The secondary sex ratio in Israel: 1980–1995

Abstract

This study deals with models and hypotheses that attempt to explain the underlying mechanisms determining the sex ratios at birth in human populations. Since the factors responsible are still questionable and research results are contradictory, we examine data available in Israel on the sex ratios at birth among two different sociodemographic groups, Jews and Moslems. Results suggest a difference between Jewish and Moslem patterns of secondary sex ratios with respect to parental age, education, and birth number. The difference may be described as a more regular and, by existing models, a more predictable pattern of secondary sex ratio among Moslems than among Jews. The possibility that Jewish religious laws play a role in this difference is discussed.     

Sex ratios at birth in a Micronesian atoll population

Abstract

The recent suggestion that typically masculinized sex ratios at birth in Micronesian populations may be related to a distinct “Micronesian pattern” of life‐course coital behavior is applied to data on the sex ratio of livebirths on Butaritari Atoll in Kiribati. The data show that sex ratios on Butaritari are highly masculinized and do not vary significantly with changes in maternal age. However, there is a discernible relationship between the length of closed intervals preceding male and female births. The lack of age‐related change in sex ratios in the Butaritari sample is inconsistent with ethnographic data regarding levels of marital coital activity in relation to increasing age and marriage duration. The Butaritari sex ratio data is argued to support the suggestion of a “Micronesian pattern,” although it is posed that further tests of this association are required.     

High Mobility Group-Box 1 (HMGB1) levels are increased in amniotic fluid of women with intra-amniotic inflammation-determined preterm birth,and the source may be the damaged fetal membranes

BackgroundHigh Mobility Group Box-1 (HMGB1) is considered a prototype alarmin molecule. Upon its extracellular release, HMGB1 engages pattern recognition receptors and the Receptor for Advanced Glycation End-products (RAGE) followed by an outpouring of inflammatory cytokines, including interleukin (IL)-6.MethodsWe assayed the amniotic fluid (AF) levels of HMGB1 and IL-6 in 255 women that either had a normal pregnancy outcome or delivered preterm. Immunohistochemistry on fetal membranes was used for cellular localization and validation of immunoassay findings. HMGB1 also was analyzed in amniochorion tissue explants subjected to endotoxin.ResultsAF HMGB1 levels are not gestational age regulated but are increased in women with intra-amniotic inflammation and preterm birth. The likely source is the damaged amniochorion, as demonstrated by immunohistochemistry and explant experiments.ConclusionsOur research supports a role for HMGB1 in the inflammatory response leading to preterm birth. As a delayed phase cytokine, in utero exposure to elevated AF HMGB1 levels may have an impact on the newborn beyond the time of birth.     

Contents Volume 34 (2003)

Abstract

Our previous studies indicated that temperature and photoperiod were not involved as temporal variables in effecting the annual changes in human conceptions in the USA. However, temperature still receives attention in the current literature as the important variable in determining the temporal pattern of conceptions. Therefore, we present here a replication of our previous study, involving two additional 11‐year cycles of birth data in the USA, from the interval 1945 thru 1966. The data are transformed to remove linear trends, to remove over‐all mean differences, and to remove differences in amplitude. The data are then clustered into the regional groups determined by the previous study. The replication was obtained when these groups exhibited similar patterns within a 11‐year period and among 11‐year periods. The data from four 11‐year intervals are presented, representing more than 100 million Caucasian births in the USA from 1945 thru 1988. The subtle changes with time are described, and a comparison with a southern hemisphere pattern indicates, along with the other data, that temperature is irrelevant in effecting the annual pattern of changes in conceptions.     

Seasonal variations of date of diagnosis and birth for neuroblastoma patients in Italy

BackgroundAnalysis of seasonal variation of diagnosis or birth of childhood cancers may provide useful insight about possible aetiological risk factors, such as infectious agents and environmental exposures, but studies on neuroblastoma are lacking.ProcedureTwo thousand seven hundred fifty-six cases of neuroblastoma, diagnosed between 1980 and 2010, registered in the Italian Neuroblastoma Registry, were included in the study. Subgroup analyses were carried out by age, gender and stage at diagnosis. Seasonal trend was assessed by a harmonic function in a Poisson regression model, adjusted for the number of live births.ResultsNo trend in the date of diagnosis was found either in the entire cohort or in the various sub-groups. Similarly, a seasonal trend of birth was not observed in the whole cohort. Conversely, in the subgroup of infants with stage 4S, a significant peak of July births was found (23.6% increment from the average, p = 0.042). The summer peak was confirmed after stratifying 4S patients by gender and period of diagnosis.ConclusionsA major effect of risk factors related to seasonality does not appear to affect the risk of developing neuroblastoma. However, the time pattern of birth observed by stage at diagnosis is consistent with the hypothesis that Stage 4S is a distinct disease with probably a different aetiology, as indicated by investigations on its metastatic pattern and its peculiar gene expression. An aetiological role of seasonally related factors, e.g., favouring the survival of defective neural crest stem cells, remains speculative and need confirmation by independent studies.     

Birth weight of offspring and insulin resistance in late adulthood: cross sectional survey

ObjectiveTo investigate the association between birth weight of offspring and mothers'' insulin resistance in late adulthood.DesignCross sectional survey.SettingGeneral practitioner''s surgeries in 23 towns in Great Britain.Participants4286 women aged 60-79 years.ResultsBirth weight of offspring was inversely related to maternal insulin resistance in late adulthood. For each 1 kg higher birth weight of offspring, women had a 15% reduction in the odds of being in the fourth with highest insulin resistance, compared to other fourths (odds ratio 0.85; 95% confidence interval 0.71 to 1.00). This increased to 27% (0.73; 0.60 to 0.90) after adjusting data for potential confounders. A U shaped relation between birth weight of offspring and diabetes in older age was found; women with the lightest and heaviest offspring had the highest prevalence of diabetes.ConclusionsBirth weight of offspring is inversely related to the mother''s insulin resistance in late adulthood, despite the association of glucose intolerance during pregnancy with heavier offspring at birth. Common genetic factors contribute to the relation between birth weight and risk of cardiovascular disease and diabetes in adults.

What is already known on this topic

Small birth weight is related to increased risk of cardiovascular disease and diabetes in adulthood; the underlying mechanisms are unclearSmall birth weight of offspring is related to parental cardiovascular disease, suggesting that common genetic factors affect birth weight and the risk of disease in adulthoodGenetic factors associated with the metabolism of insulin are plausible in linking birth weight and cardiovascular disease (the fetal insulin hypothesis)

What this study adds

Birth weight of offspring is inversely related to maternal insulin resistance in older ageGenetic factors related to both insulin resistance and birth weight explain at least part of the association between birth weight and risk of cardiovascular disease and diabetes in adulthood     

Birth weight,adult body size,and risk of colorectal cancer

BackgroundEvidence suggests that birth weight may be associated with colorectal cancer (CRC) risk later in life. Whether the association is mediated by adult body size remains unexamined.MethodCox proportional hazards models (Hazard Ratio (HR) and 95 % Confidence Intervals (CI)) were used to evaluate the association between self-reported birth weight (<6 lbs, 6-<8 lbs, ≥8 lbs) and CRC risk among 70,397 postmenopausal women from the Women’s Health Initiative. Further, we assessed whether this association was mediated by adult body size using multiple mediation analyses.ResultsCompared with birth weights of 6-< 8 lbs, birth weight ≥ 8 lbs was associated with higher CRC risk in postmenopausal women (HR = 1.31, 95 % CI 1.16–1.48). This association was significantly mediated by adult height (proportion mediated =11.4 %), weight (11.2 %), waist circumference (10.9 %), and body mass index at baseline (4.0 %). The joint effect of adult height and weight explained 21.6 % of this positive association.ConclusionOur data support the hypothesis that the intrauterine environment and fetal development may be related to the risk of developing CRC later in life. While adult body size partially explains this association, further investigation is required to identify other factors that mediate the link between birth weight and CRC.     

Maternal Glomerular Filtration Rate in Pregnancy and Fetal Size

BackgroundThe relationship of maternal glomerular filtration rate (GFR) in pregnancy to fetal size needs to be better characterized as it impacts an ongoing debate about confounding effect of maternal GFR in investigations of important environmental contaminants. We aimed to characterize the size of the association between maternal GFR and infant birth weight.ResultsMaternal GFR-CG (β: 0.73 g/ml/min, p = 0.04) and GFR-MDRD (β: 0.83 g/ml/min, p = 0.04) were associated with infant birth weight in models adjusted for maternal weight in kilograms, preeclampsia, and gestational age at delivery (days). Partial correlation coefficients for the association between infant birth weight and GFR were 0.07 for both formulas. Although the birth weight-GFR association was stronger among the women with preeclampsia, the difference from women without preeclampsia was not statistically significant.ConclusionThese data support an association between GFR during pregnancy and infant birth weight, and indicate that GFR may confound selected epidemiologic associations.     

The season‐of‐birth paradox

Abstract

Vital statistics data show a remarkably consistent seasonality in U.S. birth patterns, with peaks in late summer and winter months, and a valley in the spring. An attitude survey of college students suggests that peaks in the actual birth distribution occur in unpopular months in which to give birth; the valley in the actual birth distribution occurs in popular months. This paradoxical finding is named the Season‐of‐Birth Paradox. Explanations to resolve the paradox include biological and psychological components. A psychological mechanism—named the Misinformed Reproducer Hypothesis—is tested using NSFG data from the 1973–75 and 1979–81 cycles. Results suggest that women stop contracepting with the expectation that they will get pregnant almost immediately. When it takes several months on the average for a successful conception to occur, the actual birth distribution is shifted away from the preferred birth distribution. These results suggest that psychological as well as biological mechanisms underlie the consistent seasonality patterns in U.S. births.     

Risk Alleles in/near ADCY5, ADRA2A,CDKAL1, CDKN2A/B,GRB10, and TCF7L2 Elevate Plasma Glucose Levels at Birth and in Early Childhood: Results from the FAMILY Study

BackgroundMetabolic abnormalities that lead to type 2 diabetes mellitus begin in early childhood.ObjectivesWe investigate whether common genetic variants identified in adults have an effect on glucose in early life.Methods610 newborns, 463 mothers, and 366 fathers were included in the present study. Plasma glucose and anthropometric characteristics were collected at birth, 3, and 5 years. After quality assessment, 37 SNPs, which have demonstrated an association with fasting plasma glucose at the genome-wide threshold in adults, were studied. Quantitative trait disequilibrium tests and mixed-effects regressions were conducted to estimate an effect of the SNPs on glucose.ResultsRisk alleles for 6 loci increased glucose levels from birth to 5 years of age (ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2, 4.85x10^-3 ≤ P ≤ 4.60x10^-2). Together, these 6 SNPs increase glucose by 0.05 mmol/L for each risk allele in a genotype score (P = 6.33x10^-5). None of the associations described in the present study have been reported previously in early childhood.ConclusionOur data support the notion that a subset of loci contributing to plasma glucose variation in adults has an effect at birth and in early life.     

Fetal growth and subsequent risk of breast cancer: results from long term follow up of Swedish cohort

ObjectiveTo investigate whether size at birth and rate of fetal growth influence the risk of breast cancer in adulthood.DesignCohort identified from detailed birth records, with 97% follow up.SettingUppsala Academic Hospital, Sweden.Participants5358 singleton females born during 1915-29, alive and traced to the 1960 census.ResultsSize at birth was positively associated with rates of breast cancer in premenopausal women. In women who weighed ⩾4000 g at birth rates of breast cancer were 3.5 times (95% confidence interval 1.3 to 9.3) those in women of similar gestational age who weighed <3000 g at birth. Rates in women in the top fifths of the distributions of birth length and head circumference were 3.4 (1.5 to 7.9) and 4.0 (1.6 to 10.0) times those in the lowest fifths (adjusted for gestational age). The effect of birth weight disappeared after adjustment for birth length or head circumference, whereas the effects of birth length and head circumference remained significant after adjustment for birth weight. For a given size at birth, gestational age was inversely associated with risk (P=0.03 for linear trend). Adjustment for markers of adult risk factors did not affect these findings. Birth size was not associated with rates of breast cancer in postmenopausal women.ConclusionsSize at birth, particularly length and head circumference, is associated with risk of breast cancer in women aged <50 years. Fetal growth rate, as measured by birth size adjusted for gestational age, rather than size at birth may be the aetiologically relevant factor in premenopausal breast cancer.

What is already known on this topic

There is some evidence that birth weight is related to risk of breast cancerThe exact nature of any association and whether it differs at premenopausal and postmenopausal ages is unclearFew studies have examined the effect of other measures of birth size and of gestational age

What this study adds

There are strong positive associations between measures of birth size and rates of breast cancer at premenopausal ages that persisted after adjustment for adult risk factorsFor a given birth size, gestational age was inversely associated with risk, suggesting that the rate of fetal growth may be aetiologically relevant to premenopausal breast cancerThere was no association between birth characteristics and rates of breast cancer at postmenopausal ages     

Postnatal gestational age estimation via newborn screening analysis: application and potential

ABSTRACT

Introduction: Preterm birth is a major global health concern, contributing to 35% of all neonatal deaths in 2016. Given the importance of accurately ascertaining estimates of preterm birth and in light of current limitations in postnatal gestational age (GA) estimation, novel methods of estimating GA postnatally in the absence of prenatal ultrasound are needed. Previous work has demonstrated the potential for metabolomics to estimate GA by analyzing data captured through routine newborn screening.

Areas covered: Circulating analytes found in newborn blood samples vary by GA. Leveraging newborn screening and demographic data, our group developed an algorithm capable of estimating GA postnatally to within approximately 1 week of ultrasound-validated GA. Since then, we have built on the model by including additional analytes and validating the model’s performance through internal and external validation studies, and through implementation of the model internationally.

Expert opinion: Currently, using metabolomics to estimate GA postnatally holds considerable promise but is limited by issues of cost-effectiveness and resource access in low-income settings. Future work will focus on enhancing the precision of this approach while prioritizing point-of-care testing that is both accessible and acceptable to individuals in low-resource settings.     

Associations of maternal dietary inflammatory potential and quality with offspring birth outcomes: An individual participant data pooled analysis of 7 European cohorts in the ALPHABET consortium

BackgroundAdverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth outcomes. However, evidence on whole diet that considers complex nutrient and food interaction is rare and conflicting. We aim to elucidate the influence of whole-diet maternal dietary inflammatory potential and quality during periconceptional and antenatal periods on birth outcomes.Methods and findingsWe harmonized and pooled individual participant data (IPD) from up to 24,861 mother–child pairs in 7 European mother–offspring cohorts [cohort name, country (recruitment dates): ALSPAC, UK (1 April 1991 to 31 December 1992); EDEN, France (27 January 2003 to 6 March 2006); Generation R, the Netherlands (1 April 2002 to 31 January 2006); Lifeways, Ireland (2 October 2001 to 4 April 2003); REPRO_PL, Poland (18 September 2007 to 16 December 2011); ROLO, Ireland (1 January 2007 to 1 January 2011); SWS, United Kingdom (6 April 1998 to 17 December 2002)]. Maternal diets were assessed preconceptionally (n = 2 cohorts) and antenatally (n = 7 cohorts). Maternal dietary inflammatory potential and quality were ranked using the energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) index, respectively. Primary outcomes were birth weight and gestational age at birth. Adverse birth outcomes, i.e., low birth weight (LBW), macrosomia, small-for-gestational-age (SGA), large-for-gestational-age (LGA), preterm and postterm births were defined according to standard clinical cutoffs. Associations of maternal E-DII and DASH scores with infant birth outcomes were assessed using cohort-specific multivariable regression analyses (adjusted for confounders including maternal education, ethnicity, prepregnancy body mass index (BMI), maternal height, parity, cigarettes smoking, and alcohol consumption), with subsequent random-effects meta-analyses.Overall, the study mothers had a mean ± SD age of 29.5 ± 4.9 y at delivery and a mean BMI of 23.3 ± 4.2 kg/m². Higher pregnancy DASH score (higher dietary quality) was associated with higher birth weight [β(95% CI) = 18.5(5.7, 31.3) g per 1-SD higher DASH score; P value = 0.005] and head circumference [0.03(0.01, 0.06) cm; P value = 0.004], longer birth length [0.05(0.01, 0.10) cm; P value = 0.010], and lower risk of delivering LBW [odds ratio (OR) (95% CI) = 0.89(0.82, 0.95); P value = 0.001] and SGA [0.87(0.82, 0.94); P value < 0.001] infants. Higher maternal prepregnancy E-DII score (more pro-inflammatory diet) was associated with lower birth weight [β(95% CI) = −18.7(−34.8, −2.6) g per 1-SD higher E-DII score; P value = 0.023] and shorter birth length [−0.07(−0.14, −0.01) cm; P value = 0.031], whereas higher pregnancy E-DII score was associated with a shorter birth length [−0.06(−0.10, −0.01) cm; P value = 0.026] and higher risk of SGA [OR(95% CI) = 1.18(1.11, 1.26); P value < 0.001]. In male, but not female, infants higher maternal prepregnancy E-DII was associated with lower birth weight and head circumference, shorter birth length, and higher risk of SGA (P-for-sex-interaction = 0.029, 0.059, 0.104, and 0.075, respectively). No consistent associations were observed for maternal E-DII and DASH scores with gestational age, preterm and postterm birth, or macrosomia and LGA. Limitations of this study were that self-reported dietary data might have increased nondifferential measurement error and that causality cannot be claimed definitely with observational design.ConclusionsIn this cohort study, we observed that maternal diet that is of low quality and high inflammatory potential is associated with lower offspring birth size and higher risk of offspring being born SGA in this multicenter meta-analysis using harmonized IPD. Improving overall maternal dietary pattern based on predefined criteria may optimize fetal growth and avert substantial healthcare burden associated with adverse birth outcomes.

In this cohort analysis, Ling-Wei Chen and colleagues explore associations of maternal dietary patterns with offspring birth outcomes.     

脐动脉血流对预测子痫前期新生儿和产妇结局的价值分析

目的:探讨应用脐动脉血流用于预测子痫前期新生儿和产妇结局的临床价值。方法:选择在我院产科建档分娩的120例孕产妇作为研究对象,根据子痫前期发病情况分为子痫前期组60例与对照组60例,记录和比较两组孕产妇的一般资料、血脂、血糖水平、分娩前脐动脉血流与新生儿体重、胎盘的重量及Apgar评分,并进行相关性与危险因素分析。结果:两组孕产妇的年龄、孕次、产次、流产次数、孕周等对比差异均无统计学意义(P0.05)。子痫前期组的血清HDL-C水平低于对照组(P0.05),血清TC、TG、LDL-C、FBG水平高于对照组(P0.05)。与对照组比较,子痫前期组脐动脉S/D、RI与PI值显著升高(P0.05)。所有孕产妇都顺利完成分娩,孕产妇与新生儿都存活,子痫前期组的新生儿出生体重及Apgar评分和胎盘的重量均显著低于对照组(P0.05)。在子痫前期组中,脐动脉S/D、RI、PI值与新生儿出生体重呈现显著负相关性(P0.05)。多重线性回归分析显示子痫前期孕产妇的脐动脉S/D、RI、PI值为影响新生儿出生体重的独立危险因素(P0.05)。结论:脐动脉血流与子痫前期新生儿出生体重显著相关,脐动脉S/D、RI、PI值为影响新生儿出生体重的独立危险因素,子痫前期脐动脉血流监测可为预测新生儿和产妇结局以及预后提供参考。     

Birth characteristics and risk of lymphoma in young children

BackgroundLymphoma is the third most common childhood malignancy and comprises two types, Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). The etiology of pediatric lymphomas is largely unknown, but has been suggested to have prenatal origins.MethodsIn this population-based study, California birth certificates were identified for 478 lymphoma cases diagnosed in children 0–5 years of age between 1988 and 2007; 208,015 controls frequency-matched by birth year were randomly selected from California birth records.ResultsCompared to non-Hispanic whites, Hispanic children had an increased risk of HL (odds ratio (OR) and 95% confidence interval (CI) 2.43 [1.14, 5.17]), and in particular, were diagnosed more often with the mixed cellularity subtype. For all types of lymphoma, we observed an about twofold risk increase with indicators for high risk pregnancies including tocolysis, fetopelvic disproportion and previous preterm birth. NHL risk doubled with the complication premature rupture of membranes (OR and 95% CI 2.18 [1.12, 4.25]) and HL with meconium staining of amniotic fluids (OR and 95% CI 2.55 [1.01, 6.43]).ConclusionThese data support previously reported associations between Hispanic ethnicity and HL and suggest that pregnancy related factors, such as intra-uterine infections and factors associated with preterm labor, may be involved in lymphoma pathogenesis.     

Influence of variation in birth weight within normal range and within sibships on IQ at age 7 years: cohort study

ObjectiveTo examine the relation between birth weight and measured intelligence at age 7 years in children within the normal range of birth weight and in siblings.DesignCohort study of siblings of the same sex.Setting12 cities in the United States.Subjects3484 children of 1683 mothers in a birth cohort study during the years 1959 through 1966. The sample was restricted to children born at ⩾37 weeks gestation and with birth weights of 1500-3999 g.ResultsMean IQ increased monotonically with birth weight in both sexes across the range of birth weight in a linear regression analysis of one randomly selected sibling per family (n= 1683) with adjustment for maternal age, race, education, socioeconomic status, and birth order. Within same sex sibling pairs, differences in birth weight were directly associated with differences in IQ in boys (812 pairs, predicted IQ difference per 100 g change in birth weight =0.50, 95% confidence interval 0.28 to 0.71) but not girls (871 pairs, 0.10, −0.09 to 0.30). The effect in boys remained after differences in birth order, maternal smoking, and head circumference were adjusted for and in an analysis restricted to children with birth weight ⩾ 2500 g.ConclusionThe increase in childhood IQ with birth weight continues well into the normal birth weight range. For boys this relation holds within same sex sibships and therefore cannot be explained by confounding from family social environment.

What is already known on this topic

IQ at school age is linked to birth weight among low birthweight babiesSome evidence suggests the association might also apply to children of normal birth weight

What this study adds

IQ at age 7 years is linearly related to birth weight among children of normal birth weightThe relation was not due to confounding by maternal or socioeconomic factorsIQ is also associated with differences in birth weight between boy sibling pairs but not girls     

Breast cancer incidence by country of birth among immigrant women in British Columbia,Canada

IntroductionBreast cancer rates vary internationally and between immigrant and non-immigrant populations. We describe breast cancer incidence by birth region and country in British Columbia, Canada.MethodsWe linked population-based health and immigration databases for a population with >1.29 million immigrants to assess breast cancer incidence among immigrant and non-immigrant women. We report age-standardized incidence ratios (SIRs) by birth region and country using non-immigrant women as the standard.ResultsSIRs varied widely by both birth country and region. Low rates were found for South (SIR = 0.52, 95% CI: 0.47,0.59) and East Asian (SIR = 0.75, 95% CI: 0.72,0.79) women and a higher rate for Western Europeans (SIR = 1.15, 95% CI: 1.01,1.30).ConclusionThere is considerable variation in SIRs across some of British Columbia’s largest immigrant populations and several demonstrate significantly different risk profiles compared to non-immigrants. These findings provide unique data to support breast cancer prevention and control.     

Longitudinal somatometrical study on the growth patterns of newborn Japanese monkeys

Growth of Japanese macaques during their first year was analyzed longitudinally, using body measurements. Measurements of 44 somatometrical characters were taken on seven animals. Work with the newborn data produced a formula which fits well. The formula is: y=a (x+b) ⁿ (y=size, x=age). At first, growth was analyzed, character by character, using birth sizes and incremental increases. The results show a major growth pattern for many characters: increments vary inversely with birth size. Application of the growth formula produced two further insights: (1) growth pattern is not so simple as imagined from the birth size-increment pattern; and (2) the characters which deviate from the birth size-increment pattern have large growth only at the earliest period (in few months), in spite of their small size. Sex differences were clear within the first year, especially for characters which differ greatly between adults.     

Birth weight and childhood onset type 1 diabetes: population based cohort study

ObjectiveTo assess the associations between birth weight or gestational age and risk of type 1 diabetes.DesignPopulation based cohort study by record linkage of the medical birth registry and the National Childhood Diabetes Registry.SettingTwo national registries in Norway.ParticipantsAll live births in Norway between 1974 and 1998 (1 382 602 individuals) contributed a maximum of 15 years of observation, a total of 8 184 994 person years of observation in the period 1989 to 1998. 1824 children with type 1 diabetes were diagnosed between 1989 and 1998.ResultsThe incidence rate of type 1 diabetes increased almost linearly with birth weight. The rate ratio for children with birth weights 4500 g or more compared with those with birth weights less than 2000 g was 2.21 (95% confidence interval 1.24 to 3.94), test for trend P=0.0001. There was no significant association between gestational age and type 1 diabetes. The results persisted after adjustment for maternal diabetes and other potential confounders.ConclusionThere is a relatively weak but significant association between birth weight and increased risk of type 1 diabetes consistent over a wide range of birth weights.

What is already known on this topic

Results of case-control studies of birth weight and risk of type 1 diabetes have been inconsistentIt is possible that a relatively weak association exists, and large studies are needed to find out if this is the case

What this study adds

This is the largest study of birth weight and type 1 diabetes published to date, and the first one to use a cohort designThe incidence of type 1 diabetes increased almost linearly with increasing birth weight over a wide range of birth weights, independent of gestational age, maternal diabetes, and other potential confoundersThe trend was highly significant, but the increment in risk with increasing birth weight was still relatively low