Left-Right Locomotor Coordination in Human Neonates.

Terrestrial locomotion requires coordinated bilateral activation of limb muscles, with left-right alternation in walking or running, and synchronous activation in hopping or skipping. The neural mechanisms involved in interlimb coordination at birth are well known in different mammalian species, but less so in humans. Here, 46 neonates (of either sex) performed bilateral and unilateral stepping with one leg blocked in different positions. By recording EMG activities of lower-limb muscles, we observed episodes of left-right alternating or synchronous coordination. In most cases, the frequency of EMG oscillations during sequences of consecutive steps was approximately similar between the two sides, but in some cases it was considerably different, with episodes of 2:1 interlimb coordination and episodes of activity deletions on the blocked side. Hip position of the blocked limb significantly affected ipsilateral, but not contralateral, muscle activities. Thus, hip extension backward engaged hip flexor muscle, and hip flexion engaged hip extensors. Moreover, the sudden release of the blocked limb in the posterior position elicited the immediate initiation of the swing phase of the limb, with hip flexion and a burst of an ankle flexor muscle. Extensor muscles showed load responses at midstance. The variable interlimb coordination and its incomplete sensory modulation suggest that the neonatal locomotor networks do not operate in the same manner as in mature locomotion, also because of the limited cortical control at birth. These neonatal mechanisms share many properties with spinal mammalian preparations (i.e., independent pattern generators for each limb, and for flexor and extensor muscles, load, and hip position feedback).SIGNIFICANCE STATEMENT Bilateral coupling and reciprocal activation of flexor and extensor burst generators represent the fundamental mechanisms used by mammalian limbed locomotion. Considerable progress has been made in deciphering the early development of the spinal networks and left-right coordination in different mammals, but less is known about human newborns. We compared bilateral and unilateral stepping in human neonates, where cortical control is still underdeveloped. We found neonatal mechanisms that share many properties with spinal mammalian preparations (i.e., independent pattern generators for each limb, the independent generators for flexor and extensor muscles, load, and hip-position feedback. The variable interlimb coordination and its incomplete sensory modulation suggest that the human neonatal locomotor networks do not operate in the same manner as in mature locomotion.

Changes in the spinal segmental motor output for stepping during development from infant to adult.

Human stepping movements emerge in utero and show several milestones during development to independent walking. Recently, imaging has become an essential tool for investigating the development and function of pattern generation networks in the spinal cord. Here we examine the development of the spinal segmental output by mapping the distribution of motoneuron activity in the lumbosacral spinal cord during stepping in newborns, toddlers, preschoolers, and adults. Newborn stepping is characterized by an alternating bilateral motor output with only two major components that are active at all lumbosacral levels of the spinal cord. This feature was similar across different cycle durations of neonate stepping. The alternating spinal motor output is consistent with a simpler organization of neuronal networks in neonates. Furthermore, a remarkable feature of newborn stepping is a higher overall activation of lumbar versus sacral segments, consistent with a rostrocaudal excitability gradient. In toddlers, the stance-related motor pool activity migrates to the sacral cord segments, while the lumbar motoneurons are separately activated at touchdown. In the adult, the lumbar and sacral patterns become more dissociated with shorter activation times. We conclude that the development of human locomotion from the neonate to the adult starts from a rostrocaudal excitability gradient and involves a gradual functional reorganization of the pattern generation circuitry.

Interstitial deletion of a proximal 3p: a clinically recognisable syndrome.

Interstitial deletions of the proximal short arm of chromosome 3 occurring as constitutional aberrations are rare and a defined clinical phenotype is not established yet. We report on a 30-months-old girl with distinct facial features (square facies, plagiocephaly, broad forehead, broad nasal bridge, long philtrum and low set ears) and psychomotor/speech delay associated with an interstitial deletion of 3p12 chromosomal band, del(3)(p12p12). Clinical manifestations of our child were compared with those of other eight patients with the same deletion previously described to further delineate the proximal 3p deletion syndrome.

Does cesarean section prevent mortality and cerebral ultrasound abnormalities in preterm newborns?

OBJECTIVE: Despite the increased use of the cesarean section (CS), the rates of cerebral palsy, a frequent consequence of brain damage, have remained stable over the last decades. Whether an actual decrease in cerebral palsy has been masked by increased survival of infants delivered by CS or not, remains undefined. To investigate the role of CS, we compared risks of mortality and brain damage, as defined by ultrasound (US) abnormalities, in preterm newborns by mode of delivery. METHODS: Information on fetal, maternal, and neonatal risk factors was collected from the paired clinical records of preterm newborns and mothers. Crude and adjusted odds ratios (OR) of mortality and ultrasound abnormalities, according to mode of delivery (i.e., vaginal, elective CS, and emergency CS) were calculated. All the analyses were controlled for possible confounding by indication. RESULTS: In newborns of gestational age <32 weeks, no effect of CS on cerebral US abnormalities was found (OR 0.71 and 0.73 for emergency CS and elective CS, respectively). None of the maternal and neonatal factors were associated with both cerebral US abnormalities and mode of delivery. Among newborns of gestational age >or=32 weeks, after controlling for known and potential confounders in a multivariate model, the adjusted ORs remained close to one for both elective CS and emergency CS. CONCLUSIONS: CS does not reduce overall mortality in preterm newborns. No protective effect of CS on US abnormalities was found after stratifying by gestational age and controlling for possible confounding. These results do not encourage the widespread use of CS in preterm labor.

Vertical transmission of HCV infection: prospective study in infants born to HIV-1 seronegative women.

OBJECTIVE: We performed a long-term prospective trial in infants born to HCV positive but HIV-1 negative women, with the aim of evaluating vertical transmission of HCV and correlated risks factors. METHODS: From April 1996 to May 2002, 50 women in the 3rd trimester of pregnancy or close to delivery we enrolled in the study. Anti-HCV antibodies were detected by 2nd and 3rd generation ELISA tests (ABBOTT HCV 2nd EIA generation and MEIA Abbot Labs, IL) . Reactivity was confirmed by a commercial immunoblot (Abbott Matrix HCV 2.0) ad HCV-RNA was detected by a nested-PCR technique. Infants were prospectively followed by clinical and laboratory tests (ALT levels, anti HCV Ab and HCV RNA) every 3 or 6 months for 16 to-80 months (average: 28.5 months). RESULTS: Twenty-eight of 50 women (56%) were found positive for HCV-RNA at delivery, and in 17/50 no risk factors for HCV infection were identified. Vertical transmission of HCV was detected in 3/28 infants born to viremic mothers (10.7%), while none of the 22 non-viremic mothers transmitted the infection to their children. Prolonged HCV seronegativity was documented in one of the three infected infants. During follow-up three other infants presented a single positive PCR value; one infant resulted HCV positive at 51 months of age. All infants were anti-HCV positive at delivery due to passive acquisition of antibodies, and in the 44 uninfected infants the antibody titres decreased progressively and became negative at various intervals (3-18 months). CONCLUSION: The overall vertical transmission rate was 6% but the risk of transmission of HCV infection is limited to women that are HCV RNA positive at delivery. This study shows that vertical transmission of HCV infection possibly occurs in immunocompetent infants with no HCV antibodies detected in the serum. Furthermore, we emphasise that a prolonged follow-up is absolutely mandatory in order ot establish the occurrence of active infection.

Brain damage in preterm infants: etiological pathways.

Preterm newborns represent a high-risk population for brain damage, primarily affecting the white matter, and for related neurodevelopmental disabilities. Determinants of brain damage have been extensively investigated, but there are still many controversies on how these factors can influence the developing brain and provoke damage. The concept of etiological pathway, instead of a single determinant, appears to better explain pathogenetic mechanisms: the brain damage may represent the final outcome of exposure to several combinations of risk factors in the same pathway or in different pathways and can change according to the gestational age. The aim of this article is to review the current knowledge on the pathogenesis of brain damage in preterm infants, within the frame of two main theoretical models, the ischemic and the inflammatory pathway. The relationship between the two pathways and the contribution of genetic susceptibility to ischemic and/or inflammatory insult, in modulating the extent and severity of brain damage, is also discussed.

[Etiology of rare diseases caused by novel viral agents: a review of the most recent literature]. / Eziologia di malattie rare da nuovi agenti virali: una indagine della letteratura più recente.

The authors describe the viral pathologies that have become rare in Italy and in the rest of the western world; they also analyze some novel agents mainly imported from the tropical and Asian Countries. For some of the microorganisms, they describe the various zones at risk, ways of transmission, clinical case, recent lab methods and preventive measures.

[Perinatal infections of B19 Parvoviruses] / Infezione perinatale da Parvovirus B19 e destino del neonato.

This study is aimed at detecting perinatal infections of Parvovirus B19 (PV B19). The authors have analyzed specific antibodies (IgM and IgG) in the cord serum of 647 babies, born consecutively at the St. Eugenio Hospital in Rome. 156 of them (24%) were positive to IgG. The analysis of viral genome by PCR methods showed three positive subjects (2%). The three newborn babies did not develop any pathologies during a two-year follow-up and PCR became negative within the first 6 months. Data show that a mass pregnancy test is not useful for PV B19 detection, and that specific antibody analysis should be limited to pregnancies at risk. However healthy the infected patients may appear at birth, though, it is advisable to have them monitored for at least one year so as to avoid the risk of chronic infections.

Locomotor primitives in newborn babies and their development.

How rudimentary movements evolve into sophisticated ones during development remains unclear. It is often assumed that the primitive patterns of neural control are suppressed during development, replaced by entirely new patterns. Here we identified the basic patterns of lumbosacral motoneuron activity from multimuscle recordings in stepping neonates, toddlers, preschoolers, and adults. Surprisingly, we found that the two basic patterns of stepping neonates are retained through development, augmented by two new patterns first revealed in toddlers. Markedly similar patterns were observed also in the rat, cat, macaque, and guineafowl, consistent with the hypothesis that, despite substantial phylogenetic distances and morphological differences, locomotion in several animal species is built starting from common primitives, perhaps related to a common ancestral neural network.

Diffusion-weighted MR imaging in the early diagnosis of periventricular leukomalacia.

Diffusion-weighted imaging (DWI) has been shown to be highly sensitive in detecting acute cerebral infarction, but its use in detecting hypoxic-ischemic encephalopathy (HIE) in neonates is still controversial. Moreover, few reports concern pre-term infants with possible periventricular leukomalacia (PVL). We examined the ability of this technique to detect cerebral changes in the acute phase of PVL. Fifteen MR examinations were performed in 11 pre-term infants (mean age 3.4 days, range 2-6 days). Conventional DWI sequences, apparent diffusion coefficient (ADC) maps, and US obtained in the acute phase were compared. All the neonates underwent US follow-up up to 4 months after delivery; those with suspected PVL also underwent MRI follow-up for up to 2 months. Qualitative and quantitative evaluations were performed to assess the presence of DW changes compatible with PVL. Diffusion-weighted MRI showed signal hyperintensity associated with decreased ADC values in 3 subjects (27%). In these patients conventional MRI sequences were interpreted as normal and US (performed at the same time) as doubtful in 2 and compatible with PVL in 1 subject. The MRI and US follow-up confirmed severe damage in all these patients. In 1 neonate hemorrhages involving the germinative matrix were identified. In 8 neonates MRI was considered normal. In these subjects US follow-up (up to 4 months) confirmed no signs of PVL. Diffusion-weighted imaging may have a higher correlation with later evidence of PVL than does conventional MR imaging and US when performed in the acute phase of the disease.