Maternal Undernutrition Modulates Neonatal Rat Cerebrovascular Structure, Function, and Vulnerability to Mild Hypoxic-Ischemic Injury via Corticosteroid-Dependent and -Independent Mechanisms.

The present study explored the hypothesis that an adverse intrauterine environment caused by maternal undernutrition (MUN) acted through corticosteroid-dependent and -independent mechanisms to program lasting functional changes in the neonatal cerebrovasculature and vulnerability to mild hypoxic-ischemic (HI) injury. From day 10 of gestation until term, MUN and MUN-metyrapone (MUN-MET) group rats consumed a diet restricted to 50% of calories consumed by a pair-fed control; and on gestational day 11 through term, MUN-MET groups received drinking water containing MET (0.5 mg/mL), a corticosteroid synthesis inhibitor. P9/P10 pups underwent unilateral carotid ligation followed 24 h later by 1.5 h exposure to 8% oxygen (HI treatment). An ELISA quantified MUN-, MET-, and HI-induced changes in circulating levels of corticosterone. In P11/P12 pups, MUN programming promoted contractile differentiation in cerebrovascular smooth muscle as determined by confocal microscopy, modulated calcium-dependent contractility as revealed by cerebral artery myography, enhanced vasogenic edema formation as indicated by T2 MRI, and worsened neurobehavior MUN unmasked HI-induced improvements in open-field locomotion and in edema resolution, alterations in calcium-dependent contractility and promotion of contractile differentiation. Overall, MUN imposed multiple interdependent effects on cerebrovascular smooth muscle differentiation, contractility, edema formation, flow-metabolism coupling and neurobehavior through pathways that both required, and were independent of, gestational corticosteroids. In light of growing global patterns of food insecurity, the present study emphasizes that infants born from undernourished mothers may experience greater risk for developing neonatal cerebral edema and sensorimotor impairments possibly through programmed changes in neonatal cerebrovascular function.

Behavioral Feeding Circuit: Dietary Fat-Induced Effects of Inflammatory Mediators in the Hypothalamus.

Excessive dietary fat intake has extensive impacts on several physiological systems and can lead to metabolic and nonmetabolic disease. In animal models of ingestion, exposure to a high fat diet during pregnancy predisposes offspring to increase intake of dietary fat and causes increase in weight gain that can lead to obesity, and without intervention, these physiological and behavioral consequences can persist for several generations. The hypothalamus is a region of the brain that responds to physiological hunger and fullness and contains orexigenic neuropeptide systems that have long been associated with dietary fat intake. The past fifteen years of research show that prenatal exposure to a high fat diet increases neurogenesis of these neuropeptide systems in offspring brain and are correlated to behavioral changes that induce a pro-consummatory and obesogenic phenotype. Current research has uncovered several potential molecular mechanisms by which excessive dietary fat alters the hypothalamus and involve dietary fatty acids, the immune system, gut microbiota, and transcriptional and epigenetic changes. This review will examine the current knowledge of dietary fat-associated changes in the hypothalamus and the potential pathways involved in modifying the development of orexigenic peptide neurons that lead to changes in ingestive behavior, with a special emphasis on inflammation by chemokines.

Micro-anatomic alterations of the placenta in a non-human primate model of gestational protein-restriction.

OBJECTIVES: Maternal protein malnutrition is associated with impaired fetal growth, and lifetime consequences for the offspring. Our group has previously developed a model of protein-restriction in the non-human primate, which was associated with fetal growth restriction, stillbirth, decreased placental perfusion, and evidence of fetal hypoxia, suggesting perturbed vascular development. Our objective was to histologically characterize the micro-anatomic alterations associated with adverse pregnancy outcomes taking an approach that permits investigation of the 3D vascular structure and surrounding histology without the requirement for 3D vascular casting or relying on 2D stereology which both have methodological limitations. METHODS: Rhesus macaques were assigned in the pre-gestational period to a control diet that contained 26% protein, or study diet containing 13% protein (50% PR diet). Placental tissue was collected at delivery and processed using a clarification, immunohistochemistry, and confocal microscopy protocol published previously by our group. Three dimensional reconstructions and quantitative assessment of the vascular micro-anatomy was performed using analysis software (Imaris®) and statistical analysis accounted for maternal and fetal confounders. RESULTS: In unadjusted analysis, when comparing those pregnancies on a 50% PR diet (n = 4) with those on a control diet (n = 4), protein-restriction diet was associated with decreased maternal pre-pregnancy weight (difference of -1.975kg, 95% CI -3.267 to -0.6826). When controlling for maternal pre-pregnancy weight, fetal sex, and latency from tissue collection to imaging, a gestational protein-restriction diet was associated with decreases in total vascular length, total vascular surface area, total vascular volume, and vascular density. CONCLUSION: In this pilot study, a gestational protein-restriction diet altered the placental micro-vasculature with decreased vascular caliber and density, which may be related to the observed adverse pregnancy outcomes and perturbed placental perfusion previously demonstrated in this model.

Fetal Head Growth during Early to Mid-Gestation Associated with Weight Gain in Mothers with Hyperemesis Gravidarum: A Retrospective Cohort Study.

The epigenetic impact of malnutrition in mothers with hyperemesis gravidarum (HG) on their offspring has not been fully elucidated. Recently, several reports have demonstrated that children born to mothers with HG were small for gestational age and had low birth weight, reduced insulin sensitivity, and neurodevelopmental delays during childhood. Therefore, we examined the relationship between fetal growth and changes in the maternal body weight in HG cases. A total of 34 patients with HG were hospitalized and delivered at term between 2009 and 2012. The records of 69 cases of pregnant women without a history of HG were extracted after matching their maternal age, parity, pregestational body mass index (BMI), gestational age, and fetal sex ratio with those of the HG group for comparison. The maternal weight gain at term was less in the HG than in the control group. There was no statistical difference in birth weight, placental weight, and ultrasonic fetometric parameters expressed in standard deviation (SD) scores, including biparietal diameter, abdominal circumference, and femur length, between the HG and the control group. Whereas fetal head growth in the HG group was positively associated with maternal weight gain at 20 weeks of gestation only, this association was not observed in the control group. We herein demonstrate that maternal weight gain from the nadir is associated with fetal head growth at mid-gestation. Thus, maternal undernutrition in the first trimester of pregnancy could affect fetal brain growth and development, leading to an increased risk of neurodevelopmental delays in later life.

Fetal malnutrition-induced catch up failure is caused by elevated levels of miR-322 in rats.

If sufficient nutrition is not obtained during pregnancy, the fetus changes its endocrine system and metabolism to protect the brain, resulting in a loss of body size. The detailed mechanisms that determine the success or failure of growth catch-up are still unknown. Therefore, we investigated the mechanism by which catch-up growth failure occurs. The body weights of rat pups at birth from dams whose calorie intake during pregnancy was reduced by 40% were significantly lower than those of controls, and some offspring failed to catch up. Short-body-length and low-bodyweight rats showed blood IGF-1 levels and mRNA expression levels of IGF-1 and growth hormone receptor (GHR) in the liver that were lower than those in controls. The next generation offspring from low-bodyweight non-catch-up (LBW-NCG) rats had high expression of miR-322 and low expression of GHR and IGF-1. The expression of miR-322 showed a significant negative correlation with GHR expression and body length, and overexpression of miR-322 suppressed GHR expression. We found that insufficient intake of calories during pregnancy causes catch-up growth failure due to increased expression of miR-322 and decreased expression of GHR in the livers of offspring, and this effect is inherited by the next generation.

The "First 1,000 Days+" as Key Contributor to the Double Burden of Malnutrition.

Growth from conception through age 2 years, the "First 1,000 days," is important for long-term health of the growing fetus and child and is influenced by several factors including breastfeeding and complementary feeding. Low- and middle-income countries face a complicated array of factors that influence healthy growth, ranging from high food insecurity, poor sanitation, limited prenatal or neonatal care, and high levels of poverty that exacerbate the "vicious cycle" associated with intergenerational promotion of growth retardation. It is now well recognized that the period prior to conception, both maternal and paternal health and diet, play an important role in fetal development, giving rise to the concept of the "First 1,000 Days+". Breastfeeding and complementary feeding practices can be improved through a combination of interventions such as baby-friendly hospitals, regulations for marketing of foods and beverages to children, adequate counseling and support, and sound social and behavior change communication, but continued research is warranted to make such programs more universal and fully effective. Thus, improving the overall understanding of factors that influence growth, such as improved breastfeeding and age-appropriate and adequate complementary feeding, is critical to reducing the global prevalence of the double burden of malnutrition.

Measuring growth and medium- and longer-term outcomes in malnourished children.

Severe and moderate acute malnutrition are among the leading causes of mortality among children in low- and middle-income countries. There is strong evidence that growth assessed anthropometrically from conception to 2 years of age marks later risk of ill health. This is central to the concept of the developmental origins of adult disease and is presumed to be related to modification of developmental processes during critical "window(s)" of vulnerability. Interventions to treat acute malnutrition have resulted in dramatic increase in the number of affected children surviving. Ensuring that these children thrive to fulfil their full physical and cognitive potential is a new challenge. Integral to this challenge is the need to be able to measure how earlier insults relate to the ability to survive and thrive to productive adulthood. Despite its obvious value, routine anthropometry does not adequately indicate how earlier adverse exposures affect more refined aspects of growth. Anthropometry is inadequate for predicting how disruption of healthy growth might modulate risk of disease or any subsequent interventions that correct this risk. A clear characterisation of healthy child growth is needed for determining which component best predicts later outcomes. The extent to which postnatal acute malnutrition is a consequence of maternal factors acting preconception or in utero and their relationship to postnatal health and long-term risk of non-communicable diseases is not clear. Body-composition measurement has significant untapped potential allowing us to translate and better understand the relationship between early insults and interventions on early growth in the short-term and long-term health outcomes.

Bariatric surgery and birth defects: A systematic literature review.

BACKGROUND: Bariatric procedures are on the rise. The risk of birth defects in pregnancies following such procedures may be increased (eg, due to nutrient deficiencies) or decreased (eg, due to decreased maternal body mass index, BMI). METHODS: We conducted a systematic literature review of the association between bariatric surgery and birth defects using Ovid MEDLINE and PubMed (1946-2017). Information was abstracted on study design, exposures, outcomes, covariates and estimates of association. RESULTS: Fifteen studies met our inclusion criteria: 14 evaluated the outcome of any birth defect, and one evaluated neural tube defects. Estimates of association between bariatric surgery and birth defects were available for nine studies and ranged from 0.6 to 1.9 (all 95% confidence intervals included 1.0). When studies were stratified by surgery type, there was no obvious pattern of association. When stratified by the approach used to account for BMI, positive associations were observed in studies that did not account for maternal prepregnancy BMI or used women with normal BMI as the reference group (range: 1.3-1.9). Estimates from studies that either matched or adjusted for prepregnancy BMI were closer to the null (range: 1.1-1.2) and studies that compared to morbidly obese women reported protective associations (range: 0.6-0.7). CONCLUSIONS: Studies of the association between bariatric surgery and birth defects vary with respect to the surgical procedures included, birth defects ascertainment methods and approaches used to account for maternal BMI. Consequently, it is not possible to draw a conclusion regarding the association between bariatric surgery and birth defects. Additional studies are warranted.

[Does Malnutrition during Fetal Life Have a Potential to Be a Precipitating Factor for Developmental Disorders?]

OBJECTIVES: The developmental origins of health and disease paradigm (DOHaD) is a concept that fetal environmental factors affect adult phenotypes. We performed experiments to evaluate the DOHaD theory in developmental disorders using mouse models. METHODS: In vitro fertilization and embryo transfer techniques were used for mouse production. The AIN93G-control diet, which contains 20% protein (CD), 5% protein-restricted diet (PR), and PR with supplemental folic acid (FA) were provided as experimental diets to mothers. The body weights (BWs) of mothers and offspring, and the blood-clinical biochemistry results of mothers were examined. In addition, gene expression and genomic methylation in the brain of adult offspring and behavioral phenotypes of adult offspring were examined. RESULTS: Pregnant mothers that consumed the protein-restricted diets, namely, PR and FA, exhibited reduction in BW. The values of protein-related parameters determined by blood-clinical biochemistry decreased in the PR fed groups. The BWs of neonates and adult offspring did not change. The offspring exposed to maternal hyponutrition exhibited increased activity in the home cage and enhanced fear and anxiety-like behavior. The adult offspring of the PR-fed group and FA-fed groups exhibited different patterns of mRNA expression and genomic methylation in the brain. CONCLUSIONS: The maternal PR diet affected the progenies' behavioral phenotypes and epigenetic outcomes in the brain. However, the behavioral changes induced by maternal protein restriction were very slight. Hence, interactions between several genetic factors and environmental exposures such as maternal malnutrition may cause developmental and psychiatric disorders.

Reduced fetal vitamin D status by maternal undernutrition during discrete gestational windows in sheep.

Placental transport of vitamin D and other nutrients (e.g. amino acids, fats and glucose) to the fetus is sensitive to maternal and fetal nutritional cues. We studied the effect of maternal calorific restriction on fetal vitamin D status and the placental expression of genes for nutrient transport [aromatic T-type amino acid transporter-1 (TAT-1); triglyceride hydrolase/lipoprotein uptake facilitator lipoprotein lipase (LPL)] and vitamin D homeostasis [CYP27B1; vitamin D receptor (VDR)], and their association with markers of fetal cardiovascular function and skeletal muscle growth. Pregnant sheep received 100% total metabolizable energy (ME) requirements (control), 40% total ME requirements peri-implantation [PI40, 1-31 days of gestation (dGA)] or 50% total ME requirements in late gestation (L, 104-127 dGA). Fetal, but not maternal, plasma 25-hydroxy-vitamin D (25OHD) concentration was lower in PI40 and L maternal undernutrition groups (P<0.01) compared with the control group at 0.86 gestation. PI40 group placental CYP27B1 messenger RNA (mRNA) levels were increased (P<0.05) compared with the control group. Across all groups, higher fetal plasma 25OHD concentration was associated with higher skeletal muscle myofibre and capillary density (P<0.05). In the placenta, higher VDR mRNA levels were associated with higher TAT-1 (P<0.05) and LPL (P<0.01) mRNA levels. In the PI40 maternal undernutrition group only, reduced fetal plasma 25OHD concentration may be mediated in part by altered placental CYP27B1. The association between placental mRNA levels of VDR and nutrient transport genes suggests a way in which the placenta may integrate nutritional cues in the face of maternal dietary challenges and alter fetal physiology.

Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction.

Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies and often results in short- and long-term sequelae for offspring. The mechanisms underlying IUGR are poorly understood, but it is known that healthy placentation is essential for nutrient provision to fuel fetal growth, and is regulated by immunologic inputs. We hypothesized that in pregnancy, maternal food restriction (FR) resulting in IUGR would decrease the overall immunotolerant milieu in the placenta, leading to increased cellular stress and death. Our specific objectives were to evaluate (1) key cytokines (eg, IL-10) that regulate maternal-fetal tolerance, (2) cellular processes (autophagy and endoplasmic reticulum [ER] stress) that are immunologically mediated and important for cellular survival and functioning, and (3) the resulting IUGR phenotype and placental histopathology in this animal model. After subjecting pregnant mice to mild and moderate FR from gestational day 10 to 19, we collected placentas and embryos at gestational day 19. We examined RNA sequencing data to identify immunologic pathways affected in IUGR-associated placentas and validated messenger RNA expression changes of genes important in cellular integrity. We also evaluated histopathologic changes in vascular and trophoblastic structures as well as protein expression changes in autophagy, ER stress, and apoptosis in the mouse placentas. Several differentially expressed genes were identified in FR compared with control mice, including a considerable subset that regulates immune tolerance, inflammation, and cellular integrity. In summary, maternal FR decreases the anti-inflammatory effect of IL-10 and suppresses placental autophagic and ER stress responses, despite evidence of dysregulated vascular and trophoblast structures leading to IUGR.

Activation of placental insulin and mTOR signaling in a mouse model of maternal obesity associated with fetal overgrowth.

Fetal overgrowth is common in obese women and is associated with perinatal complications and increased risk for the child to develop metabolic syndrome later in life. Placental nutrient transport capacity has been reported to be increased in obese women giving birth to large infants; however, the underlying mechanisms are not well established. Obesity in pregnancy is characterized by elevated maternal serum insulin and leptin, hormones that stimulate placental amino acid transporters in vitro. We hypothesized that maternal obesity activates placental insulin/IGF-I/mTOR and leptin signaling pathways. We tested this hypothesis in a mouse model of obesity in pregnancy that is associated with fetal overgrowth. C57BL/6J female mice were fed a control (C) or a high-fat/high-sugar (HF/HS) pelleted diet supplemented by ad libitum access to sucrose (20%) solution. Placentas were collected at embryonic day 18.5. Using Western blot analysis, placental mTOR activity was determined along with energy, inflammatory, leptin, and insulin signaling pathways (upstream modulators of mTOR). Phosphorylation of S6 ribosomal protein (S-235/236), 4E-BP1 (T-37/46), Insulin receptor substrate 1 (Y-608), Akt (T-308), and STAT-3 (Y-705) was increased in obese dams. In contrast, expression of placental caspase-1, IкBα, IL-1ß, and phosphorylated-JNK(p46/54-T183/Y185) was unaltered. Fetal amino acid availability is a key determinant of fetal growth. We propose that activation of placental insulin/IGF-I/mTOR and leptin signaling pathways in obese mice stimulates placental amino acid transport and contributes to increased fetal growth.

[Epigenetics and Nutrition: maternal nutrition impacts on placental development and health of offspring]. / Epigénétique et Nutrition : impacts de l'alimentation maternelle sur le développement placentaire et la santé de la descendance.

The environment, defined broadly by all that is external to the individual, conditions the phenotype during development, particularly the susceptibility to develop non-communicable diseases. This notion, called Developmental Origins of Health and Disease (DOHaD), is based on numerous epidemiological studies as well as animal models. Thus, parental nutrition and obesity can predispose the offspring to develop metabolic and cardiovascular diseases in adulthood. The known underlying mechanisms include an altered development of tissues that adapt to maternal metabolic condition, and a placental dysfunction, which in turn impacts fetal growth and development. Epigenetic mechanisms modulate gene expression without affecting the DNA sequence itself. The main epigenetic marks are DNA methylation and histone post-translational modifications. These marks are erased and set-up during gametogenesis and development in order to ensure cellular identity. Therefore, they can lead to a memorisation of early environment and induce long-term alteration of cell and tissue functions, which will condition the susceptibility to non-communicable diseases. The placenta is a programming agent of adult disease. The environment, such as smoking or psychosocial stress, is able to modify epigenetic processes in placenta, such as small RNA expression and DNA methylation. We showed that placenta is sensitive to maternal obesity and maternal nutrition, in terms of histology, transcription and epigenetic marks. A clear sexual dimorphism is remarkable in the placental response to maternal environment. In adulthood, the phenotype is also different between males and females. Epigenetic mechanisms could underlie this differential response of males and females to the same environment. The DOHaD can no longer be ignored in Biology of Reproduction. The prevention of non-communicable diseases must take this new paradigm into account. Research will allow a better comprehension of the mechanisms of this early conditioning and the marked sexual dimorphism it is associated to.

A doença celíaca como causa de infertilidade feminina: uma revisão sistemática / Celiac disease as a cause of women infertility: a systematic review

A doença celíaca (DC) apresenta, além de alterações gastrintestinais, manifestações atípicas, como infertilidade. O trabalho objetivou demonstrar a relação entre DC e infertilidade feminina, bem como elucidar a importância de sua triagem, por via sorológica, em mulheres com infertilidade de causa desconhecida. Revisão sistemática de 40 artigos publicados entre 1999 e 2014, por meio de buscas sistemáticas utilizando as bases de dados MEDLINE (via PUBMED), LILACS e SciELO. A prevalência de DC no Brasil foi de um para 681 em grupos presumivelmente sadios e 1 para 293 em adultos e crianças sem queixas gastrintestinais. Foi descrito relação entre anticorpos presentes na DC e desordens do aparelho reprodutor feminino, determinando supressão de fatores de crescimento, alterações das funções secretoras da placenta, dano trofoblástico e apoptose tecidual. Além disso, a atrofia das vilosidades na DC promove deficiência nutricional, determinando oligomenorreia, metrorragia e dismenorreia. No recém-nascido, observou-se prematuridade, pré-eclâmpsia e indivíduos pequenos para idade gestacional. A grande relevância do diagnóstico se dá pelo fato de o tratamento poder prevenir danos tanto para o feto quanto para a mãe. Existe relação entre DC e infertilidade e a triagem sorológica em mulheres com infertilidade de causa desconhecida está indicada.(AU)

The celiac disease (DC) presents gastrintestinal alterations, as well as unusual signs such as infertility. The objective of this review is to demonstrate the relation between DC and woman infertility, and show the importance of its screening through serological methods in women with unexplained infertility. Systematic review of 40 published articles between 1999 and 2014, through systematic search using MEDLINE (via PUBMED), LILACS e SciELO databases. The prevalence of DC in Brazil was from one to 681 in healthy groups and from one to 293 in adults and children without gastrointestinal complaints. It was described a relation between antibodies present in DC and women reproductive system disorders, determining suppression of growth factors, alterations in the secretory placenta functions, trophoblastic damage and tissue apoptosis. Besides that, the atrophy of intestinal villus in DC promotes nutritional deficiency, determining oligomenorrhea, metrorrhagia e dysmenorrhea. In newborns, it was observed prematurity, pre-eclampsia and small individuals for gestational age. The biggest relevance of the diagnosis is due to the fact of the treatment to prevent damage for the fetus as well as the mother. There is a relation between DC and infertility so, the sorological screening in women with unexplained infertility is recommended.(AU)

Effect of fetal and infant malnutrition on metabolism in older age.

BACKGROUND: While malnutrition is an important concern in the developing world, Western countries are experiencing a pandemic of obesity and metabolic diseases. OBJECTIVE: This work reviews the current state of knowledge of the effects of malnutrition during early life on metabolism in older age. METHODS: The impact of early-life determinants on diabetes and related metabolic diseases in later life is elucidated by three different methodological approaches. First, results from animal studies in dietary manipulation models are reviewed. Second, findings from epidemiological studies that often use natural experiments to determine the effects of famines on the health status of the population are discussed. Finally, the relation between maternal or childhood malnutrition and diabetes in adulthood is explored in a big-data study using the entire population of a country across a century. RESULTS: We present overwhelming evidence that the maternal or early childhood nutritional status negatively affects both the short- and long-term health status and development of the offspring, thereby providing starting points to formulate intervention and prevention strategies. In particular, it was found that in the case of early-life exposure to famine, the risk of the offspring to develop type 2 diabetes in older age is up to 125% higher than without famine exposure. CONCLUSION: Due to its inherent complexity, an understanding of the long-term effects of maternal and childhood malnutrition on metabolism in older age necessitates interdisciplinary and big-data approaches. Only then can we hope to prevent chronic diseases at their earliest beginning.

Iron deficiency during pregnancy: the consequences for placental function and fetal outcome.

This review examines the importance of the placenta in iron metabolism during development and the effect of iron deficiency on maternal and fetal physiology. Iron is an essential micronutrient, required for a wide variety of biological processes. During pregnancy, the mother has to deplete her iron stores in order to provide the baby with adequate amounts. Trans-placental iron transfer involves binding transferrin (Tf)-bound iron to the Tf receptor, uptake into an endosome, acidification, release of iron through divalent metal transporter 1, efflux across the basolateral membrane through ferroportin and oxidation of Fe(II) by zyklopen. An additional haem transport system has been hypothesised, which may explain why certain gene knockouts are not lethal for the developing fetus. Iron deficiency is a common phenomenon during pregnancy, and the placenta adapts by up-regulating its transfer systems, maintaining iron at the expense of the mother. Despite these adaptations, deficiency cannot be completely prevented, and the offspring suffers both short- and long-term consequences. Some of these, at least, may arise from decreased expression of genes involved in the cell cycle and altered expression of transcription factors, such as c-myc, which in turn can produce, for example, kidneys with reduced numbers of nephrons. The mechanism whereby these changes are induced is not certain, but may simply be as a result of the reduced availability of iron resulting in decreased enzyme activity. Since these changes are so significant, and because some of the changes are irreversible, we believe that iron prophylaxis should be considered in all pregnancies.

Thyroid function in pregnant women: iodine deficiency after iodine enrichment program.

OBJECTIVE: Significant changes in thyroid function occur during pregnancy which can complicate the interpretation of thyroid function tests. Therefore, normative gestational related reference ranges for thyroid hormones tests are required. The aim of this study was to determine the reference ranges for free triiodothyronine (FT3), free thyroxin (FT4) and thyroid stimulating hormone (TSH) in Iranian pregnant women. METHODS: This study was a cross-sectional observational study conducted in the Obstetrics and Gynecology department, Akbarabadi University Hospital. A single blood sample from 584 pregnant women was analyzed for thyroid function. Serum levels of TSH, FT4, FT3, total T4 (TT4), T3 resin uptake (T3RU) and anti-thyroid peroxidase antibody (TPO Ab) were measured. Urinary iodine was determined in some cases. Reference intervals based on 2.5th and 97.5th percentiles were calculated. RESULTS: The composition of reference population comprising 584 women included 162 in first trimester and 422 in the third trimester. The 2.5th and 97.5th percentiles values were used to determine the reference ranges for FT3, FT4, TT4, T3RU and TSH. These values were T3 1.4 and 2.9 pmol/L, FT4 7.1 and 18 pmol/L, TT4 7.2 and 13.5 µg/dL and TSH 0.5 and 3.9 µg/L, respectively. The level of urinary iodine in 80.5% of the subjects was less than normal. CONCLUSIONS: Serum levels of thyroid hormones are different in Iranian population that could be due to racial differences or differences in iodine intake.

Monitoring and effects of iodine deficiency in pregnancy: still an unsolved problem?

Iodine is required for the production of thyroid hormone. Thyroid hormone affects many metabolic processes in the body, including maturation of the central nervous system. In early pregnancy, the fetus is dependent on maternal thyroid hormone for normal brain development. If iodine deficiency leads to inadequate production of thyroid hormone during pregnancy, irreversible brain damage can result in the fetus. Therefore, achieving adequate iodine nutrition during pregnancy is an important public health objective. Although there have been tremendous gains over the last several decades in our understanding of the effects of iodine deficiency in pregnancy and how to combat them, a number of questions remain about how best to monitor the iodine status of pregnant populations, the effects of mild to moderate iodine deficiency on maternal and child outcomes, the safe upper limit of daily iodine intake in pregnant women and the risks and benefits of iodine supplementation for mildly iodine-deficient pregnant women.

The placental origins of sudden cardiac death.

OBJECTIVE: Most sudden cardiac deaths are due to cardiac arrhythmias, and abnormalities in the autonomic nervous system could underlie them. There is growing evidence that coronary heart disease is associated with alterations of fetal development as a result of variations in the processes of placentation that control fetal nutrition. We hypothesized that placental size would be associated with sudden cardiac death. METHODS: We examined sudden cardiac death within the Helsinki Birth Cohort of 13 345 men and women. RESULTS: One hundred eighty-seven (2.7%) men and 47 (0.7%) women had sudden unexplained cardiac death outside hospital. Sudden death was associated with a thin placenta, the hazard ratio being 1.47 [95% confidence interval (CI) 1.11-1.93, P = 0.006] for each g/cm(2) decrease in thickness. Sudden death was independently associated with poor educational attainment (P < 0.0001). Both of these associations were independent of socio-economic status in later life. CONCLUSION: Sudden death may be initiated by impaired development of the autonomic nervous system in utero as a result of shallow invasion of the spiral arteries in the maternal endometrium and consequent fetal malnutrition.

Frequency and risk factors of fetal malnutrition among liveborn singleton term neonates using a computerised perinatal database, 2000-2006.

AIM: The aim of this study was to determine the frequency, risk factors and anthropometric measurements of fetally malnourished, liveborn singleton term neonates. METHODS: The computed delivery room data of 11.741 liveborn singleton term neonates was used to compare malnourished and nourished newborns. RESULTS: Of the total subjects, 577 (4.9%) were malnourished. There were no differences between the groups with regard to gender distribution, Apgar scores, maternal parity, smoking during pregnancy and type of delivery. Maternal age and neonatal gestational age (GA) were significantly lower in malnourished newborns (P < 0.001). Birthweight (BW), birth length (BL) and head circumference (HC) were significantly lower in the malnourished group compared with well-nourished group (P < 0.001). Mean BW (g) was 2724.7 ± 17.0 in the malnourished group versus 3234.3 ± 3.8 in the well-nourished group; BL (cm) was 47.8 ± 0.1 in malnourished versus 49.5 ± 0.0 in well-nourished neonates; HC (cm) was 33.25 ± 0.1 in the malnourished versus 34.3 ± 0.0 in the well-nourished group. Between the groups, there were significant differences in the ratio of small, appropriate and large for GA (P < 0.001). Of the malnourished newborns, 35.5% were small for GA, 63.3% were appropriate for GA and 1.2% were large for GA. CONCLUSION: Fetal malnutrition (FM) still exists despite the advances in current obstetric care. Neonates of adolescent mothers and of low GA are particularly at risk for FM. The BW, BL and HC of fetally malnourished neonates are lower than that of well-nourished neonates. Like term singleton appropriate and small for GA neonates, term singleton large for GA neonates could also have been fetally malnourished.