Abstract
Introduction
Elderly women are believed to experience many risks associated with pregnancy. Literature fails to provide a clear consensus on the age group in which there is a rise in risk and pathophysiology contributing. ‘Pregnancies over forty’ are increasing in society, owing to changing lifestyles and sensibilities of youth and the advent of assisted reproductive techniques. In India, studies on elderly pregnant women above 40 years of age are lacking. The aim of this study is to assess these pregnancies, their course, obstetric and perinatal outcomes in women delivering above 40 years.
Methods
The study group (Group A) comprised of pregnancies in 50 women at age ≥ 40 years on the date of delivery. The control group (Group B) had 50 women who delivered subsequent to the study group and age < 40. Various parameters and outcomes including parity, gestational age, number of gestations, co-existing medical illnesses, the incidence of hypertensive diseases of pregnancy (HDP), gestational diabetes mellitus (GDM), pre-term labor, mode of delivery, birth weight and obstetric and neonatal outcomes were compared. Chi-square test and independent T test were used for statistical analysis.
Results
While a good number of patients conceived spontaneously and with basic infertility management, i.e., 84% in the elderly gravid group (Group A) and 96% in the control group (Group B), the number of patients who required ART in Group A were statistically significant (Group A 16% and Group B 4%). Incidence of pre-existing medical diseases like hypertension, diabetes mellitus, thyroid dysfunction, other auto-immune diseases and chronic diseases were noted to be high (26%) in Group A (statistically significant difference). Incidence of HDP, GDM and fetal growth restriction were high in Group A. Tendency to have the presence of fibroid uterus was high in patients in Group A, i.e., 24%, compared to only 8% in the control group; difference was statistically significant. Proportion of pre-term deliveries were high in Group A. Cesarean section rate was high in Group A, though it was not statistically significant. Other perinatal observations and neonatal outcomes were comparable in both groups; differences were not statistically significant.
Conclusion
The study reveals an association of a high-risk course of pregnancies in women above the age of 40 years. Proportions of IVF pregnancies are higher in elderly women. Interestingly, the proportion of women in elderly group who conceived spontaneously and with basic infertility management including IUI was 84% in the present study. Medical comorbidities and incidence of fibroids were high in elderly women. Obstetric and neonatal outcomes of these pregnancies when managed efficiently are favorable.
Keywords: Advanced maternal age, Pregnancy above 40 years of age, High-risk pregnancy
Introduction
With changing social norms, late marriages and modern sensibilities of the youth, a large number of women over 40 years of age are presenting to obstetric OPD. Advancing age in women affects pregnancy from conception to delivery; these women are believed to experience many risks associated with pregnancy and its outcomes. ‘Increased incidence of infertility’ and the advent of ‘assisted reproductive techniques’ are factors contributing to pregnancies in those over forty.
The believed risks and morbidities complicating pregnancies are hypertension, diabetes mellitus (DM), obesity complicating pregnancy, uterine leiomyoma, previous cesarean section, hypertensive diseases of pregnancy (HDP), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), operative delivery, high cesarean section rate and neonatal morbidity [1, 2]. Neonates are affected due to prematurity, low birth weight, FGR and fetal distress, which also increase the rates of NICU admissions [3–5].
Type II diabetes and hypertension show an incremental increase with advancing maternal age and therefore act as mediating variables on the pathway between age and pregnancy outcome [6]. In this manner, it remains unclear if advanced maternal age in itself contributes to poor pregnancy outcomes rather than age-related comorbidity?
Literature fails to provide a clear consensus on the age group in which there is a rise of risk. In India, studies on women giving birth over the age of 40 years are lacking.
Aim of this study is to assess these pregnancies, their course, obstetric and perinatal outcomes in women with age more than 40 years.
Methods
This is an observational, prospective, case-control study. The study was conducted over 36 months over the time duration from June 2016 to May 2019. The total number of women who delivered above the age of 40 years were included in the study group. The study group (Group A) comprised of deliveries in 50 women with age ≥ 40 years on the date of delivery. The control group (Group B) had 50 women who delivered subsequent to the study group (age < 40 years). To achieve randomization, women assigned to the control group were the subsequently admitted parturient woman, who signed up for the study.
Various parameters and outcomes including parity, gestational age, number of gestations, co-existing medical illnesses, the incidence of HDP, GDM, pre-term labor, mode of delivery, birth weight and obstetric and neonatal outcomes were compared.
The recorded data were analyzed statistically using ‘statistical package for social sciences (SPSS)’ version 17. Chi-square test and independent T-test were applied for statistical analysis. A p value below 0.05 was considered significant.
Observations and Results
A total of 100 pregnant women were divided in two groups, 50 in each group.
Range of Age in Group A (study group) was ‘40 years to 47 years 2 months and in Group B (control group) was ‘25 years to 39 years 3 months.
Mean age in group A was 42.1 years, and in Group B it was 32.2 years.
Parity 19 (38%) and 13 (26%) women were primigravida in Groups A and B, respectively (Table 1). Nullipara with previous abortions are included in the multigravida group.
Table 1.
Parity
| Parity | Group A | Group B | P value |
|---|---|---|---|
| Primigravida | 19 (38%) | 13 (26%) | 0.198 NS |
| Multigravida | 31 (62%) | 37 (74%) | |
| Total | 50 (100%) | 50 (100%) |
Type of conception Out of 50 women in Group A, 35 women conceived naturally (70%); 7 conceived with Intra-uterine insemination (IUI) (14%) and 8 (16%) conceived with in vitro fertilization (IVF): advanced assisted reproductive techniques. In group B 46 out of 50 (92%) were spontaneous natural conceptions. There were 2 (4%) IUI conceptions and 2 (4%) IVF pregnancies. The comparison is statistically significant, signifying that women over 40 years of age are more likely to require assisted reproductive techniques (Table 2).
Table 2.
Type of conception
| Type of conception | Group A | Group B | P value |
|---|---|---|---|
| NATURAL | 35 (70%)* | 46 (92%) | 0.001* |
| IUI | 7 (14%) | 2 (4%) | |
| IVF | 8 (16%) | 2 (4%) | |
| Total | 50 (100%) | 50 (100%) |
By Chi-square test D.F. = 01 *Significant
Interestingly, In Group A with the inclusion of women who received basic infertility management, adding pregnancies with IUI, conception rate was 84%. To note, the protocol-based basic management of elderly women can yield good results in a population of elderly women ‘over forty.’
Number of Gestation Total numbers of twin pregnancies were two in Group A and one in Group B. All others were singleton pregnancies.
Pre-existing medical and surgical comorbidities 13 patients in Group A (26%) and 5 in Group B (10%) were diagnosed with pre-existing medical illness. These included diabetes mellitus, hypertension and others including thyroid dysfunction, autoimmune disease, thalassemia, nutritional anemia, surgical comorbidity, etc. The difference is statistically significant. Women in Group A are more prone for having a co-existing medical disease (Table 3).
Table 3.
Morbidities and outcomes
| Group A | Group B | P value | |
|---|---|---|---|
| Pre-existing medical disease | 13 (26%)* | 5 (10%) | 0.037* |
| Fibroids | 12 (24%)* | 4 (8%) | 0.0261* |
| Incidence of HDP | 7 (14%) | 4 (8%) | 0.552 |
| GDM | 3 (6%) | 4 (8%) | 0.695 |
| Fetal growth restriction | 9 (18%) | 4 (8%) | 0.234 |
| Pre-term birth | 7 (14%) | 5 (10%) | 0.538 |
| Low birth weight (birth weight < 2.5 kg) | 9 (18%) | 4 (8%) | 0.234 |
| NICU admissions | 8 (16%) | 4 (8%) | 0.355 |
By Chi-square test D.F. = 01 *Significant
Association with co-existing Fibroid Uterus 12 patients in Group A (24%) were having uterine fibroids, while only 4 patients (8%) in Group B had uterine fibroids. This difference is found to be statistically significant, signifying the association of co-existing fibroid uterus in Group A.
Incidence of hypertensive diseases of pregnancy, gestational diabetes mellitus, fetal growth restriction were compared in both the groups. Differences were not statistically significant (Table 3).
Pre-term deliveries There were 7 preterm deliveries in Group A (14%) and 5 in Group B (10%) (Table 3).
Birth weight and NICU admissions in both groups are compared in Table 3. Babies who delivered with birth weight less than 2.5 kg were 9 (18%) and 4 (8%); and those who required NICU admissions were 8 (16%) and 4 (8%) in Groups A and B, respectively. There were no statistical associations between the two groups for these outcomes.
Mode of delivery Total number of vaginal deliveries in Group A and Group B were 17 (34%) and 28 (56%) respectively. The total number of cesarean sections in Group A and Group B were were 33 (66%) and 22 (44%) respectively. The difference was not statistically significant (Table 4).
Table 4.
Mode of delivery
| Group A | Group B | P value | |
|---|---|---|---|
| Vaginal delivery (total) | 17 (34%) | 28 (56%) | 0.154 NS |
| Spontaneous vaginal delivery | 11 (22%) | 15 (30%) | |
| Operative vaginal delivery | 06 (12%) | 13 (26%) | |
| Cesarean section | 33 (66%) | 22 (44%) | |
| Emergency | 18 (36%) | 08 (16%) | |
| Elective | 15 (30%) | 14 (28%) | |
| Total | 50 (100%) | 50 (100%) |
By Chi-square test D.F. = 01
NS not significant
Various indications of cesarean section in both groups were compared (Table 5). The most common indication in Group A was ‘previous cesarean section’ (10 women: 30.30%). The most common indication in Group B (previous cesarean section) remained the same as group A. (7 women: 31.81%).
Table 5.
Indications of cesarean section
| Group A (total no. of CS 33) | Group B (total no. of CS 22) | P-value | |
|---|---|---|---|
| Previous cesarean section | 10 (30.30%) | 7 (31.81%) | 0.0127 |
| Non-progress of labor | 6 (18.18%) | 4 (16.66%) | |
| Fetal distress | 5 (15.15%) | 4 (16.66%) | |
| Breech | 3 (09.09%) | 2 (09.09%) | |
| FGR | 3 (09.09%) | 2 (09.09%) | |
| Twins | 2 (06.06%) | 1 (04.54%) | |
| CS on maternal request | 4 (12.12%) | 2 (09.09%) | 0.0198 |
Discussion
The study design and various outcomes compared in both groups were comparable and consistent with the various studies published in the literature. Similar studies with advanced maternal age were compared.
A recent Indian study by Pawde Anuya et al. from 2014, consisting of 1263 women, compared pregnancies in women less than 35 years of age and above 35 years of age. Hypertension in pregnancy, abruptio placenta, vaginal trauma, CS rate were significantly higher in elderly group [7].
A large retrospective study comprising more than a thousand pregnant women above forty from the USA in 1996 concluded that older gravidas were more likely to develop gestational diabetes (nulliparas: OR 2.7; multiparas: OR 3.8), preeclampsia (nulliparas: OR 1.8; multiparas: OR 1.9), and placenta previa (nulliparas: OR 13.0; multiparas: OR 6.4). Older women were also at increased risk for cesarean delivery (nulliparas: OR 3.1, multiparas: OR 3.3), operative vaginal delivery (nulliparas: OR 2.4, multiparas: OR 1.5) and induction of labor (nulliparas: OR 1.5; multiparas: OR 1.4) [8]. These findings are evident and remained consistent in the present study.
M. Jolly et al. compared the obstetric risks of adverse outcomes from retrospective data analysis by categorizing pregnant women into three age groups: 18–34 years, 35–40 years, > 40 years. Results showed pregnant women aged 35–40 years were at risk of the following outcomes with given Odd’s ratio: gestational diabetes, OR: 2.63 [99% interval (CI) 2.40–2.89]; placenta previa: 1.93, breech presentation: 1.37, operative vaginal delivery: 1.5, elective cesarean section: 1.77, emergency cesarean section: 1.59, postpartum hemorrhage: 1.14, delivery before 32 weeks gestation: 1.41, birth-weight below the 5th centile: 1.28 and stillbirth: 1.41. Women aged > 40 years had higher OR than this for the same risks [9]. Increased risk of association of these antenatal complications is also evident in the present study.
Ilse Delbaere et al. conducted population-based retrospective study with comparison of pregnant women between two age groups 25–29 years and age ≥ 35 years; the design was conceptualized to specifically compare younger and old patients, in order to observe the effects of advanced maternal age. Conception with ART, hypertension during pregnancy, diabetes during pregnancy were high in the elderly group and the difference was statistically significant. Adjusted Odd’s ratio was high for preterm birth, operative delivery and CS rate [10].
Ziadeh and Yahana in an institute-based large retrospective study in elderly gravida over forty concluded that nulliparous women with age 40 or over have a higher risk of operative delivery than do younger nulliparous women. This increase occurs in spite of lower birth weight and gestational age and may be explained by the increase in incidence of obstetric complications. Although maternal morbidity was increased in the older women, the overall neonatal outcome did not appear to be affected [11].
Leonie Callaway et al. and Yogev et al. compared pregnancies in women > 45 years of age. Chronic as well as gestational hypertension, pre-gestational and gestational DM, obesity, CS rate, PPH, blood transfusion, postpartum fever were high in elderly group with statistically significant association. Babies from elderly women group had hyper-bilirubinemia, metabolic complications, prolonged hospitalization [12, 13].
Such adverse outcomes were also seen in the group of elderly women from the present study.
Dietl et al. showed that when pre-existing comorbidities were handled meticulously and delivery was done at centers with good perinatal care, results in elderly women are encouraging and comparable to cohort of young women [14].
Conclusion
The presence of coexisting medical and surgical comorbidities in elderly pregnant women (over 40 years) denotes the high-risk nature of the clinical course to be anticipated by the obstetrician.
Along with pre-existing medical diseases, hypertension, diabetes mellitus, co-existing uterine fibroids were noted to be significantly high in the elderly group.
Proportion of IVF pregnancies are higher in elderly women. Interestingly, the proportion of women in the elderly group who conceived spontaneously and with basic infertility management, was 84% in the present study.
Tendency to develop fetal growth restriction and incidence of prematurity were noted to be higher in the elderly group, but not significant statistically. Perinatal outcomes were comparable in both groups.
In spite of the high-risk nature, obstetric and neonatal outcomes of these pregnancies, when managed efficiently, are favorable.
Funding
This study did not receive funds from any source.
Declarations
Conflict of interests
All authors declare they have no conflict of interest.
Ethical Standards
All authors declare that the procedures performed in the study were in accordance with the ethical standards on human experimentation and with the 1964 Helsinki Declaration and its later amendments, the latest revision 2013. Ethics committee approval not required as it is a retrospective study.
Human and Animal Rights
This article does not contain any studies with animals performed by any of the authors. Human rights are not violated.
Informed Consent
Informed consent was obtained from all individual participants included in the study.
Footnotes
Dr. Sunil E. Tambvekar is an Assistant Professor, Department of Obstetrics and Gynecology, Nowrosjee Wadia Maternity Hospital, Seth G. S. Medical College, Mumbai, India; Dr. Shilpa Adki is an Ex Consultant, IVF Specialist and Gynecologist, Indira IVF Centre, Allahabad and Asansol, India; Dr. Nozer K. Sheriar is a Consultant Obstetrician and Gynecologist, Holy Family Hospital, Hinduja Hospital, Breach Candy Hospital, Mumbai, India.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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