Medicine and Health Sciences Commons^™

Dna Methylation Patterns In Umbilical Cord Blood From Infants Of Methadone Maintained Opioid Dependent Mothers, Oluwatobi Adegboyega, Suhita Gayen Nee' Betal, Pedro Urday, Rachel Huang, Katherine Bodycot, Huda Al-Kouatly, Kolawole Solarin, Joanna Chan, Sankar Addya, Rupsa Boelig, Zubair Aghai

Department of Pediatrics Faculty Papers

Methadone maintenance treatment for opioid dependent mothers is standard of care. Infants of methadone maintained opioid dependent (MMOD) mothers have better outcomes compared to infants of opioid dependent mothers without treatment. However, when compared to non-exposed infants, infants of MMOD mothers are associated with worse outcomes. We conducted a pilot study to examine genome wide differential DNA methylation using cord blood samples from sixteen term and near-term infants of MMOD and opioid naïve mothers, excluding Infants with chorioamnionitis. A total of 152 differentially methylated loci were identified at a difference >  + 2, < - 2 and p-value < 0.05. There were 90 hypermethylated loci (59 annotated genes) and 62 hypomethylated loci (38 annotated genes) observed. The hypermethylated and hypomethylated DNA changes involved multiple genes, pathways and networks that may explain some of the changes seen in infants of MMOD mothers. Top hypermethylated and hypomethylated genes involved areas of cell growth, neurodevelopment, vision and xenobiotic metabolism functions. Our data may explain the role of key pathways and genes relevant to neonatal outcomes seen from methadone exposure in pregnancy. Functional studies on the identified pathways and genes could lead to improved understanding of the mechanisms and identify areas for intervention.

Risk Factors For Postpartum Depression And Severe Distress Among Mothers Of Very Preterm Infants At Nicu Discharge., Julie A. Hofheimer, Elisabeth C. Mcgowan, Lynne M. Smith, Samantha Meltzer-Brody, Brian S. Carter, Lynne M. Dansereau, Steven Pastyrnak, Jennifer B. Helderman, Charles R. Neal, Sheri A. Dellagrotta, Thomas Michael D O'Shea, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE:  To identify psychological, medical, and socioenvironmental risk factors for maternal postpartum depression (PPD) and severe psychological distress (SPD) at intensive care nursery discharge among mothers of very preterm infants.

STUDY DESIGN:  We studied 562 self-identified mothers of 641 infants born(NOVI) conducted in nine university-affiliated intensive care nurseries. Enrollment interviews collected socioenvironmental data, depression, and anxiety diagnoses prior to and during the study pregnancy. Standardized medical record reviews ascertained prenatal substance use, maternal and neonatal medical complications. The Edinburgh Postnatal Depression Scale and Brief Symptom Inventory were administered at nursery discharge to screen for PPD and SPD symptoms, respectively.

RESULTS: …

Social Distancing And Extremely Preterm Births In The Initial Covid-19 Pandemic Period, Vivek V Shukla, Benjamin A Carper, Namasivayam Ambalavanan, Matthew A Rysavy, Edward F Bell, Abhik Das, Ravi M Patel, Carl T D'Angio, Kristi L Watterberg, C Michael Cotten, Stephanie L Merhar, Myra H Wyckoff, Pablo J Sánchez, Neha Kumbhat, Waldemar A Carlo, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network

Student and Faculty Publications

HYPOTHESIS: Increased social distancing was associated with a lower incidence of extremely preterm live births (EPLB) during the initial COVID-19 pandemic period.

STUDY DESIGN: Prospective study at the NICHD Neonatal Research Network sites comparing EPLB (22

RESULTS: EPLB and EPIS percentages did not significantly decrease (1.58-1.45%, p = 0.07, and 0.08-0.06%, p = 0.14, respectively). SDI was not significantly correlated with percent change of EPLB (CC = 0.29, 95% CI = -0.12, 0.71) or EPIS (CC = -0.23, 95% CI = -0.65, 0.18). Percent change in mean gestational age was positively correlated with SDI (CC = 0.49, 95% CI = …

Preeclampsia, Fetal Growth Restriction, And 24-Month Neurodevelopment In Very Preterm Infants., Jennifer Check, Coral Shuster, Julie Hofheimer, Marie Camerota, Lynne M. Dansereau, Lynne M. Smith, Brian S. Carter, Sheri A. Dellagrotta, Jennifer Helderman, Howard Kilbride, Cynthia M. Loncar, Elisabeth Mcgowan, Charles R. Neal, T Michael O'Shea, Steven L. Pastyrnak, Stephen J. Sheinkopf, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized.

OBJECTIVE: To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, infants in the prospective Neonatal Neurobehavior and Outcomes in Very Preterm Infants study were enrolled between April 2014 and June 2016 from 9 US university-affiliated neonatal intensive care …

Teen Pregnancy Involvement Among African, Caribbean And Black Adolescent Boys And Girls: A Scoping Review, Emmanuela Ojukwu, Eunice Bawafaa, Emily Mckay, Harsimran Grewal, Sara Afsah, Shivangi Singh, Elizabeth Saewyc

Student and Faculty Publications

OBJECTIVES: This study aims to investigate the incidence, associated factors and interventions to address teen pregnancy involvement (TPI) among African, Caribbean and Black (ACB) adolescents in North America.

DESIGN: We conducted a scoping review of the literature, guided by the social-ecological model.

DATA SOURCES: Studies were retrieved from databases such as Ovid Medline, Ovid Embase, CINAHL, CAB Direct and Google Scholar and imported into COVIDENCE for screening.

ELIGIBILITY CRITERIA: The Joanna Briggs Institute scoping reviews protocol guided the establishment of eligibility criteria. Included studies focused on rates, associated factors and interventions related to TPI among ACB boys and girls aged …

‘Joining The Dots: Linking Prenatal Drug Exposure To Childhood And Adolescence’ – Research Protocol Of A Population Cohort Study, Kate Lawler, Mithilesh Dronavalli, Andrew Page, Evelyn Lee, Hannah Uebel, Barbara Bajuk, Lucinda Burns, Michelle Dickson, Charles Green, Lauren Dicair, John Eastwood, Ju Lee Oei

Student and Faculty Publications

INTRODUCTION: Prenatal drug exposure (PDE) is one of the most important causes of child harm, but comprehensive information about the long-term outcomes of the families is difficult to ascertain. The

METHODS AND ANALYSIS: Information from routinely collected administrative databases was linked for all births registered in New South Wales (NSW), Australia between 1 July 2001 and 31 December 2020 (n=1 834 550). Outcomes for seven mutually exclusive groups of children with varying prenatal exposure to maternal substances of addiction, including smoking, alcohol, prescription/illicit drugs and neonatal abstinence syndrome will be assessed. Key exposure measures include maternal drug use type, maternal …

‘Joining The Dots: Linking Prenatal Drug Exposure To Childhood And Adolescence’ – Research Protocol Of A Population Cohort Study, Kate Lawler, Mithilesh Dronavalli, Andrew Page, Evelyn Lee, Hannah Uebel, Barbara Bajuk, Lucinda Burns, Michelle Dickson, Charles Green, Lauren Dicair, John Eastwood, Ju Lee Oei

Student and Faculty Publications

INTRODUCTION: Prenatal drug exposure (PDE) is one of the most important causes of child harm, but comprehensive information about the long-term outcomes of the families is difficult to ascertain. The

METHODS AND ANALYSIS: Information from routinely collected administrative databases was linked for all births registered in New South Wales (NSW), Australia between 1 July 2001 and 31 December 2020 (n=1 834 550). Outcomes for seven mutually exclusive groups of children with varying prenatal exposure to maternal substances of addiction, including smoking, alcohol, prescription/illicit drugs and neonatal abstinence syndrome will be assessed. Key exposure measures include maternal drug use type, maternal …

A Qualitative Study On Mother's Occupational Engagement After A Nicu Experience, Rachel Garcia, Mary Ann Smith, Julie Heftie Ms, Otr/L

Spring 2024 Virtual OTD Capstone Symposium

Mothers who are “at-risk” for complications during pregnancy have an increased probability for mental health conditions following delivery, adversely affecting their engagement in motherhood occupations. This qualitative study identifies how best to address the needs of “at-risk” pregnant women. Through the process of conducting semi-structured interviews with women who have experienced NICU with their babies, and interviews with healthcare practitioners working in the NICU, their narrative addresses what approaches would support women while they are going through their “at-risk” pregnancies to assist them with the transition to their occupational roles as mothers and promote bonding with their baby.

Delayed Onset Of Neonatal Compartment Syndrome Associated With Compound Fetal Presentation, Nicholas Manini, Hayato Unno

Department of Medicine Faculty Papers

Neonatal compartment syndrome, although rare, has a classic presentation with sentinel skin findings and development of swelling, erythema, and tenderness of the affected extremity. Neonatal compartment syndrome requires prompt surgical intervention to preserve the affected limb and ensure its normal growth and development. Our patient was born at term via vaginal delivery complicated by a compound presentation involving the left upper extremity. No physical exam abnormalities were noted at birth, but she developed signs of neonatal compartment syndrome by 15 h of life. She was surgically treated at 22 h of life and recovered well. At one year of age, …

Epigenome-Wide Association Study Identifies Neonatal Dna Methylation Associated With Two-Year Attention Problems In Children Born Very Preterm., Marie Camerota, Barry M. Lester, Francisco Xavier Castellanos, Brian S. Carter, Jennifer Check, Jennifer Helderman, Julie A. Hofheimer, Elisabeth C. Mcgowan, Charles R. Neal, Steven L. Pastyrnak, Lynne M. Smith, Thomas Michael O'Shea, Carmen J. Marsit, Todd M. Everson

Manuscripts, Articles, Book Chapters and Other Papers

Prior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age. DNA methylation was measured from buccal swabs collected at NICU discharge using the Illumina MethylationEPIC Bead Array. Attention problems were assessed at 2 years of adjusted age using the attention problems subscale of the Child Behavior Checklist (CBCL). After adjustment for multiple testing, DNA methylation at 33 CpG sites was associated with child attention problems. Differentially methylated CpG sites were located in genes previously linked to physical and mental health, including several genes associated with ADHD in prior epigenome-wide and genome-wide association studies. Several CpG sites were located in genes previously linked to exposure to prenatal risk factors in the NOVI sample. Neonatal epigenetics measured at NICU discharge could be useful in identifying preterm children at risk for long-term attention problems and related psychiatric disorders, who could benefit from early prevention and intervention efforts.

Neonatal Intensive Care Unit Resource Use For Infants At 22 Weeks' Gestation In The Us, 2008-2021, Matthew A Rysavy, Monica M Bennett, Kaashif A Ahmad, Ravi M Patel, Zubin S Shah, Dan L Ellsbury, Reese H Clark, Veeral N Tolia

Student and Faculty Publications

IMPORTANCE: During the past decade, clinical guidance about the provision of intensive care for infants born at 22 weeks' gestation has changed. The impact of these changes on neonatal intensive care unit (NICU) resource utilization is unknown.

OBJECTIVE: To characterize recent trends in NICU resource utilization for infants born at 22 weeks' gestation compared with other extremely preterm infants (≤28 weeks' gestation) and other NICU-admitted infants.

DESIGN, SETTING, AND PARTICIPANTS: This is a serial cross-sectional study of 137 continuously participating NICUs in 29 US states from January 1, 2008, through December 31, 2021. Participants included infants admitted to the NICU. …

Prenatal Cocaine Exposure And Its Influence On Pediatric Epigenetic Clocks And Epigenetic Scores In Humans, Thiago Wendt Viola, Christina Danzer, Victor Mardini, Claudia Szobot, João Henrique Chrusciel, Laura Stertz, Joy M Schmitz, Consuelo Walss-Bass, Gabriel R Fries, Rodrigo Grassi-Oliveira

Student and Faculty Publications

The investigation of the effects of prenatal cocaine exposure (PCE) on offspring has been inconsistent, with few studies investigating biological outcomes in humans. We profiled genome-wide DNA methylation (DNAm) of umbilical cord blood (UCB) from newborns with (n = 35) and without (n = 47) PCE. We used DNAm data to (1) assess pediatric epigenetic clocks at birth and (2) to estimate epigenetic scores (ES) for lifetime disorders. We generated gestational epigenetic age estimates (DNAmGA) based on Knight and Bohlin epigenetic clocks. We also investigated the association between DNAmGA and UCB serum brain-derived neurotrophic factor (BDNF) levels. Considering the large-scale …

Pregnancy-Related Factors Responsible For Delivering Low Birth Weight Babies: An Institutional-Based Cross-Sectional Study, Jamnagar, Gujarat, Harsh K Patel, Jitesh P Mehta, Bela A Patel, Rohitkumar Ram, Dipesh V Parmar

Faculty and Staff Publications

BACKGROUND: The WHO defines LBW as "Birth weight less than 2500 grams" regardless of gestational age. Being born with a low birth weight also incurs enormous economic costs, including higher medical expenditures and social service expenses, and decreased productivity in adulthood.

OBJECTIVE: To study distribution of newborns' according to pregnancy related factors and its association with newborns' birth weight.

METHODS: An institutional based cross-sectional study. New-borns delivered at study institute were considered as study participants. Estimated final sample size was 500. Guardians (mothers) were face-to-face interviewed and also recorded data were collected from the case file and Mother and Child …

Bioactive Metabolites Of Omega-6 And Omega-3 Fatty Acids Are Associated With Inflammatory Cytokine Concentrations In Maternal And Infant Plasma At The Time Of Delivery, Rebecca Slotkowski, Matthew Van Ormer, Anum Akbar, Taija Hahka, Maranda Thompson, Rebekah Rapoza, Arzu Ulu, Melissa Thoene, Elizabeth Lyden, Maheswari Mukherjee, Ana G. Yuil-Valdes, Sathish Kumar Natarajan, Tara Nordgren, Corrine K. Hanson, Ann Anderson-Berry

Journal Articles: Pediatrics

Background & aims

Inflammation is necessary for a healthy pregnancy. However, unregulated or excessive inflammation during pregnancy is associated with severe maternal and infant morbidities, such as pre-eclampsia, abnormal infant neurodevelopment, or preterm birth. Inflammation is regulated in part by the bioactive metabolites of omega-6 (n-6) and omega-3 (n-3) fatty acids (FAs). N-6 FAs have been shown to promote pro-inflammatory cytokine environments in adults, while n-3 FAs have been shown to contribute to the resolution of inflammation; however, how these metabolites affect maternal and infant inflammation is still uncertain. The objective of this study was to predict the influence of …