8/6/2019 JournalDR

1/6

358 British Journal of Midwifery June 2010 Vol 18, No 6

CLINICAL PRACTICE

Effect of age on maternaland fetal outcomes

Within the UK maternal age at the birth

of the first child is steadily increasing

(Nwandison and Bewley, 2006; Lewis,

2007; Office for National Statistics, 2008). Women

who defer childbearing in this way do so for many

reasons. A womans decision regarding the right

time to embark upon a pregnancy may vary with

personal, family, cultural and religious beliefs.However, once a woman over 35 years of age has

made a decision to proceed with a pregnancy she

faces a grim reality.

Andersen et al (2000) noted that approximately

20% of all wanted pregnancies in 35-year-old women

will result in fetal loss (defined as stillbirths, spon-

taneous abortions, ectopic pregnancies) rising to

54.5% at 42 years of age. A woman aged 3539 years

has a risk of spontaneous abortion of 24.6%, rising

to 51% at 4044 years and 93.4% at 45 years or

more (Andersen, 2000). This means that a woman

attending antenatal clinic may previously have had

several wanted pregnancies ending in loss. That

woman may have come from a peer group within

her fertility clinic or social network where friends

have failed to achieve a pregnancy at all. Once

attending for antenatal care, expectations are high

but older women face the unpleasant prospect of

being advised of a poorer obstetric outcome than

their younger counterparts, with no realistic strat-

egies available to improve outcome. This requires

careful counselling, as anxiety itself is associated

with worse pregnancy outcomes (Alder, 2007;

Glynn et al, 2008; Wisborg, 2008).

When searching for an evidence base from

which to counsel such women the literature should

be interpreted with the following points in mind:

Any study in this group of women will only

include a small number of older mothers

(1020% >35 years; 24% >40 years (Gilbert,

1999; Jolly, 2000; Cleary-Goldman, 2005; Reddy

et al, 2006; Hoffman, 2007) and 0.005% >50

years (Donoso, 2008)

The control groups used for comparison

(e.g. 2029, 3039, 4049, >40 years of age)vary widely and older mothers often have chil-

dren with older fathers, which very few studies

correct for (Astolfi, 2004)

Primiparity, plurality and the use of assisted

reproductive technologies all increase with the

age of the population studied and independ-

ently affect the outcomes observed.

By virtue of their advanced age women have

had more time to accumulate co-morbidities. They

are more likely to have experienced surgery, had

car accidents, suffered infectious diseases, gained

weight and smoked for longer. The prevalence

of medical conditions such as hypertension anddiabetes all increase with age. These population

changes are mirrored in the ageing pregnant popu-

lation. Salihu et al (2003) noted more maternal

complications including chronic hypertension and

diabetes in women >35 years. To correct for these

co-morbidites in research may be unrealistic in

that few women of advanced age will be disease

free, but for those who are, correction allows a

more accurate estimation of risk.

Maternal and fetal outcomes

In their prospective study of 36 056 singleton

pregnancies Cleary-Goldman et al (2005) showed

that placenta praevia (adjusted odds ratio (AOR)

2.8), placental abruption (AOR 2.3) caesarean

section (CS) (AOR 2.0) and perinatal mortality

(AOR 2.2) were all increased in older mothers

when the effects of race, parity, body mass index,

education, marital status, smoking, pre-existing

medical conditions, previous adverse obstetric

outcome and use of assisted reproductive tech-

nologies (ART) were controlled for. The authors,

however, showed no statistically significant asso-

l

l

l

AbstractA womans decision regarding the right time to embark upon a

pregnancy may vary with personal, family, cultural and religiousbeliefs. However once a woman over 35 years of age has made adecision to proceed with a pregnancy she faces an increased risk ofadverse pregnancy outcome, particularly in those with co-morbidities,multiple pregnancies and/or those conceived through ovum donation.

These women need support and carefully planned obstetric care.Women seeking assisted reproductive technologies at over 35 yearsof age should be offered pre-pregnancy counselling and be advised of

the benefit of single embryo transfer. Society as a whole, midwives,obstetricians and gynaecologists, should advocate for policies thatenable women to reproduce safely without personal cost to theireducation, careers, identity and their own or their offsprings health.

Anna P Kenyon

Clinical Lecturer/sub-

specialty trainee in

maternal and fetal

medicine, Institute

for Womens Health,

University College

London

8/6/2019 JournalDR

2/6

35British Journal of Midwifery June 2010 Vol 18, No 6

CLINICAL PRACTIC

ciation between age 35 years or older and other

outcomes e.g. threatened abortion, pre-eclampsia

(PET), gestational hypertension, pre-term labour

and operative vaginal delivery. Interestingly, this

study did not show advancing age to be asso-

ciated with hypertensive complications despite

confirming that chronic hypertension was morecommon among older women. The authors suggest

this is as a result of controlling for covariates asso-

ciated with gestational hypertension and PET

e.g. history of medical conditions and use of ART

(Cleary-Goldman, 2005).

Hoffman (2007) looked only at singleton preg-

nancies in a multiethnic population and compared

women 3539 years (13 902) and 40 or more years

old (3953) with those less than 35 years. Hoffman

noted that after correcting for race, parity, chronic

hypertension, PET, diabetes, gestational diabetes

and gestational age at delivery the risk of having an

infant of low birthweight was increased:

8/6/2019 JournalDR

3/6

360 British Journal of Midwifery June 2010 Vol 18, No 6

CLINICAL PRACTICE

(OR 2.22, 95%; CI: 1.33.77) (Simchen et al, 2009).

In a study by Porreco (2005) PET was signifi-

cantly more prevalent among patients conceiving

with ovum donation (OR 2.67, 1.046.82), even

though 22% of the control group developed PET.

One of 11 women (9%) over 45 years conceiving

spontaneously developed PET compared to 20/39(51%) conceiving with ART and donor eggs (P

0.016) (Porreco, 2005). Henne (2007) reported an

increase in pre-term labour, PET and protracted

labour in women conceiving after ovum donation

correcting for parity.

StillbirthRisk of stillbirth may increase with advanced

maternal age. In the general population, still-births affect 1 in 200 pregnancies (Smith and

Fretts, 2007). The additional risk that advanced

Table 1: Studies reporting risks of stillbirth with maternal age

Ref Stillbirthdefinition

Risk Studypopulation

PopulationAge inyears (n)

ComparatorAge inyears

3540years

>40 years >45years

>50 years

Donoso(2008)

Fetal death OR(95% CI)

2 817 959 >50 (217) 2034 3.7(1.210.5)

Hoffman(2008)*

Fetal death AOR(95% CI)

126 402 >40 (3 953) 40(45 982 612singletons)

1.44**(1.381.5)

Jacobsson(2004)

Intrauterinefetal death>28 weeks

AOR(95% CI)

1 566 313 4044(31 662) >45(1,205)

2029 2.1 (1.82.4)for 4044years

3.8(2.26.4)

Salihu(2003)

Loss >20weeks

AOR(95% CI)

12 066 854 4049(3 982 062 )

2029 1.94 (1.672.26)singletons 4049 years

2.20(1.014.75)

singletons>50 (539) 0.72 (0.431.2)

multiples at 4049years

1.6(0.43.00)multiples

Gilbert(1999)

Infant death AOR(95% CI)

1 160 000 >40 (24 032) 2029 1.2 (0.8-1.8)nulliparous1.5 (1.3-1.8)multiparous

Jolly(2000)

Stillbirth OR(95% CI)

385 120 >40 (7331)3540(41 327)

1834 1.41(1.171.70)

1.83(1.292.61)

Reddy et

al (2006)

Stillbirth RR

(95% CI)

5 458 735 35-39

(545,873)>40(109,174)

40(130 857)

2034 1.28(1.241.32)

1.72(1.631.81)

* adjusted for ethnic group, parity, hypertension, pre-eclampsia, gestational diabetes** adjusted for race/parityAOR: adjusted odds ratioOR: odds ratio

8/6/2019 JournalDR

4/6

36British Journal of Midwifery June 2010 Vol 18, No 6

CLINICAL PRACTIC

maternal age poses has been investigated in

several studies (Table 1) and appears to increase

in a continuum with rising age (Andersen, 2000;

Bateman, 2006). The largest increase in risk for

women 35 years or older may start at 39 weeks

gestation and peak at 41 weeks. Extremes of

gestation are associated with the highest weeklyrisk of stillbirth (>41 weeks and 2023 weeks) and

women at 40 years or older appear to have the

largest risk (Reddy et al, 2006). The risk appears

to persist even when confounding variables are

taken into consideration. For example, in the

study by Reddy et al (2006) the effect of maternal

age persisted despite accounting for medical

disease, parity, race and ethnicity.

Fretts and Duru (2008) have suggested that the

risk of stillbirth in women >40 years of age may be

as high as 1 in 116 pregnancies at >37 weeks. This

increased risk is still observed when corrections are

made for coexisting medical conditions, which notonly are more common in women of advanced age

but also are independently associated with stillbirth

(PET, gestational diabetes mellitus, multiple preg-

nancies) (Fretts et al, 1995; Fretts, 2005; Hoffman,

2007). Fretts et al (1995) report that even when

recognized coexisting conditions that contribute to

fetal death are controlled for, women over 35 years

of age have a risk of fetal death twice as high as that

among their younger counterpart.

Causes of the increased risk remain unclear,

however, placental abruption and umbilical cord

complications all appear to rise with increasing

age (Bateman, 2006). Cleary-Goldman (2005)suggested that for singletons greater than 40

weeks gestation the risk of abruption is an

odds ratio of 2.3. Other important maternal

risk factors for stillbirth such as nulliparity

and obesity are also seen to rise in women of

advanced maternal age (Nwandison and Bewley,

2006; Lewis, 2007; Smith and Fretts, 2007; Off ice

for National Statistics, 2008). However, the

most significant contribution to the increased

risk of stillbirth in woman of advanced age is

the increased risk of unexplained fetal death

(OR 2.2, 1.33.8) (Bateman, 2006).

It should be noted that older mothers have bene-

fitted from the reduction in stillbirth in general

populations that we have seen over time, and this

is confirmed by Fretts et al (1995). Between the

years 19601993 stillbirth rates declined overall

and in women aged 35 years or older, the rate of

stillbirths per 1000 births decreased from 16.5

in 1960 to 5.8 in 19901993. The absolute risk of

stillbirth has been greatly reduced, however, the

higher relative risk for older women persists and

exactly what clinicians should do to reduce this is

not clear (Stein and Susser, 2000).

Older age, whether because of the co-morbidi-

ties that accompany it, the plurality that is observed,

or the effect of age alone, does appear to be asso-

ciated with adverse outcome. Prospective mothers

presenting pre-conception or in early pregnancy

(following referral as a result of age identified onrisk factor screening) may wish to know the risk

associated with their pregnancy (Gilbert, 1999),

and in the context of that increased risk what

interventions are available to them to improve

outcome. However, few studies have addressed

interventions in older mothers.

In considering stillbirth, Hannah et al (1992)

have shown that in any pregnancy of more than

41 weeks gestation induction of labour results in

lower rates of caesarean section than serial ante-

natal monitoring with similar rates of perinatal

morbidity and mortality. Given that women of

40 years or older have a similar stillbirth risk at39 weeks to 2529-year-olds at 41 weeks (Andersen,

2000) perhaps interventions should therefore be

offered earlier in these women.

However, a word of caution: women of advance

age may not labour as efficiently as their younger

counterparts. A Dublin group employing active

management of labour in all nulliparous women

attending their unit in spontaneous labour under-

took an analysis of outcome with respect to age.

The need for oxytocin, the incidence of prolonged

labour, instrumental delivery, intrapartum caesarean

section and intrapartum caesarean section because

of dystocia all increased with increasing maternalage (Treacy, 2006). The observed differences were

not accounted for by differences in birthweight,

epidural use or gestational age.

Heffner et al (2003) reported risks for caesarean

section by induction status, gestational age and

maternal age stratified for parity in singleton

pregnancies over 36 weeks. Maternal age greater

than 35 years was associated with an increased

caesarean section rate among nulliparous women

and maternal age over 40 years was associated with

an increased risk in multiparous women (Heffner

et al, 2003). Similar increased caesarean section

rates were reported by Gilbert et al (Gilbert, 1999);

47% caesareasn setion in nulliparous women 40

years old or more compared to 22.5% in those aged

2029 years. However the authors acknowledge

that a diagnosis of dystocia is physician-derived

and that they were unable to conclude what anxiety

maternal age brought to clinical decision making on

the part of the parturient and the doctor (Gilbert,

1999). This suggests that intervention might reduce

the risk of stillbirth, but may increase caesarean

section and maternal morbidity rates.

8/6/2019 JournalDR

5/6

362 British Journal of Midwifery June 2010 Vol 18, No 6

CLINICAL PRACTICE

ConclusionsThe risks of adverse pregnancy outcome appear

to increase with advancing maternal age, particu-

larly in those with multiple pregnancies conceived

with ovum donation. Women seeking ART over

35 years of age should be offered a full and frank

discussion and be advised of the benefit of singleembryo transfer. Society as a whole, midwives,

obstetricians and gynaecologists should advocate

for policies that enable women to reproduce safely

without personal cost to their education, careers,

identity and their own or offsprings health. BJM

Acknowledgement The author would like to thank Dr Susan Bewley without

whose inspiration and assistance this would not have

been possible and Dr M Nwandison in her contribution to

the original article. This topic is covered in greater depth

in: Kehoe S, Bewley S, Ledger W, Nikolaou D, eds (2009)

Reproductive ageing in older mothers. 56th RCOG Study

Group, London

Alder J, Fink N, Bitzer J, Hosli I, Holzgreve W (2007)

Depression and anxiety during pregnancy: A risk factor

for obstetric, fetal and neonatal outcome? A critical

review of the literature.J Matern Fetal Neonatal Med

20(3): 189209

Andersen AMN (2000) Maternal age and fetal loss: popu-

lation based register Linkage study. Br Med J. 320(7251):

170812

Astolfi P (2004) Late paternity and stillbirth risk. Hum

Reprod19(11): 2497501

Bateman BT (2006) Higher rate of stillbirth at the extremes

of reproductive age: A large nationwide sample of deliv-

eries in the United States.Am J Obstet Gynecol194(3):

8405Cleary-Goldman J C Fc (2005) Impact of maternal age on

obstetric outcome. Obstet Gynecol105(5): 98390

Donoso E (2008) Maternal, perinatal and infant outcome

of spontaneous pregnancy in the sixth decade of life.

Maturitas59(4): 3816

Fretts RC (2005) Etiology and prevention of stillbirth.Am J

Obstet Gynecol193(6): 192335

Fretts RC, Duru UA (2008) New indications for antepartum

testing: Making the case for antepartum surveillance

or timed delivery for women of advanced maternal age.

Semin Perinatol32(4): 3127

Fretts RC, Schmittdiel J, McLean FH, Usher RH, Goldman

MB (1995) Increased maternal age and the risk of fetal

death.N Engl J Med333(15): 9537

Gilbert WM (1999) Childbearing beyond age 40: Pregnancy

outcome in 24,032 cases. Obstet Gynecol93(1): 914

Glynn LM, Schetter CD, Hobel CJ, Sandman CA (2008)

Pattern of perceived stress and anxiety in pregnancy

predicts preterm birth. Health Psychology Jan;27(1): 43-51

Hannah ME, Hannah WJ, Hellmann J, Hewson S, Milner

R, Willan A (1992) Induction Of Labor As Compared

With Serial Antenatal Monitoring In Postterm

PregnancyA Randomized Controlled Trial.N Engl J

Med326(24): 158792

Heffner LJ, Elkin E, Fretts RC (2003) Impact of labor induc-

tion, gestational age, and maternal age on cesarean

delivery rates. Obstet Gynecol102(2): 28793

Henne MB (2007) Comparison of obstetric outcomes in

recipients of donor oocytes vs. women of advanced

maternal age with autologous oocytes.Journal of

Reproductive Medicine52(7): 58590Hoffman MC (2007) Pregnancy at or beyond age 40 years

is associated with an increased risk of fetal death and

other adverse outcomes.Am J Obstet Gynecol196(5)

Jacobsson B (2004) Advanced maternal age and adverse

perinatal outcome. Obstet Gynecol104(4): 72733

Jolly M (2000) The risks associated with pregnancy in

women aged 35 years or older. Hum Reprod15(11): 24337

Luke B (2007) Contemporary risks of maternal morbidity

and adverse outcomes with increasing maternal age and

plurality. Fertility and Sterility88: 28393

Lewis GE (2007) Saving mothers lives: Reviewing maternal

deaths to make motherhood safer20032005. The

Confidential Enquiry into Maternal and Child Health

(CEMACH). London

Nwandison M, Bewley S (2006) What is the right age toreproduce. Fetal and Maternal Medicine Review17(3):

185204

Office for National Statistics (2008) Birth Statistics 2004.

United Kingdom; 1940-2004. www.statistics.gov.uk/

downloads/theme_population/FM1_33/FM1_33.pdf

(accessed 20 May 2010)

Porreco RP (2005) Expectation of pregnancy outcome

among mature women. Am J Obstet Gynecol192(1):

3841

Reddy UM, Ko CW, Willinger M (2006) Maternal age

and the risk of stillbirth throughout pregnancy in the

United States.Am J Obstet Gynecol195(3): 76470

Salihu HM (2003) Childbearing beyond maternal age 50

and fetal outcomes in the United States. Obstet Gynecol

102(5): 100614Simchen MJ, Shulman A, Wiser A, Zilberberg E, Schiff E

(2009) The aged uterus: multifetal pregnancy outcome

after ovum donation in older women. Hum Reprod

24(10): 25003

Smith GCS, Fretts RC (2007) Stillbirth. Lancet370: 171525

Stein Z, Susser M (2000) The risks of having children in

later life. Br Med J320(7251): 16812

Treacy A (2006) Dystocia increases with advancing

maternal age.Am J Obstet Gynecol195(3): 7603

Wisborg K, Barklin A, Hedegaard M, Henriksen TB (2008)

Psychological stress during pregnancy and stillbirth:

prospective study. BJOG115(7): 882-5

Key pointsIt is impossible (and wrong) for others to determine when it is the righttime for a woman, or couple, to have a baby. Women who defer child-bearing do so for many reasons, both within and outside their control.Care, support and respect of these and all women should be the healthprofessionals first concern.The risks of adverse pregnancy outcome appear to increase withadvancing maternal age.Women seeking assisted reproductive technology and/or ovum dona-tion over 35 years of age should receive pre-pregnancy counselling andbe advised of the benefit of single embryo transfer.The available data suggest that in terms of physiology, age 2035 yearsremains the best age for childbearing.

l

l

l

l

8/6/2019 JournalDR

6/6