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.

Acute drug reaction to phenylephrine and tropicamide collyrium in a late-preterm newborn: a case report.

BACKGROUND: Collyrium administration is a common procedure in the neonatal ward, both in preterm and at term babies. Various molecules are used to induce mydriasis and cycloplegia: among them, phenylephrine and tropicamide are the most popular, and their administration is generally considered safe. CASE PRESENTATION: A 35 + 2 weeks-old, 2510 g, well-appearing male newborn required an ophthalmologic evaluation after a doubtful red reflex test. A collyrium with 1% phenylephrine and 0.95% tropicamide was administered prior to the consult, one drop per eye. Two minutes after the administration, the baby developed a severe apnea that required tactile stimulation. Moreover, the area around his eyes became visibly pale. Three minutes later, the baby became severely bradycardic (59 bpm), but remained in good general condition, so that resuscitation maneuvers were not required. Bradycardia lasted for almost three hours and then gradually resolved. CONCLUSIONS: Cardiopulmonary manifestations, such as bradycardia and even cardiopulmonary arrest, are severe complications that can happen after phenylephrine collyrium administration in preterm newborns. However, they have been described in babies below 1500 g or with concurrent respiratory manifestations. Our patient, on the other hand, was late preterm, and never required a ventilatory support prior to the collyrium administration. Practitioners who deal with premature babies, even if late preterm, must be aware of these possible complications and administer phenylephrine collyrium carefully, where cardiopulmonary resuscitation equipment and personnel are available.

First-trimester absent nasal bone: is it a predictive factor for pathogenic CNVs in the low-risk population?

OBJECTIVE: To evaluate the association of first-trimester absent nasal bone (NB) and genetic abnormalities at G-banding karyotype and chromosomal microarray analysis (CMA) according to the nuchal translucency (NT) thickness. METHODS: This is a retrospective cohort study of fetuses that underwent the first-trimester scan for the combined test at 11+0 to 13+6 weeks' gestation. Invasive test with G-banding karyotype and/or CMA was performed based on the result of the combined test or if fetal defects were detected or for patient's choice, after genetic counseling. All cases with absent NB in the first and second trimester underwent a detailed anomaly scan with echocardiography in the second trimester, had a longitudinal ultrasound, and postnatal follow-up up to at least 1 year. RESULTS: Between 2013 and 2018, 7228 women underwent the first-trimester scan at 11+0 to 13+6 weeks. Overall prevalence of absent NB was 1.3% (96/7228). Of those, in 86 pregnancies (1.2%), the absence of NB was confirmed also in the second trimester: 0.58% (40/6909) in the group with NT <95th centile; 6%(14/233) in the group with NT between 95 and 99th centile; and 37.2% (32/86) in the group with NT >99th centile, respectively. CMA pathogenic variants were found only in the group with NT >99th centile with a diagnostic yield of 9.4%. Fetuses with absent NB and NT between 95 and 99th centile had in 57% (8/14) a major chromosomal anomaly, while in the NT <95 centile group, there were 5% (2/40) of chromosomal abnormalities (one inherited from the father). CONCLUSION: In the first trimester, the risk for genetic syndromes detectable by CMA is related mainly to the NT thickness rather than to the absence of NB per se. In fetuses with absent NB and NT >99th centile, CMA should be performed after karyotype analysis, while for NT between 95 and 99th centile, a karyotype should be proposed as first-line procedure. Data provided by our study may be helpful in counseling women/couples when an absent NB is identified in the first trimester.

Phenotypic expression of 19q13.32 microdeletions: Report of a new patient and review of the literature.

The phenotypic manifestations of microdeletions in the 19q13.32 region are still poorly known. In this paper we report a patient who presented with hypotonia, developmental delay, facial dysmorphism, micrognathia, kyphoscoliosis, and buried penis. Chromosomal microarray revealed an interstitial 327 kb de novo microdeletion in the 19q13.32 region comprising eight genes (ARGHAP35, NPAS1, TMEM160, ZC3H4, SAE1, BBC3, MIR3190, and MIR3191). Previously reported cases of microdeletions in the 19q13.32 region were reviewed and compared to our patient, highlighting the common features of a possible 19q13.32 microdeletion syndrome.

EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy.

Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0-49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed myelination and, less frequently, thalamic signal intensity changes evolving over time. Typical muscle biopsy features included fibre size variability, central/internal nuclei, abnormal glycogen storage, presence of autophagic vacuoles and secondary mitochondrial abnormalities. Nerve biopsy performed in one case revealed subtotal absence of myelinated axons. Post-mortem examinations in three patients confirmed neurodevelopmental and neurodegenerative features and multisystem involvement. Finally, downregulation of epg5 (CG14299) in Drosophila resulted in autophagic abnormalities and progressive neurodegeneration. We conclude that EPG5-related Vici syndrome defines a novel group of neurodevelopmental disorders that should be considered in patients with suggestive features in whom mitochondrial, glycogen, or lysosomal storage disorders have been excluded. Neurological progression over time indicates an intriguing link between neurodevelopment and neurodegeneration, also supported by neurodegenerative features in epg5-deficient Drosophila, and recent implication of other autophagy regulators in late-onset neurodegenerative disease.

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.

Risk-adjusted operative delivery rates and maternal-neonatal outcomes as measures of quality assessment in obstetric care: a multicenter prospective study.

BACKGROUND: Although the evaluation of caesarean delivery rates has been suggested as one of the most important indicators of quality in obstetrics, it has been criticized because of its controversial ability to capture maternal and neonatal outcomes. In an "ideal" process of labor and delivery auditing, both caesarean (CD) and assisted vaginal delivery (AVD) rates should be considered because both of them may be associated with an increased risk of complications. The aim of our study was to evaluate maternal and neonatal outcomes according to the outlier status for case-mix adjusted CD and AVD rates in the same obstetric population. METHODS: Standardized data on 15,189 deliveries from 11 centers were prospectively collected. Multiple logistic regression was used to estimate the risk-adjusted probability of a woman in each center having an AVD or a CD. Centers were classified as "above", "below", or "within" the expected rates by considering the observed-to-expected rates and the 95% confidence interval around the ratio. Adjusted maternal and neonatal outcomes were compared among the three groupings. RESULTS: Centers classified as "above" or "below" the expected CD rates had, in both cases, higher adjusted incidence of composite maternal (2.97%, 4.69%, 3.90% for "within", "above" and "below", respectively; p = 0.000) and neonatal complications (3.85%, 9.66%, 6.29% for "within", "above" and "below", respectively; p = 0.000) than centers "within" CD expected rates. Centers with AVD rates above and below the expected showed poorer and better composite maternal (3.96%, 4.61%, 2.97% for "within", "above" and "below", respectively; p = 0.000) and neonatal (6.52%, 9.77%, 3.52% for "within", "above" and "below", respectively; p = 0.000) outcomes respectively than centers with "within" AVD rates. CONCLUSIONS: Both risk-adjusted CD and AVD delivery rates should be considered to assess the level of obstetric care. In this context, both higher and lower-than-expected rates of CD and "above" AVD rates are significantly associated with increased risk of complications, whereas the "below" status for AVD showed a "protective" effect on maternal and neonatal outcomes.

Severe neonatal hyperbilirubinemia and UGT1A1 promoter polymorphism.

OBJECTIVE: To assess whether UGT1A1 promoter polymorphisms associated with Gilbert Syndrome (GS) occur with a greater frequency in neonates with severe hyperbilirubinemia. STUDY DESIGN: In a case-control study performed at a single hospital center in Italy, 70 case subjects with severe hyperbilirubinemia (defined as bilirubin level ≥20 mg/dL or 340 µmol/L) and 70 controls (bilirubin level <12 mg/dL or 210 µmol/L) were enrolled. Both case and control subjects were full term newborns. Polymerase chain reaction analysis on blood spot was performed to determine the frequency of UGTA1A1 promoter polymorphisms in cases and controls. RESULTS: No statistical difference in the prevalence of UGTA1A1 gene variants was found between cases and controls (P = 1). Thirteen infants homozygous for (TA)7 polymorphism associated with GS were in the case group (18.6%) and 14 in the control group (20.0%). A heterozygous group was also equally distributed between cases (44.3%) and controls (42.9%). No (TA)8 repeat was found in the 2 groups. CONCLUSIONS: In our study population, GS polymorphism alone does not appear to play a major role in severe neonatal hyperbilirubinemia in neonates without signs of hemolysis.

Parental stress, depression, anxiety and participation in care in neonatal intensive care unit: a cross-sectional study in Italy comparing mothers versus fathers.

BACKGROUND: This study aimed at documenting the levels of stress, depression, anxiety and participation in care among mothers versus fathers of newborns hospitalised in a third-level neonatal intensive care unit (NICU) in Northern Italy. METHODS: Parental stress, depression and anxiety were assessed by the Parental Stressor Scale in NICU (PSS:NICU), the Edinburgh Postnatal Depression Scale (EPDS) and the State-Trait Anxiety Inventory (STAI). Participation in care was evaluated with the Index of Parental Participation. Differences between mothers and fathers were assessed with the Mood's median test and z-test, respectively for continuous and discrete variables. Multivariate analyses controlling for potential confounders were performed to confirm gender differences. RESULTS: 191 parents (112 mothers and 79 fathers) were enrolled. Mothers reported significantly higher median scores for stress (2.9 vs 2.2, p<0.001) and trait anxiety (37 vs 32, p=0.004) and higher depression rates (EPDS ≥12: 43.8% vs 19.0%, p<0.001). 'High stress' (PSS:NICU ≥3) was reported by 45.5% of mothers compared with 24.1% of fathers (p=0.004). The frequency of the three conditions simultaneously was significantly higher among mothers (20.0% vs 3.8%, p=0.016), with the vast majority of mothers (76.0%) suffering from at least one condition compared with less than half of fathers (45.3%, p<0.001). Participation in care was more frequent in mothers (median score: 19 vs 15, p<0.001), with the exception of activities related to advocacy (median 5 vs 4, p=0.053). In a multivariate analysis, gender differences in mental health outcomes did not change. CONCLUSIONS: Routine screening of mental distress among parents of infants in NICU is warranted, and gender differences need to be acknowledged in order to deliver tailored support and to promote collaboration with the family of vulnerable newborns. Knowledge and skills on how to prevent and cope with mental distress of parents should be part of the core curriculum of staff working in NICU.

Current hospital policies on breastfeeding: a survey from Italy.

BACKGROUND: The availability of an appropriate newborn feeding policy is an essential component of the promotion of breastfeeding in health facilities. The Italian Society of Neonatology (SIN) and the Italian Society of Paediatrics (SIP) have run an online survey among Maternity Hospitals to explore the existing breastfeeding policies and their characteristics. METHODS: Between February and April 2023, an online survey was carried out among 110 Italian maternity hospitals with a Neonatal Intensive Care Unit (NICU). RESULTS: Forty-nine Maternity Hospitals completed the online questionnaire. Twenty out of 49 (40.8%) reported to have a breastfeeding policy. When a policy is available, its quality appears to be suboptimal because of lack of inclusion of a family representative in the policy working group, limited options for translating breastfeeding policy into minority languages, lack of periodic assessment of their implementation. CONCLUSION: Currently, only a limited number of Italian Maternity Hospitals have developed a breastfeeding policy. Additional efforts are needed for their improvement as well as implementation.

Prenatal anteroposterior pelvic diameter cutoffs for postnatal referral for isolated pyelectasis and hydronephrosis: more is not always better.

PURPOSE: Congenital hydronephrosis and isolated pyelectasis are frequently diagnosed by prenatal ultrasound. About 80% of cases resolve spontaneously in early childhood. Currently there is no agreed on protocol for prenatal followup. Most clinicians use a renal pelvis anteroposterior diameter of greater than 4 mm as a threshold for identifying isolated pyelectasis and hydronephrosis at 33 weeks of gestation or anteroposterior diameter greater than 7 mm at 40 weeks of gestation. We sought to determine a fetal renal pelvis diameter cutoff at 20 and 30 weeks of gestation that would be able to predict significant nephron uropathy requiring surgery. MATERIALS AND METHODS: Our protocol included 2 prenatal ultrasounds at 20 and 30 weeks of gestation and 3 postnatal ultrasounds at ages 1, 6 and 12 months. Between January 2009 and December 2011 we evaluated 149 prenatal cases (130 males, 19 females) of isolated pyelectasis and 41 cases (28 males, 13 females) of hydronephrosis with a renal pelvis anteroposterior diameter of greater than 4 mm at 20 weeks of gestation. RESULTS: For isolated pyelectasis we identified cutoffs of 6 mm at 20 weeks of gestation (100% sensitivity, 84.3% specificity) and 10 mm at 30 weeks of gestation (100% sensitivity, 91.9% specificity). For hydronephrosis we identified cutoffs of 10 mm at 20 weeks of gestation (100% sensitivity, 86.1% specificity) and 12 mm at 30 weeks of gestation (100% sensitivity, 66.7% specificity). CONCLUSIONS: Using these thresholds, we could avoid a significant number of followup ultrasounds in the prenatal and postnatal periods, as well as invasive postnatal tests (ie voiding cystourethrography and mercaptoacetyltriglycine scintigraphy) without missing even a single case of obstructive nephropathy requiring surgery.