Francesca Parisi, Alice Zavatta, Roberta Milazzo, and Irene Cetin
During pregnancy, several maternal anatomical and physiological changes occur in order to ensure proper development of the growing fetus and to prepare the mother for labor and delivery. In this context, maternal adaptation to pregnancy includes numerous cardiovascular, renal, hematologic, respiratory, and metabolic changes that finally lead to increased oxygen and nutrient supply to the fetoplacental unit and to enhanced protection against postpartum hemorrhage for the mother. Table 1.1 summarizes the main mechanisms of maternal adaptation to pregnancy with a systems approach.
Table 1.1 Maternal adaptation to pregnancy
Systemic vascular resistance
Systemic blood pressure
Blood viscosity (Hct and Hb)
Protein S activity
Red blood cell mass
Prothrombin time (slightly)
Fibrinogen, factors II, VII, VIII, X, XII, XIII
Thrombin activatable fibrinolytic inhibitor, PAI-1, PAI-2
Platelet count (slightly)
Resistance to activated protein C
Renal blood flow
Urinary frequency and nocturia
Dilatation of the ureters and renal pelvis
Proteinuria and glucosuria
Excretion of HCO3−
Functional residual capacity
Lithogenicity of bile
Serum alkaline phosphatase
Serum level of AST, ALT, γ-GT
Cholesterol and triglyceride concentrations
CRP and ESR
Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; FFA, free fatty acid; Hb, hemoglobin; Hct, hematocrit; GFR, glomerular filtration rate; PAI, plasminogen activator inhibitor; PCO2, partial pressure of carbon dioxide; PO2, partial pressure of oxygen; Th, T-helper lymphocytes.
Moreover, an evolutionary revolution occurred over the last decades: the intrauterine period of development has been shown to permanently shape the adult life, mainly through epigenetic modifications that affect the postnatal phenotype of the offspring in later life (1). This concept has given a new pivotal role to obstetric care also for improving the health status and the risk of chronic disease of future generations. In this context, maternal maladaptation to pregnancy may lead to short-term derangements in intrauterine development, with abnormal fetal growth, birth weight, and morphological development, and may finally shape the risk of chronic diseases of the child and the adult as a long-term effect.
Despite the great attention given to the second half of pregnancy, the research focus has recently moved to the first trimester and the time around conception (the “periconceptional period”) in order to grant early screening and diagnosis of subsequent adverse pregnancy outcomes with long-term health effects (Figure 1.1). The periconceptional period represents a chaotic time window from a biological point of view, starting with gamete maturation, going through the events of fertilization and implantation, and ending with the development of the embryonic structures and the first stages of placentation. This period is crucial for a normal adaptation to pregnancy, and any pathological deviation in this time window may finally lead to overt diseases in the second half of pregnancy and to larger shifts in the adult phenotype than the second half of pregnancy. In fact, if it is true that perinatal morbidity and mortality and the risk of noncommunicable diseases are mainly related to complications diagnosed during the second part of pregnancy (e.g., hypertensive disorders, intrauterine growth restriction, preterm birth), it is also evident that these conditions originate during the very first stages of pregnancy and even before, thus involving the most important stages of gamete, placenta, and embryo development (2).
Figure 1.1 The periconceptional period (14 weeks before to 10 weeks after conception). The periconceptional period includes a series of complex events starting from male and female gamete maturation, going through conception, implantation, placentation, and finally to embryogenesis in the first trimester of pregnancy. Such a chaotic period is vulnerable to external parental environment and exposures. But more important, parental exposures in the periconceptional period have been shown to permanently modify the development of the gamete/placenta/embryo, finally impacting on pregnancy outcome and further programming the future health of the offspring.