Low Birth Weight and Normal Birth Weight Newborns of Kolkata, India: Comparison of Some Maternal Risk Factors

This study compared several maternal risk factors of low birth weight (LBW) between 204 normal birth weight (NBW) and 133 LBW newborns from Kolkata, India. Based on their birth weight (BW), newborns were classified as LBW (BW < 2.5 kg) and NBW (BW ≥ 2.5 kg). Results revealed that means for maternal age (MA, p < 0.05), gestational age (GA, p < 0.01), hemoglobin (Hb) concentration (p < 0.05), and per capita daily income (PCDI, p < 0.05) were significantly higher among mothers of NBW. Correlation analyses revealed that MA (r = 0.119, p < 0.05), GA (r = 0.583, p < 0.01), PCDI (r = 0.118, p < 0.05), and Hb (r = 0.138, p < 0.05) were significantly positively correlated with BW; PCDI was also significantly positively correlated (r = 0.142, p < 0.01) with Hb. Stepwise regression analyses with BW as the dependent variable revealed that GA (t = 7.915, p < 0.001) and Hb (t = 2.057, p < 0.05) were the most important predictive variables. The effect of Hb, independent of GA, was statistically significant (change in F = 4.231, p < 0.05). Because GA is not modifiable in pregnant women, there is a need to increase Hb levels among pregnant mothers. Most importantly, appropriately targeted preventive strategies, including iron supplementation, need to be implemented for health promotion.     

Birth Weight,Working Memory and Epigenetic Signatures in IGF2 and Related Genes: A MZ Twin Study

Neurodevelopmental disruptions caused by obstetric complications play a role in the etiology of several phenotypes associated with neuropsychiatric diseases and cognitive dysfunctions. Importantly, it has been noticed that epigenetic processes occurring early in life may mediate these associations. Here, DNA methylation signatures at IGF2 (insulin-like growth factor 2) and IGF2BP1-3 (IGF2-binding proteins 1-3) were examined in a sample consisting of 34 adult monozygotic (MZ) twins informative for obstetric complications and cognitive performance. Multivariate linear regression analysis of twin data was implemented to test for associations between methylation levels and both birth weight (BW) and adult working memory (WM) performance. Familial and unique environmental factors underlying these potential relationships were evaluated. A link was detected between DNA methylation levels of two CpG sites in the IGF2BP1 gene and both BW and adult WM performance. The BW-IGF2BP1 methylation association seemed due to non-shared environmental factors influencing BW, whereas the WM-IGF2BP1 methylation relationship seemed mediated by both genes and environment. Our data is in agreement with previous evidence indicating that DNA methylation status may be related to prenatal stress and later neurocognitive phenotypes. While former reports independently detected associations between DNA methylation and either BW or WM, current results suggest that these relationships are not confounded by each other.     

Modification of Epigenetic Patterns in Low Birth Weight Children: Importance of Hypomethylation of the ACE Gene Promoter

There is a growing body of evidence that epigenetic alterations are involved in the pathological mechanisms of many chronic disorders linked to fetal programming. Angiotensin-converting enzyme (ACE) appears as one candidate gene that brings new insights into the epigenetic control and later development of diseases. In this view, we have postulated that epigenetic modifications in the ACE gene might show different interactions between birth weight (BW), blood pressure levels, plasma ACE activity and ACE I/D polymorphism. To explore this hypothesis, we performed a cross-sectional study to evaluate the DNA methylation of 3 CpG sites using pyrosequencing within the ACE gene promoter of peripheral blood leukocytes from 45 LBW children compared with 70 NBW children. Our results have revealed that LBW children have lower methylation levels (P<0.001) in parallel with a higher ACE activity (P = 0.001). Adjusting for prematurity, gender, age, body mass index, and family history of cardiovascular disease did not alter these findings. We have also performed analyses of individual CpG sites. The frequency of DNA methylation was significantly different at two CpG sites (site 1: nucleotide position +555; and site 3: nucleotide position +563). In addition, we have found a significant inverse correlation between degree of DNA methylation and both ACE activity (P<0.001) and systolic blood pressure levels (P<0.001). We also observed that the methylation level was significantly lower in LBW children who are carriers of the DD genotype compared to NBW children with DD genotype (P<0.024). In conclusion, we are able to demonstrate that the hypomethylation in the 3 CpG sites of ACE gene promoter is associated with LBW in 6 to 12 year-old children. The magnitude of these epigenetic changes appears to be clinically important, which is supported by the observation that discrete changes in DNA methylation can affect systolic blood pressure and ACE protein activity levels.     

Epigenetic Regulations in Mammalian Cells: Roles and Profiling Techniques

The genome is almost identical in all the cells of the body. However, the functions and morphologies of each cell are different, and the factors that determine them are the genes and proteins expressed in the cells. Over the past decades, studies on epigenetic information, such as DNA methylation, histone modifications, chromatin accessibility, and chromatin conformation have shown that these properties play a fundamental role in gene regulation. Furthermore, various diseases such as cancer have been found to be associated with epigenetic mechanisms. In this study, we summarized the biological properties of epigenetics and single-cell epigenomic profiling techniques, and discussed future challenges in the field of epigenetics.     

Transcriptomic Profiling of Spleen in Grass-Fed and Grain-Fed Angus Cattle

The grass-fed cattle obtain nutrients directly from pastures containing limited assimilable energy but abundant amount of fiber; by contrast, grain-fed steers receive a diet that is comprised mainly of grains and serves as an efficient source of high-digestible energy. Besides energy, these two types of diet differ in a large number of nutritional components. Additionally, animals maintained on rich-energy regimen are more likely to develop metabolic disorders and infectious diseases than pasture raised individuals. Thus, we hypothesize that spleen–a relevant immune organ–may function differently under disparate regimes. The objective of this study was to find the differentially expressed genes in the spleen of grass-fed and grain-fed steers, and furtherly explore the potential involved biopathways. Through RNA sequencing (RNA-Seq), we detected 123 differentially expressed genes. Based on these genes, we performed an Ingenuity Pathway Analysis (IPA) and identified 9 significant molecular networks and 13 enriched biological pathways. Two of the pathways, Nur77 signaling in T lymphocytes and calcium-induced T lymphocyte apoptosis which are immune related, contain a pair of genes HLA-DRA and NR4A1 with dramatically altered expression level. Collectively, our results provided valuable insights into understanding the molecular mechanism of spleen under varied feeding regimens.     

Weight at Birth and Subsequent Fecundability: A Prospective Cohort Study

Objective

To examine the association between a woman''s birth weight and her subsequent fecundability.

Method

In this prospective cohort study, we included 2,773 Danish pregnancy planners enrolled in the internet-based cohort study “Snart-Gravid”, conducted during 2007–2012. Participants were 18–40 years old at study entry, attempting to conceive, and were not receiving fertility treatment. Data on weight at birth were obtained from the Danish Medical Birth Registry and categorized as <2,500 grams, 2,500–2,999 grams, 3,000–3,999 grams, and ≥4,000 grams. In additional analyses, birth weight was categorized according to z-scores for each gestational week at birth. Time-to-pregnancy measured in cycles was used to compute fecundability ratios (FR) and 95% confidence intervals (CI), using a proportional probabilities regression model.

Results

Relative to women with a birth weight of 3,000–3,999 grams, FRs adjusted for gestational age, year of birth, and maternal socio-demographic and medical factors were 0.99 (95% CI: 0.73;1.34), 0.99 (95% CI: 0.87;1.12), and 1.08 (95% CI: 0.94;1.24) for birth weight <2,500 grams, 2,500–2,999 grams, and ≥4,000 grams, respectively. Estimates remained unchanged after further adjustment for markers of the participant''s mother''s fecundability. We obtained similar results when we restricted to women who were born at term, and to women who had attempted to conceive for a maximum of 6 cycles before study entry. Results remained similar when we estimated FRs according to z-scores of birth weight.

Conclusion

Our results indicate that birth weight appears not to be an important determinant of fecundability.     

Intergenerational Predictors of Birth Weight in the Philippines: Correlations with Mother's and Father's Birth Weight and Test of Maternal Constraint

Background

Birth weight (BW) predicts many health outcomes, but the relative contributions of genes and environmental factors to BW remain uncertain. Some studies report stronger mother-offspring than father-offspring BW correlations, with attenuated father-offspring BW correlations when the mother is stunted. These findings have been interpreted as evidence that maternal genetic or environmental factors play an important role in determining birth size, with small maternal size constraining paternal genetic contributions to offspring BW. Here we evaluate mother-offspring and father-offspring birth weight (BW) associations and evaluate whether maternal stunting constrains genetic contributions to offspring birth size.

Methods/Principal Findings

Data include BW of offspring (n = 1,101) born to female members (n = 382) and spouses of male members (n = 275) of a birth cohort (born 1983–84) in Metropolitan Cebu, Philippines. Regression was used to relate parental and offspring BW adjusting for confounders. Resampling testing was used to evaluate whether false paternity could explain any evidence for excess matrilineal inheritance. In a pooled model adjusting for maternal height and confounders, parental BW was a borderline-significantly stronger predictor of offspring BW in mothers compared to fathers (sex of parent interaction p = 0.068). In separate multivariate models, each kg in mother’s and father’s BW predicted a 271±53 g (p<0.00001) and 132±55 g (p = 0.017) increase in offspring BW, respectively. Resampling statistics suggested that false paternity rates of >25% and likely 50% would be needed to explain these differences. There was no interaction between maternal stature and maternal BW (interaction p = 0.520) or paternal BW (p = 0.545).

Conclusions/Significance

Each kg change in mother’s BW predicted twice the change in offspring BW as predicted by a change in father’s BW, consistent with an intergenerational maternal effect on offspring BW. Evidence for excess matrilineal BW heritability at all levels of maternal stature points to indirect genetic, mitochondrial, or epigenetic maternal contributions to offspring fetal growth.     

Pregnancy Weight Gain and Childhood Body Weight: A Within-Family Comparison

Background

Excessive pregnancy weight gain is associated with obesity in the offspring, but this relationship may be confounded by genetic and other shared influences. We aimed to examine the association of pregnancy weight gain with body mass index (BMI) in the offspring, using a within-family design to minimize confounding.

Methods and Findings

In this population-based cohort study, we matched records of all live births in Arkansas with state-mandated data on childhood BMI collected in public schools (from August 18, 2003 to June 2, 2011). The cohort included 42,133 women who had more than one singleton pregnancy and their 91,045 offspring. We examined how differences in weight gain that occurred during two or more pregnancies for each woman predicted her children''s BMI and odds ratio (OR) of being overweight or obese (BMI≥85th percentile) at a mean age of 11.9 years, using a within-family design. For every additional kg of pregnancy weight gain, childhood BMI increased by 0.0220 (95% CI 0.0134–0.0306, p<0.0001) and the OR of overweight/obesity increased by 1.007 (CI 1.003–1.012, p = 0.0008). Variations in pregnancy weight gain accounted for a 0.43 kg/m² difference in childhood BMI. After adjustment for birth weight, the association of pregnancy weight gain with childhood BMI was attenuated but remained statistically significant (0.0143 kg/m² per kg of pregnancy weight gain, CI 0.0057–0.0229, p = 0.0007).

Conclusions

High pregnancy weight gain is associated with increased body weight of the offspring in childhood, and this effect is only partially mediated through higher birth weight. Translation of these findings to public health obesity prevention requires additional study. Please see later in the article for the Editors'' Summary     

Effect of Birth Year on Birth Weight and Obesity in Adulthood: Comparison between Subjects Born Prior to and during the Great Depression in Iceland

Background

Many epidemiological studies have linked small size at birth to adverse adult health outcomes but the relative influence of environmental exposures is less well established.

Methods

The authors investigated the impact of prenatal environmental exposure by comparing 2750 participants born before (1925–1929) and during (1930–1934) the Great Depression in Reykjavik, Iceland. Calendar year served as proxy for environmental effects. Anthropometric measurements at birth and school-age (8–13 years) were collected from national registries. Participants were medically examined as adults (33–65 years).

Results

Mean birth weight, adjusted for maternal age and parity, decreased by 97 g (95% confidence interval (CI): 39, 156) for men and 70 g (95% CI: 11, 129) for women from 1925 to 1934; growth at school-age was significantly reduced for participants growing during the Depression. As adults, women prenatally exposed to the Depression had higher body mass index (Δ0.6 kg/m², 95% CI: 0.2, 1.1), higher fasting blood glucose levels (Δ0.16 mmol/L, 95% CI: 0.07, 0.23) and greater odds of being obese 1.43 (95% CI: 1.01, 2.02) compared to unexposed counterparts. Non-significant associations were observed in men.

Conclusion

Reduction in birth weight due to rapid shifts in the economic environment appears to have a modest but significant association with later obesity for women while male offspring appear to be less affected by these conditions.     

Propionibacterium from Liver and Lung of Pigs and Guinea Pigs. 1: Physiological Identification

A total of 231 Propionibacterium strains originated from animals were identified based on key physiological properties. They comprised 218 strains derived from livers of pigs with or without milk spots, eight from lungs of pigs used in parasitic infection experiments (including controls), and three from livers and two from lungs of guinea pigs in experimental parasitic infection. All identification tests were performed in cysteine-containing media (reduced state) and incubated in an aerobic atmosphere, except the seed cultures used for inoculation and cultures for catalase test which were incubated under pure carbon dioxide. Among these strains, 212 isolates were clearly identified as P. acnes, Eleven asP. granulosum , seven as P. avidum and one as Propionibacteriu m species. For P. acnes, the key identification properties were maltose- and sucrose-negative at species level; and sorbitol-positive for type I and erythritol-positive for type II at subspecies level. All P. acnes type II strains were sorbitol-negative, but some type I strains also showed the same reaction. The P. acnes type I strains showed growth on the surface of semi-solid sugar medium and type II strains showed deep growth in the same medium. These growth modes provided an important tool for type differentiation. By summarizing all the results of adonitol–mannitol–sorbitol (AMS) reaction pattern; erythritol–trehalose (ET) reaction pattern, gelatin liquefaction, indole production and the growth mode, 34 differential patterns were established. As a result, 139 strains were classified as type I (130 from pig liver, six from pig lung, one from guinea-pig liver, two from guinea-pig lung), 68 strains as type II (64 from pig liver, 2 from pig lung, 2 from guinea-pig liver), and five strains as untypable. The two species; P. granulosum and P. avidum were first characterized by being melezitose-, maltose- and sucrose-positive. Then they were differentiated by aesculin and gelatin reactions. P. granulosum was negative for both and P. avidum was positive. One strain of Propionibacterium sp. had a unique pattern different from the other species.     

Lung Cancer and Month of Birth

A statistical study of possible relationship of month of birth to the occurrence of lung cancer was carried out at Veterans Administration Hospital, Long Beach.The distribution of the 200 lung cancer cases by month of birth did not differ significantly from that which might be expected by chance alone. These findings do not substantiate those found by Dijkstra in The Netherlands.     

Pre-Pregnancy Body Mass Index,Gestational Weight Gain,and Birth Weight: A Cohort Study in China

Objective

To assess whether pre-pregnancy body mass index (BMI) modify the relationship between gestational weight gain (GWG) and child birth weight (specifically, presence or absence of low birth weight (LBW) or presence of absence of macrosomia), and estimates of the relative risk of macrosomia and LBW based on pre-pregnancy BMI were controlled in Wuhan, China.

Methods

From June 30, 2011 to June 30, 2013. All data was collected and available from the perinatal health care system. Logistic regression models were used to estimate the independent association among pregnancy weight gain, LBW, normal birth weight, and macrosomia within different pre-pregnancy BMI groups. We built different logistic models for the 2009 Institute of Medicine (IOM) Guidelines and Chinese-recommended GWG which was made from this sample. The Chinese-recommended GWG was derived from the quartile values (25th-75th percentiles) of weight gain at the time of delivery in the subjects which comprised our sample.

Results

For LBW children, using the recommended weight gain of the IOM and Chinese women as a reference, the OR for a pregnancy weight gain below recommendations resulted in a positive relationship for lean and normal weight women, but not for overweight and obese women. For macrosomia, considering the IOM’s recommended weight gain as a reference, the OR magnitude for pregnancy weight gain above recommendations resulted in a positive correlation for all women. The OR for a pregnancy weight gain below recommendations resulted in a negative relationship for normal BMI and lean women, but not for overweight and obese women based on the IOM recommendations, significant based on the recommended pregnancy weight gain for Chinese women. Of normal weight children, 56.6% were above the GWG based on IOM recommendations, but 26.97% of normal weight children were above the GWG based on Chinese recommendations.

Conclusions

A GWG above IOM recommendations might not be helpful for Chinese women. We need unified criteria to classify adult BMI and to expand the sample size to improve representation and to elucidate the relationship between GWG and related outcomes for developing a Chinese GWG recommendation.     

Influence of Maternal Height and Weight on Low Birth Weight: A Cross-Sectional Study in Poor Communities of Northeastern Brazil

Background

Low birth weight (LBW) is associated with an increased risk of mortality, adverse metabolic conditions, and long-term chronic morbidities. The relationship between LWB and short maternal stature coupled with nutritional status was investigated in poor communities.

Methods/Principal Findings

A cross-sectional population-based study involving 2226 mother-child pairs was conducted during the period 2009-2010 in shantytowns of Maceió, Alagoas, Brazil. Associations between LBW and maternal sociodemographics, stature and nutritional status were investigated. The outcome variable was birth weight (< 2500g and ≥ 2500g). The independent variables were the age, income, educational background, stature and nutritional status (eutrophic, underweight, overweight and obese) of the mother. The frequency of LBW was 10%. Short-statured mothers (1^st quartile of stature ≤ 152cm) showed a tendency of increased risk of LBW children compared to mothers in the 4^th quartile of stature (>160.4cm) (OR: 1.42, 95% CI: 0.96 - 1.09, p = 0.078). Children from short-statured mothers weighed an average of 125g less than those from taller mothers (3.18±0.56kg vs. 3.30±0.58kg, respectively p = 0.002). Multivariate analyses showed that short stature, age < 20y (OR: 3.05, 95% CI:1.44 - 6.47) or were underweight (OR: 2.26, 95% CI:0.92 - 5.95) increased the risk of LBW, while overweight (OR: 0.38, 95% CI:0.16 - 0.95) and obesity (OR: 0.39, 95% CI:0.11 - 1.31) had lower risk for LBW. In taller mothers, lower income and underweight were associated with LBW (OR: 1.88, 95% CI: 1.07 - 3.29 and 2.85, 95% CI:1.09 - 7.47, respectively), and obese mothers showed a trend of increased risk of LBW (OR: 1.66, 95% CI:0.84 - 3.25).

Conclusions/Significance

Overweight was found to have a protective effect in short-statured mothers, indicating that a surplus of energy may diminish the risk of LBW. Short-statured younger mothers, but not taller ones, showed higher risk of LBW. The mother being underweight, regardless of stature, was associated with LBW.