Standard Deviation Increase In Birth Weight Research Articles

Application of 4-way decomposition to the analysis of placental-fetal biomarkers as intermediary variables between maternal body mass index and birthweight.

Human chorionic gonadotropin (hCG) is a placental hormone measured in pregnancy to predict individual level risk of fetal aneuploidy and other complications; yet may be useful in understanding placental origins of child development more generally. hCG was associated with maternal body mass index (BMI) and with birthweight. The primary aim here was to evaluate hCG as a mediator of maternal BMI effects on birthweight by causal mediation analysis. Subjects were 356 women from 3 U.S. sites (2010-2013). The 4-way decomposition method using med4way (STATA) was applied to screen for 5 types of effects of first trimester maternal BMI on birthweight: the total effect, the direct effect, mediation by hCG, additive interaction of BMI and hCG, and mediation in the presence of an additive interaction. Effect modification by fetal sex was evaluated, and a sensitivity analysis was performed to evaluate the assumption of unmeasured confounding. Additional placental-fetal biomarkers [pregnancy associated plasma protein A (PAPPA), second trimester hCG, inhibin-A, estriol, alpha fetoprotein] were analyzed for comparison. For first trimester hCG, there was a 0.20 standard deviation increase in birthweight at the 75th vs. 25th percentile of maternal BMI (95% CI 0.04, 0.36). Once stratified, the direct effect association was null in women carrying females. In women carrying males, hCG did not mediate the relationship. In women carrying females, there was a mediated effect of maternal BMI on birthweight by hCG in the reverse direction (-0.06, 95% CI: -0.12, 0.01), and a mediated interaction in the positive direction (0.06, 95% CI 0.00, 0.13). In women carrying males, the maternal BMI effect on birthweight was reverse mediated by PAPPA (-0.09, 95% CI: -0.17, 0.00). Sex-specific mediation was mostly present in the first trimester. Second trimester AFP was a positive mediator of maternal BMI effects in male infants only (0.06, 95% CI: -0.01, 0.13). Effect estimates were robust to potential bias due to unmeasured confounders. These findings motivate research to consider first trimester placental biomarkers and sex-specific mechanisms when quantifying the effects of maternal adiposity on fetal growth.

Maternal central obesity and birth size: a Mendelian randomization analysis

BackgroundObservational studies have illustrated that maternal central obesity is associated with birth size, including of birth weight, birth length and head circumference, but the causal nature of these associations remains unclear. Our study aimed to test the causal effect of maternal central obesity on birth size and puberty height growth using a Mendelian randomization (MR) analysis.MethodsWe performed two-sample MR using summary-level genome-wide public data. Thirty-five single nucleotide polymorphisms (SNPs), 25 SNPs and 41 SNPs were selected as instrumental variables for waist-to-hip ratio adjusted for BMI, waist circumference adjusted for BMI and hip circumference adjusted for BMI, respectively to test the causal effects of maternal central obesity on birth size and puberty height using an inverse-variance-weighted approach.ResultsIn this MR analysis, we found no evidence of a causal association between waist circumference or waist-to-hip ratio and the outcomes. However, we observed that one standard deviation (SD) increase in hip circumference (HIP) was associated with a 0.392 SD increase in birth length (p = 1.1 × 10− 6) and a 0.168 SD increase in birth weight (p = 7.1 × 10− 5), respectively at the Bonferroni-adjusted level of significance. In addition, higher genetically predicted maternal HIP was strongly associated with the puberty heights (0.835 SD, p = 8.4 × 10− 10). However, HIP was not associated with head circumference (p = 0.172).ConclusionsA genetic predisposition to higher maternal HIP was causally associated with larger offspring birth size independent of maternal BMI. However, we found no evidence of a causal association between maternal waist circumference, waist-to-hip ratio and birth size.

Maternal Central Obesity and Birth Size—A Mendelian Randomization Analysis

Background: Observational studies have illustrated that maternal central obesity is associated with birth size,including of birth weight, birth length and head circumference, but the causal nature of these associations remains unclear. Objective: To test the causal effect of maternal central obesity on birth size and puberty height growth using a Mendelian randomization (MR) analysis. Methods: We performed two-sample MR using summary-level genome-wide public data from the Genetic Investigation of Anthropometric Traits (GIANT) Consortium and the Early Growth Genetics Consortium (EGG). Thirty-five single nucleotide polymorphisms (SNPs), 25 SNPs and 41SNPs were selected as instrumental variables for waist-to-hip ratio adjust BMI (WHRadjBMI), waist circumference adjust BMI (WCadjBMI) and hip circumference adjust BMI (HIPadjBMI), respectively to test the causal effects of maternal central obesity on birth size and puberty height using an inverse-variance-weighted approach. Results: In this MR analysis, we found no evidence between genetic instrumental variables for waist circumference (WC)or waist-to-hip ratio (WHR) and the outcomes. We observed one standard deviation (SD) increase in hip circumference (HC) was associated with a 0.392 SD increase in birth length (p=1.1×10-6) and a 0.168 SD increase in birth weight (p=7.1×10-5), respectively.In addition, higher genetically predicted maternal HP was strongly associated with the puberty heights (0.835 SD, p=8.4×10-10). However,HP was not associated with head circumference(p=0.172). Conclusion: A genetic predisposition to higher maternal HC was causally associated with larger offspring birth weight,higher birth length, and puberty height independent of maternal BMI. However, we found no evidence of a causal association between maternal WC, WHR and birth size. Disclosure T. Huang: None. T. Geng: None.

Birth weight and maternal socioeconomic circumstances were inversely related to systolic blood pressure among Afro-Caribbean young adults

ObjectivesIn this study, we examined the effects of birth weight (BWT) and early life socioeconomic circumstances (SEC) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) among Jamaican young adults. Study Design and SettingLongitudinal study of 364 men and 430 women from the Jamaica 1986 Birth Cohort Study. Information on BWT and maternal SEC at child's birth was linked to information collected at 18–20 years old. Sex-specific multilevel linear regression models were used to examine whether adult SBP/DBP was associated with BWT and maternal SEC. ResultsIn unadjusted models, SBP was inversely related to BWT z-score in both men (β, −0.82 mm Hg) and women (β, −1.18 mm Hg) but achieved statistical significance for women only. In the fully adjusted model, one standard deviation increase in BWT was associated with 1.16 mm Hg reduction in SBP among men [95% confidence interval (CI): 2.15, 0.17; P = 0.021] and 1.34 mm Hg reduction in SBP among women (95% CI: 2.21, 0.47; P = 0.003). Participants whose mothers had lower SEC had higher SBP compared with those with mothers of high SEC (β, 3.4–4.8 mm Hg for men, P < 0.05 for all SEC categories and 1.8–2.1 for women, P > 0.05). ConclusionSBP was inversely related to maternal SEC and BWT among Jamaican young adults.

Parental diabetes and birthweight in 236 030 individuals in the UK Biobank Study

Background The UK Biobank study provides a unique opportunity to study the causes and consequences of disease. We aimed to use the UK Biobank data to study the well-established, but poorly understood, association between low birthweight and type 2 diabetes.Methods We used logistic regression to calculate the odds ratio for participants’ risk of type 2 diabetes given a one standard deviation increase in birthweight. To test for an association between parental diabetes and birthweight, we performed linear regression of self-reported parental diabetes status against birthweight. We performed path and mediation analyses to test the hypothesis that birthweight partly mediates the association between parental diabetes and participant type 2 diabetes status.Results Of the UK Biobank participants, 277 261 reported their birthweight. Of 257 715 individuals of White ethnicity and singleton pregnancies, 6576 had type 2 diabetes, 19 478 reported maternal diabetes (but not paternal), 20 057 reported paternal diabetes (but not maternal) and 2754 participants reported both parents as having diabetes. Lower birthweight was associated with type 2 diabetes in the UK Biobank participants. A one kilogram increase in birthweight was associated with a lower risk of type 2 diabetes (odds ratio: 0.74; 95% CI: 0.71, 0.76; P = 2 × 10−57). Paternal diabetes was associated with lower birthweight (45 g lower; 95% CI: 36, 54; P = 2 × 10−23) relative to individuals with no parental diabetes. Maternal diabetes was associated with higher birthweight (59 g increase; 95% CI: 50, 68; P = 3 × 10−37). Participants’ lower birthweight was a mediator of the association between reported paternal diabetes and participants’ type 2 diabetes status, explaining 1.1% of the association, and participants’ higher birthweight was a mediator of the association between reported maternal diabetes and participants’ type 2 diabetes status, explaining 1.2% of the association.Conclusions Data from the UK Biobank provides the strongest evidence by far that paternal diabetes is associated with lower birthweight, whereas maternal diabetes is associated with increased birthweight. Our findings with paternal diabetes are consistent with a role for the same genetic factors influencing foetal growth and type 2 diabetes.

Birth size and survival in breast cancer patients from the Uppsala Birth Cohort Study

Previous studies suggest that larger birth size is associated with a higher breast cancer incidence, but studies on birth measures and mortality in breast cancer cases are scarce. This study investigates survival of women after breast cancer diagnosis (n = 437) in the Uppsala Birth Cohort born in 1915-1929. Cox regression was used to analyze mortality from any cause after a breast cancer diagnosis. Birth measures including gestational age (GA), birth weight (BW), BW for GA, birth length, and ponderal index (PI) were converted to standard deviation (SD) scores, and all analyses were adjusted for age and calendar time at diagnosis. Analyses were performed with and without adjustment for other birth measures, reproductive history, and adult socioeconomic position. In fully adjusted analyses, one SD increase in GA was associated with 17% [95% confidence interval (CI) 6-26%] lower mortality and one SD increase in BW was associated with 29% (7-56%) higher mortality. PI showed a weaker trend in the same direction: hazard ratio = 1.16 (95% CI 1.03-1.30). Our results bring in new evidence that both high GA and low BW predict a better survival in breast cancer cases. Further studies need to investigate mediation of these associations.

OP41 Birth Size and Mortality in Breast Cancer Patients

BackgroundPrevious studies suggest that larger birth size is associated with a higher breast cancer incidence, but the few studies of birth measures and mortality in breast cancer cases have been...

Body mass index throughout the life-course and blood pressure in mid-adult life: a birth cohort study

The contribution of body mass index (BMI) at different life stages to adult blood pressure (BP) is not well known. We investigated whether changes in BMI across childhood and adulthood, and birthweight, influence BP in mid-adulthood. In 9297 participants in the 1958 British birth cohort, we analysed BMI measures at several ages (7, 11, 16, 33 and 45 years) and BP at 45 years. Positive BMI/BP associations strengthened with age; at 45 years a standard deviation (SD) increase in concurrent BMI was associated with an increase in systolic blood pressure (SBP) of 3.9 mmHg [95% confidence interval (CI) 3.6-4.2] and an elevated risk of hypertension (odds ratio 1.68; 95% CI 1.60-1.76). The effect of concurrent BMI on BP strengthened with decreasing childhood BMI; among the thinnest 10% at 11 years, SBP increased by 5.5 mmHg per SD increase in concurrent BMI; among the heaviest 10% the increase was 3.3 mmHg. Excessive BMI gain, especially recently, was associated with raised BP; allowing for BMI at 33 years, a SD increase in BMI between 33 and 45 years was associated with an SBP increase of 4.1 mmHg (95% CI 3.6-4.6). Birthweight was inversely associated with BP; SBP reduced by 1.3 mmHg (95% CI 0.9-1.7) per SD increase in birthweight, independently of BMI. High BMI and excessive BMI gain at any life stage, particularly recently, is associated with increased adult BP. Relatively thin children were vulnerable to BMI gain and increased BP in adulthood. Elevated BP associated with low birthweight was not caused by 'catch-up' growth.

Birth characteristics and adult cancer incidence: Swedish cohort of over 11,000 men and women

Associations between larger size at birth and increased rates of adult cancer have been proposed but few empirical studies have examined this hypothesis. We investigated overall and site-specific cancer incidence in relation to birth characteristics in a Swedish population-based cohort of 11,166 singletons born in 1915-1929 for whom we have detailed obstetric data and who were alive in 1960. A total of 2,685 first primary cancers were registered during follow-up from 1960 to 2001. A standard deviation (SD) increase in birth weight for gestational age (GA) was associated with (sex-adjusted) increases of 13% (95% CI = 0.03-0.23) in the rates of digestive cancers and of 17% (95% CI = 0.01-0.35) in the rates of lymphatic cancers. Women who had higher birth weights also had increased rates of breast cancer under age 50 years (by 39% per SD increase; 95% CI = 0.09-0.79), but reduced rates (by 24%; 95% CI = 0.07-0.38) of endometrial (corpus uteri) cancer at all ages. There was no evidence of associations with other cancer sites. For overall cancer incidence, men had an 8% increased risk at all ages per SD increase in birth weight for GA while women only had an increased risk under age 50 years (mainly driven by the association with breast cancer). These findings provide evidence of a modest association of birth size and adult cancer risk, resulting from positive associations with a few cancer sites and a possible inverse association with endometrial cancer.