Has advanced maternal age a real impact on intrapartum caesarean rate?

were defined according to the American College of Obste-tricians and Gynecologists (ACOG) criteria [10, 11]. GDM was diagnosed with a 100-gram oral glucose tolerance test when ≥ 2 values exceeded the Carpenter and Coustan criteria [12]. Small

Most authors suggest that maternal age is an independent risk factor for pregnancy and perinatal complications, such as gestational diabetes mellitus (GDM), hypertensive disorders, higher caesarean and instrumental delivery rates, as well as growth retardation and prematurity.
The majority of studies conclude that AMA is associated with a higher global caesarean rate.However, only a few have analyzed this rate focusing on its timing: elective or intrapartum [6].Thus, the present authors aimed to analyze whether AMA pregnant women (considering ≥ 40-yearsold patients) have an increased risk of intrapartum caesarean delivery and perinatal complications compared to younger mothers.

Materials and Methods
A retrospective cohort study was designed.The study group consisted of nulliparous women who were ≥ 40-years-old and delivered between June 1 st , and December 31 st , 2015.The control group included < 40-year-old nulliparous women who delivered between June 1 st -31 st , 2015.Gestational control and delivery were attended at a fourth-level obstetric center.The study met the center ethical criteria.
Inclusion criteria were singleton pregnancies in vertex presentation which were alive and delivered ≥ 34 +0 weeks of gestation.Multiple pregnancies, previous uterine surgery, breech presentation, fetal death, fetal malformations, and any contraindication to vaginal delivery were exclusion criteria.Sample size is shown at Figure 1.
Gestational age (GA) at delivery was based on last menstrual period and confirmed by first-trimester ultrasound scan (crownrump length, CRL).In cases of IVF, GA was established from the date of embryo transfer.Hypertensive and amniotic fluid disorders were defined according to the American College of Obstetricians and Gynecologists (ACOG) criteria [10,11].GDM was diagnosed with a 100-gram oral glucose tolerance test when ≥ 2 values exceeded the Carpenter and Coustan criteria [12].Small for gestational age (SGA) or large for gestational age (LGA) were defined as estimated fetal weight by ultrasound below the 10 th or above the 90 th percentile for GA, respectively, regarding local population birthweight curves [13].Cervical shortening criteria requiring intervention were sonographic cervical length < 25 mm at ≤ 31 +6 weeks of gestation, or < 15 mm between 32 +0 -34 +6 weeks of gestation.
When elective onset of labour (EOL) was required and Bishop score was < 6, cervical ripening was used according to the present authors' protocols [14].In case of no active phase of labour,  or Bishop score ≥ 6, induction of labour with intravenous oxitocine was begun.Indications for caesarean or instrumental delivery were suspected fetal distress, due to anomalous cardiotocography, scalp blood test < 7.20 or other situation that implied a vital risk for the fetus, and dystocia (failed induction of labour, arrest of dilation or cephalopelvic disproportion in case of caesarean section, and arrest of descent in case of instrumental delivery) [15,16].Prolonged hospitalization was defined as more than four days after a vaginal delivery or more than seven days after a caesarean section.Postpartum hemorrhage was defined according to ACOG criteria, as well as blood transfusion indications [17].Optimal values for umbilical cord arterial pH and five-minute Apgar score were considered ≥ 7.11 and ≥ 7, respectively [18,19].
Normally distributed quantitative variables were expressed as mean and standard deviation.Non-normally distributed quantitative variables were expressed as median and interquartile range.Categorical variables were expressed as proportions.
Comparisons between age groups were done using the chisquare test or Fisher's exact test for categorical variables and Student t-test for quantitative variables.Multivariate analysis was performed using forward stepwise binary logistic regression.A probability value of < 0.05 was considered significant.Results are reported as proportions, odds ratio (OR), and 95% confidence interval (95% CI).Analysis was performed using the Statistical Package for the Social Sciences (SPSS version 21).

Results
The sociodemographic characteristics and obstetric history for the study and control groups are shown in Table 1 Obstetric and perinatal outcomes are shown in Table 2.
The risk of developing GDM was three times higher in the study group [OR 3.56 (IC95% 1.40-9.05)],reaching up to 22.6%.Cervical shortening was more frequently diagnosed in ≥ 40-year-old pregnant women (7.4% and 0.8%, p = 0.032).Most of them presented premature uterine contractions, which required tocolytic treatment.If not, a cervical pessary was placed (two patients in the study group).There were no statistically significant differences regarding the incidence of hypertensive disorders, intrahepatic cholestasis, amniotic fluid, and fetal growing disorders.Differences were observed between groups regarding the onset of labour and mode of delivery.The study group had a two-fold higher probability of having an EOL [OR 2.11 (IC95% 1.10-4.05)]and almost a three-fold higher probability of an intrapartum caesarean delivery [OR 2.63 (IC95% 1.13-6.15)]compared with younger women.The most frequent cause of EOL was premature rupture of membranes (22.2% and 10.7%, respectively).
As there were statistically significant differences between groups as to BMI, ART, and GDM, a second analysis was performed.When patients with high BMI or GDM were excluded, the OR obtained was non-significant 2.11 (p = 0.07).Also, a stepwise binary logistic regression multivariate analysis was performed including AMA, BMI, GDM, and ART.Only BMI > 30 remained as a variable in the equation.
No statistically significant differences were founded related to GA at delivery (Figure 2), prematurity, intrapartum fever, meconium-stained amniotic fluid, and instrumental delivery.In relation to the indication of the caesarean or instrumental delivery (labour dystocia or fetal distress), statistically significant differences were not detected.In addition, there were no differences between groups regarding maternal complications.
Newborns to younger mothers were heavier than those born to older mothers (3,301 and 3,134 grams, p = 0.037).Although no statistically significant difference was found, a tendency for a higher rate of birth weight < 2,500 grams (11.1% and 5.8%), one-minute Apgar score < 7 (11.3% and 5.8%) and umbilical cord arterial pH ≤ 7.10 was observed in the study group (9.1% and 1.9%).Also, a tendency for birth weight ≥ 4,000 grams in the control group was seen (p = 0.06).No newborn required to be transferred to the neonatal intensive care unit.

Discussion
Delayed childbearing has increased greatly in recent decades, especially in developed countries [3].Some of the main reasons are female incorporation to working life, late emancipation and inflexible work schedules [2].Also, ART advances have made possible to gestate at 5 th and 6 th decades of life.
Most studies analyze global caesarean rate [6].Among those that focused on intrapartum caesarean delivery rates, there seems to be a consensus concerning the fact that AMA is related with higher rates compared to younger pregnant women [4,6,7,21,22], as shown in the present study.However, most authors agree on the more permissive indications to perform a caesarean section [2,[5][6][7], which could excessively increase the rate in AMA women.
As some investigators did [6,21,22], the present authors found a statistical significance between AMA and elective labour induction [OR 2.11 (IC 95% 1.10-4.05)].Bearing in mind that bibliography refers to EOL as a risk factor for caesarean section [14], it could be suggested that the higher rate of caesarean section in AMA pregnant women may be due, at least partially, to the higher rate of EOL.
Other explanations could be either an impaired contractile function of myometrium or uteroplacental insufficiency.Nevertheless, no statistically significant differences were found between groups with regards to the indication (dystocia or fetal distress) for both caesarean delivery [4,6] and instrumental delivery.Caesarean section due to maternal request or maternal age is not taken into account in the present center, in contrast to others [2,[5][6][7].Respecting the rate of instrumental delivery, statistically significant differences were not found between groups [4,6], but there is no agreement [3,7,8].
One of the main causes for perinatal morbi-mortality is prematurity, and most authors have described an increased incidence in AMA pregnancies [2,7,8,23].However, this study hardly evaluated its incidence due to its gestational age exclusion criterion.According to the present results, some authors conclude that young pregnant women have heavier newborns [2,23].On the other hand, Adashek et al. [4] obtained an opposite result.Statistically significant differences have not been described with respect to either Apgar score at one and five minutes [4,7] or umbilical cord arterial pH [4].However, the present authors found a tendency for a higher rate of pH ≤ 7.10 among AMA pregnancies.
This study focused on the intrapartum caesarean rate as the main outcome.It is important to highlight the heterogeneity between studies, some of which include multiparous women [2,5,7,8,22] and multiple gestations [2] that may be considered as a bias, excluding the one of Bell et al. [6].Also, it is a one-center study with a protocol man-agement of delivery and strict inclusion and exclusion criteria, and data was collected by a single scientist.Nonetheless, the retrospective design and the sample size are the main limits of this study.In addition, the higher prevalence of obesity in the study group appeared to act as a confounding factor as previously stated, as it may be partly responsible for the higher incidence of GDM, and both of them for the higher intrapartum caesarean rate, among other perinatal adverse outcomes.

Conclusion
Pregnancy at advanced maternal age has been linked to poor obstetric and neonatal outcomes.The present findings might shed some more light on this line and provide accurate information to AMA pregnant women about maternal and perinatal outcomes.Further investigation is needed regarding the effect of maternal age on pregnancy outcome.

Figure 2 .
Figure 2. -Gestational age (GA) in weeks at delivery [n (%)] for the study and control groups.

Table 2 .
-Obstetric and perinatal outcome for the study and control groups.
Hb: hemoglobine.LGA: large for gestational age; SGA: small for gestational age.Categorical variables are given as n (%).Measure of association are expressed as OR (95% CI).*Quantitative variables are given as mean ± standard deviation.

Table 1 .
-Characteristics and obstetric history for the study and control groups.