Normal Human Newborns Research Articles

Understanding the Development, Variations, and Defects of the Muscular System in Normal Human Embryos, Fetuses, and Newborns

There has been, until now, a limited knowledge on the development of the human muscular system, as most textbooks and atlases on human development described in detail the development of the skeletal system and other structures such as the internal organs without mentioning ‐ or doing it in a very brief way ‐ the muscular system. Moreover, within the few published works that did focus on the ontogeny of human muscles, most of them were restricted to a single muscle, a muscle group, a region, or a specific period of time (e.g. before 7 weeks of gestation). This makes the study of muscle anomalies, as well as of variations, very difficult due to the lack of good comparative models about normal development. We recently dissected 17 phenotypically ‘normal’ human newborns, fetuses and embryos between 7 and 39 weeks of development, and compared our results with the scarce literature available on the normal development of the muscular system in humans. Importantly, in the individuals dissected by us there was an indirect relationship between the ages of the fetuses and the number of seemingly fused (i.e. undifferentiated) muscles. That is, muscle anlagen in the early embryonic development often give rise to several muscles even after 7 weeks of gestation. This would contradict what is often described in the literature that by end of week 7 of gestation, all muscles resemble those of the adults (i.e. are differentiated). In addition, the number of the variations (i.e. phenotypes that deviate from the norm, within the ‘normal’ human population) per upper limbs dissected is significantly higher than the number of variations per lower limb studied, a pattern that is strikingly similar to that often reported in the literature about birth defects. Therefore, these and other results support Alberch's (1989) ill‐named “logic of monsters” theory that predicts a parallel between the variant phenotypes of the ‘normal’ populations and the defective phenotypes of genetically ‘abnormal’ individual due to the strong internal constraints that limit the number of possible outcomes. Furthermore, we present, for the first time, detailed data about the development of each head and limb human muscle from late embryonic stages to newborn configuration, and discuss the broader implications of these new data within a broad comparative and developmental framework.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Newborns crying in different contexts: discrete or graded signals?

The aim of this study was to investigate whether human infants' cries show individually and contextually discriminable acoustic parameters. 20 full-term normal human newborns (aged 1 to 4 days) had their cries recorded during routine blood withdrawal (pain context) 30 min. before a scheduled feeding (hunger context) and when subjected to kinetic stimuli during neurological examination (manipulation context). Type of cries, melodic contours, F0 parameters, but not the "macro" trend of the start of the fundamental frequency, indicated a difference in pain cries in the other two contexts. All the acoustic features considered showed an individual specificity. The peak frequencies of voiceless or partially voiced wails had the interesting property of being optimised as long distance signals. We hypothesised that this feature of infants' cries may have evolved in a time window when the infants were left in collective nurseries and not carried on the mothers' backs as maintained by the traditional view.

Reduced heat loss following sucrose ingestion in premature and normal human newborns.

To determine the energy savings caused by sucrose taste, we measured heat loss through direct calorimetry for 23 premature and normal term infants who were studied a total of 31 times. Following stabilization in the calorimeter, crying was induced by applying 1 ml cold water to the infant's foot. After 4 min, 0.1 or 0.2 ml sucrose were delivered intraorally through a remote syringe to arrest crying. Crying was accompanied by a 13.2% increase in metabolic rate that was quickly and completely reversed during crying cessation caused by sucrose taste. Heat loss was inversely and linearly related to infant body weight. The implications of these findings for minimizing crying and energy expenditure in normal newborns and especially in ill or small newborns are discussed.

A New Look at Some Old Mechanisms in Human Newborns: Taste and Tactile Determinants of State, Affect, and Action

Three studies of normal human newborns and of newborns of methadone-maintained mothers evaluated how orotactile (pacifier) and orogustatory (sucrose) stimulation, alone and in combination, affected crying behavior, heart rate, gross motor activity, eye opening, and hand-mouth coordination. For each measure of infant state, pacifier and sucrose stimulation each caused significant changes that followed very different time courses. Orotactile (pacifier) stimulation precipitated immediate changes in all behaviors, and, when the pacifier was removed, all behaviors soon reverted to baseline levels. The changes precipitated by orogustatory (sucrose) stimulation were more gradual but extended well beyond the end of sucrose administration. Although both pacifier and sucrose influences are mediated orally as opposed to in the stomach or intestine, the effects involve different brain pathways. The fact that infants born to methadone-maintained mothers did not change their behaviors during or after sucrose administration but that their reactions to pacifier stimulation could not be distinguished from those of normal infants suggests that reactions to sucrose are mediated centrally by endogenous opioids while those to the pacifier work through other central mechanisms. These findings with human newborns are consonant with those of many animal studies that have also shown rapid onset and rapid offset for contact- and suckling-induced behavioral changes, slower onset and slower offset for changes induced by taste, and opioid mediation of changes induced by the taste of sucrose. Orogustatory and orotactile influences on affect, action, and cardiovascular function are discussed from the perspectives of energetics and growth, central determinants of state, motivation, and learning during the newborn period.

In vivo hprt mutant frequencies in T-cells of normal human newborns

Mutation at the hypoxanthine-guanine phosphoribosyl transferase locus ( hprt; HPRT enzyme) in the human fetus was studied by clonal assay of placental cord blood samples from full-term newborns. Conditions for determining hprt mutant frequencies, as defined for adults, were also optimal for studies in newborns. The mean mutant frequency for 45 normal human newborns (37 male, 8 female) was 0.64 × 10 −6 (SD = 0.41 × 10 −6; median value = 0.58 × 10 −6). These values are approx. 10-fold lower than corresponding adult hprt mutant frequency values. Factors such as limiting-dilution cloning efficiencies, delay prior to study of sample, sex, cryopreservation or technician performing the assay did not significantly affect assay results. Maternal smoking did not result in elevated mutant frequency values. Most wild-type and mutant clones studied were CD4 surface antigen positive (helper/inducer). All hprt mutants analyzed lacked HPRT activity.

Natural antibacterial activity against Salmonella typhi in human cord blood.

Cord blood mononuclear cells from normal human newborns possess natural antibacterial (NA) activity against Salmonella typhi, as assessed by an in vitro test. NA activity was significantly higher than that observed in PBMC from normal adult donors. Using fractionation on nylon wool and Percoll gradient or C-dependent killing with mAb, it was found that cells of the monocyte-macrophage series and CD4+ T lymphocytes were capable of exerting NA activity in newborns, in contrast with results obtained in adults, where the effector cell was a CD4+ T lymphocyte. The capability of expressing NA activity by CD4+ T lymphocytes from cord blood was also confirmed by flow cytometry sorting. Pretreatment of cord blood mononuclear cells with F(ab')2 fragments against human IgG, but not against human IgA, abrogate the NA activity. Furthermore, human IgA anti-S. typhi cannot arm CD4+ lymphocytes in cord blood. Thus it can be suggested that in newborns, the immune system still being immature, NA activity might be the expression of a mechanism of defence against infections, acting as antibody-dependent cellular cytotoxicity expressed by monocytes and CD4+ T lymphocytes armed with preexisting maternal IgG antibodies. This differs from NA activity of adults which is only mediated by CD4+ T lymphocytes armed by IgA.

Temporal masking of auditory evoked brainstem responses in human newborns and adults.

Temporal masking effects on brainstem evoked responses (BERs) were studied in normal human newborns and adults. Forward masking prolonged the latencies of the newborn BERs significantly longer than adult BERs. The effect of backward masking on BER latencies for both newborns and adults was small, suggesting that either backward masking effects for these stimuli are mediated by structures rostral to the brainstem or that backward masking does not affect the latency of the BER. Increasing the duration of the forward masker prolonged BER latencies more for newborns than adults. Increasing the intensity of the masker prolonged BER latencies for both newborns and adults, however, there were no significant age-intensity interactions.

Neonatal electroencephalographic patterns as affected by maternal drugs administered during labor and delivery.

Effects of drugs used during labor and delivery on spontaneous (resting) and evoked brain electrical activity were studied in 45 normal human newborns 48 hours after delivery. Mothers received either anesthesia (general plus local) alone (group 1), anesthesia plus meperidine (group 2), anesthesia plus meperidine and promethazine (group 3), or anesthesia plus meperidine and diazepam (group 4). Autoregressive spectral analyses and subsequent stepwise discriminant analyses showed no differences in spontaneous brain electrical activity in the infants related to the type of drugs given to the mother. However, when auditory stimuli were reduced in intensity from 80 dB to 63 dB, a significant effect was found in newborn brain electrical activity between the anesthetic-only drug pattern (group 1) and the drug patterns of anesthetics with meperidine (group 2) and anesthetics with meperidine plus diazepam (group 4). The data suggest that this effect diminishes in the presence of promethazine (group 3). Evoked responses to visual, tactile, and olfactory stimuli remained unaffected.

The metabolism of subcutaneous adipose tissue in the immediate postnatal period of human newborns. 2. Developmental changes in the metabolism of 14 C-(U)-D-glucose and in enzyme activities of phosphofructokinase (PFK; EC. 2.7.1.11) and -hydroxyacyl-CoA dehydrogenase (HAD; EC. 1.1.1.35).

Extract: Changes in the in vitro metabolism of subcutaneous adipose tissue have been compared in normal human newborns from 2 hr to 2 weeks of age. A group of healthy adult volunteers was also included. Samples were obtained by using a needle biopsy technique. More of the isotope from 14C-(U)-D-glucose was incorporated into triglycerides (P < 0.05) and also oxidized by suspensions of adipose cells from infants 2–3 hr of age than in older infants (P < 0.01). The ratio of radioactivity in carbon dioxide to radioactivity in triglyceride was also significantly greater in 2− to 3-hr-old infants than in older neonates (P < 0.05). Thin layer chromatography of the total lipid extract showed the greatest amount of radioactivity in the triglycerides, a small amount in 1,3-diglycerides and 1,2-diglycerides, and a trace in fatty acids and monogiycerides. These findings were compared with the developmental changes in two key enzymes: phosphofructokinase (PFK), which represents the glycolytic pathway, and β-hydroxyacyl-coenzyme A (CoA) dehydrogenase (HAD), which is involved in the β oxidation of fatty acids. The activity ratio of these enzymes decreased with age. In a preparation of isolated mitochondria, HAD activity increased with age (P < 0.001). These changes in substrate utilization and enzyme activity are consistent with an active metabolism of glucose in the subcutaneous adipose tissue in the first hours of life and relatively greater catabolism of fatty acids in older newborns. Speculation: Subcutaneous adipose tissue of human newborns is in many respects more active metabolically than the same tissue in adults. For example, lipolysis and reesterification seem to be more active, at least shortly after birth, and oxygen consumption is increased. This tissue is easily and safely accessible for examination, It responds sensitively to the metabolic situation of the newborn and could be effectively used as a source of information regarding peculiarities of newborns in whom fetal development was abnormal, such as premature delivery, intrauterine growth retardation, and maternal diabetes. Such studies might provide important information for the management of high risk infants.

Somatosensory evoked potentials of the normal human neonate in REM sleep, in slow wave sleep and in waking

Averaged cerebral potentials evoked by electrical stimulation of the fingers were investigated in thirty-four full-term normal human newborns. The stimuli were delivered at intervals of at least 3 sec and generally 5–12 sec to avoid sequential interactions between the responses. They were of adequate intensity to evoke consistent responses both at the contralateral parietal projection and at the vertex, but did not interfere with the normal cycles of Slow Wave Sleep (SWS) and of Rapid Eye Movement Sleep (REMS). The sleep stages were identified by a number of established criteria: pattern of respiration, eye, face and limb movements, spontaneous EEG, submental EMG and also by the histogram of heart beat intervals (Fig. 5, 8, 9, 11). The somatosensory evoked potentials present genuine and consistent features in typical REMS and SWS runs. The mean latency and voltage of the initial surface negative component, N 1, which is characteristic of the newborn response but is no longer developed in the adult, do not differ significantly in the two sleep stages (Fig. 2, 3). The latency to the peak and the duration of N 1 are significantly increased in SWS (Fig. 4). The positive component P 1 which follows N 1 is recorded in both sleep stages. However, a second component P 2 is present only in SWS and it provides the most typical feature of that stage of sleep (Fig. 1, 5, 7, 9). As a result, the total duration of the positive deflection is much longer in SWS than in REMS (Fig. 4, E). Late negative N 2 and positive P 3 components are also influenced by the sleep stages. Interesting correlations appear between the evoked potentials recorded at the hand projection and at the vertex (Fig. 9, 10). In waking the evoked potentials appear rather similar to those in activated REMS (Fig. 7, 8). The evoked somatosensory potentials in newborns permit a consistent analysis of both “primary” and late components of the cerebral responses and the sleep stages represent one of the major parameters to be considered in their investigation.

Possible role of an enterohepatic shunt as a determinant of serum bilirubin concentrations in normal human newborns

deficiency to develop when the patient began to improve from the aplastic crisis since this is the time of marked erythroid hyperplasia. Serial studies would make it possible to determine whether evidence of folio acid deficiency is more definite at one stage of the crisis than at another. DR. SHOJANIA. I should like to emphasize that folic acid deficiency is almost certainly not the cause of most aplastic crises. However, mild deficiency of folic acid is quite common and may be a contributing factor at least in some instances.

The Morphology of Buffy Coat from Cord Blood of Normal Human Newborns

Abstract The morphology of buffy coat from cord blood of normal human newborns was investigated and the results were compared with our previous observations in adults. Direct smears from cord blood were examined. Increased alkaline phosphatase activity was found in the granulocytes. Hotchkiss PAS staining was positive in up to 2 per cent of normoblasts. The examination of buffy coat revealed 28 normoblasts per 1000 granulocytes. Nuclei and/or nuclear fragments of megakaryocytes were encountered 27 times more frequently in newborns than in adults. Myelocytes and/or metamyelocytes were seen 16 times more often in newborns. Atypical mononuclear cells were found in all the subjects examined. Giant metamyelocytes and staff cells were encountered in 10 cases.