Biomedical subjects

Ruth Morley

Publications and source records attributed to Ruth Morley.

At least 19 recordsLinked to original sources

PubMed2007

Infant nutrition and stereoacuity at age 4-6 y.

BACKGROUND: Breastfeeding has been reported to benefit visual development in children. A higher concentration of docosahexaneoic acid (DHA) in breast milk than in formula has been proposed as one explanation for this association and as a rationale for adding DHA to infant formula, but few long-term data support this possibility. OBJECTIVE: The objectives of the study were, first, to test the hypothesis that breastfeeding benefits stereoscopic visual maturation and, second, if that benefit is shown, to ascertain whether it is mediated by the dietary intake of DHA. DESIGN: Stereoacuity was measured by using the random dot E test (primary outcome), and visual acuity was measured by using the Sonksen-Silver acuity system (secondary outcome) in previously breastfed (n = 78) or formula-fed (n = 184) children aged 4-6 y who had been followed prospectively from birth. In the formula-fed group, children were randomly assigned to receive formula with either DHA or arachidonic acid (n = 94) or a control formula (n = 90) for the first 6 mo. RESULTS: Breastfed children had a significantly (P = 0.001) greater likelihood of foveal stereoacuity (high-grade or < 100 s/arc) than did formula-fed children (odds ratio: 2.5; 95% CI: 1.4, 4.5) independent of potential confounding (P = 0.005). Stereoacuity did not differ significantly between children randomly assigned to DHA-supplemented or control formula. None of the groups differed in Sonksen-Silver visual acuity. CONCLUSIONS: These findings support the hypothesis that breastfeeding benefits long-term stereoscopic development. An effect of DHA cannot be excluded, but the lack of difference in stereoacuity between infants randomly assigned to DHA-containing and those assigned to control formula raises the hypothesis that factors in breast milk other than DHA account for the observed benefits.

Breast Feeding↗

PubMed2006

Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand: a consensus statement.

Vitamin D deficiency has re-emerged as a significant paediatric health issue, with complications including hypocalcaemic seizures, rickets, limb pain and fracture. A major risk factor for infants is maternal vitamin D deficiency. For older infants and children, risk factors include dark skin colour, cultural practices, prolonged breastfeeding, restricted sun exposure and certain medical conditions. To prevent vitamin D deficiency in infants, pregnant women, especially those who are dark-skinned or veiled, should be screened and treated for vitamin D deficiency, and breastfed infants of dark-skinned or veiled women should be supplemented with vitamin D for the first 12 months of life. Regular sunlight exposure can prevent vitamin D deficiency, but the safe exposure time for children is unknown. To prevent vitamin D deficiency, at-risk children should receive 400 IU vitamin D daily; if compliance is poor, an annual dose of 150,000 IU may be considered. Treatment of vitamin D deficiency involves giving ergocalciferol or cholecalciferol for 3 months (1000 IU/day if < 1 month of age; 3000 IU/day if 1-12 months of age; 5000 IU/day if > 12 months of age). High-dose bolus therapy (300,000-500,000 IU) should be considered for children over 12 months of age if compliance or absorption issues are suspected.

Adolescent↗

PubMed2006

Birthweight and coronary heart disease in a cohort born 1857-1900 in Melbourne, Australia.

BACKGROUND: The widely observed association between birth size and risk of later coronary heart disease (CHD) has not been examined in an impoverished pre-20th century birth cohort. METHODS: Birth weights and maternal characteristics, for births between 1857 and 1900 in a charity hospital, were recorded from preserved ledgers. Names were linked to death certificates to determine age and cause of death. Death with CHD was coded using specific criteria, and survival analysis methods were used to relate risk of CHD to birth weight, allowing for competing causes of death and adjusting for potentially confounding maternal factors. RESULTS: Death certificates were traced for 8,584 (53%) of 16,272 registered live-births. Survival analyses were confined to 2,938 subjects (1,572 male, 1,366 female) who survived beyond age 40, since none of the 486 CHD cases was recorded earlier. CHD risk increased with time, but there was no evidence that it was related to birth weight, in men or women. CONCLUSIONS: We did not replicate findings in more recent cohorts. This may represent a true lack of association in a historical cohort who we believe remained impoverished through their early life. However, we acknowledge the strong possibility of misclassification of cause of death by the person filling in the death certificate and/or our coding criteria, and temporal change in diagnostic criteria for CHD. We cannot exclude the possibility that low birth weight babies 'programmed' in utero for later CHD were more likely to die in infancy, in this cohort with a high infant mortality rate.

Aged↗

PubMed2006

Maternal dietary intake in twin pregnancies: does it diminish towards term?

We tested the hypothesis that energy intake among women with twin pregnancies decreases in late gestation, as the uterus enlarges and they become increasingly uncomfortable. We asked women to recall dietary intake for the previous 24 hours, every 2 weeks from around 29 weeks of gestation, using a photographic atlas and other strategies to estimate portion size. Eighty women provided data at around 29, 31, 33 and 35 weeks of gestation. We calculated total energy intake, and energy intake from carbohydrate, fat and protein. Data were log transformed to reduce skewness. Using mixed effects linear regression models, we found minimal evidence that total energy intake changed over this time period, either before or after adjustment for potential confounding factors (95% confidence interval for relative change per week: -1.4%, 0.6%). There was weak evidence of a small decline in carbohydrate intake over time, both before and after controlling for energy intake. We cannot exclude change in energy intake or diet composition before 29 weeks or after 35 weeks of twin gestation.

Diet↗

PubMed2005

Fetal origins of adult disease.

The term 'fetal origins of adult disease' was coined on the basis of the inverse association between low birth weight and blood pressure, adult-onset diabetes, coronary heart disease, and stroke seen in numerous epidemiological studies. However, it seems unlikely that birth weight is involved in causal pathways underlying these observations, and if it were then the significance to public health of these findings is very limited because of our inability to modify birth weight to a relevant extent in humans. There has been a major focus on maternal nutrition. Despite evidence that experimental manipulation of maternal nutrition in animals influences offspring birth weight and programme measures related to cardiovascular disease, human studies in general provide limited and unconvincing evidence that differences in maternal macronutrient intake are important. Nevertheless there is a need to understand the underlying causal pathways, and the utility of studies of twins and possible mechanisms are discussed.

Animals↗

PubMed2005

Maternal 25-hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size.

CONTEXT: There is inconsistent evidence that maternal 25-hydroxyvitamin D [25-(OH)D] deficiency may impair fetal growth. OBJECTIVE: The objective of the study was to examine the relationship between maternal 25-(OH)D and PTH concentrations at less than 16 and 28 wk gestation and offspring birth size. DESIGN: This was an observational study. SETTING: The study was set at a hospital antenatal clinic. PARTICIPANTS: Women with singleton pregnancies, before 16 wk gestation, participated. INTERVENTIONS: No interventions were used. MAIN OUTCOME MEASURE: Knee-heel length at birth was the main outcome measure. RESULTS: Altogether 374 of 475 (79%) women completed this study. We found no evident relationship between birth size measures and maternal 25-(OH)D or PTH at recruitment (approximately 11 wk). Gestation length was 0.7 wk (95% confidence interval -1.3, -0.1) shorter and knee-heel length was 4.3 mm smaller (-7.3, -1.3) in infants of 27 mothers with low 25-(OH)D (<28 nmol/liter) at 28-32 wk vs. babies whose mothers had higher concentrations. This latter difference was reduced to -2.7 mm (-5.4, -0.1) after adjustment for gestation length, suggesting some of the apparent growth deficit is explained by shorter gestation. There was no evidence that other birth measures were affected. Maternal PTH concentration at 28-32 wk was positively related to knee-heel length, birth weight, and mid-upper arm and calf circumferences. These associations were independent of 25-(OH)D concentration. CONCLUSIONS: Low maternal 25-(OH)D in late pregnancy is associated with reduced intrauterine long bone growth and slightly shorter gestation. The long-term consequences for linear growth and health require follow-up. The positive relationship between maternal PTH and measures of infant size may relate to increased mineral demands by larger babies, but warrants further investigation.

Birth Weight↗

PubMed2005

Regression models for twin studies: a critical review.

Twin studies have long been recognized for their value in learning about the aetiology of disease and specifically for their potential for separating genetic effects from environmental effects. The recent upsurge of interest in life-course epidemiology and the study of developmental influences on later health has provided a new impetus to study twins as a source of unique insights. Twins are of special interest because they provide naturally matched pairs where the confounding effects of a large number of potentially causal factors (such as maternal nutrition or gestation length) may be removed by comparisons between twins who share them. The traditional tool of epidemiological 'risk factor analysis' is the regression model, but it is not straightforward to transfer standard regression methods to twin data, because the analysis needs to reflect the paired structure of the data, which induces correlation between twins. This paper reviews the use of more specialized regression methods for twin data, based on generalized least squares or linear mixed models, and explains the relationship between these methods and the commonly used approach of analysing within-twin-pair difference values. Methods and issues of interpretation are illustrated using an example from a recent study of the association between birth weight and cord blood erythropoietin. We focus on the analysis of continuous outcome measures but review additional complexities that arise with binary outcomes. We recommend the use of a general model that includes separate regression coefficients for within-twin-pair and between-pair effects, and provide guidelines for the interpretation of estimates obtained under this model.

Birth Weight↗

PubMed2005

Association between erythropoietin in cord blood of twins and size at birth: does it relate to gestational factors or to factors during labor or delivery?

We hypothesized that cord blood erythropoietin (EPO), a marker of fetal hypoxia, relates to gestational factors and not solely those associated with delivery. We investigated the association between birth weight SD score (SDS) and cord blood EPO in 290 twins (145 pairs), assessing the influence of gestational versus perinatal factors by comparing the association in those who were delivered by elective cesarean (CS) with that in other delivery modes. Blood EPO values were skewed, so geometric means are presented and log EPO values were used in statistical models. The birth size-EPO association was estimated in mixed-effects models that included terms that represented difference in log EPO and mean log EPO for each twin pair. Within-pair estimates of the association were unconfounded by maternal factors (because these were perfectly controlled). Geometric mean EPO was higher in boys versus girls (24.4 versus 17.0 IU/L; p = 0.0001) and increased with gestational age (p = 0.0003) but was similar after elective CS versus other delivery modes. The negative birth size-EPO association was stronger in infants who were delivered by elective CS than by other delivery modes [beta for log(2) EPO: -0.56 (95% CI, -0.77 to -0.36) versus -0.27 (-0.42 to -0.12), respectively; p = 0.02 for interaction). Because the association was seen after elective CS delivery, cord blood EPO must relate to factors during gestation, not just perinatal factors. There was no evidence of an association between birth weight SDS and pair mean log EPO, indicating that the association is entirely due to fetus-specific rather than pair-specific factors.

Cesarean Section↗

PubMed2005

Studies of twins: what can they tell us about the fetal origins of adult disease?

There has been much interest in evidence that people with lower birthweight have higher risk of adult cardiovascular disease, but the causal pathways underlying such observations are uncertain. Study of twins offers an opportunity to shed light on the underlying causal pathways, in particular by investigating the role of 'shared' factors vs. factors affecting each individual fetus. This involves comparing results of within-cohort vs. within-pair analyses. Twins share many factors during gestation but birthweight discordance (difference in birthweight within a twin pair) cannot be determined by these shared factors and must relate to factors affecting growth of each individual fetus. If associations seen in a cohort of twins remain in within-pair analyses, then factors specific to each individual must be involved in the underlying causal pathways. Conversely, if the relationships disappear or substantially diminish in within-pair analyses, then factors common to the pair must be involved. Comparison of findings in monozygotic vs. dizygotic twins may provide insights into the role of genetic factors, although issues related to chorionicity need to be taken into account. We tabulate published data and conclude that differences in methodology and analyses preclude informative meta-analysis, and that analysis of pooled data would provide more useful information.

Adult↗

PubMed2005

Can we generalise from findings in twins?

A number of recent studies have used data from twins to shed light on the causal pathways underlying the observed association between birthweight and cardiovascular risk factors or coronary heart disease. The issue of whether findings from twin studies are generally informative, or whether factors associated with twinning preclude generalisation, is considered here. It is concluded that the association between birthweight and later health may differ quantitatively between twins and singletons, but evidence regarding blood pressure suggests it may not differ qualitatively. However, more information is needed on a number of gestational and maternal factors, and on measures of health other than blood pressure. Placentation and issues relating to infertility and its treatment need to be recorded and, together with gestation length, may need to be taken into account in analyses.

Adult↗

PubMed2004

Maternal calcium supplementation and cardiovascular risk factors in twin offspring.

BACKGROUND: There is evidence that maternal calcium supplementation may result in lower offspring blood pressure. We hypothesized that maternal calcium supplementation also influences other cardiovascular risk factors. METHODS: In the Tasmanian Infant Health Study, supplements reportedly taken in pregnancy were recorded. Twin children of 147 participating mothers were seen at mean age 9 years. Blood pressure was measured in all 294 children and fasting blood samples taken from 230 (78%) for glucose and insulin, triacylglycerol, total cholesterol (T-C) and HDL cholesterol (HDL-C). LDL cholesterol (LDL-C) was calculated. RESULTS: Children of supplemented mothers (n = 110, 77 had venipuncture) had lower geometric mean triacylglycerol, T-C, and LDL-C than other children. After adjustment for potential confounding factors, geometric mean ratios were 0.86 (95% CI: 0.75, 0.98), 0.94, (95% CI: 0.90, 0.99) and 0.90, (95% CI: 0.83, 0.98) respectively. The association with T-C and LDL-C was seen principally among children with BMI > 17.5: estimated ratios 0.85 (95% CI: 0.79, 0.92) for total cholesterol and 0.79 (95% CI: 0.70, 0.90) for LDL cholesterol (P for interaction 0.001 and 0.009 respectively). There was no significant association between maternal calcium supplementation and child size at birth and follow up, blood pressure, fasting glucose or insulin or HDL-C. CONCLUSIONS: Maternal calcium supplementation may confer health benefits on twin offspring, especially if they are relatively fat. Calcium availability could permanently programme lipid metabolism during fetal life, directly or by influencing maternal lipid profile. Our findings need to be replicated in other studies and in singletons. If confirmed, our findings could have important implications for population health.

Adult↗

PubMed2004

Postnatal evaluation of vitamin D and bone health in women who were vitamin D-deficient in pregnancy, and in their infants.

OBJECTIVE: To determine the postnatal vitamin D status and bone health of women identified as vitamin D-deficient in pregnancy, and of their infants. DESIGN AND PARTICIPANTS: Retrospective audit conducted between 27 August and 5 November 2003. The study included women delivering between August and October 2002 at the Royal Women's Hospital, Melbourne, who had had a 25-hydroxyvitamin D (25-[OH]D) level < 30 nmol/L in pregnancy, and their infants at age 4-10 months. SETTING: The outpatient clinic at the Royal Children's Hospital, Melbourne. MAIN OUTCOME MEASURES: Maternal and infant serum levels of vitamin D, total alkaline phosphatase (tALP), parathyroid hormone (PTH), calcium and phosphorus; x-ray results in children with clinical or laboratory findings suggestive of rickets. RESULTS: Of 69 mother-infant pairs invited to participate, 47 (68%) attended. All 47 women had 25-(OH)D levels < 50 nmol/L, and 39 (83%) had levels < 30 nmol/L. Vitamin D supplements had been prescribed in pregnancy for 35 women (74%), and 19/35 reported having taken them as prescribed. None had continued to take supplements postnatally, but one had recently started taking them again. Among 45 infants from whom blood samples were successfully obtained, 18 (40%) had 25-(OH)D levels < 50 nmol/L, and 14 (31%) had levels < 30 nmol/L. Twelve of 16 breastfed infants had 25-(OH)D levels < 30 nmol/L, compared with 2/29 fed formula milk (P = 0.001). CONCLUSIONS: Most mothers who had been vitamin D-deficient in pregnancy were also deficient postnatally, indicating that treatment offered, counselling and/or treatment compliance were inadequate. Their infants, especially if breastfed, were at high risk of vitamin D deficiency and increased bone formation. Breastfed infants of mothers at high risk of vitamin D deficiency should receive vitamin D supplements.

Adult↗

PubMed2004

Risk-taking, coordination and upper limb fractures in children: a population based case-control study.

The aim of this population based case-control study was to examine the association between risk-taking behaviour, motor coordination and upper limb fractures in children aged 9-16 years. A total of 321 fracture cases and 321 randomly selected individually matched controls were studied. The number for different types of upper limb fractures was 91 for hand, 190 for wrist and forearm and 40 for upper arm. Risk-taking behaviour was determined by a 5-item interview-administered questionnaire. Motor coordination was assessed by the 8-point movement ABC that tests manual dexterity, ball skills as well as static and dynamic balance. Bone mass was assessed by dual energy X-ray absorptiometry (DXA) and metacarpal morphometry. In general, there was heterogeneity by fracture site with regard to associations. Risk-taking behaviour was associated with hand fracture risk but not other fracture sites for downhill cycling behaviour (OR: 2.0/category, 95% CI: 1.1-3.7), dare behaviour (OR: 3.3/category, 95% CI: 1.1-10.0) and total risk-taking score (OR: 2.6/category, 95% CI: 1.3-5.7). Conversely, coordination measures were associated with wrist and forearm fractures only: cutting/threading (OR: 1.2/unit, 95% CI: 1.0-1.4); flower trail (OR: 1.2/unit, 95% CI: 1.0-1.4) and dynamic balance score (OR: 1.1/unit, 95% CI: 1.0-1.2). Backward stepwise analysis selected total risk taking score for hand fracture, and dynamic balance score for wrist and forearm fracture. None of the risk-taking or coordination scores were associated with upper arm fractures. These associations were unchanged following adjustment for bone mass. In conclusion, the propensity to take risks is most strongly associated with hand fracture risk while dynamic balance is most strongly associated with wrist and forearm fracture risk in children. These results inform the development of fracture prevention strategies in children.

Adolescent↗

PubMed2004

Randomized, double-blind trial of long-chain polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants.

OBJECTIVE: To test the efficacy and safety of long-chain polyunsaturated fatty acid (LCPUFA) supplementation with gamma-linolenic acid, a precursor of arachidonic acid, and docosahexaenoic acid in preterm infants. STUDY DESIGN: Preterm (<35 weeks, < or =2000 g birth weight) infants (n=238) randomly assigned to unsupplemented or LCPUFA-supplemented formula to 9 months after term. The main outcome measure was the Bayley Mental and Psychomotor Indexes (MDI, PDI) at 18 months after term. Safety outcome measures were anthropometry (9 and 18 months), feed tolerance, infection, and clinical complications. RESULTS: There were no significant differences in neurodevelopment between groups overall. In preplanned subgroup analyses, LCPUFA-supplemented boys had significantly higher Bayley MDI than did control boys (difference, 5.7 points; 95% CI, 0.3 to 11.1; P=.04). LCPUFA-supplemented infants showed significantly greater weight gain (difference, 310 g; 95% CI, 30 to 590 g; P=.03) and length gain (difference, 1.0 cm; 95% CI, 0.02 to 1.9; P=.05) between birth and 9 months, with greater effect in boys (weight difference at 9 months, 510 g; 95% CI, 80 to 930 g; P=.02; length difference at 18 months, 1.8 cm; 95% CI, 0.1 to 1.8; P=.03). CONCLUSIONS: This trial, using the strategy of providing gamma-linolenic acid as a source of arachidonic acid, showed efficacy for growth and for neurodevelopment in boys, with no adverse effects. These data have important implications for LCPUFA-supplementation strategy in preterm infants.

Body Height↗

PubMed2004

Prematurity at birth and adolescent depressive disorder.

Association between prematurity/low birthweight and adolescent depressive disorder studied using a case-control design within a prospective cohort study of 2032 adolescents. Odds for depressive disorder were 11-fold (95% CI 2-62) higher for the premature/low-birthweight participants after regression adjustment for major confounding factors. For premature/low-birthweight females, cumulative rates of depressive disorder over 30 months were 15.2% (95% CI 11.1-20.5) v. 1.8% (95% CI 1.6-2.1) in those with normal deliveries. Physiological adaptations in utero before full term may be implicated causally in some cases of depression in adolescence.

Adolescent↗

PubMed2004

Neurodevelopment in children born small for gestational age: a randomized trial of nutrient-enriched versus standard formula and comparison with a reference breastfed group.

OBJECTIVE: Many studies have shown that children born small for gestational age (SGA) are at a neurodevelopmental disadvantage. We have shown that nutrient enrichment of formula fed to term SGA infants improves their growth and hypothesized that it also would improve their neurodevelopmental outcome. DESIGN: A randomized, controlled trial of standard term-infant (n = 147) or nutrient-enriched (n = 152) formula for the first 9 months. A reference group of 175 breastfed SGA infants was also recruited. SETTING: Subjects were recruited in 5 maternity hospitals in Cambridge, Nottingham, and Leicester, all in the United Kingdom. PARTICIPANTS: Healthy, term infants (gestation: > or =37 weeks) with birth weight <10th centile. OUTCOME MEASURES: Bayley mental and psychomotor scores at 18 months (primary) and developmental scores from Knobloch, Pasamanick, and Sherrard's developmental screening inventory at 9 months (secondary). RESULTS: There was no significant intergroup difference in Bayley Mental Development Index (MDI) or Psychomotor Development Index (PDI) scores at 18 months. However, at 9 months, children fed the enriched formula had a significantly lower developmental quotient (99.5 vs 102.0; 95% confidence interval [CI] for difference: -4.6, -0.4). A significant disadvantage was seen in girls (-5.1; 95% CI: -7.8, -2.4) but not in boys (0.9; 95% CI: -2.4, 4.2). Breastfed infants had significantly higher MDI and PDI scores at 18 months than formula-fed infants. Confounding factors accounted for approximately 34% of the observed association between breastfeeding and MDI score and none of the association between breastfeeding and PDI score. CONCLUSIONS: The previously reported enhanced linear growth in SGA children fed enriched formula was not matched by a neurodevelopmental advantage. At 9 months, girls fed the enriched formula had a significant developmental disadvantage, although this was not seen at 18 months. Later follow-up will determine any long-term effects on health or development. Meanwhile, use of enriched formula for term SGA children should not be promoted. It seems that breastfeeding may be especially beneficial for neurodevelopment in children born SGA.

Breast Feeding↗

PubMed2003

Trends in birthweight between 1857 and 1883, in Melbourne, Australia.

Epidemiological evidence suggesting that subjects with lower birthweight have an increased risk of adult cardiovascular disease has led to increased interest in factors influencing birthweight. We have documented large changes in mean birthweight over a relatively short historical period from 1857 to 1883. Mean birthweight declined progressively from 7.9 lb (3.6 kg) in the period 1857-63 to 6.9 lb (3.1 kg) in 1874-78, then rose to 7.5 lb (3.4 kg) for the period 1879-83. We found the expected relationships between infant birthweight and maternal age, parity and marital status, and identified an association between birthweight and maternal country of birth. However, neither temporal changes in recorded maternal characteristics nor external economic indicators for the colony explained the trends in birthweight. From historical information, we believe that the explanation for our findings lies primarily with the increasing poverty, disease, mental illness, alcohol abuse and criminal activity among women admitted to the hospital between 1860 and the mid-1870s, and improvements from around 1880, when old housing was replaced and prostitutes were moved out of the area. Our findings highlight the difficulty of capturing lifestyle factors using routinely collected data, and the need for historical expertise when examining historical data.

Analysis of Variance↗

PubMed2003

Mothers' health and babies' weights: the biology of poverty at the Melbourne Lying-in Hospital, 1857-83.

Birth weight remains a major focus of medical research into the relationship between pre-natal growth and life course health, and historians have used mean birth weight to assess women's standard of living. However, there are intrinsic difficulties in inferring maternal health and nutritional status from birth weight, and some of the known data sets produce puzzling results. One rich data set comes from the Melbourne Lying-in Hospital, 1857-83, and the article discusses the complex institutional, social, and economic causes that may underlie its apparently counter-intuitive anthropometric results. This data set reveals the biological effects differential social conditions can inflict, even within an otherwise affluent society.

Australia↗