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Late-preterm infants (LPT) are at increased risk for long-term neurodevelopmental sequelae and iron deficiency. The aim of the study is to assess the positive effect of iron supplementation on psychomotor development in healthy LPT. We designed a randomized placebo-controlled double-blind trial dividing the newborns into two groups. Every patient was assessed using the Griffiths Mental Development Scales (GMDS)-II edition at 12-month post-conceptional age. The study was performed at the Neonatology Unit of our Hospital, in Italy. Sixty-six healthy LPT infants born between -340/7 and -366/7 weeks of gestational age were enrolled in the study. One group received martial prophylaxis from the third week of life to 6 months of post-conceptional age (2 mg/kg/day of iron pidolate), the other received placebo. Fifty-two of the enrolled infants were assessed using the GMDS at 12-month of post-conceptional age. Statistical analysis of the mean scores of the Griffiths subscales was performed. There was a difference in the mean developmental quotient (DQ) (p < 0.01) between the two groups: iron group mean DQ 121.45 +/- 10.53 vs placebo group mean DQ 113.25 +/- 9.70. Moreover, mean scores of the Griffiths subscales A, B, and D showed significant differences between the two groups (scale A p < 0.05, scale B p < 0.02, scale D p < 0.01, respectively).Conclusions: We recommend that all LPT neonates receive iron supplementation during the first 6 months of life in order to improve their 1-year neurodevelopmental quotient.

Aims: To investigate the efficacy of a galactagogue, containing Sylimarin-phosphatidylserine (SILITIDIL) and galega consumed in the first month after delivery by mothers of preterm infants, in maintaining milk production during the first 3-6 months after delivery. Materials and Methods: Mothers of infants born at gestational age (GA) between 27 and 32 weeks, enrolled in our previous prospective, double-blind, randomized trial and randomly allocated to receive either the galactagogue (GG) or a placebo (PG), were asked about their milk production at 3 and 6 months after delivery. Results: Of the 100 mothers involved in this study, 45 of GG and 44 of PG responded comprehensively to the questions asked. At the third month after delivery, exclusive human milk administration was reported by 22 mothers of GG and 12 mothers of PG (p < 0.05), whereas 29 mothers of GG and 18 mothers of PG were able to administer >50% of the amount of milk assumed. At the sixth month of life, only eight infants received exclusive human milk (six and two of GG and PG, respectively), and the data are not sufficient for a meaningful clinical evaluation. Conclusions: It is assumed that a galactagogue during the first month after delivery improves human milk administration to preterm neonates after discharge and for the first 3 months of life.

Objective To investigate whether fetal growth restriction (FGR) diagnosis, based on pathological prenatal fetal Doppler velocimetry, is associated with bronchopulmonary dysplasia (BPD) independently of being small for gestational age (SGA) per se at birth among very preterm infants. Design Prospective, observational study. FGR was defined as failing fetal growth in utero and fetal Doppler velocimetry abnormalities. Setting Policlinico Universitario Agostino Gemelli, Roma, Italy. Patients Preterm newborns with gestational age ≤30 weeks and birth weight (BW) ≤1250 g. Main outcome measures Bronchopulmonary dysplasia. Results In the study period, 178 newborns were eligible for the study. Thirty-nine infants (22%) were considered fetal growth-restricted infants. Among the 154 survived babies at 36 weeks postmenstrual age, 12 out of 36 (33%) of the FGR group developed BPD versus 8 out of 118 (7%) of the NO-FGR group (p<0.001). BPD rate was sixfold higher among the SGA-FGR infants compared with the SGA-NO-FGR infants. In a multivariable model, FGR was significantly associated with BPD risk (OR 5.1, CI 1.4 to 18.8, p=0.01), independently from BW z-score that still remains a strong risk factor (OR 0.5, CI 0.3 to 0.9, p=0.01). Conclusion Among SGA preterm infants, BPD risk dramatically increases when placenta dysfunction is the surrounding cause of low BW. Antenatal fetal Doppler surveillance could be a useful tool for studying placenta wellness and predicting BPD risk among preterm babies. Further research is needed to better understand how FGR affects lung development.

BACKGROUND: Continuous glucose monitoring using subcutaneous sensors has been validated in adults and children with diabetes, and was found to be useful in the management of glucose control. We aimed to assess feasibility and reliability of a new continuous glucose monitoring system (CGMS) in a population of preterm neonates using a Clarke error grid (CEG) specifically modified for preterm infants. METHODS: Preterm infants were recruited within 24 h from delivery. A subcutaneous sensor connected to a CGMS was inserted and maintained for 6 days. Data collected from CGMS were compared with data obtained using a glucometer. Management of the infants followed standard protocols and was not influenced by CGMS readings. RESULTS: Twenty patients (9 males) were included. Median (range) gestational age was 32 weeks (27-36) and median (range) birth weight was 1350 g (860-3360). Average CGMS recording time was 137 h, for a total of 449 paired glucose levels. CEG and modified CEG criteria for clinical significance were met. CONCLUSION: CGMS is a safe and clinically adequate method to estimate glucose levels in preterm infants. As the glucose level can be evaluated in real time, this CGMS could be useful to reduce the number of heel sticks, to observe glycaemic trends and to promptly detect episodes of both hypo- and hyper-glycaemia.

BACKGROUND/OBJECTIVES: Human milk (HM) is the best possible food for all infants, especially for preterm ones, but lactation and breastfeeding are very difficult for mothers of preterm babies and high rates of breastfeeding difficulties have been reported. Our aim was to investigate the efficacy of a galactogogue containing silymarin-phosphatidylserine and galega in increasing milk production during the first month after delivery in a population of mothers of preterm infants. SUBJECTS/METHODS: Mothers of infants with gestational age (GA) between 27+0 and 32+6 weeks were enrolled in this prospective, double-blind, randomized trial and were randomly allocated to receive either the galactogogue containing silymarin-phosphatidylserine and galega, 5 g/day (galactogogue group, GG), or a placebo, 5 g of lactose per day (placebo group, PG) from the 3rd to the 28th day after delivery. RESULTS: Fifty mothers were included in each group. General characteristics of mothers and pregnancies were similar. Milk production was significantly greater in the GG at the 7th day of life and at the 30th day of life. Daily milk production from the 7th to the 30th day of life was 200 (110-380) ml in the GG vs 115 (60-245) ml in the PG (P<0.0001). The total production of milk during the study period was significantly higher in the GG (6523±5298 ml vs 4136±4093 ml; P<0.02). At the end of the study, 45 mothers of the GG were able to reach the target of milk supply of 200 ml/day compared with 25 mothers of the PG (P<0.01). No adverse reactions were noticed in the study groups. CONCLUSIONS: Silymarin-phosphatidylserine and galega increased milk production in mothers of preterm infants without any significant side effects.

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BACKGROUND: Infants born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse outcomes than those born at 37 weeks of gestation or later. Aim of this paper is to examine risk factors for late preterm births and to investigate the complications of the transition period in late preterm infants (LPIs). METHODS: All consecutive late preterm deliveries, excluded stillbirths, were included. Maternal and neonatal data, need for delivery room resuscitative procedures, temperature at birth (T1) and two hours after the admission (T2) were analyzed in all LPIs stratified by Gestational Age (GA) and divided into three groups (34, 35 and 36 weeks). RESULTS: Two hundred seventy-six LPIs were analyzed. Pregnancy complications were present in 72 mothers (26.1 %), more frequently at 34 weeks of gestation respect to 35 and 36 weeks (p = 0.008, p = 0.006 respectively). Forty seven LPIs (17.1 %) needed for any resuscitation and 37 (13.4 %) were ventilated at birth. LPIs at 34 weeks were significantly more likely to receive ventilation respect to those at 35 and 36. At T1 the mean temperature resulted lower at 34 weeks respect to 36 weeks (p = 0.03). At T2 respect to T1, the rate of normothermic neonates increased at 35 and 36 weeks (p = 0.003, p = 0.005, respectively). Hypoglicemia rate was similar among the groups; 66.7 % of hypoglicemic neonates were hypothermic at T1. The rate of respiratory diseases and NICU admission decreased with increasing GA. Higher number of neonates ventilated at birth developed respiratory disorders respect to those unventilated (40.5 % vs 8.4 %; p < 0.001). CONCLUSIONS: Transition period in LPIs may become critical, as resuscitation strategies can be required and heat loss can occur. LPIs, especially at 34 gestational weeks, are higher-risk group needing adequate and targeted management at birth.

AIMS: Preterm breast milk contains high levels of bioactive components, including insulin-like growth factor 1 (IGF-1), that are reduced by Holder pasteurization. Animal studies have shown that milk-borne IGF-1 is likely absorbed intact in a bioactive form by the intestines. The aim of this study was to assess if early non-pasteurized expressed breast milk nutrition may affect IGF-1 plasma levels in premature infants. We also investigated the possible association between early expressed milk nutrition and short-term outcomes. METHODS: Fifty-two preterm infants with gestational age < 31 weeks were divided into two groups according to expressed breast milk intake (< or ≥ 50 mL/Kg/day) until 32 weeks of postmenstrual age when blood sampling for IGF-1 analysis was performed. RESULTS: In our population, early expressed breast milk does not affect IGF-1 plasma levels (p 0.48). An association was observed between early expressed milk nutrition and a lower incidence of bronchopulmonary dysplasia, sepsis, feeding intolerance, need for parenteral nutrition and length of hospitalization. CONCLUSIONS: Contrary to the results in some animal studies, our results did not seem to show that early expressed breast milk can help to maintain postnatal IGF-1 near foetal levels in preterm infants. The observed protective effect of expressed breast milk on short-term outcomes can be the starting point for further study of the effects of non-pasteurized human milk in preterm infants.

Background: Neonatal blueberry muffin lesions are rare cutaneous eruptions, presenting as transient, non-blanching, red-violaceous papules, mostly localized in the trunk, head and neck, attributable to a marked dermal hematopoietic activity. Congenital infections of the TORCH complex (toxoplasmosis, other, rubella, cytomegalovirus and herpes) and hematological disorders have been classically associated with this neonatal dermatological manifestation. We report for the first time an unusual presentation of blueberry muffin lesions in a neonate born from a mother affected by severe anemia during pregnancy. Case presentation: A male, white Caucasian, neonate showed a cutaneous rash at birth, suggestive of "blueberry muffin"-like lesions. These cutaneous lesions were associated with marked elevation of the circulating nucleated red blood cells, and with ultrasound findings of peculiar brain ischemic porencephalic lesions. The clinical features of spontaneous disappearance and the association with marked erythroblastosis strongly suggest that these dermatological findings may be the consequence of an extramedullary hematopoiesis unexpectedly evoked by the intrauterine chronic exposure to hypoxia caused by severe maternal anemia. Conclusions: In conclusion, fetal hypoxia secondary to severe maternal anemia may play a causative and unreported role in the development of neonatal blueberry muffin lesions.

Early discharge (ED) of healthy “late preterm” and full term newborn infants has become a common practice because of current social and economic necessities. The average length of stay of mothers and infants after delivery shortened steadily from 1970 until the mid-1990s and in 1995, the American Academy of Pediatrics (AAP) defined early and very early discharge as stays of 48 and 24 hours, respectively, after uncomplicated vaginal delivery. The length of stay (LOS) of a child after birth has been a controversial topic over the past few decades. A Cochrane Review in 2002 found that early postnatal discharge showed no adverse effects on breastfeeding and maternal depression when accompanied by a policy of nursing/midwifery home visits. Even if this practice has become more and more widespread, there was an increased rate of early post discharge readmission for jaundice, feeding problems, excessive weight loss (WL), dehydration and hypernatremia. For this reason, it is recommended that early discharged neonates should be evaluated shortly after discharge. Our aim was to review the available data about the safety of ED as regards to the most common problems causing hospital readmission.

Objective: To evaluate the prevalence of joint laxity in children born preterm assessed in the first 2 years, the relationship between joint laxity and motor performance at preschool age, and possible changes over time in a subgroup of children followed longitudinally. Study design: The revised scale of Beighton Score was used to evaluate joint laxity in a population of 132 preschool children born preterm between 24 and 32 weeks of gestational age. All were assessed for joint laxity between 12 and 24 months of age. Children also performed the Movement Assessment Battery for Children-Second Edition between the age of 3 years and 6 months and 4 years; the age at onset of independent walking also was recorded. Results: The total Beighton Score ranged between 0 and 8. Twenty percent of the cohort showed joint laxity. No differences related to sex or gestational age were observed. Children born preterm with joint laxity achieved later independent walking and achieved lower scores on Movement Assessment Battery for Children-Second Edition than those without joint laxity. In 76 children born preterm, an assessment for joint laxity was repeated once between 25 and 36 months and again after >36 months. No statistically significant difference was observed between the 3 assessments. Conclusions: The Beighton Score can be used to assess generalized joint laxity in children born preterm. As the presence of joint laxity influenced motor competences, the possibility to early identify these infants in the first 2 years is of interest to benefit from early intervention and potentially improve gross motor skills and coordination.

Purpose: The purpose of this paper is to investigate occult spinal dysraphisms (OSD) using lumbar ultrasonography (LUS) in newborns presenting with specific skin markers or sacrococcygeal dimple. Method: From 2012 to 2015, we performed LUS in newborns with cutaneous stigmata and/or sacroccygeal dimple. Magnetic resonance imaging (MRI) was performed in all patients with abnormal ultrasound or features of neurological involvement in order to detect spinal lesions. Results: We prospectively evaluated 475 newborns who presented cutaneous stigmata performing LUS during their 4 weeks of life though 439 completed the study. All patients had a follow-up of almost 12 months. Of these, 39 presented abnormal ultrasonography and underwent MRI. In this group, spinal dysraphism was confirmed in 12 patients. When considering skin markers, dermal sinus correlated with higher risk of spinal cord lesions, on the other hand the presence of simple sacral dimple alone denoted a very low risk of occult spinal dysraphism. The simultaneous presence of more skin markers and/or the presence of lumbar ultrasonography abnormality regarding the level of the conus, pulsatility, and the position of the cord, thickness of the filum terminale, or the presence of an intratecal mass, lipoma, or dermal sinus tract indicated the necessity to perform MRI in order to detect spinal cord abnormalities because of higher risk of spinal lesions. Conclusion: LUS in newborns with specific skin markers is a valid method to select patients in which MRI can be performed to detect OSD. The presence of a simple sacral dimple alone is a negligible marker for occult neural pathology while the presence of isolated dermal sinus or more than one cutaneous marker could be considered indicative of higher risk of spinal dysraphism.

BACKGROUND: Few neurological assessments are easily performed during the first 6h after birth. AIMS: To assess a cohort of low risk term born newborns within the first 6h and at 48h after birth using the Hammersmith Neonatal Neurological Examination. STUDY DESIGN AND SUBJECTS: A population of low risk term born newborns was examined within 3h from birth or between 3 and 6h. Each infant was re-assessed at 48h, establishing the range and frequency distribution of neonatal neurological scores at each time point. RESULTS: Of the 124 full-term born newborns, 62 were assessed at 0-3h and 62 at 3-6h. All infants were re-assessed at 48h. For 23/34 of the neurological items, the range and median scores were similar across the 3 time points. In the remaining 11 items the three groups had a similar range of scores but the median scores were different with different rates of changes. In 6 of the 11 the median scores at 3-6h were similar to those observed at 48h but they appeared to be 'less mature' at 0-3h. Only in one item the median scores were consistently different at the 3 time points. CONCLUSIONS: Our results suggest that a neurological examination can already be reliably performed soon after birth. These findings will help in the interpretation of the few items that show changes with increasing postnatal age.

BACKGROUND: The analysis of early patterns of lung disease among preterm infants may help to identify predictors of pulmonary deterioration. OBJECTIVES: To analyze FIO2 requirement in the first 14 days of life among preterm infants and to find predictors of bronchopulmonary dysplasia (BPD). METHODS: Retrospective cohort study. SETTING: 3 Italian level III NICUs. POPULATION: infants born between 240/7 and 276/7 weeks' gestational age (GA) who survived to 14 days. A consecutive sample of 588 infants was analyzed. Daily mode FIO2 in the first 2 weeks of life were analyzed according to the criteria defined by Laughon et al. [Pediatrics 2009;123:1124-1131], who found 3 early respiratory patterns: consistently low FIO2 (LowFIO2), pulmonary deterioration (PD), and early persistent pulmonary deterioration (EPPD). Factors associated with pulmonary deterioration were studied by univariate and multivariate analysis. RESULTS: Forty percent of infants had low FIO2, 18% had pulmonary deterioation, 21% had early persistent pulmonary deterioration, and 21% had a previously unreported pattern (pulmonary improvement, PI). The prevalence of BPD was 7% in the LowFIO2 group, 28% in the PI group, 44% in the PD group, and 62% in the EPPD group (p = 0.000). Infants with lung deterioration were more frequently males (OR = 2.019, CI: 1.319-3.090, p = 0.001), had lower GA (OR = 0.945, CI: 0.915-0.975, p = 0.000), higher incidence of severe respiratory distress syndrome (OR = 2.956, CI: 1.430-6.112, p = 0.003), and lack of postnatal caffeine (OR = 0.167, CI: 0.052-0.541, p = 0.003). CONCLUSIONS: We report 4 distinct patterns of early respiratory disease associated with significantly different prevalence of BPD and discuss risk factors for lung deterioration.

Purpose: Neural tube defects (NTDs) occur in 1:1000 births. The etiology is complex, with the influence of environmental and genetic factors. Environmental factors, such as folate deficiency, diabetes, or hypoxia strongly contribute to the occurrence of NTD. Also, there is a strong genetic contribution to NTD, as highlighted by the number of genes so far identified in several different developmental pathways usually altered in NTD. Each gene identified so far accounts for a small percentage of all NTD cases, indicating a very high heterogeneity. Methods: Exome sequencing was performed in seven sporadic patients with severe mielomeningocele. Novel coding variants shared by two or more patients were selected for further analysis. Results: We identified in two unrelated patients two different variants in TNIP1, a gene not previously involved in NTD whose main role is downregulation of the NF-kB pathway. One variant, c.1089T>G (p.Phe363Leu), is de novo, whereas the c.1781C>T (p.Pro594Leu) is absent in the mother, but could not be tested in the father, as he was unavailable. The latter variant is a very rare variant in the ExAC database. Conclusions: These findings suggest that TNIP1 is a new potential predisposing gene to spina bifida (SB) and its pathway needs to be investigated in human NTD in order to confirm its role and to plan appropriate counseling to families.