Evidence of Subclinical mtDNA Alterations in HIV-Infected Pregnant Women Receiving Combination Antiretroviral Therapy Compared to HIV-Negative Pregnant Women

Introduction

Combination antiretroviral therapy (cART) can effectively prevent vertical transmission of HIV but there is potential risk of adverse maternal, foetal or infant effects. Specifically, the effect of cART use during pregnancy on mitochondrial DNA (mtDNA) content in HIV-positive (HIV+) women is unclear. We sought to characterize subclinical alterations in peripheral blood mtDNA levels in cART-treated HIV+ women during pregnancy and the postpartum period.

Methods

This prospective longitudinal observational cohort study enrolled both HIV+ and HIV-negative (HIV-) pregnant women. Clinical data and blood samples were collected at three time points in pregnancy (13-<23 weeks, 23-<30 weeks, 30–40 weeks), and at delivery and six weeks post-partum in HIV+ women. Peripheral blood mtDNA to nuclear DNA (nDNA) ratio was measured by qPCR.

Results

Over a four year period, 63 HIV+ and 42 HIV- women were enrolled. HIV+ women showed significantly lower mtDNA/nDNA ratios compared to HIV- women during pregnancy (p = 0.003), after controlling for platelet count and repeated measurements using a multivariable mixed-effects model. Ethnicity, gestational age (GA) and substance use were also significantly associated with mtDNA/nDNA ratio (p≤0.02). Among HIV+ women, higher CD4 nadir was associated with higher mtDNA/nDNA ratios (p<0.0001), and these ratio were significantly lower during pregnancy compared to the postpartum period (p<0.0001).

Conclusions

In the context of this study, it was not possible to distinguish between mtDNA effects related to HIV infection versus cART therapy. Nevertheless, while mtDNA levels were relatively stable over time in both groups during pregnancy, they were significantly lower in HIV+ women compared to HIV- women. Although no immediate clinical impact was observed on maternal or infant health, lower maternal mtDNA levels may exert long-term effects on women and children and remain a concern. Improved knowledge of such subclinical alterations is another step toward optimizing the safety and efficacy of cART regimens during pregnancy.     

Placental Microparticles and MicroRNAs in Pregnant Women with Plasmodium falciparum or HIV Infection

Background

During pregnancy, syncytiotrophoblast vesicles contribute to maternal tolerance towards the fetus, but also to pathologies such as pre-eclampsia. The aim of the study was to address whether Plasmodium falciparum and HIV infections in pregnancy affect the secretion, microRNA content and function of trophoblast microparticles.

Methods

Microparticles were isolated and characterized from 122 peripheral plasmas of Mozambican pregnant women, malaria- and/or HIV-infected and non-infected. Expression of placenta-related microRNAs in microparticles was analysed by qPCR and the effect of circulating microparticles on dendritic cells assessed by phenotype analysis and cytokine/chemokine measurement.

Results

Concentrations of total and trophoblast microparticles detected by flow cytometry were higher in HIV-positive (P = 0.005 and P = 0.030, respectively) compared to non-infected mothers, as well as in women delivering low birthweight newborns (P = 0.032 and P = 0.021, respectively). miR-517c was overexpressed in mothers with placental malaria (P = 0.034), compared to non-infected. Microparticles from HIV-positive induced a higher expression of MHCII (P = 0.021) and lower production of MCP1 (P = 0.008) than microparticles from non-infected women.

Conclusions

In summary, alterations in total and trophoblast microparticles associated with malaria and HIV in pregnant women may have an immunopathogenic role. The potential for placental-derived vesicles and microRNAs as biomarkers of adverse outcomes during pregnancy and malaria infection should be confirmed in future studies.     

Pre-Pregnancy BMI,Gestational Weight Gain,and the Risk of Hypertensive Disorders of Pregnancy: A Cohort Study in Wuhan,China

Background

Hypertensive disorders of pregnancy (HDP) are major causes of maternal death worldwide and the risk factors are not fully understood. Few studies have investigated the risk factors for HDP among Chinese women. A cohort study involving 84,656 women was conducted to investigate pre-pregnancy BMI, total gestational weight gain (GWG), and GWG during early pregnancy as risk factors for HDP among Chinese women.

Methods

The study was conducted between 2011–2013 in Wuhan, China, utilizing data from the Maternal and Children Healthcare Information Tracking System of Wuhan. A total of 84,656 women with a live singleton pregnancy were included. Multiple unconditional logistic regression was conducted to evaluate associations between putative risk factors and HDP.

Results

Women who were overweight or obese before pregnancy had an elevated risk of developing HDP (overweight: OR = 2.66, 95% CI = 2.32–3.05; obese: OR = 5.53, 95% CI = 4.28–7.13) compared to their normal weight counterparts. Women with total GWG above the Institute of Medicine (IOM) recommendation had an adjusted OR of 1.72 (95% CI = 1.54–1.93) for HDP compared to women who had GWG within the IOM recommendation. Women with gestational BMI gain >10 kg/m² during pregnancy had an adjusted OR of 3.35 (95% CI = 2.89–3.89) for HDP, compared to women with a gestational BMI gain <5 kg/m². The increased risk of HDP was also observed among women with higher early pregnancy (up to 18 weeks of pregnancy) GWG (>600g/wk: adjusted OR = 1.48, 95% CI = 1.19–1.84).

Conclusion

The results from this study show that maternal pre-pregnancy BMI, early GWG, and total GWG are positively associated with the risk of HDP. Weight control efforts before and during pregnancy may help to reduce the risk of HDP.     

Maternal Factors Are Associated with the Expression of Placental Genes Involved in Amino Acid Metabolism and Transport

Introduction

Maternal environment and lifestyle factors may modify placental function to match the mother’s capacity to support the demands of fetal growth. Much remains to be understood about maternal influences on placental metabolic and amino acid transporter gene expression. We investigated the influences of maternal lifestyle and body composition (e.g. fat and muscle content) on a selection of metabolic and amino acid transporter genes and their associations with fetal growth.

Methods

RNA was extracted from 102 term Southampton Women’s Survey placental samples. Expression of nine metabolic, seven exchange, eight accumulative and three facilitated transporter genes was analyzed using quantitative real-time PCR.

Results

Increased placental LAT2 (p = 0.01), y ⁺ LAT2 (p = 0.03), aspartate aminotransferase 2 (p = 0.02) and decreased aspartate aminotransferase 1 (p = 0.04) mRNA expression associated with pre-pregnancy maternal smoking. Placental mRNA expression of TAT1 (p = 0.01), ASCT1 (p = 0.03), mitochondrial branched chain aminotransferase (p = 0.02) and glutamine synthetase (p = 0.05) was positively associated with maternal strenuous exercise. Increased glutamine synthetase mRNA expression (r = 0.20, p = 0.05) associated with higher maternal diet quality (prudent dietary pattern) pre-pregnancy. Lower LAT4 (r = -0.25, p = 0.05) and aspartate aminotransferase 2 mRNA expression (r = -0.28, p = 0.01) associated with higher early pregnancy diet quality. Lower placental ASCT1 mRNA expression associated with measures of increased maternal fat mass, including pre-pregnancy BMI (r = -0.26, p = 0.01). Lower placental mRNA expression of alanine aminotransferase 2 associated with greater neonatal adiposity, for example neonatal subscapular skinfold thickness (r = -0.33, p = 0.001).

Conclusion

A number of maternal influences have been linked with outcomes in childhood, independently of neonatal size; our finding of associations between placental expression of transporter and metabolic genes and maternal smoking, physical activity and diet raises the possibility that their effects are mediated in part through alterations in placental function. The observed changes in placental gene expression in relation to modifiable maternal factors are important as they could form part of interventions aimed at maintaining a healthy lifestyle for the mother and for optimal fetal development.     

Multivitamin and Iron Supplementation to Prevent Periconceptional Anemia in Rural Tanzanian Women: A Randomized,Controlled Trial

Objective

Women’s nutritional status during conception and early pregnancy can influence maternal and infant outcomes. This study examined the efficacy of pre-pregnancy supplementation with iron and multivitamins to reduce the prevalence of anemia during the periconceptional period among rural Tanzanian women and adolescent girls.

Design

A double-blind, randomized controlled trial was conducted in which participants were individually randomized to receive daily oral supplements of folic acid alone, folic acid and iron, or folic acid, iron, and vitamins A, B-complex, C, and E at approximately single recommended dietary allowance (RDA) doses for six months.

Setting

Rural Rufiji District, Tanzania.

Subjects

Non-pregnant women and adolescent girls aged 15–29 years (n = 802).

Results

The study arms were comparable in demographic and socioeconomic characteristics, food security, nutritional status, pregnancy history, and compliance with the regimen (p>0.05). In total, 561 participants (70%) completed the study and were included in the intention-to-treat analysis. Hemoglobin levels were not different across treatments (median: 11.1 g/dL, Q1-Q3: 10.0–12.4 g/dL, p = 0.65). However, compared with the folic acid arm (28%), there was a significant reduction in the risk of hypochromic microcytic anemia in the folic acid and iron arm (17%, RR: 0.61, 95% CI: 0.42–0.90, p = 0.01) and the folic acid, iron, and multivitamin arm (19%, RR: 0.66, 95% CI: 0.45–0.96, p = 0.03). Inverse probability of treatment weighting (IPTW) to adjust for potential selection bias due to loss to follow-up did not materially change these results. The effect of the regimens was not modified by frequency of household meat consumption, baseline underweight status, parity, breastfeeding status, or level of compliance (in all cases, p for interaction>0.2).

Conclusions

Daily oral supplementation with iron and folic acid among women and adolescents prior to pregnancy reduces risk of anemia. The potential benefits of supplementation on the risk of periconceptional anemia and adverse pregnancy outcomes warrant investigation in larger studies.

Trial Registration

ClinicalTrials.gov NCT01183572     

Genome-Wide Identification of Epigenetic Hotspots Potentially Related to Cardiovascular Risk in Adult Women after a Complicated Pregnancy

Background

The physiological demands of pregnancy on the maternal cardiovascular system can catapult women into a metabolic syndrome that predisposes to atherosclerosis in later life. We sought to identify the nature of the epigenomic changes associated with the increased cardiovascular disease (CVD) risk in adult women following pre-eclampsia.

Findings

We assessed the genome wide epigenetic profile by methyl-C sequencing of monozygotic parous twin sister pairs discordant for a severe variant of pre-eclampsia. In the adult twin sisters at risk for CVD as a consequence of a complicated pregnancy, a set of 12 differentially methylated regions with at least 50% difference in methylation percentage and the same directional change was found to be shared between the affected twin sisters and significantly different compared to their unaffected monozygous sisters.

Conclusion

The current epigenetic marker set will permit targeted analysis of differentially methylated regions potentially related to CVD risk in large cohorts of adult women following complicated pregnancies.     

TRAIL Is Decreased Before 20 Weeks Gestation in Women with Hypertensive Disorders of Pregnancy

Objective

The present study evaluated maternal plasma protein profiles before the onset of hypertensive disorders of pregnancy (HDP) to assess the relationship between maternal plasma tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and HDP before 20 weeks gestation and to evaluate the discriminatory performance of plasma TRAIL levels for HDP.

Methods

A 2-phase discovery/validation study was designed. In the discovery phase, a nested case-controlled study was performed using plasma sampled at 8 to 20 weeks gestation from 20 women who later developed HDP and from 20 age- and gestational week-matched controls. Plasma was analyzed using a human protein microarray technology designed to simultaneously detect 507 proteins. The functional annotation and clustering of the differentially expressed proteins were performed using DAVID and the GO database. TRAIL levels were further validated in an independent study using plasma obtained at 8 to 20 weeks gestation from 53 women who later developed HDP and from 106 matched controls, and 62 clinical risk factors were investigated.

Results

In the protein microarray analysis, 23 proteins were differentially expressed between the two groups. The ELISA showed that women who later developed HDP had significantly lower TRAIL levels compared to women with uncomplicated pregnancies. The multivariable Cox regression analysis identified the following three factors that were entered into the final Cox regression model: gravidity (OR = 2.02, 95% CI 1.00–4.09), pre-pregnancy BMI (OR = 1.46, 95% CI 1.21–1.76) and TRAIL levels (OR = 0.97, 95% CI 0.94–0.99). The model had a significantly better discriminatory power (AUC = 0.83, 95% CI 0.75–0.88) compared to TRAIL alone as an independent predictor of HDP (AUC = 0.59, 95% CI 0.51–0.67).

Conclusion

Twenty-three differentially expressed proteins before 20 weeks gestation might be associated with the pathogenesis of HDP. Plasma TRAIL levels were associated with the development of HDP, and the combination of plasma TRAIL levels with pre-pregnancy BMI and gravidity had a good discriminatory performance for HDP before 20 weeks gestation.     

Optimal Timing of Delivery among Low-Risk Women with Prior Caesarean Section: A Secondary Analysis of the WHO Multicountry Survey on Maternal and Newborn Health

Objective

To investigate optimal timing of elective repeat caesarean section among low-risk pregnant women with prior caesarean section in a multicountry sample from largely low- and middle-income countries.

Design

Secondary analysis of a cross-sectional study.

Setting

Twenty-nine countries from the World Health Organization Multicountry Survey on Maternal and Newborn Health.

Population

29,647 women with prior caesarean section and no pregnancy complications in their current pregnancy who delivered a term singleton (live birth and stillbirth) at gestational age 37–41 weeks by pre-labour caesarean section, intra-partum caesarean section, or vaginal birth following spontaneous onset of labour.

Methods

We compared the rate of short-term adverse maternal and newborn outcomes following pre-labour caesarean section at a given gestational age, to those following ongoing pregnancies beyond that gestational age.

Main Outcome Measures

Severe maternal outcomes, neonatal morbidity, and intra-hospital early neonatal mortality.

Results

Odds of neonatal morbidity and intra-hospital early neonatal mortality were 0.48 (95% confidence interval [CI] 0.39–0.60) and 0.31 (95% CI 0.16–0.58) times lower for ongoing pregnancies compared to pre-labour caesarean section at 37 weeks. We did not find any significant change in the risk of severe maternal outcomes between pre-labour caesarean section at a given gestational age and ongoing pregnancies beyond that gestational age.

Conclusions

Elective repeat caesarean section at 37 weeks had higher risk of neonatal morbidity and mortality compared to ongoing pregnancy, however risks at later gestational ages did not differ between groups.     

Sleep Trajectories of Women Undergoing Elective Cesarean Section: Effects on Body Weight and Psychological Well-Being

Background

After cesarean section (CS), women may be at great risk for sleep disturbance, but little is known about temporal changes in their sleep patterns and characteristics. We had two aims: 1) to identify distinct classes of sleep-disturbance trajectories in women considering elective CS from third-trimester pregnancy to 6 months post-CS and 2) to examine associations of sleep trajectories with body mass index (BMI), depressive symptoms, and fatigue scores.

Methods

We analyzed data from a prospective cohort study of 139 Taiwanese pregnant women who elected CS. Sleep components were assessed using the Pittsburgh Sleep Quality Index in third-trimester pregnancy, 1 day, 1 week, 1 month, and 6 months post-CS. Data were collected on depressive symptoms, fatigue symptoms, and BMI. Sleep-quality trajectories were identified by group-based trajectory modeling.

Results

We identified three distinct trajectories: stable poor sleep (50 women, 36.0%), progressively worse sleep (67 women, 48.2%), and persistently poor sleep (22 women, 15.8%). Poor sleep was significantly associated with pre-pregnancy BMI and more baseline (third-trimester pregnancy) depressive and fatigue symptoms. At 6 months post-CS, women classified as progressively worse or persistently poor sleepers showed a trend toward higher BMI (p<0.03), more depressive symptoms (p<0.001), and higher fatigue scores (p<0.001) than those with stable poor sleep.

Conclusions

Women had three distinct sleep-disturbance trajectories before and after elective CS. These poor-sleep courses were associated with BMI and psychological well-being. Our findings suggest a need to continuously assess sleep quality among women considering elective CS and up to 6 months post-CS.     

Women’s Knowledge,Attitudes and Behavior about Maternal Risk Factors in Pregnancy

Background

The aims of this study were to assess the levels of knowledge, attitudes and behaviors of women about the main maternal risk factors in pregnancy and to identify the factors linked to the main outcomes of interest.

Materials and Methods

A cross-sectional survey was conducted in 513 pregnant women randomly selected from the gynecological ambulatory services of five hospitals located in Naples, Italy.

Results

Only 42% of women correctly knew all the main maternal risk factors in pregnancy (alcohol, smoking, passive smoking and obesity). Only 21.7% of women were very worried about causing harm to the fetus or child with their risk behaviors, and 22.3% of women reported smoking during pregnancy. Approximately one-third of women (28.9%) reported regularly drinking alcohol before pregnancy and 74.8% of these women reported stopping drinking alcohol during pregnancy. However, only 27.3% of women who were drinking alcohol during pregnancy had the intention of stopping. Only 43.7% of women indicated that during ambulatory gynecological examinations they received information from physicians about the possible damage resulting from all the main risk factors in pregnancy (alcohol, smoking, passive smoking and obesity).

Conclusion

The results indicate that pregnant women lack knowledge regarding the main maternal risk factors. Pregnant women claim to receive little information during gynecological examinations and, therefore, some continue to smoke and drink alcohol during pregnancy. Our results suggest an urgent need for the design of interventions to improve women’s levels of knowledge and to promote appropriate behavior in relation to the major risk factors in pregnancy.     

Maternal Gestational Smoking,Diabetes, Alcohol Drinking,Pre-Pregnancy Obesity and the Risk of Cryptorchidism: A Systematic Review and Meta-Analysis of Observational Studies

Background

Maternal gestational smoking, diabetes, alcohol drinking, and pre-pregnancy obesity are thought to increase the risk of cryptorchidism in newborn males, but the evidence is inconsistent.

Method

We conducted a systematic review and meta-analysis of studies on the association between maternal gestational smoking, diabetes, alcohol drinking, and pre-pregnancy obesity and the risk of cryptorchidism. Articles were retrieved by searching PubMed and ScienceDirect, and the meta-analysis was conducted using Stata/SE 12.0 software. Sensitivity analysis was used to evaluate the influence of confounding variables.

Results

We selected 32 articles, including 12 case—control, five nested case—control, and 15 cohort studies. The meta-analysis showed that maternal smoking (OR = 1.17, 95% CI: 1.11–1.23) or diabetes (OR = 1.21, 95%CI: 1.00–1.46) during pregnancy were associated with increased risk of cryptorchidism. Overall, the association between maternal alcohol drinking (OR = 0.97, 95% CI: 0.87–1.07), pre-pregnancy body mass index (OR = 1.02, 95% CI: 0.95–1.09) and risk of cryptorchidism were not statistically significant. Additional analysis showed reduced risk (OR = 0.89, 95% CI: 0.82–0.96) of cryptorchidism with moderate alcohol drinking during pregnancy. No dose—response relationship was observed for increments in body mass index in the risk of cryptorchidism. Sensitivity analysis revealed an unstable result for the association between maternal diabetes, alcohol drinking and cryptorchidism. Moderate heterogeneity was detected in studies of the effect of maternal alcohol drinking and diabetes. No publication bias was detected.

Conclusion

Maternal gestational smoking, but not maternal pre-pregnancy overweight or obesity, was associated with increased cryptorchidism risk in the offspring. Moderate alcohol drinking may reduce the risk of cryptorchidism while gestational diabetes may be a risk factor, but further studies are needed to verify this.     

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.     

Physical Activity Patterns and Factors Related to Exercise during Pregnancy: A Cross Sectional Study

Objective

To assess the physical activity levels of pregnant women and to examine the characteristics associated with the practice of exercise and the activities of daily living during pregnancy.

Methods

For this cross-sectional study, 1,279 women were recruited within 72 hours postpartum. They were interviewed about their socio-demographic data and obstetric history and were administered self-report questionnaires about exercise and daily physical activities during pregnancy. Data on the current pregnancy, labor, delivery, and newborn outcomes were collected from participants’ medical records. To analyze factors related to the practice of exercise, we used the student t-test, X², and odds ratio (OR), with a corresponding 95% confident interval (CI), followed by a multiple logistic regression. The significance level was 5%.

Results

Compared to the pre-pregnancy period, the prevalence of physical activity among participants was lower throughout pregnancy (20.1%) (p = 0.01). Half of the women interrupted practicing physical exercise due to pregnancy. The lowest prevalence of exercise was observed in the first (13.6%) and third trimesters (13.4%). Less than half of women received exercise guidance during prenatal care meetings (47.4%). Walking was the most commonly reported exercise, followed by water aerobics. Factors positively associated with exercise practice were higher educational level (OR= 1.82; CI 95% 1.28–2.60), primiparity (OR=1.49; CI 95% 1.07–2.07), exercising before pregnancy (OR= 6.45; CI 95% 4.64–8.96), and exercise guidance during prenatal care (OR=2.54; CI 95% 1.80–3.57). Mildly intense exercise and domestic activities were most frequently reported among pregnant women. There were no differences in maternal and perinatal outcomes between active and sedentary pregnant women.

Conclusion

The findings indicate that promoting physical activity remains a priority in public health policy, and women of childbearing age, especially those planning a pregnancy, should be encouraged to adopt an exercise routine or maintain an active lifestyle during pregnancy in order to avoid sedentary- and obesity-associated risks.     

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.     

Prevalence of Gestational Diabetes Mellitus and Its Risk Factors in Chinese Pregnant Women: A Prospective Population-Based Study in Tianjin,China

Objective

We compared the increases in the prevalence of gestational diabetes mellitus (GDM) based on the 1999 World Health Organization (WHO) criteria and its risk factors in Tianjin, China, over a 12-year period. We also examined the changes in the prevalence using the criteria of International Association of Diabetes and Pregnancy Study Group (IADPSG).

Methods

In 2010-2012, 18589 women who registered within 12 weeks of gestation underwent a glucose challenge test (GCT) at 24-28 gestational weeks. Amongst them, 2953 women with 1-hour plasma glucose ≥7.8 mmol/L underwent a 75-gram 2-hour oral glucose tolerance test (OGTT) and 781 women had a positive GCT but absented from the standard OGTT. An adjusted prevalence of GDM was calculated for the whole cohort of women by including an estimate of the proportion of women with positive GCTs who did not have OGTTs but would have been expected to have GDM. Logistic regression was used to obtain odds ratios and 95% confidence intervals using the IADPSG criteria. The prevalence of GDM risk factors was compared to the 1999 survey.

Results

The adjusted prevalence of GDM by the 1999 WHO criteria was 8.1%, a 3.5-fold increase as in 1999. Using the IADPSG criteria increased the adjusted prevalence further to 9.3%. Advanced age, higher pre-pregnancy body mass index, Han-nationality, higher systolic blood pressure (BP), a family history of diabetes, weight gain during pregnancy and habitual smoking were risk factors for GDM. Compared to the 1999 survey, the prevalence of overweight plus obesity had increased by 1.8 folds, age≥30 years by 2.3 folds, systolic BP by 2.3 mmHg over the 12-year period.

Conclusions

Increasing prevalence of overweight/obesity and older age at pregnancy were accompanied by increasing prevalence of GDM, further increased by change in diagnostic criteria.     

A Study on Mediation by Offspring BMI in the Association between Maternal Obesity and Child Respiratory Outcomes in the Amsterdam Born and Their Development Study Cohort

Background

A causal relationship between maternal obesity and offspring asthma is hypothesized to begin during early development, but no underlying mechanism for the found association is identified. We quantitatively examined mediation by offspring body mass index (BMI) in the association of maternal pre-pregnancy BMI on risk of asthma and wheezing during the first 7–8 years of life in a large Amsterdam born birth cohort.

Methods

For 3185 mother-child pairs, mothers reported maternal pre-pregnancy BMI and offspring outcomes “ever being diagnosed with asthma” and “wheezing in the past 12 months” on questionnaires. We measured offspring height and weight at age 5–6 years. We performed a multivariate log linear regression comparing outcomes in offspring of mothers with different BMI categories. For each category we quantified and tested mediation by offspring BMI and also investigated interaction by parental asthma.

Results

At the age of 7–8 years, 8% of the offspring ever had asthma and 7% had current wheezing. Maternal pre-pregnancy obesity was associated with higher risks of asthma (adjusted RR 2.32 (95% CI: 1.49–3.61) and wheezing (adjusted RR 2.16 (95% CI: 1.28–3.64). Offspring BMI was a mediator in the association between maternal BMI and offspring wheezing, but not for asthma. There was no interaction by parental asthma.

Conclusions

Maternal pre-pregnancy obesity was associated with higher risks of offspring asthma and wheezing. The association between maternal obesity and offspring wheezing was both direct and indirect (mediated) through the child’s own BMI.     

Adequately Diversified Dietary Intake and Iron and Folic Acid Supplementation during Pregnancy Is Associated with Reduced Occurrence of Symptoms Suggestive of Pre-Eclampsia or Eclampsia in Indian Women

Background/Objective

Pre-eclampsia or Eclampsia (PE or E) accounts for 25% of cases of maternal mortality worldwide. There is some evidence of a link to dietary factors, but few studies have explored this association in developing countries, where the majority of the burden falls. We examined the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of PE or E in Indian women.

Methods

Cross-sectional data from India’s third National Family Health Survey (NFHS-3, 2005-06) was used for this study. Self-reported symptoms suggestive of PE or E during pregnancy were obtained from 39,657 women aged 15-49 years who had had a live birth in the five years preceding the survey. Multivariable logistic regression analysis was used to estimate the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of PE or E after adjusting for maternal, health and lifestyle factors, and socio-demographic characteristics of the mother.

Results

In their most recent pregnancy, 1.2% (n=456) of the study sample experienced symptoms suggestive of PE or E. Mothers who consumed an adequately diversified diet were 34% less likely (OR: 0.66; 95% CI: 0.51-0.87) to report PE or E symptoms than mothers with inadequately diversified dietary intake. The likelihood of reporting PE or E symptoms was also 36% lower (OR: 0.64; 95% CI: 0.47-0.88) among those mothers who consumed iron and folic acid supplementation for at least 90 days during their last pregnancy. As a sensitivity analysis, we stratified our models sequentially by education, wealth, antenatal care visits, birth interval, and parity. Our results remained largely unchanged: both adequately diversified dietary intake and iron and folic acid supplementation during pregnancy were associated with a reduced occurrence of PE or E symptoms.

Conclusion

Having a adequately diversified dietary intake and iron and folic acid supplementation in pregnancy was associated with a reduced occurrence of symptoms suggestive of PE or E in Indian women.     

Early Life Exposure to Fructose Alters Maternal,Fetal and Neonatal Hepatic Gene Expression and Leads to Sex-Dependent Changes in Lipid Metabolism in Rat Offspring

Aim

Fructose consumption is associated with altered hepatic function and metabolic compromise and not surprisingly has become a focus for perinatal studies. We have previously shown that maternal fructose intake results in sex specific changes in fetal, placental and neonatal outcomes. In this follow-up study we investigated effects on maternal, fetal and neonatal hepatic fatty acid metabolism and immune modulation.

Methods

Pregnant rats were randomised to either control (CON) or high-fructose (FR) diets. Fructose was given in solution and comprised 20% of total caloric intake. Blood and liver samples were collected at embryonic day 21 (E21) and postnatal day (P)10. Maternal liver samples were also collected at E21 and P10. Liver triglyceride and glycogen content was measured with standard assays. Hepatic gene expression was measured with qPCR.

Results

Maternal fructose intake during pregnancy resulted in maternal hepatic ER stress, hepatocellular injury and increased levels of genes that favour lipogenesis. These changes were associated with a reduction in the NLRP3 inflammasome. Fetuses of mothers fed a high fructose diet displayed increased hepatic fructose transporter and reduced fructokinase mRNA levels and by 10 days of postnatal age, also have hepatic ER stress, and elevated IL1β mRNA levels. At P10, FR neonates demonstrated increased hepatic triglyceride content and particularly in males, associated changes in the expression of genes regulating beta oxidation and the NLRP3 inflammasome. Further, prenatal fructose results in sex-dependant changes in levels of key clock genes.

Conclusions

Maternal fructose intake results in age and sex-specific alterations in maternal fetal and neonatal free fatty acid metabolism, which may be associated in disruptions in core clock gene machinery. How these changes are associated with hepatic inflammatory processes is still unclear, although suppression of the hepatic inflammasome, as least in mothers and male neonates may point to impaired immune sensing.     

Malaria in Pregnancy Is a Predictor of Infant Haemoglobin Concentrations during the First Year of Life in Benin,West Africa

Background

Anaemia is an increasingly recognized health problem in Africa, particularly in infants and pregnant women. Although malaria is known to be the main risk factor of anaemia in both groups, the consequences of maternal factors, particularly malaria in pregnancy (MiP), on infant haemoglobin (Hb) concentrations during the first months of life are still unclear.

Methods

We followed-up a cohort of 1005 Beninese pregnant women from the beginning of pregnancy until delivery. A subsample composed of the first 400 offspring of these women were selected at birth and followed until the first year of life. Placental histology and blood smear at 1^st clinical antenatal visit (ANC), 2^nd ANC and delivery were used to assess malaria during pregnancy. Infant Hb concentrations were measured at birth, 6, 9 and 12 months of age. A mixed multi-level model was used to assess the association between MiP and infant Hb variations during the first 12 months of life.

Results

Placental malaria (difference mean [dm] = - 2.8 g/L, 95% CI [-5.3, -0.3], P = 0.03) and maternal peripheral parasitaemia at delivery (dm = - 4.6 g/L, 95% CI [-7.9, -1.3], P = 0.007) were the main maternal factors significantly associated with infant Hb concentrations during the first year of life. Poor maternal nutritional status and malaria infection during infancy were also significantly associated with a decrease in infant Hb.

Conclusion

Antimalarial control and nutritional interventions before and during pregnancy should be reinforced to reduce specifically the incidence of infant anaemia, particularly in Sub-Saharan countries.