Analysis of pregnancy outcomes, disease progression, and risk factors in patients with undifferentiated connective tissue disease / 北京大学学报(医学版)

OBJECTIVE@#To investigate the fetal and maternal outcomes, risk factors of disease progression and adverse pregnancy outcomes (APOs) in patients with undifferentiated connective tissue disease (UCTD).@*METHODS@#This retrospective study described the outcomes of 106 pregnancies in patients with UCTD. The patients were divided into APOs group (n=53) and non-APOs group (n=53). The APOs were defined as miscarriage, premature birth, pre-eclampsia, premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), postpartum hemorrhage (PPH), and stillbirth, small for gestational age infant (SGA), low birth weight infant (LBW) and birth defects. The differences in clinical manifestations, laboratory data and pregnancy outcomes between the two groups were compared. Logistic regression analysis was performed to analyze the risk factors for APOs and the progression of UCTD to definitive CTD.@*RESULTS@#There were 99 (93.39%) live births, 4 (3.77%) stillbirths and 3 (2.83%) miscarriage, 20 (18.86%) preterm delivery, 6 (5.66%) SGA, 17 (16.03%) LBW, 11 (10.37%) pre-eclampsia, 7 (6.60%) cases IUGR, 19 (17.92%) cases PROM, 10 (9.43%) cases PPH. Compared with the patients without APOs, the patients with APOs had a higher positive rate of anti-SSA antibodies (73.58% vs. 54.71%, P=0.036), higher rate of leukopenia (15.09% vs. 3.77%, P=0.046), lower haemoglobin level [109.00 (99.50, 118.00) g/L vs. 124.00 (111.50, 132.00) g/L, P < 0.001].Multivariate Logistic regression analysis showed that leucopenia (OR=0.82, 95%CI: 0.688-0.994) was an independent risk factors for APOs in UCTD (P=0.042). Within a mean follow-up time of 5.00 (3.00, 7.00) years, the rate of disease progression to a definite CTD was 14.15%, including 8 (7.54%) Sjögren's syndrome, 4 (3.77%) systemic lupus erythematosus (SLE), 4 (3.77%) rheumatoid arthritis and 1 (0.94%) mixed connective tissue disease. Multivariate Cox proportional risk regression analysis showed that Raynaud phenomenon (HR=40.157, 95%CI: 3.172-508.326) was an independent risk factor for progression to SLE.@*CONCLUSION@#Leukopenia is an independent risk factor for the development of APOs in patients with UCTD. Raynaud's phenmon is a risk factor for the progression of SLE. Tight disease monitoring and regular follow-up are the key measures to prevent adverse pregnancy outcomes and predict disease progression in UCTD patients with pregnancy.

Relationships between hypertensive disorders in pregnancy and obstructive sleep apnea syndrome / 中华妇产科杂志

Objective: To investigate the impact of obstructive sleep apnea syndrome (OSAS) on pregnancy outcomes, especially the relationship between OSAS and hypertensive disorders in pregnancy (HDP). Methods: A total of 228 pregnant women with high risk of OSAS who underwent sleep monitoring during pregnancy in Peking University People's Hospital from January 2021 to April 2022 were collected by reviewing their medical records for retrospective analysis. According to the diagnosis of OSAS, the pregnant women were divided into OSAS group (105 cases) and non-OSAS group (123 cases). The non-parametric Mann-Whitney U test, χ2 test or Fisher's exact test were used to compare the general data and maternal and fetal outcomes between the two groups, and the occurrence of each type of HDP was further compared. Results: (1) Compared with the non-OSAS group, the median pre-pregnancy body mass index (23.6 vs 27.6 kg/m2) and the proportion of snoring [28.9% (33/114) vs 59.2% (61/103)] in the OSAS group were higher, and the differences were both statistically significant (both P<0.001). (2) The incidence of HDP [67.6% (71/105) vs 39.0% (48/123)] and gestational diabetes mellitus [GDM; 40.0% (42/105) vs 26.8% (33/123)] of pregnant women in the OSAS group were higher than those in the non-OSAS group, and the median delivery week was shorter than that in the non-OSAS group (38.4 vs 39.0 weeks). The differences were all statistically significant (all P<0.05). Between-group differences for the delivery way, postpartum hemorrhage, the rate of intensive care unit admission, preterm birth, small for gestational age infants, neonatal asphyxia, the rate of neonatal intensive care unit admission, newborn birth weight and the proportion of umbilical artery blood pH<7.00 were not statistically significant (all P>0.05). (3) Compared with the non-OSAS group, the incidence of chronic hypertension [11.4% (14/123) vs 22.9% (24/105)] and chronic hypertension with superimposed pre-eclampsia [11.4% (14/123) vs 30.5% (32/105)] were higher in the OSAS group, and the differences were both statistically significant (both P<0.01). Conclusion: OSAS is related to HDP (especially chronic hypertension and chronic hypertension with superimposed pre-eclampsia) and GDM, which could provide a practical basis for the screening, diagnosis and treatment of OSAS in pregnant women at high risk.

Clinical characteristics of severe pre-eclampsia in a single tertiary referral center of Xiamen City / 中华妇产科杂志

Objective: To explore the key points for preventing and reducing severe pre-eclampsia (SPE) and its severe complications in the tertiary medical referral system of a second-tier city by analyzing the clinical characteristics of SPE. Methods: The clinical data of 341 patients with SPE who terminated pregnancy in Women and Children's Hospital, School of Medicine, Xiamen University, from January 1, 2020 to December 31, 2022 were retrospectively analyzed, and the pre-eclampsia (PE) risk factors, clinical characteristics and severe complications of SPE between the patients referred from primary hospitals (referral group) and the patients received regular prenatal care in the tertiary referral center (central group) were compared, as well as the influence of the referral timing on the maternal and perinatal outcomes. Results: Among the 341 cases of SPE, 92 cases were in the referral group and 249 cases were in the central group. (1) Analysis of PE risk factors: there was no statistical difference in the proportion of risk factors of PE between these two groups [75.0% (69/92) vs 71.9% (179/249); χ2=0.328, P=0.567]. (2) Analysis of clinical features: the gestational ages at the PE early warning factors onset, at the PE first symptom onset and at SPE diagnosed, pregnancy terminated and onset of SPE severe complications in the referral group were significantly earlier than those in the central group (all P<0.05), the proportions of terminating pregnancy before 32 weeks of gestation, between 32 and 34 weeks of gestation, intensive care unit (ICU), neonatal ICU hospitalization and fetal growth restriction in single pregnancies were higher than those in the central group, while the live birth rate was lower than that in the central group (all P<0.05). (3) Analysis of SPE severe complications: the rates of SPE severe complications in the referral group was higher than that in the central group [28.3% (26/92) vs 13.7% (34/249); χ2=9.885, P=0.002]. Among them, the rates of placental abruption [7.6% (7/92) vs 2.8% (7/249); χ2=3.927, P=0.048] and still birth [6.5% (6/92) vs 0.4% (1/249); χ2=9.656, P=0.002] in the referral group were significantly higher than those in the central group. (4) Analysis of referral timings: the timings included referral after onset of SPE severe complications (9.8%, 9/92), referral after SPE diagnosed (63.0%, 58/92), referral after detection of SPE early warning signs (20.7%, 19/92) and referral after detection of PE risk factors (6.5%, 6/92). The gestational ages at SPE diagnosed and pregnancy terminated in group of referral after onset of SPE severe complications and group of referral after SPE diagnosed were significantly earlier than those in group of referral after detection of PE early warning signs and group of referral after detection of PE risk factors (P<0.05). The earlier the referral, the higher the live birth rates (P<0.05). Conclusions: The tertiary referral center of the second-tier city plays an important role in reducing the maternal and perinatal damage of PE. The timing of referral in primary medical institutions is the key point of reducing the occurrence of SPE severe complications and maternal, perinatal damage of PE. It is necessary for medical institutions of all levels in all regions to improve the ability of early identification and early intervention for PE, to enhance the awareness of SPE and its severe complications prevention and control. Primary medical institutions should especially pay attention to raise the consciousness of PE risk factors and early warning signs, and to improve the ability of PE risk factors and early warning signs screening.

Regional analysis of high risk factors of hypertensive disorders in pregnancy with organ or system impairment / 中华妇产科杂志

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.

Establishment method and significance of birthweight curve and reference in single center / 中华妇产科杂志

Objective: To establish neonatal birthweight percentile curves based on single-center cohort database using different methods, compare them with the current national birthweight curves and discuss the appropriateness and significance of single-center birthweight standard. Methods: Based on a prospective first-trimester screening cohort at Nanjing Drum Tower Hospital from January 2017 to February 2022, the generalized additive models for location, scale and shape (GAMLSS) and semi-customized method were applied to generate local birthweight percentile curves (hereinafter referred to as the local GAMLSS curves, semi-customized curves) for 3 894 cases who were at low risk of small for gestation age (SGA) and large for gestation age (LGA). Infants were categorized as SGA (birth weight<10th centile) by both semi-customized and local GAMLSS curves, semi-customized curves only, or not SGA (met neither criteria). The incidence of adverse perinatal outcome between different groups was compared. The same method was used to compare the semi-customized curves with the Chinese national birthweight curves (established by GAMLSS method as well, hereinafter referred to as the national GAMLSS curves). Results: (1) Among the 7 044 live births, 404 (5.74%, 404/7 044), 774 (10.99%, 774/7 044) and 868 (12.32%, 868/7 044) cases were diagnosed as SGA according to the national GAMLSS curves, the local GAMLSS curves and the semi-customized curves respectively. The birth weight of the 10th percentile of the semi-customized curves was higher than that of the local GAMLSS curves and the national GAMLSS curves at all gestational age. (2) When comparing semi-customized curves and the local GAMLSS curves, the incidence of admission to neonatal intensive care unit (NICU) for more than 24 hours of infants identified as SGA by semi-customized curves only (94 cases) and both semi-customized and local GAMLSS curves (774 cases) was 10.64% (10/94) and 5.68% (44/774) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks of infants identified as SGA by the semi-customized curves only and both semi-customized and local GAMLSS curves was 12.77% (12/94) and 9.43% (73/774), 9.57% (9/94) and 2.71% (21/774), 24.47% (23/94) and 7.24% (56/774) respectively, which were significantly higher than those of the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. (3) When comparing semi-customized curves and the national GAMLSS curves, the incidence of admission to NICU for more than 24 hours of infants identified as SGA by semi-customized curves only (464 cases) and both semi-customized and national GAMLSS curves (404 cases) was 5.60% (26/464) and 6.93% (28/404) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); all P<0.001]. The incidence of emergency cesarean section or forceps delivery for non-reassuring fetal status (NRFS) in infants identified as SGA by semi-customized curves only and both semi-customized and national GAMLSS curves was 4.96% (23/464) and 12.38% (50/404), both significantly higher than that in the non SGA group [2.57% (159/6 176); all P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks in the semi-customized curves only group and both semi-customized and national GAMLSS curves group was 8.84% (41/464) and 10.89% (44/404), 4.31% (20/464) and 2.48% (10/404), 10.56% (49/464) and 7.43% (30/404) respectively, all significantly higher than those in the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. Conclusion: Compared with the national GAMLSS birthweight curves and the local GAMLSS curves, the birth weight curves established by semi-customized method based on our single center database is in line with our center' SGA screening, which is helpful to identify and strengthen the management of high-risk infants.

Analysis of incidence and associated factors of preterm birth based on pre-pregnancy body mass index stratification / 中华预防医学杂志

Objective: To analyze the incidence of preterm birth based on pre-pregnancy body mass index (BMI) stratification and explore the associated factors of preterm birth among pregnant women at different BMI stratifications. Methods: From February 2018 to December 2020, pregnant women who participated in China Birth Cohort Study (CBCS) and gave birth at Beijing Obstetrics and Gynecology Hospital were enrolled as the study subjects. Electronic Data Capture System and standard structured questionnaires were used to collect data related to pre-pregnancy, pregnancy, and delivery for pregnant women. Pregnant women were divided into the low-weight group, normal-weight group and overweight group based on their pre-pregnancy BMI. A Cox proportional hazards model was used to analyze the associated factors of preterm birth among pregnant women with different BMI before pregnancy. Results: A total of 27 195 singleton pregnant women were included, with a preterm birth rate of 5.08% (1 381/27 195). The preterm birth rates in the low-weight group, normal-weight group and overweight group were 4.29% (138/3 219), 4.63% (852/18 390) and 7.00% (391/5 586) respectively (P<0.001). After adjusting for relevant factors, the Cox proportional hazards model showed that the risk of preterm birth in the overweight group was 1.457 times higher than that in the normal-weight group (95%CI: 1.292-1.643). Preeclampsia-eclampsia (HR=2.701, 95%CI: 1.318-5.537) was the associated factor for preterm birth in the low-weight group. Advanced maternal age (HR=1.232, 95%CI: 1.054-1.441), history of preterm birth (HR=4.647, 95%CI: 3.314-6.515), vaginal bleeding in early pregnancy (HR=1.613, 95%CI: 1.380-1.884), and preeclampsia-eclampsia (HR=3.553, 95%CI: 2.866-4.404) were associated factors for preterm birth in the normal-weight group. Advanced maternal age (HR=1.473, 95%CI: 1.193-1.818), history of preterm birth (HR=3.209, 95%CI: 1.960-5.253), vaginal bleeding in early pregnancy (HR=1.636, 95%CI: 1.301-2.058), preeclampsia-eclampsia (HR=2.873, 95%CI:2.265-3.643), and pre-gestational diabetes mellitus (HR=1.867, 95%CI: 1.283-2.717) were associated factors for preterm birth in the overweight group. Conclusion: Pre-pregnancy overweight is an associated factor for preterm birth, and there are significant differences in the associated factors of preterm birth among pregnant women with different BMI before pregnancy.

Epidemiological characteristics of hypertensive disorders during pregnancy in a high-risk population / Características epidemiológicas de los trastornos hipertensivos durante el embarazo en una población de alto riesgo

Abstract Objectives: the aim is to determine the prevalence of hypertensive disorders and to describe the sociodemographic aspects and risk factors for preeclampsia, gestational hypertension and intrauterine growth restriction. Methods: a descriptive cross-sectional study. Maternal characteristics, history from the first prenatal visit and outcomes were obtained. The prevalence and percentages were calculated and described. Results: the prevalence of hypertensive disorders was 12.7%, preeclampsia was 8.0%, followed by gestational hypertension at 4.7%. Of the preeclampsia, 54.8% were severe and 11.9% were of early onset. Moreover, 56.5% of the severe preeclampsia had preterm deliveries. IUGR had a prevalence of 5.3%. Based on maternal history, the most relevant risk factors were a family and personal history of preeclampsia and IUGR. Conclusions: we found a considerable prevalence of preeclampsia with a high percentage of preterm deliveries, associated with varying severity. This data helps health professionals to be aware of the risk factors that can be followed up for preventing complications. The determination of the risk of developing a hypertensive disorder during pregnancy is fundamental to encouraging proper counseling and care for these women through gestation.

Resumen Objetivos: determinar la prevalencia de trastornos hipertensivos y describir los aspectos sociodemográficos y los factores de riesgo de preeclampsia, hipertensión gestacional y restricción del crecimiento intrauterino (RCIU). Métodos: estudio descriptivo de corte transversal. Se obtuvieron características maternas, antecedentes del primer control prenatal y los resultados obstétricos. Se calcularon y describieron las prevalencias y porcentajes. Resultados: la prevalencia de trastornos hipertensivos fue del 12.7%, la de la preeclampsia fue del 8.0%, seguida de la hipertensión gestacional con el 4.7%. Del total de gestantes con preeclampsia, el 54.8% fueron graves y el 11.9% fue de inicio temprano. Además, el 56.5% de las gestantes con preeclampsia severa tuvieron partos prematuros. La RCIU tuvo una prevalencia del 5.3%. Según los antecedentes maternos, los factores de riesgo más relevantes fueron los antecedentes familiares y personales de preeclampsia y RCIU. Conclusiones: se encontró una prevalencia considerable de preeclampsia con un alto porcentaje de partos prematuros, asociada a una severidad variada. Estos datos ayudan a los profesionales de la salud a conocer los factores de riesgo que se pueden monitorear para prevenir complicaciones. La determinación del riesgo de desarrollar un trastorno hipertensivo durante el embarazo es fundamental para fomentar el asesoramiento y la atención adecuados para estas mujeres durante la gestación.

Is arginine supplementation effective in preventing preeclampsia in pregnant women? / A suplementação de arginina é efetiva em prevenir pré-eclâmpsia em gestantes?

ABSTRACT: Objectives: The objective of this study was to review data from randomized controlled trials to assess whether or not the supplementation of L-Arginine (L-Arg) is effective in reducing the incidence of preeclampsia (PE) in pregnancies at risk of developing the disorder. Methods: We aimed to systematic review randomized controlled trials, including those which compared L-Arg supplementation with placebo in pregnant women at high risk of PE development, analyzing PE incidence as the main outcome. Data were collected from MEDLINE/ Pubmed, EMBASE/ Elsevier, LILACS/ BVS and Cochrane. Results: A total of 46 papers were identified in the primary search. After analysis of eligibility, inclusion and exclusion criteria, two articles (which respected in detail all the stages of evaluation) were included in the present review. A risk of bias assessment was performed. Data analysis revealed that the incidence of PE was significantly lower in both studies, and no major adverse effects were reported. The limitations of this study were the lack of standardization between the trials analyzed and the relative low number of studies included. Conclusions: The supplementation with L-Arg appears to reduce the incidence of PE in pregnant women with high risk for its development. (AU)

RESUMO: Objetivo: O objetivo deste estudo foi revisar dados de ensaios clínicos randomizados para avaliar se a suplementação de L-Arginina é efetiva para reduzir a incidência de pré-eclâmpsia em gestantes com alto risco de desenvolver a doença. Métodos: Realizamos uma revisão sistemática de ensaios clínicos randomizados, incluindo aqueles que compararam a suplementação de L-Arginina com placebo em gestantes de alto risco de desenvolvimento de pré-eclâmpsia, analisando a incidência de pré-eclâmpsia como desfecho principal. Os estudos foram selecionados do MEDLINE/ Pubmed, EMBASE/ Elsevier, LILACS/ BVS e Cochrane. Resultados: Um total de 46 estudos foram identificados na busca primária. Após análise da elegibilidade, dos critérios de inclusão e de exclusão, dois artigos (que respeitaram em detalhes todas etapas de avaliação) foram incluídos na presente revisão. Foi realizada uma avaliação de risco de viés. A análise dos dados revelou que a incidência de pré-eclâmpsia foi significativamente menor em ambos os estudos, e nenhum efeito adverso importante foi relatado. As limitações deste estudo foram a falta de padronização entre os ensaios clínicos analisados e o número relativamente baixo de estudos incluídos. Conclusão: A suplementação com L-Arginina parece reduzir a incidência de pré-eclâmpsia em gestantes de alto risco para seu desenvolvimento. (AU)

Determinación de la tasa de hospitalizaciones por complicaciones del síndrome hipertensivo del embarazo en Chile, periodo 2018 - 2021 / Determination of the rate of hospitalizations due to complications of hypertensive syndrome of pregnancy in Chile, period 2018 - 2021

Introducción: El Síndrome Hipertensivo del Embarazo (SHE) es el conjunto de condiciones patológicas derivadas del alza de presión arterial mantenida originadas antes y/o durante el curso de un embarazo. En ocasiones requiere tratamiento hospitalario. El objetivo del estudio es determinar la tasa de egreso hospitalario (TEH) por complicaciones del SHE durante el 2018-2021 en Chile. Materiales y métodos: Estudio descriptivo tipo transversal de las complicaciones por SHE en el periodo 2018-2921 en Chile según grupo etario y días de estadía hospitalaria (n=12.006). Datos obtenidos del departamento de estadística e información en salud. Se calculó TEH. No requirió aprobación del comité de ética. Resultados: La Preeclampsia tuvo más TEH con 61,48 por cada 100.000 habitantes, afectó más a mujeres de 20 a 44 años con 74.03 por 100.000 habitantes. Las complicaciones del SHE reportaron un promedio de 6,4 días de hospitalización. El Síndrome de HELLP registró más días de hospitalización con 7,2 días. Discusión: El envejecimiento poblacional, la migración, el sobrepeso-obesidad podrían influir en mayores TRH por preeclampsia. Se reportó mayores TEH de preeclampsia en mujeres de 20 a 44 años. Esto se debe posiblemente por factores cardiovasculares, maternidad tardía y la hipertensión crónica. El Síndrome de HELLP implica peor pronóstico y reportó mayores días hospitalización debido al manejo médico. Discusión: Hay escasas estadísticas nacionales sobre TEH en relación a SHE. La edad, el riesgo cardiovascular y fenómenos epidemiológicos ofrecen posibles líneas investigativas. Más estudios son requeridos para dilucidar los factores que desencadenan sus complicaciones.

Introduction: The Hypertensive Syndrome of Pregnancy (SHE) is the set of pathological conditions derived from the increase in sustained blood pressure originating before and/or during the course of a pregnancy. Sometimes it requires hospital treatment. The objective of the study is to determine the rate of hospital discharge (TEH) due to complications of EHS during 2018-2021 in Chile. Materials and Methods: Descriptive transversal type of study about the complications of hypertensive pregnancy syndrome during the period from 2018 to 2021 according to age range and number of days in the hospital (n=12.006). Data obtained from the health statistics and information department, which did not require approval of the ethics committee. Results: PE had a higher TEH with 61.48 out of 100,000 people, affecting more women aged 20 to 44 years with 74.03 per 100,000 inhabitants. Complications of hypertensive pregnancy syndrome reported an average of 6.4 hospitalization days. The HELLP syndrome had more days with a quantity of 7.2. Discussion: Population aging, migration, and overweight-obesity might influence the increase in TEH/PE. Higher TEH of PE was reported in women aged 20 to 44 years, possibly due to cardiovascular factors, late maternity, and chronic hypertension. The HELLP syndrome implies a worse prognosis and reported more days at the hospital due to medical treatment. Conclusion: There are few national statistics on TEH in relation to SHE. Age, cardiovascular risk, and epidemiological phenomena offer possible lines of investigation. More studies are required to elucidate the factors that trigger its complications.

Genetic markers for preeclampsia in Peruvian women / Marcadores genéticos de preeclampsia en mujeres peruanas

Abstract Background: Preeclampsia is a multiorgan disorder associated with maternal and perinatal morbi-mortality. In Peru, incidence is 10% and accounts for 22% of maternal deaths. Genome and genetic epidemiological studies have found an association between preeclampsia and genetic polymorphisms. Objective: To determine the association of the vascular endothelial growth factor (VEGF) +936 C/T and +405 G/C, interleukine-6 (IL-6) -174 G/C, IL-1β-511 C/T, Apo A-1-75 G/A, Apo B-100 2488 C/T (Xbal) polymorphisms with preeclampsia in pregnant Peruvian women. Methods: Were included preeclamptic and healthy (control) pregnant women. Maternal blood samples were subjected to DNA extraction, and molecular genetic analysis was conducted using the PCR-RFLP technique and following a specific protocol for each gene. Allele and genotypic frequencies in the cases and controls were compared. Results: No association was found between the VEGF+936C/T and VEGF+405 polymorphisms and preeclampsia. The frequencies of the GG genotypes and the G allele of the -174 G/C polymorphism in the IL6 gene in preeclamptic and controls showed significant differences, with higher frequencies in cases. For the -511 C/T polymorphism of the IL-1β gene, no significant differences were found in the frequencies of TT genotypes compared with CT+CC. The genotypes and alleles of the Apo-A1-75 G/A and Apo-B100 Xbal variants showed no significant differences between cases and controls. Conclusion: No association was found between the studied genetic markers and preeclampsia. However, in the -174G/C polymorphism of the IL-6 gene, significant differences were found mainly in the GG genotype and G allele.

Resumen Antecedentes: La preeclampsia es un trastorno multiorgánico asociado con la morbi-mortalidad materna y perinatal. En el Perú, su incidencia es del 10% y causa el 22% de las muertes maternas. Se encontró una asociación entre la preeclampsia y ciertos polimorfismos. Objetivo: Determinar asociación entre los polimorfismos genéticos del factor de crecimiento endotelial vascular (VEGF) +936 C/T y +405 G/C, interleucina-6 (IL-6) -174G/C, IL-1β -511 C/T, Apo A-1 -75 G/A, Apo B-100 2488 C/T (Xbal), y preeclampsia en gestantes peruanas. Métodos: Se incluyeron gestantes preeclámpticas y sanas (controles). Las muestras de sangre fueron procesadas para extracción del ADN, y el análisis se realizó con la técnica PCR-RFLP con protocolos específicos para cada gen y confirmación con secuenciamiento Sanger. Se compararon las frecuencias alélicas y genotípicas en los casos (preeclampsia) y los controles. Resultados: No se halló asociación entre los polimorfismos VEGF+936-C/T y VEGF+405 y la preeclampsia. Las frecuencias de los genotipos GG y el alelo G del polimorfismo -174-G/C en el gen IL6 en preeclámpticas y controles, mostraron diferencias significativas, con frecuencias más altas en los casos. Para el polimorfismo -511-C/T del gen IL-1β, no se encontraron diferencias significativas en las frecuencias de genotipos TT comparados con CT+CC. Los genotipos y alelos de las variantes Apo-A1-75-G/A y Apo-B100 Xbal no mostraron diferencias significativas entre los grupos Conclusión: No se encontró asociación entre los marcadores genéticos estudiados y la preeclampsia. Sin embargo, el polimorfismo -174-G/C en el gen IL6 mostró diferencias significativas principalmente en el genotipo GG y el alelo G.

Uterine vascular resistance and other maternal factors associated with the risk of developing hypertension during pregnancy

Gestational hypertension and pre-eclampsia are important causes of perinatal morbidity. The objective of the present study was to determine the increase in relative risk for developing hypertensive disorders of pregnancy based on the evaluation of pregnant women between 20 and 25 weeks of gestation, and to correlate the findings at this period with the outcome of pregnancy. We conducted a prospective cohort study, with a convenience sample of 1417 patients evaluated at this gestational age, of which 1306 were contacted at childbirth. We detected an increased relative risk of 2.69 (95%CI: 1.86 to 3.89) associated with pulsatility index of the uterine arteries, a 2.8 increase (95%CI: 1.58 to 5.03) in relative risk attributed to maternal age above 35 years, a 1.68 increase (95%CI: 1.17 to 2.40) attributed to parity greater than or equal to 3, and a 5.35 increase (95%CI: 4.18 to 6.85) attributed to chronic hypertension and obesity, with a progressive increase in relative risk according to the degree of overweight, i.e., grades 1, 2, 3, and morbid obesity (2.58, 3.06, 5.84, and 7.28, respectively).

Evaluation of angiogenic factors (PlGF and sFlt-1) in pre-eclampsia diagnosis / Avaliação dos fatores angiogênicos (PlGF e sFlt-1) no diagnóstico de pré-eclâmpsia

Abstract Objective: Recent observations support the hypothesis that an imbalance between angiogenic factors has a fundamental role in the pathogenesis of pre-eclampsia and is responsible for the clinical manifestations of the disease. The goal of the present study was to evaluate the sensitivity, specificity, and the best accuracy level of Soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in maternal serum and protein/creatinine ratio in urine sample to define the best cutoff point of these tests to discriminate between the patients with gestational hypertension and the patients with pre-eclampsia, to evaluate the possibility of using them as diagnostic methods. Methods: A prospective longitudinal study was performed, and blood samples were collected from 95 pregnant patients with hypertension to measure serum concentrations of biomarkers sFlt-1 and PlGF. Urine samples were collected for protein screening. Significance was set as p < 0.05. Results: The sFlt-1/PlGF ratio demonstrated a sensitivity of 57.5% and a specificity of 60% using 50.4 as a cutoff point. The test that showed the best accuracy in the diagnosis of pre-eclampsia was protein/creatinine ratio, with a sensitivity of 78.9% and a specificity of 70% using 0.4 as a cutoff point and showing an area under the receiver operating characteristic curve of 0.80 (p < 0.001). Conclusion: No studied laboratory test proved to be fairly accurate for the diagnosis of pre-eclampsia, except for the protein/creatinine ratio. The evidence is insufficient to recommend biomarkers sFlt-1 and PlGF to be used for the diagnosis of pre-eclampsia.

Resumo Objetivo: Pesquisas recentes sustentam a hipótese de que um desequilíbrio entre fatores angiogênicos desempenhe um papel fundamental na patogênese da pré-eclâmpsia e seja responsável pelas manifestações clínicas da doença. O objetivo do presente estudo foi avaliar a sensibilidade, a especificidade e o nível de melhor acurácia do Fator semelhante a tirosina quinase 1 (sFlt-1), Fator de crescimento placentário (PlGF), e relação sFlt-1/PlGF no soro materno e relação proteína/creatinina em amostra de urina e definir o melhor ponto de corte desses testes para distinguir pacientes com hipertensão gestacional daquelas com pré-eclâmpsia, a fim de avaliar a possibilidade de utilizá-los como métodos diagnósticos. Métodos: Foi realizado um estudo prospectivo longitudinal e foram coletadas amostras de sangue de 95 gestantes com hipertensão arterial para dosar as concentrações séricas dos biomarcadores sFlt-1 e PlGF. Amostras de urina foram coletadas para pesquisa de proteinúria. Foram consideradas significativas as diferenças com p < 0,05. Resultados: A relação sFlt-1/PlGF demonstrou sensibilidade de 57,5% e especificidade de 60% utilizando 50,4 como ponto de corte. O teste que apresentou a melhor acurácia no diagnóstico de pré-eclâmpsia foi a relação proteína/creatinina, com sensibilidade de 78,9% e especificidade de 70%, utilizando 0,4 como ponto de corte e demostrando uma área sob a curva receiver operating characteristic (ROC, na sigla em inglês) de 0,80 (p < 0,001). Conclusão: Nenhum método de rastreamento isolado se mostrou com boa acurácia para o diagnóstico de pré-eclâmpsia, exceto a relação proteína/creatinina. As evidências são insuficientes para recomendar os biomarcadores sFlt-1 e PlGF como diagnóstico de pré-eclâmpsia.

The influence of preeclampsia, advanced maternal age and maternal obesity in neonatal outcomes among women with gestational diabetes / A influência da pré-eclâmpsia, idade materna avançada e obesidade materna em desfechos neonatais entre mulheres com diabetes gestacional

Abstract Objective The present study aims to analyze adverse fetal or neonatal outcomes in women with gestational diabetes, including fetal death, preterm deliveries, birthweight, neonatal morbidity and mortality, as well as the synergic effect of concomitant pregnancy risk factors and poor obstetric outcomes, as advanced maternal age, maternal obesity and pre-eclampsia in their worsening. Methods The present cohort retrospective study included all pregnant women with gestational diabetes, with surveillance and childbirth at the Hospital da Senhora da Oliveira during the years of 2017 and 2018. The data were collected from the medical electronic records registered in health informatic programs Sclinico and Obscare, and statistical simple and multivariate analysis was done using IBM SPSS Statistics. Results The study participants included 301 pregnant women that contributed to 7.36% of the total institution childbirths of the same years, in a total of 300 live births. It was analyzed the influence of pre-eclampsia coexistence in neonatal morbidity (p = 0.004), in the occurrence of newborns of low and very low birthweight (p < 0.01) and in preterm deliveries (p < 0.01). The influence of maternal obesity (p = 0.270; p = 0.992; p = 0.684) and of advanced maternal age in these 3 outcomes was also analyzed (p = 0,806; p = 0.879; p = 0.985).Using a multivariate analysis, the only models with statistic significance to predict the three neonatal outcomes included only pre-eclampsia (p = 0.04; p < 0.01; p < 0.01). Conclusion Only coexistence of pre-eclampsia showed an association with adverse neonatal outcomes (neonatal morbidity, newborns of low and very low birthweight and preterm deliveries) and can be used as a predictor of them in women with gestational diabetes.

Resumo Objetivo O presente estudo tem como objetivo analisar desfechos fetais ou neonatais adversos em mulheres com diabetes gestacional, incluindo morte fetal, partos prematuros, peso ao nascimento, morbilidade neonatal e mortalidade, bem como o efeito sinérgico de fatores de risco e maus desfechos concomitantes da gravidez, como idade materna avançada, obesidade materna e pré-eclâmpsia no seu agravamento. Métodos O presente estudo retrospetivo de coorte incluiu todas as gestantes com diabetes gestacional, com vigilância e parto no Hospital da Senhora da Oliveira durante 2017 e 2018. Os dados foram obtidos dos registos clínicos eletrônicos dos programas informáticos de saúde Sclinico e Obscare, e a análise estatística simples e multivariada foi feita utilizando o IBM SPSS Statistics. Resultados Os participantes do estudo incluíram 301 gestantes que contribuíram para 7,36% do total de partos da instituição, num total de 300 nados vivos. Foi analisada a influência da coexistência de pré-eclâmpsia na morbilidade neonatal (p = 0,004), na ocorrência de recém-nascidos de baixo e muito baixo peso ao nascimento (p < 0,01) e em partos prematuros (p < 0,01). Também foi analisada a influência da obesidade materna (p = 0,270; p = 0,992; p = 0,684) e da idade materna avançada nesses 3 desfechos (p = 0,806; p = 0,879; p = 0.985).Usando uma análise multivariada, os únicos modelos com significância estatística para predizer os três desfechos neonatais incluíram apenas a pré-eclâmpsia (p = 0,04; p < 0,01; p < 0,01). Conclusão Apenas a coexistência de pré-eclâmpsia mostrou associação com desfechos neonatais adversos (morbilidade neonatal, recém-nascidos de baixo e muito baixo peso e partos prematuros) e pode ser utilizada como preditor destes em mulheres com diabetes gestacional.

Análisis de complejidad en la caracterización de episodios de morbilidad materno-infantil / Analysis of complexity in the characterization of maternal and child morbidity episodes

Introducción: La salud materno-infantil constituye una prioridad bien definida en el sistema sanitario de Cuba, por lo que el estudio de problemas sanitarios complejos resulta de incuestionable valor. Objetivo: Caracterizar a féminas con infecciones asociadas a la asistencia sanitaria o preeclampsia, desde el paradigma de la complejidad. Métodos: Se desarrolló una investigación compleja trietápica en el Hospital Provincial Ginecoobstétrico Mariana Grajales Coello de Santiago de Cuba, que incluyó un análisis de serie temporal y un estudio observacional, descriptivo y transversal, para lo cual se tomaron 1 896 pacientes diagnosticadas con infecciones asociadas a la asistencia sanitaria, desde el año 2004 al 2017, y 140 gestantes con preeclampsia, registradas en el quinquenio 2013-2017; además, se consideraron variables clínicas, epidemiológicas, humorales, ecográficas y anatomopatológicas. Se efectuaron análisis de series temporales (descomposición estacional, análisis espectral e identificación de componentes de la serie), de componentes principales y de redes neuronales; a la vez que se identificaron los patrones estacionales específicos y microbiológicos para las infecciones asociadas a la asistencia sanitaria. Resultados: La edad, la historia obstétrica y las fluctuaciones de la tensión arterial resultaron ser factores predictores de importancia relacionados con la preeclampsia, además de los fallos renal y hepático como agravamientos y/o complicaciones de dicha entidad clínica. Conclusiones: La utilización de métodos de análisis multinivel reveló el complejo entramado que se establece entre las variables clínicas, epidemiológicas, sociales y ambientales en relación con las infecciones asociadas a la asistencia sanitaria y la preeclampsia, lo que se evidenció con los hallazgos anatomopatológicos.

Introduction: The maternal and child health constitutes a very defined priority in the health system of Cuba, reason why the study of complex health problems is of unquestionable value. Objective: To characterize women with infections associated with the health assistance or pre-eclampsia, from the paradigm of complexity. Methods: A complex three phase investigation was carried out in Mariana Grajales Coello Provincial Gynecoobstetric Hospital in Santiago de Cuba that included a temporary series analysis and an observational, descriptive and cross-sectional study, for which 1 896 patients diagnosed with infections associated with the health assistance, from 2004 to 2017, and 140 pregnant women with pre-eclampsia, registered in the five year period 2013-2017 were selected, also, clinical, epidemiological, humoral, echographic and pathologic variables were considered. Temporary series analysis (seasonal factorization, spectral analysis and identification of the series components), of main components and neural network were carried out; at the same time that the specific seasonal and microbiological patterns were identified for the infections associated with health assistance. Results: The age, obstetric history and fluctuations of blood pressure were important prediction factors related to pre-eclampsia, besides renal and hepatic failure as worsenings and/or complications of this clinical entity. Conclusions: The use of multilevel analysis methods revealed the complex structure that is established between the clinical, epidemiological, social and environmental variables in connection with the infections associated with health assistance and pre-eclampsia, what was evidenced with the pathologic findings.

Maternal and perinatal outcomes of pregnancies complicated by chronic hypertension followed at a referral hospital / Resultados maternos e perinatais de gestantes hipertensas crônicas acompanhadas em pré-natal especializado

Abstract Objective To assess maternal and perinatal outcomes of pregnancies in women with chronic hypertension (CH). Methods Retrospective cohort of women with CH followed at a referral center for a 5 year period (2012-2017). Data were obtained from medical charts review and described as means and frequencies, and a Poisson regression was performed to identify factors independently associated to the occurrence of superimposed preeclampsia (sPE). Results A total of 385 women were included in the present study; the majority were > than 30 years old, multiparous, mostly white and obese before pregnancy. One third had pre-eclampsia (PE) in a previous pregnancy and 17% of them had organ damage associated with hypertension, mainly kidney dysfunction. A total of 85% of the patients used aspirin and calcium carbonate for pre-eclampsia prophylaxis and our frequency of sPE was 40%, with an early onset (32.98 ± 6.14 weeks). Of those, 40% had severe features of PE, including 5 cases of HELLP syndrome; however, no cases of eclampsia or maternal death were reported. C-section incidence was high, gestational age at birth was 36 weeks, and nearly a third (115 cases) of newborns had complications at birth One third of the women remained using antihypertensive drugs after pregnancy. Conclusion Chronic hypertension is related with the high occurrence of PE, C-sections, prematurity and neonatal complications. Close surveillance and multidisciplinary care are important for early diagnosis of complications.

Resumo Objetivo Avaliar os resultados maternos e perinatais em gestação de mulheres com hipertensão crônica. Métodos Coorte retrospectiva de mulheres hipertensas crônicas acompanhadas em hospital de referência por 5 anos (2012-2017). Foi realizada revisão dos prontuários médicos e os resultados são descritos em médias e frequências. A regressão de Poisson foi usada para identificar os fatores independentemente associados à ocorrência de pré-eclâmpsia superajuntada. Resultados Um total de 385 mulheres foram incluídas no presente estudo, e amaioria tinha idade > 35 anos, era multípara, majoritariamente brancas e obesas antes da gravidez. Um terço teve pré-eclâmpsia em gestação anterior, e 17% apresentavam lesão de órgão-alvo associada à hipertensão, majoritariamente disfunção renal. Um total de 85% das pacientes usaram ácido acetilsalicílico e carbonato de cálcio para a profilaxia de pré-eclâmpsia, sendo que a frequência de pré-eclâmpsia superajuntada foi de 40%, com um início prematuro (32.98 ± 6.14 semanas). Destas, 40% apresentaram sinais de gravidade associados à pré-eclâmpsia, com 5 casos de síndrome HELLP; entretanto sem nenhum caso de eclampsia ou morte materna. A incidência de cesárea foi alta, comidade gestacional de 36 semanas ao parto, e umterço dos recém-nascidos tiveram complicações ao nascimento. Um terço das mulheres permaneceu usando medicamentos anti-hipertensivos ao fim da gravidez. Conclusão A hipertensão crônica se relaciona comalta prevalência de pré-eclâmpsia, cesárea, prematuridade e complicações neonatais. Vigilância e cuidado multidisciplinar são importantes para o diagnóstico precoce das complicações.

Preeclampsia y enfermedad cardiovascular: un enfoque integral para detectar las fases subclínicas de complicaciones obstétricas y cardiovasculares / Preeclampsia and cardiovascular disease: an integrated approach to detect the subclinical stages of obstetrical and cardiovascular complications

Desde 1995 hasta la fecha la asociación entre patologías derivadas los embarazos hipertensivos y las enfermedades cardiovasculares ha generado un gran volumen de potentes evidencias epidemiológicas y clínicas. Los propósitos de esta revisión son varios. Mostrar la consistencia y magnitud de la evidencia científica. Integrar los riesgos/enfermedades cardiovasculares y los problemas obstétricos a través de la disfunción endotelial. Preconizar el seguimiento postparto de la hipertensa embarazada, como una ventana de oportunidad para beneficiar la salud de las mujeres y sus hijos. Incluir la historia obstétrica como factor de riesgo de enfermedad coronaria. Proponer cuestionarios adaptables a las prácticas locales para facilitar la pronta incorporación de los índices de riesgo obstétrico y cardiovascular en dos etapas de la vida de una mujer. Ha llegado el momento para que los equipos obstétricos, cardiológicos y las pacientes jueguen un rol en la prevención de los riesgos y enfermedades cardiovasculares.

From 1995 onwards the association between hypertensive pregnancies and cardiovascular disease has generated a great volume of epidemiologic and clinical evidence. The purposes of this review are several. To demonstrate the consistence and weight of the scientific evidence. To integrate cardiovascular risks/diseases and obstetric complications through the link of endothelial dysfunction. To advocate postpartum follow-up after a hypertensive pregnancy as a window of opportunity to benefit the health of mothers and offsprings. To include the obstetrical history as a risk factor for coronary disease. To propose questionnaires adaptable to local practices to incorporate cardiovascular and obstetrical indexes in two stages of a woman's lifetime. The time has come for obstetrical teams, cardiologists and patients to play a preventive role regarding cardiovascular risks and diseases.

Desenlaces materno-fetales de los embarazos con trastornos hipertensivos: un estudio transversal / Maternal and fetal outcomes of pregnancies with hypertensive disorders: a cross-sectional study

INTRODUCCIÓN Y OBJETIVO: Los trastornos hipertensivos asociados al embarazo son considerados un problema de salud pública. Se busca describir las características clínicas y desenlaces materno-fetales de las pacientes con esta patología, atendidas en el Hospital Universitario de Santander (HUS) durante el primer semestre de 2017. MÉTODOS: Estudio observacional retrospectivo de corte transversal. Se incluyeron las pacientes en estado de embarazo o puerperio con diagnóstico o sospecha de trastorno hipertensivo; se excluyeron aquellas que no pudieron ser clasificadas o no correspondían a éstos. RESULTADOS: Se analizaron 181 historias clínicas; la edad de las pacientes osciló entre 14 y 44 años; el 43,7% eran primigestantes; el 40,3% tuvo un control prenatal inadecuado y el 27,5% tenía antecedente de trastorno hipertensivo en gestaciones previas. El 75,1% de las pacientes fueron clasificadas como preeclampsia, 18,2% con hipertensión gestacional, 4,4% con hipertensión más preeclampsia sobreagregada y 2,2% con hipertensión crónica. El 16,9% de las pacientes con preeclampsia debutaron antes de la semana 34, de las cuales el 91,3% tenían criterios de severidad; mientras que entre las demás, el 84% presentaron criterios de severidad. CONCLUSIONES: La preeclampsia fue el trastorno hipertensivo más frecuente, predominó la presentación tardía y severa con importantes tasas de complicación maternas y fetales. Mediante la implementación de estrategias de detección temprana y adecuada atención de los trastornos hipertensivos asociados al embarazo podrían mejorarse los desenlaces materno-fetales.

BACKGROUND AND OBJECTIVE: Hypertensive disorders of pregnancy are considered a public health issue. The aim is to describe the clinical features, maternal - fetal outcomes of patients with this disease, who were admitted at the University Hospital of Santander (Bucaramanga, Colombia) during the first half of 2017. METHOD: Cross-sectional retrospective observational study. Patients in pregnancy or puerperium with diagnosis of hypertensive disorder were included; those who could not be classified or did not correspond were excluded. RESULTS: 181 clinical charts were analyzed, the age of the patients ranged between 14 and 44 years, 43.7% were nulliparous, 40.3% had an inadequate prenatal control and 27.5% had history of hypertensive disorder in previous pregnancies. 75.1% were classified as preeclampsia, 18.2% as gestational hypertension, 4.4% as hypertension and superimposed preeclampsia and 2.2% with chronic hypertension; 16.9% of the patients were of an early-onset preeclampsia before week 34, of which 91.3% had criteria of severity; among the others, 84% presented criteria of severity. CONCLUSION: Preeclampsia was the most frequent hypertensive disorder, late and severe presentation prevailed with important maternal and fetal complication rates. Through the implementation of early detection strategies and adequate care of hypertensive disorders associated with pregnancy maternal and fetal outcomes could be improved.

Interaction between NOS3 and HMOX1 on antihypertensive drug responsiveness in preeclampsia / Interação entre os genes NOS3 e HMOX1 na resposta à terapia antihipertensiva em pré-eclâmpsia

Abstract Objective We examined the interaction of polymorphisms in the genes heme oxygenase- 1 (HMOX1) and nitric oxide synthase (NOS3) in patients with preeclampsia (PE) as well as the responsiveness to methyldopa and to total antihypertensive therapy. Methods The genes HMOX1 (rs2071746, A/T) and NOS3 (rs1799983, G/T) were genotyped using TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, USA ), and the levels of enzyme heme oxygenase-1 (HO-1) were measured using enzyme-linked immunosorbent assay (ELISA). Results We found interactions between genotypes of the HMOX-1 and NOS3 genes and responsiveness tomethyldopa and that PE genotyped as AT presents lower levels of protein HO-1 compared with AA. Conclusion We found interactions between the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that the HMOX1 polymorphism affects the levels of enzyme HO-1 in responsiveness to methyldopa and to total antihypertensive therapy. These data suggest impact of the combination of these two polymorphisms on antihypertensive responsiveness in PE.

Resumo Objetivo Examinamos a interação dos polimorfismos nos genes heme oxigenase-1 (HMOX1) eóxido nítrico sintase (NOS3) empacientes compré-eclâmpsia (PE)bem como as capacidades de resposta à metildopa e à terapia anti-hipertensiva. Métodos Os polimorfismos nos genes HMOX1 (rs2071746, A/T) e NOS3 (rs1799983, G/T) foram genotipados usando TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, EUA), e os níveis da enzima heme oxigenase-1 (HO-1) foram medidos por enzyme-linked immunosorbent assay (ELISA). Resultados Foram encontradas interações entre os genótipos da HMOX-1 e NOS3 e responsividade à metildopa, e que pacientes genotipados como AT apresentam níveis mais baixos de proteína HO-1 em comparação com o genótipo AA. Conclusão Foram encontradas interações entre os genes HMOX-1 e NOS3 e responsividade à metildopa e que o polimorfismo localizado no gene HMOX1 afeta os níveis de enzima HO-1 na resposta à metildopa e à terapia anti-hipertensiva. Esses dados sugerem o impacto da combinação desses dois polimorfismos na resposta antihipertensiva na PE.