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Biomedical subjects

L J Murray

Publications and source records attributed to L J Murray.

At least 19 recordsLinked to original sources

Malignancy and mortality in a population-based cohort of patients with coeliac disease or "gluten sensitivity".

AIM: To determine the risk of malignancy and mortality in patients with a positive endomysial or anti-gliadin antibody test in Northern Ireland. METHODS: A population-based retrospective cohort study design was used. Laboratory test results used in the diagnosis of coeliac disease were obtained from the Regional Immunology Laboratory, cancer statistics from the Northern Ireland Cancer Registry and mortality statistics from the General Registrar Office, Northern Ireland. Age standardized incidence ratios of malignant neoplasms and standardized mortality ratios of all-cause and cause-specific mortality were calculated. RESULTS: A total of 13 338 people had an endomysial antibody and/or an anti-gliadin antibody test in Northern Ireland between 1993 and 1996. There were 490 patients who tested positive for endomysial antibodies and they were assumed to have coeliac disease. There were 1133 patients who tested positive for anti-gliadin antibodies and they were defined as gluten sensitive. Malignant neoplasms were not significantly associated with coeliac disease; however, all-cause mortality was significantly increased following diagnosis. The standardized incidence and mortality ratios for non-Hodgkin's lymphoma were increased in coeliac disease patients but did not reach statistical significance. Lung and breast cancer incidence were significantly lower and all-cause mortality, mortality from malignant neoplasms, non-Hodgkin's lymphoma and digestive system disorders were significantly higher in gluten sensitive patients compared to the Northern Ireland population. CONCLUSION: Patients with coeliac disease or gluten sensitivity had higher mortality rates than the Northern Ireland population. This association persists more than one year after diagnosis in patients testing positive for anti-gliadin antibodies. Breast cancer is significantly reduced in the cohort of patients with gluten sensitivity.

Adolescent↗

Tracking of energy and nutrient intakes from adolescence to young adulthood: the experiences of the Young Hearts Project, Northern Ireland.

OBJECTIVE: To assess tracking of energy and nutrient intakes between adolescence and young adulthood. DESIGN: Longitudinal study of a random sample of adolescents (aged 15 years at baseline). The extent of tracking of dietary intakes (assessed by diet history) was investigated using weighted kappa statistics (kappa). SETTING: Northern Ireland population survey. SUBJECTS: Adolescents who participated in the Young Hearts Project, Northern Ireland at age 15 years, and subsequently at young adulthood aged between 20 and 25 years (n=245 males, n=231 females). RESULTS: Despite overall increases in height and weight (both P<0.001), increases in body mass index in males (P<0.001) and body fatness in females (P<0.001), median reported intakes of energy (kJ kg(-1) day(-1)), carbohydrate (g day(-1)) and fat (g day(-1)) decreased (all P<0.001) over time. Expressed as nutrient densities (per MJ), diets at young adulthood were overall richer in thiamin, vitamin B6, total folate (all P<0.001), vitamin C (P<0.01) and vitamin D (P<0.05). Whereas the nutrient density of the males' diets decreased over time for calcium (P<0.05) and vitamin A (P<0.001), iron and riboflavin densities increased in the females' diet (P<0.001). Tracking of energy (MJ day(-1)) and nutrient intakes (expressed per MJ day(-1)) at the individual level was only poor to fair (all kappa<0.25), indicating substantial drift of subjects between the low, medium and high classes of intake with increasing age. CONCLUSIONS: These data suggest that individual dietary patterns exhibited at 15 years of age are unlikely to be predictive of dietary intakes at young adulthood.

Adolescent↗

The effect of additional teaching on medical students' drug administration skills in a simulated emergency scenario.

Medical students have difficulty calculating drug doses correctly, but better teaching improves their performance in written tests. We conducted a blinded, randomised, controlled trial to assess the benefit of online teaching on students' ability to administer drugs in a simulated critical incident scenario, during which they were scored on their ability to administer drugs in solution presented as a ratio (adrenaline) or percentage (lidocaine). Forty-eight final year medical students were invited to participate; 44 (92%) attended but only nine of the 20 students (45%) directed to the extra teaching viewed it. Nevertheless, the teaching module significantly improved the students' ability to calculate the correct volume of lidocaine (p = 0.005) and adrenaline (p = 0.0002), and benefited each student's overall performance (p = 0.0007). Drug administration error is a very major problem and few interventions are known to be effective. We show that focusing on better teaching at medical school may benefit patient safety.

Anesthesiology↗

Ten-year trends for fatness in Northern Irish adolescents: the Young Hearts Projects--repeat cross-sectional study.

OBJECTIVE: To examine secular trends in measures of fatness over a 10-y period (the 1990s) in Northern Irish schoolchildren. DESIGN: Repeat cross-sectional surveys. SUBJECTS: In total, 12- and 15-y-old children randomly selected from post-primary schools. A total of 1015 children studied between 1989 and 1990, and 2017 studied between 1999 and 2001. MEASUREMENTS: The same study methods were applied in both surveys. Body mass index (BMI) was calculated from height and weight, and percentage body fat (%BF) was derived from skinfold measurements at four sites. Dietary intake was assessed using a diet history method and habitual physical activity (PA) was estimated from a self-report questionnaire. RESULTS: Increases were seen in both height and weight in all age-sex groups. The overall prevalence of overweight/obesity increased from 15.0 to 19.6%, but 12-y-old girls contributed most to this increase (15.9-26.3%), with a modest increase observed also in 15-y-old boys. Increases in mean BMI (19.2-20.3 kg/m2) and mean %BF (25.8-27.1%) were seen in 12-y-old girls, with no significant changes in any of the other subgroups. Mean energy intake increased in girls but not in boys, while mean PA score decreased in 12-y-old girls, but was unchanged in the other three groups. All age-sex groups showed substantial increases in the sugar intake while fat intake increased in girls and decreased in boys. CONCLUSION: Increases in indices of fatness were seen among school-age children in Northern Ireland during the 1990s. Trends differed between age-sex groups with the largest changes seen in 12-y-old girls. It remains to be seen whether the large increase in overweight/obesity in this group tracks into adulthood, with consequences for chronic disease incidence in women.

Adolescent↗

Total homocysteine is not a determinant of arterial pulse wave velocity in young healthy adults.

AIMS: Hyperhomocysteinaemia has been associated with reduced pulse wave velocity (PWV) in patients with end-stage renal disease and in those with hypertension. The aim of this study was to examine the association between total homocysteine (tHcy) concentrations, the biochemical and genetic determinants of tHcy and PWV in healthy young adults. METHODS AND RESULTS: A total of 489 subjects aged 20-25 years participated. A fasting blood sample was taken and PWV measured using a non-invasive optical method. tHcy did not correlate with PWV, whether assessed at the aorto-iliac segment (P = 0.18), the aorto-radial segment (P = 0.39) or the aorto-dorsalis-pedis segment (P = 0.22). When tHcy was classified into normal (<15) and high (> or =15micromol/l), PWV did not differ between the two groups at any segment. PWV did not differ by MTHFR C677T or NOS3 G894T genotype, even when smoking and folate sub-groups were considered. Considering aortic PWV as a dependent variable, stepwise regression analysis showed that the only parameter entering the model for all segments was systolic blood pressure (aorto-iliac, P < 0.001; aorto-radial, P = 0.01; aorto-dorsalis-pedis, P = 0.001). Age, sex, COL1A1 genotype and triglycerides entered the model significantly for two of three segments. CONCLUSION: This study shows that arterial PWV is not associated with tHcy in a healthy young population.

Adult↗

Inhibitors of histone deacetylases promote hematopoietic stem cell self-renewal.

BACKGROUND: Histone deacetylases (HDAC) are associated with a variety of transcriptional repressors that control cellular differentiation and proliferation. HDAC inhibitors such as trichostatin A, trapoxin and chlamydocin could be useful tools to modulate these cellular processes. We investigated their effect on the self-renewal of hematopoietic stem cells (HSC) during ex vivo culture. METHODS: Purified murine HSC with the phenotype c-Kit+,Thy-1.1(lo), Lin(-/lo), Sca-1+ were cultured for 4 days with IL-3, IL-6 and c-Kit ligand without or with HDAC inhibitors, after which their degree of phenotypic differentiation in culture was assessed by flow cytometric analysis. To explore whether HDAC inhibitors could have a beneficial role in human HSC transplantation, mobilized peripheral blood CD34+ cells were cultured with thrombopoietin mimetic peptide, flt3 ligand, and c-Kit ligand, without or with various HDAC inhibitors. The fluorescent dye, carboxyfluorescein-diacetate succinimidylester (CFSE), was used to track division of cell subsets, and engrafting ability was evaluated in a non-obese diabetic (NOD) -SCID xenotransplantation model. RESULTS: Murine HSC cultured with HDAC inhibitors maintained a more primitive phenotype than control cultures. The number of human HSC expressing Thy-1 increased up to seven-fold during a 5-day culture with HDAC inhibitors compared with control cultures. Chlamydocin was the most effective of the HDAC inhibitors tested at promoting Thy-1 expression on human cells. CFSE tracking showed that the increase in Thy-1+ cells resulted from cell division. In a NOD-SCID repopulation assay, cells exposed to chlamydocin for 24 h displayed an average four-fold higher engrafting ability over control cells. DISCUSSION: Our studies suggest that HDAC inhibitors can induce ex vivo expansion of human HSC, and may improve engraftment in hematopoietic transplant patients when cell dose is limiting.

Animals↗

Evidence of prostate cancer screening in a UK region.

OBJECTIVE: To examine the pattern of use of prostate-specific antigen (PSA) testing in a UK region, where National Health Service policy does not recommend screening for prostate cancer. SUBJECTS AND METHODS: Data were collected on all PSA tests in Northern Ireland between 1990 and 1999. Annual rates of PSA testing were calculated by age, GP Practice and year. RESULTS: In all, 165 862 PSA tests were performed on 84 669 men, and over a third of men aged > or = 50 years had at least one PSA test. Men aged < 50 years accounted for 12.9% of first tests. The proportion of tests from primary care increased from 47.2% in 1993 to 67.0% in 1999. The mean age of men tested once decreased from 65.6 to 61.9 years (P trend < 0.001) and the proportion with an elevated PSA level also declined during the period. Repeat testing increased with PSA level (P < 0.001) but 29.4% of men with a PSA level of < or = 4 ng/mL also had repeat testing. Raised PSA values were more common from hospital than primary care (32.4% vs 20.6%, P < 0.001) and in older men. Test rates varied 100-fold across general practices, a finding not explained by sociodemographic factors, but one which reflects differential adherence to national guidelines, suggesting that general practitioners are key targets for attempting to rationalise the use of the PSA test. CONCLUSION: These findings suggest that PSA screening is taking place against evidence-based advice and has resulted in over 20 000 men being designated as having a raised PSA level, creating a need for further assessment.

Adult↗

Mortality in Barrett's oesophagus: results from a population based study.

BACKGROUND: Patients with Barrett's oesophagus have an increased risk of oesophageal adenocarcinoma but this cancer only accounts for a small proportion of deaths in these patients. Other causes of death are reportedly raised in this group. We examined cause specific mortality among individuals in a population based Barrett's oesophagus register. METHODS: We constructed a register of all patients diagnosed with columnar mucosa (including specialised intestinal metaplasia) of the oesophagus within Northern Ireland between 1993 and 1999. Deaths occurring within this cohort until 31 December 2000 were identified and mortality rates were compared with the general population. RESULTS: Overall mortality was not raised in Barrett's patients. During 7413 person years of follow up in 2373 patients there were 253 deaths (standardised mortality ratio (SMR) 96 (95% confidence interval (CI) 84-107)). Mortality from oesophageal cancer was raised in patients with specialised intestinal metaplasia (SMR 774 (95% CI 317-1231)) but only 4.7% of patients died from this cancer. Mortality from stroke (SMR 65 (95% CI 37-93)) was significantly lower than the general population while mortality from non-cancerous digestive system diseases was significantly higher (SMR 211 (95% CI 111-311)). Mortality rates from all other causes were similar to those of the general population. CONCLUSIONS: This study demonstrates that the overall mortality rate in patients with Barrett's oesophagus is closely similar to that of the general population. Oesophageal cancer mortality was raised but is an uncommon cause of death in these patients who also appear to have a reduced risk of death from stroke.

Adenocarcinoma↗

The effect of nutrient intake on bone mineral status in young adults: the Northern Ireland young hearts project.

Optimizing peak bone mass in early life may reduce osteoporosis risk in later life. Such optimization may be partly dependent upon diet. In the present study, nutrient intakes and selected lifestyle parameters were assessed in adolescent subjects (238 males, 205 females; aged 15 y) and again, in the same subjects, on one occasion in young adulthood (aged between 20 and 25 y). The extent of the relationships between these parameters and bone mineral density (BMD), dual energy X-ray absorptiometry (DXA), lumbar spine (L2-L4), and femoral neck measured concurrently with diet in young adulthood only, was assessed. Adjusted linear regression models were constructed. Variables included a measure of pubertal status (at age 15 y), age (at young adulthood), height, weight, physical activity, smoking, and mean daily intakes of energy, calcium, protein, vitamin D, phosphorus, total fat, and alcohol. In both sexes, body weight at adolescence and young adulthood was the only factor consistently positively associated with BMD at both measurement sites. Effects of nutrient intake on BMD were inconsistent. Vitamin D and calcium intakes reported by female adolescents showed significant positive relationships with BMD measured in young adulthood (vitamin D measured at the lumbar spine; calcium measured at the femoral neck). The positive relationship between vitamin D and BMD remained significant at young adulthood, but at the femoral neck rather than at the lumbar spine. Also in females, intakes of phosphorus and the calcium:phosphorus ratio (Ca:P) at adolescence were strongly negatively related to femoral neck BMD measured at young adulthood. In males, however, Ca:P reported at young adulthood had a significant positive relationship with lumbar spine BMD, whereas Ca:protein was negatively associated with BMD at the lumbar spine. Intakes of Ca reported by adolescent males also had a strong negative effect on lumbar spine BMD measured at young adulthood.

Adolescent↗

Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases.

Overexpression of the epidermal growth factor receptor (EGFR) often correlates with an aggressive tumour phenotype and poor prognosis. To examine the relevance of EGFR in colorectal cancer, we determined the expression of EGFR protein in 249 colorectal adenocarcinomas and 42 lymph node metastases using immunohistochemistry. Moreover, we investigated a (CA)(n) dinucleotide repeat polymorphism of the EGFR gene in a subset of 114 tumours. High levels of EGFR protein were observed in 123/249 (49.4%) samples. EGFR expression in colorectal carcinomas correlated with differentiation grade (P=0.014). However, there were no associations with Dukes' stage, site, patient age or gender. EGFR protein expression did not influence survival in this colorectal cancer patient cohort (P>or=0.05). Expression was not identical in paired colorectal tumours and lymph node metastases, with only 17/42 (40.5%) samples showing equivalent EGFR levels (P>0.05). The distribution of the (CA)(n) dinucleotide repeat alleles in colorectal adenocarcinomas was not associated with EGFR protein expression (P>0.05). These results indicate that while EGFR overexpression is a common event in colorectal carcinogenesis, it does not influence patient prognosis.

Adenocarcinoma↗

Relationship between physical activity and bone mineral status in young adults: the Northern Ireland Young Hearts Project.

Physical activity during the first three decades of life may increase peak bone mass and reduce future osteoporosis risk. The aim of this study was to determine the extent to which different components of physical activity may influence bone mineral status within a representative population sample of young men and women. Bone mineral density (BMD) and content (BMC) were determined at the lumbar spine and femoral neck in 242 men and 212 women, aged 20-25 years, by dual-energy X-ray absorptiometry. Physical activity was assessed by a self-report questionnaire designed to measure the frequency and duration of physical activity and its components (i.e., work, non-sports leisure, sports-related activities, and peak strain sports activities). Potential confounding factors such as height, weight, diet, and smoking habits were also assessed. In multivariate linear regression models, sports activity and peak strain sports activity undertaken by men were strongly associated with both lumbar spine BMD (beta = 0.35 [0.21, 0.49] and beta = 0.31 [0.17, 0.44], respectively) and BMC (beta = 0.33 [0.21, 0.45] and beta = 0.26 [0.14, 0.38], respectively) and femoral neck BMD (beta = 0.35 [0.21, 0.48] and beta = 0.27 [0.14, 0.40], respectively) and BMC (beta = 0.32 [0.19, 0.44] and beta = 0.29 [0.17, 0.41], respectively) (all p < 0.01), but work and non-sports leisure activities were not. In women, there were no associations between bone measurements and any component of physical activity. In models involving all subjects the gender/sports activity, but not the gender/peak strain, interaction term was statistically significant. Sports activity explained 10.4% of the observed variance in lumbar spine BMD in men, but <1% in women. These results demonstrate the importance of sports activities, especially those involving high peak strain, in determining peak bone status in young men. Failure to observe this association in women reflects their lower participation in such activities, but they may have the same capacity to benefit from these activities as men. Intervention studies are warranted to determine whether peak bone density in women can be improved by participating, during childhood and adolescence, in sports activities involving high peak strain.

Absorptiometry, Photon↗

A longitudinal study through adolescence to adulthood: the Young Hearts Project, Northern Ireland.

The Young Hearts (YH) Project is an ongoing study of biological and behavioural risk factors for cardiovascular disease in a representative sample of young people from Northern Ireland, a region of high coronary mortality. This article describes the cross-sectional clinical, dietary and lifestyle data obtained from individuals (aged 20-25 y) who participated in phase 3 of the project (YH3). A total of 489 individuals (251 males, 238 females) participated in YH3 (48.2% response rate). Some 31.1% of participants at YH3 were overweight (BMI >25 kg/m(2)) with 4.4% of males and 8.0% of females were obese (BMI >30 kg/m(2)). More females than males had a very poor fitness (55.0 vs 22.1%, chi-squared 51.70, d.f. 1, P<0.001) and did not participate in any sporting or exercise activity (38.4 vs 24.9%, chi-squared 10.26, d.f. 1, P=0.001). Over 20% of participants had a raised total serum cholesterol (>5.2 mmol/l). More females had a raised serum LDL-cholesterol (>3.0 mmol/l) than males (44.6 vs 34.6%, chi-squared 4.39, d.f. 1, P<0.05). Over 46% of participants reported energy intakes from fat above recommended levels, and 68.5% of participants had saturated fat intakes above those recommended (Dietary reference values for food energy and nutrients for the United Kingdom. HMSO: London, 1991). Just over half of the study population reported alcohol intakes in excess of recommended sensible limits set by the Royal College of Physicians (A great and growing evil: the medical consequences of alcohol abuse. Tavistock: London, 1987), with 36.7% of males and 13.4% of females reporting intakes over twice these recommended limits. A total of 37% of the study population smoked. During young adulthood, individuals may be less amenable to attend a health-related study and recruitment of participants to the current phase of the study proved a major problem. However, these data constitute a unique developmental record from adolescence to young adulthood in a cohort from Northern Ireland and provide additional information on the impact of early life, childhood and young adulthood on the development of risk for chronic disease.

Adolescent↗

Relationship between the birth cohort pattern of Helicobacter pylori infection and the epidemiology of duodenal ulcer.

BACKGROUND: Helicobacter-pylori-related duodenal ulcer (DU) is an important cause of dyspepsia. AIM: To determine the relationship between the pattern of H. pylori infection and the epidemiology of duodenal ulcer in a single population. DESIGN: Prospective two-part study of (i) patients with DU referred for endoscopy because of dyspepsia, and (ii) the incidence of H. pylori infection in the general population of the same area. METHODS: Details of 533 DU patients were recorded, and related to the pattern of H. pylori infection among 10 537 adults in the same community, determined by the (13)C-urea breath test. RESULTS: In patients with DU, birth year was more important than age in determining the rate of presentation for endoscopy (the 'birth cohort' effect). H. pylori infection showed a similar birth cohort effect, and the prevalence decreased steadily in those born in successive years, from 28.8% in the 1930s to 3.5% in the 1970s. The proportion of dyspeptic patients who had duodenal ulcers also fell progressively, from 22.2% in 1979 to 5.7% in 1998. H. pylori prevalence and duodenal ulcer incidence were closely correlated at all ages. DISCUSSION: Duodenal ulcer prevalence (as judged by the rate of referral of duodenal ulcer patients for endoscopy) is determined principally by the distribution of H. pylori infection in the local population. The birth cohort effect seen in adult duodenal ulcer patients reflects the acquisition of H. pylori in childhood. In Bristol, H. pylori prevalence and duodenal ulcer incidence are both declining to very low levels.

Adult↗

Effect of a COL1A1 Sp1 binding site polymorphism on arterial pulse wave velocity: an index of compliance.

-Reduced arterial compliance precedes changes in blood pressure, which may be mediated through alterations in vessel wall matrix composition. We investigated the effect of the collagen type I-alpha1 gene (COL1A1) +2046G>T polymorphism on arterial compliance in healthy individuals. We recruited 489 subjects (251 men and 238 women; mean age, 22.6+/-1.6 years). COL1A1 genotypes were determined using polymerase chain reaction and digestion by restriction enzyme Bal1. Arterial pulse wave velocities were measured in 3 segments, aortoiliac (PWVA), aortoradial (PWVB), and aorto-dorsalis-pedis (PWVF), as an index of compliance using a noninvasive optical method. Data were available for 455 subjects. The sample was in Hardy-Weinberg equilibrium with genotype distributions and allele frequencies that were not significantly different from those reported previously. The T allele frequency was 0.22 (95% confidence interval, 0.19 to 0.24). Two hundred eighty-three (62.2%) subjects were genotype GG, 148 (35.5%) subjects were genotype GT, and 24 (5.3%) subjects were genotype TT. A comparison of GG homozygotes with GT and TT individuals demonstrated a statistically significant association with arterial compliance: PWVF 4.92+/-0.03 versus 5.06+/-0.05 m/s (ANOVA, P=0.009), PWVB 4.20+/-0.03 versus 4.32+/-0.04 m/s (ANOVA, P=0.036), and PWVA 3.07+/-0.03 versus 3.15+/-0.03 m/s (ANOVA, P=0.045). The effects of genotype were independent of age, gender, smoking, mean arterial pressure, body mass index, family history of hypertension, and activity scores. We report an association between the COL1A1 gene polymorphism and arterial compliance. Alterations in arterial collagen type 1A deposition may play a role in the regulation of arterial compliance.

Adult↗

Infection with virulent strains of Helicobacter pylori is not associated with ischaemic heart disease: evidence from a population-based case-control study of myocardial infarction.

BACKGROUND: Although the majority of evidence does not support association between Helicobacter pylori infection and ischaemic heart disease, the nature of this relationship may differ when virulence of the infecting strains are examined. METHODS AND RESULTS: The prevalence of IgG antibody evidence of infection with CagA positive stains of H. pylori was investigated in stored plasma samples from 259 cases of myocardial infarction (aged 25-70 years, 74 males) and 259 population based controls from the same area in Northern Ireland. Two-hundred and seventy (52.1%) subjects were seropositive for anti-CagA IgG. CagA seropositivity was more common in cases than in controls: 56.4 vs 47.9%, odds ratio for seropositivity in cases (95% CI) 1.41 (1.00, 1.99). Substantial attenuation of this relationship occurred on adjustment for age, sex, number of siblings, smoking and measures of socio-economic status: odds ratio (95% CI) 1.16 (0.79, 1.70). A similar pattern was seen for seropositivity for all H. pylori strains. CONCLUSION: Infection with the more virulent strains of H. pylori, as with all strains, is not associated with myocardial infarction.

Adult↗

Season and outdoor ambient temperature: effects on birth weight.

OBJECTIVE: To determine the extent to which meteorologic factors explain seasonality in birth weight in a developed country. METHODS: Recorded birth weights were collected for all singleton live births after 36 weeks of pregnancy in Northern Ireland between 1971 and 1986. Data on daily maximum and minimum temperatures, rainfall, and hours of bright sunshine were obtained from a local climatologic station for the same period. For each birth, mean daily maximum and minimum temperatures, rainfall, and hours of bright sunshine were calculated for the trimesters of the pregnancy. Linear regression models were constructed with birth weight as the dependent variable and month of birth as a predictor variable. Months of birth were entered in the models as dummy variables. Adjustment was made for year of birth, duration of gestation, maternal age, number of previous pregnancies, sex, and social class of infants at birth and for meteorologic variables relating to each trimester. RESULTS: A clear seasonal pattern in birth weight was observed, with lowest mean birth weight in late spring and summer. Adjusted mean birth weights were 25.5 g, 29.6 g, and 31.6 g lower in May, June, and July, respectively, than in January. This seasonal variation occurred in both sexes, and in female births, it disappeared almost entirely after adjustment for mean daily maximum temperature during the second trimester of pregnancy. CONCLUSION: Infants born during late spring and summer are lighter than those born in winter, which might be the result of exposure to low winter temperatures during midgestation. Pregnant women should keep themselves warm during midpregnancy.

Birth Weight↗