Long-term Outcome Of Infants Research Articles

Association between Slow and Rapid Weight Gain before 36 Weeks of Corrected Age and 6-Year-Developmental Quotient in Infants Born at

The postnatal growth of preterm infants is influenced by various factors; however, the association between growth and long-term outcomes in extremely preterm infants remains unclear. Therefore, we aimed to determine the association between 6-year development and body weight (BW) at 36 weeks of corrected age (CA) in extremely preterm infants. We conducted a retrospective observational study including extremely preterm infants born at < 26 weeks of gestation. We defined the key standard deviation score (SDS) using BW at birth and evaluated the association between BW-related values at 36 weeks of CA and the 6-year developmental quotient (DQ). This study included 90 infants. The absolute difference between changes in the BW SDS from birth and the median changes in DQ ≥ 85 infants was significantly greater in infants with a DQ < 85 than ≥85 (median [interquartile range]: 0.80 [0.29, 1.31] vs. 0.34 [0.13, 0.55]; p = 0.001). After adjustment by the logistic regression analysis for DQ < 85, the absolute difference was statistically significant (odds ratio: 4.99, 95% confidence interval: 1.71-14.5). The correlation coefficient between the absolute difference and DQ was -0.35 (p < 0.001). There were no significant associations between a DQ < 85 and SDS or changes in SDS from birth. For infants born at <26 weeks of gestation, slow and rapid weight gain were associated with a low 6-year DQ when using values representing individual body sizes at birth. Individual backgrounds should be considered to avoid both slow and rapid weight gain for the growth management of these infants for at least up to 36 weeks of CA. Further research is needed to determine which body size has a positive impact on the long-term outcomes of infants. · The median change in BW SDS was a key factor for DQ.. · Slow/rapid weight gain were related to a low 6-year DQ.. · Individual backgrounds may be important in neonatal intensive care unit care..

Attendance in a Neonatal Follow-Up Program before and in the Time of COVID-19 Pandemic: A Mixed Prospective-Retrospective Observational Study.

Attendance to neonatal follow-up programs presents a significant factor associated with positive long-term outcomes of high-risk infants. Strategies to maximize participation benefit not only future interventions' effectiveness but also healthcare systems and society. While a number of studies have focused on attrition or loss to follow-up, no studies have focused on the contributive risk factors to abstaining from neonatal follow-up programs specifically during the COVID-19 pandemic. This study aims to reveal the main factors linked to non-compliance in a neonatal follow-up program of a tertiary hospital. In this ambidirectional observational study, data from 1137 high-risk neonates who participated in a hospital follow-up program were collected (573 before and 564 after the COVID-19 pandemic). The study sample was grouped to three groups: G1 (N = 831), who maintained participation in the program; G2 (N = 196), who discontinued; and G3 (N = 110), who never visited the outpatient clinics. Data were obtained from the hospital's Systems Applications and Products (SAP) Software and a structured questionnaire, answered by parents of newborns either discontinuing (G2) or not attending (G3) the follow-up program through a telephone contact. The most frequently reported reason for discontinuance before the pandemic onset was the parents' perception of no necessity to maintain participation (44.12%). During the COVID-19 pandemic, provider-related barriers to maintaining hospital access, inability to provide high-quality services (37.14%), and feelings of fear and insecurity (18.5%) emerged as factors for non-attendance. Citizenship and morbidity (respiratory distress syndrome, sepsis, necrotic enterocolitis, jaundice) acted as incentives to join the follow-up program during both study periods. Multiple regression analysis showed that multiple-gestation infants had higher odds of maintaining participation during the COVID-19 period (OR, 4.04; CI, 1.09-14.9). Understanding the potential impact of COVID-19 and the transformative changes in neonatal follow-up clinics is crucial for applying compliance strategies. Removing barriers to maintain family participation can lead to increased attendance rates.

Subcutaneous Semaglutide during Breastfeeding: Infant Safety Regarding Drug Transfer into Human Milk.

Postpartum mothers and their healthcare providers often face the challenge of limited data regarding the safety of drug therapies during lactation. Pregnancy can lead to sustained weight gain, and obesity can negatively impact both physical and psychological well-being. The introduction of GLP-1 agonists to augment weight loss has become a topic of interest for many postpartum mothers. Our study aims to investigate the transmission of semaglutide into human milk in the first steps to ensure the safety and health of both lactating mothers and their breastfed infants. Semaglutide quantification was performed using high-resolution liquid chromatography-mass spectrometry. InfantRisk Center Human Milk biorepository released milk samples from eight women collected at 0, 12 and 24 h post-semaglutide administration. Semaglutide was extracted using protein precipitation in methanol, followed by chromatographic separation. Linear calibration curves for the method ranged between 2.5-30 ng/mL, with a limit of detection of 1.7 ng/mL and a limit of quantification of 5.7 ng/mL (LLOQ). Semaglutide was not detected in any of the collected human milk samples. A worst-case scenario of the relative infant dose (RID) was calculated using the LLOQ as the drug concentration in milk when considering semaglutide's bioavailability and long-acting dose profile. The maximum RID projected was 1.26%, far below the standard 10% safety threshold. While questions about long-term infant outcomes, the safety of maternal nutrient intake, and the nutrient content of breast milk remain, our findings suggest that semaglutide concentrations in human milk are unlikely to pose clinical concerns for breastfed infants. These results support healthcare providers in making informed decisions regarding postpartum therapeutic interventions.

Pulmonary function and bronchopulmonary dysplasia classification: insights from the Spanish Registry.

In 2016, the Spanish Research Group on Bronchopulmonary Dysplasia (BPD) (GEIDIS) established a national registry with participation of 66 hospitals to collect information on clinical characteristics and long-term outcomes of BPD infants into adulthood. The aim of this observational study is to examine forced spirometry data in early childhood and to assess their correlation with the respiratory support required at 36weeks postmenstrual age (PMA). The study analyzed data from preterm infants with BPD born between January 2016 and December 2017 who underwent forced spirometry at 5-7years of age. Statistical analyses were conducted to investigate the relationships between spirometry results, perinatal factors, and the required respiratory support at 36weeks PMA. The study involved 143 patients with a median gestational age (GA) of 27.3weeks (range 25.7-28.7) and a median weight of 880g (range 740-1135). Abnormal spirometry results were observed in 39.2% (56) of the patients. Among patients diagnosed with BPD type 3, those requiring over 30% oxygen at 36weeks PMA exhibited an increased risk of abnormal spirometry results (OR 4.48; 95% CI 1.11-18.13) compared to those requiring positive pressure with less than 30% oxygen. In addition, this subgroup had a higher risk of developing a restrictive-mixed pattern compared to those with BPD type 1 (OR 10.65; 95% CI 2.06-54.98) and BPD type 2 (OR 6.76; 95% CI 1.09-42.06). No significant differences were found in the incidence of an obstructive pattern between BPD types. Conclusion:The requirement of more than 30% oxygen at 36weeks PMA serves as a risk indicator for pulmonary function impairment in school-aged children with BPD. These findings suggest persistent airway and parenchymal injury in this specific patient population, and highlight the importance of careful monitoring to evaluate their long-term effects on lung function. What is Known: • Premature patients with bronchopulmonary dysplasia (BPD) may present abnormalities in pulmonary function tests during school age. However, the predictive accuracy of consensus BPD severity classification remains uncertain. What is New: • The requirement of more than 30% oxygen at 36weeks postmenstrual age (PMA) indicates a potential risk of pulmonary function impairment in school-aged children with BPD. Additionally, a significant correlation has been observed between a restrictive-mixed pattern with exposure to mechanical ventilation and the development of severe forms of BPD.

Dolphin CONTINUE: a multi-center randomized controlled trial to assess the effect of a nutritional intervention on brain development and long-term outcome in infants born before 30 weeks of gestation

BackgroundPreterm born infants are at risk for brain injury and subsequent developmental delay. Treatment options are limited, but optimizing postnatal nutrition may improve brain- and neurodevelopment in these infants. In pre-clinical animal models, combined supplementation of docosahexaenoic acid (DHA), choline, and uridine-5-monophosphate (UMP) have shown to support neuronal membrane formation. In two randomized controlled pilot trials, supplementation with the investigational product was associated with clinically meaningful improvements in cognitive, attention, and language scores. The present study aims to assess the effect of a similar nutritional intervention on brain development and subsequent neurodevelopmental outcome in infants born very and extremely preterm.MethodsThis is a randomized, placebo-controlled, double-blinded, parallel-group, multi-center trial. A total of 130 infants, born at less than 30 weeks of gestation, will be randomized to receive a test or control product between term-equivalent age and 12 months corrected age (CA). The test product is a nutrient blend containing DHA, choline, and UMP amongst others. The control product contains only fractions of the active components. Both products are isocaloric powder supplements which can be added to milk and solid feeds. The primary outcome parameter is white matter integrity at three months CA, assessed using diffusion-tensor imaging (DTI) on MRI scanning. Secondary outcome parameters include volumetric brain development, cortical thickness, cortical folding, the metabolic and biochemical status of the brain, and product safety. Additionally, language, cognitive, motor, and behavioral development will be assessed at 12 and 24 months CA, using the Bayley Scales of Infant Development III and digital questionnaires (Dutch version of the Communicative Development Inventories (N-CDI), Ages and Stages Questionnaire 4 (ASQ-4), and Parent Report of Children’s Abilities – Revised (PARCA-R)).DiscussionThe investigated nutritional intervention is hypothesized to promote brain development and subsequent neurodevelopmental outcome in preterm born infants who have an inherent risk of developmental delay. Moreover, this innovative study may give rise to new treatment possibilities and improvements in routine clinical care.Trial registrationWHO International Clinical Trials Registry: NL-OMON56181 (registration assigned October 28, 2021).

Infant growth by INTERGROWTH-21st and Fenton Growth Charts: Predicting 1-year anthropometry in South African preterm infants.

Post-natal growth influences short- and long-term preterm infant outcomes. Different growth charts, such as the Fenton Growth Chart (FGC) and INTERGROWTH-21st Preterm Post-natal Growth Standards (IG-PPGS), describe different growth curves and targets. This study compares FGC- and IG-PPGS-derived weight-for-postmenstrual age z-score (WZ) up to 50 weeks postmenstrual age (PMA50) for predicting 1-year anthropometry in 321 South African preterm infants. The change in WZ from birth to PMA50 (ΔWZ, calculated using FGC and IG-PPGS) was correlated to age-corrected 1-year anthropometric z-scores for weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ) and BMI-for-age (BMIZ), and categorically compared with rates of underweight (WAZ < -2), stunting (LAZ < -2), wasting (WLZ < -2) and overweight (BMIZ > + 2). Multivariable analyses explored the effects of other early-life exposures on malnutrition risk. At PMA50, mean WZ was significantly higher on IG-PPGS (-0.56 ± 1.52) than FGC (-0.90 ± 1.52; p < 0.001), but ΔWZ was similar (IG-PPGS -0.26 ± 1.23, FGC -0.11 ± 1.14; p = 0.153). Statistically significant ΔWZ differences emerged among small-for-gestational age infants (FGC -0.38 ± 1.22 vs. IG-PPGS -0.01 ± 1.30; p < 0.001) and appropriate-for-gestational age infants (FGC + 0.02 ± 1.08, IG-PPGS -0.39 ± 1.18; p < 0.001). Correlation coefficients of ΔWZ with WAZ, LAZ, WLZ and BMIZ were low (r < 0.45), though higher for FGC than IG-PPGS. Compared with IG-PPGS, ΔWZ < -1 on FGC predicted larger percentages of underweight (42% vs. 36%) and wasting (43% vs. 39%) and equal percentages of stunting (33%), while ΔWZ > + 1 predicted larger percentages overweight (57% vs. 38%). Both charts performed similarly in multivariable analysis. Differences between FGC and IG-PPGS are less apparent when considering ΔWZ, highlighting the importance of assessing growth as change over time, irrespective of growth chart.

Nutritional support during the first week for infants with bronchopulmonary dysplasia and respiratory distress: a multicenter cohort study in China

BackgroundBronchopulmonary dysplasia (BPD) is a major complication affecting the survival rate and long-term outcomes of preterm infants. A large, prospective, multicenter cohort study was conducted to evaluate early nutritional support during the first week of life for preterm infants with a gestational age < 32 weeks and to verify nutritional risk factors related to BPD development.MethodsA prospective multicenter cohort study of very preterm infants was conducted in 40 tertiary neonatal intensive care units across mainland China between January 1, 2020, and December 31, 2021. Preterm infants who were born at a gestational age < 32 weeks, < 72 h after birth and had a respiratory score > 4 were enrolled. Antenatal and postnatal information focusing on nutritional parameters was collected through medical systems. Statistical analyses were also performed to identify BPD risk factors.ResultsThe primary outcomes were BPD and severity at 36 weeks postmenstrual age. A total of 1410 preterm infants were enrolled in this study. After applying the exclusion criteria, the remaining 1286 infants were included in this analysis; 614 (47.7%) infants were in the BPD group, and 672 (52.3%) were in the non-BPD group. In multivariate logistic regression model, the following six factors were identified of BPD: birth weight (OR 0.99, 95% CI 0.99–0.99; p = 0.039), day of full enteral nutrition (OR 1.03, 95% CI 1.02–1.04; p < 0.001), parenteral protein > 3.5 g/kg/d during the first week (OR 1.65, 95% CI 1.25–2.17; p < 0.001), feeding type (formula: OR 3.48, 95% CI 2.21–5.49; p < 0.001, mixed feed: OR 1.92, 95% CI 1.36–2.70; p < 0.001; breast milk as reference), hsPDA (OR 1.98, 95% CI 1.44–2.73; p < 0.001), and EUGR ats 36 weeks (OR 1.40, 95% CI 1.02–1.91; p = 0.035).ConclusionsA longer duration to achieve full enteral nutrition in very preterm infants was associated with increased BPD development. Breastfeeding was demonstrated to have a protective effect against BPD. Early and rapidly progressive enteral nutrition and breastfeeding should be promoted in very preterm infants.Trial registrationThe trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2000030125 on 24/02/2020) and in www.ncrcch.org (No. ISRCTN84167642 on 25/02/2020).

Effects of increased physical therapy staffing in the neonatal intensive care unit on oral feeding maturation and neurodevelopment of extremely low birth weight infants

BackgroundIt remains a matter of debate as to what extent early intervention may facilitate long-term functional outcomes of preterm infants in the neonatal intensive care unit (NICU). We aimed to examine the effect of increasing physical therapy (PT) staff dedicated to the NICU on temporal changes (initiation, duration) of PT interventions and functional outcomes (acquisition of full oral feeding and Hammersmith Neonatal Neurological Examination). MethodsExtremely low birth weight infants, retrospectively collected from an academic medical center, were allocated to two subgroups, either a baseline period (N = 48) without NICU-dedicated PT staff (non-dedicated group) or a quality improvement period (N = 42) with additional dedicated staff (dedicated group). ResultsCompared to those in the non-dedicated group, NICU infants in the dedicated group started PT earlier and had increased PT treatment for additional 14 min per day when achieving full oral feeding. The infants in the dedicated group significantly achieved full oral feeding earlier than the non-dedicated group. As for Hammersmith Neonatal Neurological Examination, there were significant differences in two items (total and tone) between the groups. ConclusionsAdditional NICU-dedicated PT staff facilitated earlier intervention and increased PT treatment in terms of daily duration. Moreover, the dedication shortened the completion of full oral feeding and improved neurological development, presumably resulting in better developmental outcome.

Long-term outcomes of infants with severe BPD

Preterm birth disrupts the normal sequence of lung development. Additionally, interventions that support gas exchange, including positive pressure ventilation and supplemental oxygen can further exacerbate lung injury, increasing the risk of developing bronchopulmonary dysplasia (BPD) in infants born preterm. Approximately 50,000 preterm infants each year in the United States develop BPD. Heterogeneous lung pathology involving the upper and lower respiratory tract can contribute to the BPD phenotype and can be age-dependent. These phenotypes include alveolar, upper airway, large airways, small airways, and vascular. Each of these phenotypes may improve, resolve, or persist at different ages, throughout childhood. The development of BPD endotypes can be influenced by gestational age and length and type of respiratory support. Although, long-term pulmonary outcomes of infants with severe BPD are variable, the presence of small airway disease is a common phenotype in school age and adolescent children. In this review we examine the more common respiratory endotypes found in infants and children with severe BPD and discuss the long-term prognosis for cardiovascular, neurological, and gastrointestinal morbidities in this patient population.

Esophageal Versus Rectal Temperature Monitoring During Whole-Body Therapeutic Hypothermia for Hypoxic–Ischemic Encephalopathy: Association with Short- and Long-Term Outcomes

To compare the short- and long-term outcomes of infants with hypoxic-ischemic encephalopathy (HIE) treated with whole-body therapeutic hypothermia (TH), monitored by esophageal vs rectal temperature. We conducted a secondary analysis of the multicenter High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial. All infants had moderate or severe HIE and were treated with whole-body TH. The primary outcome was death or neurodevelopmental impairment (NDI) at 22-36months of age. Secondary outcomes included seizures, evidence of brain injury on magnetic resonance imaging, and complications of hypothermia. Logistic regression was used with adjustment for disease severity and site as clustering variable because cooling modality differed by site. Of the 500 infants who underwent TH, 294 (59%) and 206 (41%) had esophageal and rectal temperature monitoring, respectively. There were no differences in death or NDI, seizures, or evidence of injury on magnetic resonance imaging between the 2 groups. Infants treated with TH and rectal temperature monitoring had lower odds of overcooling (OR 0.52, 95% CI 0.34-0.80) and lower odds of hypotension (OR 0.57, 95% CI 0.39-0.84) compared with those with esophageal temperature monitoring. Although infants undergoing TH with esophageal monitoring were more likely to experience overcooling and hypotension, the rate of death or NDI was similar whether esophageal monitoring or rectal temperature monitoring was used. Further studies are needed to investigate whether esophageal temperature monitoring during TH is associated with an increased risk of overcooling and hypotension.

Long-Term Outcome of Neonates and Infants whose Mothers Tested Positive for SARS-CoV-2 during Pregnancy - a Pilot of the Post-CRONOS Project.

Long-term effects on infants of mothers with SARS-CoV-2 infection during pregnancy are increasingly discussed in the literature. Besides potential neurodevelopment impairments after intrauterine SARS-CoV-2 exposure, there might be differences in the postnatal pediatric care of those children, like the timing of preventive medical examinations (PME) or vaccinations. In this first national long-term follow-up study of women included in the CRONOS registry, we describe maternal impressions of their child´s development and the prevalence of regulatory disorders, and we analyze the timing of PMEs and vaccinations. 773 women who were enrolled between April 3, 2020, and August 24, 2021, in the CRONOS registry were eligible to be contacted by the study coordinators and asked to fill out a web-based questionnaire. 110/773 (14%) women completed the questionnaire. Their children were between the ages of 12 and 31 months (median 20 months). All mothers were satisfied with their child´s development, milestones were achieved in a timely fashion. The reported prevalence for excessive crying, sleeping, and feeding disorders was 11%, 18-32%, and 7%, respectively. PMEs were mostly not delayed, but only 54% of infants received their first vaccination within their first 60 days of life. In summary, our exploratory findings suggest that developmental milestones in infancy are reached in time after maternal SARS-CoV-2 infection during pregnancy. However, there are effects on the implementation of PMEs and vaccinations. EINFüHRUNG: In der Literatur werden zunehmend potenzielle Langzeitfolgen für Säuglinge nach intrauteriner SARS-CoV-2-Exposition diskutiert. Neben möglichen Beeinträchtigungen der neurologischen Entwicklung können Unterschiede in der pädiatrischen postnatalen Betreuung bei diesen Kindern z. B. bei der Durchführung von Vorsorgeuntersuchungen (sog. U´s) oder Impfungen bestehen. In dieser ersten nationalen Langzeit-Follow-up-Studie aus dem CRONOS-Register beschreiben wir mütterliche Eindrücke zur Entwicklung ihres Kindes, sowie die Prävalenz von Regulationsstörungen. Wir analysieren den Zeitpunkt von U´s und Impfungen. 773 Frauen, die zwischen dem 03.04.2020 und dem 24.08.2021 in CRONOS aufgenommen wurden, wurden von den Studienkoordinatoren kontaktiert und gebeten, einen webbasierten Fragebogen auszufüllen. 110/773 (14%) Frauen füllten den Fragebogen aus, ihre Kinder waren zwischen 12 und 31 Monate alt (Median 20 Monate). Alle Mütter waren mit der Entwicklung ihres Kindes zufrieden, Meilensteine der Entwicklung wurden zeitgerecht erreicht. Die berichtete Prävalenz für exzessives Schreien, Schlaf- und Fütterstörungen betrug 11%, 18-32% bzw. 7%. U´s wurden meist zeitgerecht durchgeführt, aber nur 54% der Säuglinge erhielten ihre erste Impfung innerhalb der ersten 60 Lebenstage. Zusammenfassend deuten unsere explorativen Ergebnisse darauf hin, dass Entwicklungsmeilensteine im Säuglingsalter nach mütterlicher SARS-CoV-2-Infektion in der Schwangerschaft rechtzeitig erreicht werden. Es zeigen sich jedoch Auswirkungen auf die Durchführung von Vorsorgen und Impfungen.

Are Cervical Pessaries Effective in Preventing Preterm Birth?

Preterm births are a significant concern, as they can have serious consequences for both infants and mothers. It is crucial to identify risk factors associated with preterm birth and to implement effective interventions, such as progesterone, cervical pessary, and cervical cerclage, to prevent it. This systematic review aims to evaluate the efficacy of cervical pessary in reducing spontaneous preterm delivery. However, cervical pessaries have limited research and conflicting findings when compared to other interventions for preventing preterm labor. Therefore, this review seeks to analyze various studies to evaluate their overall effectiveness and better understand their role in treating this vulnerable population. The literature search was conducted using PubMed between January and September 2023, and the systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The results of this review highlight the importance of continued research into mitigation strategies for preterm birth. There is some evidence that indicates that using cervical pessaries before 34 weeks can be effective. While some studies have reported positive outcomes when cervical pessaries are combined with other treatments like progesterone, there is no solid statistical evidence to support this claim. Furthermore, additional research is needed to comprehend the impact of singleton pregnancies and long-term outcomes for both mothers and infants.

Accuracy of Umbilical Cord Complete Blood Count in Detecting Early-Onset Neonatal Thrombocytopenia.

Neonatal thrombocytopenia (NTCP) is a common hematological disorder whose platelet count falls below the normal limitof 150 x 109/L. NTCP can causelate complications if left untreated. The current study aimed to evaluate the accuracy of the umbilical cord complete blood count (UC CBC) in detecting early-onsetneonatal thrombocytopenia(EO-NTCP). Further, the prevalence of NTCP was also investigated. Methods: A cross-sectional study with a matched control was conducted on all newborns delivered at a tertiary care center in Jeddah, Saudi Arabia, between May 2016 and 2019. After exclusions, 40 neonateswith EO-NTCP (cases) and 80 without EO-NTCP (controls) were included. The case-to-control ratio was 1:2. The results of UC CBC were compared with those of follow-up CBC, performed within 72 hours.A p-value of <0.05 was considered statistically significant. All data were analyzed using IBM SPSS version 28 for Windows (IBM Corp., Armonk, NY). The prevalence of NTCP was approximately 1.02% (111/10,936). Lack of antenatal care was found in12 (30%) neonates with EO-NTCP vs. 10 (12.5%)neonates without EO-NTCP (p = 0.02). Neonates with EO-NTCP were more likely to have experiencedintrauterine growth restriction (5 (37.5%) vs. 5 (6.3%), p < 0.001)and oligohydramnios (5 (12.5%) vs. 0 (0%), p = 0.003). Neonates who developed EO-NTCP were more likely to be admitted to the NICU (34 (85%) vs. 35 (43.8%), p < 0.001) and receiveantibiotics (22 (55%) vs. 25 (31.3%), p = 0.012). Also, neonates with EO-NTCP were more frequently diagnosed with neonatal sepsis (7 (17.5%) vs. 3 (3.8%), p = 0.015)and more likely to receiveplatelet transfusions (15 (37.5% vs. 1 (1.3%), p < 0.001). They also had a higher median length of hospital stay(13 (interquartile range (IQR) 3-28) vs. 4(IQR 2-9) days, p = 0.006). The mortality rates of neonates with EO-NTCP and those without were 6 (15%) vs. 2 (2.5%) neonates (p = 0.016). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of UC CBC were 62.50%, 97.50%, 20.40%, and 99.61%, respectively. The prevalence of EO-NTCP in King Abdulaziz Medical City is comparable to international and national figures, and itis associated with preceding maternal comorbidities, serious neonatal morbidity, and even mortality. Therefore, proper antenatal care is vital in preventing maternal and neonatal morbidities, including the risks of NTCP and itsrelatedcomplications. With high NPV, using UC CBC as a universal screening method could assist in safely discharging newborns. However, because of its low sensitivity, a comprehensive clinical examination with confirmatory laboratory tests are stillthe cornerstone in diagnosing EO-NTCP. Future trials should aim to study the cost-effectiveness of universal UC CBC and the long-term outcomes of infants diagnosed with EO-NTCP.

Intrauterine Detection of Ureaplasma Species after Vaginal Colonization in Pregnancy and Neonatal Outcome

Introduction: Intrauterine infection with Ureaplasma species (U.spp.) is mostly a result of vaginal colonization with subsequent ascending infection and is associated with adverse pregnancy outcome. Little is known about rates and risk factors for ascending infection. Aim of the current study was to analyse the frequency of ascending U.spp. infection in vaginally colonized pregnant women delivering preterm and subsequent short- and long-term outcome of infants. Methods: Women delivering ≤32 weeks of gestation with available data on vaginal U.spp. colonization in early pregnancy as well as amniotic and placental colonization screening during caesarean section were included. Neonatal short- and long-term outcome was analysed depending on vaginal and intrauterine colonization. Results: Seventy-two women giving birth to 104 preterm infants were included. Intrauterine microbial invasion was found in 23/72 (31.9%) pregnancies. The most commonly detected organisms were U.spp. (52.2%), followed by E. coli (21.7%) and Enterococcus faecalis (17.4%). Intrauterine growth of U.spp. occurred exclusively after previous vaginal colonization in early pregnancy (42/72; 58.3%) and was found in 12/42 (28.6%) cases. Ascending U.spp. infection mainly occurred in pregnancies delivering <28 weeks after preterm rupture of membranes or preterm labour (9/17, 52.3%). Intrauterine detection of U.spp., but not vaginal colonization, was associated with a significantly higher rate of severe intraventricular haemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and unfavourable psychomotor outcome. Conclusion: Ascending U.spp. infection after previous vaginal colonization occurred in almost one-third of pregnancies delivering ≤32 weeks, with particularly high rates in those <28 weeks, and was associated with adverse outcome of preterm infants.

The Cohort of Indonesian Preterm Infants for Long-term Outcomes (CIPTO) study: a protocol

BackgroundIndonesia has high numbers of preterm birth, i.e., around 600,000 preterm births annually. It imposes a significant burden on the Indonesia’s healthcare system. Indonesia therefore requires its own evidence-based reference to manage premature neonates and ex-preterm infants who subsequently survived. No long-term study on preterm infants in Indonesia has been conducted, therefore we aim to evaluate growth and development on ex-preterm infants until the pre-pubertal stage.MethodsWe at the Cipto Mangunkusumo General Hospital (CMGH) designed a prospective cohort study of preterm infants, i.e., the Cohort of Indonesian Preterm Infants for Long-term Outcomes (CIPTO) study. At least 500 subjects will be recruited with an estimation of two-year recruitment (i.e., the recruitment phase will be completed before 2024). The CIPTO study will observe long-term outcomes of ex-preterm infants, primarily on growth and developmental milestones until 8 years old. Aims of this study are to determine the ex-preterm outcomes and to generate an evidence-based reference of preterm care for ensuring optimum outcomes. The pre-specified long-term outcomes in this study are survival rates, growth outcomes, neurodevelopmental outcomes, feeding behavior, as well as hearing and vision impairments. Growth and neurodevelopmental outcomes will be assessed at 0, 2, 4, 6, 9, 12, 15, 18 and 24 months of corrected age as well as at 3, 4, 5, 6, 7 and 8 years old.DiscussionThe CIPTO study is the first prospective cohort in Indonesia focusing on preterm infants born at the CMGH. With a follow up until 8 years old, this study may provide useful insights to generate an evidence-based, Indonesia’s health care reference in managing premature infants and ensuring the optimum outcomes of ex-preterm infants.

A randomised controlled trial in preterm infants comparing prophylactic with selective “less invasive surfactant administration” (pro.LISA)

BackgroundRespiratory distress syndrome is the main cause of mortality and morbidity in preterm infants. “Less invasive surfactant administration” (LISA), which describes intratracheal surfactant administration to spontaneously breathing infants via a small diameter tube, is recommended as the first-line treatment in preterm infants with more than 30% supplemental oxygen. Prophylactic use of LISA in preterm infants with less than 30% supplemental oxygen was not tested in randomised controlled trials yet, and long-term outcome data of the procedure are scarce.MethodsPreterm infants with a gestational age between 25 weeks + 0 days and 28 weeks + 6 days who are breathing spontaneously on continuous positive airway pressure with supplemental oxygen at or below 30% in the first hour of life will be randomised to a prophylactic LISA treatment with 100–200 mg surfactant intratracheally per kilogramme bodyweight (intervention group) or will continue the continuous positive airway pressure treatment (control group). Participants will have follow-up until age 5 years. At that time, the children will be tested by spirometry, and forced expiratory volume within 1-s z-scores will be compared between the intervention and control groups as the primary outcome parameter of the trial. Secondary endpoints include additional lung function parameters, endurance, motor development, intelligence, and sensitivity for infectious lung diseases. Short-term safety assessment will be done after completed enrolment (n = 698) and discharge of all infants. This safety assessment will include in-hospital mortality and short-term complications.DiscussionRobust data concerning the possible long-term benefits of prophylactic LISA treatment are lacking. The current observational data from the German Neonatal Network indicate that approximately 50% of preterm infants with supplemental oxygen at or below 30% within the first hour of life are treated with LISA. The pro.LISA trial will provide short- and long-term outcomes of preterm infants receiving prophylactic treatment and will clarify if prophylactic treatment should be given to all preterm infants or if the current practice of selective treatment if supplemental oxygen exceeds 30% is more appropriate.Trial registrationGerman Clinical Trials Register DRKS00028086. Prospectively registered on 8 February 2022.

Apgar Score and Neurodevelopmental Outcomes at Age 5 Years in Infants Born Extremely Preterm

The Apgar score is used worldwide as an assessment tool to estimate the vitality of newborns in their first minutes of life. Its applicability to estimate neurodevelopmental outcomes in infants born extremely preterm (EPT; <28 weeks' gestation) is not well established. To investigate the association between the Apgar score and neurodevelopmental outcomes in infants born EPT. This cohort study was conducted using data from the Effective Perinatal Intensive Care in Europe-Screening to Improve Health in Very Preterm Infants in Europe (EPICE-SHIPS) study, a population-based cohort in 19 regions of 11 European countries in 2011 to 2012. Clinical assessments of cognition and motor function at age 5 years were performed in infants born EPT and analyzed in January to July 2023. Apgar score at 5 minutes of life categorized into 4 groups (0-3, 4-6, 7-8, and 9-10 points). Cognitive and motor outcomes were assessed using the Wechsler Preschool and Primary Scale of Intelligence test of IQ derived from locally normed versions by country and the Movement Assessment Battery for Children-Second Edition. Parents additionally provided information on communication and problem-solving skills using the Ages and Stages Questionnaire, third edition (ASQ-3). All outcomes were measured as continuous variables. From the total cohort of 4395 infants born EPT, 2522 infants were live born, 1654 infants survived to age 5 years, and 996 infants (478 females [48.0%]) followed up had at least 1 of 3 outcome measures. After adjusting for sociodemographic variables, perinatal factors, and severe neonatal morbidities, there was no association of Apgar score with IQ, even for scores of 3 or less (β = -3.3; 95% CI, -10.5 to 3.8) compared with the score 9 to 10 category. Similarly, no association was found for ASQ-3 (β = -2.1; 95% CI, -24.6 to 20.4). Congruent results for Apgar scores of 3 or less were obtained for motor function scores for all children (β = -4.0; 95% CI, -20.1 to 12.1) and excluding children with a diagnosis of cerebral palsy (β = 0.8, 95% CI -11.7 to 13.3). This study found that low Apgar scores were not associated with longer-term outcomes in infants born EPT. This finding may be associated with high interobserver variability in Apgar scoring, reduced vitality signs and poorer responses to resuscitation after birth among infants born EPT, and the association of more deleterious exposures in the neonatal intensive care unit or of socioeconomic factors with greater changes in outcomes during the first 5 years of life.

The Effect of Postnatal Cytomegalovirus Infection on (Micro)structural Cerebral Development in Very Preterm Infants at Term-Equivalent Age

Introduction: There are some data indicating a negative impact of postnatal cytomegalovirus (CMV) infection on long-term neurodevelopmental outcome of preterm infants. So far, there is only little knowledge about a cerebral imaging correlate of these neurodevelopmental alterations induced by postnatal CMV infection in preterm infants. The aim of the current study was to investigate the effect of postnatal CMV infection on the incidence of brain injury and on microstructural brain maturation in very preterm infants at term-equivalent age. Methods: Infants <32 gestational weeks (02/2011–11/2018) received cerebral MRI including axial diffusion-weighted images at term-equivalent age. All infants were screened for CMV infection using urine/saliva samples, and infection was regarded as acquired postnatal if a sample became positive >5 postnatal days. We compared brain injury as well as fractional anisotropy and apparent diffusion coefficient in 14 defined cerebral regions between infants with and without postnatal CMV infection. Results: 401 infants were eligible, of whom 18 (4.5%) infants had a postnatal CMV infection. There were no significant differences in rates of brain injury or in microstructural brain development between both groups. This applied equally to the subgroup of infants <28 gestational weeks. Conclusion: Although infants with postnatal CMV infection were born more immature and more frequently suffered from complications related to immaturity, we neither observed a higher rate of preterm brain injury nor disadvantageous alterations in microstructural brain maturation at term-equivalent age.

Consensus Panel Recommendations for the Pharmacological Management of Pregnant Women with Depressive Disorders.

The initiative of a consensus on the topic of antidepressant and anxiolytic drug use in pregnancy is developing in an area of clinical uncertainty. Although many studies have been published in recent years, there is still a paucity of authoritative evidence-based indications useful for guiding the prescription of these drugs during pregnancy, and the data from the literature are complex and require expert judgment to draw clear conclusions. For the elaboration of the consensus, we have involved the scientific societies of the sector, namely, the Italian Society of Toxicology, the Italian Society of Neuropsychopharmacology, the Italian Society of Psychiatry, the Italian Society of Obstetrics and Gynecology, the Italian Society of Drug Addiction and the Italian Society of Addiction Pathology. An interdisciplinary team of experts from different medical specialties (toxicologists, pharmacologists, psychiatrists, gynecologists, neonatologists) was first established to identify the needs underlying the consensus. The team, in its definitive structure, includes all the representatives of the aforementioned scientific societies; the task of the team was the evaluation of the most accredited international literature as well as using the methodology of the "Nominal Group Technique" with the help of a systematic review of the literature and with various discussion meetings, to arrive at the drafting and final approval of the document. The following five areas of investigation were identified: (1) The importance of management of anxiety and depressive disorders in pregnancy, identifying the risks associated with untreated maternal depression in pregnancy. (2) The assessment of the overall risk of malformations with the antidepressant and anxiolytic drugs used in pregnancy. (3) The evaluation of neonatal adaptation disorders in the offspring of pregnant antidepressant/anxiolytic-treated women. (4) The long-term outcome of infants' cognitive development or behavior after in utero exposure to antidepressant/anxiolytic medicines. (5) The evaluation of pharmacological treatment of opioid-abusing pregnant women with depressive disorders. Considering the state of the art, it is therefore necessary in the first instance to frame the issue of pharmacological choices in pregnant women who need treatment with antidepressant and anxiolytic drugs on the basis of data currently available in the literature. Particular attention must be paid to the evaluation of the risk/benefit ratio, understood both in terms of therapeutic benefit with respect to the potential risks of the treatment on the pregnancy and on the fetal outcome, and of the comparative risk between the treatment and the absence of treatment; in the choice prescription, the specialist needs to be aware of both the potential risks of pharmacological treatment and the equally important risks of an untreated or undertreated disorder.

Longitudinal cohort study investigating neurodevelopmental and socioemotional outcomes in school-entry aged children after open heart surgery in Australia and New Zealand: the NITRIC follow-up study protocol

IntroductionDespite growing awareness of neurodevelopmental impairments in children with congenital heart disease (CHD), there is a lack of large, longitudinal, population-based cohorts. Little is known about the contemporary neurodevelopmental profile...