Forecasting Fetal Buprenorphine Exposure through Maternal-Fetal Physiologically Based Pharmacokinetic Modeling.

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.

Antibiotic exposure prevents acquisition of beneficial metabolic functions in the preterm infant gut microbiome.

Background: Aberrations in the preterm microbiome following antibiotic therapy have been reported in previous studies. The objective of this study was to probe potential underlying mechanisms between this observation and susceptibility to adverse prematurity-related outcomes.

Results: Metagenomic shotgun sequencing was performed on 133 stool and 253 skin samples collected at 1 and 3 weeks of age from 68 infants born at <36 weeks postmenstrual age and birth weight <2000 g.

A review of pregnancy-induced changes in opioid pharmacokinetics, placental transfer, and fetal exposure: Towards fetomaternal physiologically-based pharmacokinetic modeling to improve the treatment of neonatal opioid withdrawal syndrome.

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.

Utility of Repeat Testing for Congenital Hypothyroidism in Infants with Very Low Birth Weight.

Objective: To assess for possible missed hypothyroidism in infants of very low birth weight (VLBW) whose initial newborn screening (NBS) was within normal reference range.

Study Design: We analyzed serum thyroid-stimulating hormone (TSH) obtained at 36 weeks of corrected gestational age or at hospital discharge if earlier (retest TSH) in infants with VLBW in the neonatal intensive care unit to determine the prevalence and factors associated with retest TSH ≥5 mU/L, a concentration requiring close follow-up for hypothyroidism. Utility of alternative cut-offs for NBS TSH also was assessed.

Physiologically-Based Pharmacokinetic Modeling to Investigate the Effect of Maturation on Buprenorphine Pharmacokinetics in Newborns with Neonatal Opioid Withdrawal Syndrome.

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.

Opioid Treatment for Neonatal Opioid Withdrawal Syndrome: Current Challenges and Future Approaches.

Chronic intrauterine exposure to psychoactive drugs often results in neonatal opioid withdrawal syndrome (NOWS). When nonpharmacologic measures are insufficient in controlling NOWS, morphine, methadone, and buprenorphine are first-line medications commonly used to treat infants with NOWS because of in utero exposure to opioids. Research suggests that buprenorphine may be the leading drug therapy used to treat NOWS when compared with morphine and methadone.

Epidemiological Investigation on the Current Practice of Umbilical Cord Clamping in China.

Objective: Despite known benefits, the timing of and method used for umbilical cord clamping (UCC) in neonates remain controversial in China, as well as internationally. The objective of this study was to assess knowledge, attitudes, and practice of UCC amongst health care providers in China, as recommended by medical professional organizations.

Study Design: A web-based questionnaire on cord clamping practices was administered to midwives, obstetricians, and neonatologists in 126 hospitals from 16 provinces.

Impact of Institutional Breastfeeding Support in Very Low-Birth Weight Infants.

Feeding of human milk is associated with improved health outcomes in preterm infants. Mothers of preterm infants have difficulty establishing and maintaining an adequate milk supply. Our institution participated in Best Fed Beginnings (BFB), a national breastfeeding quality improvement collaborative, in 2012.

Pharmacotherapy of neonatal opioid withdrawal syndrome: a review of pharmacokinetics and pharmacodynamics.

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.

Physiologic Indirect Response Modeling to Describe Buprenorphine Pharmacodynamics in Newborns Treated for Neonatal Opioid Withdrawal Syndrome.

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.

Surfactant phospholipids act as molecular switches for premature induction of quorum sensing-dependent virulence in .

The virulence behaviors of many Gram-negative bacterial pathogens are governed by quorum-sensing (QS), a hierarchical system of gene regulation that relies on population density by producing and detecting extracellular signaling molecules. Although extensively studied under conditions, adaptation of QS system to physiologically relevant host environment is not fully understood. In this study, we investigated the influence of lung environment on the regulation of virulence factors by QS in a mouse model of acute pneumonia.

Utilizing Pediatric Physiologically Based Pharmacokinetic Models to Examine Factors That Contribute to Methadone Pharmacokinetic Variability in Neonatal Abstinence Syndrome Patients.

Chronic intrauterine exposure to psychoactive drugs often results in neonatal abstinence syndrome (NAS). NAS is the symptomatic drug withdrawal in newborns that generally occurs after in utero chronic opioid exposure. Methadone is an opioid analgesic commonly prescribed for pharmacologic management of NAS.

Buprenorphine pharmacotherapy for the management of neonatal abstinence syndrome in methadone-exposed neonates.

We aimed to compare the outcomes of pharmacotherapy with either buprenorphine or methadone in infants treated for neonatal abstinence syndrome (NAS) secondary to intrauterine exposure to methadone. This is a multi-center, retrospective cohort study to assess length of treatment (LOT), hospital length of stay (LOS), and cumulative opioid exposure between infants treated with either methadone or buprenorphine for NAS secondary to in utero exposure to methadone. Infants delivered at a gestational age ≥35 weeks and a maternal history of opioid-use disorder and/or urine drug screen positive for methadone, and postnatal pharmacotherapy for NAS with either buprenorphine or methadone as first-line opioid replacement therapy, were eligible.

Decreasing birth asphyxia: utility of statistical process control in a low-resource setting.

The neonatal period is a critical time for survival of the child. A disproportionate amount of neonatal deaths occur in low-resource countries and are attributable to perinatal events, especially birth asphyxia. This project aimed to reduce the incidence of birth asphyxia by 20% by June 2014 through training in neonatal resuscitation and improving the availability of resuscitation equipment in the delivery room in the National Hospital Abuja, Nigeria.

Suggestions for Model-Informed Precision Dosing to Optimize Neonatal Drug Therapy.

Evidence for dosing, efficacy, and safety of most medications used to treat neonates is sparse. Thus, dosing is usually derived by extrapolation from adult and pediatric pharmacologic data with scaling by body weight or body surface area. This may lead to drug dosing that is unsafe or ineffective.

Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding.

Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood.

Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome: A Pilot Study.

Objective: To characterize the population pharmacokinetics of oral methadone in neonates requiring pharmacologic treatment of neonatal abstinence syndrome and to develop a pharmacokinetic (PK) model toward an evidence-based treatment protocol.

Study Design: Based on a methadone dosing protocol, serum concentrations of methadone and its metabolites were assessed by high performance liquid chromatography-tandem mass spectrometry from dried blood spots. Population PK analysis was performed to determine the volume of distribution and clearance of oral methadone.

Natural Anti-Infective Pulmonary Proteins: In Vivo Cooperative Action of Surfactant Protein SP-A and the Lung Antimicrobial Peptide SP-BN.

The anionic antimicrobial peptide SP-B(N), derived from the N-terminal saposin-like domain of the surfactant protein (SP)-B proprotein, and SP-A are lung anti-infective proteins. SP-A-deficient mice are more susceptible than wild-type mice to lung infections, and bacterial killing is enhanced in transgenic mice overexpressing SP-B(N). Despite their potential anti-infective action, in vitro studies indicate that several microorganisms are resistant to SP-A and SP-B(N).

Impact of Early Sodium Supplementation on Hyponatremia and Growth in Premature Infants: A Randomized Controlled Trial.

Background: We tested the hypothesis that sodium supplementation in early preterm infants prevents late-onset hyponatremia and improves growth without increasing common morbidities during birth hospitalization.

Materials And Methods: This was a randomized, masked controlled trial of 4 mEq/kg/d of sodium (intervention) versus sterile water (placebo) from days-of-life 7 to 35 in infants born at <32 weeks corrected gestational age. The primary outcome was weight gain in the first 6 weeks of life.

Prolonged QTc interval in association with medium-chain acyl-coenzyme A dehydrogenase deficiency.

Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency is the most common disorder of mitochondrial fatty acid oxidation. We report a term male infant who presented at 3 days of age with hypoglycemia, compensated metabolic acidosis, hypocalcemia, and prolonged QTc interval. Pregnancy was complicated by maternal premature atrial contractions and premature ventricular contractions.

Vitamin D status of early preterm infants and the effects of vitamin D intake during hospital stay.

Objectives: To evaluate vitamin D (vitD) status in early preterm infants (EPTIs) at birth and during birth hospitalisation on current vitD intake.

Design/methods: Serum 25-hydroxyvitamin-D [25(OH)D] concentrations, vitD intake and risk factors for low vitD status were assessed in 120 infants born at ≤32 weeks gestation.

Results: Mean (SD) serum 25(OH)D at birth was 46.

Vitamin D nutrition in pregnancy: current opinion.

There is increasing interest in vitamin D nutrition during pregnancy because of widespread reports of a high prevalence of low vitamin D status in pregnant women. While vitamin D is important for calcium and phosphorus homeostasis and for bone health, it also plays important roles in many other physiologic functions in the body. Consistent with the expanded role of vitamin D, recent observational studies have demonstrated that low vitamin D status in pregnancy is associated with multiple potential adverse maternal, fetal, and infant outcomes and contributes to low vitamin D status in infants at birth.

Persistence of LPS-induced lung inflammation in surfactant protein-C-deficient mice.

Pulmonary surfactant protein-C (SP-C) gene-targeted mice (Sftpc(-/-)) develop progressive lung inflammation and remodeling. We hypothesized that SP-C deficiency reduces the ability to suppress repetitive inflammatory injury. Sftpc(+/+) and Sftpc(-/-) mice given three doses of bacterial LPS developed airway and airspace inflammation, which was more intense in the Sftpc(-/-) mice at 3 and 5 days after the final dose.