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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.

Human neonatal motoneurons show high synchronized discharge timings that modulate the generation of fast movements., Motoneurons of neonatal rodents show synchronous activity that modulates the development of the neuromuscular system. However, the characteristics of the activity of human neonatal motoneurons are largely unknown. Using a noninvasive neural interface, we identified the discharge timings of individual spinal motoneurons in human newborns. We found highly synchronized activities of motoneurons of the tibialis anterior muscle, which were associated with fast leg movements. Although neonates’ motor units exhibited discharge rates similar to those of adults, their synchronization was significantly greater than in adults. Moreover, neonatal motor units showed coherent oscillations in the delta band, which is directly translated into force generation. These results suggest that motoneuron synchronization in human neonates might be an important mechanism for controlling fast limb movements, such as those of primitive reflexes. In addition to help revealing mechanisms of development, the proposed neural interface might monitor children at risk of developing motor disorders.

The accomplishment of mature locomotor movements relies upon the integrated coordination of the lower and upper limbs and the trunk. Human adults normally swing their arms and a quadrupedal limb coordination persists during bipedal walking despite a strong corticospinal control of the upper extremities that allows to uncouple this connection during voluntary activities. Here we investigated arm–leg coordination during stepping responses on a surface in human neonates. In eight neonates, we found the overt presence of alternating arm–leg oscillations, the arms moving up and down in alternation with ipsilateral lower limb movements. These neonates moved the diagonal limbs together, and the peak of the arm-to-trunk angle (i.e., maximum vertical excursion of the arm) occurred around the end of the ipsilateral stance phase, as it occurs during typical adult walking. Although episodes of arm–leg coordination were sporadic in our sample of neonates, their presence provides significant evidence for a neural coupling between the upper and lower limbs during early ontogenesis of locomotion in humans.

Objective: To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit. Study design: This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants. Results: Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants. Conclusion: Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage. Trial registration: isrctn.org: ISRCTN53107700.

Lutein (LT) is a naturally occurring xanthophyll carotenoid most predominant in the central nervous system (CNS), but its neurotrophic role is still debated. We therefore investigated whether cord blood concentrations correlated with a well-established neurobiomarker, namely activin A.We conducted a prospective study on the distribution of LT and activin A in arterial cord blood of healthy preterm (n=50) and term (n=82) newborns according to weeks of gestational age (wGA) and gender.LT and activin A showed a pattern of concentration characterized by higher levels (P0.01, for all) at 33-36 wGA followed by a progressive decrease (P0.01, for all) from 37 onwards with a dip at term. Both LT and activin A were gender-dependent with significantly (P0.01, for all) higher levels in all recruited females and after sub-grouping for preterm and term births. LT (R=0.33; P0.001) correlated with wGA at sampling. There were significant positive correlations between lutein and activin A in male (R=0.93; P0.001) and female (R=0.89; P0.001) groups.The present data showing a correlation between LT and activin A support the notion of a neurotrophic role gender-dependent for LT and open the way to further investigations correlating LT with well-established biochemical markers of CNS development/damage.

AIM: Despite advances in perinatal management, there is a flat trend in incidences of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterm infants. The main feature of BPD development in preterm infants is an imbalance between increased exposure to free radicals and inadequate antioxidant defences. We investigated the associations between BPD and lipid hydro-peroxide (LOOH) and glutathione (GSH) concentrations in bronchoalveolar lavage fluid (BALF). METHODS: In this prospective study, BALF samples were collected from 44 preterm infants with RDS and oxidative stress markers were measured in 11 with BPD and 33 controls without BPD. RESULTS: LOOH levels were significantly higher (p

Objective: Metabolomics is a technique used to non-invasively determine a snapshot of the current metabolic status of an organism by analyzing intact tissue or bio-fluids. The aim of the present preliminary study was to analyze metabolic profiles in preterm infants complicated by respiratory distress syndrome (RDS) trough bronchoalveolar lavage fluid (BALF) measurement. Methods: Twelve BALF samples collected at birth prior surfactant, post-surfactant during mechanical ventilation and at extubation time-points, were analyzed by proton nuclear magnetic resonance spectroscopy and Gas chromatography-Mass Spectrometry (GC-MS). Results: GC-MS analysis identified 25 metabolites of whom 10 had a known molecular structure. They were: undecane, decanoic acid, dodecanoic acid, hexadecanoic acid, octadecanoic acid, hexadecanoic acid methyl ester, 9-octadecanoic acid, tetracosanoic acid, myristic acid, phosphate. These metabolites were over-expressed in BALF collected during mechanical ventilation after surfactant administration. Conclusions: The present preliminary data suggest that metabolic profile in BALF of RDS infants is becoming possible opening a new cue of metabolomics as promising tool in management of sick premature infants.

Background The increased number of childbearing women with autoimmune diseases leads to a growing interest in studying relationship among maternal disease, therapy, pregnancy and off-spring. The aim of this study was to determine the impact of autoimmune disease on pregnancy and on neonatal outcome, taking into account the maternal treatment and the transplacental autoantibodies passage. Methods We studied 70 infants born to 70 pregnant women with autoimmune disease attended in Fondazione IRCCS Policlinico San Matteo, Pavia, Italy from June 2005 to June 2012. Maternal and neonatal characteristics were collected and relevant clinical, laboratory, therapeutics, sonographic and electrocardiographic investigations were recorded and analyzed. Results We observed a high rate of spontaneous abortions in medical history, 29 %, and 18.6 % of preterm births and 22.9 % of low birth weight (< 2500 g). Transplacental autoantibodies passage wasn’t related to maternal or obstetrical complication, but anti-Ro/SSA positive pregnancies correlated with abnormal fetal heart rate (P = 0.01). Pregnant women on therapy showed an higher incidence of maternal (p = 0.002), obstetric (p = 0.007) complications and an increased rate of intrauterine growth restriction (p = 0.01) than the untreated ones. Conclusions Autoimmune diseases in pregnancy require to be carefully monitored to ensure the best possible management of mothers, fetuses and newborns due to the high rate of morbidity specially in case of maternal polytherapy and/or anti-Ro/SSA positivity.

An appropriate stabilization before transport is essential to reduce adverse events [1-5]. The aim of this study was to describe the characteristics of a cohort of newborns transported and to evaluate the association between stabilization time and change of Transport Risk Index of Physiologic Stability (TRIPS score)[6].

Cortisol production by the human fetal adrenal cortex has been shown to be not adequate at early gestation. This is due to an inefficient expression of 3β-hydroxysteroid dehydrogenase, the enzyme that catalyzes the synthesis of progesterone from pregnenolone, before about 23 weeks of gestation. Whereas, the fetal adrenal cortex it is able to produce dehydroepiandrosterone sulphate for placental estrogen synthesis and to convert placental progesterone to cortisol [1,2]. During the last trimester of pregnancy the fetal adrenal gland undergoes significant anatomical and functional maturation for adaptation to extra-uterine life and cortisol production increases greatly in the last two months of gestation. Cortisol increases synthesis of surfactant, enhances the reabsorption of lung fluid, promotes the conversion of T4 to T3, favors the closure of the ductus arteriosus and maturation of liver and intestinal enzymes [2]. Adrenal insufficiency can be caused by rare conditions such as adrenocortical hypoplasia or congenital enzymatic deficiencies of steroidogenesis, with clinical variables depending on the hormone involved. In preterm infants, the developmental immaturity, combined with increased demands in critical illness, may result in insufficient cortisol production to maintain homeostasis in the face of acute stress or illness, despite apparently normal cortisol levels. This condition is known as “transient or relative adrenal insufficiency” (TAI) [3,4]. TAI usually appears in the first week of life and normalizes in the second week. Infants with TAI can exhibit refractory hypotension (hypotension not responsive to volume expanders and inotropic drugs, but responsive to corticosteroids), respiratory distress, patent ductus arteriosus and bronchopulmonary dysplasia (BPD) [2,3]. Diagnosis of TAI is not easy because many other conditions can cause hypotension in VLBW infants: hypovolemia, myocardial dysfunction, deficient vascular tone, hyaline membrane disease, infection or a combinations of these factors. In addition, normal basal cortisol levels are extremely variable in preterms and to date there is no consensus on the diagnosis of adrenal insufficiency based on tests with adrenocorticotropic hormone (ACTH) [5-8]. Appropriate dose and duration of steroid therapy have not been established yet. On the other hand refractory and persistent hypotension is associated with intraventricular hemorrhage, periventricular leukomalacia, increased mortality and neurological disability [9]. Poor adrenal response has been shown to be associated with later development of BPD and with death [10,11]. For these reasons further studies are needed to evaluate the efficacy and safety of glucocorticoids in the treatment of cardiovascular failure due to TAI in ill preterm and term infants [12,13].