The influence of ambient temperature on birth outcomes in Brisbane, Australia

Lately, there has been increasing interest in the association between temperature and adverse birth outcomes including preterm birth (PTB) and stillbirth. PTB is a major predictor of many diseases later in life, and stillbirth is a devastating event for parents and families. The aim of this study was to assess the seasonal pattern of adverse birth outcomes, and to examine possible associations of maternal exposure to temperature with PTB and stillbirth. We also aimed to identify if there were any periods of the pregnancy where exposure to temperature was particularly harmful. A retrospective cohort study design was used and we retrieved individual birth records from the Queensland Health Perinatal Data Collection Unit for all singleton births (excluding twins and triplets) delivered in Brisbane between 1 July 2005 and 30 June 2009. We obtained weather data (including hourly relative humidity, minimum and maximum temperature) and air-pollution data (including PM10, SO2 and O3) from the Queensland Department of Environment and Resource Management. We used survival analyses with the time-dependent variables of temperature, humidity and air pollution, and the competing risks of stillbirth and live birth. To assess the monthly pattern of the birth outcomes, we fitted month of pregnancy as a time-dependent variable. We examined the seasonal pattern of the birth outcomes and the relationship between exposure to high or low temperatures and birth outcomes over the four lag weeks before birth. We further stratified by categorisation of PTB: extreme PTB (< 28 weeks of gestation), PTB (28–36 weeks of gestation), and term birth (≥ 37 weeks of gestation). Lastly, we examined the effect of temperature variation in each week of the pregnancy on birth outcomes. There was a bimodal seasonal pattern in gestation length. After adjusting for temperature, the seasonal pattern changed from bimodal, to only one peak in winter. The risk of stillbirth was statistically significant lower in March compared with January. After adjusting for temperature, the March trough was still statistically significant and there was a peak in risk (not statistically significant) in winter. There was an acute effect of temperature on gestational age and stillbirth with a shortened gestation for increasing temperature from 15 °C to 25 °C over the last four weeks before birth. For stillbirth, we found an increasing risk with increasing temperatures from 12 °C to approximately 20 °C, and no change in risk at temperatures above 20 °C. Certain periods of the pregnancy were more vulnerable to temperature variation. The risk of PTB (28–36 weeks of gestation) increased as temperatures increased above 21 °C. For stillbirth, the fetus was most vulnerable at less than 28 weeks of gestation, but there were also effects in 28–36 weeks of gestation. For fetuses of more than 37 weeks of gestation, increasing temperatures did not increase the risk of stillbirth. We did not find any adverse affects of cold temperature on birth outcomes in this cohort. My findings contribute to knowledge of the relationship between temperature and birth outcomes. In the context of climate change, this is particularly important. The results may have implications for public health policy and planning, as they indicate that pregnant women would decrease their risk of adverse birth outcomes by avoiding exposure to high temperatures and seeking cool environments during hot days.

Assessment of preterm infants' readiness to commence breastfeeding

Preterm infants commence breastfeeding when health-care professionals deem them to be ready. However, the optimal timing for commencement of breastfeeding is unclear. Currently, there is little guidance for neonatal care providers to decide when to initiate breastfeeding among preterm infants. A mixed-methods study was conducted to develop and test the Preterm Sucking Readiness (PTSR) scale in four phases. The first phase involved a chart audit to explore the use of age as a criterion by investigating when preterm infants meet feeding milestones as well as other factors that may affect an infant’s readiness to engage in nutritive sucking behaviour. The second phase utilised focus groups to explore and define how neonatal care providers decide when to commence breastfeeding. To gain consensus on the criteria mentioned by the focus groups, a Delphi survey was conducted in phase 3, involving neonatal providers across Australia and New Zealand. Phase 4 of the study involved an observational study that was used to test the six-item PTSR. The age at which specific feeding milestones were reached was consistent with what has been previously described in the literature. The chart audit showed that the time taken to the first feeding attempt in the preterm infant population was affected by gestational age at birth, birth weight, and specific interventions. Staff also considered age along with other criteria when deciding when to initiate feeding. Consensus on nine criteria for inclusion into the six-item PTSR was achieved using the Delphi technique. Three items of PTSR showed significant differences between the preterm and fullterm infant groups. Only two items, feeding-readiness behaviour and low pulse oximetry during handling, explained the variance in breastfeeding behaviour. The inter-rater variability ranged between moderate and very good for the PTSR items. The results of this study indicate the importance of assessing behavioural cues as an indication of breastfeeding readiness in the preterm infant population, once an infant is deemed physiologically stable. Age continues to be a factor in some clinicians' decisions to commence breastfeeding. However, age alone cannot be used to decide if an infant is ready to engage in breastfeeding. Further research is needed to confirm these findings.

Repeated intrauterine exposures to inflammatory stimuli attenuated transforming growth factor-β signaling in the ovine fetal lung

Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications after preterm birth and is associated with intrauterine exposure to bacteria. Transforming growth factor-β (TGFβ) is implicated in the development of BPD. Objectives: We hypothesized that different and/or multiple bacterial signals could elicit divergent TGFβ signaling responses in the developing lung. Methods: Time-mated pregnant Merino ewes received an intra-amniotic injection of lipopolysaccharide (LPS) and/or Ureaplasma parvum serovar 3 (UP) at 117 days' and/or 121/122 days' gestational age (GA). Controls received an equivalent injection of saline and or media. Lambs were euthanized at 124 days' GA (term = 150 days' GA). TGFβ1, TGFβ2, TGFβ3, TGFβ receptor (R)1 and TGFβR2 protein levels, Smad2 phosphorylation and elastin deposition were evaluated in lung tissue. Results: Total TGFβ1 and TGFβ2 decreased by 24 and 51% after combined UP+LPS exposure, whereas total TGFβ1 increased by 31% after 7 days' LPS exposure but not after double exposures. Alveolar expression of TGFβR2 decreased 75% after UP, but remained unaltered after double exposures. Decreased focal elastin deposition after single LPS exposure was prevented by double exposures. Conclusions: TGFβ signaling components and elastin responded differently to intrauterine LPS and UP exposure. Multiple bacterial exposures attenuated TGFβ signaling and normalized elastin deposition.

New venture internationalisation

This paper investigates the international background and international activities of Australian start-up firms. Findings of interest in this paper include: • Due to their small scale, young age and distant location firm founders then to favour the domestic market rather that engage internationally. • Firms that do engage internationally tend to do so at the very early stages of venture creation. • Firms that do engage in exporting activities tend to rely on intermediaries rather than more direct forms of export actions.

Lung recruitment manoeuvres for reducing respiratory morbidity in mechanically ventilated neonates

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the evidence supporting the use of recruitment manoeuvres in mechanically ventilated neonates and identify the optimal method of lung recruitment. To determine the effects of lung recruitment manoeuvres in neonates receiving ventilatory support on neonatal mortality and development of chronic lung disease when compared to no recruitment. If data are available, subgroup analyses will include: chronological age, gestational age, lung pathophysiology and pre-existing lung disease, mode and length of ventilation, timing and frequency of recruitment techniques.

Attainment of early feeding milestones in preterm neonates

Objective: This study aimed to document the ages at which preterm neonates commence suckle-feeds and attain exclusive suckle-feeding, as well as the time taken to transition from commencement of suckle-feeds to exclusive suckle-feeding. It was hypothesized that gestational age (GA) at birth and degree of neonatal morbidity would influence the timing of these early feeding milestones. Study Design: A chart review was conducted for all neonates born <37;0 weeks GA admitted to a tertiary level perinatal facility over a 12-month period (n=735). Complete data relating to attainment of feeding milestones were available on 472 neonates. Results: Correlation analysis indicated that both a low GA at birth and a high neonatal morbidity rating were statistically significantly correlated with an increased transition time from commencement of suckle-feeds to exclusive suckle-feeding. Cox regression indicated that both of these variables were statistically significant risk factors for a delayed GA at attainment of exclusive suckle-feeding. Conclusion: Preterm neonates who were less mature at birth and/or who displayed a greater degree of neonatal morbidity took longer to transition from starting suckle-feeds to achieving independent suckle-feeding, and were more mature at attainment of independent suckle-feeding.

Persistent organic pollutants in matched breast milk and infant faeces samples

Assessing blood concentration of persistent organic pollutants (POPs) in infants is difficult due to the ethical and practical difficulties in obtaining sufficient quantities of blood. To determine whether measuring POPs in faeces might reflect blood concentration during infancy, we measured the concentrations of a range of POPs (i.e. polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs)) in a pilot study using matched breast milk and infant faecal samples obtained from ten mother-child pairs. All infants were breast fed, with 8 of them also receiving solid food at the time of faecal sampling. In this small dataset faecal concentrations (range 0.01-41ngg-1 lipid) are strongly associated with milk concentrations (range 0.02-230ngg-1 lipid). Associations with other factors generally could not be detected in this dataset, with the exception of a small effect of age or growth. Different sources (external or internal) of exposure appeared to directly influence faecal concentrations of different chemicals based on different inter-individual variability in the faeces-to-milk concentration ratio Rfm. Overall, the matrix of faeces as an external measure of internal exposure in infants looks promising for some chemicals and is worth assessing further in larger datasets.

IL-10 in Human Newborns : Ontogeny of IL-10 secretion and relation to the secretion of IFN-g, immunoglobulin M, G, and A, and mononuclear cell composition in newborns

The purpose of this work was to elucidate the ontogeny of interleukin-10 (IL-10) secretion from newborn mononuclear cells (MCs), and to examine its relation to the secretion of interferon-g (IFN-g) and immunoglobulins (Igs). The initial hypothesis was that the decreased immunoglobulin (Ig) synthesis of newborn babies was the result of immature cytokine synthesis regulation, which would lead to excessive IL-10 production, leading in turn to suppressed IFN-g secretion. Altogether 57 full-term newborns and 34 adult volunteers were enrolled. Additionally, surface marker compositions of 29 premature babies were included. Enzyme-linked immunoassays were used to determine the amount of secreted IL-10, IFN-g, and Igs, and the surface marker composition of MC were analyzed with a FACScan flow cytometer. The three most important findings were: 1. Cord blood MC, including CD5+ B cells, are able to secrete IL-10. However, when compared with adults, the secretion of IL-10 was decreased. This indicates that reasons other than excessive IL-10 secretion are responsible of reduced IFN-g secretion in newborns. 2. As illustrated by the IL-10 and IFN-g secretion pattern, newborn cytokine profile was skewed towards the Th2 type. However, approximately 25% of newborns had an adult like cytokine profile with both good IL10 and IFN-g secretion, demonstrating that fullterm newborns are not an immunologically homogenous group at the time of birth. 3. There were significant differences in the surface marker composition of MCs between individual neonates. While gestational age correlated with the proportion of some MC types, it is evident that there are many other maternal and fetal factors that influence the maturity and nature of lymphocyte subpopulations in individual neonates. In conclusion, the reduced ability of neonates to secrete Ig and IFN-g is not a consequence of high IL-10 secretion. However, individual newborns differ significantly in their ability to secrete cytokines as well as Igs.

Visual Impairment in Finnish Children : Prevalence, causes and morbidity of full-term and preterm children with visual impairment born from 1972 through 1989

The prevalence and the causes of childhood visual impairment in Finland during the 1970s and the 1980s were investigated, with special attention to risk factors and further prevention of visual impairment in children. The primary data on children with visual impairment were obtained from the Finnish Register of Visual Impairment, one of the patient registers kept up by the National Research and Development Centre for Welfare and Health (Stakes). The data were supplemented from other registers in Stakes and from patient records of the children in Finnish central hospitals. Visual impairment had been registered in 556 children from a population of 1,138,326 children between ages 0-17, born from 1972 through 1989. The age-specific prevalence of registered visual impairment was 49/100,000 in total. Of them, 23/100,000 were blind children and 11/100,000 were children born prematurely. Boys were impaired more often and more severely than girls. Congenital malformations (52%), systemic diseases (48%), and multiple impairments (50%) were common. The main ophthalmic groups of visual impairment were retinal diseases (35%), ocular malformations (29%), and neuro-ophthalmological disorders (29%). Optic nerve atrophy was the most common diagnosis of visual impairment (22%), followed by congenital cataract (11%), retinopathy of prematurity (10%), and cerebral visual impairment (8%). Genetic factors (42%) were the most common etiologies of visual impairment, followed by prenatal (30%) and perinatal (21%) factors. The highest rates of blindness were seen in cerebral visual impairment (83%) and retinopathy of prematurity (82%). Retinopathy of prematurity had developed in the children born at a gestational age of 32 weeks or earlier. Significant risks for visual impairment were found in the association with preterm births, prenatal infections, birth asphyxia, neonatal respiratory difficulties, mechanical ventilation lasting over two weeks, and hyperbilirubinemia. A rise in blind and multi-impaired children was seen during the study period, associating with increases in the survival of preterm infants with extremely low birth weight. The incidence of visual impairment in children born prematurely was seven times higher than in children born at full term. A reliable profile of childhood visual impairment was obtained. The importance of highly qualified antenatal, neonatal, and ophthalmological care was clearly proved. The risks associated with pre- and perinatal disorders during pregnancy must be emphasized, e.g. the risks associated with maternal infections and the use of tobacco, alcohol, and drugs during pregnancy. Obvious needs for gene therapies and other new treatments for hereditary diseases were also proved.

Developmental origins of physiological stress reactivity

The model of developmental origins of health and disease proposes that organisms during fetal period utilize cues that enable their adaptation in the postnatal environment they are likely to live, having short-term advantages when trying to survive in environment but simultaneously in the long run have costs for health. A large body of epidemiological research has found that low birth weight, a marker of intrauterine conditions, is associated with cardiovascular (CV) disease. Since the reported associations of birth weight with normal variation in the resting blood pressure (BP), a major predictor of CV disease risk, have been modest, a key candidate mediating the link has been CV and hypothalamus-pituitary-adrenal axes (HPAA) reactivity to stress. In addition, not only weight at birth but also gestational age and early postnatal growth may have independent associations to stress reactivity. The aim of this thesis was to investigate whether pre- and postnatal growth and gestational age are associated with CV and HPAA activity before, during and after stress in childhood and in late adulthood. Altogether 287 men and women aged 60-70 and 299 boys and girls aged 7-9 underwent Trier Social Stress Test. Several indices of HPAA and CV were measured and birth size and gestational age were obtained from birth records. Results showed that low birth weight was associated with low HPAA activity during psychosocial stress, and rapid gain in BMI during years 7-11 was related to heightened stress reactivity to psychosocial stress. Size at birth in children and gestational age and early postnatal (0-2 years) gain in height in adults were associated with CV stress responses; however, in a sex-specific manner. Given that CV stress responses and HPAA activity are markers of CV disease vulnerability, our results may partly explain the associations between early environment and later CV disease.

Human parvovirus infections during pregnancy : Special reference to the child-care employees

Human parvovirus B19 (B19V) is known to cause anemia, hydrops fetalis, and fetal death especially during the first half of pregnancy. Women who are in occupational contact with young children are at increased risk of B19V infection. The role of the recently discovered human parvovirus, human bocavirus (HBoV), in reproduction is unknown. The aim of this research project was to establish a scientific basis for assessing the work safety of pregnant women and for issuing special maternity leave regulations during B19V epidemics in Finland. The impact of HBoV infection on the pregnant woman and her fetus was also defined. B19V DNA was found in 0.8% of the miscarriages and in 2.4% of the intrauterine fetal death (IUFD; fetal death after completed 22 gestational weeks). All control fetuses (from induced abortions) were B19V-DNA negative. The findings on hydropic B19V DNA-positive IUFDs with evidence of acute or recent maternal B19V infection are in line with those of previous Swedish studies. However, the high prevalence of B19V-related nonhydropic IUFDs noted in the Swedish studies was mostly without evidence of maternal B19V infection and was not found during the third trimester. HBoV was not associated with miscarriages or IUFDs. Almost all of the studied pregnant women were HboV-IgG positive, and thus most probably immune to HBoV. All preterm births, perinatal deaths, smallness for gestational age (SGA) and congenital anomaly were recorded among the infants of child-care employees in a nationwide register-based cohort study over a period of 14 years. Little or no differences in the results were found between the infants of the child-care employees and those of the comparison group. The annual B19V seroconversion rate was over two-fold among the child-care employees, compared to the women in the comparison group. The seropositivity of the child-care employees increased with age, and years from qualification/joining the trade union. In general, the child-care employees are not at increased risk for adverse pregnancy outcome. However, at the population level, the risk of rare events, such as adverse pregnancy outcomes attributed to infections, could not be determined. According to previous studies, seronegative women had a 5 10% excess risk of losing the fetus during the first half of their pregnancy, but thereafter the risk was very low. Therefore, an over two-fold increased risk of B19V infection among child-care employees is considerable, and should be taken into account in the assessment of the occupational safety of pregnant women, especially during the first half of their pregnancy.

Dopamine receptors in human foetal brains:Characterization, regulation and ontogeny of [3H]spiperone binding sites in striatum

Eighteen corpora striata from normal human foetal brains ranging in gestational age from 16 to 40 weeks and five from post natal brains ranging from 23 days to 42 years were analysed for the ontogeny of dopamine receptors using [3H]spiperone as the ligand and 10 mM dopamine hydrochloride was used in blanks. Spiperone binding sites were characterized in a 40-week-old foetal brain to be dopamine receptors by the following criteria: (1) It was localized in a crude mitochondrial pellet that included synaptosomes; (2) binding was saturable at 0.8 nM concentration; (3) dopaminergic antagonists spiperone, haloperidol, pimozide, trifluperazine and chlorpromazine competed for the binding with IC50 values in the range of 0.3–14 nM while agonists—apomorphine and dopamine gave IC50 values of 2.5 and 10 μM, respectively suggesting a D2 type receptor.Epinephrine and norepinephrine inhibited the binding much less efficiently while mianserin at 10 μM and serotonin at 1 mM concentration did not inhibit the binding. Bimolecular association and dissociation rate constants for the reversible binding were 5.7 × 108 M−1 min−1 and 5.0 × 10−2 min−1, respectively. Equilibrium dissociation constant was 87 pM and the KD obtained by saturation binding was 73 pM.During the foetal age 16 to 40 weeks, the receptor concentration remained in the range of 38–60 fmol/mg protein or 570–1080 fmol/g striatum but it increased two-fold postnatally reaching a maximum at 5 years Significantly, at lower foetal ages (16–24 weeks) the [3H]spiperone binding sites exhibited a heterogeneity with a high (KD, 13–85 pM) and a low (KD, 1.2–4.6 nM) affinity component, the former accounting for 13–24% of the total binding sites. This heterogeneity persisted even when sulpiride was used as a displacer. The number of high affinity sites increased from 16 weeks to 24 weeks and after 28 weeks of gestation, all the binding sites showed only a single high affinity.GTP decreased the agonist affinity as observed by dopamine competition of [3H]spiperone binding in 20-week-old foetal striata and at all subsequent ages. GTP increased IC50 values of dopamine 2 to 4.5 fold and Hill coefficients were also increased becoming closer to one suggesting that the dopamine receptor was susceptible to regulation from foetal life onwards.

An investigation into the feasibility of fetal lung maturity prediction using statistical textural features

Fetal lung and liver tissues were examined by ultrasound in 240 subjects during 24 to 38 weeks of gestational age in order to investigate the feasibility of predicting the maturity of the lung from the textural features of sonograms. A region of interest of 64 X 64 pixels is used for extracting textural features. Since the histological properties of the liver are claimed to remain constant with respect to gestational age, features obtained from the lung region are compared with those from liver. Though the mean values of some of the features show a specific trend with respect to gestation age, the variance is too high to guarantee definite prediction of the gestational age. Thus, we restricted our purview to an investigation into the feasibility of fetal lung maturity prediction using statistical textural features. Out of 64 features extracted, those features that are correlated with gestation age and less computationally intensive are selected. The results of our study show that the sonographic features hold some promise in determining whether the fetal lung is mature or immature.

Expression of Sonic Hedgehog During Cell Proliferation in the Human Cerebellum

The regulation of cell proliferation in the external granular layer (EGL) of the developing cerebellum is important for its normal patterning. An important signal that regulates EGL cell proliferation is Sonic hedgehog (Shh). Shh is secreted by the Purkinje cells (PC) and has a mitogenic effect on the granule cell precursors of the EGL. Deregulation of Shh signaling has been associated with abnormal development, and been implicated in medulloblastomas, which are tumors that arise from the cerebellum. Given the importance of the Shh pathway in cerebellum development and disease, there has been no systematic study of its expression pattern during human cerebellum development. In this study, we describe the expression pattern of Shh, its receptor patched, smoothened, and its effectors that belong to the Gli family of transcription factors, during normal human cerebellum development from 10 weeks of gestational age, and in medulloblastomas that represents a case of abnormal cell proliferation in the cerebellum. This expression pattern is compared to equivalent stages in the normal development of cerebellum in mouse, as well as in tumors. Important differences between human and mouse that reflect differences in the normal developmental program between the 2 species are observed. First, in humans there appears to be a stage of Shh signaling within the EGL, when the PC are not yet the source of Shh. Second, unlike in the postnatal mouse cerebellum, expression of Shh in the PC in the postnatal human cerebellum is downregulated. Finally, medulloblastomas in the human but not in patched heterozygote mouse express Shh. These results highlight cross-species differences in the regulation of the Shh signaling pathway.

The descriptive epidemiology of congenital and acquired cryptorchidism in a UK infant cohort.

INTRODUCTION: Recent studies in other European countries suggest that the prevalence of congenital cryptorchidism continues to increase. This study aimed to explore the prevalence and natural history of congenital cryptorchidism in a UK centre. METHODS: Between October 2001 and July 2008, 784 male infants were born in the prospective Cambridge Baby Growth Study. 742 infants were examined by trained research nurses at birth; testicular position was assessed using standard techniques. Follow-up assessments were completed at ages 3, 12, 18 and 24 months in 615, 462, 393 and 326 infants, respectively. RESULTS: The prevalence of cryptorchidism at birth was 5.9% (95% CI 4.4% to 7.9%). Congenital cryptorchidism was associated with earlier gestational age (p<0.001), lower birth weight (p<0.001), birth length (p<0.001) and shorter penile length at birth (p<0.0001) compared with other infants, but normal size after age 3 months. The prevalence of cryptorchidism declined to 2.4% at 3 months, but unexpectedly rose again to 6.7% at 12 months as a result of new cases. The cumulative incidence of "acquired cryptorchidism" by age 24 months was 7.0% and these cases had shorter penile length during infancy than other infants (p = 0.003). CONCLUSIONS: The prevalence of congenital cryptorchidism was higher than earlier estimates in UK populations. Furthermore, this study for the first time describes acquired cryptorchidism or "ascending testis" as a common entity in male infants, which is possibly associated with reduced early postnatal androgen activity.