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

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.

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

American Journal of Perinatology ◽

10.1055/s-0037-1617453 ◽

2018 ◽

Vol 35 (09) ◽

pp. 809-814 ◽

Cited By ~ 2

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.

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

Journal of Perinatal Medicine ◽

10.1515/jpm-2020-0349 ◽

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.

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Ureaplasma parvum genotype, combined vaginal colonisation with Candida albicans, and spontaneous preterm birth in an Australian cohort of pregnant women

BMC Pregnancy and Childbirth ◽

10.1186/s12884-016-1110-x ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 23

Author(s):

Matthew S. Payne ◽

Demelza J. Ireland ◽

Rory Watts ◽

Elizabeth A. Nathan ◽

Lucy L. Furfaro ◽

...

Keyword(s):

Candida Albicans ◽

Preterm Birth ◽

Pregnant Women ◽

Spontaneous Preterm Birth ◽

Ureaplasma Parvum ◽

Australian Cohort

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Comparison of early pregnancy serum concentration of neopterin, neopterin/creatinine ratio, C‑reactive protein, and chitotriosidase, in pregnant women with birth at term and spontaneous preterm birth

Experimental and Therapeutic Medicine ◽

10.3892/etm.2020.8784 ◽

2020 ◽

Author(s):

Dan Navolan ◽

Dana Stoian ◽

Roxana Bohiltea ◽

Zorin� Crainiceanu ◽

Marius Craina ◽

...

Keyword(s):

Preterm Birth ◽

Serum Concentration ◽

Pregnant Women ◽

Early Pregnancy ◽

Creatinine Ratio ◽

C Reactive Protein ◽

Spontaneous Preterm Birth ◽

Reactive Protein

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RELATIONSHIP OF MATERNAL VITAMIN B12 STATUS IN PREGNANCY WITH PRETERM BIRTH AND MATERNAL HEALTH RISKS

International Medical Journal ◽

10.37436/2308-5274-2020-2-7 ◽

2020 ◽

pp. 32-38

Author(s):

VICTORIA LAZAROVA SPASOVA ◽

LILIA IVANOVA KOLEVA ◽

MARIETA ANTONOVA POPOVA ◽

VALENTINA BOYANOVA PETKOVA ◽

MILEN VENTZISLAVOV DIMITROV

Keyword(s):

Preterm Birth ◽

Vitamin B12 ◽

Pregnant Women ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Inverse Association ◽

Maternal Vitamin ◽

B12 Deficiency ◽

The Impact ◽

In Pregnancy

Vitamin B12 is known to be vital for cell growth and population during pregnancy. This retrospective and prospective case−control study was aimed to disclose a health risk for pregnant women with vitamin B12 deficiency, as well as the one of the preterm birth. The main tasks set and performed in this research were as follows: to compare the obstetrics anamnesis between the women who gave birth on term and women who gave birth before term; to find the prevalence of vitamin B12 insufficiency in pregnancy; to determine its association with preterm birth and low birth weight; to examine its association with spontaneous abortions, and to investigate its relationship with obesity and hemoglobin levels in pregnant women. The conducted investigation involved 107 women who gave birth before the 37th week of gestation and 101 women who gave birth after the 37th week of gestation at the outpatient clinic of the University Hospital "Maichin Dom" in Bulgaria. Our study revealed a correlation between maternal vitamin B12 deficiency, overweight and low hemoglobin level. Our results showed no significant correlation between serum vitamin B12 level and the risk of preterm birth. However, we found an inverse association between vitamin B12 level and overweight before pregnancy and at the time of giving birth. As well there was confirmed the strong connection between meat consumption and vitamin B12 level. The paper emphasizes that the deficiency of the vitamin occurs most likely in the women with inadequate diets. Such a deficiency is actually confirmed to have serious health consequences for pregnant women and their offspring. Therefore further profound and numerous studies should be performed to properly assess the correlation between vitamin B12 and preterm birth, as well as to understand better the impact of vitamin B12 over pregnant women. Key words: vitamin B12, preterm birth, pregnancy, overweight, hemoglobin.

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Maternal Iodine Status and Associations with Birth Outcomes in Three Major Cities in the United Kingdom

Nutrients ◽

10.3390/nu11020441 ◽

2019 ◽

Vol 11 (2) ◽

pp. 441 ◽

Cited By ~ 9

Author(s):

Charles Snart ◽

Claire Keeble ◽

Elizabeth Taylor ◽

Janet Cade ◽

Paul Stewart ◽

...

Keyword(s):

Birth Weight ◽

Preterm Birth ◽

Pregnant Women ◽

Birth Outcomes ◽

Inductively Coupled Plasma ◽

Urinary Iodine ◽

World Health ◽

Spontaneous Preterm Birth ◽

Foetal Development ◽

Iodine Status

Severe iodine deficiency in mothers is known to impair foetal development. Pregnant women in the UK may be iodine insufficient, but recent assessments of iodine status are limited. This study assessed maternal urinary iodine concentrations (UIC) and birth outcomes in three UK cities. Spot urines were collected from 541 women in London, Manchester and Leeds from 2004–2008 as part of the Screening for Pregnancy End points (SCOPE) study. UIC at 15 and 20 weeks’ gestation was estimated using inductively coupled plasma-mass spectrometry (ICP-MS). Associations were estimated between iodine status (UIC and iodine-to-creatinine ratio) and birth weight, birth weight centile (primary outcome), small for gestational age (SGA) and spontaneous preterm birth. Median UIC was highest in Manchester (139 μg/L, 95% confidence intervals (CI): 126, 158) and London (130 μg/L, 95% CI: 114, 177) and lowest in Leeds (116 μg/L, 95% CI: 99, 135), but the proportion with UIC <50 µg/L was <20% in all three cities. No evidence of an association was observed between UIC and birth weight centile (−0.2% per 50 μg/L increase in UIC, 95% CI: −1.3, 0.8), nor with odds of spontaneous preterm birth (odds ratio = 1.00, 95% CI: 0.84, 1.20). Given the finding of iodine concentrations being insufficient according to World Health Organization (WHO) guidelines amongst pregnant women across all three cities, further studies may be needed to explore implications for maternal thyroid function and longer-term child health outcomes.

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Serum apolipoprotein A-II and alpha-2-antiplasmin levels in midtrimester can be used as predictors of preterm delivery

Journal of International Medical Research ◽

10.1177/0300060520952280 ◽

2020 ◽

Vol 48 (9) ◽

pp. 030006052095228

Author(s):

Jianxia Huang ◽

Yuhong Yang ◽

Pei He

Keyword(s):

Preterm Birth ◽

Pregnant Women ◽

Preterm Delivery ◽

Coagulation Cascade ◽

Protein Markers ◽

Spontaneous Preterm Birth ◽

Retrospective Case ◽

Normal Delivery ◽

Apolipoprotein A ◽

Group D

Objective To identify serum protein markers in midtrimester that predict preterm delivery. Methods A retrospective case–control study randomly selected patients that experienced spontaneous preterm birth and healthy control patients that experienced a normal delivery at term. A proteomic analysis was undertaken using the data-independent acquisition method. Results A total of 30 singleton pregnant women were randomly selected from 12 800 pregnant women: 15 women had a spontaneous preterm birth (group Y) and 15 age- and body mass index-matched women gave birth at term (group D). All of the patients provided serum at 15–20 weeks of gestation. A total of 39 differentially expressed proteins were identified. Compared with group D, 24 proteins were upregulated and 15 were downregulated in the preterm group Y. Using Kyoto Encyclopedia of Genes and Genomes pathway enrichment, the 24 upregulated proteins were significantly enriched in the complement and coagulation cascade pathways. Search Tool for the Retrieval of Interacting Genes Furthermore (STRING) analysis showed that apolipoprotein A-II (apoA-II) and alpha-2-antiplasmin (α2-AP), two upregulated proteins, were key nodes in the STRING protein–protein network. Conclusions These findings suggest that apoA-II and α2-AP might be new markers for predicting preterm delivery in the midtrimester.

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