Document Type : Original Research Article
Authors
- Soheila Dabiran 1
- Shahla Khosravi 1
- Leila Pourali 2
- Sedigheh Ayati 2
- Zahra Mohaddes Ardebili 3
- Shamim Delavari 4
1 Department of Socio-Medicine, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Obstetrics and Gynecology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3 School of Medicine, Tehran, Iran
4 School of Medicine, Azad University, Mashhad, Iran
Abstract
Background & Objective: Delayed childbearing has become a worldwide phenomenon, yet the association between advanced maternal age (AMA ≥35 years) and pregnancy outcomes remains unclear. This issue has also been inadequately explored in Iran. To assess the relationship between pregnancy complications and AMA in the Iranian context.
Materials & Methods: This cross-sectional study involved 891 women who had consecutive pregnancies and were referred for delivery to an academic hospital at Mashhad university of medical sciences, Mashhad , Iran, from March 2015 to March 2019 for The women were considered into the two age groups, namely, a 20 to 34year group and an AMA group, who were then assessed in terms of complications of late childbearing, such as preeclampsia, gestational hypertension, and gestational diabetes mellitus (GDM); mode of delivery; and five-minute Apgar score. The data were analyzed using the chi-square test and the Mann–Whitney U test in SPSS version 9. The P<0.05 was considered statistically significant.
Results: The AMA group exhibited lower five-minute Apgar scores and a significantly higher prevalence of preeclampsia, gestational hypertension, and GDM (p < 0.05). The two groups also substantially differed concerning
quality of prenatal care (p < 0.001). Regarding the mode of delivery, cesarean section was more prevalent in the AMA group, whereas vaginal delivery was more common in the younger group (p < 0.001).
Conclusion: With regard to trend to pregnancy in higher maternal age and higher pregnancy complication in this population, precise preconception counseling is crucial to educating couples for early childbearing at younger age.
Highlights
✅ With regard to trend to pregnancy in higher maternal age and higher pregnancy complication in this population, precise preconception counseling is crucial to educating couples for early childbearing at younger age.
Keywords
Main Subjects
Women who postpone childbirth up to the age of 35 years or older are classified as having reached advanced maternal age (AMA) and this option is chosen by many women because of educational, social, and economic factors (1). Accordingly, delayed childbirth has been a globally prevalent phenomenon in the last two to three decades. In the United States, for example, studies reported a four-year delay in the average age of first pregnancies among women (2). This pattern has become an equally increasing occurrence in developing countries .The Statistical Center of Iran indicated that the mean age of first marriage in the country increased by 4.7 years from 1957 to 2002, thereby also elevating the mean age of first pregnancy (3). In Shiraz, 2.01% of mothers are 40 years or older (4)-a huge demographic shift that has become an important public health issue in the region.
Recent evidence regarding the association between prenatal outcomes and maternal age remains largely clouded by confounding age-related factors (5,6). This challenge is compounded by debates regarding the extent to which maternal age, rather than age-related comorbidity, is solely responsible for adverse obstetric outcomes (5,7). Reports from different countries indicated that compared with younger females, women aged≥35 years are noticeably more susceptible to pregnancy complications (1, 2, 8) and preexisting medical conditions, such as diabetes (8), ypertension (8,9), low birth weight, prenatal mortality, preterm birth, and gestational age-related rates of stillbirth (3, 5, 7, 10). Some studies, however, confirmed that no important differences exist between young and old mothers in terms of pregnancy complications, maternal and prenatal results, birth weights, and gestational age (4,11). Research has provided controversial data or mixed findings on prenatal and neonatal outcomes (7)-a problem that potentially stems from the lack of clear definitions of AMA despite the volume of investigations devoted to this issue.
The studies that focused on the Iranian context also highlighted the higher prevalence of adverse pregnancy complications in AMA than in younger mothers (4,11), but adequate prenatal care may ensure maternal prognosis that are similar to those of younger pregnant women (12-14). One of the most challenging issues is abnormal placental adhesion which is more prevalent in advanced maternal age; even happening in primigravid older women (15). Unfortunately, many couples are not educated for the importance of maternal age at the time of pregnancy and thus postpone this important issue for the later years of reproductive age. Moreover, in recent years, childbearing is encouraged by government policies through media, so we encounter many women who want to have another child at age >35 years. On the basis of these considerations, the current research was conducted to assess adverse maternal and neonatal outcomes in women ≥35 years who had no medical disease before pregnancy and compare these with the outcomes of healthy younger women.
Participants
This analytical cross-sectional study involved 891 women who had consecutive pregnancies and were referred to Ghaem Hospital for delivery, which is affiliated with Mashhad University of Medical Sciences (MUMS). The sample was limited to women referred to the hospital for delivery from March 2015 to March 2019. Those with diabetes, chronic hypertension, hepatic and nephrotic diseases, heart disease, and autoimmune and thyroid disorders were excluded from the study. The selected participants were divided into two groups: one consisting of 20 to 34 old pregnant women (n=571) and the other comprising pregnant women who were 35 years or older (n=320).
Procedure and design
The groups were compared in terms of prenatal care, and maternal and newborn complications, such as preterm delivery, placental abruption, eclampsia and preeclampsia, gestational diabetes mellitus (GDM), cesarean delivery, maternal mortality, neonatal conditions, admission into the neonatal intensive care unit (NICU), and low birth weight. Regular prenatal care was defined as involving monthly visits from the discovery of pregnancy up to the 28th week of gestation, biweekly visits from the 28th to 36th weeks of pregnancy, and weekly visits from the 36th week of pregnancy up to delivery. Inadequate prenatal care was defined as a prenatal care frequency of, at most, once during pregnancy. The quality of prenatal cares between these two manners; determined as the irregular prenatal care. Laboratory and sonographic evaluation was carried out in accordance with standard protocols. Finally, the pregnancy outcomes of the two groups were compared. The main outcomes were to compare maternal and neonatal complications consist of preeclampsia, eclampsia, gestational hypertension, gestational diabetes, placenta abruption, intra uterine fetal death, low birth weight, low Apgar score and NICU admission.
The study protocol and the use of anonymized archival data were approved by the Ethical Committee of MUMS with ethical code number of IR.MUMS.fm.REC.1395.506.
Statistical analysis
To illuminate the research questions and hypotheses, we carried out the research in two stages. The first involved descriptive statistical analysis, and the second featured inferential statistical analysis. In the descriptive statistical analysis, each of the variables (Table 1) related to the two groups of participants was examined. Given the qualitative nature of all the variables, frequency tables and columnar graphs were drawn for each of the age groups. The results of this stage were used as bases for intuitively determining the differences in variables between the participant groups. In the inferential statistical analysis, we used correlation tables and a chi-square test to inquire into the correlation between the age groups and the level of each variable. The final data analysis was conducted using SPSS version 9. The normality of data distribution was verified using the Kolmogorov–Smirnov test. The differences in baseline and clinical characteristics between the groups were analyzed using a chi-square test and the Mann–Whitney U test for normally and non-normally distributed data, respectively. The P<0.05 was considered statistically significant.
Table 1. Maternal baseline characteristics
|
Characteristics |
Maternal age |
P-value * |
|
|
20–34 |
≥ 35 |
|
|
|
Maternal age ¶ (years) Gestational age (weeks) Prenatal care regular irregular inadequate |
27.60 ± 4.5 38.00 ± 5.0
478 (87.8) 8 (1.5) 58 (10.6) |
38.50 ± 2.6 37.00 ± 8.0
230 (75.1) 5 (1.6) 71 (23.2) |
< 0.001 < 0.001
< 0.001 |
|
PMH1 |
|
|
|
|
History of Gestational Diabetes |
36 (6) |
21 (6) |
0.880 |
|
Preeclampsia |
18 (3) |
15 (4) |
0.244 |
|
Third Trimester Bleeding |
533 (93) |
291 (90) |
0.191 |
|
Gravidity § |
2.00 ± 1.2 |
3.50 ± 1.8 |
< 0.001 |
* P value was evaluated using Chi-square test (P value < 0.05 denotes significance)
¶ Data are expressed as mean ± Standard Deviation (SD)
§ Data were analyzed using Mann-Whitney’s U-test
1 PMH: Past Medical History
About 891 women recruited in this study (571 women in 20-34 years group and 320 women in ≥35 year group). The mean ages of the women were 27.60 ± 4.5 and 38.50 ± 2.6 in the young and AMA groups, respectively, indicating a significant difference in this regard (P < 0.001). We examined maternal baseline characteristics, including the past history of third trimester bleeding and history of gestational diabetes and preeclampsia in the previous pregnancies, and found no significant difference between the two groups in terms of these variables (Table 1). Preeclampsia occurred in 21 cases in the AMA group, whereas this condition occurred in 19 cases in the younger group (P = 0.025).
Table 2. Pregnancy outcomes with association to maternal age
|
Outcomes |
Maternal age |
P-value* |
|
|
20–34 |
≥ 35 |
|
|
|
Mode of delivery |
|
|
< 0.001 |
|
Vaginal delivery |
469 (84.0) |
216 (68.5) |
|
|
Cesarean section |
89 (15.9) |
99 (31.4) |
|
|
Eclampsia |
2 (0.3) |
1 (0.3) |
0.925 |
|
Preeclampsia |
19 (3.3) |
21 (6.5) |
0.025 |
|
Gestational hypertension Gestational diabetes |
12 (2.1) 36 (6.3) |
20 (6.2) 37 (11.5) |
0.001 0.006 |
|
Placental abruption |
5 (0.8) |
4 (1.2) |
0.592 |
|
Neonatal conditions |
|
|
0.083 |
|
Live birth |
544 (96.8) |
300 (95.5) |
|
|
Stillbirth |
11(1.9) |
6 (1.9) |
|
|
Intrauterine death |
4 (0.7) |
8 (2.5) |
|
|
Birth weight (grams) |
|
|
0.340 |
|
< 2500 |
107 (18.8) |
73 (22.9) |
|
|
≥ 2500 |
457 (80.5) |
243 (76.4) |
|
|
Apgar score at 5 minutes |
|
|
< 0.001 |
|
< 7 |
35 (6.1) |
46 (14.6) |
|
|
> 7 |
527 (92.7) |
269 (85.3) |
|
|
NICU admission |
72 (13.4) |
46 (15.2) |
0.451 |
¶ Data are expressed as mean ± Standard Deviation (SD)
§ Data were analyzed using Mann-Whitney’s U-test
* P value was evaluated using Chi-square and Mann-Whitney’s U-test (P value < 0.05 denotes significance)
Gestational hypertension was significantly higher among the AMA subjects (N = 20) than among the younger group (N = 12) (P=0.002). The inferential statistical results showed that the prevalence of gestational diabetes was significantly higher in the AMA group (P = 0.006). As presented in Table 2, the incidence of cesarean sections was noticeably more frequent among the AMA mothers, whereas vaginal delivery was the prevalent delivery mode for the younger mothers (P < 0.001). The AMA group substantially differed from the younger ones in terms of the quality of prenatal care, which showed that older women had more inadequate and irregular prenatal care than younger group (P < 0.001). The occurrence of a five-minute Apgar scores lower than 7 significantly increased in the AMA group compared with the other group (P < 0.001). More details are provided in Table 2.
The groups exhibited no substantial difference with respect to NICU admission, eclampsia, and placental abruption. The same absence of significant differences was observed between the groups in terms of the prevalence of mean gestational age and low birth weight (<2500 g). Furthermore, the difference between the groups in terms of the prevalence of neonatal conditions, including stillbirths, lives births, and intrauterine deaths, was negligible (Table 2). Because no maternal deaths occurred, no related associations could be assessed.
The findings indicated that older women are more likely to have poor prenatal outcomes than younger females, consistent with the results of some previous studies (11,16). We found lower five-minute Apgar scores of infants and a significantly higher prevalence of preeclampsia, gestational hypertension, GDM, inadequate prenatal care, and cesarean delivery among the AMA subjects than among the younger women. Nevertheless, no significant difference was found between the groups with regard to the prevalence of placental abruption, eclampsia, neonatal conditions, birth weight, and NICU admission. In our study, the past history of comorbidities like gestational diabetes, preeclampsia, third trimester vaginal bleeding were the same in both groups (table 1), but our findings revealed that AMA was associated with the increased prevalence of preeclampsia (P=0.025) which is in line with the results of similar studies (17,18). This result can be attributed to the fact that aging is accompanied by alterations in carbohydrate metabolism, which increase blood glucose levels and impairment in vessel walls. Age-induced increases in blood pressure are more considerable during pregnancy, in advanced age. Poor uterine vascularization is believed to cause a deficiency in placental perfusion that is probably related to preeclampsia (19).
In line with a study (19), this study showed that the infants of older women exhibited a higher risk of presenting a five-minute Apgar score below 7 (P<0.001). Our research also aligns with that of Wen et al., (20) who found a correlation between AMA and low Apgar scores. Contrastingly, a study reported that neonatal outcomes, including birth weight and five-minute Apgar scores lower than 7, were unaffected by maternal age (21). The difference between the results of this study and our study may be due to no significant differences between the two groups in terms of maternal morbidities which affect the neonatal outcomes. Although the fifth minutes Apgar score was lower in AMA group, but the need for NICU admission and neonatal condition in the first 48 hours of birth was the same; There is a possibility that dvanced neonatal resuscitation procedures in delivery room make this advantage. These results were supported by some previous studies (22-24); but another study showed significant poor neonatal outcomes in terms of preterm delivery, low birth weight and perinatal mortality (21); these different results may be mainly due to morbidities like pregestational hypertension or overt diabetes and maternal age≥40.
Strength and Limitations
As some previous study showed, better perinatal out comes by increasing the prenatal care services (25). One of the strength of the current study was evaluating the mode of prenatal care and the frequency of regular care in each group. The other strength was inclusion of the women without any pregestational morbidity,which could eliminate some important confounders that affect adverse pregnancy outcomes.
This study has encumbered by some limitations. First, our analyses did not consider some variables that are known to be associated with fetal and neonatal morbidity and mortality, such as smoking, obesity, maternal syphilis, and difficult labor. Second, because we used medical records as our primary data source, missing or incomplete data or errors in these records could have affected data quality. We tried to minimize these shortages by training our data collectors, who work as clinical staff, before the initiation of the study.
Third, we did not divide the advanced age group into women aged 35 to 40 and above 40, which prevented a more accurate comparison. More research is needed to determine appropriate and timely interventions for reducing the impact of AMA on pregnancy outcomes.
Conclusion
AMA was associated with adverse pregnancy outcomes including GDM, gestational hypertension, preeclampsia, low five-minute Apgar scores which indicating that this female population is more susceptible to adverse pregnancy outcomes than younger women. Couples should be educated and encouraged to start childbearing at younger age; so preconception counseling in early marriage for all women should cover this important issue.
The present study has been adopted from the medical thesis (code No: 8723101039). This study was conducted with the financial and spiritual supports of the Deputy of Research at Mashhad University of Medical Sciences within a proposal approved by Code No: 950299. The ethical code number of this study was, IR.MUMS.fm.REC.1395.506.
Funding Source
The author(s) received no financial support for the research, authorship, and/or publication of this article.
All authors declare that they have no conflicts of interest.
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