Prenatal drug exposure is a global public health problem that will never be completely eliminated. Some drugs are essential for maternal health but many others are used recreationally and for non-medical reasons. Both legal and illegal drugs of addiction and dependency have the potential to cause permanent and even intergenerational harm to the developing child and understanding the direct impact of drugs of addiction on child neurodevelopmental and mental health is difficult and confounded by many social, environmental and possibly, genetic factors. Furthermore, many drugs are not clear neuroteratogens and their impact on the child may be indolent and not appreciated for a long time after exposure has occurred. Despite this, there are numerous windows of opportunity to improve the eventual outcomes of the child including utilising the enormous benefits of neuroplasticity and general principles of basic health care and support. This chapter will discuss current understanding of the impact of drugs of addiction on the growing child and offer possible mitigation strategies to improve outcomes.

Surfactant therapy in preterm and term born infants has been a huge success story. In the meantime, we have very detailed answers to the five essential questions of each medical therapy: which infant should be treated, when, with which drug, in/at what dose, and via which route of administration. The answers to these questions depend on the gestational age of the infant. We have focused on preterm infants <28 weeks of gestation as they are the most vulnerable and may have the maximum benefit of appropriate treatment. Therefore, we performed a sub-group analysis for data available from the published trials in infants less than 28 weeks who received less/minimal invasive surfactant administration/therapy [LISA/MIST] versus intubation-surfactant-extubation (INSURE). The need for mechanical ventilation (MV) was significantly reduced by 28 % (RR:0.72, 95%CI:0.64-0.80, n = 548 infants) after LISA/MIST. The incidence of bronchopulmonary dysplasia (BPD) was significantly decreased by 30 % (RR:0.70, 95%CI:0.66-0.75, n = 6528 infants) after LISA/MIST. No difference in mortality was noted between the two groups. In the current review, we discuss the applicability of guidelines to individual patient groups like the infants <28 weeks and emphasize the individual assessment of published data by the treating physician.

Neonatal tone abnormalities can often be the first indication of cerebral palsy (CP) and need regular developmental assessments by a multidisciplinary team. The need for early diagnosis and treatment during the height of neural plasticity is crucial. Currently, the number of clinical practice guidelines and the quality of evidence for treatment of tone in neonates is insufficient. In this review, we discuss the physiology of tone abnormalities including structural-functional components of motor control and time-dependent etiology of injury. We provide a guideline for assessment of a neonate with concern for tone abnormalities including a discussion on available diagnostic and functionality rating scales. Lastly, we describe the importance of a multidisciplinary care team involving the patient's caregiver as well as non-pharmacological, pharmacological, and surgical treatment options for tone abnormalities. We stress the importance of regular, serial examinations for tone as these neonates get older to assess eligibility for additional interventions.

Delirium is a common and serious complication of critical illness that has been increasingly recognized in pediatric patients. There have been several published cases of delirium in newborns and infants over the last decade, though research on neonatal delirium is severely lacking. The true prevalence of delirium and its associated consequences in this population remain unknown, although the risk of delirium in this population appears to be elevated compared to older youth. The current approach to management of delirium in neonates is extrapolated from older children. In the present review, the pathophysiology and clinical presentation of delirium are outlined. Strategies for prevention, evaluation, and management of delirium in neonates are explored.

The major focus of neonatal research for many years has been the smallest and most vulnerable infants born before 32 weeks of gestation. More recently it has become clear that a gradient of risk for adverse outcomes spans the whole spectrum of gestational age, from those born at the margins of viability, to those born close to their estimated date of delivery. Whilst effect sizes may be smaller for the more mature babies born late preterm and early term, the size of the problem is related to very large numbers with less severe difficulties, yet whose problems affect many domains of health, development and education, and may have impact across the whole life course. Our knowledge of the mechanisms and influencing factors contributing to outcomes of individuals born late preterm and early term is inadequate. The unique challenges associated with managing pregnancies, babies, children, adults and families affected by late preterm or early term birth in the face of limited evidence mandate further research to guide practice and optimise short- and long-term outcomes.

Social determinants of health are social, economic and environmental factors known to influence health and development of infants, children and adults. Advancing equity in brain health relies upon interdisciplinary collaboration and recognition of the impact of social determinants on brain health through the lifespan and across generations. Critical periods of fetal, infant and early childhood development encompass intrinsic genetic and extrinsic environmental influences with complex gene-environment interactions. This review discusses the influence of social determinants on the continuum of brain health from preconception and pregnancy health, through fetal, infant and childhood neurodevelopment into adulthood. Opportunities for intervention to address the social determinants of brain health across the life cycle are highlighted.

The human brain undergoes rapid changes from the fetal stage to two years postnatally, during which proper structural and functional maturation lays the foundation for later cognitive and behavioral development. Multimodal magnetic resonance imaging (MRI) techniques, especially structural MRI (sMRI), diffusion MRI (dMRI), functional MRI (fMRI), and perfusion MRI (pMRI), provide unprecedented opportunities to non-invasively quantify these early brain changes at whole brain and regional levels. Each modality offers unique insights into the complex processes of both typical neurodevelopment and the pathological mechanisms underlying psychiatric and neurological disorders. Compared to a single modality, multimodal MRI enhances discriminative power and provides more comprehensive insights for understanding and improving neurodevelopmental and mental health outcomes, particularly in high-risk populations. Machine learning- and deep learning-based methods have demonstrated significant potential for predicting future outcomes using multimodal brain MRI acquired during early childhood. Here, we review the unique characteristics of various MRI techniques for imaging early brain development and describe the common approaches to analyze these modalities. We then discuss machine learning approaches in predicting future neurodevelopmental and clinical outcomes using multimodal MRI information during early childhood, highlighting the potential of identifying biomarkers for early detection and personalized interventions in atypical development.

Over the past last 50 years, patent ductus arteriosus (PDA) continues to be the leading hot topic debated worldwide in search of best treatment approach and the uncertainty around whether to treat or not treat a PDA. With the availability of bedside echocardiography and the increasing number of neonatologists acquiring this skill, on one hand there is better understanding of PDA physiology during transitional circulation and objectivity in management, but on the other hand clinicians are uncertain about benefits in health outcomes. Evidence from recent trials utilizing early selective treatment guided by bedside echocardiography should help in dispelling some myths if not providing the answer about how to manage the PDA.

Perinatal medicine has made significant advancements in recent decades. This has improved care and outcomes for infants. As we strive to improve neurodevelopmental outcomes, we must understand the influence the maternal/placental/fetal (MPF) triad has on fetal development and postnatal health and disease. Our understanding of the MPF triad remains incomplete, however research is continuing to develop our understanding. Through further research and incorporating what is currently known into how we deliver perinatal care, we have the opportunity to improve outcomes for infants. This review focuses on what is currently known about the structure and function of the placenta and the influence of the MPF triad. Current modalities for assessment of the MPF triad and future avenues for research will also be discussed. Understanding the relationship between the MPF triad, neurodevelopment and long-term health and disease has the potential to open new avenues for disease prevention and treatment through the lifespan.

Unique from other fetal anatomical systems, the central nervous system (CNS) starts development early in the embryonic period shortly after fertilization before most patients are even aware they are pregnant. Maturation throughout pregnancy involve complicated structural and functional changes, most likely below the resolution of testing to detect. During this time, the fetal CNS is susceptible to lesions that reflect trimester-specific adverse events. Neonatal neurological status with childhood sequelae can result from combinations of antenatal, peripartum and neonatal adverse events. Person-specific clinical management choices must consider the timing of multiple mechanisms that can alter neurodevelopment including genetic causes, aetiologies after conception as well as communicable and non-communicable conditions that result in anomalous or destructive brain lesions. The appearance of the fetal brain also changes significantly through gestation as different structures mature and the cerebral cortex in particular increases in size and complexity. Therefore, obstetrical imagers and maternal fetal medicine physicians need to be aware of the expected evolving appearances of the healthy fetal brain as the fetus advances in gestation. Often when fetal CNS pathology is detected or anticipated during pregnancy, there is understandably significant parental anxiety regarding the long-term implications of their child's neurodevelopmental prognosis. In these instances, Maternal Fetal Medicine specialists often collaborate with Pediatric Neurologists in the antenatal period regarding diagnoses that anticipate neonatal or later childhood neurologic sequelae. Potential adverse outcomes are discussed with prospective parents to be integrated into choices based on shared decisions.

This review of neurogenetics serves as a primer for clinicians practicing in fetal-neonatal medicine. The review provides an update on neurogenetics, understanding the language of genetics, genetic testing approaches, and interpretation of genetic test results. Common examples of neurogenetic disease in fetal-neonatal medicine are used to enhance basic concepts. The results of genetic testing and their implications for patients and families are outlined. Genetics is becoming foundational to clinical practice across specialties. The advances are improving the speed of diagnosis, facilitating early treatments, and improving outcomes in neurogenetic disorders. A basic understanding of genetics is foundational to appropriate clinical-decision making and interpretation of those results to describe common fetal-neonatal neurological phenotypes.

Worldwide polycrises continue to challenge the World Health Organization's proposed 2030 sustainable development goals. Continuity of brain care bundles helps attain these goals by sustaining brain health over successive generations. Factors representing social drivers of health must incorporate transdisciplinary care into equitable intervention choices. Drivers are more effectively addressed by combining maternal and pediatric assessments to address morbidity and mortality across each lifespan. Care bundles comprise at least three evidenced-based interventions collectively implemented during a clinical experience to achieve a desired outcome. Synergy among stakeholders prioritize communication, responsibility, compliance and trust when choosing bundles in response to changing clinical conditions. A prenatal transdisciplinary model continues after birth with infant and family-centered developmental care practices through discharge to supplement essential skin-to-skin contact. Fetal-neonatal neurology training encourages participation in this model of brain health care to more effectively choose neurodiagnostic and neuroprotective options. Shared clinical decisions evaluate interventions from conception through the first 1000 days. At least eighty percent of brain connectivity will have been completed during this first critical/sensitive period of neuroplasticity. The developmental origins of health and disease concept offers neurology subspecialists a life-course perspective when choosing brain health strategies. Toxic stressor interplay from reproductive and pregnancy diseases and adversities potentially impairs embryonic, fetal and neonatal brain development. Continued exposures throughout maturation and aging worsen outcome risks, particularly during adolescence and reproductive senescence. Intragenerational and transgenerational use of care bundles will guide neuromonitoring and neuroprotection choices that strengthen preventive neurology strategies.

The first 1000 days of life are of paramount importance for neonatal development. Premature newborns are exposed early to the external environment, modifying the fetal exposome and leading to overexposure in some sensory domains and deprivation in others. The resulting neurodevelopmental effects may persist throughout the individual's lifetime. Several neonatal neuromonitoring techniques can be used to investigate neural mechanisms in early postnatal development. EEG is the most widely used, as it is easy to perform, even at the patient's bedside. It is not expensive and provides information with a high temporal resolution and relatively good spatial resolution when performed in high-density mode. Functional near-infrared spectroscopy (fNIRS), a technique for monitoring vascular network dynamics, can also be used at the patient's bedside. It is not expensive and has a good spatial resolution at the cortical surface. These two techniques can be combined for simultaneous monitoring of the neuronal and vascular networks in premature newborns, providing insight into neurodevelopment before term. However, the extent to which more general conclusions about fetal development can be drawn from findings for premature neonates remains unclear due to considerable differences in environmental and medical situations. Fetal MEG (fMEG, as an alternative to EEG for preterm infants) and fMRI (as an alternative to fNIRS for preterm infants) can also be used to investigate fetal neurodevelopment on a trimester-specific basis. These techniques should be used for validation purposes as they are the only tools available for evaluating neuronal dysfunction in the fetus at the time of the gene-environment interactions influencing transient neuronal progenitor populations in brain structures. But what do these techniques tell us about early neurodevelopment? We address this question here, from two points of view. We first discuss spontaneous neural activity and its electromagnetic and hemodynamic correlates. We then explore the effects of stimulating the immature developing brain with information from exogenous sources, reviewing the available evidence concerning the characteristics of electromagnetic and hemodynamic responses. Once the characteristics of the correlates of neural dynamics have been determined, it will be essential to evaluate their possible modulation in the context of disease and in at-risk populations. Evidence can be collected with various neuroimaging techniques targeting both spontaneous and exogenously driven neural activity. A multimodal approach combining the neuromonitoring of different functional compartments (neuronal and vascular) is required to improve our understanding of the normal functioning and dysfunction of the brain and to identify neurobiomarkers for predicting the neurodevelopmental outcome of premature neonate and fetus. Such an approach would provide a framework for exploring early neurodevelopment, paving the way for the development of tools for earlier diagnosis in these vulnerable populations, thereby facilitating preventive, rescue and reparative neurotherapeutic interventions.

Neonatal encephalopathy (NE) is a significant cause of neonatal mortality in low- and middle-income (LAMI) countries, with far-reaching impacts on families and national human capital. Quantifying the disease burden in monetary terms is crucial for resource allocation and public health prioritization, yet data on the economic impact of NE-related neonatal mortality and prevention is limited. This study estimates the country-specific disease burden and economic impacts of NE for the ten countries with the highest death tolls in 2019. Using data from the Global Burden of Disease (GBD) Collaborative Network, we analyzed NE-specific mortality trends and calculated years of life lost (YLLs) based on life expectancy, with and without age weighting and discounting. Economic losses were evaluated using the value per statistical life (VSL) and value per statistical life year (VSLY) methodologies, with sensitivity analyses incorporating variable discount rates. In 2019, the ten countries with the highest NE burden was estimated at 138,763 neonatal deaths. YLLs ranged from 4.5 million with discounting to 9.8 million without. While nine of these countries reduced overall neonatal mortality from 2010 to 2019, six saw rising NE-specific mortality. Economic losses were estimated at $80 billion using the VSL method and between $72 billion and $163 billion using VSLY. Despite overall progress in reducing neonatal mortality, targeted funded strategies are needed to address NE in LAMI countries. Burden of NE could be reduced with improved strategic access to quality antenatal care and effective peripartum practices through efficient and enhanced resource allocation.

Cerebral palsy (CP) is a clinical term used to describe a spectrum of movement and posture disorders resulting from non-progressive disturbances in the developing fetal brain. The clinical diagnosis of CP does not include pathological or aetiological defining features, therefore both genetic and environmental causal pathways are encompassed under the CP diagnostic umbrella. In this review, we explore several genetic causal pathways, including both monogenic and polygenic risks, and present evidence supporting the multifactorial contributions to CP. Historically, CP has been associated with various risk factors such as pre-term birth, multiple gestation, intrauterine growth restriction (IUGR), maternal infection, and perinatal asphyxia. Thus, we also examine genetic predispositions that may contribute to these risk factors. Understanding the specific aetiology of CP enables more tailored treatments, especially with the increasing potential for early genetic testing.

Survival rates for extremely low birth weight (ELBW) infants have improved over the recent years, yet morbidity remains high. This review explores respiratory management strategies for this unique cohort and how it may impact their long-term outcomes. Although there is a preference towards non-invasive respiratory support in less immature infants, ELBW infants often require invasive ventilation. This comes with an increased risk of bronchopulmonary dysplasia, adverse neurodevelopmental outcomes and lifelong respiratory impairment. There are a range of options available to reduce volutrauma and minimise lung injury, including volume targeted ventilation and high-frequency ventilation. In the absence of high-quality evidence focussing on ELBW infants, much of current practice is inferred from studies involving infants with a broader range of gestational ages and experiences at high-volume centres. This highlights the need for further research targeted to this specific population with a focus on long-term respiratory health.

Pediatric neurocritical care is a field dedicated to providing specialized assessment and care of critically-ill children with neurologic disease or at risk of neurologic compromise. Fellowship programs for providers interested in specializing in pediatric neurocritical care are growing and developing to meet the needs of trainees and the patient populations that they serve. Fetal and neonatal neurocritical care fellowship remains a separate opportunity for training; however, inclusion of fetal and neonatal neurology education into pediatric neurocritical care broadens understanding of normal and pathologic anatomy and physiology, diagnostic interpretation of the developing brain, targeted management interventions, family counseling and prognostication, and long-term optimization of outcomes. For instance, the care of neurologic injury in congenital heart disease emphasizes the incorporation of medical education across the lifespan. Additionally, neonates requiring NICU admission and care are more likely to require future PICU care and be served by neurocritical care providers. Furthermore, neonates with neurologic injury or at risk for neurologic injury are not exclusively admitted to neonatal units. Education across the age-spectrum inclusive of fetal and neonatal neurology is valuable for trainees in understanding underlying disease processes, management, and sequelae and promotes the growth of the field of pediatric neurocritical care.