A RCT of peer-mentoring for first-time mothers in socially disadvantaged areas (the moments study)

Objective: Interventions to reduce health inequalities for young children and their mothers are important: involving peers is recommended, but evidence of value for this approach is limited. The authors aimed to examine the effect of an innovative tailored peer-mentoring programme, based on perceived needs, for first-time mothers in socio-economically deprived communities. Design: Randomised controlled trial; parallel qualitative study with purposive samples using semistructured interviews. Setting: Socio-economically disadvantaged areas, Belfast. Participants: Primigravidae, aged 16-30 years, without significant co-morbidity. Intervention: Peer-mentoring by a lay-worker fortnightly during pregnancy and monthly for the following year, tailored to participants' wishes (home visits/telephone contacts), additional to usual care. Main outcome measures: Infant psychomotor and mental development (Bayley Scales of Infant Development (BSID-II)) at 1 year, assessed by an observer blinded to group allocation. Mothers' health at 1 year postnatal (SF-36). Results: Of 534 women invited, 343(64%) participated; 85%, with their children, completed outcome assessments (140 of 172 intervention; 152 of 171 controls). Intervention and control groups did not differ in BSID-II psychomotor (mean difference 1.64, 95% CI -0.94 to 4.21) or mental (-0.81, -2.78 to 1.16) scores, nor SF-36 physical functioning (-5.4, -11.6 to 0.7) or mental health (-1.8, -6.1 to 2.6). Women valued advice given in context of personal experience of child-rearing. Mentors gained health-related knowledge, personal skills and new employment opportunities. Conclusions: Despite possible longer-term social advantage, this peer-mentoring programme showed no benefit for infant development or maternal health at 1 year. Further rigorous evaluation of important outcomes of complex interventions promoting health for children in socially disadvantaged communities is warranted. Trial registration no: ISRCTN 55055030.

The 67-kd laminin receptor is preferentially expressed by proliferating retinal vessels in a murine model of ischemic retinopathy.

Endothelial cell association with vascular basement membranes is complex and plays a critical role in regulation of cell adhesion and proliferation. The interaction between the membrane-associated 67-kd receptor (67LR) and the basement membrane protein laminin has been studied in several cell systems where it was shown to be crucial for adhesion and attachment during angiogenesis. As angiogenesis in the pathological setting of proliferative retinopathy is a major cause of blindness in the Western world we examined the expression of 67LR in a murine model of hyperoxia-induced retinopathy that exhibits retinal neovascularization. Mice exposed to hyperoxia for 5 days starting at postnatal day 7 (P7) and returned to room air (at P12) showed closure of the central retinal vasculature. In response to the ensuing retinal ischemia, there was consistent preretinal neovascularization starting around P17, which persisted until P21, after which the new vessels regressed. Immunohistochemistry was performed on these retinas using an antibody specific for 67LR. At P12, immunoreactivity for 67LR was absent in the retina, but by P17 it was observed in preretinal proliferating vessels and also within the adjacent intraretinal vasculature. Intraretinal 67LR immunoreactivity diminished beyond P17 until by P21 immunoreactivity was almost completely absent, although it persisted in the preretinal vasculature. Control P17 mice (not exposed to hyperoxia) failed to demonstrate any 67LR immunoreactivity in their retinas. Parallel in situ hybridization studies demonstrated 67LR gene expression in the retinal ganglion cells of control and hyperoxia-exposed mice. In addition, the neovascular intra- and preretinal vessels of hyperoxia-treated P17 and P21 mice labeled strongly for 67LR mRNA. This study has characterized 67LR immunolocalization and gene expression in a murine model of ischemic retinopathy. Results suggest that, although the 67LR gene is expressed at high levels in the retinal ganglion cells, the mature receptor protein is preferentially localized to the proliferating retinal vasculature and is almost completely absent from quiescent vessels. The differential expression of 67LR between proliferating and quiescent retinal vessels suggests that this laminin receptor is an important and novel target for future chemotherapeutic intervention during proliferative vasculopathies.

Reduced Nitro-oxidative Stress and Neural Cell Death Suggests a Protective Role for Microglial Cells in TNFα−/− Mice in Ischemic Retinopathy

Purpose. Neovascularization occurs in response to tissue ischemia and growth factor stimulation. In ischemic retinopathies, however, new vessels fail to restore the hypoxic tissue; instead, they infiltrate the transparent vitreous. In a model of oxygen-induced retinopathy (OIR), TNFa and iNOS, upregulated in response to tissue ischemia, are cytotoxic and inhibit vascular repair. The aim of this study was to investigate the mechanism for this effect.

Methods. Wild-type C57/BL6 (WT) and TNFa-/- mice were subjected to OIR by exposure to 75% oxygen (postnatal days 7–12). The retinas were removed during the hypoxic phase of the model. Retinal cell death was determined by TUNEL staining, and the microglial cells were quantified after Z-series capture with a confocal microscope. In situ peroxynitrite and superoxide were measured by using the fluorescent dyes DCF and DHE. iNOS, nitrotyrosine, and arginase were analyzed by real-time PCR, Western blot analysis, and activity determined by radiolabeled arginine conversion. Astrocyte coverage was examined after GFAP immunostaining.

Results. The TNFa-/- animals displayed a significant reduction in TUNEL-positive apoptotic cells in the inner nuclear layer of the avascular retina compared with that in the WT control mice. The reduction coincided with enhanced astrocytic survival and an increase in microglial cells actively engaged in phagocytosing apoptotic debris that displayed low ROS, RNS, and NO production and high arginase activity.

Conclusions. Collectively, the results suggest that improved vascular recovery in the absence of TNFa is associated with enhanced astrocyte survival and that both phenomena are dependent on preservation of microglial cells that display an anti-inflammatory phenotype during the early ischemic phase of OIR.

Worldwide childhood type 1 diabetes incidence - what can we learn from epidemiology?

Type 1 diabetes is the most common form of diabetes in most part of the world, although reliable data are still unavailable in several countries. Wide variations exist between the incidence rates of different populations, incidence is lowest in China and Venezuela (0.1 per 100 000 per year) and highest in Finland and Sardinia (37 per 100 000 per year). In most populations girls and boys are equally affected. In general, the incidence increases with age, the incidence peak is at puberty. After the pubertal years, the incidence rate significantly drops in young women, but remains relatively high in young adult males up to the age 29-35 years. Prospective national and large international registries (DIAMOND and EURODIAB) demonstrated an increasing trend in incidence in most regions of the world over the last few decades and increases seem to be the highest in the youngest age group. Analytical epidemiological studies have identified environmental risk factors operating early in life which might have contributed to the increasing trend in incidence. These include enteroviral infections in pregnant women, older maternal age (39-42 years), preeclampsia, cesarean section delivery, increased birthweight, early introduction of cow's milk proteins and an increased rate of postnatal growth (weight and height). Optimal vitamin D supplementation during early life has been shown to be protective. Some of these environmental risk factors such as viruses may initiate autoimmunity toward the beta cell, other exposures may put on overload on the already affected beta cell and thus accelerate the disease process.

Inhibition of platelet-derived growth factor promotes pericyte loss and angiogenesis in ischemic retinopathy

We investigated whether inhibition of platelet-derived growth factor (PDGF) receptor tyrosine kinase activity would affect pericyte viability, vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor-2 (VEGFR-2) expression and angiogenesis in a model of retinopathy of prematurity (ROP). ROP was induced in Sprague Dawley rats by exposure to 80% oxygen from postnatal (P) days 0 to 11 (with 3 hours/day in room air), and then room air from P12-18 (angiogenesis period). Shams were neonatal rats in room air from P0-18. STI571, a potent inhibitor of PDGF receptor tyrosine kinase, was administered from P12-18 at 50 or 100 mg/kg/day intraperitoneal (i.p.). Electron microscopy revealed that pericytes in the inner retina of both sham and ROP rats appeared normal; however STI571 induced a selective pericyte and vascular smooth muscle degeneration. Immunolabeling for caspase-3 and a-smooth muscle cell actin in consecutive paraffin sections of retinas confirmed that these degenerating cells were apoptotic pericytes. In all groups, VEGF and VEGFR-2 gene expression was located in ganglion cells, the inner nuclear layer, and retinal pigment epithelium. ROP was associated with an increase in both VEGF and VEGFR-2 gene expression and blood vessel profiles in the inner retina compared to sham rats. STI571 at both doses increased VEGF and VEGFR-2 mRNA and exacerbated angiogenesis in ROP rats, and in sham rats at 100 mg/kg/day. In conclusion, PDGF is required for pericyte viability and the subsequent prevention of VEGF/VEGFR-2 overexpression and angiogenesis in ROP.

Levels of Neonatal Thyroid Hormone in Preterm Infants and Neurodevelopmental Outcome at 51/2 Years: Millennium Cohort Study

Context: Transient hypothyroxinemia is the commonest thyroid dysfunction of premature infants, and recent studies have found adverse associations with neurodevelopment. The validity of these associations is unclear because the studies adjusted for a differing range of factors likely to influence neurodevelopment. Objective: The aim was to describe the association of transient hypothyroxinemia with neurodevelopment at 5.5 yr corrected age. Design: We conducted a follow-up study of a cohort of infants born in Scotland from 1999 to 2001 =34 wk gestation. Main Outcome Measures: We measured scores on the McCarthy scale adjusted for 26 influences of neurodevelopment including parental intellect, home environment, breast or formula fed, growth retardation, and use of postnatal drugs. Results: A total of 442 infants =34 wk gestation who had serum T4 measurements on postnatal d 7, 14, or 28 and 100 term infants who had serum T4 measured in cord blood were followed up at 5.5 yr. Infants with hypothyroxinemia (T4 level = 10th percentile on d 7, 14, or 28 corrected for gestational age) scored significantly lower than euthyroid infants (T4 level greater than the 10th percentile and less than the 90th percentile on all days) on all McCarthy scales, except the quantitative. After adjustment for confounders of neurodevelopment, hypothyroxinemic infants scored significantly lower than euthyroid infants on the general cognitive and verbal scales. Conclusions: Our findings do not support the view that the hypothyroxinemic state, in the context of this analysis, is harmless in preterm infants. Many factors contribute both to the etiology of hypothyroxinemia and neurodevelopment; strategies for correction of hypothyroxinemia should acknowledge its complex etiology and not rely solely on one approach.

Sibling recognition in the rat

Mechanisms determining the ability of individuals to recognize their kin can be broadly divided into those prenatally determined and those postnatally determined. The role of both of these possibilities was examined in an investigation of sibling recognition in the rat (Rattus norvegicus). Rat pups were tested for their preference for ‘siblings’, (either littermates and genetic siblings—natural siblings; just littermates—any recognition due to postnatal factors; or just genetic siblings—any recognition due to prenatal factors) as opposed to unfamiliar age-mates between the ages of 6 and 22 days, and also for their ability to detect conspecific odour. The results indicate that rats can recognize their siblings (Experiment V) and this can be achieved solely postnatally (Experiments I, VI), or solely prenatally (Experiments II, VII). Other results demonstrated that rats, as early as day 2, and probably earlier, can detect and respond preferentially to conspecific odours (Experiments III, IV and VIII). The possibilities of how these mechanisms, both postnatal and prenatal, function in the acquisition of sibling recognition are discussed. This is the first study in which individuals separated from all genetic relations postnatally are shown to posses the ability to recognize kin.

Deletion of Gremlin1 increases cell proliferation and migration responses in mouse embryonic fibroblasts

Gremlin1 (Grem1) is an antagonist of bone morphogenetic proteins (BMPs) that plays a critical role in embryonic and postnatal development. Grem1 has been implicated as both a promoter and an inhibitor of cell proliferation driven by BMP-4 and other mitogens in a diverse range of cell types. Recent data showed that Grem1 can trigger angiogenesis via vascular endothelial growth factor receptor (VEGFR2) binding, highlighting that the precise modalities of Grem1 signalling require further elucidation.

Fetal brain function in response to maternal alcohol consumption: Early evidence of damage

Background: Studies of the adverse neurobehavioral effects of maternal alcohol consumption on the fetus have been largely confined to the postnatal period, after exposure to alcohol has finished. This study explored the brain function of the fetus, at the time of exposure to alcohol, to examine its effect on information processing and stability of performance. Methods: Five groups of fetuses, defined by maternal alcohol consumption patterns, were examined: control (no alcohol); moderate (5 to 10 units/wk either drunk evenly across the week or as a binge, in 2 to 3 days); heavy (20+ units/wk drunk evenly or as a binge). Fetal habituation performance was examined on 3 occasions, separated by 7 days, beginning at 35 weeks of gestation. The number of trials required to habituate on each test session and the difference in performance across test sessions were recorded. Results: Fetuses exposed to heavy binge drinking required significantly more trials to habituate and exhibited a greater variability in performance across all test sessions than the other groups. Maternal drinking, either heavily but evenly or moderately as a binge, resulted in poorer habituation, and moderate binge drinking resulted in greater variability compared with no, or even, drinking. Conclusions: Decreased information processing, reflected by poorer habituation, and increased variability in performance may reflect the initial manifestations of structural damage caused by alcohol to the brain. These results will lead to a greater understanding of the effects of alcohol on the fetus's brain, enable the antenatal identification of fetal alcohol spectrum disorders, and lead to the early implementation of better management strategies. © 2012 by the Research Society on Alcoholism.


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PREDICTION OF NETILMICIN DISPOSITION IN NEONATES

Multiple regression analyses of data from 33 neonates who received netilmicin therapy showed that concurrent treatment with other drugs (Drg), creatinine clearance (CL(cr)), gestational age (GA), and an apgar score of less than 6 at 1 min (Agl') were significant determinants of netilmicin clearance. Apparent volume of distribution was significantly affected by postnatal age (PNA), gender, the presence of ascites and/or oedema (A/O), and whether or not the neonate was small for gestational age (SGA). The following formulae were obtained: CL (ml min-1 kg-1) = -0.108 - 0.210 (Drg) + 0.152(CL(cr)) + 0.019(GA) -0.128(Agl') (multiple R = 0.725, p

Oxidative stress and increased type-IV collagenase levels in bronchoalveolar lavage fluid from newborn babies

Oxidative stress may increase lung permeability by upregulation of matrix-metalloproteinase-9 (MMP-8), a type-IV collagenase that can disrupt alveolar basement membranes. We have compared a marker of oxidative stress (protein carbonyl residues) with levels of MMP-8 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), in bronchoalveolar lavage samples from newborn babies. Bronchoalveolar lavage samples (n = 87, two from each time point) were taken in the first 6 postnatal days from 41 ventilated babies: 18 of

Prenatal and early sucking influences on dietary preference in newborn, weaning, and young adult cats

Early experiences are of potential importance in shaping long-term behavior. This study examined the relative influence of prenatal and/or early postnatal experience of chemosensory stimuli on subsequent olfactory and dietary preferences of cats as newborns, at 9-10 weeks, and at 6 months. Cats were exposed to vanillin or 4-ethylguaiacol via their mother's diet either prenatally, postnatally, perinatally (prenatal and postnatal), or experienced no exposure to the stimuli (control). Newborns were given a two-choice olfactory test between the familiar "odor" and no odor; 9-10 week olds were tested for their preference between two food treats, one flavored with the familiar stimulus and the other unflavored; at 6 months, cats were given a choice of two bowls of food, one flavored with the familiar stimulus and the other unflavored. At all ages, cats preferred the familiar, and avoided the unfamiliar, stimulus. Perinatal exposure exerted the strongest influence on preference. Prenatal exposure influenced preference at all ages and postnatal exposure exerted a stronger effect as the cat aged. We conclude that long-term chemosensory and dietary preferences of cats are influenced by prenatal and early (nursing) postnatal experience, supporting a natural and biologically relevant mechanism for the safe transmission of diet from mother to young. © The Author 2012. Published by Oxford University Press. All rights reserved.

Public health education for midwives and midwifery students: a mixed methods study

Background: Current national and international maternity policy supports the importance of addressing public health goals and investing in early years. Health care providers for women during the reproductive and early postnatal period have the opportunity to encourage women to make choices that will impact positively on maternal and fetal health. Midwives are in a unique position, given the emphasis of the philosophy of midwifery care on building relationships and incorporating a holistic approach, to support women to make healthy choices with the aim of promoting health and preventing ill health. However, exploration of the educational preparation of midwives to facilitate public health interventions has been relatively limited. The aim of the study was to identify the scope of current midwifery pre registration educational provision in relation to public health and to explore the perspectives of midwives and midwifery students about the public health role of the midwife.

Methods: This was a mixed methods study incorporating a survey of Higher Educational Institutions providing pre registration midwifery education across the UK and focus groups with midwifery students and registered midwives.

Results: Twenty nine institutions (53% response) participated in the survey and nine focus groups were conducted (59 participants). Public health education was generally integrated into pre registration midwifery curricula as opposed to taught as a discrete subject. There was considerable variation in the provision of public health topics within midwifery curricula and the hours of teaching allocated to them. Focus group data indicated that it was consistently difficult for both midwifery students and midwives to articulate clearly their understanding and definition of public health in relation to midwifery.

Conclusions: There is a unique opportunity to impact on maternal and infant health throughout the reproductive period; however the current approach to public health within midwifery education should be reviewed to capitalise on the role of the midwife in delivering public health interventions. It is clear that better understanding of midwifery public health roles and the visibility of public health within midwifery is required in order to maximise the potential contribution of midwives to achieving short and long term public health population goals.

A systematic review of systematic reviews to improve maternal mental health and well-being

Objective: to identify non-invasive interventions in the perinatal period that could enable midwives to offer effective support to women within the area of maternal mental health and well-being.

Methods: a total of 9 databases were searched: MEDLINE, PubMed, EBSCO (CINAHL/British Nursing Index), MIDIRS Online Database, Web of Science, The Cochrane library, CRD (NHS EED/DARE/HTA), Joanne Briggs Institute and EconLit. A systematic search strategy was formulated using key MeSH terms and related text words for midwifery, study aim, study design and mental health. Inclusion criteria were articles published from 1999 onwards, English language publications and articles originating from economically developed countries, indicated by membership of the Organisation for Economic Co-operation and Development (OECD). Data were independently extracted using a data collection form, which recorded data on the number of papers reviewed, time frame of the review, objectives, key findings and recommendations. Summary data tables were set up outlining key data for each study and findings were organised into related groups. The methodological quality of the reviews was assessed based on predefined quality assessment criteria for reviews.

Findings: 32 reviews were identified as examining interventions that could be used or co-ordinated by midwives in relation to some aspect of maternal mental health and well-being from the antenatal to the postnatal period and met the inclusion criteria. The review highlighted that based on current systematic review evidence it would be premature to consider introducing any of the identified interventions into midwifery training or practice. However there were a number of examples of possible interventions worthy of further research including midwifery led models of care in the prevention of postpartum depression, psychological and psychosocial interventions for treating postpartum depression and facilitation/co-ordination of parent-training programmes. No reviews were identified that supported a specific midwifery role in maternal mental health and well-being in pregnancy, and yet, this is the point of most intensive contact.

Key conclusions and implications for practice: This systematic review of systematic reviews provides a valuable overview of the current strengths and gaps in relation to maternal mental health interventions in the perinatal period. While there was little evidence identified to inform the current role of midwives in maternal mental health, the review provides the opportunity to reflect on what is achievable by midwives now and in the future and the need for high quality randomised controlled trials to inform a strategic approach to promoting maternal mental health in midwifery.

Score for neonatal acute physiology-II and neonatal pain predict corticospinal tract development in premature newborns

Premature infants are at risk for adverse motor outcomes, including cerebral palsy and developmental coordination disorder. The purpose of this study was to examine the relationship of antenatal, perinatal, and postnatal risk factors for abnormal development of the corticospinal tract, the major voluntary motor pathway, during the neonatal period. In a prospective cohort study, 126 premature neonates (24-32 weeks' gestational age) underwent serial brain imaging near birth and at term-equivalent age. With diffusion tensor tractography, mean diffusivity and fractional anisotropy of the corticospinal tract were measured to reflect microstructural development. Generalized estimating equation models examined associations of risk factors on corticospinal tract development. The perinatal risk factor of greater early illness severity (as measured by the Score for Neonatal Acute Physiology-II [SNAP-II]) was associated with a slower rise in fractional anisotropy of the corticospinal tract (P = 0.02), even after correcting for gestational age at birth and postnatal risk factors (P = 0.009). Consistent with previous findings, neonatal pain adjusted for morphine and postnatal infection were also associated with a slower rise in fractional anisotropy of the corticospinal tract (P = 0.03 and 0.02, respectively). Lessening illness severity in the first hours of life might offer potential to improve motor pathway development in premature newborns.