4 Discussion
Based on our findings, educational level was the only factor significantly different between groups among sociodemographic factors. Advanced-age mothers had less education than those aged 20–34 years old. Mothers with higher levels of education had a lower risk of several prenatal adverse outcomes.6 A recent meta-analysis across 12 European countries found a 48% risk excess of preterm births associated with low maternal education.7 Such findings should not be overlooked. Among comorbidities, chronic hypertension, cardiovascular disease, overt diabetes, and thyroid dysfunction were more prevalent among mothers at an advanced age. These co-morbidities are more common in advanced-age mothers and are independently associated with adverse pregnancy and childbirth outcomes.1,8
According to the findings of this study, advanced maternal age is a significant risk factor for a variety of adverse maternal and neonatal outcomes even after adjusting for covariates. In terms of adverse maternal outcomes, advanced age increased the risk of gestational diabetes, preeclampsia, placenta abnormalities (previa/acreta), postpartum hemorrhage, and maternal intensive care unit admission. Compared with mothers aged 20–34 years, advanced-age mothers had a significantly higher risk of gestational diabetes (aOR: 3.18, 95%CI: 1.56–6.95). However, we did not observe an age-related increase in the risk of macrosomia. These findings are consistent with a previous study conducted by Kahvechi et al.5 Clinical studies have shown that there is already resistance to insulin action with physiological aging, resulting in slightly elevated glycemia. Fulop et al. explained the decline in insulin sensitivity with age due to the progressive deterioration of pancreatic-cell function. Because of decreased insulin sensitivity and increased serum lipid levels, the prevalence of glucose intolerance rises with age.9
Consistent with other studies,3,5 advanced-age mothers were nearly three times more likely to encounter preeclampsia than their adult counterparts (aOR: 2.91, 95%CI: 1.35–4.72). Duckitt et al. found that maternal age greater than 40 years doubles the risk of preeclampsia.10 Furthermore, Saftlas et al. demonstrated that the risk of severe preeclampsia increases sharply after the age of 35.11 Another study, on the other hand, found no link between preeclampsia and maternal age, which was interpreted as a result of controlling for covariates for gestational hypertension and preeclampsia, such as comorbidities.12 It could be argued that because such comorbidities are most likely caused by old age, they should not be adjusted for because they are intermediate variables.
In this study, the risk of placenta abnormalities (placenta previa and placenta acreta) was slightly higher in advanced-age mothers (aOR: 1.09, 95%CI: 0.77–1.94). Advancing maternal age appears to increase the risk of placenta previa independent of other factors. A population-based, case-control study showed that mothers aged 34 years or older had a two to three times higher risk of placenta previa than mothers under 20 years old.13 Another study by Biro et al. reported that advanced maternal age was independently associated with placenta previa (OR 2.2).14 However, it has been reported that the risk of adverse maternal and neonatal outcomes for mothers with placenta previa was not substantially affected by maternal age if their different risk profiles were considered.15 The placenta acreta spectrum has also been linked to advanced maternal age. One reason for the increased risk of placenta acreta in older mothers is that they are more likely to be multiparous and have a history of cesarean section. However, the prevalence of acreta in nulliparous mothers calls this interpretation into question. Our findings also show that even after controlling for covariates like parity and history of cesarean section, there is still a link between the risk of acreta and increasing maternal age, though this risk is low.
This study also discovered a link between maternal age and mode of delivery. The rising pregnancy rate at advanced maternal age corresponds to the increasing rate of CS. According to several studies, advanced maternal age is a risk factor for CS.3,5 Bayrampour et al. discovered an increased risk of cesarean birth among mothers of advanced maternal age compared to younger mothers in a systematic review of twenty-one studies for nulliparous and multiparous.16 The current study found that advanced-age mothers were more than three times more likely than their adult counterparts to have their babies delivered via CS (aOR: 3.16, 95%CI: 1.51–3.87). This odd is higher than those reported in Ethiopia (OR 2.7),3 Turkey (OR 2.6),5 and Ireland (OR 1.8).8 This could be because the proportion of malpresentation (breech and transverse) was higher in advanced-age mothers in our study. Other poor obstetrical factors, including preeclampsia, gestational diabetes, and placenta abnormalities, were commonly seen in advanced-age mothers, and CS could have been considered for maternal reasons.
Another finding of our study was the increased risk of postpartum hemorrhage (aOR: 1.94, 95%CI: 1.24–2.61) in advanced age. Previous research has linked advanced maternal age to postpartum hemorrhage, but there is still no agreement. According to Kramer et al., maternal age of 35 years (aOR, 1.5; 95% CI, 1.5–1.6) increased the risk of postpartum hemorrhage.17 Sheen et al. proposed that mothers over 45 years of age were at the highest risk for postpartum hemorrhage during delivery hospitalizations.18 A meta-analysis, however, found no link between the maternal age of 35 years and postpartum hemorrhage.19 Furthermore, another study discovered that getting older protects against postpartum hemorrhage.20 CS, abnormal placentation, and stillbirth are among the factors that have been linked to postpartum hemorrhage.21 The higher Incidence of CS, placenta abnormalities, and stillbirth in our study could justify the increased risk of postpartum hemorrhage in advanced-age mothers. All of the above adverse maternal outcomes place advanced-age mothers at a higher risk of intensive care unit admission (aOR: 1.36, 95% CI: 1.15–1.99).
In terms of neonatal outcomes, advanced-age mothers had a higher rate of preterm birth, LBW, stillbirth, and neonatal intensive care unit admission. According to our findings, advanced age doubled the risk of preterm birth (aOR: 2.36, 95%CI: 1.65–4.83). Preterm birth is the most crucial determinant of neonatal morbidity and mortality, and it has a significant impact on it. However, the relationship between prematurity and advanced maternal age is still debated in the literature. Confounders identified in our studies, such as placenta previa, hypertensive complications, and maternal medical history, are the most significant influence on the risk of preterm birth. Several studies have attempted to investigate the specific impact of advanced maternal age after adjustment for confounders, but the evidence is still conflicting.22,23 According to some studies, there is a U-shaped relationship between maternal age and the risk of preterm birth even after adjustment for confounders, with the lowest risk age being 24–30 years and sharply increased risk after the age of 40 years.24,25
In contrast, some studies have found a higher risk of preterm birth among younger mothers (30–34 years).26,27 This disparity could be explained by differences in sociodemographic or clinical risk factors across studies. Preterm birth is thought to be the leading cause of birth asphyxia,28 childbirth injury,29,30 and neonatal mortality.31 Despite the higher prevalence of preterm birth, there were no significant differences in the need for resuscitation, asphyxia, childbirth injury, and neonatal mortality rates between the groups in our study.
The prevalence of meconium fluid was lower in advanced-age mothers than in adults (9.8% vs. 12.5%). Bivariate regression also revealed that advanced-age mothers had a lower risk of meconium fluid than adults. This could be explained by the lower rate of post-term pregnancy, as post-term pregnancy is a risk factor for a higher rate of meconium fluid32; however, multivariate logistic regression found no correlation between advanced age and the Incidence of meconium fluid.
In our study, advanced-age mothers were more likely to have LBW newborns (aOR: 1.35, 95%CI: 0.97–2.96). Mehari et al. discovered that advanced-age mothers were three times more likely to have LBW newborns.3 In contrast, two studies from Malaysia4 and Turkey5 found no link between maternal age and LBW. Although most research documents a positive association between advanced maternal age and the risk of LBW,3,33 a subset of studies suggests that the association may be confounded by preexisting medical conditions, obstetrical history, and maternal social characteristics.3,5 A study that determined whether the association between advanced maternal age and the risk of LBW is due to maternal age or other confounding factors found that advanced maternal age is not independently associated with the risk of LBW.34
Advanced-age mothers were at higher risk for stillbirth (aOR: 1.18, 95%CI: 1.01–3.16). Advanced maternal age is an independent risk factor for stillbirth in nulliparous35 and multiparous mothers.8 Mothers of advanced maternal age are at higher risk of stillbirth throughout gestation; the peak risk period is 37–41 weeks.36 It is currently unknown the best way to prevent stillbirth in mothers aged 35 and above. The case for beginning antepartum surveillance at 37 weeks is that the risk of stillbirth at this gestational age is comparable to other high-risk conditions for which testing is routinely performed (chronic hypertension, diabetes, cholestasis, etc.). However, insufficient evidence confirms that antenatal testing for advanced maternal age alone reduces stillbirth or improves perinatal outcomes.37 Consistent with a previous study,5 admission to a NICU was more likely in the advanced-age mothers (aOR: 2.09, 95%CI: 0.73–3.92); however, the risk of neonatal congenital malformations, and need for resuscitation were not associated with maternal age.
The strength of our study is that our study registers are of high quality and in accordance with childbirth records. We investigated various factors associated with advanced maternal age, including pregnancy, childbirth, and neonatal outcome. The population study sample size was large enough to reflect the situation regarding obstetric challenges among all advanced maternal-age pregnancies during the study period. Our study was conducted retrospectively, which is still a limitation. The database did not allow for the precise timing of the various events during pregnancy. More data was missing for some variables, such as body mass index and weight gain during pregnancy, known as risk factors for adverse prenatal outcomes. We also were unable to evaluate the differences in prenatal screening tests and fetal chromosomal differences between groups due to missing data. Because our study group of 40 years and older was small in size, we lacked the power to detect risks of rare outcomes; thus, we did not conduct a subgroup analysis to determine the effect of very advanced age on the risk of adverse obstetric outcomes.
