**4. Physiological homeostasis changes that may affect elderly mothers' health**

During pregnancy, a series of physiological homeostatic changes take place in a woman's body that activate numerous adaptive mechanisms, mainly cardiovascular, respiratory, and hemodynamic. These changes are essential for the evolution and progress of a normal pregnancy. Adaptive mechanisms can be compromised as a consequence of underlying diseases, which appear more frequently in women of advanced age.

diabetes mellitus type 2 appears more often after the fourth decade of life and affects directly the renal function. Renal function–affected women need to be closely monitored during

Multiple Pregnancy in Women of Advanced Reproductive Age

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These are only some of the major adaptive mechanisms in a woman's body during pregnancy, but there are many more subtle changes that occur in this period. We should pay attention to any minimal sign of hemodynamic decompensation especially in pregnant women of advanced age who are more likely to suffer from diseases, previously undiagnosed, as a result

There are not many studies specifically evaluating obstetric outcomes in twin pregnancies in advanced maternal age, and most of them are retrospective. These studies usually set the threshold for advanced maternal age at the "classic" 35 years, but in current times, this threshold should probably be reconsidered. A recent study by Zhu et al. [39] showed that, in twin pregnancies, advanced maternal age was associated with a higher risk of post-partum haemorrhage, gestational diabetes, and preterm delivery. However, other studies do not

Much more attention has been paid to the obstetric complications in twins resulting from ART. Particularly, they are at increased risk of placenta praevia, caesarean section birth, preterm birth, and low birth weight [41]. Again, other studies showed no significant differences [42]. What we can be sure of is that twin pregnancies represent a huge demand for the body and that they do come with a higher obstetrical risk. Advanced age mothers' physical fitness

We defined preterm delivery as birth prior to 37 weeks of gestation. Preterm birth complicates 5–18% of pregnancies and is the leading cause of neonatal death and the second cause of childhood death below the age of 5 years [43]. We should distinguish between preterm deliveries medically indicated secondary to foetal or maternal complications during pregnancy, such as preeclampsia, intrauterine growth restriction, or gestational diabetes, from those that occur after spontaneous onset of labour. Many studies have described multiple risk factors for preterm birth [44–47], although others propose this entity is a syndrome caused by multiple

Twin pregnancy has been classically described as one of the risk factors associated with preterm birth. Although multiple gestation accounts for only 2–3% of all births, this type of gestation constitute 17% of births before 37 weeks of gestation and 23% of birth before 32 weeks [48]. The mechanism for preterm birth in multiple gestations may be related to the increased uterine distension; however, some studies suggest that the increased amount of oestrogen,

**5. Obstetric complications in twin pregnancy related to age**

demonstrate any significantly increased risk over controls [40].

necessarily cannot be the same to compensate for this fact.

pregnancy.

of ageing of their organs.

**5.1. Preterm delivery**

pathologic processes [43].

The increase in cardiac output, extracellular volume, and arterial compliance and the decrease in arterial blood pressure (BP) and peripheral resistance are some of the cardiovascular changes that occur in pregnant mothers [33]. Mean BP decreases during pregnancy presenting its lower values in the middle of the second trimester and then it starts to increase reaching values comparable to non-pregnant women at the end of pregnancy. In addition, redistribution of blood flow to different organs is essential in order to cover for the higher metabolic requirements, and so venous return and cardiac output raise dramatically [34]. There are also hormonal factors that favour these changes to appear. Oestrogens and relaxin are both involved in the production of nitrous oxide (NO), which produces vasodilatation during pregnancy and facilitates the distribution of blood to key organs [35, 36]. Ageing is associated with structural changes in the vascular wall, which leads to loss of arterial elasticity and reduced arterial compliance. Cardiovascular adaptive mechanisms could be impaired in elderly mothers due to pre-existing hypertensive disorders or venous insufficiency; therefore, they are at high risk of suffering from complications such as preeclampsia and placental insufficiency, increasing morbidity and mortality for both the mother and the baby.

Modifications in the respiratory system also take place during pregnancy. Pulmonary function is affected by location and orientation changes of the airway and configuration of the thorax due to the presence of the gravid uterus as well as hormonal effects. The elevation of the diaphragm decreases the lung's vertical diameter and subsequently enlarges the transversal and anteroposterior diameters. The displacement of the diaphragm produces a progressive decline in expiratory reserve volume and residual volume. Progesterone, cortisol, and relaxin produce dilatation of the airway in pregnant women reducing pulmonary resistance [37]. Ageing is associated with structural changes not only in the chest bones and diaphragm but also in the lung tissue. The dilatation of the alveoli decreases the exchange surface increasing the residual volume and functional residual capacity. These physiological changes added to those typical from pregnancy can cause alterations in the ventilation-perfusion ratio in elderly mothers.

Dilatation of the renal pelvis and ureters is characteristic during pregnancy on account of the growth of the uterus and the effect of hormones, such as progesterone, that cause relaxation of the smooth muscle. This predisposes women to suffer from urinary tract infections during pregnancy. Renal function is also modified during this period with an increased blood flow and glomerular filtration up to 60% [38]. Precisely for that reason, we should be aware of any medical pre-existing renal dysfunction that can worsen during pregnancy. For example, diabetes mellitus type 2 appears more often after the fourth decade of life and affects directly the renal function. Renal function–affected women need to be closely monitored during pregnancy.

These are only some of the major adaptive mechanisms in a woman's body during pregnancy, but there are many more subtle changes that occur in this period. We should pay attention to any minimal sign of hemodynamic decompensation especially in pregnant women of advanced age who are more likely to suffer from diseases, previously undiagnosed, as a result of ageing of their organs.
