**2. Pregnant women, scientifically complexed population**

There are various concepts about the characteristics of vulnerable populations; however, it is generally accepted that a vulnerable group is one whose ability to protect their own interest or grant their consent is physically, psychologically, or socially compromised. Since the development of ethical principles in research, children, psychiatric patients, prisoners, and pregnant women have been included in this group; however, in recent years it has been intended to remove pregnant women from this group. The National Institutes of Health (NIH) through the Office of Research on Women's Health recommended as early as 2010 that pregnant women should be considered as a scientifically complex rather than vulnerable group, this being for the reason that this group has the same capacity and autonomy for decision making as its nonpregnant counterparts, including the decision of whether or not to participate in a clinical trial [3].

Scientific complexity arises from the special physiological conditions of pregnancy and from the ethical considerations of the balance between maternal well-being and fetal well-being.

Pregnancy is accompanied by important physiological changes and their knowledge is an element of great value for the proper management of the obstetric patient. Practically, all the body's system of the pregnant woman is adapted to house the product, among them are changes at the ocular, musculoskeletal, skin and mucous, hepatic, hematological, renal, and gastrointestinal levels. The most relevant changes occur at the uterine level, systemic vascular resistance is reduced due to high flow and low resistance circuit in the uteroplacental circulation. In pregnancy, uterine blood flow significantly increases to allow perfusion of intervillous placental spaces and fetal development. The trophoblast invades the uterine spiral arteries; vascular smooth muscle cells are lost and replaced by the fibrinoid material, converting them into large dilated blood vessels allowing greater perfusion of the placenta [4]. These changes pose a challenge for the researcher as they make it very difficult to define not only the possible therapeutic results of an intervention, but also to adapt the intervention to these new changes that are not present in nonpregnant women. In a pathological condition such as preeclampsia, this may represent a greater challenge, because of restrictions on research in a physiological pregnancy, ignorance or doubts about the effects of the intervention on the organism, or pathological adaptations that may affect the intervention that is intended to be performed are greater.

The ethical complexity is established in the possibility that the intervention applied in key phases causes a teratogenic risk or that affects the adaptation of the product to extrauterine life, and more worrying, the possibility of long-term toxicity. This is why it is necessary that preclinical teratogenicity studies have been completed prior to the intervention in pregnant women. Also, it is recommended to start the new interventions after the 12th week of gestation, when the organogenesis is finished and finally, it is recommended to follow the fetus and newborn [5]. However, these special considerations do not seem to be sufficient, as there are currently two forms of research in the group of pregnant women: the first consists of interventions unrelated to pregnancy that may benefit only the mother [3]. It seems that the previous recommendations were formulated with this type of research, since the use of thalidomide has contemplated the possibility of developing drugs that may attenuate different discomforts during pregnancy. The clinical investigation currently has to verify that the pharmacological interventions do not cause damage to the product and not only benefit the mother. The second type of research concerns interventions that may potentially benefit the mother and her fetus [3]. This aspect is more related to the development of pharmacological interventions for pathologies in pregnancy, specifically speaking of preeclampsia, the treatments are not indicated at the same time for the mother and for the fetus. Betamimetics used to prevent preterm birth are not intended to treat the mother and may even complicate maternal health. In contrast, depending on the severity of hypertension, the drugs could have a toxic effect on the fetus. These two aspects should be considered when deciding to experiment with a new therapeutic product or scheme [5].
