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Maternal breast cancer risk in relation to birthweight and gestation of her offspring.

ABSTRACT: BACKGROUND:Parity and age at first pregnancy are well-established risk factors for breast cancer, but the effects of other characteristics of pregnancies are uncertain and the literature is inconsistent. METHODS:In a cohort of 83,451 parous women from the general population of the UK, which collected detailed information on each pregnancy and a wide range of potential confounders, we investigated the associations of length of gestation and birthweight of offspring in a woman's pregnancies with her breast cancer risk, adjusting for a full range of non-reproductive as well as reproductive risk factors unlike in previous large studies. RESULTS:Gestation of the first-born offspring was significantly inversely related to the risk of pre-menopausal breast cancer (p trend?=?0.03; hazard ratio (HR) for 26-31 compared with 40-41 weeks, the baseline group, = 2.38, 95% confidence interval (CI) 1.26-4.49), and was borderline significantly related to risk of breast cancer overall (p trend?=?0.05). Risk was significantly raised in mothers of high birthweight first-born (HR for breast cancer overall?=?1.53, 95% CI 1.06-2.21 for ??4500 g compared with 3000-3499 g, the baseline group). For gestation and birthweight of most recent birth, there were no clear effects. Analyses without adjustment for confounders (other than age) gave similar results. CONCLUSIONS:Our data add to evidence that short gestation pregnancies may increase the risk of breast cancer, at least pre-menopausally, perhaps by hormonal stimulation and breast proliferation early in pregnancy without the opportunity for the differentiation that occurs in late pregnancy. High birthweight first pregnancies may increase breast cancer risk, possibly through the association of birthweight with oestrogen and insulin-like growth factor 1 levels.

SUBMITTER: Swerdlow AJ

PROVIDER: S-EPMC6172803 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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Maternal breast cancer risk in relation to birthweight and gestation of her offspring.

Swerdlow Anthony J AJ Wright Lauren B LB Schoemaker Minouk J MJ Jones Michael E ME

Breast cancer research : BCR 20181005 1

<h4>Background</h4>Parity and age at first pregnancy are well-established risk factors for breast cancer, but the effects of other characteristics of pregnancies are uncertain and the literature is inconsistent.<h4>Methods</h4>In a cohort of 83,451 parous women from the general population of the UK, which collected detailed information on each pregnancy and a wide range of potential confounders, we investigated the associations of length of gestation and birthweight of offspring in a woman's pre ...[more]

PMID: 30286782

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Project description:The health effects of diet are long term and persistent. Few cohort studies have investigated the influence of maternal dietary patterns during different gestational periods on offspring's health outcomes. This study investigated the associations between maternal dietary patterns in the mid- and late-gestation and infant's neurodevelopment at 1 year of age in the Jiangsu Birth Cohort (JBC) Study. A total of 1178 mother-child pairs were available for analysis. A semiquantitative food frequency questionnaire (FFQ) was used to investigate dietary intake at 22-26 and 30-34 gestational weeks (GWs). Neurodevelopment of children aged 1 year old was assessed using Bayley-Ⅲ Screening Test. Principal component analysis (PCA) and Poisson regression were used to extract dietary patterns and to investigate the association between dietary patterns and infant neurodevelopment. After adjusting for potential confounders, the maternal 'Aquatic products, Fresh vegetables and Homonemeae' pattern in the second trimester was associated with a lower risk of being non-competent in cognitive and gross motor development, respectively (cognition: aRR = 0.84; 95% CI 0.74-0.94; gross motor: aRR = 0.80; 95% CI 0.71-0.91), and the similar pattern, 'Aquatic products and Homonemeae', in the third trimester also showed significant association with decreased risk of failing age-appreciate cognitive and receptive communication development (cognition: aRR = 0.89; 95% CI 0.80-0.98; receptive communication: aRR = 0.91; 95% CI 0.84-0.99). Notably, adherence to the dietary pattern with relatively high aquatic and homonemeae products in both trimesters demonstrated remarkable protective effects on child neurodevelopment with the risk of being non-competent in cognitive and gross motor development decreasing by 59% (95% CI 0.21-0.79) and 63% (95% CI 0.18-0.77), respectively. Our findings suggested that adherence to the 'Aquatic products and Homonemeae' dietary pattern during pregnancy may have optimal effects on offspring's neurodevelopment.

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Project description:Aims/hypothesisHigher maternal BMI during pregnancy is associated with higher offspring birthweight, but it is not known whether this is solely the result of adverse metabolic consequences of higher maternal adiposity, such as maternal insulin resistance and fetal exposure to higher glucose levels, or whether there is any effect of raised adiposity through non-metabolic (e.g. mechanical) factors. We aimed to use genetic variants known to predispose to higher adiposity, coupled with a favourable metabolic profile, in a Mendelian randomisation (MR) study comparing the effect of maternal 'metabolically favourable adiposity' on offspring birthweight with the effect of maternal general adiposity (as indexed by BMI).MethodsTo test the causal effects of maternal metabolically favourable adiposity or general adiposity on offspring birthweight, we performed two-sample MR. We used variants identified in large, published genetic-association studies as being associated with either higher adiposity and a favourable metabolic profile, or higher BMI (n = 442,278 and n = 322,154 for metabolically favourable adiposity and BMI, respectively). We then extracted data on the metabolically favourable adiposity and BMI variants from a large, published genetic-association study of maternal genotype and offspring birthweight controlling for fetal genetic effects (n = 406,063 with maternal and/or fetal genotype effect estimates). We used several sensitivity analyses to test the reliability of the results. As secondary analyses, we used data from four cohorts (total n = 9323 mother-child pairs) to test the effects of maternal metabolically favourable adiposity or BMI on maternal gestational glucose, anthropometric components of birthweight and cord-blood biomarkers.ResultsHigher maternal adiposity with a favourable metabolic profile was associated with lower offspring birthweight (-94 [95% CI -150, -38] g per 1 SD [6.5%] higher maternal metabolically favourable adiposity, p = 0.001). By contrast, higher maternal BMI was associated with higher offspring birthweight (35 [95% CI 16, 53] g per 1 SD [4 kg/m2] higher maternal BMI, p = 0.0002). Sensitivity analyses were broadly consistent with the main results. There was evidence of outlier SNPs for both exposures; their removal slightly strengthened the metabolically favourable adiposity estimate and made no difference to the BMI estimate. Our secondary analyses found evidence to suggest that a higher maternal metabolically favourable adiposity decreases pregnancy fasting glucose levels while a higher maternal BMI increases them. The effects on neonatal anthropometric traits were consistent with the overall effect on birthweight but the smaller sample sizes for these analyses meant that the effects were imprecisely estimated. We also found evidence to suggest that higher maternal metabolically favourable adiposity decreases cord-blood leptin while higher maternal BMI increases it.Conclusions/interpretationOur results show that higher adiposity in mothers does not necessarily lead to higher offspring birthweight. Higher maternal adiposity can lead to lower offspring birthweight if accompanied by a favourable metabolic profile.Data availabilityThe data for the genome-wide association studies (GWAS) of BMI are available at https://portals.broadinstitute.org/collaboration/giant/index.php/GIANT_consortium_data_files . The data for the GWAS of body fat percentage are available at https://walker05.u.hpc.mssm.edu .

Dataset Information

Maternal breast cancer risk in relation to birthweight and gestation of her offspring.

Publications

Maternal breast cancer risk in relation to birthweight and gestation of her offspring.

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