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1.
J Pediatr ; 222: 52-58.e1, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32423682

RESUMO

OBJECTIVES: To categorize newborn infants in Hamilton County, Ohio by late pregnancy fetal opioid exposure status and to assess their first-year healthcare utilization. STUDY DESIGN: We used a population-based cohort of 41 136 live births from 2014-2017 and analyzed healthcare encounters in the first year of life from electronic health records. We prospectively assessed for the presence of opioids in maternal urine collected at delivery and for a diagnosis of newborn neonatal abstinence syndrome (NAS). At birth, infants were classified as unexposed to opioids, exposed to opioids and diagnosed with NAS, or subclinically exposed to opioids (exposure that did not result in NAS). RESULTS: The prevalence of newborn opioid exposure was 37 per 1000 births. The duration of the hospital birth encounter was significantly longer for infants with subclinical exposure compared with unexposed infants (10% increase; 95% CI, 7%-13%). However, duration for infants with subclinical exposure was shorter compared to those with NAS. Neither subclinical exposure nor NAS was associated with total emergency department visits. Subclinical exposure was associated with increased odds of having at least 1 hospitalization in the first year. However, the total length of stay for hospitalizations was 82% that of the unexposed group (95% CI, 75%-89%). Infants with NAS had a 213% longer total length of stay compared with the unexposed group (95% CI, 191%-237%). CONCLUSIONS: Subclinical and overt opioid exposure among newborn infants was associated with increased first-year healthcare utilization. From 2014 to 2017, this cost the Hamilton County healthcare system an estimated $1 109 452 for longer birth encounters alone.


Assuntos
Analgésicos Opioides/efeitos adversos , Síndrome de Abstinência Neonatal/diagnóstico , Síndrome de Abstinência Neonatal/epidemiologia , Transtornos Relacionados ao Uso de Opioides , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Complicações na Gravidez , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Prevalência
2.
J Pediatr ; 196: 305-308, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29395169

RESUMO

In this retrospective cohort study, we assessed the incidence of torticollis in infants with a history of neonatal abstinence syndrome. Understanding the elevated risk of torticollis in this population is important for early identification and treatment.


Assuntos
Síndrome de Abstinência Neonatal/complicações , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Torcicolo/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Gravidez , Estudos Retrospectivos , Fatores de Risco , Torcicolo/etiologia , Estados Unidos/epidemiologia
3.
Am J Perinatol ; 35(4): 405-412, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29112997

RESUMO

OBJECTIVE: The objective of this study was to compare duration of opioid treatment and length of stay outcomes for neonatal abstinence syndrome (NAS) using sublingual buprenorphine versus traditional weaning with methadone or morphine. STUDY DESIGN: This retrospective cohort analysis evaluated infants treated for NAS at a single community hospital from July 2013 through June 2017. A standardized weaning protocol was introduced in June 2015, allowing for treatment with sublingual buprenorphine regardless of type of intrauterine opioid exposure. General linear models were used to calculate adjusted mean duration of opioid treatment and length of hospitalization with 95% confidence intervals for infants treated with buprenorphine compared with traditional weaning with either methadone or morphine. RESULTS: A total of 360 infants were treated with either buprenorphine (n = 174) or a traditional opioid (n = 186). Infants treated with buprenorphine experienced a 3.0-day reduction in opioid treatment duration of 7.4 (6.3-8.5) versus 10.4 (9.3-11.5) days (p < 0.001) and a 2.8-day reduction in length of stay of 12.4 (11.3-13.6) versus 15.2 (14.1-16.4) days (p < 0.001). CONCLUSION: Our study provides an independent confirmation that among infants experiencing NAS following a wide array of intrauterine opioid exposures, buprenorphine weaning supports a shortened treatment duration compared with conventional weaning agents.


Assuntos
Analgésicos Opioides/administração & dosagem , Buprenorfina/administração & dosagem , Tempo de Internação/estatística & dados numéricos , Síndrome de Abstinência Neonatal/tratamento farmacológico , Esquema de Medicação , Feminino , Humanos , Recém-Nascido , Masculino , Metadona/administração & dosagem , Morfina/administração & dosagem , Tratamento de Substituição de Opiáceos , Estudos Retrospectivos , Fatores de Tempo
4.
J Pediatr ; 170: 39-44.e1, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26703873

RESUMO

OBJECTIVES: To compare the duration of opioid treatment and length of stay among infants treated for neonatal abstinence syndrome (NAS) by using a pilot buprenorphine vs conventional methadone treatment protocol. STUDY DESIGN: This retrospective cohort analysis evaluated infants who received pharmacotherapy for NAS at 6 hospitals in Southwest Ohio from January 2012 through August 2014. A single neonatology provider group used a standardized methadone protocol across all 6 hospitals. However, at one of the sites, infants were managed with a buprenorphine protocol unless they had experienced chronic in utero exposure to methadone. Linear mixed models were used to calculate adjusted mean duration of opioid treatment and length of inpatient hospitalization with 95% CIs in infants treated with oral methadone compared with sublingual buprenorphine. The use of adjunct therapy was examined as a secondary outcome. RESULTS: A total of 201 infants with NAS were treated with either buprenorphine (n = 38) or methadone (n = 163) after intrauterine exposure to short-acting opioids or buprenorphine. Buprenorphine therapy was associated with a shorter course of opioid treatment of 9.4 (CI 7.1-11.7) vs 14.0 (12.6-15.4) days (P < .001) and decreased hospital stay of 16.3 (13.7-18.9) vs 20.7 (19.1-22.2) days (P < .001) compared with methadone therapy. No difference was detected in the use of adjunct therapy (23.7% vs 25.8%, P = .79) between treatment groups. CONCLUSION: The choice of pharmacotherapeutic agent is an important determinant of hospital outcomes in infants with NAS. Sublingual buprenorphine may be superior to methadone for management of NAS in infants with select intrauterine opioid exposures.


Assuntos
Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Metadona/uso terapêutico , Síndrome de Abstinência Neonatal/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Adulto , Analgésicos Opioides/efeitos adversos , Protocolos Clínicos , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Tempo de Internação , Modelos Lineares , Masculino , Síndrome de Abstinência Neonatal/etiologia , Ohio , Transtornos Relacionados ao Uso de Opioides/etiologia , Estudos Retrospectivos
5.
Matern Child Health J ; 20(9): 1923-32, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27146395

RESUMO

Objective Despite practice recommendations that all newborns be examined within 3-5 days after discharge, many are not seen within this timeframe. Our objective was to determine the association between care coordination and timing of newborn follow-up. Methods This retrospective study evaluated 6251 newborns from eight maternity hospitals who scheduled a primary care appointment at one of two academic pediatric practices over 3.5 years. Two programs were sequentially implemented: (1) newborn discharge coordination, and (2) primary care intake coordination. Primary outcome was days between discharge and follow-up, dichotomized as ≤ or >5 days. Number of rescheduled appointments and loss to follow-up were also assessed. Adjusted relative risks (RR) and odds ratios (OR) were determined by piecewise generalized linear and logistic regression. Results Among 5943 newborns with a completed visit, 52.9 % were seen within 5 days of discharge (mean 6.7 days). After multivariable adjustment, the pre-exposure period (8 months) demonstrated a downward monthly trend in completing early follow-up (RR 0.93, p < 0.001). After initial program implementation, we observed a 3 % monthly increase (RR 1.03, p < 0.001 for test of slope change from pre-exposure to post-exposure), such that likelihood of recommended follow-up increased by roughly 72 % after discharge coordinator implementation and roughly 33 % after primary care coordinator implementation. The latter was also associated with a 13 % monthly decrease in odds of loss to follow-up (OR 0.87, p < 0.001). Conclusions for Practice Care coordination increases adherence among low income families to recommended newborn follow-up after birth hospitalization.


Assuntos
Continuidade da Assistência ao Paciente/organização & administração , Visita a Consultório Médico/estatística & dados numéricos , Pediatria/organização & administração , Atenção Primária à Saúde/organização & administração , Estudos de Coortes , Feminino , Seguimentos , Pesquisas sobre Atenção à Saúde , Humanos , Recém-Nascido , Perda de Seguimento , Masculino , Alta do Paciente , Estudos Retrospectivos , Tempo
6.
J Pediatr ; 167(6): 1221-5.e1, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26477866

RESUMO

OBJECTIVE: To evaluate neonatal abstinence syndrome (NAS) treatment outcomes achieved using an optimized methadone weaning protocol developed using pharmacokinetic (PK) modeling compared with standard methadone weaning. STUDY DESIGN: This pre-post cohort study evaluated 360 infants who completed pharmacologic treatment for NAS with methadone as inpatients at 1 of 6 nurseries in southwest Ohio between January 2012 and March 2015. Infants were initially treated with a standard methadone weaning protocol (n = 267). Beginning in July 2014, infants were treated with a revised methadone weaning protocol developed using PK modeling (n = 93). Linear mixed models were used to calculate adjusted mean primary outcomes, including total duration of methadone treatment, total administered methadone dosage, and length of inpatient hospital stay, which were compared between weaning protocols. The use of adjunctive therapy for NAS treatment was examined as a secondary outcome. RESULTS: Infants who received NAS treatment with the revised protocol experienced a shorter duration of methadone treatment (13.1 vs 16.4 days; P < .001) and shorter duration of inpatient treatment (18.3 vs 21.7 days; P < .001) compared with infants receiving standard methadone weaning. No difference was observed in total methadone dosage administered (0.52 vs 0.52 mg/kg; P = .97) or in the use of adjunctive therapy (22.6% vs 25.5%; P = .68) between groups. CONCLUSION: Refinement of a standard methadone weaning protocol using PK modeling was associated with reduced duration of opioid weaning and shortened length of stay for pharmacologic treatment of NAS.


Assuntos
Analgésicos Opioides/uso terapêutico , Metadona/uso terapêutico , Síndrome de Abstinência Neonatal/terapia , Adulto , Analgésicos Opioides/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Tempo de Internação , Masculino , Metadona/administração & dosagem , Modelos Biológicos , Ohio , Gravidez , Complicações na Gravidez
7.
J Pediatr ; 166(3): 582-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25454935

RESUMO

OBJECTIVE: To evaluate the efficacy of a universal maternal drug testing protocol for all mothers in a community hospital setting that experienced a 3-fold increase in neonatal abstinence syndrome (NAS) over the previous 5 years. STUDY DESIGN: We conducted a retrospective cohort study between May 2012 and November 2013 after the implementation of universal maternal urine drug testing. All subjects with positive urine tests were reviewed to identify a history or suspicion of drug use, insufficient prenatal care, placental abruption, sexually transmitted disease, or admission from a justice center, which would have prompted urine testing using our previous risk-based screening guidelines. We also reviewed the records of infants born to mothers with a positive toxicology for opioids to determine whether admission to the special care nursery was required. RESULTS: Out of the 2956 maternal specimens, 159 (5.4%) positive results were recorded. Of these, 96 were positive for opioids, representing 3.2% of all maternity admissions. Nineteen of the 96 (20%) opioid-positive urine tests were recorded in mothers without screening risk factors. Seven of these 19 infants (37%) required admission to the special care nursery for worsening signs of NAS, and 1 of these 7 required pharmacologic treatment. CONCLUSION: Universal maternal drug testing improves the identification of infants at risk for the development of NAS. Traditional screening methods underestimate in utero opioid exposure.


Assuntos
Analgésicos Opioides/efeitos adversos , Síndrome de Abstinência Neonatal/diagnóstico , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Medicamentos sob Prescrição/efeitos adversos , Adulto , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Síndrome de Abstinência Neonatal/epidemiologia , Síndrome de Abstinência Neonatal/etiologia , Ohio/epidemiologia , Transtornos Relacionados ao Uso de Opioides/complicações , Gravidez , Complicações na Gravidez , Prevalência , Curva ROC , Estudos Retrospectivos
8.
Pharmaceutics ; 16(3)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38543269

RESUMO

Buprenorphine readily crosses the placenta, and with greater prenatal exposure, neonatal opioid withdrawal syndrome (NOWS) likely grows more severe. Current dosing strategies can be further improved by tailoring doses to expected NOWS severity. To allow the conceptualization of fetal buprenorphine exposure, a maternal-fetal physiologically based pharmacokinetic (PBPK) model for sublingual buprenorphine was developed using Simcyp (v21.0). Buprenorphine transplacental passage was predicted from its physicochemical properties. The maternal-fetal PBPK model integrated reduced transmucosal absorption driven by lower salivary pH and induced metabolism observed during pregnancy. Maternal pharmacokinetics was adequately predicted in the second trimester, third trimester, and postpartum period, with the simulated area under the curve from 0 to 12 h, apparent clearance, and peak concentration falling within the 1.25-fold prediction error range. Following post hoc adjustment of the likely degree of individual maternal sublingual absorption, umbilical cord blood concentrations at delivery (n = 21) were adequately predicted, with a geometric mean ratio between predicted and observed fetal concentrations of 1.15 and with 95.2% falling within the 2-fold prediction error range. The maternal-fetal PBPK model developed in this study can be used to forecast fetal buprenorphine exposure and would be valuable to investigate its correlation to NOWS severity.

9.
Clin Perinatol ; 50(3): 729-742, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37536775

RESUMO

Breastfeeding is the biologic norm for newborn feeding, and exclusive breastfeeding for the first 6 months of life is universally endorsed by leading global and national organizations. Despite these recommendations, many people do not meet their breastfeeding goals and controversies surrounding breastfeeding problems exist. Medical issues can present challenges for the clinician and parents to successfully meet desired feeding outcomes. There are studies evaluating these common controversies and medical conundrums, and clinicians should provide evidence-based recommendations when counseling families about newborn feeding.


Assuntos
Aleitamento Materno , Recém-Nascido , Feminino , Humanos , Lactente
10.
Pharmacol Ther ; 234: 108045, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34813863

RESUMO

Physiologically-based pharmacokinetic (PBPK) modeling has emerged as a useful tool to study pharmacokinetics (PK) in special populations, such as pregnant women, fetuses, and newborns, where practical hurdles severely limit the study of drug behavior. PK in pregnant women is variable and everchanging, differing greatly from that in their nonpregnant female and male counterparts typically enrolled in clinical trials. PBPK models can accommodate pregnancy-induced physiological and metabolic changes, thereby providing mechanistic insights into maternal drug disposition and fetal exposure. Fueled by the soaring opioid epidemic in the United States, opioid use during pregnancy continues to rise, leading to an increased incidence of neonatal opioid withdrawal syndrome (NOWS). The severity of NOWS is influenced by a complex interplay of extrinsic and intrinsic factors, and varies substantially between newborns, but the extent of prenatal opioid exposure is likely the primary driver. Fetomaternal PBPK modeling is an attractive approach to predict in utero opioid exposure. To facilitate the development of fetomaternal PBPK models of opioids, this review provides a detailed overview of pregnancy-induced changes affecting the PK of commonly used opioids during gestation. Moreover, the placental transfer of these opioids is described, along with their disposition in the fetus. Lastly, the implementation of these factors into PBPK models is discussed. Fetomaternal PBPK modeling of opioids is expected to provide improved insights in fetal opioid exposure, which allows for prediction of postnatal NOWS severity, thereby opening the way for precision postnatal treatment of these vulnerable infants.


Assuntos
Síndrome de Abstinência Neonatal , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/efeitos adversos , Feminino , Feto , Humanos , Recém-Nascido , Masculino , Modelos Biológicos , Síndrome de Abstinência Neonatal/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Placenta , Gravidez
11.
J Perinatol ; 42(8): 1026-1031, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35177791

RESUMO

OBJECTIVE: To report substance and polysubstance use at the time of delivery. STUDY DESIGN: A cross-sectional study was performed on mothers consented for universal drug testing (99%) during hospital admission at six delivery hospitals in Cincinnati, Ohio. Mass spectrometry urinalysis detected positivity rates of 46 substances. Rates of positive drug tests for individual and common co-occurring substances measured were reported. RESULTS: 2531 maternal samples were tested (88%) and 33% contained cotinine, 11.3% THC, 7.2% opioids, 3.8% cocaine, and 1.9% methamphetamines. Polysubstance use prevalence was as high as 15%. Among mothers testing positive for methadone or buprenorphine, 93% also tested positive for cotinine and 39% tested positive for a third substance in addition to cotinine. CONCLUSIONS: Substance use at delivery is more prevalent than previously reported. Many mothers testing positive for opioids also test positive for other substances, which may increase overdose risk and exacerbate neonatal opioid withdrawal syndrome (NOWS).


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/efeitos adversos , Buprenorfina/uso terapêutico , Cotinina , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia
12.
Obstet Gynecol ; 140(5): 878-881, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36201781

RESUMO

We examined how breastfeeding advice in the context of cannabis use differed by race and ethnicity. Data from the 2017-2018 PRAMS (Pregnancy Risk Assessment Monitoring System) survey were used to assess differences in breastfeeding guidance related to cannabis use among 1,213 individuals who self-reported cannabis use 3 months before or during pregnancy. A multivariable logistic regression model was specified to examine the extent to which the odds of receiving prenatal advice against breastfeeding if using cannabis differed by self-reported race and ethnicity. We found that non-Hispanic Black people were four times more likely than non-Hispanic White people to be advised against breastfeeding if using cannabis (adjusted odds ratio 4.1, 95% CI 2.1-8.2). Pregnant non-Hispanic Black people were disproportionately advised not to breastfeed if using cannabis.


Assuntos
Aleitamento Materno , Cannabis , Humanos , Gravidez , Feminino , Aleitamento Materno/psicologia , Etnicidade , População Branca , Aconselhamento
13.
Clin Pharmacol Ther ; 111(2): 496-508, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34679189

RESUMO

Neonatal opioid withdrawal syndrome (NOWS) is a major public health concern whose incidence has paralleled the opioid epidemic in the United States. Sublingual buprenorphine is an emerging treatment for NOWS, but given concerns about long-term adverse effects of perinatal opioid exposure, precision dosing of buprenorphine is needed. Buprenorphine pharmacokinetics (PK) in newborns, however, is highly variable. To evaluate underlying sources of PK variability, a neonatal physiologically-based pharmacokinetic (PBPK) model of sublingual buprenorphine was developed using Simcyp (version 19.1). The PBPK model included metabolism by cytochrome P450 (CYP) 3A4, CYP2C8, UDP-glucuronosyltransferase (UGT) 1A1, UGT1A3, UGT2B7, and UGT2B17, with additional biliary excretion. Maturation of metabolizing enzymes was incorporated, and default CYP2C8 and UGT2B7 ontogeny profiles were updated according to recent literature. A biliary clearance developmental profile was outlined using clinical data from neonates receiving sublingual buprenorphine as NOWS treatment. Extensive PBPK model validation in adults demonstrated good predictability, with geometric mean (95% confidence interval (CI)) predicted/observed ratios (P/O ratios) of area under the curve from zero to infinity (AUC0-∞ ), peak concentration (Cmax ), and time to reach peak concentration (Tmax ) equaling 1.00 (0.74-1.33), 1.04 (0.84-1.29), and 0.95 (0.72-1.26), respectively. In neonates, the geometric mean (95% CI) P/O ratio of whole blood concentrations was 0.75 (95% CI 0.64-0.87). PBPK modeling and simulation demonstrated that variability in biliary clearance, sublingual absorption, and CYP3A4 abundance are likely important drivers of buprenorphine PK variability in neonates. The PBPK model could be used to guide development of improved buprenorphine starting dose regimens for the treatment of NOWS.


Assuntos
Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Buprenorfina/administração & dosagem , Modelos Biológicos , Síndrome de Abstinência Neonatal/tratamento farmacológico , Tratamento de Substituição de Opiáceos , Administração Intravenosa , Administração Sublingual , Adulto , Idoso , Analgésicos Opioides/farmacocinética , Biotransformação , Buprenorfina/efeitos adversos , Buprenorfina/farmacocinética , Criança , Pré-Escolar , Citocromo P-450 CYP3A/metabolismo , Cálculos da Dosagem de Medicamento , Feminino , Eliminação Hepatobiliar , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Síndrome de Abstinência Neonatal/sangue , Síndrome de Abstinência Neonatal/diagnóstico , Absorção pela Mucosa Oral , Resultado do Tratamento , Adulto Jovem
14.
Pediatr Qual Saf ; 6(5): e453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476305

RESUMO

INTRODUCTION: Individuals with opioid use disorder often report feelings of shame and describe feeling judged negatively. These feelings are especially true for pregnant women with opioid use disorder. The Ohio Perinatal Quality Collaborative conducted a multimodal quality improvement initiative for infants born with Neonatal Abstinence Syndrome (NAS). An important component of the project was focused on improving staff attitudes toward mothers of infants with NAS. METHODS: The Ohio Perinatal Quality Collaborative implemented an education program for healthcare providers at 39 participating hospital units regarding opioid use as a chronic disease and principles of nonjudgmental, trauma-informed care. Healthcare providers partnered with the mother of infants with NAS in the care of the infant and connected with local community resources. This work was a subcomponent of an overall multimodal quality improvement project. Healthcare provider attitudes were measured with the "Attitude Measurement: Brief Scales" questionnaire anonymously, at 3 different time points throughout the project. Attitude change was measured by pretraining and posttraining scores. ANOVA methods were used to compare individual items and a summary score across the 3 surveys. RESULTS: Summary scores improved significantly from 18.99 at baseline (January-March 2014) to 19.94 (P < 0.0001) in February 2015 and were maintained at 20.05 in July 2016. CONCLUSIONS: A nonjudgmental attitude toward mothers of infants with NAS is an important component of compassionate care. Improving healthcare provider attitudes can benefit a mother of an infant with NAS and help preserve the mother-infant dyad.

15.
Clin Pharmacokinet ; 60(2): 249-259, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32939690

RESUMO

BACKGROUND AND OBJECTIVE: Buprenorphine has been shown to be effective in treating infants with neonatal opioid withdrawal syndrome. However, an evidence-based buprenorphine dosing strategy has not been established in the treatment of neonatal opioid withdrawal syndrome because of a lack of exposure-response data. The aim of this study was to develop an integrated pharmacokinetic and pharmacodynamic model to predict buprenorphine treatment outcomes in newborns with neonatal opioid withdrawal syndrome. METHODS: Clinical data were obtained from 19 newborns with a median (range) gestational age of 37 (34-41) weeks enrolled in a pilot pharmacokinetic study of buprenorphine. Sparse blood sampling, comprising three specimens obtained around the second dose of buprenorphine, was performed using heel sticks with dried blood spot technology. Standardized neonatal opioid withdrawal syndrome severity scores (Finnegan scores) were collected every 3-4 h based on symptoms by bedside nursing staff. Mean Finnegan scores were used as a pharmacodynamic marker in the exposure-response modeling. The blood concentration-Finnegan score relationship was described using a physiologic indirect response model with inclusion of natural disease remission. RESULTS: A total of 52 buprenorphine blood concentrations and 780 mean Finnegan scores were available for the pharmacokinetic/pharmacodynamic modeling and exposure-response analysis. A one-compartment model with first-order absorption adequately described the pharmacokinetic data. The buprenorphine blood concentration at 50% of maximum effect for the inhibition of disease progression was 0.77 ng/mL (95% confidence interval 0.32-1.2). The inclusion of natural disease remission described as a function of postnatal age significantly improved the model fit. CONCLUSIONS: A buprenorphine pharmacokinetic/pharmacodynamic model was successfully developed. The model could facilitate model-informed optimization of the buprenorphine dosing regimen in the treatment of neonatal opioid withdrawal syndrome.


Assuntos
Buprenorfina , Síndrome de Abstinência Neonatal , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Síndrome de Abstinência Neonatal/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Resultado do Tratamento
16.
Expert Opin Drug Metab Toxicol ; 17(1): 87-103, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33049155

RESUMO

INTRODUCTION: Neonatal opioid withdrawal syndrome (NOWS) often arises in infants born to mothers who used opioids during pregnancy. Morphine, methadone, and buprenorphine are the most common first-line treatments, whereas clonidine and phenobarbital are generally reserved for adjunctive therapy. These drugs exhibit substantial pharmacokinetic (PK) and pharmacodynamic (PD) variability. Current pharmacological treatments for NOWS are based on institutional protocols and largely rely on empirical treatment of patient symptoms. AREAS COVERED: This article reviews the PK/PD of NOWS pharmacotherapies with a focus on the implication of physiological development and maturation. Body size-standardized clearance is consistently low in neonates, except for methadone. This can be ascribed to underdeveloped metabolic and elimination pathways. The effects of pharmacogenetics have been clarified especially for morphine. The PK/PD relationship of medications used in the treatment of NOWS is generally understudied. EXPERT OPINION: Providing an appropriate opioid dose in neonates is challenging. Advancements in quantitative pharmacology and PK/PD modeling approaches facilitate identification of key factors driving PK/PD variability and characterization of exposure-response relationships. PK/PD model-informed simulations have been widely employed to define age-appropriate pediatric dosing regimens. The model-informed approach holds promise to aid more rational use of medications in the treatment of NOWS.


Assuntos
Síndrome de Abstinência Neonatal/tratamento farmacológico , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/complicações , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacocinética , Analgésicos Opioides/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Humanos , Recém-Nascido , Farmacogenética , Gravidez , Complicações na Gravidez
17.
J Perinatol ; 41(10): 2417-2423, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33758398

RESUMO

OBJECTIVE: To report a more accurate prevalence estimate of late pregnancy nicotine exposures. STUDY DESIGN: A cross-sectional study during a 2-month period in 2019. Participants were women delivering in any of the six county maternity hospitals who consented to universal drug testing at the time of delivery as part of routine hospital admission. RESULTS: Of 2531 tested samples, 18.7% tested positive for high levels of cotinine indicating primary smoking or other primary use of tobacco products. Together, 33.0% of the study population tested positive for nicotine exposure during late pregnancy compared to vital records which reported 8.2% cigarette smoking during the third trimester of pregnancy and 10.5% cigarette smoking at any time during pregnancy through maternal self-report. CONCLUSION: Captured vital birth smoking measures vastly underreport actual primary exposures to nicotine products. Vital birth data also fail to capture secondhand exposures which constitute a significant proportion of the population.


Assuntos
Fumar Cigarros , Cotinina , Estudos Transversais , Feminino , Humanos , Espectrometria de Massas , Gravidez , Autorrelato
18.
Obstet Gynecol ; 135(2): 387-395, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31923064

RESUMO

OBJECTIVE: To quantify the reported prevalence and trend of maternal hepatitis C virus (HCV) infection in the United States (2009-2017) and identify maternal characteristics and obstetric outcomes associated with HCV infection during pregnancy. METHODS: We conducted a population-based retrospective cohort study of all live births in the United States for the period 2009 through 2017 using National Center for Health Statistics birth records. We estimated reported prevalence and trends over this time period for the United States. We also evaluated demographic factors and pregnancy outcomes associated with maternal HCV infection for a contemporary U.S. cohort (2014-2017). RESULTS: During the 9-year study period, there were 94,824 reported cases of maternal HCV infection among 31,207,898 (0.30%) live births in the United States. The rate of maternal HCV infection increased from 1.8 cases per 1,000 live births to 4.7 cases per 1,000 live births (relative risk [RR] 2.7, 95% CI 2.6-2.8) in the United States. After adjusting for various confounders in the contemporary U.S. cohort (2014-2017), demographic characteristics associated with HCV infection included non-Hispanic white race (adjusted RR 2.8, 95% CI 2.7-2.8), Medicaid insurance (adjusted RR 3.3, CI 3.2-3.3), and cigarette smoking (adjusted RR 11.1, CI 10.9-11.3). Co-infection during pregnancy with hepatitis B (adjusted RR 19.2, CI 18.1-20.3), gonorrhea, chlamydia, or syphilis were also associated with maternal HCV infection. Obstetric and neonatal outcomes associated with maternal HCV infection included cesarean delivery, preterm birth, maternal intensive care unit admission, blood transfusion, having small-for-gestational-age neonates (less than the 10th percentile) birth weight, neonatal intensive care unit admission, need for assisted neonatal ventilation, and neonatal death. CONCLUSION: The reported prevalence of maternal HCV infection has increased 161% from 2009 to 2017.


Assuntos
Hepatite C/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Feminino , Previsões , Idade Gestacional , Hepacivirus , Hepatite B/complicações , Hepatite B/epidemiologia , Hepatite C/complicações , Humanos , Recém-Nascido , Nascido Vivo/epidemiologia , Modelos Logísticos , Análise Multivariada , Gravidez , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Prevalência , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
19.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913133

RESUMO

BACKGROUND: Despite the standardization of care, formula feeding varied across sites of the Ohio Perinatal Quality Collaborative (OPQC). We used orchestrated testing (OT) to learn from this variation and improve nonpharmacologic care of infants with neonatal abstinence syndrome (NAS) requiring pharmacologic treatment in Ohio. METHODS: To test the impact of formula on length of stay (LOS), treatment failure, and weight loss among infants hospitalized with NAS, we compared caloric content (high versus standard) and lactose content (low versus standard) using a 22 factorial design. During October 2015 to June 2016, OPQC sites joined 1 of 4 OT groups. We used response plots to examine the effect of each factor and control charts to track formula use and LOS. We used the OT results to revise the nonpharmacologic bundle and implemented it during 2017. RESULTS: Forty-seven sites caring for 546 NAS infants self-selected into the 4 OT groups. Response plots revealed the benefit of high-calorie formula (HCF) on weight loss, treatment failure, and LOS. The nonpharmacologic treatment bundle was updated to recommend HCF when breastfeeding was not possible. During implementation, HCF use increased, and LOS decreased from 17.1 to 16.4 days across the OPQC. CONCLUSIONS: OT revealed that HCF was associated with shorter LOS in OPQC sites. Implementation of a revised nonpharmacologic care bundle was followed by additional LOS improvement in Ohio. Despite some challenges in the implementation of OT, our findings support its usefulness for learning in improvement networks.


Assuntos
Ingestão de Energia , Fórmulas Infantis , Tempo de Internação/estatística & dados numéricos , Síndrome de Abstinência Neonatal/terapia , Feminino , Humanos , Recém-Nascido , Lactose/administração & dosagem , Metadona/administração & dosagem , Metadona/efeitos adversos , Morfina/administração & dosagem , Morfina/efeitos adversos , Ohio , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Melhoria de Qualidade/organização & administração , Aumento de Peso
20.
Contemp Clin Trials ; 93: 106014, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32353544

RESUMO

Opioid use disorder (OUD) in pregnant women has increased significantly in recent years. Maintaining these women on sublingual (SL) buprenorphine (BUP) is an evidence-based practice but BUP-SL is associated with several disadvantages that an extended-release (XR) BUP formulation could eliminate. The National Drug Abuse Treatment Clinical Trials Network (CTN) is conducting an intent-to-treat, two-arm, open-label, pragmatic randomized controlled trial, Medication treatment for Opioid-dependent expectant Mothers (MOMs), to compare mother and infant outcomes of pregnant women with OUD treated with BUP-XR, relative to BUP-SL. A second aim is to determine the relative economic value of utilizing BUP-XR. Approximately 300 pregnant women with an estimated gestational age (EGA) of 6-30 weeks, recruited from 12 sites, will be randomized in a 1:1 ratio to BUP-XR or BUP-SL, balancing on site, EGA, and BUP-SL status (taking/not taking) at the time of randomization. Participants will be provided with study medication and attend weekly medication visits through 12 months postpartum. Participants will be invited to participate in two sub-studies to evaluate the: 1) mechanisms by which BUP-XR may improve mother and infant outcomes; and 2) effects of prenatal exposure to BUP-XR versus BUP-SL on infant neurodevelopment. This paper describes the key design decisions for the main trial made during protocol development. This Investigational New Drug (IND) trial uniquely uses pragmatic features where feasible in order to maximize external validity, hence increasing the potential to inform clinical practice guidelines and address multiple knowledge gaps for treatment of this patient population.


Assuntos
Buprenorfina/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Administração Sublingual , Buprenorfina/administração & dosagem , Preparações de Ação Retardada , Feminino , Humanos , Antagonistas de Entorpecentes/administração & dosagem , Gravidez , Projetos de Pesquisa
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