Zachary M. Ferraro

Maternal–Fetal Nutrient Transport in Pregnancy Pathologies: The Role of the Placenta

Appropriate in utero growth is essential for offspring development and is a critical contributor to long-term health. Fetal growth is largely dictated by the availability of nutrients in maternal circulation and the ability of these nutrients to be transported into fetal circulation via the placenta. Substrate flux across placental gradients is dependent on the accessibility and activity of nutrient-specific transporters. Changes in the expression and activity of these transporters is implicated in cases of restricted and excessive fetal growth, and may represent a control mechanism by which fetal growth rate attempts to match availability of nutrients in maternal circulation. This review provides an overview of placenta nutrient transport with an emphasis on macro-nutrient transporters. It highlights the changes in expression and activity of these transporters associated with common pregnancy pathologies, including intrauterine growth restriction, macrosomia, diabetes and obesity, as well as the potential impact of maternal diet. Molecular signaling pathways linking maternal nutrient availability and placenta nutrient transport are discussed. How sexual dimorphism affects fetal growth strategies and the placenta’s response to an altered intrauterine environment is considered. Further knowledge in this area may be the first step in the development of targeted interventions to help optimize fetal growth.

Excessive gestational weight gain predicts large for gestational age neonates independent of maternal body mass index

Objective: To determine the effects of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) on large-for-gestational-age (LGA) birth weight (≥90th % ile). Methods: We examined 4321 mother-infant pairs from the Ottawa and Kingston (OaK) birth cohort. Multivariate logistic regression (controlling for gestational and maternal age, pre-pregnancy weight, parity, smoking) were performed and odds ratios (ORs) calculated. Results: Prior to pregnancy, a total of 23.7% of women were overweight and 16.2% obese. Only 29.3% of women met GWG targets recommended by the Institute of Medicine (IOM), whereas 57.7% exceeded the guidelines. Adjusting for smoking, parity, age, maternal height, and achieving the IOM’s recommended GWG, overweight (OR 1.99; 95%CI 1.17–3.37) or obese (OR 2.64; 95% CI 1.59–4.39) pre-pregnancy was associated with a higher rate of LGA compared to women with normal BMI. In the same model, exceeding GWG guidelines was associated with higher rates of LGA (OR 2.86; 95% CI 2.09–3.92), as was parity (OR 1.49; 95% CI 1.22–1.82). Smoking (OR 0.53; 95%CI 0.35–0.79) was associated with decreased rates of LGA. The adjusted association with LGA was also estimated for women who exceeded the GWG guidelines and were overweight (OR 3.59; 95% CI 2.60–4.95) or obese (OR 6.71; 95% CI 4.83–9.31). Conclusion: Pregravid overweight or obesity and gaining in excess of the IOM 2009 GWG guidelines strongly increase a woman’s chance of having a larger baby. Lifestyle interventions that aim to optimize GWG by incorporating healthy eating and exercise strategies during pregnancy should be investigated to determine their effects on LGA neonates and down-stream child obesity.

Can we modify the intrauterine environment to halt the intergenerational cycle of obesity

Child obesity is a global epidemic whose development is rooted in complex and multi-factorial interactions. Once established, obesity is difficult to reverse and epidemiological, animal model, and experimental studies have provided strong evidence implicating the intrauterine environment in downstream obesity. This review focuses on the interplay between maternal obesity, gestational weight gain and lifestyle behaviours, which may act independently or in combination, to perpetuate the intergenerational cycle of obesity. The gestational period, is a crucial time of growth, development and physiological change in mother and child. This provides a window of opportunity for intervention via maternal nutrition and/or physical activity that may induce beneficial physiological alternations in the fetus that are mediated through favourable adaptations to in utero environmental stimuli. Evidence in the emerging field of epigenetics suggests that chronic, sub-clinical perturbations during pregnancy may affect fetal phenotype and long-term human data from ongoing randomized controlled trials will further aid in establishing the science behind ones predisposition to positive energy balance.

Role of leptin in pregnancy: Consequences of maternal obesity

Maternal obesity is associated with increased risks of pregnancy complications. Excessive fat mass, common to obese women, has the potential to influence production and secretion of adipose tissue derived proteins called adipokines. The adipokine leptin is involved in the regulation of multiple aspects of maternal metabolic homeostasis. In addition, leptin has been shown to be important for placentation and maternal-fetal exchanges processes regulating growth and development. In later stages of a healthy pregnancy, central leptin resistance occurs to allow increased nutrient availability for the fetus. Disruption of the signaling capacity of leptin associated with obesity is emerging as a potential risk factor leading to pregnancy complications as a result of aberrant fuel partitioning in utero. In this review we discuss the influence of obesity on the roles of leptin and leptin resistance at the central and placental level.

Maternal Obesity and Occurrence of Fetal Macrosomia: A Systematic Review and Meta-Analysis

Objective. To determine a precise estimate for the contribution of maternal obesity to macrosomia. Data Sources. The search strategy included database searches in 2011 of PubMed, Medline (In-Process & Other Non-Indexed Citations and Ovid Medline, 1950–2011), and EMBASE Classic + EMBASE. Appropriate search terms were used for each database. Reference lists of retrieved articles and review articles were cross-referenced. Methods of Study Selection. All studies that examined the relationship between maternal obesity (BMI ≥30 kg/m2) (pregravid or at 1st prenatal visit) and fetal macrosomia (birth weight ≥4000 g, ≥4500 g, or ≥90th percentile) were considered for inclusion. Tabulation, Integration, and Results. Data regarding the outcomes of interest and study quality were independently extracted by two reviewers. Results from the meta-analysis showed that maternal obesity is associated with fetal overgrowth, defined as birth weight ≥ 4000 g (OR 2.17, 95% CI 1.92, 2.45), birth weight ≥4500 g (OR 2.77,95% CI 2.22, 3.45), and birth weight ≥90% ile for gestational age (OR 2.42, 95% CI 2.16, 2.72). Conclusion. Maternal obesity appears to play a significant role in the development of fetal overgrowth. There is a critical need for effective personal and public health initiatives designed to decrease prepregnancy weight and optimize gestational weight gain.

The Potential Impact of Physical Activity During Pregnancy on Maternal and Neonatal Outcomes

Introduction: Pregnancy is a critical period of body weight regulation. Maternal obesity and excessive gestational weight gain have become increasingly common and contribute to poor obstetrical outcomes for mother and baby. Regular participation in physical activity may improve risk profiles in pregnant women. Purpose and Methods: Our objectives were to provide an overview of maternal-fetal exercise physiology, summarize current evidence on the effects of physical activity during pregnancy on maternal-fetal outcomes, and review the most recent clinical practice guidelines. In addition, we summarize the findings in the context of the current obesity epidemic and discuss implications for clinical practice. A literature review was completed in which we queried OVID (Medline), EMBASE, and PSYCHINFO databases with title words “exercise or physical activity” and “pregnancy or gestation” from 1950 to March 1, 2010. A total of 212 articles were selected for review. Recommendations: Care providers should recommend physical activity to most pregnant women (i.e., those without contraindications) and view participation as a safe and beneficial component of a healthy pregnancy. Target Audience: Obstetricians & Gynecologists and Family Physicians Learning Objectives: After participating in this CME activity, physicians should be better able to classify the potential impact of physical activity on maternal glycemic control and fetal growth outcomes. Assess maternal lifestyle and provide recommendations on appropriate gestational weight gain, evaluate pregnant women for contraindications to physical activity participation, make individualized recommendations for exercise participation, and educate patients on the merits of physical activity for health benefit.

The Maternal Obesity Management (MOM) Trial Protocol: A lifestyle intervention during pregnancy to minimize downstream obesity

BACKGROUND Maternal obesity and/or high gestational weight gain (GWG) are associated with downstream child obesity. Pregnancy represents a critical period for prevention as women are highly motivated and more receptive to behavior change. OBJECTIVE This pilot study was developed to test the feasibility of intervening with the mother, specifically keeping her GWG within the Institute of Medicine (IOM) limits, with the intended target of preventing obesity in her child downstream. We are testing the practicality of delivering a structured physical activity and nutrition intervention to pregnant women during gestation and then following mom and baby to 24 months of age. STUDY DESIGN This study is a two-arm, parallel group, randomized controlled trial being conducted in Ottawa. Pregnant women, with pregravid BMI >18.5, between 12 and 20 weeks gestation are randomized to one of two groups: intervention (n=30) who receive the MOM trial Handbook (guide to healthy gestation) plus a structured physical activity and nutrition program, or a standard clinical care control group (n=30). The intervention lasts 25-28 weeks (6 months) depending on anticipated delivery date, with follow-up assessment on mother and child at 3, 6, 12 and 24 months post-delivery. SIGNIFICANCE Pregnancy, a critical time of growth, development and physiological change, provides an opportunity for early lifestyle intervention. The goal of identifying an effective lifestyle program for the gestational period that leads to healthy fetal development and subsequently normal weight offspring, less likely to develop obesity and its co-morbidities, is unique and could possibly attenuate the inter-generational cycle of obesity.

The effects of dietary polyphenols on reproductive health and early development

BACKGROUND Emerging evidence from clinical and epidemiological studies suggests that dietary polyphenols play an important role in the prevention of chronic diseases, including cancer, cardiovascular disease, diabetes and neurodegenerative disorders. Although these beneficial health claims are supported by experimental data for many subpopulation groups, some studies purport that excessive polyphenol consumption may have negative health effects in other subpopulations. The ever-growing interest and public awareness surrounding the potential benefits of natural health products and polyphenols, in addition to their widespread availability and accessibility through nutritional supplements and fortified foods, has led to increased consumption throughout gestation. Therefore, understanding the implications of polyphenol intake on obstetrical health outcomes is of utmost importance with respect to safe consumption during pregnancy. METHODS Using relevant keywords, a literature search was performed to gather information regarding polyphenol pharmacology and the molecular mechanisms by which polyphenols exert their biological effects. The primary focus of this paper is to understand the relevance of these findings in the context of reproductive physiology and medicine. RESULTS Evidence from both in vitro experiments and in vivo studies using animals and humans demonstrates that polyphenols regulate key targets related to oxidative stress, inflammation and advanced glycation end products. Although the majority of these studies have been conducted in the context of chronic diseases, such as cancer and diabetes, several of the key targets influenced by polyphenols are also related to a variety of obstetrical complications, including pre-eclampsia, intrauterine growth restriction and preterm birth. Polyphenols have also been shown to influence fertility and sexual development, fetal health and the bioavailability of nutrients. CONCLUSIONS Further research leading to a thorough understanding of the physiological roles and potential clinical value that polyphenol consumption may play in pregnancy is urgently needed to help inform patient safety.

Validity of SC-StepRx pedometer-derived moderate and vigorous physical activity during treadmill walking and running in a heterogeneous sample of children and youth

BackgroundThe purpose of this study was to determine the validity of the SC-StepRx pedometer to assess moderate and vigorous physical activity during treadmill walking and running in a heterogeneous sample of children and youth aged 10-17 years.MethodsPhysical activity intensity assessed via indirect calorimetry served as the criterion standard. A convenience sample of 40 participants (20 boys, 20 girls) wore 6 SC-StepRx pedometers, 2 ActiGraph GT3X accelerometers, 2 Actical accelerometers, 1 Walk4Life MVP pedometer and 1 NL-1000 pedometer while walking/running at speeds approximating 2, 3, 4, 6 and 7 METs. Associations between indirect calorimetry and each activity monitor were assessed using linear regression analyses in SAS 9.2.ResultsEstimates of moderate and vigorous physical activity from all monitors were significantly associated with the criterion standard of indirect calorimetry. The strongest associations with the criterion measure were observed for the SC-StepRx with moderate/vigorous thresholds of 110/130 steps•minute−1, and the NL-1000 (R2 = 0.82, p <0.05). The SC-StepRx with moderate/vigorous thresholds of 110/130 steps•minute−1 also exhibited the highest combined sensitivity (92.9%) and specificity (96.5%) for correctly identifying a bout of moderate-to-vigorous physical activity.ConclusionsThis study demonstrates that the SC-StepRx pedometer is a valid tool for the measurement of moderate and vigorous physical activity in children and youth.

The Potential Value of Sleep Hygiene for a Healthy Pregnancy: A Brief Review

The quality of the intrauterine environment influences maternal-fetal health and also offspring predisposition to obesity and cardiometabolic disease later in life. Several determinants, including but not limited to pregravid obesity and excessive gestational weight gain, alter the developmental milieu, fetal growth, and child obesity risk. However, the role of sleep and its relationship to healthy pregnancy is not fully established. Given the host of psychosocial and physiological complications associated with childhood obesity, targeting the gestational period is purported to be an opportune time for preventive intervention. Many longitudinal studies suggest that short sleep duration is a risk factor for the development of impaired glycemia and obesity. However, there is a dearth of information concerning the role of sleep hygiene and its role in a healthy pregnancy. Reports note disrupted and poorer quality of sleep during gestation and highlight an association between reduced sleep and risk of gestational diabetes mellitus. Given the lack of well-designed human trials assessing the value of sleep and healthy pregnancy outcomes, this review summarizes current evidence which suggests that incorporating sleep recommendations and utilizing time management strategies that encourage a healthful night s sleep may improve the health of the mom and the baby.