Acasa > Reviste de specialitate > Obstetrica şi Ginecologia > Pregnancy outcome at very advanced maternal age: the experience of a level 2 center
ORIGINAL ARTICLES

Pregnancy outcome at very advanced maternal age: the experience of a level 2 center

 Rezultatele naşterii la vârste materne foarte avansate – experienţa unui centru de nivel 2

Mihai Muntean, Vlăduţ Săsăran, Sonia-Teodora Luca, Victoria Nyulas, Claudiu Mărginean

First published: 30 iunie 2023

Editorial Group: MEDICHUB MEDIA

DOI: 10.26416/ObsGin.71.2.2023.8873

Abstract

Background. Advanced maternal age has been linked to unfavorable perinatal outcomes. This study aimed to evaluate the perinatal outcomes in patients with very advanced maternal age. Materials and method. We retrospectively reviewed the records of patients admitted to the Obstetrics and Gynecology Clinic of the Mureş County Clinical Hospital, Romania, between 1 September 2016 and 1 September 2023. The study group comprised 17 patients, while the control group consisted of 661 patients, aged 18-44 years old, who gave birth between 1 January 2023 and 30 June 2023. Results. Patients from rural areas with very advanced maternal age had more pregnancies and births than the control group. The majority of pregnancies were achieved naturally, with a significantly higher incidence of preterm birth before 34 weeks. There were no statistically significant differences in the incidence of pregnancy-induced hypertension and intrauterine growth restriction between groups, while obesity and gestational diabetes were significantly associated with very advanced maternal age. Caesarean section was the most common mode of delivery. Newborns of mothers with very advanced age were more frequently male, had low birth weight, and were frequently admitted to the intensive care unit. Conclusions. Advanced maternal age is associated with an increased risks of gestational diabetes, premature birth, caesarean section, and delivering small-for-gestational-age newborns. Therefore, patients with advanced maternal age require careful obstetric surveillance.
 

Keywords
very advanced maternal age, perinatal outcomes, gestational diabetes mellitus, prematurity

Rezumat

Background. Vârsta maternă foarte avansată se asociază cu rezultate adverse perinatale. Obiective. Obiectivul acestui studiu a fost de a evalua rezultatele perinatale la pacientele cu vârstă maternă foarte avansată. Materiale şi metodă. Am evaluat retrospectiv informaţiile din foile de observaţie ale pacientelor cu vârste cuprinse între 45 şi 50 de ani, internate în Clinica de obstetrică şi ginecologie a Spitalului Clinic Judeţean Mureş între 1 septembrie 2016 şi 1 septembrie 2023. Lotul de studiu a fost alcătuit din 17 paciente, iar ca lot de control, am utilizat informaţiile din folie de observaţie a 661 de paciente, cu vârste cuprinse între 18 şi 44 de ani, care au născut în perioada 1 ianuarie 2023 – 30 iunie 2023. Rezultate. Pacientele cu vârstă foarte avansată au provenit preponderent din mediul rural şi au avut mai multe sarcini şi naşteri decât pacientele din lotul de control. Marea lor majoritate au obţinut sarcinile în mod spontan, iar incidenţa naşterii premature sub 34 de săptămâni a fost semnificativ statistic mai mare. Obezitatea şi diabetul gestaţional au fost semnificativ statistic asociate cu vârsta maternă foarte avansată şi nu au existat diferenţe semnificative statistic între loturi cu privire la hipertensiunea indusă de sarcină şi restricţia de creştere intrauterină. Calea de naştere preponderentă a fost prin operaţie cezariană, iar în ceea ce priveşte nou-născuţii din mame cu vârstă foarte avansată, aceştia au fost mai frecvent de sex masculin, cu greutate mică la naştere şi au fost mai des internaţi în secţia de terapie intensivă. Concluzii. Vârsta maternă foarte avansată este un factor de risc pentru diabetul gestaţional, naşterea prematură, naşterea prin operaţie cezariană şi nou-născuţi mici pentru vârsta gestaţională, astfel încât pacientele cu vârsta maternă foarte avansată necesită supraveghere obstetricală deosebită. 
 

Cuvinte cheie
very advanced maternal age perinatal outcomes gestational diabetes mellitus prematurity

Introduction

The reproductive age of individuals in developed countries has increased in recent decades. However, as age increases, fertility tends to decrease, leading to a higher demand for assisted human reproduction techniques. Additionally, the risk of pregnancy-related complications also increases with age(1). Traditionally, women over the age of 35 years old are considered to have an advanced maternal age. However, there is a division of opinions regarding the very advanced maternal age, with some considering 40 years old as the benchmark(2), while others taking 45 years old as the benchmark(3).

Some authors suggest that pregnancies in patients over 40 are associated with various complications, such as a higher rate of genetic syndromes(4), spontaneous abortion in the first trimester, pregnancy-induced hypertension, preeclampsia, gestational diabetes(2), and a higher rate of caesarean delivery(4). However, other authors(5) found no association between very advanced maternal age and adverse perinatal outcomes.

Our study aimed to evaluate the pregnancy outcomes of patients with very advanced maternal age (above 45 years old).

Materials and method

We gathered information retrospectively from the records of patients aged between 45 and 50 years old who gave birth in the Obstetrics and Gynecology Clinic of the Mureş County Clinical Hospital, Romania, from 1 September 2016 to 1 September 2023. The data we collected included information about maternal age, residential area, gestation, parity, mode of conception, the number of fetuses, gestational age at birth, route of delivery, complications during pregnancy such as hypertension, gestational diabetes and intrauterine growth restriction, complications at birth such as perineal tears and postpartum bleeding, indication for caesarean delivery, birth weight, Apgar score below 7 at 5 minutes, and the need for neonatal intensive care.

To compare the data, we also extracted information from the records of births of pregnant women aged 18-44 years old at birth, which took place between 1 January 2023 and 30 June 2023. We collected information on maternal demographics, mode of conception, the number of fetuses, complications during pregnancy, mode of delivery, complications after delivery, birth weight, and Apgar score below 7 at 5 minutes. These data will be used as a control for comparison. In this study, we included pregnant women over 45 years old with a gestational age of at least 20 weeks. Pregnant women under 45 years old or with a gestational age under 20 weeks were excluded. We defined low birth weight (LBW) as a birth weight of 2500 g or less(6), and large for gestational age (LGA) as a birth weight higher than 4500 g(7). Gestational diabetes mellitus was diagnosed based on the criteria of the International Association of Diabetes and Pregnancy Study Groups Consensus Panel (IADPSG)(8). Hypertension in pregnancy was diagnosed according to the criteria of the American College of Obstetricians and Gynecologists (ACOG)(9). Fetal growth restriction was defined as estimated fetal weight below the 10th percentile for gestational age(7), while obesity was defined as a Body Mass Index (BMI) over 30 kg/m2(10).

The Romanian Society of Obstetrics and Gynecology provides guidelines for the use of oxytocin during labor, the management of postpartum bleeding, perineal tears, and indications for caesarean delivery(11-14). The Ethics Committee of the Obstetrics and Gynecology Clinic of the Mureş County Clinical Hospital granted permission for the study. Statistical analysis was conducted using SPSS V.20 software. The Kolmogorov-Smirnov test was used to determine data normality, while categorical data were analyzed using the Chi square and Fischer tests. Numerical variables were compared using the ANOVA or Kruskal-Wallis test, based on data distribution. The significance threshold was set at alpha=0.05.

Results

Between 1 September 2016 and 1 September 2023, there were 17 births in patients over the age of 45 years old, in the Obstetrics and Gynecology Clinic of the Mureş County Clinical Hospital. This represented 0.15% of the total of 10,669 births that occurred during the same period.

For comparison purposes, the control group consisted of 661 pregnant women who gave birth in the Obstetrics and Gynecology Clinic of the Mureş County Clinical Hospital between 1 January 2023 and 30 June 2023. The control group was further divided into two subgroups based on age: one group aged 18-34 years old and the other aged 35-44 years old. This division allowed us to evaluate and compare the results obtained in the patients of the study group.

In our study group, most patients (88.2%) became pregnant spontaneously. Out of those, 13 patients (76.4%) were multigesta and multipara. More detailed information is available in Table 1. The average age of patients in the study group at the time of delivery was 45 years old.

In the control group, the majority (60.2%) of patients aged 18-34 were from rural areas, while most (65.6%) patients aged 35-44 were from urban areas. It was found that most patients with single fetal pregnancy in both the study and control groups achieved pregnancy spontaneously (p<0.0001). Only one patient in the study group had multiple pregnancy (triplet) which was obtained through assisted reproductive techniques (ART), compared to the control groups where only one multiple pregnancy occurred spontaneously.

The study group of patients with single pregnancy gave birth at around 37.8 (±2.6) weeks of gestational age. On the other hand, the 18-34-year-old group had an average gestational age at birth of 38.6 (±1.83) weeks, while the 35-44-year-old group had an average gestational age at birth of 38.5 (±1.37) weeks. However, there was no statistically significant difference in gestational age between the groups (p=0.28).

There was one patient with multiple pregnancy (triplets) in the study group who gave birth at 34 weeks, while the patients from the 18-34-year-old group and the 35-44-year-old group gave birth at 35 weeks and 38 weeks of pregnancy, respectively.

In the study group, 23.5% of patients gave birth at ≤34 weeks, compared to only 1.5% and 2% of pregnant women from the 18-34-year-old group and the 35-44-year-old group, respectively. This difference was statistically significant (p<0.0001).

The incidence of intrauterine fetal death was 5.8% in the study group. Furthermore, 41.2% of patients in the study group were obese, which was significantly higher than the percentages of 7.4% in the 18-34-year-old group and 14.5% in the 35-44-year-old group (p<0.0001) (Table 1).

Regarding the complications that occurred during pregnancy, 11.8% of the patients in the study group developed gestational diabetes mellitus during pregnancy, compared to 0.9% of the patients aged between 18 and 34 years old and 9.4% of the patients aged between 35 and 44 years old (p<0.0001). There was no statistically significant difference between the groups regarding the incidence of pregnancy-induced hypertension (p=0.99), fetal growth restriction (p=0.8), and intrauterine fetal death (p=0.14).

Regarding the mode of delivery, 47.1% of the patients in the study group gave birth vaginally, compared to 61.9% of the patients in the 18-34-year-old group and 26% of the patients in the 35-44-year-old age group (Table 2). Regarding vaginal birth after caesarean section, no patients in the study group and in the 35-44-year-old age group had vaginal birth after caesarean section, compared to five patients (0.9%) in the 18-34-year-old group (p=0.6). Oxytocin was used for the stimulation of labor or for the treatment of hypotonia in the fourth stage of labor in 23.5% of the patients in the study group, compared to 49% of the 18-34-year-old group and 19.8% of the 35-44-year-old group. Regarding complications after delivery, there was no statistically significant difference between the groups in terms of perineal injuries (p=0.22), but there was a statistically significant difference in terms of postpartum bleeding (p=0.02).

Regarding caesarean delivery, 52.9% of the patients in the study group gave birth by caesarean section, compared to 38.1% of patients in the 18-34-year-old group and 74% of patients in the 35-44-year-old group.

Regarding indications for caesarean delivery, post-caesarean scarred uterus was the most common cause of caesarean delivery. Moreover, 5.9% of the patients in the study group were patients with a scarred uterus, compared to 18.1% of the patients in the 18-34-year-old group and 38.5% of the patients aged between 35 and 44 years old (p<0.0001). Placenta praevia was another indication for caesarean section that was statistically significantly more frequent in the study group than in the control groups, the other indications not being statistically significantly different between groups (Table 2).

There were statistically significant differences between groups in terms of neonatal birth weight (p=0.002). Newborns from mothers over 45 years old weighed 3274±495.7 g, those from mothers aged 18-34 years old weighed 2930±596.4 g, and those from mothers aged 35-44 years old weighed 3285±547.9 g. We found a significant difference regarding the incidence of low birth weight (LBW; p=0.01), the patients in the study group having a higher incidence of LBW compared to the other two control groups. Regarding large for gestational age (LGA), there was a statistically significant difference between groups (p=0.01); we found LGA newborns in the control groups and none in the study group. Regarding the sex of the newborns, there were more boys than girls in the study group, as well as in the control groups, but the difference was not statistically significant. Regarding the Apgar score below 7 at 5 minutes after birth, there was a statistically significant difference between the study group and the control groups, in the study group being an incidence of 11.8% for the Apgar score below 7 at 5 minutes (p<0.0001). Neonatal intensive care unit (NICU) admission was more frequent in the study group (p<0.0001) than in the control groups.

Discussion

The data from studies evaluating the effect of advanced maternal age on pregnancy outcomes are conflicting(2,3,5,15). This study aims to assess the risks for mothers and neonates with advanced maternal age.

In our study, the incidence of births in patients with very advanced maternal age was 0.15%. Our incidence was lower than that described by Simchen et al.(16) and Laskov et al.(17), this difference being probably caused by the high percentage of pregnancies obtained through assisted reproductive techniques (ART) – 55% and 88% respectively, in those cohorts – compared to our case, where we had only 11.8% pregnancies achieved through ART. In our study, we observed that women with very advanced maternal age mostly came from rural areas, were grand multigesta and multipara. On the other hand, patients aged between 35 and 44 years old mainly came from urban areas but had lower rates of pregnancy and childbirth. In their study, Callaway et al.(5) had mainly multiparous patients from the urban area, and Kahveci et al.(2) had studied only primiparous patients. Regarding multiple pregnancies, in the study group we had only one patient with multiple pregnancy (triplets) whose pregnancy was achieved by ART. Pregnant women with multiple pregnancy (twins) in the control groups achieved pregnancies spontaneously.

The pregnant women in our study gave birth at an average gestational age of 37.8 weeks, without being statistically different from the control groups. We found an incidence of premature birth under 34 weeks of 23.5%, statistically significantly higher than in the control groups. Our rate of preterm birth in study group was higher than what Callaway et al.(5) and Kahveci et al.(2) found. The leading causes of a higher percentage of preterm birth in our study group were: premature rupture of membranes, premature labor, multiple pregnancy (triplets), and drug induction of labor for intrauterine fetal death. Obesity was statistically significantly more frequent in patients with a very advanced maternal age. Regarding complications during pregnancy, we found statistically significant differences only in terms of gestational diabetes mellitus. Dysfunction of pancreatic b cells, insulin resistance and chronic inflammation found in obese pregnant women of very advanced age explain the higher incidence of gestational diabetes mellitus in this group of patients(18). There were no statistically significant differences between the groups in terms of hypertension/preeclampsia, fetal growth restric­tion and intrauterine fetal death. Other authors(2,3,5,15-17) found significant differences between groups in terms of gestational diabetes mellitus, but also in terms of hypertension, preeclampsia, fetal growth restriction and perinatal death.

Regarding the mode of delivery, patients with very advanced maternal age gave birth by caesarean section in 52.9% of cases, mainly due to obstetric emergencies (cephalopelvic disproportion, fetal distress, placenta praevia), compared to the 74% rate of caesarean section in patients in the age group 35-44 years old and 38.1% caesarean section rate in the age group of 18-34 years old, in both groups the most frequent indication for caesarean section being repeated caesarean section. A similar or higher caesarean delivery rate was also found by other researchers(2,3,5,15,17), but the indications for caesarean section were mainly elective caesarean section and repeated caesarean section, mainly due to the nulliparity or anxiety of the patients.

Regarding vaginal delivery, the patients in the study group, compared to the 18-34-year-old group, needed less stimulation of labor with oxytocin, had less perineal tears and postpartum bleeding. In general, the postpartum evolution of the patients in our study group had a good evolution, but Laskov et al.(17) found a rate of 1.1% of admission in intensive care units. The main indications for admission were severe preeclampsia, respiratory failure and disseminated intravascular coagulation (DIC).

Regarding neonatal outcomes, newborns of mothers in the study group had a higher weight than those in the 18-34-year-old group, but less than those in the 35-44-year-old group, an explanation of these differences resulting from the fact that patients in the study group had a higher incidence of obesity compared to the 18-34-year-old group. On the contrary, Berger et al.(19) found an association between advanced maternal age (>35 years old) and LBW under 2500 g. The incidence of LBW was higher in the study group, mainly due to the higher incidence of premature birth. Simchen et al.(16) obtained the same results, but Kahveci et al.(2) did not find any association between very advanced maternal age and LBW. Regarding the gender of the newborns, the male gender was more common in the study group, but the difference was not statistically significant, the same results being obtained by Yu et al.(20) APGAR score below 7 at 5 minutes and NICU admission were higher in the study group in patients who delivered at 34 weeks. The same results were observed by Smithson et al.(3) and Laskov et al.(17)

The main limitations of our study are that it is a single-center study, with a small number of women in our study group, with lack of data regarding the educational level and reasons for delaying pregnancy. 

Conclusions

Advanced maternal age is associated with an increased risks of gestational diabetes, premature birth, caesarean section, and delivering small-for-gestational-age newborns. As a result, patients with advanced maternal age need to undergo careful obstetric surveillance.

Table 1. Demographic and obstetric characteristics of the study group and comparison groups
Table 1. Demographic and obstetric characteristics of the study group and comparison groups
Table 2. Complications during pregnancy and obstetrical outcomes
Table 2. Complications during pregnancy and obstetrical outcomes
Table 3. Neonatal outcomes
Table 3. Neonatal outcomes












Conflict of interest: none declared  
Financial support: none declared
This work is permanently accessible online free of charge and published under the CC-BY. 

Bibliografie

  1. Seshadri S, Morris G, Serhal P, Saab W. Assisted conception in women of advanced maternal age. Best Pract Res Clin Obstet Gynaecol. 2021 Jan;70:10-20.
  2. Kahveci B, Melekoglu R, Evruke IC, Cetin C. The effect of advanced maternal age on perinatal outcomes in nulliparous singleton pregnancies. BMC Pregnancy Childbirth. 2018 Aug 22;18(1):343.
  3. Smithson SD, Greene NH, Esakoff TF. Pregnancy outcomes in very advanced maternal age women. Am J Obstet Gynecol MFM. 2022 Jan;4(1):100491.
  4. Canhaço EE, Bergamo AM, Lippi UG, Lopes RG. Perinatal outcomes in women over 40 years of age compared to those of other gestations. Einstein (Sao Paulo). 2015 Jan-Mar;13(1):58-64.
  5. Callaway LK, Lust K, McIntyre HD. Pregnancy outcomes in women of very advanced maternal age. Aust N Z J Obstet Gynaecol. 2005 Feb;45(1):12-6.
  6. Hughes MM, Black RE, Katz J. 2500-g Low Birth Weight Cutoff: History and Implications for Future Research and Policy. Matern Child Health J. 2017 Feb;21(2):283-289.
  7. Damhuis SE, Ganzevoort W, Gordijn SJ. Abnormal Fetal Growth: Small for Gestational Age, Fetal Growth Restriction, Large for Gestational Age: Definitions and Epidemiology. Obstet Gynecol Clin North Am. 2021 Jun;48(2):267-279.
  8. International Association of Diabetes and Pregnancy Study Groups Consensus Panel; Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, Damm P, Dyer AR, Leiva Ad, Hod M, Kitzmiler JL, Lowe LP, McIntyre HD, Oats JJ, Omori Y, Schmidt MI. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010 Mar;33(3):676-82. 
  9. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins – Obstetrics. ACOG Practice Bulletin No. 203: Chronic Hypertension in Pregnancy. Obstet Gynecol. 2019 Jan;133(1):e26-e50.
  10. Reichetzeder C. Overweight and obesity in pregnancy: their impact on epigenetics. Eur J Clin Nutr. 2021 Dec;75(12):1710-1722.
  11. SOGR. Inducerea travaliului, 2019. www://sogr.ghiduri-clinice.
  12. SOGR. Hemoragiile în postpartum, revizuit 2023. www://sogr.ghiduri-clinice.
  13. SOGR. Asistenţa naşterii în prezentaţia craniană, 2019. www://sogr.ghiduri-clinice.
  14. SOGR. Operaţia cezariană, 2019. www://sogr.ghiduri-clinice.
  15. Phadungkiatwattana P, Rujivejpongsathron J, Tunsatit T, Yanase Y. Analyzing pregnancy outcomes in women of extremely advanced maternal age (> or = 45 years). J Med Assoc Thai. 2014 Jan;97(1):1-6.
  16. Simchen MJ, Yinon Y, Moran O, Schiff E, Sivan E. Pregnancy outcome after age 50 [published correction appears in Obstet Gynecol. 2007 Apr;109(4):1002]. Obstet Gynecol. 2006;108(5):1084-1088.
  17. Laskov I, Birnbaum R, Maslovitz S, Kupferminc M, Lessing J, Many A. Outcome of singleton pregnancy in women ≥ 45 years old: a retrospective cohort study. J Matern Fetal Neonatal Med. 2012 Nov;25(11):2190-3.
  18. Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The Pathophysiology of Gestational Diabetes Mellitus. Int J Mol Sci. 2018 Oct 26;19(11):3342.
  19. Berger BO, Wolfson C, Reid LD, Strobino DM. Adverse Birth Outcomes Among Women of Advanced Maternal Age with and Without Health Conditions in Maryland. Womens Health Issues. 2021 Jan-Feb;31(1):40-48.
  20. Yu T, Chen TS, Liang FW, Kuo PL. Does sex matter? Association of fetal sex and parental age with pregnancy outcomes in Taiwan: a cohort study. BMC Pregnancy Childbirth. 2020 Jun 8;20(1):348.