114 results for 2000, Harding, Jane, Journal article

  • Multi-nutrient fortification of human milk for preterm infants

    Brown, JVE; Embleton, ND; Harding, Jane; McGuire, W (2016)

    Journal article
    The University of Auckland Library

    Exclusively breast milk-fed preterm infants may accumulate nutrient deficits leading to extrauterine growth restriction. Feeding preterm infants with multi-nutrient fortified human breast milk rather than unfortified breast milk may increase nutrient accretion and growth rates and may improve neurodevelopmental outcomes. Objectives To determine whether multi-nutrient fortified human breast milk improves important outcomes (including growth and development) over unfortified breast milk for preterm infants without increasing the risk of adverse effects (such as feed intolerance and necrotising enterocolitis). Search methods We used the standard search strategy of the Cochrane Neonatal Review Group. This included electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (until February 2016), as well as conference proceedings and previous reviews. Selection criteria Randomised and quasi-randomised controlled trials that compared feeding preterm infants with multi-nutrient (protein and energy plus minerals, vitamins or other nutrients) fortified human breast milk versus unfortified (no added protein or energy) breast milk. Data collection and analysis We extracted data using the standard methods of the Cochrane Neonatal Review Group. We separately evaluated trial quality, data extracted by two review authors and data synthesised using risk ratios (RRs), risk differences and mean differences (MDs). We assessed the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results We identified 14 trials in which a total of 1071 infants participated. The trials were generally small and weak methodologically. Meta-analyses provided low-quality evidence that multi-nutrient fortification of breast milk increases in-hospital rates of growth (MD 1.81 g/kg/d, 95% confidence interval (CI) 1.23 to 2.40); length (MD 0.12 cm/wk, 95% CI 0.07 to 0.17); and head circumference (MD 0.08 cm/wk, 95% CI 0.04 to 0.12). Only very limited data are available for growth and developmental outcomes assessed beyond infancy, and these show no effects of fortification. The data did not indicate other potential benefits or harms and provided low-quality evidence that fortification does not increase the risk of necrotising enterocolitis in preterm infants (typical RR 1.57, 95% CI 0.76 to 3.23; 11 studies, 882 infants). Authors' conclusions Limited available data do not provide strong evidence that feeding preterm infants with multi-nutrient fortified breast milk compared with unfortified breast milk affects important outcomes, except that it leads to slightly increased in-hospital growth rates.

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  • Global Motion Perception in 2-Year-Old Children: A Method for Psychophysical Assessment and Relationships With Clinical Measures of Visual Function

    Yu, Tzu-Ying; Jacobs, Robert; Anstice, Nicola; Paudel, Nabin; Harding, Jane; Thompson, Benjamin; CHYLD Study Team (2013-12)

    Journal article
    The University of Auckland Library

    Purpose. We developed and validated a technique for measuring global motion perception in 2-year-old children, and assessed the relationship between global motion perception and other measures of visual function. Methods. Random dot kinematogram (RDK) stimuli were used to measure motion coherence thresholds in 366 children at risk of neurodevelopmental problems at 24 ?? 1 months of age. RDKs of variable coherence were presented and eye movements were analyzed offline to grade the direction of the optokinetic reflex (OKR) for each trial. Motion coherence thresholds were calculated by fitting psychometric functions to the resulting datasets. Test???retest reliability was assessed in 15 children, and motion coherence thresholds were measured in a group of 10 adults using OKR and behavioral responses. Standard age-appropriate optometric tests also were performed. Results. Motion coherence thresholds were measured successfully in 336 (91.8%) children using the OKR technique, but only 31 (8.5%) using behavioral responses. The mean threshold was 41.7 ?? 13.5% for 2-year-old children and 3.3 ?? 1.2% for adults. Within-assessor reliability and test???retest reliability were high in children. Children's motion coherence thresholds were significantly correlated with stereoacuity (LANG I & II test, ?? = 0.29, P < 0.001; Frisby, ?? = 0.17, P = 0.022), but not with binocular visual acuity (?? = 0.11, P = 0.07). In adults OKR and behavioral motion coherence thresholds were highly correlated (intraclass correlation = 0.81, P = 0.001). Conclusions. Global motion perception can be measured in 2-year-old children using the OKR. This technique is reliable and data from adults suggest that motion coherence thresholds based on the OKR are related to motion perception. Global motion perception was related to stereoacuity in children.

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  • Maternal undernutrition and endocrine development

    Harding, Jane; Behrensdorf Derraik, Jose; Bloomfield, Francis (2010)

    Journal article
    The University of Auckland Library

    Maternal undernutrition, whether it occurs before conception, throughout gestation or during lactation, may lead to physiological adaptations in the fetus that will affect the health of the offspring in adult life. The timing, severity, duration and nature of the maternal nutritional insult may affect the offspring differently. Other factors determining outcome following maternal undernutrition are fetal number and gender. Importantly, effects of maternal undernutrition may be carried over into subsequent generations. This review examines the endocrine pathways disrupted by maternal undernutrition that affect the long-term postnatal health of the offspring. Maternal and childhood undernutrition are highly prevalent in low- and middle-income countries, and, in developed countries, unintentional undernutrition may arise from maternal dieting. It is, therefore, important that we better understand the mechanisms driving the long-term effects of maternal undernutrition, as well as identifying treatments to ameliorate the associated mortality and morbidity.

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  • Evidence for fetal glucocorticoid excess as a cause of adult cardiovascular disease

    Bloomfield, Francis; Harding, Jane (2006)

    Journal article
    The University of Auckland Library

    Purpose of review: Animal experiments demonstrating associations between birth weight and postnatal phenotypes that may increase the risk of cardiovascular disease, such as hypertension, obesity, anxiety, and increased glucocorticoid activity, support the human epidemiologic findings of an association between reduced size at birth and adult cardiovascular disease. Here we review the evidence for exposure of the fetus to excess glucocorticoid as the key underlying mechanism. Recent findings: Administration of synthetic glucocorticoids to, and undernutrition of, pregnant animals both results in reduced birth weight and the relevant postnatal phenotypes. However, in the latter paradigm direct evidence of fetal exposure to excess endogenous glucocorticoids of often lacking. Thirty-year-old offspring of pregnant women given glucocorticoids for threatened preterm labour have minimal evidence of increased cardiovascular risk factors. Summary: Exposure of the fetus to inappropriate amounts of glucocorticoids can result in a postnatal phenotype that may predispose to cardiovascular disease, although the fact that surrogate endpoints are often studied in animal experiments must be borne in mind. However, assumptions that effects of other interventions, such as maternal undernutrition, are mediated via exposure of the fetus to excess glucocorticoids are often not supported by direct evidence. The value of available human data should not be overlooked.

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  • Cot-side electroencephalography for outcome prediction in preterm infants: Observational study

    West, CR; Harding, Jane; Williams, CE; Nolan, M; Battin, Malcolm (2011-03)

    Journal article
    The University of Auckland Library

    Objective: To assess the use of two-channel electroencephalographical (EEG) recordings for predicting adverse neurodevelopmental outcome (death or Bayley II mental developmental index/psychomotor developmental index < 70) in extremely preterm infants and to determine the relationship between quantitative continuity measures and a specialist neurophysiologist assessment of the same EEG segment for predicting outcome. Design: Observational study. Setting: The study was conducted in a neonatal intensive care unit. Patients: Preterm infants born s assessment was a better predictor of adverse outcome than the continuity measures (positive predictive value 95% CI 75 (54% to 96%) vs 41 (22% to 60) at 25-??V threshold, negative predictive value 88 (80% to 96%) vs 84 (74% to 94%) and positive likelihood ratio 9.0 (3.2 to 24.6) vs 2.0 (1.2 to 3.6)). All the infants with definite seizures identified by the neurophysiologist had poor outcomes. Conclusions: Modified cot-side EEG has potential to assist with identification of extremely preterm infants at risk for adverse neurodevelopmental outcomes. However, analysis by a neurophysiologist performed better than the currently available continuity analyses.

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  • Effects of sex, litter size and periconceptional ewe nutrition on offspring behavioural and physiological response to isolation

    Hernandez, CE; Matthews, LR; Oliver, Mark; Bloomfield, Francis; Harding, Jane (2010-12-02)

    Journal article
    The University of Auckland Library

    Maternal periconceptional undernutrition alters fetal hypothalamic???pituitary???adrenal (HPA) axis development. However, the effects of this early nutritional insult on postnatal HPA axis function and stress-related behaviours are unknown. We investigated in sheep the effects of different periods of undernutrition, and of sex and litter size, on offspring behavioural and cortisol responses to isolation stress. We studied four nutritional groups: controls well nourished throughout pregnancy (n=39), or ewes undernourished (UN,10???15% body weight reduction) before mating (!60 to 0 d, n=26), after mating (!2 to +30 d, n=20) or both (!60 to +30 d, n=36). At 4 and 18 months of age, offspring were isolated for 5 min, their behaviour video recorded, and plasma cortisol concentrations measured. Offspring of all undernourished groups demonstrated 50% fewer escape attempts than controls at 4 months of age, and offspring of UN!60 +30 ewes had 20% lower plasma cortisol area under the curve in response to isolation at 18 months. Females had higher cortisol concentrations and vocalised more than males at 4 and 18 months, and were more active at 18 months. After isolation, UN!2 +30 males had higher cortisol concentrations than UN!2 +30 females whereas in all other groups males had lower concentrations than females. Singleton males made more escape attempts than females, whereas in twins females made more escape attempts than males. These !ndings suggest that maternal periconceptional undernutrition in sheep can suppress behavioural reactions and cortisol secretion in response to isolation stress in the offspring into adulthood, and that these effects differ between males and females.

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  • Effects of sex, litter size and periconceptional ewe nutrition on the ewe-lamb bond.

    Hernandez Verduzco, CE; Matthews, LR; Oliver, Mark; Bloomfield, Francis; Harding, Jane (2009)

    Journal article
    The University of Auckland Library

    Undernutrition restricted to the time around conception in sheep alters endocrine and metabolic responses in the offspring. Studies in rats suggest that such an early insult can also alter the behaviour of the offspring. We studied the effects of mild maternal periconceptional undernutrition (10-15% body weight reduction) on the lamb's response to separation from and reunion with the mother, and on the ewe-lamb bond, evaluated as the preference for each other over an alien ewe/lamb in a test enclosure, at 24 h 1 and 4 weeks of age. Lamb birth weight was not affected by maternal nutrition. Maternal periconceptional undernutrition did not affect the lambs' responses to separation and reunion (number of vocalisations, times to leave pen and achieve proximity with ewes) or the bond between ewes and lambs (percentage of time spent near their own dam/lamb). However, there were effects of sex, litter size and time on lambs' responses to separation and reunion and on the ewe-lamb bond. Female lambs vocalised more during separation (P <= 0.001). We conclude that periconceptional undernutrition does not affect offspring response to separation from the mother or the bond between ewes and lambs, but that these behaviours are affected by sex and litter size for up to 4 weeks after birth.

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  • Accuracy of caregivers' recall of hospital admissions: implications for research

    Burakevych, N; McKinlay, Christopher; Alsweiler, Jane; Harding, Jane; CHYLD Study team (2015-11)

    Journal article
    The University of Auckland Library

    AIM: To determine the accuracy of caregivers' recall of hospital admissions in early childhood. METHODS: Prospective cohort study of babies born at risk of neonatal hypoglycaemia at Waikato Hospital, New Zealand, a regional public hospital and sole provider of acute inpatient care to over 100,000 children. Caregivers' recall of children's hospital admissions up to 4.5 years were compared with medical records. Accuracy of recall was related to neonatal and socio-demographic characteristics. RESULTS: Out of 267 children, 179 (67%) visited hospital and 106 (40%) were admitted at least once. The most frequent reasons for admission were for respiratory (29%) and gastrointestinal (18%) problems. Of 106 children admitted to hospital, 27 (25%) caregivers did not recall the admission and only 37 (35%) accurately recalled the number of admissions. The accuracy of recall was lower for gastrointestinal (38%) and surgical (40%) problems, while recall of respiratory (64%) and ear, nose and throat (60%) admissions was more accurate. Low socio-economic status and multiple admissions were associated with less accurate recall of number of admissions. CONCLUSION: Caregivers do not accurately report hospital admissions. Questionnaire data about use of hospital facilities should be interpreted cautiously, and may not be sufficiently accurate for use in research studies.

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  • Differential regulation of igf1 and igf1r mRNA levels in the two hepatic lobes following intrauterine growth restriction and its treatment with intra-amniotic insulin-like growth factor-1 in ovine fetuses

    Darp, RA; de Boo, HA; Phua, Hui; Oliver, Mark; Behrensdorf Derraik, Jose; Harding, Jane; Bloomfield, Francis (2010)

    Journal article
    The University of Auckland Library

    Intrauterine growth restriction (IUGR) has life-long health implications, yet there is no effective prenatal treatment. Daily intra-amniotic administration of insulin-like growth factor (IGF)-1 to IUGR fetal sheep improves fetal gut maturation but suppresses hepatic igf1 gene expression. Fetal hepatic blood supply is regulated, in part, by shunting of oxygen- and nutrient-rich umbilical venous blood through the ductus venosus, with the left hepatic lobe predominantly supplied by umbilical venous blood and the right hepatic lobe predominantly supplied by the portal circulation. We hypothesised that: (1) once-weekly intra-amniotic IGF-1 treatment of IUGR would be effective in promoting gut maturation; and (2) IUGR and its treatment with intra-amniotic IGF-1 would differentially affect igf1 and igf1r mRNA expression in the two hepatic lobes. IUGR fetuses received 360 ??g IGF-1 or saline intra-amniotically once weekly from 110 until 131 days gestation. Treatment of IUGR fetuses with IGF-1 reversed impaired gut growth. In unembolised, untreated control fetuses, igf1 mRNA levels were 19% lower in the right hepatic lobe than in the left; in IUGR fetuses, igf1 and igf1r mRNA levels were sixfold higher in the right lobe. IGF-1 treatment reduced igf1 and igf1r mRNA levels in both lobes compared with IUGR fetuses. Thus, weekly intra-amniotic IGF-1 treatment, a clinically feasible approach, reverses the impaired gut development seen in IUGR. Furthermore, igf1 and igf1r mRNA levels are differentially expressed in the two hepatic lobes and relative expression in the two lobes is altered by both IUGR and intra-amniotic IGF-1 treatment.

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  • Cardiovascular adaptations to pregnancy in sheep and effects of periconceptional undernutrition

    Rumball, Christopher; Bloomfield, Francis; Harding, Jane (2008-01)

    Journal article
    The University of Auckland Library

    The objective of this study was to describe the effects of pregnancy on blood volume and uterine blood flow in sheep, and to test the hypothesis that the effects of peri conceptional undernutrition on the late-gestation fetus are mediated by alterations in these parameters. Singleton-bearing ewes that had been undernourished preconception, postconception, both, or neither, underwent estimation of blood volume in mid and late gestation, and measurement of uterine blood flow in late gestation. Seven non-pregnant ewes were also studied. Pregnancy resulted in a 31% greater red cell volume in mid-gestation (21.0 +/- 1.3 vs 16.1 +/- 0.8 ml/kg, p < 0.05), but no significant change in plasma or blood volume. However maternal blood volume was correlated with uterine blood flow (r(2) = 0.22, p = 0.05) and fetal size (r(2) = 0.20, p = 0.02). Uterine blood flow was 13% greater in the undernourished groups than controls (1847 +/- 100 vs 1641 +/- 79 ml/min, p < 0.01). The large increase in maternal blood volume integral to a successful human pregnancy was not present in sheep. The increased uterine blood flow after periconceptional undernutrition suggests that nutritional signals before and in early pregnancy influence fetal nutrient supply in late gestation. (c) 2007 Elsevier Ltd. All rights reserved.

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  • Periconceptional undernutrition of ewes impairs glucose tolerance in their adult offspring

    Todd, SE; Oliver, Mark; Jaquiery, Anne; Bloomfield, Francis; Harding, Jane (2009)

    Journal article
    The University of Auckland Library

    Maternal undernutrition throughout pregnancy can have long-term effects on the health of adult offspring. Undernutrition around the time of conception alters growth, metabolism, and endocrinology of the sheep fetus. bill the impact on offspring after birth is largely unknown. We determined the effect of maternal periconceptional Undernutrition in sheep oil glucose tolerance in the offspring before and after puberty. Undernourished (UN) ewes were fed individually to maintain weight loss of 10-15%, bodyweight from 61 d before until 30 d after mating. 08-spring (24 UN, 30 control) underwent an i.v. glucose tolerance test at 4 and 10 mo of awe. Glucose tolerance was similar in both groups at 4 mo. Insulin area under the curve increased by 33% between 4 and 10 mo (101 +/- 8 versus 154 +/- 12 ng . min . mL(-1), p < 0.0001). At 10 mo. UN offspring had a 10% greater glucose area under the curve than controls (809 +/- 22 versos 712 +/- 20 mM . min, p < 0.01), a reduced first phase insulin response (p = 0.003) which was particularly apparent in females and in singletons, and a decreased insulin:glucose ratio (p = 0.01). We conclude that maternal undernutrition around the time of conception results in impaired glucose tolerance in postpubertal offspring.

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  • Variable interpretation of ultrasonograms may contribute to variation in the reported incidence of white matter damage between newborn intensive care units in New Zealand

    Harris, Deborah; Bloomfield, Francis; Teele, R; Harding, Jane; Australian New Zealand Neonatal Ne (2006-01)

    Journal article
    The University of Auckland Library

    Background: The incidence of cerebral white matter damage reported to the Australian and New Zealand Neonatal Network (ANZNN) varies between neonatal intensive care units (NICUs).Hypothesis: Differences in the capture, storage, and interpretation of the cerebral ultrasound scans could account for some of this variation.Methods: A total of 255 infants of birth weight < 1500 g and gestation < 32 weeks born between 1997 and 2002 and drawn equally from each of the six NICUs in New Zealand were randomly selected from the ANZNN database. Half had early cerebral ultrasound scans previously reported to ANZNN as normal, and half had scans reported as abnormal. The original scans were copied, anonymised, and independently read by a panel of three experts using a standardised method of reviewing and reporting.Results: There was considerable variation between NICUs in methods of image capture, quality, and completeness of the scans. There was only moderate agreement between the reviewers' reports and the original reports to the ANZNN (kappa 0.45-0.51) and between the reviewers (kappa 0.54-0.64). The reviewers reported three to six times more white matter damage than had been reported to the ANZNN.Conclusion: Some of the reported variation in white matter damage between NICUs may be due to differences in capture and interpretation of cerebral ultrasound scans.

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  • Amniotic IGF-I supplementation of growth-restricted fetal sheep alters IGF-I and IGF receptor type 1 mRNA and protein levels in placental and fetal tissues

    Shaikh, Shamim; Bloomfield, Francis; Bauer, Michael; Phua, Hui; Gilmour, RS; Harding, Jane (2005-07)

    Journal article
    The University of Auckland Library

    We have previously reported that chronic intra-amniotic supplementation of the late gestation growth-restricted (IUGR) ovine fetus with IGF-I (20 mu g/day) increased gut growth but reduced liver weight and circulating IGF-I concentrations. Here we report mRNA and protein levels of IGF-I, the type I IGF receptor (IGF-1R) and IGF-binding proteins (IGFBP)-1, -2 and -3 in fetal gut, liver, muscle and placenta from fetuses in that earlier study in an attempt to explain these contrasting results. mRNA and protein were extracted from tissues obtained at post mortem at 131 days of gestation (term, 145 days) from three groups of fetuses (control, IUGR+saline and IUGP,+IGF-I, n=9 per group). Control fetuses were unembolised and untreated. In the IUGR groups, growth restriction was induced from 113 to 120 days by placental embolisation; from 120 to 130 days fetuses were treated with daily intra-amnotic injections of either saline or 20 mu g IGF-I mRNA was measured by RT-PCR or real-time RT-PCR, and protein by Western blot. In liver, muscle and placenta, IGF-I mRNA and protein levels were reduced by between 8 and 30% in IGF-I-treated fetuses compared with saline-treated fetuses and controls with no change in IGF-I R mRNA or protein levels. In contrast, in the gut, IGF-I mRNA and protein levels were not significantly altered with IGF-I treatment, but IGF-1R levels were increased, especially in the jejunum. Immunolocalisation demonstrated that IGF-1R expression was confined to the luminal aspect of the gut. mRNA levels of all three IGFBPs were reduced in the gut of IGF-I-treated fetuses, but hepatic expression was significantly increased. These data demonstrated tissue-specific regulation of IGF-I, IGF-1R and IGFBPs-1, -2 and -3 in response to intra-amniotic IGF-I supplementation, though the underlying mechanisms remain obscure.

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  • Periconceptional Events Perturb Postnatal Growth Regulation in Sheep

    Jaquiery, Anne; Oliver, Mark; Bloomfield, Francis; Harding, Jane (2011)

    Journal article
    The University of Auckland Library

    Periconceptional undernutrition and twin conception alter intrauterine growth and metabolism and are associated with later adverse metabolic outcomes. The contribution of postnatal growth to these outcomes is less well defined. We investigated whether maternal periconceptional undernutrition or twin conception altered postnatal growth regulation in ways that could lead to metabolic disease. Single and twin offspring of ewes undernourished (UN) from 61 d before until 30 d after mating, fed to achieve and maintain 10-15% weight loss (UN), were compared with offspring of maintenance-fed controls (N). At 2 h and 1, 6, and 12 wk after birth, lambs were weighed and plasma hormone and metabolite concentrations analyzed. Milk intake, measured by deuterium oxide dilution, was inversely related to birth weight only in N singles, although twins had the greatest postnatal growth velocity. Positive associations were seen between milk intake, growth velocity, and leptin concentrations in N, but not UN, offspring. We conclude that periconceptional undernutrition alters the relationships between regulators of postnatal growth, including nutrient intake and key hormonal axes, in both singles and twins without affecting size at birth or postnatal growth velocity. Dissociation of growth from its key regulators is one possible mechanism underlying adverse metabolic outcomes after periconceptional undernutrition.

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  • Antenatal Glucocorticoids for Late Preterm Birth?

    Crowther, Caroline; Harding, Jane (2016-04-07)

    Journal article
    The University of Auckland Library

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  • Lactate, rather than ketones, may provide alternative cerebral fuel in hypoglycaemic newborns

    Harris, Deborah; Weston, PJ; Harding, Jane (2015)

    Journal article
    The University of Auckland Library

    OBJECTIVE: Alternative cerebral fuels are reputed to provide neuroprotection during hypoglycaemia, particularly in breastfed babies. We measured concentrations of alternative cerebral fuels in hypoglycaemic babies in the first 48???h. PATIENT AND METHODS: Babies were ???35???weeks, ???48???h old and at risk of hypoglycaemia (infant of diabetic, preterm, small or large). Plasma glucose, ??-hydroxybutyrate, lactate and insulin concentrations were measured in babies who had been hypoglycaemic (1???h. RESULTS: Samples were taken from 35 hypoglycaemic babies at 3.7; 1.8-39.6 (median; range) hours after birth. Concentrations of glucose and ??-hydroxybutyrate were low (2.03; 0.19-3.39???mM and 0.06; 0.00-1.20???mM), but lactate concentrations varied widely (3.06; 0.02-7.96???mM). Infants of diabetics had lower ??-hydroxybutyrate and higher insulin concentrations, but mode of feeding did not influence plasma concentrations of alternative cerebral fuels. CONCLUSIONS: Hypoglycaemic babies within the first 48???h after birth are unlikely to receive neuroprotection from ketones. However, lactate may provide an alternative cerebral fuel for many. Lactate, rather than ketones, may provide alternative cerebral fuel in hypoglycaemic newborns. TRIAL REGISTRATION NUMBER: ACTRN12608000623392.

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  • Effects of periconceptional undernutrition on maternal taurine concentrations in sheep

    Thorstensen, Eric; Behrensdorf Derraik, Jose; Oliver, Mark; Jaquiery, Anne; Bloomfield, Francis; Harding, Jane (2012)

    Journal article
    The University of Auckland Library

    Taurine has an important role in numerous physiological processes, including many aspects of fetal development such as development of the pancreas and brain, and requirements increase during pregnancy. Periconceptional undernutrition has long-term effects on pancreas and brain function of the offspring, but the effects on maternal taurine economy are unknown. We, therefore, studied the effects of different periods of periconceptional undernutrition on maternal plasma and urine taurine concentrations before and during pregnancy. Four groups of singleton-bearing ewes were studied (n 10-11): controls fed ad libitum, and groups undernourished from 60??d before until mating (PreC), from 2??d before mating until 30??d after mating (PostC) or from 60??d before until 30??d after mating (Pre+PostC). In PreC ewes, plasma taurine concentrations remained at control levels for the first 30??d, and then decreased through the remainder of undernutrition, but recovered by 30??d after mating; urinary taurine excretion was low at mating, but recovered similarly. In PostC ewes, plasma taurine concentrations recovered after 2 weeks despite ongoing undernutrition; urinary taurine excretion had recovered by 30??d after mating. Pre+PostC ewes followed the same pattern as PreC for the first 60??d, but plasma taurine concentrations and urinary excretion recovered slowly, and did not reach the control levels until 97??d. These data suggest that different periods of mild periconceptional undernutrition in sheep have different but substantial effects on maternal taurine homoeostasis. These effects may be one mechanism by which maternal periconceptional undernutrition alters development of the offspring with implications for adult health.

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  • Effect of periconceptional undernutrition in sheep on late gestation expression of mRNA and protein from genes involved in fetal adrenal steroidogenesis and placental prostaglandin production

    Connor, KL; Bloomfield, Francis; Oliver, Mark; Harding, Jane; Challis, JRG (2009)

    Journal article
    The University of Auckland Library

    In sheep, maternal periconceptional undernutrition precociously activates fetal hypothalamic-pituitary-adrenal function in a high proportion of animals, resulting in preterm birth. We investigated whether the effects of periconceptional undernutrition were mediated through genes encoding enzymes involved in adrenal steroidogenesis and in placental production and metabolism of steroids and prostaglandins. Singleton-bearing ewes were fed ad libitum (control, N) throughout gestation or undernourished from 60 days before until 30 days after mating. Fetal adrenal and placentome tissues were collected on gestational day 131. Fetal adrenal P450C17 protein expression was significantly increased with undernutrition. Placental prostaglandin endoperoxide synthase-2 expression was not different between groups. In undernourished pregnancies, there were significant positive correlations between fetal plasma adrenocorticotrophic hormone and cortisol concentrations and between fetal plasma adrenocorticotrophic hormone concentrations and placental prostaglandin endoperoxide synthase-2 messenger RNA (mRNA) and protein. These studies suggest that periconceptional undernutrition affects fetal adrenal P450C17, consistent with an elevation in plasma cortisol, and this occurs prior to activation of placental prostaglandin endoperoxide synthase-2 expression at gestational day 131.

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  • Do Alterations in Placental 11 beta-Hydroxysteroid Dehydrogenase (11 beta HSD) Activities Explain Differences in Fetal Hypothalamic-Pituitary-Adrenal (HPA) Function Following Periconceptional Undernutrition or Twinning in Sheep?

    Connor, KL; Challis, JRG; van Zijl, P; Rumball, CW; Alix, S; Jaquiery, Anne; Oliver, Mark; Harding, Jane; Bloomfield, Francis (2009-12)

    Journal article
    The University of Auckland Library

    Periconceptional undernutrition (UN) in sheep accelerates fetal hypothalamic-pituitary-adrenal (HPA) axis activation, resulting in preterm birth. In contrast, twin conception suppresses fetal HPA function and delays prepartum HPA activation. We hypothesized that these dissimilar effects on fetal HPA activity result from different influences of maternal glucocorticoid (GC) on maturation of the fetal HPA axis, mediated via different activities of placental 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) isozymes. We examined the effects of twinning and maternal periconceptional UN from 60 days before until 30 days after mating on the ontogeny of placental 11 beta HSD-1 and -2 enzyme activities. At day 85 of gestation, placental 11 beta HSD-2 activity was lower in UN than in normally nourished (N) fetuses (P < .05) and was higher in twins than in singletons (P < .05). Furthermore, placental 11 beta HSD-1 activity was not different between nutritional groups but was higher in twins than in singletons (P = .01). At day 85, fetal plasma cortisol (P < .001) and cortisone (P < .001) concentrations were lower in UN than in N fetuses, but the cortisol to cortisone ratio was higher in UN than in N fetuses (P = .01). There was no effect of fetus number on plasma cortisol or cortisone concentrations or on the ratio of cortisol to cortisone at day 85. Therefore, periconceptional UN and twinning may result in the alterations of placental 11 beta HSD isozyme activities at particular times during gestation. Changes in these activities during critical periods of fetal development could affect transplacental transfer or placental generation of GCs that reach the fetus, potentially influencing the timing of activation of the fetal HPA axis, fetal maturation, and hence the development and health later in life.

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  • Arginine and mixed amino acids increase protein accretion in the growth-restricted and normal ovine fetus by different mechanisms

    De Boo, Hendrina; Van Zijl, PL; Smith, DEC; Kulik, W; Lafeber, HN; Harding, Jane (2005-08)

    Journal article
    The University of Auckland Library

    Protein metabolism may be perturbed in intrauterine growth restriction (IUGR). Arginine is indispensable for growth and nitrogen balance in young mammals. Fetuses with IUGR therefore may benefit from arginine supplementation. The purpose of this study was to determine 1) the effects of IUGR on protein metabolism in the ovine fetus and 2) the effects of arginine or mixed amino acid (AA) infusion on protein metabolism in these fetuses. Pregnant ewes and their fetuses were catheterized at 110 d gestation and randomly assigned to control or IUGR groups. IUGR was induced by repetitive placental embolization. Parameters of fetal protein metabolism were determined from [ring-H-2(5)]phenylatanine kinetics at baseline and in response to a 4-h infusion of either arginine or an isonitrogenous AA mixture. There were no differences in protein metabolism between control and IUGR groups either at baseline or in response to arginine or AA treatment. Both arginine and AA infusion increased fetal protein accretion in both groups. Arginine did this by decreasing protein turnover, synthesis, and breakdown. AAs increased protein turnover and synthesis while decreasing protein breakdown. AA infusion resulted in a significantly higher increase in protein accretion than arginine infusion. Thus, in the ovine fetus, placental embolization has no clear effect on protein metabolism. Arginine and AAs both stimulate protein accretion but do so in distinctly different ways. Mixed AA infusion has a greater effect on protein accretion than arginine alone and therefore maybe a better strategy for stimulating fetal growth.

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