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2.
Artículo en Inglés | MEDLINE | ID: mdl-38765512

RESUMEN

• The balanced vaginal microbiome is the main factor defending the vaginal environment against infections. Lactobacilli play a key role in this regard, maintaining the vaginal pH within the normal range (3.8 to 4.5). •Hormonal and immune adaptations resulting from pregnancy influence changes in the vaginal microbiome during pregnancy. •An altered vaginal microbiome predisposes to human immunodeficiency virus (HIV) infection. •Bacterial vaginosis is the main clinical expression of an imbalanced vaginal microbiome. •Vulvovaginal candidiasis depends more on the host's conditions than on the etiological agent. •Trichomonas vaginalis is a protozoan transmitted during sexual intercourse. •The use of probiotics is not approved for use in pregnant women.


Asunto(s)
Complicaciones Infecciosas del Embarazo , Vulvovaginitis , Humanos , Femenino , Embarazo , Vulvovaginitis/microbiología , Microbiota , Vagina/microbiología , Vaginosis Bacteriana
3.
J Clin Pharmacol ; 64(5): 568-577, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38305718

RESUMEN

Nifedipine is used for treating mild to severe hypertension and preventing preterm labor in pregnant women. Nevertheless, concerns about nifedipine fetal exposure and safety are always raised. The aim of this study was to develop and validate a maternal-placental-fetal nifedipine physiologically based pharmacokinetic (PBPK) model and apply the model to predict maternal, placental, and fetal exposure to nifedipine at different pregnancy stages. A nifedipine PBPK model was verified with nonpregnant data and extended to the pregnant population after the inclusion of the fetoplacental multicompartment model that accounts for the placental tissue and different fetal organs within the Simcyp Simulator version 22. Model parametrization involved scaling nifedipine transplacental clearance based on Caco-2 permeability, and fetal hepatic clearance was obtained from in vitro to in vivo extrapolation encompassing cytochrome P450 3A7 and 3A4 activities. Predicted concentration profiles were compared with in vivo observations and the transplacental transfer results were evaluated using 2-fold criteria. The PBPK model predicted a mean cord-to-maternal plasma ratio of 0.98 (range, 0.86-1.06) at term, which agrees with experimental observations of 0.78 (range, 0.59-0.93). Predicted nifedipine exposure was 1.4-, 2.0-, and 3.0-fold lower at 15, 27, and 39 weeks of gestation when compared with nonpregnant exposure, respectively. This innovative PBPK model can be applied to support maternal and fetal safety assessment for nifedipine at various stages of pregnancy.


Asunto(s)
Intercambio Materno-Fetal , Modelos Biológicos , Nifedipino , Placenta , Nifedipino/farmacocinética , Nifedipino/administración & dosificación , Humanos , Embarazo , Femenino , Placenta/metabolismo , Células CACO-2 , Feto/metabolismo , Adulto , Citocromo P-450 CYP3A/metabolismo
5.
Radiol Bras ; 56(4): 179-186, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37829588

RESUMEN

Objective: To evaluate the capacity of fetal Doppler, maternal, and obstetric characteristics for the prediction of cesarean section due to intrapartum fetal compromise (IFC), a 5-min Apgar score < 7, and an adverse perinatal outcome (APO), in a high-risk population. Materials and Methods: This was a prospective cohort study involving 613 singleton pregnant women, admitted for labor induction or at the beginning of spontaneous labor, who underwent Doppler ultrasound within the last 72 h before delivery. The outcome measures were cesarean section due to IFC, a 5-min Apgar score < 7, and any APO. Results: We found that maternal characteristics were neither associated with nor predictors of an APO. Abnormal umbilical artery (UA) resistance index (RI) and the need for intrauterine resuscitation were found to be significant risk factors for cesarean section due to IFC (p = 0.03 and p < 0.0001, respectively). A UA RI > the 95th percentile and a cerebroplacental ratio (CPR) < 0.98 were also found to be predictors of cesarean section due to IFC. Gestational age and a UA RI > 0.84 were found to be predictors of a 5-min Apgar score < 7 for newborns at < 29 and ≥ 29 weeks, respectively. The UA RI and CPR presented moderate accuracy in predicting an APO, with areas under the ROC curve of 0.76 and 0.72, respectively. Conclusion: A high UA RI appears to be a significant predictor of an APO. The CPR seems to be predictive of cesarean section due to IFC and of an APO in late preterm and term newborns.


Objetivo: Avaliar a capacidade do Doppler fetal e características materno-obstétricas na predição de cesariana por comprometimento fetal intraparto (CFI), índice de Apgar de 5º min < 7 e desfecho perinatal adverso (DPA) em uma população de alto risco. Materiais e Métodos: Estudo de coorte prospectivo envolvendo 613 parturientes admitidas para indução ou em início de trabalho de parto espontâneo que realizaram ultrassonografia Doppler nas 72 horas anteriores ao parto. Os desfechos foram cesariana por CFI, índice de Apgar de 5º min < 7 e DPA. Resultados: As características maternas não foram associadas nem preditoras de DPA. Índice de resistência (IR) da artéria umbilical (AU) anormal (p = 0,03) e necessidade de medidas de ressuscitação intrauterina (p < 0,0001) permaneceram como fatores de risco significativos para cesariana por CFI. IR AU > 95º e razão cerebroplacentária (RCP) < 0,98 foram preditores de cesariana. Idade gestacional e IR AU > 0,84 foram os preditores de índice de Apgar de 5º min < 7 para recém-nascidos < 29 e ≥ 29 semanas, respectivamente. IR AU e RCP apresentaram acurácia moderada na predição de DPA (área sob a curva ROC de 0,76 e 0,72, respectivamente). Conclusão: IR UA mostrou-se preditor significativo de DPA. RCP revelou-se possível preditora de cesariana por CFI e DPA em recémnascidos prematuros tardios e a termo.

6.
Pharmaceutics ; 15(10)2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37896187

RESUMEN

Inflammation can regulate hepatic drug metabolism enzymes and transporters. The impact of inflammation on renal drug transporters remains to be elucidated. We aimed to quantify the effect of inflammation (caused by acute pyelonephritis) on the in vivo activity of renal OAT1/3, using the probe drug furosemide. Pregnant women (second or third trimester) received a single oral dose of furosemide 40 mg during acute pyelonephritis (Phase 1; n = 7) and after its resolution (Phase 2; n = 7; by treatment with intravenous cefuroxime 750 mg TID for 3-7 days), separated by 10 to 14 days. The IL-6, IFN-γ, TNF-α, MCP-1, and C-reactive protein plasma concentrations were higher in Phase I vs. Phase II. The pregnant women had a lower geometric mean [CV%] furosemide CLsecretion (3.9 [43.4] vs. 6.7 [43.8] L/h) and formation clearance to the glucuronide (1.1 [85.9] vs. 2.3 [64.1] L/h) in Phase 1 vs. Phase 2. Inflammation reduced the in vivo activity of renal OAT1/3 (mediating furosemide CLsecretion) and UGT1A9/1A1 (mediating the formation of furosemide glucuronide) by approximately 40% and 54%, respectively, presumably by elevating the plasma cytokine concentrations. The dosing regimens of narrow therapeutic window OAT drug substrates may need to be adjusted during inflammatory conditions.

7.
Femina ; 51(10): 614-626, 20231030. ilus
Artículo en Portugués | LILACS | ID: biblio-1532465

RESUMEN

Até este momento da pandemia de COVID-19, embora as gestantes não tenham maior risco de se infectar do que a população geral, elas têm maiores riscos de desenvolver formas graves e demandar cuidados de UTI e ventilação invasiva, so- bretudo aquelas que apresentam comorbidades. No Brasil, a mortalidade materna por COVID-19 está entre as mais elevadas do mundo. A transmissão vertical do SARS-CoV-2 parece ser um evento raro, e até o momento não se observou aumento da ocorrência de abortos e malformações. Entretanto, a COVID-19 está associada a elevadas taxas de prematuridade, baixo peso ao nascer e admissão em UTI neona- tal. Em adaptação a esse novo cenário, são indicados cuidados especiais durante o ciclo gravídico-puerperal, sendo útil destacar: o espaço crescente da telemedicina no pré-natal; a não obrigatoriedade da realização de cesariana em caso de gestan- te infectada no momento do parto e a liberação da amamentação pelas puérperas com COVID-19.


Asunto(s)
Humanos , Femenino , Embarazo , Recién Nacido , Lactante , Complicaciones del Embarazo , Trastornos Puerperales/prevención & control , COVID-19/epidemiología , Respiración Artificial/instrumentación , Recién Nacido de Bajo Peso , Unidades de Cuidado Intensivo Neonatal , Telemedicina/instrumentación , Embarazo de Alto Riesgo , Parto , Nacimiento Prematuro/prevención & control , Disnea/complicaciones , Tratamiento Farmacológico de COVID-19/métodos
8.
J Pharm Biomed Anal ; 235: 115635, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37634358

RESUMEN

Furosemide (FUR) has been used in probe drugs cocktails for in vivo evaluation of the renal transporters OAT1 and OAT3 activities in studies of drug-drug interactions (generally using probenecid as an inhibitor) and drug-disease interactions. The objective of this study was to develop and validate methods for FUR and its glucuronide metabolite (FUR-GLU) analysis in plasma, plasma ultrafiltrate and urine for application in pharmacokinetics studies: a pilot drug-drug interaction study in pregnant women (n = 2), who received a single oral dose of FUR (40 mg) and in another occasion a single oral dose of probenecid (750 mg) before a single oral dose of FUR (40 mg), and in non-pregnant women participants (n = 12), who only received a single oral dose of FUR (40 mg). The samples preparation for FUR in 50 µL of plasma and plasma lysate were carried by acidified liquid-liquid extraction, while 50 µL of urine and 200 µL of plasma ultrafiltrate were simply diluted with the mobile phase. The methods presented linearities in the range of 0.50 - 2500 ng/mL of plasma and plasma lysate, 0.125 - 250 ng/mL of plasma ultrafiltrate, and 50 - 20,000 ng/mL of urine. FUR-GLU methods presented linearities in the range of 0.125 - 250 ng/mL of plasma ultrafiltrate and 50 - 20,000 ng/mL of urine. Precision and accuracy evaluations showed coefficients of variation and relative errors < 15%. In the pregnant women participants, the mean values of FUR CLrenal, CLsecretion, CLformation. FUR-GLU and CLnon-renal were all reduced when probenecid was administered with FUR (8.24 vs 2.89 L/h, 8.15 vs 2.80 L/h, 3.86 vs 1.75 L/h, 48.26 vs 22.10 L/h, respectively). Non-pregnant women presented similar values of FUR CLrenal, CLsecretion, CLformation. FUR-GLU to the pregnant women who received FUR only. Finally, FUR fraction unbound (fu) resulted in values of approximately 1% in pregnant women and to 0.22% in non-pregnant women. These developed and validated methods for FUR and FUR-GLU quantification in multiple matrices can allow the further investigation of UGT1A9/1A1 and the fu when FUR is administered as an OAT 1 and 3 in vivo probe.


Asunto(s)
Furosemida , Glucurónidos , Femenino , Humanos , Cromatografía Líquida de Alta Presión , Probenecid , Espectrometría de Masas en Tándem
9.
J Clin Pharmacol ; 63(9): 1053-1060, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37260039

RESUMEN

This work aimed to evaluate the total, unbound, renal, and hepatic clearances of raltegravir (RAL) and the formation and elimination clearances of raltegravir glucuronide (RAL GLU) in pregnant women living with HIV. The participants received RAL 400 mg twice daily during the third trimester (n = 15) of gestation, delivery (n = 15), and the postpartum period (n = 8). Pharmacokinetic parameter values were calculated on the basis of plasma and urine data using noncompartmental methods. RAL clearances for the third trimester of gestation were as follows: total clearance: geometric mean, 63.63 L/h (95% CI, 47.5-85.25); renal clearance: geometric mean, 2.56 L/h (95% CI, 1.96-3.34); hepatic clearance: geometric mean, 60.52 L/h (95% CI, 44.65-82.04); and unbound clearance: geometric mean, 281.14 L/h (95% CI, 203.68-388.05). RAL GLU formation and elimination clearances for the third trimester of gestation were 7.57 L/h (95% CI, 4.94-11.6) and 8.71 L/h (95% CI, 6.71-11.32), respectively. No differences were observed in RAL GLU pharmacokinetic parameters between the third trimester of gestation and the postpartum period, except for higher formation (7.57 vs 4.03 L/h) and elimination (8.71 vs 4.92 L/h) clearances during the third trimester. The findings based on plasma and urine data are consistent with an increase in the hepatic uridine 5' diphospho-glucuronosyltransferase isoenzymes activities involved in RAL metabolism during pregnancy, and the formation of RAL GLU is a minor route of RAL elimination. Compared to the postpartum period, in the third trimester of gestation, the similar RAL plasma exposure in pregnant women reinforces the maintenance of an RAL regimen including a 400-mg oral dose twice daily during pregnancy.


Asunto(s)
Glucurónidos , Infecciones por VIH , Femenino , Humanos , Embarazo , Raltegravir Potásico/farmacocinética , Mujeres Embarazadas , Infecciones por VIH/tratamiento farmacológico , Periodo Posparto
11.
Rev Bras Ginecol Obstet ; 45(2): 59-64, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36977402

RESUMEN

OBJECTIVE: To evaluate the seroprevalence of toxoplasmosis among puerperal women cared for at a tertiary university hospital and the level of understanding of these puerperal women about toxoplasmosis, vertical transmission, and its prophylaxis. METHODS: For this cross-sectional study, we evaluated 225 patients using presential interviews, prenatal documentation, and electronic medical records. Data were stored using Research Electronic Data Capture (REDCap) software. Prevalence rates were estimated by the presence of reactive IgG antibodies against Toxoplasma gondii. Data analysis was performed using the chi-square test and calculation of the odds ratio (OR). Seroreactivity to T. gondii and exposure variables (age, educational level, and parity) were analyzed using a confidence interval (95%CI) and a significance level of 5% (p < 0.05). RESULTS: The seropositivity rate for T. gondii was 40%. There was no association between seroprevalence and age. Primiparity was a protective factor against seropositivity and low education was a risk factor. CONCLUSION: Knowledge of T. gondii infection and its transmission forms was significantly limited, presenting a risk for acute maternal toxoplasmosis and vertical transmission of this protozoan. Increasing the education level regarding the risk of toxoplasmosis during pregnancy could reduce the rates of infection and vertical transmission of this parasite.


OBJETIVO: Avaliar a soroprevalência de toxoplasmose entre puérperas atendidas em um hospital universitário terciário e o nível de compreensão dessas puérperas sobre toxoplasmose, transmissão vertical e sua profilaxia. MéTODOS: Para esse estudo transversal, foram avaliadas 225 pacientes utilizando entrevistas presenciais, documentação de pré-natal e prontuário eletrônico. Os dados foram armazenados usando o software Research Electronic Data Capture (REDCap). As taxas de prevalência foram estimadas pela presença de anticorpos IgG reativos contra o Toxoplasma gondii. A análise dos dados foi realizada por meio do teste do qui-quadrado e cálculo do odds ratio (OR). A sororreatividade ao T. gondii e as variáveis de exposição (idade, escolaridade e paridade) foram analisadas, utilizando-se intervalo de confiança (IC95%) e nível de significância de 5% (p < 0,05). RESULTADOS: A taxa de soropositividade para T. gondii foi de 40%. Não houve associação entre soroprevalência e idade. A primiparidade foi fator de proteção contra a soropositividade e a baixa escolaridade foi fator de risco. CONCLUSãO: O conhecimento da infecção por T. gondii e suas formas de transmissão foi significativamente limitado, apresentando risco para toxoplasmose materna aguda e transmissão vertical desse protozoário. Aumentar o nível de escolaridade quanto ao risco de toxoplasmose durante a gravidez pode reduzir as taxas de infecção e transmissão vertical desse parasita.


Asunto(s)
Toxoplasma , Toxoplasmosis , Femenino , Humanos , Embarazo , Anticuerpos Antiprotozoarios , Estudios Transversales , Inmunoglobulina M , Factores de Riesgo , Estudios Seroepidemiológicos , Centros de Atención Terciaria , Toxoplasmosis/epidemiología
14.
Rev. bras. ginecol. obstet ; 45(2): 59-64, Feb. 2023. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1449708

RESUMEN

Abstract Objective To evaluate the seroprevalence of toxoplasmosis among puerperal women cared for at a tertiary university hospital and the level of understanding of these puerperal women about toxoplasmosis, vertical transmission, and its prophylaxis. Methods For this cross-sectional study, we evaluated 225 patients using presential interviews, prenatal documentation, and electronic medical records. Data were stored using Research Electronic Data Capture (REDCap) software. Prevalence rates were estimated by the presence of reactive IgG antibodies against Toxoplasma gondii. Data analysis was performed using the chi-square test and calculation of the odds ratio (OR). Seroreactivity to T. gondii and exposure variables (age, educational level, and parity) were analyzed using a confidence interval (95%CI) and a significance level of 5% (p < 0.05). Results The seropositivity rate for T. gondii was 40%. There was no association between seroprevalence and age. Primiparity was a protective factor against seropositivity and low education was a risk factor. Conclusion Knowledge of T. gondii infection and its transmission forms was significantly limited, presenting a risk for acute maternal toxoplasmosis and vertical transmission of this protozoan. Increasing the education level regarding the risk of toxoplasmosis during pregnancy could reduce the rates of infection and vertical transmission of this parasite.


Resumo Objetivo Avaliar a soroprevalência de toxoplasmose entre puérperas atendidas em um hospital universitário terciário e o nível de compreensão dessas puérperas sobre toxoplasmose, transmissão vertical e sua profilaxia. Métodos Para esse estudo transversal, foram avaliadas 225 pacientes utilizando entrevistas presenciais, documentação de pré-natal e prontuário eletrônico. Os dados foram armazenados usando o software Research Electronic Data Capture (REDCap). As taxas de prevalência foram estimadas pela presença de anticorpos IgG reativos contra o Toxoplasma gondii. A análise dos dados foi realizada por meio do teste do qui-quadrado e cálculo do odds ratio (OR). A sororreatividade ao T. gondii e as variáveis de exposição (idade, escolaridade e paridade) foram analisadas, utilizando-se intervalo de confiança (IC95%) e nível de significância de 5% (p < 0,05). Resultados A taxa de soropositividade para T. gondii foi de 40%. Não houve associação entre soroprevalência e idade. A primiparidade foi fator de proteção contra a soropositividade e a baixa escolaridade foi fator de risco. Conclusão O conhecimento da infecção por T. gondii e suas formas de transmissão foi significativamente limitado, apresentando risco para toxoplasmose materna aguda e transmissão vertical desse protozoário. Aumentar o nível de escolaridade quanto ao risco de toxoplasmose durante a gravidez pode reduzir as taxas de infecção e transmissão vertical desse parasita.


Asunto(s)
Humanos , Femenino , Embarazo , Toxoplasmosis , Educación en Salud , Prevalencia , Transmisión Vertical de Enfermedad Infecciosa
15.
Artículo en Inglés | MEDLINE | ID: mdl-36714276

RESUMEN

Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.

16.
Fetal Pediatr Pathol ; 42(1): 131-136, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35414337

RESUMEN

Background. Adams-Oliver syndrome is a congenital disease whose main findings are aplasia cutis congenita of the scalp and terminal transverse limb defects. The pathogenesis is unknown, but it is postulated that ischemic events in susceptible tissues cause the lesions in the embryonic period.Case report. We present a newborn with a severe phenotype of Adams-Oliver syndrome. The infant's mother had a SARS-CoV-2 infection in the first trimester of pregnancy. Prenatal ultrasound indicates a probable worsening of the disease after the first trimester.Conclusion. This study shows a previously unpublished severe AOS phenotype in a term newborn. There are some signs that the disease could have progressed beyond the first trimester, either spontaneously or by the inflammatory mechanisms of SARS-CoV-2.


Asunto(s)
COVID-19 , Displasia Ectodérmica , Deformidades Congénitas de las Extremidades , Humanos , SARS-CoV-2 , COVID-19/complicaciones , Displasia Ectodérmica/complicaciones , Deformidades Congénitas de las Extremidades/diagnóstico , Cuero Cabelludo/anomalías
17.
J Clin Pharmacol ; 63(2): 219-227, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36087110

RESUMEN

This study evaluates the influence of pregnancy and HIV infection in conjunction with the use of raltegravir, lamivudine, and tenofovir disoproxil fumarate (combined antiretroviral therapy [cART]) on intestinal P-glycoprotein (P-gp) and hepatic organic anion transporter polypeptide (OATP) 1B1/1B3 and/or breast cancer resistance protein (BCRP) drug transporter activity using rosuvastatin (OATP1B/BCRP) and fexofenadine (P-gp) probes. Single oral doses of 5-mg rosuvastatin and 60-mg fexofenadine were administered to women living with HIV under cART in the third trimester of gestation (n = 15) and postpartum period (n = 10). A control group of 12 healthy nonpregnant women also was investigated. Pharmacokinetic parameters were estimated by using a noncompartmental method and evaluated by t test (P < .05). The rosuvastatin area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-last ) value was higher in the third trimester of pregnancy (19.5 [95%CI, 16.8-22.3] ng • h/mL] when compared to postpartum (13.3 [95%CI, 9.3-17.5] ng • h/mL), while the fexofenadine AUC0-last values did not differ between the third trimester of pregnancy (738.0 [95%CI, 611.4-864.6] ng • h/mL) and postpartum period (874.9 [95%CI, 408.2-1342.0] ng• h/mL). The rosuvastatin AUC0-last values did not differ between healthy nonpregnant women (13.8 [95%CI, 10.0-17.6] ng • h/mL) and women living with HIV in the postpartum period (13.3 [95%CI, 9.3-17.5] ng • h/mL), and the fexofenadine AUC0-last values did not differ between the 2 investigated groups (603.6 [95%CI, 467.5-739.7] ng • h/mL vs 874.9 [95%CI, 408.2-1342.0] ng • h/mL). It is suggested that gestation inhibits the hepatic OATP1B1/1B3 and/or BCRP activity but does not alter intestinal P-gp activity. The influence of HIV infection in conjunction with use of cART on OATP1B/BCRP and intestinal P-gp activity was not observed.


Asunto(s)
Neoplasias de la Mama , Infecciones por VIH , Transportadores de Anión Orgánico , Humanos , Femenino , Embarazo , Rosuvastatina Cálcica/farmacocinética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Mujeres Embarazadas , Infecciones por VIH/tratamiento farmacológico , Transportador 1 de Anión Orgánico Específico del Hígado/metabolismo , Interacciones Farmacológicas , Proteínas de Neoplasias/metabolismo
18.
Ther Drug Monit ; 45(2): 159-172, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36127797

RESUMEN

BACKGROUND: More than 90% of pregnant women take at least one drug during pregnancy. Drug dose adjustments during pregnancy are sometimes necessary due to various pregnancy-induced physiological alterations frequently associated with lower plasma concentrations. However, the clinical relevance or benefits of therapeutic drug monitoring (TDM) in pregnant women have not been specifically studied. Clinical pharmacokinetic studies in pregnant women are incredibly challenging for many reasons. Despite this, regulatory agencies have made efforts to encourage the inclusion of this population in clinical trials to achieve more information on the pharmacotherapy of pregnant women. This review aims to provide support for TDM recommendations and dose adjustments in pregnant women. METHODS: The search was conducted after a predetermined strategy on PubMed and Scopus databases using the MeSH term "pregnancy" alongside other terms such as "Pregnancy and dose adjustment," "Pregnancy and therapeutic drug monitoring," "Pregnancy and PBPK," "Pregnancy and pharmacokinetics," and "Pregnancy and physiological changes." RESULTS: The main information on TDM in pregnant women is available for antiepileptics, antipsychotics, antidepressants, antibiotics, antimalarials, and oncologic and immunosuppressive drugs. CONCLUSIONS: More data are needed to support informed benefit-risk decision making for the administration of drugs to pregnant women. TDM and/or pharmacokinetic studies could ensure that pregnant women receive an adequate dosage of an active drug. Mechanistic modeling approaches potentially could increase our knowledge about the pharmacotherapy of this special population, and they could be used to better design dosage regimens.


Asunto(s)
Antimaláricos , Mujeres Embarazadas , Embarazo , Femenino , Humanos , Monitoreo de Drogas , Antibacterianos , Preparaciones Farmacéuticas
19.
Radiol. bras ; 56(4): 179-186, 2023. tab
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1514660

RESUMEN

Abstract Objective: To evaluate the capacity of fetal Doppler, maternal, and obstetric characteristics for the prediction of cesarean section due to intrapartum fetal compromise (IFC), a 5-min Apgar score < 7, and an adverse perinatal outcome (APO), in a high-risk population. Materials and Methods: This was a prospective cohort study involving 613 singleton pregnant women, admitted for labor induction or at the beginning of spontaneous labor, who underwent Doppler ultrasound within the last 72 h before delivery. The outcome measures were cesarean section due to IFC, a 5-min Apgar score < 7, and any APO. Results: We found that maternal characteristics were neither associated with nor predictors of an APO. Abnormal umbilical artery (UA) resistance index (RI) and the need for intrauterine resuscitation were found to be significant risk factors for cesarean section due to IFC (p = 0.03 and p < 0.0001, respectively). A UA RI > the 95th percentile and a cerebroplacental ratio (CPR) < 0.98 were also found to be predictors of cesarean section due to IFC. Gestational age and a UA RI > 0.84 were found to be predictors of a 5-min Apgar score < 7 for newborns at < 29 and ≥ 29 weeks, respectively. The UA RI and CPR presented moderate accuracy in predicting an APO, with areas under the ROC curve of 0.76 and 0.72, respectively. Conclusion: A high UA RI appears to be a significant predictor of an APO. The CPR seems to be predictive of cesarean section due to IFC and of an APO in late preterm and term newborns.


Resumo Objetivo: Avaliar a capacidade do Doppler fetal e características materno-obstétricas na predição de cesariana por comprometimento fetal intraparto (CFI), índice de Apgar de 5º min < 7 e desfecho perinatal adverso (DPA) em uma população de alto risco. Materiais e Métodos: Estudo de coorte prospectivo envolvendo 613 parturientes admitidas para indução ou em início de trabalho de parto espontâneo que realizaram ultrassonografia Doppler nas 72 horas anteriores ao parto. Os desfechos foram cesariana por CFI, índice de Apgar de 5º min < 7 e DPA. Resultados: As características maternas não foram associadas nem preditoras de DPA. Índice de resistência (IR) da artéria umbilical anormal (p = 0,03) e necessidade de medidas de ressuscitação intrauterina (p < 0,0001) permaneceram como fatores de risco significativos para cesariana por CFI. IR AU > 95º e razão cerebroplacentária (RCP) < 0,98 foram preditores de cesariana. Idade gestacional e IR AU > 0,84 foram os preditores de índice de Apgar de 5º min < 7 para recém-nascidos < 29 e ≥ 29 semanas, respectivamente. IR AU e RCP apresentaram acurácia moderada na predição de DPA (área sob a curva ROC de 0,76 e 0,72, respectivamente). Conclusão: IR UA mostrou-se preditor significativo de DPA. RCP revelou-se possível preditora de cesariana por CFI e DPA em recémnascidos prematuros tardios e a termo.

20.
AJOG Glob Rep ; 2(4): 100125, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36478664

RESUMEN

BACKGROUND: Labor is a physiological process triggered by mechanical and hormonal events that promote uterine contractions to expel the fetus. OBJECTIVE: This study aimed to evaluate the effectiveness of a nonpharmacologic childbirth care protocol in women in the active phase of labor in improving obstetrical and perinatal outcomes. STUDY DESIGN: This was a randomized trial with concealed allocation, assessor blinding, and intention-to-treat analysis. A total of 80 low-risk primigravida women at the end of pregnancy admitted at the beginning of the active phase of labor participated in the study. The participants were divided into an experimental group (n=40) and a control group (n=40). Women in the experimental group received 4 interventions: ambulation at 4 to 6 cm of cervical dilation, alternation of maternal postures, transcutaneous electrical nerve stimulation at 6 to 7 cm, and a warm shower bath at >7 cm. The control group received only routine obstetrical care during labor. The parturient could request pharmacologic analgesia at any time during the study. The main outcome measures were the duration of the active phase of the first stage of labor, the duration of the expulsive phase of labor, and the prevalence of labor dystocia as assessed by the partograph. The researchers collected other maternal and neonatal data from official birth records. RESULTS: The parturients who received the nonpharmacologic protocol had a shorter active phase of the first stage of labor (444 minutes in the control group and 373 minutes in the experimental group; P=.02), presented rupture of membranes later in labor (7 cm in the control group and 8 cm in the experimental group; P<.01), requested pharmacologic analgesia with more significant cervical dilation (5 cm in the control group and 8 cm in the experimental group; P<.01), requested fewer additional doses of analgesics, and had lower labor dystocia rates than the patients in the control group. In addition, there was no difference in other maternal and perinatal variables between the control group and the experimental group. CONCLUSION: The implementation of a sequential nonpharmacologic protocol composed of ambulation, transcutaneous electrical nerve stimulation with change of upright positions, and warm shower bath has the potential to reduce labor pain, as reflected in decreased and delayed use of pharmacologic analgesia and reduced duration of the active phase of labor and dystocia rates. Maternity hospitals should provide this protocol, and women should be encouraged to request this childbirth care protocol.

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