Isolated Short Fetal Femur Length in the Second Trimester and the Association with Adverse Perinatal Outcome: Experiences from a Tertiary Referral Center

Objective

To determine the association between isolated mid-trimester short fetal femur length and adverse perinatal outcome.

Methods

This is a retrospective cohort study of patients with singleton gestations routinely assessed by second trimester ultrasound examination during 2006-2013. A fetal isolated short femur was defined as a femur length (FL) below the 5^th percentile in a fetus with an abdominal circumference greater than the 10^th percentile. Cases of aneuploidy, skeletal dysplasia and major anomalies were excluded. Primary outcomes of interest included the risk of small for gestational age neonates, low birth weight and preterm birth (PTB). Secondary outcome parameters were a 5-min Apgar score less than 7 and a neonatal intensive care unit admission. A control group of 200 fetuses with FL ≥ 5th percentile was used to compare primary and secondary outcome parameters within both groups. Chi-square and Student’s t-tests were used where appropriate.

Results

Out of 608 eligible patients with a short FL, 117 met the inclusion criteria. Isolated short FL was associated with an increased risk for small for gestational age (19.7% versus 8.0%, p = 0.002) neonates, low birth weight (23.9% versus 8.5%, p<0.001), PTB (19.7% versus 6.0%, p<0.001) and neonatal intensive care unit admissions (13.7% versus 3.5%, p = 0.001). The incidence of a 5-min Apgar score less than 7 was similar in both groups.

Conclusion

Isolated short FL is associated with a subsequent delivery of small for gestational age and Low birth weight neonates as well as an increased risk for PTB. This information should be considered when counseling patients after mid-trimester isolated short FL is diagnosed.     

Automatic Quantitative MRI Texture Analysis in Small-for-Gestational-Age Fetuses Discriminates Abnormal Neonatal Neurobehavior

Background

We tested the hypothesis whether texture analysis (TA) from MR images could identify patterns associated with an abnormal neurobehavior in small for gestational age (SGA) neonates.

Methods

Ultrasound and MRI were performed on 91 SGA fetuses at 37 weeks of GA. Frontal lobe, basal ganglia, mesencephalon and cerebellum were delineated from fetal MRIs. SGA neonates underwent NBAS test and were classified as abnormal if ≥1 area was <5^th centile and as normal if all areas were >5^th centile. Textural features associated with neurodevelopment were selected and machine learning was used to model a predictive algorithm.

Results

Of the 91 SGA neonates, 49 were classified as normal and 42 as abnormal. The accuracies to predict an abnormal neurobehavior based on TA were 95.12% for frontal lobe, 95.56% for basal ganglia, 93.18% for mesencephalon and 83.33% for cerebellum.

Conclusions

Fetal brain MRI textural patterns were associated with neonatal neurodevelopment. Brain MRI TA could be a useful tool to predict abnormal neurodevelopment in SGA.     

Heritability estimates of body size in fetal life and early childhood

Background

The objective was to estimate the heritability for height and weight during fetal life and early childhood in two independent studies, one including parent and singleton offsprings and one of mono- and dizygotic twins.

Methods

This study was embedded in the Generation R Study (n = 3407, singletons) and the Netherlands Twin Register (n = 33694, twins). For the heritability estimates in Generation R, regression models as proposed by Galton were used. In the Twin Register we used genetic structural equation modelling. Parental height and weight were measured and fetal growth characteristics (femur length and estimated fetal weight) were measured by ultrasounds in 2^nd and 3^rd trimester (Generation R only). Height and weight were assessed at multiple time-points from birth to 36 months in both studies.

Results

Heritability estimates for length increased from 2^nd to 3^rd trimester from 13% to 28%. At birth, heritability estimates for length in singletons and twins were both 26% and 27%, respectively, and at 36 months, the estimates for height were 63% and 72%, respectively. Heritability estimates for fetal weight increased from 2^nd to 3^rd trimester from 17% to 27%. For birth weight, heritability estimates were 26% in singletons and 29% in twins. At 36 months, the estimate for twins was 71% and higher than for singletons (42%).

Conclusions

Heritability estimates for height and weight increase from second trimester to infancy. This increase in heritability is observed in singletons and twins. Longer follow-up studies are needed to examine how the heritability develops in later childhood and puberty.     

Optimal Skin-to-Stone Distance Is a Positive Predictor for Successful Outcomes in Upper Ureter Calculi following Extracorporeal Shock Wave Lithotripsy: A Bayesian Model Averaging Approach

Objectives

To investigate whether skin-to-stone distance (SSD), which remains controversial in patients with ureter stones, can be a predicting factor for one session success following extracorporeal shock wave lithotripsy (ESWL) in patients with upper ureter stones.

Patients and Methods

We retrospectively reviewed the medical records of 1,519 patients who underwent their first ESWL between January 2005 and December 2013. Among these patients, 492 had upper ureter stones that measured 4–20 mm and were eligible for our analyses. Maximal stone length, mean stone density (HU), and SSD were determined on pretreatment non-contrast computed tomography (NCCT). For subgroup analyses, patients were divided into four groups. Group 1 consisted of patients with SSD<25^th percentile, group 2 consisted of patients with SSD in the 25^th to 50^th percentile, group 3 patients had SSD in the 50^th to 75^th percentile, and group 4 patients had SSD≥75^th percentile.

Results

In analyses of group 2 patients versus others, there were no statistical differences in mean age, stone length and density. However, the one session success rate in group 2 was higher than other groups (77.9% vs. 67.0%; P = 0.032). The multivariate logistic regression model revealed that shorter stone length, lower stone density, and the group 2 SSD were positive predictors for successful outcomes in ESWL. Using the Bayesian model-averaging approach, longer stone length, lower stone density, and group 2 SSD can be also positive predictors for successful outcomes following ESWL.

Conclusions

Our data indicate that a group 2 SSD of approximately 10 cm is a positive predictor for success following ESWL.     

Methodologies for Pre-Validation of Biofilters and Wetlands for Stormwater Treatment

Background

Water Sensitive Urban Design (WSUD) systems are frequently used as part of a stormwater harvesting treatment trains (e.g. biofilters (bio-retentions and rain-gardens) and wetlands). However, validation frameworks for such systems do not exist, limiting their adoption for end-uses such as drinking water. The first stage in the validation framework is pre-validation, which prepares information for further validation monitoring.

Objectives

A pre-validation roadmap, consisting of five steps, is suggested in this paper. Detailed methods for investigating target micropollutants in stormwater, and determining challenge conditions for biofilters and wetlands, are provided.

Methods

A literature review was undertaken to identify and quantify micropollutants in stormwater. MUSIC V5.1 was utilized to simulate the behaviour of the systems based on 30-year rainfall data in three distinct climate zones; outputs were evaluated to identify the threshold of operational variables, including length of dry periods (LDPs) and volume of water treated per event.

Results

The paper highlights that a number of micropollutants were found in stormwater at levels above various worldwide drinking water guidelines (eight pesticides, benzene, benzo(a)pyrene, pentachlorophenol, di-(2-ethylhexyl)-phthalate and a total of polychlorinated biphenyls). The 95^th percentile LDPs was exponentially related to system design area while the 5^th percentile length of dry periods remained within short durations (i.e. 2–8 hours). 95^th percentile volume of water treated per event was exponentially related to system design area as a percentage of an impervious catchment area.

Conclusions

The out-comings of this study show that pre-validation could be completed through a roadmap consisting of a series of steps; this will help in the validation of stormwater treatment systems.     

Visual vs Fully Automatic Histogram-Based Assessment of Idiopathic Pulmonary Fibrosis (IPF) Progression Using Sequential Multidetector Computed Tomography (MDCT)

Objectives

To describe changes over time in extent of idiopathic pulmonary fibrosis (IPF) at multidetector computed tomography (MDCT) assessed by semi-quantitative visual scores (VSs) and fully automatic histogram-based quantitative evaluation and to test the relationship between these two methods of quantification.

Methods

Forty IPF patients (median age: 70 y, interquartile: 62-75 years; M:F, 33:7) that underwent 2 MDCT at different time points with a median interval of 13 months (interquartile: 10-17 months) were retrospectively evaluated. In-house software YACTA quantified automatically lung density histogram (10^th-90^th percentile in 5^th percentile steps). Longitudinal changes in VSs and in the percentiles of attenuation histogram were obtained in 20 untreated patients and 20 patients treated with pirfenidone. Pearson correlation analysis was used to test the relationship between VSs and selected percentiles.

Results

In follow-up MDCT, visual overall extent of parenchymal abnormalities (OE) increased in median by 5 %/year (interquartile: 0 %/y; +11 %/y). Substantial difference was found between treated and untreated patients in HU changes of the 40th and of the 80th percentiles of density histogram. Correlation analysis between VSs and selected percentiles showed higher correlation between the changes (Δ) in OE and Δ 40^th percentile (r=0.69; p<0.001) as compared to Δ 80^th percentile (r=0.58; p<0.001); closer correlation was found between Δ ground-glass extent and Δ 40^th percentile (r=0.66, p<0.001) as compared to Δ 80^th percentile (r=0.47, p=0.002), while the Δ reticulations correlated better with the Δ 80^th percentile (r=0.56, p<0.001) in comparison to Δ 40^th percentile (r=0.43, p=0.003).

Conclusions

There is a relevant and fully automatically measurable difference at MDCT in VSs and in histogram analysis at one year follow-up of IPF patients, whether treated or untreated: Δ 40^th percentile might reflect the change in overall extent of lung abnormalities, notably of ground-glass pattern; furthermore Δ 80^th percentile might reveal the course of reticular opacities.     

Long-Term Survival of Individuals Born Small and Large for Gestational Age

Background

Little is known on long-term survival and causes of death among individuals born small or large for gestational age. This study investigates birth weight in relation to survival and causes of death over time.

Methods

A national cohort of 1.7 million live-born singletons in Denmark was followed during 1979–2011, using the Danish Civil Registration System, the Medical Birth Registry and the Cause of Death Registry. Cox proportional hazards were estimated for the impact of small (SGA) and large (LGA) gestation weight and mortality overall, by age group and birth cohort.

Results

Compared to normal weight children, SGA children were associated with increased risk of dying over time. Though most of the deaths occurred during the first year of life, the cumulative mortality risk was increased until 30 years of age. The hazard ratios [HR] for dying among SGA children ages <2 years were: 3.47 (95% CI, 3.30–3.64) and 1.06 (95% CI, 0.60–1.87) in 30 years and older. HR for dying among SGA adults (20–29 years) were: 1.20 (95% CI, 0.99–1.46) in years 1979–1982 and 1.61 (95% CI, 1.04–2.51) in years 1989–1994. The SGA born had increased risk of dying from infection, heart disease, respiratory disease, digestive disease, congenital malformation, perinatal conditions, and accidents, suicide, and homicide. Individuals born LGA were associated with decreased mortality risk, but with increased risk of dying from malignant neoplasm.

Conclusions

Survival has improved independently of birth weight the past 30 years. However, children born SGA remain at significantly increased risk of dying up till they turn 30 years of age. Individuals born LGA have lower mortality risk but only in the first two years of life.     

Do Gene Variants Influencing Adult Adiposity Affect Birth Weight? A Population-Based Study of 24 Loci in 4,744 Danish Individuals

Background

Several obesity risk alleles affecting adult adiposity have been identified by the recent wave of genome wide association studies. We aimed to examine the potential effect of these variants on fetal body composition by investigating the variants in relation to birth weight and ponderal index of the newborn.

Methodology/Principal Findings

Midwife records from the Danish State Archives provided information on mother''s age, parity, as well as birth weight, birth length and prematurity of the newborn in 4,744 individuals of the population-based Inter99 study. Twenty-four risk alleles showing genome-wide associations with adult BMI and/or waist circumference were genotyped. None of the 24 risk variants tested showed an association with birth weight or ponderal index after correction for multiple testing. Birth weight was divided into three categories low (≤10^th percentile), normal (10^th–90^th percentile) and high birth weight (≥90th percentile) to allow for non-linear associations. There was no difference in the number of risk alleles between the groups (p = 0.57). No interactions between each risk allele and birth weight in the prediction of adult BMI were observed. An obesity risk score was created by summing up risk alleles. The risk score did not associate with fetal body composition. Moreover there was no interaction between the risk score and birth weight/ponderal index in the prediction of adult BMI.

Conclusion

24 common variants associated with adult adiposity did not affect or interact with birth weight among Danes suggesting that the effects of these variants predominantly arise in the post-natal life.     

Development of a Fetal Weight Chart Using Serial Trans-Abdominal Ultrasound in an East African Population: A Longitudinal Observational Study

Objective

To produce a fetal weight chart representative of a Tanzanian population, and compare it to weight charts from Sub-Saharan Africa and the developed world.

Methods

A longitudinal observational study in Northeastern Tanzania. Pregnant women were followed throughout pregnancy with serial trans-abdominal ultrasound. All pregnancies with pathology were excluded and a chart representing the optimal growth potential was developed using fetal weights and birth weights. The weight chart was compared to a chart from Congo, a chart representing a white population, and a chart representing a white population but adapted to the study population. The prevalence of SGA was assessed using all four charts.

Results

A total of 2193 weight measurements from 583 fetuses/newborns were included in the fetal weight chart. Our chart had lower percentiles than all the other charts. Most importantly, in the end of pregnancy, the 10^th percentiles deviated substantially causing an overestimation of the true prevalence of SGA newborns if our chart had not been used.

Conclusions

We developed a weight chart representative for a Tanzanian population and provide evidence for the necessity of developing regional specific weight charts for correct identification of SGA. Our weight chart is an important tool that can be used for clinical risk assessments of newborns and for evaluating the effect of intrauterine exposures on fetal and newborn weight.     

Prenatal Exposure to Cadmium,Placental Permeability and Birth Outcomes in Coastal Populations of South Africa

Background

The impact of prenatal exposure to cadmium (Cd) on birth outcomes is an area of concern. This study aimed to assess an impact of prenatal Cd exposure on birth outcomes in distinct coastal populations of South Africa.

Methods

Cadmium was measured in maternal blood (CdB) (n = 641), cord blood and in maternal urine (n = 317). This investigation assessed the associations between CdB (non-transformed) and birth outcomes across the 25^th, 50th, and 75th percentile for birth weight, birth length and head circumference, to test for a linear trend. Associations between natural log-transformed maternal CdB, size at birth and other factors were further evaluated using linear mixed-effects modelling with random intercepts.

Results

The average gestational age in the total sample was 38 weeks; 47% of neonates were female, average birth weight was 3065 g and 11% were of low birth weight (< 2500 g). The geometric mean (GM) of the maternal CdB level was 0.25 μg/L (n = 641; 95% CI, 0.23–0.27). The cord blood Cd level was 0.27 μg/L (n = 317; 95% CI, 0.26–0.29) and urine (creatinine-corrected) Cd level was 0.27 μg/L (n = 318; 95% CI, 0.24–0.29). The CdB cord:maternal ratio in the sub-cohort was 1, suggesting that the placenta offers no protective mechanism to the foetus. An inverse association was found between CdB and the lower birth weight percentile in female neonates only (β = - 0.13, p = 0.047). Mothers who reported eating vine vegetables daily had lower levels of CdB (β = - 0.55, p = 0.025). Maternal smoking was associated with an elevation in natural log-transformed CdB levels in both male and female cohorts.

Discussion

Significant inverse associations between prenatal Cd exposure and birth anthropometry were found in female neonates but not in male neonates, suggesting potential sex differences in the toxico-kinetics and toxico-dynamics of Cd.     

Characterization and Correction of Geometric Distortions in 814 Diffusion Weighted Images

Introduction

Diffusion Weighted Imaging (DWI), which is based on Echo Planar Imaging (EPI) protocols, is becoming increasingly important for neurosurgical applications. However, its use in this context is limited in part by significant spatial distortion inherent to EPI.

Method

We evaluated an efficient algorithm for EPI distortion correction (EPIC) across 814 DWI scans from 250 brain tumor patients and quantified the magnitude of geometric distortion for whole brain and multiple brain regions.

Results

Evaluation of the algorithm’s performance revealed significantly higher mutual information between T1-weighted pre-contrast images and corrected b = 0 images than the uncorrected b = 0 images (p < 0.001). The distortion magnitude across all voxels revealed a median EPI distortion effect of 2.1 mm, ranging from 1.2 mm to 5.9 mm, the 5^th and 95^th percentile, respectively. Regions adjacent to bone-air interfaces, such as the orbitofrontal cortex, temporal poles, and brain stem, were the regions most severely affected by DWI distortion.

Conclusion

Using EPIC to estimate the degree of distortion in 814 DWI brain tumor images enabled the creation of a topographic atlas of DWI distortion across the brain. The degree of displacement of tumors boundaries in uncorrected images is severe but can be corrected for using EPIC. Our results support the use of distortion correction to ensure accurate and careful application of DWI to neurosurgical practice.     

Height at Late Adolescence and Incident Diabetes among Young Men

Background

Short stature was suggested as a risk factor for diabetes onset among middle age individuals, but whether this is the case among young adults is unclear. Our goal was to assess the association between height and incident diabetes among young men.

Methods and Findings

Incident diabetes was assessed among 32,055 men with no history of diabetes, from the prospectively followed young adults of the MELANY cohort. Height was measured at two time points; at adolescence (mean age 17.4±0.3 years) and grouped according to the US-CDC percentiles and at young adulthood (mean age 31.0±5.6 years). Cox proportional hazards models were applied. There were 702 new cases of diabetes during a mean follow-up of 6.3±4.3 years. There was a significant increase in the crude diabetes incidence rate with decreasing adolescent height percentile, from 4.23 cases/10⁴ person-years in the <10^th percentile group to 2.44 cases/10⁴ person-years in the 75^th≤ percentile group. These results persisted when clinical and biochemical diabetes risk factors were included in multivariable models. Compared to the 75^th≤ percentile group, height below the 10^th percentile was associated with a hazard ratio (HR) of 1.64 (95%CI 1.09–2.46, p = 0.017) for incident diabetes after adjustment for age, body mass index (BMI), fasting plasma glucose, HDL-cholesterol and triglyceride levels, white blood cells count, socioeconomic status, country of origin, family history of diabetes, sleep quality and physical activity. At age 30 years, each 1-cm decrement in adult height was associated with a 2.5% increase in diabetes adjusted risk (HR 1.025, 95%CI 1.01–1.04, p = 0.001).

Conclusions

Shorter height at late adolescence or young adulthood was associated with an increased risk of incident diabetes among young men, independent of BMI and other diabetes risk factors.     

Application of Probabilistic Multiple-Bias Analyses to a Cohort- and a Case-Control Study on the Association between Pandemrix?and Narcolepsy

Background

An increase in narcolepsy cases was observed in Finland and Sweden towards the end of the 2009 H1N1 influenza pandemic. Preliminary observational studies suggested a temporal link with the pandemic influenza vaccine Pandemrix™, leading to a number of additional studies across Europe. Given the public health urgency, these studies used readily available retrospective data from various sources. The potential for bias in such settings was generally acknowledged. Although generally advocated by key opinion leaders and international health authorities, no systematic quantitative assessment of the potential joint impact of biases was undertaken in any of these studies.

Methods

We applied bias-level multiple-bias analyses to two of the published narcolepsy studies: a pediatric cohort study from Finland and a case-control study from France. In particular, we developed Monte Carlo simulation models to evaluate a potential cascade of biases, including confounding by age, by indication and by natural H1N1 infection, selection bias, disease- and exposure misclassification. All bias parameters were evidence-based to the extent possible.

Results

Given the assumptions used for confounding, selection bias and misclassification, the Finnish rate ratio of 13.78 (95% CI: 5.72–28.11) reduced to a median value of 6.06 (2.5^th- 97.5^th percentile: 2.49–15.1) and the French odds ratio of 5.43 (95% CI: 2.6–10.08) to 1.85 (2.5^th—97.5^th percentile: 0.85–4.08).

Conclusion

We illustrate multiple-bias analyses using two studies on the Pandemrix^™-narcolepsy association and advocate their use to better understand the robustness of study findings. Based on our multiple-bias models, the observed Pandemrix^™-narcolepsy association consistently persists in the Finnish study. For the French study, the results of our multiple-bias models were inconclusive.     

Severe Obesity and Cardiometabolic Risk in Children: Comparison from Two International Classification Systems

Objectives

There is no agreed-upon definition for severe obesity (Sev-OB) in children. We compared estimates of Sev-OB as defined by different cut-points of body mass index (BMI) from the Centers for Disease Control and Prevention (CDC) or the World Health Organization (WHO) curves and the ability of each set of cut-points to screen for the presence of cardiometabolic risk factors.

Research Design and Methods

Cross-sectional, multicenter study involving 3,340 overweight/obese young subjects. Sev-OB was defined as BMI ≥99^th percentile or ≥1.2 times the 95^th percentile of the CDC or the WHO curves. High blood pressure, hypertriglyceridemia, low High Density Lipoprotein -cholesterol and impaired fasting glucose were considered as cardiometabolic risk factors.

Results

The estimated prevalence of Sev-OB varied widely between the two reference systems. Either using the cut-point ≥99^th percentile or ≥1.2 times the 95^th percentile, less children were defined as Sev-OB by CDC than WHO (46.8 vs. 89.5%, and 63.3 vs. 80.4%, respectively p<0.001). The CDC 99^th percentile had lower sensitivity (58.5 vs 94.2), higher specificity (57.6 vs 12.3) and higher positive predictive value (34.4 vs 28.9) than WHO in identifying obese children with ≥2 cardiometabolic risk factors. These differences were mitigated using the 1.2 times the 95^th percentile (sensitivity 73.9 vs. 88.1; specificity 40.7 vs. 22.5; positive predictive value 32.1 vs. 30.1). Substantial agreement between growth curves was found using the 1.2 times the 95^th percentile, in particular in children ≤10 years.

Conclusions

Estimates of Sev-OB and cardiometabolic risk as defined by different cut-points of BMI are influenced from the reference systems used. The 1.2 times the 95^th percentile of BMI of either CDC or WHO standard has a discriminatory advantage over the 99^th percentile for identifying severely obese children at increased cardiometabolic risk, particularly under 10 years of age.     

Association between Soluble (Pro)Renin Receptor Concentration in Cord Blood and Small for Gestational Age Birth: A Cross-Sectional Study

Objective

The (pro)renin receptor [(P)RR] has been recognized as a multifunctional receptor. The purpose of this study was to assess the association between plasma soluble (P)RR [s(P)RR] concentration in human cord blood (i.e., neonatal blood at birth) and small for gestational age (SGA) birth.

Methods

Participants were women with a singleton pregnancy who delivered at the National Center for Child Health and Development between January 2010 and December 2011. Inclusion criteria were availability of maternal pre-pregnancy and paternal body mass index, and the absence of structural anomalies in neonates. s(P)RR concentration in cord blood was measured in 621 neonates. The 621 pairs of mothers and neonates were categorized into four groups based on quartiles of s(P)RR concentrations in cord blood. SGA was defined as a birth weight below the 10^th percentile for gestational age. Logistic regression analysis was performed to assess the association between cord plasma s(P)RR concentration (quartiles) and incidence of SGA births.

Results

Among 621 neonates, 55 (8.9%) were diagnosed as SGA (SGA group) and 566 (91.1%) were not (non-SGA group). Average s(P)RR concentration in cord blood was 66.1±12.6 ng/ml (mean±standard deviation). There were 155 pairs in the first plasma s(P)RR concentration quartile (Q1: <58.2 ng/ml), 153 pairs in the second quartile (Q2: 58.2–65.1 ng/ml), 157 pairs in the third quartile (Q3: 65.1–73.1 ng/ml) and 156 pairs in the fourth quartile (Q4: >73.1 ng/ml). The distribution of SGA births was 18 (11.6%) in Q1, 14 (9.2%) in Q2, 16 (10.2%) in Q3 and 7 (4.5%) in Q4, respectively. The odds ratio of SGA births was 0.24 (95% confidence interval: 0.08–0.71) for the fourth quartile compared to the first quartile in multivariate models. The P-value for trend was also significant (P = 0.020).

Conclusion

High s(P)RR concentration is associated with a lower SGA birth likelihood.     

Metabolomic Profile of Umbilical Cord Blood Plasma from Early and Late Intrauterine Growth Restricted (IUGR) Neonates with and without Signs of Brain Vasodilation

Objectives

To characterize via NMR spectroscopy the full spectrum of metabolic changes in umbilical vein blood plasma of newborns diagnosed with different clinical forms of intrauterine growth restriction (IUGR).

Methods

23 early IUGR cases and matched 23 adequate-for-gestational-age (AGA) controls and 56 late IUGR cases with 56 matched AGAs were included in this study. Early IUGR was defined as a birth weight <10^th centile, abnormal umbilical artery (UA) Doppler and delivery <35 weeks. Late IUGR was defined as a birth weight <10^th centile with normal UA Doppler and delivery >35 weeks. This group was subdivided in 18 vasodilated (VD) and 38 non-VD late IUGR fetuses. All AGA patients had a birth weight >10^th centile. ¹H nuclear magnetic resonance (NMR) metabolomics of the blood samples collected from the umbilical vein at delivery was obtained. Multivariate statistical analysis identified several metabolites that allowed the discrimination between the different IUGR subgroups, and their comparative levels were quantified from the NMR data.

Results

The NMR-based analysis showed increased unsaturated lipids and VLDL levels in both early and late IUGR samples, decreased glucose and increased acetone levels in early IUGR. Non-significant trends for decreased glucose and increased acetone levels were present in late IUGR, which followed a severity gradient when the VD and non-VD subgroups were considered. Regarding amino acids and derivatives, early IUGR showed significantly increased glutamine and creatine levels, whereas the amounts of phenylalanine and tyrosine were decreased in early and late-VD IUGR samples. Valine and leucine were decreased in late IUGR samples. Choline levels were decreased in all clinical subforms of IUGR.

Conclusions

IUGR is not associated with a unique metabolic profile, but important changes are present in different clinical subsets used in research and clinical practice. These results may help in characterizing comprehensively specific alterations underlying different IUGR subsets.     

The Effect of Fetal and Childhood Growth over Depression in Early Adulthood in a Southern Brazilian Birth Cohort

Background

Poor nutrition and growth during fetal life and childhood might be associated with depression in adulthood; however, studies evaluating these associations present controversial results, especially when comparing studies using different proxies for fetal growth. We evaluated the association of fetal and childhood growth/nutrition with depression, in adulthood, using different approaches and measurement methods.

Method

In 1982, hospital births (n = 5914) in Pelotas, southern Brazil, were examined and have been prospectively followed. At 30 years, the presence of major depression and depressive symptoms severity was evaluated using the Mini International Neuropsychiatric Interview (MINI) and Beck Depression Inventory (BDI-II). The present study assessed their association with birth weight, premature birth, small for gestational age (SGA), stunting and conditional growth during childhood.

Results

At 30 years, 3576 individuals were evaluated and 7.9% had major depression. Low birth weight (PR = 1.01 95%CI [0.64–1.60]), having been born SGA (PR = 0.87 95%CI [0.64–1.19]) and premature birth (PR = 1.22 95%CI [0.72–2.07]) were not associated with major depression in multivariable models. However, those born SGA who were also stunted in childhood had a higher prevalence of major depression (PR = 1.87 95%CI [1.06–3.29]) and greater odds of scoring a higher level of depression in the BDI-II (OR = 2.18 95%CI [1.34–3.53]).

Conclusion

In this Brazilian cohort of young adults, those born SGA who were also stunted during childhood had a higher risk of depression in adulthood. Our results show that the effect of growth impairment on depression is cumulative.     

Smoking Ban and Small-For-Gestational Age Births in Ireland

Background

Ireland introduced a comprehensive workplace smoke-free legislation in March, 2004. Smoking-related adverse birth outcomes have both health care and societal cost implications. The main aim of this study was to determine the impact of the Irish smoke-free legislation on small-for-gestationa- age (SGA) births.

Methods and Findings

We developed a population-based birthweight (BW) percentile curve based on a recent study to compute SGA (BW <5^th percentile) and very SGA (vSGA - BW<3^rd percentile) for each gestational week. Monthly births born between January 1999 and December 2008 were analyzed linking with monthly maternal smoking rates from a large referral maternity university hospital. We ran individual control and CUSUM charts, with bootstrap simulations, to pinpoint the breakpoint for the impact of ban implementation ( = April 2004). Monthly SGA rates (%) before and after April 2004 was considered pre and post ban period births, respectively. Autocorrelation was tested using Durbin Watson (DW) statistic. Mixed models using a random intercept and a fixed effect were employed using SAS (v 9.2). A total of 588,997 singleton live-births born between January 1999 and December 2008 were analyzed. vSGA and SGA monthly rates declined from an average of 4.7% to 4.3% and from 6.9% to 6.6% before and after April 2004, respectively. No auto-correlation was detected (DW = ∼2). Adjusted mixed models indicated a significant decline in both vSGA and SGA rates immediately after the ban [(−5.3%; 95% CI −5.43% to −5.17%, p<0.0001) and (−0.45%; 95% CI: −0.7% to −0.19%, p<0.0007)], respectively. Significant gradual effects continued post the ban periods for vSGA and SGA rates, namely, −0.6% (p<0.0001) and −0.02% (p<0.0001), respectively.

Conclusions

A significant reduction in small-for-gestational birth rates both immediately and sustained over the post-ban period, reinforces the mounting evidence of the positive health effect of a successful comprehensive smoke-free legislation in a vulnerable population group as pregnant women.     

Maternal Antioxidant Levels in Pregnancy and Risk of Preeclampsia and Small for Gestational Age Birth: A Systematic Review and Meta-Analysis

Background

Oxidative stress in preeclampsia and small for gestational age (SGA) birth suggests antioxidant supplementation could prevent these conditions. However, it remains unclear whether maternal antioxidant levels are systematically lower in these pregnancies.

Objective

To conduct a systematic review of the association between maternal antioxidant levels during pregnancy and preeclampsia or SGA.

Methods

We searched PubMed, Embase, and several other databases from 1970–2013 for observational studies that measured maternal blood levels of non-enzymatic antioxidants (vitamins A, C, E, and carotenoids) during pregnancy or within 72 hours of delivery. The entire review process was done in duplicate. Study quality was assessed using the Newcastle-Ottawa Scale and additional questions. We pooled the standardized mean difference (SMD) across studies, stratified by outcome and pregnancy trimester, and investigated heterogeneity using meta-regression.

Results

We reviewed 1,882 unique citations and 64 studies were included. Most studies were small with important risk of bias. Among studies that addressed preeclampsia (n = 58) and SGA (n = 9), 16% and 66%, respectively, measured levels prior to diagnosis. The SMDs for vitamins A, C, and E were significantly negative for overall preeclampsia, but not for mild or severe preeclampsia subtypes. Significant heterogeneity was observed in all meta-analyses and most could not be explained. Evidence for lower carotenoid antioxidants in preeclampsia and SGA was limited and inconclusive. Publication bias appears likely.

Conclusions

Small, low-quality studies limit conclusions that can be drawn from the available literature. Observational studies inconsistently show that vitamins C and E or other antioxidants are lower in women who develop preeclampsia or SGA. Reverse causality remains a possible explanation for associations observed. New clinical trials are not warranted in light of this evidence; however, additional rigorous observational studies measuring antioxidant levels before clinical detection of preeclampsia and SGA may clarify whether levels are altered at a causally-relevant time of pregnancy.     

Reliability of Single-Use PEEP-Valves Attached to Self-Inflating Bags during Manual Ventilation of Neonates – An In Vitro Study

Introduction

International resuscitation guidelines suggest to use positive end-expiratory pressure (PEEP) during manual ventilation of neonates. Aim of our study was to test the reliability of self-inflating bags (SIB) with single-use PEEP valves regarding PEEP delivery and the effect of different peak inflation pressures (PIP) and ventilation rates (VR) on the delivered PEEP.

Methods

Ten new single-use PEEP valves from 5 manufacturers were tested by ventilating an intubated 1kg neonatal manikin containing a lung model with a SIB that was actuated by an electromechanical plunger device. Standard settings: PIP 20cmH₂O, VR 60/min, flow 8L/min. PEEP settings of 5 and 10cmH₂O were studied. A second test was conducted with settings of PIP 40cmH₂O and VR 40/min. The delivered PEEP was measured by a respiratory function monitor (CO₂SMO⁺).

Results

Valves from one manufacturer delivered no relevant PEEP and were excluded. The remaining valves showed a continuous decay of the delivered pressure during expiration. The median (25^th and 75^th percentile) delivered PEEP with standard settings was 3.4(2.7–3.8)cmH₂O when set to 5cmH₂O and 6.1(4.9–7.1)cmH₂O when set to 10cmH₂O. Increasing the PIP from 20 to 40 cmH₂O led to a median (25^th and 75^th percentile) decrease in PEEP to 2.3(1.8–2.7)cmH₂O and 4.3(3.2–4.8)cmH₂O; changing VR from 60 to 40/min led to a PEEP decrease to 2.8(2.1–3.3)cmH₂O and 5.0(3.5–6.2)cmH₂O for both PEEP settings.

Conclusion

Single-use PEEP valves do not reliably deliver the set PEEP. PIP and VR have an effect on the delivered PEEP. Operators should be aware of these limitations when manually ventilating neonates.