1 Section of Endocrinology and Metabolic Medicine (The Mint Wing), ICSM at St Mary's, 2 Department of Pathology, St Mary's Hospital, Paddington, London, W2 1NY, 3 Department of Epidemiology, ICSM at St Mary's, Paddington, London, W2 1PG, and 4 4Department of Reproductive Science and Medicine, ICSM at St Mary's, Paddington, London, W2 1NY, UK
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Abstract |
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Key words: age/obstetric/outcome/pregnancy/risk
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Introduction |
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To clarify these issues we have reviewed a large number of consecutive singleton pregnancies using a validated database (Cleary et al., 1994a,b
). We aimed to test the hypothesis that older maternal age is associated with increased risk of adverse outcomes for mother and baby and to quantify this risk after allowing for confounding factors.
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Materials and methods |
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The subjects were divided into groups according to maternal age at delivery: 1834; 3540; and >40 years old. Women aged <18 years old were excluded from the analysis. The raw frequencies of the various outcomes of pregnancy in the maternal age groups were calculated and multiple logistic regression models were then constructed to examine the magnitude and significance of the independent effect of age. All models included maternal age, body mass index, ethnic group, parity, history of hypertension and history of diabetes mellitus. Other confounding factors of specific relevance to a particular outcome were included as appropriate. The results are presented as frequencies by age group and odds ratios (OR) with 99% confidence intervals (CI). Birthweight was expressed as a delta value (the number of SD by which the observed birthweight differed from the expected normal mean for males and females for each week of gestation) in order to account for the influence of gestational age and sex on birthweight. All analyses were carried with Statistical Analysis Software version 6.12 (SAS Institute Inc, Rayleigh, NC, USA) using a UNIX server, SUN SPARC STATION 20 running SOLARIS 2.6 operating system (Sun Microsystems Inc, Palo Alto, CA, USA).
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Results |
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Induction of labour was more common in older women who were also more likely to be delivered by Caesarean section or have an operative vaginal delivery. Despite the higher proportion of older women having a fetus with a breech presentation, fewer had a vaginal breech delivery. A greater proportion of older women had a postpartum haemorrhage of >1000 ml. The risk for preterm delivery and stillbirth was significantly greater in the older women. The incidences of small for gestational age and large for gestational age babies were higher in the older women. More of the women aged 35 years breast-fed their babies.
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Discussion |
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The greatest differences between older women and controls were identified in the mode of delivery. One possible explanation is that obstetricians may have a lower threshold for intervention in older women. An alternative explanation is that myometrial function deteriorates with age (Rosenthal and Paterson Brown, 1998). This mechanism may also be relevant to the increased age-related risk of breech presentation and postpartum haemorrhage, as uterine atony is the most common cause of postpartum haemorrhage.
There was a wider distribution of birthweight in the older women. The increased likelihood of older women delivering a small for gestational age baby may be related to poorer placental perfusion or transplacental flux of nutrients (Godfrey et al., 1999). The increased likelihood of an older woman delivering a large for gestational age baby is unlikely to be due to a genetic effect and implies differences in the fetal environment in older pregnant women compared with younger pregnant women. These differences may be due to age-related changes in maternal metabolism. Fetal macrosomia is more common in the obese non-diabetic mother, compared with lean mothers with gestational diabetes (Maresh et al., 1989
). Although non-diabetic obese women are glucose tolerant by definition, their increased insulin resistance may cause other perturbations in metabolism increasing nutrient availability to the fetus. The expanded Pedersen hypothesis describes how an increased flux of nutrients across the placenta could cause fetal hyperinsulinaemia and accelerated fetal growth (Pedersen, 1977
; Freinkel and Metzger, 1978
). Insulin-resistant individuals have higher fasting plasma triglyceride concentrations (Robinson et al., 1993
), and greater leucine turnover (Robinson et al., 1992
). Amino acids stimulate secretion of insulin and so an increased flux of amino acids to the fetus would stimulate fetal hyperinsulinaemia. Triglycerides are energy rich and placental lipases can cleave triglycerides and transfer free fatty acids to the fetal circulation providing increased energy delivery to the fetus (Thomas, 1987
).
Older women were more likely to deliver preterm and more likely to deliver at <32 weeks gestation when there is a greater risk of perinatal morbidity and mortality. Urinary tract infection is associated with preterm labour (Heffner et al., 1993) and occurred more frequently in the women aged >40 years. There was no evidence of increased genital tract infection in the older women to account for the increased risk of preterm delivery.
The risk of stillbirth was significantly higher in the older women. The risks of aneuploidy and fatal congenital anomalies increase with maternal age and, despite antenatal screening, they are likely to have contributed to the increased rate of stillbirth. A past history of infertility is not recorded on SMMIS but it is likely that a higher proportion of women with previous infertility will have accumulated in the older cohorts. There is a four-fold increase in the risk of fetal death in women with previous infertility (Whitley et al., 1999). Impaired placental function has already been discussed as a possible cause for the increased incidence of small for gestational age babies in the older women and may have also contributed to the increased rate of stillbirth. There has been speculation that there are long-term effects on the offspring of delayed parenthood due to a number of mechanisms including the exposure of gametes to increased oxidative stress (Tarín et al., 1998
) and these could also be relevant to the increased risk of stillbirth.
Older women were significantly more likely to breast-feed than younger women and this may reflect more positive attitudes to breast-feeding in older women. This may be an example of one of the advantages of delayed childbirth. Older women are also likely to have greater financial resources, social stability, and age-related attributes such as emotional maturity, wisdom and experience of life (Fonteyn and Isada, 1988).
In conclusion, the results of this study showed that pregnant women aged 35 years are at increased risk of complications in pregnancy compared with younger women.
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Acknowledgments |
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Notes |
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6 To whom correspondence should be addressed at: Department of Reproductive Science and Medicine, ICSM at St Mary's, Paddington, London W2 1NY, UK. E-mail: l.regan{at}ic.ac.uk
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References |
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Submitted on May 11, 2000; accepted on July 10, 2000.