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.     

IgM-Antibodies against Phosphorylcholine in Mothers and Normal or Low Birth Weight Term Newborn Infants

Objective

To determine levels of athero-protective IgM antibodies against phosphorylcholine in mothers and term-born normal or low birth weight infants.

Approach

Twenty three mother-infant pairs were studied, of whom 16 infants were within the normal weight range for gestational age (NGA; 3652[504] g) and 7 were small for gestational age (SGA; birth weight: 2715[255] g), the latter <2SD below the Swedish reference data mean for normal fetal growth. All infants were born at term (mean±SD 40.5±1.1 weeks). Serum was available from 6 mothers with SGA and 14 with NGA infants. Participating mothers were aged 34.0±3.9 years (no difference between groups). Fourteen neonates were boys and seven were girls. Levels of anti-PC IgM were determined by ELISA.

Results

Neonatal IgM anti-PC levels were low (undetectable in 8 infants out of which 3 were SGA) with a median of 76[range 0–2.51] U/ml. Maternal IgM anti-PC levels were significantly higher (median 7198[range: 25.32–656.0]) U/ml) and the proportion of mothers in highest quartile (>75th percentile) was larger in mothers of NGA-infants (43%) vs. those of SGA-infants (0%, p = 0.032).

Conclusions

IgM anti-PC levels are low at birth, which suggests that these antibodies do not play a “housekeeping” role in immune function during fetal life/development, but arise predominately on exposure to external antigens after birth. Furthermore, low maternal IgM anti-PC levels may play a role in placental insufficiency, contributing to poor fetal growth and a small-for-date baby. This preliminary observation may have implications for the future risk of atherosclerosis/cardiovascular disease development in pregnant women and their offspring.     

DNA methylation of IGF2, GNASAS,INSIGF and LEP and being born small for gestational age

Being born small for gestational age (SGA), a proxy for intrauterine growth restriction (IUGR) and prenatal famine exposure are both associated with a greater risk of metabolic disease. Both associations have been hypothesized to involve epigenetic mechanisms. We investigated whether prenatal growth restriction early in pregnancy was associated with changes in DNA methylation at loci that were previously shown to be sensitive to early gestational famine exposure. We compared 38 individuals born preterm (<32 weeks) and with a birth weight too low for their gestational age (less than −1SDS; SGA) with 75 individuals born preterm but with a birth weight appropriate for their gestational age (greater than −1SDS) and a normal postnatal growth (greater than −1SDS at three months post term; AGA). The SGA individuals were not only lighter at birth, but also had a smaller length (p = 3.3 × 10⁻¹³) and head circumference at birth (p = 4.1 × 10⁻¹³). The DNA methylation levels of IGF2, GNASAS, INSIGF and LEP were 48.5, 47.5, 79.4 and 25.7% respectively. This was not significantly different between SGA and AGA individuals. Risk factors for being born SGA, including preeclampsia and maternal smoking, were also not associated with DNA methylation at these loci. Growth restriction early in development is not associated with DNA methylation at loci shown to be affected by prenatal famine exposure. Our and previous results by others indicate that prenatal growth restriction and famine exposure may be associated with different epigenetic changes or non-epigenetic mechanisms that may lead to similar later health outcomes.Key words: SGA, DOHAD, IUGR, DNA methylation, famine, IGF2, LEP, INS, GNASAS     

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.     

DNA Methylation of IGF2DMR and H19 Is Associated with Fetal and Infant Growth: The Generation R Study

Changes in epigenetic programming of embryonic growth genes during pregnancy seem to affect fetal growth. Therefore, in a population-based prospective birth cohort in the Netherlands, we examined associations between fetal and infant growth and DNA methylation of IGF2DMR, H19 and MTHFR. For this study, we selected 69 case children born small-for-gestational age (SGA, birth weight <-2SDS) and 471 control children. Fetal growth was assessed with serial ultrasound measurements. Information on birth outcomes was retrieved from medical records. Infant weight was assessed at three and six months. Methylation was assessed in DNA extracted from umbilical cord white blood cells. Analyses were performed using linear mixed models with DNA methylation as dependent variable. The DNA methylation levels of IGF2DMR and H19 in the control group were, median (90% range), 53.6% (44.5–61.6) and 30.0% (25.6–34.2) and in the SGA group 52.0% (43.9–60.9) and 30.5% (23.9–32.9), respectively. The MTHFR region was found to be hypomethylated with limited variability in the control and SGA group, 2.5% (1.4–4.0) and 2.4% (1.5–3.8), respectively. SGA was associated with lower IGF2DMR DNA methylation (β = −1.07, 95% CI −1.93; −0.21, P-value = 0.015), but not with H19 methylation. A weight gain in the first three months after birth was associated with lower IGF2DMR DNA methylation (β = −0.53, 95% CI −0.91; −0.16, P-value = 0.005). Genetic variants in the IGF2/H19 locus were associated with IGF2DMR DNA methylation (P-value<0.05), but not with H19 methylation. Furthermore, our results suggest a possibility of mediation of DNA methylation in the association between the genetic variants and SGA. To conclude, IGF2DMR and H19 DNA methylation is associated with fetal and infant growth.     

The Growing Trend of Moderate Preterm Births: An Ecological Study in One Region of Brazil

Background

Preterm birth is a serious public health problem, as it is linked to high rates of neonatal and child morbidity and mortality, with Brazil listed among the countries with the ten highest numbers of premature births. Nonetheless, knowledge is scarce regarding prematurity and associated factors in mid-sized cities. The objective of this study was to analyze the trend of preterm births and associated factors in a municipality located in the state of Paraná, Brazil.

Methods

This was an ecological time series study of births recorded into the Live Birth Information System for residents of Maringá, Paraná, Brazil, between 2000 and 2013. The polynomial regression model was used for trend analysis of preterm birth, characteristics of the mother, gestation and delivery, and newborn. The association with preterm birth was analyzed using odds ratio (OR).

Results

A total of 61,634 live births were analyzed, of which 5,632 were preterm births. Prematurity increased from 7.9% in 2000 to 11.2% in 2013 –an average increase of 0.54% per year (r² = 0.93)–with a growing share of moderate preterm births (32 to <37 weeks), which rose from 7.0% in 2000 to 9.7% in 2013. Between 2011 and 2013, multiple pregnancy (OR = 16.64; CI = 13.24–20.92), inadequate number of prenatal visits (OR = 2.81; CI = 2.51–3.15), Apgar score below 7 at 1 (OR = 4.07; CI = 3.55–4.67) and 5 minutes (OR = 10.88; CI = 7.71–15.36), low birth weight (OR = 38.75; CI = 33.72–44.55) and congenital malformations (OR = 3.18; CI = 2.14–4.74) were associated with preterm birth. A growing trend was observed for multiple pregnancies, with an average annual increase of 0.32% (r² = 0.90), as well as for C-section birth (2.38% yearly increase). Of all newborn characteristics, Apgar score below 7 at 5 minutes (-0.19% per year) and low birth weight (-1.43%) decreased, whereas congenital malformations rose (0.20% per year).

Conclusions

Efforts are required to prevent premature delivery, particularly during the moderate period, as well as greater care during the prenatal period towards expectant mothers bearing multiple pregnancies, birth defects, in addition to reducing C-section birth as it may be linked to preterm birth.     

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.     

Changes in Birth Weight between 2002 and 2012 in Guangzhou,China

Background

Recent surveillance data suggest that mean birth weight has begun to decline in several developed countries. The aim of this study is to examine the changes in birth weight among singleton live births from 2002 to 2012 in Guangzhou, one of the most rapidly developed cities in China.

Methods

We used data from the Guangzhou Perinatal Health Care and Delivery Surveillance System for 34108 and 54575 singleton live births with 28–41 weeks of gestation, who were born to local mothers, in 2002 and 2012, respectively. The trends in birth weight, small (SGA) and large (LGA) for gestational age and gestational length were explored in the overall population and gestational age subgroups.

Results

The mean birth weight decreased from 3162 g in 2002 to 3137 g in 2012 (crude mean difference, −25 g; 95% CI, −30 to −19). The adjusted change in mean birth weight appeared to be slight (−6 g from 2002 to 2012) after controlling for maternal age, gestational age, educational level, parity, newborn''s gender and delivery mode. The percentages of SGA and LGA in 2012 were 0.6% and 1.5% lower than those in 2002, respectively. The mean gestational age dropped from 39.2 weeks in 2002 to 38.9 weeks in 2012. In the stratified analysis, we observed the changes in birth weight differed among gestational age groups. The mean birth weight decreased among very preterm births (28–31 weeks), while remained relatively stable among other gestational age subcategories.

Conclusions

Among local population in Guangzhou from 2002 to 2012, birth weight appeared to slightly decrease. The percentage of SGA and LGA also simultaneously dropped, indicating that newborns might gain a healthier weight for gestational age.     

Thresholds of glycemia,insulin therapy,and risk for severe retinopathy in premature infants: A cohort study

BackgroundHyperglycemia in preterm infants may be associated with severe retinopathy of prematurity (ROP) and other morbidities. However, it is uncertain which concentration of blood glucose is associated with increased risk of tissue damage, with little consensus on the cutoff level to treat hyperglycemia. The objective of our study was to examine the association between hyperglycemia and severe ROP in premature infants.Methods and findingsIn 2 independent, monocentric cohorts of preterm infants born at <30 weeks’ gestation (Nantes University Hospital, 2006–2016, primary, and Lyon-HFME University Hospital, 2009–2017, validation), we first analyzed the association between severe (stage 3 or higher) ROP and 2 markers of glucose exposure between birth and day 21—maximum value of glycemia (MaxGly_1–21) and mean of daily maximum values of glycemia (MeanMaxGly_1–21)—using logistic regression models. In both the primary (n = 863 infants, mean gestational age 27.5 ± 1.4 weeks, boys 52.5%; 38 with severe ROP; 54,083 glucose measurements) and the validation cohort (n = 316 infants, mean gestational age 27.4 ± 1.4 weeks, boys 51.3%), MaxGly_1–21 and MeanMaxGly_1–21 were significantly associated with an increased risk of severe ROP: odds ratio (OR) 1.21 (95% CI 1.14–1.27, p < 0.001) and OR 1.70 (95% CI 1.48–1.94, p < 0.001), respectively, in the primary cohort and OR 1.17 (95% CI 1.05–1.32, p = 0.008) and OR 1.53 (95% CI 1.20–1.95, p < 0.001), respectively, in the validation cohort. These associations remained significant after adjustment for confounders in both cohorts. Second, we identified optimal cutoff values of duration of exposure above each concentration of glycemia between 7 and 13 mmol/l using receiver operating characteristic curve analyses in the primary cohort. Optimal cutoff values for predicting stage 3 or higher ROP were 9, 6, 5, 3, 2, 2, and 1 days above a glycemic threshold of 7, 8, 9, 10, 11, 12, and 13 mmol/l, respectively. Severe exposure was defined as at least 1 exposure above 1 of the optimal cutoffs. Severe ROP was significantly more common in infants with severe exposure in both the primary (10.9% versus 0.6%, p < 0.001) and validation (5.2% versus 0.9%, p = 0.030) cohorts. Finally, we analyzed the association between insulin therapy and severe ROP in a national population-based prospectively recruited cohort (EPIPAGE-2, 2011, n = 1,441, mean gestational age 27.3 ± 1.4, boys 52.5%) using propensity score weighting. Insulin use was significantly associated with severe ROP in overall cohort crude analyses (OR 2.51 [95% CI 1.13–5.58], p = 0.024). Adjustment for inverse propensity score (gestational age, sex, birth weight percentile, multiple birth, spontaneous preterm birth, main pregnancy complications, surfactant therapy, duration of oxygen exposure between birth and day 28, digestive state at day 7, caloric intake at day 7, and highest glycemia during the first week) and duration of oxygen therapy had a large but not significant effect on the association between insulin treatment and severe ROP (OR 0.40 [95% CI 0.13–1.24], p = 0.106). Limitations of this study include its observational nature and, despite the large number of patients included compared to earlier similar studies, the lack of power to analyze the association between insulin use and retinopathy.ConclusionsIn this study, we observed that exposure to high glucose concentration is an independent risk factor for severe ROP, and we identified cutoff levels that are significantly associated with increased risk. The clinical impact of avoiding exceeding these thresholds to prevent ROP deserves further evaluation.

In this cohort study, Elsa Kermorvant-Duchemin and colleagues examine the association between hyperglycemia and severe retinopathy of prematurity in infants.     

Associations of maternal dietary inflammatory potential and quality with offspring birth outcomes: An individual participant data pooled analysis of 7 European cohorts in the ALPHABET consortium

BackgroundAdverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth outcomes. However, evidence on whole diet that considers complex nutrient and food interaction is rare and conflicting. We aim to elucidate the influence of whole-diet maternal dietary inflammatory potential and quality during periconceptional and antenatal periods on birth outcomes.Methods and findingsWe harmonized and pooled individual participant data (IPD) from up to 24,861 mother–child pairs in 7 European mother–offspring cohorts [cohort name, country (recruitment dates): ALSPAC, UK (1 April 1991 to 31 December 1992); EDEN, France (27 January 2003 to 6 March 2006); Generation R, the Netherlands (1 April 2002 to 31 January 2006); Lifeways, Ireland (2 October 2001 to 4 April 2003); REPRO_PL, Poland (18 September 2007 to 16 December 2011); ROLO, Ireland (1 January 2007 to 1 January 2011); SWS, United Kingdom (6 April 1998 to 17 December 2002)]. Maternal diets were assessed preconceptionally (n = 2 cohorts) and antenatally (n = 7 cohorts). Maternal dietary inflammatory potential and quality were ranked using the energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) index, respectively. Primary outcomes were birth weight and gestational age at birth. Adverse birth outcomes, i.e., low birth weight (LBW), macrosomia, small-for-gestational-age (SGA), large-for-gestational-age (LGA), preterm and postterm births were defined according to standard clinical cutoffs. Associations of maternal E-DII and DASH scores with infant birth outcomes were assessed using cohort-specific multivariable regression analyses (adjusted for confounders including maternal education, ethnicity, prepregnancy body mass index (BMI), maternal height, parity, cigarettes smoking, and alcohol consumption), with subsequent random-effects meta-analyses.Overall, the study mothers had a mean ± SD age of 29.5 ± 4.9 y at delivery and a mean BMI of 23.3 ± 4.2 kg/m². Higher pregnancy DASH score (higher dietary quality) was associated with higher birth weight [β(95% CI) = 18.5(5.7, 31.3) g per 1-SD higher DASH score; P value = 0.005] and head circumference [0.03(0.01, 0.06) cm; P value = 0.004], longer birth length [0.05(0.01, 0.10) cm; P value = 0.010], and lower risk of delivering LBW [odds ratio (OR) (95% CI) = 0.89(0.82, 0.95); P value = 0.001] and SGA [0.87(0.82, 0.94); P value < 0.001] infants. Higher maternal prepregnancy E-DII score (more pro-inflammatory diet) was associated with lower birth weight [β(95% CI) = −18.7(−34.8, −2.6) g per 1-SD higher E-DII score; P value = 0.023] and shorter birth length [−0.07(−0.14, −0.01) cm; P value = 0.031], whereas higher pregnancy E-DII score was associated with a shorter birth length [−0.06(−0.10, −0.01) cm; P value = 0.026] and higher risk of SGA [OR(95% CI) = 1.18(1.11, 1.26); P value < 0.001]. In male, but not female, infants higher maternal prepregnancy E-DII was associated with lower birth weight and head circumference, shorter birth length, and higher risk of SGA (P-for-sex-interaction = 0.029, 0.059, 0.104, and 0.075, respectively). No consistent associations were observed for maternal E-DII and DASH scores with gestational age, preterm and postterm birth, or macrosomia and LGA. Limitations of this study were that self-reported dietary data might have increased nondifferential measurement error and that causality cannot be claimed definitely with observational design.ConclusionsIn this cohort study, we observed that maternal diet that is of low quality and high inflammatory potential is associated with lower offspring birth size and higher risk of offspring being born SGA in this multicenter meta-analysis using harmonized IPD. Improving overall maternal dietary pattern based on predefined criteria may optimize fetal growth and avert substantial healthcare burden associated with adverse birth outcomes.

In this cohort analysis, Ling-Wei Chen and colleagues explore associations of maternal dietary patterns with offspring birth outcomes.     

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     

Association of Second and Third Trimester Weight Gain in Pregnancy with Maternal and Fetal Outcomes

Objective

To investigate the association between weekly weight gain, during the second and third trimesters, classified according to the 2009 Institute of Medicine (IOM/NRC) recommendations, and maternal and fetal outcomes.

Methods

Gestational weight gain was evaluated in 2,244 pregnant women of the Brazilian Study of Gestational Diabetes (Estudo Brasileiro do Diabetes Gestacional – EBDG). Outcomes were cesarean delivery, preterm birth and small or large for gestational age birth (SGA, LGA). Associations between inadequate weight gain and outcomes were estimated using robust Poisson regression adjusting for pre-pregnancy body mass index, trimester-specific weight gain, age, height, skin color, parity, education, smoking, alcohol consumption, gestational diabetes and hypertensive disorders in pregnancy.

Results

In fully adjusted models, in the second trimester, insufficient weight gain was associated with SGA (relative risk [RR] 1.72, 95% confidence interval [CI] 1.26–2.33), and excessive weight gain with LGA (RR 1.64, 95% CI 1.16–2.31); in third trimester, excessive weight gain with preterm birth (RR 1.70, 95% CI 1.08–2.70) and cesarean delivery (RR 1.21, 95% CI 1.03–1.44). Women with less than recommended gestational weight gain in the 2^nd trimester had a lesser risk of cesarean deliveries (RR 0.82, 95% CI 0.71–0.96) than women with adequate gestational weight gain in this trimester.

Conclusion

Though insufficient weight gain in the 3^rd trimester was not associated with adverse outcomes, other deviations from recommended weight gain during second and third trimester were associated with adverse pregnancy outcomes. These findings support, in part, the 2009 IOM/NRC recommendations for nutritional monitoring during pregnancy.     

Red Blood Cell Distribution Width Is Associated with Severity of Leukoaraiosis

Red blood cell distribution width (RDW) is one of the routine hematologic parameters reported in the complete blood count test, which has been recognized as strong prognostic marker for various medical conditions, especially cardiovascular disease. We evaluated that RDW was also associated with the leukoaraiosis; common radiological finding of brain and that has been strongly associated with risk of stroke and dementia. In the present study, we included 1006 non-stroke individuals who underwent brain MRI and routine complete blood count test including RDW. Fazekas scale was used to measure the severity of leukoaraiosis based on fluid-attenuated inversion recovery image, and the severity was dichotomized to mild-degree (Fazekas scale: 0–1) and severe-degree leukoaraiosis (Fazekas scale: 2–3). Univariate and multivariate logistic regression models were constructed to evaluate independent risk factor for severe-degree of leukoaraiosis. Mean age of 1006 subjects was 64.34 ± 9.11 year, and mean of RDW was 12.97 ± 0.86%. The severe-degree of leukoaraiosis (Fazekas scale ≥ 2) was found in 28.83%. In the multivariate logistic regression, 4^th quartile of RDW (> 13.3%) were significantly associated with the presence of severe-degree of leukoaraiosis (adjusted odds ratio, 1.87; 95% confidence interval, 1.20–2.92) compared to the 1^st quartile of RDW (< 12.5%). The significance was not changed after adjustments for hemoglobin and other hematologic indices. These findings suggest that RDW is independently associated with severity of leukoaraiosis.     

Risk of Childhood Overweight after Exposure to Tobacco Smoking in Prenatal and Early Postnatal Life

Objective

To investigate the association between exposure to mothers smoking during prenatal and early postnatal life and risk of overweight at age 7 years, while taking birth weight into account.

Methods

From the Danish National Birth Cohort a total of 32,747 families were identified with available information on maternal smoking status in child''s pre- and postnatal life and child''s birth weight, and weight and height at age 7 years. Outcome was overweight according to the International Obesity Task Force gender and age specific body mass index. Smoking exposure was categorized into four groups: no exposure (n = 25,076); exposure only during pregnancy (n = 3,343); exposure only postnatally (n = 140); and exposure during pregnancy and postnatally (n = 4,188). Risk of overweight according to smoking status as well as dose-response relationships were estimated by crude and adjusted odds ratios using logistic regression models.

Results

Exposure to smoking only during pregnancy, or both during pregnancy and postnatally were both significantly associated with overweight at 7 years of age (OR: 1.31, 95% CI: 1.15–1.48, and OR: 1.76, 95% CI: 1.58–1.97, respectively). Analyses excluding children with low birth weight (<2,500 gram) revealed similar results. A significant prenatal dose-response relationship was found. Per one additional cigarette smoked per day an increase in risk of overweight was observed (OR: 1.02, 95% CI: 1.01–1.03). When adjusting for quantity of smoking during pregnancy, prolonged exposure after birth further increased the risk of later overweight in the children (OR 1.28, 95% CI:1.09–1.50) compared with exposure only in the prenatal period.

Conclusions

Mother''s perinatal smoking increased child''s OR of overweight at age 7 years irrespective of birth weight, and with higher OR if exposed both during pregnancy and in early postnatal life. Clear dose-response relationships were observed, which emphasizes the need for prevention of any tobacco exposure of infants.     

The Association of Neighborhood Social Capital and Ethnic (Minority) Density with Pregnancy Outcomes in the Netherlands

Background

Perinatal morbidity rates are relatively high in the Netherlands, and significant inequalities in perinatal morbidity and mortality can be found across neighborhoods. In socioeconomically deprived areas, ‘Western’ women are particularly at risk for adverse birth outcomes. Almost all studies to date have explained the disparities in terms of individual determinants of birth outcomes. This study examines the influence of neighborhood contextual characteristics on birth weight (adjusted for gestational age) and preterm birth. We focused on the influence of neighborhood social capital – measured as informal socializing and social connections between neighbors – as well as ethnic (minority) density.

Methods

Data on birth weight and prematurity were obtained from the Perinatal Registration Netherlands 2000–2008 dataset, containing 97% of all pregnancies. Neighborhood-level measurements were obtained from three different sources, comprising both survey and registration data. We included 3.422 neighborhoods and 1.527.565 pregnancies for the birth weight analysis and 1.549.285 pregnancies for the premature birth analysis. Linear and logistic multilevel regression was performed to assess the associations of individual and neighborhood level variables with birth weight and preterm birth.

Results

We found modest but significant neighborhood effects on birth weight and preterm births. The effect of ethnic (minority) density was stronger than that of neighborhood social capital. Moreover, ethnic (minority) density was associated with higher birth weight for infants of non-Western ethnic minority women compared to Western women (15 grams; 95% CI: 12,4/17,5) as well as reduced risk for prematurity (OR 0.97; CI 0,95/0,99).

Conclusions

Our results indicate that neighborhood contexts are associated with birth weight and preterm birth in the Netherlands. Moreover, ethnic (minority) density seems to be a protective factor for non-Western ethnic minority women, but not for Western women. This helps explain the increased risk of Western women in deprived neighborhoods for adverse birth outcomes found in previous studies.     

Joint and Independent Associations of Gestational Weight Gain and Pre-Pregnancy Body Mass Index with Outcomes of Pregnancy in Chinese Women: A Retrospective Cohort Study

Objective

To explore the joint and independent effects of gestational weight gain (GWG) and pre-pregnancy body mass index (BMI) on pregnancy outcomes in a population of Chinese Han women and to evaluate pregnant women’s adherence to the 2009 Institute of Medicine (IOM) gestational weight gain guidelines.

Methods

This was a multicenter, retrospective cohort study of 48,867 primiparous women from mainland China who had a full-term singleton birth between January 1, 2011 and December 30, 2011. The independent associations of pre-pregnancy BMI, GWG and categories of combined pre-pregnancy BMI and GWG with outcomes of interest were examined using an adjusted multivariate regression model. In addition, women with pre-pregnancy hypertension were excluded from the analysis of the relationship between GWG and delivery of small-for-gestational-age (SGA) infants, and women with gestational diabetes (GDM) were excluded from the analysis of the relationship between GWG and delivery of large-for-gestational-age (LGA) infants.

Results

Only 36.8% of the women had a weight gain that was within the recommended range; 25% and 38.2% had weight gains that were below and above the recommended range, respectively. The contribution of GWG to the risk of adverse maternal and fetal outcomes was modest. Women with excessive GWG had an increased likelihood of gestational hypertension (adjusted OR 2.55; 95% CI = 1.92–2.80), postpartum hemorrhage (adjusted OR 1.30; 95% CI = 1.17–1.45), cesarean section (adjusted OR 1.31; 95% CI = 1.18–1.36) and delivery of an LGA infant (adjusted OR 2.1; 95% CI = 1.76–2.26) compared with women with normal weight gain. Conversely, the incidence of GDM (adjusted OR 1.64; 95% CI = 1.20–1.85) and SGA infants (adjusted OR 1.51; 95% CI = 1.32–1.72) was increased in the group of women with inadequate GWG. Moreover, in the obese women, excessive GWG was associated with an apparent increased risk of delivering an LGA infant. In the women who were underweight, poor weight gain was associated with an increased likelihood of delivering an SGA infant. After excluding the mothers with GDM or gestational hypertension, the ORs for delivery of LGA and SGA infants decreased for women with high GWG and increased for women with low GWG.

Conclusions

GWG above the recommended range is common in this population and is associated with multiple unfavorable outcomes independent of pre-pregnancy BMI. Obese women may benefit from avoiding weight gain above the range recommended by the 2009 IOM. Underweight women should avoid low GWG to prevent delivering an SGA infant. Pregnant women should therefore be monitored to comply with the IOM recommendations and should have a balanced weight gain that is within a range based on their pre-pregnancy BMI.     

Characterization of UDP-glucose dehydrogenase isoforms in the medicinal legume Glycyrrhiza uralensis

Uridine 5′-diphosphate (UDP)-glucose dehydrogenase (UGD) produces UDP-glucuronic acid from UDP-glucose as a precursor of plant cell wall polysaccharides. UDP-glucuronic acid is also a sugar donor for the glycosylation of various plant specialized metabolites. Nevertheless, the roles of UGDs in plant specialized metabolism remain poorly understood. Glycyrrhiza species (licorice), which are medicinal legumes, biosynthesize triterpenoid saponins, soyasaponins and glycyrrhizin, commonly glucuronosylated at the C-3 position of the triterpenoid scaffold. Often, several different UGD isoforms are present in plants. To gain insight into potential functional differences among UGD isoforms in triterpenoid saponin biosynthesis in relation to cell wall component biosynthesis, we identified and characterized Glycyrrhiza uralensis UGDs (GuUGDs), which were discovered to comprise five isoforms, four of which (GuUGD1–4) showed UGD activity in vitro. GuUGD1–4 had different biochemical properties, including their affinity for UDP-glucose, catalytic constant, and sensitivity to feedback inhibitors. GuUGD2 had the highest catalytic constant and highest gene expression level among the GuUGDs, suggesting that it is the major isoform contributing to the transition from UDP-glucose to UDP-glucuronic acid in planta. To evaluate the contribution of GuUGD isoforms to saponin biosynthesis, we compared the expression patterns of GuUGDs with those of saponin biosynthetic genes in methyl jasmonate (MeJA)-treated cultured stolons. GuUGD1–4 showed delayed responses to MeJA compared to those of saponin biosynthetic genes, suggesting that MeJA-responsive expression of GuUGDs compensates for the decreased UDP-glucuronic acid pool due to consumption during saponin biosynthesis.     

Nevirapine Concentration in Hair Samples Is a Strong Predictor of Virologic Suppression in a Prospective Cohort of HIV-Infected Patients

Effective antiretroviral (ARV) therapy depends on adequate drug exposure, yet methods to assess ARV exposure are limited. Concentrations of ARV in hair are the product of steady-state pharmacokinetics factors and longitudinal adherence. We investigated nevirapine (NVP) concentrations in hair as a predictor of treatment response in women receiving ARVs. In participants of the Women’s Interagency HIV Study, who reported NVP use for >1 month from 2003–2008, NVP concentrations in hair were measured via liquid-chromatography-tandem mass-spectrometry. The outcome was virologic suppression (plasma HIV RNA below assay threshold) at the time of hair sampling and the primary predictor was nevirapine concentration categorized into quartiles. We controlled for age, race/ethnicity, pre-treatment HIV RNA, CD4 cell count, and self-reported adherence over the 6-month visit interval (categorized ≤ 74%, 75%–94% or ≥ 95%). We also assessed the relation of NVP concentration with changes in hepatic transaminase levels via multivariate random intercept logistic regression and linear regression analyses. 271 women contributed 1089 person-visits to the analysis (median 3 of semi-annual visits). Viral suppression was least frequent in concentration quartile 1 (86/178 (48.3%)) and increased in higher quartiles (to 158/204 (77.5%) for quartile 4). The odds of viral suppression in the highest concentration quartile were 9.17 times (95% CI 3.2–26, P < 0.0001) those in the lowest. African-American race was associated with lower rates of virologic suppression independent of NVP hair concentration. NVP concentration was not significantly associated with patterns of serum transaminases. Concentration of NVP in hair was a strong independent predictor of virologic suppression in women taking NVP, stronger than self-reported adherence, but did not appear to be strongly predictive of hepatotoxicity.     

Migrant Background and Weight Gain in Early Infancy: Results from the German Study Sample of the IDEFICS Study

Objective

To examine variations in infant weight gain between children of parents with and without migrant background and to investigate how these differences are explained by pre- and perinatal factors.

Methods

We used data on birth weight and weight at six months from well-child check-up books that were collected from a population-based German sample of children in the IDEFICS study (n = 1,287). We calculated unadjusted and adjusted means for weight z-scores at birth and six months later. We applied linear regression for change in weight z-score and we calculated odds ratios and 95% confidence intervals (95% CI) for rapid weight gain by logistic regression, adjusted for biological, social and behavioural factors.

Results

Weight z-scores for migrants and Germans differed slightly at birth, but were markedly increased for Turkish and Eastern European infants at age six months. Turkish infants showed the highest change in weight z-score during the first 6 months (ß = 0.35; 95% CI 0.14–0.56) and an increased probability of rapid weight gain compared with German infants. Examination of the joint effect of migrant and socioeconomic status (SES) showed the greatest change in weight z-scores in Turkish infants from middle SES families (ß = 0.77; 95% CI 0.40–1.14) and infants of parents from Eastern European countries with high SES (ß = 0.72; 95% CI 0.13–1.32).

Conclusions

Our results support the hypothesis that migrant background is an independent risk factor for infant weight gain and suggest that the onset of health inequalities in overweight starts in early infancy.