Growth Pattern of Preterm Neonates with Fetal Growth Restriction: A Prospective Cohort Study.

OBJECTIVES: To compare the growth of preterm neonates with fetal growth restriction (FGR) and preterm neonates born appropriate-for-gestational-age (AGA) from birth to 12-18 mo of corrected age (CA). METHODS: In this prospective cohort study, 85 preterm neonates with FGR and 85 gestation- and gender-matched AGA neonates were followed up from birth till 12-18 mo corrected age. Anthropometric indices were compared at specific time points and the risk factors for underweight status were analyzed. RESULTS: Mean gestational age of the cohort was 32.8 ± 2.1 wk. Mean birth weight was 1414 ± 248 g in the FGR and 1806 ± 416 g in AGA neonates. At 12-18 mo of corrected age, a significantly greater proportion of FGR infants were wasted (24.3% vs. 7.2%, P = 0.005). A greater proportion of FGR infants were underweight (27% vs. 17.4%, P = 0.11), stunted (41.9% vs. 36.2%, P = 0.30), and microcephalic (27% vs. 23.1%, P = 0.36), although the differences were not statistically significant. Significant catch-up growth from 40 wk postmenstrual age (PMA) to 12-18 mo corrected age in weight (52.8% vs. 13.1%, P <0.001) and length (37.9% vs. 8.7%, P <0.001) was observed in the FGR neonates. The z-score of weight for age at 3 mo (adjusted OR 0.65, 95% CI: 0.52-0.8; P <0.001), the median time to full feeds (aOR: 1.10, 95% CI: 1.04-1.15; P = 0.001), and hypothyroidism (aOR 2.44, 95% CI: 1.46-4.08; P = 0.001), were independent predictors of underweight status at 12-18 mo. CONCLUSIONS: At 12-18 mo of corrected age, a significantly greater proportion of preterm FGR neonates were wasted compared to AGA ones. The former also exhibited significantly greater catch-up growth than the latter.

Evaluation of levosimendan as treatment option in a large case-series of preterm infants with cardiac dysfunction and pulmonary hypertension.

Levosimendan as a calcium-sensitizer is a promising innovative therapeutical option for the treatment of severe cardiac dysfunction (CD) and pulmonary hypertension (PH) in preterm infants, but no data are available analyzing levosimendan in cohorts of preterm infants. The design/setting of the evaluation is in a large case-series of preterm infants with CD and PH. Data of all preterm infants (gestational age (GA) < 37 weeks) with levosimendan treatment and CD and/or PH in the echocardiographic assessment between 01/2018 and 06/2021 were screened for analysis. The primary clinical endpoint was defined as echocardiographic response to levosimendan. Preterm infants (105) were finally enrolled for further analysis. The preterm infants (48%) were classified as extremely low GA newborns (ELGANs, < 28 weeks of GA) and 73% as very low birth weight infants (< 1500 g, VLBW). The primary endpoint was reached in 71%, without difference regarding GA or BW. The incidence of moderate or severe PH decreased from baseline to follow-up (24 h) in about 30%, with a significant decrease in the responder group (p < 0.001). The incidence of left ventricular dysfunction and bi-ventricular dysfunction decreased significantly from baseline to follow-up (24 h) in the responder-group (p = 0.007, and p < 0.001, respectively). The arterial lactate level decreased significantly from baseline (4.7 mmol/l) to 12 h (3.6 mmol/l, p < 0.05), and 24 h (3.1 mmol/l, p < 0.01).  Conclusion: Levosimendan treatment is associated with an improvement of both CD and PH in preterm infants, with a stabilization of the mean arterial pressure during the treatment and a significant decrease of arterial lactate levels. Future prospective trials are highly warranted. What is Known: • Levosimendan as a calcium-sensitizer and inodilator is known to improve the low cardiac output syndrome (LCOS), and improves ventricular dysfunction, and PH, both in pediatric as well as in adult populations. Data related to critically ill neonates without major cardiac surgery and preterm infants are not available. What is New: • This study evaluated the effect of levosimendan on hemodynamics, clinical scores, echocardiographic severity parameters, and arterial lactate levels in a case-series of 105 preterm infants for the first time. Levosimendan treatment in preterm infants is associated with a rapid improvement of CD and PH, an increase of the mean arterial pressure, and a significant decrease in arterial lactate levels, as surrogate marker for a LCOS. • How this study might affect research, practice, or policy. As no data are available regarding the use of levosimendan in this population, our results hopefully animate the research community to conduct future prospective trails analyzing levosimendan in randomized controlled trials (RCT) and observational control studies. Additionally, our results potentially motivate clinicians to introduce levosimendan as second second-line therapy in cases of severe CD and PH in preterm infants without improvement using standard treatment strategies.

Current Trends in Antifungal Prophylaxis for High-Risk Neonates in Neonatal Intensive Care Units in India: A Nationwide Survey.

Background Prophylactic antifungals are often used in high-risk babies in neonatal intensive care units (NICUs) to reduce invasive fungal infections (IFIs). However, existing guidelines regarding prophylactic antifungal usage do not clearly define the high-risk population. This study aimed to assess the practices related to prophylactic antifungal use in NICUs in India. Methods For this cross-sectional study, an online structured questionnaire was completed by neonatologists who worked in level 3 NICUs in 12 states in India during the period June 2022 to August 2022. Results Data from 151 NICUs were analyzed. 71.7% of respondents were from private hospitals, and 28.3% were from government hospitals. Nearly one-fourth of the units (28.5%) used antifungal prophylaxis in all extremely low birth weight (ELBW) babies, while another one-fourth (25.8%) used a case-based approach. The remaining NICUs (45.7%) did not use prophylactic antifungals. Among the users, the preferred antifungal was fluconazole; 3 mg/kg and 6 mg/kg were the dosage regimens used. The commonly used interval for administering fluconazole was 72 hours (69.2% of units). The intravenous route was the preferred route of administration (84.1%). Factors that influenced the non-users were the low incidence of fungal infections in their NICUs and concern about the development of resistance. It was noted that the users felt strongly about the need for further recommendations from pediatric societies and more studies on the efficacy of antifungals. Conclusion There is considerable variation in the use of prophylactic antifungals across NICUs in India. Among the users, uniformity in the choice of antifungal and interval of administration was observed. Further recommendations from pediatric societies, including the definitions of neonates at-risk of fungal infections, are required to ensure consistency in practice and help clinicians decide whether or not to use prophylactic antifungals.

Cardiopulmonary Exercise Testing in Childhood in Late Preterms: Comparison to Early Preterms and Term-Born Controls.

Background: Late preterm (340−366 weeks gestational age [GA]) infants may have abnormal pulmonary development and possible exercise physiology parameters. We aim to assess the effect of late prematurity on exercise capacity in childhood and to compare it to early preterm (EP) (born < 300 GA), and to term healthy control (TC) (>370 week GA). Methods: Late preterm and early preterm (7−10 years) completed a cardiopulmonary exercise test (CPET) and spirometry and were compared to EP and to TC. Results: Eighty-four children (age 9.6 ± 1.0 years, 48% girls) participated. Twenty-one former LP were compared to 38 EP (15 with Bronchopulmonary dysplasia (BPD) [EP+], 23 without BPD [EP−]) and to 25 TC children. Peak oxygen uptake (peakV̇O2) was statistically lower than in the TC, but within the normal range, and without difference from the EP (LP 90.2 ± 15.1%, TC 112.4 ± 16.9%, p < 0.001; EP+ 97.3 ± 25.5%, EP− 85.4 ± 20.8%, p = 0.016 and p < 0.001, respectively, when compared with TC). Lung function (FEV1) was lower than normal only in the EP+ (75.6 ± 14.9% predicted, compared with 12.5 ± 87.8 in EP−, 87.5 ± 16.9 in LP and 91.0 ± 11.7 in TC). Respiratory and cardiac limitations were similar between all four study groups. Conclusions: This study demonstrated lower exercise capacity (peakV̇O2) in former LP children compared with healthy term children. Exercise capacity in LP was comparable to that of EP, with and without BPD. However, the exercise test parameters, specifically peakV̇O2, were within the normal range, and no significant physiological exercise limitations were found.

Use of Antibiotics in Preterm Newborns.

Due to complex maturational and physiological changes that characterize neonates and affect their response to pharmacological treatments, neonatal pharmacology is different from children and adults and deserves particular attention. Although preterms are usually considered part of the neonatal population, they have physiological and pharmacological hallmarks different from full-terms and, therefore, need specific considerations. Antibiotics are widely used among preterms. In fact, during their stay in neonatal intensive care units (NICUs), invasive procedures, including central catheters for parental nutrition and ventilators for respiratory support, are often sources of microbes and require antimicrobial treatments. Unfortunately, the majority of drugs administered to neonates are off-label due to the lack of clinical studies conducted on this special population. In fact, physiological and ethical concerns represent a huge limit in performing pharmacokinetic (PK) studies on these subjects, since they limit the number and volume of blood sampling. Therapeutic drug monitoring (TDM) is a useful tool that allows dose adjustments aiming to fit plasma concentrations within the therapeutic range and to reach specific drug target attainment. In this review of the last ten years' literature, we performed Pubmed research aiming to summarize the PK aspects for the most used antibiotics in preterms.

Improving Post-discharge Practice of Kangaroo Mother Care: Perspectives From Communities in East-Central Uganda.

Introduction: Kangaroo mother care (KMC) is among the most cost-effective and easily accessible solutions for improving the survival and wellbeing of small newborns. In this study, we examined the barriers and facilitators to continuity of KMC at home following hospital discharge in rural Uganda. Methods: We conducted this study in five districts in east-central Uganda, within six hospitals and at the community level. We used a qualitative approach, with two phases of data collection. Phase 1 comprised in-depth interviews with mothers who practiced KMC with their babies and caretakers who supported them and key informant interviews with health workers, district health office staff, community health workers, and traditional birth attendants. We then conducted group discussions with mothers of small newborns and their caretakers. We held 65 interviews and five group discussions with 133 respondents in total and used a thematic approach to data analysis. Results: In hospital, mothers were sensitized and taught KMC. They were expected to continue practicing it at home with regular returns to the hospital post-discharge. However, mothers practiced KMC for a shorter time at home than in the hospital. Reasons included being overburdened with competing domestic chores that did not allow time for KMC and a lack of community follow-up support by health workers. There were increased psycho-social challenges for mothers, alongside some dangerous practices like placing plastic cans of hot water near the baby to provide warmth. Respondents suggested various ways to improve the KMC experience at home, including the development of a peer-to-peer intervention led by mothers who had successfully done KMC and community follow-up of mothers by qualified health workers and community health workers. Conclusion: Despite wide acceptance of KMC by health workers, challenges to effective implementation persist. Amid the global and national push to scale up KMC, potential difficulties to its adherence post-discharge in a rural, resource-limited setting remain. This study provides insights on KMC implementation and sustainability from the perspectives of key stakeholders, highlighting the need for a holistic approach to KMC that incorporates its adaptability to community settings and contexts.

Extraction of Premature Newborns' Spontaneous Cries in the Real Context of Neonatal Intensive Care Units.

Cry analysis is an important tool to evaluate the development of preterm infants. However, the context of Neonatal Intensive Care Units is challenging, since a wide variety of sounds can occur (e.g., alarms and adult voices). In this paper, a method to extract cries is proposed. It is based on an initial segmentation between silence and sound events, followed by feature extraction on the resulting audio segments and a cry and non-cry classification. A database of 198 cry events coming from 21 newborns and 439 non-cry events was created. Then, a set of features-including Mel-Frequency Cepstral Coefficients-issued from principal component analysis, was computed to describe each audio segment. For the first time in cry analysis, noise was handled using harmonic plus noise analysis. Several machine learning models have been compared. The K-Nearest Neighbours approach showed the best results with a precision of 92.9%. To test the approach in a monitoring application, 412 h of recordings were automatically processed. The cries automatically selected were replayed and a precision of 92.2% was obtained. The impact of errors on the fundamental frequency characterisation was also studied. Results show that despite a difficult context, automatic cry extraction for non-invasive monitoring of vocal development of preterm infants is achievable.

Comparison of the Canadian vs. the international risk scoring tool for respiratory syncytial virus prophylaxis in moderate-to-late preterm infants.

Aim: The study objective was to compare the Pediatric Investigators Collaborative Network on Infections in Canada risk scoring tool (CRST) that determines need for respiratory syncytial virus (RSV) prophylaxis in infants 33-35 weeks gestational age during the RSV season, with the newly developed international risk scoring tool (IRST). Methods: Children 33-35 weeks gestational age born during the 2018-2021 RSV seasons were prospectively identified following birth and scored with the validated CRST and IRST, that comprises seven and three variables respectively, into low- moderate- and high-risk groups that predict RSV-related hospitalization. Correlations between total scores on the two tools, and cut-off scores for the low-, moderate- and high-risk categories were conducted using the Spearman rank correlation. Results: Over a period of 3 RSV seasons, 556 infants were scored. Total risk scores on the CRST and the IRST were moderately correlated (rs = 0.64, p < 0.001). A significant relationship between the risk category rank on the CRST and the risk category rank on the IRST (rs = 0.53; p < 0.001) was found. The proportion of infants categorized as moderate risk for RSV hospitalization by the CRST and IRST were 19.6% (n = 109) and 28.1% (n = 156), respectively. Conclusion: The IRST may provide a time-efficient scoring alternative to the CRST with three vs. seven variables, and it selects a larger number of infants who are at moderate risk for RSV hospitalization for prophylaxis. A cost-utility analysis is necessary to justify country-specific use of the IRST, while in Canada a cost comparison is necessary between the IRST vs. the currently approved CRST prior to adoption.

Biomarkers of renal function in preterm neonates at 72 h and 3 weeks of life

Abstract Objective: Serum levels of creatinine in neonates are quite variable and suffer interference from the immature kidney and maternal creatinine concentration. The aim of this study was to measure novel biomarkers of glomerular and tubular function in healthy preterm neonates at 72 h and 3 weeks of life. Methods: Urine samples were collected in 40 preterm neonates with 28-34 incomplete weeks of gestational age. None of the participants had comorbidities, malformations and infections. The samples were collected at 72 h of life and at 3 weeks after birth. Measurements of Calbindin, Collagen IV, FABP1, αGST, IP-10, KIM-1, Osteoactivin, Renin, TFF-3, TIMP-1, α-1-Microglobulin, Albumin, Clusterin, Cystatin C, EGF, Lipocalin-2/NGAL and Osteopontin were performed using panels 1 and 2 of multiplex kits of kidney injury. Data were analyzed using the software GraphPad Prism version 6.0. Results: The preterm neonates included 55% of males with gestational age of 30 ± 1 weeks. The most frequent maternal condition associated with preterm birth was preeclampsia (80%). Molecules related to glomerular function showed a significant increase in the concentrations obtained at 3 weeks of life compared to 72 h of life. Markers related to tubular injury (KIM-1 and NGAL) also showed an increase. On the other hand, cystatin C did not change. Conclusion: The elevation of molecules related to glomerular function indicates an increase of glomerular filtration rate from 72 h up until 3 weeks of life, which was not clearly detected with the measurement of cystatin C.

Clinical Outcomes of Single vs. Two-Strain Probiotic Prophylaxis for Prevention of Necrotizing Enterocolitis in Preterm Infants.

Background: The administration of live microbiota (probiotic) via enteral route to preterm infants facilitates intestinal colonization with beneficial bacteria, resulting in competitive inhibition of the growth of pathogenic bacteria preventing gut microbiome dysbiosis. This dysbiosis is linked to the pathogenesis of necrotizing enterocolitis (NEC), an acquired multi-factorial intestinal disease characterized by microbial invasion of the gut mucosa, particularly affecting preterm infants. Probiotic prophylaxis reduces NEC; however, variations in strain-specific probiotic effects, differences in administration protocols, and synergistic interactions with the use of combination strains have all led to challenges in selecting the optimal probiotic for clinical use. Aim: To compare any differences in NEC rates, feeding outcomes, co-morbidities in preterm infants receiving single or two-strain probiotics over a 4-year period. The two-strain probiotic prophylaxis was sequentially switched over after 2 years to the single strain probiotic within this 4-year study period, in similar cohort of preterm infants. Methods: During two consecutive equal 2-year epochs, preterm infants (<32 weeks and or with birth weight <1,500 g) receiving two-strain (Lactobacillus acidophilus and Bifidobacterium bifidum) and single strain (Bifidobacterium breve M-16 V,) probiotic prophylaxis for prevention of NEC were included in this retrospective, observational study. The primary outcome included rates of NEC; secondary outcomes included prematurity related co-morbidities and feeding outcomes. Time to reach full enteral feeds was identified as the first day of introducing milk feeds at 150 ml/kg/day. Results: There were 180 preterm infants in the two-strain, 196 in the single strain group from the two equal consecutive 2-year epochs. There were no differences in the NEC rates, feeding outcomes, all-cause morbidities except for differences in rates of retinopathy of prematurity. Conclusion: In our intensive-care setting, clinical outcomes of single vs. two-strain probiotic prophylaxis for prevention of NEC were similar. Although our study demonstrates single strain probiotic may be equally effective than two-strain in the prevention of NEC, small sample size and low baseline incidence of NEC in our unit were not sufficiently powered to compare single vs. two-strain probiotic prophylaxis in preventing NEC. Further clustered randomized controlled trials are required to study the effects of single vs. multi-strain probiotic products for NEC prevention in preterm infants.

Retinopathy of Prematurity in the University of Calabar Teaching Hospital, Calabar, Nigeria: An Early Report of a Screening Service.

Background: Retinopathy of prematurity (ROP) is an important cause of childhood blindness worldwide. This blindness is avoidable through regular screening of preterm infants and prompt intervention for those with the condition. Aims/Objectives: This study aimed to determine the pattern of presentation of ROP and the risk factors for its development among preterm infants in the Neonatal Unit of the University of Calabar Teaching Hospital, Calabar, Nigeria. Design of Study: This study is a prospective, longitudinal study. Settings: The study was carried out in the Special Care Baby Unit, Sick Baby Unit, and Neonatal Clinic of the Department of Paediatrics and Child Health, University of Calabar Teaching Hospital, Calabar, Nigeria. Materials and Methods: All preterm infants whose mothers had given informed consent to participate were enrolled. Ocular examination was performed by a trained ophthalmologist. ROP was staged and documented using the revised version of the International Classification of ROP. Data were entered into a questionnaire and analysed using IBM SPSS version 22. Results: Of the 53 neonates recruited into the study, ROP was detected in 11 (21%) neonates, of which 9 (82%) had stage 1 disease, 2 (18%) had stage 2, and none had stage 3. ROP was more common in females, 7 (63.6%), than their male counterparts 4 (36.4%). ROP was higher among those with gestational age (GA) ≤30 weeks [9 (81.8%)] when compared with those with GA >30 weeks [2 (18.2%)] (P = 0.016). Other risk factors for ROP assessed by this study were found not to be significantly associated with the occurrence of ROP. Conclusion: ROP was present in 21% of the neonates, and the majority had stage 1 disease. This finding emphasizes the need for screening of all preterm neonates for ROP in order to forestall avoidable blindness which could result from this condition.

Biomarkers of renal function in preterm neonates at 72h and 3weeks of life.

OBJECTIVE: Serum levels of creatinine in neonates are quite variable and suffer interference from the immature kidney and maternal creatinine concentration. The aim of this study was to measure novel biomarkers of glomerular and tubular function in healthy preterm neonates at 72h and 3 weeks of life. METHODS: Urine samples were collected in 40 preterm neonates with 28-34 incomplete weeks of gestational age. None of the participants had comorbidities, malformations and infections. The samples were collected at 72h of life and at 3 weeks after birth. Measurements of Calbindin, Collagen IV, FABP1, αGST, IP-10, KIM-1, Osteoactivin, Renin, TFF-3, TIMP-1, α-1-Microglobulin, Albumin, Clusterin, Cystatin C, EGF, Lipocalin-2/NGAL and Osteopontin were performed using panels 1 and 2 of multiplex kits of kidney injury. Data were analyzed using the software GraphPad Prism version 6.0. RESULTS: The preterm neonates included 55% of males with gestational age of 30±1 weeks. The most frequent maternal condition associated with preterm birth was preeclampsia (80%). Molecules related to glomerular function showed a significant increase in the concentrations obtained at 3 weeks of life compared to 72h of life. Markers related to tubular injury (KIM-1 and NGAL) also showed an increase. On the other hand, cystatin C did not change. CONCLUSION: The elevation of molecules related to glomerular function indicates an increase of glomerular filtration rate from 72h up until 3 weeks of life, which was not clearly detected with the measurement of cystatin C.

Attenuated brain responses to speech sounds in moderate preterm infants at term age.

Recent findings have revealed that very preterm neonates already show the typical brain responses to place of articulation changes in stop consonants, but data on their sensitivity to other types of phonetic changes remain scarce. Here, we examined the impact of 7-8 weeks of extra-uterine life on the automatic processing of syllables in 20 healthy moderate preterm infants (mean gestational age at birth 33 weeks) matched in maturational age with 20 full-term neonates, thus differing in their previous auditory experience. This design allows elucidating the contribution of extra-uterine auditory experience in the immature brain on the encoding of linguistically relevant speech features. Specifically, we collected brain responses to natural CV syllables differing in three dimensions using a multi-feature mismatch paradigm, with the syllable/ba/ as the standard and three deviants: a pitch change, a vowel change to/bo/ and a consonant voice-onset time (VOT) change to/pa/. No significant between-group differences were found for pitch and consonant VOT deviants. However, moderate preterm infants showed attenuated responses to vowel deviants compared to full terms. These results suggest that moderate preterm infants' limited experience with low-pass filtered speech prenatally can hinder vowel change detection and that exposure to natural speech after birth does not seem to contribute to improve this capacity. These data are in line with recent evidence suggesting a sequential development of a hierarchical functional architecture of speech processing that is highly sensitive to early auditory experience.

Ductal size indexed to weight and body surface area correlates with morbidities in preterm infants ≤32 weeks.

OBJECTIVES: To assess ductal size correlated to spontaneous closure, pharmacological or surgical treatment; to index ductal diameter to body weight and body surface area; to evaluate the morbidities. STUDY DESIGN: Retrospective study on preterms ≤32 weeks, birth weight ≤1500 g, extremely low birth weight (ELBW) and very low birth weight (VLBW). Inclusion criteria: patent ductus arteriosus (PDA) with a diameter ≥1 millimeter (mm) at 72 h from birth; need for ibuprofen treatment on the basis of a hemodynamically significant ductus arteriosus (HsPDA). RESULTS: One hundred infants with the diagnosis of PDA have been included. We observed a prevalence of spontaneous closure in 34% of newborns (41.3% VLBW versus 26.7% ELBW). The percentage of response to a single course of ibuprofen was of 62% (68.5% ELBW versus 54.3% VLBW). The mean of absolute ductal diameter was of 2.26 ± 0.62 mm in ELBW and 2.18 ± 0.42 mm in VLBW. The indexing of ductus size to body weight demonstrated a higher value in ELBW than VLBW (2.76 ± 0.97 mm/kg versus 1.84 ± 0.40 mm/kg). CONCLUSIONS: Our results confirmed that HsPDA can develop in presence of a ductus >1.5 mm as absolute value or >1.4 mm/kg as indexed to body weight. In ELBW infants the ductal size indexed for body weight and body surface area could be more predictive of spontaneous closure or need for pharmacological treatment compared to the absolute value of ductal size. A strong association between HsPDA and short- or long-term morbidities was confirmed particularly in ELBW.

Which long line do we use in very low birth weight neonates; umbilical venous catheter or peripherally inserted central catheter?

BACKGROUND: Umbilical venous catheters (UVC) and peripherally inserted central catheters (PICC) are commonly used in preterms. UVC is cheap, easy to insert but has shorter dwell time. UVC is replaced after 7 days due to the risk of complications. This is associated with increased cost, work, and risk of nosocomial infections. The aim of this study was to determine the antenatal and postnatal factors that predict the need for a central line for more than 7 days, thus helping select between UVC or PICC on day 1 of life in babies ≤1500 grams. METHODS: We retrospectively collected antenatal and postnatal data of VLBW neonates over a period of 1 year who needed CL during their NICU stay. We then divided them into two cohorts. Group 1: CL ≤7 days. Group 2: CL > 7 days. RESULTS: Sepsis and catheter complications were lower with use of a single CL or duration being ≤7 days. Birth weight, incomplete/no antenatal steroids, need for resuscitation, low Apgar's, RDS, hs-PDA, and initiation of feeds beyond 24 hours of birth were significant. The score was devised based on factors found significant that had an acceptable AUC of 0.767 on ROC analysis with a score of 1 or above having 74.8% sensitivity and 67.7% specificity for prediction of need for CL > 7 days. CONCLUSIONS: Birth weight ≤1000 grams, incomplete steroids and need for resuscitation at birth were predictive of the need of CL beyond seven days, on day one of life.

Metabolic changes in early neonatal life: NMR analysis of the neonatal metabolic profile to monitor postnatal metabolic adaptations.

BACKGROUND: A major challenge from the moment a child is delivered is the adaptation to the extrauterine life, where rapid metabolic changes take place. The study of these changes during the first days of human life may assist in the understanding of the metabolic processes that occur at this critical period, which is likely to provide significant clinical insights. To date, metabolomics has become a powerful field, ideal for the monitoring of such dynamic variations, since it offers the possibility to identify alterations in metabolic profiles, even on daily basis. METHODS: The study included 253 healthy newborns (GA 35 to 40 weeks) from the region of Western Greece. Urine samples were collected immediately after birth and at the third day of life. NMR-based metabolomics was used to compare the metabolic urinary profiles of newborns from the first and third day of their life, assessing the impact of six perinatal factors; delivery mode, prematurity, maternal smoking, gender, nutrition and neonatal jaundice. RESULTS: Analysis of urine metabolic fingerprint from the first and third day of life, coupled with multivariate statistics, provides insights into the details of early life metabolic profile differentiation. Αt the third day of life metabolic adaptations are evident, as many differences were noted in urine of healthy neonates within the first 72 h postpartum. Trends in differentiation of metabolites levels between the two groups, late preterm and term newborns, have been also observed. CONCLUSIONS: Newborn's urine metabolic profiles confirmed the rapid changes in their metabolism after birth. Further, ongoing research will enable us to develop one reference model of urinary metabolomics in healthy newborns during the period of adaptation to the extra-uterine life.

Blue LED phototherapy in preterm infants: effects on an oxidative marker of DNA damage.

BACKGROUND: Phototherapy is used on the majority of preterm infants with unconjugated hyperbilirubinaemia. The use of fluorescent tube phototherapy is known to induce oxidative DNA damage in infants and has largely been replaced by blue light-emitting diode phototherapy (BLP). To date, it is unknown whether BLP also induces oxidative DNA damage in preterm infants. OBJECTIVE: To determine whether BLP in preterm infants induces oxidative DNA damage as indicated by 8-hydroxy-2'deoxyguanosine (8-OHdG). DESIGN: Observational cohort study. METHODS: Urine samples (n=481) were collected in a cohort of 40 preterm infants (24-32 weeks' gestational age) during the first week after birth. Urine was analysed for the oxidative marker of DNA damage 8-OHdG and for creatinine, and the 8-OHdG/creatinine ratio was calculated. Durations of phototherapy and levels of irradiance were monitored as well as total serum bilirubin concentrations. RESULTS: BLP did not alter urinary 8-OHdG/creatinine ratios (B=0.2, 95% CI -6.2 to 6.6) at either low (10-30 µW/cm2/nm) or high (>30 µW/cm2/nm) irradiance: (B=2.3, 95% CI -5.7 to 10.2 and B=-3.0, 95% CI -11.7 to 5.6, respectively). Also, the 8-OHdG/creatinine ratios were independent on phototherapy duration (B=-0.1, 95% CI -0.3 to 0.1). CONCLUSIONS: BLP at irradiances up to 35 µW/cm2/nm given to preterm infants ≤32 weeks' gestation does not affect 8-OHdG, an oxidative marker of DNA damage.

Late preterms: are they all the same?

Very preterm infants (VPT) and, especially extreme low gestational age (ELGA) preterms, often on the threshold of viability, make the headlines of both, the scientific as well as the popular press. However, all together they represent between 1 and 2% of all livebirths. Late preterms (LPT) those born between 34/07 and 36/06 weeks, on the other hand, may account for up to 80% of all preterms and for some 5-8% of all births. Although mortality is low they are prone to increasing neonatal morbidities posing a considerable medical, financial and psychosocial burden. In the last years, for many reasons, LPT appear to have increased considerably throughout the western world. But are LPT neonates all the same? In spite of overlapping gestational ages (GA) LPT may behave quite differently depending on circumstances surrounding their pre- and postnatal events. We can identify three different classes of LPT neonates: spontaneous late preterms (SpLPT) born in the absence of previous maternal illnesses and/or pregnancy related disorders; Induced LPT (IdLPT) due to maternal/fetal complications and those babies being born after 34-week gestation from postponed delivery at an earlier GA (PtLPT) - and they are quite different babies, with different behavior, despite a common and same gestational age.

Visual Outcome of Preterm Infants Screened in a Tertiary Care Hospital.

OBJECTIVE: The aim of this study is to assess the incidence of retinopathy of prematurity (ROP) in preterm infants and to compare the visual outcomes in babies with and without ROP. MATERIALS AND METHODS: A consecutive cohort of 812 preterm babies were recruited with gestational age ≤32 weeks and or birth weight ≤1500 g. The outcome was assessed at the end of 15 months by determining fixation behavior, cycloplegic refraction, and vision by Cardiff cards. Incidence of visual outcomes with 95% confidence limits and relative risks were estimated. Chi-squared test and t-test were used as tests of significance. RESULTS: The incidence of ROP was 25%. The incidence of myopia, hypermetropia, astigmatism, and strabismus were 15.8% (14.3-17.3), 6% (5.1-7.1), 55.6% (53.6-57.7), and 1.8% (1.4%-2.5%), respectively, in the cohort. The most common refractive error in terms of spherical equivalence was myopia (19.8% in ROP and 14.4% in non-ROP group). The mean visual acuity measured by Cardiff Acuity cards was 0.282 and 0.27 logarithm of the minimum angle of resolution units (right eye) and 0.293 and 0.277 (left eye) in patients with and without ROP, respectively. Strabismus was present in 5% of ROP group and 0.8% of non-ROP group babies. Babies with ROP had six times (risk ratio-6.02; 95% confidence interval 2.8-12.8) higher chance of developing strabismus than those without ROP. CONCLUSIONS: Ophthalmological morbidities in premature infants such as refractive errors and strabismus are high in addition to complications like ROP. The incidence of these conditions is more in infants with ROP when compared to non-ROP group.

Pertussis hospitalizations among term and preterm infants: clinical course and vaccine effectiveness.

BACKGROUND: Pertussis causes severe disease in young unvaccinated infants, with preterms potentially at highest risk. We studied pertussis in hospitalized infants as related to gestational age (GA) and vaccination history. METHODS: Medical record data of 0-2y old patients hospitalized for pertussis during 2005-2014 were linked to vaccination data. Multivariable logistic regression was used to study the association between GA and vaccination history on the clinical disease course. We compared vaccine effectiveness (VE) against hospitalization for pertussis between term and preterm infants (i.e., <37w GA) using the screening method as developed by Farrington. RESULTS: Of 1187 records, medical data from 676 were retrieved. Of these, 12% concerned preterms, whereas they are 8% of Dutch birth cohorts. Median age at admission was 3 m for preterms and 2 m for terms (p < 0.001). Preterms more often had received pertussis vaccination (62% vs 44%; p = 0.01) and more often had coinfections (37% vs 21%; p = 0.01). Preterms tended more often to have complications, to require artificial respiration or to need admittance to the intensive care unit (ICU). Preterms had longer ICU stays (15d vs 9d; p = 0.004). Vaccinated preterms and terms had a lower median length of hospital stay and lower crude risks of apneas and the need for artificial respiration, additional oxygen, and ICU admittance than those not vaccinated. After adjustment for presence of coinfections and age at admittance, these differences were not significant, except the lower need of oxygen treatment in vaccinated terms. Effectiveness of the first vaccination against pertussis hospitalizations was 95% (95% CI 93-96%) and 73% (95% CI 20-91%) in terms and preterms, respectively. Effectiveness of the second dose of the primary vaccination series was comparable in both groups (86 and 99%, respectively). CONCLUSIONS: Infants hospitalized for pertussis suffer from severe disease. Preterms were overrepresented, with higher need for intensive treatment and less VE of first vaccination. These findings stress the need for alternative prevention, in particular prenatal vaccination of mothers, to reduce pertussis in both groups.