Clinical Research Directory

Implementation Outcomes and Cost-effectiveness of Developmental Monitoring for Children Exposed to HIV

The goal of this study is to learn about how to best carry out neurodevelopmental screening methods (tests to see if a young child can use support with brain development) in routine clinic visits in Botswana and Kenya among children age 16-24 months old. The main questions it aims to answer are: 1. when used in routine clinic visits by healthcare workers, how many children are able to get screened; 2. are the screening tools appropriate and how can they best be used; 3. how much time and money does it take to use the screening methods? The investigators will compare two screening methods chosen by healthcare workers at the beginning of the study. Children will undergo a brief test of their brain development to see if they need further evaluation and support. Caregivers will be asked to complete a short survey to see what they thought of the screening test. Healthcare workers will complete brief surveys and interviews to see what they thought of carrying out the screening tests and how use of the screening tests can be improved in their clinics.

Impact of Hospital to Home: Optimizing Preterm Infant Environment for Surgical Neonates and Their Parents (H-HOPE)

Infants born with congenital defects may require major surgery in the neonatal period. These infants are at risk for neurodevelopmental impairments. Additionally, their parents are at higher risk for adverse mental health outcomes. Early relationships are essential to healthy growth and development in all children. Relationships between parents and infants born with a congenital defect are negatively impacted by separation due to hospitalization; parental and infant stress exposures; and alterations in infant behavior and parental mental health. Benefits of H-HOPE intervention on infant neurodevelopment outcomes have been observed in healthy and at-risk term and preterm infant populations but never evaluated in infants with congenital defects. The purpose of this study is to examine impact of the Hospital to Home: Optimizing Preterm Infant Environment (H-HOPE) intervention versus standard ICU care for infants born with a congenital defect requiring neonatal surgery, and their parents. The main questions to be answered include: 1. Does H-HOPE improve pre-feeding state and behavior, oral feeding progression, and growth in infants born with a congenital defect requiring neonatal surgery? 2. Does H-HOPE neurodevelopmental outcomes in infants born with a congenital defect requiring neonatal surgery? 3. Does H-HOPE improve parental mental health outcomes among parents of infants born with a congenital defect requiring neonatal surgery? 4. Does H-HOPE improve parent-infant interactions among infants born with a congenital defect requiring neonatal surgery and their parents? 5. Does H-HOPE improve neuroendocrine function among infants born with a congenital defect requiring neonatal surgery and their parents? 6. Do parents of infants born with congenital defects requiring surgery experience participating in the H-HOPE intervention positively? Results of this study may provide preliminary evidence supporting use of H-HOPE to positively impact short- and long-term outcomes for these infants and their parents.

The MOM-CARE Trial : Evaluating Antenatal and Postnatal MMSPlus for Improved Infant Birth and Growth Outcomes

This clinical trial aims to learn if MMS Plus improves infant health compared to standard MMS during pregnancy and the postnatal period in women living in peri-urban areas of Karachi, Pakistan. It will also evaluate how MMS Plus affects infant growth during the first 6 months of life. The main questions it aims to answer are: 1. Does MMS Plus during pregnancy reduce the risk of poor infant outcomes compared to standard MMS, as measured on a 5-point ordinal scale ranging from perinatal mortality to term birth with appropriate, small, or large-for-gestational-age infants? 2. Does postnatal MMS Plus improve infant length velocity at 6 months of age among exclusively breastfed infants compared to standard MMS and iron/folic acid (IFA) supplementation? Researchers will compare: 1. MMS Plus versus standard MMS during pregnancy (antenatal phase) 2. MMS Plus versus standard MMS versus IFA after birth (postnatal phase) Participants will: 1. Be randomly assigned to receive either MMS Plus or standard MMS during pregnancy 2. Be re-randomized after delivery to receive either MMS Plus, standard MMS, or IFA supplements during the postnatal period 3. Receive supplements under double-blind conditions 4. Be followed through childbirth and until the infant is 6 months of age 5. Attend regular clinic visits for health monitoring, infant assessments, and data collection. This phase III adaptive randomized controlled trial will occur in three peri-urban catchment areas of Karachi, Pakistan.

Turkish Version of the BRIEF-Hammersmith Infant Neurological Examination (HINE)

The American Academy of Pediatrics defines high-risk infants as those with preterm birth, special health care needs, family risk factors, and those at risk of early death. Factors such as premature birth, perinatal asphyxia, hypoxic-ischemic encephalopathy (HIE), periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), chronic lung disease, seizures, meningitis, hyperbilirubinemia, twin/triplet pregnancy, and intrauterine growth restriction are risk factors that can result in morbidity and mortality in infants. Regular neurological examinations and neuromotor tests are necessary for at-risk infants to identify developmental problems early and to initiate early intervention programs.In developing countries, regular follow-up and early rehabilitation of at-risk infants are not successfully implemented. 5,6 The lengthy test batteries and busy clinics are among the most significant reasons. Therefore, the development and dissemination of shorter, valid, and reliable tests is of great importance. The Hammersmith Neonatal Neurological Examination (HINE), one of the gold standard methods, consists of 26 items and takes 15-20 minutes to administer.Due to the number of items and the duration, it is not frequently used routinely. In response to this clinical need, the HINE short scale was developed in 2024.The aim of the study is to have a Turkish version of the Abstract-HINE test in Turkey and to study its validity and reliability in high-risk infants.

Maternal Risk, Fetal-Neonatal Brain Connectivity, and Early Neurodevelopment: A Longitudinal Observational Study

This study aims to understand how a pregnant woman's health, lifestyle, and psychological state-especially when associated with known risk factors-might influence the developing brain of her baby, both before and after birth. Specifically, the research investigates whether differences in brain connectivity observed through fetal and neonatal magnetic resonance imaging (MRI) can predict how a child will develop cognitively, emotionally, and behaviorally from birth through early childhood. This is a prospective, observational study that will follow 160 pregnant women and their children over time. Participants will be enrolled at the Gynecology and Obstetrics Unit of San Raffaele Hospital in Milan. Using advanced brain imaging techniques (resting-state functional MRI), the study will examine how key brain systems-such as those involved in movement, hearing, vision, language, and attention-are connected during fetal life and shortly after birth. The study also evaluates how these patterns of brain connectivity relate to later developmental outcomes, assessed through standard neuropsychological tests from birth up to 6 years of age. One of the study's core hypotheses is that early patterns of brain connectivity-especially when combined with detailed profiles of maternal health and risk-can serve as early markers of a child's neurodevelopmental path. To explore this, the study uses an integrated approach that combines imaging data with clinical and psychological information from the mother (e.g., her stress levels, medical history, and lifestyle habits). Participants are grouped based on the "Maternal Frailty Inventory," a tool that captures the cumulative risk profile of each mother. The sample will include mothers with both low and medium-high risk scores. This grouping allows researchers to investigate how varying degrees of maternal risk are reflected in the baby's early brain organization and how this, in turn, influences developmental milestones. A secondary aim of the study is to investigate how emotional responses to music may affect fetal brain activity. During the fetal MRI, mothers will listen to selected musical pieces. Researchers will examine if the baby's brain is influenced by the mother's emotional state. Ultimately, the study hopes to build predictive models-using artificial intelligence and advanced statistical techniques-that can estimate a child's developmental trajectory based on early brain imaging and maternal data. This could provide an important step toward early identification of children who might benefit from developmental support or intervention, even before symptoms appear.

The Premature Gut Microbiome and the Influence on Neonatal Immunity, Brain Development and White Matter Injury

Recent advances in neonatal intensive care have dramatically increased the survival rate of extremely premature infants but the number of survivors with severe morbidity and lifelong neurodevelopmental impairment remains high. Perinatal white matter injury is the predominant form of brain injury in premature infants, often leading to adverse neurodevelopmental outcome. Intrauterine and neonatal infection and inflammation have been identified as major risk factors of neonatal brain injury. The fragile gut microbiome of premature infants seems to play an important role in health and disease as distortions of the microbiome occur prior to sepsis and necrotizing enterocolitis. Furthermore, the close link of the gut microbiome to neurological and psychiatric diseases in animal models suggests that the microbiome may influence brain maturation and development in preterm infants. Recent studies have underlined the importance of regulatory T cells as well as γδ T cells in brain injury, which can be directly influenced by the gut microbiome. It is therefore likely that an underdeveloped or distorted gut microbiome affects host immune response and may be a risk factor for neurodevelopmental disabilities in extremely premature infants who are already challenged by the unphysiologic early extrauterine environment after premature birth which affects maturation of the gut microbiome and immune system as well as neurophysiological maturation alike. Therefore, the overarching aim of the PreMiBraIn study is to elucidate the role of the gut-immune-brain axis on neonatal brain injury and its impact on long-term neurodevelopmental outcome of extremely premature infants. The study cohort will consist of a total of 60 extremely premature infants with a gestational age \< 28 weeks and birth weight \< 1000 grams. The investigators seek to characterize the orchestrated dynamics of the maturation of the gut microbiome and the subsequent impact on maturation of innate and adaptive immune mechanisms as well as neurophysiological maturation and neurodevelopmental outcome. Furthermore, the investigators will assess the value of the microbiome as a prognostic indicator for neonatal brain injury as well as short- and long-term neurodevelopmental outcome of extremely premature infants. This goal will be achieved by state-of-the-art techniques using 16s rRNA gene sequencing of the gut microbiome, holistic analysis of T cell biology using flow cytometry, whole transcriptome analysis and proteomics as well as neurophysiological measurements (amplitude-integrated EEG, near-infrared spectroscopy, visual evoked potentials) and cranial MRI of extremely premature infants. Short- and long-term neurological outcome will be investigated using Bayley Scales of Infant Development, Third Edition at one and two years corrected age, and Kaufmann-Assessment Battery for Children at five years of age. The investigators expect to find microbiome signatures that are predictive for later neurodevelopmental disabilities which may then be used for early screening and intervention and may suggest personalized therapeutic options. The prospects of precision medicine targeting the gut-immune-brain axis in extremely premature infants hold the opportunity to improve the overall outcome of these high-risk patients.