Articoli di riviste sul tema "Infants switched at birth – Fiction"

T cell–dependent immune responses develop soon after birth, whereas it takes 2 yr for humans to develop T cell–independent responses. We used this dissociation to analyze the repertoire diversification of IgM+IgD+CD27+ B cells (also known as “IgM memory” B cells), comparing these cells with switched B cells in children <2 yr of age, with the aim of determining whether these two subsets are developmentally related. We show that the repertoire of IgM+IgD+CD27+ B cells in the spleen and blood displays no sign of antigen-driven activation and expansion on H-CDR3 spectratyping, despite the many antigenic challenges provided by childhood vaccinations. This repertoire differed markedly from those of switched B cells and splenic germinal center B cells, even at the early stage of differentiation associated with μ heavy chain expression. These data provide evidence for the developmental diversification of IgM+IgD+CD27+ B cells, at least in very young children, outside of T cell–dependent and –independent immune responses.

ABSTRACTBackgroundBreast‐fed infants grow more slowly than bottle‐fed infants. This growth deceleration sometimes alarms health care personnel to the point of considering other forms of nutrition.ObjectivesTo evaluate the final adult anthropometric outcome associated with breast or formula feeding during infancy.DesignHeight and weight data were collected from eight well‐baby clinics representing various ethnic origins, lifestyles, and socioeconomic backgrounds. Children were measured every 1 to 2 months for the first 6 months, every 3 months until 2 years of age, and yearly thereafter, until they reached their final height. Longitudinal data were collected from 1960 healthy children (961 boys). Overall, 613 of the children were breast fed for 1 year and 218 for 6 months.ResultsThe magnitude of the decline in Z scores of breast‐fed vs. bottle‐fed infants, between birth and 1 year of age was not as great for height as for weight −0.2 and −0.3 respectively, and disappeared at 2 years of age. The weight for height decreased between birth and the end of the first year in breast‐fed children by 0.3 (Z score). Children switched to bottle feeding exhibited a growth spurt. However, there was no difference in the final heights or weights of breast‐fed children compared with bottle‐fed children 165.3 ± 6.2 (n = 134) versus 164.9 ± 6.4 (n = 195) in females, respectively, and 175.3 ± 6.8 (n = 122) versus 175.8 ± 7.1 (n = 162) in males, respectively. Adult obesity in this sample population (n = 637) was correlated with maternal obesity. Maternal BMI SD correlated with offspring BMI SD at 18 years of age (r = 0.873, P < 0.001) but not with breast feeding. Adult BMI was similar between the breast‐fed and bottle‐fed groups.ConclusionsDespite their slower growth rate, breast‐fed children reach the same final height as bottle‐fed children. Breast‐fed infants should be monitored according to specifically designed growth charts. Obesity in adult life is correlated with factors not related to breast feeding.

Background and AimConcentrated standardised parenteral nutrition (CSPN) may reduce the delay in commencing parenteral nutrition (PN) in preterm infants compared with conventional individualised PN. Optimisation of early nutrition, with emphasis on earlier commencement of PN to include amino acids and addition of lipids within 24 hours of birth, ameliorates early postnatal growth failure.1 2 Cumulative nutritional deficit often seen in significantly preterm infants may lead to poor neurodevelopmental outcome.3 4 CSPN was introduced in our neonatal unit in December 2017 with the objective of improving early nutrition. The aim of this service evaluation was to assess the suitability of CSPN and its impact on the growth of preterm infants in our tertiary level neonatal unit.MethodsIn December 2017, the neonatal PN provided was switched from individualised PN to CSPN based on a modified ‘SCAMP’ regimen. Retrospective and prospective growth parameter data was collected for infants receiving PN within 24 hours of birth born between September to November 2017 (individualised PN arm) and from September to November 2018 (CSPN arm). Infants were excluded if they died or transferred out of the local neonatal service before day 28 of life, or died before transitioning from PN to full enteral feeds. Weight and head circumference at birth, 28 days old and 36 weeks corrected gestation/discharge were converted to z scores using the LMS method. The Mann-Whitney test was used to compare continuous data. Annual PN expenditure, and wastage of ordered PN, before and after the switch to CSPN, was calculated using the pharmacy stock management system, pharmacist and finance records.Results20 infants (mean gestational age 28 weeks) and 21 infants (mean gestational age 29.6 weeks) were included in the CSPN and individualised PN groups respectively. There were no differences in demographic data of each group. CSPN was commenced earlier (median 8 hours old (n=20)) than individualised PN (median 25 hours old (n=19)), (U=42, p<0.0001). There was no statistical difference in the change in weight z score from birth at 28 days old (median -0.47 (n=20) CSPN vs -0.66 (n=19) individualised PN, U=178.5, p=0.75) and at 36 weeks corrected gestation/discharge (median -0.72 (n=20) CSPN vs -0.86 (n=21) individualised PN, U=106, p=0.7). There was insufficient data collected to analyse effect on head circumference. Replacing individualised PN with CSPN resulted in a 37% reduction in procurement costs, despite an increase in the wastage of ordered PN from 7.2% to 8.5%.ConclusionA PN strategy using concentrated standardised PN can be implemented successfully in a tertiary neonatal unit setting in the United Kingdom and allows earlier commencement of PN. Use of CSPN appeared to have no adverse effect on weight gain, although small sample size may account for the lack of statistical significance in improvement of weight z score seen. Improved rates of head circumference documentation for our patients are required. Introducing CSPN resulted in a considerable reduction in procurement costs, and identifying strategies to minimise wastage of CSPN bags would further improve cost-effectiveness.ReferencesMorgan C, McGowan P, Herwitker S, et al. Postnatal head growth in preterm infants: a randomised controlled parenteral nutrition study. Pediatrics 2014;133:e120–8.Moyses HE, Johnson MJ, Leaf AA, et al. Early parenteral nutrition and growth outcomes in preterm infants: a systematic review and meta-analysis. Am J Clin Nutr 2013;97:816–26.Ehrenkranz RA, Dusick AM, Vohr BR, et al. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics 2006;117:1253–61.Dusick AM, Poindexter BB, Ehrenkranz RA, et al. Growth failure in the preterm infant: can we catch up?Semin Perinatol 2003;27:302–10.

Abstract Objectives The gut microbiota of preterm infants (PTI) differs from that of term infants, with higher abundances of pathogenic bacteria and late acquisition of beneficial bacteria. This dysbiosis is affected by different types of milk and milk fortifiers fed to PTI, exposure to antibiotics after birth, and long hospitalization periods. Different enterotypes have been proposed to classify the gut bacteria ecosystems in adults, but little data exits regarding the PTI gut microbiota. Thus, the objective herein was to investigate gut microbial enterotypes of PTI infants. Methods PTI were followed from birth until NICU discharge. Data including daily feeding information and medications were obtained from the medical records. Freshly voided stool samples were collected, bacterial DNA was extracted and the V3-V4 regions of the 16S rRNA were sequenced. Enterotypes were determined using the partitioning around medoids clustering algorithm and the Jensen-Shannon divergence method using RStudio. Results A total of 551 stool samples were collected from 97 PTI. At genus level, two enterotypes were obtained; enterotype A (EA) was characterized by a high abundance (62%) of Escherichia-Shigella and Staphylococcus, whereas Enterobacteriaceae, Clostridium sensu stricto 1 and Klebsiella accounted 55% of relative abundance for Enterotype B (EB). Alpha diversity (Shannon index) was higher (P &lt; 0.0001) in EB. In the earliest sample collected after birth (2.2 ± 1.1 weeks of life), the majority of PTI (64%) belonged to EB, but 37% of PTI switched enterotypes during their hospital stay, most of these changed from EA to EB. The change on enterotypes occurred at 4.6 ± 2.7 weeks of life. Bovine milk-based fortifier (BMF) and abundance of Escherichia-Shigella were positively associated in EA, whereas, this correlation was negative for EB. Similarly, Enterobacteriaceae abundance was positively correlated with the use of antibiotics in EA, but was negatively correlated in EB. Conclusions The gut microbiota of PTI was more likely to belong to a more diverse enterotype. There were opposite effects between both enterotypes to exposure to BMF and antibiotics. This suggests that responses to dietary and clinical factors could be dependent upon the characteristics of the gut microbiota of PTI. Funding Sources Seed grant Carle Foundation Hospital and University of Illinois. CONACyT Graduate Fellowship.

Infants were recruited in four centres in North-West Italy. 138 infants were assessed for eligibility, 113 ones underwent randomisation and 105 completed the study. Newborns aged less than 10 days of life, with gestational age between 37 and 42 weeks, birth weight from 2,500 to 4,300 g and normal physical examination were recruitable. Premature infants and infants affected by outcomes of perinatal hypoxia or necrotising enterocolitis have been excluded. Patients were randomly assigned to receive five drops containing Lactobacillus reuteri DSM 17938 (108 cfu) with 400 UI of vitamin D3 or only 400 UI of vitamin D3 daily. The primary endpoints concern the administration of pain relieving agents (cimetropium bromide at least three times per week or simethicone at least five times per week) from baseline to 12 weeks. Additional analyses were done on the percentage of infants that switched from an exclusive breastfeeding to a partial or exclusive formula feeding from baseline to 12 weeks. Data concerning the number of calls to the paediatricians and the number of visits at paediatricians’ ambulatories due to infantile colic have been collected by paediatrician and analysed. Comparing the two groups, the relative risk was 0.04 (95% confidence interval (CI)=0.01-0.31) for cimetropium bromide, 0.24 (95% CI=0.14-0.41) for simethicone and 0.37 (95% CI=0.17-0.80) for the administration of infant formula, showing a protective action of L. reuteri. The treatment group showed a lower number of paediatric consultations related to episodes of infant colic than the control group (P<0.0001). L. reuteri DSM 17938 supplementation at the tested dosage could reduce parental discomfort due to infantile colic. The consumption of this probiotic is associated with a reduction of paediatric consultations for infantile colic, as well as use of pain relieving agents and of infant formula.

The present study aimed to compare the bilevel volume guarantee (VG) and pressure-regulated volume control (PRVC) modes of the GE® Carescape R860 model ventilator and test the safety and feasibility of these two modes in preterm neonates. Infants who were less than 30 weeks of gestational age were included. After randomization, initial ventilator settings were adjusted for each patient. After the first 2 h of ventilation, the patients were switched to the other ventilator mode for 2 h. The ventilator parameters, vital signs, and blood gas values were evaluated. The study included a total of 28 patients, 14 in the PRVC group and 14 in the bilevel VG group. The mean birth weight was 876 g (range: 530–1170) and the mean gestational age was 26.4 weeks (range: 24–29). The patients’ peak inspiratory pressure (PIP2 and PIP3) was lower after ventilation in bilevel VG mode than in PRVC mode (13 vs. 14 cmH2O, respectively; paired samples t-test, p = 0.008). After 2 h of bilevel VG ventilation, the mean heart rate decreased from 149/min to 140/min (p = 0.001) and the oxygen saturation increased from 91% to 94% (p = 0.01). Both the PRVC and bilevel VG modes of GE ventilators can be used safely in preterm infants, and bilevel VG mode was associated with more favorable early clinical findings. Studies including more patients and comparing with other modes will clarify and provide further evidence on this subject.

AbstractOur main aim of this article was to show that central venous catheter (CVC) can be an easy-to-use, less-complicated catheter application such as peripherally inserted central catheter and umbilical catheter placement in the neonatal intensive care unit. We here described our experience with subclavian vein catheterization. Neonates who had venous access through subclavian central catheterization were assessed retrospectively. Data such as gestational age, age at the time of catheter insertion, birth weight, and gender were collected. In addition, problems related to catheterization during hospitalization were documented. This study comprised 40 newborns, 22 male and 18 female, with a mean gestational week of 29.57 ± 3.80 weeks and a mean gestational weight of 2067.50 ± 545.97 g. Due to occlusion, catheters were switched in five cases twice and in three cases once, totaling 53 catheterizations on 40 newborns. None of our patients had pneumothorax or hemothorax. On the postoperative 8th and 21st days, the catheter was withdrawn due to catheter infection in two (5%) patients, and catheter cultures revealed coagulase negative Staphylococcus aureus in both cases. Even in preterm infants, subclavian central venous catheterization is a safe and straightforward technique of gaining venous access in expert hands in the neonatal intensive care unit.

Abstract Background Population-based neonatal screening using T-cell receptor excision circles (TRECs) identifies infants with profound T lymphopenia, as seen in cases of severe combined immunodeficiency, and in a subgroup of infants with 22q11 deletion syndrome (22q11DS). Purpose To investigate the long-term prognostic value of low levels of TRECs in newborns with 22q11DS. Methods Subjects with 22q11DS and low TRECs at birth (22q11Low, N=10), matched subjects with 22q11DS and normal TRECs (22q11Normal, N=10), and matched healthy controls (HC, N=10) were identified. At follow-up (median age 16 years), clinical and immunological characterizations, covering lymphocyte subsets, immunoglobulins, TRECs, T-cell receptor repertoires, and relative telomere length (RTL) measurements were performed. Results At follow-up, the 22q11Low group had lower numbers of naïve T-helper cells, naïve T-regulatory cells, naïve cytotoxic T cells, and persistently lower TRECs compared to healthy controls. Receptor repertoires showed skewed V-gene usage for naïve T-helper cells, whereas for naïve cytotoxic T cells, shorter RTL and a trend towards higher clonality were found. Multivariate discriminant analysis revealed a clear distinction between the three groups and a skewing towards Th17 differentiation of T-helper cells, particularly in the 22q11Low individuals. Perturbations of B-cell subsets were found in both the 22q11Low and 22q11Normal group compared to the HC group, with larger proportions of naïve B cells and lower levels of memory B cells, including switched memory B cells. Conclusions This long-term follow-up study shows that 22q11Low individuals have persistent immunologic aberrations and increased risk for immune dysregulation, indicating the necessity of lifelong monitoring. Clinical Implications This study elucidates the natural history of childhood immune function in newborns with 22q11DS and low TRECs, which may facilitate the development of programs for long-term monitoring and therapeutic choices.

Caring is an important issue of education in a society that aims for a welfare state. The education world has prepared care policies for infants, elementary and secondary schools, and uses them as an outlet for the era of low birth rates. However, despite high social interest, the understanding of care tends to remain in the dimension of 'providing services'. In this paper, I consider the relationship between 'caregiver = caretaker' of Nel Noddins, a pioneer of caring theory, to examine the characteristics of caring relationships through reciprocity, a concept that is often confused with services. In reciprocity, human relationships are understood from the perspective of exchange, which is likely to be confused with an exchange economy that often pursues exchange and satisfaction. In order to comprehensively approach and view this problem, it is switched to the problem of exchange and gift theory that the post-structuralist philosophy was interested in and sheds new light. When someone gives a gift, the recipient follows the pattern of exchange gifts that are appreciated and returned later. On the other hand, it seems impossible to give a pure gift without wishing for return, but in this study, to dismantle the exchange economy thinking by positioning teaching-learning, caring-care taking that occurs in schools as a pure gift, first, it was analyzed focusing on the state of commitment of the caregiver as a state of pure gift, and second, it was reasoned that caring was placed in a larger virtuous cycle of gift. Although caring belongs to the realm of pure gift, it is easy to be recovered by gift exchange or currency exchange, and is often damaged due to its nature. Care is clearly being taken in various contexts, but it is not caring in itself. Gifts occur where care takes place. The topic of pure gift needs to continue to be questioned as the central theme of educational care theory.

Abstract Introduction: The direct antiglobulin test (DAT) detects the presence of IgG and/or C3 on the red blood cell (RBC) membrane and is used to diagnose autoimmune hemolytic anemias as well as hemolytic disease of the fetus and newborn (HDFN). A positive DAT in a neonate occurs when maternal IgG crosses the placenta and binds to fetal RBCs, which may lead to hemolysis and clinical manifestations of HDFN such as hyperbilirubinemia. Historically, DATs in umbilical cord blood samples were performed manually. We have recently switched to using the Ortho Vision Analyzer (gel technology) for this purpose in our institution, and noticed a trend toward stronger positive reactions. The purpose of this study was to compare the DAT results obtained with the conventional tube method and the gel method, and their association with hyperbilirubinemia and/or the need for phototherapy in the neonates tested. Methods: We retrospectively reviewed all cord DAT results of infants born between January 2016 and June 2018. We included all tests of neonates of blood group A or B born to blood group O mothers who had a positive DAT and performed a retrospective chart review to collect the following data: DAT strength, gestational age, birth weight, hematocrit, blood type, initial and peak serum total bilirubin levels, use of phototherapy, antibody screening results, and transfusion history. Neonates whose mothers had a positive antibody screen were excluded from the analysis. Results: During the study-period, 100 ABO-incompatible neonates with a positive DAT were tested by the tube and gel methods (50 with each methodology) and met our inclusion criteria. Their demographic information and laboratory results, including the strength of the positive DAT are in Table 1. There was a clear trend toward stronger DAT results since the gel methodology was introduced; the most common result in the Ortho Vision Analyzer was 1+ positive (52%), and 40% of neonates had a 2+ positive result. The latter was only seen in 2% with the tube method. Furthermore, although there were no significant differences in any demographic or laboratory parameters between the two groups of neonates, an increased percentage of those tested with the new methodology (23/50 or 46%) received phototherapy compared with 14/50 (28%) of those tested manually (Figure 1). Conclusions: We found that the Ortho Vision Analyzer produced stronger DAT results compared to the tube method without evidence of increased hemolysis. It is essential that Transfusion Medicine physicians communicate the change in methodology to neonatologists to make them aware of the reason for the stronger DAT results in order to avoid unnecessary phototherapy. Disclosures No relevant conflicts of interest to declare.

Abstract Background The relationship of maternal HBeAg and infants’ response to hepatitis B vaccine remains controversial. This study aims to observe the dynamic changes in infant birth HBV markers and study the time-varying effects of maternal HBeAg on vaccination response of infants born to women with chronic HBV infection. Methods 3163 infants born to HBsAg positive mothers including 1737 with maternal HBeAg positive in group A and 1426 negative in group B were enrolled eventually. Demographic information and laboratory tests were collected at birth, 7-12th and 24th month. The dynamic changes of infant HBV markers and HBsAb titers at different time points were compared between the two groups. Results The infant HBV markers at birth displayed different modes. During the follow-up, we observed a significant downward trend in the positive rates of HBsAg, HBeAg, HBeAb and HBcAb. The HBsAg of two groups switched to negative at 7–12 months and HBeAg in Group A became negative at 24 months. The HBsAb titers of the infants in the two groups were 576.91(192.8–1000.0) vs 719.67(208.1–1000.0) at 7–12 months (Z = -3.049, P = 0.002) and 783.5(227.8–1000.0) vs 891.4(234.0–1000.0) at 24 months (Z = -0.853, P = 0.394). High HBV DNA viral load (OR 1.260, 95% CI 1.139–1.395, P < 0.001) and maternal HBeAg level (OR 1.003, 95% CI 1.002–1.003, P < 0.001) were associated with the higher HBeAg positive rate of infants. Conclusions Maternal HBeAg did affect the infants’ immune response to vaccination and reduce the anti-response at 7-12th month temporarily, but these influences were negligible by 24th months after birth, which proved that the maternal HBeAg would not induce immune tolerance of infants from a long-term perspective.

Abstract Objectives Mitochondrial mutations in HIV-exposed uninfected (HEU) infants after cessation of ART are rarely studied. We analysed a group of HEU newborns born to mothers with late HIV diagnosis who received three doses of ART immediately after birth. We observed mitochondrial DNA (mtDNA) mutations at different times of withdrawal. Methods The study was based on a clinical trial conducted from 2015 to 2020. Newborns of the intervention group who met the criteria for this study received triple antiretroviral drugs, zidovudine + lamivudine + nevirapine, within 2 h after the birth, as post-partum prophylaxis, and at 14 days were switched to zidovudine + lamivudine + lopinavir/ritonavir, which was continued until 6 weeks of age. From August to November 2019, blood samples from HEU infants were also collected after ceasing 12 months of ART, and analysed for mtDNA. Results Our study found that mtDNA mutations remained prevalent in HEU infants a few years after three ARTs were stopped immediately after birth. Among them, D-loop, ND1 and CYTB are the first three mutated regions during different withdrawal periods. This pattern of mutations is similar to, but not exactly consistent with, HIV-infected children receiving standard ART. Conclusions Further studies are needed to determine the effects of these mutations on the development of HEU infants and whether stopping ART leads to the restoration of mitochondrial function.

INTRODUCTION: Although breast milk is considered the optimal nutrition for infants, it is also the primary cause of postnatal cytomegalovirus (CMV) infection. Preterm infants with postnatal CMV infections are susceptible to a variety of life-threatening conditions. CASE SUMMARY: Twin male infants were delivered via emergency caesarian section at 27 weeks’ gestation secondary to maternal complete uterine rupture. The Apgar scores at 1 and 5 min were 1 and 1 for the older twin (Twin A) and 0 and 3 for the younger twin (Twin B). Their birth weights were 1203 g (+ 0.65SD) and 495 g (– 3.79SD) respectively. On day 41, laboratory blood test results for Twin B showed a moderate elevation in C-reactive protein (CRP), thrombocytopenia. CMV quantitative polymerase chain reaction (qPCR) tests in Twin B’s urine and blood as well as in the mother’s breast milk were positive, but stored, dried umbilical cord CMV qPCR tests were negative. Twin B was diagnosed with a postnatal CMV infection secondary to infected breast milk and ganciclovir was commenced on day 52. Treatment was switched to valganciclovir at 74 days of age, but a negative CMV-DNA level in the blood was not achieved. Postnatal CMV infection in this infant led to an exacerbation of pre-existing bronchopulmonary dysplasia (BPD) and he demised at 182 days of age. CONCLUSION: Postnatal cytomegalovirus infections may lead to exacerbations of BPD. Early use of raw breast milk in preterm infants should be done with careful consideration of this potential complication.

IntroductionFactors influencing vaccine immune priming in the first year of life involve both innate and adaptive immunity but there are gaps in understanding how these factors sustain vaccine antibody levels in healthy infants. The hypothesis was that bioprofiles associated with B cell survival best predict sustained vaccine IgG levels at one year.MethodsLongitudinal study of plasma bioprofiles in 82 term, healthy infants, who received standard recommended immunizations in the United States, with changes in 15 plasma biomarker concentrations and B cell subsets associated with germinal center development monitored at birth, soon after completion of the initial vaccine series at 6 months, and prior to the 12-month vaccinations. Post vaccination antibody IgG levels to Bordetella pertussis, tetanus toxoid, and conjugated Haemophilus influenzae type B (HiB) were outcome measures.ResultsUsing a least absolute shrinkage and selection operator (lasso) regression model, cord blood (CB) plasma IL-2, IL-17A, IL-31, and soluble CD14 (sCD14) were positively associated with pertussis IgG levels at 12 months, while CB plasma concentrations of APRIL and IL-33 were negatively associated. In contrast, CB concentrations of sCD14 and APRIL were positively associated with sustained tetanus IgG levels. A separate cross-sectional analysis of 18 mother/newborn pairs indicated that CB biomarkers were not due to transplacental transfer, but rather due to immune activation at the fetal/maternal interface. Elevated percentages of cord blood switched memory B cells were positively associated with 12-month HiB IgG levels. BAFF concentrations at 6 and 12 months were positively associated with pertussis and HiB IgG levels respectively.DiscussionSustained B cell immunity is highly influenced by early life immune dynamics beginning prior to birth. The findings provide important insights into how germinal center development shapes vaccine responses in healthy infants and provide a foundation for studies of conditions that impair infant immune development.

ABSTRACT During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context. IMPORTANCE Humans are colonized by microbes at birth, a process that is important to health and development. However, much remains to be known about the fine-scale microbial dynamics that occur during the colonization period. We conducted a genome-resolved study of microbial community composition, replication rates, and proteomes during the first 3 months of life of both healthy and sick premature infants. Infants were found to be colonized by similar microbes, but each underwent a distinct colonization trajectory. Interestingly, related microbes colonizing different infants were found to have distinct proteomes, indicating that microbiome function is not only driven by which organisms are present, but also largely depends on microbial responses to the unique set of physiological conditions in the infant gut.

Abstract Introduction Antiretroviral therapy (ART) is very effective in preventing vertical transmission of HIV but some women on ART experience different virologic, immunologic, and safety profiles. While most pregnant women are closely monitored for short-term effects of ART during pregnancy, few women receive similar attention beyond pregnancy. We aimed to assess retention in care and clinical and laboratory-confirmed outcomes over 3 years after starting ART under Malawi’s Option B + program. Methods We conducted a prospective cohort study of pregnant women newly diagnosed with HIV who started tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/3TC/EFV) for the first time at Bwaila Hospital in Lilongwe, Malawi between May 2015 and June 2016. Participants were followed for 3 years. We summarized demographic characteristics, pregnancy outcomes, and clinical and laboratory adverse events findings using proportions. Log-binomial regression models were used to estimate the overall risk ratios (RR) and the corresponding 95% confidence interval (CI) for the association between index pregnancy (i.e. index pregnancy vs. subsequent pregnancy) and preterm birth, and index pregnancy and low birthweight. Results Of the 299 pregnant women who were enrolled in the study, 255 (85.3%) were retained in care. There were 340 total pregnancies with known outcomes during the 36-month study period, 280 index pregnancies, and 60 subsequent pregnancies. The risks of delivering preterm (9.5% for index pregnancy and13.5% for subsequent pregnancy: RR = 0.70; 95% CI: 0.32–1.54), or low birth weight infant (9.8% for index pregnancy and 4.2% for subsequent pregnancy: RR = 2.36; 95% CI: 0.58–9.66) were similar between index and subsequent pregnancies. Perinatally acquired HIV was diagnosed in 6 (2.3%) infants from index pregnancies and none from subsequent pregnancies. A total of 50 (16.7%) women had at least one new clinical adverse event and 109 (36.5%) women had at least one incident abnormal laboratory finding. Twenty-two (7.3%) women switched to second line ART: of these 64.7% (8/17) had suppressed viral load and 54.9% (6/17) had undetectable viral load at 36 months. Conclusion Most of the women who started TDF/3TC/EFV were retained in care and few infants were diagnosed with perinatally acquired HIV. Despite switching, women who switched to second line therapy continued to have higher viral loads suggesting that additional factors beyond TDF/3TC/EFV failure may have contributed to the switch. Ongoing support during the postpartum period is necessary to ensure retention in care and prevention of vertical transmission.

Abstract Background Early antiretroviral therapy (ART) is recommended for infants with human immunodeficiency virus (HIV) infection. However, few antiretroviral options are available for neonates. Methods The Early Infant Treatment Study in Botswana tested HIV-exposed infants within 96 hours of birth, and HIV-infected infants started nevirapine (NVP) 6 mg/kg twice daily, zidovudine (ZDV), and lamivudine (3TC) at age &lt; 7 days. NVP trough concentrations were tested at 1 and 2 weeks. NVP was switched to ritonavir-boosted lopinavir (LPV/r) at week 2, 3, 4, or 5 according to delivery gestational age. Results Forty HIV-infected infants started ART at median age 2 days (range, 1–5 days). NVP trough concentrations were highly variable and below therapeutic target (3000 ng/mL) for 50% of 2-week measurements; concentrations did not correlate with viral decline at weeks 2, 4, or 12. Two deaths unrelated to ART occurred through 24 weeks. Only 1 unscheduled treatment modification was required. Within 4 weeks of transition to LPV/r, 9 (22.5%) had transient HIV RNA increases, likely due to poor LPV/r palatability. At 12 weeks, 22 (55%) of 40 were &lt;40 copies/mL (93% &lt;400 copies/mL); by 24 weeks, 27 of 38 (71%) were &lt; 40 copies/mL (84% &lt; 400 copies/mL). HIV-1 RNA response at 12 and 24 weeks did not differ by baseline HIV RNA or other factors. Conclusions NVP/ZDV/3TC started in the first week of life was safe and effective, even when trough NVP levels were below target. Transient viral increases occurred following transition to LPV/r, but by 12 and 24 weeks most children achieved and maintained viral suppression. Clinical Trials Registration U01AII4235.

Abstract Background The World Health Organization (WHO) recommends balanced energy and protein (BEP) supplementation be provided to all pregnant women living in undernourished populations, usually defined as having a prevalence > 20% of underweight women, to reduce the risk of stillbirths and small-for-gestational-age neonates. Few geographies meet this threshold, however, and a large proportion of undernourished women and those with inadequate gestational weight gain could miss benefiting from BEP. This study compares the effectiveness of individual targeting approaches for supplementation with micronutrient-fortified BEP vs. multiple micronutrient supplements (MMS) alone as control in pregnancy in improving birth outcomes. Methods The TARGET-BEP study is a four-arm, cluster-randomized controlled trial conducted in rural northwestern Bangladesh. Eligible participants are married women aged 15–35 years old identified early in pregnancy using a community-wide, monthly, urine-test-based pregnancy detection system. Beginning at 12–14 weeks of gestation, women in the study area comprising 240 predefined sectors are randomly assigned to one of four intervention arms, with sector serving as the unit of randomization. The interventions involving daily supplementation through end of pregnancy are as follows: (1) MMS (control); (2) BEP; (3) targeted BEP for those with pre-pregnancy body mass index (BMI) < 18.5 kg/m2 and MMS for others; (4) targeted BEP for those with pre-pregnancy BMI < 18.5 kg/m2, MMS for others, and women with inadequate gestational weight gain switched from MMS to BEP until the end of pregnancy. Primary outcomes include birth weight, low birth weight (< 2500 g), and small for gestational age, defined using the 10th percentile of the INTERGROWTH-21st reference, for live-born infants measured within 72 h of birth. Project-hired local female staff visit pregnant women monthly to deliver the assigned supplements, monitor adherence biweekly, and assess weight regularly during pregnancy. Trained data collectors conduct pregnancy outcome assessment and measure newborn anthropometry in the facility or home depending on the place of birth. Discussion This study will assess the effectiveness of targeted balanced energy and protein supplementation to improve birth outcomes among pregnant women in rural Bangladesh and similar settings. Trial registration ClinicalTrials.gov NCT05576207. Registered on October 5th, 2022.

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 (&lt;32 weeks and or with birth weight &lt;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.

We present the case of a 36-year-old female who was diagnosed at birth with CHI that caused severe hypoglycaemia unresponsive to Diazoxide. Subtotal pancreatectomy was performed at the age of three weeks. Later, histological analysis of her pancreas in a research setting revealed a focal form of CHI. Genetic testing was not available at that time. The patient developed pancreatic exocrine deficiency and insulin-dependent diabetes at the age of 9 years. In 2016, a genetic test revealed a missense heterozygous variant in the ABCC8 gene inherited from her father and classified as having a recessive inheritance. The geneticist concluded that the risk of CHI for her offspring would be low (1/600), making pregnancy favourable. As there was no consanguinity in the family, testing the future father was deemed unnecessary (carrier frequency 1/150 in the general population). The pregnancy occurred spontaneously in 2020 and at a gestational age of 28 weeks, the mother went into premature labour. An emergency C-section was performed in April 2021 resulting in the birth of bichorial bi-amniotic male twins. Following birth, both newborns experienced persistent severe hypoglycaemia which required glucagon treatment and intravenous glucose infusion initially, followed by Diazoxide from day 51 after birth, without satisfactory response. Continuous intravenous Octreotide treatment was introduced on day 72. Due to the recurrence of hypoglycaemia episodes despite reaching maximum doses of Octreotide, from day 92 the treatment was switched to Pasireotide. Genetic tests revealed the same genotypes for both infants: the exon 39 missense variant (c.4716C&gt;A; p.Ser1572Arg) inherited from their mother and a truncating variant in exon 28 (c.3550del; p.Val1184*), inherited from their asymptomatic father. As a result of inheriting two recessive variants of the ABCC8 gene, the children were diagnosed with a diffuse form of CHI, consistent with the diazoxide-unresponsive presentation. This situation is very rare outside consanguinity. This case emphasises the significance of genetic counselling for individuals with a history of rare diseases outside the context of consanguinity, as there is a potential risk of recurrence. Prenatal diagnosis can lead to better outcomes for affected neonates, as well as help families make informed decisions about future pregnancies.

Abstract Background: Hypophosphatemic rickets (HR) is usually an inherited disorder, but it may also occur in several clinical settings as an acquired condition due to phosphate absorption and internal distribution issues. Recently it was described the association between the use of the elemental amino-acid based formula (AAF) and HR. Herein we report two male twins presenting this condition. Clinical case: Two monozygotic preterm (28 weeks + 5 days) brothers, born with extremely low birth weight (895 and 995 grams, -1,4 SDS and -0.9 SDS, respectively), received total parental nutrition from the 1st to the 7th day of life. Afterwards they started oral diet with milk and human milk fortifier FM85 for preventing metabolic bone disease of prematurity. After some weeks they developed abdominal distension, vomiting and hematochezia. Allergy to cow milk protein was suspected and the infants started receiving extensively hydrolyzed milk formula. So, FM85 was suspended and they were put on tricalcium phosphate (12.9%) supplementation from the 4th week of life on. As the gastrointestinal symptoms persisted, the formula was exchanged for elemental formula Neocate at 2 months of age, with improvement of those symptoms. After the 5th week of life the patients developed hypophosphatemia (2.8 mg/dL, reference 4.8-7.4 mg/dL), hyperphosphatasemia (1,619 IU/L and 2,173 IU/L; reference 70-350 IU/L) and low urinary phosphate excretion, keeping normal calcium and PTH ser um levels. Radiographic skeletal inventory showed under mineralized bones with irregular metaphyseal margins, but no signs of fractures. Calcium and phosphate supplementation doses were increased in attempt to correct the metabolic disturbances, and calcitriol was also started. Nevertheless, hypophosphatemia, hyperphosphatasemia and hypophosphaturia persisted. At 4 months of age, Neocate was switched to Alfamino, still an AAF. After that, phosphate serum levels went up until normalization and alkaline phosphatase started to decrease. Calcium and phosphate supplementation were decreased to keep their serum levels at the normal range for age. The boys were then discharged from hospital when they were 4 months old (45 days of life of corrected age), but the family could not afford Alfamino, switching back to Neocate. After that their phosphate serum levels went below normal range again. Conclusion: To our knowledge, this is the first report on monozygotic twins presenting AAF Neocate-related HR. The underlying mechanisms of Neocate induced hypophosphatemia is still elusive, since its content of phosphate and calcium:phosphate ratio are similar to other AAFs. These cases reinforce the importance of evaluating phosphate metabolism in infants receiving AAF while the pathophysiology of this condition is not entirely understood.

Abstract Background Sepsis is the third leading cause of neonatal death in low and middle-income countries, accounting for one third of all deaths in Ethiopia. A concerning issue is the increasing number of multidrug-resistant microorganisms facilitated by suboptimal antibiotic stewardship. The study aims to identify clusters of newborns switching antibiotic lines for sepsis in a neonatal intensive care unit (NICU) in Ethiopia, and to explore their potential association with sepsis outcomes. Methods A retrospective cohort study was conducted including all newborns discharged with a diagnosis of probable neonatal sepsis from the St. Luke Catholic Hospital NICU between April and July 2021. The antibiotic management protocol included two lines according to WHO guidelines and a third line based on internal hospital guidelines. In the cluster analysis, the Gower distance was estimated based on the antibiotics employed in the different lines and the duration of each line. Mortality and respiratory distress (RD) were the response variables. Results In the study period, 456 newborns were admitted to the NICU and 196 (42.8%) had probable neonatal sepsis. Four antibiotic management clusters were identified. Cluster 1 (n = 145, 74.4%) had no antibiotic switches, using only the first line. Cluster 2 (n = 26, 13.3%) had one switch from the first to the second line. Cluster 4 (n = 9, 4.6%) had two switches: from first to second and then to third line. In cluster 3 (n = 15, 7.7%), newborns were switched from ceftriaxone/cloxacillin as second line to off-protocol antibiotics. There were no differences in sex, age, weight on admission or crude mortality between clusters. Cluster 3 included a higher frequency of infants who did not breathe at birth (53.3%, p = 0.011) and that necessitated bag ventilation (46.7%, p = 0.039) compared to the other clusters. Conclusions The first antibiotic line failed in one out of four newborns with probable sepsis while third-generation cephalosporins were insufficient in one in ten patients. Cluster analysis can provide valuable insights into antibiotic treatment patterns and their potential implications. This approach may support antibiotic stewardship and aid in contrasting antimicrobial resistance in limited resource settings.

Abstract Introduction Trichomoniasis is the most prevalent non-viral sexually transmitted infection (STI) in the world, affecting ~4.1% of women and ~1.3% of men aged 40–59 in the United States. Women with T. vaginalis are at 2- to 3-fold increased risk for acquiring human immunodeficiency virus (HIV). Trichomoniasis is also associated with vaginitis, pelvic inflammatory disease, post-hysterectomy cuff cellulitis and other STIs. In addition, it can cause infertility and increase a woman’s risk for adverse pregnancy outcomes including preterm birth, premature rupture of membranes, and delivery of low birthweight infants. In men, trichomoniasis is associated with non-gonococcal urethritis, although men are frequently asymptomatic and may seek treatment only after knowing that their female partners are infected. Current CDC treatment guidelines recommend concurrent treatment of both partners to prevent transmission and reinfection. Objectives To evaluate the efficacy and tolerability of secnidazole in women and men with trichomoniasis. Because logistical and statistical considerations precluded the inclusion of men in the clinical trial, we conducted a systematic literature search (19May2020) to identify other studies of secnidazole in male patients with trichomoniasis. Secnidazole is FDA-approved for the treatment of bacterial vaginosis in women. Methods In a randomized clinical trial (RCT), women with a diagnosis of trichomoniasis received a single, oral dose of secnidazole 2g or placebo at baseline (Visit 1). At Visit 2 (days 6–12), they were evaluated for test of cure (TOC) and switched to the opposite treatment. The primary endpoint was microbiological cure (ie, InPouch™ culture negative for T. vaginalis) at the TOC visit. Adverse events (AEs) were monitored. A trained research associate used ProQuest Dialog™ to search BIOSIS Previews, EMBASE, and MEDLINE using search terms related to secnidazole, clinical trials, men/males, and trichomoniasis. Results For the RCT, 147 women were enrolled; the modified intent-to-treat population included 131 randomized patients. Cure rates were 92.2% and 1.5% for secnidazole and placebo (P&lt;0.001). The most commonly reported AEs were vulvovaginal candidiasis (2.7%) and nausea (2.7%). No serious AEs were reported. For the systematic review, 4 studies were identified, which included 211 men who received secnidazole for treatment of trichomoniasis. In one study that included only men (n=85), the cure rate 5 days after treatment was 100%. In the 3 studies that included men and women, cure rates were 92–97%. For studies reporting AEs, the most common were nausea (4–9%), and dyspepsia (0.5–1.1%). Pharmacokinetics data showed no clinically meaningful differences in secnidazole exposure (Cmax, AUC) between men and women; however, the mean (±SD) half-life (hours) was longer in men versus women (20.2 hours [±3.1] vs. 14.3 hours [±1.3]). Conclusions In a RCT of women with trichomoniasis, cure rates were significantly higher after single-dose secnidazole versus placebo, and tolerability profiles were comparable between treatment groups. In a systematic literature review of secnidazole for trichomoniasis in men, cure rates, tolerability, and pharmacokinetics data were comparable to those in women. Disclosure Yes - Lupin Pharmaceuticals, Inc. Industry initiated, executed and funded study – Yes.

Illegitimacy is a multifaceted concept, powerful because it has the ability to define both itself and its antithesis; what it is not. The first three definitions of the word “illegitimate” in the Oxford English Dictionary – to use an illegitimate academic source – begin with that negative: “illegitimate” is “not legitimate’, ‘not in accordance with or authorised by law”, “not born in lawful wedlock”. In fact, the OED offers eight different usages of the term “illegitimate”, all of which rely on the negation or absence of the legitimate counterpart to provide a definition. In other words, something can only be illegitimate in the sense of being outside the law, if a law exists. A child can only be considered illegitimate, “not born in lawful wedlock” if the concept of “lawful wedlock” exists.Not only individual but national identity can be constructed by defining what – or who – has a legitimate reason to be a part of that collective identity, and who does not. The extent to which the early years of Australian colonial history was defined by its punitive function can be mapped by an early usage of the term “illegitimate” as a means of defining the free settlers of Australia. In an odd reversal of conventional associations of “illegitimate”, the “illegitimates” of Australia were not convicts. They were people who had not been sent there for legitimate – (legal) reasons and who therefore did not fit into the depiction of Australia as a penal colony. The definition invites us to consider the relationship between Australia and Britain in those early years, when Australia provided Britain with a means of constructing itself as a “legitimate” society by functioning as a location where undesirable elements could be identified and excluded. The “illegitimates” of Australia challenged Australia’s function of rendering Britain a “legitimate” society. As a sense of what is “illegitimate” in a particular context is codified and disseminated, a corresponding sense of what is “legitimate” is also created, whether in the context of the family, the law, academia, or the nation. As individuals and groups label and marginalise what is considered unwanted, dangerous, superfluous or in other ways unsatisfactory in a society, the norms that are implicitly accepted become visible. Rather as the medical practice of diagnosis by exclusion enables a particular condition to be identified because other potential conditions have been ruled out, attempts to “rule out” forms of procreation, immigration, physical types, even forms of performance as illegitimate enable a legitimate counterpart to be formed and identified. Borrowing a thought from Tolstoy’s Anna Karenina, legitimates are all alike and formed within the rules; the illegitimates are illegitimate in a variety of ways. The OED lists “illegitimate” as a noun or adjective; the word’s primary function is to define a status or to describe something. Less commonly, it can be used as a verb; to “illegitimate” someone is to bastardise them, to render them no longer legitimate, to confer and confirm their illegitimate status. Although this has most commonly been used in terms of a change in parents’ marital status (for example Queen Elizabeth I of England was bastardised by having her parents’ marriage declared invalid; as had been also the case with her older half-sister, Mary) illegitimisation as a means of marginalising and excluding continues. In October 2014, Australian Immigration Minister Scott Morrison introduced legislation designed to retrospectively declare that children born in Australia to parents that have been designated “unlawful maritime arrivals” should inherit that marginalised status (Mosendz, Brooke). The denial of “birthright citizenship”, as it is sometimes called, to these infants illegitimises them in terms of their nationality, cutting them away from the national “family”. Likewise the calls to remove Australian nationality from individuals engaging in prohibited terrorist activities uses a strategy of illegitimisation to exclude them from the Australian community. No longer Australian, such people become “national bastards”.The punitive elements associated with illegitimacy are not the only part of the story, however. Rather than being simply a one-way process of identification and exclusion, the illegitimate can also be a vital source of generating new forms of cultural production. The bastard has a way of pushing back, resisting efforts at marginalisation. The papers in this issue of M/C consider the multifarious ways in which the illegitimate refuses to conform to its normative role of defining and obeying boundaries, fighting back from where it has been placed as being beyond the law. As previously mentioned, the OED lists eight possible usages of “illegitimate”. Serendipitously, the contributions to this issue of M/C address each one of them, in different ways. The feature article for this issue, by Katie Ellis, addresses the illegitimisation inherent in how we perceive disability. With a profusion of bastards to choose from in the Game of Thrones narratives, Ellis has chosen to focus on the elements of physical abnormality that confer illegitimate status. From the other characters’ treatment of the dwarf Tyrion Lannister, and other disabled figures within the story, Ellis is able to explore the marginalisation of disability, both as depicted by George R. R. Martin and experienced within the contemporary Australian community. Several contributions address the concept of the illegitimate from its meaning of outside the law, unauthorised or unwarranted. Anne Aly’s paper “Illegitimate: When Moderate Muslims Speak Out” sensitively addresses the illegitimate position to which many Muslims in Australia feel themselves relegated. As she argues, attempting to avoid being regarded as “apologists for Islam” yet simultaneously expected to act as a unifying voice for what is in fact a highly fragmented cultural mix, places such individuals in an insupportable, “illegitimate” position. Anne Aly also joins Lelia Green in exploring the rhetorical strategies used by various Australian governments to illegitimate specific cohorts of would-be Australian migrants. “Bastard immigrants: asylum seekers who arrive by boat and the illegitimate fear of the other” discusses attempts to designate certain asylum seekers as illegitimate intruders into the national family of Australia in the context of the ending of the White Australia policy and the growth of multicultural Australia. Both papers highlight the punitive impact of illegitimisation on particular segments of society and invite recognition of the unlawfulness, or illegitimacy, of the processes themselves that have been used to create such illegitimacy.Illegitimate processes and incorrect inferences, and the illegitimisation of an organisation through media representation which ignores a range of legitimate perspectives are the subject of Ashley Donkin’s work on the National School Chaplaincy and Student Welfare Program (NSCSWP). As Donkin notes, this has been a highly controversial topic in Australia, and her research identifies the inadequacies and prejudices that, she argues, contributed to an illegitimate representation of the programme in the Australian media. Without arguing for or against the NSCSWP, Donkin’s research exposes the extent of prejudiced reporting in the Australian media and its capacity to illegitimise programmes (or, indeed, individuals). Interesting here, and not entirely irrelevant (although not directly addressed in Donkin’s paper), is the notion of prejudice as being an opinion formed or promulgated prior to considering the equitable, just or judicial/judged position. Analogous to the way in which the illegitimate is outside the law, the prejudiced only falls within the law through luck, rather than judgement, since ill-advised opinion has guided its formation. Helen Vella Bonavita explores why illegitimacy is perceived as evil or threatening, looking to anthropologists Mary Douglas and Edmund Leach. Using Shakespeare’s Henry V as a case study, Vella Bonavita argues that illegitimacy is one of the preeminent metaphors used in literature and in current political discourses to articulate fears of loss of national as well as personal identity. As Vella Bonavita notes, as well as being a pollutant that the centre attempts to cast to the margins, the illegitimate can also be a potent threat, a powerful figure occupying an undeniable position, threatening the overturning of the established order. The OED’s definition of illegitimate as “one whose position is viewed in some way as illegitimate” is the perspective taken by Crystal Abidin and Herawaty Abbas. In her work “I also Melayu OK”, Abidin explores the difficult world of the bi-racial person in multi-ethnic Singapore. Through a series of interviews, Abbas describes the strategies by which individuals, particularly Malay-Chinese individuals, emphasise or de-emphasise particular linguistic or cultural behaviours in order to overcome their ambivalent cultural position and construct their own desired socially legitimate identity. Abidin’s positive perspective nonetheless evokes its shadow side, the spectre of the anti-miscegenation laws of a range of racist times and societies (but particularly Apartheid South Africa), and those societies’ attempts to outlaw any legitimisation of relationships, and children, that the law-makers wished to prohibit. The paper also resonates with the experience of relationships across sectarian divides and the parlous circumstances of Protestant –Catholic marriages and families during the 1970s in the north of Ireland, or of previously-acceptable Serbo-Croatian unions during the disintegration of the former Socialist Federal Republic of Yugoslavia in the 1990s. Herawaty Abbas and Brooke Collins-Gearing reflect on the process of academic self-determination and self-construction in “Dancing with an illegitimate feminism: a female Buginese scholar's voice in Australian Academia”. Abbas and Collins-Gearing address the research journey from the point of view of a female Buginese PhD candidate and an Indigenous Australian supervisor. With both candidate and supervisor coming from traditionally marginalised backgrounds in the context of Western academia, Abbas and Collins-Gearing chart a story of empowerment, of finding a new legitimacy in dialogue with conventional academic norms rather than conforming to them. Three contributions address the illegitimate in the context of the illegitimate child, moving from traditional associations of shame and unmarried pregnancy, to two creative pieces which, like Abidin, Abbas and Collins-Gearing, chart the transformative process that re-constructs the illegitimate space into an opportunity to form a new identity and the acceptance, and even embrace, of the previously de-legitimising authorities. Gardiner’s work, “It is almost as if there were a written script: child murder, concealment of birth and the unmarried mother in Western Australia” references two women whose stories, although situated almost two hundred years apart in time, follow a similarly-structured tale of pregnancy, shame and infant death. Kim Coull and Sue Bond in “Secret Fatalities and Liminalities” and “Heavy Baggage and the Adoptee” respectively, provide their own stories of illuminative engagement with an illegitimate position and the process of self-fashioning, while also revisiting the argument of the illegitimate as the liminal, a perspective previously advanced by Vella Bonavita’s piece. The creative potential of the illegitimate condition is the focus of the final three pieces of this issue. Bruno Starrs’s “Hyperlinking History and the Illegitimate Imagination” discusses forms of creative writing only made possible by the new media. Historic metafiction, the phrase coined by Linda Hutcheon to reflect the practice of inserting fictional characters into historical situations, is hardly a new phenomenon, but Starrs notes how the possibilities offered by e-publishing enable the creation of a new level of metafiction. Hyperlinks to external sources enable the author to engage the reader in viewing the book both as a work of fiction and as self-conscious commentary on its own fictionality. Renata Morais’ work on different media terminologies in “I say nanomedia, You say nano-media: il/legitimacy, interdisciplinarity and the anthropocene” also considers the creative possibilities engendered by interdisciplinary connections between science and culture. Her choice of the word “anthropocene,” denoting the geological period when humanity began to have a significant impact on the world’s ecosystems, itself reflects the process whereby an idea that began in the margins gains force and legitimacy. From an informal and descriptive term, the International Commission on Stratigraphy have recently formed a working group to investigate whether the “Anthropocene” should be formally adopted as the name for the new epoch (Sample).The final piece in this issue, Katie Lavers’ “Illegitimate Circus”, again traces the evolution of a theatrical form, satisfyingly returning in spirit if not in the written word to some of the experiences imagined by George R. R. Martin for his character Tyrion Lannister. “Illegitimate drama” was originally theatre which relied more on spectacle than on literary quality, according to the OED. Looking at the evolution of modern circus from Astley’s Amphitheatre through to the Cirque du Soleil spectaculars, Lavers’ article demonstrates that the relationship between legitimate and illegitimate is not one whereby the illegitimate conforms to the norms of the legitimate and thereby becomes legitimate itself, but rather where the initial space created by the designation of illegitimate offers the opportunity for a new form of art. Like Starrs’ hyperlinked fiction, or the illegitimate narrators of Coull or Bond’s work, the illegitimate art form does not need to reject those elements that originally constituted it as “illegitimate” in order to win approval or establish itself. The “illegitimate”, then, is not a fixed condition. Rather, it is a status defined according to a particular time and place, and which is frequently transitional and transformative; a condition in which concepts (and indeed, people) can evolve independently of established norms and practices. Whereas the term “illegitimate” has traditionally carried with it shameful, dark and indeed punitive overtones, the papers collected in this issue demonstrate that this need not be so, and that the illegitimate, possibly more than the legitimate, enlightens and has much to offer.ReferencesMosendz, Polly. “When a Baby Born in Australia Isn’t Australian”. The Atlantic 16 Oct. 2014. 25 Oct. 2014 ‹http://www.theatlantic.com/international/archive/2014/10/when-a-baby-born-in-australia-isnt-australian/381549/›Baskin, Brooke. “Asylum Seeker Baby Ferouz Born in Australia Denied Refugee Status by Court”. The Courier Mail 15 Oct. 2014. 25 Oct. 2014 ‹http://www.couriermail.com.au/news/queensland/asylum-seeker-baby-ferouz-born-in-australia-denied-refugee-status-by-court/story-fnihsrf2-1227091626528›.Sample, Ian. “Anthropocene: Is This the New Epoch of Humans?” The Guardian 16 Oct. 2014. 25 Oct. 2014 ‹http://www.theguardian.com/science/2014/oct/16/-sp-scientists-gather-talks-rename-human-age-anthropocene-holocene›.