The reproductive performance of women at 40 years and over

Results The mean age of the study and control groups were 41.46 ± 1.38 (range 40–47) and 27.40 ± 1.67 (range 25–30) years, respectively. The mean parity of the study group, 4.24 ± 2.35 was statistically higher than for the control group, 1.69 ± 1.39, P < 0.0001. The past history of previous preterm delivery (10.1% versus 4.4%) and previous caesarean section (24.4% versus 11.9%) were more significant in the study group, P = 0.0562 and 0.0053, respectively. Women of 40 years and over presented significantly more medical complications. The incidence of caesarean section in the study group was significantly higher (31.0% versus 16.3%), P = 0.0027, OR 2.310, CI 1.356–3.935. The overall maternal and perinatal outcomes in both groups were comparable and satisfactory. Conclusion Advanced maternal age of 40 years and over was not associated with adverse maternal and perinatal outcome, although the incidence of caesarean section was significantly increased in these women. Keywords Advanced maternal age Obstetric outcome 1 Introduction Adverse pregnancy outcome has been observed in women of advanced maternal age, although some controversy still exists from published reports [1–4] . There has been a linkage between the risk of fetal death including spontaneous abortions and increasing maternal age [5–8] . According to one recent report [9] , half of pregnancies at age 42 years planned to be carried to term ended in fetal death, while the risk of spontaneous abortions in women aged 45 years or more was 74.7%. An increased incidence of caesarean operations has been reported in women aged 35 years and over [1,10–15] , and increased operative vaginal deliveries has also been observed [1] . Women carrying pregnancies at age 35 years and beyond were traditionally described as “elderly gravidas”, although trends in published studies have advanced this age to 40 years. However, due to the many advances in Assisted Reproductive Technology enabling patients to achieve pregnancies at the perimenopausal ages and beyond [16] , the “age” of “elderly gravidas” may now appear to be further advanced. An increasing number of women are delaying child birth till the fourth and fifth decade for a variety of reasons, including the pursuit of higher educational goals and delayed marriages. In Kuwait, we have a population of professional women who have inadvertently delayed marriage (because of pursuit of higher educational goals), and consequently child birth to the later years. The urge to have larger families, which is prevalent in Kuwait and in the Middle East, also implies that some of our patients in Kuwait voluntarily continue childbearing up to and beyond 40 years. The objective of our study was to evaluate the reproductive performance of our women at age 40 years and beyond, and to assess if they were at increased risk. 2 Materials and methods A retrospective study of all the women aged 40 years and over who delivered singleton pregnancies at Maternity Hospital, Kuwait, between 1 January 2000 and 30 June 2002, was undertaken. A total of 168 women were thus identified and they formed the study group. Another group of 160 women aged 25–30 years, who delivered during the same period, formed our control group. Each of the 160 control patients was selected on the basis of choosing the first woman aged 25–30 years, whose delivery occurred immediately after the delivery of our study patient of 40 years and over. The ages of women were the ages at the time of delivery. Multiple pregnancies with their confounding effects were excluded from our study population, as such pregnancies could have increased adverse outcome. The medical records of the patients were reviewed to obtain details of social history, history of prior medical, surgical and gynaecological disorders, prior obstetric outcomes, and antepartum, intrapartum and postpartum events pertinent to the index pregnancy. A previous medical, surgical or gynaecological disorder usually referred to the existence of diabetes mellitus, chronic hypertension, cardiac diseases, asthma/respiratory disorders, renal diseases, thyroid and other endocrine disorders, anaemias and haemoglobinopathies, uterine malformations, primary/secondary infertility, uterine leiomyomata with or without operations, gastrointestinal disorders or previous surgeries, before the current pregnancy. We also tried to identify such antenatal complications as gestational diabetes, pregnancy-induced hypertension, antepartum haemorrhage (placenta praevia, abruptio placentae, unclassified bleeding disorders, etc), preterm labour and premature rupture of membranes which were present in the index pregnancy. Intrapartum complications, including fetal distress, abnormal labour, chorio amnionitis and postpartum complications, such as postpartum haemorrhage and puerperal disorders, such as genital sepsis and deep vein thrombosis/pulmonary embolism were all looked for in the records. The fetal outcome was carefully followed by searching through the records in the labour ward and in the neonatal unit. The policy of the department as regards vaginal delivery after caesarean section (VBAC) is to allow patients who have had one previous caesarean section for a non-recurrent cause a vaginal delivery in the next pregnancy with the prerequisites that the pelvis should be adjudged adequate for the current fetus, and labour should be carefully and intensively monitored. Such a pregnancy should not have any major obstetric indications requiring repeat caesarean section. This policy was adopted for all the patients in the study and control groups. 2.1 Statistical analysis The results were presented as frequencies. Various events in the study and control groups were compared using the Chi-square test and the Fisher exact two-tailed test. The odds ratio (OR) and the confidence interval (CI) at 95% were calculated. The Welch t -test was also used for non-parametric data. All the analysis were performed using the SPSS 10 package of Windows 2000. For all the analyses, a P ≤ 0.05 was considered as significant. 3 Results The clinical characteristics of the study population are demonstrated in Table 1 . The mean age of the patients in the study and control groups were 41.46 ± 1.38 (range 40–47) years and 27.40 ± 1.67 (range 25–30) years, respectively. The mean parity of the study group, 4.24 ± 2.35, was significantly higher than the mean parity of the control group, 1.69 ± 1.39, P < 0.0001. There were only four primigravidae (2.5%) in the study group compared with 33 (20.6%) in the control group; these numbers as they relate to the study group, were too small for comparative studies with the control group in any meaningful way, and so the bulk of our entire study population is based on multiparous women. It is noteworthy to state that there were significantly more primigravida in the control group compared with the study group (20.6% versus 2.5%, P < 0.0001, odds ratio 0.939, CI 0.032–0.2719. There were, however, no significant abnormalities in the primigravida (study and control groups), apart from the fact that one of the primigravidae in the age group 40 years and over, was delivered by caesarean section. There were significantly more Kuwaitis in the study group (61.9%) than in the control group (45.0%), P = 0.0031, odds ratio 1.986, CI 1.278–3.085. The non-Kuwaitis consisted of Arabs of various nationalities (Egyptians, Syrians, Lebanese, etc.), Indians, Filipinos, Pakistanis, Bangladeshis and Africans. The ethnic distribution of the patients in the study and control groups were similar to the trend in the hospital; however, it is pertinent to state that Kuwaitis and Arabs tended to have more children, and thus were of higher parity. More patients in the study group had previous spontaneous miscarriages (overall 39.3%, first trimester 35.7%) as compared with the controls (overall 15.0%, first trimester 14.4%), this difference was statistically significant ( P < 0.0001). The past history of previous preterm delivery (10.1% versus 4.4%) and previous caesarean section (24.4% versus 11.9%) were significantly more prevalent in the study group, P < 0.0562 and 0.0053, respectively. As expected, the women who were of 40 years and over (the older women) had reported significantly more past medical disorders 19.1% versus 2.5%, P < 0.0001, odds ratio 9.176, CI 3.164–26.615; these disorders included diabetes mellitus, essential hypertension, cardiac disease, iron deficiency anaemia and haemoglobinopathy. Whereas 98.1% of all the pregnancies in the control group were spontaneous, 91.7% of the pregnancies in the study group were spontaneous, P = 0.011 odds ratio 0.210, CI 0.059–0.746. Four percent of pregnancies in the older women had their pregnancies initiated by assisted reproductive technological methods. There was a significantly higher overall incidence of antenatal complications in the study group as compared with the control group, 57.1% versus 12.5%, P < 0.0001, odds ratio 9.333, CI 5.334–16.331 ( Table 2 ). The medical disorders of diabetes mellitus (pregestational insulin-dependent and non-insulin-dependent diabetes and gestational diabetes) and essential hypertension were significantly more prevalent in the older women, 40 years and more, compared with the control group: 17.3% versus 6.3%, P = 0.00021, OR 3.129, CI 1.471–6.659 and 6.5% versus 0.0, P = 0.0008, OR 23.438, CI 1.369–401.42, respectively. Pregnancy-induced hypertension (PIH) was also more prevalent in the study group (18.5% versus 3.8%, P < 0.0001, OR 5.808 and CI 2.351–14.345, and although 3.6% of the patients in study group presented with premature rupture of membranes, no such complication was observed in the control group P = 0.030. We were rather surprised to record only two cases of intrapartum haemorrhage, both of which were due to placenta praevia. The incidence for induction of labour in the study group was 24.4%, and this was significantly higher than the figure of 11.9% recorded for the control group, P = 0.005, OR 2.396, CI 1.322–4.342. The incidence for induction for the study group is higher than the overall rate of 16.4% for the department. The indications for induction were mainly pregnancy-induced hypertension (8.9% versus 1.9%), diabetes mellitus (4.8% versus 2.5%) in the study and control groups, and postdates (5.6% versus 3.0%) in the control group compared with the study group. Other indications for induction of labour in the study group were premature rupture of membranes, intrauterine fetal death (IUFD), intrauterine fetal growth restriction/intrauterine growth retardation, essential hypertension, diminished fetal movements, antepartum haemorrhage and non-reactive non-stress test (NST). The obstetric outcome of the patients is laid out in Table 3 . The incidence of caesarean section was significantly higher in the women 40 years and over compared with the control group, 31.0% versus 16.3%, P = 0.0027, (OR 2.310, 95% CI 1.356–3.395); although the incidence of operative vaginal delivery (ventouse and forceps) was higher in the study group, the difference was not statistically significant. The gestational age at delivery, 38.06 ± 2.456 weeks for the older women, was significantly lower than the figure of 39.31 ± 1.605 weeks for the control group, P = 0.0001 by Welch's t -test. The overall perinatal outcomes of the study and control groups were comparable and quite satisfactory. It is however pertinent to point out the following differences observed in the results. The mean birth weight of the babies in both groups were not significantly different; there was however a significant difference in the ratio of babies who were 2500 g or less at birth in the study and control groups: 10.7% versus 3.8%, P = 0.0189, OR 3.080, CI 1.190–7.973. The risk factors associated with low birth weight are usually more prevalent in older women and this must have accounted for the significant difference reported. The aetiological factors associated with low birth weight of <2500 g in the study group were: IUGR, three cases (1.8%); PIH, four cases (2.4%); PROM, four cases (2.4%); fetal anomaly, four cases (2.4%); and diabetes mellitus with IUGR, two cases (1.2%), whereas in the control group, the factors were mainly PIH and diabetes mellitus. Induction of labour was performed to deliver these babies. Thirty percent of these low birth weight babies were admitted to the NICU and they all made satisfactory progress. More than 90% of all the babies in both groups had Apgar scores of 7 or more. Although virtually, all the babies (99.4%) of the control group had Apgar scores of 7 or more, quite a corresponding high proportion, 91.1% of the babies in the study group had Apgar scores of 7 or more: these figures which are apparently comparable are however significantly different P = 0.0004, OR 0.0641, CI 0.0083–0.4918. A small percentage of babies in the study group had low Apgar scores. These babies had features of fetal anomaly, IUGR and PIH, which contributed to these low Apgar scores. The babies responded to resuscitation and survived all through the perinatal period. They remained under the care of the neonatologist for varying periods and they were eventually discharged from hospital. We cannot comment on the long-term effects of the low Apgar scores on the babies, since such information was not available to us. There were two fetal deaths in the study group which were due to multiple congenital anomalies incompatible with life. There was no significant difference in the incidence of congenital anomalies in the study and control groups. The congenital fetal anomalies recorded were: congenital heart disease, hydrocephalus and cleft palate. Apart from two cases of severe preeclampsia in the puerperium in the women 40 years and over, the overall puerperium was essentially uneventful in the study and control groups. No significant adverse intrapartum or postpartum maternal morbidity was observed, and no maternal mortality was reported. 4 Comment In our study, the babies of the women 40 years and over had a rather less satisfactory immediate neonatal performance than those of the younger women, especially when the ratio of higher Apgar scores are scrutinised and when the fetal deaths (due to congenital fetal anomalies incompatible with life) and the low Apgar scores in the study group are also considered. However, the mean birth weights of the babies in the study and control groups were similar inspite of the fact that the maternal age of 40 and over was more significantly associated with low birth weight of <2500 g because these mothers had greater risk factors predisposing them to low birth weight as previously stated. The incidences of congenital fetal anomaly were similar in both groups. A small percentage of the babies in the study group had low Apgar scores, although a much smaller percentage of the control group also had low Apgar scores. Over 90% of all the babies in both groups had high Apgar scores of 7 and above; it should of course be noted that a significantly higher percentage of babies in the control group compared with the study group (99.4% versus 91.1%, P = 0.0004) had higher Apgar scores of 7 and above. It does appear therefore that advanced maternal age of 40 and over was not associated with significant adverse neonatal outcome. This finding is supported by many previous reports [17–20] , although some other reports [4,21] have reported contrary findings. Many of these reports have included both nulliparous and multiparous women in their studies and have discussed the probability of parity having some impact on fetal outcome, with nulliparity contributing to adverse fetal outcome and multiparity having no significant impact. As previously stated, most of our study and control patients were multiparous patients with mean parity (4.24 ± 2.35 and 1.69 ± 1.39), (a generally accepted favourable parity range in terms of significant impact on fetal outcome), and so we should not really expect much adverse fetal outcome in our study. This information may be a plausible explanation for the positive findings reported above; however, another study [1] has also reported that advanced maternal age did not adversely affect neonatal outcome, regardless of parity, thus supporting our findings as reported. The incidence of previous miscarriages was higher in the women 40 years and over than in the younger controls. There were also more congenital fetal anomalies in the older women, although the difference was not significant. Advanced maternal age has been associated with increased risk of spontaneous miscarriages and fetal anomalies [1,5–8,16] . A higher incidence of medical complications, including diabetes mellitus and hypertension, was reported in our women 40 years and over compared with the younger controls. This finding is in keeping with findings in many other reports [1,4,16,18,22] . Various reasons have been adduced to explain these findings, including increasing obesity with ageing, underlying vascular endothelial changes and damage with ageing. Diabetes mellitus and obesity are frequently encountered in our population in Kuwait and these may have played an additional role in our study population. It was difficult to assess the exact role of obesity in our patient population, as such data were not readily available in all the case records we evaluated. This is one of the unfortunate difficulties encountered in retrospective studies. The incidence of caesarean section was significantly higher in the women 40 years and over than in the younger controls: an observation that has been previously reported in many other studies [1,3,4,10–15,17,20–22] . A higher (though not significantly higher) incidence of operative vaginal deliveries was also reported in this study. Various reasons, such as medical disorders, obstetric complications and fetal indications, have been adduced to explain this higher incidence of caesarean section in women of advanced maternal age, all of which were applicable in the current study. The deterioration of myometrial function with age as proposed [23] is another factor accounting for some disorders of labour contributing to the increased caesarean sections reported in this and other studies. It is a well-documented obstetric practice that obstetricians may have a lowered threshold for caesarean section in women of advanced age (since these women who are approaching the end of their reproductive career may have no further pregnancies), such as our women of 40 years and over in this study, because these pregnancies are considered as “premium” pregnancies. Some of these “premium” pregnancies have been achieved after intervention with assisted reproductive technology techniques and need every attention to ensure safe deliveries. The fact that obstetricians have a lower threshold for operative intervention (caesarean section included) in older women has been emphasised in many previous reports [1,20,21,23] . This ready resort to caesarean section is in keeping with previous reports, and the practice was most probably an additional factor in the increased incidence of caesarean section in our study population. Many previous studies on the obstetric performance of women of advanced age have included a good proportion of nulliparous patients in their studies. Many of such women may have delayed child-birth electively for a variety of reasons as has been cited previously in this paper. Whereas these reasons also applied to some of our patients, a majority of our study population were multiparous women continuing their prolonged reproductive roles in the society, and contributing to the desired larger family sizes and to the overall population of Kuwait and other Arab nations. The significantly higher incidence for the induction of labour reported in the women 40 years and over in our study has also been observed in previous reports [21] . The medical complications which were more prevalent in the study population contributed to the higher incidence for induction for women 40 years and over. A rather striking unexpected finding in this study was the rather significantly low incidence of antepartum haemorrhage (placenta praevia, abruptio placentae and incidental haemorrhage) and the total absence of postpartum haemorrhage in the entire study (only two cases of antepartum haemorrhage [placenta praevia] in this study). Ageing of the mother, repeated pregnancies and high parity have all being associated with placenta praevia, factors that were present in our study population. We have not been able to advance reasons for this unexpected finding in our study; antepartum haemorrhage and postpartum haemorrhage are certainly encountered in our hospital and the incidence follows the trend generally reported in the literature. The overall maternal and perinatal outcome reported in our women 40 years and over are satisfactory, and as previously stated, have also been observed in previous studies. We believe that a number of factors help explain the above findings. These include the fact that we have well-equipped medical facilities, high-quality obstetric personnel and a policy of early intervention, low incidence of antenatal, intrapartum and postpartum complications in the study population, and generally a healthy patient population who tend to be of higher socio-economic status. Advanced maternal age of 40 years and over was associated with a significantly higher incidence of antenatal complications (diabetes mellitus, essential hypertension and pregnancy-induced hypertension) which contributed to the increased incidence of induction of labour observed. A significantly increased incidence of caesarean section was also reported in these women of 40 years and over, although the overall maternal and perinatal outcome were not adversely affected. References [1] A. Bianco J. Stone L. Lynch R. Lapinski G. Berkowitz R.L. Berkowitz Pregnancy outcome at age 40 and older Obstet Gynecol 87 1996 917 922 [2] S. Cnattingius M.R. Forman H.W. Berendes L. 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