Advanced maternal age and pregnancy
outcomes: a multicountry assessment
M Laopaiboon,a P Lumbiganon,b N Intarut,a R Mori,c T Ganchimeg,c JP Vogel,d,e JP Souza,e

AM G€ulmezoglu,e on behalf of the WHO Multicountry Survey on Maternal Newborn Health

Research Network
a
Faculty of Public Health, Department of Biostatistics & Demography, Khon Kaen University, Khon Kaen, Thailand

b
Faculty of Medicine,

Department of Obstetrics & Gynaecology, Khon Kaen University, Khon Kaen, Thailand
c
Department of Health Policy, National Center for

Child Health and Development, Tokyo, Japan d Faculty of Medicine, Dentistry and Health Sciences, School of Population Health, University

of Western Australia, Crawley, Australia e Department of Reproductive Health and Research, UNDP/UNFPA/UNICEF/WHO/World Bank

Special Programme of Research, Development and Research Training in Human Reproduction (HRP), World Health Organization, Geneva,

Switzerland

Correspondence: Prof. P Lumbiganon, Faculty of Medicine, Department of Obstetrics & Gynaecology, Khon Kaen University, Khon Kaen,

Thailand. Email [email protected]

Accepted 16 January 2014.

Objective To assess the association between advanced maternal

age (AMA) and adverse pregnancy outcomes.

Design Secondary analysis of the facility-based, cross-sectional

data of the WHO Multicountry Survey on Maternal and Newborn

Health.

Settings A total of 359 health facilities in 29 countries in Africa,

Asia, Latin America, and the Middle East.

Sample A total of 308 149 singleton pregnant women admitted to

the participating health facilities.

Methods We estimated the prevalence of pregnant women with

advanced age (35 years or older). We calculated adjusted odds

ratios of individual severe maternal and perinatal outcomes in

these women, compared with women aged 20–34 years, using a
multilevel, multivariate logistic regression model, accounting for

clustering effects within countries and health facilities. The

confounding factors included facility and individual

characteristics, as well as country (classified by maternal mortality

ratio level).

Main outcome measures Severe maternal adverse outcomes,

including maternal near miss (MNM), maternal death (MD), and

severe maternal outcome (SMO), and perinatal outcomes,

including preterm birth (<37 weeks of gestation), stillbirths, early
neonatal mortality, perinatal mortality, low birthweight (<2500 g),
and neonatal intensive care unit (NICU) admission.

Results The prevalence of pregnant women with AMA was 12.3%

(37 787/308 149). Advanced maternal age significantly increased

the risk of maternal adverse outcomes, including MNM, MD, and

SMO, as well as the risk of stillbirths and perinatal mortalities.

Conclusions Advanced maternal age predisposes women to

adverse pregnancy outcomes. The findings of this study

would facilitate antenatal counselling and management of women

in this age category.

Keywords Advanced maternal age, maternal death, maternal near

miss, perinatal outcomes, pregnancy outcomes, severe maternal

outcomes.

Please cite this paper as: Laopaiboon M, Lumbiganon P, Intarut N, Mori R, Ganchimeg T, Vogel JP, Souza JP, G€ulmezoglu AM, on behalf of the WHO

Multicountry Survey on Maternal Newborn Health Research Network. Advanced maternal age and pregnancy outcomes: a multicountry assessment. BJOG

2014; 121 (Suppl. 1): 49–56.

Introduction

Advanced maternal age (AMA) is generally defined as

pregnancy in women aged 35 years or older. As maternal

age increases, fertility declines and the rate of spontaneous

abortion increases.1 Women over 35 years of age represent

a significant proportion of pregnancies in higher-income

countries: a historical cohort of 6619 singleton pregnancies

between 2004 and 2007 from Norway found a 33.4% prev-

alence of AMA.
2
A recent report from Taiwan indicated

that the proportion of women with AMA at delivery

increased from 11.4 to 19.1%.3 A large, population-based

cohort study in the UK showed an 18.2% prevalence of

maternal ages of 35 years or older.4 There is a clear trend

in higher-income countries towards delaying childbirth to

later reproductive years.5,6 Lower-income countries differ

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DOI: 10.1111/1471-0528.12659

www.bjog.org
Original article

significantly in the sociodemographic characteristics of

expectant mothers and the availability of obstetric care

services; however, AMA still represents a significant – and
growing – fraction of pregnant women in these countries.7

Studies of pregnancies in older women from higher-in-

come countries have shown higher inherent risks for a

number of maternal and perinatal morbidities. A popula-

tion-based cohort study in Australia, demonstrated that

women with AMA were more likely to have pre-existing

medical conditions, obstetric complications, and adverse

labour and birth outcomes.8 A retrospective cohort study

in Taiwan between July 1990 and December 2003,

involving 39 763 women who delivered after 24 weeks of

gestation, found that women aged 35–39 years had a
significantly increased risk for operative vaginal and

caesarean deliveries, whereas women aged 40 years and

older were at increased risk for preterm delivery.
3
The

risk of trisomy 21 and chromosomal abnormalities also

increases with increasing maternal age.1 A popula-

tion-based cohort study consisting of 215 344 births in

the UK found that women aged 40+ years at delivery
had a significantly increased risk of stillbirth, preterm

and very preterm birth, macrosomia, extremely large for

gestational age, and caesarean delivery.
4
Advanced mater-

nal age was also found to be associated with an

increased risk of fetal death from intrapartum asphyxia

at term.9 There are sparse data on pregnancy outcomes

of older women in lower-income countries. Furthermore,

it is difficult to extrapolate the literature from developed

higher-income to lower-income countries, where ecologi-

cal differences, decreased access to antenatal care and

delivery services, and dramatically higher rates of mater-

nal and perinatal morbidity and mortality complicate

comparisons.

In 2009, the WHO developed a standard definition for

maternal near miss (MNM) based on markers of organ dys-

function.10 There have been no reports evaluating severe

maternal outcome (SMO), maternal death (MD), and MNM

in women of AMA, probably because of the extremely low

incidence of these outcomes in higher-income countries.

This report aims to evaluate the association between

AMA and severe maternal and perinatal outcomes using

the 2010–2011 WHO Multicountry Survey on Maternal
and Newborn Health (WHOMCS) data set of over 314 000

deliveries from 29 countries.

Methods

Study design and setting
The design of the WHOMCS is described in detail else-

where.11,12 In brief, this is a multicentre, cross-sectional

study aimed to determine the prevalence of MNM cases in

a worldwide network of health facilities. It was approved

by the World Health Organization Ethical Review

Committee and implemented in a random sample of 359

health facilities in 29 countries from Africa, Asia, Latin

America, and the Middle East. Because of the financial and

practical constraints, we did not conduct the survey in

developed countries, except Japan, which volunteered to

participate. A stratified, multistage cluster sampling strategy

was used to select countries, provinces, and health facilities.

The study population included women giving birth, all

MNM cases, regardless of the gestational age and delivery

status, and all maternal deaths during the study period

between 1 May 2010 and 31 December 2011.

Data collection took place at two levels: at the individual

level and at the facility level. At the individual level, data

related to the pregnancy outcomes, severe complications,

and their management, for the women included in the

study, and for their respective newborns, were extracted

from the medical records of the participating facilities by

trained data collectors. The data were completed in the

pre-established form at hospital discharge, transfer, or

death. There was no contact between data collectors and

the women included in the study; however, data clarifica-

tion was occasionally sought from facility staff. At the facil-

ity level, data characteristics of each health facility,

including infrastructure, obstetric and intensive care

services, and their ability to identify and manage severe

complications, were collected through a specific survey

among the professionals responsible for the participating

facilities. Data were collected for 2 months if the health

facility had 6000 deliveries or more per year, and for

3 months if the health facility had less than 6000 deliveries

per year. If the anticipated sample size for a country was

anticipated to be less than 3000 women, the data collection

period was 4 months in all facilities. Online data entries

were performed in each country, either at the health facil-

ity or at a central level, depending on the logistics and

available infrastructure, in the web-based data management

system developed by the Centro Rosarino de Estudios

Perinatales (CREP), Rosario, Argentina. Data quality

control was undertaken by having data managers from

CREP and Thailand monitor data validity and consistency

during data collection and online entries.

Study population
In this analysis, the population included all women aged at

least 20 years who gave birth to singleton babies, either live

births or stillbirths, at the participating facilities. The

women were classified into four maternal age categories:

20–34, 35–39, 40–44, and 45 years of age or older. Women
aged less than 20 years were excluded from this analysis. A

study on the association between teenage pregnancy

(<20 years) and adverse pregnancy outcomes will be pub-
lished in a separate paper.

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Laopaiboon et al.

Variables and definitions
We defined AMA as women aged 35 years or older. Preg-

nancy adverse outcomes were classified into maternal and

perinatal outcomes. For maternal outcomes, we studied

severe maternal outcomes, including MNM, MD, and

SMO. In accordance with the WHO MNM approach, we

defined MNM as a woman who nearly died but survived a

complication that occurred during pregnancy, childbirth,

or within 42 days of termination of pregnancy. MD was

the death of a woman while pregnant or within 42 days of

termination of pregnancy. SMO was defined as women

having had a maternal death or a MNM up to 7 days after

giving birth or having an abortion, irrespective of gesta-

tional age or delivery status.11

For perinatal outcomes, we studied preterm birth, still-

birth, early neonatal mortality, perinatal mortality, low

birthweight (<2500 g), and neonatal intensive care unit
(NICU) admission. We defined preterm birth as any birth

before 37 weeks of gestation. Stillbirth was any death of a

fetus after 22 weeks of gestation or weighing ≥500 g. Early
neonatal mortality was the death of a liveborn baby within

the first 7 days of life.

Potential confounding factors were taken from both

facility and individual characteristics. The potential facility

confounding factors included the availability of a blood

bank, an adult intensive care unit (AICU) for adverse

maternal outcomes, and an NICU for adverse perinatal

outcomes. The potential individual confounding factors

included maternal demographic and labour characteristics,

i.e. marital status, maternal education (years of school

attendance), and parity. Labour characteristics included

onset of labour, fetal presentation, and mode of delivery.

Countries were stratified by the level of maternal mortality

ratio (MMR),11 and counted as a confounding factor at the

country level.

Statistical analysis
For this analysis, women aged 20–34 years represented the
reference group. Frequencies were used to describe country

groups, baseline maternal characteristics, and prevalence of

pregnancy outcomes in relation to the maternal age groups.

The association between each AMA group and each adverse

outcome was analysed using a multilevel, multivariate logis-

tic regression model by the procedure GLIMMIX in SAS 9.1

(SAS Institute Inc, Cary, NC), USA. This procedure was

intended to account for clustering effects within countries

and health facilities. The analysis was also adjusted for the

potential confounding factors, including maternal and health

facility characteristics and country groups. For this analysis

maternal school attendance was classified according to the

United Nations Educational, Scientific and Cultural Organi-

zation (UNESCO) international standard classification of

education. This classification allocates individuals to one of

five categories that correspond to the level of education

expected after a given number of years of education: no

education (0 years); primary (1–6 years); lower secondary
(7–9 years); upper secondary (10–12 years); post-secondary/
tertiary (>12 years). The risks of maternal and perinatal
outcomes associated with each AMA group were presented

by adjusted odds ratios (aORs), with corresponding 95%

confidence intervals (95% CIs). Statistical analysis was

performed using SAS 9.1.

Results

During the study period there were 308 149 women with

singleton deliveries, after excluding women who did not

deliver vaginally or by caesarean section, such as laparot-

omy for ectopic pregnancy, etc. (360 women), and women

with missing maternal age (79), in the WHOMCS. A total

of 276 291 women (89.6% from 308 149) were 20 years or

older. In this report, the overall prevalence of AMA (preg-

nant women aged 35 years and over) was 12.3%. The high-

est prevalence of 9.5% was seen in women aged

35–39 years, and only 0.5% was seen in women aged
45 years or older (Figure 1). The prevalence of AMA varied

greatly among the participating countries, from 2.8% in

Nepal to 31.1% in Japan (Figure 2).

Maternal and neonatal characteristics were quite similar

among the four maternal age groups: 20–34, 35–39,
40–44, and 45 years of age or older. However, more than
40% of the women aged 20–34, 35–39, and 40–44 years
were from countries with a moderate MMR. Interestingly,

68.5% of the women aged 45 years or older were from

countries with very high MMR. Single marital status was

more common (14.9%) in the very advanced age group,

with women aged 45 years or older, whereas less than

10% was seen in the other age groups. Less education

was observed with increasing maternal age. Caesarean

section rates were 28, 36, 37, and 23% in women aged

20–34, 35–39, 40–44, and 45 years or older, respectively
(Table 1).

Prevalence of severe adverse pregnancy outcomes
The prevalence of MNM, MD, and SMO increased with

maternal age, as shown in Table 2. The SMO ratio varied

from 5/1000 live births in women aged 20–34 years up to
20/1000 live births in women aged 45 years or older. For

perinatal outcomes, an increasing trend was observed in

the prevalence of fetal and perinatal mortalities. The rates

of stillbirths and perinatal mortalities per 1000 total births

were 19 and 27 in women aged 20–34 years, and up to 43
and 53 in women aged 45 years or older, respectively. The

prevalence of preterm births, early neonatal mortality, low

birthweight, NICU admission, and Apgar score <7 at
5 minutes were also increased in women with AMA.

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Advanced maternal age and pregnancy outcomes

Association between advanced maternal age and
maternal severe adverse outcomes
The aORs of the association between maternal age and

maternal severe adverse outcomes (MNM, MD, and SMO)

are presented in Table 3. Increased aORs of the three severe

adverse outcomes were significantly associated with AMA in

women in age groups of 35 years or older, when compared

with women aged 20–34 years. However, the increasing
trends of MNM, MD, and SMO with AMA were not signifi-

cant. The 95% CIs for aORs overlapped among AMA groups.

Association of advanced maternal age and
perinatal adverse outcomes
The aORs of the association between maternal age and

perinatal adverse outcomes are also shown in Table 3. The

risk of stillbirths and perinatal mortalities significantly

increased with increasing AMA; however, the increased

trends of these outcomes were not significant, as the 95%

CIs for aORs overlapped among AMA groups. Preterm

birth, early neonatal mortality, low birthweight, NICU

admission, and Apgar score <7 at 5 minutes were signifi-
cantly associated with some AMA groups when compared

with women aged 20–34 years. There was no evidence to
support the association between high AMA (45 years of age

or older) and preterm birth, early neonatal mortality, low

birthweight, and NICU admission compared with women

aged 20–34 years.

Discussion

Main findings
The overall prevalence of AMA in this large multicountry

analysis was 12.3%, ranging from 2.8% in Nepal to 31.1%

in Japan. Advanced maternal age was found to be signifi-

cantly associated with severe maternal adverse outcomes,

including MNM, MD, and SMO. It was also found to be

significantly associated with fetal and perinatal mortalities.

Excluding the data from Japan did not change the results

of these associations.

Strengths and limitations
To our knowledge, this analysis is the first report to

describe the significant risk of AMA on MNM, MD, and

SMO. The WHOMCS was conducted in 359 health facili-

ties from 29 countries in Africa, Asia, Latin America,

and the Middle East, and involved 276 291 pregnant

women. All of these countries except Japan are develop-

ing countries, where there were no previous reports

addressing these associations. We used pre-tested, stan-

dardised data collection forms by trained data collectors

and methodology from the previous WHO global survey;

however, our analysis did not have information on some

variables known to be associated with fetal and neonatal

mortality, including smoking, obesity, diabetes, syphilis,

and difficult labour. As we used medical records as our

Figure 1. Study flow chart.

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Laopaiboon et al.

Table 1. Maternal and neonatal characteristics in relation to maternal age

Characteristics Maternal age (years)

Total 20–34 35–39 40–44 ≥45
276 291 238 504 29 245 7015 1527

Country groups

Low MMR 7273 (2.6) 5476 (2.3) 1452 (5.0) 327 (4.7) 18 (1.2)

Moderate MMR 118 385 (42.9) 100951 (42.3) 13669 (46.7) 3364 (48.0) 401 (26.3)

High MMR 63 671 (23.0) 59736 (25.1) 3211 (11.0) 663 (9.5) 61 (4.0)

Very high MMR 86 962 (31.5) 72341 (30.3) 10913 (37.3) 2661 (37.9) 1047 (68.6)

Marital status

Married/cohabiting 251 555 (92.1) 216712 (91.9) 27239 (94.0) 6510 (93.2) 1094 (85.1)

Single 21 625 (7.9) 19228 (8.2) 1733 (6.0) 472 (6.8) 192 (14.9)

Maternal school attendance, in years

0 43 074 (15.6) 35 202 (14.8) 5791 (19.8) 1636 (23.3) 445 (29.1)

1–6 (primary) 33 982 (12.3) 28 965 (12.1) 3771 (12.9) 1029 (14.7) 217 (14.2)

7–9 (lower secondary) 47 876 (17.3) 43 013 (18.0) 3812 (13.0) 890 (12.7) 161 (10.5)

10–12 (upper secondary) 79 645 (28.8) 71 066 (29.8) 6808 (23.3) 1573 (22.4) 198 (13.0)

>12 (tertiary) 71 714 (26.0) 60 258 (25.3) 9063 (31.0) 1887 (26.9) 506 (33.1)

Parity

Primiparous 86 838 (31.4) 83 220 (34.9) 2773 (9.5) 574 (8.2) 271 (17.8)

Multiparous 189 452 (68.6) 155 284 (65.1) 26 472 (90.5) 6441 (91.8) 1255 (82.2)

Onset of labour

Spontaneous 211 871 (76.8) 184 792 (77.6) 20 888 (71.5) 4965 (70.9) 1226 (80.3)

Induced 29 094 (10.6) 25 649 (10.8) 2708 (9.3) 615 (8.8) 122 (8.0)

No labour 34 903 (12.7) 27 693 (11.6) 5604 (19.2) 1428 (20.4) 178 (11.7)

Mode of delivery

Vaginal delivery 196 194 (71.0) 171 805 (72.0) 18 804 (64.3) 4406 (62.8) 1179 (77.2)

Caesarean section 80 097 (29.0) 66 699 (28.0) 10 441 (35.7) 2609 (37.2) 348 (22.8)

Fetal presentation

Non-cephalic 12 114 (4.4) 9970 (4.2) 1606 (5.5) 462 (6.6) 76 (5.0)

Cephalic 263 627 (95.6) 228 095 (95.8) 27 556 (94.5) 6534 (93.4) 1442 (95.0)

Figure 2. Prevalence of women with advanced maternal age by country.

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Advanced maternal age and pregnancy outcomes

primary data source, missing data or errors in these

records could have affected data quality; however, we

have tried our best to minimize this bias as much as

possible by intensively training our data collectors before

the study. Clinical staff were available for data collectors

to consult, as necessary.

Interpretation (findings in light of other evidence)
The prevalence of AMA in this analysis varied greatly

across countries. Previous reports on the prevalence of

AMA varied from 33.4% in Norway to 11.4% in Taiwan;
2,3

however, we have demonstrated that even in lower-income

countries AMA accounts for a significant proportion of all

deliveries.

Advanced maternal age has been previously shown to

increase the risk of gestational diabetes, antepartum haem-

orrhage, and placenta praevia.13 The prevalence of

pre-existing hypertension, placenta praevia, suspected intra-

uterine growth restriction, and gestational diabetes also

appear to increase with maternal age.8 AMA also indepen-

dently increases the risk of operative vaginal and caesarean

deliveries.3,14–16 Studies of AMA have largely not explored

SMO, however, probably because of the size of the sample

needed for such a study in a high-income setting, where

SMO is infrequent. Our analyses therefore focused on eval-

uating the associations between AMA and MNM, MD, and

SMO that have not been evaluated before, especially in

developed or developing countries.

This report indicates that AMA (all age groups) signifi-

cantly increased the risk of fetal and perinatal mortalities.

Previous reports indicated that women with AMA had an

increased risk of fetal death.3,4 Women with AMA also

had significantly increased risks of antepartum and intra-

partum stillbirth.
17

Lisonkova et al., using the causal fetu-

s-at-risk model, showed that mothers of AMA had a

consistently increased risk of perinatal death at all gesta-

tional ages.18 Other reports also showed that women with

AMA had a significantly increased risk of perinatal

death.3,19 Our studies showed that women with AMA had

a significantly increased risk of preterm birth, early neo-

natal mortality, low birthweight, NICU admission, and

Apgar score <7 at 5 minutes, although not across all
AMA groups. Previous studies have reported the associa-

tion between AMA and preterm labour.3,4,13,19 AMA was

found to be significantly associated with low birth-

weight.13,19

The findings clearly show a significantly increased risk of

severe adverse maternal outcomes with AMA, whereas just

a slightly increased risk of adverse perinatal outcomes was

demonstrated. The explanation is that the prevalence of

perinatal outcomes was only slightly higher among AMA

groups than those of the reference group (20–34 years). In
addition, the prevalence of low birthweight and NICU

admission in women with very advanced age (45 years of

age or older) was even lower than those of the reference

group.

The public health focus generally tends to be on adoles-

cents or younger women in terms of risks associated with

pregnancy. Although a much greater focus on contraceptive

availability and reproductive health education for adoles-

cents is indeed warranted, women over 35 years of age rep-

resent a larger, and growing, population group that also

Table 2. Prevalence of adverse pregnancy outcomes in relation to maternal age

Outcomes Maternal age (years)

Total 20–34 35–39 40–44 ≥45

Maternal 276 291 238 504 29 245 7015 1527

MNM** 1372 (5) 1007 (4) 243 (9) 98 (14) 24 (16)

MD** 270 (1) 207 (1) 43 (2) 15 (2) 5 (3)

SMO** 1642 (6) 1214 (5) 286 (10) 113 (17) 29 (20)

Neonatal; total births 276 291 238 504 29 245 7015 1527

Live births 270 744 234 057 28 445 6780 1462

Preterm birth (<37 weeks)* 16 966 (61) 14 352 (60) 1964 (67) 548 (78) 102 (67)

Stillbirths* 5547 (20) 4447 (19) 800 (27) 235 (34) 65 (43)

Early neonatal mortality** 2297 (9) 1962 (8) 249 (9) 71 (11) 15 (10)

Perinatal mortality* 7776 (28) 6357 (27) 1036 (35) 303 (43) 80 (53)

Low birthweight (<2500 g)** 28 543 (105) 24 985 (107) 2649 (93) 774 (114) 135 (92)

NICU admission** 17 247 (64) 14 498 (62) 2044 (72) 633 (93) 72 (49)

Apgar score <7 at 5 minutes** 6896 (26) 5887 (25) 721 (25) 214 (32) 74 (51)

*Per 1000 total births.

**Per 1000 live births.

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Laopaiboon et al.

has inherently higher risks of severe adverse outcomes

compared with women aged 20–34 years.

Conclusion

Advanced maternal age significantly increases the risk of

MNM, MD, and SMO. It also significantly increases the risk

of preterm birth, fetal mortality, early neonatal mortality,

perinatal mortality, low birthweight, NICU admission, and

birth asphyxia. International and national maternal health

policies should focus more on AMA pregnancies. More

research is needed to find appropriate and timely interven-

tions to reduce the impact of AMA on pregnancy outcomes.

Disclosure of interests
We declare that we have no conflicts of interest to disclose.

Contribution to authorship
PL, ML, RM, TG, JV, JPS, and MG conceptualised the

research question. PL and ML drafted the analysis plan.

ML and NI analysed the data. PL and ML drafted the arti-

cle. All authors critically reviewed and approved the final

version of the article.

Details of ethics approval
The HRP Specialist Panel on Epidemiological Research

reviewed and approved the study protocol for technical

content. This study was approved by the World Health

Organization Ethical Review Committee and the relevant

ethical clearance mechanisms in all countries (protocol ID

A65661; 27 October 2009).

Funding
This study was financially supported by the UNDP/UN-

FPA/UNICEF/WHO/World Bank Special Programme of

Research, Development and Research Training in Human

Reproduction (HRP); World Health Organization (WHO);

United States Agency for International Development

(USAID); Ministry of Health, Labour and Welfare of Japan;

and Gynuity Health Projects. The sponsors had no role in

data collection, analysis, or interpretation of the data, the

writing of the report, or the decision to submit for publica-

tion. All authors had access to the analysis plan, the out-

puts of that analysis, and could see the data if they wished

to do so. All authors participated in the final discussion

and approved the submission.

Acknowledgements
The authors wish to thank all members of the WHO Multi-

country Survey on Maternal and Newborn Health Research

Network, including regional and country coordinators, data

collection coordinators, facility coordinators, data collectors,

and all of the staff of participating facilities who made the

survey possible. We also thank Annette Peters for her kind

assistance in copy-editing. Further information on the

Multicountry Survey on Maternal and Newborn Health and

derivatives can be found at: http://www.who.int/reproduc-

tivehealth/topics/maternal_perinatal/nearmiss/en/

References

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Med 2004;351:1927–9.

2 Wang Y, Tanbo T, Abyholm T, Henriksen T. The impact of advanced

maternal age and parity on obstetric and perinatal outcomes in

singleton gestations. Arch Gynecol Obstet 2011;284:31–7.

3 Hsieh TT, Liou JD, Hsu JJ, Lo LM, Chen SF, Hung TH. Advanced

maternal age and adverse perinatal outcomes in an Asian

population. Eur J Obstet Gynecol Reprod Biol 2010;148:21–6.

4 Kenny LC, Lavender T, McNamee R, O’Neill SM, Mills T, Khashan AS.

Advanced maternal age and adverse pregnancy outcome: evidence

from a large contemporary cohort. PLoS ONE 2013;8:e56583.

Table 3. Association between maternal age and adverse pregnancy

outcomes

Outcomes Maternal age (years)

aOR* (95% CI)

35–39 40–44 ≥45

Maternal**

MNM 1.5 (1.3, 1.8) 2.2 (1.7, 2.8) 3.5 (2.2, 5.5)

MD 1.7 (1.2, 2.6) 2.6 (1.4, 4.7) 4.3 (1.5, 12.1)

SMO 1.6 (1.4, 1.8) 2.3 (1.8, 2.8) 3.7 (2.4, 5.6)

Neonatal***

Preterm birth

(<37 weeks)

1.2 (1.1, 1.2) 1.4 (1.2, 1.5) 1.3 (0.9, 1.6)

Stillbirths 1.5 (1.4, 1.7) 1.8 (1.5, 2.1) 2.1 (1.5, 2.8)

Early neonatal

mortality

1.2 (1.0, 1.4) 1.4 (1.1, 1.8) 1.4 (0.7, 2.7)

Perinatal mortality 1.4 (1.3, 1.5) 1.7 (1.5, 1.9) 1.9 (1.5, 2.6)

Low birth weight

(<2500 g)

1.1 (1.0, 1.1) 1.4 (1.3, 1.5) 1.2 (0.9, 1.5)

NICU

admission****

1.2 (1.1, 1.2) 1.6 (1.4, 1.7) 1.1 (0.8, 1.5)

Apgar score <7

at 5 minutes

1.0 (0.9, 1.1) 1.4 (1.2, 1.6) 1.6 (1.2, 2.3)

*Reference group: 20–34 years.

**Models were adjusted for country groups by MMR levels, blood

bank, adult intensive care unit, marital status, maternal school

attendance (in years), parity, onset of labour, fetal presentation, and

mode of delivery. The country and facility levels were also adjusted

as random effects.

***Models were adjusted for country groups by MMR levels, blood

bank, neonatal intensive care unit, marital status, maternal school

attendance (in years), parity, onset of labour, fetal presentation, and

mode of delivery. The country and facility levels were also adjusted

as random effects.

****Models were adjusted for country groups by MMR levels,

marital status, maternal school attendance (in years), parity, onset of

labour, fetal presentation, and mode of delivery. The country and

facility levels were also adjusted as random effects.

55ª 2014 RCOG
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Laopaiboon et al.

European Journal of Obstetrics & Gynecology and Reproductive Biology 242 (2019) 178–181

Full length article

Impact of advanced maternal age on adverse infant outcomes:
A Japanese population-based study

Shigeki Koshidaa,*, Hisatomi Arimab, Takako Fujiic, Yoshiya Itod, Takashi Murakamie,
Kentaro Takahashia

a Perinatal Center, Shiga University of Medical Science, Japan
b Department of Preventive Medicine & Public Health, Fukuoka University, Japan
c Department of Neurosurgery, Shiga University of Medical Science, Japan
d Department of Clinical Medicine, Japanese Red Cross Hokkaido College of Nursing, Japan
e Department of Obstetrics and Gynecology, Shiga University of Medical Science, Japan

A R T I C L E I N F O

Article history:
Received 6 June 2019
Received in revised form 12 August 2019
Accepted 21 August 2019

Keywords:
Maternal age
Infant outcome
Small for gestational age
Low birth weight
Preterm births

A B S T R A C T

Objective: The number of births among women of higher age has been rapidly increasing in many
countries for several decades. While recent epidemiological studies on the impact of maternal age on
infant outcomes in developed countries have evaluated the outcomes of singleton infants, few
population-based studies have investigated all deliveries including multiple births. Thus, we aimed to
assess the impact of maternal age on adverse infant outcomes using data from all birth certificates,
including multiple births, in Shiga prefecture, Japan.
Study design: The data from all birth certificates in Shiga Prefecture from 2013 to 2014 (23,294 births from
23,048 mothers) were obtained. We evaluated the impact of maternal age on adverse infant outcomes,
including small for gestational age (SGA), low birth weight (LBW), and preterm birth (PTB). A
multivariable logistic regression analysis was performed to determine adjusted odds ratios (aORs) for
infant outcomes with various maternal factors, including multiple pregnancies. Statistical analysis for
trend was performed using the Jonckheere-Terpstra test.
Results: The incidence rates of adverse infant outcomes began to increase at a maternal age of 30 years. A
maternal age of �35 years was associated with significantly increased risks of adverse infant outcomes,
including SGA (adjusted odds ratio [aOR]: 1.15, 95% confidence interval [95% CI]: 1.03–1.29), LBW (aOR:
1.29, 95% CI: 1.16–1.43), and PTB (aOR: 1.17, 95%CI: 1.04–1.33).
Conclusions: The risk of adverse infant outcomes was significantly increased in women older than 35
years of age. These data would be useful for younger women to decide family-planning in advance.

© 2019 Elsevier B.V. All rights reserved.

Contents lists available at ScienceDirect

European Journal of Obstetrics & Gynecology and
Reproductive Biology

journal homepage: www.else vie r.com/locat e/e jogrb

Introduction

Over the past four decades, there has been an increasing trend
for women in high-income countries to delay childbearing [1–3].
This trend is due to several changes, including the pursuit-by
women-of higher education and career advancement, fertility
control through contraception methods, and financial problems
[4,5]. There rate of delayed childbearing is remarkably high in
Japan, where the average of maternal age at first birth is the 5th
highest among OECD countries, after South Korea, Italy, Spain, and
Switzerland [6]. While the total number of births in Japan has
decreased by approximately 20% over the past 20 years, both the

* Corresponding author.
E-mail address: [email protected] (S. Koshida).

https://doi.org/10.1016/j.ejogrb.2019.08.011
0301-2115/© 2019 Elsevier B.V. All rights reserved.

number and proportion of the births from women of advanced
maternal age (AMA), defined as �35 years of age, have rapidly
increased for several decades; there were 118,553 (9.8%) births to
women of AMA in 1996 and 278,162 (28.5%) in 2016 [7]. Thus, the
evaluation of Japanese data may be useful to study the impact of
AMA on perinatal issues.

AMA has been reported to be associated with various adverse
perinatal outcomes, including fetal growth restriction, preterm
birth (PTB), placental abruption, and preeclampsia [8]. As small for
gestational age (SGA) infants, low birth weight (LBW), and PTB, are
considered to be associated with a high risk of neonatal mortality
and morbidity [9–11], it is important to study the impact of
maternal age on infant outcomes. Recent epidemiological studies
on the impact of maternal age on infant outcomes have evaluated
the outcomes of singleton infants [4,12–14]; however, few
population-based studies in developed countries have investigated

Fig. 1. Outline of this survey GA, gestational age.

Table 1
Profile of the perinatal factors analyzed in this study.

Characteristics of this study n (%)

Mother n = 23,048
Maternal age at delivery (years) 31.0 � 0.03
Advanced maternal age (� 35years) 5887 [25]
Gestational age at birth (weeks) 38.7 � 0.01
Parity (Multiparous/Primiparous) 12,859 (56)/10,189 (44)
Plurality (Singleton/Multiple) 22,791 (99)/257 (1)

Infants (n = 23,294)
Birth weight (g) 2999 � 432
Gender (male/female) 12,022 (52)/11,272 (48)
Preterm birth (<37 weeks) 1451 (6.2)
Low birth weight infants (<2500 g) 2217 (9.5)
Multiple births 503 (2.2)
Small for gestational age (BW < 10 percentile) 1725 (7.4)

Data represent the mean � standard deviation or n (%).

S. Koshida et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 242 (2019) 178–181 179

all deliveries, including multiple births. Accounting for approxi-
mately 3% of total births in developed countries [15,16], multiple
birth is associated with a higher risk of adverse infant outcomes,
including PTB, LBW, and SGA, in comparison to singleton birth [17].
Enrolling all deliveries in a target region, including multiple births,
is essential for the accurate assessment of the impact of maternal
age.

Thus, we studied the impact of maternal age, investigating all
birth certificates in one prefecture of Japan, Shiga. In Shiga, there
are approximately 13,000 annual births and no specific of obstetric
issues. The results of a population-based study in Shiga may
represent the general data of Japan, and reflect the problems
associated with AMA birth throughout the world.

Materials and methods

Study design

This population-based cross-sectional study was performed in
Shiga Prefecture, Japan from 2013 to 2014.

Data collection

There are approximately 13,000 annual births in 30 primary
obstetric clinics and 11 hospitals in Shiga Prefecture. Information
from all birth certificates in Shiga prefecture between January 2013
and December 2014 was obtained with permission from the
Ministry of Health, Labor and Welfare, Japan. We obtained
maternal data (maternal age and gestational age [GA] at delivery,
parity, and plurality), and infant data (weight and height at birth,
and sex).

Infant outcomes

Low birth weight (LBW) was defined as a birth weight of
<2500 g. Preterm birth (PTB) was defined as GA < 37 weeks. SGA
was defined as birth weight below the 10th percentile of the
Japanese neonatal anthropometric chart for GA at birth [18].

Population

This study included 26,524 births during the 2-year study
period. We excluded 3230 births from the analyses for the
following reasons: birth took place outside of Shiga (n = 3009),
insufficient data (n = 190), and GA � 42 weeks (n = 31).
Previous studies in Japan only included singleton births
[19,20]. In contrast, the present population-based study
included both multiple births and singleton births. Thus, a total
of 23,294 births from 23,048 mothers were included in the
present study.

Statistical analyses

The incidence rates of the abovementioned infant outcomes
were estimated by the number of outcomes divided by the
total number of births in each age group. The P value for trend
was estimated using the Jonckheere-Terpstra test. We also
estimated impact of AMA on the incidence of adverse infant
outcomes using multivariable logistic regression models, the
results of which were presented as adjusted odds ratios (aOR)
with 95% confidence intervals (CIs). The multivariable models
included maternal age, plurality, and parity as covariates.
P values of <0.05 were considered to indicate statistical
significance. All statistical analyses were performed using the
IBM SPSS software program, (ver.22 IBM Japan, Tokyo, Japan)
(Fig. 1).

Results

Characteristics

The characteristics of the study population are shown in Table 1.
Among 23,048 mothers, the average maternal age was 31 years and
the average gestational age at delivery was 38 weeks. Five
thousand eight hundred eighty-seven (26%) women were classi-
fied as AMA (�35 years of age at delivery). Forty-four percent of the
women were primiparous and 1% of the women had multiple
pregnancies. Among 23,294 infants, the average birth weight was
2999 g. The incidence rates of PTB (GA < 37 weeks) and LBW
(<2500 g) were 6.2% and 9.5%, respectively. There were 503
multiple-birth infants (2.2%) and 1725 (7.4%) SGA infants.

Incidence of adverse infant outcomes according to maternal age

Fig.2 shows the incidence of adverse infant outcomes, including
SGA, LBW, and PTB, according to the maternal age. The incidence of
these outcomes gradually increased according to the maternal age
with a rapid increase from 30 to 35 years. The incidence rates of
each outcome in women of 30–34 years of age, 35–39 years of age,
and �40 years of age, were as follows: SGA, 7.2%, 8.0%, and 9.0%,
respectively; LBW, 9.1%, 10.9%, and 13.3%; and PTB, 6.0%, 7.1%, and
8.5%. The P values for trend for SGA, LBW, and PTB were 0.01,
<0.001 and <0.001, respectively.

Maternal factors associated with adverse infant outcomes

In comparison to women of <35 years of age, those of �35 years
of age hernal age. The incidence of these outcomes gradually
increased according to the maternal age with a rapid increase from
30 to 35 years. The incidence rates of each outcome in women of
30–34 years of age, 35–39 years of age, and �40 years of age, were
as follows: SGA, 7.2%, 8.0%, and 9.0%, respectively; LBW, 9.1%, 10.9%,

Fig. 2. Incidence of adverse infant outcomes according to maternal age Bold line,
incidence of LBW; gray line, SGA; dotted line, PTB;LBW, low birth weight; SGA, small
for gestational age; PTB, preterm birth.

180 S. Koshida et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 242 (2019) 178–181

and 13.3%; and PTB, 6.0%, 7.1%, and 8.5%. The P values for trend for
SGA, LBW, and PTB were 0.01, <0.001 and <0.001, respectively.

Maternal factors associated with adverse infant outcomes

In comparison to women of <35 years of age, those of �35
years of age hernal age. The incidence of these outcomes
gradually increased according to the maternal age with a rapid
increase from 30 to 35 years. The incidence rates of each outcome
in women of 30–34 years of age, 35–39 years of age, and �40
years of age, were as follows: SGA, 7.2%, 8.0%, and 9.0%,
respectively; LBW, 9.1%, 10.9%, and 13.3%; and PTB, 6.0%, 7.1%,
and 8.5%. The P values for trend for SGA, LBW, and PTB were 0.01,
<0.001 and <0.001, respectively.

Maternal factors associated with adverse infant outcomes

In comparison to women of <35 years of age, those of �35 years
of age had significantly higher risks of adverse infant outcomes,
even after adjustment for plurality and parity (SGA: aOR, 1.15; 95%
CI, 1.03–1.29; p = 0.013, LBW: aOR, 1.29; 95% CI, 1.16–1.43; p < 0.001,
and PTB: aOR, 1.17; 95% CI, 1.04–1.33; p = 0.012) (Table 2).

Comment

Our analysis of all birth certificate data from a two-year period
in Shiga Prefecture, Japan revealed that women of AMA had a
significantly higher incidence of adverse infant outcomes, includ-
ing SGA, LBW, and PTB. Additionally, we showed that a maternal
age of >30 years was associated with an increased risk of adverse
infant outcomes.

Table 2
Maternal factors associated with adverse infant outcomes.

Small for gestational age Low birth w

n (%) aOR (95% CI) p n (%)

Maternal age
<35 1236 (72) Reference 1541 (70)
�35 489 (28) 1.15 (1.03–1.29) 0.013 676 (30)

Plurality
Singleton 1593 (92) Reference 1851 (84)
Multiple births 132 (8) 4.62 (3.77–5.68) <0.001 366 (17)

Parity
Primiparous 813 (47) 1.13 (1.02–1.25) 0.015 1109 (50)
Multiparous 912 (53) Reference 1108 (50)

The multivariable logistic regression analysis of maternal factors associated with adve
aOR, adjusted odds ratio; CI, confidential interval.

First, women of AMA had a significantly higher incidence of
adverse neonatal outcomes. The finding that AMA was associated
with adverse infant outcomes such as SGA, LBW, and PTB, was
consistent with a recent meta-analysis of AMA births in many
countries [8]. While previous epidemiological studies in developed
countries targeted only singleton infants [4,12–14], we enrolled all
deliveries, including multiple births, and evaluated the impact of
maternal age by a multivariable logistic regression analysis of
maternal factors, including multiple pregnancies. To our knowl-
edge, this is the first current population-based study in a
developed country to evaluate the impact of AMA on adverse
infant outcomes, including SGA, LBW, and PTB, and include all
regional deliveries including multiple births based on birth
certificates.

In addition, our finding was also consistent with recent
Japanese population-based

studies [19,20], which had limitations with respect to the target
population. The study by Ogawa et al. only included data from
deliveries in tertiary perinatal centers in Japan and did not include
data from non-tertiary centers, such as general hospitals and
primary obstetric clinics [19]. As approximately 40% of Japanese
deliveries take place in primary obstetric clinics, the study
potentially included a target population bias. In contrast, our
study covered deliveries in all obstetric institutions in our region,
primary obstetric clinics, general hospitals, and tertiary centers in
our region. Another recent population-based study by Kyozuka
et al. in Japan showed that higher maternal age (�30 years) at the
first childbirth was associated with adverse infant outcomes,
including LBW, PTB, and SGA [20]; however, the study population
was limited to primiparous women whereas our study included
both multiparous and primiparous women. In the present study
the combination of primiparous delivery and AMA was not
identified as an independent risk factor for adverse infant
outcomes (data not shown). Our results indicated that, in
comparison to pregnancies in younger women, AMA birth was
associated with a high risk of adverse infant outcomes in both
multiparous and primiparous women.

Next, our finding that a maternal age of �30 years was
associated with an increased risk of adverse infant outcomes,
including SGA, is consistent with a previous study [20]. Although
placental dysfunction is a major cause of fetal growth restriction
(FGR), which is used as a proxy for SGA, the relationship between
maternal aging and the placental function is not completely
understood [21]. Another cause of FGR is the compromised oocyte
quality in older women [22]. In addition to compromised genetic
quality, some studies using mouse models have indicated that
oocyte aging is associated with epigenetic changes [23,24]. One
possible explanation for the increased risks of PTB and LBW at
higher maternal age is a significant increase in the rate of both

eight Preterm birth

aOR (95% CI) p n (%) aOR (95% CI) p

Reference 1014 (70) Reference
1.29 (1.16–1.43) <0.001 437 (30) 1.17 (1.04–1.33) 0.012

Reference 1180 (81) Reference
29.3 (24.0-35.9) <0.001 271 (19) 21.2 (17.6–25.5) <0.001

1.30 (1.18–1.42) <0.001 648 (45) 0.97 (0.87–1.09) 0.654
Reference 803 (55) Reference

rse infant outcomes.

S. Koshida et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 242 (2019) 178–181 181

elective and emergency caesarean delivery in women of >30 years
of age [12]. As births certificates in Japan do not include data on the
mode of delivery, we could not evaluate the association between
the rate of caesarean delivery and maternal age.

We have several limitations in this study. First, we were unable to
assess maternal perinatal information, such as the method of
conception,which couldsignificantlyaffect infantoutcomesbecause
we used data from birth certificates, which contain limited
information. Some reports have indicated that conception using
assisted reproductive technology (ART) is associated with a higher
rate of adverse infant outcomes in comparison to pregnancies
achieved without ART [5,19,25]. As older women can be expected to
undergo fertility treatment (including ART) more frequently than
younger women, the analysis of maternal age in our study possibly
includes the influence of fertility treatments. Second, we could not
evaluate neonatal medical data, such as the pH of the umbilical cord
artery or Apgar score, which have a significant impact on the neuro-
developmental outcomes of infants, because birth certificates lack
these data. As almost all Japanese deliveries occur in obstetric clinics
or hospitals in which obstetricians/pediatricians/midwives attend
and routinely check their Apgar scores, it would be possible to
include the Apgar score on birth certificates.

In conclusion, women of advanced maternal age have a
significantly higher incidence of adverse infant outcomes, includ-
ing SGA, LBW, and PTB. Our data would be useful for helping
younger women determine the optimal time for child-bearing.

Funding

This study was supported by Grant-in-Aid for Scientific
Research of Japan, Grant Number JP15K08803.

Author’s contribution

SK, TM, and KT conceived the idea for the study. SK, and TF
performed the data collection for the original studies. HA and YI
performed statistical analyses. SK wrote the first draft. All authors
revised the article, and approved the final version.

Declaration of Competing Interest

The authors declare no conflicts of interest in association with
the present study.

Acknowledgements

The authors thank all of the members who collected the birth
certificate data: Ayako Okuda, Masae Torii, Yumiko Nakamura,
Asuka Yoshioka, Keiko Isojima, Yukiko Samejima and Youko
Hosomi.

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Research Article
Risk of Selected Fetal Adverse Pregnancy Outcomes at Advanced
Maternal Age: A Retrospective Cohort Study in Debre Markos
Referral Hospital, Northwest Ethiopia

Bikila Tefera Debelo ,1 Melaku Hunie Asratie ,2 and Abayneh Aklilu Solomon 3

1Department of Midwifery, College of Medicine and Health Science, Ambo University, Ambo, Ethiopia
2Department of Women’s and Family Health, School of Midwifery, College of Medicine and Health Sciences,
University of Gondar, Gondar, Ethiopia
3Department of Clinical Midwifery, School of Midwifery, College of Medicine and Health Sciences, University of Gondar,
Gondar, Ethiopia

Correspondence should be addressed to Bikila Tefera Debelo; [email protected]

Received 22 June 2020; Revised 3 August 2020; Accepted 7 December 2020; Published 24 December 2020

Academic Editor: Curt W. Burger

Copyright © 2020 Bikila Tefera Debelo et al. )is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction. Pregnancy at an advanced maternal age is defined as pregnancy at 35 years or older. Today, women postpone pregnancy
due to different socioeconomic and personal reasons. However, there was limited evidence on fetal adverse outcomes’ association
with pregnancy at an advanced maternal age in Ethiopia and particularly in the study area. )is study was aimed at assessing the effect
of pregnancy at an advanced age on selected neonatal adverse pregnancy outcomes in Debre Markos Referral Hospital, Ethiopia,
2019. Methods. Institution-based retrospective cohort study was conducted on 303 exposed (35 years and older) and 604 nonexposed
(20–34 years old) immediate postpartum women who delivered at Debre Markos Referral Hospital after 28 weeks of gestation. All
exposed women who fulfilled the inclusion criteria were sampled, and systematic random sampling was employed for those in the
nonexposed group. )e data were collected from 1st of July to 30th of December, 2019, by face-to-face interview and extraction from
maternal chart using a structured questionnaire and data extraction checklist, respectively. Binary logistic regression (bivariate and
multivariable) model was fitted, and wealth index was analyzed by principal component analysis. Adjusted relative risk with respect
to 95% confidence interval was employed for the strength and directions of association between advanced maternal age and selected
adverse pregnancy outcomes, respectively. P-value of <0.05 was used to declare statistical significance. Results. )e incidence of
adverse neonatal outcomes including stillbirth, preterm birth, and low birth weight in the advanced maternal age group was 13.2%,
19.8%, and 16.5%, respectively. )e incidence of stillbirth, preterm birth, and low birth weight in the nonexposed group was 3.1%,
8.4%, and 12.4%, respectively. )e advanced maternal age group had three times the risk of stillbirth compared with the nonexposed
group (ARR = 3.14 95% CI (1.30–7.00)). )e advanced maternal age group had 2.66 times the risk of delivering preterm fetus
(ARR = 2.66 95% CI (1.81–3.77)) compared with the younger counterparts. Low birth weight was not significantly associated with
pregnancy at an advanced maternal age. Conclusion. Fetal adverse outcomes including stillbirth and preterm birth were significantly
associated with pregnancy at an advanced maternal age.

1. Background

Advanced maternal age (AMA) is defined as pregnancy at a
maternal age of 35 years or older [1]. AMA pregnancy varies
across countries, from 33.4% in Norway to 11.4% in Taiwan
[2, 3]. )e proportion of pregnancy at AMA in three dif-
ferent continents, Latin America, Middle East Asia, and
Africa, is 12.3% [2].

Different reasons for postponing pregnancy were de-
scribed by different studies. Occupational and socioeco-
nomic, personal and marriage problems, childbearing desire
and conception issues, and infertility were among the rea-
sons for late-age pregnancy [4].

Pregnancy at AMA is associated with different adverse
neonatal outcomes; however, there are contradicting ideas
about those adverse outcomes. Pregnancy at AMA is

Hindawi
Obstetrics and Gynecology International
Volume 2020, Article ID 1875683, 7 pages
https://doi.org/10.1155/2020/1875683

associated with stillbirth, even though the mechanism is not
entirely clear [5].

Pregnancy in women of advanced maternal age is com-
plicated by intrauterine fetal death (IUFD) and neonatal death
[6]. Perinatal adverse outcomes like preterm birth, early
neonatal death, low birth weight, neonatal intensive care unit
(NICU) admission, and APGAR score of less than seven at five
minutes are significantly associated with AMA [2].

)e adverse outcome in AMA pregnancy stems from
inadequate cardiovascular adaptation during pregnancy,
which impedes the hemodynamic changes for supporting
the fetus [7]. )is might explain the fact that pregnancy in
AMA is associated with intrauterine growth restriction and
placental abruption [8]. Pregnancy-associated complications
in AMA affect the future glucose metabolism of the newborn
[9].

Biologically, according to the royal college of obstetri-
cians and gynecologists, the optimum period for child-
bearing is between 20 and 35 years of age [10]. Pregnancy at
later maternal age is an emerging public health issue.
Women should be supported, rather than constrained, in
their life choices. However, both women and society need to
be aware of the possible problems that older mothers may
encounter. )ere is an urgent need for better public in-
formation on the issues surrounding later maternity. Despite
all these, the effect of AMA pregnancy on pregnancy out-
comes is contradictory and reported differently by different
studies [11].

Ethiopia has done a tremendous job in preventing
teenage pregnancy; however, the pregnancy in older-aged
women is given less concern even though postponing
pregnancy due to the educational and socioeconomic
condition is increasing. Pregnancy in AMA is studied and
approached poorly in Ethiopia. A significant number of
mothers included in the Ethiopian Demographic Health
Survey (EDHS) were AMA although their birth outcomes
were not assessed. )erefore, this study aims at assessing the
effect of advanced maternal age pregnancy on neonatal
outcomes.

2. Methods

2.1. Study Design, Setting, and Period. An institution-based
retrospective cohort study was conducted in Debre Markos
Referral Hospital, Northwest Ethiopia, from 1st July to 20th
December 2019. Debre Markos is a city located 300 kilometers
far from Addis Ababa, the capital of Ethiopia, and 256km from
Bahir-Dar, the capital of Amhara National Regional State. )e
hospital provides health services to more than 3.5 million
populations. Currently, about 100 health centers and two
district hospitals are available in the catchment area of the
referral hospital. )ere are 109 nurses, 3 health officers, 16
general practitioners, and 2 emergency surgeons and 28 spe-
cialists. )e gynecologic and obstetric ward has 36 midwives, 14
general practitioners, and 7 gynecologists. )e ward has a total
of 60 beds. According to the 2011 E.C. six-month report of
Debre Markos referral hospital, 3005 women had delivered at
the hospital of which 5% were stillbirth.

2.2. Source and Study Population. Women aged 20–34 years
and 35 years or older at Debre Markos Referral Hospital
catchment area were the source population for the exposed
and nonexposed groups, respectively. All women aged
between 20 and 34 years and 35 years or older who gave
birth after 28 weeks of gestation at Debre Markos Referral
Hospital during the data collection were the study pop-
ulation for the exposed and the nonexposed groups, re-
spectively. All postpartum women aged 20 years or older
who gave multiple births and women with medical com-
plications, including chronic hypertension, diabetes mel-
litus, CHF, and thyrotoxicosis, were excluded from the
study.

2.3. Sample Size Determination and Sampling Procedures.
)e sample size was calculated by using epi info software
version 7.2.1.0. )e assumptions for the calculation were
95% confidence level, 80% power, ratio of the nonexposed to
the exposed group of 2, and 10% nonrespondent rate. A total
of 912 mothers were included in the study by adding 10 %
nonrespondent rate, 304 from the advanced maternal age
group and 608 women from mothers aged 20 to 34 years
[1, 12].

Systematic random sampling was employed for the
nonexposed group, and all advanced maternal age mothers
who fulfilled the inclusion criteria were included in the
exposed group. Two to one ratio of nonexposed and exposed
groups was used to increase the study power making
the sample size of nonexposed group twice the exposed
group.

All consecutive women aged 35 and above who fulfilled the
inclusion criteria were selected as an exposed group. As for the
nonexposed group, 20–34 aged mothers were selected by
systematic random sampling, K was calculated by dividing the
six-month report of Debre Markos Referral Hospital delivery
service, which was 3005 deliveries by the total sample for the
nonexposed group; that is, K � (3005/608) � 5. )erefore, a
random sample was taken among the first five women and
every five women were included in the nonexposed group. For
every exposure, two nonexposures were included by a sys-
tematic random sampling technique.

2.4. Study Variables and Measurement

Dependent/outcome variables are as follows: fetal
outcomes: preterm birth, low birth weight, and
stillbirth.
Exposure variable is maternal age. Other predictor
variables are as follows: gravidity, parity, alive children,
educational level, residence, marital status, occupation,
sex of the infant, number of prenatal visits, previous
pregnancy adverse outcomes, health insurance, and
wealth quintile.
Advanced maternal age pregnancy is defined as
pregnancy in women aged 35 years or older [2].
Exposed group includes women at an advanced age [1].

2 Obstetrics and Gynecology International

Nonexposed group includes women aged 20–34 years
[1].
Preterm birth is any birth before 37 completed weeks of
gestation or at greater than 28 weeks [13].
Stillbirth is a fetus with no signs of life before the
complete expulsion or extraction from its mother and
after a predefined duration of gestation; after delivery, it
is confirmed that the fetus does not show any evidence
of life and cannot be resuscitated [14].
Low birth weight is a birth weight of less than 2500
grams regardless of the gestational age [15].

2.5. Data Collection Instruments and Quality Assurance
Measures. Structured questionnaires and data extraction
checklists developed based on literature with modification to
this study setting were used as a data collection tool. )e
questionnaires were developed in English and those col-
lected from the mother directly were translated to the local
language, Amharic, by language expertise and back to En-
glish for consistency.

Exposure variable which was maternal age and other
sociodemographic and economic factors were collected
from mothers by face-to-face interview, whereas neonatal
outcomes were extracted from the mothers’ chart. Data
was collected by five final year MSc students, three males
and two females. )ey are all instructors at local uni-
versities. )e data was collected during the postpartum
period and at the time of discharge daily. Training of data
collectors and a supervisor was made to ensure the quality
of the collected data. Principal investigator and super-
visors had made spot-checking and reviewed all the
completed questionnaires and checklists to ensure com-
pleteness and consistency of the collected information.
)e data collection process was supervised by two on-site
supervisors, and data entry was carried out by the prin-
cipal investigator.

2.6. Data Processing and Analysis. )e data gathered and
extracted through the structured questionnaire and check-
lists, respectively, were entered to EPI- DATA version
4.6.0.0, coded, cleaned, and exported to SPSS version 23 for
analysis.

Descriptive statistics comparing the neonatal outcomes
across the two groups were presented by frequency and
percentage. )e wealth quintile was analyzed by using
principal component analysis (PCA) for urban and rural
participants separately and the final outputs were grouped
based on the EDHS 2016 wealth quintile grouping.

)e women were classified into maternal age cate-
gories: 20–34 years old (nonexposed group) and 35 years
old or older, and each pregnancy outcome was dichot-
omized as “yes or no” for analysis. )e following potential
confounders were included in the adjusted models:
sociodemographic, economic, and obstetric factors. Only
variables that reached a P-value of less than 0.2 in the
bivariable logistic regression analysis were included in
the multivariable logistic regression model. A P-value less

than 0.2 and 0.05 was taken as a cut of value to be sig-
nificant in bivariable and multivariable logistic regres-
sions, respectively. Associations between maternal age
and neonatal adverse outcomes were assessed, and its
strength is presented using adjusted relative risk (aRR)
and 95% confidence intervals.

Both bivariable and multivariable logistic regressions
were used to assess the association between selected adverse
neonatal pregnancy outcomes and exposure variable, ma-
ternal age.

Both crude and adjusted relative risks were calculated
from the crude and adjusted odds ratio, respectively, which
in turn were obtained from the logistic regression outputs.
)e formula used to calculate the relative risk was RR �
OR/(1 − Io) + (Io × OR) [16, 17], where Io is incidence in
the nonexposed group, and OR represents the crude and
adjusted depending on the relative risk calculated (crude
OR for crude RR and adjusted OR for adjusted RR).
Similarly, 95% confidence interval for the RR was obtained
by applying the same correction to the confidence interval
bounds of the OR.

Table 1: Distribution of sociodemographic characteristics over
grouped maternal age in Debre Markos referral hospital, Northwest
Ethiopia, 2019 (NE � 303 and NNe � 604).

Characteristics
Nonexposed group

(%)
Exposed group

(%)
Place of residence
Urban 443 (73.3) 119 (39.3)
Rural 161 (26.66) 184 (60.7)
Maternal educational status
No formal education 164 (27.2) 233 (76.9)
Primary education 108 (17.9) 25 (8.3)
Secondary education 154 (25.5) 22 (7.3)
College and above 178 (29.5) 23 (7.6)
Maternal occupational status
Government
employee

118 (19.5) 20 (6.6)

Self-employed 157 (26) 43 (14.2)
Housewife 288 (47.7) 161 (53.1)
Others1a 41 (6.8) 79 (26.1)
Marital status
Married 585 (96.9) 293 (96.7)
Others1b 19 (3.1) 10 (3.3)
Educational status of the husband
No formal education 145 (24.8) 182 (62.1)
Primary education 105 (18) 46 (15.7)
Secondary education 149 (25.5) 30 (10.2)
College and above 186 (31.8) 35 (12)
Occupational status of the husband
Government
employee

150 (25.6) 45 (15.4)

Farmer 165 (28.2) 184 (62.8)
Others1c (270) 44.7 64 (21.8)
Health insurance
Yes 169 (28) 172 (56.8)
No 435 (72) 131 (43.2)
NE-total in exposed group, NNe-total in nonexposed group.

1afarmer, un-
employed, student 1bsingle, divorced, widowed, separated 1cself-employed,
un-employed, student.

Obstetrics and Gynecology International 3

3. Results

3.1. Socioeconomic and Demographic Characteristics of the
Study Participants. In this study, a total of 912 women were
included, 608 from the nonexposed group and 304 from the
exposed group. )e response rate for the nonexposed group
was 99.2%, where four sampled women declined to par-
ticipate, and 99.7% for the exposed group, where one woman
declined to participate.

About 73% of the nonexposed group was of urban
residence, and 60.7% of the exposed group was of rural
residence. More than one quarter (29.5%) of the nonexposed
group had a college and/or above education, and one in six
of them was a government employee. More than three fourth

(76.9%) of the exposed group had no formal education, and
more than half (53.1%) of them were housewives (Table 1).

More than one fifth (nearly 22%) of the respondents’
wealth quintile falls in the lowest category of the 2016
Ethiopian Demographic Halth Survey’s wealth quintile
classification, and about 25% of the participants’ wealth
quintile was fourth (Figure 1).

3.2. Obstetric Characteristics of the Study Participants.
More than half of the nonexposed group were impregnated
with their first child, and 92.4% of the exposed group had
become pregnant more than once. More than one third
(34.7%) of the exposed group were grand multiparous.
About 93.4% of the exposed group did have ANC follow-up,
and 97% of the nonexposed group had ANC follow-up
(Table 2).

3.3. Fetal Pregnancy Outcomes. )e incidence of stillbirth
among the AMA and nonexposed groups was 13.2% and
3.1%, respectively. )e incidence of PTB and LBW in the
AMA group was 19.8 and 16.5%, respectively (Figure 2).

3.4. Selected Adverse Neonatal Pregnancy Outcomes and
Pregnancy at an Advanced Maternal Age. Binary logistic
regression was fitted to assess the association between ma-
ternal age and selected adverse neonatal pregnancy outcomes
and other factors. All factors with P-value≤0.2 were taken to
multivariate analysis along with maternal age for further
analysis, thus controlling for potential confounding effects. A
backward LR method of analysis was applied and model
fitness was checked by Hosmer-Lemeshow goodness-of-fit.

Maternal age was associated with stillbirth in bivariable
logistic analysis; other factors including place of residence,
parity, gravidity, mother and husband’s educational status,
health insurance, wealth quintile, ANC follow-up, and
mother and husband’s occupational status were also asso-
ciated with stillbirth and hence included in multivariable

Lowest
Second
Middle

Fourth
Highest

22%

22%

16%

25%

15%

Figure 1: Distribution of wealth quintile of the participants in
Debre Markos referral hospital, Northwest Ethiopia, 2019
(NE � 303 and NNe � 604).

Table 2: Distribution of obstetrics related characteristics over
grouped maternal age in Debre Markos referral hospital, Northwest
Ethiopia, 2019 (NE � 303 and NNe � 604).

Characteristics Nonexposed group (%) Exposed group (%)
Gravidity
Primigravida 318 (52.6) 23 (7.6)
Multigravida 286 (47.4) 280 (92.4)
Preceding birth interval (NE � 277 and NNe � 263)
<2 years 29 (11) 20 (7.2)
≥2 years 234 (89) 257 (92.8)
Parity
Primiparous 341 (56.5) 26 (8.6)
Multiparous 249 (41.2) 172 (56.8)
Grand multiparous 14 (2.3) 105 (34.7)
ANC follow-up
Yes 586 (97) 283 (93.4)
No 18 (3) 20 (6.6)
Number of ANC Visit (NE � 283 and NNe � 586)
Less than 4 188 (32.1) 111 (39.2)
4 and more 398 (67.9) 172 (60.8)
Iron folate supplemented (NE � 283 and NNe � 586)
Yes 562 (96) 274 (96.8)
No 24 (4) 9 (3.2)
Previous adverse px outcomes
Yes 113 (18.7) 150 (49.5)
No 491 (81.3) 153 (50.5)

3.1

96.9

12.4

87.6

8.4

91.6

13.2

86.8

16.5

83.5

19.8

80.2

0

20

40

60

80

100

120

Ye
s

N
o

Ye
s

N
o

Ye
s

N
o

Still birth LBW PTB

Pe
rc

en
ta

ge

Selected adverse neonatal outcomes

Nonexposed group (20–34 years)
Exposed group (>=35 years)

Figure 2: Distribution of selected neonatal adverse pregnancy
outcomes over grouped maternal age in Debre Markos referral
hospital, Northwest Ethiopia, 2019 (NE � 303 and NNe � 604).

4 Obstetrics and Gynecology International

analysis. )e AMA group had three times the risk of still-
birth compared with the nonexposed group (ARR � 3.14
95% CI (1.30–7.00)) (Table 3).

Low birth weight was not significantly associated with
maternal age on binary logistic level (Table 3).

Advanced maternal age pregnancy was significantly
associated with PTB and so were other socioeconomic and
obstetrics factors like number of alive children, wealth
index, husband’s occupational status, gravidity, husband’s
educational status, mother’s educational status, parity,
ANC follow-up, previous adverse pregnancy outcomes,
health insurance, and place of residence at binary logistic
analysis level. Maternal age was entered into the multi-
variable logistic analysis alongside with those factors as-
sociated with preterm birth to control for confounding
effects. )e AMA group had 2.66 times the risk of deliv-
ering preterm fetus (ARR � 2.66 95% CI (1.81–3.77))
compared with the younger counterparts (Table 3).

4. Discussion

)is study was aimed at assessing the fetal adverse outcomes
associated with advanced maternal age. Accordingly, the risks
of stillbirth and low birth weight were higher in pregnancy at
an advanced maternal age compared with the younger
counterparts. Low birth weight, however, was not significantly
associated with pregnancy at an advanced maternal age.

)e incidence of stillbirth in the exposed group is higher
compared with the nonexposed group, 13.2% versus 3.1%.
)is incidence of stillbirth in the exposed group is lower
compared with the study done in Ghana, which reported
incidence of still birth in the exposed group to be 20.7% and
the in nonexposed group to be 5% [1]. )e difference in
incidence could be due to the difference in study design and
study setting implicating different maternal and fetal and/or
neonatal care practices. )is difference in maternal
healthcare practice across the two countries could contribute
to the difference in the incidence of still birth.

)is study also reported the incidence of PTB to be
19.8% in the exposed group and 8.4% in the nonexposed
group. )is finding is lower than the 77.6% of PTB incidence
in the AMA group reported by the prospective cohort study
done in Ghana [1]. )is variation could be due to the dif-
ference in the study design and setting.

)e current study has also reported the incidence of
LBW in the exposed group to be 16.5%. )is incidence is
lower than the incidence of LBW reported by the study done
in Ghana, which was 44.8% [1]. )is variation could be
explained by the difference in the study setting.

)e current study found that the AMA group had three
times the risk of stillbirth compared with the nonexposed
group. )is finding is in accord with the study done in
Denmark, Risk of Adverse Pregnancy Outcomes at Ad-
vanced Maternal Age [18], a multicountry assessment of
AMA and pregnancy outcomes [2]. Similarly, the current
finding is consistent with a prospective study done in Ghana
which concluded the AMA increased the risk of stillbirth [1].
)e decreased placental perfusion in mothers with increased
age could explain this increased risk of stillbirth in the AMA
group [19].

Different studies, however, had different conclusions
about the association between AMA and stillbirth. Among
the studies that are in contrast with the current study are the
studies done in Oman which stated that there is no increased
risk of stillbirth in AMA group compared with nonexposed
group [20], a study done in three UK hospitals [21]. )e
study done on the risk of adverse pregnancy outcomes at
advanced maternal age had also concluded that no statis-
tically significant difference was observed for pregnant
women aged ≥40 years [18].

According to the current study, low birth weight is not
significantly associated with maternal age. )is finding is
consistent with studies done in high-income developing
countries which stated that there is no significant difference
in low birth weight between AMA and nonexposed group
[22]. )e studies done in Yaoundé, Cameroon [12], and

Table 3: Bivariate and multivariable analysis of maternal age and other variables associated with selected fetal adverse outcomes in Debre
Markos referral hospital, Northwest Ethiopia, 2019 (NE � 303 and NNe � 604).

Stillbirth3a
Crude RR (95% C.I.) Adjusted RR (95% C.I.)

No Yes
Maternal age
Nonexposed group 585 19 1 1
AMA group 263 40 4.22 (2.53–6.75)∗∗ 3.14 (1.30–7.00)∗

LBW
No Yes

Nonexposed group 529 75 1
AMA group 253 50 1.33 (0.96–1.83)

PTB3b

No Yes
Nonexposed group 553 51 1 1
AMA group 243 60 2.36 (1.68–3.23)∗∗ 2.66 (1.81–3.77)∗∗
3aAdjusted for: Place of residence, maternal occupational status, maternal educational status, gravidity, parity, ANC follow-up, previous adverse pregnancy
outcome(s), wealth quintile, health insurance. Hosmer-Lemeshow Goodness-of-fit P-value � 0.252. 3bAdjusted for: number of alive child(ren), wealth
quintile, husband occupational status, gravidity, husband educational status, maternal educational status, parity, ANC follow-up, previous adverse pregnancy
outcomes, health insurance, place of residence. CI, Confidence Interval; RR, Risk Ratio. Hosmer-Lemeshow Goodness-of-fit, P-value � 0.974.∗P-value<0.05,
∗∗P-value <0.001 RR � OR/(1 − Io) + (Io × OR), Io incidence in the nonexposed group, OR- Odds ratio.

Obstetrics and Gynecology International 5

prospective cohort study in Ghana [1], however, concluded
that neonates from women of the AMA group are at in-
creased risk of low birth weight. )is difference can be
explained by the difference in study setting pertaining to
variation in clinical advancement and obstetrical practice.

)is study has also revealed that preterm delivery has
increased in the AMA group compared with the younger
aged women. )e AMA group had 2.66 times the risk of
delivering preterm fetus compared with the younger
counterparts. )is finding supports the prospective cohort
study done in Ghana which concluded that preterm birth
was one of the other independent factors associated with the
AMA group [1]. )is increased risk of PTB could be at-
tributed by the increased hypoxic placenta originating from
placental insufficiency and incomplete maternal artery
remodeling, both of which can cause PTB either iatrogen-
ically or spontaneously [23].

5. Limitations of the Study

)is is a baseline study and is also the first to be conducted in
the country; hence, future studies on longitudinal cohorts
including all adverse fetal outcomes would help gaining
additional insights into pregnancy at an advanced maternal
age and adverse fetal pregnancy-related outcomes.

6. Conclusion

According to the current study, the incidence of adverse fetal
pregnancy outcomes was higher in the AMA group com-
pared with the nonexposed group. )e fetal adverse out-
comes were statistically associated with advanced maternal
age. AMA pregnancy also increases the risk of fetal adverse
outcomes (stillbirth and preterm birth) compared with the
younger counterparts, and on the contrary, LBW was not
significantly associated with AMA.

Abbreviations

AMA: Advanced maternal age
ARR: Adjusted relative risk
PTB: Preterm birth
SB: Stillbirth.

Data Availability

)e datasets used and/or analyzed during the current study are
available from the corresponding author on reasonable request.

Ethical Approval

Ethical clearance letter was obtained from the Ethical Review
Committee of the School of Midwifery, under the delegation of
the Institution Review Board (IRB) of the University of Gondar.

Consent

Informed written consent was obtained from each study
subject after the data collectors had clearly explained the
aims of the study to collect information.

Disclosure

)e funder had no role in the design of the study, collection,
analysis, interpretation of the data, and manuscript writing.

Conflicts of Interest

)e authors declare that they have no conflicts of interest.

Authors’ Contributions

B. D. theorized the research problem, designed the study,
participated in the data collection, analyzed the data, drafted
the paper, and prepared the manuscript. M. A. and S. A.
revised the research design, performed data analysis, and
revised the manuscript. All authors of the manuscript have
read and approved its content.

Acknowledgments

)e authors are grateful to the participants of the study who
shared their time to give their genuine responses, data
collectors, and supervisors of the study, and Debre Markos
Referral Hospital for the cooperation. )e financial support
for this thesis was obtained from the University of Gondar.

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Obstetrics and Gynecology International 7

ORIGINAL RESEARCH ARTICLE

The trend in the relationship of advanced maternal age to preterm birth
and low birthweight

Kitae Sohna,b

aSchool of Economics and Finance, Curtin University, Perth, Australia; bDepartment of Economics, Konkuk University, Seoul, South Korea

ABSTRACT
Purpose: As women in developed countries tend to delay childbearing, it becomes more important
to understand the relationship of advanced maternal age to birth outcomes. We aimed to estimate
the trend in the relationship of advanced maternal age to preterm birth and low birthweight.
Materials and methods: We analysed 4,264,417 ethnically homogeneous, singleton firstborns,
born in hospitals to married couples in South Korea in 1997–2014. We regressed an indicator for
preterm birth or low birthweight on advanced maternal age, the baby’s sex, advanced paternal
age, and a set of socioeconomic status (SES) variables by year. We then collected the coefficient on
advanced maternal age and charted its trend. We repeated the same procedure for
4,153,313 second- and third births.
Results: When we controlled for only the baby’s sex, the relationship between advanced maternal
age and preterm birth dramatically weakened in the 2000s and slightly more thereafter: being an
older mother was related to a 3.5% point increase in preterm birth in the late 1990s, but this figure
decreased to less than 2% points by the early 2010s. Controlling for advanced paternal age slightly
decreased the relationship and controlling for SES hardly affected the relationship. We obtained
almost the same results for low birthweight. Second- and third-borns exhibited a declining, much
weaker influence of advanced maternal age on the birth outcomes.
Conclusions: In relative terms, mothers of advanced age were more likely to deliver preterm and
low birthweight babies than younger mothers. In absolute terms, however, the risk was small in
the 1990s and much smaller in the early 2010s.

ARTICLE HISTORY
Received 1 May 2017
Revised 14 August 2017
Accepted 23 August 2017
Published online 26 Septem-
ber 2017

KEYWORDS
Maternal age; preterm birth;
low birthweight; South
Korea

Introduction

As women in developed countries tend to delay childbear-
ing [1,2], it becomes more important to understand the
relationship of advanced maternal age to birth outcomes.
Among birth outcomes, preterm birth and low birthweight
are important as they are related to adverse developmen-
tal, health, educational and economic outcomes in child-
hood and adulthood [3]. Researchers have typically tried to
determine whether advanced maternal age is adversely
related to these birth outcomes. Some studies reported no
statistically significant relationship [4–6], but literature
reviews concluded that the relationship did exist [7–9].

We contributed to the literature by charting the trend
in the relationship over a period of 18 years in a homoge-
neous population. The trend can offer useful information
to medicine and the public. For example, if the relation-
ship has weakened, one can use this information to deter-
mine the mechanisms of the weakening and incidentally
the relationship itself. Alternatively, a health care provider
can counsel potential older mothers, paying less attention
to their ages and more attention to other risk factors
such as smoking and obesity. Policymakers can even haz-
ard to assess the importance of advanced maternal age in
the future and allocate resources accordingly. A popula-
tion study is attractive because, by definition, the results
are generalizable; a hospital-based study can never be
free from this concern. Since the population in our study

was large, we exploited a large number of observations,
enhancing estimation precision and reducing the possibil-
ity of a false negative. Furthermore, our choice of a
homogeneous group alleviated bias arising from omitted
variables.

Researchers often neglect that babies born to older
mothers tend to be born to older fathers (see studies cited
in [7–9]); in our data, the correlation coefficient between
maternal and paternal age was 0.64 for firstborns and 0.68
for second- and third-borns. It is, however, important to
control for paternal age because advanced paternal age is
also adversely related to birth outcomes [10,11]. Without
controlling for paternal age, it is difficult to determine
whether the putative relationship between advanced
maternal age and adverse birth outcomes concerns mater-
nal or paternal age. If the relationship concerns paternal
age, one needs to revisit the literature. If it concerns mater-
nal age, one can proceed to assess the relative strength of
paternal age in mediating the relationship vis-�a-vis other
potential mediators, such as socioeconomic status (SES).

South Korea provides an interesting case for several rea-
sons. Almost all Korean citizens are ethnically the same
[12]. In addition, Korea’s land area is relatively small, its
land size being similar to Indiana’s. Hence, the population
is similarly affected by macro conditions, such as culture,
geography, climate, food, lifestyle, and public policy.
Moreover, Korea has led a group of countries with

CONTACT Kitae Sohn [email protected] School of Economics and Finance, Curtin University, Perth, WA, Australia
Supplemental data for this article can be accessed here.

� 2017 The European Society of Contraception and Reproductive Health

THE EUROPEAN JOURNAL OF CONTRACEPTION & REPRODUCTIVE HEALTH CARE, 2017
VOL. 22, NO. 5, 363–368
https://doi.org/10.1080/13625187.2017.1372569

extremely low fertility rates.1 Since advanced maternal age
is closely related to low fertility, our results are of great
interest to this group of countries. As total fertility rates
have decreased even in many developing countries (not-
ably, China), our results are also relevant to some develop-
ing countries.

Methods

We analysed publicly available birth information on all
births at South Korea in 1997–2014. A person enjoys legal
rights only if his or her birth was reported to the govern-
ment. Hence, the data probably permitted observation of
all births in Korea during the period. We included babies
who were as homogeneous as possible, while maintaining
representativeness: ethnically Korean singletons born in
hospitals to married couples. Marriage in Korea is socially a
prerequisite to birth: of all births during the period, the
highest proportion of babies outside marriage (including
births with no information on the status) was only 2.35% in
2009. Babies born to married couples could differ from
those born to unmarried couples, and the former were rep-
resentative in our data. We thus considered only babies
born to married couples. During the period, about 98% of
births took place in hospitals, and these hospitals provided
birth information, such as birthweight and gestational
length. Birth information supplied by hospitals is presum-
ably more accurate than that provided by other locations,2

and babies born in hospitals were representative and could
differ from those born in other locations. We thus consid-
ered only babies born in hospitals.

Despite Korea’s extremely low total fertility rate [2],
accompanied by a higher standard of living [13,14], almost
all married couples have at least one child: of married
women aged 20–44 in a nationally representative survey,
90% reported having at least one child in 2012 [15, p. 130].
Since fertility was higher before this year, the rate must
have been higher in earlier years. In contrast, having a
second child is not as prevalent as having a first child, so
the family background of firstborns could differ from that
of babies of higher parity. We thus focused on firstborns,
but for completeness, we briefly reported results for
second- and third-births combined. Twins are significantly
lighter than singletons for reasons other than advanced
maternal age, and twins accounted for less than 4% of all
births in 2014. We thus considered only singletons. The
Korean population has long consisted of one ethnic group
[12], and Statistics Korea disclosed information on parental
citizenship (roughly identical to ethnicity) for 2010–2013
(but not for 2014). Of 436,455 births recorded in 2013,
94.05% were born to Korean mothers and Korean fathers.
To consider babies of the same ethnicity, we included only
babies born to Korean mothers and Korean fathers.

To reduce bias and enhance estimation precision, we
excluded observations with extreme values. We restricted
birthweights to 500 g or greater, gestational lengths to 22
weeks or longer. Since the number of the excluded obser-
vations was minuscule, the exclusion was inconsequential
(not shown). Since teenage births are extremely rare in
Korea (e.g., 0.59% in 2014), we restricted maternal ages to
20–49; ages younger than 20 exhibited very imprecisely
measured estimates (not shown). Smoking is an important

determinant of birth outcomes [16], but our data did not
contain this information. This lack of information is, how-
ever, inconsequential because almost no pregnant women
in Korea were smokers. For example, when Jhun et al.
[17] tested 1057 urine samples from pregnant women
who visited 30 randomly sampled obstetric clinics and
hospitals for prenatal care in 2006, only 3.0% turned out
to be cotinine-validated smokers. We detailed the process
of excluding observations in Supplementary Appendix
Table A-2.

In this study, preterm birth refers to birth at a gesta-
tional length <37 weeks, and low birthweight refers to a
birthweight <2500 g. We used a cut-off age of 35 years to
define advanced maternal age and justified this age below.
Considering the age difference in a couple (about three
years, see Table 1), we defined the paternal age 40 years
and older as advanced paternal age – older mothers and
fathers for brevity.3 In addition to the baby’s sex and pater-
nal age, we controlled for the following covariates: parental
education (at least a college education vs. otherwise), par-
ental occupation (nine categories) and municipality fixed
effects (the number varied depending on the birth year,
but fluctuated around 250 categories). By controlling for
municipality fixed effects, we compared babies born in the
same municipality. This is an effective way of comparing
babies who were as homogeneous as possible because a
municipality in Korea is small in size (e.g., the greatest
number of births took place in Songpa-gu during the
period, and its size is only slightly greater than half of
Manhattan’s). Education and occupation are important
components of SES, and residential area reflects the resi-
dent’s SES. We thus attempted to control for parental SES
by controlling for this set of covariates. The number of
observations were 4,264,417 for firstborns and 4,153,313 for
second- and third-births.

Since our main aim was to chart the trend in the rela-
tionship between advanced maternal age and the birth
outcomes, we first estimated the following specification by
a linear probability model (LPM) for each year:4

Yim ¼ b1oldmomim þ b2sexim þ b3olddadim þ Ximb3 þ mm þ uim
(1)

where Yim refers to an indicator of preterm birth or low
birthweight of baby i born in municipality m, oldmom to
whether the mother was aged 35 þ or not, sex to the
baby’s sex, olddad to whether the father was aged 40þ
or not, X to a set of covariates, m to municipality fixed
effects, u to the error term and the b’s to coefficients to
estimate. We took advantage of the large number of
observations by flexibly controlling for all covariates in
dummy form. We then plotted the trend of b1 over the
18 years studied.

Our secondary aim was to estimate the relative power
of advanced paternal age (versus SES) in mediating the
relationship between advanced maternal age and the birth
outcomes. We thus incrementally added the independent
variables. The first set consisted of oldmom and sex. We
then added olddad. We next replaced olddad with SES
(namely, X and m) since we competed olddad with SES. For
completeness, we finally controlled for both olddad and
SES. In preliminary analyses, we checked whether estima-
tion results varied by sex and confirmed that they did not.
We thus pooled boys and girls.

364 K. SOHN

Results

Background results

Table 1 presents descriptive statistics. To save space, we
only described the variables of interest (for more, see
[18,19]). The percentage of older mothers was 6.3% for first-
borns and 15.2% for second- and third-borns. The percent-
age of preterm births was 3.6% for firstborns and 3.9% of
second- and third-borns. The corresponding figures for low
birthweights was 3.5% and 2.9%.

Researchers typically use a cut-off point for advanced
maternal age at 35, 40, or even 45 years [4,20,21]. Since we
had a large number of observations, we could precisely
estimate the relationship between each year of maternal
age and the birth outcomes by pooling all birth years and
regressing each of the birth outcomes on a series of mater-
nal age dummies (and the baby’s sex); the age 20 was the
reference age. Supplementary Figure A-1 shows the coeffi-
cient on each year of age with capped spikes indicating
95% confidence intervals. The wider confidence intervals
for 40þ indicate a small number of babies born to mothers
in this age range. Relative to 20, the probability of having a
preterm birth was slightly lower in the 20s, but switched to
be higher between 30 and 35. We obtained the same

results for low birthweight (Figure A-2 in the
Supplementary appendix). At 35þ, the probability was dis-
cernibly higher. Considering the wide confidence intervals
for 40þ and the discernible difference in 35þ, we defined
advanced maternal age as 35þ. Another reason for this
cut-off point is that it is common in the literature [22];
choosing it thus facilitates the comparison of our results
with others.

Trends in the relationship of advanced maternal age
to birth outcomes

Figure 1 shows that when we controlled for only the baby’s
sex (thick solid line), the relationship between advanced
maternal age and preterm birth dramatically weakened in
the 2000s and slightly more thereafter: being an older
mother was related to about a 3.5% point increase in pre-
term birth in the late 1990s, but this figure decreased to
under 2% points by the early 2010s. When we added
olddad (thick dashed line), the trend in the relationship
slightly shifted down. When we replaced olddad with SES
(thin solid line), the trend almost reverted to the original
one, indicating that SES hardly mediated the relationship.
Comparisons of the thick dashed line and thin solid line

Table 1. Descriptive statistics.

Firstborn 2nd and 3rd-born

Continuous variable Mean (SD) Mean (SD)
Girl’s birthweight (g) 3202 (426) 3226 (422)
Boy’s birthweight (g) 3296 (441) 3330 (435)
Maternal age (year) 28.4 (3.8) 30.7 (3.8)
Paternal age (year) 31.1 (4.1) 33.5 (4.0)

Discrete variable % %
Maternal age <35 years 93.7 84.8
Maternal age � 35 years 6.3 15.2
Paternal age <40 years 96.7 92.9
Paternal age � 40 years 3.3 7.2
Gestational length

�36 3.6 3.9
37 4.5 6.9
38 14.5 25.0
39 24.6 25.8
40 40.2 32.6
�41 12.6 5.7

Birthweight �2500 g 96.5 97.2
Birthweight <2500 g 3.5 2.9
Girls 48.6 47.6
Boys 51.4 52.4
Maternal education < College or above 41.6 52.0
Maternal education � College or above 58.4 48.1
Maternal Occupation

Manager 0.6 0.5
Professional 7.8 5.0
Clerical and kindred 14.2 8.3
Sales and service worker 3.7 2.8
Farmer, fisherman, forest worker 0.3 0.6
Craftsman 0.4 0.2
Operative 0.1 0.1
Labourer 0.2 0.1
Student, housewife, unemployed, missing, or soldier 72.7 82.3

Paternal education < College or above 37.5 43.6
Paternal education � College or above 62.5 56.4
Paternal occupation

Manager 3.1 3.6
Professional 12.2 10.8
Clerical and kindred 44.3 41.7
Sales and service worker 18.9 21.0
Farmer, fisherman, forest worker 1.6 2.5
Craftsman 7.8 8.6
Operative 3.7 4.2
Labourer 1.7 2.2
Student, housewife, unemployed, missing, or soldier 6.6 5.5

N 4,264,417 4,153,313

SD: standard deviation.

THE EUROPEAN JOURNAL OF CONTRACEPTION & REPRODUCTIVE HEALTH CARE 365

indicate that advanced paternal age exerted more influence
on the mediation than SES. As expected, when we con-
trolled for both olddad and SES (thin dotted line), the trend
was almost identical to that with only olddad.

We repeated the same exercise with low birthweight
and obtained almost the same results (Figure A-3 in the
Supplementary appendix). Note that the proportion of pre-
term births increased from 2.6% in 1997 to 4.5% in 2014;
the corresponding figures for low birthweights were 2.9%
and 4.2% (Figure A-4 in the Supplementary appendix), but
the relationship between advanced maternal age and the
birth outcomes weakened in absolute terms. Hence, the
effect of advanced maternal age on the birth outcomes fur-
ther decreased in relative terms. We measured the relative
size of the coefficient on advanced maternal age by divid-
ing the coefficient by the mean of the birth outcome for
each birth year. To estimate the total relationship between
advanced maternal age and the birth outcomes, we con-
trolled for only the baby’s sex. Figure 2 shows a fast
decrease up to 2007 and thereafter a slow decrease for
both outcomes. In the late 1990s, being an older mother
was related to an increase in the birth outcomes by more
than 100% of the mean of the outcomes, but by 2014, the
figure decreased to about 40%. We repeated the exercise

for second- and third-borns and found the same downward
trends (Figure 3). The only difference was that the levels for
second- and third-borns were lower than those for first-
borns by about 40% points. Hence, advanced maternal age
poses a substantially lower risk for preterm births and low
birthweights in the later years of the study. It is unclear
what drove the upward trends in preterm birth and low
birthweight, but it is clear that advanced maternal age was
not the main driver.

Discussion

Differences in results and conclusions

We charted the trends in the relationship of advanced
maternal age to preterm birth and low birthweight. This
exercise improved on the literature in that it went beyond
asking whether the relationship existed. We found not only
did the relationship exist during the entire period but also
that it weakened over time. Some researchers argued that
they did not find a statistically significant relationship
between advanced maternal age and birth outcomes,
including preterm birth and low birthweight. We believe
that they were false negatives because they considered a
small number of older mothers. For example, Grimes and
Gross [6] dismissed the difference between 30% and 24%
in the rate of low birthweight between 149 hypertensive
mothers aged 35þ vs. 462 hypertensive mothers aged 34�,
saying that it was not statistically significant. In contrast,
Kirz et al. [5] found a statistically significant difference, but
their finding is counter-intuitive: 54 mothers aged 35þ
experienced a lower rate of low birthweights than 251
mothers aged 20–25 (6.5% vs. 9.9%). Even if the two find-
ings were true, the concern of selection remains because
they analysed not a national population of babies but a
selected group, babies who were delivered at a single hos-
pital. Another example worsens this concern. Berkowitz
et al. [4] estimated an adjusted odds ratio of 1.0 for pre-
term birth between mothers aged 20–29 and mothers aged
35þ and concluded that there was no difference between
the two groups. This ratio does not present a grave con-
cern for a false negative or a counter-intuitive outcome.
However, most of the older women in their study were
white (87.2% were whites), married (90.6% were married),

.2

.4

.6

.8

A
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va

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ce

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a
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1997 2002 2007 2012
Birth Year

Preterm Birth Low Birthweight

Figure 3. Trends in the relative strength of the relationship of advanced
maternal age to preterm birth and low birthweight: Second- and third-borns.
To estimate the coefficient on the dummy for advanced maternal age, we
controlled for only the baby’s sex.

.015

.02

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.03

.035

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M

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te

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1997 2002 2007 2012

Birth Year

Sex Sex & Paternal Age
Sex & SES Sex, Paternal Age, & SES

Figure 1. Trends in the strength of the relationship between advanced
maternal age and preterm birth: firstborns. Sex refers to the baby’s sex, par-
ental age to a dummy indicating a paternal age of 35þ, and SES to parental
education and occupation and municipality fixed effects.

.4

.6

.8

1

1.2

1.4

A
d
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1997 2002 2007 2012
Birth Year

Preterm Birth Low Birthweight

Figure 2. Trends in the relative strength of the relationship of advanced
maternal age to preterm birth and low birthweight: firstborns. To estimate
the coefficient on the dummy for advanced maternal age, we controlled for
only the baby’s sex.

366 K. SOHN

college educated (94.5% attended college), non-smoking
(96.5% did not smoke during pregnancy), and healthy
(88.2% reported no chronic medical conditions). Therefore,
external validity is doubtful.

We left the possibility open that we failed to control for
important mediators or confounders, and we are sympa-
thetic to the conclusion of Newburn-Cook and Onyskiw [8]
in their literature review: maternal age exerts an effect on
both gestational age and birthweight but it is unclear
whether maternal age exerts an independent and direct
impact on the birth outcomes or acts indirectly through its
association with age-dependent confounders. This lack of
information can be a critical limitation if one attempts to
determine the existence of the relationship between
advanced maternal age and the birth outcomes and to
identify the mechanisms behind the relationship. However,
this is not what we pursued. Since we aimed to chart the
trend in the relationship and to run a race between
advanced paternal age and SES, the lack of information
should not detract from this study.

Furthermore, given the homogeneity of babies in our
data and the extensive array of covariates in our specifica-
tion, it appears that advanced maternal age exerts inde-
pendent and direct effects on the birth outcomes. If this
interpretation is unconvincing, at least, we can say that
whatever the mechanisms were, their influence weakened
over time. What then can explain the weakening? Risk fac-
tors for preterm birth and low birthweight include socio-
demographic risk factors, medical risks before pregnancy,
risks of the current pregnancy, a lack of prenatal care, and
environmental and behaviour risks [23,24]. Considering the
short period, we could eliminate genetic and constitutional
influences. We instead argue that the fast improvement in
the monetary and nonmonetary standard of living can
explain our results. For example, the increase in Korean
GDP per capita in 1953–2000 (14.9 times) was the greatest
among 142 countries [25]. A better growth environment
increases height and decreases age at menarche [26–35],
and it is revealing that the speed of increasing height and
of decreasing age at menarche in Korea was fastest in the
world [14]. Furthermore, the close connection between the
early growth environment and health in adulthood, known
as the fetal origins hypothesis [36], implies that Korean
mothers of the same age became healthier; mothers in the
late 30s in 2014 might be as healthy as or even healthier
than those in the early 30s in 1997. The growing purchas-
ing power allowed Korean mothers to fully utilize the
development of medical technology and consequently to
be healthier and to mitigate the said risk factors. One
measure of health succinctly summarises the improvement
in health. Life expectancy at birth for Koreans increased
fastest among OECD countries [37] from 52.4 years in 1960
to 78.5 years in 2005, or 5.8 years per decade. If our explan-
ations are plausible, future research will replicate our results
for countries that experienced or are experiencing fast eco-
nomic growth.

Although the relationship between advanced maternal
age and the birth outcomes weakened over time, the rela-
tionship was not small in relative terms even when it was
the weakest. When we controlled for only the baby’s sex,
the relationship was still about 40% of the mean of the
birth outcome (Figure 2). That said, we assure worried
future mothers of advanced age that in absolute terms, the

risk of preterm birth and low birthweight is small, and if
the trend continues, will be smaller. When we controlled
for only the baby’s sex, thereby estimating the maximum
relationship, the probability of having preterm birth was
3.7% points greater for older mothers than the rest in
1997–1999 but 1.9% points in 2012–2014. The figure for
low birthweight decreased from 3.4% points to 1.9% points.
We thus agree with the conclusion of Carolan and
Frankowska [7] and Usta and Nassar [9] in their literature
reviews that although the likelihood of adverse birth out-
comes increases with maternal age, the outcomes are gen-
erally favourable for older mothers in the absence of pre-
existing medical conditions. We can say the same to future
fathers of advanced age.

Conclusions

We analyzed more than eight million babies born in South
Korea in 1997–2014 and obtained encouraging results for
mothers of advanced age. In relative terms, mothers of
advanced age were more likely to deliver preterm and low
birthweight babies than younger mothers. In absolute
terms, however, the risk was small in the late twentieth
century and became much smaller by the second decade
of this century.

Acknowledgements

I am grateful to the anonymous reviewer and Irving Sivin for helpful
comments and suggestions.

Disclosure statement

There is no conflict of interest.

Notes

1. Detailed data are available at: https://data.oecd.org/pop/fertility-
rates.htm.

2. Gestational length in the hospital report was determined by
either the last menstrual period or an ultrasound exam, the latter
being quite accurate. The data did not indicate which method
was used, but indirect evidence suggests that the length was
accurate. We analysed publicly available data on all infant deaths
between 2009 and 2014, which contained information as to
whether the mother received prenatal care. Prenatal care in
Korea involves ultrasound exams, and if it does not adversely
affect birth outcomes (the opposite is the intention), this
information should provide lower bounds of percentages of
mothers who received prenatal care for all births. Table A-1 in
the Supplementary appendix shows that most received prenatal
care, implying that hospitals provide accurate gestational lengths
for most births.

3. Slightly varying the cut-off points for advanced maternal and
paternal ages did not change the substance of our results (not
shown).

4. Applying a probit or logit regression did not change the
substance of our results (not shown).

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368 K. SOHN

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