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Abstract Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Objectives: To describe how SARS-CoV-2 infection at the time of delivery affected maternal and neonatal outcomes across four major waves of the COVID-19 pandemic in Italy., Methods: This is a large, prospective, nationwide cohort study collecting maternal and neonatal data in case of maternal peripartum SARS-CoV-2 infection between February 2020 and March 2022. Data were stratified across the four observed pandemic waves., Results: Among 5201 COVID-19-positive mothers, the risk of being symptomatic at delivery was significantly higher in the first and third waves (20.8-20.8%) than in the second and fourth (13.2-12.2%). Among their 5284 neonates, the risk of prematurity (gestational age <37 weeks) was significantly higher in the first and third waves (15.6-12.5%). The risk of intrauterine transmission was always very low, while the risk of postnatal transmission during rooming-in was higher and peaked at 4.5% during the fourth wave. A total of 80% of positive neonates were asymptomatic., Conclusion: The risk of adverse maternal and neonatal outcomes was significantly higher during the first and third waves, dominated by unsequenced variants and the Delta variant, respectively. Postnatal transmission accounted for most neonatal infections and was more frequent during the Omicron period. However, the paucity of symptoms in infected neonates should lead us not to separate the dyad., Competing Interests: Declaration of Competing Interest All authors have no competing interests to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The thermal servo-controlled systems are routinely used in neonatal intensive care units (NICUs) to accurately manage patient temperature, but their role during the immediate postnatal phase has not been previously assessed., Objective: To compare two modalities of thermal management (with and without the use of a servo-controlled system) immediately after birth., Study Design and Setting: Multicentre, unblinded, randomised trial conducted 15 Italian tertiary hospitals., Participants: Infants with estimated birth weight <1500 g and/or gestational age <30 +6 weeks., Intervention: Thermal management with or without a thermal servo-controlled system during stabilisation in the delivery room., Primary Outcome: Proportion of normothermia at NICU admission (axillary temperature 36.5°C-37.5°C)., Results: At NICU admission, normothermia was achieved in 89/225 neonates (39.6%) with the thermal servo-controlled system and 95/225 neonates (42.2%) without the thermal servo-controlled system (risk ratio 0.94, 95% CI 0.75 to 1.17). Thermal servo-controlled system was associated with increased mild hypothermia (36°C-36.4°C) (risk ratio 1.48, 95% CI 1.09 to 2.01)., Conclusions: In very low birthweight infants, thermal management with the servo-controlled system conferred no advantage in maintaining normothermia at NICU admission, while it was associated with increased mild hypothermia. Thermal management of preterm infants immediately after birth remains a challenge., Trial Registration Number: NCT03844204., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate whether in a historical cohort of preterm infants, body composition at term equivalent age (TEA) correlated with Bayley scores at 2 years of corrected age., Study Design: Ninety-five preterm babies were admitted to our neonatal intensive unit and underwent air-displacement plethysmography assessment at TEA. Of these, 74 completed Bayley tests at 2 years. We used multiple linear regression analysis to assess the association of body composition with Bayley scores., Results: Mean gestational age and birthweight of our population were respectively 29.8 (±2.2) weeks and 1150 (±330) grams. Higher fat-free mass (FFM) z-score was associated with higher language (adjusted r = 0.28, p = 0.03) and motor composite scores (adjusted r = 0.33, p = 0.03) in both univariate and multiple regression analysis including birth weight, sex, maternal university degree, mechanical ventilation, and bilingualism., Conclusions: In our study FFM at term equivalent age was associated with higher Bayley composite motor and language scores at 2 years., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., Competing Interests: The study has been approved by the Institutional Review Board of IRCCS “Burlo Garofolo” (RC32/2012), and all procedures performed were in accordance with the 1964 Helsinki declaration. Informed consent was obtained from mothers of infants.Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Objective: The objective of the study was to compare thoracic fluid content (TFC) between newborn infants with and without respiratory distress. We tested the hypothesis that TFC would be higher in infants with respiratory distress., Study Design: A total of 96 newborn infants, gestational age 37.9 (2.6) weeks, were enrolled at birth. TFC by electrical bioimpedance was recorded within 3 h after birth (TFC1) and at 24 h of life (TFC2)., Results: TFC1 was higher in infants with respiratory distress at birth (76.8 (24.9) versus 61.6 (16.1) 1 KOhm -1 , P<0.0005). The association was independent from gestational age and mode of delivery. TFC2 was independently associated with respiratory distress at 24 h of life (adjusted coefficient b=0.5 (s.d. 0.02), P=0.02)., Conclusion: TFC by electric bioimpedance independently correlated with the presence of respiratory distress at birth and at 24 h of life in late preterm and term newborn infants.

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 (R 2 = 0.26, p = 0.001), weight (R 2 = 0.25, p = 0.001), length (R 2 = 0.16, p = 0.01), fat mass (R 2 = 0.15, p = 0.01) and fat-free mass at term (R 2 = 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., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: The objective of the study was to study the effect of short-term left-lateral position on cardiovascular parameters in hemodynamically stable newborns., Study Design: Cardiac output (CO), stroke volume (SV), systemic vascular resistance index (SVRI) and heart rate (HR) were measured by electric velocimetry in hemodynamically stable newborns without respiratory support in the supine, left-lateral and back-to-supine positions, each kept for 10 min., Results: Thirty-two newborns were enrolled, birth weight 2134 (1818 to 2460) g, gestational age 34.5±2.4 weeks. CO and SV decreased significantly from supine to left-lateral position (CO supine: 193.4 (168.0 to 229.6) ml kg -1 min -1 ; CO left-lateral: 172.0 (154.9 to 201.6) ml kg -1 min -1 , P<0.0001; SV supine: 3.0 (2.7 to 4.0) ml; SV left-lateral: 2.7 (2.4 to 3.2) ml, P<0.0004). Conversely, SVRI increased in left-lateral position: SVRI supine: 18865±9244 dyns cm -5  m -2 ; SVRI left-lateral: 21203±10059 dyns cm -5  m -2 , P<0.0001). All variables returned to the initial value when infants were back in the supine position. HR and blood pressure did not change., Conclusion: In stable infants, CO and SV decrease and SVRI increases, in left-lateral position.

Aim: Body mass index (BMI)-for-age curves have been developed in the USA, but not compared with other populations. This study created gender-specific intrauterine BMI-for-age curves for Italian preterm infants and compared them with the USA version., Methods: Data on 92 262 newborn infants, born at 26-42 weeks of gestational age in the north-eastern Italian region of Friuli Venezia Giulia between 2005 and 2013, were analysed to create gender-specific BMI-for-age curves. Gender-specific and age-specific BMI Z scores for Italian infants were calculated using the parameters of the USA growth curves and the World Health Organization charts., Results: Gender-specific BMI-for-age at birth curves were developed for premature Italian infants from 26 gestational weeks. The comparison with the USA charts showed no significant difference in BMI percentiles in Italian infants born at ≤33 gestational weeks, but infants born at ≥34 gestational weeks had a significantly higher BMI than the USA population, by 0.2 standard deviations., Conclusion: We developed the first European BMI-for-age at birth curves for premature infants. According to our findings, the Italian curves were comparable to the USA curves for the subgroup of infants born at ≤33 gestational weeks, but not ≥34 gestational weeks., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Early and prolonged skin-to-skin contact (SSC) after birth between a mother and her newborn has been shown to generate beneficial effects on the mother-infant relationship and breastfeeding. Close mother-infant body contact immediately after birth positively enhances exclusive breastfeeding during the hospital stay, with a dose-response relationship. Skin-to-skin contact may ease the infant's transition to extra-uterine life and helps regulate the infant's body temperature and nursing behavior. However, reports of sudden unexpected postnatal collapse (SUPC) soon after birth, in healthy term neonates, in association with SSC, have raised concerns about the safety of this practice. Based on available evidence, we developed a surveillance protocol in the delivery room and postnatal ward of the Institute for Maternal and Child Health of Trieste (Italy). The aim of our protocol is (a) to promote safe mother and infant bonding and (b) to establish successful breastfeeding, without increasing the risk of SUPC. As there is no known effective intervention to prevent SUPC, our protocol has been conceived as a potential best practice., (© The Author(s) 2014.)

Body mass index (BMI) is correlated with body fatness and risk of related diseases in children and adults. Proportionality indexes such as BMI and ponderal index (PI) have been suggested as complementary measures in neonatal growth assessment. Yet, they are still not used in neonates and their correlation with fatness is unknown. The aim of the study was to test the hypothesis that BMI z-score would predict neonatal adiposity. Body composition measurements (ie, fat mass, fat-free mass) by air displacement plethysmography (PEA POD, LMI, Concord-USA), weight and length were obtained in 200 infants ≥36 weeks' gestational age (GA) at birth. Linear regression analysis showed a direct association between BMI z-score and %fat mass (r(2)=0.43, p<0.0001). This association was confirmed independently from sex, GA and maternal prepregnancy BMI. BMI z-score predicted adiposity better than PI. However, both BMI z-score and PI were poor predictors of adiposity at birth.

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.

Aspiration of uncontaminated amniotic fluid as a cause of neonatal respiratory distress is scarcely documented. A term neonate who presented with early onset respiratory distress with a radiographic appearance of an aspiration syndrome is therefore reported. Differential diagnosis and implication of this diagnosis in the management of neonatal respiratory distress are discussed. This case highlights amniotic fluid aspiration as a possible cause of severe respiratory distress even in the absence of meconium stained fluid.

Aim: To evaluate the impact of endothelial progenitor cells (EPCs), a subset of committed circulatory stem cells, on the development of bronchopulmonary dysplasia (BPD) and other short term outcomes in a cohort of extremely premature newborns., Methods: Progenitor cells were quantified by flow cytometry at birth in 36 neonates born <=28 weeks of gestation and at 36 postmenstrual weeks in 18 of them. Cells expressing the stemness markers CD34, CD133, or both were defined as circulating progenitor cells (CPCs). EPCs were defined as CPCs co-expressing the endothelial marker KDR., Results: Mean (SD) gestational age and birth weight of the infants studied were 26.2(1.5) weeks and 761.6(171.8) grams, respectively. EPC levels at birth did not differ between infants who subsequently developed BPD (n=9) and those who did not (n=24) [CD34(+)KDR(+) EPCs: 81(34-41) vs 80(56-110), p=0.7] and were not correlated with the duration of mechanical ventilation or O2-dependence, nor with the need of surfactant replacement. Infants with a hemodynamically significant patent ductus arteriosus (PDA) (n=22) had significantly lower EPC levels at birth than those with no PDA (n=11) [CD34(+)KDR(+) cells: 47(34-92) vs 142(84.5-221), p=0.008]. Data from the 18 infants studied both at birth and at 36 postmenstrual weeks showed that, while CPCs sharply decline over time, levels of all EPCs phenotypes are preserved after delivery., Conclusions: Levels of EPCs at birth did not affect the risk of developing BPD in our group of extremely premature neonates. However, the association between low EPC counts at birth and PDA may be clinically relevant, and deserves further studies., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The behaviour of the renin-angiotensin-aldosterone system was evaluated in 16 acromegalic patients, of whom 7 were hypertensive. The patients were studied in basal conditions, after suppression with 9alpha-fluorohydrocortisone, and after stimulation with furosemide. Baseline and after furosemide PRA were significantly lower in acromegalic hypertensive patients than in the normotensive group. Mean urinary aldosterone excretion was found at the upper limits of the normal range; it was occasionally elevated, but the values were not satistically different in the two groups. There was a suppression after 9 alpha fluorohydrocortisone in both groups, though it did not reached the 50%. These data show that there is a disorder of the renin-angiotensin-aldosterone system in acromegalic subjects. This defective regulation is sometimes similar to that present in primary aldosteronism. In fact in two patients a typical phlebographic and scintigraphic picture of primary aldosteronism has been found; surgery, performed in both patients, revealed a large cortical adenoma in one case and a macronodular hyperplasia in the second case. However, the relationship between this adrenal abnormalities and hypertension in acromegaly are not yet completely clarified.