体外受精出生儿童心血管代谢差异的随访研究

根据"成人疾病的发育期起因"学说,在生命早期的关键或敏感时期,对环境刺激的适应性反应可通过生理、代谢及重要内分泌系统的永久性程序重排而产生长期影响.产前发育期中编制心血管及代谢功能障碍长期程序的特定时间窗口已经确定.     

Cardiometabolic differences in children born after in vitro fertilization: follow-up study

CONTEXT: Increasing evidence suggests that adverse conditions during early prenatal life are associated with cardiometabolic dysfunction in postnatal life. In vitro fertilization (IVF) conception may be an early prenatal life event with long-term health consequences. OBJECTIVE: Our objective was to investigate several cardiometabolic measures in 8- to 18-yr-old IVF singletons and spontaneously conceived controls born from subfertile parents. DESIGN AND SETTING: This follow-up study was conducted at the VU University Medical Center, Amsterdam, The Netherlands. PARTICIPANTS: Blood pressure was examined in 225 IVF-conceived children and 225 age- and gender-matched spontaneously conceived control children. Several indicators of insulin resistance were studied in a pubertal subpopulation (131 IVF children and 131 controls). MAIN OUTCOME MEASURES: Blood pressure, fasting glucose, and fasting insulin were determined. RESULTS: Systolic and diastolic blood pressure levels were higher in IVF children than controls (109 +/- 11 vs. 105 +/- 10 mm Hg, P < 0.001; and 61 +/- 7 vs. 59 +/- 7 mm Hg, P < 0.001, respectively). Children born after IVF were also more likely to be in the highest systolic and diastolic blood pressure quartiles (odds ratio = 2.1, 95% confidence interval 1.4, 3.3; odds ratio = 1.9, 95% confidence interval 1.2, 3.0, respectively). Furthermore, higher fasting glucose levels were observed in pubertal IVF children (5.0 +/- 0.4 vs. 4.8 +/- 0.4 mmol/liter in controls; P = 0.005). Blood pressure and fasting glucose differences could not be explained by current body size, birth weight, and other early life factors or by parental characteristics, including subfertility cause. CONCLUSIONS: These findings highlight the importance of continued cardiometabolic monitoring of IVF-conceived children and might contribute to current knowledge about periconceptional influences and their consequences in later life.     

Body composition and metabolic factors in obese children and adolescents

OBJECTIVE: Body composition is associated with metablic factors in adults; however, data are limited regarding obese children. This study was undertaken to assess body composition, regional fat distribution, and metabolic factors in obese 6-18-y-old children and adolescents. DESIGN: Cross-sectional assessment. SUBJECTS: Thirty-six obese children and adolescents, (mean+/-s.e.m.) age 11.8+/-0.5 y, BMI 34.1+/-1.2 kg/m(2). MEASUREMENTS: Body composition was assessed by dual energy X-ray absorptiometry and computerized tomography. Fasting insulin, glucose and leptin levels, and the homeostasis model assessment of insulin sensitivity (HOMA-IR) were assessed. RESULTS: The girls had significantly lower glucose levels than the boys. The ethnic group differences (African American children vs white children) in fat mass, total CT fat, subcutaneous CT fat, insulin level, leptin level, and higher HOMA-IR were not significant after adjusting for age or pubertal stage. These differences in abdominal fat and subcutaneous abdominal fat were also not independent of total body fat or BMI. No ethnic group differences in visceral abdominal fat were noted. Insulin level and HOMA IR were associated with leptin level (independent of fat mass) and fat mass. Leptin level was associated with fat mass, total CT fat, and subcutaneous CT fat; however the associations between the CT fat measures and leptin were not independent of total body fat mass. CONCLUSIONS: Neither visceral abdominal fat, subcutaneous abdominal fat, insulin levels, or insulin resistance differed by ethnic group when adjusted for age or pubertal status. This contrasts with findings in adults and non-obese children which suggest lower levels of visceral fat and higher insulin levels and insulin resistance in African American children and adolescents.     

Prevalence of asthma and other allergic diseases in children born after in vitro fertilisation

BackgroundChildren born after in vitro fertilisation (IVF) are under greater risk of development of some health problems than those children born after spontaneous conception. Yet it is not exactly known what the prevalence of asthma and other allergic diseases among these children is.Aims of the studyTo investigate the prevalence of asthma, allergic rhinitis and atopic dermatitis in children born after IVF, and controls born after spontaneous pregnancy using questionnaires of International Study of Asthma and Allergies in Children (ISAAC).MethodsWe recruited 158 children (mean age: 4.60 ± 2.14 years) born after IVF pregnancies and 102 children (mean age: 5.27 ± 2.8 years) as control group to investigate the prevalences of asthma, atopic dermatitis and allergic rhinitis. The questions in the questionnaire were asked to the parents by telephone or face to face.ResultsWheezing ever has been reported in 19 % of the children born after IVF and in 17.6 % of the control group (p > 0.05). No significant differences were found between groups, in terms of use of any anti-asthma drugs, physician diagnosed asthma and admission to emergency room with wheezing (p > 0.05). In addition, prevalence of allergic rhinitis and atopic dermatitis were also comparable between two groups (p > 0.05).ConclusionsPrevalences of asthma, allergic rhinitis and atopic dermatitis are similar in children born after IVF and children born after spontaneous conception.     

Body composition in children with galactosaemia

Summary Body composition in classical galactosaemia has not been studied. Patients with classical galactosaemia, an inherited disorder of galactose metabolism caused by deficiency of galactose-1-phosphate uridyltransferase (GALT, EC 2.7.7.10), might be at risk for an abnormal body composition because of intrinsic factors related to galactosaemia and/or diet-related factors. The aim of this study was to evaluate the body composition of children with classical galactosaemia. The studied population was a previously reported group of classical galactosaemia patients (13 male and 27 female, ages 3–17 years) with decreased height, weight, weight-for-height and insulin-like growth factor-I (IGF-I) Z-scores. Body composition data were obtained by dual-energy X-ray absorptiometry (DXA). In order to correct for height, fat mass (FM) and lean tissue mass (LTM) were divided by squared height. Mid-parental target height Z-scores were assessed and compared to actual height Z-scores. Linear and multiple regression analysis were done to investigate the relationship between body composition and IGF-I, dietary intake and growth data. We found decreased height Z-scores when compared to mid-parental target height Z-scores. Mean scores for FM and LTM (both adjusted for height) were decreased. LTM (adjusted for height) and height Z-score were correlated with IGF-I Z-score. FM (adjusted for height) was correlated with soy intake. No correlation was found between soy intake and IGF-I Z-score. In this limited group of patients, height is decreased and body composition is abnormal. The decreased levels of IGF-I and/or soy nutrition might play a role in these findings.     

Body composition and lipodystrophy in prepubertal HIV-infected children

ObjectiveTo identify lipodystrophy in prepubertal HIV-infected children using anthropometric parameters and body composition assessment.MethodsCross-sectional study including 40 prepubertal HIV-infected children of both genders seen at the Care Center of the Division of Pediatric Infectious Diseases – Universidade Federal de São Paulo, São Paulo city, Brazil, was carried out from August to December 2008. Age, clinical and immunological status, prophylaxis, transmission and highly active antiretroviral therapy were recorded. Body mass index z-score and height-for-age z-score were calculated to characterize the nutritional status. Circumferences were measured with flexible tape and skinfolds were assessed by an adipometry. Fat mass and lean mass were determined by dual-energy X-ray absorptiometry. Presence of clinical signs of lipodystrophy was assessed by a trained clinician. Data were analyzed using SPSS 12.0 software.ResultsThe mean age and standard deviation were 9.8 (1.2) years, 50% were girls and 82.5% children from B and C categories. Clinical lipodystrophy and dislypidemia were present in 27.5% and 70%, respectively. The trunk to arm ratio and the limb to trunk ratio had positive association with lipodystrophy. Patients with lipodystrophy had short stature, higher triglycerides values and lower HDL-cholesterol.ConclusionThe ratios obtained by skinfolds and dual-energy X-ray absorptiometry measurements can be considered as indicators of preclinical lipodystrophy. The cutoff points have not been determined yet; however, continuous assessment may be useful to identify early body composition changes.     

Pneumonitis and eosinophilia after in vitro fertilization treatment

A 33-year-old woman presented to the emergency department (ED) with tachypnea, tachycardia, and hypoxia, complaining of dyspnea and paroxysms of dry cough for 2 days. The patient had undergone an unsuccessful in vitro fertilization procedure 1 month earlier and had had another embryo implantation 6 days earlier. She had been receiving intramuscular injections of estradiol and progesterone in sesame oil to support implantation. A chest radiograph demonstrated extensive bilateral pulmonary consolidation; a leukocytosis count of 19.7 x 10(9) with 20% eosinophils was noted on a CBC count. A MEDLINE search yielded a case report in infertility literature describing an eosinophilic pneumonitis with similar clinical features after injections of progesterone in sesame oil. Treatment with intravenous corticosteroids was initiated in the ED, resulting in symptom and chest radiograph result improvement within 2 days and sparing the patient further imaging and antibiotic therapy.     

Insulin resistance and body composition in preterm born children during prepubertal ages

Background Premature born children may show insulin resistance in childhood which may be due to intrauterine or postnatal adverse environmental factors. Objective Aim of this study was to evaluate insulin resistance and body composition in preterm born children born appropriate for gestational age (AGA) or small for gestational age (SGA) and relations with IGF‐I, IGFBP‐3 axis. Methods Ninety‐three preterm born children grouped as premature SGA (n = 30) and premature AGA (n = 63) were evaluated at age 4·6 ± 0·2 years and 4·7 ± 0·1 years with respect to their glucose, insulin, IGF‐I, IGFBP‐3, IGFBP‐1, leptin levels and body composition by dual‐energy X‐ray absorptiometry. Their data were compared to that of body mass index (BMI) matched term SGA (n = 42) and term AGA (n = 44) children of age 4·5 ± 0·2 and 3·8 ± 0·1 years. All children had height appropriate for their target height. Insulin resistance was evaluated by basal insulin and homeostasis model assessment for insulin resistance (HOMA‐IR). Results Basal insulin level was similar in preterm AGA (4·3 ± 1·4 pmol/l) and term AGA (7·9 ± 6·4 pmol/l) children at similar and normal BMI levels. Preterm SGA children had insulin levels (5·0 ± 3·6 pmol/l) similar to preterm AGA children but significantly lower than that in term SGA children (23·7 ± 20·8 pmol/l) (P = 0·001). Similar results were obtained for HOMA‐IR. Term SGA children had also significantly lower IGFBP‐1 levels. Body composition, leptin and IGFBP‐3 did not differ between the respective groups. IGF‐I was lower in preterm AGA (5·0 ± 0·6 nmol/l) than in term AGA (8·3 ± 1·2 nmol/l) (P < 0·001) children. Conclusions Premature born AGA and SGA children do not have insulin resistance when compared to term children if they have made a catch‐up growth appropriate for their target height and have normal BMI. The similar insulin levels in preterm SGA and preterm AGA children together with increased insulin levels in term SGA children points to the fact that it is the intrauterine restriction in the third trimester that has an adverse effect on future adverse metabolic outcome.     

The risk of metabolic derangements is higher in children and adolescents with overweight or obesity born small for gestational age

Background and aimsBirth weight (BW) has been associated with the risk of obesity and metabolic derangements in children and adults. The aims of this study were: i. to evaluate the distribution of BW in a sample of overweight and obese children and adolescents compared with the general reference population; ii. to explore the relationship between the BW and insulin resistance and other cardiometabolic derangements in a population of children and adolescents with overweight and obesity.Methods and results710 overweight and obese children and adolescents were recruited and categorized into small (SGA), appropriate (AGA), and large (LGA) for gestational age, according to the BW percentile. Arterial blood pressure, lipid profile, glucose metabolism and hepatic steatosis were evaluated to assess cardiometabolic obesity-related derangements. The distribution of BW categories in our population was significantly different compared with the general population (SGA 6.9% vs. 8.6%, AGA 74.6% vs. 81.4%, LGA 18.5% vs. 10%; p < 0.0001). We found a higher frequency of prediabetes conditions (21.7% vs 8.9%, OR 2.97, 95% CI 1.38–6.38, p = 0.005) and borderline/high low-density lipoprotein cholesterol (31.8% vs 18.6%, OR 2.13, 95% CI 1.09–4.18, p = 0.033) in overweight and obese children born SGA compared to those born non-SGA, independently of age, sex, and BMI.ConclusionsBW is a risk factor of cardiometabolic derangements in a population of children and adolescents with overweight and obesity. Therefore, adequate obesity prevention strategies should be planned for children born SGA to minimize their risk to become obese and to reduce their short- and long-term cardiometabolic risks.     

Incidence of retinoblastoma in children born after in-vitro fertilisation

Every year, 3000 women in the Netherlands are treated with in-vitro fertilisation (IVF), and results from studies suggest that the offspring of these women do not have a heightened risk of cancer. Between November, 2000, and February, 2002, we diagnosed retinoblastoma in five patients born after IVF. To calculate the relative risk of the disease, we assumed that the proportion of children conceived by IVF in the Netherlands is between 1.0 and 1.5%, and that the five patients who we diagnosed with the disease represent all new cases in the Netherlands during that period. Relative risks for retinoblastoma were significantly raised (7.2 [95% CI 2.4-17.0], and 4.9 [1.6-11.3], for 1% and 1.5% rates, respectively). This possible association of an increased risk of retinoblastoma in a population-based study needs to be established.     

Body image perception of children and adolescents with psychiatric disorders

Interviews with 75 adolescents and children in a South Florida psychiatric hospital showed that patients expressed significantly less dissatisfaction with both height and weight than a group of 565 adolescents from the same geographical area. The dissatisfaction expressed by patients was more like that of a sub-group of the students with comparable ethnic characteristics. Patients reported that significant others concurred with their own judgements of body size. One half of patients who were judged by the researcher to be of normal weight wanted to be thinner. The recommendation is made that patients need help with body image perception and management because of the high percentage of dissatisfaction (85 per cent) even though hospitalization for psychiatric disorders does not appear to increase body-image problems.     

Growth, body composition and hormonal axes in children and adolescents

Growth and physical maturation are dynamic processes that encompass a broad range of cellular and somatic changes. Most investigators who study growth have focused on linear growth (change in height over time), but alterations in the relative body proportions, body composition, and the regional distribution of body fat (upper body vs lower body, axial vs appendicular, and sc vs deep visceral) are essential elements for growth and sexual maturation. In fact, cardiovascular risk assessment in the adult relies heavily on the regional distribution of body fat. The antecedents for the adult pattern of fat are clearly present in the adolescent, if not the younger child. Standards for each of these parameters have been developed for multiple ethnic and racial populations and aid materially in the identification of children with normal growth and physical development, variations within the broad normal (physiological) range, and those with clearly pathological growth patterns.     

Body composition changes in children receiving human growth hormone

Skinfold thickness was found to decrease during the first 6–10 wk and then remain constant when human growth hormone therapy was begun in 34 growth hormone-deficient children. Linear growth increased at a constant rate during the first 6 mo. Two children, who routinely received their injection in the same arm at the same site, developed a localized area of markedly diminished subcutaneous fat at the injection site, Height, weight, total-body potassium, and triceps skinfold thickness were measured at 2-mo intervals in nine children receiving human growth hormone. Total-body potassium was measured with the 54-Nal detector whole-body counter of the Brookhaven National Laboratory. The study extended over a period of 20 consecutive mo. Triceps skinfold thickness rapidly decreased during the initiation of therapy with growth hormone, and returned to pretreatment values during a 5-mo control period when therapy was temporarily discontinued. Rate of weight gain was most rapid during this 5-mo control period and was reduced during two periods when growth hormone was being administered. Total body potassium and height increased very little during the control period when weight gain was greatest, and both increased rapidly during the two periods of growth hormone treatment. The data show clearly the initial changes in body fat and lean tissue that occur when human growth hormone is administered to children with growth deficiency.     

Body composition and in vitro lipid metabolism of overfed hypophysectomized rats

Hypophysectomized (hypox) rats were fed ad libitum or were tube-fed increasing levels of their normal food intake. Sham operated (sham) rats were tube-fed to maintain their normal rate of growth or were fed 150 percent of their ad libitum food intake. This was equivalent to the highest intake of hypox rats. Overfeeding continued for 20 days. Overfeeding hypox rats increased body weight almost entirely by hypertrophy and hyperplasia of body fat depots. Overfeeding did not promote growth of lean tissue in hypox rats. Serum insulin increased with higher levels of food intake and extreme overfeeding resulted in hyperinsulinemia and hyperglycemia in hypox rats. Serum thyroid hormones and corticosterone were lower in hypox than sham rats and were not significantly changed by overfeeding. Adipose and hepatic fatty acid synthesis and esterification and adipose glycerol release were measured in vitro. Although serum insulin increased, peripheral tissue of overfed hypox rats remained insulin resistant. Rates of hepatic and adipose lipid synthesis and adipose lipolysis appeared to be determined by nutrient availability rather than being dependent upon pituitary factors.