Rich-club organization of the newborn human brain.

Combining diffusion magnetic resonance imaging and network analysis in the adult human brain has identified a set of highly connected cortical hubs that form a "rich club"--a high-cost, high-capacity backbone thought to enable efficient network communication. Rich-club architecture appears to be a persistent feature of the mature mammalian brain, but it is not known when this structure emerges during human development. In this longitudinal study we chart the emergence of structural organization in mid to late gestation. We demonstrate that a rich club of interconnected cortical hubs is already present by 30 wk gestation. Subsequently, until the time of normal birth, the principal development is a proliferation of connections between core hubs and the rest of the brain. We also consider the impact of environmental factors on early network development, and compare term-born neonates to preterm infants at term-equivalent age. Though rich-club organization remains intact following premature birth, we reveal significant disruptions in both in cortical-subcortical connectivity and short-distance corticocortical connections. Rich club organization is present well before the normal time of birth and may provide the fundamental structural architecture for the subsequent emergence of complex neurological functions. Premature exposure to the extrauterine environment is associated with altered network architecture and reduced network capacity, which may in part account for the high prevalence of cognitive problems in preterm infants.

Clinical outcomes of Staphylococcus capitis isolation from neonates, England, 2015-2021: a retrospective case-control study.

OBJECTIVE: Staphylococcus capitis, a coagulase-negative staphylococci (CoNS) species, has been increasingly detected from UK sterile site samples and has caused neonatal unit outbreaks worldwide. We compared survival to discharge and 30-day mortality for the detection of S. capitis versus other CoNS species. METHODS: In this retrospective case-control study, we included hospitalised infants with any CoNS species detected from a normally sterile body site up to 90 days of age. We linked English laboratory reports from the Second Generation Surveillance System database, mortality data from the Personal Demographics Service, and neonatal unit admissions from the National Neonatal Research Database. In primary analysis, multivariable logistic regression was used, with two co-primary outcomes: survival to discharge and death within 30 days of positive specimen date. Sensitivity analyses using multiply imputed datasets followed. RESULTS: We identified 16 636 CoNS episodes relating to 13 745 infants. CoNS episodes were highest among infants born extremely preterm (22-27 weeks) and with extremely low birth weight (400-999 g). In primary analysis, there were no differences in survival to discharge (p=0.71) or 30-day mortality (p=0.77) between CoNS species. In sensitivity analyses, there were no differences in outcomes between infection with four of the most common CoNS species (Staphylococcus epidermidis, S. capitis, Staphylococcus haemolyticus and Staphylococcus warneri) but the remaining CoNS species were at higher risk of adverse outcomes when treated in aggregate. CONCLUSION: Infants with S. capitis detected from sterile site samples did not experience significant differences in either survival to discharge or 30-day mortality compared with infants with detection of other common CoNS species.

Delayed finding of congenital duodenal obstruction following congenital diaphragmatic hernia repair.

Congenital diaphragmatic hernia (CDH) is encountered in just under 1 in 6000 live births, while congenital duodenal obstruction is seen once every 8000 live births. These congenital anomalies have only been reported together as part of the VACTERL syndrome and therefore in isolation represent an incredibly rare occurrence. This is a case report of a girl born at 34 weeks gestation who had an antenatal diagnosis of left CDH. Five days following operative repair of this, there was extensive pneumoperitoneum and pneumothorax. Upper gastrointestinal contrast study showed a perforation of the duodenum and at laparotomy, a duodenal web was found in the fourth part of the duodenum with perforation immediately proximal. Following duodenoduodenostomy, the postoperative recovery was good. She achieved full enteral feeds and was discharged home. This case highlights the importance of considering rare associations if postoperative recovery is not as expected to prevent delay in undergoing definitive treatment.

The imperative of arachidonic acid in early human development.

This review is about the role of arachidonic acid (ArA) in foetal and early growth and development. In 1975 and '76, we reported the preferential incorporation of ArA into the developing brain of rat pups, its conservation as a principal component in the brains of 32 mammalian species and the high proportion delivered by the human placenta for foetal nutrition, compared to its parent linoleic acid (LA). ArA is quantitatively the principal acyl component of membrane lipids from foetal red cells, mononuclear cells, astrocytes, endothelium, and placenta. Functionally, we present evidence that ArA, but not DHA, relaxes the foetal mesenteric arteries. The placenta biomagnifies ArA, doubling the proportion of the maternal level in cord blood. The proportions of ArA and its allies (di-homo-gamma-linolenic acid (DGLA), adrenic acid and ω6 docosapentaenoic acid) are similar or higher than the total of ω3 fatty acids in human milk, maintaining the abundant supply to the developing infant. Despite the evidence of the importance of ArA, the European Food Standard Agency, in 2014 rejected the joint FAO and WHO recommendation on the inclusion of ArA in infant formula, although they recommended DHA. The almost universal dominance of ArA in the membrane phosphoglycerides during human organogenesis and prenatal growth suggests that the importance of ArA and its allies in reproductive biology needs to be re-evaluated urgently.

Trends in coagulase-negative staphylococci (CoNS), England, 2010-2021.

Objective: To review the epidemiology of coagulase-negative staphylococci (CoNS) in England over the recent 12 year period. Methods: Laboratory-confirmed CoNS reported from sterile sites in patients in England to the UK Health Security Agency (UKHSA) between 2010 and 2021 were extracted from the national laboratory database and analysed. Results: Overall, 668 857 episodes of CoNS were reported. Unspeciated CoNS accounted for 56 % (374 228) of episodes, followed by Staphylococcus epidermidis (26 %; 174 050), S. hominis (6.5 %; 43 501) and S. capitis (3.9 %; 25 773). Unspeciated CoNS increased by 8.2 % (95 % CI, 7.1-9.3) annually between 2010 and 2016, then decreased annually by 6.4 % (95 % CI: -4.8 to -7.9) until 2021. Speciated CoNS increased by 47.6 % (95 % CI, 44.5-50.9) annually between 2010 and 2016 and increased annually by 8.9 % (95 % CI: 5.1 to 12.8) until 2021. Antimicrobial susceptibility profiles differed by species. Conclusions: Reports of CoNS from normally sterile body sites in patients in England increased between 2010 and 2016 and remained stable between 2017 and 2021. There has been a striking improvement in species-level identification of CoNS in recent years. Monitoring trends in CoNS epidemiology is crucial for development of observational and clinical intervention studies on individual species.

Pilot feasibility study of a digital technology approach to the systematic electronic capture of parent-reported data on cognitive and language development in children aged 2 years.

BACKGROUND: The assessment of language and cognition in children at risk of impaired neurodevelopment following neonatal care is a UK standard of care but there is no national, systematic approach for obtaining these data. To overcome these challenges, we developed and evaluated a digital version of a validated parent questionnaire to assess cognitive and language development at age 2 years, the Parent Report of Children's Abilities-Revised (PARCA-R). METHODS: We involved clinicians and parents of babies born very preterm who received care in north-west London neonatal units. We developed a digital version of the PARCA-R questionnaire using standard software. Following informed consent, parents received automated notifications and an invitation to complete the questionnaire on a mobile phone, tablet or computer when their child approached the appropriate age window. Parents could save and print a copy of the results. We evaluated ease of use, parent acceptability, consent for data sharing through integration into a research database and making results available to the clinical team. RESULTS: Clinical staff approached the parents of 41 infants; 38 completed the e-registration form and 30 signed the e-consent. The digital version of the PARCA-R was completed by the parents of 21 of 23 children who reached the appropriate age window. Clinicians and parents found the system easy to use. Only one parent declined permission to integrate data into the National Neonatal Research Database for approved secondary purposes. DISCUSSION: This electronic data collection system and associated automated processes enabled efficient systematic capture of data on language and cognitive development in high-risk children, suitable for national delivery at scale.

Neurodevelopment, nutrition and genetics. A contemporary retrospective on neurocognitive health on the occasion of the 100th anniversary of the National Institute of Nutrition, Hyderabad, India.

In celebration of the centenary of the National Institute of Nutrition (NIN), Hyderabad, India (1918-2018), a symposium highlighted the progress in nutrition knowledge made over the century, as well as major gaps in implementation of that knowledge. Brain famine caused by a shortage of nutrients required for perinatal brain development has unfortunately become a global reality, even as protein-calorie famine was largely averted by the development of high yield crops. While malnutrition remains widespread, the neglect of global food policies that support brain development and maintenance are most alarming. Brain disorders now top the list of the global burden of disease, even with obesity rising throughout the world. Neurocognitive health, remarkably, is seldom listed among the non-communicable diseases (NCDs) and is therefore seldom considered as a component of food policy. Most notably, the health of mothers before conception and through pregnancy as mediated by proper nutrition has been neglected by the current focus on early death in non-neurocognitive NCDs, thereby compromising intellectual development of the ensuing generations. Foods with balanced essential fatty acids and ample absorbable micronutrients are plentiful for populations with access to shore-based foods, but deficient only a few kilometres away from the sea. Sustained access to brain supportive foods is a priority for India and throughout the world to enable each child to develop to their intellectual potential, and support a prosperous, just, and peaceful world. Nutrition education and food policy should place the nutritional requirements for the brain on top of the list of priorities.

Neurodevelopmental impairment among infants born to mothers infected with human immunodeficiency virus and uninfected mothers from three peri-urban primary care clinics in Harare, Zimbabwe.

AIM: The aim of this article is to document the risk of neurodevelopmental impairment (NDI) among infants enrolled in a programme for the prevention of mother-to-child transmission of HIV (human immunodeficiency virus) in Zimbabwe using the Bayley Infant Neurodevelopmental Screener (BINS). METHOD: We prospectively followed up infants at three primary care clinics in Harare, Zimbabwe. Neurodevelopmental assessments using the BINS were conducted during the first 12 months of life. NDI risk category and associated risk factors were examined. RESULTS: Of the 598 infants assessed, 305 (51%) were female and 293 (49%) were male. Sixty-five infants (11%) were infected with HIV, 188 (31%) were exposed but uninfected, 287 (48%) were unexposed, and 58 (10%) were of unknown status. The prevalence of a high risk of NDI was 9.4% (95% confidence interval [CI] 7.1-11.1%): 9.2% in males and 9.6% in females. Of the 598 infants, 549 (92%) had ever been breastfed, 49% of whom had mothers infected with HIV. The risk of NDI was higher among infants infected early with HIV, i.e. by 3 months of age (p value <0.001). The NDI high-risk category included twice as many infants infected with HIV as uninfected infants (odds ratio [OR] 2.1; 95% CI 1.0-4.3). After adjusting for other factors, head circumference and family financial subsistence remained risk factors for NDI with an OR of 2.22 (1.04-4.82) and 2.55 (1.02-6.36) respectively. INTERPRETATION: The background prevalence of high-risk NDI category of 9.4% across groups seems high but is similar to that reported previously in developing countries. Integration of an early infant neurodevelopmental screening programme into child HIV management protocols will assist in the early referral of children exposed to HIV.

Thoracoscopic Repair of Congenital Diaphragmatic Hernia in Preterm Neonate at 1 Kilogram.

We report the first successful primary thoracoscopic repair of congenital diaphragmatic hernia (CDH) in a preterm infant born at 28 weeks of gestation weighing 1,043 g. Left-sided CDH was incidentally diagnosed on postnatal chest X-ray on day 1. The neonate subsequently underwent thoracoscopic repair with primary closure of the defect on day 8 weighing 1,150 g. Intraoperative arterial blood gas monitoring including end tidal carbon-dioxide remained within normal range throughout. Postoperative recovery was uneventful. One year neurodevelopmental outcome was normal for age with no CDH recurrence.

Gestational diabetes mellitus prediction? A unique fatty acid profile study.

OBJECTIVE: To elucidate whether women at risk of gestational diabetes mellitus (GDM) have a unique fatty acid profile compared to women considered normal healthy controls (NHC). METHODS: Three hundred pregnant women were randomized to a control group (NHC) (n = 50) and to one of three high risk groups (n = 250), one of which was GDM (n = 50). At recruitment participants' booking bloods were taken and analyzed for lipid profiles. The GDM group's fatty acid profile is reported here. RESULTS: GDM women compared to NHC had elevated levels of omega 6 (n-6) fatty acids compared to omega 3 (n-3) fatty acids (p = 0.01), of linoleic acid (LA) to docosahexaenoic acid (DHA) p = 0.001, sequentially distorted levels of n-6 fatty acids LA and arachidonic acid (ArA) p = 0.035, as well as significantly depressed levels of n-3 DHA (p = 0.01). CONCLUSION: This paper shows that GDM women have a unique fatty acid profile with elevated levels of n-6 fats, depressed levels of n-3 fats and an abnormal pattern of sequential n-6 metabolism. This profile probably results from a combination of factors including underexpression and or poor utilization of desaturase enzymes, suboptimal dietary fatty acids intake, poor micronutrient status or dysbiosis of the microbiome. These results help inform development of a clinical predictive tool.

Peri-conception maternal lipid profiles predict pregnancy outcomes.

In this study, healthy women and those at high-risk of adverse pregnancy outcomes (pre-eclampsia, fetal growth restriction, gestational diabetes) were selected to assess the effect of fatty acid supplementation. The purpose of this paper is to report two novel findings (i) at recruitment the receiver operating characteristic (ROC) for erythrocyte oleic acid predicted spontaneous delivery at 34 weeks gestation (ROC=0.926 n=296) for all women entering the study. Further analysis revealed oleic and all monounsaturated fatty acids were similarly predictive with or without a supplement during the pregnancy. (ii) At delivery, we observed a biomagnification of saturated fatty acids from mother to fetus with the reverse for monounsaturates. The major conclusions are (i) the status of the mother in the months prior to conception is a stronger predictor of preterm delivery than the events during the pregnancy. (ii) Saturated fats may be playing an important function in supporting fetal membrane growth.