First Month Of Postnatal Life Research Articles

Brain age prediction and deviations from normative trajectories in the neonatal connectome

Structural and functional connectomes undergo rapid changes during the third trimester and the first month of postnatal life. Despite progress, our understanding of the developmental trajectories of the connectome in the perinatal period remains incomplete. Brain age prediction uses machine learning to estimate the brain’s maturity relative to normative data. The difference between the individual’s predicted and chronological age—or brain age gap (BAG)—represents the deviation from these normative trajectories. Here, we assess brain age prediction and BAGs using structural and functional connectomes for infants in the first month of life. We use resting-state fMRI and DTI data from 611 infants (174 preterm; 437 term) from the Developing Human Connectome Project (dHCP) and connectome-based predictive modeling to predict postmenstrual age (PMA). Structural and functional connectomes accurately predict PMA for term and preterm infants. Predicted ages from each modality are correlated. At the network level, nearly all canonical brain networks—even putatively later developing ones—generate accurate PMA prediction. Additionally, BAGs are associated with perinatal exposures and toddler behavioral outcomes. Overall, our results underscore the importance of normative modeling and deviations from these models during the perinatal period.

Population pharmacokinetics of benznidazole in neonates, infants and children using a new pediatric formulation.

There is a major need for information on pharmacokinetics (PK) of benznidazole (BNZ) in children with Chagas disease (CD). We conducted a multicentre population PK, safety and efficacy study in children, infants and neonates with CD treated with BNZ (formulated in 100 mg tablets or 12.5 mg dispersible tablets, developed by the pharmaceutical company LAFEPE, in a collaboration with DNDi). 81 children 0-12 years old were enrolled at 5 pediatric centers in Argentina. Diagnosis of T. cruzi infection was confirmed by direct microscopic examination, or at least two positive conventional serological tests. Subject enrolment was stratified by age: newborns to 2 years (minimum of 10 newborns) and >2-12 years. BNZ 7.5 mg/kg/d was administered in two daily doses for 60 days. Five blood samples per child were obtained at random times within pre-defined time windows at Day 0 at 2-5 h post-dose; during steady state, one sample at Day 7 and at Day 30; and two samples at 12-24 h after final BNZ dose at Day 60. The primary efficacy endpoint was parasitological clearance by qualitative PCR at the end of treatment. Forty-one (51%) patients were under 2 years of age (including 14 newborns <1 month of age). Median age at enrolment was 22 months (mean: 43.2; interquartile range (IQR) 7-72 months). The median measured BNZ Cmax was 8.32 mg/L (IQR 5.95-11.8; range 1.79-19.38). Median observed BNZ Cmin (trough) concentration was 2 mg/L (IQR 1.25-3.77; range 0.14-7.08). Overall median simulated Css was 6.3 mg/L (IQR 4.7-8.5 mg/L). CL/F increased quickly during the first month of postnatal life and reached adult levels after approximately 10 years of age. Negative qPCR was observed at the end of treatment in all 76 patients who completed the treatment. Five patients discontinued treatment (3 due to AEs and 2 due to lack of compliance). We observed lower BNZ plasma concentrations in infants and children than those previously reported in adults treated with comparable mg/kg doses. Despite these lower concentrations, pediatric treatment was well tolerated and universally effective, with a high response rate and infrequent, mild AEs. Registered in clinicaltrials.gov #NCT01549236.

A meta-analysis of mental rotation in the first years of life.

Mental rotation, the cognitive process of moving an object in mind to predict how it looks in a new orientation, is coupled to intelligence, learning, and educational achievement. On average, adolescent and adult males solve mental rotation tasks slightly better (i.e., faster and/or more accurate) than females. When such behavioral differences emerge during development, however, remains poorly understood. Here we analyzed effect sizes derived from 62 experiments conducted in 1705 infants aged 3-16 months. We found that male infants recognized rotated objects slightly more reliably than female infants. This difference survives correction for small degrees of publication bias. These findings indicate that gender differences in mental rotation are small and not robustly detectable in the first months of postnatal life. RESEARCH HIGHLIGHTS: We analyzed effect sizes of 62 mental rotation experiments including 1705 infants. Looking time reveals that 3-16-months-old infants are able to perform mental rotation. Mental rotation is slightly more reliable in male infants compared to female infants. Gender difference in mental rotation is robust to small degrees of publication bias.

Signal in the noise: Dimensions of predictability in the home auditory environment are associated with neurobehavioral measures of early infant sustained attention.

The home auditory environment influences the development of early language abilities, and excessive noise exposure is increasingly linked with deficits in language and reading scores in children. However, fewer studies have considered the role of noise exposure in shaping the development of attentional processing in early infancy, a foundational neurocognitive skill relevant for learning. Here, we used passive at-home auditory recording to investigate how multiple dimensions of infants' home auditory environments, including both the quantity and the predictability of auditory input, impacts neural and behavioral measures of sustained attention in a sociodemographically diverse sample of 3-month-old infants (N= 98 infants, 62 males; age M=3.48 months, SD=0.39; 52% Hispanic/Latino). Results indicated that infants who were exposed to more predictable patterns of auditory input in the home demonstrated longer overall time in sustained attention during laboratory assessments. In addition, infants' who experienced more predictable auditory input also demonstrated greater relative increases in electroencephalography frontal theta power during periods of sustained attention, a neural marker relevant to information processing and attentional control. These findings provide novel evidence into the importance of the predictability of early environmental inputs in shaping developing cortical circuitry and attentional systems from the first months of postnatal life.

Global Adipose Tissue Remodeling During the First Month of Postnatal Life in Mice.

During the first month of postnatal life, adipose tissue depots of mice go through a drastic, but transient, remodeling process. Between postnatal days 10 and 20, several white fat depots display a strong and sudden surge in beige adipocyte emergence that reverts until day 30. At the same time, brown fat depots appear to undergo an opposite phenomenon. We comprehensively describe these events, their depot specificity and known environmental and genetic interactions, such as maternal diet, housing temperature and mouse strain. We further discuss potential mechanisms and plausible purposes, including the tempting hypothesis that postnatal transient remodeling creates a lasting adaptive capacity still detectable in adult animals. Finally, we propose postnatal adipose tissue remodeling as a model process to investigate mechanisms of beige adipocyte recruitment advantageous to cold exposure or adrenergic stimulation in its entirely endogenous sequence of events without external manipulation.

Association of Cardiovascular Disease with Retinopathy of Prematurity

ABSTRACT Purpose To determine the associations of presence and types of cardiovascular diseases (CVDs) with development of retinopathy of prematurity (ROP) in premature infants undergoing ROP examinations. Study Design We performed secondary analyses of data from the multi-center Postnatal Growth and ROP Validation Study (GROP-2). CVD was categorized based on pulmonary blood flow (PBF), systemic blood flow (SBF), pulmonary hypertension (PPHN), or dysrhythmia. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were calculated from multivariable logistic regression models that included any ROP or severe ROP as outcome variable and any CVD or type of CVD as independent variable, with adjustment of covariates including birth weight (BW), gestational age (GA), and days on supplemental oxygen in the first month of postnatal life. Result Among 3980 infants, 528 (13.3%) had CVD (304 had increased PBF, 101 had decreased PBF, and 49 had PPHN), 1643 (40.4%) developed ROP, and 503 (12.6%) developed severe ROP. In multivariable analyses, presence of CVD was not significantly associated with increased risk of any ROP (aOR = 1.15, 95% CI: 0.90–1.46, p = .26) or severe ROP (aOR = 0.98, 95% CI: 0.72–1.34, p = .92). However, there were trends associating CVD resulting in increased PBF with a higher risk of ROP (aOR = 1.32, 95% CI: 0.97–1.80, p = .08) and PPHN with a higher risk of severe ROP (aOR = 2.04, 95% CI: 0.96–4.35, p = .07). When adjusting only for BW and GA, these associations were significant (aOR = 1.47, 95% CI: 1.09–1.99, and aOR = 2.35, 95% CI: 1.19–4.65, respectively). Conclusion CVD with increased PBF likely increases the risk of ROP. PPHN likely increases the risk of severe ROP.

Perinatal stroke – a neurodevelopmental nightmare

Perinatal stroke is a polymorphic syndrome caused by a cerebral vascular injury. It occurs between 20 weeks of gestation and the first month of postnatal life, the highest risk being near birth. Perinatal stroke includes a variety of lesions, depending on the vessel affected, the time of diagnosis and the type of lesion. Cumulative maternal, fetal and intrapartum risk factors determine the complex etiopathogenic mechanism. Stroke can be detected early in the neonatal period or in childhood. The symptoms can be easily overlooked, and imaging investigations are relevant for diagnosis and prognosis. The management of acute stroke and the neuroprotective treatment are essential to prevent the adverse effects on the immature brain. Perinatal brain damage has effects on motor and cognitive function, affecting the quality of life.

The Impact of Hypoxic Exposures in Different Periods of Prenatal Development on Electrical Activity of the Rabbit Auditory Cortex in the First Month of Postnatal Life

The Impact of Hypoxic Exposures in Different Periods of Prenatal Development on Electrical Activity of the Rabbit Auditory Cortex in the First Month of Postnatal Life

Daily oxygen supplementation and risk of retinopathy of prematurity

Although higher blood oxygen saturation levels increase the risk of severe retinopathy of prematurity (ROP), complicated measures of respiratory status are impractical as screening criteria. We sought to determine if a simple, clinically useful measure of ROP risk can be developed using degree or duration of oxygen supplementation during the first month of postnatal life.

Microstructural changes of the wall of uterine horn in the domestic cat (Felis silvestris catus) during postnatal development

The study describes the details of histological changes occurring during the postnatal development of the wall of the uterine horn in the European shorthair domestic cat. Light microscope observations and morphometric analysis were carried out to investigate the rate of development of the wall of the uterine horns in order to estimate the maturing time. Uterine horns of newborn and 1week-old cats are fetal-like and showing smooth, nonfolded endometrium lined with pseudostratified epithelium, deprived of uterine glands, and poorly developed two-layered myometrium. The lamina propria of the mucosa becomes folded in the first month of postnatal life. At the same time, the primordia of the uterine glands appear, elongating, doubling in number and reaching the basal layer by sixth month of age. In six-month-old cats, the lamina propria of the mucosa is formed into the functional and basal layer and its thickness increases rapidly. Until the sixth month of age, the inner circular muscle layer is the widest part of the myometrium, the outer longitudinal layer is the thinnest, while the width of the vascular layer is an intermediate value between the width of the inner and outer layer. From the seventh month of age, the proportion of the thickness of the inner and outer layer is reversed and the vascular layer becomes the thinnest part of the myometrium. Between seventh and twelfth month of age, the structure of the wall of the uterine horn does not change significantly, as the longitudinal mucosal folds limiting the narrow lumen of the uterine horns, and the arrangement of the layers in the wall is assigned to a pattern according to which the endometrium represents about 40% of the total width of the wall, while the myometrium is about 60%. In the studied time span of postnatal life, the average thickness of the wall of the uterine horn increases 9.4 -fold, the thickness of the lamina propria and mucosal folds increases 6.9-fold and 3.8-fold, respectively, while the thickness of the myometrium increases 17.3-fold. Summing up, the process of maturation of the wall of the uterine horns in the domestic cat lasts up to sixth month of postnatal life and includes the formation of the endometrial longitudinal folds, appearance and development of the uterine glands, division of the lamina propria of the mucosa into the functional and basal layers, and continued development of the circular, vascular and longitudinal muscle layers.

Association of Maternal Prepregnancy Body Mass Index With Fetal Growth and Neonatal Thalamic Brain Connectivity Among Adolescent and Young Women

Higher maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is associated with adverse long-term outcomes for offspring, including obesity, poorer cognitive and social abilities, and increased risk of psychiatric disorders. Less clear is whether higher maternal BMI disrupts fetal growth and brain development. To investigate the association of maternal prepregnancy BMI with fetal growth and neonatal functional connectivity. This prospective longitudinal cohort study was conducted from 2012 to 2017. Participants included nulliparous pregnant adolescent and young adult women, aged 14 to 19 years who were recruited in the second trimester through Columbia University Irving Medical Center and Weill Cornell Medical College. Women received routine prenatal care and had no major health problems at the time of recruitment. Data were analyzed from January 2018 to March 2020. Maternal prepregnancy BMI. The main outcomes were fetal growth, measured as estimated fetal weight, and neonatal functional connectivity, measured using magnetic resonance imaging. Prepregnancy BMI and fetal ultrasonographic measurements were obtained from electronic health record review. Resting-state brain imaging data were acquired in infants within the first month of postnatal life. Functional connectivity was measured using intrinsic functional distribution and seed-based methods. Among 129 women recruited, 105 had ultrasonographic data from at least 2 points and were included in analyses. The mean (SD) age at delivery was 17.82 (1.31) years. Maternal prepregnancy BMI was positively associated with the slope of estimated fetal weight (β = 0.668; 95% CI, 0.163 to 1.175; P = .01) but not with fetal head circumference (β = -0.004; 95% CI, -0.024 to 0.016; P = .70). In a subsample of 45 infants with magnetic resonance imaging data, maternal prepregnancy BMI was positively correlated with global connectivity in the left thalamus. Using this thalamic region as a seed, higher maternal BMI was associated with greater local thalamic (both hemispheres) and lower frontothalamic connectivity. These results suggest that maternal prepregnancy BMI was associated with the development of regulation of body weight and thalamic functional brain connectivity in offspring even during fetal development.

Biomarkers of male hypogonadism in childhood and adolescence.

The objective of this review was to characterize the use of biomarkers of male hypogonadism in childhood and adolescence. The hypothalamic-pituitary-gonadal (HPG) axis is active during fetal life and over the first months of postnatal life. The pituitary gland secretes follicle stimulating hormone (FSH) and luteinizing hormone (LH), whereas the testes induce Leydig cells to produce testosterone and insulin-like factor 3 (INSL), and drive Sertoli cells to secrete anti-Müllerian hormone (AMH) and inhibin B. During childhood, serum levels of gonadotropins, testosterone and insulin-like 3 (INSL3) decline to undetectable levels, whereas levels of AMH and inhibin B remain high. During puberty, the production of gonadotropins, testosterone, and INSL3 is reactivated, inhibin B increases, and AMH decreases as a sign of Sertoli cell maturation. Based on our knowledge of the developmental physiology of the HPG axis, these biomarkers can be used in clinical practice to interpret the physiopathology of hypogonadism. Additionally, these markers can have diagnostic value in different forms of hypogonadism that may appear during childhood and adolescence.

Retinoic Acid Is Required for Oligodendrocyte Precursor Cell Production and Differentiation in the Postnatal Mouse Corpus Callosum.

Myelination of the CNS relies on the production and differentiation of oligodendrocyte (OL) precursor cells (OPCs) into mature OLs. During the first month of postnatal life, OPCs that populate the corpus callosum (CC) arise from neural stem cells (NSCs) in the subcallosal subventricular zone (SVZ), and then differentiate to generate myelinating OLs. However, the signals that regulate these processes are not fully understood. In this study, we show that endogenous expression of the retinoic acid (RA)-synthesizing enzyme retinaldehyde dehydrogenase 2 (RALDH2) is required for OPC generation and differentiation in the postnatal subcortical white matter. In male and female pups, conditional deletion of Raldh2 reduced OPC numbers and differentiation. Moreover, decreased OPC numbers coincided with reductions in NSC survival and expression of the sonic hedgehog (SHH) signaling effector protein Gli1 in the SVZ. Additionally, GFAP expression in the CC was decreased, and cortical neuron numbers were altered. Our work suggests a role for endogenous RALDH2-dependent RA synthesis in OPC production and differentiation in the CC, as well as in the development of other cell types derived from NSCs in the embryonic ventricular zone (VZ) and SVZ, as well as the postnatal subcallosal SVZ.

Correlations between the Visual Apparatus and Dental Occlusion: A Literature Review.

Background The development of visual functions takes place in the first months of postnatal life and is completed around the one year of age. In this period, the maturation of the retina and the visual pathways occur, and binocular bonds are established at the level of the visual cortex. During this phase and then for a few years, a certain plasticity of the visual functions remains, which seem therefore susceptible to change both in a pejorative sense (by pathogens) and in an improving sense (for example, by therapeutic measures). This plasticity involves also the oculomotor system. Due to this plasticity, many researchers believe that there are some functional correlations between the visual and the stomatognathic apparatus. But the scientific evidence of this statement has not been clarified yet. Aim The purpose of this review is therefore to analyze the clinical data in this field and finally to establish their level of evidence. Studies have been collected from the main databases, based on keywords. Results The results showed a middle level of evidence since most of the data derive from case-control studies and cross-sectional studies. Conclusions The level of evidence allows establishing that there is a correlation between ocular disorders (myopia, hyperopia, astigmatism, exophoria, and an unphysiological gait due to ocular convergence defects) and dental occlusion, but it is not possible to establish the cause-effect relationship. Future studies should be aimed at establishing higher levels of evidence (prospective, controlled, and randomized studies).

Ontogeny and Thermogenic Role for Sternal Fat in Female Sheep.

Brown adipose tissue acting through a unique uncoupling protein (UCP1) has a critical role in preventing hypothermia in newborn sheep but is then thought to rapidly disappear during postnatal life. The extent to which the anatomical location of fat influences postnatal development and thermogenic function in adulthood, particularly following feeding, is unknown, and we examined both in our study. Changes in gene expression of functionally important pathways (i.e., thermogenesis, development, adipogenesis, and metabolism) were compared between sternal and retroperitoneal fat depots together with a representative skeletal muscle over the first month of postnatal life, coincident with the loss of brown fat and the accumulation of white fat. In adult sheep, implanted temperature probes were used to characterize the thermogenic response of fat and muscle to feeding and the effects of reduced or increased adiposity. UCP1 was more abundant in sternal fat than in retroperitoneal fat and was retained only in the sternal depot of adults. Distinct differences in the abundance of gene pathway markers were apparent between tissues, with sternal fat exhibiting some similarities with muscle that were not apparent in the retroperitoneal depot. In adults, the postprandial rise in temperature was greater and more prolonged in sternal fat than in retroperitoneal fat and muscle, a difference that was maintained with altered adiposity. In conclusion, sternal adipose tissue retains UCP1 into adulthood, when it shows a greater thermogenic response to feeding than do muscle and retroperitoneal fat. Sternal fat may be more amenable to targeted interventions that promote thermogenesis in large mammals.

The Development of Tactile Perception.

Touch is the first of our senses to develop, providing us with the sensory scaffold on which we come to perceive our own bodies and our sense of self. Touch also provides us with direct access to the external world of physical objects, via haptic exploration. Furthermore, a recent area of interest in tactile research across studies of developing children and adults is its social function, mediating interpersonal bonding. Although there are a range of demonstrations of early competence with touch, particularly in the domain of haptics, the review presented here indicates that many of the tactile perceptual skills that we take for granted as adults (e.g., perceiving touches in the external world as well as on the body) take some time to develop in the first months of postnatal life, likely as a result of an extended process of connection with other sense modalities which provide new kinds of information from birth (e.g., vision and audition). Here, we argue that because touch is of such fundamental importance across a wide range of social and cognitive domains, it should be placed much more centrally in the study of early perceptual development than it currently is.

Omega-3 LCPUFA supplement: a nutritional strategy to prevent maternal and neonatal oxidative stress.

There is controversy about fish-oil supplementation and oxidative damage. This ambiguity should be explored to elucidate its role as modulator of oxidative stress, especially during gestation and postnatal life. This is the objective of this study. One hundred ten pregnant women were divided in two groups: control group CT (400 mL/day of the control dairy drink); supplemented group FO (400 mL/day of the fish oil-enriched dairy drink (±400-mg EPA-DHA/day)). Different biomarkers of oxidative damage were determined in the mother's at enrolment, at delivery and at 2.5 and 4 months postpartum and newborns at delivery and at 2.5 months postpartum. Omega-3 LC-PUFA supplementation during pregnancy and lactation decreased plasma hydroperoxides especially in newborn at delivery (P = 0.001) and 2.5 months (P = 0.006), increased superoxide dismutase (SOD) and catalase (CAT) in mothers at delivery (P = 0.024 (SOD)) and after 2.5 months (P = 0.040 (CAT)) and in newborns at 2.5 months (P = 0.035 (SOD); P = 0.021 (CAT)). Also, supplementation increased α-tocoferol in mothers at 2.5 months (P = 0.030) and in umbilical cord artery (P = 0.039). Higher levels of CoQ10 were found in mothers at delivery (P = 0.039) as well as in umbilical cord vein (P = 0.024) and artery (P = 0.036). Our supplementation prevents the oxidative stress in the mother and neonate during the first months of postnatal life, being a potential preventive nutritional strategy to prevent functional alterations associated with oxidative stress that have an important repercussion for the neonate development in the early postnatal life.

Breastfeeding over two years is associated with longer birth intervals, but not measures of growth or health, among children in Kilimanjaro, TZ.

Breastfeeding has been associated with numerous health and well-being benefits for both children and their mothers, including prolonging the birth interval to the subsequent sibling. The clearest associations between breastfeeding and health outcomes, per se, reflect exclusive breastfeeding in the first months of postnatal life and are most evident during infancy. Fewer studies explore the consequences of breastfeeding for multiple years. In this article, we ask whether breastfeeding for more than 2 years is associated with discernible health and well-being benefits to children. Data were collected from 315 children, aged 2 to 7, and their caretakers residing in Kilimanjaro, Tanzania. Basic demographic and health information was solicited, and anthropometric and blood markers of health were evaluated. Our results indicate a strong positive relationship between breastfeeding for 2 or more years and interbirth interval, but little evidence for a relationship between prolonged breastfeeding and several indicators of child growth and health. We suggest that these relationships may support the recently rekindled birth spacing hypothesis, positing selection for longer interbirth intervals, rather than, or in addition to, more direct health benefits associated with breastfeeding for 2 or more years. Our results may indicate attenuating health benefits associated with longer breastfeeding.

Early Alterations in Functional Connectivity and White Matter Structure in a Transgenic Mouse Model of Cerebral Amyloidosis

Impairment of brain functional connectivity (FC) is thought to be an early event occurring in diseases with cerebral amyloidosis, such as Alzheimer's disease. Regions sustaining altered functional networks have been shown to colocalize with regions marked with amyloid plaques burden suggesting a strong link between FC and amyloidosis. Whether the decline in FC precedes amyloid plaque deposition or is a consequence thereof is currently unknown. The sequence of events during early stages of the disease is difficult to capture in humans due to the difficulties in providing an early diagnosis and also in view of the heterogeneity among patients. Transgenic mouse lines overexpressing amyloid precursor proteins develop cerebral amyloidosis and constitute an attractive model system for studying the relationship between plaque and functional changes. In this study, ArcAβ transgenic and wild-type mice were imaged using resting-state fMRI methods across their life-span in a cross-sectional design to analyze changes in FC in relation to the pathology. Transgenic mice show compromised development of FC during the first months of postnatal life compared with wild-type animals, resulting in functional impairments that affect in particular the sensory-motor cortex already in preplaque stage. These functional alterations were accompanied by structural changes as reflected by reduced fractional anisotropy values, as derived from diffusion tensor imaging. Our results suggest cerebral amyloidosis in mice is preceded by impairment of neuronal networks and white matter structures. FC analysis in mice is an attractive tool for studying the implications of impaired neuronal networks in models of cerebral amyloid pathology.

Cytochrome P450 Genetic Polymorphism in Neonatal Drug Metabolism: Role and Practical Consequences towards a New Drug Culture in Neonatology

The cytochrome P450 superfamily (CYP450) in humans is formed by 57 functional monooxygenases critical for the metabolism of numerous endogenous and exogenous compounds. The superfamily is organized into 18 families and 44 subfamilies. CYP nomenclature is based on the identity of amino acids. The most important functions of the CYP450 are related to metabolism of endogenous compounds, detoxification of exogenous xenobiotics and decomposition of the vast majority of currently used drugs. The expression of CYP450 enzymes in the human body is characterized by a marked substrate and tissue specificity, the most important being localized in the liver, but also present in kidney, lung, brain, breast, prostate and in the small intestine. The human cytochrome P450 3A gene family (CYP3A) accounts for the largest portion of CYP450 proteins in human liver and includes 4 genes: CYP3A4, CYP3A5, CYP3A7, CYP3A43. Multiple and complex genetic variations, marked interindividual, interethnic and gender variability have been reported regarding CYP3A isoform expression and activity. Multiple factors may affect CYP3A expression and activity, such as inducers like rifampicin, phenobarbital, 3-methylcholantrene, beta-naphtoflavone, and dexamethasone. The maturation of organ systems, paralleled by ontogeny of drug-metabolizing enzymes during fetal life and in the first months of postnatal life, surely exerts profound effects on drug disposition, probably being the predominant factor accounting for age-associated changes in drug clearance. In fact, drug dosage in the perinatal period represents a continuous challenge for neonatologists. The purpose of this article is to provide a brief review of the pharmacokinetic differences between neonates and adults, showing the peculiarities of liver CYP450-related drug metabolism in the perinatal period and at birth, and to report the toxic mechanisms of liver injury in neonates, due to the most frequently utilized drugs in NICU centers.