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Evidence for Long-Term Developmental Deficits in the High Risk Human...
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Evidence for Long-Term Developmental Deficits in the High Risk Human Neonate

A special issue of Children (ISSN 2227-9067). This special issue belongs to the section "Pediatric Neonatology".

Deadline for manuscript submissions: closed (15 June 2023) | Viewed by 4383

Special Issue Editor

Prof. Dr. Marie J. Hayes

E-Mail Website
Guest Editor
Department of Psychology and Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME, USA
Interests: maternal and infant health; prenatal opioid exposure; developmental deficits in the high risk human neonate

Special Issue Information

Dear Colleagues,

The United States’ opioid addiction epidemic has dramatically affected women of childbearing age and their offspring. The standard of care for pregnant women with opioid dependence is daily methadone replacement therapy, a long acting μ-opioid receptor agonist that crosses the placental barrier. In animal models, prenatal and postnatal opioid exposure is associated with long-term reproductive and behavioral effects. In human studies, fetal exposure in the third trimester causes a striking increase in neonatal abstinence syndrome (NAS), requiring hospitalization and pharmacological replacement therapy using methadone or morphine for weeks to months postnatally to resolve symptoms. NAS treatment strategies have improved in the last decade; however, little is known about longer-term developmental deficits due to prenatal and/or postnatal opioid exposure. One significant concern is the difficulty of separating opioid exposure from the teratogenic consequences of comorbid substances of abuse (e.g., tobacco, alcohol, marijuana) commonly present in addiction. Second, maternal psychological competence has been shown to be impaired with opioid dependence, lending to concern regarding infant attachment and social development. Finally, most opioid-exposed children are raised with economic adversity and social deprivation, which are known to negatively impact child development.

This Special Issue is soliciting contributions that shed light on this important interdisciplinary topic and welcomes submissions that reflect longitudinal and well-controlled studies on prenatal opioid exposure and enduring consequences for child development. 

Prof. Dr. Marie J. Hayes
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Children is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • prenatal opioid exposure
  • teratogens
  • developmental outcomes
  • environmental risk
  • behavior adaptation
  • executive function
  • alcohol and tobacco

Published Papers (3 papers)

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12 pages, 818 KiB  
Article
Neonatal Abstinence Syndrome in Infants with Prenatal Exposure to Methadone versus Buprenorphine
by Alla Kushnir, Ravi Bhavsar, Emad Hanna and Thomas Hegyi
Children 2023, 10(6), 1030; https://doi.org/10.3390/children10061030 - 08 Jun 2023
Cited by 3 | Viewed by 1875
Abstract
Neonatal abstinence syndrome (NAS) has been of increasing concern. Studies suggest that prenatal exposure to buprenorphine may be preferred to methadone in regard to neonatal withdrawal. Our aim was to determine whether the incidence and severity of NAS are different between babies prenatally [...] Read more.
Neonatal abstinence syndrome (NAS) has been of increasing concern. Studies suggest that prenatal exposure to buprenorphine may be preferred to methadone in regard to neonatal withdrawal. Our aim was to determine whether the incidence and severity of NAS are different between babies prenatally exposed to methadone or buprenorphine in pregnancy. This retrospective analysis of infants ≥ 35-weeks-old exposed to methadone/buprenorphine alone or in conjunction with other substances in utero. They were divided into four groups: 1—methadone alone (Met), 2—buprenorphine alone (Bup), 3 and 4—those exposed to methadone and buprenorphine, respectively, in conjunction with other drugs (Met+ and Bup+). The frequency of NAS treatment, duration of treatment (LOT) and length of stay (LOS) were compared between groups. Of the 290 mothers, 59% were in the Met group, 18% in the Bup group, 14% in the Met or Bup and another opiate group, and 9% took methadone or buprenorphine plus various other substances. Infants born to Met/Met+ mothers had a four-times higher likelihood of developing NAS (p < 0.001). There was no difference in the LOS (p = 0.08) or LOT (p = 0.11) between groups. The buprenorphine treatment in pregnancy decreased the risk of babies developing NAS. However, once the NAS required pharmacological treatment, the type of maternal prenatal exposure did not affect the LOS or LOT. Full article
(This article belongs to the Special Issue Evidence for Long-Term Developmental Deficits in the High Risk Human Neonate)
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11 pages, 1250 KiB  
Article
Reduced Hippocampal Volumes in Children with History of Hypoxic Ischemic Encephalopathy after Therapeutic Hypothermia
by Katie M. Pfister, Sally M. Stoyell, Zachary R. Miller, Ruskin H. Hunt, Elizabeth P. Zorn and Kathleen M. Thomas
Children 2023, 10(6), 1005; https://doi.org/10.3390/children10061005 - 02 Jun 2023
Cited by 1 | Viewed by 1049
Abstract
Hypoxic ischemic encephalopathy (HIE) remains a significant cause of disability despite treatment with therapeutic hypothermia (TH). Many survive with more subtle deficits that affect daily functioning and school performance. We have previously shown an early indication of hippocampal changes in infants with HIE [...] Read more.
Hypoxic ischemic encephalopathy (HIE) remains a significant cause of disability despite treatment with therapeutic hypothermia (TH). Many survive with more subtle deficits that affect daily functioning and school performance. We have previously shown an early indication of hippocampal changes in infants with HIE despite TH. The aim of this study was to evaluate the hippocampal volume via MRI and memory function at 5 years of age. A cohort of children followed from birth returned for a 5-year follow-up (n = 10 HIE treated with TH, n = 8 healthy controls). The children underwent brain MRI and neurodevelopmental testing to assess their brain volume, general development, and memory function. Children with HIE had smaller hippocampal volumes than the controls despite no differences in the total brain volume (p = 0.02). Children with HIE generally scored within the average range on developmental testing. Though there was no difference in the memory scores between these groups, there was a positive within-group correlation between the hippocampal volume and memory scores in children with HIE (sentence recall r = 0.66, p = 0.038). There was no relationship between newborn memory function and 5-year hippocampal size. Children with HIE treated with TH experienced significant and lasting changes to the hippocampus despite improvements in survival and severe disability. Future studies should target diminishing injury to the hippocampus to improve overall outcomes. Full article
(This article belongs to the Special Issue Evidence for Long-Term Developmental Deficits in the High Risk Human Neonate)
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14 pages, 865 KiB  
Systematic Review
School-Age Outcomes of Antenatal Magnesium Sulphate in Preterm Infants
by Akira Kobayashi, Masato Ito, Erika Ota and Fumihiko Namba
Children 2023, 10(8), 1324; https://doi.org/10.3390/children10081324 - 31 Jul 2023
Viewed by 1138
Abstract
Background: Antenatal magnesium sulphate (MgSO4) therapy given to women at risk of preterm birth reduced the risk of cerebral palsy in early childhood. However, its effect on longer-term neurological outcomes remains uncertain. This study aimed to assess the effects of antenatal [...] Read more.
Background: Antenatal magnesium sulphate (MgSO4) therapy given to women at risk of preterm birth reduced the risk of cerebral palsy in early childhood. However, its effect on longer-term neurological outcomes remains uncertain. This study aimed to assess the effects of antenatal MgSO4 therapy on school-age outcomes of preterm infants. Methods: We conducted a systematic review and meta-analysis. We searched MEDLINE, EMBASE, CENTRAL, and CINAHL for randomized controlled trials (RCTs). Two reviewers independently evaluated the eligibility for inclusion and extracted data. Results: Ten RCTs were included. Only two of them were on school-age outcomes. Antenatal MgSO4 therapy had no impact on cerebral palsy, hearing impairment, neurosensory disability, and death at school-age. Meta-analysis on mental retardation and visual impairment was not able to be performed due to different methods of evaluation. In the analysis of short-term outcomes conducted as secondary outcomes, antenatal MgSO4 therapy increased the risk of maternal adverse events with any symptom (3 RCTs; risk ratio 2.79; 95% confidence interval 1.10 to 7.05, low certainty of evidence) but was not associated with any neonatal symptoms. Conclusions: The number of cases was insufficient to determine the impact of antenatal MgSO4 therapy on school-age outcomes. Further accumulation of long-term data is required. Full article
(This article belongs to the Special Issue Evidence for Long-Term Developmental Deficits in the High Risk Human Neonate)
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