- Email: [email protected]
The older obstetric patient
Problem-based learning in obstetrics
The older obstetric patient
flexibility and control over their reproductive lives. In addition, assisted reproduction techniques (ART) such as ovum donation have allowed women to increase their fertility. In the 21st century motherhood at or beyond the edge of reproductive age is increasingly common. Terms for the ‘older’ obstetric patient have included ‘mature’, ‘advanced’, ‘very advanced’ and ‘geriatric’. The International Federation of Obstetricians and Gynaecologists (FIGO) provided the earliest definition of the ‘older obstetric patient’ in 1958, specifying an age over 35 years for the ‘elderly primigravida’. ‘Advanced maternal age’ has been used as a MESH heading for Index Medicus since 1981, but improvements in women’s general health have led to this term tending to be reserved for pregnancies in women at or over 40 years of age.
Mehrnoosh Aref-Adib Theresa Freeman-Wang
Q2
Ifat Ataullah
Abstract The past few decades have seen a changing demographic phenomenon with many women electing to delay childbearing. With changes in societal norms, women have sought to achieve their educational and career aspirations before embarking on motherhood. Assisted reproduction techniques, including ovum donation, have increased the options for women choosing this delay. This article aims to review recent published studies to understand the risks associated with delaying childbearing – both maternal and fetal. The review includes papers published since the last update and looks at complications of early pregnancy, including ectopic pregnancy, miscarriage and chromosomal abnormality. It also reviews maternal morbidity, including complications of hypertensive diseases and diabetes. It aims to seek both advantages and disadvantages to delaying childbearing, so that both patient and obstetrician are fully informed. In previous reviews the authors have been positive with regards to the risks of delaying childbearing. However, the burden of evidence now suggests that pregnancy in this age group has higher risks – to both the mother and her fetus. This increased risks, however, must be weighed against the potential advantages of delaying childbearing – both financial and emotional, and must also be considered in the context of the small absolute numbers of complications. The majority of older mothers have low risk and uneventful pregnancies. With good antenatal and obstetric care it should be possible to achieve obstetric outcomes for many older mothers similar to those of younger mothers.
Birth trends and maternal age As in many other countries worldwide, one of the most dramatic changes in fertility in England and Wales in the last 30 years has been a shift towards women postponing childbearing until their late 20s and 30s. In England and Wales the mean age at first birth was 24.3 years in 1976, and 27.6 years in 2005. Forty or above is now an increasingly common age at which to begin a family. Women aged 35–39 had birth rates of 34.4 in 1000 in 1991, compared to 53.8 in 1000 in 2005. Women aged 35–39 accounted for 13% of total maternities in 2005, compared with only 6% in 1991 (Figure 1). The number of live births for women over 40 has almost doubled in the last decade from 12 103 in 1996 to 23 703 in 2006. In the USA there has been a similar trend. Between 1980 and 2004 the proportion of first births increased three-fold in women over 30 years (from 8.6 to 25.4%), six-fold in women over 35 years (from 1.3 to 8.3%) and 15-fold in women over 40 years (from 0.1 to 1.5%).
1980
Keywords maternal age; obstetric outcome; perinatal outcome 1985
Introduction
Year
1990
In recent decades there has been a dramatic change in women’s roles in many societies. Professional and educational goals have become increasingly important. The revolution in the availability of safe, effective contraception and the legalization of termination of pregnancy are important factors in giving women
1995
2002
2005
Mehrnoosh Aref-Adib BA MBBS is ST1 Obstetrics & Gynaecology, Whittington Hospital, Department of Women’s Health, Jenner Building, Magdala Avenue, London N19 5NF, UK.
0
Q1
20
30
40
Live births (%) <20
Theresa Freeman-Wang MRCOG is Consultant Gynaecologist, Whittington Hospital, Department of Women’s Health, Jenner Building, Magdala Avenue, London N19 5NF, UK.
20–24
25–29
30–34
35–39
40+
Figure 1 Proportion of babies born to mothers of varying age group, 1980–2005, showing trend of increased percentage born to mothers in older age groups and fewer in younger mothers. Data kindly provided by the Vital Statistics Office (ONS).
Ifat Ataullah MRCOG is Consultant Obstetrician, Kingston Hospital, Galsworthy Road, Kingston-upon-Thames, Surrey KT2 7QB, UK.
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10
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Problem-based learning in obstetrics
Miscarriage and ectopic pregnancy rates
7
The risk of miscarriage increases sharply as women reach their late 30s. Women aged 40 years have a 30% chance of miscarriage of a clinically recognized pregnancy (Figure 2). This rises to > 50% for women over 45 years old. A recent large population-based case-control study in the UK showed that there was no difference in the odds of miscarriage for women aged below 35, but a five-fold increase in risk over the age of 40, compared to controls aged 25–29.This is in part due to the effect of maternal age on the frequency of autosomal trisomies, but there is also an increase in euploid losses. Ectopic pregnancy rates also increase with age (Figure 3). Research from women undergoing assisted conception has shown there are increased tubular lesions with advancing maternal age. The incidence of ectopic pregnancy after ART is 4%, which is two to three times higher than the background incidence. It is plausible that the increased tubular dysfunction with age results from longer exposure to the risks of developing pelvic inflammatory disease or having experienced previously unrecognized subclinical infection.
Risk of ectopic pregnancy (%)
6
5
4
3
2
1
0 10
15
20
25
30
35
40
45
Maternal age at conception (years) Figure 3 Risk of ectopic pregnancy according to maternal age at conception. Reproduced by kind permission from Nybo Anderson. Maternal age and fetal loss: a population based register linkage study. BMJ 2000; 320: 1710.
Antenatal screening and counselling for older women It is well known that the risk for trisomies 21, 18 and 13 increases with advancing maternal age (Table 1). It is important to counsel women appropriately regarding their risks and prenatal diagnosis. Serum/ultrasound-based screening combined with maternal age has been demonstrated to be efficient and effective. The National Screening Committee produced a policy document in 2004 recommending: 1. The integrated test is the most effective 2. The integrated serum test if a nuchal translucency service is not available 3. The quadruple test for women who book later than the first trimester
4. The combined test for women who choose first trimester screening. The integrated test has the highest detection rate (85%) of chromosomal abnormalities for the lowest false-positive rate (0.9%) of all the tests. The detection rate is higher at 92% for women over 35 years old compared with 81% for women in the 15–34-year age group. As there is greater accuracy of non-invasive screening in the older age group and a risk of miscarriage associated with invasive testing (0.5–1% with amniocentesis), it is important that women are made aware of all the available screening techniques, so as to be able to make informed decisions.
100
Information for women
Risk of spontaneous abortion (%)
90
A recent study in Canada showed that many women are unaware of the potential consequences of delaying childbearing: 85% of women were aware of potential conception difficulties, 18.8%
1978–82 1983–87 1988–92
80 70 60
Estimated risk for trisomies in relation to maternal age at birth
50 40 30 20 10 0 10
15
20
25
30
35
40
45
50
Maternal age at conception (years) Figure 2 Risk of spontaneous abortion according to maternal age at conception. Reproduced by kind permission from Nybo Anderson. Maternal age and fetal loss: a population based register linkage study. BMJ 2000; 320: 1709.
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Age of mother
Risk of Down syndrome
Risk of trisomy 18
Risk of trisomy 13
20 30 35 40 42 44
1:1530 1:900 1:360 1:100 1:55 1:30
1:18 013 1:10 554 1:4202 1:1139 1:644 No recent data
1:42 423 1:24 856 1:9876 1:3544 1:1516 No recent data
years years years years years years
Data supplied by the Fetal Medicine Foundation.
Table 1
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Problem-based learning in obstetrics
were aware of the risks of caesarean section and 21% were aware of potential preterm delivery. The study concluded that missed opportunities in pre-conception counselling and education should be addressed to allow informed choice. Another study looking at the information needs of over 35-year-old mothers found that these women were at times ‘overwhelmed’ by ‘knowing too much’. Health professionals had given this group large amounts of health information, thinking this is what they required. The authors concluded that health professionals should understand the needs of the group and give information where appropriate.
2.87). However, two other studies have not shown an increased risk. Cleary-Goldman et al found the risk for 35–39 year olds and those over 40 years not to be increased when compared to those younger than 35 years of age (35–39 years: OR 0.9; CI 0.7–1.0. > 40 years: OR 1.1; CI 0.7–1.6). Jacobsson et al concluded from their study that paradoxically older age was protective against mild pre-eclampsia, but could not explain this. Women in the 40–44 age group were less likely than those in the 20–29 age group to develop mild pre-eclampsia (OR 0.58; CI 0.53–0.64) but more likely to develop severe pre-eclampsia (OR 1.4; CI 1.26–1.56).
Q3
Q4
Diabetes Gestational diabetes is more common in the older pregnant woman. The incidence of type 2 diabetes mellitus in 35–44-yearold women is more than double that in 25–35 year olds. Approximately 4% of pregnancies are complicated by diabetes. Both type 1 and type 2 diabetes mellitus are associated with increased risks of vascular complications, including pregnancy-induced hypertension, pre-eclampsia and post-partum haemorrhage. Due to concern about an increase in unexplained stillbirth in pregnancies complicated by diabetes, some advise early delivery at 38 weeks. Joseph et al found a nearly three-fold increased risk of preterm delivery in mothers with diabetes in the 35–39 year age group compared to those aged 20–24 (OR 2.85; CI 1.89–4.28). Jacobsson et al also found this increased risk when comparing 40–44 year olds with 20–29 year olds (OR 3.43; CI 3.04–3.86). This odds ratio increased with increasing age. Data from the FASTER trial also support this increased risk of preterm delivery, but to a lesser extent: 35–39 year olds (OR 1.8; CI 1.5–2.1); over 40s (OR 2.4; CI 1.9–3.1; p < 0.001). Again the absolute numbers in these studies were small. The incidence of gestational diabetes in the over 45s was 4.7% compared to 1% in the Swedish study by Jacobsson et al. The FASTER trial found an incidence of 7.3% in the over 40s compared to 2.9% in the under 35 age group.
Medical complications There is a general belief that women over the age of 35 years have an increased risk of complications during pregnancy. However, prospective population-based studies do not exist and available publications give conflicting views. The ages used to define the older obstetric patient vary. The pregnancy complications commonly addressed are hypertension, diabetes, cardiovascular disease, placental abnormalities, uterine abnormalities and multiple gestation. It is difficult to tease out the effect of confounding factors such as parity, pre-existing diabetes and/or hypertension. The studies that suggest the ‘older obstetric patient’ to be a ‘highrisk’ entity tend to be based on small numbers. Hypertension Actuarial data show that systolic and diastolic blood pressures increase with advancing age. The incidence of treated chronic hypertension is 3.4 in 1000 for women younger than 34 years old, but this rises to 21.3 in 1000 for those aged 35–44 years old. Several studies have shown a two- to six-fold increase in both chronic and pregnancy-induced hypertension in older women. Joseph et al evaluated the outcome of 157 445 deliveries in Canada between 1988 and 2002. They used 20–24 years as a reference band, and compared this age band with the higher age bands of 35–39 years and over 40 years. Women aged 35–39 were twice as likely to have hypertension (OR 2.32; CI 1.97–2.72) and women over 40 were three times more likely (OR 3.55; CI 2.63–4.80). Jacobsson et al studied 1 566 313 births in Sweden between 1987 and 2001. The risk of pregnancy-induced hypertension was three-fold higher in women aged 40–44 years compared to those aged 20–29 years (OR 3.29; CI 3.01–3.59), and women over 45 were six times more likely to develop hypertension (OR 6.38; CI 4.67–8.72). The overall incidence of hypertension, however, was low – 3.4% in the over 45 population, compared to 0.5% in the 20–29-year-old age group. Results reported by Cleary-Goldman et al from the FASTER (The First and Second Trimester Evaluation of Risk) trial looking at 36 056 singleton births in the USA conflict with the above findings. Women aged 35–39 were not found to have increased risks of gestational hypertension (OR 0.8; CI 0.7–1.0) and nor were those over 40 (OR 1.0; CI 0.8–1.4).
Labour and delivery Caesarean section rates (CSR) rise with increasing maternal age (Figure 4). The national CSR in the Royal College of Obstetricians and Gynaecologists (RCOG) Sentinel Audit 2001 was 21.3%. For mothers aged between 35 and 39 years, the CSR was 28% and it was 33% for those between 40 and 50 years old, compared to a CSR of only 13.4% for those younger than 20 years of age. This observed risk remained after adjustments for demographic and obstetric risk factors. Several studies have investigated obstetric interventions in relation to advancing maternal age. Treacy et al looked at 10 737 nullipara deliveries between 1998 and 2002: the need for oxytocin augmentation, incidence of prolonged labour, emergency CS and instrumental delivery indicated for dystocia all increased in a continuum with advancing maternal age. This supports the theory that there may be progressive myometrial dysfunction with age, leading to dysfunctional labour. The study did find, however, that oxytocin augmentation corrected most cases of dystocia in spontaneous first-time labours, irrespective of maternal age. Some women undergo elective induction or caesarean delivery because of real or perceived risks. Other hypotheses to explain this association include decreased pelvic compliance of the bony joints, reduced oxytocin receptors and reduced maternal effort
Pre-eclampsia Studies looking at pre-eclampsia also show conflicting results. Salihu et al evaluated the outcome of 12 066 854 deliveries in the USA between 1997 and 1999. The pre-eclampsia rate was 36.4 in 1000 for the 20–29 age group, but up to 85.3 in 1000 for the 40–49 age group. Duckitt et al found the risk of pre-eclampsia doubled for multiparous women aged 40 or over (OR = 1.96, CI = 1.34 to
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Problem-based learning in obstetrics
increase in preterm delivery from 9.3% in singleton births to 42.9% in twins (p < 0.001). The perinatal mortality rate is fourfold higher for multiple pregnancies compared to singleton.
Caesarean section rate (%)
35
30
Perinatal mortality and morbidity
25
There have been reports that antepartum haemorrhage, postpartum haemorrhage and abruption, as well as placenta praevia are associated with advanced maternal age. Possible reasons for this include increased caesarean section rate, fibroids and agerelated myometrial changes. The risk of placental abruption in the Cleary-Goldman study was double in women aged 40 and over compared to those aged 20–29 years (OR 2.3; CI 1.3–3.8; p < 0.02), but not significantly increased in 35–39 year olds (OR 1.3; CI 0.0–1.8; p 0.21). Again, the overall incidence was low – 1.6% in the over 40 year olds, compared to 0.7% in the 20–29 year olds. The Jacobsson et al study showed smaller increased odds for 35–39 year olds (OR 1.64; CI 1.24–2.16).
There are increased risks of preterm delivery, low birth weight, macrosomia, stillbirth and perinatal mortality (PNM) with advanced maternal age (Figures 5 and 6). Despite antenatal screening, the risk of aneuploidy and fetal anomalies is likely to contribute to the increased risk of stillbirth. In 2004 the PNM mortality rate in England and Wales was lowest for the 30–34 year age group at 4.93 in 1000 live and stillbirths, and highest for women over 45 years at 15.0. Both babies > 4000 g and babies < 2500 g are more common in older women. This is consistent with higher rates of diabetes, hypertensive disorders and maternal obesity. Some studies show that when other factors such as pre-eclampsia, maternal weight and smoking are taken into account there is no direct association between maternal age and fetal weight. Reddy et al looked at 5 458 735 singleton births on the US register between 2001 and 2002 and found that at 37–41 weeks’ gestation the risk of stillbirth for 35–39 year olds was 1 in 382 compared to 1 in 267 for women aged 40 or over. The relative risk of stillbirth for 35–39 year olds compared to a younger cohort was 1.32 (CI 1.22–1.43) and for over 40s was 1.88 (CI 1.64–2.16). The authors concluded that the most at-risk period was between 37 and 41 weeks’ gestation. An interesting study by Luke et al looked at infant deaths and compared the causes stratified by age group and parity. They found that older multiparas had a lower percentage of infant death from accident, homicide or neglect. For mothers aged over 45 year, the risk rate was 0.7% compared to 3.4% in 30–34 year olds. However, in older primiparas this figure was much higher – 6.7% of deaths were due to accident or homicide compared to 1.7% in the 30–34-year-old age group.
Multiple pregnancy
Maternal mortality
With the increase in ART the risk of older women having multiple pregnancy increases. For in vitro fertilization (IVF), between 35% and 50% of pregnancies are thought to be multiple. The maternal and fetal risks of multiple pregnancy make thorough counselling of women extremely important. An extensive literature describes links between multiple pregnancy and poor fetal outcome. With this in mind, since 2004 the Human Fertilization and Embryology Authority (HFEA) has limited the number of embryos transferred to two per cycle for women under 40 years and to three per cycle for those 40 years and over. A study by Oakley et al looking at ART and multiplicity concluded that 73 deaths in 2001 could have been avoided if the babies had been born as singletons. In 2002 the maternal mortality rate for multiple pregnancies was 20.2 in 100 000 compared to 13.0 for singleton pregnancies. In 2000 the European Society of Human Reproduction and Embryology (ESHRE) group reviewed the risks of multiple gestation. It concluded that maternal complications such as pre-eclampsia increased from 4.8% in singleton births to 8.3% in twins and to 11% in triplets (p < 0.001). Concerning fetal risks, twins are more likely to have intrauterine growth restriction and prematurity. The ESHRE group found an
Between 2000 and 2002 there were 242 recorded maternal deaths in the UK. The mortality rate for this triennium increased from
20
15
10 15
20
25
30
35
40
45
Maternal age (years) Figure 4 Caesarean section rate by maternal age. Reproduced by kind permission from the RCOG Sentinel Audit 2001.
with increasing maternal age. Equally, older women may be more assertive and articulate their own wishes for intervention.
Placental abnormalities
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Risk of stillbirth (%)
0.9 0.8 0.7 0.6 0.5 0.4 0.3 <19
20–24
25–29
30–34
35–39
40–44
>45
Maternal age at conception (years) Figure 5 Risk of stillbirth according to maternal age at conception. Reproduced by kind permission from Nybo Anderson. Maternal age and fetal loss: a population based register linkage study. BMJ 2000; 320: 1710.
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UK found that 2 of 13 maternal deaths due to and 6 of 31 survivors of amniotic fluid embolism were aged over 35 years, suggesting age was not necessarily a risk factor in this group.
Rate per 1,000 live births
15
Stillbirth rate
10
Neonatal death rate
Psychiatric mortality/morbidity A recent study looking at psychiatric admissions post delivery found that the age-specific incidence of overall risk of hospital admission for parents decreased with increasing age.
5
Psychological aspects of pregnancy
0
<20
20–24
25–29
30–34
35–39
40–44
>45
Women in their 30s and 40s may have a healthier lifestyle and look after themselves better in terms of nutrition and exercise. Mature women may have a more positive perception of their bodies and more readily tolerate the symptoms of pregnancy. The older mother may be in a better financial position to offer her child greater material and educational advantages. Women pursuing a career may be more satisfied to have achieved their goals before embarking on motherhood. There is evidence that older mothers are more likely to breast feed. In some studies that have controlled for social factors and parity, children of older mothers do better at school than those of very young parents. One study of women delivering in Canada between 1988 and 2002 looked at maternal characteristics by age. Older women were more likely to have a high income (26% of 35–39 year olds compared to 2.5% of 20–24 year olds), were more likely to be married (83.2% of 35–39 year olds compared to 43.6% of 20–24 year olds) and were less likely to smoke (18.4% of 35–39 year olds compared to 39.2% of 20–24 year olds).
Maternal age (years) Figure 6 Maternal age-specific stillbirth and neonatal mortality rates in England, Wales and Northern Ireland, 2005. Derived from ONS data.
11.4 in 100 000 to 13.1 in 100 000. Increased maternal age was cited as an independent risk factor in the key findings of the last Confidential Enquiry into Maternal Deaths (CEMD) in England and Wales. Maternal mortality more than doubles in women over 35 years compared to those younger than 30 (Figure 7). Thrombosis was identified as the largest direct cause of maternal death in the last CEMD. Age was again highlighted as a risk factor. The rate of pulmonary embolism doubled in the age groups over 35 years compared to those younger than 20 years. Hypertension was the second leading direct cause of maternal death in the 2000–2002 CEMD. As discussed above, the risk of hypertension is higher in older mothers. The recent report also emphasizes the importance of psychiatric causes of maternal death. Of 26 suicides (the leading cause of maternal death), almost half were in women over the age of 30 years. Five deaths due to amniotic fluid embolism were reported. Only one of the women was aged under 25 years.
Conclusion Recent decades have seen an increase in the trend of delaying childbearing. Better availability of contraception, education and career opportunities for women and the introduction of assisted conception allow increased choice on when to have children. However with this choice comes risk. Women should be informed of this risk before making their decisions. Recently published studies suggest that both maternal and fetal risk increase with increasing age. Early pregnancy complications, such as ectopic pregnancy and miscarriage, increase. Women in the older age groups have been shown in the majority (but not all) of studies to be at increased risk of hypertension, pre-eclampsia and diabetes. Maternal death occurs more frequently, although the actual numbers of deaths are small. Pregnancy complications such as hypertension may be up to six- fold higher but still have a low absolute incidence of 3%. However, a recent study by Luke et al showed that the majority of older women have low-risk pregnancies. For the 40–44year-old group the overall percentage of pregnancies that were low risk was 81.6% compared to 86.3% for 30–34 year olds. Reassuringly, the percentage of low-risk pregnancies for the over 45-year-old age group was 78.3% (p < 0.0001). In addition, there can be advantages to delaying childbearing: the older age groups are often better educated, financially more secure and, possibly, emotionally better prepared for pregnancy. At present there are no prospective studies. Potential benefits of delaying childbearing should be included in further studies to allow accurate comparison of risks and benefits of pregnancy in advanced maternal age. Despite the apparent risks of pregnancy,
Amniotic fluid embolism In the past 18 years amniotic fluid embolism has been responsible for 60 deaths in the UK, accounting for 8% of the total number of direct maternal deaths. A large retrospective study of amniotic fluid embolism in Canada found that maternal age over 35 years doubled the risk of amniotic fluid embolism (OR 1.9; CI 1.4–2.7). Another recent study reviewing the amniotic fluid embolism register in the
Rate per 100,000 maternities
40 35 30 25 20 15 10 5 0 <20
20–24
25–29
30–34
35–39
>40
Maternal age (years) Figure 7 Maternal mortality rate, direct and indirect deaths, by maternal age in United Kingdom 1985–2002. Reproduced with kind permission from CEMACH CEMD 2000–2002.
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labour and delivery associated with increasing maternal age, it is important to keep in perspective that the majority of women in this category have successful pregnancies and healthy children, and the risks are very small in absolute numbers. Good antenatal care, with appropriate and accurate information, can have a positive influence on the overall outcome. ◆
Reddy U, Ko CW, Willinger M. Maternal age and the risk of stillbirth throughout pregnancy in the United States. Am J Obstet Gynecol 2006; 195: 764–770. Salihu HM, Shumpert MN, Slay M, Kirky RS, Alexander G. Childbearing beyond maternal age 50 and fetal outcomes in the United States. Obstet Gynecol 2003; 102: 1006–1014. Schmid TE, Eskenazi B, Baumgartner A, et al. The effects of male age on sperm DNA damage in healthy non-smokers. Hum Reprod 2007; 22: 180–187. The ESHRE (European Society for Human Reproduction and Embryology) Workshop Group. Multiple gestation pregnancy. Hum Reprod 2000; 15: 1856–1864. Treacy A, Robson M, O’Hetlihy C. Dystocia increases with advancing maternal age. Am J Obstet Gynecol 2006; 195: 760–763. Tufnell DJ. United Kingdom amniotic fluid embolism register. BJOG 2005; 112: 1625–1629.
Further reading Blickstein I. Motherhood at or beyond the edge of reproductive age. Int J Fertil 2003; 48: 17–24. Callaway L, Lust K, Mcintyre HD. Pregnancy outcomes in women of very advanced maternal age. Aust N Z J Obstet Gynaecol 2005; 45: 12–16. Carolan M. Health literacy and the information needs and dilemmas of first time mothers over 35 years. J Clin Nurs 2007; 16: 1162–1172. Cleary-Goldman J, Malone F, Vidaver J, et al. Impact of maternal age on obstetric outcome. Obstet Gynecol 2005; 105: 983–990. Confidential Enquiry into Maternal Deaths in the United Kingdom, Why Mothers Die 2000–2002, 6th Report. London: Royal College of Obstetricians and Gynaecologists, 2004. de La Rochebrochard E, Thonneau P. Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study. Hum Reprod 2002; 17: 1649–1656. Duckitt K, Harrington D. Risk of pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ 2005; 330: 565. Jacobsson B, Ladfors L, Milsom I. Advanced maternal age and adverse perinatal outcome. Obstet Gynecol 2004; 104: 727–733. Joseph K, Allen A, Dodds L, Turner LA, Scott H, Liston R. The perinatal effects of delayed childbearing. Obstet Gynecol 2005; 105: 1410–1418. Kramer MS, Rouleau J, Baskett TF, Joseph KS. Maternal Health study group of the Canadian perinatal surveillance system. Amnioticfluid embolism and medical induction of labour: a retrospective population-based cohort study. Lancet 2006; 368: 1444–1448. Laufer N, Simon A, Samueloff A, Yaffe H, Milwidsky A, Gielchinsky Y. Successful spontaneous pregnancies in women older than 45 years. Fertil Steril 2004; 81: 1328–1332. Luke B, Borwm M. Elevated risks of pregnancy complications and adverse outcomes with increasing maternal age. Hum Reprod 2007; 22: 1264–1272. Maconochie N, Doyle P, Prior S, Simmons R. Risk factors for first trimester miscarriage- results from a UK-population-based casecontrol study. BJOG 2007; 114: 170–186. Mulvey S, Zachariah R, McIlwaine K, Wallace EM. Do women prefer to have tests for Down syndrome that have the lowest screen positive rate or the highest detection rate? Prenat Diagn 2003; 23: 828–832. Munk Olsen T, Munk Laursen T, Bocker Pedersen C, Mors O, Bo Mortensen P. New parents and mental disorders. A populationbased register study. JAMA 2006; 296: 2582–2589. National Sentinel Caesarean Section Audit. Section 5.3. London: RCOG Press, 2001. Nybo Anderson AM, Wohlfhart J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ 2000; 320: 1708–1712. Oakley L, Doyle P. Predicting the impact of in vitro fertilisation and other forms of assisted conception on perinatal and infant mortality In England and Wales: examining the role of multiplicity. BJOG 2006; 113: 738–741. Office of National Statistics. Population Trends. Winter 2003 No 114. www.statistics.gov.uk
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Practice points Pre-pregnancy counselling. Advanced maternal age is associated with: • Lower fertility rates, a higher risk of chromosomal abnormality, a higher risk of miscarriage (30%) and ectopic pregnancy • Ovum donation with assisted conception may be the most effective way to achieve a pregnancy in women over 40 years of age • Women should be advised about the risks of Down syndrome and other aneuploidies. They should be made aware of available screening techniques, their accuracy and effectiveness, as well as the inherent risks of definitive testing with amniocentesis or chorionic villus sampling • Aim to provide simple, clear, non-judgemental and appropriate levels of information, as for most women this approach is associated with the lowest levels of anxiety Antenatal care • Reassurance and psychological support • Pre-existing medical conditions must be taken into account when planning antenatal care, especially the risks of hypertension, diabetes and cardiovascular problems, which need a multidisciplinary approach to management Intrapartum and delivery • Carers should be aware of the increased frequency of severe complications that may threaten the health and life of the older obstetric patient
Research directions • Long term outcome for women delaying childbearing • Long term outcome for children born to older mothers • Social impact of delayed childbearing • Prospective studies comparing pregnancy outcome in cohorts of younger and older mothers • Is there an age-related deterioration in myometrial function? • Abnormal placentation: is it age related?
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© 2007 Elsevier Ltd. All rights reserved.
The older obstetric patient
flexibility and control over their reproductive lives. In addition, assisted reproduction techniques (ART) such as ovum donation have allowed women to increase their fertility. In the 21st century motherhood at or beyond the edge of reproductive age is increasingly common. Terms for the ‘older’ obstetric patient have included ‘mature’, ‘advanced’, ‘very advanced’ and ‘geriatric’. The International Federation of Obstetricians and Gynaecologists (FIGO) provided the earliest definition of the ‘older obstetric patient’ in 1958, specifying an age over 35 years for the ‘elderly primigravida’. ‘Advanced maternal age’ has been used as a MESH heading for Index Medicus since 1981, but improvements in women’s general health have led to this term tending to be reserved for pregnancies in women at or over 40 years of age.
Mehrnoosh Aref-Adib Theresa Freeman-Wang
Q2
Ifat Ataullah
Abstract The past few decades have seen a changing demographic phenomenon with many women electing to delay childbearing. With changes in societal norms, women have sought to achieve their educational and career aspirations before embarking on motherhood. Assisted reproduction techniques, including ovum donation, have increased the options for women choosing this delay. This article aims to review recent published studies to understand the risks associated with delaying childbearing – both maternal and fetal. The review includes papers published since the last update and looks at complications of early pregnancy, including ectopic pregnancy, miscarriage and chromosomal abnormality. It also reviews maternal morbidity, including complications of hypertensive diseases and diabetes. It aims to seek both advantages and disadvantages to delaying childbearing, so that both patient and obstetrician are fully informed. In previous reviews the authors have been positive with regards to the risks of delaying childbearing. However, the burden of evidence now suggests that pregnancy in this age group has higher risks – to both the mother and her fetus. This increased risks, however, must be weighed against the potential advantages of delaying childbearing – both financial and emotional, and must also be considered in the context of the small absolute numbers of complications. The majority of older mothers have low risk and uneventful pregnancies. With good antenatal and obstetric care it should be possible to achieve obstetric outcomes for many older mothers similar to those of younger mothers.
Birth trends and maternal age As in many other countries worldwide, one of the most dramatic changes in fertility in England and Wales in the last 30 years has been a shift towards women postponing childbearing until their late 20s and 30s. In England and Wales the mean age at first birth was 24.3 years in 1976, and 27.6 years in 2005. Forty or above is now an increasingly common age at which to begin a family. Women aged 35–39 had birth rates of 34.4 in 1000 in 1991, compared to 53.8 in 1000 in 2005. Women aged 35–39 accounted for 13% of total maternities in 2005, compared with only 6% in 1991 (Figure 1). The number of live births for women over 40 has almost doubled in the last decade from 12 103 in 1996 to 23 703 in 2006. In the USA there has been a similar trend. Between 1980 and 2004 the proportion of first births increased three-fold in women over 30 years (from 8.6 to 25.4%), six-fold in women over 35 years (from 1.3 to 8.3%) and 15-fold in women over 40 years (from 0.1 to 1.5%).
1980
Keywords maternal age; obstetric outcome; perinatal outcome 1985
Introduction
Year
1990
In recent decades there has been a dramatic change in women’s roles in many societies. Professional and educational goals have become increasingly important. The revolution in the availability of safe, effective contraception and the legalization of termination of pregnancy are important factors in giving women
1995
2002
2005
Mehrnoosh Aref-Adib BA MBBS is ST1 Obstetrics & Gynaecology, Whittington Hospital, Department of Women’s Health, Jenner Building, Magdala Avenue, London N19 5NF, UK.
0
Q1
20
30
40
Live births (%) <20
Theresa Freeman-Wang MRCOG is Consultant Gynaecologist, Whittington Hospital, Department of Women’s Health, Jenner Building, Magdala Avenue, London N19 5NF, UK.
20–24
25–29
30–34
35–39
40+
Figure 1 Proportion of babies born to mothers of varying age group, 1980–2005, showing trend of increased percentage born to mothers in older age groups and fewer in younger mothers. Data kindly provided by the Vital Statistics Office (ONS).
Ifat Ataullah MRCOG is Consultant Obstetrician, Kingston Hospital, Galsworthy Road, Kingston-upon-Thames, Surrey KT2 7QB, UK.
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10
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Problem-based learning in obstetrics
Miscarriage and ectopic pregnancy rates
7
The risk of miscarriage increases sharply as women reach their late 30s. Women aged 40 years have a 30% chance of miscarriage of a clinically recognized pregnancy (Figure 2). This rises to > 50% for women over 45 years old. A recent large population-based case-control study in the UK showed that there was no difference in the odds of miscarriage for women aged below 35, but a five-fold increase in risk over the age of 40, compared to controls aged 25–29.This is in part due to the effect of maternal age on the frequency of autosomal trisomies, but there is also an increase in euploid losses. Ectopic pregnancy rates also increase with age (Figure 3). Research from women undergoing assisted conception has shown there are increased tubular lesions with advancing maternal age. The incidence of ectopic pregnancy after ART is 4%, which is two to three times higher than the background incidence. It is plausible that the increased tubular dysfunction with age results from longer exposure to the risks of developing pelvic inflammatory disease or having experienced previously unrecognized subclinical infection.
Risk of ectopic pregnancy (%)
6
5
4
3
2
1
0 10
15
20
25
30
35
40
45
Maternal age at conception (years) Figure 3 Risk of ectopic pregnancy according to maternal age at conception. Reproduced by kind permission from Nybo Anderson. Maternal age and fetal loss: a population based register linkage study. BMJ 2000; 320: 1710.
Antenatal screening and counselling for older women It is well known that the risk for trisomies 21, 18 and 13 increases with advancing maternal age (Table 1). It is important to counsel women appropriately regarding their risks and prenatal diagnosis. Serum/ultrasound-based screening combined with maternal age has been demonstrated to be efficient and effective. The National Screening Committee produced a policy document in 2004 recommending: 1. The integrated test is the most effective 2. The integrated serum test if a nuchal translucency service is not available 3. The quadruple test for women who book later than the first trimester
4. The combined test for women who choose first trimester screening. The integrated test has the highest detection rate (85%) of chromosomal abnormalities for the lowest false-positive rate (0.9%) of all the tests. The detection rate is higher at 92% for women over 35 years old compared with 81% for women in the 15–34-year age group. As there is greater accuracy of non-invasive screening in the older age group and a risk of miscarriage associated with invasive testing (0.5–1% with amniocentesis), it is important that women are made aware of all the available screening techniques, so as to be able to make informed decisions.
100
Information for women
Risk of spontaneous abortion (%)
90
A recent study in Canada showed that many women are unaware of the potential consequences of delaying childbearing: 85% of women were aware of potential conception difficulties, 18.8%
1978–82 1983–87 1988–92
80 70 60
Estimated risk for trisomies in relation to maternal age at birth
50 40 30 20 10 0 10
15
20
25
30
35
40
45
50
Maternal age at conception (years) Figure 2 Risk of spontaneous abortion according to maternal age at conception. Reproduced by kind permission from Nybo Anderson. Maternal age and fetal loss: a population based register linkage study. BMJ 2000; 320: 1709.
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Age of mother
Risk of Down syndrome
Risk of trisomy 18
Risk of trisomy 13
20 30 35 40 42 44
1:1530 1:900 1:360 1:100 1:55 1:30
1:18 013 1:10 554 1:4202 1:1139 1:644 No recent data
1:42 423 1:24 856 1:9876 1:3544 1:1516 No recent data
years years years years years years
Data supplied by the Fetal Medicine Foundation.
Table 1
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Problem-based learning in obstetrics
were aware of the risks of caesarean section and 21% were aware of potential preterm delivery. The study concluded that missed opportunities in pre-conception counselling and education should be addressed to allow informed choice. Another study looking at the information needs of over 35-year-old mothers found that these women were at times ‘overwhelmed’ by ‘knowing too much’. Health professionals had given this group large amounts of health information, thinking this is what they required. The authors concluded that health professionals should understand the needs of the group and give information where appropriate.
2.87). However, two other studies have not shown an increased risk. Cleary-Goldman et al found the risk for 35–39 year olds and those over 40 years not to be increased when compared to those younger than 35 years of age (35–39 years: OR 0.9; CI 0.7–1.0. > 40 years: OR 1.1; CI 0.7–1.6). Jacobsson et al concluded from their study that paradoxically older age was protective against mild pre-eclampsia, but could not explain this. Women in the 40–44 age group were less likely than those in the 20–29 age group to develop mild pre-eclampsia (OR 0.58; CI 0.53–0.64) but more likely to develop severe pre-eclampsia (OR 1.4; CI 1.26–1.56).
Q3
Q4
Diabetes Gestational diabetes is more common in the older pregnant woman. The incidence of type 2 diabetes mellitus in 35–44-yearold women is more than double that in 25–35 year olds. Approximately 4% of pregnancies are complicated by diabetes. Both type 1 and type 2 diabetes mellitus are associated with increased risks of vascular complications, including pregnancy-induced hypertension, pre-eclampsia and post-partum haemorrhage. Due to concern about an increase in unexplained stillbirth in pregnancies complicated by diabetes, some advise early delivery at 38 weeks. Joseph et al found a nearly three-fold increased risk of preterm delivery in mothers with diabetes in the 35–39 year age group compared to those aged 20–24 (OR 2.85; CI 1.89–4.28). Jacobsson et al also found this increased risk when comparing 40–44 year olds with 20–29 year olds (OR 3.43; CI 3.04–3.86). This odds ratio increased with increasing age. Data from the FASTER trial also support this increased risk of preterm delivery, but to a lesser extent: 35–39 year olds (OR 1.8; CI 1.5–2.1); over 40s (OR 2.4; CI 1.9–3.1; p < 0.001). Again the absolute numbers in these studies were small. The incidence of gestational diabetes in the over 45s was 4.7% compared to 1% in the Swedish study by Jacobsson et al. The FASTER trial found an incidence of 7.3% in the over 40s compared to 2.9% in the under 35 age group.
Medical complications There is a general belief that women over the age of 35 years have an increased risk of complications during pregnancy. However, prospective population-based studies do not exist and available publications give conflicting views. The ages used to define the older obstetric patient vary. The pregnancy complications commonly addressed are hypertension, diabetes, cardiovascular disease, placental abnormalities, uterine abnormalities and multiple gestation. It is difficult to tease out the effect of confounding factors such as parity, pre-existing diabetes and/or hypertension. The studies that suggest the ‘older obstetric patient’ to be a ‘highrisk’ entity tend to be based on small numbers. Hypertension Actuarial data show that systolic and diastolic blood pressures increase with advancing age. The incidence of treated chronic hypertension is 3.4 in 1000 for women younger than 34 years old, but this rises to 21.3 in 1000 for those aged 35–44 years old. Several studies have shown a two- to six-fold increase in both chronic and pregnancy-induced hypertension in older women. Joseph et al evaluated the outcome of 157 445 deliveries in Canada between 1988 and 2002. They used 20–24 years as a reference band, and compared this age band with the higher age bands of 35–39 years and over 40 years. Women aged 35–39 were twice as likely to have hypertension (OR 2.32; CI 1.97–2.72) and women over 40 were three times more likely (OR 3.55; CI 2.63–4.80). Jacobsson et al studied 1 566 313 births in Sweden between 1987 and 2001. The risk of pregnancy-induced hypertension was three-fold higher in women aged 40–44 years compared to those aged 20–29 years (OR 3.29; CI 3.01–3.59), and women over 45 were six times more likely to develop hypertension (OR 6.38; CI 4.67–8.72). The overall incidence of hypertension, however, was low – 3.4% in the over 45 population, compared to 0.5% in the 20–29-year-old age group. Results reported by Cleary-Goldman et al from the FASTER (The First and Second Trimester Evaluation of Risk) trial looking at 36 056 singleton births in the USA conflict with the above findings. Women aged 35–39 were not found to have increased risks of gestational hypertension (OR 0.8; CI 0.7–1.0) and nor were those over 40 (OR 1.0; CI 0.8–1.4).
Labour and delivery Caesarean section rates (CSR) rise with increasing maternal age (Figure 4). The national CSR in the Royal College of Obstetricians and Gynaecologists (RCOG) Sentinel Audit 2001 was 21.3%. For mothers aged between 35 and 39 years, the CSR was 28% and it was 33% for those between 40 and 50 years old, compared to a CSR of only 13.4% for those younger than 20 years of age. This observed risk remained after adjustments for demographic and obstetric risk factors. Several studies have investigated obstetric interventions in relation to advancing maternal age. Treacy et al looked at 10 737 nullipara deliveries between 1998 and 2002: the need for oxytocin augmentation, incidence of prolonged labour, emergency CS and instrumental delivery indicated for dystocia all increased in a continuum with advancing maternal age. This supports the theory that there may be progressive myometrial dysfunction with age, leading to dysfunctional labour. The study did find, however, that oxytocin augmentation corrected most cases of dystocia in spontaneous first-time labours, irrespective of maternal age. Some women undergo elective induction or caesarean delivery because of real or perceived risks. Other hypotheses to explain this association include decreased pelvic compliance of the bony joints, reduced oxytocin receptors and reduced maternal effort
Pre-eclampsia Studies looking at pre-eclampsia also show conflicting results. Salihu et al evaluated the outcome of 12 066 854 deliveries in the USA between 1997 and 1999. The pre-eclampsia rate was 36.4 in 1000 for the 20–29 age group, but up to 85.3 in 1000 for the 40–49 age group. Duckitt et al found the risk of pre-eclampsia doubled for multiparous women aged 40 or over (OR = 1.96, CI = 1.34 to
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Problem-based learning in obstetrics
increase in preterm delivery from 9.3% in singleton births to 42.9% in twins (p < 0.001). The perinatal mortality rate is fourfold higher for multiple pregnancies compared to singleton.
Caesarean section rate (%)
35
30
Perinatal mortality and morbidity
25
There have been reports that antepartum haemorrhage, postpartum haemorrhage and abruption, as well as placenta praevia are associated with advanced maternal age. Possible reasons for this include increased caesarean section rate, fibroids and agerelated myometrial changes. The risk of placental abruption in the Cleary-Goldman study was double in women aged 40 and over compared to those aged 20–29 years (OR 2.3; CI 1.3–3.8; p < 0.02), but not significantly increased in 35–39 year olds (OR 1.3; CI 0.0–1.8; p 0.21). Again, the overall incidence was low – 1.6% in the over 40 year olds, compared to 0.7% in the 20–29 year olds. The Jacobsson et al study showed smaller increased odds for 35–39 year olds (OR 1.64; CI 1.24–2.16).
There are increased risks of preterm delivery, low birth weight, macrosomia, stillbirth and perinatal mortality (PNM) with advanced maternal age (Figures 5 and 6). Despite antenatal screening, the risk of aneuploidy and fetal anomalies is likely to contribute to the increased risk of stillbirth. In 2004 the PNM mortality rate in England and Wales was lowest for the 30–34 year age group at 4.93 in 1000 live and stillbirths, and highest for women over 45 years at 15.0. Both babies > 4000 g and babies < 2500 g are more common in older women. This is consistent with higher rates of diabetes, hypertensive disorders and maternal obesity. Some studies show that when other factors such as pre-eclampsia, maternal weight and smoking are taken into account there is no direct association between maternal age and fetal weight. Reddy et al looked at 5 458 735 singleton births on the US register between 2001 and 2002 and found that at 37–41 weeks’ gestation the risk of stillbirth for 35–39 year olds was 1 in 382 compared to 1 in 267 for women aged 40 or over. The relative risk of stillbirth for 35–39 year olds compared to a younger cohort was 1.32 (CI 1.22–1.43) and for over 40s was 1.88 (CI 1.64–2.16). The authors concluded that the most at-risk period was between 37 and 41 weeks’ gestation. An interesting study by Luke et al looked at infant deaths and compared the causes stratified by age group and parity. They found that older multiparas had a lower percentage of infant death from accident, homicide or neglect. For mothers aged over 45 year, the risk rate was 0.7% compared to 3.4% in 30–34 year olds. However, in older primiparas this figure was much higher – 6.7% of deaths were due to accident or homicide compared to 1.7% in the 30–34-year-old age group.
Multiple pregnancy
Maternal mortality
With the increase in ART the risk of older women having multiple pregnancy increases. For in vitro fertilization (IVF), between 35% and 50% of pregnancies are thought to be multiple. The maternal and fetal risks of multiple pregnancy make thorough counselling of women extremely important. An extensive literature describes links between multiple pregnancy and poor fetal outcome. With this in mind, since 2004 the Human Fertilization and Embryology Authority (HFEA) has limited the number of embryos transferred to two per cycle for women under 40 years and to three per cycle for those 40 years and over. A study by Oakley et al looking at ART and multiplicity concluded that 73 deaths in 2001 could have been avoided if the babies had been born as singletons. In 2002 the maternal mortality rate for multiple pregnancies was 20.2 in 100 000 compared to 13.0 for singleton pregnancies. In 2000 the European Society of Human Reproduction and Embryology (ESHRE) group reviewed the risks of multiple gestation. It concluded that maternal complications such as pre-eclampsia increased from 4.8% in singleton births to 8.3% in twins and to 11% in triplets (p < 0.001). Concerning fetal risks, twins are more likely to have intrauterine growth restriction and prematurity. The ESHRE group found an
Between 2000 and 2002 there were 242 recorded maternal deaths in the UK. The mortality rate for this triennium increased from
20
15
10 15
20
25
30
35
40
45
Maternal age (years) Figure 4 Caesarean section rate by maternal age. Reproduced by kind permission from the RCOG Sentinel Audit 2001.
with increasing maternal age. Equally, older women may be more assertive and articulate their own wishes for intervention.
Placental abnormalities
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Risk of stillbirth (%)
0.9 0.8 0.7 0.6 0.5 0.4 0.3 <19
20–24
25–29
30–34
35–39
40–44
>45
Maternal age at conception (years) Figure 5 Risk of stillbirth according to maternal age at conception. Reproduced by kind permission from Nybo Anderson. Maternal age and fetal loss: a population based register linkage study. BMJ 2000; 320: 1710.
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UK found that 2 of 13 maternal deaths due to and 6 of 31 survivors of amniotic fluid embolism were aged over 35 years, suggesting age was not necessarily a risk factor in this group.
Rate per 1,000 live births
15
Stillbirth rate
10
Neonatal death rate
Psychiatric mortality/morbidity A recent study looking at psychiatric admissions post delivery found that the age-specific incidence of overall risk of hospital admission for parents decreased with increasing age.
5
Psychological aspects of pregnancy
0
<20
20–24
25–29
30–34
35–39
40–44
>45
Women in their 30s and 40s may have a healthier lifestyle and look after themselves better in terms of nutrition and exercise. Mature women may have a more positive perception of their bodies and more readily tolerate the symptoms of pregnancy. The older mother may be in a better financial position to offer her child greater material and educational advantages. Women pursuing a career may be more satisfied to have achieved their goals before embarking on motherhood. There is evidence that older mothers are more likely to breast feed. In some studies that have controlled for social factors and parity, children of older mothers do better at school than those of very young parents. One study of women delivering in Canada between 1988 and 2002 looked at maternal characteristics by age. Older women were more likely to have a high income (26% of 35–39 year olds compared to 2.5% of 20–24 year olds), were more likely to be married (83.2% of 35–39 year olds compared to 43.6% of 20–24 year olds) and were less likely to smoke (18.4% of 35–39 year olds compared to 39.2% of 20–24 year olds).
Maternal age (years) Figure 6 Maternal age-specific stillbirth and neonatal mortality rates in England, Wales and Northern Ireland, 2005. Derived from ONS data.
11.4 in 100 000 to 13.1 in 100 000. Increased maternal age was cited as an independent risk factor in the key findings of the last Confidential Enquiry into Maternal Deaths (CEMD) in England and Wales. Maternal mortality more than doubles in women over 35 years compared to those younger than 30 (Figure 7). Thrombosis was identified as the largest direct cause of maternal death in the last CEMD. Age was again highlighted as a risk factor. The rate of pulmonary embolism doubled in the age groups over 35 years compared to those younger than 20 years. Hypertension was the second leading direct cause of maternal death in the 2000–2002 CEMD. As discussed above, the risk of hypertension is higher in older mothers. The recent report also emphasizes the importance of psychiatric causes of maternal death. Of 26 suicides (the leading cause of maternal death), almost half were in women over the age of 30 years. Five deaths due to amniotic fluid embolism were reported. Only one of the women was aged under 25 years.
Conclusion Recent decades have seen an increase in the trend of delaying childbearing. Better availability of contraception, education and career opportunities for women and the introduction of assisted conception allow increased choice on when to have children. However with this choice comes risk. Women should be informed of this risk before making their decisions. Recently published studies suggest that both maternal and fetal risk increase with increasing age. Early pregnancy complications, such as ectopic pregnancy and miscarriage, increase. Women in the older age groups have been shown in the majority (but not all) of studies to be at increased risk of hypertension, pre-eclampsia and diabetes. Maternal death occurs more frequently, although the actual numbers of deaths are small. Pregnancy complications such as hypertension may be up to six- fold higher but still have a low absolute incidence of 3%. However, a recent study by Luke et al showed that the majority of older women have low-risk pregnancies. For the 40–44year-old group the overall percentage of pregnancies that were low risk was 81.6% compared to 86.3% for 30–34 year olds. Reassuringly, the percentage of low-risk pregnancies for the over 45-year-old age group was 78.3% (p < 0.0001). In addition, there can be advantages to delaying childbearing: the older age groups are often better educated, financially more secure and, possibly, emotionally better prepared for pregnancy. At present there are no prospective studies. Potential benefits of delaying childbearing should be included in further studies to allow accurate comparison of risks and benefits of pregnancy in advanced maternal age. Despite the apparent risks of pregnancy,
Amniotic fluid embolism In the past 18 years amniotic fluid embolism has been responsible for 60 deaths in the UK, accounting for 8% of the total number of direct maternal deaths. A large retrospective study of amniotic fluid embolism in Canada found that maternal age over 35 years doubled the risk of amniotic fluid embolism (OR 1.9; CI 1.4–2.7). Another recent study reviewing the amniotic fluid embolism register in the
Rate per 100,000 maternities
40 35 30 25 20 15 10 5 0 <20
20–24
25–29
30–34
35–39
>40
Maternal age (years) Figure 7 Maternal mortality rate, direct and indirect deaths, by maternal age in United Kingdom 1985–2002. Reproduced with kind permission from CEMACH CEMD 2000–2002.
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labour and delivery associated with increasing maternal age, it is important to keep in perspective that the majority of women in this category have successful pregnancies and healthy children, and the risks are very small in absolute numbers. Good antenatal care, with appropriate and accurate information, can have a positive influence on the overall outcome. ◆
Reddy U, Ko CW, Willinger M. Maternal age and the risk of stillbirth throughout pregnancy in the United States. Am J Obstet Gynecol 2006; 195: 764–770. Salihu HM, Shumpert MN, Slay M, Kirky RS, Alexander G. Childbearing beyond maternal age 50 and fetal outcomes in the United States. Obstet Gynecol 2003; 102: 1006–1014. Schmid TE, Eskenazi B, Baumgartner A, et al. The effects of male age on sperm DNA damage in healthy non-smokers. Hum Reprod 2007; 22: 180–187. The ESHRE (European Society for Human Reproduction and Embryology) Workshop Group. Multiple gestation pregnancy. Hum Reprod 2000; 15: 1856–1864. Treacy A, Robson M, O’Hetlihy C. Dystocia increases with advancing maternal age. Am J Obstet Gynecol 2006; 195: 760–763. Tufnell DJ. United Kingdom amniotic fluid embolism register. BJOG 2005; 112: 1625–1629.
Further reading Blickstein I. Motherhood at or beyond the edge of reproductive age. Int J Fertil 2003; 48: 17–24. Callaway L, Lust K, Mcintyre HD. Pregnancy outcomes in women of very advanced maternal age. Aust N Z J Obstet Gynaecol 2005; 45: 12–16. Carolan M. Health literacy and the information needs and dilemmas of first time mothers over 35 years. J Clin Nurs 2007; 16: 1162–1172. Cleary-Goldman J, Malone F, Vidaver J, et al. Impact of maternal age on obstetric outcome. Obstet Gynecol 2005; 105: 983–990. Confidential Enquiry into Maternal Deaths in the United Kingdom, Why Mothers Die 2000–2002, 6th Report. London: Royal College of Obstetricians and Gynaecologists, 2004. de La Rochebrochard E, Thonneau P. Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study. Hum Reprod 2002; 17: 1649–1656. Duckitt K, Harrington D. Risk of pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ 2005; 330: 565. Jacobsson B, Ladfors L, Milsom I. Advanced maternal age and adverse perinatal outcome. Obstet Gynecol 2004; 104: 727–733. Joseph K, Allen A, Dodds L, Turner LA, Scott H, Liston R. The perinatal effects of delayed childbearing. Obstet Gynecol 2005; 105: 1410–1418. Kramer MS, Rouleau J, Baskett TF, Joseph KS. Maternal Health study group of the Canadian perinatal surveillance system. Amnioticfluid embolism and medical induction of labour: a retrospective population-based cohort study. Lancet 2006; 368: 1444–1448. Laufer N, Simon A, Samueloff A, Yaffe H, Milwidsky A, Gielchinsky Y. Successful spontaneous pregnancies in women older than 45 years. Fertil Steril 2004; 81: 1328–1332. Luke B, Borwm M. Elevated risks of pregnancy complications and adverse outcomes with increasing maternal age. Hum Reprod 2007; 22: 1264–1272. Maconochie N, Doyle P, Prior S, Simmons R. Risk factors for first trimester miscarriage- results from a UK-population-based casecontrol study. BJOG 2007; 114: 170–186. Mulvey S, Zachariah R, McIlwaine K, Wallace EM. Do women prefer to have tests for Down syndrome that have the lowest screen positive rate or the highest detection rate? Prenat Diagn 2003; 23: 828–832. Munk Olsen T, Munk Laursen T, Bocker Pedersen C, Mors O, Bo Mortensen P. New parents and mental disorders. A populationbased register study. JAMA 2006; 296: 2582–2589. National Sentinel Caesarean Section Audit. Section 5.3. London: RCOG Press, 2001. Nybo Anderson AM, Wohlfhart J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ 2000; 320: 1708–1712. Oakley L, Doyle P. Predicting the impact of in vitro fertilisation and other forms of assisted conception on perinatal and infant mortality In England and Wales: examining the role of multiplicity. BJOG 2006; 113: 738–741. Office of National Statistics. Population Trends. Winter 2003 No 114. www.statistics.gov.uk
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Practice points Pre-pregnancy counselling. Advanced maternal age is associated with: • Lower fertility rates, a higher risk of chromosomal abnormality, a higher risk of miscarriage (30%) and ectopic pregnancy • Ovum donation with assisted conception may be the most effective way to achieve a pregnancy in women over 40 years of age • Women should be advised about the risks of Down syndrome and other aneuploidies. They should be made aware of available screening techniques, their accuracy and effectiveness, as well as the inherent risks of definitive testing with amniocentesis or chorionic villus sampling • Aim to provide simple, clear, non-judgemental and appropriate levels of information, as for most women this approach is associated with the lowest levels of anxiety Antenatal care • Reassurance and psychological support • Pre-existing medical conditions must be taken into account when planning antenatal care, especially the risks of hypertension, diabetes and cardiovascular problems, which need a multidisciplinary approach to management Intrapartum and delivery • Carers should be aware of the increased frequency of severe complications that may threaten the health and life of the older obstetric patient
Research directions • Long term outcome for women delaying childbearing • Long term outcome for children born to older mothers • Social impact of delayed childbearing • Prospective studies comparing pregnancy outcome in cohorts of younger and older mothers • Is there an age-related deterioration in myometrial function? • Abnormal placentation: is it age related?
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