This descriptive and exploratory observational case series examined intestinal colonisation and subsequent bacteraemia due to ESBL-producing Klebsiella pneumoniae (ESBL-Kp) in preterm neonates in Morocco. Prospective bacteriological cultures and antibiotic susceptibility testing were supported by phenotypic methods, including Brilliance ESBL Agar and the NG-Test CARBA-5 assay, for the rapid detection of ESBL and carbapenemase producers. Molecular analysis using PCR was also undertaken to identify specific resistance genes. A total of 567 rectal swabs were collected from 339 preterm neonates, yielding 293 K. pneumoniae isolates. ESBL-producing strains were identified in 53.6% of the neonates (182/339). Detected resistance genes included blaSHV (26.3%), blaCTX-M-1 (42.8%), blaTEM (30.2%), blaOXA-48 (50.0%), blaNDM(15.3%), and blaVIM (4.9%). Principal risk factors for colonisation were low birth weight (OR 1.69), very preterm birth (OR 6.24), enteral tube feeding (OR 2.02), and prolonged use of third-generation cephalosporins (OR 1.26). Among the neonates studied, 32 (9.4%) developed healthcare-associated bacteraemia, with 56.2% of these cases preceded by intestinal colonisation with ESBL-Kp. Clinically, severe respiratory distress and alveolar haemorrhage were strongly associated with increased mortality (aRR = 29.32 and 4.45, respectively). The findings highlight the clinical importance of early screening to guide infection control and antimicrobial stewardship in neonatal intensive care settings.

The estimated global preterm birth rate in 2020(1) was more than 10% of livebirths or 13.4 million infants. Despite the importance of neonatal nutrition in optimising growth, neurodevelopment, and later metabolic disease risk, there is inconsistency in nutrition recommendations for preterm infants(2). Incomplete or inconsistent reporting of outcomes in nutrition intervention studies is part of the reason for the lack of consensus on optimal nutrition. To reduce uncertainty in measuring or reporting nutritional intake and growth outcomes in preterm studies, a consensus process is needed to identify relevant measures for patients, parents/caregivers, researchers, and health professionals. We aimed to develop a minimum reporting set (MRS) for measures of nutritional intake and growth in preterm nutrition studies. We collaborated with a group of international researchers from 13 countries and registered this study at the COMET initiative (registration number 3185). The target population was individuals born preterm at any gestational age and study location whose nutritional intake was assessed before first hospital discharge and whose growth was assessed at any age. Measures reported in preterm nutrition studies were systematically reviewed and used to develop the real-time Delphi survey(3) using Surveylet (Calibrum) software, including 13 questions about nutritional intake and 14 about growth outcomes. We used a snowball process to recruit participants from the consumer, healthcare provider, and researcher stakeholder groups with expertise in preterm infants, nutrition, and growth to rate the importance of each measure on a 9-point Likert scale. Participants initially rated the survey items without seeing other participants’ responses, saved and refreshed the page to see the anonymous responses of other participants, and had the option to change their rating and provide reasons for their answers. Participants’ final scores for each item will be used to identify the consensus criteria for that item(3). To date, we have recruited 246 participants from 31 countries across 5 continents, including 58 (24%) consumers, 156 (63%) healthcare professionals, and 26 (11%) researchers. Preliminary findings indicate that 12 measures of nutritional intake and 4 of growth have met the criteria for inclusion in the MRS. However, participant recruitment and survey responses are ongoing. A final consensus meeting is planned for November 2024 to confirm the MRS.

The iron regulation mechanisms are not exactly the same between adulthood and the early postnatal period. Also, neonatal iron status is different in full-term versus preterm infants because the prenatal/gestational period, when hepatic iron accumulates, is shortened. Newborns, especially premature infants, are at high risk of iron deficiency due to inadequate iron stores, which constitute the primary source of iron to satisfy the neonate’s increasing iron requirements. In addition, frequent blood transfusions and congenital haemochromatosis may induce iron overload in the affected neonate. To understand the cause of neonatal iron deficiency/overload and to promote the development of effective therapeutic interventions in humans, different animal models have been generated by genetic engineering, low-/high-iron diets, phlebotomy/transfusion and surgical manipulation. These models use various laboratory and domestic animals to study iron imbalance. They serve as surrogate models for experiments that are ethically or practically unfeasible to conduct on human neonates. Although an animal model for studying neonatal iron disorders may not fully replicate the complexities of human diseases, it is designed to model specific aspects of these conditions. Combined data from multiple models can help to offset the limitations inherent in each individual model. In this review, we outline approaches to induce neonatal iron disorders, current animal models of full-term and preterm neonates, and recommendations for diagnosis.

Patent ductal arteriosus stenting is an alternative procedure in patients with pulmonary-ductal-dependent circulation. Stent embolization is one of the major acute complications of ductal stenting procedure. We describe the case of a stent embolization into the abdominal aorta during the deployment of ductal stent in a premature low-weight infant (1.850 kg), affected by critical pulmonary stenosis and duct-dependent pulmonary circulation. The stent was successfully retrieved through a 4F Flexor catheter without vascular complication by using a new approach.

Preterm birth exposes the neonate to hypoxic-ischaemic and excitotoxic insults that impair neurodevelopment and are magnified by the premature loss of placentally supplied, inhibitory neurosteroids. The cerebellum is a neuronally dense brain region, which undergoes critical periods of development during late gestation, when preterm births frequently occur. We propose that neurosteroid replacement therapy using tiagabine and zuranolone will protect the cerebellum against preterm-associated insults. Guinea pig dams received c-section surgery preterm (gestational age (GA) 64) or at term (GA70) with preterm pups administered tiagabine (2.5 mg/kg/day), zuranolone (1 mg/kg/day) or vehicle (15% β-cyclodextrin) until term equivalent age (GA70). Behavioural testing was performed at corrected postnatal day 8 (PND8) and PND41 with tissue collection occurring at PND42. Neurodevelopmental markers (MBP, OLIG2 and NeuN) were assessed within the cerebellum by immunohistochemistry, whilst GABAergic and glutamatergic pathway expression was quantified using high throughput RT-PCR. Zuranolone and, to a lesser extent, tiagabine were able to protect against hyperactive behaviour at PND8 in males, whilst in females, a less marked hyperactive phenotype was present with neither treatment impacting behaviour further. Both treatments improved MBP staining, whilst tiagabine was found to restore oligodendrocyte maturation in females only. GABAergic and glutamatergic pathway expression was found to be restored by both treatments in females. Overall, this study demonstrates the neuroprotective attributes of neurosteroid replacement therapy using tiagabine and zuranolone, thereby demonstrating their potential to mitigate long-term neurodevelopmental impairments. Furthermore, the sexually dimorphic effects observed suggest future investigations may show increased benefit by using sex-specific treatment regimes.

Children born growth-restricted are well recognized to be at an increased risk of poor neurodevelopmental outcomes. This prospective study examined the influence of chest-to-head circumference ratio at birth on neurodevelopment in the first three years among children enrolled in the Japan Environment and Children’s Study. We analyzed information of 84,311 children (43,217 boys, 41,094 girls). Children were divided into low, normal, and high chest-to-head circumference ratio groups. Neurodevelopment was assessed every six months (from 6 months to 3 years) using the Ages and Stages Questionnaire (Japanese translation), with delays defined as scores below 2 standard deviations from the mean. Additionally, we evaluated the contributions of chest and head circumference to the observed association. Linear mixed-effect regression revealed increased risk of delays in communication, gross motor, fine motor, problem-solving, and personal-social skills in the low-ratio group compared to the normal-ratio group. Adjusted risk ratios were in the range of 1.14 – 1.39 in boys and 1.16 – 1.37 in girls, with no such increase observed in the high-ratio group. The heightened risk in the low-ratio group was likely associated with a relatively narrow chest rather than a large head. The area under the ROC curves in predicting any developmental delay at three years for newborn measurements ranged from 0.513 to 0.526 in boys and 0.509 to 0.531 in girls. These findings suggest that a low chest-to-head circumference ratio may indicate children who are at risk for neurodevelopmental deficits. However, the ability to predict poor neurodevelopmental outcomes at three years of age is limited.

The estimated global preterm birth rate in 20201 was more than 10% of livebirths or 13.4 million infants. Nutrition in the neonatal period is a key factor to optimise growth, neurodevelopment, and later metabolic disease risk2. There is no consensus on optimal nutrition for preterm infants, leading to substantial practice variation3. We aimed to assess the quality of nutritional guidelines for preterm infants, the consistency of recommendations, and the gaps in these recommendations. This review is reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 checklist. The study protocol was registered with PROSPERO (CRD42022327248). We searched six databases and 44 websites for nutritional guidelines for preterm infants before first hospital discharge, which were endorsed, prepared, or authorised by a regional, national, or international body, written in English, and published between 2012-2023. Two reviewers independently screened articles and extracted relevant data including nutritional recommendations (ranges or descriptions), the quality of recommendations (certainty of evidence and strength of recommendation), and gaps in recommendations, defined as those identified by the guidelines or when recommendations were based on very low certainty evidence. Disagreements were resolved by discussion or a third reviewer. Four reviewers appraised the included guidelines using AGREE II. We identified 7051 records, 27 guidelines were included in the review, 26% of which were of high quality. Most guidelines lacked stakeholder involvement and rigour of development. Twelve guidelines had recommendations for macronutrient intake, 18 for micronutrient intake, 12 for feeding, eight for fortification, and 14 for monitoring of nutritional adequacy. Only two guidelines provided recommendations for all five of these aspects. We found considerable variation in recommendations, many of which lacked details of certainty of evidence and strength of recommendation. Recommendations for feeding types and breastmilk fortification were consistent among high quality guidelines, but recommendations varied for intakes of almost all nutrients and monitoring of nutritional adequacy. Different guidelines gave different certainty of evidence for the same recommendations. Most gaps in recommendations were due to a very low certainty of evidence. Future development of nutritional guidelines for preterm infants should follow the standard guideline development method and ensure rigorous process including stakeholders’ involvement to improve the reporting of strength of recommendation, certainty of evidence, and gaps in recommendation. Evidence is needed to support recommendations about macro and micronutrient intakes, breastmilk fortification, and markers on adequacy of intake of different nutrients.

Breast-feeding is associated with fewer comorbidities in very-low-birth-weight (VLBW) preterm infants. Bronchopulmonary dysplasia (BPD) of VLBW infants is a multifactorial pathology in which nutritional aspects may be of special importance. The aim of this study is to determine, in a cohort of VLBW infants, whether breast milk nutrition is associated with a reduced prevalence and severity of BPD. A retrospective study was conducted to record the intake of mother’s own milk (MOM), pasteurised donor human milk or preterm formula milk in the first 2 weeks of postnatal life of 566 VLBW newborns at our hospital during the period January 2008–December 2021. After applying the relevant exclusion criteria, data for 489 VLBW infants were analysed; 195 developed some degree of BPD. Moderate or severe BPD is associated with less weight gain. Moreover, the preferential ingestion of breast milk in the first and second postnatal weeks had effects associated with lower OR for BPD, which were statistically demonstrable for mild (OR 0·16; 95 % CI 0·03, 0·71) and severe (OR 0·08; 95 % CI 0·009, 0·91) BPD. Breast-feeding during the first weeks of postnatal life is associated with a reduced prevalence of BPD, which is frequently associated with less weight gain as a result of greater respiratory effort with greater energy expenditure.

Compared to preterm appropriate for gestational age (AGA) fetuses, fetuses with fetal growth restriction (FGR) have earlier visualisation of coronary artery blood flow (CABF) but impaired cardiac function. This dichotomy remains uncharacterised during postnatal life. This study compared CABF and cardiac function in preterm FGR infants, against AGA infants during the postnatal period. FGR was defined as birthweight < 10th centile for gestation and sex with absent/reversed antenatal umbilical artery Doppler. Diastolic CABF was measured in the left anterior descending coronary artery. Twenty-eight FGR infants were compared with 26 AGA infants (gestation and birthweight, 29.7 ± 1.3 vs 29.9 ± 1 weeks, P = 0.6 and 918 ± 174 vs 1398 ± 263g, P < 0.001, respectively). Echocardiography was performed in the second week of life. FGR infants had higher CABF (velocity time integral, 2.4 ± 0.9 vs 1.6 ± 0.8 cm, P = 0.002). Diastolic function was impaired (↑ trans-mitral E/A ratio in FGR infants; 0.84 ± 0.05 vs 0.79 ± 0.03, P = 0.0002) while the systolic function was also affected (mean velocity of circumferential fibre shortening [mVCFc], 1.9 ± 0.3 vs 2.7 ± 0.5 circ/s, P < 0.001). Indexing CABF to cardiac function noted significant differences between the groups (CABF: E/A [FGR vs AGA], 2.9 ± 1.1 vs 2.1 ± 1, P = 0.01 and CABF: mVCFc [FGR vs AGA], 1.3 ± 0.5 vs 0.6 ± 0.3, P < 0.001). Diastolic blood pressure (BP) was significantly higher, and CABF to diastolic BP ratio trended higher in FGR infants (30 ± 2 vs 25 ± 3 mmHg, P < 0.001 and 0.08 ± 0.03 vs 0.06 ± 0.03, P = 0.059, respectively). Greater CABF in FGR infants did not translate into better cardiac function. This dichotomy may be a persistent response to fetal hypoxaemia (fetal programming) and/or reflection of altered cardiac architecture.

Adolescent pregnancy is associated with adverse birth outcomes. However, the determinants of these outcomes are understudied. The present study sought to identify the predictors of adverse birth outcomes among pregnant adolescents in Ghana. In this prospective health centre-based study, 416 pregnant adolescents, aged 13–19 years old, were followed, and 270 birth outcomes were evaluated. We collected data on socio-demographic variables, eating behaviour, household hunger scale (HHS), lived poverty index (LPI) and compliance to antenatal interventions. The prevalence of low birth weight (LBW) and preterm births (PTB) were 15⋅2 and 12⋅5 %, respectively. Pregnant adolescents with no formal education (AOR 9⋅0; P = 0⋅004; 95 % CI 2⋅1, 39⋅8), those who experienced illness (AOR 3⋅0; P = 0⋅011; 95 % CI 1⋅3, 7⋅0), those who experienced hunger (OR 2⋅9; P = 0⋅010; 95 % CI 1⋅3, 6⋅5) and those with high LPI (OR 2⋅5; P = 0⋅014; 95 % CI 1⋅2, 5⋅3) presented increased odds of delivering preterm babies compared with those who have had secondary education, did not experience any illness, were not hungry or having low LPI, respectively. Pregnant adolescents who used insecticide-treated net (ITN) (AOR 0⋅4; P = 0⋅013; 95 % CI 0⋅2, 0⋅9) presented reduced odds LBW children; while those who experienced illness (AOR 2⋅7; P = 0⋅020; 95 % CI 1⋅2, 6⋅0), poorer pregnant adolescents (OR 2⋅5; P = 0⋅014; 95 % CI 1⋅1, 4⋅8) and those who experienced hunger (AOR 3⋅0; P = 0⋅028; 95 % CI 1⋅1, 8⋅1) presented increased odds of LBW children compared with those who used ITN, were not ill, were not poor or did not experience hunger. Adverse birth outcomes were associated with ANC compliance and socioeconomic factors of the pregnant adolescents. Hence, strengthening antenatal uptake and compliance by pregnant adolescents, promoting their livelihood and socioeconomic status, and interventions to prevent teenage pregnancies are strongly recommended.

There has been an increase in the use of extracorporeal membrane oxygenation for severe neonatal cardiac failure. However, the frequency of complications is high, particularly in preterm and low-birth-weight neonates. Herein, we present combination treatment with transcatheter balloon atrioseptostomy and bilateral pulmonary artery banding in a collapsed preterm neonate. This strategy can be an alternative to circulatory support using extracorporeal membrane oxygenation.

Emerging evidence demonstrates a link between preterm birth (PTB) and later life cardiovascular disease (CVD). We conducted a systematic review and meta-analysis to compare conventional CVD risk factors between those born preterm and at term. PubMed, CINAHL, SCOPUS, and EMBASE databases were searched. The review protocol is registered in PROSPERO (CRD42018095005). CVD risk factors including systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index, lipid profile, blood glucose, and fasting insulin among those born preterm (<37 weeks’ gestation) were compared with those born at term (≥37 weeks’ gestation). Subgroup analyses based on gender, age, gestational at birth (<32 weeks’ gestation and <28 weeks’ gestation), and PTB associated with small for gestational age or average for gestational age were also performed. Fifty-six studies provided data on 308,987 individuals. Being born preterm was associated with 3.26 mmHg (95% confidence interval [CI] 2.08 to 4.44) higher mean SBP and 1.32 mmHg (95% CI: 0.61 to 2.04) higher mean DBP compared to being born at term. Subgroup analyses demonstrated that SBP was higher among (a) preterm compared to term groups from early adolescence until adulthood; (b) females born preterm but not among males born preterm compared to term controls; and (c) those born at <32 weeks or <28 weeks compared to term. Our meta-analyses demonstrate higher SBP and DBP among those born preterm compared to term. The difference in SBP is evident from early adolescence until adulthood.

Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22–3.06; aOR2 = 2.05, 95% CI: 1.33–3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30–3.11; aOR2 = 2.51, 95% CI: 1.69–3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03–2.45; aOR2 = 1.99, 95% CI: 1.05–3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.

Percutaneous closure of patent ductus arteriosus is well established in infants weighing >5 kg, but data regarding outcome of preterm especially very low birth weight infants is minimal. Although surgical ligation of patent ductus arteriosus is the preferred and well-accepted modality of treatment after failure of drug therapy in preterm infants, it has also got its own demerits in such a small and fragile subset. Device closure in infants weighing <1.5 kg is rarely attempted because of high chances of complications, especially acute arterial injury due to the arterial sheath. We received a 1.4-kg ventilator-dependent infant for closure of large patent ductus arteriosus. Percutaneous closure of patent ductus arteriosus was done successfully and the infant was discharged on room air with a weight of 1.8 kg. We present here an innovative technique in which successful patent ductus arteriosus device closure was done in a 1.4-kg infant without using arterial sheath.