EBP review 2

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

49ª 2014 RCOG The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

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.

50 ª 2014 RCOG The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

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.

51ª 2014 RCOG The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

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.

52 ª 2014 RCOG The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

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.

53ª 2014 RCOG The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

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.

54 ª 2014 RCOG The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

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

1 Heffner LJ. Advanced maternal age–how old is too old? N Engl J

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.

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