**5.2. Preeclampsia**

As we have seen before, mean BP decreases during the first and second trimesters secondary to the reduction of peripheral resistances and starts to increase reaching values similar to non-pregnant women in the third trimester.

Preeclampsia (PE) is a hypertensive disorder that appears during pregnancy. PE is a major obstetric complication that causes 15–20% of maternal mortality worldwide, especially in developing countries [52]. It is characterised by the presence of high BP (> 140/90 mmHg) and proteinuria (> 300 mg/dL) beyond 20 weeks of pregnancy. The finding of higher values of BP before this stage of pregnancy is considered chronic hypertension, which can also worsen in the second half of pregnancy, with what we call superimposed preeclampsia. The physiopathology of this multisystemic disorder still remains unknown.

In the last decades, several aetiologies have been described. Some authors suggest that it appears secondary to an abnormal vascular response of the uterine blood vessels to trophoblast invasion, causing platelet aggregation and endothelial dysfunction [52–54]. The increase of BP during pregnancy can also have an effect on the foetus, developing complications such as low birth weight, oligoamnios, and intrauterine growth restriction [54, 55]. In addition, preeclampsia is considered severe when it affects multiple organs, finally producing pulmonary oedema, renal failure, seizures, thrombocytopenia, elevation of liver enzymes, and disseminated intravascular coagulation [54].

The rate of preeclampsia ranges between 2 and 7% in healthy nulliparous women [54, 56, 57]. These rates increase to 14% in twin pregnancies [58]. Preeclampsia is regarded as typical of the first pregnancy. In spite of this, the risk of developing preeclampsia in subsequent pregnancies raises till 18% [58].

Numerous studies proposed several risk factors to classify a specific group of women who are at a high risk of developing preeclampsia, including nulliparity, older age, chronic hypertension, and diabetes mellitus [59–61]. Other studies indicate that, after adjusting for other cofounders, women of advanced maternal age are 1.5 times more likely to have preeclampsia compared to those under 35 years of age [62]. Multiple pregnancy is a moderate risk factor for the development of pre-eclampsia during pregnancy. Women with multiple pregnancy, who have any of the other moderate risk factors for pre-eclampsia (first pregnancy, age 40 years or older, pregnancy interval of more than 10 years, BMI of 35 kg/m2 or more at first visit, or family history of preeclampsia), should receive a daily aspirin dose [63].

As we have seen before, single-embryo transfer is the main technique to reduce the rate of twin pregnancies. We should focus our effort on identifying those women with pre-existing medical conditions who are predisposed to suffer PE and, if applying ART, enforce the importance of achieving a singleton gestation to avoid adverse perinatal outcomes.
