ORIGINAL ARTICLES

111
American Journal of Perinatology, Volume 19, Number 1, 2002. Address for correspondence and reprint requests: Dr. Muhieddine A.-F.
Seoud, American University of Beirut, 850 Third Avenue, New York, NY 10022.
1
Department of Obstetrics and Gynecology, American
University of Beirut Medical Center, Beirut, Lebanon. Copyright 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New
York, NY 10001, USA. Tel: +1(212) 584-4662. 0735-1631,p;2002,19,01,001,008,ftx,en;ajp36770x.
Impact of Advanced Maternal Age
on Pregnancy Outcome
Muhieddine A.-F. Seoud, M.D.,
1
Anwar H. Nassar, M.D.,
1
Ihab M. Usta, M.D.,
1
Ziad Melhem, M.D.,
1
Alia Kazma, M.S.,
1
and Ali M. Khalil, M.D.
1
ABSTRACT
The aim of this study was to compare the pregnancy outcome and deliv-
ery complications in women 40 years or older (cases) to that of women 20 to 30
years old (controls). Over a 5-year period, 319 cases had a singleton delivery in
our institution. These women were compared with 326 controls. Parity was sig-
nificantly higher in cases compared with controls (3.2 vs. 1.8). Advanced mater-
nal age, compared with younger age, was associated with significantly higher
rates of preterm delivery (16.0 vs. 8.0%), cesarean delivery (CS) (31.3 vs. 13.5%),
and the occurrence of one or more antepartum complications (29.5 vs. 16.6%).
When the two groups were subdivided according to parity, rates of preterm deliv-
ery, CS, preeclampsia, gestational diabetes, chronic hypertension, and labor in-
duction were each significantly higher among older multiparas compared with
control multiparas. However, only preterm delivery, CS rates, and uterine fibroids
were found to be significantly higher in older nulliparous compared with young
nulliparous women. We conclude that multiparous women at least 40 years old
have a higher antepartum complication rate including intrauterine fetal death
compared with younger women.
KEYWORDS: Advanced maternal age, pregnancy outcome
An increasing number of women are delay-
ing their childbirth because of social, economical,
and educational factors. In developed countries,
women are more involved with their professional
career and thus delay their childbearing until the
fourth and fifth decade, and most of them are
nulliparous at the time of delivery. In developing
countries, most of these women are multiparous.
Women above the age 35 have traditionally been
termed elderly gravidas.
1,2
Recently, more interest
has been focused on women who are more than 40
years old especially with the widespread use of as-
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2 AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 19, NUMBER 1 2002
sisted reproductive technologies. There are sev-
eral reports of pregnancies with egg donation even
in postmenopausal women above the age of 50.
3,4
Only a few years ago, such women were discour-
aged from getting pregnant because of the higher
maternal and perinatal morbidity and mortal-
ity.
1,2,5
However, recently many studies have shown
a favorable outcome in such elderly pregnant
women.
6,7
We, thus, conducted our study to try
to determine the frequency of adverse obstetrical
outcome in women 40 years or older in comparison
with women 20 to 30 years old at our institution.
MATERIALS AND METHODS
Between January 1992 and December 1996, 329
women 40 years or older (cases) were delivered of
a singleton pregnancy beyond 20 weeks of gesta-
tion at the American University of Beirut Medical
Center. These women were compared with another
group of 329 women (controls), between the ages
of 20 to 30 years, who delivered immediately after
each case. After excluding 13 patients with incom-
plete data, 319 cases and 326 controls were entered
for analysis. Cases and controls were matched for
parity, (nulliparous to nulliparous and multiparous
to multiparous). Nulliparas included women who
had not previously delivered a viable fetus (>24
weeks of gestation). Multiparas included women
who had at least one prior pregnancy that pro-
gressed beyond 24 weeks of gestation, regardless of
the actual parity number. Multiple gestations, with
their inherent increased risk of adverse outcome,
5
were excluded. We studied the following preg-
nancy complications and outcomes: preterm deliv-
ery (defined as delivery at <37 weeks of gestation),
chronic hypertension, gestational diabetes, pre-
eclampsia, fibroid uterus, intrauterine growth re-
striction (defined as fetal weight <5th percentile
for gestational age), placental abruption, operative
vaginal delivery, cesarean delivery, birth weight,
Apgar score at 5 minutes <7, congenital malfor-
mation, and intrauterine fetal death (IUFD). The
same variables were compared after stratification
according to parity. Data analysis was performed
using SPSS statistical program. Independent sam-
ple Students t-test was used for comparison of
means of continuous variables with normal or ap-
proximately normal distributions. Discrete vari-
ables were analyzed by using Chi-square analysis
for assessment of association or for comparison of
independent proportions. A p value of <0.05 was
considered statistically significant. Multiple step-
wise logistic regression analysis was used to iden-
tify the multivariate predictors of the following
adverse outcomes: cesarean section (CS), preterm
delivery, and obstetrical complications (gestational
diabetes, preeclampsia, and placental abruption).
The independent variables included in the model
were maternal age (at least 40 years or 20 to 30
years) and parity (nulliparous or multiparous) and
relevant co-variates.
RESULTS
The mean age of women above 40 was 41.7 2.1
years compared with 26.5 3.2 years in the con-
trol group. Whereas 9.4% of the patients over age
40 had used assisted reproductive technology, this
was used in only 2.1% of the control group (p =
0.000). Gravidity (5.2 3.2 vs. 3.2 1.6; p =
0.000) and parity (3.2 2.7 vs. 1.8 1.3;
p = 0.000) were significantly higher in cases com-
pared with controls. The mean gestational age at
delivery was significantly lower in the study group
(38.1 3.1 weeks vs. 38.8 2.8 weeks; p = 0.011).
Although more cases required induction compared
with controls (15.4 vs. 9.5%; p = 0.000), there was
no significant difference in the rate of operative
vaginal delivery (24.7 vs. 29.4%) or in the duration
of labor (374 244 minutes vs. 373 281 min-
utes). Inductions were done for a medical or ob-
stetrical indication in 65.3% of cases versus 41.9%
of controls. Cesarean delivery was significantly
higher in cases compared to controls (n = 100;
31.3% vs. n = 44; 13.5%). The most frequent in-
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ADVANCED MATERNAL AGE ON PREGNANCY OUTCOME/SEOUD ET AL 3
Table 1 Obstetrical and Medical Complications in
Pregnancies Over the Age of 40 Years Compared with
Women 20 to 30 Years Old
40 Years 2030 Years
Complication n = 319 (%) n = 326 (%) P Value
Preterm delivery 16.0 8.0 0.002
Gestational diabetes 5.3 0.9 0.000
Growth retardation 1.6 0.9 0.458
Placental abruption 1.9 1.2 0.508
Preeclampsia 4.4 0.9 0.006
Chronic hypertension 4.7 0.9 0.004
Fibroid uterus 3.8 0.9 0.017
Any obstetrical 29.5 16.6 0.000
complication
Table 2 Perinatal Outcome of Pregnancies in Both
Groups
40 Years 2030 Years
n = 319 n = 326 P Value
Birth weight (g)* 3149 764 3216 628 0.225
5-min Apgar score
<7 (%) 1.6 1.0 0.117
Chromosomal 0.9 0.0 0.243
abnormalities (%)
Congenital 1.9 0.6 0.280
malformation (%)
Intrauterine fetal 5.3 1.2 0.009
death (%)
*Data presented as mean standard deviation.
dications for CS in cases and controls were prior
CS (43.2 vs. 50.0%), nonreassuring fetal tracing
(16.8% vs. 15.9%), abnormal presentation (11.6%
vs. 18.2%), and arrest disorders (10.5 vs. 4.5%), re-
spectively. Moreover, parity did not seem to affect
the indication for CS in either group.
Advanced maternal age was associated with
a higher rate of pregnancy complications including
preterm delivery, gestational diabetes, preeclamp-
sia, chronic hypertension, and uterine myomas
compared with controls (Table 1). There was one
maternal death in the advanced maternal age
group. This was a 43-year-old multigravida with
no prenatal care who presented at 39 weeks gesta-
tion with eclampsia and was delivered by cesarean
section of a live female newborn with Apgar scores
of 3 and 4 at 1 and 5 minutes, respectively. Her
postpartum course was complicated by intracere-
bral hemorrhage to which she succumbed.
Table 2 summarizes the perinatal outcome
variables. The study group had a significantly higher
number of IUFDs. After excluding the 2 study pa-
Table 3 Obstetrical and Medical Complications in Cases Versus Controls: Analysis by Parity
Nulliparous Multiparous
40 Years 2030 years 40 Years 2030 Years
n = 53 n = 51 P n = 266 n = 275 P
Mean age (y)

41.5 1.6 25.2 3.3 41.7 2.2 26.7 3.1

Gestational age (wk)

38.0 3.6 38.9 2.2 0.106 38.2 3.3 38.7 2.9 0.039
Preterm delivery (%) 22.6 7.8 0.037 14.7 8.0 0.014
Cesarean delivery (%) 32.1 9.8 0.005 31.2 14.2 0.000
Labor induction (%) 9.4 13.7 0.367 16.5 8.7 0.000
Duration of labor (min)

527 224 538 330 0.874 346 238 341 260 0.827
Oper. vag. delivery (%) 63.9 54.3 0.384 16.9 24.6 0.058
Gestational diabetes (%) 3.8 0.0 0.154* 5.6 1.1 0.000
Placental abruption (%) 1.9 2.0 0.978 1.9 1.1 0.454
Preeclampsia (%) 5.7 5.9 0.961* 4.1 0.0 0.001
Chronic HTN (%) 1.9 2.0 0.978 5.3 0.7 0.002
Fibroid uterus (%) 7.5 0.0 0.045* 3.0 1.1 0.117
Any obst. complication 28.3 17.6 0.197 29.7 16.4 0.000
*Cells with expected frequency <5 are more than 33%.

Data presented as mean standard deviation.

Abbreviations: Oper. vag. delivery, operative vaginal delivery; Chronic HTN, Chronic hypertension; obst., obstetrical.
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4 AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 19, NUMBER 1 2002
tients where the IUFD occurred intrapartum during
termination for a prenatally diagnosed chromosomal
abnormality (trisomy 21), the mean gestational age
at intrauterine fetal death was 31.2 weeks in the
cases versus 23.3 weeks in the controls. All 4 fetal
deaths in the control group occurred at 24 weeks
gestation while only (4/17) 24.0% of such deaths oc-
curred at this gestational age in the cases. Of the re-
maining 13 IUFD, 8 (61.5%) did not have an identi-
fiable risk factor (preeclampsia, diabetes, postdates
or prematurity).
In Tables 3 and 4, the obstetrical, medical,
and perinatal complications were analyzed accord-
ing to parity. Multiparous cases had significantly
higher rates of preterm delivery, CS, preeclamp-
sia, gestational diabetes, chronic hypertension, and
labor induction compared with multiparous con-
trols. However, only preterm delivery, CS rates, and
Table 5 Maternal Morbidity in Pregnancies Over 40: Results of the Multiple Regression Models
OR 95% CI
Risk factors for cesarean delivery
Age (y)
2039 1.00
40 2.67 1.774.02 0.0000
Obstetric complications
None 1.00
Single or multiple 2.47 1.533.99 0.0002
Risk factors for preterm delivery
Obstetrical complications
None 1.00
Single or multiple 9.40 5.3216.6 0.000
Age (y)
2039 1.00
40 1.77 1.023.06 0.04
Risk factors for obstetrical complications
Medical complications
No 1.00
Yes 6.98 3.0915.7 0.000
Age (y)
2039 1.00
40 2.14 1.463.16 0.000
Table 4 Perinatal Outcome in Pregnancies Above the Age of 40 Years: Analysis by Parity
Nulliparous Multiparous
40 Years 2030 Years 40 Years 2030 Years
n = 53 n = 51 P n = 266 n = 275 P
Birth weight (g)

3075 804 3228 628 0.460 3163 757 3214 630 0.228
5-min Apgar score <7 (%) 2.0 0.0 0.05* 1.5 1.2 0.345
Congenital malformation (%) 1.9 0.0 0.977* 1.9 0.7 0.430
Intrauterine fetal death (%) 5.6 1.9 0.664 5.3 1.1 0.014
*Cells with expected frequency <5 are more than 33%.

Data presented as means standard deviation.

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ADVANCED MATERNAL AGE ON PREGNANCY OUTCOME/SEOUD ET AL 5
uterine fibroids were found to be significantly
higher in nulliparous cases compared with younger
nulliparas. The only significant difference in peri-
natal outcomes was a higher rate of IUFD in mul-
tiparous cases compared with multiparous controls
despite similar birth weights, rates of depressed
newborns, and congenital malformations (Table 4).
In nulliparous women, the numbers in each category
were too small to draw meaningful conclusions. The
results of the multiple stepwise regression analysis
are listed in Table 5. Parity was not found to have
a significant impact on the variables analyzed. The
OR for a CS delivery was 2.7 in women above 40,
2.5 with one or more obstetrical complications. In
addition, the OR for preterm delivery was 1.8 for
women above 40, and 9.4 in the presence of an
obstetrical complication. Moreover, for obstetrical
complications the OR was 7.0 for patients who
had preexisting medical complications (hyperten-
sion, anemia, thyroid disorders, cardiac diseases,
renal disorders, diabetes), while the OR for obstetri-
cal complications was 2.1 in women over 40.
DISCUSSION
Until recently, advanced maternal age was consid-
ered one of the risk factors for an adverse maternal
and perinatal outcome. However, more women in
developed countries are delaying their childbirth for
various reasons and recent studies have reported a
more favorable outcome.
6,7
In developing countries,
pregnancies above 40 are, in most cases, just a con-
tinuation of the reproductive life of these women.
This study is one of the largest to compare a
group of women at least 40 years old, to a matched
group, aged 20 to 30, who are usually considered to
have the lowest maternal and perinatal morbidity
and mortality. The majority of women in the study
group were multiparous (83.7%), a rate similar to
reports from the same region.
7
Despite controlling
for parity, the mean parity was significantly higher
in elderly women compared with controls. This is
due to the fact that multiparity was defined as at
least one previous pregnancy that has reached via-
bility stage, not taking into account the actual par-
ity number.
Medical or obstetrical indications accounted
for 65.3% of labor inductions in cases versus 41.9%
in controls. This might have contributed to the
higher incidence of labor induction seen in cases
compared with controls. Pregnancy complications
were twice more likely to occur in elderly pregnant
women compared with controls. Preterm deliveries
were twice as common in older women. The dif-
ference in preterm delivery rate remained signifi-
cantly higher in cases even after excluding pa-
tients with medical or obstetrical indications for
induction (11.3 vs. 4.6%), indicating an inherent
increased risk for spontaneous preterm labor in
elderly women. The incidence of gestational dia-
betes, preeclampsia, chronic hypertension was also
higher in the cases. It is worth mentioning that
testing for gestational diabetes is universal for all
our obstetrical patients regardless of age. Thus, the
higher incidence of gestational diabetes observed
in the elderly women is not secondary to under-
stating the incidence in the younger women. The
reasons for this increased frequency of complica-
tions vary according to the complication. Chronic
hypertension and gestational diabetes are easier to
explain, as both are affected by age. The incidence
of chronic hypertension increases with age, and
older women have more difficulty with their carbo-
hydrate metabolism with most studies suggesting
at least doubling of the incidence.
7,8
Moreover,
preeclampsia is reported to be more frequent at
the extremes of reproductive age. The etiology of
preeclampsia is still unclear and it is frequently
difficult to separate preexisting hypertension from
pregnancy induced hypertension. In fact, some
studies did not find a higher incidence of pre-
eclampsia in older women.
9
In our series, preeclampsia, chronic hyper-
tension, and gestational diabetes were more fre-
quent in multiparous elderly women compared with
multiparous controls. This did not hold true for
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6 AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 19, NUMBER 1 2002
nulliparas. The cesarean section rate was 2.5 times
higher in our study groups compared with controls
and this was true for both nulliparous and multi-
parous patients. This has been reported in virtu-
ally all studies.
7,10
The most frequent indications in
both groups were repeat CS, followed by nonre-
assuring fetal tracing, and abnormal presentation.
However, the chance of delivering by CS was al-
most doubled for any indication in cases compared
with controls. In some studies the incidence of ab-
normal labor is higher in older patients, the basis of
which is not clear.
6
This was not demonstrable in
our study. The presence of a higher rate of obstet-
rical complications and chronic medical illnesses in
the study group might have contributed indirectly
to the higher incidence of CS. These patients are
more likely to have elective repeat CS and abnor-
mal fetal heart tracings. Although 15.2% of cases
had cesarean delivery for a nonreassuring fetal heart
tracing compared with 14.3% in controls, there was
no difference in the percentage of Apgar score <7 at
5 minutes in both groups which might be explained
by the fact that physicians might have a lower
threshold to perform a CS in this group of patients
with a precious pregnancy. This might have been a
contributing factor to the rather high incidence of
cesarean delivery in cases knowing that the average
rate of primary CS is 14.4% while the rate of total
CS is about 23.1% at our institution.
Perinatal outcome was also significantly af-
fected by age. Although the incidence of intrauter-
ine growth restriction was similar in both groups
in our series, older women had a higher incidence
of intrauterine fetal death and infants with Apgar
scores <7 at 5 minutes. Even after excluding the 4
cases of fetal death occurring 24 weeks gestation
and the 5 cases in which there was an identifiable
risk factor for fetal death, 61.5% of cases of IUFD
occurred without an identifiable risk factor in the
advanced maternal age group versus none in the
controls. If this is reproduced in other studies, then
routine antenatal fetal heart resting might have to
be recommended in pregnant women at age 40 or
more. This increased risk has been reported in
some,
8
but not all previous studies.
6
The higher
incidence of medical and obstetrical complications
might explain some, but not all, cases of intrauter-
ine fetal death.
Congenital malformations were diagnosed
antenatally in most of the cases and were found to
be similar in cases and controls. Both minor and
major anomalies, defined as anomalies that had a
major impact on neonatal morbidity or mortality
such as polycystic kidney disease, were included.
Only a minor anomaly (cleft lip) was incidentally
found in 1/17 of all the intrauterine fetal deaths
that occurred in the elderly group. Thus, congeni-
tal anomalies were not a major contributor to the
higher incidence of fetal death seen in the cases.
In some studies, the incidence of chromosomal
abnormalities was similar in elderly and younger
women, and this was attributed to the aggressive
prenatal genetic counseling and screening that
these women have in developed countries.
6
In our
population, the acceptance rate of prenatal diagno-
sis is low especially in the young population
11
and
this might explain why the 3 cases of chromosomal
abnormalities were seen in the advanced maternal
age group (0.9%).
Furthermore, the results of the multiple
regression analysis emphasized the importance of
each variable in terms of the outcome. It is evident
that as far as the high CS rate and the preterm de-
livery, age and obstetrical complications are more
important than parity. Medical complication are
more important than age in relation to the devel-
opment of obstetrical complications.
The above data is important to counsel
women over the age of 40 who are considering
pregnancy.
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