Management of newly diagnosed chronic myeloid leukaemia during a twin pregnancy using leucapheresis: Case report and review of the literature

A case of chronic myeloid leukaemia diagnosed as an incidental finding in a 32-year-old woman, pregnant with twins at 11 weeks gestation, is presented. Management of the patient was with leucapheresis and supportive care until spontaneous delivery of two morphologically normal infants (one male, one female) at 37 weeks gestation. Special considerations while employing leucapheresis in pregnant patients are discussed.

Is the raised volume rapid thoracic compression technique ready for use in clinical trials in infants with cystic fibrosis?

The European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) has established a Standardization Committee to undertake a rigorous evaluation of promising outcome measures with regard to use in multicentre clinical trials in cystic fibrosis (CF). The aim of this article is to present a review of literature on clinimetric properties of the infant raised-volume rapid thoracic compression (RVRTC) technique in the context of CF, to summarise the consensus amongst the group on feasibility and answer key questions regarding the promotion of this technique to surrogate endpoint status.

METHODS: A literature search (from 1985 onwards) identified 20 papers that met inclusion criteria of RVRTC use in infants with CF. Data were extracted and tabulated regarding repeatability, validity, correlation with other outcome measures, responsiveness and reference values. A working group discussed the tables and answered 4 key questions.

RESULTS: Overall, RVRTC in particular forced expiratory volume in 0.5s, showed good clinimetric properties despite presence of individual variability. Few studies showed a relationship between RVRTC and inflammation and infection, and to date, data remains limited regarding the responsiveness of RVRTC after an intervention. Concerns were raised regarding feasibility in multi-centre studies and availability of reference values.

CONCLUSION: The ECFS-CTN Working Group considers that RVRTC cannot be used as a primary outcome in clinical trials in infants with CF before universal standardization of this measurement is achieved and implementation of inter-institutional networking is in place. We advise its use currently in phase I/II trials and as a secondary endpoint in phase III studies. We emphasise the need for (1) more short-term variability and longitudinal 'natural history' studies, and (2) robust reference values for commercially available devices.

Retinopathy of prematurity: Causes, prevention and treatment

Advances in neonatal intensive care have improved survival rates in extremely premature an infant, which has led to an increase of Retinopathy of Prematurity (ROP) in the developed world. Left untreated, infants are at risk of developing strabismus, myopia, vitreous haemorrhage, vitreo-retinal fibrosis, retinal detachment, secondary angle closure glaucoma and ultimately complete loss of vision. The improvements in the understanding and treatment of ROP have been supported by seminal research, and its complexity is still being explored. However the importance of early screening and treatment is essential in the prevention and treatment of this disease. The following paper will examine the causes and treatments of ROP, as well as implications for future neonatal practice.

The effectiveness, acceptability and cost-effectiveness of psychosocial interventions for maltreated children and adolescents: An evidence synthesis

DESIGN We will address our research objectives by searching the published and unpublished literature and conducting an evidence synthesis of i) studies of the effectiveness of psychosocial interventions provided for children and adolescents who have suffered maltreatment, ii) economic evaluations of these interventions and iii) studies of their acceptability to children, adolescents and their carers. SEARCH STRATEGY: Evidence will be identified via electronic databases for health and allied health literature, social sciences and social welfare, education and other evidence based depositories, and economic databases. We will identify material generated by user-led,voluntary sector enquiry by searching the internet and browsing the websites of relevant UK government departments and charities. Additionally, studies will be identified via the bibliographies of retrieved articles/reviews; targeted author searches; forward citation searching. We will also use our extensive professional networks, and our planned consultations with key stakeholders and our study steering committee. Databases will be searched from inception to time of search. REVIEW STRATEGY Inclusion criteria: 1) Infants, children or adolescents who have experienced maltreatment between the ages of 0 17 years. 2) All psychosocial interventions available for maltreated children and adolescents, by any provider and in any setting, aiming to address the sequelae of any form of maltreatment, including fabricated illness. 3) For synthesis of evidence of effectiveness: all controlled studies in which psychosocial interventions are compared with no-treatment, treatment as usual, waitlist or other-treated controls. For a synthesis of evidence of acceptability we will include any design that asks participants for their views or provides data on non-participation. For decision-analytic modelling we may include uncontrolled studies. Primary and secondary outcomes will be confirmed in consultation with stakeholders. Provisional primary outcomes are psychological distress/mental health (particularly PTSD, depression and anxiety, self-harm); ii) behaviour; iii) social functioning; iv) cognitive / academic attainment, v) quality of life, and vi) costs. After studies that meet the inclusion criteria have been identified (independently by two reviewers), data will be extracted and risk of bias (RoB) assessed (independently by two reviewers) using the Cochrane Collaboration RoB Tool (effectiveness), quality hierarchies of data sources for economic analyses (cost-effectiveness) and the CASP tool for qualitative research (acceptability). Where interventions are similar and appropriate data are available (or can be obtained) evidence synthesis will be performed to pool the results. Where possible, we will explore the extent to which age, maltreatment history (including whether intra- or extra-familial), time since maltreatment, care setting (family / out-of-home care including foster care/residential), care history, and characteristics of intervention (type, setting, provider, duration) moderate the effects of psychosocial interventions. A synthesis of acceptability data will be undertaken, using a narrative approach to synthesis. A decision-analytic model will be constructed to compare the expected cost-effectiveness of the different types of intervention identified in the systematic review. We will also conduct a Value of information analysis if the data permit. EXPECTED OUTPUTS: A synthesis of the effectiveness and cost effectiveness of psychosocial interventions for maltreated children (taking into account age, maltreatment profile and setting) and their acceptability to key stakeholders.

Brain responses to audiovisual speech mismatch in infants are associated with individual differences in looking behaviour

Research on audiovisual speech integration has reported high levels of individual variability, especially among young infants. In the present study we tested the hypothesis that this variability results from individual differences in the maturation of audiovisual speech processing during infancy. A developmental shift in selective attention to audiovisual speech has been demonstrated between 6 and 9 months with an increase in the time spent looking to articulating mouths as compared to eyes (Lewkowicz & Hansen-Tift. (2012) Proc. Natl Acad. Sci. USA, 109, 1431–1436; Tomalski et al. (2012) Eur. J. Dev. Psychol., 1–14). In the present study we tested whether these changes in behavioural maturational level are associated with differences in brain responses to audiovisual speech across this age range. We measured high-density event-related potentials (ERPs) in response to videos of audiovisually matching and mismatched syllables /ba/ and /ga/, and subsequently examined visual scanning of the same stimuli with eye-tracking. There were no clear age-specific changes in ERPs, but the amplitude of audiovisual mismatch response (AVMMR) to the combination of visual /ba/ and auditory /ga/ was strongly negatively associated with looking time to the mouth in the same condition. These results have significant implications for our understanding of individual differences in neural signatures of audiovisual speech processing in infants, suggesting that they are not strictly related to chronological age but instead associated with the maturation of looking behaviour, and develop at individual rates in the second half of the first year of life.

Motor delays in MDMA (ecstasy) exposed infants persist to 2years

Background Recreational use of 3,4 methylenedioxymethamphetamine (ecstasy, MDMA) is increasing worldwide. Its use by pregnant women causes concern due to potentially harmful effects on the developing fetus. MDMA, an indirect monoaminergic agonist and reuptake inhibitor, affects the serotonin and dopamine systems. Preclinical studies of fetal exposure demonstrate effects on learning, motor behavior, and memory. In the first human studies, we found prenatal MDMA exposure related to poorer motor development in the first year of life. In the present study we assessed the effects of prenatal exposure to MDMA on the trajectory of child development through 2 years of age. We hypothesized that exposure would be associated with poorer mental and motor outcomes. Materials and Methods The DAISY (Drugs and Infancy Study, 2003–2008) employed a prospective longitudinal cohort design to assess recreational drug use during pregnancy and child outcomes in the United Kingdom. Examiners masked to drug exposures followed infants from birth to 4, 12, 18, and 24 months of age. MDMA, cocaine, alcohol, tobacco, cannabis, and other drugs were quantified through a standardized clinical interview. The Bayley Scales (III) of Mental (MDI) and Motor (PDI) Development and the Behavior Rating Scales (BRS) were primary outcome measures. Statistical analyses included a repeated measures mixed model approach controlling for multiple confounders. Results Participants were pregnant women volunteers, primarily white, of middle class socioeconomic status, average IQ, with some college education, in stable partner relationships. Of 96 women enrolled, children of 93 had at least one follow-up assessment and 81 (87%) had ≥ two assessments. Heavier MDMA exposure (M = 1.3 ± 1.4 tablets per week) predicted lower PDI (p < .002), and poorer BRS motor quality from 4 to 24 months of age, but did not affect MDI, orientation, or emotional regulation. Children with heavier exposure were twice as likely to demonstrate poorer motor quality as lighter and non-exposed children (O.R. = 2.2, 95%, CI = 1.02–4.70, p < .05). Discussion Infants whose mothers reported heavier MDMA use during pregnancy had motor delays from 4 months to two years of age that were not attributable to other drug or lifestyle factors. Women of child bearing age should be cautioned about the use of MDMA and MDMA-exposed infants should be screened for motor delays and possible intervention.

Troubles of one neophyte researcher in getting qualitative research on parthneships in a daycare setting with disadvantaged toddlers

This study is about the troubles encountered by one researcher in getting qualitative research on partnerships between families, in disadvantaged situations and educators in toddler day care settings and how they affect the quality of care as perceived by parents and educators. The study focuses on the conflicts and tensions as perceived by families and educators. A secondary goal of the study is to develop a greater understanding of how day care training programs might incorporate the findings to prepare day care educators to work with families in disadvantaged circumstances. The study is done through a qualitative lens using an ecological framework. The study spans a three month period and is set up in a non-profit, parent-controlled day care center. Detailed 'narratives of experience' are constructed from the participants' reflections on the events. Three main barriers or conflicts have emerged from the study. They are time, fear and a difference in perceptions between the families and the educators. The thesis concludes with advice to researchers who may be contemplating setting up a similar study and some suggestions are proposed for day care training programs. These suggestions include reflections of the researcher and how she implemented changes in her own teaching.

Virtual Infants in Zoo Indigo’s Under the Covers This is Now, This is Live…

The article This is Live this is now (2011), contextualises the performance Under the Covers (2009) by Zoo Indigo. The journal article is written by Ildiko Rippel on behalf of Zoo Indigo theatre company (Rosie Garton and Ildiko Rippel) and it is published in the online Body, Space and Technology Journal:

The Activity of Breast Milk and Monoclonal HIV-specific Antibodies in Mother-to-Child Transmission

Mother-to-child transmission of HIV is a unique setting that allows us to explore both the correlates of protective immunity and the characteristics of transmitted variants. This thesis first describes the levels and functional capacity of breast milk HIV-specific antibodies in 19 women with high plasma viral loads. Neutralizing antibodies (Nabs) were detected in breast milk supernatant (BMS) of 4 of 19 women examined, were of low potency and were not associated with infant infection. The low NAb activity in BMS was reflected in binding antibody levels with HIV envelope specific IgG titers being 2.2 log10 lower in BMS versus plasma. In contrast, non- neutralizing antibodies (nNAbs) capable of antibody dependent cell-mediated cytotoxicity (ADCC) were detected in the BMS from all 19 women. BMS ADCC activity was associated with envelope-specific IgG titers (p = 0.014) and was inversely associated with infant infection risk (p = 0.039). Our data indicate that BMS has limited HIV neutralizing activity, however, BMS ADCC activity is a correlate of transmission that may impact infant infection risk. In the second part of this thesis the neutralization sensitivity of 111 variants of diverse subtypes obtained from mothers and infants was determined against 7 HIVspecific broadly neutralizing monoclonal antibodies (mAbs) (NIH45-46w, VRC01, PGT128, PGT121, PG9 PGT145 and b12). Maternal and infant variants did not differ in their neutralization sensitivity to these mAbs and neither did variants from transmitting versus those from non-transmitting women. However, subtype A viruses were iii significantly more sensitive to neutralization by NIH45-46w and VRC01 (p= 0.0001 in both cases) and PGT145 (p=0.03) compared to non-subtype A viruses. Together, NIH45- 46w and PGT128 neutralization profiles resulted in 100% coverage of the variants tested. These data suggest that the epitopes targeted by these mAbs are present and accessible in both circulating and transmitted variants and that a combination of antibodies would provide maximum coverage against diverse subtypes commonly found in HIV endemic regions. Overall, this data suggest that an antibody based HIV vaccine capable of eliciting antibodies of multiple specificities that can mediate ADCC and/or neutralizing activity can provide protection and conquer the genetic diversity displayed by HIV.

Sexual dimorphism in relation to adipose tissue and intrahepatocellular lipid deposition in early infancy

Sexual dimorphism in adiposity is well described in adults, but the age at which differences first manifest is uncertain. Using a prospective cohort, we describe longitudinal changes in directly measured adiposity and intrahepatocellular lipid (IHCL) in relation to sex in healthy term infants. At median ages of 13 and 63 days, infants underwent quantification of adipose tissue depots by whole-body magnetic resonance imaging and measurement of IHCL by in vivo proton magnetic resonance spectroscopy. Longitudinal data were obtained from 70 infants (40 boys and 30 girls). In the neonatal period girls are more adipose in relation to body size than boys. At follow-up (median age 63 days), girls remained significantly more adipose. The greater relative adiposity that characterises girls is explained by more subcutaneous adipose tissue and this becomes increasingly apparent by follow-up. No significant sex differences were seen in IHCL. Sex-specific differences in infant adipose tissue distribution are in keeping with those described in later life, and suggest that sexual dimorphism in adiposity is established in early infancy.

Applying gaze-contingent training within community settings to infants from diverse SES backgrounds

Even in infancy children from low-SES backgrounds differ in frontal cortex functioning and, by the start of preschool, they frequently show poor performance on executive functions including attention control. These differences may causally mediate later difficulties in academic learning. Here, we present a study to assess the feasibility of using computerized paradigms to train attention control in infants, delivered weekly over five sessions in early intervention centres for low-SES families. Thirty-three 12-month-old infants were recruited, of whom 23 completed the training. Our results showed the feasibility of repeat-visit cognitive training within community settings. Training-related improvements were found, relative to active controls, on tasks assessing visual sustained attention, saccadic reaction time, and rule learning, whereas trend improvements were found on assessments of short-term memory. No significant improvements were found in task switching. These results warrant further investigation into the potential of this method for targeting ‘at-risk’ infants in community settings.

Nutritional Evaluation and Optimisation in Neonates: a randomized, double-blind controlled trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition

Background: Parenteral nutrition is central to the care of very immature infants. Current international recommendations favor higher amino acid intakes and fish oil–containing lipid emulsions. Objective: The aim of this trial was to compare 1) the effects of high [immediate recommended daily intake (Imm-RDI)] and low [incremental introduction of amino acids (Inc-AAs)] parenteral amino acid delivery within 24 h of birth on body composition and 2) the effect of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (SMOF) with that of soybean oil (SO)-based lipid emulsion on intrahepatocellular lipid (IHCL) content. Design: We conducted a 2-by-2 factorial, double-blind, multicenter randomized controlled trial. Results: We randomly assigned 168 infants born at ,31 wk of gestation. We evaluated outcomes at term in 133 infants. There were no significant differences between Imm-RDI and Inc-AA groups for nonadipose mass [adjusted mean difference: 1.0 g (95% CI: 2108, 111 g; P = 0.98)] or between SMOF and SO groups for IHCL [adjusted mean SMOF:SO ratio: 1.1 (95% CI: 0.8, 1.6; P = 0.58]. SMOF does not affect IHCL content. There was a significant interaction (P = 0.05) between the 2 interventions for nonadipose mass. There were no significant interactions between group differences for either primary outcome measure after adjusting for additional confounders. Imm-RDI infants were more likely than Inc-AA infants to have blood urea nitrogen concentrations .7 mmol/L or .10 mmol/L, respectively (75% compared with 49%, P , 0.01; 49% compared with 18%, P , 0.01). Head circumference at term was smaller in the Imm-RDI group [mean difference: 20.8 cm (95% CI: 21.5, 20.1 cm; P = 0.02)]. There were no significant differences in any prespecified secondary outcomes, including adiposity, liver function tests, incidence of conjugated hyperbilirubinemia, weight, length, mortality, and brain volumes. Conclusion: Imm-RDI of parenteral amino acids does not benefit body composition or growth to term and may be harmful. This trial was registered at www.isrctn.com as ISRCTN29665319 and at eudract.ema.europa.eu as EudraCT 2009-016731-34.

Association between birth weight and neuromotor performance: a twin study

The development of neonatal intensive care has led to an increase in the prevalence of children with low birth weight and associated morbidity. The objectives of this study are to verify (1) The association between birth weight (BW) and neuromotor performance? (2) Is the neuromotor performance of twins within the normal range? (3) Are intra-pair similarities in neuromotor development of Monozygotic (MZ) and Disygotic (DZ) twins of unequal magnitude? The sample consisted of 191 children (78 MZ and 113 DZ), 8.9+3.1 years of age and with an average BW of 2246.3+485.4g. In addition to gestational characteristics, sports participation and Zurich Neuromotor Assessment (ZNA) were observed at childhood age. The statistical analysis was carried out with software SPSS 18.0, the STATA 10 and the ZNA performance scores. The level of significance was 0.05. For the neuromotor items high intra and inter-investigator reliabilities were obtained (0.793and Apgar 5´ accounted for <26% of the variance. Twins showed elevated percentages of subjects (32.7%<76.9%) with low performance

Behavioural development in a matching-to-sample task and token use by an infant chimpanzee reared by his mother

Animal Cognition, V.6, pp. 259–267

The effects of parental sensitivity and involvement in caregiving on mother–infant and father–infant attachment in a portuguese sample

In the present longitudinal study, we investigated attachment quality in Portuguese mother–infant and in father–infant dyads, and evaluated whether attachment quality was related to parental sensitivity during parent–infant social interaction or to the amount of time each parent spent with the infant during play and in routine caregiving activities (e.g., feeding, bathing, play). The sample consisted of 82 healthy full-term infants (30 girls, 53 boys, 48 first born), and their mothers and fathers from mostly middle-class households. To assess parental sensitivity, mothers and fathers were independently observed during free play interactions with their infants when infants were 9 and 15 months old. The videotaped interactions were scored by masked coders using the Crittenden’s CARE-Index. When infants were 12 and 18 months old, mother–infant and father–infant dyads were videotaped during an adaptation of Ainsworth’s Strange Situation. Parents also described their level of involvement in infant caregiving activities using a Portuguese version of the McBride and Mills Parent Responsibility Scale. Mothers were rated as being more sensitive than fathers during parent–infant free play at both 9 and 15 months. There also was a higher prevalence of secure attachment in mother–infant versus father–infant dyads at both 12 and 18 months. Attachment security was predicted by the amount of time mothers and fathers were involved in caregiving and play with the infant, and with parents’ behavior during parent–infant free play.