The Impact of Hepatitis C Virus Infection on Buprenorphine Dose in Pregnancy.

OBJECTIVE: Buprenorphine (BUP) is commonly used for opioid maintenance therapy in pregnancy. Our goal was to determine whether liver dysfunction related to hepatitis C virus (HCV) infection impacts BUP dosing requirements in pregnancy. STUDY DESIGN: This was a retrospective cohort study of pregnant women with antenatal exposure to BUP to compare dosing between individuals positive versus negative for HCV infection. Spearman correlation tests were used to assess the relationship between BUP dose and HCV status. RESULTS: HCV infection was present in 103 (39%) of the patients. Patients with HCV infection required lower dose increases of BUP throughout pregnancy (p = 0.02). HCV viral load was positively correlated with the liver enzymes aspartate transaminase (r = 0.30, p = 0.003) and alanine transaminase (r = 0.25, p = 0.01). There was a negative correlation between HCV viral load and BUP dose during the second trimester (r = -0.27, p = 0.01) and third trimester (r = -0.20, p = 0.04). CONCLUSION: Women with HCV infection required less of an increase in BUP dose throughout pregnancy compared with women without HCV infection. Severity of HCV infection, as measured by viral load and liver enzymes, was also associated with BUP dosing.

Prenatal Opioid Exposure, Neonatal Abstinence Syndrome/Neonatal Opioid Withdrawal Syndrome, and Later Child Development Research: Shortcomings and Solutions.

: The opioid epidemic has brought with it an increasing focus on the incidence of Neonatal Abstinence Syndrome (NAS) (also known as Neonatal Opioid Withdrawal Syndrome) in neonates prenatally exposed to opioids, and recently, in the putative long-term effects of NAS on child development. The purpose of the present paper is three-fold: (1) outline shortcomings regarding the current research relating NAS to child development; (2) propose solutions to minimize these shortcomings; and (3) recommend an alternative conceptual framework to understanding developmental problems in later childhood presumed to be a result of NAS. The paper focuses on issues regarding definitions of the population of interest, choice of comparison groups, matching practices, statistical analyses, and an implicit single-cause fallacy related to NAS. It offers possible solutions to the problems identified in each of these areas. Use of a NAS or Neonatal Opioid Withdrawal Syndrome diagnosis as a main indicator of adverse developmental outcomes poses potential radiating harm to the child and the family and misses the opportunity to see the complexities of interpersonal, intrapersonal, and environmental factors that contribute to the long-term developmental trajectories of children.

Determining the Initiation of Opiate Misuse Resulting in Opioid Use Disorder in Pregnant Women.

The aim of this study was to explore the "opiate misuse footprint" made by obstetrics and gynecology physicians in prescribing opioid medications for postpartum pain control that led to opioid misuse and opioid use disorder. Data were collected using intake information and anonymous surveys administered to pregnant women at local methadone clinics in Indianapolis, Indiana, in 2016-2017. Results from this study revealed that 40% of the 33 participants stated that the first drug they became addicted to was prescription opioids; 71% stated that the first opiate they became addicted to was a prescription pain medication. Prescription opioids were mainly obtained from emergency medicine physicians and friends. Reported use of opioids within the past four months was high, with the most commonly used drugs being methadone (57.6%) and heroin (42.4%). A majority of participants also endorsed a history of sexual and physical abuse, recent incarceration, and mental health disorders. As a large number of pregnant women with opioid use disorder reported their initial drug of misuse as prescription pain medications, it is important to avoid overprescribing opioids in reproductive-age women.

Characterization of Maternal and Fetal CYP3A-Mediated Progesterone Metabolism.

INTRODUCTION: Progesterone is critical for maintaining pregnancy and onset of labor. We evaluated CYP450-mediated progesterone meta-bolism, specifically the contribution of CYP3A isoforms. MATERIALS AND METHODS: In vitro progesterone metabolism was characterized in human liver microsomes (HLMs) with and without selective cytochrome P450 inhibitors and in recombinant CYP3A4, CYP3A5, and CYP3A7. 6ß-hydroxyprogesterone (6ß-OHP) and 16α-hydroxyprogesterone (16α-OHP) metabolites were quantified by HPLC/UV and fit to the Michaelis-Menten equation to determine Km and Vmax. The effect of CYP3A5 expression on progesterone clearance was determined by in vitro in vivo extrapolation. RESULTS: Ketoconazole inhibited formation of both 6ß-OHP and 16α-OHP more than 95%. 6ß-OHP and 16α-OHP were both produced by CYP3A4 (2.3 and 1.3 µL/min/pmol, respectively) to a greater extent than by CYP3A5 (0.09 and 0.003 µL/min/pmol) and CYP3A7 (0.004 and 0.003 µL/min/pmol). CONCLUSIONS: Maternal clearance of progesterone by hepatic CYP450's is driven primarily by CYP3A4, with limited contributions from CYP3A5 and CYP3A7.

The Impact of Gestational Age at Delivery on Urologic Outcomes for the Fetus with Hydronephrosis.

OBJECTIVE: Compare short-term urologic outcomes with delivery timing in fetuses with severe hydronephrosis. METHODS: An ultrasound database was queried for severe hydronephrosis. Cases were categorized into late preterm/early term (36 0/7 - 38 6/7 weeks) and full term (39 0/7 weeks or greater) groups. Baseline characteristics were compared using standard statistical methods. Spearman's correlation analysis was performed for grade and severity of hydronephrosis on first postnatal ultrasound with gestational age at delivery. RESULTS: Of 589 cases, 79 (33 late preterm/early term, 46 full term) met criteria. Baseline characteristics were similar between groups. Spearman's correlation coefficients (rs) indicated that increased postnatal Society for Fetal Urology grade, rs= -0.26 (95% CI [-.48, -.002]), and severity of hydronephrosis, rs= -0.39 (95% CI [-.59, -.14]), both correlated with earlier delivery. CONCLUSION: Late preterm/early term delivery resulted in worse short-term postnatal renal outcomes. Unless otherwise indicated, delivery for fetal hydronephrosis should be deferred until 39 weeks.

Short-term tocolytics for preterm delivery - current perspectives.

Administration of short-term tocolytic agents can prolong pregnancy for women in preterm labor. Prolonging pregnancy has many benefits because it allows for other proven interventions, such as antenatal corticosteroid administration, to be accomplished. This review provides an overview of currently utilized tocolytic agents and the evidence demonstrating their efficacy for prolonging pregnancy by at least 48 hours. General pharmacological principles for the clinician regarding drugs in pregnancy are also briefly discussed. In general, while the choice of the best first-line short-term tocolytic drug is not clear, it is evident that use of these agents has a clear place in current obstetric therapeutics.

Combination antiretroviral therapy with protease inhibitors in HIV-infected pregnancy.

OBJECTIVE: To evaluate the possible association between protease inhibitor (PI) and premature birth and low birth-weight in HIV-infected pregnancies. MATERIALS AND METHODS: Data were collected retrospectively for maternal and pregnancy characteristics, antiretroviral medication, lowest CD4 count and highest viral load during pregnancy, and pregnancy outcomes. χ(2) Analysis, Student's t-test, and multiple logistic regression analysis were performed. RESULTS: Data from 161 HIV-infected women who delivered singleton gestation were analyzed. Fifty-three received an antepartum regimen with PI, 84 received a regimen without PI, and six did not receive antepartum treatment. The mean estimated gestational age (EGA)± SD at delivery was 37.7 ± 3.2 weeks. The premature birth rate was 18.4%. No difference was detected between women receiving the antiretroviral regimen including PI and those on the regimen without PI or on no antepartum medication with regard to: EGA ± SD at delivery (37.7 ± 3.2 vs. 37.6 ± 3.1 weeks, respectively, P=0.87), rate of premature birth (14% vs. 20.6%, respectively, P=0.32) and low birth-weight (12.5% vs. 20.2%, respectively, P=0.25). In multiple logistic regression analysis, PI was not associated with premature birth or low birth-weight. CONCLUSION: Women receiving antiretroviral therapy with PI have a similar rate of premature birth and low birth-weight as women receiving antiretroviral therapy without PI or on no medication.

Update on gestational diabetes.

As the rate of obesity increases in adolescent and adult women in the United States, practitioners of obstetrics see higher rates of gestational diabetes. Recent clinical studies suggest that women with gestational diabetes have impaired pancreatic beta-cell function and reduced beta-cell adaptation resulting in insufficient insulin secretion to maintain normal glycemia. Despite recent evidence that even mild hyperglycemia is associated with adverse pregnancy outcomes, controversies still exist in screening, management, and treatment of gestational diabetes. Initial studies regarding glyburide for treatment of gestational diabetes are promising. Overall, only about half of the women with gestational diabetes are screened in the postpartum period, an ideal time for education and intervention, to decrease incidence of glucose intolerance and progression to type 2 diabetes.