A Systematic Review of Interventions to Improve Mental Health and Substance Use Outcomes for Individuals with Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorder.

Individuals with fetal alcohol spectrum disorder (FASD) experience remarkably high rates of mental health and substance use challenges, beginning early in life and extending throughout adulthood. Proactive intervention can help to mitigate some of these negative experiences. Although the literature on FASD intervention is growing, there is currently a lack of consolidated evidence on interventions that may improve mental health and substance use outcomes in this population. Informed by a life course perspective, we undertook a systematic review of the literature to identify interventions that improve mental wellness through all developmental stages for people with prenatal alcohol exposure (PAE) and FASD. A total of 33 articles were identified, most of which were focused on building skills or strategies that underlie the well-being of children with PAE and FASD and their families. Other interventions were geared toward supporting child and family wellness and responding to risk or reducing harm. There was a notable lack of interventions that directly targeted mental health and substance use challenges, and a major gap was also noted in terms of interventions for adolescents and adults. Combined, these studies provide preliminary and emerging evidence for a range of intervention approaches that may support positive outcomes for individuals with FASD across the life course.

Prenatal Ethanol Exposure and Postnatal Environmental Intervention Alter Dopaminergic Neuron and Microglia Morphology in the Ventral Tegmental Area During Adulthood.

BACKGROUND: Prenatal ethanol exposure (PE) impairs midbrain dopaminergic (DA) neuron function, which might contribute to various cognitive and behavioral deficits, including attention deficits and increased addiction risk, often observed in individuals with fetal alcohol spectrum disorders. Currently, the underlying mechanisms for PE-induced deficits are unclear. PE could lead to neuroinflammation by activating microglia, which play an important role in synaptic function. In the present study, we investigated PE effects on microglial activation and DA neuron density and morphology in the ventral tegmental area (VTA). Since postnatal environmental enrichment can reduce neuroinflammation and ameliorate several PE-induced behavioral deficits, we examined if a postnatal environmental intervention strategy using neonatal handling and postweaning complex housing could reverse PE effects on VTA DA neurons and microglia. METHODS: Pregnant rats received 0 or 6 g/kg/d ethanol by 2 intragastric intubations on gestation days 8 to 20. After birth, rats were reared in the standard laboratory or enriched condition. Male adult rats (8 to 12 weeks old) were used for immunocytochemistry. RESULTS: The results showed that PE decreased VTA DA neuron body size in standardly housed rats. Moreover, there was a significant decrease in numbers of VTA microglial branches and junctions in PE rats, suggesting morphological activation of microglia and possible neuroinflammation. The PE effects on microglia were normalized by postnatal environmental intervention, which also decreased the numbers of microglial branches and junctions in control animals, possibly via reduced stress. CONCLUSIONS: Our findings show an association between PE-induced morphological activation of microglia and impaired DA neuron morphology in the VTA. Importantly, postnatal environmental intervention rescues possible PE-induced microglial activation. These data support that environmental intervention can be effective in ameliorating cognitive and behavioral deficits associated with VTA DA neuron dysfunctions, such as attention deficits and increased addiction risk.

Red cell alloimmunization: A 2020 update.

Management of maternal red cell alloimmunization has been revolutionized over the last 60 years. Advances in the prevention, screening, diagnosis, and treatment of alloimmune-induced fetal anemia make this condition an exemplar for contemporary practice in fetal therapy. Since survival is now an expectation, attention has turned to optimization of long-term outcomes following an alloimmunized pregnancy. In this review, the current management of red cell alloimmunization is described. Current research and future directions are discussed with particular emphasis on later life outcomes after alloimmune fetal anemia.

Neonatal Hypocalcemia in the Infant of a Diabetic Mother.

Neonatal hypocalcemia (NHC) is one of the most common disorders of calcium metabolism in infants admitted to the NICU. Presentation can range from asymptomatic to generalized seizures or tetany. In this case study, an infant with NHC is presented along with an overview of the pathophysiology, prevalence, diagnosis, and management of NHC for neonatal clinicians.

State Strategies to Address Opioid Use Disorder Among Pregnant and Postpartum Women and Infants Prenatally Exposed to Substances, Including Infants with Neonatal Abstinence Syndrome.

Since 1999, the rate of opioid use disorder (OUD) has more than quadrupled, from 1.5 per 1,000 delivery hospitalizations to 6.5 (1), with similar increases in incidence of neonatal abstinence syndrome (NAS) observed for infants (from 2.8 per 1,000 live births to 14.4) among Medicaid-insured deliveries (2). CDC's response to the opioid crisis involves strategies to prevent opioid overdoses and related harms by building state capacity and supporting providers, health systems, and payers.* Recognizing systems gaps in provision of perinatal care and services, CDC partnered with the Association of State and Territorial Health Officials (ASTHO) to launch the Opioid Use Disorder, Maternal Outcomes, and Neonatal Abstinence Syndrome Initiative Learning Community (OMNI LC). OMNI LC supports systems change and capacity building in 12 states.† Qualitative data from participating states were analyzed to identify strategies, barriers, and facilitators for capacity building in state-defined focus areas. Most states focused on strategies to expand access to and coordination of quality services (10 of 12) or increase provider awareness and training (nine of 12). Fewer states focused on data, monitoring, and evaluation (four of 12); financing and coverage (three of 12); or ethical, legal, and social considerations (two of 12). By building capacity to strengthen health systems, state-identified strategies across all focus areas might improve the health trajectory of mothers, infants, and families affected by the U.S. opioid crisis.

The Women and Children's Infectious Diseases Center: An integrated approach to congenital infectious diseases.

Congenital infectious diseases, transmitted during the course of pregnancy, are estimated to affect nearly one in every hundred births worldwide. These infections may be associated with fetal and infant adverse health outcomes, due to congenital malformations caused by in utero transmission of the infectious organism itself (as is the case with cytomegalovirus, toxoplasmosis, syphilis and Zika virus), or due to chronic infection in the infant (as is the case with human immunodeficiency virus [HIV] and hepatitis B and C). In addition, children who are exposed, yet uninfected, may still suffer from the consequences of exposure to infectious pathogens or to the drugs given to treat pregnant women and prevent in utero transmission (as may be the case with HIV infection).

[Upcoming challenges in providing care for thalidomide impaired individuals]. / Behindertenspezifische Herausforderungen bei der pflegerischen Versorgung von contergangeschädigten Menschen ­ eine Bedarfsanalyse.

Upcoming challenges in providing care for thalidomide impaired individuals Abstract. Background: Between 1957 and 1962 an approximate 5000 children were born in Germany with severe birth defects as their mothers took the substance Thalidomide during pregnancy as a sedative and effective relief from morning sickness. Objective: The aim of this study was to describe the care and assistance needed by the individuals impaired by Thalidomide and indicate upcoming challenges. A further aim was to determine the association between the impairment type and the care needed. Methods: Cross sectional study, 202 individuals impaired by Thalidomide were examined by two orthopedists as well as surveyed via questionnaire. They were also evaluated mentally by either a psychiatrist or psychotherapist. The need for care was determined by the acquired legal status for long-term care. Results: The sample divides roughly into two groups: the ones with impairments in their extremities and those who are not affected in their extremities. Many of the ones affected in their extremities are already dependent on assistance and need to be nursed. Those who are depending on assistance and care are mostly informally cared for. Conclusions: The prevalence for long-term care is already higher than in the age-adjusted general population in Germany, while formal care is underutilized. Therefore a challenge will be to make a shift from informal care to professional care providers as the informally caring (sometimes actually the parents of the impaired) are aging along with the ones they care for.

An experimental test of the fetal programming hypothesis: Can we reduce child ontogenetic vulnerability to psychopathology by decreasing maternal depression?

Maternal depression is one of the most common prenatal complications, and prenatal maternal depression predicts many child psychopathologies. Here, we apply the fetal programming hypothesis as an organizational framework to address the possibility that fetal exposure to maternal depressive symptoms during pregnancy affects fetal development of vulnerabilities and risk mechanisms, which enhance risk for subsequent psychopathology. We consider four candidate pathways through which maternal prenatal depression may affect the propensity of offspring to develop later psychopathology across the life span: brain development, physiological stress regulation (hypothalamic-pituitary-adrenocortical axis), negative emotionality, and cognitive (effortful) control. The majority of past research has been correlational, so potential causal conclusions have been limited. We describe an ongoing experimental test of the fetal programming influence of prenatal maternal depressive symptoms using a randomized controlled trial design. In this randomized controlled trial, interpersonal psychotherapy is compared to enhanced usual care among distressed pregnant women to evaluate whether reducing prenatal maternal depressive symptoms has a salutary impact on child ontogenetic vulnerabilities and thereby reduces offspring's risk for emergence of later psychopathology.

Prenatal programming of postnatal plasticity revisited-And extended.

Two sets of evidence reviewed herein, one indicating that prenatal stress is associated with elevated behavioral and physiological dysregulation and the other that such phenotypic functioning is itself associated with heightened susceptibility to positive and negative environmental influences postnatally, raises the intriguing hypothesis first advanced by Pluess and Belsky (2011) that prenatal stress fosters, promotes, or "programs" postnatal developmental plasticity. Here we review further evidence consistent with this proposition, including new experimental research systematically manipulating both prenatal stress and postnatal rearing. Collectively this work would seem to explain why prenatal stress has so consistently been linked to problematic development: stresses encountered prenatally are likely to continue postnatally, thereby adversely affecting the development of children programmed (by prenatal stress) to be especially susceptible to environmental effects. Less investigated are the potential benefits prenatal stress may promote, due to increased plasticity, when the postnatal environment proves to be favorable. Future directions of research pertaining to potential mechanisms instantiating postnatal plasticity and moderators of such prenatal-programming effects are outlined.

Alcohol Intervention for Adolescents with Fetal Alcohol Spectrum Disorders: Project Step Up, a Treatment Development Study.

BACKGROUND: Project Step Up proposed to reduce alcohol consumption and alcohol-related negative outcomes in adolescents with fetal alcohol spectrum disorders (FASD). METHODS: The 54 participants (30 females, 24 males) were assigned to either Project Step Up Intervention (SUI) or Control conditions and were assessed prior to intervention, immediately following intervention, and at 3-month follow-up. Adolescents in the SUI condition participated in a 6-week, 60-minute group intervention that provided alcohol education and promoted adaptive responses to alcohol-related social pressures. Caregivers attended concurrent but separate sessions on the effects of prenatal alcohol exposure on the brain and how to handle parenting challenges associated with alcohol use in teens with FASD. RESULTS: Thirty-three percent (n = 18) of adolescents were classified as light/moderate drinkers, and 67% (n = 36) were abstinent/infrequent drinkers based on their lifetime drinking histories. Results revealed a significant decrease in self-reported alcohol risk and in alcohol-related negative behaviors (Cohen's d = 1.08 and 0.99) in light/moderate drinkers in the SUI compared to the Control group. These results were partially sustained at 3-month follow-up. Furthermore, adolescents in the abstinent/infrequent group exhibited no increase in alcohol-related outcomes suggesting that the group intervention used in this study was not iatrogenic. CONCLUSIONS: The success of this treatment development study provides preliminary support for effective treatment of adolescents with FASD to prevent or reduce alcohol use and its negative consequences in this high risk population.

Prenatal Maternal Occupational Exposure and Postnatal Child Exposure to Elemental Mercury.

OBJECTIVES: Young children are highly vulnerable to elemental mercury toxicity, and elementary mercury exposure in young children in China unfortunately occurs regularly because of the wide use of fluorescent lamps, glass thermometers, and other mercury-contained items. This study aimed to summarize such recent cases in a referral clinic and to make recommendations for postexposure treatment and prevention of future exposure. METHODS: Patients were evaluated between January 2007 and December 2009 in environmental health facilities throughout China and were referred to our clinic. A total of 6 children younger than 4 years with significant elemental mercury exposure were included in this case series analysis. The total mercury content in blood and hair (fetal hair if necessary) and average 24-hour urine mercury concentrations were analyzed. Meso-2,3-dimercaptosuccinic acid or surgery was prescribed for the patient if necessary. RESULTS: Young children were found to be exposed in 3 ways as follows: prenatal exposure through maternal occupational contact in compact fluorescent-lamp factories (2 cases), broken thermometers (3 cases), and other causes of accidental inhalation of mercury vapor during the embryonic and lactation periods (1 case). For 3 cases caused by broken thermometers, x-ray images helped to identify the position of mercury residues. Local excision was used to remove mercury from the floor of the mouth in 1 case. One child was prescribed oral meso-2,3-dimercaptosuccinic acid, and a good response was received. CONCLUSIONS: Substitution of mercury-in-glass thermometers and vigilance to prevent women of childbearing age from occupational mercury exposure were suggested. Treatment selection should vary according to patient situations.

ß-Endorphin neuronal transplantation into the hypothalamus alters anxiety-like behaviors in prenatal alcohol-exposed rats and alcohol-non-preferring and alcohol-preferring rats.

BACKGROUND: Alcohol exposure has adverse effects on stress physiology and behavioral reactivity. This is suggested to be due, in part, to the effect of alcohol on ß-endorphin (ß-EP)-producing neurons in the hypothalamus. In response to stress, ß-EP normally provides negative feedback to the hypothalamic-pituitary-adrenal axis and interacts with other neurotransmitter systems in the amygdala to regulate behavior. We examined whether ß-EP neuronal function in the hypothalamus reduces the corticosterone response to acute stress, attenuates anxiety-like behaviors, and modulates alcohol drinking in rats. METHODS: To determine whether ß-EP neuronal transplants modulate the stress response, anxiety behavior, and alcohol drinking, we implanted differentiated ß-EP neurons into the paraventricular nucleus (PVN) of the hypothalamus of normal, prenatal alcohol-exposed, and alcohol-preferring (P) and alcohol-non-preferring (NP) rats. We then assessed corticosterone levels in response to acute restraint stress and other markers of stress response in the brain and anxiety-like behaviors in the elevated plus maze and open-field assays. RESULTS: We showed that ß-EP neuronal transplants into the PVN reduced the peripheral corticosterone response to acute stress and attenuated anxiety-like behaviors. Similar transplants completely reduced the hypercorticosterone response and elevated anxiety behaviors in prenatal alcohol-exposed adult rats. Moreover, we showed that ß-EP reduced anxiety behavior in P rats with minimal effects on alcohol drinking during and following restraint stress. CONCLUSIONS: These data further establish a role of ß-EP neurons in the hypothalamus for regulating physiological stress response and anxiety behavior and resemble a potential novel therapy for treating stress-related psychiatric disorders in prenatal alcohol-exposed children and those genetically predisposed to increased alcohol consumption.

Enhancing hepatic fatty acid oxidation as a strategy for reversing metabolic disorders programmed by maternal undernutrition during gestation.

BACKGROUND/AIMS: Moderate maternal calorie-restriction during gestation programmes offspring for a major propensity to develop metabolic alterations in adulthood. We aimed to assess whether increased hepatic fatty-acid oxidation (FAO), at early ages, by gene transfer of Cpt1am (active mutant of carnitine palmitoyltransferase-1a), may be a strategy for reversing metabolic disturbances associated to maternal calorie-restriction during gestation in rats. METHODS: AAV-Gfp (control) and AAV-Cpt1am vectors were administered by tail vein injection in 18-day-old control-pups and the offspring of 20% calorie-restricted rats during gestation (CR). After weaning, animals were fed with normal-fat diet. At the age of 4 months, they were moved to HF-diet and sacrificed at the age of 6 months to collect tissues. Locomotive activity, energy expenditure and blood pressure were measured. RESULTS: Under HF-diet, CR-animals showed higher HOMA-IR, adipocyte diameter and hepatic triglyceride accumulation than controls; these alterations were reverted in Cpt1am-injected animals. In liver, this treatment ameliorated inflammatory state, decreased expression of lipogenesis-related genes and partially restored the decreased expression of leptin-receptor occurring in CR-animals. Treatment also reverted the decreased energy expenditure and the increased blood pressure of CR-animals. CONCLUSION: Increasing hepatic FAO through AAV-Cpt1am injection at juvenile ages prevents some metabolic disorders associated to gestational maternal calorie-restriction.

Practitioner review: maternal mood in pregnancy and child development--implications for child psychology and psychiatry.

BACKGROUND: The empirical base suggesting a link between prenatal maternal anxiety, stress or depression and cognitive, behavioral, and biological outcomes in the infant and child has increased dramatically in the past 10 years. METHODS: In this review, we consider the relevance of prenatal maternal mood for child mental health practitioners; the empirical base for a likely causal impact of the link between prenatal anxiety, depression, or stress and child outcomes; the degree to which the available evidence is sufficient for informing or altering clinical practice; and the possible role of prenatal interventions for promoting child health and development. A selective review of PubMed, Cochrane Library and other sources was undertaken. FINDINGS: Clinically significant links between maternal prenatal distress and child behavioral and cognitive outcomes have been reported; predictions to stress physiology, immunology, and neurodevelopment have been reported but the effect sizes and clinical significance is less clear. Several candidate mechanisms have been proposed, with some supporting evidence. Many behavioral treatments for prenatal maternal distress exist, but their application to promoting child health is largely unknown. CONCLUSIONS: Research on maternal prenatal distress is a good example of translational research and offers a strong paradigm for promoting interdisciplinary clinical research on child health and development.

Reversing valproic acid-induced autism-like behaviors through a combination of low-frequency repeated transcranial magnetic stimulation and superparamagnetic iron oxide nanoparticles.

Transcranial magnetic stimulation (TMS) is a neurostimulation device used to modulate brain cortex activity. Our objective was to enhance the therapeutic effectiveness of low-frequency repeated TMS (LF-rTMS) in a rat model of autism spectrum disorder (ASD) induced by prenatal valproic acid (VPA) exposure through the injection of superparamagnetic iron oxide nanoparticles (SPIONs). For the induction of ASD, we administered prenatal VPA (600 mg/kg, I.P.) on the 12.5th day of pregnancy. At postnatal day 30, SPIONs were injected directly into the lateral ventricle of the brain. Subsequently, LF-rTMS treatment was applied for 14 consecutive days. Following the treatment period, behavioral analyses were conducted. At postnatal day 60, brain tissue was extracted, and both biochemical and histological analyses were performed. Our data revealed that prenatal VPA exposure led to behavioral alterations, including changes in social interactions, increased anxiety, and repetitive behavior, along with dysfunction in stress coping strategies. Additionally, we observed reduced levels of SYN, MAP2, and BDNF. These changes were accompanied by a decrease in dendritic spine density in the hippocampal CA1 area. However, LF-rTMS treatment combined with SPIONs successfully reversed these dysfunctions at the behavioral, biochemical, and histological levels, introducing a successful approach for the treatment of ASD.

Mild exercise plus levothyroxine ameliorate deficits of spatial navigation, anxiety profile, and hippocampal BDNF in hypothyroid male offspring rats.

PURPOSE: Levothyroxine (LEV) monotherapy cannot completely improve cognitive and behavioral impairments induced by hypothyroidism, whereas a combination therapy of exercise and LEV may ameliorate these deficits. This study aimed to determine the effects of mild-intensity forced exercise and LEV treatment on the anxiety profile and cognitive functions in male offspring of hypothyroid dams. METHOD: Twenty-four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6-propyl-2-thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty-four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 µg/kg, i.p.) with or without forced mild-intensity exercise. After 14 days of interventions, anxiety-like behaviors, spatial learning and memory, and hippocampal brain-derived neurotrophic factor (BDNF) levels were evaluated. FINDING: A pre and postnatal PTU-induced model of hypothyroidism increased anxiety-like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety-like behaviors. Exercise plus LEV more effectively improved anxiety-like behaviors and spatial learning than exercise or LEV alone. CONCLUSION: Practically, these pre-clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism.

Translation of an evidence-based social skills intervention for children with prenatal alcohol exposure in a community mental health setting.

BACKGROUND: Children with prenatal alcohol exposure (PAE) have significant social skills deficits and are often treated in community mental health settings. However, it remains unclear whether these children can be effectively treated using manualized, evidence-based interventions that have been designed for more general mental health populations. METHODS: To shed light on this issue, the effectiveness of Children's Friendship Training (CFT) versus Standard of Care (SOC) was assessed for 85 children ages 6 to 12 years with and without PAE in a community mental health center. RESULTS: Children participating in CFT showed significantly improved knowledge of appropriate social skills, improved self-concept, and improvements in parent-reported social skills compared to children in the SOC condition. Moreover, results revealed that within the CFT condition, children with PAE performed as well as children without PAE. Findings indicated that CFT, an evidence-based social skills intervention, yielded greater gains than a community SOC social skills intervention and was equally effective for children with PAE as for those without PAE. CONCLUSIONS: Results suggest that children with PAE can benefit from treatments initiated in community settings in which therapists are trained to understand their unique developmental needs, and that they can be successfully integrated into treatment protocols that include children without PAE.

A review of social skills deficits in individuals with fetal alcohol spectrum disorders and prenatal alcohol exposure: profiles, mechanisms, and interventions.

BACKGROUND: Individuals gestationally exposed to alcohol experience a multitude of sociobehavioral impairments, including deficits in adaptive behaviors such as social skills. METHODS: The goal of this report is to critically review research on social skills deficits in individuals with prenatal alcohol exposure, including individuals with and without fetal alcohol spectrum disorders (FASD). RESULTS: Social deficits are found in alcohol-exposed children, adults, and adolescents with and without a clinical presentation. These deficits tend to persist across the lifespan and may even worsen with age. Social deficits in this population appear to be independent of facial dysmorphology and IQ and are worse than can be predicted based on atypical behaviors alone. Abnormalities in neurobiology, executive function, sensory processing, and communication likely interact with contextual influences to produce the range of social deficits observed in FASD. CONCLUSIONS: Future investigations should strive to reconcile the relationship between social skills deficits in FASD and variables such as gender, age, cognitive profile, and structural and functional brain impairments to enable better characterization of the deficits observed in this population, which will enhance diagnosis and improve remediation.