Newborn Human Infants Research Articles

Hormonal Determinants of Growth and Weight Gain in the Human Fetus and Preterm Infant.

The factors controlling linear growth and weight gain in the human fetus and newborn infant are poorly understood. We review here the changes in linear growth, weight gain, lean body mass, and fat mass during mid- and late gestation and the early postnatal period in the context of changes in the secretion and action of maternal, placental, fetal, and neonatal hormones, growth factors, and adipocytokines. We assess the effects of hormonal determinants on placental nutrient delivery and the impact of preterm delivery on hormone expression and postnatal growth and metabolic function. We then discuss the effects of various maternal disorders and nutritional and pharmacologic interventions on fetal and perinatal hormone and growth factor production, growth, and fat deposition and consider important unresolved questions in the field.

Universal and culturally specific aspects of sensitive responsiveness to young children

ABSTRACT Human newborn infants are evolutionarily predisposed to communicate. Caretakers may interpret their signals, more or less correctly, as meaningful and intentional. Reliable responsiveness is the essence of the attachment system; appropriate and prompt responses to instant’s’ signals support secure quality of attachment. Other signals, if sensitively responded to, support curiosity for the world. From birth onward infants experience and learn whether their signals will be answered, and in what way, by whom, and when, thereby developing into their own culture. Videos from seven cultures, presented here, demonstrate the ubiquity of maternal responsiveness. They present a solid basis for future data from cultural and from biological anthropology. Carefully videotaped observations elucidate differences in meaning and function of sensitive caregiver–infant interactions for the emotional and cultural development of children in various cultures.

Toxicological safety assessment of the human-identical milk oligosaccharide 3'-sialyllactose sodium salt.

Human breastmilk is a mixture of nutrients, hormones and bioactive molecules that are vital for infant growth and development. Infant formula (IF) lacks many of these compounds, most notably human milk oligosaccharides (HMOs), which are abundant in breastmilk but scarce in IF. Sialyllactoses, such as 3'-sialyllactose, constitute a large portion of the HMO fraction. To produce IF that matches breastmilk more closely, biosynthesized human-identical milk oligosaccharides (structurally identical to HMOs) such as 3'-sialyllactose sodium salt (3'-SL) are proposed for use in IF and foods for the general population. The safety assessment of 3'-SL comprised in vitro genotoxicity tests and a 90-day oral (gavage) toxicity study. This is the first 90-day study conducted with 3'-SL using neonatal rats (7days old at the start of dosing-equivalent age to newborn human infants in terms of central nervous system and reproductive development), demonstrating the safety of 3'-SL for consumption by infants, the most sensitive age group. The neonatal rats received 3'-SL at doses up to 5,000mg/kg body weight (BW)/day and reference controls received 5,000mg/kg BW/day of fructooligosaccharide (an ingredient approved for use in IF) for comparison with the high-dose 3'-SL group, followed by a 4-week recovery period. There was no evidence of genotoxicity in vitro. In the absence of any test item-related adverse effects in the 90-day study, the high dose (5,000mg/kg BW/day) was established as the no-observed-adverse-effect level. This confirms the safety of 3'-SL for use in IF for infants, as well as in functional foods for the general population.

Caffeine Protects Against Anticonvulsant-Induced Impaired Neurogenesis in the Developing Rat Brain.

In preterm infants, phenobarbital is the first-line antiepileptic drug for neonatal seizures while caffeine is used for the treatment of apnea. Data from experimental animals suggest that phenobarbital and other anticonvulsants are toxic for the developing brain, while neuroprotective effects have been reported for caffeine both in newborn rodents and preterm human infants. To characterize the interaction of phenobarbital and caffeine in the hippocampus of the developing rodent brain, we examined the effects of both drugs given separately or together on postnatal neurogenesis after administration to neonatal rats throughout postnatal day (P) 4 to P6. Phenobarbital treatment (50mg/kg) resulted in a significant decrease of proliferative capacity in the dentate gyrus. Phenobarbital also reduced expression of neuronal markers (doublecortin (DCX), calretinin, NeuN), neuronal transcription factors (Pax6, Sox2, Tbr1/2, Prox1), and neurotrophins (NGF, BDNF, NT-3) up to 24h after the last administration. The phenobarbital-mediated impairment of neurogenesis was largely ameliorated by preconditioning with caffeine (10mg/kg). In contrast, caffeine alone reduced proliferative capacity and expression of the neuronal markers DCX and NeuN at 6h, but increased expression of neurotrophins and neuronal transcription factors at 6 and 12h. These results indicate that administration of phenobarbital during the vulnerable phase of brain development negatively interferes with neuronal development, which can be prevented in part by co-administration of caffeine.

Spirit Birds at Neolithic Çatalhöyük

ABSTRACTAs they soar into the air and dive below the water's surface, birds inspire awe for their superhuman capacity to pass among earth, air, and water. People often see birds as spirits, or as messengers to and from the spirit world. Whereas at earlier sites in the region birds made a significant contribution to human diet, at Neolithic Çatalhöyük in Central Anatolia their nutritional significance is small. Body part distributions suggest that for the most part feathers were more important than meat. Bird remains, mainly the feathery parts of wings, appear in a number of special deposits at Çatalhöyük. Together with artistic representations, these deposits suggest that cranes and vultures played key roles in life cycle transitions and were invoked mimetically through dance. Additionally, waterbirds, particularly in association with newborn human infants, may have mediated between human and spirit worlds. Although there is little indication that Çatalhöyük residents made much use of brightly coloured feathers, bird wing deposits do attest to the importance of colour symbolism at the site. Thus bird remains offer material evidence of aspects of Neolithic cosmology and ontology, as well as social structure.

Breast milk is conditionally perfect

Breast milk is the universal preferred nutrition for the newborn human infant. New mother have been encouraged to exclusively breastfeed by health care professionals and consumer-advocacy forums for years, citing “breast milk is the perfect food”. The benefits are numerous and include psychological, convenience, economical, ecological and nutritionally superior.Human milk is a composite of nutritional choices of the mother, commencing in the pre-conceptual era. Events influencing the eventual nutritional profile of breast milk for the neonate start with pre-conceptual dietary habits through pregnancy and finally to postpartum. Food choices do affect the nutritional profile of human breast milk.It is not known who coined the phrase “breast milk is the perfect food” but it is widely prevalent in the literature. While breast milk is highly nutritive, containing important immunological and growth factors, scientific investigation reveals a few short-falls. Overall, human breast milk has been found to be low in certain nutrients in developed countries: vitamin D, iodine, iron, and vitamin K. Additional nutrient deficiencies have been documented in resource-poor countries: vitamin A, vitamin B 12, zinc, and vitamin B 1/thiamin.Given these findings, isn’t it more accurate to describe breast milk as “conditionally perfect”? Correcting the impression that breast milk is an inherently, automatically comprehensive enriched product would encourage women who plan to breastfeed an opportunity to concentrate on dietary improvement to optimizes nutrient benefits ultimately to the neonate. The more immediate result would improve pre-conceptual nutritional status.Here, we explore the nutritional status of groups of young women; some of whom will become pregnant and eventually produce breast milk. We will review the available literature profiling vitamin, mineral, protein and caloric content of breast milk. We highlight pre-existing situations needing correction to optimize conception and fetal development.While alternative forms of infant nutrition carry standard product labels of nutrient adequacy, this information does not apply universally to all breast milk. Infant formulas are fortified with various amounts of vitamins, minerals, supplemental protein concentrates, nucleic factors, omega 3 fatty acids and any important new nutritional finding. Infant formulas are manufactured to be consistent in composition and are monitored closely for quality. Not true for human breast milk.Any nutrient deficiency existing in pregnancy will ultimately be carried forward via lactation. It is a biological impossibility for a lactating woman to transfer nutrients via breast milk she does not have!

Nociceptive Cortical Activity Is Dissociated from Nociceptive Behavior in Newborn Human Infants under Stress

SummaryNewborn infants display strong nociceptive behavior in response to tissue damaging stimuli, and this is accompanied by nociceptive activity generated in subcortical and cortical areas of the brain [1, 2]. In the absence of verbal report, these nociceptive responses are used as measures of pain sensation in newborn humans, as they are in animals [3, 4]. However, many infants are raised in a physiologically stressful environment, and little is known about the effect of background levels of stress upon their pain responses. In adults, acute physiological stress causes hyperalgesia [5, 6, 7], and increased background stress increases pain [8, 9, 10], but these data cannot necessarily be extrapolated to infants. Here we have simultaneously measured nociceptive behavior, brain activity, and levels of physiological stress in a sample of 56 newborn human infants aged 36–42 weeks. Salivary cortisol (hypothalamic pituitary axis), heart rate variability (sympathetic adrenal medullary system), EEG event-related potentials (nociceptive cortical activity), and facial expression (behavior) were acquired in individual infants following a clinically required heel lance. We show that infants with higher levels of stress exhibit larger amplitude cortical nociceptive responses, but this is not reflected in their behavior. Furthermore, while nociceptive behavior and cortical activity are normally correlated, this relationship is disrupted in infants with high levels of physiological stress. Brain activity evoked by noxious stimulation is therefore enhanced by stress, but this cannot be deduced from observation of pain behavior. This may be important in the prevention of adverse effects of early repetitive pain on brain development.

A Study on Consumer Satisfaction Towards Nestle Baby Foods in Salem City

A Newborn human being is called a baby. The word probably came from the first spoken sound, “ba-ba”, made by many small babies. The newborn human infant is very helpless and depends on adult people for its survival. Newborn babies are perfectly formed by tiny human beings are usually weight between two and four kg. Premature babies weight 900 grams or even less and have to be kept alive in a special apparatus called an incubator. If they were kept free from grams and are carefully fed, they can live and grow to a normal size. They feed on milk which may be provided by sucking at their mother’s breasts, a method of feeding which is characteristic of all animals. Milk for the baby is especially suited to their needs. Children are valuable assets of a nation and it is their welfare that strengthens its social and economic development. Infant and child mortality is one of the key items in this Indian demographic scene. Thus, the importance of the subject of infant feeding hardly needs emphasis. It is subject, which concerns about 25-30 million babies that are born annually in our country and several millions of mothers who will be rearing them.

Human fetal intestinal epithelial cells metabolize and incorporate branched chain fatty acids in a structure specific manner

BackgroundBranched chain fatty acids (BCFA) are constituents of gastrointestinal (GI) tract in healthy newborn human infants, reduce the incidence of necrotizing enterocolitis (NEC) in a neonatal rat model, and are incorporated into small intestine cellular lipids in vivo. We hypothesize that BCFA are taken up, metabolized and incorporated into human fetal cells in vitro. MethodsHuman H4 cells, a fetal non-transformed primary small intestine cell line, were incubated with albumin-bound non-esterified anteiso-17:0, iso-16:0, iso-18:0 and/or iso-20:0, and FA profiles in lipid fractions were analyzed. ResultsAll BCFA were readily incorporated as major constituents of cellular lipids. Anteiso-17:0 was preferentially taken up, and was most effective among BCFA tested in displacing normal (n-) FA. The iso BCFA were preferred in reverse order of chain length, with iso-20:0 appearing at lowest level. BCFA incorporation in phospholipids (PL) followed the same order of preference, accumulating 42% of FA as BCFA with no overt morphological signs of cell death. Though cholesterol esters (CE) are at low cellular concentration among lipid classes examined, CE had the greatest affinity for BCFA, accumulating 65% of FA as BCFA. BCFA most effectively displaced lower saturated FA. Iso-16:0, iso-18:0 and anteiso-17:0 were both elongated and chain shortened by ±C2. Iso-20:0 was chain shortened to iso-18:0 and iso-16:0 but not elongated. ConclusionsNontransformed human fetal intestinal epithelial cells incorporate high levels of BCFA when they are available and metabolize them in a structure specific manner. These findings imply that specific pathways for handling BCFA are present in the lumen-facing cells of the human fetal GI tract that is exposed to vernix-derived BCFA in late gestation.

Can newborn infants imitate?

For several decades, scientists have held that newborn human infants can imitate adult behaviors like mouth opening, tongue protruding, and finger movements. This has been difficult to explain. In particular, it is not clear how newborn infants could know enough about their own bodies and movements, and how these map onto the bodies and movements of others, to be able to match their own felt movements to the seen movements of others. Prominent theories posit the existence of inborn mechanisms that automatically link visual input from the movements of others to the infant's already existing motor programs to produce the same movements. Such mechanisms would be instances of the inheritance of specific knowledge. In this review, we explain how current data argue against the existence of an inborn mechanism for linking seen actions with programs for performing those actions. We then sketch an alternative, multicausal explanation for the gradual development of imitation across infancy and beyond. WIREs Cogn Sci 2017, 8:e1410. doi: 10.1002/wcs.1410 For further resources related to this article, please visit the WIREs website.

Congenital Anomalies of the Male Genitalia and Risk of Autism Spectrum Disorders

Introduction Prenatal exposure to ortho-phthalates has been suggested as a possible risk factor for Autism Spectrum Disorders (ASD) through their anti-androgenic activity. In rats, prenatal exposure to phthalates causes hypospadias (abnormal positioning of the urethral opening) and cryptorchidism (undescended testis), two common male reproductive tract disorders. An ecological analysis of human newborn infants showed a strong correlation between these two disorders and ASD, but this association has not been extensively studied on an individual level. Methods We analyzed all male singleton live births (n=147,171) from January 1, 1999 through December 31, 2008 occurring in a large Israeli healthcare organization. Boys with cryptorchidism (n=3,649) or hypospadias (n=2,342) were identified via ICD-9 codes. ASD cases (n=1,329) were identified by ICD-9 code and verified by review of medical records. Analyses were conducted using generalized additive mixed effect models with random component accounting for family clusters. Results In multivariable-adjusted analyses, the odds ratio (OR) for ASD among boys with hypospadias or cryptorchidism was 1.31 (95% confidence interval (CI): 1.01-1.68). For cryptorchidism only the OR was 1.44 (95% CI: 1.06-1.96) and for hypospadias only was 1.07 (95% CI: 0.70-1.64). Restricting to boys who underwent surgical correction strengthened the results for cryptorchidism (OR: 1.77; 95% CI: 1.16-2.72), but not hypospadias. Conclusions Boys with cryptorchidism were at higher risk of ASD, but we did not observe an increased risk among boys with hypospadias. Differences in ASD risk between the disorders may reflect variations in critical windows of exposure to a hypoandrogenic in-utero environment, or effects of other singling systems involved in the etiology of the disorders. Understanding the links between cryptorchidism and ASD could shed light on mechanisms of ASD pathogenesis.

Transplant Tolerance Induction in Newborn Infants: Mechanisms, Advantages, and Potential Strategies.

Although several tolerance induction protocols have been successfully implemented in adult renal transplantation, no tolerance induction approach has, as yet, been defined for solid organ transplantations in young infants. Pediatric transplant recipients have a pressing demand for the elaboration of tolerance induction regimens. Indeed, since they display a longer survival time, they are exposed to a higher level of risks linked to long-term immunosuppression (IS) and to chronic rejection. Interestingly, central tolerance induction may be of great interest in newborns, because of their immunological immaturity and the important role of the thymus at this early stage in life. The present review aims to clarify mechanisms and strategies of tolerance induction in these immunologically premature recipients. We first introduce the discovery and mechanisms of neonatal tolerance in murine experimental models and subsequently analyze tolerance induction in human newborn infants. Hematopoietic mixed chimerism in neonates is also discussed based on in utero hematopoietic stem cell (HSC) transplant studies. Then, we review the recent advances in tolerance induction approaches in adults, including the infusion of HSCs associated with less toxic conditioning regimens, regulatory T cells/facilitating cells/mesenchymal stem cells transplantation, costimulatory blockade, and thymus manipulation. Finally, IS withdrawal in pediatric solid organ transplant is discussed. In conclusion, the establishment of transplant tolerance induction in infants is promising and deserves further investigations. Future studies could focus on the selection of patients, on less toxic conditioning regimens, and on biomarkers for IS minimization or withdrawal.

Eye-Mouth Associated Movement in the Human Newborn and Very Young Infant

BackgroundThe aim of this study is to demonstrate that goal-directed eye-mouth associated movement exists in the newborn and very young infant. MethodsThe participants were 17 healthy term newborns or very young infants whose ages at the time of the first examination ranged from 1 to 24 days. The examiner held the tip of an index finger 20 to 30 cm in front of a participant's mouth, then suddenly moved it directly toward the mouth. Thirteen of the participants were also examined with the examiner's palm as the visual stimulus. The response was judged to be positive if clear mouth opening was elicited as the fingertip or palm was approaching the mouth. ResultsIn the examinations using a fingertip, the frequency of a positive response as to the total number of examinations in the different age groups within the first two months of life ranged between 43.9% and 48.8%, and precipitously decreased to 6.3% at two months of age. A positive response was not elicited from age three months. On the other hand, in the examinations using a palm, the frequency of a positive response was 5.0% in the newborns, and 6.7% in the infants aged between seven days and one month. A positive response was never obtained from two months of age. ConclusionThis study demonstrated that visually guided mouth opening toward an approaching target exists in the human newborn. The eye-mouth associated movement may be controlled through rudimentary but functional visuomotor circuits in the brain interconnecting different cortices.

Spindle Bursts in Neonatal Rat Cerebral Cortex.

Spontaneous and sensory evoked spindle bursts represent a functional hallmark of the developing cerebral cortex in vitro and in vivo. They have been observed in various neocortical areas of numerous species, including newborn rodents and preterm human infants. Spindle bursts are generated in complex neocortical-subcortical circuits involving in many cases the participation of motor brain regions. Together with early gamma oscillations, spindle bursts synchronize the activity of a local neuronal network organized in a cortical column. Disturbances in spindle burst activity during corticogenesis may contribute to disorders in cortical architecture and in the activity-dependent control of programmed cell death. In this review we discuss (i) the functional properties of spindle bursts, (ii) the mechanisms underlying their generation, (iii) the synchronous patterns and cortical networks associated with spindle bursts, and (iv) the physiological and pathophysiological role of spindle bursts during early cortical development.

Influence of prenatal maternal stress on umbilical cord blood cytokine levels

Purpose Prenatal maternal stress (PNMS) is known to influence fetal programming and development. Thus far, the effects of PNMS on the developing immune system have mainly been documented in animal studies. This study aimed to examine the association between PNMS and immune cytokine profiles in the umbilical cord blood of newborn human infants.

Microbial metaproteomics for characterizing the range of metabolic functions and activities of human gut microbiota

The human gastrointestinal tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome is not merely a collection of opportunistic parasites, but rather provides important functions to the host that are absolutely critical to many aspects of health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial metaproteomics provides the ability to characterize the human gut microbiota functions and metabolic activities at a remarkably deep level, revealing information about microbiome development and stability as well as their interactions with their human host. Generally, microbial and human proteins can be extracted and then measured by high performance MS-based proteomics technology. Here, we review the field of human gut microbiome metaproteomics, with a focus on the experimental and informatics considerations involved in characterizing systems ranging from low-complexity model gut microbiota in gnotobiotic mice, to the emerging gut microbiome in the GI tract of newborn human infants, and finally to an established gut microbiota in human adults.

Fetal consequences of maternal antiretroviral nucleoside reverse transcriptase inhibitor use in human and nonhuman primate pregnancy.

Here we present fetal genotoxicity and mitochondrial toxicity, induced by nucleoside reverse transcriptase inhibitors (NRTIs), in HIV-1-infected pregnant women treated to prevent mother-to-child HIV-1 transmission, and in virus-free pregnant patas monkeys. In the offspring of pregnant patas monkeys given human-equivalent NRTI protocols, aneuploidy was found in cultured bone marrow cells taken at birth, 1, and 3 years of age. In some newborn human infants, the offspring of HIV-1-infected mothers given zidovudine (AZT) therapy, aneuploidy, mitochondrial DNA (mtDNA) depletion, morphologically damaged mitochondria, and reduction in cardiac left ventricular muscle were observed. NRTI-exposed human and patas umbilical cords had similar levels of mtDNA depletion and mitochondrial morphological damage. NRTI-exposed patas offspring showed a compensatory increase in heart mtDNA, and a 50% loss of brain mtDNA at 1 year of age. Mitochondrial morphological damage and mtDNA loss were persistent in blood cells of NRTI-exposed infants up to 2 years of age, and in heart and brain from NRTI-exposed patas up to 3 years of age (human equivalent of 15 years). Whereas use of NRTIs in human pregnancy protects many thousands of children worldwide, some HIV-1-uninfected infants born to HIV-1-infected mothers receiving antiretroviral drug therapy sustain toxicities that may have adverse consequences later in life.

The contrast sensitivity of the newborn human infant.

To measure the binocular contrast sensitivity (CS) of newborn infants using a fixation-and-following card procedure. The CS of 119 healthy newborn infants was measured using stimuli printed on cards under the descending method of limits (93 infants) and randomized/masked designs (26 infants). One experienced and one novice adult observer tested the infants using vertical square-wave gratings (0.06 and 0.10 cyc/deg; 20/10,000 and 20/6000 nominal Snellen equivalent); the experienced observer also tested using horizontal gratings (0.10 cyc/deg) and using the Method of Constant Stimuli while being kept unaware of the stimulus values. The CS of the newborn infant was 2.0 (contrast threshold = 0.497; 95% confidence interval: 0.475-0.524) for vertically oriented gratings and 1.74 (threshold = 0.575; 95% confidence interval: 0.523-0.633) for horizontally oriented gratings (P < 0.0006). The standard deviation of infant CS was comparable to that obtained by others on adults using the Pelli-Robson chart. The two observers showed similar practice effects. Randomization of stimulus order and masking of the adult observer had no effect on CS. The CS of individual newborn human infants can be measured using a fixation-and-following card procedure.

Functional magnetic resonance imaging can be used to explore tactile and nociceptive processing in the infant brain.

AimDespite the importance of neonatal skin stimulation, little is known about activation of the newborn human infant brain by sensory stimulation of the skin. We carried out functional magnetic resonance imaging (fMRI) to assess the feasibility of measuring brain activation to a range of mechanical stimuli applied to the skin of neonatal infants.MethodsWe studied 19 term infants with a mean age of 13 days. Brain activation was measured in response to brushing, von Frey hair (vFh) punctate stimulation and, in one case, nontissue damaging pinprick stimulation of the plantar surface of the foot. Initial whole brain analysis was followed by region of interest analysis of specific brain areas.ResultsDistinct patterns of functional brain activation were evoked by brush and vFh punctate stimulation, which were reduced, but still present, under chloral hydrate sedation. Brain activation increased with increasing stimulus intensity. The feasibility of using pinprick stimulation in fMRI studies was established in one unsedated healthy full-term infant.ConclusionDistinct brain activity patterns can be measured in response to different modalities and intensities of skin sensory stimulation in term infants. This indicates the potential for fMRI studies in exploring tactile and nociceptive processing in the infant brain.

IS-045 Consciousness At The Basis Of Developmental Care

The newborn human infant particularly the preterm infant was previously regarded as a sensory-motor organism without consciousness. By the introduction of developmental care neonatal nurses and doctors commenced to regard the preterm patient as an autonomous person with consciousness although at a minimal level. The thalamocortical connections from the sense organs are established from about the 23rd gestational week, indicating that the neuronal global workspace can function (see ref 1 ). From about 25 weeks cortical responses in the somatosensory area have been recorded by near-infrared spectroscopy (NIRS) and facial expressions similar to adults sustaining pain have been observed in preterm infants after 25 weeks The preterm infant is aware of its body, itself and to some extent of the outside world. It recognises faces, vowels and smells it has been exposed to. Recent NIRS studies have shown that the preterm brain reacts differently to female versus male voices. 2 It expresses emotions like joy. By functional MR it has been demonstrated that there is a spontaneous resting activity encompassing the somatosensory, auditory and visual cortex, although there is less activity in association area and the prefrontal cortex as compared with adults. There is an incomplete default mode network which is assumed to be related to consciousness. 3 References Lagercrantz H, Hanson, M., Ment, L., Rodeck, C. (Eds) The Newborn Brain 2nd ed. Cambridge University Press, 2010 Mahmoudzadeh M et al . Syllabic discrimination in premature human infants. PNAS . 2013;110:4846–4851 Raichle M. The brain’s dark energy. Scientific American . 2010;302:44–49