Cortical activation and oxygen perfusion in preterm newborns during kangaroo mother care: A pilot study.

AIM: This study aimed to assess the functional activation of preterm newborns' cerebral cortex during kangaroo mother care. Possible effects of gestational age and previous kangaroo mother care experience were also considered. METHODS: Fifteen preterm newborns were recruited (gestational age: 24-32 weeks). Cortical activation was assessed in frontal, motor and primary somatosensory cortices after 15 and 30 min of kangaroo mother care by multichannel near-infrared spectroscopy (gestational age at assessment: 30-36 weeks). Both oxy- and deoxy-haemoglobin variations were analysed by t-test. Possible effects of gestational age and previous kangaroo mother care experience on cortical activation were studied by regression analysis. RESULTS: After 15 min, bilateral activations (oxy-haemoglobin increase) were observed in frontal, somatosensory and motor cortices. After 30 min, the right motor and primary somatosensory cortices were found activated. Deoxy-haemoglobin increased after 15 min, returning to baseline at 30 min. After 15 min, there was a positive effect of gestational age at the assessment on both haemoglobin concentrations and a negative effect of previous kangaroo mother care on deoxy-haemoglobin increase. CONCLUSION: Motor and somatosensory cortices, particularly on the right side, showed significant activation during kangaroo mother care. Kangaroo mother care seems to benefit activated cortical areas by improving oxygen supply.

Empathy at birth: Mother's cortex synchronizes with that of her newborn in pain.

Early neonatal relation with the caregiver is vital for newborn survival and for the promotion of an appropriate neural development. The aim of this study was to assess if the empathic cortical response of a mother to her baby's pain is synchronized with the neonatal cortical response to the painful stimulation. We used hyperscanning, a functional neuroimaging approach that allows studying functional synchronization between two brains. Sixteen mother-newborn dyads were recruited. Maternal and neonatal cortical activities were simultaneously monitored, by near-infrared spectroscopy, during a heel prick performed on the baby and observed by the mother. Multiple paired t test was used to identify cortical activation, and wavelet transform coherence method was used to explore possible synchronization between the maternal and neonatal cortical areas. Activations were observed in mother's parietal cortex, bilaterally, and in newborn's superior motor/somatosensory cortex. The main functional synchronization analysis showed that mother's left parietal cortex activity cross-correlated with that of her newborn's superior motor/somatosensory cortex. Such synchronization dynamically changed throughout assessment, becoming positively cross-correlated only after the leading role in synchronizing cortical activities was taken up by the newborn. Thus, maternal empathic cortical response to baby pain was guided by and synchronized to the newborn's cortical response to pain. We conclude that, in case of potential danger for the infant, brain areas involved in mother-newborn relationship appear to be already co-regulated at birth.

Higher growth, fat and fat-free masses correlate with larger cerebellar volumes in preterm infants at term.

AIM: Smaller cerebellar volumes in very low-birthweight (VLBW) infants at term have been related to adverse cognitive outcomes, and this study evaluated whether these volumes were associated with a growth in body composition during hospital stays. METHODS: We prospectively recruited 42 VLBW infants from an Italian neonatal unit between January 2013 and August 2015. Cerebellar volumes and body composition were measured by magnetic resonance imaging (MRI) and air-displacement plethysmography, respectively, at 40 weeks of gestational age and anthropometric and nutritional data were collected. We also included 20 term-born controls. RESULTS: The mean gestational age and birthweight of the VLBW infants were 29.4 (±1.9) weeks and 1120 (±290) g. There was a positive correlation between cerebellar volumes and daily weight gain from birth to term (R2 = 0.26, p = 0.001), weight (R2 = 0.25, p = 0.001), length (R2 = 0.16, p = 0.01), fat mass (R2 = 0.15, p = 0.01) and fat-free mass at term (R2 = 0.20, p = 0.003). In multiple regression analysis, daily weight gain, mechanical ventilation and postconceptional age at MRI were independently associated with cerebellar volumes. Anthropometric data and cerebellar volumes were similar between VLBW and control infants. CONCLUSION: Higher growth, higher fat mass and fat-free mass were associated with larger cerebellar volumes in VLBW infants at term.

Impact of Surgery for Neonatal Gastrointestinal Diseases on Weight and Fat Mass.

OBJECTIVE: To compare growth, fat mass (FM), and fat-free mass in surgical infants vs matched controls at similar postconceptional age (PCA). STUDY DESIGN: Anthropometric and body composition measurements by air-displacement plethysmography (PeaPod-Infant Body Composition System; LMI, Concord, California) were performed at the same PCA in 21 infants who received gastrointestinal surgery and in 21 controls matched for gestational age, birth weight, and sex. RESULTS: Despite similar anthropometry at birth, postsurgical infants were shorter (50.4 [4.7] cm vs 53.2 [4.1] cm, P = .001), lighter (3516 [743] g vs 3946 [874] g, P < .001), and had lower FM content (%FM 14.8 [4.7]% vs 20.2 [5.8]%, P < .0001) than their peers at similar PCA (43 [4] weeks). All surgical infants but 1 (20/21) received parenteral nutrition (PN). Mean PN duration was 40 (30) days. Five infants in the control group received PN because of prematurity for 15 (9-30) days. Nine infants in the surgical group and 1 in the control group had PN-associated cholestasis. CONCLUSIONS: Neonates having surgery for gastrointestinal diseases were shorter, had lower weight, and lower FM content than their peers, despite receiving more PN. Body composition evaluation and monitoring may help optimize growth in these newborns.

Deletion of glutathione-s-transferase m1 reduces azathioprine metabolite concentrations in young patients with inflammatory bowel disease.

GOALS: To investigate, in young patients with inflammatory bowel disease (IBD) treated with azathioprine, the association between genetic polymorphisms of thiopurine-S-methyl-transferase (TPMT), inosine-triphosphate-pyrophosphatase (ITPA), and glutathione-S-transferases (GST), involved in azathioprine metabolism, the concentration of the main metabolites of azathioprine, thioguanine nucleotides (TGNs) and the methylated nucleotides (MMPN), and the dose of the medication. BACKGROUND: Azathioprine is widely used in IBD as an immunosuppressive agent, particularly to maintain remission in patients with steroid refractory disease. Azathioprine is a prodrug and requires conversion to its active form mercaptopurine, which has no intrinsic activity, and is activated by the enzymes of the purine salvage pathway to TGNs. Polymorphisms in genes of enzymes involved in azathioprine metabolism influence the efficacy and toxicity of treatment. STUDY: Seventy-five young patients with IBD treated with azathioprine at least for 3 months were enrolled and genotyped for the selected genes; for these patients, TGN and MMPN metabolites were measured by high performance liquid chromatography in erythrocytes. RESULTS: GST-M1 deletion was associated with lower TGN/dose ratio (P=0.0030), higher azathioprine dose requirement (P=0.022), and reduced response to therapy (P=0.0022). TPMT variant genotype was associated with lower MMPN concentration (P=0.0064) and increased TGN/dose ratio (P=0.0035). ITPA C94A polymorphism resulted in an increased MMPN concentration (P=0.037). CONCLUSIONS: This study describes the effect of candidate genetic polymorphisms in TPMT, ITPA, and GST-M1 on azathioprine pharmacokinetics in IBD patients, showing, for the first time, relevant effects of GST-M1 genotype on azathioprine metabolites concentration.

Longitudinal growth and body composition of twins versus singletons in the first month of life.

BACKGROUND: Although twin gestation is well recognized to be associated with impaired fetal and postnatal growth, specific data about body composition of twins in the first month of life are scarce. OBJECTIVE: The aim of this study was to compare the body composition of twins, evaluated with air-displacement plethysmography, to that of singletons of similar gestational age and adequacy of growth, during the first month of life. We tested the hypothesis that the quality of growth would be similar. METHODS: Anthropometric and air-displacement plethysmography measurements were performed in 18 pairs of twins and in 36 singleton neonates, longitudinally, from birth to the 30th day of life. Each twin was matched to a singleton infant of similar gestational age and birth weight z-score. RESULTS: With regard to anthropometric measures, the only difference was a lower weight in twins versus singletons on the 15th day of life. With regard to body composition, we did not find any difference between groups at any time point. Fat mass increased significantly from day 1 to day 30 in both twins and singletons. CONCLUSION: In terms of body composition, twins do not differ from singletons of similar gestational age and weight, either at birth or in early postnatal life.

Final adult height in childhood-onset inflammatory bowel disease.

BACKGROUND: Long-term growth may be compromised in patients with inflammatory bowel disease (IBD). The aims of the study were to evaluate the final height in a cohort of patients with pediatric-onset IBD with respect to genetic target and to determine factors influencing long-term growth. METHODS: This is a monocentric retrospective cohort study. All patients with diagnosed prepubertal onset IBD were enrolled. Patients were classified into two groups on the basis of the achievement of target height at time of the last follow-up. Clinical parameters were also recorded. RESULTS: Eighty-tow patients were identified: 42 with Crohn's disease (CD) and 40 with ulcerative colitis (UC). The mean age at diagnosis was 11.0 (SD 4.0) years. Eighty-nine percent of patients achieved final target height. Mean difference between final and target height was -1.2 cm (SD: 5,4). No statistical significance was detected between CD and UC patients final height (P=0.16). Growth failure at the diagnosis and disease severity were the only factors associated with final height achievement failure (P=0.001 and P=0.01 respectively). CONCLUSIONS: Most part of CD and UC patients achieve the target final height. Disease severity and low height at diagnosis seem to be the two best predictive factors for low final height.

Venipuncture activates the cerebral cortex in children with intellectual disability.

OBJECTIVE: To evaluate the pattern of cortical activation during a painful procedure, such as a venipuncture, in children with intellectual disability and compare it with that of cognitively healthy children. STUDY DESIGN AND SETTING: A cohort study was conducted and cortical activation was assessed by multichannel cerebral near-infrared spectroscopy to monitor variations in oxyhaemoglobin and deoxyhaemoglobin (Hbb) in children with and without intellectual disability during a venipuncture for blood sampling with topical anaesthesia. Pain and distress were assessed as well using different validated pain scales (visual analogue scale and Non-Communicating Children's Pain Checklist-Postoperative Version for children with intellectual disability), and compared between groups. PARTICIPANTS: 16 children with severe to profound intellectual disability and 20 cognitively healthy peers (age range: 4-17 years). RESULTS: When Hbb was analysed, children with intellectual disability exhibited a bilateral activation of the somatosensory (p<0.006) and right motor cortex (p=0.0045), whereas cognitively healthy peers never showed a cortical activation. Children with intellectual disability also showed more pain than controls (p=0.001). CONCLUSIONS: When subjected to a painful procedure, only children with intellectual disability show an activation of the cerebral cortex, even if topical anaesthesia is applied, and express more pain than cognitively healthy peers. The role of other issues in painful procedures, such as anxiety, fear or physical restraint, deserves further investigation.

Change in body composition of premature infants from parenteral nutrition discontinuation to term equivalent age.

AIM: To compare body composition (BC) of premature infants at parenteral nutrition (PN) suspension and at term equivalent age (TEA). METHODS: Body weight, fat mass (FM), fat free mass (FFM) and FM as % of body weight were measured in infants born at <32 gestational weeks by air-displacement plethysmography at PN suspension and at TEA in a tertiary level hospital. Z-scores were calculated for BC and anthropometric measurements. Nutritional and clinical data were obtained during hospital stay. BC, weight and length were measured at birth in a sample of infants born at term for comparison. RESULTS: Thirty premature infants with birth weight of 1198 ± 270 g and gestational age of 29.8 ± 1.8 weeks were included. At PN suspension, at 32.6 ± 1.6 postconceptional weeks, FFM z-score was similar to FFM z-score measured at TEA, at 39.8 ± 0.7 postconceptional weeks (-1.43 ± 1.27 vs -1.78 ± 1.64, p = 0.26), while FM z-score and %FM z-score at PN suspension were lower than those measured at TEA (FM z-score: 0.23 ± 0.62 versus 2.04 ± 1.00, p < 0.0001 and %FM z-score: 0.66 ± 0.76 versus 2.08 ± 1.07, p < 0.0001). At TEA, weight and length of premature infants were similar to those of term-born infants (3130 ± 340 g vs 3350 ± 340 g; 49.2 ± 2.4 cm vs 50.2 ± 2.5 cm, respectively), but %FM was higher (21.3 ± 4.2% vs 9.2 ± 4.4%, p < 0.001); higher exclusive enteral caloric and protein intakes were associated with a decrease in FM z-scores from PN suspension to TEA. CONCLUSION: In our sample of premature infants, fat free mass z-score was similar, while fat mass and % fat mass z-scores increased substantially from parenteral nutrition suspension to term-equivalent age. Nutritional intakes during exclusive enteral nutrition did not seem to contribute to such increase.

Cerebral Hemodynamics During Neonatal Cerebrospinal Fluid Removal.

BACKGROUND: Standard treatment of neonatal posthemorrhagic hydrocephalus is cerebrospinal fluid removal. The aim of this study was to assess how much cerebrospinal fluid volume removal, by ventricular reservoir taps, is needed to improve cerebral hemodynamics and oxygenation in neonatal posthemorrhagic hydrocephalus. METHODS: Cerebral hemodynamics and oxygenation were continuously monitored by near-infrared spectroscopy in four newborns (one term and three preterm) during 28 ventricular reservoir taps. At each tap, 10 mL/kg of cerebrospinal fluid was removed. Near-infrared spectroscopy detected changes in the concentration of oxy-hemoglobin and total hemoglobin, considered as estimates of cerebral blood flow and volume, respectively. Cerebral tissue oxygenation index was also measured. During cerebrospinal fluid removal, variation in cerebral blood flow, volume, and oxygenation were analyzed by repeated measures analysis of variance. The associations between changes in cerebral hemodynamics and oxygenation, during cerebrospinal fluid removal and after its conclusion, were analyzed by Pearson's r correlation coefficient. RESULTS: A significant increase in cerebral blood flow and volume was already evident at 50% of targeted cerebrospinal fluid volume removal (P < 0.001). Although cerebral tissue oxygenation index absolute value remained unchanged, variations in cerebral blood flow and oxygenation were positively correlated, both during cerebrospinal fluid removal and after its conclusion (r = 0.57; P = 0.002). CONCLUSIONS: On the basis of the results from this small cohort, the volume of cerebrospinal fluid removal associated with an improvement in cerebral hemodynamics and perfusion seems to be less than the traditional 10 mL/kg. Further research is needed to define the potential role of near-infrared spectroscopy monitoring to individualize cerebrospinal fluid removal.

TAS2R38 bitter taste genotype is associated with complementary feeding behavior in infants.

BACKGROUND: Genetically mediated sensitivity to bitter taste has been associated with food preferences and eating behavior in adults and children. The aim of this study was to assess the association between TAS2R38 bitter taste genotype and the first complementary food acceptance in infants.Parents of healthy, breastfed, term-born infants were instructed, at discharge from the nursery, to feed their baby with a first complementary meal of 150 mL at 4 to 6 months of age. They recorded the day when the child ate the whole meal in a questionnaire. Additional data included food composition, breastfeeding duration, feeding practices, and growth at 6 months. Infants' TAS2R38 genotypes were determined at birth, and infants were classified as "bitter-insensitive" (genotype AVI/AVI) and "bitter-sensitive" (genotypes AVI/PAV or PAV/PAV). RESULTS: One hundred seventy-six infants and their mothers were enrolled; completed data were available for 131/176 (74.4%) infants (gestational age 39.3 ± 1.1 weeks, birth weight 3390 ± 430 g). Bitter-insensitive were 45/131 (34.3%), and bitter-sensitive were 86/131 (65.6%). Thirty-one percent of bitter-insensitive infants consumed the whole complementary meal at first attempt, versus 13% of bitter-sensitive ones (p = 0.006). This difference was significant independently of confounding variables such as sex, breastfeeding, or foods used in the meal. Growth at 6 months did not differ between the two groups. CONCLUSIONS: Differences in TAS2R38 bitter taste gene were associated with acceptance of the first complementary food in infants, suggesting a possible involvement in eating behavior at weaning.

Infant Analgesia With a Combination of Breast Milk, Glucose, or Maternal Holding.

OBJECTIVES: We studied neonatal cortical brain response to 4 types of nonpharmacological analgesia (oral glucose, expressed breast milk, maternal holding plus oral glucose, breastfeeding). We aimed to assess the differential effect of oral solutions (glucose, breast milk) given alone or combined with the maternal-infant relationship (holding, breastfeeding). METHODS: Eighty healthy term newborns undergoing a heel stick were randomly assigned to 4 parallel groups of 20 infants each: group 1, infants received a glucose solution on a changing table; group 2, infants received expressed breast milk on a changing table; group 3, infants received a glucose solution in their mothers' arms; and group 4, infants were breastfed by their mothers. Cortical activation in parietal, temporal, and frontal cortices was assessed by multichannel near-infrared spectroscopy. Pain expression was also evaluated. RESULTS: Oral glucose alone or combined with maternal holding was associated with no cortical activation during heel stick. Expressed breast milk was associated with localized bilateral activation of somatosensory and motor cortices (P < .01). Breastfeeding was associated with extensive bilateral activation of somatomotor, somatosensory, and right parietal cortices (P < .01). Pain expression was lower with the maternal-infant relationship (P = .007). CONCLUSIONS: Oral glucose, either alone or combined with maternal holding, appears to block or weaken cortical pain processing. Breast milk alone is associated with localized cortical activation. Breastfeeding is associated with extensive activation and may act by extending cortical processing. Maternal relationship, both combined with oral glucose and in breastfeeding, shows the greatest analgesic effect, although the neural patterns involved are distributed differently.

Bolus feeding has no effect on cerebral hemodynamics, irrespective of gestational age.

OBJECTIVE: By multichannel near-infrared spectroscopy, we studied if gestational age has any influence on preterm cerebral hemodynamics, during bolus feeding. METHODS: Oxy-haemoglobin (HbO2), as cerebral blood flow estimate, and the ratio between HbO2 and total haemoglobin (HbO2/HbTot), as cerebral oxygenation estimate, were assessed in 40 stable premature infants, during a 10 min bolus feeding. RESULTS: We found no effect of any of the gestational ages studied (25-34 weeks) either on cerebral blood flow or on oxygenation, during a bolus feeding procedure. CONCLUSIONS: Bolus feeding appears not to affect cerebral hemodynamics of uncritically preterm infants, irrespective of gestational age.

Maternal cortical response to baby pain and postpartum depressive symptoms.

Decreased maternal empathic abilities toward infants have been reported with postpartum depression (PPD). The aims of this study were: (1) To identify mothers' cortical regions activated by the observation of their own newborn's pain; (2) To study the relation between such cortical activation and PPD symptoms. By optical topography, a functional neuroimaging system, we assessed mothers' cortical activation when watching their own newborns during a heel-prick. PPD symptoms and newborn's pain expression were also assessed. Watching their newborn in pain activated mothers' left somatosensory cortex (P=0.003) and right superior temporal cortex (P=0.002). PPD score showed a negative correlation with left somatosensory cortex activation (rs=-0.41; P=0.026), that decreased as PPD symptoms increased. To conclude, an activation of cortical areas, previously associated with empathy for pain, can be demonstrated in the mother shortly after birth. Such response appeared to be dampened by PPD symptoms.

The cortical response to a noxious procedure changes over time in preterm infants.

The aim of the study was to investigate whether cortical response to a repeated noxious procedure may change over time in preterm infants. Possible reasons for change are: (1) advancing maturation of central nervous system; and (2) increasing experience with noxious procedures during hospital stay. Sixteen preterm infants were recruited, with a postmenstrual age (PMA) ranging between 29 and 36 weeks. Newborns were assessed during a heel-prick procedure, once a week for at least 3 consecutive times. Multichannel near-infrared spectroscopy was used to detect cortical activation, by measuring increase in cortical oxy-haemoglobin (HbO2). Parietal, temporal, and posterior frontal areas were monitored bilaterally. By regression analysis, we studied the effect of (1) increasing PMA and (2) increasing number of heel pricks, on the magnitude of cortical activation. We observed a bilateral nociceptive event-related activation of the posterior frontal cortex, mainly contralateral to the side pricked. Additionally, we found a significant positive effect of PMA, as HbO2 progressively increased in the posterior frontal cortex (P < 0.001), bilaterally, over time. Conversely, the degree of cortical activation decreased as the number of noxious events increased (P < 0.002). We conclude the following: (1) Preterm newborns showed a significant activation of the posterior frontal cortex in association with noxious stimuli; (2) Cortical activation was progressively greater with increasing PMA; (3) There was an inverse relationship between cortical activation and the number of heel pricks. We speculate that such findings may be due to both endogenous cortical maturation and experience-dependent neuroplasticity of the developing brain (eg, synaptogenesis, synaptic pruning).