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Biomedical subjects

A Sherriff

Publications and source records attributed to A Sherriff.

At least 19 recordsLinked to original sources
PubMed2005

Maternal age of menarche is not associated with asthma or atopy in prepubertal children.

BACKGROUND: Maternal sex hormones in pregnancy can theoretically influence the developing fetal immune system and modulate the subsequent development of atopic disorders. Early onset of menarche has been linked to increased oestrogen levels in adult women. A study was undertaken to examine the association between early onset menarche in pregnant women and asthma and atopic status of their children at 7 years of age. METHODS: The Avon Longitudinal Study of Parents and Children (ALSPAC) is a longitudinal birth cohort study in which pregnant women, resident in Avon (UK), were recruited on the basis of an expected date of delivery between 1 April 1991 and 31 December 1992. Maternal age at menarche was assessed from prenatal questionnaires administered to the women. Clinical outcomes in the children were based on mothers' responses to self-completion questionnaires and included asthma, eczema, and hay fever. The atopic status of the child was objectively assessed by skin prick tests to a panel of common aeroallergens at the age of 7 years. Analyses used multivariable logistic regression with a diverse range of possible confounders. RESULTS: Complete data were available on 5765 woman and child pairs. The prevalence of ever reported asthma to 7 years was 20.4%, eczema 58.6%, hay fever 12.1%, and atopy (defined as any positive (>2 mm weal) response) was present in 20.6%. There were no significant differences in mean age of menarche between mothers of children with and without each of the primary outcomes. Adjusted odds ratios (95% CI) for the latest age of menarche (16+ years) compared with the lowest (<12 years) reference group were 1.41 (1.00 to 1.99) for asthma, 0.98 (0.73 to 1.91) for eczema, 0.95 (0.62 to 1.44) for hay fever, and 0.98 (0.68 to 1.42) for atopy. CONCLUSION: No consistent association was found between maternal age at menarche and asthma, eczema, hay fever or atopy in their children during early childhood.

Adolescent↗
PubMed2005

Frequent use of chemical household products is associated with persistent wheezing in pre-school age children.

BACKGROUND: In the UK and other developed countries the prevalence of asthma symptoms has increased in recent years. This is likely to be the result of increased exposure to environmental factors. A study was undertaken to investigate the association between maternal use of chemical based products in the prenatal period and patterns of wheeze in early childhood. METHODS: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC), the frequency of use of 11 chemical based domestic products was determined from questionnaires completed by women during pregnancy and a total chemical burden (TCB) score was derived. Four mutually exclusive wheezing patterns were defined for the period from birth to 42 months based on parental questionnaire responses (never wheezed, transient early wheeze, persistent wheeze, and late onset wheeze). Multinomial logistic regression models were used to assess the relationship between these wheezing outcomes and TCB exposure while accounting for numerous potential confounding variables. Complete data for analysis was available for 7019 of 13, 971 (50%) children. RESULTS: The mean (SD) TCB score was 9.4 (4.1), range 0-30. Increased use of domestic chemical based products was associated with persistent wheezing during early childhood (adjusted odds ratio (OR) per unit increase of TCB 1.06 (95% confidence interval (CI) 1.03 to 1.09)) but not with transient early wheeze or late onset wheeze. Children whose mothers had high TCB scores (>90th centile) were more than twice as likely to wheeze persistently throughout early childhood than children whose mothers had a low TCB score (<10th centile) (adjusted OR 2.3 (95% CI 1.2 to 4.4)). CONCLUSION: These findings suggest that frequent use of chemical based products in the prenatal period is associated with persistent wheezing in young children. Follow up of this cohort is underway to determine whether TCB is associated with wheezing, asthma, and atopy at later stages in childhood.

Body Burden↗
PubMed2004

Mode of delivery is not associated with asthma or atopy in childhood.

BACKGROUND: Caesarean-section delivery has been associated with the subsequent development of atopy and wheezing in childhood. OBJECTIVE: To examine the association between mode of delivery (vaginal vs. caesarean section) and development of atopy, asthma and wheezing disorders in a population-based cohort of children. METHODS: The Avon Longitudinal Study of Parents and Children is a longitudinal birth cohort of children born 1 April 1991 to 31 December 1992. Mode of delivery was categorized as vaginal (including forceps and ventouse extractions) or caesarean section (elective and emergency). Primary outcomes were parental report of asthma or wheezing between 69 and 81 months of age, physician-diagnosed asthma (PDA) at 91 months of age and atopy at 7 years by skin prick testing. Possible confounding factors were considered in a multivariable logistic regression model. RESULTS: Total livebirths were 14,062, from which were selected 12 367 born to mothers resident in a defined area and delivered in one of two major obstetric hospitals. Of these infants, 10,980 (88.8%) were delivered vaginally and 1387 (11.2%) by caesarean section. Outcome data were available for 7495 (61%) subjects (asthma 69-81 months); 7389 (60%) (wheeze 69-81 months); 7196 (58%) (PDA 91 months) and 5916 (48%) (atopy 7 years). Adjusted odds ratios [95%confidence interval] for caesarean section compared with vaginal delivery were not statistically significant for any outcome we considered: asthma 69-81 months 1.16 [0.9, 1.5]; wheeze 69-81 months 0.95 [0.7, 1.3]; PDA 1.14 [0.9, 1.4]; atopy 1.04 [0.8, 1.3]. CONCLUSION: Delivery by caesarean section was not associated with the subsequent development of asthma, wheezing or atopy in later childhood in this population.

Adult↗
PubMed2004

Umbilical cord trace elements and minerals and risk of early childhood wheezing and eczema.

It has been suggested that foetal nutrition might influence the inception of wheezing and atopic disorders in childhood but specific nutrients have not been implicated. In the Avon Longitudinal Study of Parents and Children umbilical cord samples were assayed for trace elements and minerals, and mothers were asked about wheezing and eczema in their children. Associations of cord concentrations of selenium, zinc, copper, manganese, magnesium, iron, lead and mercury with wheezing at 30-42 months, with wheezing patterns defined by the presence or absence of transient infant, later onset or persistent wheezing at 0-6 months and 30-42 months, respectively (n=2,044), and with eczema at 18-30 months (n=2,173), were analysed. Cord selenium was negatively associated with persistent wheeze (adjusted odds ratio (OR) per doubling concentration: 0.67). Cord iron was negatively associated with later onset wheeze (OR: 0.86) and with eczema (OR: 0.90). Children with high cord concentrations of selenium and iron were less likely than those with low concentrations to wheeze transiently in infancy. The level of foetal exposure to selenium and iron may possibly influence the risk of wheezing and eczema in early childhood although, in view of the multiple analyses carried out, it is possible that the main findings occurred by chance.

Biomarkers↗
PubMed2002

An interaction between the IL-4Ralpha gene and infection is associated with atopic eczema in young children.

BACKGROUND: A gain of function mutation (Q551- > R) in the IL-4 receptor alpha-chain (IL-4Ralpha) has been found to be associated with atopy in some studies but not others. The different results may be explained by interactions between the IL-4Ralpha polymorphism and environmental factors. OBJECTIVES: To identify interactions between the R551 mutation and environmental factors that are associated with atopy. METHODS: DNA from the Children in Focus (CiF) cohort of the Avon Longitudinal Study of Parents and Children (ALSPAC) was genotyped by heteroduplex formation for the presence of the R551 polymorphism. The data were then analysed for associations with flexural eczema as an indicator of atopic eczema, skin prick tests to allergens and serum IgE levels, and for interactions with environmental factors. RESULTS: A significant (P = 0.02) positive association was seen between the R551 polymorphism and flexural eczema in children up to 6 months of age who had not been given antibiotics, but not in children who had been given antibiotics. This association was maintained as a trend until 30 to 42 months of age but was no longer statistically significant. There was no significant association between the R551 polymorphism and positive skin prick tests or levels of serum IgE at 61 months of age, consistent with the effect of the R551 polymorphism being restricted to early life. CONCLUSION: There is an association between the R551 polymorphism and flexural eczema in children at 6 months of age who have not had infection requiring treatment with antibiotics. Restriction of the R551 association with eczema to children who have not had antibiotics lends support to the 'hygiene hypothesis', which states that exposure to infection in childhood can protect against allergic disease.

Bacterial Infections↗
PubMed2002

Hygiene levels in a contemporary population cohort are associated with wheezing and atopic eczema in preschool infants.

BACKGROUND: The hygiene hypothesis states that insufficient exposure to certain infectious agents during childhood increases the risk of developing asthma and atopic diseases. Improvements in hygiene levels may be partly responsible for this decline in exposure. AIMS: To assess whether hygiene levels in infancy are associated with wheeze and/or atopic eczema, independent of a number of possible confounding factors. METHODS: Data were gathered from the Avon Longitudinal Study of Parents and Children (ALSPAC). Parental self completion questionnaires provided symptom data on infant wheeze and atopic eczema at 0-6 months and 30-42 months, respectively. A simple hygiene score was derived using questionnaire responses at 15 months, which ranged from least hygienic to most hygienic. Multivariable logistic regression models analysed the effect of hygiene scores on health outcomes, while adjusting for a number of important confounding variables. RESULTS: Increasing hygiene scores were independently associated with wheezing (OR = 1.04; 95% CI: 1.00 to 1.08) and atopic eczema (OR = 1.04; 95% CI: 1.01 to 1.07) between 30 and 42 months, but not in the first six months. The odds ratio was higher for atopic eczema if the rash was reported to have become sore and oozy (OR = 1.09; 95% CI: 1.02 to 1.16). CONCLUSIONS: High levels of hygiene at 15 months of age were independently associated with wheeze and atopic eczema reported between 30 and 42 months, and there was an increased risk for children with more severe eczema during this period. The importance of hygiene in public health should not be dismissed; however, the creation of a sterile environment through excessive cleanliness may potentially be harmful to the immune system.

Child, Preschool↗
PubMed2002

Factors associated with different hygiene practices in the homes of 15 month old infants.

BACKGROUND: Improved hygiene in Westernised regions of the world may be partly responsible for the increased prevalence of diseases of the immune system, such as asthma and atopy. There is a paucity of data on cleanliness norms in young children in the UK and there has been no attempt to identify factors that influence the adoption of particular hygiene practices in the home. AIMS: To examine levels of hygiene in a contemporary cohort of children and identify social and lifestyle factors influencing hygiene practices in the home. METHODS: The sample under study are participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Parental self completion questionnaires provided data on hygiene levels in children at 15 months of age, and a hygiene score was derived from these responses. Multivariable logistic regression models investigated associations between high hygiene scores (top quintile) and a number of perinatal, maternal, social, and environmental factors. RESULTS: Maternal smoking during pregnancy, low maternal educational achievement, and living in local authority housing were factors independently associated with high hygiene scores, as was increased use of chemical household products. High hygiene scores were inversely related to living in damp housing and attendance at day care. There were no gender or ethnic differences in hygiene score. CONCLUSION: Important data on cleanliness norms for infants have been presented. The adoption of hygiene practices is influenced to some degree by social, lifestyle, and environmental factors-with higher hygiene scores occurring in more socially disadvantaged groups. Increased use of chemical household products in the more socially disadvantaged groups within ALSPAC has emerged as an important confounder in any study of hygiene and ill health.

Animals↗
PubMed2002

Paracetamol use in pregnancy and wheezing in early childhood.

BACKGROUND: We recently reported links between frequent paracetamol (acetaminophen) use and wheezing and asthma in adults and children, but data are lacking on possible effects of prenatal exposure on wheezing in early childhood. METHODS: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC) women were asked twice during pregnancy (at 18-20 weeks and 32 weeks) about their usage of paracetamol and aspirin. Six months after birth, and at yearly intervals thereafter, mothers were asked about wheezing and eczema symptoms in their child. The effects of paracetamol and aspirin use in pregnancy on the risk in the offspring of wheezing at 30-42 months (n=9,400) and eczema at 18-30 months (n=10,216) and on their risk of different wheezing patterns (defined by presence or absence of wheezing at <6 months and at 30-42 months) were examined. RESULTS: Paracetamol was taken frequently (most days/daily) by only 1% of women. After controlling for potential confounders, frequent paracetamol use in late pregnancy (20-32 weeks), but not in early pregnancy (<18-20 weeks), was associated with an increased risk of wheezing in the offspring at 30-42 months (adjusted odds ratio (OR) compared with no use 2.10 (95% CI 1.30 to 3.41); p=0.003), particularly if wheezing started before 6 months (OR 2.34 (95% CI 1.24 to 4.40); p=0.008). Assuming a causal relation, only about 1% of wheezing at 30-42 months was attributable to this exposure. Frequent paracetamol use in pregnancy was not associated with an increased risk of eczema. Frequent aspirin use in pregnancy was associated with an increased risk of wheezing only at <6 months. CONCLUSIONS: Frequent use of paracetamol in late pregnancy may increase the risk of wheezing in the offspring, although such an effect could explain only about 1% of the population prevalence of wheezing in early childhood.

Acetaminophen↗
PubMed2001

Applications of neural networks for gene finding.

A basic description of artificial neural networks is given and applications of neural nets to problems in human gene mapping are discussed. Specifically, three data types are considered: (1) affected sibpair data for nonparametric linkage analysis, (2) case-control data for disequilibrium analysis based on genetic markers, and (3) family data with trait and marker phenotypes and possibly environmental effects.

Environmental Exposure↗
PubMed2001

Risk factor associations with wheezing patterns in children followed longitudinally from birth to 3(1/2) years.

BACKGROUND: There is a paucity of detailed longitudinal data on wheeze in early childhood. Not all children who wheeze in early infancy will continue to wheeze into childhood and beyond. This study aims to investigate possible risk factors for different patterns of wheeze in the pre-school years. SUBJECTS AND METHODS: Study participants were part of the Avon Longitudinal Study of Parents and Children (ALSPAC). Maternal reports of child wheeze between birth and 6 months and again between 30 and 42 months were gathered prospectively. Children were categorized into early wheeze, persistent wheeze or late onset wheeze. A large number of risk factors were assessed for each wheezing phenotype using multivariable logistic regression models. RESULTS: Over 70% of children who wheezed in the first 6 months did not wheeze 3 years later. Wheezing between 0-6 months was independently associated with the presence of older siblings, male sex, delivery between April and December, bottle feeding, young maternal age, prenatal tobacco smoke exposure, atopy and parental history of asthma. From within this group of early wheezers, risk factors for wheeze that persisted beyond 6 months included pre-term delivery, young maternal age, living in rented local authority housing, atopy and a maternal (not paternal) history of asthma. Atopy and a family history of asthma emerged as the main predictors of wheeze that developed after 6 months of age. CONCLUSION: It is clear that a number of wheezing syndromes exist by 3(1/2) years, albeit with some degree of overlap. Detailed follow-up of this cohort is underway to determine whether risk factor associations determined in the first 3(1/2) years have long-term significance for the clinical entity termed 'asthma'.

Child, Preschool↗
PubMed2001

Should infants be screened for anaemia? A prospective study investigating the relation between haemoglobin at 8, 12, and 18 months and development at 18 months.

AIMS: To investigate the relation between haemoglobin in children followed longitudinally from 8 to 18 months, and developmental outcome at 18 months. METHODS: The Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) is a longitudinal survey of a geographically defined population of children born in 1991-92. In a randomly selected subsample, blood samples were assayed for Hb at 8, 12, and 18 months; a developmental assessment was carried out at 18 months on 1141 children using the Griffiths Scales of Mental Development. RESULTS: There was a strong quadratic association between Hb at 8 months and performance on the locomotor subscale at 18 months. Average scores increased with increasing Hb up to 95 g/l; there was little additional developmental benefit in Hb levels beyond 95 g/l. Infants with Hb <95 g/l at 8 months of age scored on average 6 points lower on the locomotor subscale than infants with Hb >/= 95 g/l; infants with Hb <90 g/l at 8 months scored 12 points lower on the locomotor subscale than children with Hb >/= 90 g/l. CONCLUSIONS: Low Hb concentrations (</= 95 g/l) in 8 month old children are associated with impaired motor development at 18 months. This cut off point corresponds to the 5th centile of Hb at 8 months. The results indicate that if there is an adverse effect of low Hb on developmental outcome, screening may be more effective at 8 months or earlier, rather than after this age. We propose to examine the importance of infant anaemia in relation to more accurate and detailed long term outcomes as the children get older.

Analysis of Variance↗
PubMed2001

Pre- and postnatal parental smoking and wheeze in infancy: cross cultural differences. Avon Study of Parents and Children (ALSPAC) Study Team, European Longitudinal Study of Pregnancy and Childhood (ELSPAC) Co-ordinating Centre.

In longitudinal cohort studies, the relationships between prenatal and postnatal tobacco smoke exposure and infant wheezing illnesses were compared in two geographically defined populations in Avon, UK and Brno and Znojmo in the South Moravian Region of the Czech Republic. Pregnant females living in defined regions and with expected dates of delivery between defined dates were recruited. Females completed self-report questionnaires during pregnancy and when their infant was 6 months old. For this analysis, responses to questions about smoking during pregnancy, environmental tobacco smoke (ETS) exposure and reported wheezing illnesses of infants at 6 months after birth were used. Odds ratios for wheeze in relation to the smoking variables were calculated with adjustment for potential confounding effects. The prevalence of smoking during pregnancy was higher in Avon (17.5%) than the Czech Republic (7.1%). Exposure of infants to ETS during the first 6 months after birth was also reported to be higher in Avon (35.5%) than the Czech Republic (9.7%). The prevalence of reported wheezing by 6 months of age was 21.4% in Avon and 10.3% in Brno and Znojmo. In Avon, there was a significant relationship between infant wheeze and maternal smoking during pregnancy (odds ratio (95% confidence interval) 1.30 (1.09-1.56), p=0.004) but not with environmental exposure after birth (1.11 (0.98-1.25)). In contrast, in Brno and Znojmo in the Czech Republic, there was a significant relationship between infant wheeze and ETS exposure (1.66 (1.17-2.36), p=0.04) but not with maternal smoking during pregnancy (0.99 (0.64-1.55)). This study demonstrated an apparent difference in the associations between prenatal and postnatal tobacco smoke exposure and infant wheezing illnesses in two populations with different smoking prevalence. The relationships were independent of a number of potential confounding variables that have been associated with infant wheezing. Possible explanations of these observations include dose-related effects of prenatal and postnatal tobacco smoke exposure of infants.

Adult↗
PubMed2001

Tooth extraction, bleeding and pain control.

Local anaesthesia is used routinely in dental surgery; it is effective in both pain control and--through the vasoconstrictors often contained within it--the reduction of bleeding. The extraction of deciduous teeth under general anaesthesia is often carried out without these local effects. There are no previous studies to investigate the combined effect of local anaesthesia with general anaesthesia on blood loss and pain control. A randomised, controlled clinical trial was carried out with one hundred children aged 3-5 years. Ethical approval and informed consent were obtained. Surface anaesthetic cream (EMLA) was placed on the hand into which the intravenous access was to be placed. One to two ml of blood was taken at the time of induction as a baseline of the patient's level of haematin pigment. Children in the experimental group were given one quarter of a cartridge (0.5 ml) of local anaesthetic containing epinephrine (1:80,000) in each quadrant before tooth extraction; all blood in swabs, suction equipment and disposables was collected and digested with NaOH. The children were observed for 11 minutes post-operatively for any signs of distress. Total blood loss was calculated by comparison of the baseline sample and the shed blood digests. This study showed that using local anaesthesia for dental extractions under general anaesthesia was associated with decreased blood loss (p = 0.001). The second finding--which has not been reported before--was that this use of local anaesthesia was shown to cause distress to this age group of children upon recovery from the general anaesthetic (p <0.0001). The use of local anaesthetic in this situation provided a useful reduction in post-operative bleeding. However, its use was associated with greater post-operative distress.

Analgesics↗
PubMed1999

Use of a modified Robbins device to directly compare the adhesion of Staphylococcus epidermidis RP62A to surfaces.

Staphylococcus epidermidis is a frequent cause of infection associated with the use of biomedical devices. Flow cell studies of the interaction between bacteria and surfaces do not generally allow direct comparison of different materials using the same bacterial suspension. The use of a modified Robbins Device (MRD) to compare the adhesion to different surfaces of Staph. epidermidis RP62A grown in continuous culture was investigated. Adhesion to glass was compared with siliconized glass, plasma-conditioned glass, titanium, stainless steel and Teflon. Attachment to siliconized glass was also compared with glass under differing ionic strength, and divalent cation concentrations. Both the differences in numbers adhering and changes in adhesion (slope) through the MRD were compared. There was a trend towards higher numbers adhering to the discs at the in-flow end of the MRD than at the outflow end, probably reflecting depletion of adherent bacteria in the interacting stream. Adhesion of Staph. epidermidis RP62A to siliconized glass and Teflon was reduced when compared to glass with increasing flow rates. Adhesion to stainless steel was not affected by flow rate and titanium gave a different slope of adhesion through the MRD when compared with glass, suggesting an interaction with different sub-populations within the interacting stream. Differences between siliconized glass and glass at flow rates of 300 ml h-1 were abolished by the addition of calcium or EDTA and reduced by the addition of magnesium. Increasing ionic strength reduced the statistical significance of the differences between glass and siliconized glass. Pre-conditioning of glass with pooled human plasma reduced adhesion compared with untreated glass and again gave a different slope to glass. The MRD linked to a chemostat can be used to compare directly bacterial adhesion to potential biomaterials. Variable depletion of the interacting stream should be taken into account in the interpretation of results. Divalent cation concentration, substrate properties and flow rate were important determinants of the comparative adhesion of Staph. epidermidis RP62A to surfaces.

Bacterial Adhesion↗
PubMed1999

Haemoglobin and ferritin concentrations in children aged 12 and 18 months. ALSPAC Children in Focus Study Team.

AIMS: To define the normal ranges and investigate associated factors for haemoglobin and ferritin in British children at 12 and 18 months of age, and to estimate correlations between both haemoglobin and ferritin concentrations at 8, 12, and 18 months of age. SUBJECTS AND METHODS: Subjects were part of the "children in focus" sample, randomly selected from the Avon longitudinal study of pregnancy and childhood. Capillary blood samples were taken from 940 children at 12 months and 827 children at 18 months of age. RESULTS: Haemoglobin was distributed normally and ferritin was distributed log normally at 12 and 18 months of age. Ninety five per cent reference ranges were established from empirical centiles of haemoglobin and ferritin. Haemoglobin concentrations at 18 months were associated with sex and maternal education. Concentrations of ferritin at 12 and 18 months of age were associated with birth weight and current weight. Girls at 12 months, but not at 18 months, had 8% higher ferritin concentrations than boys. Haemoglobin and ferritin concentrations were significantly correlated over time (8-12 months: rHb = 0.26, rFer = 0.46; 12-18 months: rHb = 0.37, rFer = 0.34; 8-18 months: rHb = 0.22, rFer = 0.24). CONCLUSION: Iron stores are depleted by rapid growth in infancy. A definition of anaemia based on the fifth centile gives cut off points at 12 and 18 months of age of haemoglobin < 100 g/l, and for iron deficiency of ferritin < 16 micrograms/l and < 12 micrograms/l, respectively. Because children below the fifth centile at one time point differ from those six months later, it is unclear whether screening would be effective.

Age Factors↗
PubMed1999

Cord blood leptin is associated with size at birth and predicts infancy weight gain in humans. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

Recent discoveries of human genetic leptin deficiency have demonstrated its importance in regulating weight gain in early childhood. To investigate whether normal variation in leptin and insulin levels in cord blood could influence infancy growth, we assayed samples from 197 infants from a representative birth cohort, who were measured at birth, 4, 8, 12 and 24 months. Cord leptin levels correlated most closely with weight and ponderal index (kg/m3) at birth, but also with length and head circumference (all p<0.0005). Independent of birth size, females had higher leptin levels than males (p<0.0005). Cord levels of leptin, but not insulin, were negatively related to weight gain (p<0.005) from birth to 4 months, and accounted for 9.4% of the variance in weight gain, compared with breast/bottle feeding (3.5%) and early/late introduction of solids (1%). The effect of leptin levels on weight gain was independent of birthweight, and was still evident at 24 months. The wide variation in infancy growth ('catch-up' or 'catch-down') may be partly determined by leptin levels preset in utero. Our data support a role for leptin in the regulation of infancy weight gain, and suggest a mechanism whereby infants may 'catch-up' in growth postnatally following an adverse intrauterine environment.

Birth Weight↗
PubMed1998

Association of the INS VNTR with size at birth. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

Size at birth is an important determinant of perinatal survival and has also been associated with the risk for cardiovascular disease and type 2 diabetes in adult life. Common genetic variation that regulates fetal growth could therefore influence perinatal survival and predispose to the development of adult disease. We have tested the insulin gene (INS) variable number of tandem repeats (VNTR) locus, which in Caucasians has two main allele sizes (class I and class III; ref. 3), as a functional candidate polymorphism for association with size at birth, as it has been shown to influence transcription of INS (refs 3-5). In a cohort of 758 term singletons (Avon Longitudinal Study of Pregnancy and Childhood; ALSPAC) followed longitudinally from birth to 2 years, we detected significant genetic associations with size at birth: class III homozygotes had larger mean head circumference (P=0.004) than class I homozygotes. These associations were amplified in babies who did not show postnatal realignment of growth (45%), and were also evident for length (P=0.015) and weight (P=0.009) at birth. The INS VNTR III/II genotype might have bestowed a perinatal survival during human history by conferring larger size at birth. Common genetic variation of this kind may contribute to reported associations between birth size and adult disease.

Birth Weight↗