Rapid recovery of fat mass in small for gestational age preterm infants after term

Background

Preterm small for gestational age (SGA) infants may be at risk for increased adiposity, especially when experiencing rapid postnatal weight gain. Data on the dynamic features of body weight and fat mass (FM) gain that occurs early in life is scarce. We investigated the postnatal weight and FM gain during the first five months after term in a cohort of preterm infants.

Methodology/Principal Findings

Changes in growth parameters and FM were prospectively monitored in 195 infants with birth weight ≤1500 g. The infants were categorized as born adequate for gestational age (AGA) without growth retardation at term (GR−), born AGA with growth retardation at term (GR+), born SGA. Weight and FM were assessed by an air displacement plethysmography system. At five months, weight z-score was comparable between the AGA (GR+) and the AGA (GR−), whereas the SGA showed a significantly lower weight.The mean weight (g) differences (95% CI) between SGA and AGA (GR−) and between SGA and AGA (GR+) infants at 5 months were −613 (−1215; −12) and −573 (−1227; −79), respectively. At term, the AGA (GR+) and the SGA groups showed a significantly lower FM than the AGA (GR−) group. In the first three months, change in FM was comparable between the AGA (GR+) and the SGA groups and significantly higher than that of the AGA (GR−) group.The mean difference (95% CI) in FM change between SGA and AGA (GR−) and between AGA (GR+) and AGA (GR−) from term to 3 months were 38.6 (12; 65); and 37.7 (10; 65). At three months, the FM was similar in all groups.

Conclusions

Our data suggests that fetal growth pattern influences the potential to rapidly correct anthropometry whereas the restoration of fat stores takes place irrespective of birth weight. The metabolic consequences of these findings need to be elucidated.     

Early-life determinants of total and HDL cholesterol concentrations in 8-year-old children; the PIAMA birth cohort study

Background

Adult cholesterol concentrations might be influenced by early-life factors, such as breastfeeding and birth weight, referred to as “early programming”. How such early factors exert their influence over the life course is still poorly understood. Evidence from studies in children and adolescents is scarce and conflicting. We investigated the influence of 6 different perinatal risk factors on childhood total and HDL cholesterol concentrations and total-to-HDL cholesterol ratio measured at 8 years of age, and additionally we studied the role of the child''s current Body Mass Index (BMI).

Methods

Anthropometric measures and blood plasma samples were collected during a medical examination in 751 8-year-old children participating in the prospective Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study. Linear and logistic regression were performed to estimate associations of total and HDL cholesterol concentrations with breastfeeding, birth weight, infant weight gain, maternal overweight before pregnancy, gestational diabetes and maternal smoking during pregnancy, taking into account the child''s current BMI.

Results

Linear regressions showed an association between total-to-HDL cholesterol ratio and maternal pre-pregnancy overweight (β = 0.15, Confidence Interval 95% (CI): 0.02, 0.28), rapid infant weight gain (β = 0.13, 95%CI: 0.01, 0.26), and maternal smoking during pregnancy (β = 0.14, 95%CI: 0.00, 0.29). These associations were partly mediated by the child''s BMI.

Conclusion

Total-to-HDL cholesterol ratio in 8-year-old children was positively associated with maternal pre-pregnancy overweight, maternal smoking during pregnancy and rapid infant weight gain.     

Defining smallness for gestational age in the early years of the Danish Medical Birth Registry

Background

Being born small for gestational age (SGA) is associated with decreased insulin sensitivity and increased blood pressure in childhood, but the association with clinical disease in early adulthood is less certain. The Danish Medical Birth Registry has registered all births in Denmark since 1973, but due to variable data quality, data is most often used only from 1981 onwards, and birth registers in other countries may have similar problems for the early years. We wanted to examine whether the data can be used for identification of children born SGA and used in future research.

Methodology/Principal Findings

All persons born between 1974 and 1996 were identified in the Danish Medical Birth Registry (n = 1.704.890). Immigrants and children without data on gestational age and birth weight were excluded, and a total of 1.348.106 children were included in the analysis. The difference between the different variables used in the history of the registry were examined, and the quality of data in the birth registry from 1974-1981 was examined and compared to subsequent years.Data on birth weight and gestational age in the early years of the registry is inconsistent, and the identification of children born SGA is inaccurate, with 49% false-positives. The biggest source of error is due to the rough and inaccurate intervals used for gestational age. By using –3 standard deviations as a cut-off for the identification of children born SGA, the number of false-positives was reduced to 9%, while the amount of false-negatives were increased.

Conclusion

Choosing –3 standard deviations for identifying children born SGA is a viable, though not optimal solution for identifying children born SGA. Overall the data in the registry is of sufficient quality to be used in further medical research.     

Caloric restriction induces changes in insulin and body weight measurements that are inversely associated with subsequent weight regain

Background

Successful weight maintenance following weight loss is challenging for many people. Identifying predictors of longer-term success will help target clinical resources more effectively. To date, focus has been predominantly on the identification of predictors of weight loss. The goal of the current study was to determine if changes in anthropometric and clinical parameters during acute weight loss are associated with subsequent weight regain.

Methodology

The study consisted of an 8-week low calorie diet (LCD) followed by a 6-month weight maintenance phase. Anthropometric and clinical parameters were analyzed before and after the LCD in the 285 participants (112 men, 173 women) who regained weight during the weight maintenance phase. Mixed model ANOVA, Spearman correlation, and linear regression were used to study the relationships between clinical measurements and weight regain.

Principal Findings

Gender differences were observed for body weight and several clinical parameters at both baseline and during the LCD-induced weight loss phase. LCD-induced changes in BMI (Spearman’s ρ = 0.22, p = 0.0002) were inversely associated with weight regain in both men and women. LCD-induced changes in fasting insulin (ρ = 0.18, p = 0.0043) and HOMA-IR (ρ = 0.19, p = 0.0023) were also associated independently with weight regain in both genders. The aforementioned associations remained statistically significant in regression models taking account of variables known to independently influence body weight.

Conclusions/Significance

LCD-induced changes in BMI, fasting insulin, and HOMA-IR are inversely associated with weight regain in the 6-month period following weight loss.     

Delivery of a small for gestational age infant and greater maternal risk of ischemic heart disease

Background

Delivery of a small for gestational age (SGA) infant has been associated with increased maternal risk of ischemic heart disease (IHD). It is uncertain whether giving birth to SGA infant is a specific determinant of later IHD, independent of other risk factors, or a marker of general poor health. The purpose of this study was to investigate the association between delivery of a SGA infant and maternal risk for IHD in relation to traditional IHD risk factors.

Methods and Findings

Risk of maternal IHD was evaluated in a population based cross-sectional study of 6,608 women with a prior live term birth who participated in the National Health and Nutrition Examination Survey (1999–2006), a probability sample of the U.S. population. Sequence of events was determined from age at last live birth and at diagnosis of IHD. Delivery of a SGA infant is strongly associated with greater maternal risk for IHD (age adjusted OR; 95% CI: 1.8; 1.2, 2.9; p = 0.012). The association was independent of the family history of IHD, stroke, hypertension and diabetes (family history-adjusted OR; 95% CI: 1.9; 1.2, 3.0; p = 0.011) as well as other risk factors for IHD (risk factor-adjusted OR; 95% CI: 1.7; 1.1, 2.7; p = 0.025). Delivery of a SGA infant was associated with earlier onset of IHD and preceded it by a median of 30 (interquartile range: 20, 36) years.

Conclusions

Giving birth to a SGA infant is strongly and independently associated with IHD and a potential risk factor that precedes IHD by decades. A pregnancy that produces a SGA infant may induce long-term cardiovascular changes that increase risk for IHD.     

Increased birth weight associated with regular pre-pregnancy deworming and weekly iron-folic acid supplementation for Vietnamese women

Background

Hookworm infections are significant public health issues in South-East Asia. In women of reproductive age, chronic hookworm infections cause iron deficiency anaemia, which, upon pregnancy, can lead to intrauterine growth restriction and low birth weight. Low birth weight is an important risk factor for neonatal and infant mortality and morbidity.

Methodology

We investigated the association between neonatal birth weight and a 4-monthly deworming and weekly iron-folic acid supplementation program given to women of reproductive age in north-west Vietnam. The program was made available to all women of reproductive age (estimated 51,623) in two districts in Yen Bai Province for 20 months prior to commencement of birth weight data collection. Data were obtained for births at the district hospitals of the two intervention districts as well as from two control districts where women did not have access to the intervention, but had similar maternal and child health indicators and socio-economic backgrounds. The primary outcome was low birth weight.

Principal Findings

The birth weights of 463 infants born in district hospitals in the intervention (168) and control districts (295) were recorded. Twenty-six months after the program was started, the prevalence of low birth weight was 3% in intervention districts compared to 7.4% in control districts (adjusted odds ratio 0.29, 95% confidence interval 0.10 to 0.81, p = 0.017). The mean birth weight was 124 g (CI 68 - 255 g, p<0.001) greater in the intervention districts compared to control districts.

Conclusions/Significance

The findings of this study suggest that providing women with regular deworming and weekly iron-folic acid supplements before pregnancy is associated with a reduced prevalence of low birth weight in rural Vietnam. The impact of this health system-integrated intervention on birth outcomes should be further evaluated through a more extensive randomised-controlled trial.     

Maternal influenza immunization and reduced likelihood of prematurity and small for gestational age births: a retrospective cohort study

Background

Infections during pregnancy have the potential to adversely impact birth outcomes. We evaluated the association between receipt of inactivated influenza vaccine during pregnancy and prematurity and small for gestational age (SGA) births.

Methods and Findings

We conducted a cohort analysis of surveillance data from the Georgia (United States) Pregnancy Risk Assessment Monitoring System. Among 4,326 live births between 1 June 2004 and 30 September 2006, maternal influenza vaccine information was available for 4,168 (96.3%). The primary intervention evaluated in this study was receipt of influenza vaccine during any trimester of pregnancy. The main outcome measures were prematurity (gestational age at birth <37 wk) and SGA (birth weight <10th percentile for gestational age). Infants who were born during the putative influenza season (1 October–31 May) and whose mothers were vaccinated against influenza during pregnancy were less likely to be premature compared to infants of unvaccinated mothers born in the same period (adjusted odds ratio [OR] = 0.60; 95% CI, 0.38–0.94). The magnitude of association between maternal influenza vaccine receipt and reduced likelihood of prematurity increased during the period of at least local influenza activity (adjusted OR = 0.44; 95% CI, 0.26–0.73) and was greatest during the widespread influenza activity period (adjusted OR = 0.28; 95% CI, 0.11–0.74). Compared with newborns of unvaccinated women, newborns of vaccinated mothers had 69% lower odds of being SGA (adjusted OR = 0.31; 95% CI, 0.13–0.75) during the period of widespread influenza activity. The adjusted and unadjusted ORs were not significant for the pre-influenza activity period.

Conclusions

This study demonstrates an association between immunization with the inactivated influenza vaccine during pregnancy and reduced likelihood of prematurity during local, regional, and widespread influenza activity periods. However, no associations were found for the pre-influenza activity period. Moreover, during the period of widespread influenza activity there was an association between maternal receipt of influenza vaccine and reduced likelihood of SGA birth. Please see later in the article for the Editors'' Summary     

Effects of genetic variants in ADCY5, GIPR, GCKR and VPS13C on early impairment of glucose and insulin metabolism in children

Objective

Recent genome-wide association studies identified novel candidate genes for fasting and 2 h blood glucose and insulin levels in adults. We investigated the role of four of these loci (ADCY5, GIPR, GCKR and VPS13C) in early impairment of glucose and insulin metabolism in children.

Research Design and Methods

We genotyped four variants (rs2877716; rs1260326; rs10423928; rs17271305) in 638 Caucasian children with detailed metabolic testing including an oGTT and assessed associations with measures of glucose and insulin metabolism (including fasting blood glucose, insulin levels and insulin sensitivity/secretion indices) by linear regression analyses adjusted for age, sex, BMI-SDS and pubertal stage.

Results

The major allele (C) of rs2877716 (ADCY5) was nominally associated with decreased fasting plasma insulin (P = 0.008), peak insulin (P = 0.009) and increased QUICKI (P = 0.016) and Matsuda insulin sensitivity index (P = 0.013). rs17271305 (VPS13C) was nominally associated with 2 h blood glucose (P = 0.009), but not with any of the insulin or insulin sensitivity parameters. We found no association of the GIPR and GCKR variants with parameters of glucose and insulin metabolism. None of the variants correlated with anthropometric traits such as height, WHR or BMI-SDS, which excluded potential underlying associations with obesity.

Conclusions

Our data on obese children indicate effects of genetic variation within ADCY5 in early impairment of insulin metabolism and VPS13C in early impairment of blood glucose homeostasis.     

Impact of early growth on postprandial responses in later life

Background

Low birth weight and slow growth during infancy are associated with increased rates of chronic diseases in adulthood. Associations with risk factors such as fasting glucose and lipids concentrations are weaker than expected based on associations with disease. This could be explained by differences in postprandial responses, which, however, have been little studied. Our aim was to examine the impact of growth during infancy on postprandial responses to a fast-food meal (FF-meal) and a meal, which followed the macro-nutrient composition of the dietary guidelines (REC-meal).

Methodology/Principal Findings

We recruited 24 overweight 65–75 year-old subjects, 12 with slow growth during infancy (SGI-group) and 12 with normal early growth. All the subjects were born at term. The study meals were isocaloric and both meals were consumed once. Plasma glucose, insulin, triglycerides (TG) and free fatty acids (FFA) were measured in fasting state and over a 4-h period after both meals. Subjects who grew slowly during infancy were also smaller at birth. Fasting glucose, insulin or lipid concentrations did not differ significantly between the groups. The TG responses were higher for the SGI-group both during the FF-meal (P = 0.047) and the REC-meal (P = 0.058). The insulin responses were significantly higher for the SGI-group after the FF-meal (P = 0.036). Glucose and FFA responses did not differ significantly between the groups.

Conclusions

Small birth size and slow early growth predict postprandial TG and insulin responses. Elevated responses might be one explanation why subjects who were small at birth and experiencing slow growth in infancy are at an increased risk of developing cardiovascular diseases in later life.     

Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians

Background

A feature of the Asian Indian phenotype is low birth weight with increased adult type 2 diabetes risk. Most populations show consistent associations between low birth weight and adult type 2 diabetes. Recently, two birth weight-lowering loci on chromosome 3 (near CCNL1 and ADCY5) were identified in a genome-wide association study, the latter of which is also a type 2 diabetes locus. We therefore tested the impact of these genetic variants on birth weight and adult glucose/insulin homeostasis in a large Indian birth cohort.

Methodology/Principal Findings

Adults (n = 2,151) enrolled in a birth cohort (established 1969-73) were genotyped for rs900400 (near CCNL1) and rs9883204 (ADCY5). Associations were tested for birth weight, anthropometry from infancy to adulthood, and type 2 diabetes related glycemic traits. The average birth weight in this population was 2.79±0.47 kg and was not associated with genetic variation in CCNL1 (p = 0.87) or ADCY5 (p = 0.54). Allele frequencies for the ‘birth weight-lowering’ variants were similar compared with Western populations. There were no significant associations with growth or adult weight. However, the ‘birth weight-lowering’ variant of ADCY5 was associated with modest increase in fasting glucose (β 0.041, p = 0.027), 2-hours glucose (β 0.127, p = 0.019), and reduced insulinogenic index (β -0.106, p = 0.050) and 2-hour insulin (β -0.058, p = 0.010).

Conclusions

The low birth weight in Asian Indians is not even partly explained by genetic variants near CCNL1 and ADCY5 which implies that non-genetic factors may predominate. However, the ‘birth-weight-lowering’ variant of ADCY5 was associated with elevated glucose and decreased insulin response in early adulthood which argues for a common genetic cause of low birth weight and risk of type 2 diabetes.     

MVPA is associated with lower weight gain in 8-10 year old children: a prospective study with 1 year follow-up

Background

Studies relating physical activity (PA) to weight gain in children have produced mixed results, although there is some evidence for stronger associations with more intense physical activities. The present study tested the hypothesis that weight gain over one year in 8–10 year olds would be more strongly predicted by moderate and vigorous physical activity (MVPA) than total physical activity (total PA) or sedentary behaviour.

Methodology

Participants were 280 children taking part in the Physical Exercise and Appetite in Children Study (PEACHES). Weight status was assessed using body mass index (BMI), fat mass index (FMI), and waist circumference (WC) in school Year 4 (baseline; age 8.7 yrs) and Year 5 (follow-up; age 9.7 yrs). Physical activity was measured at baseline using the Actigraph GT1M accelerometer to assess total PA (mean accelerometers counts per minute), MVPA; ≥4000 counts per minute) and sedentary time (<100 counts per minute).

Principal Findings

After adjustment for baseline BMI, SES, sex and ethnicity, MVPA was significantly associated with follow–up BMI (adjusted β = −0.07; p = 0.002). This association was independent of total PA or sedentary time. Similar results were observed for FMI; again MVPA was significantly associated with follow up FMI (β = −0.16; p = 0.001) independent of total PA or sedentary time. The pattern was similar for WC (β = −0.07), but the association between MVPA and WC did not reach significance at p = 0.06.

Conclusion

The results of this study strongly support promotion of MVPA in children.     

Chronic maternal depression is associated with reduced weight gain in latino infants from birth to 2 years of age

Background

Latino children are at increased risk for mirconutrient deficiencies and problems of overweight and obesity. Exposures in pregnancy and early postpartum may impact future growth trajectories.

Objectives

To evaluate the relationship between prenatal and postnatal maternal depressive symptoms experienced in pregnancy and infant growth from birth to 2 years of age in a cohort of Latino infants.

Methods

We recruited pregnant Latina mothers at two San Francisco hospitals and followed their healthy infants to 24 months of age. At 6, 12 and 24 months of age, infants were weighed and measured. Maternal depressive symptoms were assessed prenatally and at 4-6 weeks postpartum. Women who had high depressive symptoms at both time periods were defined as having chronic depression. Logistic mixed models were applied to compare growth curves and risk for overweight and underweight based on exposure to maternal depression.

Results

We followed 181 infants to 24 months. At 12 and 24 months, respectively, 27.4% and 40.5% were overweight, and 5.6% and 2.2% were underweight. Exposure to chronic maternal depression was associated with underweight (OR = 12.12, 95%CI 1.86-78.78) and with reduced weight gain in the first 2 years of life (Coef = -0.48, 95% CI -0.94—0.01) compared with unexposed infants or infants exposed to episodic depression (depression at one time point). Exposure to chronic depression was also associated with reduced risk for overweight in the first 2 years of life (OR 0.28, 95%CI 0.03-0.92).

Conclusions

Exposure to chronic maternal depression in the pre- and postnatal period was associated with reduced weight gain in the first two years of life and greater risk for failure to thrive, in comparison with unexposed infants or those exposed episodically. The infants of mothers with chronic depression may need additional nutritional monitoring and intervention.     

Fetal Growth Is Associated with Maternal Fasting Plasma Glucose at First Prenatal Visit

Aims

Fasting plasma glucose (FPG) concentration measured at the first prenatal visit is a predictor of gestational diabetes mellitus (GDM); however, whether this test is indicative of fetal growth has not been clarified. Thus, the purpose of this study was to determine whether birth weight and birth length were related to FPG levels at the first prenatal visit.

Materials and Methods

Research samples were collected from pregnant women who took an FPG test at their first prenatal visit (10–24 gestational weeks), received regular prenatal care, and delivered in our center. FPG value, maternal pre-gravid BMI, weight gain before FPG test, before and after Oral Glucose Tolerance Test (OGTT), neonatal birthweight, birth length, Ponderal Index and birthing method were recorded for analysis. Data were analyzed by independent sample t test, Pearson correlation, and Chi-square test, followed by partial correlation or logistic regression to confirm differences. Statistical significance level was α = 0.05.

Results

2284 pregnant women, including 462 GDM and 1822 with normal glucose tolerance (NGT) were recruited for the present study. FPG concentration at the first prenatal visit was associated with neonatal birth weight (partial correlation coefficient r′ = 0.089, P<0.001) and birth length (partial correlation coefficient r′ = 0.061, P = 0.005), but not with Ponderal Index or birthing method. Maternal pre-gravid BMI was associated with FPG value (partial correlation coefficient r′ = 0.113, P<0.001). FPG concentration at the first prenatal visit (OR = 2.945, P<0.001), weight gain before OGTT test (OR = 1.039, P = 0.010), and age (OR = 1.107, P<0.001) were independent related factors of GDM.

Conclusion

Fasting plasma glucose concentration at the first prenatal visit is associated with fetal growth. Maternal pre-gravid BMI and weight gain are related to glucose metabolism.     

Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study

Background

Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects.

Aim

We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake.

Methods and Findings

Participants, aged 20–60 years at baseline, came from five European countries. Cases (‘weight gainers’) were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a ‘weight gainer’ (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin β gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2×10⁻⁷).

Conclusions

We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation.     

Maternal psychosocial stress during pregnancy and placenta weight: evidence from a national cohort study

Background

To study in a large-scale cohort with prospective data the associations between psychosocial stress during pregnancy and placenta weight at birth. Animal data suggest that the placenta is involved in stress-related fetal programming.

Methodology/Principal Findings

We defined a priori two types of psychosocial stress during pregnancy, life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). We estimated the associations of maternal stress during pregnancy with placenta weight at birth, controlled for length of gestation, by predicting gestational age- and sex-specific z-scores of placenta weight through multiple regression analysis, adjusted for potential confounders (N = 78017 singleton pregnancies). Life stress (per increase in stress score by 1, range: 0–18) during pregnancy was associated with increased placenta weight at birth (z-score, reported in 10⁻³; B, 14.33; CI, 10.12–18.54). In contrast, emotional symptoms during pregnancy were not associated with placenta weight at birth.

Conclusions/Significance

Maternal life stress but not emotional symptoms during pregnancy was associated with increased placenta weight at birth; yet, the association-estimate was rather small. Our results may contribute to a better understanding of the role of the placenta in the regulation of intrauterine processes in response to maternal stress.     

Maternal Prepregnancy Body Mass Index and Gestational Weight Gain on Pregnancy Outcomes

Objective

The aim of the present study was to evaluate the single and joint associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) with pregnancy outcomes in Tianjin, China.

Methods

Between June 2009 and May 2011, health care records of 33,973 pregnant women were collected and their children were measured for birth weight and birth length. The independent and joint associations of prepregnancy BMI and GWG based on the Institute of Medicine (IOM) guidelines with the risks of pregnancy and neonatal outcomes were examined by using Logistic Regression.

Results

After adjustment for all confounding factors, maternal prepregnancy BMI was positively associated with risks of gestational diabetes mellitus (GDM), pregnancy-induced hypertension, caesarean delivery, preterm delivery, large-for-gestational age infant (LGA), and macrosomia, and inversely associated with risks of small-for-gestational age infant (SGA) and low birth weight. Maternal excessive GWG was associated with increased risks of pregnancy-induced hypertension, caesarean delivery, LGA, and macrosomia, and decreased risks of preterm delivery, SGA, and low birth weight. Maternal inadequate GWG was associated with increased risks of preterm delivery and SGA, and decreased risks of LGA and macrosomia, compared with maternal adequate GWG. Women with both prepregnancy obesity and excessive GWG had 2.2–5.9 folds higher risks of GDM, pregnancy-induced hypertension, caesarean delivery, LGA, and macrosomia compared with women with normal prepregnancy BMI and adequate GWG.

Conclusions

Maternal prepregnancy obesity and excessive GWG were associated with greater risks of pregnancy-induced hypertension, caesarean delivery, and greater infant size at birth. Health care providers should inform women to start the pregnancy with a BMI in the normal weight category and limit their GWG to the range specified for their prepregnancy BMI.     

Birth weight, breast cancer and the potential mediating hormonal environment

Background

Previous studies have shown that woman’s risk of breast cancer in later life is associated with her infants birth weights. The objective of this study was to determine if this association is independent of breast cancer risk factors, mother’s own birth weight and to evaluate association between infants birth weight and hormonal environment during pregnancy. Independent association would have implications for understanding the mechanism, but also for prediction and prevention of breast cancer.

Methods and Findings

Risk of breast cancer in relation to a first infant’s birth weight, mother’s own birth weight and breast cancer risk factors were evaluated in a prospective cohort of 410 women in the Framingham Study. Serum concentrations of estriol (E3), anti-estrogen alpha-fetoprotein (AFP), and pregnancy-associated plasma protein-A (PAPP-A) were measured in 23,824 pregnant women from a separate prospective cohort, the FASTER trial. During follow-up (median, 14 years) 31 women (7.6 %) were diagnosed with breast cancer. Women with large birth weight infants (in the top quintile) had a higher breast cancer risk compared to other women (hazard ratio (HR), 2.5; 95% confidence interval (CI), 1.2–5.2; P = 0.012). The finding was not affected by adjustment for birth weight of the mother and traditional breast cancer risk factors (adjusted HR, 2.5; 95% CI, 1.2–5.6; P = 0.021). An infant’s birth weight had a strong positive relationship with the mother’s serum E3/AFP ratio and PAPP-A concentration during pregnancy. Adjustment for breast cancer risk factors did not have a material effect on these relationships.

Conclusions

Giving birth to an infant with high birth weight was associated with increased breast cancer risk in later life, independently of mother’s own birth weight and breast cancer risk factors and was also associated with a hormonal environment during pregnancy favoring future breast cancer development and progression.     

First-borns carry a higher metabolic risk in early adulthood: evidence from a prospective cohort study

Background

Birth order has been associated with early growth variability and subsequent increased adiposity, but the consequent effects of increased fat mass on metabolic risk during adulthood have not been assessed. We aimed to quantify the metabolic risk in young adulthood of being first-born relative to those born second or subsequently.

Methodology and Principal Findings

Body composition and metabolic risk were assessed in 2,249 men, aged 17–19 years, from a birth cohort in southern Brazil. Metabolic risk was assessed using a composite z-score integrating standardized measurements of blood pressure, total cholesterol, high density lipoprotein, triglycerides and fat mass. First-borns had lower birth weight z-score (Δ = −0.25, 95%CI −0.35, −0.15,p<0.001) but showed greater weight gain during infancy (change in weight z-score from birth to 20 months: Δ = 0.39, 95%CI 0.28–0.50, p<0.0001) and had greater mean height (Δ = 1.2 cm, 95%CI: 0.7–1.6, p<0.0001) and weight (Δ = 0.34 kg, 95%CI: 0.13–0.55, p<0.002) at 43 months. This greater weight and height tracked into early adulthood, with first-borns being significantly taller, heavier and with significantly higher fat mass than later-borns. The metabolic risk z-score was significantly higher in first-borns.

Conclusions/Significance

First-born status is associated with significantly elevated adiposity and metabolic risk in young adult men in Brazil. Our results, linking cardiovascular risk with life history variables, suggest that metabolic risk may be associated with the worldwide trend to smaller family size and it may interact with changes in behavioural or environmental risk factors.     

Gestational weight gain and body mass index in children: results from three german cohort studies

Introduction

Previous studies suggested potential priming effects of gestational weight gain (GWG) on offspring’s body composition in later life. However, consistency of these effects in normal weight, overweight and obese mothers is less clear.

Methods

We combined the individual data of three German cohorts and assessed associations of total and excessive GWG (as defined by criteria of the Institute of Medicine) with offspring’s mean body mass index (BMI) standard deviation scores (SDS) and overweight at the age of 5–6 years (total: n = 6,254). Quantile regression was used to examine potentially different effects on different parts of the BMI SDS distribution. All models were adjusted for birth weight, maternal age and maternal smoking during pregnancy and stratified by maternal pre-pregnancy weight status.

Results

In adjusted models, positive associations of total and excessive GWG with mean BMI SDS and overweight were observed only in children of non- overweight mothers. For example, excessive GWG was associated with a mean increase of 0.08 (95% CI: 0.01, 0.15) units of BMI SDS (0.13 (0.02, 0.24) kg/m² of ‘real’ BMI) in children of normal-weight mothers. The effects of total and excessive GWG on BMI SDS increased for higher- BMI children of normal-weight mothers.

Discussion

Increased GWG is likely to be associated with overweight in offspring of non-overweight mothers.     

Childhood growth, IQ and education as predictors of white blood cell telomere length at age 49-51 years: the Newcastle Thousand Families Study

Background

Telomere length is emerging as a potential factor in the pathogenesis of cardiovascular disease. We investigated whether birth weight, infant growth, childhood cognition and adult height, as well as a range of lifestyle, socio-economic and educational factors, were associated with white blood cell telomere length at age 49–51 years.

Methods

The study included 318 members of the Newcastle Thousand Families Study, a prospectively followed birth cohort which includes all individuals born in Newcastle, England in May and June 1947, who attended for clinical examination at age 49–51 years, and had telomere length successfully measured using real-time PCR analyses of DNA extracted from peripheral blood mononuclear cells.

Results

No association was found between birth weight and later telomere length. However, associations were seen with other factors from early life. Education level was the only predictor in males, while telomere length in females was associated with gestational age at birth, childhood growth and childhood IQ.

Conclusions

While these findings may be due to chance, in particular where differing associations were seen between males and females, they do provide evidence of early life associations with telomere length much later in life. Our findings of sex differences in the education association may reflect the sex differences in achieved education levels in this generation where few women went to university regardless of their intelligence. Our findings do not support the concept of telomere length being on the pathway between very early growth and later disease risk.