Neonatal sleep development and early learning in infants with prenatal opioid exposure.

The aim of this chapter is to examine the role of sleep and cognition in the context of the cumulative risk model examining samples of at-risk infants and maternal-infant dyads. The cumulative risk model posits that non-optimal developmental outcomes are the result of multiple factors in a child's life including, but not limited to, prenatal teratogenic exposures, premature birth, family socioeconomic status, parenting style and cognitions as well as the focus of this volume, sleep. We highlight poor neonatal sleep as both an outcome of perinatal risk as well as a risk factor to developing attentional and cognitive capabilities during early childhood. Outcomes associated with and contributing to poor sleep and cognition during infancy are examined in relation to other known risks in our clinical population. Implications of this research and recommendations for interventions for this population are provided.

Critical Illness and the Frailty Syndrome: Mechanisms and Potential Therapeutic Targets.

Frailty is a syndrome characterized by decreased reserves across multiple physiologic systems resulting in functional limitations and vulnerability to new stressors. Physical frailty develops over years in community-dwelling older adults but presents or worsens within days in the intensive care unit (ICU) because common mechanisms governing age-related physical frailty are often exacerbated by critical illness. The hallmark of physical frailty is a combined loss of muscle mass, force, and endurance. About one-third of ICU patients have frailty before hospitalization, which increases their risk for both short- and long-term disability and mortality. While there are several valid ways to measure clinical frailty in patients before or after an ICU admission, the mechanistic underpinnings of frailty in critically ill patients and ICU survivors have not been thoroughly investigated. Furthermore, therapeutic interventions to treat frailty during and after time in the ICU are lacking. In this narrative review, we examine studies that identify potential biological mechanisms underlying the development and propagation of physical frailty in both aging and critical illness (eg, inflammation, mitochondrial myopathy, and neuroendocrinopathy). We discuss specific aspects of these frailty mechanisms in older adults, critically ill patients, and ICU survivors that may represent therapeutic targets. Consistent with complexity underlying frailty, this syndrome is unlikely to result from an excess of a single harmful mediator or deficit of a single protective mediator. Rather, frailty occurs in the presence of an incompletely understood state of multisystem dysregulation. We further describe knowledge gaps that warrant clinical and translational research in frailty and critical care with an overall goal of developing effective frailty treatments in critically ill patients and ICU survivors.

Neonatal abstinence syndrome: Neurobehavior at 6 weeks of age in infants with or without pharmacological treatment for withdrawal.

Use and abuse of prescription opioids and concomitant increase in Neonatal Abstinence Syndrome (NAS), a condition that may lead to protracted pharmacological treatment in more than 60% of infants, has tripled since 2000. This study assessed neurobehavioral development using the NICU Network Neurobehavioral Scale in 6-week old infants with prenatal methadone exposure who did (NAS+; n = 23) or did not (NAS-; n = 16) require pharmacological treatment for NAS severity determined by Finnegan Scale. An unexposed, demographically similar group of infants matched for age served as comparison (COMP; n = 21). NAS+, but not NAS- group, had significantly lower scores on the regulation (p < .01) and quality of movement (p < .01) summary scales than the COMP group. The NAS+ and NAS- groups had higher scores on the stress-abstinence scale than the COMP group (p < .05). NAS diagnosis (NAS +) was associated with poorer regulation and quality of movement at 6 weeks of age compared to infants without prenatal methadone exposure from the same demographic.

Quantitative determination of telavancin in pregnant baboon plasma by solid-phase extraction and LC-ESI-MS.

The increasing incidence and severity of methicillin- and vancomycin-resistant infections during pregnancy prompted further development of telavancin. The understanding of the pharmacokinetics of telavancin during pregnancy is critical to optimize dosing. Due to ethical and safety concerns the study is conducted on the pregnant baboons. A method using solid-phase extraction coupled with liquid chromatography-single quadrupole mass spectrometry for the quantitative determination of telavancin in baboon plasma samples was developed and validated. Teicoplanin was used as an internal standard. Telavancin was extracted from baboon plasma samples by using Waters Oasis(®) MAX 96-Well SPE plate and achieved extraction recovery was >66% with variation <12%. Telavancin was separated on Waters Symmetry C18 column with gradient elution. Two SIM channels were monitored at m/z 823 and m/z 586 to achieve quantification with simultaneous confirmation of telavancin identification in baboon plasma samples. The linearity was assessed in the range of 0.188µg/mL to75.0µg/mL, with a correlation coefficient of 0.998. The relative standard deviation of this method was <11% for within- and between-run assays, and the accuracy ranged between 96% and 114%.

Brief report: Teen sexting and psychosocial health.

The current study examines whether adolescents who report sexting exhibit more psychosocial health problems, compared to their non-sexting counterparts. Participants included 937 ethnically diverse male and female adolescents recruited and assessed from multiple high schools in southeast Texas. Measures included self-report of sexting, impulsivity, alcohol and drug use, and depression and anxiety symptoms. Teen sexting was significantly associated with symptoms of depression, impulsivity, and substance use. When adjusted for prior sexual behavior, age, gender, race/ethnicity, and parent education, sexting was only related to impulsivity and substance use. While teen sexting appears to correlate with impulsive and high-risk behaviors (substance use), we did not find sexting to be a marker of mental health.

Development of auditory event-related potentials in infants prenatally exposed to methadone.

Developmental features of the P2 auditory ERP in a change detection paradigm were examined in infants prenatally exposed to methadone. Opiate dependent pregnant women maintained on methadone replacement therapy were recruited during pregnancy (N = 60). Current and historical alcohol and substance use, SES, and psychiatric status were assessed with a maternal interview during the third trimester. Medical records were used to collect information regarding maternal medications, monthly urinalysis, and breathalyzer to confirm comorbid drug and alcohol exposures. Between birth and 4 months infant ERP change detection performance was evaluated on one occasion with the oddball paradigm (.2 probability oddball) using pure-tone stimuli (standard = 1 kHz and oddball = 2 kHz frequency) at midline electrode sites, Fz, Cz, Pz. Infant groups were examined in the following developmental windows: 4-15, 16-32, or 33-120 days PNA. Older groups showed increased P2 amplitude at Fz and effective change detection performance at P2 not seen in the newborn group. Developmental maturation of amplitude and stimulus discrimination for P2 has been reported in developing infants at all of the ages tested and data reported here in the older infants are consistent with typical development. However, it has been previously reported that the P2 amplitude difference is detectable in neonates; therefore, absence of a difference in P2 amplitude between stimuli in the 4-15 days group may represent impaired ERP performance by neonatal abstinence syndrome or prenatal methadone exposure.

Teen sexting and its association with sexual behaviors.

OBJECTIVE: To examine the prevalence of sexting behaviors as well as their relation to dating, sex, and risky sexual behaviors using a large school-based sample of adolescents. DESIGN: Data are from time 2 of a 3-year longitudinal study. Participants self-reported their history of dating, sexual behaviors, and sexting (sent, asked, been asked, and/or bothered by being asked to send nude photographs of themselves). SETTING: Seven public high schools in southeast Texas. PARTICIPANTS: A total of 948 public high school students (55.9% female) participated. The sample consisted of African American (26.6%), white (30.3%), Hispanic (31.7%), Asian (3.4%), and mixed/other (8.0%) teens. MAIN OUTCOME MEASURE: Having ever engaged in sexting behaviors. RESULTS: Twenty-eight percent of the sample reported having sent a naked picture of themselves through text or e-mail (sext), and 31% reported having asked someone for a sext. More than half (57%) had been asked to send a sext, with most being bothered by having been asked. Adolescents who engaged in sexting behaviors were more likely to have begun dating and to have had sex than those who did not sext (all P < .001). For girls, sexting was also associated with risky sexual behaviors. CONCLUSIONS: The results suggest that teen sexting is prevalent and potentially indicative of teens' sexual behaviors. Teen-focused health care providers should consider screening for sexting behaviors to provide age-specific education about the potential consequences of sexting and as a mechanism for discussing sexual behaviors.

Opioid dependency in pregnancy and length of stay for neonatal abstinence syndrome.

OBJECTIVE: To examine opioid replacement therapy in pregnancy and effect on neonatal outcomes, including length of hospital stay for neonatal abstinence syndrome. DESIGN: Retrospective descriptive study. SETTING: Labor and delivery unit and neonatal intensive care unit (NICU), Eastern Maine Medical Center, Bangor, Maine. PARTICIPANTS: One hundred fifty-two opioid-dependent pregnant women on methadone maintenance therapy (MMT) (n = 136) or buprenorphine maintenance therapy (BMT) (n = 16) during pregnancy and their neonates. The neonates were born between January 1, 2005 and December 31, 2007. METHODS: A review of the electronic medical record (EMR) was conducted of all opioid-dependent women who were maintained on MMT or BMT at the time of admission for labor and delivery and their neonates. RESULTS: Maternal methadone dose and concomitant in-utero exposure to benzodiazepines prolonged the length of hospital stay for neonates. Length of stay was shorter in breastfed neonates than formula-fed neonates or neonates who received formula and breast milk. Neonates with prenatal exposure to MMT spent more days in the hospital (21 vs. 14 days) for treatment of neonatal abstinence syndrome (NAS) than infants with prenatal exposure to BMT. CONCLUSION: These findings are consistent with previous research on the simultaneous use of methadone and benzodiazepines during pregnancy and provide further direction for the treatment of opioid dependency during pregnancy. Harm reduction strategies for opioid-dependent pregnant women in substance abuse treatment with MMT may one day include guidance on daily treatment doses and recommendations to avoid the concomitant use of benzodiazepines to lessen NAS. Breastfeeding should be recommended to shorten length of stay. Understanding perinatal and neonatal outcomes of pregnant women on methadone or buprenorphine will help to identify optimal treatment for opioid dependency in pregnancy.

Sleep fragmentation and evidence for sleep debt in alcohol-exposed infants.

BACKGROUND: Infants exposed prenatally to alcohol are at increased risk for poor neurodevelopmental outcome including Sudden Infant Death Syndrome. AIM: To examine the relationship between prenatal alcohol exposure, sleep, arousal and sleep-related spontaneous motor movements in early infancy. STUDY DESIGN: Low-income women (N=13) were interviewed regarding pre- and pregnancy rates of alcohol, cigarette smoking and other substance use in the perinatal period. Infants were examined in a laboratory nap study using EEG, videography and actigraphy at 6-8 weeks of age. Estimates of maternal pre- and pregnancy alcohol use were used to divide infants into high vs. low maternal alcohol use groups. SUBJECTS: Mother-infant dyads recruited from a family practice clinic. OUTCOME MEASURES: Sleep-related spontaneous movements, behavioral state, and maternal assessments of infant alertness and irritability. RESULTS: Pre-pregnancy rates of alcohol consumption including binge drinking correlated with maternal report of poor infant alertness, and increased irritability. High maternal exposure groups showed increased sleep fragmentation, e.g., frequency and duration of wakefulness following sleep onset and decreased active sleep. Bout analysis of the temporal structure of sleep-related spontaneous movements showed significantly reduced bout duration associated with high maternal alcohol use. CONCLUSION: These results present evidence that prenatal alcohol exposure disrupts postnatal sleep organization and suppresses spontaneous movements during sleep, and increased sleep fragmentation promotes sleep deprivation. Results are consistent with the SIDS model of chronic sleep debt and suggest that attenuated sleep-related movements should be examined as an important modulator of cardiorespiratory functions during sleep in high-risk groups.