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Objective To pilot measurement of hair cortisol concentration (HCC) in pregnant women with opioid use disorder and their infants over time and study the potential utility of hair cortisol as a biomarker of chronic stress in this population. Study Design In this pilot prospective cohort study of mother–infant dyads with and without prenatal opioid exposure, we obtained mother–infant HCCs at delivery and again within 1 to 3 months' postpartum. HCCs were compared between the opioid and control groups and between the two time points. Results There were no significant differences between opioid and control group maternal or infant HCCs at either time point. However, within the opioid-exposed group, there was a significant increase in infant HCCs across the two time points. Conclusion This pilot study describes our experience with the measurement of HCCs in opioid-exposed mother–infant dyads. Key Points Maternal stress impacts fetal and child health. Many stressors in pregnant women with opioid use disorder. Hair cortisol may be a useful stress biomarker. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Neonatal abstinence syndrome (NAS) after in‐utero opioid exposure remains a poorly understood condition with multiple factors contributing to severity. Exposure to maternal stress may be one contributing factor. Hair cortisol measurement represents a novel technique for assessing prenatal stress. In this pilot study, the association between maternal hair cortisol levels and NAS severity was examined in 70 postpartum women with opioid use disorder within 72 hr of delivery. Infants were monitored for NAS and treated according to institutional protocol. Forty‐four (63%) of the infants were pharmacologically treated for NAS, with a mean length of hospital stay (LOS) for all infants of 14.2 (SD 9.0) days. The mean cortisol level in the mothers was 131.8 pg/mg (SD 124.7). In bivariate analysis, higher maternal hair cortisol levels were associated with shorter infant LOS (R = −.26, p =.03) and fewer infant opioid treatment days (R = −.28, p =.02). Results were no longer statistically significant in regression models after adjusting for maternal opioid and smoking. In conclusion, we demonstrated the feasibility of hair cortisol assaying within the first few days after delivery in mothers with opioid use disorder as a novel marker for NAS. The findings suggest that maternal stress may impact the severity of infant opioid withdrawal. [ABSTRACT FROM AUTHOR]

Problem: Medication for opioid use disorder (MOUD) is recommended for persons with opioid use disorder (OUD) during pregnancy. However, knowledge gaps exist about best practices for management of OUD during pregnancy and these data are needed to guide clinical care., Period Covered: 2014-2021., Description of the System: Established in 2019, the Maternal and Infant Network to Understand Outcomes Associated with Medication for Opioid Use Disorder During Pregnancy (MAT-LINK) is a surveillance network of seven clinical sites in the United States. Boston Medical Center, Kaiser Permanente Northwest, The Ohio State University, and the University of Utah were the initial clinical sites in 2019. In 2021, three clinical sites were added to the network (the University of New Mexico, the University of Rochester, and the University of South Florida). Persons receiving care at the seven clinical sites are diverse in terms of geography, urbanicity, race and ethnicity, insurance coverage, and type of MOUD received. The goal of MAT-LINK is to capture demographic and clinical information about persons with OUD during pregnancy to better understand the effect of MOUD on outcomes and, ultimately, provide information for clinical care and public health interventions for this population. MAT-LINK maintains strict confidentiality through robust information technology architecture. MAT-LINK surveillance methods, population characteristics, and evaluation findings are described in this inaugural surveillance report. This report is the first to describe the system, presenting detailed information on funding, structure, data elements, and methods as well as findings from a surveillance evaluation. The findings presented in this report are limited to selected demographic characteristics of pregnant persons overall and by MOUD treatment status. Clinical and outcome data are not included because data collection and cleaning have not been completed; initial analyses of clinical and outcome data will begin in 2023., Results: The MAT-LINK surveillance network gathered data on 5,541 reported pregnancies with a known pregnancy outcome during 2014-2021 among persons with OUD from seven clinical sites. The mean maternal age was 29.7 (SD = ±5.1) years. By race and ethnicity, 86.3% of pregnant persons were identified as White, 25.4% as Hispanic or Latino, and 5.8% as Black or African American. Among pregnant persons, 81.6% had public insurance, and 84.4% lived in urban areas. Compared with persons not receiving MOUD during pregnancy, those receiving MOUD during pregnancy were more likely to be older and White and to have public insurance. The evaluation of the surveillance system found that the initial four clinical sites were not representative of demographics of the South or Southwest regions of the United States and had low representation from certain racial and ethnic groups compared with the overall U.S. population; however, the addition of three clinical sites in 2021 made the surveillance network more representative. Automated extraction and processing improved the speed of data collection and analysis. The ability to add new clinical sites and variables demonstrated the flexibility of MAT-LINK., Interpretation: MAT-LINK is the first surveillance system to collect comprehensive, longitudinal data on pregnant person-infant dyads with perinatal outcomes associated with MOUD during pregnancy from multiple clinical sites. Analyses of clinical site data demonstrated different sociodemographic characteristics between the MOUD and non-MOUD treatment groups., Public Health Actions: MAT-LINK is a timely and flexible surveillance system with data on approximately 5,500 pregnancies. Ongoing data collection and analyses of these data will provide information to support clinical and public health guidance to improve health outcomes among pregnant persons with OUD and their children., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. The Maternal and Infant Network to Understand Outcomes Associated with Medication for Opioid Use Disorder During Pregnancy (MAT-LINK) is funded by the Assistant Secretary for Planning and Evaluation’s Office of the Secretary Patient-Centered Outcomes Research Trust Fund. All clinical site coauthors report funding for MAT-LINK. Katherine A. Sward reports funding from the National Institutes of Health for work with the Helping to End Addiction Long-Term (HEAL) Pain Management Effectiveness Research Network as a Data Coordinating Center. Vikrant G. Deshmukh reports a National Cancer Institute/University of Wisconsin subaward for investigating COVID-19 complications among smokers. Pilar M. Sanjuan reports funding as a principal investigator from the National Institute on Alcohol Abuse and Alcoholism for Project REACT (neural underpinnings of emotional regulation and drinking to cope); the National Institute on Drug Abuse for Project Vida (prenatal opioid use disorder and posttraumatic stress disorder); and the National Institute of Mental Health for Project Raptor (attention and post-traumatic stress disorder) and as a coinvestigator from the National Institute on Alcohol Abuse and Alcoholism on Project AsCENd (neuroimaging of child attention development); the National Institute on Drug Abuse Helping to End Addiction Long-Term initiative for Integrative Management of chronic Pain and OUD for Whole Recovery (pain and prenatal opioid use) and for the HEALthy Brain and Child Development study; and relationships with New Mexico Postpartum Support International as a board chair and the New Mexico Perinatal Collaborative as a board member. Jessie R. Maxwell reports funding from the National Institute on Drug Abuse for work as a coinvestigator on the HEALthy Brain and Childhood Development studies; the National Institutes of Health for work as a Helping to End Addiction Long-Term initiative alternate principal investigator; the National Institute on Alcohol Abuse and Alcoholism for work as a principal investigator on a project; the National Institute on Alcohol Abuse and Alcoholism for work as a coinvestigator on a local project; and the IDeA States Pediatric Clinical Trials Network for work as site principal investigator, work as a junior investigator, and meeting attendance as a member of the leadership committee. Neil S. Seligman reports funding from PreTel Inc. and Mae Stone Goode for work not related to this report; Natera for consulting fees; UpToDate for writing; and various legal reviews. Judette Louis reports funding from TD Bank for an institutional grant; Wolters Kluwer for an UpToDate piece on sleep apnea during pregnancy; Hologic for a one-time fee; Elsevier for serving as a textbook editor; Goldasich, Vick & Fulk for a fee; Sleep Disorder Research Advisory Board for being a member; the National Institutes of Health for work on a personalized integrated chronotherapy for perinatal depression; March of Dimes for travel expenses related to being a board member; Society for Maternal-Fetal Medicine for travel expenses related to being a board member; American Board of Obstetrics and Gynecology for travel expenses related to being a board member; and Preeclampsia Foundation for blood pressure cuffs for her institution. Tanner Wright reports funding from Duke University for a National Institutes of Health–funded project on Eating, Sleeping, Consoling for Neonatal Opioid Withdrawal Syndrome (ESC-NOW): a Function-Based Assessment and Management Approach; the National Institute on Drug Abuse for CADENCE (Continuous and Data-driven Care); the American Academy of Pediatrics for work as a subject matter expert on maternal–infant health and opioid use; and the National Advanced Practice and Low Risk Neonatal Nurses Conferences for presentations on neonatal opioid withdrawal syndrome. No other potential conflicts of interest were disclosed.

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Epigenetic variation of DNA methylation of the mu-opioid receptor gene ( OPRM1 ) has been identified in the blood and saliva of individuals with opioid use disorder (OUD) and infants with neonatal opioid withdrawal syndrome (NOWS). It is unknown whether epigenetic variation in OPRM1 exists within placental tissue in women with OUD and whether it is associated with NOWS outcomes. In this pilot study, the authors aimed to 1) examine the association between placental OPRM1 DNA methylation levels and NOWS outcomes, and 2) compare OPRM1 methylation levels in opioid-exposed versus non-exposed control placentas., Methods: Placental tissue was collected from eligible opioid ( n = 64) and control ( n = 29) women after delivery. Placental DNA was isolated and methylation levels at six cytosine-phosphate-guanine (CpG) sites within the OPRM1 promoter were quantified. Methylation levels were evaluated for associations with infant NOWS outcome measures: need for pharmacologic treatment, length of hospital stay (LOS), morphine treatment days, and treatment with two medications. Regression models were created and adjusted for clinical co-variates. Methylation levels between opioid and controls placentas were also compared., Results: The primary opioid exposures were methadone and buprenorphine. Forty-nine (76.6%) of the opioid-exposed infants required pharmacologic treatment, 10 (15.6%) two medications, and average LOS for all opioid-exposed infants was 16.5 (standard deviation 9.7) days. There were no significant associations between OPRM1 DNA methylation levels in the six CpG sites and any NOWS outcome measures. No significant differences were found in methylation levels between the opioid and control samples., Conclusions: No significant associations were found between OPRM1 placental DNA methylation levels and NOWS severity in this pilot cohort. In addition, no significant differences were seen in OPRM1 methylation in opioid versus control placentas. Future association studies examining methylation levels on a genome-wide level are warranted., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest.