Supplementary Figure 1, Tables 1-4 from JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia

OBJECTIVES:Haiti remains a principal placement country for intercountry adoptees to the United States. This project reports the health status of children adopted from Haiti arriving to the U.S. and compares them to intercountry adoptees from other regions.METHODS:A retrospective chart review was conducted of adoptees placed in the U.S. from Haiti (n=87), age and sex matched with intercountry adoptees placed in the U.S. from Asia (n=87) and Latin America (n=87) between January 2010 and November 2019. Data on immunization status, contagious diseases, and nutrition and growth were analyzed via linear, logistic, and multinomial regression.RESULTS:After adjusting for age, sex, and standardized height, children adopted from Haiti, compared to adoptees from Latin America and Asia, demonstrated a lack of immunity to hepatitis B (OR=5.89;6.87), increased immunity to hepatitis A (OR=0.38;0.30), infection by two or more parasites (OR=8.43;38.48), high lead levels (OR=23.79;7.04), and anemia (OR=15.25;9.18). Unexpectedly, children adopted from Haiti had greater standardized height (-1.28 vs. -1.82 and -2.13) and standardized weight (-0.32 vs. -0.57 and -1.57) than their counterparts from Latin America and Asia.CONCLUSIONS:Children adopted from Haiti face complex medical challenges undoubtedly related to the country's low socioeconomic status (SES) and the impact of recurrent natural disasters and governmental neglect on public health infrastructure. Appropriate care is critical in preventing and avoiding transmission of infectious diseases in adoptees and family members. The high incidence of anemia and elevated lead levels may further exacerbate the developmental effects of early institutional deprivation.

Worldwide, millions of children live in institutions, which runs counter to both the UN-recognised right of children to be raised in a family environment, and the findings of our accompanying systematic review of the physical, neurobiological, psychological, and mental health costs of institutionalisation and the benefits of deinstitutionalisation of child welfare systems. In this part of the Commission, international experts in reforming care for children identified evidence-based policy recommendations to promote family-based alternatives to institutionalisation. Family-based care refers to caregiving by extended family or foster, kafalah (the practice of guardianship of orphaned children in Islam), or adoptive family, preferably in close physical proximity to the biological family to facilitate the continued contact of children with import-ant individuals in their life when this is in their best interest. 14 key recommendations are addressed to multinational agencies, national governments, local authorities, and institutions. These recommendations prioritise the role of families in the lives of children to prevent child separation and to strengthen families, to protect children without parental care by providing high-quality family-based alternatives, and to strengthen systems for the protection and care of separated children. Momentum for a shift from institutional to family-based care is growing internationally-our recommendations provide a template for further action and criteria against which progress can be assessed.

Millions of children worldwide are brought up in institutional care settings rather than in families. These institutions vary greatly both in terms of their organisational principles and structure, and in terms of the quality of care provided. Although institutions are universally recognised as providing suboptimal caregiving environments, consensus is still needed on how to interpret the evidence relating to the size, range, and persistence of the effect of institutional care on the development and wellbeing of children. This absence of consensus has led to disagreement as to whether policy should focus on eliminating, transforming, or improving institutions. Institutionalisation and deinstitutionalisation of children 2: policy and practice recommendations for global, national, and local actorsWorldwide, millions of children live in institutions, which runs counter to both the UN-recognised right of children to be raised in a family environment, and the findings of our accompanying systematic review of the physical, neurobiological, psychological, and mental health costs of institutionalisation and the benefits of deinstitutionalisation of child welfare systems. In this part of the Commission, international experts in reforming care for children identified evidence-based policy recommendations to promote family-based alternatives to institutionalisation. Full-Text PDF A child's right to family“People who say it cannot be done, should not interrupt those who are doing it.” This quote by George Bernard Shaw was used as the title of an article about a severely disabled boy in Rwanda with cerebral palsy who made remarkable developmental gains after being deinstitutionalised and placed in a foster family by Hope for Homes for Children,1 an organisation at the forefront of a growing global movement to eliminate institutional care. The first part of the Lancet Group Commission on institutionalisation and deinstitutionalisation of children in The Lancet Psychiatry by Marinus van IJzendoorn and colleagues2 highlights the necessity of deinstitutionalising children, and the second part in The Lancet Child and Adolescent Health by Philip Goldman and colleagues3 provides a blueprint for achieving this goal. Full-Text PDF Institutionalisation and deinstitutionalisation of children: the Executive Summary from a Lancet Group CommissionThis Lancet Group Commission advocates global reform of the care of separated children through the progressive replacement of institutional provision with safe and nurturing family-based care. It provides essential information on both the global scale of institutionalisation and its physical, social, and mental health consequences. It presents a pragmatic roadmap for carefully managed change. Here we outline the ten key messages from the Commission. Full-Text PDF If not now, then when? The importance of intervening early to provide family-based environments for all childrenPoverty, social deprivation, and disasters threaten children's development, and hinder their ability to thrive, to be physically and mentally healthy, to be happy and build positive relationships, and to become productive adults. Far too many children around the world are growing up in adversity. In 2019, globally, an estimated 386 million children were living in extreme poverty.1 In 2016, a global survey of 96 countries reported 1 billion children aged 2–17 years had experienced either physical, sexual, or emotional abuse in the past year. Full-Text PDF Children in institutional settingsIt is difficult to imagine now, but during the 1970s there were nearly 40 000 children living in institutions in England. The experience could be horrific for children. The reports of the abuse and maltreatment of many of those children that took place are widespread and led to a marked decline in the use of institutional homes for children and a drive towards fostering for most children entering care.1 Full-Text PDF Institutionalisation and deinstitutionalisation of childrenThe Lancet Group Commission on institutionalisation and deinstitutionalisation of children1 provides powerful scientific support for the dangers of placing children in institutions compared with raising children in families or foster families. However, we believe that this support is undermined in a follow-up policy analysis by Philip Goldman and colleagues,2 who justify placing children in group homes for so-called short-term placement “with the objective of child reintegration” and if “reintegration is not possible or in the child's best interests.” The latter category includes children with physical or psychiatric needs—ie, children with disabilities. Full-Text PDF

Purpose This pilot intervention aims to reduce stigma towards children with disabilities living in family-based care. Materials and methods Kusamala + is a pre-post evaluation of a pilot community-based intervention in two low-income compounds in Lusaka, Zambia. Door-to-door canvassing and community referrals were used to identify and enroll children with disabilities. Parents/guardians and community members completed surveys regarding stigma and support. Health professionals supervised, trained, and provided ongoing support for 2-3 community caregivers (CCGs). CCG's provided home-based education, referrals, playgroups, and social support for 20-25 families each. Community events were held at health facilities, churches and community spaces to reduce community-level stigma towards children with disabilities. Results Staff identified 632 children with disabilities. Staff completed over 4500 home visits, 288 children joined playgroups, made 775 referrals, and over 23,000 attended community sensitization events. Longitudinal data was available for 129 families with a child with a disability. Over one year, families and community members reported less perceived rejection by family and peers but less agreement that children with disabilities should be treated the same as other children. Conclusion Kusamala + was a feasible, acceptable and broad reach with limited program impact. Future work will incorporate lessons learned with a focus on sustainability and scalability.

Existing over many centuries, adoption has been challenged in recent years by evidence about practices that do not respond to the principles, ethics and laws under which it should be enacted. Written from a multidisciplinary and international perspective, this article outlines the place of adoption in the child protection system, as well as its core elements of permanence and stability. Recent demographic changes in adoption throughout the world are first examined. The negative consequences of children's exposure to early adversities and the postadoption developmental trajectory of adopted people are also summarized. The focus of the argument is that adoption provides a legitimate model for the alternative care of children if undertaken within a rights and ethics framework that emphasizes children's best interests. as set out in international conventions and national laws. Implications for adoption policy and practice are presented.

Objectives To determine the effects of foster care vs institutional care, as well as disruptions in the caregiving environment on physical development through early adolescence. Study design This was a randomized controlled trial of 114 institutionalized, though otherwise healthy, children from 6 orphanages and 51 never institutionalized control children living in birth families (family care group) in Bucharest, Romania. Children were followed from baseline (21 months, range 5-31) through age 12 years for caregiving disruptions and growth trajectories and through age 14 years for pubertal development. Results Children randomized to the foster care group showed greater rates of growth in height, weight, and body mass index (BMI) through age 12 years than institutionalized group. Tanner development was delayed in institutionalized group boys compared with foster care group and family care group boys at 12 but not 14 years. There were no differences in Tanner development and age of menarche among foster care group, institutionalized group, and family care group girls at ages 12 and 14 years. More disruptions in caregiving between 30 months and 12 years moderated decreases in growth rates of height in foster care group and weight in foster care group and institutionalized group across age. institutionalized group boys with >= 2 disruptions showed lower Tanner scores at age 12 vs institutionalized group and foster care group boys with <2 disruptions. foster care group girls with >= 2 disruptions had higher Tanner scores at age 14 vs foster care group girls with <2 disruptions. Age of menarche was not affected by caregiving disruptions. Conclusions For children who experienced early institutionalization, stable placement within family care is essential to ensuring the best outcomes for physical developmental.

Internationally adopted (IA) children have often experienced early adversity and are at risk for long-term deficiencies in multiple developmental domains. This study examined the association between IA children's joint attention (JA) soon after arrival and later cognitive, communicative, and socioemotional competency 6 months' postadoption. We expected a child's initial JA would positively predict later cognitive, communication, and social ability. IA children (n = 63) adopted from Eastern Europe were seen soon after their arrival into the United States to assess their JA. Their socioemotional competency, social communication, and cognitive abilities were measured at a follow-up session 6 months' postadoption. We found that higher order JA was positively associated with measures of social relatedness. Furthermore, individual hierarchical regressions of each measure of JA (higher order JA, initiating JA, responding to JA, and initiating behavior requests [BR]) considered with age-at-adoption showed that each measure was an independent and positive predictor of Mullen outcomes in the receptive and expressive language domains. These results suggest that JA may be a sensitive predictor of subsequent functioning in the social, communicative, and cognitive domains. Thus, assessing JA soon after arrival has the potential to identify at-risk IA children, and interventions targeting JA may support those children in overcoming the negative impacts of early adversity.

The authors present a case of diffuse intrinsic pontine glioma presenting in a newborn with stridor and respiratory distress that progressed to respiratory failure. Magnetic resonance imaging (MRI) of the brain revealed findings compatible with the diagnosis of diffuse intrinsic pontine glioma. The family pursued palliative care and postmortem examination confirmed WHO grade III astrocytoma.

Aim: To assess the status of nutrients relevant for brain development in internationally adoptees from disparate global regions and determine whether identified deficiencies are associated with neurodevelopment.Methods: Participants included children adopted from Post-Soviet States (n = 15), Ethiopia (n = 26) or China (n = 17), ages 8-18 months. A comprehensive nutritional battery and a neurodevelopmental assessment were completed at baseline (within one month of arrival) and follow-up (six months later).Results: At baseline, 35% were stunted, and 68% had at least one abnormal nutritional biochemical marker. The most common were low retinol-binding protein (33%), zinc deficiency (29%), vitamin D insufficiency/deficiency (21%), and iron deficiency (15%). There was significant catch-up growth in height and weight at follow-up, but little improvement in micronutrient deficiencies. Iron deficiency was associated with lower cognitive scores on the Bayley Scales of Infant Development-III, p = 0.027, and slower speed of processing, p = 0.012. Zinc deficiency was associated with compromised memory functioning, p = 0.001.Conclusion: Nutrient deficiencies were common during the early adoption period in internationally adoptees from three global regions, and iron and zinc deficiencies were associated with poorer neurodevelopmental outcomes. Results emphasise the importance of monitoring micronutrient status at arrival and during the early adoption period, irrespective of country of origin.

The main objective of this study was to assess the developmental status of children living in the severely adverse environment of institutional care and the examination of risk factors with regard to developmental status, including degree of stunting and emotional-behavioral and anemia status. The Bayley Scales of Infant Development were used to assess development status in 103 children aged 14.9 months (SD = 6.8) in six Kazakh institutions. The Behavioral Rating Scales were used to assess emotional-behavioral regulation. Physical growth measures were converted to z scores using World Health Organization growth charts. Venous blood was collected for assessment of anemia. Our findings indicated that young children in institutions were developmentally compromised, with duration of institutional care correlated with the severity of delay. Negative predictors of developmental status included: Poor emotional-behavioral regulation, degree of stunting and age at assessment. A particularly large percentage of children were found to be anemic. Additionally, low birth weight was found to be a significant negative predictor of development. Our findings indicate that institutional care has a detrimental impact on the development and emotional regulation of young children. Time in institutional care is a negative predictor for cognitive status for children placed at birth. Moreover stunting was found to be a useful indicator of the degree of impact of early adversity on cognitive development. Particular attention is needed for special-needs children such as those with low birth weight, since their development was found to be more sensitive to early adversity than that of normal birth weight children.

Background: Internationally adopted children have often experienced early adversity and growth suppression as a consequence of institutional care. Furthermore, these children are at risk for impaired cognitive development due to their early adverse experiences. This study examined the association between physical growth, the growth hormone (GH) system, and general cognitive functioning post-adoption. Based on previous research, we expected to find that a child's initial physical growth status and normalization of the growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis would be positive predictors of general cognitive functioning.Methods: Post-institutionalized children (n = 46) adopted from Eastern Europe were seen approximately 1 month after their arrival into the USA to determine baseline measurements. They were seen again 6 and 30 months later for two follow-up sessions. Measures included anthropometry, insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), Mullen Scales of Early Learning, and Stanford-Binet Intelligence Scales. Information about parental education was also collected.Results: We found that a child's general cognitive functioning at 30 months post-adoption was predicted by their general developmental scores at 6 months post-adoption, their initial height status, and markers of the growth hormone system. Children with lower initial IGFBP-3 standard deviation (SD) scores had higher verbal IQ scores at 30 months. Furthermore, a child's initial height was found to be a significant positive predictor of non-verbal IQ.Conclusions: These results suggest an association between a child's suppressed physical growth in response to early adversity and alterations in GH system functioning and subsequent recovery in cognitive functioning.

Despite efforts of the government to reform child protection, Russia continues to rely on institutional care due to the lack of support services for families in crisis, children with disabilities, and foster and adoptive parents.The project goal was to establish a replicable professional model that would direct the child welfare system in the Nizhny Novgorod Region away from institutional care and toward services for young children and their families that reduce the risk of institutionalization. The program was carried out over a 3-year period through a public-private partnership, which included the Ministries of Social Policy and Health of the Nizhny Novgorod Region, Firefly, and KPMG with partial funding by the United States Agency for International Development (USAID). Participation of professionals was excellent, attitudinal changes were extensive, and there were significant improvements in the understanding and utilization of early intervention concepts. The number of visits to program sites increased from essentially none to almost 1,000/month during the course of the project. Difficulties employing standardized child-based measures of success and developing ministry data-collection systems were encountered. Changes within the child welfare system in Russia are possible, but require a knowledgeable and adequately funded and supported program within regions receptive to change.

This article describes the nutritional and developmental status of young children living in Baby Houses (orphanages for children ages 0-3 years) in Kazakhstan. In 2009/2010, 308 children under age 3 years living in 10 Baby Houses were measured for height/length and weight. The Bayley Scales of Infant Development (N. Bayley, 2006) were used to assess mental and motor development. Blood was collected on a subsample to assess key nutritional factors. The World Health Organization growth charts were used to calculate Z-scores. Cut points for wasting (moderate to severe low weight for length/height growth), underweight (low weight for age), stunting (low length/height for age), development, and biomarkers used established guidelines. Most (n = 286) children had complete data on z-scores. Of these, 22.1% were experiencing wasting, 31.5% were underweight, and 36.7% had stunting. The nutritional status of the children, based on blood biomarkers, revealed that 37.1% of the children were anemic, 21.4% had low albumin, 38.1% had low vitamin D, 5.5% were iodine-deficient, and 2% had low serum zinc. One half had mild to significant mental and motor delays. Children living at these Baby Houses in Kazakhstan have substantial nutritional deficits and developmental delays. Focused attention is needed to provide a nutritionally enhanced diet and improved developmental opportunities to improve the long-term outcomes for these children.

To determine the occurrence of vision and hearing deficits in international adoptees and their associations with emotional, behavioral and cognitive problems. The Minnesota International Adoption Project (MnIAP) was a 556-item survey that was mailed to 2,969 parents who finalized an international adoption in Minnesota (MN) between January 1990 and December 1998 and whose children were between 4 and 18 years-old at the time of the survey. Families returned surveys for 1,906 children (64%); 1,005 had complete data for analyses. The survey included questions about the child's pre-adoption experiences and post-placement medical diagnoses, and the Child Behavior Checklist (CBCL). Multivariate logistic regression assessed associations between hearing and vision problems and problems identified by the CBCL. Information on hearing and vision screening and specific vision and hearing problems was also collected via a telephone survey (HVS) from 96/184 children (52%) seen between June 1999 and December 2000 at the University of Minnesota International Adoption Clinic. In both cohorts, 61% of children had been screened for vision problems and 59% for hearing problems. Among those children screened, vision (MnIAP = 25%, HVS = 31%) and hearing (MnIAP = 12%, HVS = 13%) problems were common. For MnIAP children, such problems were significant independent predictors for T scores >67 for the CBCL social problems and attention subscales and parent-reported, practitioner-diagnosed developmental delay, learning and speech/language problems, and cognitive impairment. Hearing and vision problems are common in international adoptees and screening and correction are available in the immediate post-arrival period. The importance of identifying vision and hearing problems cannot be overstated as they are risk factors for development and behavior problems.