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Estrada, María Angélica Miglino, Ximena Flores Chávez, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8682776/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 17 You are reading this latest preprint version Abstract Objective To determine the relationship between capillary cortisol, maternal mental health and biopsychosocial factors, along with obstetric pathologies and placental morphometry. Methods We studied a cohort of 114 pregnant women admitted after their first prenatal visit from Family Health Centers in Concepción, Chile. Sociodemographic data, mental health and obstetric pathologies were collected. Lifetime violence was assessed, and depressive symptoms were evaluated using the Edinburgh Postnatal Depression Scale and the psychosocial risk factors scale. Cortisol levels were measured in hair samples during the first, second, and third gestational trimesters. An analysis of the morphology and morphometry of term placentas was also performed. Results Average capillary cortisol levels were 4.1 ± 4.3 ng/ml in the first trimester, 11.5 ± 14.8 ng/ml in the second, and 6.6 ± 4.5 ng/ml in the third trimester. A significant association was observed between capillary cortisol and a history of emotional and/or physical violence (p = 0.042). An association was also found between pre-existing mental health conditions, gestational diabetes, and hypertensive disorders of pregnancy (p < 0.05). Regarding placental analysis, a significant difference in terminal villi volume density was identified between groups with different cortisol levels (p = 0.008). Conclusion Levels of capillary cortisol are associated with pre-pregnancy mental health history, biopsychosocial factors, obstetric complications, and placental villous volume density, highlighting the relevance of preconception screening to reduce fetal and infant morbidity and mortality. Capillary cortisol Mental health in pregnancy Psychosocial factors Obstetric complications Placental morphometry Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Mental health is an integral part of people’s health and well-being. This issue is essential for leading a fulfilling life and contributing to society. In this regard, it is not just the absence of illness, but the ability to cope with adversity [1]. People who are exposed to adverse circumstances in their lives, especially during their earliest years, will present a greater risk of suffering from a mental health condition later in life [2]. There have been documented several risk and protective factors that influence mental health, including individual factors related to emotional skills, genetics, or substance misuse, as well as social and environmental factors such as poverty, violence, and lack of support networks [1, 3, 4]. Should these conditions occur during gestation and child-rearing, the repercussions are more likely to be transgenerational [2, 5]. The number of pregnant women with chronic stress, with diagnosis of major depression prior to pregnancy, and depressive symptoms detected during pregnancy, are currently reaching alarming levels. The global prevalence of the major depressive disorder at some point during pregnancy has been reported to reach between 12.7% and 37% among the pregnant women population [6]. Regarding stress, it is estimated that between 25% and 40% of women have experienced chronic prenatal stress [7, 8]. The afore mentioned diagnoses are directly related to the release of adrenocorticotropic hormone (ACTH) and a persistently elevated production of cortisol. They are also closely linked to adverse childhood environments [9], histories of violence and neglect [10], substance abuse [11] and mental health disorders, especially depression and anxiety [5, 12, 13]. These facts have been associated with an exacerbated production of glucocorticoids, which disrupts the hypothalamic-pituitary-adrenal (HPA) axis response system [14, 15]. Psychosocial risk factors and mental health disorders, such as depression, anxiety and chronic stress, have been studied by analyzing their possible relationship with premature birth, low birth weight, preeclampsia, intrauterine growth restriction, and gestational diabetes [16, 17, 18, 19]. Such psychosocial factors induce an adverse pregnancy outcome, concomitantly with risks factors that increase perinatal morbidity and mortality [8]. To determine this risk, obstetric ultrasound monitoring is usually performed in conjunction with Doppler blood flow assessment of the right and left uterine arteries in order to establish the flow received by the fetus from the uterine bed [20, 21]. Uterine artery Doppler abnormalities, such as increased pulsatility index (PI) and/or persistent diastolic notch, have been associated with complications linked to placental perfusion insufficiency, including pre-eclampsia and fetal growth restriction [22, 23]. Since the PI shows a progressive physiological decrease throughout gestation, its value is considered abnormal when it is above the 95 th percentile for the corresponding gestational age, a criterion used for identifying alterations in uteroplacental perfusion [20, 21]. The role of elevated cortisol in poor perfusion and how this might impact the development of angiogenesis in the placental villi is still poorly understood. Cortisol measurements can be performed in different biological matrices, such as samples of urine, saliva or blood. The values obtained using this methodology reflect the cortisol level at a specific time, which can be affected by the circadian variation of the HPA axis [24, 25, 26] thus constituting a challenge for the study. Other methods exist, however, that allow for a more stable retrospective evaluation, such as the measurement of cortisol in hair, emerging as a promising biomarker that reflects the cortisol accumulated in the hair follicle, as its constant growth provides an integration of cortisol production over weeks or months [26, 27]. This reinforces its usefulness for characterizing the long-term functioning of the HPA axis in various clinical conditions aa well as in chronic stress [26, 27, 28]. The objective of this research was to relate capillary cortisol levels and mental health, biopsychosocial factors during pregnancy, obstetric pathologies such as hypertensive syndrome of pregnancy and gestational diabetes, along with placental morphology, with the aim of understanding their role in fetal development. METHODS A closed dynamic cohort was used, which included a sample of 114 pregnant women, from a population base captured before 14 weeks of gestation in the prenatal control admissions from four Family Health Centers and the Guillermo Gran Benavente Hospital in Concepción, Chile. Only healthy pregnant women who were not taking medication and had no alcohol or drug dependency problems were included in our study. This research was approved by the Quality Committee of each Family Health Center involved, the Ethics Committee of the Health Service, and the Guillermo Grant Benavente Hospital in Concepción, Chile (CEC-SSC Code: 23-11-55). The background information was collected at the start of prenatal care and throughout the pregnancy. The complete process is explained in detail below: Background collection: Background information was gathered through a questionnaire on the participants' clinical and sociodemographic history. The instrument included age, occupation, previous and current obstetric history, mental health diagnoses prior to pregnancy, maternal weight and height, paternal history and presence of associated pathologies. Instruments used: Life course violence screening : The life course violence screening instrument, developed by the International Planned Parenthood Federation/Western Hemisphere Region (IPPF_RHO), was used [29, 30]. This instrument includes five sections intended to identify psychological, physical, sexual (in adulthood and childhood) and economic violence that occurred during childhood, adolescence, youth or in previous pregnancies, also allowing the identification of the type of aggressor (known or unknown) and, if applicable, in a family relationship. The instrument has demonstrated high reproducibility and stability for the detection of different types of violence against women, with kappa concordance values ranging from 0.63 to 1.00 [30,31]. Edinburgh Postnatal Depression Scale (EPDS ): A 10-item screening instrument designed to assess the presence of depressive symptoms during the perinatal period was applied. Each item was answered using a four-point Likert scale (0–3), with a total score ranging from 0 to 30 points. This scale does not constitute a diagnostic tool per se, but rather a screening instrument for identifying probable perinatal depression. In the Chilean pregnant population, the EPDS has demonstrated adequate psychometric properties, with high internal consistency (Cronbach’s α = 0.914) [32, 33]. Psychosocial Risk Scale in Pregnancy (EPsA) . This instrument was used to characterize maternal psychosocial risk. The EPSA is part of the guidelines of the Chilean Ministry of Health and is routinely applied in prenatal care in primary health care [34]. Hair sample collection : Hair samples approximately 3 cm in length were collected, corresponding to a retrospective three-month period of hormonal exposure. The first sample was obtained after the first prenatal visit; the second and third samples were collected three and six months after enrollment, respectively. Some losses to follow-up were recorded due to the participant’s change of address and pregnancy loss. The samples were obtained from the posterior vertex region of the head, following methodological recommendations previously published [35, 36]. For the analysis, the 3 cm proximal to the scalp were considered. The hair samples were washed with 15 ml pure isopropanol (2-propanol, ≥99.9%, Merck, code 1010404000) to remove external contaminants and subsequently subjected to a four-wash cycle with HPLC-grade methanol, using volumes of 1 ml, 0.5 ml, 1 ml, and 0.5 ml, respectively. The hair samples were left to stand for 4 days for complete evaporation of the methanol before being analyzed. Subsequently, the cortisol level was quantified by a chemiluminescence immunoassay autoanalyzer (CLIA), using the commercial Snibe kit (China) on the MAGLUMI 800 equipment. The extraction and analysis protocols were designed by the research team, following some previously published methodological guidelines [35, 36, 37]. Collection and evaluation of the placenta : The morphological and morphometric characteristics of each placenta were established, including the type of placenta and the insertion zone of the umbilical cord, weight, area and thickness of the placenta, number of cotyledons, the presence and number of thrombi, length of the umbilical cord, the number of blood vessels, as well as the identification of fibrin deposits and false and true knots of the umbilical cord. After macroscopic analysis, three cotyledons per placenta were randomly selected, using as a referential frame the quadrants defined in the macroscopic planimetry. These cotyledons were subsequently processed for the histological and morphometric analysis. Each selected cotyledon was subdivided into several fragments by perpendicular cuts, generating similar-sized fractions 1x1 cm. Subsequently, three fragments were randomly selected for histological processing. This procedure reduced the volume of tissue processed while maintaining the spatial representativeness of the cotyledon and capturing structural heterogeneity along the Z-axis. Serial histological sections were made from each fragment, separated by 100 µm, and stained using the standard Hematoxylin-Eosin technique. Following a uniform systematic sampling design with random start (SURS), three slides per block were selected. The whole procedure is depicted in Figure 1. Figure 1. Placental sampling and stereological workflow: A. Schematic representation of the whole placenta showing cotyledon selection. B. Detailed view of one of the selected cotyledons and the chorionic plate, including sampling regions: (B1) superficial region, (B2) deep region, and (B3) chorionic plate region. C. Systematic uniform random sampling of histological sections obtained from the selected tissue regions. D. Tissue block obtained from the selected regions for histological processing. For the microscopic analysis, the slides were scanned using an Olympus VS120 microscope and over each region of interest a grid of fields (tiles) of equal size (1536 × 1152 pixels) and uniform spacing was generated. To determine the number of fields, the error coefficient (EC) was first calculated using 3 reference-cotyledon samples. It was estimated that the EC should be ≤ 5%, and for this study, an EC of ≈ 1.0% was calculated. The formula EC(Vv) ≈ √[ Vv (1 − Vv) / ΣPreference], Vv corresponding to ‘Volume density’ was used, where the total number of counted points is fundamental. Using the grid of fields previously described, 5 fields were randomly selected per region (superficial, deep, and chorionic plate), resulting in a total of 45 fields per placenta. A total of 10 placentas were analyzed, divided into a group of 5 cases belonging to placentas with high cortisol levels and another group of 5 placentas with values close to the sample mean. In each selected field, the M42 test grid was applied for the estimation of Vv, counting the points that contacted terminal villi. Obstetric ultrasound evaluation : Follow-up was performed with serial obstetric ultrasound plus Doppler evaluation of the right and left uterine arteries by means of the PI measurement, calculating the average of these two measurements during the first trimester of pregnancy, between 11-13+6 weeks; the second trimester, between 22-26 weeks; and in the third trimester, between 32-34 weeks of gestation. The data obtained were both qualitative and quantitative, analyzed using univariate methods. For quantitative variables, the mean, standard deviation, median, minimum, and maximum values were calculated. For qualitative variables, absolute and relative percentage frequencies were calculated. A bivariate analysis was used to determine differences in the distribution of cortisol measurement values, according to psychosocial variables, using the non-parametric Mann Whitney test or the Student's t -test. When the cortisol levels were correlated with the average uterine artery PI results, the Spearman's rank correlation coefficient was used, while normality was assessed using the Shapiro-Wilk test. Data was tabulated in an Excel database and analyzed using the SPSS V.25 statistical software. A confidence level of α = 0.05 was applied. RESULTS A total of 114 pregnant women were enrolled in the present study, with an average age of 29.73 ± 5.23 years. Of these, 87.72% were in a stable relationship, while the average age of the father was 30.95 ± 7.95 years. Regarding the biological history, the average weight at the start of pregnancy was 72.87 ± 17.99 kg, with an average body mass index (BMI) of 28.66 ± 5.85 kg/m² at the start of pregnancy. As for obstetric history, 49.12% of the women were multiparous and 48.21% had a previous vaginal delivery. In the current pregnancy, 15.79% of the participants developed gestational diabetes (GD) and/or hypertensive disorders of pregnancy (HDP), such as preeclampsia and/or eclampsia. The psychosocial characterization of the sample was also carried out, observing that 36.3% (n = 80) of the participants presented psychosocial risk. Depressive symptoms were also investigated using the EPDS, as already mentioned, obtaining an average score of 6 ± 7 in participants with a score higher than 1 point (n = 63). It was also found that 18.4% of pregnant women presented a history of diagnosis of a mental health condition, such as depression (endogenous or major), anxiety, or both, throughout their lives and that they were not currently under any pharmacological or therapeutic treatment. In relation to the history of violence throughout life, this was classified as emotional, physical and/or sexual harm, which could have occurred during childhood, adolescence, adulthood, a previous pregnancy or in more than one period. All data is depicted in Table I. TABLE I. Demographic characteristics of participating parents Variable \(\:\stackrel{-}{\varvec{x}}\pm\:\varvec{s}\) Age at pregnancy (years) Range 29,73 ± 5,23 19–42 Father’s age (years) Range 30,95 ± 7,95 19–50 Weight (kilograms) Range 72,87 ± 17,99 40,7–99,6 Variable n (%) Stable partner 100 (87,7) First pregnancy 58 (50,9) Multiparous 56 (49,1) Previous vaginal delivery 27 (48,2) Previous cesarean delivery 19 (33,9) Patologies during pregnancy (DG-SHE) 18 (15,8) History of mental health disorders 21 (18,4) History of violence during the life cycle Emocional trauma Yes 58 (51,8) No 54 (48,2) Physical damage Yes 47 (42,3) No 64 (57,7) Forced to have sex Yes 43 (38,4) No 69 (61,6) Remembers being touched in her childhood Yes 49 (44,1) No 62 (55,9) Data are presented as n (%) for categorical variables and mean ± s for continuous variables. Capillary cortisol levels varied throughout pregnancy. In the first trimester, the average value was 4.1 ± 4.3 ng/ml, in the second trimester it reached 11.5 ± 14.8 ng/ml, and in the third trimester it was 6.6 ± 4.5 ng/ml. These values were correlated with the variables described previously. The pulsatility index (PI) of the right and left uterine arteries was also determined, and its average showed a progressive decrease throughout the pregnancy. In the first ultrasound, the average PI was 1.38 ± 0.37. In the second ultrasound, the PI decreased to 0.90 ± 0.24, while the lowest value was observed in the third ultrasound, with an average of 0.65 ± 0.13 (see Table II). This downward trend reflects a progressive reduction in uterine vascular resistance as pregnancy progresses, consistent with a physiological uteroplacental vascular remodeling process. TABLE II. Capillary cortisol level and uterine artery pulsatility index (UAPI) in the first, second and third trimesters of pregnancy Variables n \(\:\stackrel{-}{\varvec{x}}\pm\:\varvec{s}\) \(\:{\varvec{M}}_{\varvec{e}}\) Min. - Max. Capillary cortisol level 1st trimester (ng/ml) 112 4,1 ± 4,3 2,5 0,5–30,6 1st RLU 112 927541 ± 112214 956644 493879–1105531 2nd trimester (ng/ml) 92 11,5 ± 14,8 10,3 0,5–132 2nd RLU 92 753561 ± 152842 752671 152679–1078298 3rd trimester (ng/ml) 69 6,6 ± 4,5 5,5 0,5–18,2 3rd RLU3 69 844978 ± 113004 857872 594269–1080962 Pulsatility index of uterine arteries 1st Ultrasound IP 90 1,38 ± 0,37 1,35 0,61 − 2,32 2nd Ultrasound IP 80 0,9 ± 0,24 0,9 0,4 − 1,6 3rd Ultrasound IP 53 0,65 ± 0,13 0,63 0,43 − 1 \(\:\stackrel{-}{x}\) : Mean, \(\:s\) : Standard deviation, \(\:{M}_{e}\) : Media, Min.: Minimum value, Max.: Maximum value. The association between capillary cortisol levels measured in the first, second and third trimesters of pregnancy and the dimensions of the lifetime violence screening questionnaire (IPPF_RHO) was also analyzed. The results, displayed in Table III, showed a statistically significant association between second-trimester capillary cortisol levels and a history of emotional and/or physical violence (p < 0.042). However, this association did not persist when analyzing the third trimester. The relationship between cortisol levels of the first trimester and EPDS and EPsA scores was also evaluated and the results are depicted in Table IV. None of these variables showed a statistically significant relationship with capillary cortisol levels. TABLE III. Capillary cortisol levels in the first, second, and third trimesters according to the type of emotional, physical, and sexual violence. Variables Emotional violence n \(\:\stackrel{-}{\varvec{x}}\pm\:\varvec{s}\) \(\:{\varvec{M}}_{\varvec{e}}\) Min. - Max. p - value Capillary cortisol levels 1st trimester (ng/ml) Yes 58 4 ± 4 2,5 0,5–19,3 0,26 No 53 4,3 ± 4,6 2,5 0,5–30,6 2nd trimester (ng/ml) Yes 47 8,9 ± 6,9 7,5 0,5–26 0,042 No 44 14,5 ± 19,8 11,8 0,5–132 3rd trimester (ng/ml) Yes 34 6,9 ± 5 5,4 0,5–18,2 0,854 No 34 6,4 ± 4,2 5,6 0,5–16,4 Physical violence 1st trimester (ng/ml) Yes 47 4,2 ± 5,5 2,5 0,5–30,6 0,043 No 63 4,1 ± 3,2 2,5 0,5–13,6 2nd trimester (ng/ml) Yes 36 11,2 ± 21,7 7,1 0,5–132 0,028 No 54 11,7 ± 7,9 11,1 0,5–44,7 3er trimestre (ng/ml) Yes 25 6,9 ± 4,9 5,2 0,5–18,2 0,851 No 42 6,6 ± 4,4 5,7 0,5–16,5 Sexual violence 1st trimestre (ng/ml) Yes 43 4,5 ± 4,4 2,5 0,5–19,3 0,842 No 68 3,8 ± 4,2 2,5 0,5–30,6 2nd trimester (ng/ml) Yes 35 10 ± 6,9 10,3 0,5–26 0,912 No 56 12,6 ± 18,1 10,4 0,5–132 3rd trimester (ng/ml) Yes 25 6,1 ± 4,1 5,9 0,5–16,5 0,633 No 43 6,9 ± 4,8 5,5 0,5–18,2 \(\:\stackrel{-}{x}\) : Mean, \(\:s\) : Standard deviation, \(\:{M}_{e}\) : Media, Min.: Minimum value, Max.: Maximum value TABLE IV. Association of capillary cortisol level in the first trimester of pregnancy with the Edinburgh Postnatal Depression Scale (EPDS) and Psychosocial Risk Scale (EPsA) Variables EPDS Score Correlation coeffecient p-value 1st trimester (ng/ml) -0,048 0,711 1st RLU 0,003 0,984 Mean result (ng/ml) 0,280 0,089 Mean RLU -0,249 0,132 EPsA Score EPsA n \(\:\stackrel{-}{\varvec{x}}\pm\:\varvec{s}\) \(\:{\varvec{M}}_{\varvec{e}}\) Min. Max. p -value 1st trimester (ng/ml) With risk 29 5,82 ± 6,49 2,5 0,5–30,56 0,907 Without risk 51 3,99 ± 3,16 2,5 0,5–13,4 1st RLU With risk 29 899322 ± 151558 956611 493879–1105531 0,409 Without risk 51 925567 ± 99551 945567 684264–1101126 Mean result (ng/ml) With risk 29 9,87 ± 14,45 6,8 0,5–81,3 0,158 Without risk 51 6,77 ± 4,35 6,4 0,8–23,6 Mean RLU With risk 29 825942 ± 149543 826162 323279–1105531 0,433 Without risk 51 846923 ± 88742 853517 685731–1022752 \(\:\stackrel{-}{x}\) : Mean, \(\:s\) : Standard deviation, \(\:{M}_{e}\) : Media, Min.: Minimum value, Max.: Maximum value. Capillary cortisol in the first, second, and third trimesters of pregnancy were analyzed in relation to the history of mental health pathologies prior to pregnancy, showing a statistically significant association between cortisol levels in the second trimester and the presence of depression, anxiety, or both, with a p-value of 0.033. Likewise, gestational diabetes (GD) and hypertensive syndrome of pregnancy (HSP), whether preeclampsia, eclampsia or both, showed statistically significant associations with capillary cortisol levels in the first and second trimesters of pregnancy, with p values of 0.015 and 0.013, respectively (see Table V). TABLE V. Association of capillary cortisol levels in the first, second, and third trimesters according to a history of mental health disorders and pathologies during pregnancy. Variables Mental Health Pathologies n \(\:\stackrel{-}{\varvec{x}}\pm\:\varvec{s}\) \(\:{\varvec{M}}_{\varvec{e}}\) Min. Max. p value 1st trimester (ng/ml) Yes 21 6,4 ± 7,3 2,5 0,5–30,6 0,059 No 91 3,5 ± 3 2,5 0,5–13,6 2nd trimester (ng/ml) Yes 15 20,7 ± 31,4 16 2,3–132 0,033 No 77 9,7 ± 7,7 9,2 0,5–44,7 3rd trimester (ng/ml) Yes 12 9 ± 4,9 7,5 2,1–16,5 0,051 No 57 6,1 ± 4,3 4,7 0,5–18,2 Mean (ng/ml) Yes 12 8,37 ± 3,22 8,47 3,11–12,73 0,086 No 55 6,62 ± 3,58 6,06 1,17 − 13,73 Pathologies during pregnancy 1er trimester (ng/ml) Yes 18 5,2 ± 4,2 3,5 2,5–19,3 0,015 No 28 3,1 ± 1,8 2,5 0,5–10,4 2nd trimester (ng/ml) Yes 16 14,8 ± 7,4 16,1 0,5–26 0,013 No 23 8,9 ± 6,3 9,2 0,5–20,6 3rd trimester (ng/ml) Yes 14 7,6 ± 3,9 7,8 0,5–14,1 0,474 No 21 6,9 ± 4,5 5,6 0,5–16,4 Mean (ng/ml) Yes 14 8,9 ± 3,42 8,56 3,11–13,7 0,034 No 21 6,47 ± 3,54 5,78 1,17 − 13,68 \(\:\stackrel{-}{x}\) : Mean, \(\:s\) : Standard deviation, \(\:{M}_{e}\) : Media, Min.: Minimum value, Max.: Maximum value. Capillary cortisol levels in the first, second, and third trimesters of pregnancy were analyzed in relation to the uterine artery pulsatility index (UAPI). As is shown in Table VI, no statistically significant association was observed between UAPI and cortisol levels during the first and third trimesters. However, in the second trimester of pregnancy, a statistically significant association (p < 0.01) was found between UAPI and the capillary cortisol value at that stage. TABLE VI. Association of capillary cortisol levels in the first, second, and third trimesters according to the uterine artery index during pregnancy. Variables Correlation coeffecient p-value IP. AU 1st ultrasound 1st trimester (ng/ml) -0,014 0,893 1st RLU 0,062 0,562 IP. AU 2nd ultrasound 2nd trimester (ng/ml) 0,307 0,01 2nd RLU -0,312 0,009 IP. AU 3rd ultrasound 3rd trimester (ng/ml) -0,057 0,725 3rd RLU 0,09 0,576 Morphological and morphometric characteristics of the human placenta were also determined (n = 72). In this regard, 97.2% of the placentas were of the discoidal type. Regarding umbilical cord insertion, 77.78% (n = 56) evidenced a central insertion, which was the most frequent form of presentation. The average placental weight was 542.9 g, while the average thickness was 17.32 mm, and the average placental area was 292.01 cm² (see Table VII). TABLE VII. Morphological and morphometric characteristics of the term human placenta. Variable (Placentas n = 72) \(\:\stackrel{-}{\varvec{x}}\pm\:\varvec{s}\) Weight (grams) Range 542,90 ± 101,31 333–811 Thickness (mm) Range 17,32 ± 6,85 7–37 Area (cm 2 ) Range 292,01 ± 57,93 165–484 Cotyledons (unit) Range 17,92 ± 5,76 6–33 Variable (Placentas n = 72) n (%) Thrombi 14 (19,4) Fibrin deposits 67 (93,01) Discoidal placenta 70 (97,22) Succenturiated placenta 2 (2,78) Placenta with velamentous insertion of the umbilical cord 1 (1,39) Data are presented as n (%) for categorical variables and mean ± s for continuous variables. In addition to the morphological evaluation described above (See Fig. 2 A–B) the Vv of the terminal villi was determined in samples obtained from the superficial chorion, deep chorion, and chorionic plate (See Fig. 2 C–D). The average terminal villi Vv in the studied group was 24.89% (See Fig. 2 C–D). When comparing the groups according to capillary cortisol levels (Fig. 3 ), a statistically significant difference was observed in the percentage of terminal villi volume density between the groups with high capillary cortisol levels and those with values close to the group average, with p = 0.008 (see Table VIII). Fetal surface of the human placenta showing the chorionic plate, which constitutes the fetal surface of the placenta and is covered by the amnion. The central insertion of the umbilical cord is evident. Scale bar: 1 cm. Maternal surface of the human placenta showing the cotyledons (arrow b) and intercotyledonary grooves. (white line) Scale bar: 1 cm. Histological section of the human placenta, corresponding to the superficial chorion, illustrating the general organization of placental tissue. Hemoatoxylin-Eosin Staining. Scale bar: 1 mm. Terminal placental villi at higher magnificationwith application of the M42 grid for stereological point counting used to estimate volume density. Scale bar: 50 µm. Table VIII. Association of high capillary cortisol level according to terminal villi volume density. Variable cortisol level Percentage of terminal villi Groups \(\:\stackrel{-}{\varvec{x}}\pm\:\varvec{s}\) \(\:{\varvec{M}}_{\varvec{e}}\) Min - Max. p - value Medium 5 29,88 \(\:\pm\:\text{5,11}\) 31,2 23,8–36 0,008 High 5 18,44 \(\:\pm\:\text{4,94}\) 18,1 10,7–22,9 \(\:\stackrel{-}{x}\) : Mean, \(\:s\) : Standard deviation, \(\:{M}_{e}\) : Media, Min.: Minimum value, Max.: Maximum value. DISCUSSION Maternal cortisol production is regulated by the hypothalamic-pituitary-adrenal (HPA) axis, whose activation has been consistently associated with various mental health pathologies, particularly depression and anxiety [ 5 , 12 , 13 ], as well as with the social and environmental conditions in which people live [ 9 , 10 , 11 ]. These associations have been documented mainly through the measurement of cortisol performed in short-term biological matrices, such as saliva and blood, which only reflect acute or short-term hormone levels regulated by circadian variation [ 24 , 25 , 26 ]. From a physiological point of view, it is important to consider that cortisol levels normally increase two to three times toward the end of pregnancy. This is due to the progressive increase in placental secretion of corticotropin-releasing hormone (CRH), which acts through positive feedback on the HPA axis [ 38 ]. This event does not interfere with the findings of the present study, in which a rise in cortisol was observed in the second trimester and a stabilization in the third trimester, when evaluated retrospectively using capillary cortisol, a technique that reflects the hormonal exposure accumulated over time. The results of the present study are consistent with the previously described evidence, in which a statistically significant association has been observed between the presence of mental health pathologies diagnosed before gestation and the levels of cortisol detected in the hair of pregnant women. However, they differ in their methodological approach, since in our study the analysis was based on capillary cortisol measured in each trimester of pregnancy, allowing for a longitudinal assessment of hormonal exposure. Unfortunately, these differences hinder the standardization of the assessment and, therefore, the establishment of reference values for normality. The technique used in the present study allows for a retrospective evaluation of cortisol exposure, reflecting the cumulative secretion of the hormone over prolonged periods, offering a more stable approach to HPA axis activity, as it is less susceptible to circadian variations and biases associated with the collection of traditional matrices [ 24 , 25 , 26 , 27 ]. Studies that have compared capillary cortisol with repetitive daytime saliva collection schemes, for example, daytime measurements for 3 days (3 times/day) in each quarter, have shown greater validity and reliability of cortisol values measured in hair, by avoiding the methodological difficulties associated with collection, making these results much more reliable [ 35 , 37 ]. In the present study, although the participants had a history of mental health conditions prior to pregnancy, they were not receiving active pharmacological or therapeutic intervention at the time of the evaluation, not specifically due to discharge from the Health Care System. These findings reinforce the importance of incorporating mental health assessment and management into preconception check-ups, promoting timely interventions, education on the continuity of treatments and the prevention of therapeutic dropout, as well as the integration of the psychosocial team in the follow-up of women during the reproductive process. Regarding the subject of environmental conditions, several studies have focused on the impact of chronic stress during pregnancy, associated with psychosocial risk factors, and on its effects on both maternal cortisol production and the offspring [ 39 , 40 , 41 ]. However, the available literature does not always clearly distinguish whether such psychosocial risk conditions originate specifically during pregnancy or whether they correspond to pre-existing situations in the woman's life before pregnancy. The results of this study contribute to clarify this aspect, by showing that psychosocial factors and mood changes occurring during pregnancy are not necessarily associated with high levels of maternal cortisol. In contrast, the presence of previously diagnosed mental health conditions is associated with increased cortisol production throughout pregnancy. These findings suggest that a woman's prior psychosocial history may play a more significant role in the sustained activation of the HPA axis than isolated pregnancy stressors. It is worth noting that, in current clinical practice, prenatal check-ups routinely incorporate screening for psychosocial risk factors and depressive symptoms during pregnancy [ 42 ], although pre-pregnancy psychosocial conditions are not systematically assessed. Among the identified vulnerability factors, violence emerges as a fundamental component to consider, not only that present during pregnancy, but also that experienced in early stages of life, such as childhood and adolescence. This perspective is consistent with evidence from adverse childhood experiences (ACES) studies [ 2 , 5 , 43 ], which have shown that such early exposures are associated with effects on physical and mental health in adulthood. These effects include lasting alterations in HPA regulation, as well as an increased risk of developing cardiovascular diseases throughout life [ 44 ]. In accordance with this evidence, the results of the present study show an association between elevated cortisol levels and the presence of obstetric cardiovascular pathologies, such as hypertensive disorders of pregnancy, preeclampsia, and gestational diabetes—conditions that share similarities with cardiovascular alterations described in non-pregnant populations [ 45 , 46 ]. However, the available evidence in pregnant populations that integrates these variables remains limited, reinforcing the need for further research in this area. For the assessment of fetal well-being in the context of cardiovascular pathologies of pregnancy, the measurement of blood flow in the uterine arteries during the first, second, and third trimesters of gestation is routinely used. Alterations in this flow, expressed as an increase in the PI, have been associated with poor uteroplacental perfusion and a higher risk of adverse perinatal outcomes [ 22 , 23 ]. In this study, the PI values obtained in the different trimesters were within ranges considered normal and were also consistent with the angiogenic and vasculogenic changes expected during pregnancy. However, a statistically significant association was observed between the second-trimester PI and maternal cortisol levels, suggesting a possible interaction between activation of the hypothalamic-pituitary-adrenal axis and uteroplacental vascular adaptation. It is well known that the placenta, as a central organ in maternal-fetal exchange, plays a fundamental role in the well-being of the fetus, and its dysfunction has been related to various obstetric pathologies, such as hypertensive syndrome of pregnancy, intrauterine growth restriction and acute fetal distress, conditions that increase perinatal morbidity and mortality [ 47 , 48 ]. In this study, a significant relationship was found between maternal cortisol levels and placental terminal villi Vv, a finding consistent with previous reports describing alterations in villi volume in pathologies such as gestational diabetes and hypertensive disorders of pregnancy [ 49 , 50 ]. Considering that terminal villi constitute the main functional unit for gas and nutrient exchange, modifications in their structural organization could represent adaptive mechanisms against conditions of intrauterine deprivation [ 51 ]. These alterations would have the potential to interfere with fetal growth and development, contributing to fetal programming processes that not only impact child health, but could also influence the risk of diseases in adult life [ 52 ]. CONCLUSIONS During pregnancy, various psychosocial risk factors are investigated that can negatively interfere with both the course of the pregnancy and the well-being of the child. The results of this study demonstrate the need to further evaluate mental health history prior to pregnancy, even in women who are not under active control for these conditions at the time of pregnancy. Likewise, the psychosocial history during childhood and adolescence emerges as a relevant element, given that experiences at this stage of life can have a sustained impact on cortisol production and, consequently, modulate the functioning of the hypothalamic-pituitary-adrenal axis, a phenomenon widely described in the general population. In the context of pregnancy, this sustained activation of the HPA axis could contribute to the development of cardiovascular pathologies typical of this stage, with a direct and cascading impact on neonatal and infant morbidity and mortality. Taken together, the background information provided in this work reinforces the relevance of incorporating a longitudinal and life course perspective in the assessment of psychosocial risk during pregnancy, which should be considered not only in prenatal care, but also in preconception assessments, in order to promote more comprehensive maternal and child health care. It should be noted that this study presents some limitations that must be considered when interpreting its results and that are essential to address in future research. Among these, the evaluation of capillary cortisol stands out, since there are currently no standardized reference values that allow for a clear classification of the results within ranges considered normal or pathological. This situation is attributable to the heterogeneity of the analytical methodologies and collection methods used. Furthermore, gaps remain in our understanding of how the hypothalamic-pituitary-adrenal axis adapts during pregnancy and how elevated or decreased cortisol levels might interfere with placental function and the regulation of this hormone. Finally, a differentiated characterization of the effects of depression, depressive symptoms, and other mental health diagnoses is necessary to advance toward a more precise understanding of their biological and clinical implications during pregnancy. Declarations Funding This study was funded by the Doctoral Scholarship of the National Research and Development Agency (ANID), Chile (Register number: 21212312). Conflict of interest The authors declare that they have no conflicts of interest. Consent for publication . All authors have read and approved the manuscript and consent to its publication. Data availability The datasets generated and/or analyzed during this study are available upon reasonable request to the corresponding author. Materials availability The materials used in this study are available upon reasonable request to the corresponding author. Code availability: Not aplicable Acknowledgements The authors wish to express their gratitude to the Víctor Manuel Fernández, Tucapel, Santa Sabina, and O’Higgins Family Health Centers, as well as to the Guillermo Grant Benavente Hospital in Concepción, Chile. This gratitude is also extended to each woman who participated and placed her trust in this research. Author contributions JE participated in the drafting of the introduction, conceptualization, data collection, data analysis, manuscript drafting, review, and editing. MM participated in the review and analysis of the methodology. MDS participated in the supervision, manuscript review, and editing. XF performed the uterine artery Doppler assessments. MG contributed to the supervision and sponsorship of the Maternal-Fetal Research Laboratory (LIMaF). 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8682776","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":595423531,"identity":"0a006208-1f47-48a1-bd8f-a2f1cee0eb1d","order_by":0,"name":"Jusselit T. 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Schematic representation of the whole placenta showing cotyledon selection. B. Detailed view of one of the selected cotyledons and the chorionic plate, including sampling regions: (B1) superficial region, (B2) deep region, and (B3) chorionic plate region. C. Systematic uniform random sampling of histological sections obtained from the selected tissue regions. D. Tissue block obtained from the selected regions for histological processing.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8682776/v1/2742ab57dec0124756143142.jpg"},{"id":103397934,"identity":"c7aa72db-3bd2-49d6-8047-0cb198b9793f","added_by":"auto","created_at":"2026-02-25 08:58:21","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":220490,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMacroscopic and histological features of the human placenta and stereological analysis.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Fetal surface of the human placenta showing the chorionic plate, which constitutes the fetal surface of the placenta and is covered by the amnion. The central insertion of the umbilical cord is evident. Scale bar: 1 cm.\u003c/p\u003e\n\u003cp\u003e(B) Maternal surface of the human placenta showing the cotyledons (arrow b) and intercotyledonary grooves. (white line) Scale bar: 1 cm.\u003c/p\u003e\n\u003cp\u003e(C) Histological section of the human placenta, corresponding to the superficial chorion, illustrating the general organization of placental tissue. Hemoatoxylin-Eosin Staining. Scale bar: 1 mm.\u003c/p\u003e\n\u003cp\u003e(D) Terminal placental villi at higher magnification\u003cdel\u003e, \u003c/del\u003ewith application of the M42 grid for stereological point counting used to estimate volume density. Scale bar: 50 µm.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8682776/v1/b39a463356e3f98485215f0f.jpg"},{"id":103398107,"identity":"474ac8da-a3c5-4cc8-93a7-84e0f33ccc98","added_by":"auto","created_at":"2026-02-25 08:58:48","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":31856,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTerminal villi volume density according to capillary cortisol group.\u003c/strong\u003e The box plot shows the distribution of Vv in the medium and high cortisol groups. The center line represents the median; the boxes correspond to the interquartile range (25\u003csup\u003eth\u003c/sup\u003e–75\u003csup\u003eth\u003c/sup\u003e percentiles); and the whiskers indicate the minimum and maximum values. The point identified as “110” corresponds to an individual outlier within the high cortisol group.\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8682776/v1/09006ad6b1f39889b0092015.jpg"},{"id":103398169,"identity":"34825e17-f028-450b-b4b0-1c1ecd2e4b3d","added_by":"auto","created_at":"2026-02-25 08:59:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1786249,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8682776/v1/a08d4a41-4388-4e4a-b5f1-b2d721b74d61.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mental health in pregnancy and capillary cortisol: Associations with biopsychosocial factors, obstetric complications and placental morphometry","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eMental health is an integral part of people’s health and well-being. This issue is essential for leading a fulfilling life and contributing to society. In this regard, it is not just the absence of illness, but the ability to cope with adversity [1]. \u0026nbsp;People who are exposed to adverse circumstances in their lives, especially during their earliest years, will present a greater risk of suffering from a mental health condition later in life [2]. \u0026nbsp;There have been documented several risk and protective factors that influence mental health, including individual factors related to emotional skills, genetics, or substance misuse, as well as social and environmental factors such as poverty, violence, and lack of support networks [1, 3, 4]. \u0026nbsp;Should these conditions occur during gestation and child-rearing, the repercussions are more likely to be transgenerational [2, 5]. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;The number of pregnant women with chronic stress, with diagnosis of major depression prior to pregnancy, and depressive symptoms detected during pregnancy, are currently reaching alarming levels. \u0026nbsp;The global prevalence of the major depressive disorder at some point during pregnancy has been reported to reach between 12.7% and 37% among the pregnant women population [6]. Regarding stress, it is estimated that between 25% and 40% of women have experienced chronic prenatal stress [7, 8]. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;The afore mentioned diagnoses are directly related to the release of adrenocorticotropic hormone (ACTH) and a persistently elevated production of cortisol. They are also closely linked to adverse childhood environments [9], histories of violence and neglect [10], substance abuse [11] and mental health disorders, especially depression and anxiety [5, 12, 13]. These facts have been associated with an exacerbated production of glucocorticoids, which disrupts the hypothalamic-pituitary-adrenal (HPA) axis response system [14, 15].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Psychosocial risk factors and mental health disorders, such as depression, anxiety and chronic stress, have been studied by analyzing their possible relationship with premature birth, low birth weight, preeclampsia, intrauterine growth restriction, and gestational diabetes [16, 17, 18, 19]. \u0026nbsp;Such psychosocial factors induce an adverse pregnancy outcome, concomitantly with risks factors that increase perinatal morbidity and mortality [8]. \u0026nbsp;To determine this risk, obstetric ultrasound monitoring is usually performed in conjunction with Doppler blood flow assessment of the right and left uterine arteries in order to establish the flow received by the fetus from the uterine bed [20, 21]. \u0026nbsp;Uterine artery Doppler abnormalities, such as increased pulsatility index (PI) and/or persistent diastolic notch, have been associated with complications linked to placental perfusion insufficiency, including pre-eclampsia and fetal growth restriction [22, 23]. \u0026nbsp;Since the PI shows a progressive physiological decrease throughout gestation, its value is considered abnormal when it is above the 95\u003csup\u003eth\u003c/sup\u003e percentile for the corresponding gestational age, a criterion used for identifying alterations in uteroplacental perfusion [20, 21].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;The role of elevated cortisol in poor perfusion and how this might impact the development of angiogenesis in the placental villi is still poorly understood. \u0026nbsp;Cortisol measurements can be performed in different biological matrices, such as samples of urine, saliva or blood. The values obtained using this methodology reflect the cortisol level at a specific time, which can be affected by the circadian variation of the HPA axis [24, 25, 26] thus constituting a challenge for the study. \u0026nbsp;Other methods exist, however, that allow for a more stable retrospective evaluation, such as the measurement of cortisol in hair, emerging as a promising biomarker that reflects the cortisol accumulated in the hair follicle, as its constant growth provides an integration of cortisol production over weeks or months [26, 27]. This reinforces its usefulness for characterizing the long-term functioning of the HPA axis in various clinical conditions aa well as in chronic stress [26, 27, 28].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;The objective of this research was to relate capillary cortisol levels and mental health, biopsychosocial factors during pregnancy, obstetric pathologies such as hypertensive syndrome of pregnancy and gestational diabetes, along with placental morphology, with the aim of understanding their role in fetal development.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eA closed dynamic cohort was used, which included a sample of 114 pregnant women, from a population base captured before 14 weeks of gestation in the prenatal control admissions from four Family Health Centers and the Guillermo Gran Benavente Hospital in Concepci\u0026oacute;n, Chile. Only healthy pregnant women who were not taking medication and had no alcohol or drug dependency problems were included in our study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;This research was approved by the Quality Committee of each Family Health Center involved, the Ethics Committee of the Health Service, and the Guillermo Grant Benavente Hospital in Concepci\u0026oacute;n, Chile (CEC-SSC Code: 23-11-55). The background information was collected at the start of prenatal care and throughout the pregnancy. The complete process is explained in detail below:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBackground collection:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBackground information was gathered through a questionnaire on the participants\u0026apos; clinical and sociodemographic history. The instrument included age, occupation, previous and current obstetric history, mental health diagnoses prior to pregnancy, maternal weight and height, paternal history and presence of associated pathologies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstruments used:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eLife course violence screening\u003c/u\u003e: The life course violence screening instrument, developed by the International Planned Parenthood Federation/Western Hemisphere Region (IPPF_RHO), was used [29, 30]. This instrument includes five sections intended to identify psychological, physical, sexual (in adulthood and childhood) and economic violence that occurred during childhood, adolescence, youth or in previous pregnancies, also allowing the identification of the type of aggressor (known or unknown) and, if applicable, in a family relationship.\u003c/p\u003e\n\u003cp\u003eThe instrument has demonstrated high reproducibility and stability for the detection of different types of violence against women, with kappa concordance values ranging from 0.63 to 1.00 [30,31].\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eEdinburgh Postnatal Depression Scale (EPDS\u003c/u\u003e): A 10-item screening instrument designed to assess the presence of depressive symptoms during the perinatal period was applied. Each item was answered using a four-point Likert scale (0\u0026ndash;3), with a total score ranging from 0 to 30 points. \u0026nbsp;This scale does not constitute a diagnostic tool per se, but rather a screening instrument for identifying probable perinatal depression. In the Chilean pregnant population, the EPDS has demonstrated adequate psychometric properties, with high internal consistency (Cronbach\u0026rsquo;s \u0026alpha; = 0.914) [32, 33].\u003c/p\u003e\n\u003cp\u003e\u003cu\u003ePsychosocial Risk Scale in Pregnancy (EPsA)\u003c/u\u003e. This instrument was used to characterize maternal psychosocial risk. The EPSA is part of the guidelines of the Chilean Ministry of Health and is routinely applied in prenatal care in primary health care [34].\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eHair sample collection\u003c/u\u003e: Hair samples approximately 3 cm in length were collected, corresponding to a retrospective three-month period of hormonal exposure. The first sample was obtained after the first prenatal visit; the second and third samples were collected three and six months after enrollment, respectively. Some losses to follow-up were recorded due to the participant\u0026rsquo;s change of address and pregnancy loss. \u0026nbsp;The samples were obtained from the posterior vertex region of the head, following methodological recommendations previously published [35, 36]. For the analysis, the 3 cm proximal to the scalp were considered. \u0026nbsp;The hair samples were washed with 15 ml pure isopropanol (2-propanol, \u0026ge;99.9%, Merck, code 1010404000) to remove external contaminants and subsequently subjected to a four-wash cycle with HPLC-grade methanol, using volumes of 1 ml, 0.5 ml, 1 ml, and 0.5 ml, respectively.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;The hair samples were left to stand for 4 days for complete evaporation of the methanol before being analyzed. Subsequently, the cortisol level was quantified by a chemiluminescence immunoassay autoanalyzer (CLIA), using the commercial Snibe kit (China) on the MAGLUMI 800 equipment. The extraction and analysis protocols were designed by the research team, following some previously published methodological guidelines [35, 36, 37].\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCollection and evaluation of the placenta\u003c/u\u003e: The morphological and morphometric characteristics of each placenta were established, including the type of placenta and the insertion zone of the umbilical cord, weight, area and thickness of the placenta, number of cotyledons, the presence and number of thrombi, length of the umbilical cord, the number of blood vessels, as well as the identification of fibrin deposits and false and true knots of the umbilical cord.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; After macroscopic analysis, three cotyledons per placenta were randomly selected, using as a referential frame the quadrants defined in the macroscopic planimetry. These cotyledons were subsequently processed for the histological and morphometric analysis. \u0026nbsp;Each selected cotyledon was subdivided into several fragments by perpendicular cuts, generating similar-sized fractions 1x1 cm. Subsequently, three fragments were randomly selected for histological processing. This procedure reduced the volume of tissue processed while maintaining the spatial representativeness of the cotyledon and capturing structural heterogeneity along the Z-axis.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Serial histological sections were made from each fragment, separated by 100 \u0026micro;m, and stained using the standard Hematoxylin-Eosin technique. Following a uniform systematic sampling design with random start (SURS), three slides per block were selected. The whole procedure is depicted in Figure 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 1. Placental sampling and stereological workflow:\u003c/strong\u003e A. Schematic representation of the whole placenta showing cotyledon selection. B. Detailed view of one of the selected cotyledons and the chorionic plate, including sampling regions: (B1) superficial region, (B2) deep region, and (B3) chorionic plate region. C. Systematic uniform random sampling of histological sections obtained from the selected tissue regions. D. Tissue block obtained from the selected regions for histological processing.\u003c/p\u003e\n\u003cp\u003eFor the microscopic analysis, the slides were scanned using an Olympus VS120 microscope and over each region of interest a grid of fields (tiles) of equal size (1536 \u0026times; 1152 pixels) and uniform spacing was generated. \u0026nbsp; To determine the number of fields, the error coefficient (EC) was first calculated using 3 reference-cotyledon samples. It was estimated that the EC should be \u0026le; 5%, and for this study, an EC of \u0026asymp; 1.0% was calculated. The formula EC(Vv) \u0026asymp; \u0026radic;[ Vv (1 \u0026minus; Vv) / \u0026Sigma;Preference], Vv corresponding to \u0026lsquo;Volume density\u0026rsquo; was used, where the total number of counted points is fundamental.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Using the grid of fields previously described, 5 fields were randomly selected per region (superficial, deep, and chorionic plate), resulting in a total of 45 fields per placenta. A total of 10 placentas were analyzed, divided into a group of 5 cases belonging to placentas with high cortisol levels and another group of 5 placentas with values close to the sample mean. \u0026nbsp;In each selected field, the M42 test grid was applied for the estimation of Vv, counting the points that contacted terminal villi.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eObstetric ultrasound evaluation\u003c/u\u003e: Follow-up was performed with serial obstetric ultrasound plus Doppler evaluation of the right and left uterine arteries by means of the PI measurement, calculating the average of these two measurements during the first trimester of pregnancy, between 11-13+6 weeks; the second trimester, between 22-26 weeks; and in the third trimester, between 32-34 weeks of gestation. The data obtained were both qualitative and quantitative, analyzed using univariate methods. For quantitative variables, the mean, standard deviation, median, minimum, and maximum values were calculated. For qualitative variables, absolute and relative percentage frequencies were calculated.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;A bivariate analysis was used to determine differences in the distribution of cortisol measurement values, according to psychosocial variables, using the non-parametric Mann Whitney test or the Student\u0026apos;s \u003cem\u003et\u003c/em\u003e-test. \u0026nbsp; When the cortisol levels were correlated with the average uterine artery PI results, the Spearman\u0026apos;s rank correlation coefficient was used, while normality was assessed using the Shapiro-Wilk test. \u0026nbsp;Data was tabulated in an Excel database and analyzed using the SPSS V.25 statistical software. \u0026nbsp;A confidence level of \u0026alpha; = 0.05 was applied.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eA total of 114 pregnant women were enrolled in the present study, with an average age of 29.73\u0026thinsp;\u0026plusmn;\u0026thinsp;5.23 years. Of these, 87.72% were in a stable relationship, while the average age of the father was 30.95\u0026thinsp;\u0026plusmn;\u0026thinsp;7.95 years. Regarding the biological history, the average weight at the start of pregnancy was 72.87\u0026thinsp;\u0026plusmn;\u0026thinsp;17.99 kg, with an average body mass index (BMI) of 28.66\u0026thinsp;\u0026plusmn;\u0026thinsp;5.85 kg/m\u0026sup2; at the start of pregnancy. As for obstetric history, 49.12% of the women were multiparous and 48.21% had a previous vaginal delivery. In the current pregnancy, 15.79% of the participants developed gestational diabetes (GD) and/or hypertensive disorders of pregnancy (HDP), such as preeclampsia and/or eclampsia. The psychosocial characterization of the sample was also carried out, observing that 36.3% (n\u0026thinsp;=\u0026thinsp;80) of the participants presented psychosocial risk.\u003c/p\u003e \u003cp\u003eDepressive symptoms were also investigated using the EPDS, as already mentioned, obtaining an average score of 6\u0026thinsp;\u0026plusmn;\u0026thinsp;7 in participants with a score higher than 1 point (n\u0026thinsp;=\u0026thinsp;63). It was also found that 18.4% of pregnant women presented a history of diagnosis of a mental health condition, such as depression (endogenous or major), anxiety, or both, throughout their lives and that they were not currently under any pharmacological or therapeutic treatment. In relation to the history of violence throughout life, this was classified as emotional, physical and/or sexual harm, which could have occurred during childhood, adolescence, adulthood, a previous pregnancy or in more than one period. All data is depicted in Table I.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTABLE I. Demographic characteristics of participating parents\u003c/b\u003e \u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{\\varvec{x}}\\pm\\:\\varvec{s}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at pregnancy (years)\u003c/p\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29,73\u0026thinsp;\u0026plusmn;\u0026thinsp;5,23\u003c/p\u003e \u003cp\u003e19\u0026ndash;42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFather\u0026rsquo;s age (years)\u003c/p\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30,95\u0026thinsp;\u0026plusmn;\u0026thinsp;7,95\u003c/p\u003e \u003cp\u003e19\u0026ndash;50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kilograms)\u003c/p\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72,87\u0026thinsp;\u0026plusmn;\u0026thinsp;17,99\u003c/p\u003e \u003cp\u003e40,7\u0026ndash;99,6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStable partner\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (87,7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (50,9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiparous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (49,1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious vaginal delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (48,2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious cesarean delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (33,9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatologies during pregnancy (DG-SHE)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (15,8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of mental health disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (18,4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of violence during the life cycle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmocional\u0026nbsp;trauma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58\u0026nbsp;(51,8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54\u0026nbsp;(48,2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical damage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47\u0026nbsp;(42,3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64\u0026nbsp;(57,7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eForced to have sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43\u0026nbsp;(38,4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69\u0026nbsp;(61,6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRemembers being touched in her childhood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49\u0026nbsp;(44,1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62\u0026nbsp;(55,9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eData are presented as n (%) for categorical variables and mean\u0026thinsp;\u0026plusmn;\u0026thinsp;s for continuous variables.\u003c/p\u003e \u003cp\u003eCapillary cortisol levels varied throughout pregnancy. In the first trimester, the average value was 4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3 ng/ml, in the second trimester it reached 11.5\u0026thinsp;\u0026plusmn;\u0026thinsp;14.8 ng/ml, and in the third trimester it was 6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5 ng/ml. These values were correlated with the variables described previously.\u003c/p\u003e \u003cp\u003eThe pulsatility index (PI) of the right and left uterine arteries was also determined, and its average showed a progressive decrease throughout the pregnancy. In the first ultrasound, the average PI was 1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37. In the second ultrasound, the PI decreased to 0.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24, while the lowest value was observed in the third ultrasound, with an average of 0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13 (see Table II). This downward trend reflects a progressive reduction in uterine vascular resistance as pregnancy progresses, consistent with a physiological uteroplacental vascular remodeling process.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTABLE II. Capillary cortisol level and uterine artery pulsatility index (UAPI) in the first, second and third trimesters of pregnancy\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{\\varvec{x}}\\pm\\:\\varvec{s}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\varvec{M}}_{\\varvec{e}}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMin. - Max.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCapillary cortisol level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1st trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4,1\u0026thinsp;\u0026plusmn;\u0026thinsp;4,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,5\u0026ndash;30,6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1st RLU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e927541\u0026thinsp;\u0026plusmn;\u0026thinsp;112214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e956644\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e493879\u0026ndash;1105531\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2nd trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e11,5\u0026thinsp;\u0026plusmn;\u0026thinsp;14,8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,5\u0026ndash;132\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2nd RLU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e753561\u0026thinsp;\u0026plusmn;\u0026thinsp;152842\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e752671\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e152679\u0026ndash;1078298\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3rd trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6,6\u0026thinsp;\u0026plusmn;\u0026thinsp;4,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,5\u0026ndash;18,2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3rd RLU3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e844978\u0026thinsp;\u0026plusmn;\u0026thinsp;113004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e857872\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e594269\u0026ndash;1080962\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003ePulsatility index of uterine arteries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1st Ultrasound IP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1,38\u0026thinsp;\u0026plusmn;\u0026thinsp;0,37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,61\u0026thinsp;\u0026minus;\u0026thinsp;2,32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2nd Ultrasound IP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0,9\u0026thinsp;\u0026plusmn;\u0026thinsp;0,24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,4\u0026thinsp;\u0026minus;\u0026thinsp;1,6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3rd Ultrasound IP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0,65\u0026thinsp;\u0026plusmn;\u0026thinsp;0,13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0,63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,43\u0026thinsp;\u0026minus;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cspan class=\"InlineEquation\"\u003e \u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{x}\\)\u003c/span\u003e \u003c/span\u003e: Mean, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:s\\)\u003c/span\u003e\u003c/span\u003e: Standard deviation, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{M}_{e}\\)\u003c/span\u003e\u003c/span\u003e: Media, Min.: Minimum value, Max.: Maximum value.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThe association between capillary cortisol levels measured in the first, second and third trimesters of pregnancy and the dimensions of the lifetime violence screening questionnaire (IPPF_RHO) was also analyzed. The results, displayed in Table III, showed a statistically significant association between second-trimester capillary cortisol levels and a history of emotional and/or physical violence (p\u0026thinsp;\u0026lt;\u0026thinsp;0.042). However, this association did not persist when analyzing the third trimester.\u003c/p\u003e\u003cp\u003eThe relationship between cortisol levels of the first trimester and EPDS and EPsA scores was also evaluated and the results are depicted in Table IV. None of these variables showed a statistically significant relationship with capillary cortisol levels.\u003c/p\u003e\u003cp\u003e \u003cb\u003eTABLE III. Capillary cortisol levels in the first, second, and third trimesters according to the type of emotional, physical, and sexual violence.\u003c/b\u003e \u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabc\" border=\"1\"\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEmotional\u003c/p\u003e \u003cp\u003eviolence\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{\\varvec{x}}\\pm\\:\\varvec{s}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\varvec{M}}_{\\varvec{e}}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMin. - Max.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep - value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCapillary cortisol levels\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1st trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;19,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,3\u0026thinsp;\u0026plusmn;\u0026thinsp;4,6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;30,6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e2nd trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8,9\u0026thinsp;\u0026plusmn;\u0026thinsp;6,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0,042\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14,5\u0026thinsp;\u0026plusmn;\u0026thinsp;19,8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11,8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;132\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e3rd trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,9\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;18,2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,854\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,4\u0026thinsp;\u0026plusmn;\u0026thinsp;4,2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5,6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;16,4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003ePhysical violence\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1st trimester\u003c/p\u003e \u003cp\u003e(ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,2\u0026thinsp;\u0026plusmn;\u0026thinsp;5,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;30,6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,043\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,1\u0026thinsp;\u0026plusmn;\u0026thinsp;3,2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;13,6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e2nd trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11,2\u0026thinsp;\u0026plusmn;\u0026thinsp;21,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0,028\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11,7\u0026thinsp;\u0026plusmn;\u0026thinsp;7,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;44,7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e3er trimestre (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,9\u0026thinsp;\u0026plusmn;\u0026thinsp;4,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5,2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;18,2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,851\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,6\u0026thinsp;\u0026plusmn;\u0026thinsp;4,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;16,5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eSexual violence\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1st trimestre (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,5\u0026thinsp;\u0026plusmn;\u0026thinsp;4,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;19,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,842\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3,8\u0026thinsp;\u0026plusmn;\u0026thinsp;4,2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;30,6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e2nd trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u0026thinsp;\u0026plusmn;\u0026thinsp;6,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,912\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12,6\u0026thinsp;\u0026plusmn;\u0026thinsp;18,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;132\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e3rd trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,1\u0026thinsp;\u0026plusmn;\u0026thinsp;4,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;16,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,633\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,9\u0026thinsp;\u0026plusmn;\u0026thinsp;4,8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;18,2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{x}\\)\u003c/span\u003e\u003c/span\u003e: Mean, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:s\\)\u003c/span\u003e\u003c/span\u003e: Standard deviation, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{M}_{e}\\)\u003c/span\u003e\u003c/span\u003e: Media, Min.: Minimum value, Max.: Maximum value\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003e \u003cb\u003eTABLE IV. Association of capillary cortisol level in the first trimester of pregnancy with the Edinburgh Postnatal Depression Scale (EPDS) and Psychosocial Risk Scale (EPsA)\u003c/b\u003e \u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabd\" border=\"1\"\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c8\" namest=\"c2\"\u003e \u003cp\u003eEPDS Score\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCorrelation coeffecient\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1st trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003e-0,048\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0,711\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1st RLU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003e0,003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0,984\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003cp\u003eresult\u003c/p\u003e \u003cp\u003e(ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003e0,280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0,089\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean RLU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003e-0,249\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0,132\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c8\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eEPsA Score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eEPsA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{\\varvec{x}}\\pm\\:\\varvec{s}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\varvec{M}}_{\\varvec{e}}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e\u003cb\u003eMin.\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eMax.\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003ep -value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1st trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWith risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5,82\u0026thinsp;\u0026plusmn;\u0026thinsp;6,49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;30,56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,907\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWithout\u003c/p\u003e \u003cp\u003erisk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3,99\u0026thinsp;\u0026plusmn;\u0026thinsp;3,16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;13,4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1st RLU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWith risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e899322\u0026thinsp;\u0026plusmn;\u0026thinsp;151558\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e956611\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e493879\u0026ndash;1105531\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,409\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWithout\u003c/p\u003e \u003cp\u003erisk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e925567\u0026thinsp;\u0026plusmn;\u0026thinsp;99551\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e945567\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e684264\u0026ndash;1101126\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003cp\u003eresult\u003c/p\u003e \u003cp\u003e(ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWith risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9,87\u0026thinsp;\u0026plusmn;\u0026thinsp;14,45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6,8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;81,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,158\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWithout\u003c/p\u003e \u003cp\u003erisk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,77\u0026thinsp;\u0026plusmn;\u0026thinsp;4,35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0,8\u0026ndash;23,6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMean RLU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWith risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e825942\u0026thinsp;\u0026plusmn;\u0026thinsp;149543\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e826162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e323279\u0026ndash;1105531\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,433\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWithout\u003c/p\u003e \u003cp\u003erisk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e846923\u0026thinsp;\u0026plusmn;\u0026thinsp;88742\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e853517\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e685731\u0026ndash;1022752\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cspan class=\"InlineEquation\"\u003e \u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{x}\\)\u003c/span\u003e \u003c/span\u003e: Mean, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:s\\)\u003c/span\u003e\u003c/span\u003e: Standard deviation, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{M}_{e}\\)\u003c/span\u003e\u003c/span\u003e: Media, Min.: Minimum value, Max.: Maximum value.\u003c/p\u003e \u003cp\u003eCapillary cortisol in the first, second, and third trimesters of pregnancy were analyzed in relation to the history of mental health pathologies prior to pregnancy, showing a statistically significant association between cortisol levels in the second trimester and the presence of depression, anxiety, or both, with a p-value of 0.033. Likewise, gestational diabetes (GD) and hypertensive syndrome of pregnancy (HSP), whether preeclampsia, eclampsia or both, showed statistically significant associations with capillary cortisol levels in the first and second trimesters of pregnancy, with p values of 0.015 and 0.013, respectively (see Table V).\u003c/p\u003e \u003cp\u003e \u003cb\u003eTABLE V. Association of capillary cortisol levels in the first, second, and third trimesters according to a history of mental health disorders and pathologies during pregnancy.\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabe\" border=\"1\"\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMental Health\u003c/p\u003e \u003cp\u003ePathologies\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{\\varvec{x}}\\pm\\:\\varvec{s}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\varvec{M}}_{\\varvec{e}}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMin. Max.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1st trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,4\u0026thinsp;\u0026plusmn;\u0026thinsp;7,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;30,6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,059\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3,5\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;13,6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e2nd trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20,7\u0026thinsp;\u0026plusmn;\u0026thinsp;31,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2,3\u0026ndash;132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0,033\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9,7\u0026thinsp;\u0026plusmn;\u0026thinsp;7,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9,2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;44,7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e3rd trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;4,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2,1\u0026ndash;16,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,1\u0026thinsp;\u0026plusmn;\u0026thinsp;4,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;18,2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMean (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8,37\u0026thinsp;\u0026plusmn;\u0026thinsp;3,22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8,47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3,11\u0026ndash;12,73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,086\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,62\u0026thinsp;\u0026plusmn;\u0026thinsp;3,58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6,06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,17\u0026thinsp;\u0026minus;\u0026thinsp;13,73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003ePathologies during pregnancy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1er trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5,2\u0026thinsp;\u0026plusmn;\u0026thinsp;4,2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2,5\u0026ndash;19,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0,015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3,1\u0026thinsp;\u0026plusmn;\u0026thinsp;1,8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;10,4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e2nd trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14,8\u0026thinsp;\u0026plusmn;\u0026thinsp;7,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0,013\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8,9\u0026thinsp;\u0026plusmn;\u0026thinsp;6,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9,2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;20,6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e3rd trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7,6\u0026thinsp;\u0026plusmn;\u0026thinsp;3,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7,8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;14,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,474\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,9\u0026thinsp;\u0026plusmn;\u0026thinsp;4,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5,6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,5\u0026ndash;16,4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMean (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8,9\u0026thinsp;\u0026plusmn;\u0026thinsp;3,42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8,56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3,11\u0026ndash;13,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0,034\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,47\u0026thinsp;\u0026plusmn;\u0026thinsp;3,54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5,78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,17\u0026thinsp;\u0026minus;\u0026thinsp;13,68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cspan class=\"InlineEquation\"\u003e \u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{x}\\)\u003c/span\u003e \u003c/span\u003e: Mean, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:s\\)\u003c/span\u003e\u003c/span\u003e: Standard deviation, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{M}_{e}\\)\u003c/span\u003e\u003c/span\u003e: Media, Min.: Minimum value, Max.: Maximum value.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eCapillary cortisol levels in the first, second, and third trimesters of pregnancy were analyzed in relation to the uterine artery pulsatility index (UAPI). As is shown in Table VI, no statistically significant association was observed between UAPI and cortisol levels during the first and third trimesters. However, in the second trimester of pregnancy, a statistically significant association (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) was found between UAPI and the capillary cortisol value at that stage.\u003c/p\u003e\u003cp\u003e \u003cb\u003eTABLE VI. Association of capillary cortisol levels in the first, second, and third trimesters according to the uterine artery index during pregnancy.\u003c/b\u003e \u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabf\" border=\"1\"\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCorrelation coeffecient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIP. AU\u003c/p\u003e \u003cp\u003e1st ultrasound\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1st trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,893\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1st RLU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,062\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,562\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIP. AU\u003c/p\u003e \u003cp\u003e2nd ultrasound\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2nd trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,307\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0,01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2nd RLU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,312\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0,009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIP. AU\u003c/p\u003e \u003cp\u003e3rd ultrasound\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3rd trimester (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,057\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,725\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3rd RLU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,576\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMorphological and morphometric characteristics of the human placenta were also determined (n\u0026thinsp;=\u0026thinsp;72). In this regard, 97.2% of the placentas were of the discoidal type. Regarding umbilical cord insertion, 77.78% (n\u0026thinsp;=\u0026thinsp;56) evidenced a central insertion, which was the most frequent form of presentation. The average placental weight was 542.9 g, while the average thickness was 17.32 mm, and the average placental area was 292.01 cm\u0026sup2; (see Table VII).\u003c/p\u003e \u003cp\u003e \u003cb\u003eTABLE VII. Morphological and morphometric characteristics of the term human placenta.\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabg\" border=\"1\"\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable (Placentas n\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{\\varvec{x}}\\pm\\:\\varvec{s}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (grams)\u003c/p\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e542,90\u0026thinsp;\u0026plusmn;\u0026thinsp;101,31\u003c/p\u003e \u003cp\u003e333\u0026ndash;811\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThickness (mm)\u003c/p\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17,32\u0026thinsp;\u0026plusmn;\u0026thinsp;6,85\u003c/p\u003e \u003cp\u003e7\u0026ndash;37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArea (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e292,01\u0026thinsp;\u0026plusmn;\u0026thinsp;57,93\u003c/p\u003e \u003cp\u003e165\u0026ndash;484\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCotyledons (unit)\u003c/p\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17,92\u0026thinsp;\u0026plusmn;\u0026thinsp;5,76\u003c/p\u003e \u003cp\u003e6\u0026ndash;33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable (Placentas n\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombi\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (19,4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFibrin deposits\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (93,01)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiscoidal placenta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (97,22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuccenturiated placenta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2,78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlacenta with velamentous insertion\u003c/p\u003e \u003cp\u003eof the umbilical cord\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1,39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eData are presented as n (%) for categorical variables and mean\u0026thinsp;\u0026plusmn;\u0026thinsp;s for continuous variables.\u003c/p\u003e \u003cp\u003eIn addition to the morphological evaluation described above (See Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA\u0026ndash;B) the Vv of the terminal villi was determined in samples obtained from the superficial chorion, deep chorion, and chorionic plate (See Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC\u0026ndash;D).\u003c/p\u003e \u003cp\u003eThe average terminal villi Vv in the studied group was 24.89% (See Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC\u0026ndash;D). When comparing the groups according to capillary cortisol levels (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), a statistically significant difference was observed in the percentage of terminal villi volume density between the groups with high capillary cortisol levels and those with values close to the group average, with p\u0026thinsp;=\u0026thinsp;0.008 (see Table VIII).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eFetal surface of the human placenta showing the chorionic plate, which constitutes the fetal surface of the placenta and is covered by the amnion. The central insertion of the umbilical cord is evident. Scale bar: 1 cm.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eMaternal surface of the human placenta showing the cotyledons (arrow b) and intercotyledonary grooves. (white line) Scale bar: 1 cm.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eHistological section of the human placenta, corresponding to the superficial chorion, illustrating the general organization of placental tissue. Hemoatoxylin-Eosin Staining. Scale bar: 1 mm.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTerminal placental villi at higher magnificationwith application of the M42 grid for stereological point counting used to estimate volume density. Scale bar: 50 \u0026micro;m.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003e \u003cb\u003eTable VIII. Association of high capillary cortisol level according to terminal villi volume density.\u003c/b\u003e \u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabh\" border=\"1\"\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003cp\u003ecortisol\u003c/p\u003e \u003cp\u003elevel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003ePercentage of terminal villi\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{\\varvec{x}}\\pm\\:\\varvec{s}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\varvec{M}}_{\\varvec{e}}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eMin - Max.\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003ep - value\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29,88 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\text{5,11}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31,2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23,8\u0026ndash;36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18,44 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\text{4,94}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10,7\u0026ndash;22,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cspan class=\"InlineEquation\"\u003e \u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{x}\\)\u003c/span\u003e \u003c/span\u003e: Mean, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:s\\)\u003c/span\u003e\u003c/span\u003e: Standard deviation, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{M}_{e}\\)\u003c/span\u003e\u003c/span\u003e: Media, Min.: Minimum value, Max.: Maximum value.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eMaternal cortisol production is regulated by the hypothalamic-pituitary-adrenal (HPA) axis, whose activation has been consistently associated with various mental health pathologies, particularly depression and anxiety [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], as well as with the social and environmental conditions in which people live [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. These associations have been documented mainly through the measurement of cortisol performed in short-term biological matrices, such as saliva and blood, which only reflect acute or short-term hormone levels regulated by circadian variation [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFrom a physiological point of view, it is important to consider that cortisol levels normally increase two to three times toward the end of pregnancy. This is due to the progressive increase in placental secretion of corticotropin-releasing hormone (CRH), which acts through positive feedback on the HPA axis [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. This event does not interfere with the findings of the present study, in which a rise in cortisol was observed in the second trimester and a stabilization in the third trimester, when evaluated retrospectively using capillary cortisol, a technique that reflects the hormonal exposure accumulated over time.\u003c/p\u003e \u003cp\u003eThe results of the present study are consistent with the previously described evidence, in which a statistically significant association has been observed between the presence of mental health pathologies diagnosed before gestation and the levels of cortisol detected in the hair of pregnant women. However, they differ in their methodological approach, since in our study the analysis was based on capillary cortisol measured in each trimester of pregnancy, allowing for a longitudinal assessment of hormonal exposure. Unfortunately, these differences hinder the standardization of the assessment and, therefore, the establishment of reference values for normality. The technique used in the present study allows for a retrospective evaluation of cortisol exposure, reflecting the cumulative secretion of the hormone over prolonged periods, offering a more stable approach to HPA axis activity, as it is less susceptible to circadian variations and biases associated with the collection of traditional matrices [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies that have compared capillary cortisol with repetitive daytime saliva collection schemes, for example, daytime measurements for 3 days (3 times/day) in each quarter, have shown greater validity and reliability of cortisol values measured in hair, by avoiding the methodological difficulties associated with collection, making these results much more reliable [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. In the present study, although the participants had a history of mental health conditions prior to pregnancy, they were not receiving active pharmacological or therapeutic intervention at the time of the evaluation, not specifically due to discharge from the Health Care System. These findings reinforce the importance of incorporating mental health assessment and management into preconception check-ups, promoting timely interventions, education on the continuity of treatments and the prevention of therapeutic dropout, as well as the integration of the psychosocial team in the follow-up of women during the reproductive process.\u003c/p\u003e \u003cp\u003eRegarding the subject of environmental conditions, several studies have focused on the impact of chronic stress during pregnancy, associated with psychosocial risk factors, and on its effects on both maternal cortisol production and the offspring [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. However, the available literature does not always clearly distinguish whether such psychosocial risk conditions originate specifically during pregnancy or whether they correspond to pre-existing situations in the woman's life before pregnancy.\u003c/p\u003e \u003cp\u003eThe results of this study contribute to clarify this aspect, by showing that psychosocial factors and mood changes occurring during pregnancy are not necessarily associated with high levels of maternal cortisol. In contrast, the presence of previously diagnosed mental health conditions is associated with increased cortisol production throughout pregnancy. These findings suggest that a woman's prior psychosocial history may play a more significant role in the sustained activation of the HPA axis than isolated pregnancy stressors.\u003c/p\u003e \u003cp\u003eIt is worth noting that, in current clinical practice, prenatal check-ups routinely incorporate screening for psychosocial risk factors and depressive symptoms during pregnancy [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e], although pre-pregnancy psychosocial conditions are not systematically assessed. Among the identified vulnerability factors, violence emerges as a fundamental component to consider, not only that present during pregnancy, but also that experienced in early stages of life, such as childhood and adolescence. This perspective is consistent with evidence from adverse childhood experiences (ACES) studies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e], which have shown that such early exposures are associated with effects on physical and mental health in adulthood. These effects include lasting alterations in HPA regulation, as well as an increased risk of developing cardiovascular diseases throughout life [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn accordance with this evidence, the results of the present study show an association between elevated cortisol levels and the presence of obstetric cardiovascular pathologies, such as hypertensive disorders of pregnancy, preeclampsia, and gestational diabetes\u0026mdash;conditions that share similarities with cardiovascular alterations described in non-pregnant populations [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. However, the available evidence in pregnant populations that integrates these variables remains limited, reinforcing the need for further research in this area.\u003c/p\u003e \u003cp\u003eFor the assessment of fetal well-being in the context of cardiovascular pathologies of pregnancy, the measurement of blood flow in the uterine arteries during the first, second, and third trimesters of gestation is routinely used. Alterations in this flow, expressed as an increase in the PI, have been associated with poor uteroplacental perfusion and a higher risk of adverse perinatal outcomes [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In this study, the PI values obtained in the different trimesters were within ranges considered normal and were also consistent with the angiogenic and vasculogenic changes expected during pregnancy. However, a statistically significant association was observed between the second-trimester PI and maternal cortisol levels, suggesting a possible interaction between activation of the hypothalamic-pituitary-adrenal axis and uteroplacental vascular adaptation.\u003c/p\u003e \u003cp\u003eIt is well known that the placenta, as a central organ in maternal-fetal exchange, plays a fundamental role in the well-being of the fetus, and its dysfunction has been related to various obstetric pathologies, such as hypertensive syndrome of pregnancy, intrauterine growth restriction and acute fetal distress, conditions that increase perinatal morbidity and mortality [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. In this study, a significant relationship was found between maternal cortisol levels and placental terminal villi Vv, a finding consistent with previous reports describing alterations in villi volume in pathologies such as gestational diabetes and hypertensive disorders of pregnancy [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Considering that terminal villi constitute the main functional unit for gas and nutrient exchange, modifications in their structural organization could represent adaptive mechanisms against conditions of intrauterine deprivation [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. These alterations would have the potential to interfere with fetal growth and development, contributing to fetal programming processes that not only impact child health, but could also influence the risk of diseases in adult life [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eDuring pregnancy, various psychosocial risk factors are investigated that can negatively interfere with both the course of the pregnancy and the well-being of the child. The results of this study demonstrate the need to further evaluate mental health history prior to pregnancy, even in women who are not under active control for these conditions at the time of pregnancy.\u003c/p\u003e \u003cp\u003eLikewise, the psychosocial history during childhood and adolescence emerges as a relevant element, given that experiences at this stage of life can have a sustained impact on cortisol production and, consequently, modulate the functioning of the hypothalamic-pituitary-adrenal axis, a phenomenon widely described in the general population.\u003c/p\u003e \u003cp\u003eIn the context of pregnancy, this sustained activation of the HPA axis could contribute to the development of cardiovascular pathologies typical of this stage, with a direct and cascading impact on neonatal and infant morbidity and mortality.\u003c/p\u003e \u003cp\u003eTaken together, the background information provided in this work reinforces the relevance of incorporating a longitudinal and life course perspective in the assessment of psychosocial risk during pregnancy, which should be considered not only in prenatal care, but also in preconception assessments, in order to promote more comprehensive maternal and child health care.\u003c/p\u003e \u003cp\u003eIt should be noted that this study presents some limitations that must be considered when interpreting its results and that are essential to address in future research. Among these, the evaluation of capillary cortisol stands out, since there are currently no standardized reference values that allow for a clear classification of the results within ranges considered normal or pathological. This situation is attributable to the heterogeneity of the analytical methodologies and collection methods used.\u003c/p\u003e \u003cp\u003eFurthermore, gaps remain in our understanding of how the hypothalamic-pituitary-adrenal axis adapts during pregnancy and how elevated or decreased cortisol levels might interfere with placental function and the regulation of this hormone. Finally, a differentiated characterization of the effects of depression, depressive symptoms, and other mental health diagnoses is necessary to advance toward a more precise understanding of their biological and clinical implications during pregnancy.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the Doctoral Scholarship of the National Research and Development Agency (ANID), Chile (Register number: 21212312).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have read and approved the manuscript and consent to its publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during this study are available upon reasonable request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe materials used in this study are available upon reasonable request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability:\u0026nbsp;\u003c/strong\u003eNot aplicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors wish to express their gratitude to the V\u0026iacute;ctor Manuel Fern\u0026aacute;ndez, Tucapel, Santa Sabina, and O\u0026rsquo;Higgins Family Health Centers, as well as to the Guillermo Grant Benavente Hospital in Concepci\u0026oacute;n, Chile. This gratitude is also extended to each woman who participated and placed her trust in this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJE participated in the drafting of the introduction, conceptualization, data collection, data analysis, manuscript drafting, review, and editing.\u003c/p\u003e\n\u003cp\u003eMM participated in the review and analysis of the methodology.\u003c/p\u003e\n\u003cp\u003eMDS participated in the supervision, manuscript review, and editing.\u003c/p\u003e\n\u003cp\u003eXF performed the uterine artery Doppler assessments.\u003c/p\u003e\n\u003cp\u003eMG contributed to the supervision and sponsorship of the Maternal-Fetal Research Laboratory (LIMaF).\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003eCorrespondence should be addressed to JE.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWho.int. 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Eur J Obstet Gynecol Reprod Biol [Internet]. 2025;308:181\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1016/j.ejogrb.2025.03.015\u003c/span\u003e\u003cspan address=\"10.1016/j.ejogrb.2025.03.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Disponible en:.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAye ILMH, Tong S, Charnock-Jones DS, Smith GCS. The human placenta and its role in reproductive outcomes revisited. Physiol Rev [Internet]. 2025;105(4):2305\u0026ndash;76. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1152/physrev.00039.2024\u003c/span\u003e\u003cspan address=\"10.1152/physrev.00039.2024\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Disponible en:.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFaa G, Fanos V, Manchia M, Van Eyken P, Suri JS, Saba L. The fascinating theory of fetal programming of adult diseases: A review of the fundamentals of the Barker hypothesis. J Public Health Res [Internet]. 2024;13(1):22799036241226817. Disponible en: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1177/22799036241226817\u003c/span\u003e\u003cspan address=\"10.1177/22799036241226817\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Capillary cortisol, Mental health in pregnancy, Psychosocial factors, Obstetric complications, Placental morphometry","lastPublishedDoi":"10.21203/rs.3.rs-8682776/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8682776/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo determine the relationship between capillary cortisol, maternal mental health and biopsychosocial factors, along with obstetric pathologies and placental morphometry.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe studied a cohort of 114 pregnant women admitted after their first prenatal visit from Family Health Centers in Concepci\u0026oacute;n, Chile. Sociodemographic data, mental health and obstetric pathologies were collected. Lifetime violence was assessed, and depressive symptoms were evaluated using the Edinburgh Postnatal Depression Scale and the psychosocial risk factors scale. Cortisol levels were measured in hair samples during the first, second, and third gestational trimesters. An analysis of the morphology and morphometry of term placentas was also performed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAverage capillary cortisol levels were 4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3 ng/ml in the first trimester, 11.5\u0026thinsp;\u0026plusmn;\u0026thinsp;14.8 ng/ml in the second, and 6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5 ng/ml in the third trimester. A significant association was observed between capillary cortisol and a history of emotional and/or physical violence (p\u0026thinsp;=\u0026thinsp;0.042). An association was also found between pre-existing mental health conditions, gestational diabetes, and hypertensive disorders of pregnancy (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Regarding placental analysis, a significant difference in terminal villi volume density was identified between groups with different cortisol levels (p\u0026thinsp;=\u0026thinsp;0.008).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eLevels of capillary cortisol are associated with pre-pregnancy mental health history, biopsychosocial factors, obstetric complications, and placental villous volume density, highlighting the relevance of preconception screening to reduce fetal and infant morbidity and mortality.\u003c/p\u003e","manuscriptTitle":"Mental health in pregnancy and capillary cortisol: Associations with biopsychosocial factors, obstetric complications and placental morphometry","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-25 08:56:01","doi":"10.21203/rs.3.rs-8682776/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-30T07:57:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-25T20:39:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-12T17:27:06+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-11T17:28:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-09T01:34:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-05T13:08:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"316390339768108855911372949048164210521","date":"2026-03-05T12:35:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"152297980773486283166025303357163512977","date":"2026-03-02T21:05:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"106439205746039398161269711190909514327","date":"2026-02-28T17:37:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"254294877569245623996261536271680734722","date":"2026-02-28T07:44:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"74189374419078687220658525907791232451","date":"2026-02-27T15:14:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"103315324259641204947958612967707602789","date":"2026-02-27T13:53:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-19T13:42:03+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-28T05:14:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-26T11:53:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-26T11:50:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2026-01-23T22:52:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dd3a5f01-c151-4eda-a8da-dd94ffb835f3","owner":[],"postedDate":"February 25th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-28T05:53:07+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-25 08:56:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8682776","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8682776","identity":"rs-8682776","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
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