Advanced maternal age and adverse perinatal outcome.

Abstract

The aim of this study was to investigate the influence of maternal age on perinatal and obstetric outcome in women aged 40-44 years and those 45 years or older and to estimate whether adverse outcome was related to intercurrent illness and pregnancy complications.
National prospective, population-based, cohort study in women aged 40-44 years and those 45 years or older and in a control group of women aged 20-29 years who delivered during the period 1987-2001. Adjusted odds ratios (OR) were calculated after adjustments for significant malformations, maternal pre-existing diseases, and smoking. Main outcome measures were perinatal mortality, intrauterine fetal death, neonatal death, preterm birth, and preeclampsia.
During the 15-year period, there were 1,566,313 deliveries (876,361 women were 20-29 years of age, 31,662 were 40-44 years, and 1,205 were > or = 45 years). Perinatal mortality was 1.4%, 1.0%, and 0.5% in women 45 years or older, 40-44, and 20-29 years, respectively. Adjusted OR for perinatal mortality was 2.4 (95% confidence interval [CI] 1.5-4.0) in women aged 45 years or older, compared with 1.7 (95% CI 1.5-1.9) in women 40-44 years. Adjusted OR for intrauterine fetal death was 3.8 (95% CI 2.2-6.4) in women aged 45 years or older, compared with 2.1 (95% CI 1.8-2.4) in women 40-44 years. Preterm birth, gestational diabetes, and preeclampsia were more common among women 40-44 years of age and those 45 years or older. Perinatal mortality was increased in women with intercurrent illness or pregnancy complications compared with women without these conditions, but there was no evidence that these factors became more important with increasing age.
Perinatal mortality, intrauterine fetal death, and neonatal death increased with age. There was also an increase in intercurrent illnesses and pregnancy complications with increasing age, but this did not entirely explain the observed increase in perinatal mortality with age.
II-3

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Advanced Maternal Age and Adverse Perinatal
Outcome
Bo Jacobsson, MD, PhD, Lars Ladfors, MD, PhD, and Ian Milsom, MD, PhD
OBJECTIVE: The aim of this study was to investigate the
influence of maternal age on perinatal and obstetric out-
come in women aged 40–44 years and those 45 years or
olderandtoestimatewhetheradverseoutcomewasrelated
to intercurrent illness and pregnancy complications.
METHODS: National prospective, population-based, cohort
study in women aged 40–44 years and those 45 years or
older and in a control group of women aged 20–29 years
who delivered during the period 1987–2001. Adjusted odds
ratios (OR) were calculated after adjustments for signifi-
cant malformations, maternal pre-existing diseases, and
smoking. Main outcome measures were perinatal mortal-
ity, intrauterine fetal death, neonatal death, preterm birth,
and preeclampsia.
RESULTS: During the 15-year period, there were 1,566,313
deliveries (876,361 women were 20–29 years of age, 31,662
were 40–44 years, and 1,205 were > 45 years). Perinatal
mortality was 1.4%, 1.0%, and 0.5% in women 45 years or
older, 40–44, and 20–29 years, respectively. Adjusted OR for
perinatal mortality was 2.4 (95% confidence interval ?CI?
1.5–4.0) in women aged 45 years or older, compared with 1.7
(95% CI 1.5–1.9) in women 40–44 years. Adjusted OR for
intrauterine fetal death was 3.8 (95% CI 2.2–6.4) in women
aged45yearsorolder,comparedwith2.1(95%CI1.8–2.4)in
women 40–44 years. Preterm birth, gestational diabetes, and
preeclampsia were more common among women 40–44
years of age and those 45 years or older. Perinatal mortality
was increased in women with intercurrent illness or preg-
nancy complications compared with women without these
conditions, but there was no evidence that these factors be-
came more important with increasing age.
CONCLUSION: Perinatal mortality, intrauterine fetal death,
and neonatal death increased with age. There was also an
increase in intercurrent illnesses and pregnancy complica-
tions with increasing age, but this did not entirely explain
the observed increase in perinatal mortality with age.
(Obstet Gynecol 2004;104:727–33.
ican College of Obstetricians and Gynecologists.)
LEVEL OF EVIDENCE: II-3
© 2004 by The Amer-
During the last 3 decades, there has been an increasing
trend among women in the industrialized world to delay
childbearing. In Sweden, the mean maternal age at the
birth of the first child increased between 1974 and 2001
from 24.4 to 28.5 years.1The corresponding mean ma-
ternalageincreasedfrom21.4to24.9yearsintheUnited
Statesandfrom25.6to28.0yearsinJapanbetween1970
and 2000.2
The proportion of women delivering in their 40s has
also increased, especially during the last decade. In Swe-
den, the numbers of women giving birth between 40 and
44 years of age and at age 45 or older increased from 5.0
to 10.3 and from 0.2 to 0.5 live births per 1,000 women,
respectively, from the early 1980s to 2001.3In England
and Wales, the number of women giving birth between
40 and 44 years and at 45 years or older increased from
5.1 to 8.4 and 0.3 to 0.5 live births per 1,000 women,
respectively, between 1991 and 2001.4In the United
States, the number of women giving birth between 40
and 44 years and at 45 years or older increased from 3.8
to 7.4 and 0.2 to 0.4 live births per 1,000 women,
respectively, between 1981 and 1999.5
It is a well-established fact that fecundity decreases
and the risk for miscarriage increases with age.6However,
the enormous advances in reproductive medicine have
compensated, to some extent, for this natural decrease in
fecundity, and nowadays even postmenopausal women
have become pregnant through oocyte donation.7The
influence of advanced maternal age and delayed childbear-
ingonperinataloutcomehavepreviouslybeenstudied,but
most studies have evaluated outcome in women aged 35
years or older.6It has been shown that pregnant women
aged 35 years or older experience an increased risk of
intrauterine fetal death, pregnancy-induced hypertension,
gestational diabetes, and delivery by cesarean.6
Most studies that have dealt with advanced maternal
age are hospital-based; there are very few population-
based studies.8,9Two hospital-based studies have inves-
tigated women aged 45 years or older.10,11The aim of
this national population-based study was to 1) investi-
gate the influence of maternal age on perinatal and
From the Perinatal Centre, Department of Obstetrics and Gynecology, Sahlgrenska
University Hospital/O¨stra, Go ¨teborg, Sweden.
The study was supported by the Go ¨teborg Medical Society and Sahlgrenska
Academy at Go ¨teborg University.
VOL. 104, NO. 4, OCTOBER 2004
© 2004 by The American College of Obstetricians and Gynecologists.
Published by Lippincott Williams & Wilkins.
727
0029-7844/04/$30.00
doi:10.1097/01.AOG.0000140682.63746.be

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obstetric outcome in women aged 40–44 years and
those 45 years or older and 2) explore whether the
increased risk of perinatal mortality could be explained
by the increased occurrence of intercurrent illnesses and
pregnancy complications among older women.
MATERIALS AND METHODS
The Swedish Medical Birth Register, managed by the
National Board of Health and Welfare, contains data on
more than 99% of all births in Sweden.12Information is
collected prospectively by the staff responsible for the
careofthepatientandincludesdemographicdata,repro-
ductive history, and complications during pregnancy,
delivery, and the neonatal period. Copies of the stan-
dardized individual antenatal, obstetric, and pediatric
records are forwarded to the Birth Registry, where the
information is automatically entered into a database and
stored. All births and deaths are validated every year
through individual record linkage to the Swedish Regis-
ter of the total population, using the mothers’ and in-
fants’ unique national registration numbers, which are
assigned to each Swedish resident at birth. The register
has been validated and quality is controlled on a yearly
basis.Maternalcomplicationsduringpregnancyarecon-
sidered to be of acceptable quality.12
The women included in the study are part of the
homogenous, low-risk population typical for Sweden.
Severe poverty does not really exist in Sweden, and
access to adequate prenatal and obstetrical care is good.
More than 80% of women have an intermediate or high
level of education, and the prevalence of drug/alcohol
abuse is low in comparison with many other countries.
Pre-existing maternal diseases and medical complica-
tions in pregnancy and delivery are recorded in the birth
registry according to the Swedish version of the Interna-
tional Classification of Diseases, 9th Revision (ICD-9)
1987–1996. From 1997, the Swedish version of the Inter-
national Classification of Diseases, 10th Revision (ICD-10)
was used. Smoking and marriage/cohabitation status were
also recorded at the first antenatal visit and categorized as
eithernonsmoking(ie,non-dailysmoking)orsmokingand
either marriage/cohabitation or not. Intercurrent illness was
defined as the presence of a prepregnancy history of exist-
ing hypertensive disease, diabetes, bronchial asthma, dis-
seminated lupus erythematosus, or inflammatory bowel
disease, and these were recorded at the first antenatal visit.
Complication during pregnancy was defined as a history of
gestational diabetes, pregnancy-induced hypertension, or
preeclampsia during the pregnancy.
Pregnancy outcomes, such as stillbirth, birth weight,
gestational age at delivery, and infant gender, are re-
corded in the delivery or pediatric records. Validation of
the Birth Register has concluded that data on birth
weight, gestational age, and stillbirth are correctly re-
corded.12The Birth Register includes information on all
live births, as well as stillbirths, occurring at 28 com-
pleted gestational weeks or later. Information necessary
to determine maternal mortality was obtained from the
national Causes of Death Register. The study was ap-
proved by the Ethics Committee, Faculty of Medicine,
University of Go ¨teborg, and by the governing board of
the Swedish Medical Birth Register.
From 1987 to 2001, there were 1,566,313 recorded
births. All deliveries in women aged 40–44 (n ? 31,662)
years and 45 years or older (n ? 1,205) and in a control
Table 1. Demographic Characteristics and Medical History Grouped According to Maternal Age
Group A: 20–29 y
(n ? 876,361)
776,542/816,720 (95.1)
171,245 (20.8)
446,735 (51.0)
2,027 (0.23)
2,653 (0.36)
3,119 (0.36)
Group B: 40–44 y
(n ? 31,662)
26,247/28,761 (91.3)
5,710 (18.0)
5,418 (17.1)
Group C: ? 45 y
(n ? 1,205)
975/1,088 (89.6)
170 (15.6)
183 (15.2)
17 (1.41)
Significance of
difference between
A, B, C (P ? .05)
A-B, A-C, B-C
A-C, B-C
A-B, A-C
A-B, A-C, B-C
NS
NS
A-C, B-C
Married or cohabiting
Smoking during pregnancy
Primiparous
Hypertensive disease
Diabetes mellitus
Renal disease
Disseminated lupus
erythematosus
Bronchial asthma
Ulcerative colitis
One or more of the
intercurrent diseases above
Multiple pregnancy
Significant malformation
NS, not significant.
Data are expressed as n (%).
296 (0.93)
180 (0.57)
182 (0.57)
37 (0.12)
4 (0.33)
6 (0.50)
3 (0.25)542 (0.06)
27,204 (3.10)
2,274 (0.26)
36,808 (4.20)
908 (2.87)
118 (0.37)
1,628 (5.14)
40 (3.32)
9 (0.75)
74 (6.14)
NS
A-C, B-C
A-C, B-C
18,921 (2.16)
15,269 (1.74)
904 (2.86)
803 (2.54)
40 (3.32)
34 (2.82)
A-B, A-C
A-B, A-C
728Jacobsson et al
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group of all women aged 20–29 years (n ? 876,361)
were included in this study.
Gestational age was calculated by using information
from date of birth and estimated date of delivery as
determined in early pregnancy. This is usually based on
a second-trimester ultrasound scan performed at no later
than18completedweeksofgestation,whichwasoffered
to all pregnant women in Sweden during the study
period. More than 95% of pregnant women avail them-
selves of this opportunity.13
Small for gestational age (SGA) was defined as a birth
weight below 2 standard deviations from the mean
weight corrected for gestational age and gender.14Large
for gestational age (LGA) was defined as a birth weight
more than 2 standard deviations from the mean weight
corrected for gestational age and gender.14
Perinatal mortality was defined as stillbirth or death
duringdays0–6.Neonataldeathwasdefinedasbornalive
and death during days 0–28. Perinatal death was defined
as stillbirth or neonatal death. Stillbirth was defined as a
deadfetus(bothantepartumandintrapartum)bornat28
completed gestational weeks or later (information on
weeks 22–27 is not available in the Registry according to
Swedish legislation). All mortality and death data were
expressed as deaths per 1,000 deliveries.
Dichotomous data were tested for significance with
the Fisher exact test, and adjustments (multiplication by
3) of the P values due to multiple comparisons were
performed by the Bonferroni method (Table 1). Logistic
regressionwasusedtoanalyzeselectedantepartumcom-
plications (diabetes mellitus, hypertensive disease, mild
and severe preeclampsia, and placenta previa) (Table 2),
as well as intrapartal variables (mode of delivery, induc-
tion of labor, and sphincter tears of the third and fourth
degree) (Table 3) and perinatal mortality according to the
presence or absence of intercurrent illness and/or preg-
nancy complications (Table 4), in comparing the different
agegroups.Usingmultiplelogisticregressionanalysis,peri-
natal outcomes were adjusted for nulliparity, married/
cohabitating,significantmalformations,smoking,maternal
disease, and multiple pregnancy (Tables 5 and 6).
Oddsratios(OR)werecalculated,withwomen20–29
years of age as the reference group, with 95% confidence
intervals (CI). Statistical software (SAS 8.12; SAS Insti-
tute Inc, Cary, NC) was used for the analysis.
RESULTS
The proportion of women giving birth between ages 40
and 44 years and at 45 years or older has increased
Table 2. Selected Antepartum Complications Grouped According to Maternal Age
20–29 y (n ? 876,361)
Gestational diabetes
OR (95% CI)
Pregnancy-induced hypertension
OR (95% CI)
Mild preeclampsia
OR (95% CI)
Severe preeclampsia
OR (95% CI)
Placenta previa
OR (95% CI)
OR, odds ratio; CI, confidence interval.
Data are expressed as n (%) and OR (95% CI).
40–44 y (n ? 31,662)
307 (0.97)
3.43 (3.04–3.86)
564 (1.78)
3.29 (3.01–3.59)
393 (1.24)
0.58 (0.53–0.64)
356 (1.12)
1.40 (1.26–1.56)
232 (0.73)
4.61 (4.01–5.30)
? 45 y (n ? 1,205)
16 (1.33)
4.71 (2.87–7.73)
41 (3.40)
6.38 (4.67–8.72)
8 (0.66)
0.31 (0.15–0.62)
18 (1.49)
1.86 (1.17–2.97)
2 (0.17)
1.04 (0.26–4.16)
2,496 (0.28)
1
4,811 (0.55)
1
18,473(2.11)
1
7,074 (0.81)
1
1,402 (0.16)
1
Table 3. Peripartum Information and Maternal Age
20–29 y (n ? 876,361)
728,274 (83.10)
1
49,856 (5.69)
1
59,163 (6.75)
1
90,599 (9.92)
1
16,822 (1.92)
1
40–44 y (n ? 31,662)
22,556 (71.24)
0.50 (0.49–0.51)
3,044 (9.61)
1.75 (1.68–1.84)
1,741 (5.50)
0.80 (0.76–0.84)
7,425 (23.45)
2.66 (2.58–2.73)
796 (2.51)
1.32 (1.23–1.42)
? 45 y (n ? 1,205)
785 (65.15)
0.38 (0.34–0.43)
156 (12.95)
2.47 (2.08–2.92)
57 (4.73)
0.69 (0.53–0.90)
365 (30.29)
3.77 (3.33–4.26)
42 (3.49)
1.85 (1.36–2.51)
Normal delivery
OR (95% CI)
Induction of labor
OR (95% CI)
Operative vaginal delivery
OR (95% CI)
Cesarean delivery
OR (95% CI)
Anal sphincter tears (third and fourth degree)
OR (95% CI)
OR, odds ratio; CI, confidence interval.
Data are expressed as n (%) and OR (95% CI).
729
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during the study period (Fig. 1, A and B). During the
study period (1987–2001), the number of women giving
birth between ages 40 and 44 years increased from 6 to
10 live births per 1,000 women. The corresponding
increase for women aged 45 years or older was from 0.2
to 0.3 live births per 1,000 women.
Demographic characteristics and medical history,
grouped according to maternal age, are shown in Table 1.
Table 4. Perinatal Mortality According to Presence or Absence of Intercurrent Illness and/or Pregnancy Complications
20–29 y40–44 y
? 45 y
Intercurrent illness
OR (95% CI)
Pregnancy complication
OR (95% CI)
Intercurrent illness or pregnancy complication
OR (95% CI)
No intercurrent illness or pregnancy complication
OR (95% CI)
OR, odds ratio; CI, confidence interval.
Data are expressed as n (%) and OR (95% CI).
222/35,155 (0.63)
1
217/30,481 (0.71)
1
453/67,289 (0.67)
1
4,260/809,072 (0.53)
1
16/1,530 (1.05)
1.66 (1.00–2.77)
15/1,363 (1.10)
1.55 (0.92–2.63)
33/2,991 (1.10)
1.65 (1.15–2.35)
269/28,671 (0.94)
1.79 (1.58—2.05)
0/71
0/73
0/147
17/1,058 (1.61)
3.09 (1.91–4.99)
Table 5. Perinatal Outcome According to Maternal Age, Adjusted for Nulliparity, Married/Cohabitation, Significant
Malformations, Smoking, Maternal Disease, and Multiple Pregnancy
20–29 y (n ? 876,361)
Perinatal mortality 4,713 (0.54)
AOR (95% CI)1
Perinatal death (including death within
first 28 days)
AOR (95% CI)1
Intrauterine fetal death2,785 (0.32)
AOR (95% CI)1
Neonatal death (including death within
days 0–28)
AOR (95% CI)1
AOR, adjusted odds ratio; CI, confidence interval.
Data are expressed as n (%) and AOR (95% CI).
40–44 y (n ? 31,662)
302 (0.95)
1.67 (1.48–1.88)
343 (1.08)
? 45 y (n ? 1,205)
17 (1.41)
2.45 (1.51–3.98)
20 (1.66) 5,246 (0.60)
1.68 (1.50–1.89)
203 (0.64)
2.07 (1.79–2.40)
140 (0.44)
2.57 (1.64–4.04)
14 (1.16)
3.76 (2.22–6.40)
6 (0.50)2,461 (0.29)
1.29 (1.08–1.54)1.42 (0.62–3.23)
Table 6. Peripartum Information According to Maternal Age, Adjusted for Nulliparity, Married/Cohabitation, Significant
Malformations, Smoking, Maternal Disease, and Multiple Pregnancy
20–29 y (n ? 876,361)
Preterm birth ? 37 wk54,309 (6.20)
AOR (95% CI)1
Preterm birth ? 34 wk15,931 (1.80)
AOR (95% CI)1
Preterm birth ? 32 wk8,953 (1.01)
AOR (95% CI)1
Small for gestational age21,874 (2.56)
AOR (95% CI)1
Large for gestational age26,033 (2.97)
AOR (95% CI)1
Mild preeclampsia18,473 (2.11)
AOR (95% CI)1
Severe preeclampsia7,074 (0.81)
AOR (95% CI)1
Preeclampsia25,547 (2.92)
AOR (95% CI)1
Placenta previa1,402 (0.16)
AOR (95% CI)1
AOR, adjusted odds ratio; CI, confidence interval.
Data are expressed as n (%) and AOR (95% CI).
40–44 y (n ? 31,662)
2,762 (8.72)
1.54 (1.47–1.60)
915 (2.89)
1.57 (1.46–1.69)
569 (1.80)
1.65 (1.51–1.80)
1,151 (3.77)
1.94 (1.80–2.09)
1,506 (4.76)
1.63 (1.55–1.72)
393 (1.24)
0.59 (0.53–0.65)
356 (1.12)
1.29 (1.16–1.44)
749 (2.37)
1.27 (1.18–1.37)
232 (0.73)
4.10 (3.55–4.73)
? 45 y (n ? 1,205)
113 (9.38)
1.63 (1.32–2.00)
33 (3.53)
1.88 (1.36–2.59)
27 (2.24)
1.94 (1.30–2.88)
58 (5.03)
2.67 (2.04–3.49)
63 (5.23)
1.80 (1.40–2.32)
8 (0.66)
0.31 (0.15–0.62)
18 (1.49)
1.64 (1.03–2.62)
26 (2.16)
1.16 (0.78–1.71)
2 (0.17)
0.92 (0.23–3.38)
730 Jacobsson et al
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Fewer women in the age groups 40–44 years and 45 years
or older smoked and lived with the child’s father than
women in the age group 20–29 years. The older women
had more pre-existing diagnoses of hypertension, dissemi-
nated lupus erythematosus, and ulcerative colitis, but not
diabetes mellitus or renal disease.
The risk of developing gestational diabetes, pregnan-
cy-induced hypertension, severe preeclampsia, or pla-
centa previa increased with increasing maternal age, but
there was a decreased risk of mild preeclampsia (Tables
2 and 6). The number of uncomplicated deliveries was
lower in older women (Table 3). Both induction of labor
and cesarean delivery were increased, but not operative
vaginal delivery (not corrected for multiparty). In
women aged 45 years or older, 1 of every 3 women was
delivered by cesarean. The risk of experiencing an anal
sphincter tear increased with increasing age.
AdjustedORswerecalculatedregardingperinatalout-
come. Perinatal mortality, perinatal death (including
death within the first 28 days of life), and intrauterine
fetal death all increased with increasing maternal age.
Neonatal death (defined as death within 28 days) was
also increased in women aged 40–44 years (Table 5).
The absolute risk of an intrauterine fetal death or the
death of the live-born child within the first 27 days of life
was 1.1% in women aged 40 years or older and 1.7% in
women 45 years or older. Adjusted ORs were also
calculated for other important perinatal outcome mea-
sures:pretermbirth,SGA,LGA,andpreeclampsia(mild
and severe), and these outcomes were all found to be
associated with increased maternal age (Table 6).
Perinatal mortality was increased in women with in-
tercurrent illness or pregnancy complications compared
with women not experiencing these conditions, in both
women aged 20–29 years and 40–44 years (Table 4).
However, there was no evidence that intercurrent illness
orpregnancycomplicationsbecomemoreimportantrisk
factors for perinatal death with increasing age (20–29
years: OR 1.28, 95% CI 1.16–1.41; 40–44 years: OR
1.17, 95% CI 0.82–1.69). Similar results were obtained
forintrauterinefetaldeathandperinataldeathinwomen
grouped in the corresponding manner.
During the course of this study, which stretched over
15years,therewere21maternaldeathsintheagegroups
studied. Maternal mortality, grouped according to
age group, was calculated (age group 20–29 years: 12/
876,361, which is equivalent to 1.4/100,000 deliveries;
age group 40–44 years: 7/31,662, which is equivalent to
22.1/100,000 deliveries; age group ? 45 years: 2/1,205,
which is equivalent to 166.0/100,000 deliveries). Mater-
nal mortality was compared between groups: age group
40–44 years versus age group 20–29 years OR 16.2
(95% CI 6.38–41.2); age group 45 years or older versus
age group 20–29 years OR 121 (95% CI 27–542).
DISCUSSION
This study has demonstrated an increase in perinatal
mortality, perinatal death, intrauterine fetal death, and
neonataldeathinrelationtomaternalageinchildbearing
womenfromthelastpartoftheirfertileperiod,ie,40–44
years of age and 45 years or older. In addition, there was
also an increase in the preterm birth rate and the preva-
lence of SGA, LGA, and preeclampsia with advancing
maternal age, and again, the highest prevalences were
seeninwomen45yearsofageorolder.Ourdatasuggest
thattheincreasedoccurrenceofperinatalmortality,peri-
natal death, and intrauterine fetal death in older women
could not be explained by the increased frequency of
intercurrentillnessorpregnancycomplicationsobserved
in these women. One can, however, have possible reser-
vations regarding the validity of this conclusion, if preg-
nancy complications had been underreported, but on
the other hand, we see no reason why underreporting
should differ between the various age groups.
Being pregnant and giving birth at the age of forty or
more years was relatively common until the middle of
the 20th century.14Women often had their first child
Fig. 1.
period 1987–2001 who were aged 40–44 years (A) and 45
years or older (B).
Jacobsson. Maternal Age and Pregnancy Outcome. Obstet Gynecol 2004.
Percentages of women giving birth during the
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early and their last child late during the reproductive
period.14The major difference during the last 3 decades
isthatwomenaremoreoftenusingthelatterpartoftheir
reproductive period to have all their children,1and this
trend of postponing childbearing has not yet shown any
tendency to decrease.1Several studies have investigated
perinatal outcome in women aged 40 years or old-
er,9,15–21and 2 of the studies have presented population-
based data.8,9The study by Cnattingius et al8was pop-
ulation-based and demonstrated a higher prevalence of
late fetal death but was unable to demonstrate a higher
prevalence of early neonatal death in women who deliv-
ered at the age of 40–52 years, compared with 35- to
39-year-oldwomen.Intheirstudythenumberofwomen
aged40yearsorolderwaslimited(n?1,069),anditwas
not possible to compare women aged 40–44 years with
those 45 years or older. Thus, it was not possible to
demonstrate an increase in perinatal mortality, perinatal
death, intrauterine fetal death, and neonatal death with
increasing age in women aged 40 years or older as was
demonstrated in the present study. In the study by
Gilbert et al,9increased infant and neonatal death could
only be demonstrated in multiparous women 40 years of
age or older compared with the younger control group,
andagainnodistinctionwasmadebetweenwomenaged
40–44 years and those who were 45 years of age or
older.
There are only 2 earlier studies published regarding
perinatal outcome in childbearing women aged 45 years
or older; both studies are hospital-based and the size of
the studies was insufficient to study perinatal mortali-
ty.10,11Dildy et al10presented 79 cases from their hospi-
tal and also performed a review of the literature between
1948 and 1996 of studies presenting data from women
aged 45 years or older. Also, Dulitzki et al11have pre-
sented a hospital-based, case-control study with 109
women. The size and comprehensiveness of our present
study provided us the opportunity to study the impor-
tant perinatal outcome variables.
The present study was based on a large national
population-based cohort where 31,662 women aged
40–44 years and 1,205 women aged 45 years or older
were included in the analyses. It was also possible,
because of the design of the Swedish Medical Birth
Register, to adjust for important pre-existing maternal
conditions, nulliparity, significant malformations, multi-
ple pregnancies, smoking, and cohabitation. The ability
to link the Swedish Medical Birth Register to other
relevantnationalpopulationregistersenhancedthequal-
ity control of the data available for the important mor-
tality figures. Being able to adjust for parity and impor-
tant potential confounding factors enhanced our ability
to investigate the specific influence of age on perinatal
outcome.Noattemptwasmadetoadjustfortheuseofin
vitro fertilization techniques or oocyte donation because
thevalidityofthisinformationcontainedintheantenatal
records alone has been considered to be of poorer qual-
ity.22During the study period, oocyte donation was not
legally available in Sweden, but it is possible that there
may be a few cases in our material because some women
may have undergone oocyte donation treatment abroad
and were subsequently delivered in Sweden. Another
possible limitation of this study is that it covers a 15-year
time period, and treatment policies have changed during
the course of the study.
We conclude that there is an increase in perinatal and
neonatal death with increasing age, as well as an increase
in pregnancy complications, eg, preterm delivery, SGA,
LGA, gestational diabetes, pregnancy-induced hyperten-
sion, severe preeclampsia, and anal sphincter tears.
However, although maternal and fetal outcome is com-
promised, pregnancies in women aged 40–44 years and
45 years or older still may be considered to be relatively
safe because the occurrence of perinatal death is rare. An
important observation in this study is that the increased
risk of bad perinatal outcome is not due to the increased
occurrenceofmaternalpre-existingdiseaseorpregnancy
complications in the older women. Our findings are of
importance for gynecologists and obstetricians, as well as
the general public, when providing information to the in-
creasing numbers of presumptive parents where the
woman is aged 40 years or older. However, from the
clinician’s perspective, there is no simple measure that
could be applied to prevent the poor outcome.
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Address reprint requests to: Bo Jacobsson, MD, PhD, Depart-
ment of Obstetrics and Gynecology, Sahlgrenska University
Hospital/O¨stra, S-416 85 Go ¨teborg, Sweden; e-mail: bo.
jacobsson@obgyn.gu.se.
Received March 27, 2004. Received in revised form June 18, 2004.
Accepted July 1, 2004.
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Maternal Age and Pregnancy Outcome