Fetal Growth versus Birthweight: The Role of Placenta versus Other Determinants

in utero. We aimed to study the effects of maternal characteristics on both birthweight and fetal growth in third trimester and introduce placental weight as a possible determinant of both birthweight and fetal growth in third trimester.The STORK study is a prospective cohort study including 1031 healthy pregnant women of Scandinavian heritage with singleton pregnancies. Maternal determinants (age, parity, body mass index (BMI), gestational weight gain and fasting plasma glucose) of birthweight and fetal growth estimated by biometric ultrasound measures were explored by linear regression models. Two models were fitted, one with only maternal characteristics and one which included placental weight.Placental weight was a significant determinant of birthweight. Parity, BMI, weight gain and fasting glucose remained significant when adjusted for placental weight. Introducing placental weight as a covariate reduced the effect estimate of the other variables in the model by 62% for BMI, 40% for weight gain, 33% for glucose and 22% for parity. Determinants of fetal growth were parity, BMI and weight gain, but not fasting glucose. Placental weight was significant as an independent variable. Parity, BMI and weight gain remained significant when adjusted for placental weight. Introducing placental weight reduced the effect of BMI on fetal growth by 23%, weight gain by 14% and parity by 17%.In conclusion, we find that placental weight is an important determinant of both birthweight and fetal growth. Our findings indicate that placental weight markedly modifies the effect of maternal determinants of both birthweight and fetal growth. The differential effect of third trimester glucose on birthweight and growth parameters illustrates that birthweight and fetal growth are not identical entities

Patterns of Early Gut Colonization Shape Future Immune Responses of the Host

The most important trigger for immune system development is the exposure to microbial components immediately after birth. Moreover, targeted manipulation of the microbiota can be used to change host susceptibility to immune-mediated diseases. Our aim was to analyze how differences in early gut colonization patterns change the composition of the resident microbiota and future immune system reactivity. Germ-free (GF) mice were either inoculated by single oral gavage of caecal content or let colonized by co-housing with specific pathogen-free (SPF) mice at different time points in the postnatal period. The microbiota composition was analyzed by denaturing gradient gel electrophoresis for 16S rRNA gene followed by principal component analysis. Furthermore, immune functions and cytokine concentrations were analyzed using flow cytometry, ELISA or multiplex bead assay. We found that a single oral inoculation of GF mice at three weeks of age permanently changed the gut microbiota composition, which was not possible to achieve at one week of age. Interestingly, the ex-GF mice inoculated at three weeks of age were also the only mice with an increased pro-inflammatory immune response. In contrast, the composition of the gut microbiota of ex-GF mice that were co-housed with SPF mice at different time points was similar to the gut microbiota in the barrier maintained SPF mice. The existence of a short GF postnatal period permanently changed levels of systemic regulatory T cells, NK and NKT cells, and cytokine production. In conclusion, a time window exists that enables the artificial colonization of GF mice by a single oral dose of caecal content, which may modify the future immune phenotype of the host. Moreover, delayed microbial colonization of the gut causes permanent changes in the immune system

Characterization of Diarrheagenic Enteroaggregative Escherichia coli in Danish Adults—Antibiotic Treatment Does Not Reduce Duration of Diarrhea

Enteroaggregative Escherichia coli (EAEC) is frequently isolated from sporadic cases of diarrhea and in outbreaks of gastroenteritis in several regions of the world. The pathophysiology of EAEC continues to be enigmatic, and the efficacy of antibiotic treatment in EAEC-associated diarrhea has been discussed. Since the level of antibiotic resistance is increasing, it is essential to restrict the use of antibiotics to prevent further resistance development. We aimed to investigate EAEC strains in adult Danish patients suffering from diarrhea and from healthy controls. We examined the antibiotic resistance in EAEC strains, the clinical response to antibiotic treatment in EAEC diarrheal cases, and the distribution of virulence genes in diarrheal cases. The EAEC strains were collected from patients suffering from diarrhea in a Danish multicenter study. A medical doctor interviewed the patients by using a questionnaire regarding gastrointestinal symptoms, exposures, and use of antibiotic and over-the-counter antidiarrheal drugs. Follow-up was performed after 3–5 months to inquire about differential diagnosis to gastrointestinal disease. A multiplex polymerase chain reaction characterized virulence genes in diarrheal cases. Finally, the level of antibiotic resistance was examined by using the disc diffusion method. Asymptomatic carriage of EAEC in the adult Danish population was rare, in contrast to findings in healthy Danish children. The duration of diarrhea was not shortened by antibiotic treatment, specifically ciprofloxacin treatment, or by over-the-counter antidiarrheal drugs. Follow-up revealed no pathology in diarrheal patients apart from irritable bowel syndrome in two patients. A high number of patients suffered from long-term diarrhea, which was associated with the enterotoxin EAST-1 and a high virulence factor score. A high level of antibiotic resistance was observed and 58% of the EAEC strains were multidrug resistant. Multidrug resistance was most pronounced in cases of travelers' diarrhea, and it was seen that antibiotic treatment did not reduce the duration of diarrhea

Maternal factors associated with fetal growth and birthweight are independent determinants of placental weight and exhibit differential effects by fetal sex.

INTRODUCTION: Maternal nutritional and metabolic factors influence the developmental environment of the fetus. Virtually any nutritional factor in the maternal blood has to pass the placental membranes to reach the fetal blood. Placental weight is a commonly used measure to summarize placental growth and function. Placental weight is an independent determinant of fetal growth and birthweight and modifies the associations between maternal metabolic factors and fetal growth. We hypothesized that maternal factors known to be related to fetal growth, newborn size and body composition are determinants of placental weight and that effects of maternal metabolic factors on placental weight differ between the genders. METHODS: The STORK study is a prospective longitudinal study including 1031 healthy pregnant women of Scandinavian heritage with singleton pregnancies. Maternal determinants (parity, body mass index, gestational weight gain and fasting plasma glucose) of placental weight were explored by linear regression models, stratified by fetal sex. RESULTS: Parity, maternal BMI, gestational weight gain and fasting glucose had positive effects on placental weight. There was a sex specific effect in these associations. Fasting glucose was significantly associated with placental weight in females but not in males. CONCLUSION: Maternal factors known to influence fetal growth, birthweight and neonatal body composition are determinants of placental weight. The effect of maternal factors on placental weight is influenced by sex as illustrated in the relation between maternal glucose and placental weight

Newborn body fat: associations with maternal metabolic state and placental size.

BACKGROUND: Neonatal body composition has implications for the health of the newborn both in short and long term perspective. The objective of the current study was first to explore the association between maternal BMI and metabolic parameters associated with BMI and neonatal percentage body fat and to determine to which extent any associations were modified if adjusting for placental weight. Secondly, we examined the relations between maternal metabolic parameters associated with BMI and placental weight. METHODS: The present work was performed in a subcohort (n = 207) of the STORK study, an observational, prospective study on the determinants of fetal growth and birthweight in healthy pregnancies at Oslo University Hospital, Norway. Fasting glucose, insulin, triglycerides, free fatty acids, HDL- and total cholesterol were measured at week 30-32. Newborn body composition was determined by Dual-Energy X-Ray Absorptiometry (DXA). Placenta was weighed at birth. Linear regression models were used with newborn fat percentage and placental weight as main outcomes. RESULTS: Maternal BMI, fasting glucose and gestational age were independently associated with neonatal fat percentage. However, if placental weight was introduced as a covariate, only placental weight and gestational age remained significant. In the univariate model, the determinants of placenta weight included BMI, insulin, triglycerides, total- and HDL-cholesterol (negatively), gestational weight gain and parity. In the multivariable model, BMI, total cholesterol HDL-cholesterol, gestational weight gain and parity remained independent covariates. CONCLUSION: Maternal BMI and fasting glucose were independently associated with newborn percentage fat. This effect disappeared by introducing placental weight as a covariate. Several metabolic factors associated with maternal BMI were associated with placental weight, but not with neonatal body fat. Our findings are consistent with a concept that the effects of maternal BMI and a number of BMI-related metabolic factors on fetal fat accretion to a significant extent act by modifying placental weight

Effect of maternal factors on placental weight (g) for girls (n = 482).

<p>Results from univariate and multiple linear regression models.</p><p>*Fasting glucose at visit 1 and fasting glucose at visit 3 were entered separately in the multiple models, but only fasting glucose at visit 3 remained statistically significant and was entered in the final model presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087303#pone-0087303-t005" target="_blank">Table 5</a>.</p

Effect of maternal factors on placental weight (g) for boys (n = 549).

<p>Results from univariate and multiple linear regression models.</p

Characteristics of the newborns.

<p>*difference between boys and girls, independent sample t-test.</p

Characteristics of the mothers.

<p>*according to WHO-criteria; ≥7.8 mmol/l 2 hours after 75 g glucose.</p><p># BP>140/90 and proteinuria.</p