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Objective The objective of this study is to investigate the effects of maternal perinatal depression symptoms and infant treatment status for neonatal abstinence syndrome (NAS) on maternal perceptions of infant regulatory behavior at 6 weeks of age. Methods Mothers and their infants (N = 106; 53 dyads) were recruited from a rural, White cohort in Northeast Maine. Mothers in medication-assisted treatment (methadone) and their infants (n = 35 dyads) were divided based on the infant’s NAS pharmacological treatment (n = 20, NAS+ group; n = 15, NAS− group) and compared with a demographically similar, nonexposed comparison group (n = 18 dyads; COMP group). At 6 weeks postpartum, mothers reported their depression symptoms Beck Depression Inventory—2nd Edition) and infant regulatory behaviors [Mother and Baby Scales (MABS)]. Infant neurobehavior was assessed during the same visit using the Neonatal Network Neurobehavioral Scale (NNNS). Results Mothers in the NAS+ group showed significantly higher depression scores than the COMP group (p < .05) while the NAS− group did not. Across the sample, mothers with higher depression scores reported higher infant “unsettled-irregularity” MABS scores, regardless of group status. Agreement between maternal reports of infant regulatory behaviors and observer-assessed NNNS summary scares was poor in both the NAS+ and COMP groups. Conclusions Postpartum women in opioid recovery with infants requiring pharmacological intervention for NAS are more at risk for depression which may adversely influence their perceptions of their infants’ regulatory profiles. Unique, targeted attachment interventions may be needed for this population.

INTRODUCTION: Sleep disorder is often the first symptom of age-related cognitive decline in Mild Cognitive Impairment (MCI), or early Alzheimer’s disease. Patient or family sleep complaints in primary care do not reliably lead to screening for sleep or cognitive loss. In this study, poor sleep and arousability were examined using movement arousals, a novel biobehavioral marker of cumulative sleep loss, identified by periodic (circa 4 min) sleep movements (SM). We report that SM events trigger respiratory upregulation (RR) in healthy, but not in MCI-related, sleep. Time latency (TL) between SM-RR events is proposed as a marker of sleep loss and potentially of neurodegeneration associated with cognitive loss in MCI.METHOD. Community-dwelling older adults (N=95; 62-90 years) were tested in the home bed for two days on an “under the sheets” mattress overlay with high sensitivity for respiration and all movement, including micro-movements of SM. Wrist actigraphy (7 days) and standard sleep self-reports were collected as well. A suite of neurocognitive testing identified three groups: Normal Cognition (NC; n=45); clinic diagnosed MCI (MCI-DX; n= 17); and MCI-Consensus determined by an expert panel (MCI-CON; n=33 consensus or pre-clinical MCI) groups.RESULTS: In adjusted cohort analyses, sleep fragmentation (SF) and WASO predicted poorer memory performance selectively. Actigraphy revealed greater sleep latency (SL; pDISCUSSION: MCI cognitive phenotype was detected with a novel sleep biomarker TL, associated with the tight gap between SM-RR coupling, which is proposed as a corollary of sleep quality/loss that affects the autonomic regulation of respiration during sleep. Movement arousals are less effective in initiating respiratory upregulation in MCI which suggests a potential mechanism for neurodegenerative changes and cognitive loss in early MCI.

Although prenatal opioid exposure and postnatal withdrawal (neonatal abstinence syndrome) are associated with infant neurobehavioral deficits, little is known about the impact of continued maternal opioid treatment in the postnatal period on maternal responsivity and relationship to mother's oxytocin release during dyadic interactions in the Still Face paradigm. Mother and infant dyads (N = 14) were recruited and comprised of mothers on opioid replacement throughout pregnancy and postpartum (opioid-exposed group, n = 7) and a demographically controlled, non-exposed group (n = 7). Salivary oxytocin was collected following 10 min of infant separation before and immediately after a 6-min Still Face paradigm. Oxytocin measures correlated strongly with sensitive and prosocial maternal behaviors in response to infant initiation. Opioid-exposed compared to non-exposed mothers had significantly lower pre-test to post-test rise in salivary oxytocin concentration level as well as fewer sensitive behaviors during the reunion condition of the Still Face paradigm. Maternal opioid dependence during early infancy may impair maternal responsivity and sensitivity through suppression of the oxytocin reflex to infant stimulation.

This pilot study examined changes in cancer-related post-traumatic stress symptoms (PTSS) across time for siblings of children with cancer. Siblings (N = 32; aged 8-18) completed a measure of anxiety, the Child PTSD Symptom Scale (CPSS), and the PTSD section of the Structured Clinical Interview for DSM-IV-TR (SCID) at twelve (SD = .9) and eighteen months (SD = 1.3) post-diagnosis. Moderate-to-severe PTSS was reported by 12 siblings (38%) at T1 and 7 (22%) at T2. Cluster analysis of PTSS data revealed five patterns: Few symptoms, stable across time (31%, n = 10); Mild symptoms, decreasing across time (16%, n = 5); Mild, stable symptoms (28%, n = 9); Moderate/severe symptoms, decreasing across time but remaining moderate (19%, n = 6); and Moderate/severe, stable symptoms (6%, n = 2). SCID data and anxiety scores distinguished siblings in the final two clusters from those with more favorable PTSS levels/trajectories. Additional research with larger samples is needed to validate these trajectories and examine factors that distinguish siblings with consistently elevated cancer-related PTSS from those with mild or significantly improving symptoms.

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.

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.

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

Introduction Late-life depression has been proposed as a precursor to amnestic Mild Cognitive Impairment (aMCI), the prodrome of Alzheimer’s disease. Both conditions are associated with sleep and cognitive problems. We hypothesized that MCI and current depressive symptoms would co-occur more frequently, but express distinct sleep phenotypes. Methods Independently living older adults (N=80), age 62-90 (M=71.78, SD=5.98), were recruited from a geriatric psychiatry clinic and the community for a home sleep study. A clinical decision board and neurocognitive battery were used to determine MCI status. Participants completed the CES-D and depression history interview where endorsement of current depression was considered positive. Sleep was examined with wrist actigraphy for 7 days. Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Stanford Sleepiness Scale (SSS) provided subjective sleep quality. Results Based on these criteria, 41.2% of the sample were determined to be MCI (n=33); the remainder were deemed normative for age (NC; n=47). Chi-square analyses showed a higher frequency of MCI were positive for current depression than expected (14.2%; p=0.017). Repeated-measures MANOVA, using current depression symptoms and MCI as factors, revealed MCI was associated with longer sleep latency (p=0.035) and wake bout time (p=0.039); whereas, current depression was associated with longer sleep latency, more fragmentation/WASO, and lower sleep efficiency (p’s Conclusion Despite distinct sleep disordered phenotypes, the interaction of MCI and current depression is associated with delayed sleep onset, use sleep medication and report of sleep disturbances. Support This project was sponsored by: NASA, Maine Space Consortium; AG 056176, AG 053164 Vice President for Research, U. Maine; Maine Technology Institute; DoD Phase I SBIR and R44AG059536-01 SBIR Phase II Award.

Background and Objectives There is significant variability in severity of neonatal abstinence syndrome (NAS) due to in utero opioid exposure. Our previous study identified single nucleotide polymorphisms (SNPs) in the prepronociceptin (PNOC) and catechol-O-methyltransferase (COMT) genes that were associated with differences in NAS outcomes. This study looks at the same SNPs in PNOC and COMT in an independent cohort in an attempt to replicate previous findings. Methods For the replication cohort, full-term opioid-exposed newborns and their mothers (n = 113 pairs) were studied. A DNA sample was obtained and genotyped for five SNPs in the PNOC and COMT genes. The association of each SNP with NAS outcomes (length of hospitalization, need for pharmacologic treatment, and total opioid days) was evaluated, with an experiment-wise significance level set at α

Objectives To assess whether preeclampsia was associated with expiratory airflow at school-age in children born either extremely preterm ( Study design Participants comprised 3 cohorts of children born extremely preterm/ELBW in the state of Victoria, Australia, in 1991-1992, 1997, or 2005. Expiratory airflows were measured at age 8 years, and results converted to z scores. Data were compared between those exposed to preeclampsia with those unexposed to preeclampsia; analyses were then adjusted for confounding perinatal variables. Analyses were repeated within subgroups of extremely preterm only and ELBW only. Results Respiratory data were available for 544 of 717 (76%) survivors, of whom 95 (17%) had been exposed to preeclampsia. On univariable analysis, those exposed to preeclampsia had better z scores for flows for the forced expired volume in 1 second (zFEV1) (mean difference 0.29, 95% CI 0.04-0.53; P = .022) and zFEV1/forced vital capacity (mean difference 0.33, 95% CI 0.04-0.61; P = .025); the difference persisted for zFEV1 after adjustment for confounding perinatal variables. Analyses confined to those born extremely preterm revealed little evidence for associations between preeclampsia and airflow. In analyses confined to those born ELBW, preeclampsia was associated with better zFEV1, which persisted after adjustment (mean difference 0.33, 95% CI 0.04-0.63; P = .025). Conclusions Exposure to maternal preeclampsia was not associated with worse expiratory airflow in children born extremely preterm/ELBW; in fact, some airflows were better.

Neonatal abstinence syndrome (NAS) due to in-utero opioid exposure has significant variability of severity. Preliminary studies have suggested that epigenetic variation within the μ-opioid receptor (OPRM1) gene impacts NAS. We aimed to determine if DNA methylation in OPRM1 within opioid-exposed mother-infant dyads is associated with differences in NAS severity in an independent cohort. Full-term opioid-exposed newborns and their mothers (N = 68 pairs) were studied. A DNA sample was obtained and then assessed for level of DNA methylation at 20 CpG sites within the OPRM1 promoter region by next-generation sequencing. Infants were monitored for NAS and treated with replacement opioids according to institutional protocol. The association between DNA methylation level at each CpG site with NAS outcome measures was evaluated using linear and logistic regression models. Higher methylation levels within the infants at the -18 (11.4% vs 4.4%, P = .0001), -14 (46.1% vs 24.0%, P = .002) and +23 (26.3% vs 12.9%, P = .008) CpG sites were associated with higher rates of infant pharmacologic treatment. Higher levels of methylation within the mothers at the -169 (R = 0.43, P = .008), -152 (R = 0.40, P = .002) and +84 (R = 0.44, P = .006) sites were associated point-wise with longer infant length of stay. Maternal associations remained significant point-wise for -169 (β = 0.07, P = .007) and on an experiment-wise level for +84 (β = -0.10, P = .003) using regression models. These results suggest an association of higher levels of OPRM1 methylation at specific CpG sites and increased NAS severity, replicating prior findings. These findings have important implications for personalized treatment regimens for infants at high risk for severe NAS.

Methadone versus morphine for treatment of neonatal abstinence syndrome: A prospective randomized clinical trial

Objective Neonatal abstinence syndrome (NAS) from in utero opioid exposure is highly variable with genetic factors appearing to play an important role. Epigenetic changes in cytosine:guanine (CpG) dinucleotide methylation can occur after drug exposure and may help to explain NAS variability. We correlated DNA methylation levels in the mu-opioid receptor (OPRM1) promoter in opioid-exposed infants with NAS outcomes. Study design DNA samples from cord blood or saliva were analyzed for 86 infants who were being treated for NAS according to institutional protocol. Methylation levels at 16 OPRM1 CpG sites were determined and correlated with NAS outcome measures, including need for treatment, treatment with $2 medications, and length of hospital stay. We adjusted for covariates and multiple genetic testing. Results Sixty-five percent of infants required treatment for NAS, and 24% required $2 medications. Hypermethylation of the OPRM1 promoter was measured at the � 10 CpG in treated vs nontreated infants (adjusted difference d = 3.2% [95% CI, 0.3-6.0%], P = .03; nonsignificant after multiple testing correction). There was hypermethylation at the � 14 (d = 4.9% [95% CI, 1.8%-8.1%], P =. 003),� 10 (d =5 .0% [95% CI, 2.3-7.7%],P = .0005), and +84 (d = 3.5% [95% CI, 0.6-6.4], P = .02) CpG sites in infants requiring $2 medications, which remained significant for � 14 and � 10 after multiple testing correction. Conclusions Increased methylation within the OPRM1 promoter is associated with worse NAS outcomes, consistent with gene silencing. (J Pediatr 2014;165:472-8).

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.

Recent rise in rates of opiate replacement therapy among pregnant women have resulted in increasing number of infants requiring treatment for neonatal abstinence syndrome. Short- and long-term developmental outcomes associated with prenatal opiate exposure are discussed, including symptoms and severity of neonatal abstinence syndrome (NAS), and early cognitive and motor delays. Maternal and infant risk factors are discussed, and include patterns of maternal substance use during pregnancy, genetic risk, polysubstance exposure pharmacologic treatment for NAS and breastfeeding. The importance of characterizing corollary environmental risk factors is also considered.

There is significant variability in severity of neonatal abstinence syndrome (NAS) due to in utero opioid exposure. Our previous study identified single nucleotide polymorphisms (SNPs) in the prepronociceptin (PNOC) and catechol-O-methyltransferase (COMT) genes that were associated with differences in NAS outcomes. This study looks at the same SNPs in PNOC and COMT in an independent cohort in an attempt to replicate previous findings.For the replication cohort, full-term opioid-exposed newborns and their mothers (n = 113 pairs) were studied. A DNA sample was obtained and genotyped for five SNPs in the PNOC and COMT genes. The association of each SNP with NAS outcomes (length of hospitalization, need for pharmacologic treatment, and total opioid days) was evaluated, with an experiment-wise significance level set at α .003 and point-wise level of α .05. SNP associations in a combined cohort of n = 199 pairs (replication cohort plus 86 pairs previously reported), were also examined.In the replication cohort, mothers with the COMT rs4680 G allele had infants with a reduced risk for treatment with two medications for NAS (adjusted OR = .5, p = .04), meeting point-wise significance. In the combined cohort, infants with the PNOC rs4732636 A allele had a reduced need for medication treatment (adjusted OR 2.0, p = .04); mothers with the PNOC rs351776 A allele had infants who were treated more often with two medications (adjusted OR 2.3, p = .004) with longer hospitalization by 3.3 days (p = .01). Mothers with the COMT rs740603 A allele had infants who were less often treated with any medication (adjusted OR .5, p = .02). Though all SNP associations all met point wise and clinical significance, they did not meet the experiment-wise significance threshold.We found differences in NAS outcomes depending on PNOC and COMT SNP genotype. This has important implications for identifying infants at risk for severe NAS who could benefit from tailored treatment regimens. Further testing in a larger sample is warranted. This has important implications for prenatal prediction and personalized treatment regimens for infants with NAS. (Am J Addict 2017;26:42-49).

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.

Yawning has been observed in foetuses and preterm infants. The aim of this study was to assess the frequency and the 24 h distribution of yawning in preterm infants. Twelve low-risk infants between 31 and 40 weeks of post-conceptional age (PCA) were continuously video-recorded for 24 h in their incubator. Spontaneous yawning was defined as opening of the mouth to its full extension in a dramatic stretch movement. The results showed that the rate of yawning across the 24-h period was 1.10/h. The highest incidence of yawns was in the waking motility pattern when compared to active sleep or quiet sleep motility patterns. Between 31 and 40 weeks, yawn incidence significantly decreased mainly during the day. The marked decrease in yawn frequency with age may be related to the development of circadian and homeostatic control of sleep and wake.

Infancy and early childhood sleep–wake behaviours from current and retrospective parental reports were used to explore the relationship between sleeping arrangements and parent–child nighttime interactions at both time points. Children (N=45) from educated, middle-class families, mostly breastfed in infancy, composed a convenience sample that was recruited from a university preschool in the Northeast US. Parents responded to the Sleep Habits Inventory, a 19-item Likert-style inventory measuring sleep-related behaviours during the last week, and the Sleeping Arrangements Questionnaire, a 30-question, open-ended, short-answer-style instrument which queries both retrospective infancy and current sleep location, bedtime routine, night waking and parent–child interactions during the sleep period. Co-sleeping in early childhood was associated with sleep location in infancy (i.e. proximity to the mother's bed) during wake–sleep transitions and night feedings. Security object use during infancy was inversely related to early childhood co-sleeping (calling for the parents, night waking, poor bedtime routine and fear of the dark). Results showed that early childhood co-sleeping in this sample was reactive, i.e. associated with current parent-seeking, night waking and social contact during wake–sleep transitions. These findings suggest that co-sleeping in early childhood is related to social experiences during infancy, particularly the amount of parent social contact and security object use. Copyright © 2007 John Wiley & Sons, Ltd.

There is significant variability in the severity of neonatal abstinence syndrome (NAS) due to in-utero opioid exposure. We wanted to determine if single nucleotide polymorphisms (SNPs) in key candidate genes contribute to this variability.Full-term opioid-exposed newborns and their mothers (n=86 pairs) were studied. DNA was genotyped for 80 SNPs from 14 genes utilizing a custom designed microarray. The association of each SNP with NAS outcomes was evaluated.SNPs in two opioid receptor genes in the infants were associated with worse NAS severity: (1) The PNOC rs732636 A allele (OR=3.8, p=0.004) for treatment with 2 medications and a longer hospital stay (LOS) of 5.8 days (p=0.01), and (2) The OPRK1 rs702764 C allele (OR=4.1, p=0.003) for treatment with 2 medications. The OPRM1 rs1799971 G allele (β=-6.9 days, p=0.02) and COMT rs740603 A allele (β=-5.3 days, p=0.01) were associated with shorter LOS. The OPRD1 rs204076 A allele in the mothers was associated with a longer LOS by 6.6 days (p=0.008). Results were significant point-wise but did not meet the experiment-wide significance level.These findings suggest that SNPs in opioid receptor and the PNOC genes are associated with NAS severity. However, further testing in a large sample is warranted. This has important implications for prenatal prediction and personalized treatment regimens for infants at highest risk for severe NAS.

Objective. To examine factors associated with the phenomenon of yonaki, or sleep-related nighttime crying (SRNC), in Japanese childrenMethods. A cross-sectional design incorporating parental self-report was used to investigate relationships between developmental, psychologic, and constitutional/physiological factors in the incidence of SRNC. Participants were the parents of 170 infants, 174 toddlers, and 137 children at a well-infant clinic in Tokyo, Japan.Results. The lifetime incidence rates of SRNC were 18.8% (infants), 64.9% (toddlers), and 59.9% (children). At all ages, children were most likely to cosleep with their parents; however, infants with reported SRNC were found to cosleep more frequently, whereas infants without SRNC were more likely to sleep in separate, child-dedicated beds. Toddlers with frequent SRNC were more likely to have irregular bedtimes and to have nonparental day care than were those without SRNC. Preschoolers who typically slept 9.5 to 10.5 hours per night were less likely to report SRNC than were children with longer or shorter nighttime sleep durations. In all groups, children with frequent SRNC were more likely to suffer from chronic eczema, and toddlers and preschoolers with SRNC exhibited bruxism more frequently.Conclusions. The traditional Japanese arrangement of cosleeping represents an environment in which parents are readily accessible to children during waking episodes. Physical proximity to the parents in infancy, but not at other ages, is associated with SRNC. The higher incidence of bruxism, chronic eczema, and day care use among children with frequent SRNC supports the hypothesis that nighttime anxiety may promote SRNC.

Objective To examine patterns of behavioral states of premature newborns before and after nursing interventions. Design Secondary analysis of videotaped data, using a repeated measures design. Setting 18-bed neonatal intensive-and intermediate-care unit in a 400-bed suburban teaching hospital. Participants Forty medically stable premature newborns with an average postconceptional age of 32.79 weeks at the time of testing. Main outcome measure Behavioral states measured by observations of videotape recordings. Results Five-hour observations of behavioral states revealed that newborns showed more quiet sleep, F (2, 38) = 5.65, p = .023, and fewer waking episodes, F (2, 38) = 14.4, p = .001, in the 30 minutes after nursing interventions than in the 30 minutes before. This repeated measures ANOVA analysis accounted for effects of caffeine or theophylline. Neither the frequency nor the duration of nursing interventions predicted duration or frequency of behavioral states before or after interventions. Some newborns experience waking outside the context of nursing interventions. Conclusions For medically stable newborns, nursing interventions are generally followed by sleep, possibly indicating satiety after feeding or significant energy expenditure. The findings also may suggest that some newborns show anticipation of feeding by waking, although 50% of the newborns did not experience any waking prior to interventions. Further research is needed to examine associations between specific types of nursing interventions and newborn behavioral responses, as well as the relationship of behavioral state patterns and newborn development.

In vulnerable individuals, postpartum depression may be triggered by the disruption of neuropsychological processes during pregnancy and parturition. It is proposed that in Western societies pre- and postnatal psychological and instrumental needs are poorly met and this crisis may interact with neurophysiological factors in compromising maternal psychological functioning. The influence of developmental factors and psychological and physical stressors are discussed in relation to women’s neuropsychological health during the peripartal transition. It is hypothesized that the environmental milieu may support, neglect or derail the mother’s psychobiological transition from pregnancy to effective postnatal parenting and resumption of family and work roles.

Developmental changes in the temporal organization of spontaneous movements during sleep was studied in children between 9 months and 11 years of age. Subjects were monitored in the home environment for the entire sleep period using actigraphy and videography. Rhythmicity in sleep-related spontaneous movements was examined using FFT and chisquare periodogram time series analyses. A dominant periodicity of 60–120 minutes was identified which was found to progressively lengthen with age. A microanalysis of the temporal structure of movements revealed a developmental decline in bout duration, but a paradoxical increase in bout frequency. These results show that motor activity becomes less robust and more fragmented as development progresses while retaining underlying rhythmic integrity, and argue for the dynamic influence of CNS maturation on the organization and expression of sleep-related spontaneous movements. © 1998 John Wiley & Sons, Inc. Dev Psychobiol 32: 13–21, 1998

Postmature infants calm less when presented with sucrose solutions than term infants. To further assess the influence of postmaturity on sucrose responsivity, several motoric responses were examined in healthy term neonates and chronically stressed postmature (> or = 288 days gestational age (GA) e.g., > 41 weeks) neonates with Clifford's Syndrome tested between 5-91 h of age. Following baseline observations, each subject was presented with 0.1 ml of a 14% sucrose solution for 10 s each min for 5 min, and observations were continued for 5 min following stimulation. During sucrose stimulation and poststimulation phases, postmature infants showed more tremors during quiet state than term infants. Across conditions, postmature infants exhibited increased finger sucking, rhythmic sucking, but less mouth opening and arm movements than healthy, term infants. Sequence analysis revealed that short-latency mouthing, repetitive movements of the upper and lower lips, followed sucrose infusion reliably in postmature infants, but not term infants. These results suggest that postmaturity is associated with: 1. Increased oral behaviors associated with arousal and self soothing; and 2. Increased sucrose reactivity, as indicated by contingent mouthing and increased tremors.

Importance Neonatal abstinence syndrome (NAS) caused by in utero opioid exposure is a growing problem; genetic factors influencing the incidence and severity have not been previously examined. Single-nucleotide polymorphisms (SNPs) in the μ-opioid receptor (OPRM1), multidrug resistance (ABCB1), and catechol-o-methyltransferase (COMT) genes are associated with risk for opioid addiction in adults. Objective To determine whether SNPs in the OPRM1, ABCB1, and COMT genes are associated with length of hospital stay and the need for treatment of NAS. Design, Setting, and Participants Prospective multicenter cohort study conducted at 5 tertiary care centers and community hospitals in Massachusetts and Maine between July 2011 and July 2012. DNA samples were genotyped for SNPs, and then NAS outcomes were correlated with genotype. Eighty-six of 140 eligible mother-infant dyads were enrolled. Infants were eligible if they were 36 weeks' gestational age or older and exposed to methadone or buprenorphine in utero . Main Outcomes and Measures Primary outcome measure was length of hospital stay, with between-group differences expressed as β and calculated with linear regression models. Secondary outcome measures included need for any medical treatment for NAS and treatment with 2 or more medications. Results Infants with the OPRM1 118A>G AG/GG genotype had shortened length of stay (β = −8.5 days; 95% CI, −14.9 to −2.1 days; P = .009) and were less likely to receive any treatment than AA infants (48% vs 72%; adjusted odds ratio, 0.76; 95% CI, 0.63-0.96; P = .006). The COMT 158A>G AG/GG genotype was associated with shortened length of stay (β = −10.8 days; 95% CI, −18.2 to −3.4 days; P = .005) and less treatment with 2 or more medications (18% vs 56%; adjusted odds ratio, 0.68; 95% CI, 0.55-0.86; P = .001) than the AA genotype. Associations with the ABCB1 SNPs were not significant. Conclusions and Relevance Among infants with NAS, variants in the OPRM1 and COMT genes were associated with a shorter length of hospital stay and less need for treatment. These preliminary findings may provide insight into the mechanisms underlying NAS.

Cette etude a examine les interactions parent-enfant pendant le debut du sommeil et les reveils durant la nuit chez un echantillon d'enfants d'âge prescolaire d'une petite ville rurale. Le role du co-sommeil par rapport aux habitudes de sommeil et aux reveils la nuit a ete examine en utilisant des rapports etablis par les parents des patterns actuels et passes. Les resultats revelerent que les Dormeurs Solitaires s'engageaient dans des routines plus complexes au moment du sommeil, et faisaient preuve d'un attachement plus long et plus fort a des objects de securite et a des aides au sommeil que les Co-Dormeurs. Les facteurs precurseurs au co-sommeil dans la petite enfance etaient les suivants: l'allaitement, l'allaitement nocturne dans le lit des parents, et le retour au sommeil dans le lit des parents.

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.

A wide range of conditions fall under the category of Mild Traumatic Brain Injury (mTBI) diagnosis. In this article, we focus on a new method during sleep to detect mTBI associated with neuro-cognitive impairment that is not apparent using standard neuro-imaging methods. A wireless pressure sensor system comprising a piezo-resistive flexible substrate paired with a microcontroller and a radio is designed and built to provide information relevant to mTBI detection. The collected information is then processed with a software program to remove noise and interference, and detect both sleep states and cardio-respiratory movements. (5 pages)

Spontaneous movements of premature infants between 25 and 34 weeks conceptional age were observed for 1 hr on two or three occasions. Subjects had low-risk prognoses and were clinically stable at the time of testing. Behavioral acts were scored using a 0/1 time sampling technique in 60 continuous, 1-min time blocks. Temporal associations between individual movements were found using chi-square analyses. Some associated behaviors contained combinations consistent with neonatal action patterns, for example, single and bilateral leg kicking, head turning, and mouthing. Features of state organization were also evident in that general motor activity (GM), which has been used as a marker of active sleep (AS) in neonates, was found to cluster temporally with startle, facial, and head movements but not eye movements. Behavioral quiescence (> or = 5 s) was dissociated from AS-related behaviors (GM, facial, head, and eye movements). Combinations of state-segregated behaviors were more likely to exhibit co-occurrence within 1-min intervals in infants 30 weeks conceptional age and older.

Neonatal treatment with monoamine reuptake inhibitors results in a constellation of neurobehavioral alterations in adult rats that may model human depression. Since alterations in circadian rhythmicity have been reported in both depressed patients and in animal depression models, the present study examined the effects of neonatal desipramine treatment (5.0 mg/kg SC from postnatal day 7 through 22) on free-running circadian drinking rhythms. Rhythmicity was examined in constant darkness (DD), constant light (LL), and during adult desipramine treatment (0.25 mg/ml via the drinking water). Compared with saline-treated controls, neonatal desipramine lengthened free-running period in DD, blunted the period-altering effect of LL, and potentiated the period-altering effect of adult desipramine treatment. Neonatal desipramine treatment also increased circadian amplitude and spectral magnitude, but did not modify the effects of light or adult desipramine on these parameters. These results provide further evidence that behavioral depression is associated with alterations in circadian rhythmicity, and are consistent with the hypothesis that such relationships are mediated by brain monoaminergic systems.

Sleep–wake behaviours and temperament were examined longitudinally for trait stability and relationship to behavioural state regulation from infancy to early childhood. Subjects were 120 low-risk, full-term infants from a middle class sample. At 6 weeks, parents completed three consecutive days of the Baby's Day Diary which measures sleep, wake, fuss, feed and cry states and the Infant Characteristics Questionnaire. At 16 months, parents assessed sleep behaviours with the Sleep Habits Inventory and temperament with the Toddler Symptom Checklist. At 24 months, parents repeated 3 days of the Baby's Day Diary. Structural Equation Modelling was used to examine the cross-age hypotheses for sleep–wake and temperament associations. From early infancy to toddlerhood, sleep–wake behaviours and irritable temperament were notably stable but independent in this cohort. Copyright © 2011 John Wiley & Sons, Ltd.

The spontaneous motor activity of clinically stable premature infants, 26–36 weeks gestational age, was investigated. Movements were recorded using a pressure-sensitive transducer positioned below the infant's head and torso. Behavior samples were digitized every 0.5 s during 2 and 3-hr continuous recording sessions. Time-series analyses revealed prominent motility cycles of circa 80 min and circa 30 min. These results are consistent with periodicities in motility and REM activation observed in full-term neonates. The longer rhythms of 70–100 min of motility found in this study establish that these periods are present at this stage of development independent of maternal zeitgebers. Developmental changes in motility rhythms and movement burst durations were also observed. Bout durations became somewhat longer in older ( > 30 weeks) infants, but the relative time devoted to movement per session was comparable in older and younger (≤ 30 weeks) infants. © 1993 Wiley & sons. Inc.

A soft thresholding technique is used in an attempt to improve the accuracy of signals with low signal-to-noise ratios (SNR). Focusing initially on EEG signals from high-risk infants, the technique has provided us with valuable information on the nature of the signal to improve estimation methods for this type of data.

To determine if apneic preterm infants currently treated with methylxanthines develop evidence of sleep deprivation from cumulative arousal and motor activational effects. Sleep, wake, arousal and actigraphic movements were monitored in extubated clinically stable premature infants (N=37). Neonates were free of other medications for >72 h and were grouped based on methylxanthine exposure: >5 days with caffeine (n=14), >5 days theophylline (n=13) or no prior exposure (n=10). Duration of methylxanthine treatment predicted increased arousals, wakefulness and actigraphic movements, and decreased active sleep. Recording from 1200 to 0500 hours, methylxanthine-treated groups showed reductions in all arousal parameters: waking state, number of wake epochs, brief arousals and composite arousal index, and shorter fast-burst, sleep-related motility than untreated controls. In apneic preterms, chronic methylxanthine treatment appears to produce sleep deprivation secondary to the stimulatory action of methylxanthines on arousal and motor systems.

Low risk, premature infants between 30 to 35 weeks post-conceptual age (PCA) residing in an neonatal intensive care unit environment were observed in the home incubator for spontaneous yawning from 2400 to 0500 hr. Videorecordings were analyzed for the behavioral states of quiet sleep (QS), active sleep (AS), wake (W), and drowse (D) in 3-min epochs as well as the contextual behaviors before and after yawn events using a 1-min window. Yawning periods predicted higher levels of motoric activation than nonyawn periods. Sequence analysis of preceding and following states with or without yawns were examined for stability or change. All states with or without yawn events had state stability for the preceding and following epochs, with two exceptions: 1) D state with yawning was associated with state change in the preceding 3-min epoch (most often W), and 2) D state without yawning was associated with state change in the following epoch (W or AS). Yawns were not present in QS. The results suggest that yawning is associated with increased behavioral arousal that is not state-specific. However, yawning in D state predicts state transitions in the preceding, but not the following, epoch. It is proposed that D may be an unstable state that becomes more stable when yawning is present.

This study examined prior use and psychosocial factors associated with alcohol and/or drug use in pregnant women from a predominantly Caucasian, rural clinic in northeastern Maine.We conducted archival record reviews of 217 pregnant women who delivered at the Family Practice Clinic of Eastern Maine Medical Center As part of the standard initial prenatal visit during thefirst trimester, a nurse practitioner interviewed and collected data from pregnant women concerning pre-pregnancy and current-pregnancy use of alcohol, tobacco, and other drugs. Data were available for 212 subjects.The reported prevalence of pre-pregnancy alcohol abuse in this sample was 25%. Women in this cohort reported a significant decrease in tobacco and alcohol use following pregnancy awareness. However, pre-pregnancy alcohol intake levels and years of alcohol use were associated with alcohol intake during pregnancy. Other markers of maternal alcohol intake during pregnancy included tobacco use patterns and history of drug use. Family history of alcohol problems and drug use were associated with maternal substance use history and use by the father of the baby. Levels of maternal alcohol use during the current pregnancy were negatively associated with an alcohol problem in the father of the baby.Alcohol and other substance use were relatively common in our sample of rural Caucasian women in Maine. Several risk factors can be identified, and awareness of these risk factors may assist physicians in the diagnosis of substance abuse among pregnant women.

Study objective Temperament was explored as a factor in both night-waking and bedsharing in preschool-aged children. Design Bedsharers and solitary sleepers were categorized based on the frequency of current bedsharing. MANOVA was used to examine associations among temperament and sleep measures. Setting Two preschools affiliated with a rural university in the Northeast United States. Participants. 67 children between 2.4-5.6 years of age from two University-affiliated preschools were studied. Intervention Child temperament was rated by parents and teachers using the Carey Temperament Scale and compared to night-waking, current sleep habits, and the circumstances in which bedsharing occurred Measurements and results Parents and preschool teachers completed the Carey Temperament Scale for 3-7 year olds. Parents also scored the Sleep Habits Inventory and the Sleeping Arrangements Inventory, which provided a current and retrospective history of the child's sleep location and sleep patterns. Parents' ratings showed that bedsharers have less regular bedtimes; difficulty with sleep onset; more night-waking; and seek out the parents following awakening during the night. Temperamentally, bedsharers were found to be more intense and exhibit less adaptability and rhythmicity. However, teachers' temperament ratings did not predict bedsharing and were not concordant with parental ratings. Conclusions These findings suggest that bedsharing at preschool age is a complex phenomenon related to parents' ratings of child temperament, sleep habits, and disturbances such as night waking. Implications for the clinical assessment of sleep disorders are discussed.

In vulnerable individuals, postpartum depression may be triggered by the disruption of neuropsychological processes during pregnancy and parturition. It is proposed that in Western societies pre- and postnatal psychological and instrumental needs are poorly met and this crisis may interact with neurophysiological factors in compromising maternal psychological functioning. The influence of developmental factors and psychological and physical stressors are discussed in relation to women's neuropsychological health during the peripartal transition. It is hypothesized that the environmental milieu may support, neglect or derail the mother's psychobiological transition from pregnancy to effective postnatal parenting and resumption of family and work roles.

IN THIS ISSUE OF JAMA, PATRICK ET AL 1 DESCRIBE THE EFfects on newborn infants of the widespread availability of prescription opiate medications. These medications provide superior pain control for cancer and chronic pain, but have been overprescribed, diverted, and sold illegally, creating a new opiate addiction pathway and a public health burden for maternal and child health. Overdose mortality and dependence rates are highest among disadvantaged, young adults in rural areas (eg, Maine and Kentucky). Young women are nearly as likely as men to abuse opiate medications, leading to an increase in opiate-dependent newborns treated for withdrawal syndrome or neonatal abstinence syndrome (NAS). The standard of care for opiate addiction during pregnancy is methadone maintenance and psychiatric care. Patrick et al demonstrate that the increase in NAS (from an incidence of 1.20 [95% CI, 1.04-1.37] per 1000 hospital births per year in 2000 to 3.39 [95% CI, 3.12-3.67] per 1000 hospital births per year in 2009) has created a health care encumbrance primarily for state Medicaid budgets. In affected states, methadone treatment programs have expanded rapidly and voluntary prescription monitoring programs identify opiate medication use patterns (ie, opiate prescriptions are tracked and individuals who are “shopping” for physicians to prescribe opiates can be identified). However, the burden of addiction on state Medicaid budgets threatens retrenchment of recently established programs despite increased need. This poses a crisis of care for affected fetuses and newborns. However, without accessible treatment of both maternal opiate addiction and new methods of treating NAS, state and federal systems may pay in the future because many of these infants require special services for developmental and behavioral disorders. Patrick et al also observed that over the last decade, there has been no improvement in NAS treatment efficiency as measured by length of stay (LOS). Furthermore, health care expenditures for NAS have increased during the same period. Even within the context of the status quo of medically managed prenatal methadone treatment, opiate-exposed infants risk adverse effects besides the specter of protracted withdrawal. In their analyses of hospital complications of infants with NAS, Patrick et al confirmed other data demonstrating increased rates of prematurity, respiratory disease, and seizures. Opiate withdrawal is often compounded by comorbid polydrug exposure and maternal psychiatric medications, such as antidepressants and benzodiazepines, which have their own withdrawal syndromes. Although the withdrawal from these agents is milder than opiates, such combinatorial withdrawal complicates neonatal care and often extends LOS. Neonatal abstinence syndrome withdrawal severity affects adaptation to postnatal life in critical regulatory areas of sleep, feeding, and autonomic function. Although 60% to 80% of infants exposed in utero to opiates develop NAS and require prolonged hospitalization, averaging 16 days in the study by Patrick et al, there is still considerable uncertainty regarding optimal detoxification protocols and criteria for opiate withdrawal status typically based on symptoms assessed by the Finnegan score calculated every few hours from birth to day 5. Hospitals and clinicians burdened by the increase in NAS incidence can expend substantial efforts to develop treatment protocols to decrease LOS. As outlined by Patrick et al, most clinicians use oral opiate medication (eg, methadone or morphine) and, in difficult cases, a second-line nonopiate drug with -aminobutyric acid (eg, phenobarbital), benzodiazepine (eg, clonazapam), or anti-adrenergic (eg, clonidine) action. Novel pharmacotherapy research is needed to improve maternal opiate maintenance strategies to protect the fetus from in utero withdrawal, and to reduce the incidence and severity of NAS. These efforts have been frustrated by lack of controlled clinical trials. Methadone maintenance therapy during pregnancy is currently idiosyncratic (eg, lack of standardization in maternal care related todosing)andbasedonmaternalwithdrawal symptoms as gestation progresses. Research aimed at predicting which newborns are most at risk for a difficult withdrawal, or will require prompt treatment, has yielded few leads. In the adult pain management literature, individual genetic differences have been found to predict opiate response and dose