scholarly journals Impact of Obesity on the Rate of Recurrent Spontaneous Preterm Birth in Women Treated with 17-alpha Hydroxyprogesterone Caproate

2018 ◽  
Vol 35 (09) ◽  
pp. 809-814 ◽  
Author(s):  
Lara Lemon ◽  
Allison Serra ◽  
Shringi Sharma ◽  
Raman Venkataramanan ◽  
Steve Caritis ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Controlled Trial ◽  
Plasma Concentrations ◽  
Pharmacokinetic Studies ◽  
Maternal Body Mass Index ◽  
Omega 3 ◽  
Spontaneous Preterm Birth ◽  
Obesity Class ◽  
Hydroxyprogesterone Caproate ◽  
The Impact

Objective We sought to determine if the rate of recurrent spontaneous preterm birth (PTB) in women treated with 17-α hydroxyprogesterone caproate (17-OHPC) is modified by maternal body mass index (BMI). Study Design We performed a secondary analysis of the Maternal-Fetal Medicine Units Network omega-3 fatty acid supplementation to prevent recurrent PTB randomized controlled trial. All women received 17-OHPC. Results A total of 708 women were included. Rates of spontaneous PTB did not vary significantly by BMI category. With stratification by obesity class and gestational age at delivery, the unadjusted risk for PTB using earlier gestational cutoffs (< 35, 32, and 28 weeks) demonstrated an association between preterm delivery and increasing severity of obesity. With adjustment for potential confounders, there was no statistically significant relationship between BMI and spontaneous PTB. Conclusion We demonstrated that the risk of PTB in women receiving 250 mg 17-OHPC is not dependent on maternal BMI after adjustment for confounding variables. Pharmacokinetic studies have demonstrated a wide variation in plasma concentration of 17-OHPC across the population with likely considerable overlap in plasma concentrations among the obese and nonobese population. Further studies are needed to evaluate the impact of BMI on efficacy of 17-OHPC prior to any dose adjustment in this population.

Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth

2021 ◽  
pp. 38-42
Author(s):  
Emily A. Oliver ◽  
Amanda Roman-Camargo
Keyword(s):  
Preterm Birth ◽  
Child Health ◽  
Human Development ◽  
Intraventricular Hemorrhage ◽  
Controlled Trial ◽  
Supplemental Oxygen ◽  
Spontaneous Preterm Birth ◽  
Increased Risk ◽  
Hydroxyprogesterone Caproate ◽  
History Of

Women with a history of spontaneous preterm birth have an increased risk of recurrent preterm birth. In this randomized placebo-controlled trial funded by the National Institute of Child Health and Human Development, patients between 16 and 20 weeks of gestation with a history of spontaneous preterm birth were administered intramuscular 17 alpha-hydroxyprogesterone caproate (17P) or placebo, weekly until 36 weeks of gestation. Treatment with 17P significantly reduced the rate of preterm birth (36.3% vs. 54.9%, p <0.001). Rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen were all significantly decreased in the 17P group. In women with a history of spontaneous preterm birth, weekly 17P decreases the rate of recurrent preterm birth.

scholarly journals Clinical Pharmacology Aspects of Some Tocolytic Drugs Used in Pregnant Women at Risk of Preterm Birth

2019 ◽  
Vol 9 (3) ◽  
pp. 162-166
Author(s):  
E. A. Sоkоvа ◽  
R. A. Chilova ◽  
O. A. Demidova ◽  
K. O. Akopov
Keyword(s):  
Preterm Birth ◽  
Pregnant Women ◽  
Preterm Labour ◽  
Plasma Concentrations ◽  
Cyclooxygenase Inhibitors ◽  
Pharmacokinetic Parameters ◽  
Clinical Effects ◽  
Spontaneous Preterm Birth ◽  
Rational Pharmacotherapy ◽  
The Impact

Spontaneous preterm birth is one of the most pressing issues in obstetrics, as it remains one of the leading causes of newborn morbidity and mortality. Pending issues of aetiology, pathogenesis, and absence of medicinal products indicated for the treatment of spontaneous preterm labour pose a challenge for rational pharmacotherapy. The paper presents the results of a scientific literature review on the problem of rational pharmacotherapy of spontaneous preterm labour using tocolytic drugs — calcium channel blockers, cyclooxygenase inhibitors. The paper summarises specific pharmacokinetic parameters of these drugs during pregnancy. It discusses pharmacogenetic aspects of using tocolytic drugs in pregnant women and their potential clinical effects. It was demonstrated that women with threatened miscarriage had high interindividual variability in nifedipine plasma concentrations depending on CYP3A5 genotype. It was shown that certain genetic polymorphisms of CYP2C9 may lead to an increased metabolic rate and an increase in indomethacin clearance resulting in the reduction of its efficacy. Yet, there is minimal research regarding this issue. Therefore, further research is needed to assess the impact of CYP3A5 and CYP2C9 genotypes on the efficacy and safety of nifedipine and indomethacin used as tocolytic drugs in obstetrics.

Women with high plasma levels of PBDE-47 are at increased risk of preterm birth

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Morgan R. Peltier ◽  
Michael J. Fassett ◽  
Yuko Arita ◽  
Vicki Y. Chiu ◽  
Jiaxiao M. Shi ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Los Angeles ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Plasma Concentrations ◽  
First Trimester ◽  
High Plasma ◽  
Thyroid Stimulating Hormone ◽  
Spontaneous Preterm Birth ◽  
Increased Risk

Abstract Objectives Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. Methods Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. Results We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. Conclusions These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.

A Possible Mechanism of Action of 17α-Hydroxyprogesterone Caproate: Enhanced IL-10 Production

2021 ◽  
Author(s):  
Christina J. Megli ◽  
Alisse Hauspurg ◽  
Raman Venkataramanan ◽  
Steve N. Caritis
Keyword(s):  
Mechanism Of Action ◽  
Cytokine Production ◽  
Plasma Concentrations ◽  
In Vitro Study ◽  
Vitro Study ◽  
Clinical Samples ◽  
Omega 3 ◽  
Tnf Α ◽  
Hydroxyprogesterone Caproate

Objective The rate of recurrent spontaneous preterm birth (PTB) was reduced by 33% in the Maternal-Fetal Medicine Unit (MFMU) Network trial of 17α-hydroxyprogesterone caproate (17-OHPC), but the mechanism of action, 17 years later, remains elusive. The robustness of the interleukin-10 (IL-10) response to lipopolysaccharide (LPS) stimulation of leukocytes in pregnant women with a prior PTB correlates with gestational age at delivery. This study sought to determine if there is a relationship between the concentration of 17-OHPC and response to LPS stimulation. Study Design We performed a secondary analysis of data from the Omega-3 MFMU trial which evaluated the effectiveness of omega-3 fatty acid supplementation in reducing recurrent PTB. We utilized previously characterized data from a subanalyses of the Omega-3 trial of IL-10 and tumor necrosis factor alpha (TNF-α) levels from peripheral blood mononuclear cells stimulated with LPS. Blood was obtained from enrolled women at 16 to 22 weeks' gestation (baseline) and 25 to 28 weeks' gestation (posttreatment). All women received 17-OHPC and plasma 17-OHPC concentrations were measured at 25 to 28 weeks' gestation. We analyzed these data to determine if there was a relationship between 17-OHPC concentration and cytokine production. We then performed an in vitro study to determine if 17-OHPC could directly alter cytokine production by THP-1-derived macrophages. Results In the clinical samples, we found that 17-OHPC plasma concentrations were correlated with the quantity of the LPS-stimulated production of IL-10. TNF-α production after LPS stimulation was unrelated to 17-OHPC concentration. In the in vitro study, we demonstrate a 17-OHPC concentration dependent increase in IL-10 production. Conclusion In women receiving 17-OHPC for PTB prevention, we demonstrate a relationship between plasma 17-OHPC and LPS-stimulated IL-10 production by circulating leukocytes. We also demonstrate that, in vitro, 17-OHPC treatment affects IL-10 production by LPS-stimulated macrophages. Collectively, these findings support an immunomodulatory mechanism of action of 17-OHPC in the prevention of recurrent PTB. Key Points

Eligibility, Utilization, and Effectiveness of 17-Alpha Hydroxyprogesterone Caproate (17OHPC) in a Statewide Population-Based Cohort of Medicaid Enrollees

2021 ◽  
Author(s):  
Xi Wang ◽  
Stephanie M. Garcia ◽  
Katherine S. Kellom ◽  
Rupsa C. Boelig ◽  
Meredith Matone
Keyword(s):  
Preterm Birth ◽  
Neonatal Intensive Care ◽  
Population Based ◽  
Primary Objective ◽  
Birth Certificates ◽  
Spontaneous Preterm Birth ◽  
Initiation Rate ◽  
Live Births ◽  
Hydroxyprogesterone Caproate ◽  
Comparison Groups

Objectives The primary objective was to estimate the initiation and adherence rates of 17 α-hydroxyprogesterone caproate (17OHPC) among eligible mothers in a statewide population-based cohort of Medicaid enrollees. The secondary objectives were to (1) determine the association of maternal sociodemographic and clinical characteristics with 17OHPC utilization and (2) assess the real-world effectiveness of 17OHPC on recurrent preterm birth prevention and admission to neonatal intensive care unit (NICU). Study Design This is a retrospective cohort study using a linked, longitudinal administrative dataset of birth certificates and medical assistance claims. Medicaid-enrolled mothers in Pennsylvania were included in this study if they had at least one singleton live birth from 2014 to 2016 following at least one spontaneous preterm birth. Maternal Medicaid claims were used to ascertain the use of 17OHPC from various manufacturers, including compounded formulations. Propensity score matching was used to create a covariate balance between 17OHPC treatment and comparison groups. Results We identified 4,781 Medicaid-covered 17OHPC-eligible pregnancies from 2014 to 2016 in Pennsylvania, 3.4% of all Medicaid-covered singleton live births. The population-based initiation rate was 28.5% among eligible pregnancies. Among initiators, 50% received ≥16 doses as recommended, while 10% received a single dose only. The severity of previous spontaneous preterm birth was the strongest predictor for the initiation and adherence of 17OHPC. In the matched treatment (n = 1,210) and comparison groups (n = 1,210), we found no evidence of 17OHPC effectiveness. The risks of recurrent preterm birth (relative risk [RR] 1.10, 95% confidence interval [CI] 0.97–1.24) and births admitted to NICU (RR 1.00, 95% CI 0.84–1.18) were similar in treated and comparison mothers. Conclusion The 17OHPC-eligible population represented 3.4% of singleton live births. Less than one-third of eligible mothers initiated treatment. Among initiators, 50% were treatment adherent. We found no difference in the risk of recurrent preterm birth or admission to NICU between treatment and comparison groups. Key Points

Effectiveness of 17-OHP for Prevention of Recurrent Preterm Birth: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Blair J. Wylie ◽  
Andrew L. Beam ◽  
Joe B. Hakim ◽  
Amy Zhou ◽  
Sonia Hernandez-Diaz ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Propensity Score ◽  
Evidence Base ◽  
Inclusion Criteria ◽  
Spontaneous Preterm Birth ◽  
Real World Data ◽  
Recurrence Rates ◽  
Key Points ◽  
Hydroxyprogesterone Caproate ◽  
Risk Ratios

Objective 17-α-hydroxyprogesterone caproate (17-OHP) has been recommended by professional societies for the prevention of recurrent preterm birth, but subsequent clinical studies have reported conflicting efficacy results. This study aimed to contribute to the evidence base regarding the effectiveness of 17-OHP in clinical practice using real-world data. Study Design A total of 4,422 individuals meeting inclusion criteria representing recurrent spontaneous preterm birth (sPTB) were identified in a database of insurance claims, and 568 (12.8%) received 17-OHP. Crude and propensity score-matched recurrence rates and risk ratios (RRs) for the association of receiving 17-OHP on recurrent sPTB were calculated. Results Raw sPTB recurrence rates were higher among those treated versus not treated; after propensity score matching, no association was detected (26.3 vs. 23.8%, RR = 1.1, 95% CI: 0.9–1.4). Conclusion We failed to identify a beneficial effect of 17-OHP for the prevention of spontaneous recurrent preterm birth in our observational, U.S. based cohort. Key Points

scholarly journals Comparison of pharmacokinetics of omega-3 fatty acid supplements in monoacylglycerol or ethyl ester in humans: a randomized controlled trial

2020 ◽  
Author(s):  
Laurie Chevalier ◽  
Mélanie Plourde
Keyword(s):  
Plasma Concentration ◽  
Ethyl Ester ◽  
Controlled Trial ◽  
Plasma Concentrations ◽  
Controlled Clinical Trial ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Post Dose ◽  
Double Blind ◽  
Omega 3 Fatty Acid

Abstract Background A diet low in omega-3 fatty acids (n-3 FA) results in low plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the two main long chain n-3 FA. n-3 FA supplements on the market are esterified in triglycerides (TG) or ethyl ester (EE); the latter is absorbed less than other esterification forms. The objective of this study was to test and compare the pharmacokinetics of n-3 FA esterified in monoacylglycerides (MAG), a predigested form, with the EE form. Methods This study was a randomized, double-blind, crossover, controlled, clinical trial. Ten men and ten women between 18 and 60 years old were recruited. Participants received a single oral dose of 3 g of n-3 FA esterified in EE or MAG. Eleven blood samples were collected over 24 h post-dose. Plasma total lipids were extracted, methylated, and analyzed using gas chromatography. Results After receiving the MAG form, plasma EPA and DHA peaked at a concentration 3 and 2.5 times higher, respectively, than with the EE form. When provided in MAG form, n-3 FA plasma concentration during the absorption phase was on average 3–5 times higher than in EE form. When n-3 FAs were provided esterified in MAG, their concentration 24 h post-dose was higher than in EE. Males had a lower n-3 FA plasma concentration than females when n-3 FAs were provided in EE but there was no sexe difference when provided in MAG. Conclusions Plasma concentration of DHA and EPA was higher when provided in MAG than EE form.

Sign in / Sign up

Export Citation Format

Share Document