Development Of Diseases In Adulthood Research Articles

Are babies getting heavier? Birth weight trends in England and Wales 1986 to 2012

Introduction Birth weight (BW) is associated with environmental exposures such as air pollution and is a strong predictor of infant mortality, morbidity and development of adult disease. Information on trends is important for environmental epidemiology studies of BW. Work from the 1980s indicated a shift towards heavier births; this study looks at more recent trends. Methods Data on 17.2 million live, single births from 1986-2012 from the Office for National Statistics (ONS) births register were investigated for temporal trends in mean annual BW and changes in the proportions of very low (<1500g), low (<2500g) and high (≥4,000g) BW. Analysis used multiple linear and logistic regression adjusted for maternal age, marital status, area-level deprivation and ethnicity. Data on 4.7 million live, single births from NHS Number for Babies (NN4B), which has information on individual ethnicity and gestational age, was investigated for more recent trends (2006-2012) as well as stratified into pre-term and term births. Results Over the 27 years of the study there was an increase in the BW of live, single births of 1.59g per year (95% CI [1.54-1.63]) for females and 1.63g per year [1.58-1.68] for males. This increase in mean BW was driven by increases between 1986-1991 and 2007-2012, with a 16 year period between showing no increase. Over the study period, there was a decreased risk of being born low BW but an 8% increased risk in males and 10% increased risk in females of being born high BW. In NN4B (2006-2012) the annual increase in BW was 4.41g per year [4.04-4.78] for males and 3.94g per year [3.58-4.30] for females, with the annual increase greater in pre-term compared to term births. Conclusions Since 1986 the BW distribution of live, single births in England and Wales has shifted towards heavier births. The increase in BW from 2007 coincides with introduction of a ban on smoking in public places in the UK, which has been associated with increases in BW in short-term studies.

Pathoanatomical and clinical aspects of the placenta in preterm birth

Prematurely born children show a clearly elevated risk for perinatal morbidity, long-term pediatric morbidities and development of chronic diseases in adulthood compared to babies born at term. The pathoanatomical investigation of placentas from preterm births is useful for assessing the etiology, the risk of recurrence and the prognosis for the child. The focus is on presenting the clinical and pathoanatomical characteristics of acute chorioamnionitis as a frequent cause of preterm induction of labor and pregnancy-induced hypertension, in particular preeclampsia as a frequent reason for elective cesarean section. Other lesions, sometimes of unclear etiology associated with preterm birth and substantially elevated risk of recurrence are reviewed. The clinical correlations and therapeutic options of the various diseases are discussed taking the risk of recurrence into consideration. Examination of placentas, association with the clinical course and a literature search. Acute chorioamnionitis and omphalovasculitis can be histologically subdivided into different stages which correlate with the clinical severity and the prognosis for the newborn child. Chronic deciduitis, chronic chorioamnionitis, villitis of unknown etiology, massive perivillous fibrin deposition and chronic histiocytic intervillositis are entities of unclear etiology associated with recurrent abortion and preterm birth. Autoimmune diseases and thrombophilia are occasionally associated with these pathologically defined lesions. Pregnancy-associated hypertensive disease and particularly preeclampsia as the cause of intrauterine developmental delay and elective cesarean section often show characteristic pathoanatomical placental lesions, which can give indications for the severity and duration of the disease and the prognosis for the child. Early onset (<34 weeks of gestation) and late onset preeclampsia show clinical and morphological differences. Subsequent pregnancies are classified as being at risk and screening for preeclampsia should be clinically performed.

Influence of gestational salt restriction in fetal growth and in development of diseases in adulthood.

Recent studies reported the critical role of the intrauterine environment of a fetus in growth or the development of disease in adulthood. In this article we discussed the implications of salt restriction in growth of a fetus and the development of growth-related disease in adulthood. Salt restriction causes retardation of fatal growth or intrauterine death thereby leading to low birth weight or decreased birth rate. Such retardation of growth along with the upregulation of the renin angiotensin system due to salt restriction results in the underdevelopment of cardiovascular organs or decreases the number of the nephron in the kidney and is responsible for onset of hypertension in adulthood. In addition, gestational salt restriction is associated with salt craving after weaning. Moreover, salt restriction is associated with a decrease in insulin sensitivity. A series of alterations in metabolism due to salt restriction are probably mediated by the upregulation of the renin angiotensin system and an epigenetic mechanism including proinflammatory substances or histone methylation. Part of the metabolic disease in adulthood may be programmed through such epigenetic changes. The modification of gene in a fetus may be switched on through environment factors or life style after birth. The benefits of salt restriction have been assumed thus far; however, more precise investigation is required of its influence on the health of fetuses and the onset of various diseases in adulthood.

Parental smoking during pregnancy and the risk of gestational diabetes in the daughter.

Fetal exposure to parental smoking may have long-term impact on the development of disease in adulthood. We examined the association of parental smoking during pregnancy with risk of gestational diabetes mellitus (GDM) in the daughter. We included 15,665 singleton pregnancies from 10,152 women in the Nurses' Health Study II cohort whose mothers participated in the Nurses' Mothers' Cohort Study. Data on maternal and paternal smoking during pregnancy and associated covariates were recalled by the mothers. GDM diagnosis was self-reported by the daughters and was validated by medical record review in a previous study. We used log-binomial models with generalized estimating equations to estimate relative risks (RRs) and 95% confidence intervals (CIs). We observed a positive association between maternal heavy smoking during pregnancy and risk of GDM in the daughter. The multivariable-adjusted RRs (95% CIs) of GDM among women whose mothers did not smoke during pregnancy, continued smoking 1-14, 15-24, and ≥ 25 cigarettes/day were 1.00 (reference), 1.05 (0.81-1.35), 1.27 (0.95-1.70) and 1.98 (1.18-3.30), respectively (P for trend = 0.01). Further adjustment for the women's perinatal variables, adult-life characteristics and body mass index during various periods of life modestly attenuated the association. No association was observed between paternal smoking during the pregnancy period and risk of GDM in the daughter. Maternal heavy smoking (≥ 25 cigarettes/day) during pregnancy was associated with higher risk of gestational diabetes in the daughter. Further studies are warranted to confirm our findings and to elucidate the underlying mechanisms.

Morbidity Due to Obesity, Hypertension and Diabetes II Attributable to Non-Breastfeeding and Low Birth Weight during the 1000 Days of Life: Estimation of the Population Attributable Fraction

Introduction: There is evidence that malnutrition during the first 1000 days of life contributes to the development of chronic diseases in adulthood and therefore may produce a lasting impact on the health of the population. Colombia, like other middle-income countries suffers the double burden of malnutrition in pregnant women and children under 5 years. Also, chronic diseases have positioned within the leading causes of morbidity and mortality. Objective: The aim is to estimate the burden of disease of noncommunicable chronic diseases-NCD’s (hypertension, obesity, diabetes mellitus II) in adults attributable to nutritional risk factors (no-breastfeeding and low birthweight) in the period of 1000 days in Colombia. Methods: The population attributable fraction and the number of NCD’s (hypertension, diabetes mellitus II and obesity) cases due to the risk factors (low birthweight and no-breastfeeding) were estimated. Prevalences of NCD’s and risk factors of interest were taken from national health surveys. Effect measures (odds ratios/relative risks) of the associations 1—low birthweight and hypertension, diabetes mellitus II and 2—no-breastfeeding and obesity were obtained after a systematic literature search. Results: It was estimated that not receiving breastfeeding in the 1000 days could contribute up to 29.9% of all cases of obesity, equivalent to about 4,009,779 cases across the country. Low birth weight could contribute up to 2.1% of cases of hypertension in men and to 4.0% of cases in women, equivalent to 103.769 cases across the country. In addition, low birth weight could contribute to 6.3% of diabetes mellitus II cases, which is equivalent to 23.857 cases in the country. Conclusion: In Colombia, risk factors during the first 1000 days like not receiving breastfeeding and having low birth weight could contribute up to 4,113,549 cases of obesity, hypertension and diabetes mellitus II, with important implications for the health of the population and the Colombian health system.

Transgenerational left ventricular hypertrophy and hypertension in offspring after uteroplacental insufficiency in male rats.

Epidemiological studies have shown an association between low birthweight and adult disease development with transmission to subsequent generations. The aim of the present study was to examine the effect of intrauterine growth restriction in rats, induced by uteroplacental insufficiency, on cardiac structure, number, size, nuclearity, and adult blood pressure in first (F1) and second (F2) generation male offspring. Uteroplacental insufficiency or sham surgery was induced in F0 Wistar-Kyoto pregnant rats in late gestation giving rise to F1 restricted and control offspring, respectively. F1 control and restricted females were mated with normal males, resulting in F2 control and restricted offspring, respectively. F1 restricted male offspring were significantly lighter at birth (P < 0.05), but there were no differences in birthweight of F2 offspring. Left ventricular weights and volumes were significantly increased (P < 0.05) in F1 and F2 restricted offspring at day 35. Left ventricular cardiomyocyte number was not different in F1 and F2 restricted offspring. At 6 months-of-age, F1 and F2 restricted offspring had elevated blood pressure (8-15 mmHg, P < 0.05). Our findings demonstrate the emergence of left ventricular hypertrophy and hypertension, with no change in cardiomyocyte number, in F1 restricted male offspring, and this was transmitted to the F2 offspring. The findings support transgenerational programming effects.

DNA damage and its cellular response in mother and fetus exposed to hyperglycemic environment.

The increased production of reactive oxygen species (ROS) plays a key role in pathogenesis of diabetic complications. ROS are generated by exogenous and endogenous factors such as during hyperglycemia. When ROS production exceeds the detoxification and scavenging capacity of the cell, oxidative stress ensues. Oxidative stress induces DNA damage and when DNA damage exceeds the cellular capacity to repair it, the accumulation of errors can overwhelm the cell resulting in cell death or fixation of genome mutations that can be transmitted to future cell generations. These mutations can lead to and/or play a role in cancer development. This review aims at (i) understanding the types and consequences of DNA damage during hyperglycemic pregnancy; (ii) identifying the biological role of DNA repair during pregnancy, and (iii) proposing clinical interventions to maintain genome integrity. While hyperglycemia can damage the maternal genetic material, the impact of hyperglycemia on fetal cells is still unclear. DNA repair mechanisms may be important to prevent the deleterious effects of hyperglycemia both in mother and in fetus DNA and, as such, prevent the development of diseases in adulthood. Hence, in clinical practice, maternal glycemic control may represent an important point of intervention to prevent the deleterious effects of maternal hyperglycemia to DNA.

Aspartate aminotransferase-platelet ratio index, adiponectin and body mass index in children with fatty liver

Obesity in children is becoming a global epidemic. Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent and potentially serious complication of childhood obesity. Adiponectin level was decreased on obese children. Adiponectin is a protective factor against non-alcoholic fatty liver disease on obesity. The early identification of fibrosis is important in children with NAFLD in order to prevent the development of liver disease in adulthood. One of non-invasive procedure to predict liver fibrosis is the aspartate aminotransferase (AST)-platelet ratio index (APRI). The purpose of our study was to assess a correlation between APRI, adiponectin and body mass index (BMI) in obese children with fatty liver. A cross-sectional study was conducted from August to September 2007. Subjects were obese children from one junior high school in Semarang, Indonesia. Complete blood count, transaminase enzyme measurement, adiponectin level and abdominal ultrasound (USG) were performed on each subject. Only subjects with bright liver on USG underwent APRI analysis. Spearman’s correlation was used for statistical analysis. Of 37 obese children, 19 children had bright liver on USG. The mean APRI was 0.16 (0.119). The mean Adiponectin was 4.04. Only one obese subject (5.0%) with bright liver had an APRI > 0.5. APRI was significantly correlated to alanine amino transferase (ALT) levels (r = 0.62), but not significantly correlated to BMI (r = 0.35) and adiponectin (r = 0.45). There was no correlation between BMI, ALT (r = 0.16), AST (r = 0.16), and adiponectin (r = 0.30). This study suggest that obese children with fatty liver might have high APRI levels indicating the presence of liver fibrosis. However, there is no correlation between APRI, adiponectin and BMI.

Early Growth Patterns Associated with Cardiovascular Disease

Clearly, the development of cardiovascular disease in adulthood is influenced by growth very early in life, even prior to birth. Substantial evidence indicates that impaired fetal growth and subsequent low birth weight are associated with adult cardiovascular disease and related mortality, and there is emerging evidence that elevated birth weight has similar associations. Patterns of rapid and slow infant growth are each associated with multiple cardiovascular disease processes, and rapid growth during childhood is also predictive of adult cardiovascular disease. Additionally, early adiposity rebound is linked to obesity and diabetes mellitus later in life.

Association of adipokines with cardiovascular risk factors in low birth weight children: a case–control study

Our aim was to investigate plasma levels of adiponectin, monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) in low birth weight (LBW) children and to determine correlations among these adipokines and birth weight and cardiovascular disease risk factors. In a case-control study, the concentrations of adiponectin, MCP-1 and PAI-1 were measured in 180 schoolchildren (ages 6-11 years). MCP-1 and PAI-1 levels were significantly elevated in LBW children. Conversely, adiponectin concentration was significantly reduced in these children. Similar findings were observed after adjustment for current age, gender and abdominal circumference. Because the children with LBW had altered adipokine levels, as well as higher abdominal circumference, HOMA-IR and systolic blood pressure (SBP), we evaluated the correlation among these variables. These analyses showed that adiponectin levels were inversely correlated with systolic blood pressure (SBP) (r = -0.501; P < 0.001), HOMA-IR (r = -0.293; P = 0.023) and waist circumference (r = -0.317; P = 0.014). The proinflammatory markers were positively correlated with HOMA-IR (PAI-1: r = 0.358; P = 0.005) and waist circumference (PAI-1: r = 0.571; P < 0.001 and MCP-1: r = 0.267; P = 0.039). Adipokines levels were correlated with cardiovascular risk factors in LBW children, and these compounds could be involved in the mechanism that links birth weight to the development of cardiovascular diseases in adulthood.

Influence of angiotensin II type 1 receptor-associated protein on prenatal development and adult hypertension after maternal dietary protein restriction during pregnancy

An adverse relationship between suboptimal fetal environments and the development of adult diseases, such as hypertension, type II diabetes, and cardiovascular disease, has been reported in numerous studies. The purpose of this study was to investigate the strain difference of offspring’s response to maternal malnutrition during pregnancy and the involvement of the renin-angiotensin system (RAS) in the development of adult hypertension using C57BL/6J (C57) mice and angiotensin II (Ang II) type 1 receptor-associated protein-transgenic (ATRAP-Tg) mice. Pregnant dams were fed an isocaloric diet containing either 20% (normal protein; NP) or 8% (low protein; LP) protein. Birth weight was significantly reduced in C57-LP offspring, but not in ATRAP-Tg-LP offspring. Arterial blood pressure was higher in C57-LP offspring than in the other groups. In contrast, ATRAP-Tg-LP offspring did not show an increase in blood pressure compared with NP offspring. Renal angiotensin II type 1 (AT1) receptor expression was not altered by maternal malnutrition, whereas angiotensin II type 2 receptor expression was significantly decreased in C57-LP offspring. In conclusion, these findings suggest that a suboptimal intrauterine environment induces adult hypertension because of an alteration of expression of RAS components, which was partly suppressed by sustained ATRAP overexpression via attenuation of the AT1 receptor-mediated pathological response.

Update

Intrauterine growth restriction (IUGR) is a major cause of perinatal mortality and morbidity worldwide and, among survivors, seems to be associated with the development of adult disease in later life. Adolescents and adults who display poor growth in utero and/or are born small for gestational age (

Highlights for the Management of a Child with Hypertension

Over the past several decades, childhood hypertension has undergone a considerable conceptual change, as hypertension is a predictor of future development of cardiovascular disease in adults. Childhood hypertension has distinctive features that distinguish it from hypertension in adults. Pediatric hypertension is often secondary. It is widely believed that therapeutic intervention at an early age favorably modifies the long-term outcome of hypertension. Despite its significance as a cause for morbidity, childhood hypertension is underdiagnosed and less studied with many basic issues remaining contentious.

Renal morphophysiological changes in Wistar rats with malnutrition intra uterine

Many epidemiological studies suggest that the intra uterine environment is extremely important in determining the future of individual health. Changes in maternal nutritional status, reflected in birth weight may program the offspring to the development of diseases in adulthood. Studies with animals exposed to intrauterine malnutrition have suggested a reduction in the number of clusters in addition to increased blood pressure. To review the literature morphophysiology changes in the kidney of adult Wistar rats exposed to malnutrition during intrauterine life. We performed a search in the following databases: PubMed, MEDLINE, SCIENCE DIRECT, LILACS. The main search terms were malnutrition and renal function in Portuguese and English. We included original articles involving albino rats. We excluded review articles as well as those involving humans. According to Franco et al (2009) renal function and the number of glomeruli reduced by poor on intrauterine development, predisposing offspring to kidney disease in adulthood. According to Chen (2009) ultra-glomerular structure is not affected by maternal malnutrition suggesting that this factor does not contribute to the pathogenesis of hypertension after maternal malnutrition. Viana-son et al (2009) believes that stress on placents, causes disruption on sodium pumps in the proximal tubules of the kidney, resulting hypertension. The intrauterine malnutrition appears to interfere with the programming of kidney function with changes in glomerular morphophysiology, however, its mechanisms remain uncertain. We suggest further studies of the type and randomized clinical trials aimed at understanding the factors that trigger this process.

P1-33 Adult DNA methylation in relation to prenatal nutrition and risk factors for cardio-vascular disease

Epigenetic changes may play an important role in the development of adult disease. Exposure to a prenatal famine environment has been associated with a persistent decrease in DNA methylation of...

Variable placental thickness affects placental functional efficiency independent of other placental shape abnormalities.

Our previous work suggests that stressors that impact placental vascular growth result in a deformed chorionic surface shape, which reflects an abnormal placental three-dimensional shape. We propose to use variability of placental disk thickness as a reflector of deviations in placental vascular growth at the finer level of the fetal stems. We hypothesize that increased variability of thickness is associated with abnormal chorionic surface shape, but will be a predictor of reduced placental functional efficiency (smaller baby for a given placental weight) independent of shape. These measures may shed light on the mechanisms linking placental growth to risk of adult disease. The sample was drawn from the Pregnancy, Infection and Nutrition Study. In all, 94.6% of the cohort consented to placental examination. Of the 1023 delivered at term, those previously sectioned by the Pathology Department were excluded, leaving 587 (57%) cases with intact placentas that were sliced and photographed. The chorionic surface shape and the shape of a central randomly oriented placental slice were analyzed and measures were compared using correlation. Lower mean placental disk thickness and more variable disk thickness were each strongly and significantly correlated with deformed chorionic plate shapes. More variable disk thickness was strongly correlated with reduced placental efficiency independent of abnormal chorionic surface shape. Variability of placental disk thickness, simple to measure in a single randomly oriented central slice, may be an easily acquired measure that is an independent indicator of lowered placental efficiency, which may in turn program the infant and result in increased risk for development of adult diseases.

Oxidative stress elevated DNA damage and homocysteine level in normal pregnant women in a segment of Pakistani population

Maternal oxidative stress during pregnancy may impair fetal growth and help in the development of diseases in adulthood. The aim of current study was to assess total oxidation status (TOS), related parameters and their relationship to DNA damage (%) and homocysteine level in normal pregnant women in low-income participants. In a cross-sectional study healthy women were grouped as normal, while age matched nulliparous and singleton pregnancies were included for first, second and third trimester groups. TOS (P<0.01), melanodialdehyde (MDA) (P<0.001), aspartate aminotransferase (AST) (P<0.01), triiodothyronine (T3) (P<0.01), thyroxine (T4) (P<0.01), and homocysteine (P<0.001), in pregnant women were significantly higher as compared to normal healthy women. While serum total proteins (P<0.01), albumin (P<0.01) and total antioxidant status (TAS) (P<0.001) decreased significantly as compared to normal healthy women. Women in third trimester showed a significantly high level of body temperature (P<0.01), triglyceride (P<0.01), LDL-cholesterol (P<0.05), AST (P<0.01), T3 (P<0.01), homocysteine (P<0.001), TOS (P<0.01) and MDA (P<0.001) but a lower concentration of serum proteins, albumin and TAS at the end of the pregnancy. Pearson correlation indicated a positive relationship of homocysteine with triglycerides (P<0.027), TOS (P<0.01), MDA (P<0.035) and had a negative relationship with total protein (P<0.026). DNA damage was strongly related with T3 (P<0.008), TOS (P<0.02), MDA (P<0.037) and MBI (P<0.048) profiles of pregnant women. These changes were considered normal for pregnant women having optimum blood pressure and normal child birth. Hormonal influences and hemodilution may contribute towards the observed changes in this study.

Fever in Pregnancy and Offspring Mortality—A Longitudinal Study of a Cohort From 1927 to 1937 on the Faroe Islands

Adverse influences in utero may have a causal relationship with adult health. Size at birth appears to be associated with morbidity and mortality later in life, and a number of reports have suggested that infections occurring during pregnancy may be associated with preterm birth or stillbirth and other adverse perinatal effects as well as the subsequent development of disease in adults. This cohort study investigated the relationship between pregnancy complications, specifically fever in utero, and adult health in a birth cohort comprised of individuals born during 1927-1937 in an isolated island community with high birth weight. Complete medical records including maternal data, complications during pregnancy and birth, and newborn data were extracted from medical registries. Dates of death and identifiable ICD-recorded causes of death were also extracted. Multiple Cox regression was used for mortality analyses. The final dataset contained 4208 individuals, including 2234 were men and 1974 were women, who were followed-up from 1949 to 2002. During the study period, 521 men in the birth cohort died, of whom 319 had an ICD-classified cause of death. Fever during the pregnancy of male offspring was associated with increased all-cause mortality (rate ratio [RR], 1.505; 95% confidence interval [CI], 1.084-1.926; P = 0.057). There was also an association with increased rates of premature death (RR, 1.943; 95% CI, 1.486-2.400; P = 0.004) and cancer (RR, 2.625; 95% CI, 1.845-3.405; P = 0.015). Complete mortality data were available for the 250 women in the cohort who had died; 139 had an ICD-classified cause of death. Unlike male offspring, no association was found with all-cause mortality or premature death, and only a slight trend was found with cancer death. In both male and female offspring, there was no association between fever during pregnancy and the occurrence of death from ischemic heart disease. These findings are the first to show that fever as an indicator of infection during pregnancy is associated with increased disease-specific mortality among offspring in adult life.

Fever in Pregnancy and Offspring Mortality: A Longitudinal Study of a Cohort From 1927 to 1937 on the Faroe Islands

Adverse influences in utero may have a causal relationship with adult health. Size at birth appears to be associated with morbidity and mortality later in life, and a number of reports have suggested that infections occurring during pregnancy may be associated with preterm birth or stillbirth and other adverse perinatal effects as well as the subsequent development of disease in adults. This cohort study investigated the relationship between pregnancy complications, specifically fever in utero, and adult health in a birth cohort comprised of individuals born during 1927–1937 in an isolated island community with high birth weight. Complete medical records including maternal data, complications during pregnancy and birth, and newborn data were extracted from medical registries. Dates of death and identifiable ICD-recorded causes of death were also extracted. Multiple Cox regression was used for mortality analyses. The final dataset contained 4208 individuals, including 2234 were men and 1974 were women, who were followed-up from 1949 to 2002. During the study period, 521 men in the birth cohort died, of whom 319 had an ICD-classified cause of death. Fever during the pregnancy of male offspring was associated with increased all-cause mortality (rate ratio [RR], 1.505; 95% confidence interval [CI], 1.084–1.926; P = 0.057). There was also an association with increased rates of premature death (RR, 1.943; 95% CI, 1.486–2.400; P = 0.004) and cancer (RR, 2.625; 95% CI, 1.845–3.405; P = 0.015). Complete mortality data were available for the 250 women in the cohort who had died; 139 had an ICD-classified cause of death. Unlike male offspring, no association was found with all-cause mortality or premature death, and only a slight trend was found with cancer death. In both male and female offspring, there was no association between fever during pregnancy and the occurrence of death from ischemic heart disease. These findings are the first to show that fever as an indicator of infection during pregnancy is associated with increased disease-specific mortality among offspring in adult life.

Influences of perinatal conditions on adult body size and intellectual performance: a register-based cohort study

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