Higher Offspring Birth Weight Research Articles

Maternal Health, Pregnancy and Offspring Factors, and Maternal Thyroid Cancer Risk: A Nordic Population-Based Registry Study.

Thyroid cancer incidence is higher in women than men, especially during the reproductive years, for reasons that remain poorly understood. Using population-based registry data from 4 Nordic countries through 2015, we examined associations of perinatal characteristics with risk of maternal thyroid cancer. Cases were women diagnosed with thyroid cancer ≥2 years after last birth (n= 7,425, 83% papillary). Cases were matched to controls (n= 67,903) by mother's birth year, country, and county of residence. Odds ratios (ORs) were estimated using conditional logistic regression models adjusting for parity. Older age at first pregnancy, postpartum hemorrhage (OR= 1.18, 95% (confidence interval) CI: 1.08, 1.29), and benign thyroid conditions (ORs ranging from 1.64 for hypothyroidism to 10.35 for thyroid neoplasms) were associated with increased thyroid cancer risk, as were higher offspring birth weight (per 1-kg increase, OR= 1.17, 95% CI: 1.12, 1.22) and higher likelihood of offspring being large for gestational age (OR= 1.26, 95% CI: 1.11, 1.43). Unmarried/noncohabiting status (OR= 0.91, 95% CI: 0.84, 0.98), maternal smoking (OR= 0.75, 95% CI: 0.67, 0.84), and preterm birth (OR= 0.90, 95% CI: 0.83, 0.98) were associated with reduced risk. Several factors (e.g., older age at first pregnancy, maternal smoking, goiter, benign neoplasms, postpartum hemorrhage, hyperemesis gravidarum, and neonatal jaundice) were associated with advanced thyroid cancer. These findings suggest that some perinatal exposures may influence maternal thyroid cancer risk.

Higher maternal adiposity reduces offspring birthweight if associated with a metabolically favourable profile

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.Graphical abstract

Increased α-Linolenic Acid Intake during Pregnancy is Associated with Higher Offspring Birth Weight

BackgroundThe amount and type of fat in the maternal diet during pregnancy are important contributors to fetal growth. The importance of plant-based omega-3 fatty acid (α-linolenic acid, ALA) intake in fetal growth has not been previously examined. ObjectiveWe sought to determine the association of maternal ALA intake during pregnancy with birth weight and body composition of the offspring. MethodsMothers and their newborn infants (n = 224) were recruited from the Royal Prince Alfred Hospital, Australia. Maternal diet during pregnancy was assessed using a validated food frequency questionnaire. Plasma fatty acid composition was analyzed in a subset of mothers (n = 41). Newborn body composition was assessed using air-displacement plethysmography. All analyses were adjusted for gestational age, sex, physical activity, and total energy intake. ResultsDietary fatty acid intakes were positively associated with plasma phospholipid fatty acids for total omega-3 fatty acids (β = 0.452, P = 0.003), ALA (β = 0.339, P = 0.03), linoleic acid (β = 0.353, P = 0.03), eicosapentaenoic acid (β = 0.407, P = 0.009), and docosahexaenoic acid (β = 0.388, P = 0.01). Higher maternal intake of ALA (% total fat) was associated with higher offspring birth weight [189.7-g increase per 1% higher ALA (95% CI: 14, 365 g); P = .04], although individually neither newborn fat mass nor fat-free mass was significant. Birth weight increased across tertiles of maternal ALA intake (PANOVA = 0.05), with birth weight being 221 g (95% CI: 12, 429 g) higher in those with the highest maternal ALA intake compared with those with the lowest intake (P = 0.04). Mothers of infants born small for gestational age (n = 32) had a lower ALA intake than those born appropriate for gestational age (n = 162) or large for gestational age [(n = 21); P = 0.05]. ConclusionsIn otherwise healthy women giving birth at a major tertiary hospital in Australia, intake of ALA during pregnancy is associated with higher offspring birth weight. This may have implications for dietary strategies aimed at optimizing fetal growth via modification of maternal diet.

Assessing causality in associations between maternal adiposity and obstetric and perinatal outcomes: A Mendelian randomization study

Background Observational studies consistently suggest that maternal obesity is related to a number of adverse perinatal outcomes. However, which of these are causal or due to confounding is unclear. We aimed to carry out Mendelian randomization (MR), which uses genetic variants robustly associated with the exposure of interest as instrumental variables (IV), to determine the causal effect of maternal BMI on clinically important obstetric and perinatal outcomes. Methods Data from White European individuals in nine cohorts (ALSPAC, BiB, DNBC-PTB, HAPO, EFSOCH, Generation R, GOYA, Project Viva and INMA) were used (n = 5230 to 24,875 for different outcomes). First, multivariable regression associations between maternal BMI (pre-pregnancy or at the start of pregnancy) and 23 outcomes were examined adjusting for a range of potential confounders. Second, we combined 32 or 97 (depending on availability in cohorts) established genetic variants that have been shown to be robustly associated with BMI in a weighted allele score and used this in IV analyses to obtain causal estimates (allele score Wald ratios) of maternal BMI on each of the outcomes. We used MR-Egger, inverse variance weighting and weighted median IV analysis in sensitivity analysis to explore potential bias due to horizontal pleiotropy. When available, MR analyses for outcomes that could be influenced by offspring genetic predisposition to higher BMI were adjusted for offspring genotype. Results In standard multivariable analysis, a 1 standard deviation (SD, ∼ 4.95 kg/m2) higher maternal BMI was associated with a 0.12 SD (95% CI 0.11–0.14) higher offspring birthweight, 1.73 (95% CI 1.64–1.84) odds ratio (OR) of gestational hypertension and 1.30 (95% CI 1.17–1.93) OR of induced labor. In MR analyses, a 1 standard deviation higher maternal BMI was associated with a 0.11 SD (95% CI 0.06–0.17) higher offspring birthweight, 1.51 (95% CI 1.17–1.93) OR of gestational hypertension and 1.30 (95% CI 1.01–1.72) OR of induced labour. We also found positive associations of maternal BMI with birth length, caesarean delivery, any hypertensive disorder of pregnancy and membrane rupture before onset of contractions in multivariable regression analyses. MR point estimates for effects of BMI on these outcomes were in the same direction and of a similar magnitude to multivariable results, but the 95% confidence intervals were wide and included the null. Lastly, in multivariable regression analyses we found a positive association of BMI with gestational diabetes, which was not supported by MR results. Results from MR Egger regression, inverse variance weighted and weighted median methods were generally consistent and did not suggest strong bias by pleiotropy. Conclusions Our findings support a causal effect of increased maternal BMI on higher birthweight and greater odds of gestational hypertension and induction of labor. MR causal estimates were consistent with associations for many other outcomes. We are currently working with more studies to provide more precise estimates.

The impact of maternal flood-related stress and social support on offspring weight in early childhood.

The current study examined the moderating role of social support in the association between prenatal maternal stress (PNMS) and childhood body mass index (BMI) in the context of the Iowa floods of 2008. In addition, the mediating role of offspring birthweight was examined in the association between PNMS and childhood BMI. We recruited women from eastern Iowa who were pregnant in 2008 when disastrous floods occurred. Self-report measures of PNMS and cognitive appraisal of the flood's consequences were obtained shortly after the disaster. Social support was assessed during pregnancy. Offspring anthropometric measures were collected at birth and 30months. Moderated mediation results indicated that greater PNMS predicted greater BMI at age 30months through effects on higher birthweight as a mediator, but only for participants with low social support. High social support (satisfaction or number) buffered the effect of PNMS or a negative appraisal of the flood on birthweight. The combination of high PNMS or a negative appraisal of the flood's consequences and low social support resulted in higher offspring birthweight, which predicted greater BMI at 30months. Providing strong social support to pregnant women following a stressor might buffer the effects of PNMS on offspring birthweight and later obesity.

Programming of Adiposity in Childhood and Adolescence: Associations With Birth Weight and Cord Blood Adipokines.

Context:Exposure to maternal adiposity during pregnancy is associated with higher offspring birth weight and greater adiposity through childhood and adult life. As birth weight reflects the summation of lean and fat mass, the extent to which fat mass at birth tracks into later life is unknown.Objective:To determine whether fat mass at birth is associated with child and adolescent adiposity.Design, Setting, and Participants:UK birth cohort with markers of neonatal fat mass; cord blood leptin, adiponectin, and birth weight and adiposity outcomes at age 9 (n = 2775) and 17 years (n = 2138).Main Outcomes:Offspring body mass index (BMI), waist circumference, dual-energy X-ray absorptiometry–determined fat mass, and obesity at age 9 and 17 years.Results:Higher cord blood leptin was associated with higher z scores of fat mass [difference in mean per 10 pg/mL: 0.03 standard deviation (SD); 95% confidence interval (CI), 0.00 to 0.06], waist circumference (0.04 SD; 95% CI, 0.00 to 0.07), and BMI (0.04 SD; 95% CI, 0.00 to 0.08) at age 9. However, by age 17 the adjusted results were attenuated to the null. Cord blood adiponectin was not associated with measures of adiposity at age 9. At age 17, cord blood adiponectin was positively associated with fat mass (0.02 SD per 10 μg/mL; 95% CI, 0.02 to 0.03) and waist circumference (0.04 SD per 10 μg/mL; 95% CI, 0.03 to 0.05). Birth weight was positively associated with waist circumference (0.03 SD per 100 g; 95% CI, 0.02 to 0.04) and BMI (0.02 SD per 100 g; 95% CI, 0.00 to 0.03), but not fat mass or odds of obesity. Cord blood leptin and adiponectin were not associated with obesity at either age.Conclusions:Increased cord blood leptin and adiponectin, known surrogates of fetal fat mass, were weakly associated with increased fat mass in late childhood and adolescence, respectively.