Quantitative ultrasonographic examination of cerebral white matter by pixel brightness intensity as marker of middle-term neurodevelopment: a prospective observational study.

Non-cystic white matter (WM) injury has become prevalent among preterm newborns and is associated with long-term neurodevelopmental impairment. Magnetic resonance is the gold-standard for diagnosis; however, cranial ultrasound (CUS) is more easily available but limited by subjective interpretation of images. To overcome this problem, we enrolled in a prospective observational study, patients with gestational age at birth < 32 weeks with normal CUS scans or grade 1 WM injury. Patients underwent CUS examinations at 0-7 days of life (T0), 14-35 days of life (T1), 370/7-416/7 weeks' postmenstrual age (T2), and 420/7-520/7 weeks' postmenstrual age (T3). The echogenicity of parieto-occipital periventricular WM relative to that of homolateral choroid plexus (RECP) was calculated on parasagittal scans by means of pixel brightness intensity and its relationship with Bayley-III assessment at 12 months' corrected age was evaluated. We demonstrated that: (1) Left RECP values at T1 negatively correlated with cognitive composite scores; (2) Right RECP values at T2 and T3 negatively correlated with language composite scores; (3) Left RECP values at T1 and T2 negatively correlated with motor composite scores. Thus, this technique may be used as screening method to early identify patients at risk of neurodevelopmental issues and promptly initiate preventive and therapeutic interventions.

The effects of industrial chemicals bonded to plastic materials in newborns: A systematic review.

BACKGROUND: Phthalates are a family of industrial chemicals noncovalently bonded to plastic materials to enhance flexibility and durability. These compounds are extensively used in a variety of consumer products and even in many medical devices. Newborns present a higher susceptibility to phthalates. OBJECTIVE: To assess the short- and long-term health consequences of exposure to phthalates during the neonatal period. METHODS: Systematic review in accordance with the PRISMA statements. Eligible articles in English language were searched in MEDLINE, Scopus, ISI Web of Science, and Ovid databases using the following terms: "phthalate", "newborn", and "neonate". Unpublished data were searched in ClinicalTrials.gov website. All in vivo studies of any design published before May 16th, 2023 and fulfilling the following criteria were included: 1) investigations in which preterm and/or term newborns underwent one or more measurement of concentrations of phthalates on biological samples taken during the neonatal period; 2) studies in which quantitative measurement of phthalates was related to any kind of health outcome. Subgroup analysis was conducted by type of outcome. The quality assessment was performed according to the criteria from the "NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies". RESULTS: 11,895 records were identified; finally, 5 articles were included for review. A mixture of phthalates was associated with improved performance on the NNNS summary scales of Attention, Handling, and Non-optimal reflexes before NICU discharge. At 2 months' corrected age, some phthalates were positively associated with problem-solving and gross motor abilities; increased levels of mono (2-ethylhexyl) phthalate, mono (2-ethyl-5-carboxypentyl) phthalate, and sum of di (2-ethylhexyl) phthalate (DEHP) metabolites (∑3DEHP and ∑4DEHP) were associated with worse fine motor performance. Furthermore, DEHP was associated with transient alteration of gut microbiota and increased IgM production after vaccine. A linear positive association between a mixture of phthalates and slope of the first growth spurt was even reported in preterm newborns. No relationship emerged between phthalates and bronchopulmonary dysplasia. Three studies out of 5 had fair quality. CONCLUSION: Given some methodological issues and the paucity of related studies, further investigations of flawless quality aimed at clarifying the relationship between early exposure to phthalates and health outcomes are needed.

Symptoms of post-traumatic stress disorder in parents of preterm newborns: A systematic review of interventions and prevention strategies.

Background: Preterm birth and subsequent NICU admission can be a traumatic experience for parents who may subsequently develop post-traumatic stress (PTS) disorder (PTSD). Given that developmental issues are common among children of parents with PTSD, interventions for prevention and treatment are essential. Objective: To assess the most effective non-pharmacological interventions to prevent and/or treat PTS symptoms in parents of preterm newborns. Methods: Systematic review performed in accordance with the PRISMA statements. Eligible articles in English language were searched in MEDLINE, Scopus, and ISI Web of Science databases using the following medical subject headings and terms: "stress disorder, post-traumatic," "parents," "mothers," "fathers," "infant, newborn," "intensive care units, neonatal," and "premature birth." The terms "preterm birth" and "preterm delivery" were also used. Unpublished data were searched in ClinicalTrials.gov website. All intervention studies published until September 9th, 2022 and including parents of newborns with gestational age at birth (GAb) <37 weeks which underwent ≥1 non-pharmaceutical interventions for prevention and/or treatment of PTS symptoms related to preterm birth were included. Subgroup analyses were conducted by type of intervention. The quality assessment was performed according to the criteria from the RoB-2 and the "NIH Quality Assessment Tool for Before-After studies." Results: Sixteen thousand six hundred twenty-eight records were identified; finally, 15 articles (1,009 mothers, 44 fathers of infants with GAb ≤ 366/7 weeks) were included for review. A good standard of NICU care (effective as sole intervention: 2/3 studies) and education about PTSD (effective in association with other interventions: 7/8 studies) could be offered to all parents of preterm newborns. The 6-session Treatment Manual is a complex intervention which revealed itself to be effective in one study with low risk of bias. However, the effectiveness of interventions still remains to be definitively established. Interventions could start within 4 weeks after birth and last 2-4 weeks. Conclusion: There is a wide range of interventions targeting PTS symptoms after preterm birth. However, further studies of good quality are needed to better define the effectiveness of each intervention.

Early nutritional intake influences the serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor in preterm newborns.

Introduction: Parenteral nutrition (PN) may have detrimental effects on neurodevelopment in preterm newborns. Moreover, enteral nutrition (EN) seems to be protective. To understand the mechanisms of how neurological development can be influenced by the route of administration of nutritional intake, we investigated the relationship between the serum levels of the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and nutritional intake received in early life by preterm newborns. Materials and methods: Specimens of blood were obtained at 28 days of life (DOL) for NGF/BDNF determination in neonates <32 weeks of gestation and/or with birth weight <1,500 g, consecutively observed in the neonatal intensive care unit. We analyzed the relation between amino acid content and energy intake and NGF/BDNF measurements at 28 DOL. PN protein intake was referred to as the total amounts of amino acid intake received daily. Results: We enrolled 20 newborns (gestational age 30.45 ± 1.76 weeks, birth weight 1,340 ± 352.63 g). Serum NGF value at 28 DOL was positively correlated with enteral protein and energy intake (r = 0.767; r = 0.746, p < 0.001), whereas, negatively correlated with parenteral amino acid and energy intake (r = -0.652, p < 0.001; r = -0.466, p < 0.05). Similar significant correlations were described between BDNF level at 28 DOL and enteral energy intake (r = 0.493, p < 0.05). Multivariate regression analysis showed that NGF level at 28 DOL depends on enteral protein and energy intake administrated in the 1st week of life. Conclusion: Neurotrophin values varied according to the route of nutrition administration in preterm newborns. NGF/BDNF serum levels are influenced positively and negatively by EN and PN, respectively.

Risk factors and preventive strategies for post-traumatic stress disorder in neonatal intensive care unit.

Background: Preterm birth and admission to the neonatal intensive care unit (NICU) could induce post-traumatic stress disorder (PTSD). PTSD is an important factor to focus on, as it is associated with parental mental health difficulties and with changes in caregiving quality such as increased intrusiveness, reduced sensitivity, and increased attachment insecurity for the child. Aims: We aimed to study the main risk factors, in the early life of newborns, and preventive measures for PTSD in parents of neonates hospitalized in the NICU. Methods: We included parents of preterm newborns, consecutively admitted to the NICU of the University La Sapienza of Rome. The presence of PTSD following preterm birth and NICU admission was assessed using the Clinician-administered PTSD scale (CAPS) at enrollment and at 28-30 days following NICU admission or the moment of discharge. We also evaluated the Family Environment Scale which measures the social environment of all types of families; the Parental Stressor Scale which measures parental anxiety and stress; the Spielberger State-Trait Anxiety Inventory consisting of two parts measuring the State (response to present situation) and Trait (pre-disposition to be anxious) anxieties separately, and the Beck Depression Inventory Second Edition assessing depressive symptoms. Results: We found, in a multivariate analysis, that the gestational age of newborns admitted to NICU significantly (ß = 2.678; p = 0.040) influences the occurrence of PTSD. We found that the cases showed significantly (ß = 2.443; p = 0.020) more pathological Parental Stressor Scale sights and sounds scores compared to controls. The early Kangaroo-Care (KC) significantly (ß = -2.619; p = 0.015) reduces the occurrence of PTSD. Conclusion: Post-traumatic stress disorder in parents of preterm newborns is a pathological condition that should be properly managed, in the very first days after birth. The NICU environment represents a main risk factor for PTSD, whereas KC has been demonstrated to have a protective role in the occurrence of PTSD.

1H-magnetic resonance spectroscopy and its role in predicting neurodevelopmental impairment in preterm neonates: A systematic review.

To assess the diagnostic utility of proton (1H) magnetic resonance spectroscopy in early diagnosis of neurodevelopmental impairment in preterm newborns. Systematic review performed in compliance with the PRISMA statements. Eligible articles were searched in MEDLINE, Scopus, and ISI Web of Science databases using the following medical subject headings and terms: "magnetic resonance spectroscopy," "infant," and "newborn." Studies of any design published until 20 December 2021 and fulfilling the following criteria were selected: (1) studies including newborns with gestational age at birth <37 weeks which underwent at least one 1H-MRS scan within 52 weeks' postmenstrual age and neurodevelopmental assessment within 4 years of age; (2) studies in which preterm newborns with congenital infections, genetic disorders, and brain congenital anomalies were clearly excluded. Data regarding the relationship between metabolite ratios in basal ganglia, thalamus, and white matter, and neurodevelopment were analysed. The quality assessment of included studies was performed according to the criteria from the QUADAS-2. N-acetylaspartate (NAA)/choline (Cho) was the most studied metabolite ratio. Lower NAA/Cho ratio in basal ganglia and thalamus was associated with adverse motor, cognitive, and language outcomes, and worse global neurodevelopment. Lower NAA/Cho ratio in white matter was associated with cognitive impairment. However, some associations came from single studies or were discordant among studies. The quality of included studies was low. 1H-MRS could be a promising tool for early diagnosis of neurodevelopmental impairment. However, further studies of good quality are needed to define the relationship between metabolite ratios and neurodevelopment.

Enteral and parenteral energy intake and neurodevelopment in preterm infants: A systematic review.

OBJECTIVES: We performed a systematic review to study the effect of enteral and parenteral energy intakes on neurodevelopment (NDV) and cerebral growth in preterm infants, evaluated by NDV scales, magnetic resonance imaging, and head circumference (HC). METHODS: The MEDLINE, Scopus, and ISI Web of Knowledge databases were searched, using the following medical subject headings and terms: "Premature infants," "nutrition," "brain," "nervous system/growth," and "development." A manual search of the reference lists of all eligible articles was conducted. Studies in which the intervention applied was different energy intakes in parenteral nutrition and/or enteral nutrition (EN) during the first weeks of life and NDV was investigated were included. Data regarding nutrition and NDV were collected and analyzed. RESULTS: Thirty-five studies were included, of which 12 were randomized controlled trials (RCTs) and 23 were cohort studies. Eight RCTs and 15 cohort studies investigated NDV using NDV scales. Of these studies, two RTCs and five cohort studies found no significant difference in NDV evaluated with the Bayley scale between neonates fed high-caloric nutrition and those who received lower energy intakes during early life. In one RCT and two cohort studies was observed a positive effect of EN on NDV. Conversely, in one cohort study, a negative correlation between parenteral energy intake and NDV was described. The analysis of the data from RCTs and cohort studies showed greater HC in the groups receiving aggressive parenteral and total enhanced nutrition, respectively. However, two RCTs and one cohort study did not report any differences in terms of HC. Inconclusive results were reported by studies that investigated cerebral growth by magnetic resonance imaging. The studies observing a positive effect of enhanced nutrition on cerebral and basal ganglia growth, caudate nucleus, cerebellum, and thalami volume investigated only the influence of EN. CONCLUSIONS: The impact of energy intake during early life on NDV remains undefined. A positive impact on brain development encourages the administration of recommended energy intake, mainly by EN, and suggests a more cautious approach to enhanced nutritional strategies by the parenteral route. Further studies are advocated to elucidate the optimal nutritional intervention for preterm infants to improve NDV.

Effects of early energy intake on neonatal cerebral growth of preterm newborn: an observational study.

Current guidelines for preterm newborns recommend high energy nutrition soon after birth in order to limit growth retardation. However, long-term effects of this nutritional approach are still debated, and it has been demonstrated that cerebral growth depends on protein intake in early life. A negative impact of early high energy intake by parenteral nutrition (PN) has been reported for patients in critically ill conditions, observed in intensive care unit. We aimed at evaluating the impact of energy intake on cerebral growth in preterm neonates early in life. We included preterm newborns with gestational age < 32 weeks or birth weight (BW) < 1500 g. Measurement of cerebral structures was performed by cranial Ultrasonography (cUS) between 3 and 7 days of life (DOL, T0) and at 28 DOL (T1). We evaluated the relation between energy intake and cerebral growth in the first 28 DOL. We observed in 109 preterm newborns a significant (p < 0.05) negative correlation between energy intake received by PN and right caudate head growth (r = - 0.243*) and a positive correlation between total energy intake and transverse cerebellum diameter (r = 0.254*). Multivariate analysis showed that energy intake administered by enteral nutrition (EN), independently increased growth of left caudate head (ß = 0.227*) and height cerebellar vermis (ß = 0.415*), while PN independently affected growth of both right and left caudate head (ß = - 0.164* and ß = - 0.228*, respectively) and cerebellum transverse diameter (ß = - 0.849*). The route of energy administration may exert different effects on cerebral growth in early life. High energy intake administered through EN seems to be positively correlated to cerebral growth; conversely, PN energy intake results in a poorer cerebral growth evaluated with cUS.

Impact of joint management of a COVID-19 mother and her newborn on the virus transmission: a case report.

BACKGROUND: Since last year, COVID-19, the disease caused by the novel Sars-Cov-2 virus, has been globally spread to all the world. COVID-19 infection among pregnant women has been described. However, transplacental transmission of Sars-Cov-2 virus from infected mother to the newborn is not yet established. The appropriate management of infants born to mothers with confirmed or suspected COVID-19 and the start of early breastfeeding are being debated. CASE PRESENTATION: We report a case of the joint management of a healthy neonate with his mother tested positive for Covid-19 before the delivery and throughout neonatal follow-up. The infection transmission from the mother to her baby is not described, even after a long period of contact between them and breastfeeding. CONCLUSION: It may consider an appropriate practice to keep mother and her newborn infant together in order to facilitate their contact and to encourage breastfeeding, although integration with infection prevention measures is needed.

Energy-enhanced parenteral nutrition and neurodevelopment of preterm newborns: A cohort study.

OBJECTIVES: Preterm births are at higher risk for neurodevelopment (NDV) disabilities. To limit long-term consequences, guidelines recommend aggressive parenteral nutrition (PN) soon after birth. The aim of this study was to examine the effects of energy-enhanced PN in the first week of life on long-term NDV in preterm neonates. METHODS: We compared two cohorts of newborns (group A: energy-enhanced PN and group B: energy-standard PN) with different energy intake in the first 7 d of life (DoL) given by PN with the same protein amount, to study the influences of an energy-enhanced PN on NDV at 24 mo of life evaluated with the Bayley Scale of Infant Development-III edition. RESULTS: We analyzed 51 newborns (A: n = 24 versus B: n = 27). The two cohorts were similar in baseline characteristics (gestational age group A 29 wk, 95% confidence interval [CI], 28-30 wk versus group B 29 wk, 95% CI, 28-30 wk; birth weight A: 1214 g, 95% CI, 1062-1365 g versus B 1215 g, 95% CI, 1068-1363 g; boys A 62.5% versus B 55.6%). Infants in cohort B showed significantly (P < 0.05) better gross motor, total scaled, and total composite motor scores (A: 8 (1) versus B 9 (2); A 17 (4) versus B 19 (5); A 91 (12) versus B 97 (15); respectively). Cohort A showed a higher percentage of infants with delayed socioemotional competence (A 30.4% versus B 7.7%, P < 0.05). No differences were found in growth parameters at 24 mo of life. Linear regression analysis showed that socioemotional competence and motor score were negatively associated with energy intake of the first 7 DoL given by PN. CONCLUSIONS: A more aggressive PN strategy results in lower motor score and socioemotional competence performance at 24 mo of life. More caution might be advocated for an energy-enhanced PN protocol, particularly in neonates with lower birth weight, for long-term NDV in preterm neonates.

Early Protein Intake Influences Neonatal Brain Measurements in Preterms: An Observational Study.

Introduction: To limit extrauterine growth restriction, recent guidelines on nutrition of preterm neonates recommended high protein intake since the first day of life (DOL). The impact of this nutritional strategy on the brain is still controversial. We aimed to evaluate the effects of protein intake on early cerebral growth in very low birth weight newborns. Materials and Methods: We performed serial cranial ultrasound (cUS) scans at 3-7 DOL and at 28 DOL in very low birth weight newborns consecutively observed in the neonatal intensive care unit. We analyzed the relation between protein intake and cerebral measurements at 28 DOL performed by cUS. Results: We enrolled 100 newborns (gestational age 29 ± 2 weeks, birth weight 1,274 ± 363 g). A significant (p < 0.05) positive correlation between enteral protein intake and biparietal diameter (r = 0.490**), occipital-frontal diameter (r = 0.608**), corpus callosum (length r = 0.293*, genu r = 0.301*), caudate head (right r = 0.528**, left r = 0.364**), and cerebellum (transverse diameter r = 0.440**, vermis height r = 0.356**, vermis width r = 0.377**) was observed at 28 DOL. Conversely, we found a significant negative correlation of protein intake given by parenteral nutrition (PN) with biparietal diameter (r = -0.524**), occipital-frontal diameter (r = -0.568**), body of corpus callosum (r = -0.276*), caudate head (right r = -0.613**, left r = -0.444**), and cerebellum (transverse diameter r = -0.403**, vermis height r = -0.274*, vermis width r = -0.462**) at 28 DOL. Multivariate regression analysis showed that measurements of occipital-frontal diameter, caudate head, and cerebellar vermis at 28 DOL depend positively on protein enteral intake (r = 0.402*, r = 0.305*, and r = 0.271*) and negatively by protein parenteral intake (r = -0.278*, r = -0.488*, and r = -0.342*). Conclusion: Brain development in neonatal life depends on early protein intake. High protein intake affects cerebral structures' measurements of preterm newborn when administered by PN. Positive impact on brain development encourages the administration of recommended protein intake mainly by enteral nutrition.

Consecutive siblings, each with two separate small bowel atresias.

The familial occurrence of multiple-level intestinal atresia in newborn is extremely uncommon, with very sporadic similar cases reported in the literature. We present a case of multiple intestinal atresia in two consecutive siblings who successfully underwent surgical repair.