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Biomedical subjects

J S Forsyth

Publications and source records attributed to J S Forsyth.

At least 19 recordsLinked to original sources

Pre-eclampsia and the later development of type 2 diabetes in mothers and their children: an intergenerational study from the Walker cohort.

AIMS/HYPOTHESIS: Studies have shown a relationship between pre-eclampsia and later coronary artery disease. This study investigated whether there is a relationship between pre-eclampsia and the development of type 2 diabetes in mothers and their babies and how this is affected by infant birthweight. SUBJECTS AND METHODS: This was an intergenerational cohort study. The study population comprised 7,187 mothers who gave birth and 8,648 babies who were born in Dundee, Scotland between 1952 and 1958. Their later diabetic status was defined from 1980 to 2003 by linkage to population-based datasets. RESULTS: There were 810 (11.3%) mothers with pre-eclampsia and 745 (10.4%) who subsequently developed type 2 diabetes. Logistic regression showed an increased risk of developing type 2 diabetes for mothers with pre-eclampsia, unadjusted odds ratio (OR) 1.37 (95% CI 1.10-1.71), p=0.005. This relationship persisted after adjustment for infant birthweight, OR 1.40 (95% CI 1.12-1.75), p=0.003. Of the babies born between 1952 and 1958, 221 (2.6%) had developed type 2 diabetes, 137 of them male (2.9% of male subjects in study population) and 84 female (2.2% of female subjects). The relationship between pre-eclampsia in the mother and the risk of type 2 diabetes in the offspring did not reach statistical significance, OR 1.38 (95% CI 0.90-2.10). Babies with birthweight in the lowest quintile (adjusted for sex, gestation and birth order) had an increased risk of developing type 2 diabetes, OR for lowest quintile vs highest quintile 1.84 (95% CI 1.24-2.72), p=0.002. CONCLUSIONS/INTERPRETATION: Pre-eclampsia is associated with increased risk of developing type 2 diabetes in the mother, but birthweight is a more important determinant of future risk for the offspring.

Birth Weight↗

Angiotensin converting enzyme activity in infancy is related to birth weight.

AIMS: (a) To measure infant angiotensin converting enzyme (ACE) activity in healthy term infants at birth and during the first three months of life. (b) To determine the relation between serum ACE activity and infant feeding practice during this period. (c) To investigate the relation between serum ACE activity and birth weight and other potential contributing factors including acid-base status at birth, gestation, and maternal ACE genotype. METHODS: Prospective study of term infants, with clinical and feeding data collected from parents and medical records, and serum ACE measured in the infant at birth and 1 and 3 months of age, and in the mother at the time of birth and one to three months after birth. RESULTS: At birth and 1 and 3 months of age, infant serum ACE activity was twice that of maternal ACE activity. Infant ACE activity at birth and 1 and 3 months did not significantly differ between breast and formula fed infants. There was a highly significant negative correlation between infant ACE activity at 3 months and birth weight (r = -0.52; p < 0.001). This persisted after the conversion of birth weights to z scores (r = -0.34; p = 0.03). ACE activity at 3 months was also related to placental weight (r = -0.30; p = 0.02) and maternal age (r = -0.30; p = 0.05). The strong correlation between serum ACE activity and birth weight z score persisted after adjustment for maternal age and placental weight (r = -0.34; p = 0.03). CONCLUSION: As ACE is increasingly identified as a risk factor for cardiovascular disease, serum ACE activity in infancy may contribute to the link between low birth weight and later cardiovascular events.

Aging↗

Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomised controlled trial.

OBJECTIVE: To determine whether supplementation of infant formula milk with long chain polyunsaturated fatty acids (LCPUFAs) influences blood pressure in later childhood. DESIGN: Follow up of a multicentre, randomised controlled trial. SETTING: Four study centres in Europe. PARTICIPANTS: 147 formula fed children, with a reference group of 88 breastfed children. INTERVENTION: In the original trial newborn infants were randomised to be fed with a formula supplemented with LCPUFAs (n=111) or a formula without LCPUFAs but otherwise nutritionally similar (n=126). In the present follow up study the blood pressure of the children at age 6 years was measured. MAIN OUTCOME MEASURES: Systolic, diastolic, and mean blood pressure. RESULTS: 71 children in the LCPUFA supplementation group (64% of the original group) and 76 children in the non-supplementation group (60%) were enrolled into the follow up study. The LCPUFA group had significantly lower mean blood pressure (mean difference -3.0 mm Hg (95% confidence interval -5.4 mm Hg to -0.5 mm Hg)) and diastolic blood pressure (mean difference -3.6 mm Hg (-6.5 mm Hg to -0.6 mm Hg)) than the non-supplementation group. The diastolic pressure of the breastfed children (n=88 (63%)) was significantly lower than that of the non-supplemented formula group but did not differ from the LCPUFA formula group. CONCLUSIONS: Dietary supplementation with LCPUFAs during infancy is associated with lower blood pressure in later childhood. Blood pressure tends to track from childhood into adult life, so early exposure to dietary LCPUFAs may reduce cardiovascular risk in adulthood.

Blood Pressure↗

Long-chain polyunsaturated fatty acids in infant nutrition: effects on infant development.

In the past year, two groups of investigators reported the effects of feeding n-3 and n-6 long chain polyunsaturated fatty acids on term-infant development. In general, these small randomised studies, along with two recent large randomised clinical trials, one with preterm and one with term infants, confirm and extend data on efficacy from smaller clinical studies reported in the past ten years. In addition, two independent systematic reviews published this year evaluated all but the most recent studies. Both systematic reviews concluded that there were benefits of feeding long chain polyunsaturated fatty acids to preterm infants in the short-term and acknowledged the absence of studies to address their effects on long-term visual development in infants. The continuing controversy as to the need for long chain polyunsaturated fatty acids by term infants is highlighted by the different conclusions reached in the systematic reviews. A middle view can also be supported by the data; that is, that fewer term infants than preterm infants can benefit from these fatty acids because of greater long chain polyunsaturated fatty acid accumulation in utero. Differences in intrauterine accumulation of these fatty acids may also play a role in inconsistent results among term studies.

Child Development↗

A randomised controlled study of the effect of long chain polyunsaturated fatty acid supplementation on stool hardness during formula feeding.

BACKGROUND: The passage of hard stools is significantly more common in formula fed infants than breast fed infants and this might be the result of differences in fat absorption between breast and formula fed infants. Experimental studies indicate that long chain polyunsaturated fatty acids (LCPUFAs) might influence fat hydrolysis and absorption. AIM: To investigate the relation of LCPUFA supplementation to stool frequency and consistency during the first 4 months of life. DESIGN: Double blind, randomised, controlled study of 88 healthy infants. RESULTS: 1905 stools (858 from LCPUFA supplemented infants, 1047 non-supplemented infants) were examined. The mean (SEM) number of stools passed for each three day study period was significantly less in the LCPUFA group (5.5 (0.3) v 6.2 (0.2); p < 0.05). In both groups, there was a significant reduction in the number of stools passed with age (p < 0.001). During the first 3 months, the mean (SEM) percentage of hard stools passed by infants in the LCPUFA supplemented group was 7.7 (2.1) compared with 19.2 (2.8) for unsupplemented infants (p = 0.001). CONCLUSION: The prevalence of hard stools is significantly reduced in infants fed a formula that is supplemented with LCPUFAs.

Breast Feeding↗

Effect of long-chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age.

BACKGROUND: Long-chain polyunsaturated fatty acids (LCPUFA) are important for normal visual and brain development. Although present in human milk, LCPUFA have until recently been absent from artificial formulas, and infants may have limited ability to synthesise LCPUFA. To determine the clinical significance of this relative deficiency of LCPUFA, we undertook a randomised trial of the relation between LCPUFA supplementation and infant cognitive behaviour. METHODS: 44 term infants had been randomised to a formula supplemented with LCPUFA (21) or not supplemented with LCPUFA (23), which they had taken from birth to age 4 months. Infant cognitive behaviour was assessed at 10 months of age by a means-end problem-solving test--the intentional execution of a sequence of steps to achieve a goal. The problem required three intermediate steps to achieve the final goal, uncovering and retrieving a hidden toy. FINDINGS: Infants who received LCPUFA-supplemented formula had significantly more intentional solutions than infants who received the no-LCPUFA formula (median 2.0 vs 0, p=0.021). Intention scores (median 14.0 vs 11.5 [maximum 18]) were also increased in this group (p=0.035). INTERPRETATION: These findings suggest that term infants may benefit from LCPUFA supplementation, and that the effects persist beyond the period of supplementation. Since higher problem-solving scores in infancy are related to higher childhood IQ scores, supplementation with LCPUFA may be important for the development of childhood intelligence.

Cognition↗

Relation of infant diet to childhood health: seven year follow up of cohort of children in Dundee infant feeding study.

OBJECTIVE: To investigate the relation of infant feeding practice to childhood respiratory illness, growth, body composition, and blood pressure. DESIGN: Follow up study of a cohort of children (mean age 7.3 years) who had detailed infant feeding and demographic data collected prospectively during the first two years of life. SETTING: Dundee. SUBJECTS: 674 infants, of whom 545 (81%) were available for study. Data on respiratory illness were available for 545 children (mean age 7.3 (range 6.1-9.9) years); height for 410 children; weight and body mass index for 412 children; body composition for 405 children; blood pressure for 301 children (mean age 7.2 (range 6.9-10.0) years). MAIN OUTCOME MEASURES: Respiratory illness, weight, height, body mass index, percentage body fat, and blood pressure in relation to duration of breast feeding and timing of introduction of solids. RESULTS: After adjustment for the significant confounding variables the estimated probability of ever having respiratory illness in children who received breast milk exclusively for at least 15 weeks was consistently lower (17.0% (95% confidence interval 15.9% to 18.1%) for exclusive breast feeding, 31.0% (26.8% to 35.2%) for partial breast feeding, and 32.2% (30.7% to 33.7%) for bottle feeding. Solid feeding before 15 weeks was associated with an increased probability of wheeze during childhood (21.0% (19.9% to 22.1%) v 9.7% (8.6% to 10.8%)). It was also associated with increased percentage body fat and weight in childhood (mean body fat 18.5% (18.2% to 18.8%) v 16.5% (16.0% to 17.0%); weight standard deviation score 0.02 (-0.02 to 0.06) v -0.09 (-0.16 to 0.02). Systolic blood pressure was raised significantly in children who were exclusively bottle fed compared with children who received breast milk (mean 94.2 (93.5 to 94.9) mm Hg v 90.7 (89.9 to 91.7) mm Hg). CONCLUSIONS: The probability of respiratory illness occurring at any time during childhood is significantly reduced if the child is fed exclusively breast milk for 15 weeks and no solid foods are introduced during this time. Breast feeding and the late introduction of solids may have a beneficial effect on childhood health and subsequent adult disease.

Blood Pressure↗

Influence of long-chain polyunsaturated fatty acids on infant cognitive function.

Long-chain polyunsaturated fatty acids (LCPUFA) are important for normal visual and cortical development. In a previous study of the effects of LCPUFA on cognitive function of term infants at the age of 3 mon, we indicated that infants with evidence of reduced growth parameters at birth and impaired attention control as manifested by a late peak fixation during infant habituation assessment may benefit from LCPUFA supplementation. The aim of this prospective study was to determine whether LCPUFA supplementation and late peak fixation are related to means-end problem-solving ability in these same infants at the age of 9 mon. Term infants (58) were randomized to one of two formulas containing either LCPUFA or no LCPUFA and completed 4 mon of feeding with their formula. Cognitive function was assessed at 3 mon of age by measures of infant habituation. Infants (20 LCPUFA and 20 no-LCPUFA) completed the problem-solving assessment at 9 mon. The no-LCPUFA group had lower scores on both measures of intention and number of solutions, but neither of these differences was significant. Analysis of covariance for the effects of group and peak fixation, covaried with gestation and birth weight, showed that the number of solutions was significantly reduced in the late peak-fixation infants receiving no LCPUFA (P<0.02). Intention scores tended to be reduced in this group (P<0.06). The late peak-fixation infants who received LCPUFA had solution and intention scores similar to early peak-fixation infants receiving LCPUFA or no LCPUFA. These findings suggest that in term infants who have reduced growth parameters at birth and who show evidence of impaired attention control, information processing and problem-solving ability in infancy may be enhanced by LCPUFA supplementation.

Adult↗

Low birthweight infants and total parenteral nutrition immediately after birth. III. Randomised study of energy substrate utilisation, nitrogen balance, and carbon dioxide production.

This study aimed to investigate energy substrate utilisation and nitrogen balance in low birthweight infants receiving total parenteral nutrition during the first days of life, and in particular, to determine the effect of two different glucose intakes on carbon dioxide production. Twenty infants (mean (SE) birthweight 1314 (65) g, mean (SE) gestation 30.9 (0.4) weeks) were recruited to the study. Immediately after birth they were randomised to a carbohydrate intake of 8 g/kg/day (5.5 mg/kg/minute) or 12 g/kg/day (8.3 mg/kg/minute). After 24 hours they were changed to the alternative regimen which was continued for a further 24 hours. Fat and protein intakes were kept constant throughout the study. Indirect calorimetry was performed during each of the regimens, urine was collected for urinary nitrogen, and substrate utilisation calculated for 12 infants. The carbohydrate utilisation rate was increased during the higher carbohydrate intake. Lipid utilisation rates were significantly different, with net lipid synthesis occurring during high carbohydrate intake. Protein utilisation rates were not influenced by the different carbohydrate intakes. The mean plasma glucose concentration was higher during the high carbohydrate intake but the mean highest and lowest values were not significantly different during the two study periods. A plasma glucose below 2.6 mmol/l was recorded more frequently during the low glucose intake (9/20 v 5/20). Capillary PCO2 values measured during high and low glucose intakes were similar (5.9 (0.2) v 6.2 (0.3) kPa. Carbon dioxide production rates were increased during the higher carbohydrate intake but the differences were not significant. Similarly, there was no significant difference in the respiratory quotients (RQ), oxygen consumption, or energy expenditure during the two study periods.

Calorimetry, Indirect↗

Low birthweight infants and total parenteral nutrition immediately after birth. I. Energy expenditure and respiratory quotient of ventilated and non-ventilated infants.

The aim of this study was to determine the energy expenditure and respiratory quotient (RQ) of ventilated and non-ventilated low birthweight infants during the first five days of life, in order to determine optimal feeding regimens. Eighty six infants, of birthweight less than 1750 g, were grouped according to whether they were artificially ventilated or breathing air spontaneously, and whether they were parenterally or enterally fed at the time of study. Energy expenditure and respiratory quotient were measured during days 1-5 and the relation of energy expenditure to several explanatory variables was investigated using multiple regression analysis. The energy expenditure of ventilated infants was less than that of spontaneously breathing infants; the differences were significant on days 1-3. The respiratory quotient (mean (SE)) was greater in intravenously fed infants compared with milk-fed--0.99 (0.03) v 0.92 (0.01) (P < 0.05), with 42% of studies of infants receiving total parenteral nutrition (TPN) producing an RQ of > 1.0 compared with 16.6% of milk-fed infants (P < 0.01). There was a significant correlation between glucose intake and RQ (r = 0.39, P < 0.001). The activity scores were measured during 75 studies and scores were significantly higher in spontaneously breathing milk-fed infants compared with ventilated parenterally fed infants. Factors independently related to energy expenditure were: postnatal age (P < 0.01); milk feeds (P < 0.01); and physical activity (P < 0.05). A mix of carbohydrate and fat from day 1 may not only meet energy needs but may also reduce respiratory quotient.

Calorimetry, Indirect↗

Low birthweight infants and total parenteral nutrition immediately after birth. II. Randomised study of biochemical tolerance of intravenous glucose, amino acids, and lipid.

This randomised study aimed to compare the biochemical tolerance of three parenteral regimens administered during the first 48 hours of life. Twenty nine infants were randomised to either: (a) glucose 10%; (b) glucose 10%/amino acids; (c) glucose 10%/amino acids/lipid. Blood samples for plasma amino acid profiles, cholesterol, and triglyceride concentrations were taken on arrival in the neonatal unit and again between 36 and 48 hours of life. Arterial or capillary blood gas analysis and blood glucose estimates were performed routinely during the first 48 hours of life. There was a sharp decline in plasma amino acid concentrations in the group following (a) compared with the two groups following (b) and (c) regimens. In all groups plasma triglyceride and cholesterol were not significantly different before and after 48 hours of lipid infusion. Peak mean (SE) bilirubin concentrations (203 (12) v 181 (19) v 220 (20) mumol/l) and the need for phototherapy (nine v eight v five infants) were similar for each of the groups. Hypoglycaemia occurred most frequently during the (b) regimen and least commonly in the (c) group. There are potential health gains from giving parenteral nutrition to low birthweight infants immediately after birth, and this study indicates that restriction of nutritional intake immediately after birth in preterm infants may cause significant metabolic disturbance. This can be prevented by starting a regimen of intravenous amino acids and lipid immediately after birth.

Amino Acids↗

Neonatal cerebral Doppler flow velocity waveforms in the uncomplicated pre-term infant: reference values.

In a longitudinal study of 217 infants delivering at < 37 completed weeks gestation, Doppler flow velocity waveforms were obtained and resistance index (RI) values calculated from the middle (MCA) and anterior (ACA) cerebral arteries during the first 10 days of life. One hundred thirty-seven of these infants were non-acidotic at delivery and during the early neonatal period, and had normal cerebral ultrasound scans throughout the study period. These infants formed the reference group. In three gestational subgroups considered (< or = 32 weeks, 33-34 weeks, > or = 35 weeks) from the reference group, the median RI for both the ACA and MCA was noted to fall significantly during the first 12 h of life (P < 0.01 for all groups). For infants delivering at > or = 33 weeks gestation, both MCA and ACA RI values reached a steady state with no significant change in the median value for the remainder of the study period. For infants delivering at < or = 32 weeks, there was a further significant fall in both the MCA and ACA RI between 12 and 24 h of life (P < 0.05), after which a steady state value was reached. During the first 12 h of life the RI for both vessels was significantly higher in infants delivering at < or = 32 weeks compared to the more mature infants (P < 0.01), but for the remainder of the study period, there were no significant differences in RI values between the gestational subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Neonatal cerebral Doppler flow velocity waveforms in the pre-term infant with cerebral pathology.

In a longitudinal study of 217 infants delivering at < 37 completed weeks gestation, Doppler flow velocity waveforms were obtained, and resistance index (RI) values calculated from the middle (MCA) and anterior (ACA) cerebral arteries during the first 10 days of life. Sixty infants demonstrated ultrasound evidence of cerebral pathology, of which five cases were congenital, and an additional 13 cases were complicated by patent ductus arteriosus during the study period. The Doppler data obtained during the first week of life from the remaining 42 infants who developed cerebral pathology, and 15 infants who had evidence of metabolic acidosis at delivery without ultrasound evidence of cerebral pathology were compared with local reference data obtained from non-acidotic infants with normal cranial ultrasound from 24 h of age. In those infants who had evidence of minor periventricular haemorrhage alone (Grade I/II PVH), there was no significant difference between the ACA or MCA RI during the study period compared with the reference data. In those groups of infants who demonstrated major PVH (Grade III/IV) or persistent periventricular flares, the ACA and MCA RI was found to be consistently significantly higher than the reference group throughout the study period. In those infants who developed ultrasound evidence of periventricular cystic leukomalacia (PVCL), the MCA RI was significantly lower than the reference data between 48 and 72 h of age, there being no significant difference in the ACA RI. The Doppler findings in those infants with evidence of metabolic acidosis at delivery (umbilical arterial pH < 7.20; BD > 8 mmol/l) but with normal ultrasound findings were similar to those infants who developed PVCL, namely a significant fall in MCA RI between 48 and 72 h of life, with no significant difference in the ACA RI during the study period. These findings suggest that variable changes in cerebral vascular resistance occur with the evolution of, or as a consequence of the development of cerebral pathology in the pre-term infant, and these changes of increased and decreased vascular resistance are discussed. Further investigation of the changes occurring in the cerebral circulation in the early neonatal period of infants who develop PVCL is required to clarify the vascular changes taking place, but if the findings of this study are confirmed, this technique may provide a means of identifying infants at risk of developing ischaemic cerebral pathology at an early stage when it may be possible to initiate therapeutic intervention to limit the cerebral damage.

Acidosis↗

Relation between early introduction of solid food to infants and their weight and illnesses during the first two years of life.

OBJECTIVE: To assess the relations between early introduction of solid food and infant weight, gastrointestinal illness, and allergic illnesses during the first two years of life. DESIGN: Prospective observational study of infants followed up for 24 months after birth. SETTING: Community setting in Dundee. PATIENTS: 671 newborn infants, of whom 455 were still available for study at 2 years of age. MAIN OUTCOME MEASURES: Infants' diet, weight, and incidence of gastrointestinal illness, respiratory illness, napkin dermatitis, and eczema at 2 weeks and 2, 3, 4, 6, 9, 12, 15, 18, 21, and 24 months of age. RESULTS: The infants given solid food at an early age (at < 8 weeks or 8-12 weeks) were heavier than those introduced to solids later (after 12 weeks) at 4, 8, 13, and 26 weeks of age (p < 0.01) but not at 52 and 104 weeks. At their first solid feed those given solids early were heavier than infants of similar age who had not yet received solids. The incidence of gastrointestinal illness, wheeze, and nappy dermatitis was not related to early introduction of solids. There was a significant but less than twofold increase in respiratory illness at 14-26 weeks of age and persistent cough at 14-26 and 27-39 weeks of age among the infants given solids early. The incidence of eczema was increased in the infants who received solids at 8-12 weeks of age. CONCLUSION: Early introduction of solid food to infants is less harmful than was previously reported. Longer follow up is needed, but, meanwhile, a more relaxed approach to early feeding with solids should be considered.

Body Weight↗

Factors associated with variation in plasma copper levels in preterm infants of very low birth weight.

At 2-weekly intervals from age 4-14 weeks, the possible effects on plasma copper concentration of gestation, multiple birth, fractional weight change from birth (W/BW) and, up to 10 weeks, average daily total copper intake from birth were explored in 43 preterm infants of very low birth weight. There was no significant association between the logarithm of the plasma copper concentration (ln Cu) and multiple birth at any time and no significant association between ln Cu and gestation was found from 4-12 weeks. From age 4-10 weeks, there was a significant negative correlation between ln Cu and W/BW and at 4, 6 and 10 weeks there was also a significant negative correlation between ln Cu and copper intake. W/BW and copper intake were correlated throughout. At 14 weeks, ln Cu correlated positively with gestation and negatively with W/BW but, at this age, gestation and W/BW were correlated. The maximum total variation (R2) in ln Cu explained by its regression on gestation, multiple birth, W/BW and/or copper intake combined was only about 31% (at 10 weeks). The potential for copper depletion may be greater in rapidly growing infants.

Birth Weight↗

An indirect calorimetry system for ventilator dependent very low birthweight infants.

With neurodevelopmental outcome of very low birthweight (VLBW) infants being adversely affected by inadequate nutrition during the first few weeks of life, there is an urgent need for more specific nutritional data on the sick VLBW ventilator dependent infant. The development of a new mass spectrometry gas analysis indirect calorimetry system which is non-invasive and can operate over several hours or days is described. Technical evaluation of each of the components of the system indicates a total random error of less than 5%. Systematic error was determined using gas infusions which simulated carbon dioxide production and oxygen consumption. The relative error in the measurement of carbon dioxide production was less than or equal to 1.5% (coefficient of variation (CV) 6.0%)) with carbon dioxide infusion rates ranging from 3.86 to 13.98 ml/min. The relative error in oxygen 'consumption' was less than or equal to 4.3% (CV 2.8%) for infusions of oxygen at rates of 7.5 to 14.80 ml/min. With nitrogen infusions simulating oxygen consumptions of 2.0 and 5.5 ml/min the relative error in the calculated nitrogen infusion was 1.5% (CV 4.1%) and 1.4% (CV 5.7%) respectively. Clinical studies on 10 infants demonstrated a mean energy expenditure of 161.7 kJ/kg/day and a respiratory quotient in excess of 1.0. The energy expenditure of ventilated VLBW infants may be less than previously indicated and the energy mix and nitrogen content of parenteral nutrition regimens recommended for these infants may be inappropriate.

Calorimetry↗