An Approach for Improving the Detection and Quantitation of Buprenorphine and Its Metabolites in Maternal and Neonatal Hair.

Background: Buprenorphine (BUP) use is prevalent in pregnant women with opioid use disorder (OUD). Drug monitoring during pregnancy is critical for optimizing dosing regimen and achieving the desired clinical outcomes. Hair can be used as a critical biological matrix for monitoring long-term exposure to drugs.

Vaginal administration of 17-alpha hydroxyprogesterone caproate appears to be safe in non-pregnant female rats and rabbits.

Intramuscular (250 mg once weekly) or subcutaneous (275 mg once weekly) injections of 17-hydroxyprogesterone caproate (17-OHPC) has been utilised to prevent recurent spontaneous preterm birth in pregnant women with a short cervix or those with a prior preterm birth but its efficacy in these conditions has been questioned. It is unclear whether adequate concentrations of 17-OHPC reach the suspected target organs such as the cervix and uterus following either IM or SC administration.The objective of this study was to determine feasibility and safety of vaginal administration of 17-OHPC in adult female Sprague Dawley rats and female New Zealand rabbits.

Optimizing drug therapy during pregnancy: a spotlight on population pharmacokinetic modeling.

Introduction: Optimizing drug therapy during pregnancy is crucial for ensuring the safety of mothers and babiesPhysiological changes that occur during pregnancy can significantly alter the pharmacokinetics of medications. Population pharmacokinetic (PopPK) modeling is a valuable tool to guide drug dosing regimens in pregnant women.

Areas Covered: This narrative review summarizes the current literature on the application of PopPK modeling to optimize drug therapy during human pregnancy.

The association between perinatal depressive symptoms and child neurodevelopment.

Background: Perinatal depression has been suggested to adversely impact child neurodevelopment. However, the complexity of the early childhood environment challenges conclusive findings.

Objective: To evaluate whether there is an association between perinatal depressive symptoms and child intelligence quotient (IQ) at 5 years of age.

A Pharmacologic Evaluation of Buprenorphine in Pregnancy and the Postpartum Period.

Background: The dosing regimen in the package insert for sublingual buprenorphine is similar for pregnant and nonpregnant people despite the physiologic changes seen during pregnancy.

Aims: To compare plasma buprenorphine pharmacokinetics during and after pregnancy and relate buprenorphine concentration to the pharmacodynamic endpoints of pupil diameter, Clinical Opioid Withdrawal Scale (COWS), and craving scores.

Study Design: Prospective cohort of 22 pregnant people undergoing 33 pharmacologic studies (6-8 hours each) during pregnancy or postpartum.

Progression of Gestational Subclinical Hypothyroidism and Hypothyroxinemia to Overt Hypothyroidism After Pregnancy: Pooled Analysis of Data from Two Randomized Controlled Trials.

To examine the incidence of overt hypothyroidism 1 and 5 years after pregnancies where screening before 21 weeks identified subclinical hypothyroidism (SH) or hypothyroxinemia (HT). Secondary analysis of two multicenter treatment trials for either SH or HT diagnosed between 8 and 20 weeks gestation. Current analyses focus only on individuals randomized to the placebo groups in the two parallel studies.

Drugs in Human Milk Part 1: Practical and Analytical Considerations in Measuring Drugs and Metabolites in Human Milk.

Human milk is a remarkable biofluid that provides essential nutrients and immune protection to newborns. Breastfeeding women consuming medications could pass the drug through their milk to neonates. Drugs can be transferred to human milk by passive diffusion or active transport.

The dosing regimen for 17-hydroxyprogesterone caproate was suboptimal: lessons for future pharmacotherapy for pregnant women.

Background: Makena (17-hydroxyprogesterone caproate) was approved by the United States Food and Drug Administration for the prevention of recurrent spontaneous preterm birth in 2011 under the accelerated approval pathway, but fundamental pharmacokinetic or pharmacodynamic (Phase 1 and Phase 2) studies were not performed. At the time, there were no dose-response or concentration-response data. The therapeutic concentration was not known.

Selection of a suitable animal model to evaluate secretion of drugs in the human milk: a systematic approach.

Lack of data on drug secretion in human milk is a concern for safe use of drugs during postpartum.Clinical studies are often difficult to perform; despite substantial improvements in computational methodologies such as physiologically based pharmacokinetic modelling, there is limited clinical data to validate such models for many drugs.Various factors that are likely to impact milk to plasma ratio were identified.

Simplified processing and rapid quantification of buprenorphine, norbuprenorphine, and their conjugated metabolites in human plasma using UPLC-MS/MS: Assessment of buprenorphine exposure during opioid use disorder treatment.

Opioid use disorder (OUD) is a chronic neurobehavioral ailment and is prevalent in pregnancy. OUD is commonly treated with methadone or buprenorphine (BUP). Pregnancy is known to alter the pharmacokinetics of drugs and may lead to changes in drug exposure and response.

Concentrations of Fluoxetine Enantiomers Decline During Pregnancy and Increase After Birth.

Rationale: 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.

Association of Mild Iodine Insufficiency during Pregnancy with Child Neurodevelopment in Patients with Subclinical Hypothyroidism or Hypothyroxinemia.

Objective: Our objective was to evaluate whether iodine status in pregnant patients with either subclinical hypothyroidism or hypothyroxinemia in the first half of pregnancy is associated with measures of behavior and neurodevelopment in children through the age of 5 years.

Study Design: This is a secondary analysis of a multicenter study consisting of two randomized, double-masked, placebo-controlled treatment trials conducted in parallel. Patients with a singleton gestation before 20 weeks' gestation underwent thyroid screening using serum thyrotropin and free thyroxine.

Genetic Predisposition to Adverse Neurodevelopmental Outcome of Extremely Low Birth Weight Infants.

Objective: This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants.

Study Design: We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication.

Simultaneous quantitation of ketamine, norketamine and dehydronorketamine in human milk using a novel ultra high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) assay.

There is a paucity of data on the transfer of ketamine from maternal blood into human milk. Quantification of ketamine in human milk provides information about the potential exposure of the infant to ketamine and its metabolites from the mother during lactation. A highly specific, reproducible, and sensitive UPLC-MS/MS based analytical method was developed and validated for the quantitation of ketamine and its metabolites (norketamine and dehydronorketamine) in human milk.

Outcomes of induction vs prelabor cesarean delivery at <33 weeks for hypertensive disorders of pregnancy.

Background: Hypertensive disorders of pregnancy are the leading cause of indicated preterm birth; however, the optimal delivery approach for pregnancies complicated by preterm hypertensive disorders of pregnancy remains uncertain.

Objective: This study aimed to compare maternal and neonatal morbidity in patients with hypertensive disorders of pregnancy who either went induction of labor or prelabor cesarean delivery at <33 weeks' gestation. In addition, we aimed to quantify the length of induction of labor and rate of vaginal delivery in those who underwent induction of labor.

Relationship between plasma concentration of 17-hydroxyprogesterone caproate and gestational age at preterm delivery.

Background: 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.

A cocktail probe approach to evaluate the effect of hormones on the expression and activity of CYP enzymes in human hepatocytes with conditions simulating late stage of pregnancy.

Purpose: Pregnancy-mediated physiological and biochemical changes contribute to alterations in the pharmacokinetics of certain drugs. There is a paucity of data on the systematic evaluation of the underlying mechanisms. The objective of the current study was to examine the impact of changes in circulating and tissue hormonal concentration during the late stage of pregnancy on the activity and expression of hepatic cytochrome P450 (CYP) enzymes using a cocktail probe approach.

Effect of formulation and route of administration on the distribution of 17-hydroxyprogesterone caproate in rats.

Weekly intramuscular (250 mg/week) or subcutaneous (275 mg/week) injections of 17-hydroxyprogesterone caproate (17-OHPC) is the only treatment option for the prevention of preterm birth in women with a prior history of preterm delivery.The objective of the current study was to determine the relative distribution of 17-OHPC in selected tissues in adult female SD rats after IM (oily formulation or solution), IV (solution), PO (solution), or intravaginal (suppository) administration.Plasma, uterus, adipose, and liver samples were collected at various times and analysed by LC-MS-MS.

Applications of Volumetric Absorptive Microsampling Technique: A Systematic Critical Review.

Methods: A novel microsampling device called Volumetric Absorptive microsampling (VAMS), developed in 2014, appears to have resolved the sample inhomogeneity inherent to dried blood spots, with improved precision in the volume of sample collected for measuring drug concentration. A literature search was conducted to identify several analytical and pharmacokinetic studies that have used VAMS in recent years.

Results: The key factors for proper experimental design and optimization of the extraction of drugs and metabolites of interest from the device were summarized.

Long-term neurodevelopmental follow-up of children exposed to pravastatin in utero.

Background: Preeclampsia, especially before term, increases the risk of child neurodevelopmental adverse outcomes. Biological plausibility, preclinical studies, and pilot clinical trials conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Obstetric-Fetal Pharmacology Research Centers Network support the safety and use of pravastatin to prevent preeclampsia.

Objective: This study aimed to determine the effect of antenatal pravastatin treatment in high-risk pregnant individuals on their child's health, growth, and neurodevelopment.

The Association between Infant Birth Weight, Head Circumference, and Neurodevelopmental Outcomes.

Objective: The aim of this study was to evaluate whether being small for gestational age (SGA) or large for gestational age (LGA) or having a small or large head circumference (HC) at birth is associated with adverse neurodevelopmental outcomes.

Study Design: This is a secondary analysis of a multicenter negative randomized trial of thyroxine therapy for subclinical hypothyroid disorders in pregnancy. The primary outcome was child intelligence quotient (IQ) at 5 years of age.

Short-term neonatal outcomes of pregnancies complicated by maternal obesity.

Background: Maternal obesity complicates a high number of pregnancies. The degree to which neonatal outcomes are adversely affected is unclear.

Objective: This study aimed to evaluate neonatal outcomes of pregnancies complicated by maternal obesity.

Associations between postpartum pain type, pain intensity and opioid use in patients with and without opioid use disorder: a cross-sectional study.

Background: Pain is a multidimensional construct. The purpose of this cross-sectional, single-centre study was to evaluate the relationship between postpartum pain type with pain intensity and opioid use in people with and without opioid use disorder (OUD).

Methods: Postpartum pain type was coded from McGill Pain Questionnaire and Patient-Reported Outcome Measurement Information System (PROMIS) inventories in people with or without OUD after childbirth in a 4-month period.

Changes in Sertraline Plasma Concentrations Across Pregnancy and Postpartum.

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.

Obstacles to Optimal Antenatal Corticosteroid Administration to Eligible Patients.

Objective: Administration of antenatal corticosteroids (ANCS) is recommended for individuals expected to deliver between 24 and 34 weeks of gestation. Properly timed administration of ANCS achieves maximal benefit. However, more than 50% of individuals receive ANCS outside the recommended window.