Determination of the relationships between drug dosage, maternal and infant (cord blood) plasma drug concentrations, and serotonin reuptake inhibitor (SRI) bioeffect on offspring neurobehavior is crucial to assessing the effects of gestational SRI exposure. Measurement of maternal and cord blood platelet serotonin (5-HT) provides an index of inhibitory bioeffect at the 5-HT transporter and complements other measures of drug exposure. Three groups of mother-infant pairs were evaluated: (1) mothers with depression untreated with SRIs (DEP, n = 17), (2) mothers treated for depression with SRIs (DEP + SRI, n = 17), and (3) mothers who were not depressed and untreated (ND, n = 29).
View Article and Find Full Text PDFArch Womens Ment Health
December 2024
Purpose: Estrogen levels fall sharply after parturition and have long been considered an etiologic contributor to postpartum depression (PPD); however, no differences have been reported in plasma hormone concentrations in people who develop PPD. We examine the question: What is the current view of estrogen and the neurophysiologic processes it impacts in the development and treatment of PPD?
Methods: A literature review of the role of estrogen on candidate hormonal and epigenetic systems in the peripartum period was performed, including landmark historical studies and recent publications on estrogen-related research. The authors reviewed these papers and participated in reaching consensus on a conceptual framework of estrogen activity within the complexity of pregnancy physiology to examine its potential role for driving novel interventions.
The effectiveness of antidepressant treatment for mood disorders is often limited by either a poor response or the emergence of adverse effects. These complications often necessitate multiple drug trials. This clinical challenge intensifies during pregnancy, when medications must be selected to improve the likelihood of response and optimize reproductive outcomes.
View Article and Find Full Text PDFRationale: Few studies of the effect of the dynamic physiologic changes during pregnancy on plasma concentrations of fluoxetine (FLX) have been published.
Objectives: We determined the change in concentration to dose (C/D) ratios of R- and S-FLX and R- and S-norfluoxetine monthly during pregnancy and postpartum, assessed their relationships to cytochrome P450 (CYP) 2D6 and CYP2C9 metabolizer phenotypes, and evaluated the course of their depressive and anxiety symptoms.
Methods: In this observational study, 10 FLX-treated pregnant individuals provided blood samples at steady state every 4 weeks during pregnancy and once postpartum for measurement of plasma FLX and norfluoxetine enantiomer concentrations.
Objective: The primary purpose of this article is to identify factors that are associated with worsening mood and anxiety trajectories across the perinatal period among pregnant individuals receiving treatment with a selective-serotonin reupdate inhibitor.
Methods: This secondary analysis of primary data from the original article, Trajectories of Depressive and Anxiety Symptoms Across Pregnancy and Postpartum in Selective Serotonin Reuptake Inhibitor-Treated Women, explores if number of lifetime episodes of depression as characterized in the Mini-International Neuropsychiatric Interview, elevated maternal adverse childhood experiences (ACE) score, or specific obstetric or neonatal factors from the Peripartum Events Scale (PES) were associated with membership in trajectory groups with the highest symptom burden.
Results: No difference in ACE scores or obstetric or neonatal factors were associated with membership in the trajectory groups using Wilcoxon rank sum tests and bi-variable logistic regression.
Most of the interventions performed by obstetric providers involve the administration of drugs. Pregnant patients are pharmacologically and physiologically different from nonpregnant young adults. Therefore, dosages that are effective and safe for the general public may be inadequate or unsafe for the pregnant patient and her fetus.
View Article and Find Full Text PDFPregnant people have traditionally been excluded from therapeutic research by restrictions intended for fetal protection. Despite a movement toward inclusion, concerns for the feasibility and safety of including pregnant people in studies continue to limit this research. This article reviews the history of research guidelines in pregnancy and illustrates ongoing challenges, as seen in the development of vaccines and therapies during the coronavirus disease 2019 pandemic and investigation of statins for preeclampsia prevention.
View Article and Find Full Text PDFBackground: The effectiveness of 17-hydroxyprogesterone caproate is unclear as trials have provided conflicting results. With the absence of fundamental pharmacologic studies addressing dosing or the relationship between drug concentration and gestational age at delivery, the effectiveness of the medication cannot be evaluated.
Objective: This study aimed to evaluate the relationship between plasma concentrations of 17-hydroxyprogesterone caproate and preterm birth rates and gestational age at preterm delivery and to assess the safety of the 500-mg dose.
Obstet Gynecol Clin North Am
March 2023
Obstet Gynecol Clin North Am
March 2023
Since the recognition of pregnancy as a special pharmacokinetic population in the late 1990s, investigations have expanded our understanding of obstetric pharmacology. Many of the basic physiologic changes that occur during pregnancy impact on drug absorption, distribution, or clearance. Activities of hepatic metabolizing enzymes are variably altered by pregnancy, resulting in concentrations sufficiently different for some drugs that efficacy or toxicity may be affected.
View Article and Find Full Text PDFRetinoids and vitamin A are essential for multiple biological functions, including vision and immune responses, as well as the development of an embryo during pregnancy. Despite its importance, alterations in retinoid homeostasis during normal human pregnancy are incompletely understood. We aimed to characterize the temporal changes in the systemic retinoid concentrations across pregnancy and postpartum period.
View Article and Find Full Text PDFObjectives: This study aimed to evaluate the prevalence of obstetric and gynecologic (Ob/Gyn) hospitalists and determine if an association exists between the presence of Ob/Gyn hospitalists and severe maternal morbidity (SMM).
Methods: This observational study included data from hospitals listed in the USA TODAY 's 2019 article titled, "Deadly deliveries: Childbirth complication rates at maternity hospitals." Telephone and email surveys of staff in these hospitals identified the presence or absence of continuous providers in the hospital 24 hours, 7 days a week (24/7 coverage) and the types of providers who are employed, then compared these responses with the SMM cited by USA TODAY .
Objective: Tracking perinatal mood and anxiety disorders is championed by the American Psychiatric Association and the International Marcé Society for Perinatal Mental Health. We conducted this study to examine trajectories of monthly depressive and anxiety symptoms through pregnancy and postpartum.
Methods: This is a prospective longitudinal observational cohort study of pregnant women interviewed at baseline (≤18th gestational week), every four weeks through delivery and at 6 and 14 weeks postpartum at three urban academic medical centers ( = 85) and a single rural health center ( = 3) from 2016 to 2020.
Major depressive disorder (MDD) is a common disorder in pregnancy. Although sertraline is the most frequently prescribed antidepressant for pregnant people in the United States, limited information about its pharmacokinetics in pregnancy is available. Our objectives were to characterize plasma sertraline concentration to dose (C/D) ratios across pregnancy and postpartum and investigate the effect of pharmacogenetic variability on sertraline elimination.
View Article and Find Full Text PDFThe pharmacokinetics of lithium, the gold standard for the treatment of bipolar disorder, are well described in nonpregnant patients. Because lithium is commonly prescribed to women of childbearing age, more data are essential to characterize lithium pharmacokinetics during the perinatal period. Lithium is primarily eliminated by the kidney.
View Article and Find Full Text PDFBackground: Preeclampsia remains a major cause of maternal and neonatal morbidity and mortality. Biologic plausibility, compelling preliminary data, and a pilot clinical trial support the safety and utility of pravastatin for the prevention of preeclampsia.
Objective: We previously reported the results of a phase I clinical trial using a low dose (10 mg) of pravastatin in high-risk pregnant women.
Objective: Mental health care for women includes decision support to prepare for major life events, including preconception planning for treatment during pregnancy and the postpartum period. The authors discuss contraceptive choices and their effectiveness, side effects, and impact on psychiatric symptoms. The Centers for Disease Control and Prevention's recommendations, Medical Eligibility Criteria for Contraceptive Use, provided the structure for review of contraceptive choices.
View Article and Find Full Text PDFHepatic drug metabolism is a major route of drug elimination, mediated by multiple drug-metabolizing enzymes. Any changes in the rate and extent of hepatic drug metabolism can lead to altered drug efficacy or toxicity. Accumulating clinical evidence indicates that pregnancy is accompanied by changes in hepatic drug metabolism.
View Article and Find Full Text PDFPharmacologic interventions play a major role in obstetrical care throughout pregnancy, labor and delivery and the postpartum. Traditionally, obstetrical providers have utilized standard dosing regimens developed for non-obstetrical indications based on pharmacokinetic knowledge from studies in men or non-pregnant women. With the recognition of pregnancy as a special pharmacokinetic population in the late 1990s, investigators have begun to study drug disposition in this unique patient dyad.
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