that as
the maternal age increases, preterm birth and the caesarean
delivery rates increases. Also, our findings indicate that parity
is an important variable for the pregnancy complication risks
in the advanced maternal age group. Hence, it is important
that pregnant women of advanced maternal age be informed
about the complications that may arise for both themselves
and their babies, and pregnancy follow-ups should be per-
formed with new protocols that are appropriate for advanced
maternal age. Further studies on this topic are currently
required in order to determine these new protocols due to
the differences in the literature in terms of outcomes of
advanced maternal age pregnancies.
Disclosure of interest
The authors report no conflict of interest
ORCID
Emrah Beyan http://orcid.org/0000-0002-1662-5051
JOURNAL OF OBSTETRICS AND GYNAECOLOGY 7
€ ur
Suriye Og€ http://orcid.org/0000-0002-8993-674X
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