The Spanish Environment and Childhood Research Network (INMA study)

Prenatal and early life exposure to environmental agents, including dietary exposure, is associated with child health and human development and predisposes to late adult effects. Children are more vulnerable than adults to chemical, physical and biological hazards in air, water and soil, because they are still growing and their immune system and detoxification mechanisms are not fully developed. The physical, social and intellectual development of children from conception to the end of adolescence requires a protected environment that is also protective of their health. Following WHO and European Union recommendations, the Cooperative Environment and Childhood Research Network was funded by the Spanish Ministry of Health to study effects of environment and diet on foetal and early childhood development in different geographical areas of Spain. This network integrates different multidisciplinary research groups and is comprised of six cohorts--three pre-existing and three de novo--which will prospectively follow up 3600 pregnant women from start of pregnancy until the children are 4-6-year old.     

Mediterranean diet adherence during pregnancy and fetal growth: INMA (Spain) and RHEA (Greece) mother-child cohort studies

Dietary intake of specific nutrients or food groups during pregnancy could influence fetal growth, but scant evidence is available on effects of dietary patterns. The aim of this study was to evaluate the impact of Mediterranean diet (MD) adherence during pregnancy on fetal growth in two population-based mother-child cohorts in Spain and Greece. We studied 2461 mother-newborn pairs from the Spanish multi-centre 'INMA' study (Atlantic area: INMA-Atlantic; Mediterranean area: INMA-Mediterranean), and 889 pairs from the 'RHEA' study in Crete, Greece. Maternal diet during pregnancy was assessed by FFQ and MD adherence was evaluated through an a priori score. Fetal growth restriction was based on a customised model, and multivariate log-binomial and linear regression models were used to adjust for several confounders. MD scores differ significantly between the cohorts with women in INMA-Atlantic reporting higher intakes of fish and dairy products, while women in the Mediterranean area reported higher intakes of cereals, vegetables and fruits. Women with high MD adherence had a significantly lower risk of delivering a fetal growth-restricted infant for weight (risk ratios: 0·5; 95?% CI 0·3, 0·9) in the INMA-Mediterranean cohort. Stratified analysis by smoking revealed that higher MD adherence increased birth weight and birth length in smoking mothers, whereas this effect was not apparent in non-smoking mothers. The results of the present study show that several types of MD exist across European Mediterranean regions. High MD adherence may modify the detrimental effect of smoking on birth size, but overall effects of diet were not universal for the studies in this analysis.     

Placental metal concentrations and birth outcomes: The Environment and Childhood (INMA) project

Objective

To examine the association of placental levels of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and chromium (Cr) with birth outcomes (birth weight, length, and head circumference, low birth weight [LBW], gestational age, preterm delivery, and small for gestational age [SGA]) in mother-child pairs from the Environment and Childhood (INMA) Project in Spain.

Effects of lead exposure before pregnancy and dietary calcium during pregnancy on fetal development and lead accumulation

Millions of women of child-bearing age have substantial bone lead stores due to lead exposure as children. Dietary calcium ingested simultaneously with lead exposure can reduce lead absorption and accumulation. However, the effects of dietary calcium on previously accumulated maternal lead stores and transfer to the fetus have not been investigated. We studied the effects of lead exposure of female rats at an early age on fetal development during a subsequent pregnancy. We gave 5-week-old female Sprague-Dawley rats lead as the acetate in their drinking water for 5 weeks; controls received equimolar sodium acetate. This was followed by a 1-month period without lead exposure before mating. We randomly assigned pregnant rats (n = 39) to diets with a deficient (0.1%) or normal (0.5%) calcium content during pregnancy. A total of 345 pups were delivered alive. Lead-exposed dams and their pups had significantly higher blood lead concentrations than controls, but the concentrations were in the range of those found in many pregnant women. Pups born to dams fed the calcium-deficient diet during pregnancy had higher blood and organ lead concentrations than pups born to dams fed the 0. 5% calcium diet. Pups born to lead-exposed dams had significantly (p<0.0001) lower mean birth weights and birth lengths than controls. There were significant inverse univariate associations between dam or pup organ lead concentrations and birth weight or length. The 0.5% calcium diet did not increase in utero growth. Stepwise regression analysis demonstrated that greater litter size and female sex were significantly associated with reduced pup birth weight and length. However, lead exposure that ended well before pregnancy was significantly (p<0.0001) associated with reduced birth weight and length, even after litter size, pup sex, and dam weight gain during pregnancy were included in the regression analysis. The data demonstrate that an increase in dietary calcium during pregnancy can reduce fetal lead accumulation but cannot prevent lead-induced decreases in birth weight and length. The results provide evidence that dietary nutrients can influence the transfer of toxins to the fetus during pregnancy. If these results are applicable to women, an increase in diet calcium during pregnancy could reduce the transfer of lead from prepregnancy maternal exposures to the fetus.     

孕期低浓度铅暴露对胎儿发育的影响及干预研究

目的探讨孕期低浓度铅暴露早期干预对胎儿发育及对婴幼儿发育的影响。方法孕妇于孕早期常规抽取静脉血查血清铅、锌、钙、铁水平,并随机分为观察组与对照组,观察组于孕早期开始进行干预,对照组按常规生活,于产前产时再次抽取两组孕妇静脉血和新生儿脐血查血清铅、锌、钙、铁,并追踪观察两组婴幼儿的MDI(智力发育指数)和PDI(运动发育指数),进行综合评估,对两组的结果进行统计学分析。结果所有孕妇均存在不同程度铅暴露,孕妇血铅水平与血清锌、钙、铁水平多呈负相关性,及时补充血清锌、钙、铁等微量元素,并进行生活行为干预,可明显改善新生儿预后,两组婴幼儿的平均MDI和PDI具有显著性差异。结论孕早期对血铅阳性的孕妇进行干预,可以有效降低孕妇血铅和胎儿血铅水平,提高出生人口素质。     

Diet during early pregnancy and development of gestational diabetes

Diet composition may be a modifiable predictor of risk for abnormal glucose tolerance during pregnancy. Prior studies suggest that diets high in total fat, saturated fat, red and processed meats, and with high glycaemic load increase the risk of developing gestational diabetes mellitus (GDM), while polyunsaturated fats, carbohydrates and fibre are protective. The aim of this study was to investigate associations of these and other nutrients and foods, including n-3 fatty acids, trans fats, whole grains and dietary patterns, with risk of GDM. We studied 1733 women with singleton pregnancies enrolled in Project Viva, a prospective pregnancy and birth cohort study in eastern MA. Using multinomial logistic regression, we examined associations of first trimester diet, assessed by validated food frequency questionnaire, with results of glucose tolerance testing at 26-28 weeks of gestation. A total of 91 women developed GDM and 206 women had impaired glucose tolerance (IGT). Pre-pregnancy body mass index (BMI) was a strong predictor for GDM risk (OR 3.44 [95% CI 1.88, 6.31] for pre-pregnancy BMI > or =30 vs. <25 kg/m(2)). After adjustment for confounders, the OR [95% CI] for risk of GDM for total dietary fat was 1.00 [0.96, 1.05], for saturated fat 0.98 [0.88, 1.08], for polyunsaturated fat 1.09 [0.94, 1.26], for trans fat 0.87 [0.51, 1.49], and for carbohydrates 1.00 [0.96, 1.03] per each 1% of total energy. The adjusted OR [95% CI] for risk of GDM for a one standard deviation increase in energy-adjusted glycaemic load (32 units, about two soft drinks) was 0.96 [0.76, 1.22] and for each daily serving of whole grains was 0.90 [0.73, 1.13]. Dietary patterns and intake of red and processed meats were not predictive of glucose tolerance outcome. Estimates for IGT were similar to those for GDM. Intake of n-3 fatty acids was associated with increased GDM risk (OR 1.11 [95% CI 1.02, 1.22] per each 300 mg/day), but not with IGT risk. Except for this finding, perhaps due to chance, these data do not show that nutrient or food intake in early pregnancy is linked to risk of GDM. Nutritional status entering pregnancy, as reflected by pre-pregnancy BMI, is probably more important than pregnancy diet in development of GDM.     

孕期PM2.5暴露与子代认知-运动发育间关联性研究

目的 分析孕早期和孕中期PM2.5暴露与子代认知-运动发育间关联性,为孕期防护提供依据。方法 选取2014年6月-2015年4月期间来本院建卡并分娩的孕妇190例,于孕期建卡时进行问卷调查,获取孕妇的居住地址、房屋类型以及楼层分布等信息,通过渗透系数获得室外PM2.5进入室内部分的浓度,作为孕期PM2.5暴露水平。并于婴儿产后42 d体检时应用“年龄发育进程问卷-第三版”(ASQ-3)进行认知-运动发育水平评估。通过两独立样本t检验和多因素线性回归等方法分析孕期PM2.5暴露与子代认知-运动发育间的关联性。结果 孕早期正常暴露组孕妇所生婴儿粗大运动能区得分和精细运动能区得分均高于暴露超标组婴儿,且正常暴露组婴儿五个能区总分也高于暴露超标组婴儿,差异均有统计学意义(P<0.05)。孕早期孕妇暴露PM2.5水平每增高一个单位,ASQ-3各能区得分平均降低0.53~0.62分,ASQ-3总分平均降低2.0分,且以上差异有统计学意义(P<0.05)。与孕早期的PM2.5暴露效应不同,在孕中期虽然PM2.5暴露水平增高也呈现出ASQ-3多能区得分降低的趋势,但差异无统计学意义(P>0.05)。结论 相对于孕中期的PM2.5暴露,孕早期的暴露更容易对子代认知-运动发育水平产生影响,因此针对大气PM2.5的防护应从孕早期就开始并且应重点做好孕早期的暴露防护。     

Air pollution exposure during pregnancy, ultrasound measures of fetal growth, and adverse birth outcomes: a prospective cohort study

Background: Air pollution exposure during pregnancy might have trimester-specific effects on fetal growth.Objective: We prospectively evaluated the associations of maternal air pollution exposure with fetal growth characteristics and adverse birth outcomes in 7,772 subjects in the Netherlands.Methods: Particulate matter with an aerodynamic diameter < 10 μm (PM₁₀) and nitrogen dioxide (NO₂) levels were estimated using dispersion modeling at the home address. Fetal head circumference, length, and weight were estimated in each trimester by ultrasound. Information on birth outcomes was obtained from medical records.Results: In cross-sectional analyses, NO₂ levels were inversely associated with fetal femur length in the second and third trimester, and PM₁₀ and NO₂ levels both were associated with smaller fetal head circumference in the third trimester [–0.18 mm, 95% confidence interval (CI): –0.24, –0.12 mm; and –0.12 mm, 95% CI: –0.17, –0.06 mm per 1-μg/m³ increase in PM₁₀ and NO₂, respectively]. Average PM₁₀ and NO₂ levels during pregnancy were not associated with head circumference and length at birth or neonatally, but were inversely associated with birth weight (–3.6 g, 95% CI: –6.7, –0.4 g; and –3.4 g, 95% CI: –6.2, –0.6 g, respectively). Longitudinal analyses showed similar patterns for head circumference and weight, but no associations with length. The third and fourth quartiles of PM₁₀ exposure were associated with preterm birth [odds ratio (OR) = 1.40, 95% CI: 1.03, 1.89; and OR = 1.32; 95% CI: 0.96, 1.79, relative to the first quartile]. The third quartile of PM₁₀ exposure, but not the fourth, was associated with small size for gestational age at birth (SGA) (OR = 1.38; 95% CI: 1.00, 1.90). No consistent associations were observed for NO₂ levels and adverse birth outcomes.Conclusions: Results suggest that maternal air pollution exposure is inversely associated with fetal growth during the second and third trimester and with weight at birth. PM₁₀ exposure was positively associated with preterm birth and SGA.     

Fish intake during pregnancy and early cognitive development of offspring

BACKGROUND: Fish is a source of many nutrients that can be beneficial during pregnancy, as well as a source of neurotoxicant contaminants such as methylmercury. Previous investigations of fish intake in relation to neurodevelopment have focused on possible damage from contaminants, whereas potential benefits of fish consumption have been relatively unexplored METHODS: We evaluated the association between maternal fish intake during pregnancy and offspring's early development of language and communication skills in a cohort of 7421 British children born in 1991-1992. Fish intake by the mother and child was measured by questionnaire. The child's cognitive development was assessed using adaptations of the MacArthur Communicative Development Inventory at 15 months of age and the Denver Developmental Screening Test at 18 months of age. Mercury was measured in umbilical cord tissue for a subset of 1054 children RESULTS: Total mercury concentrations were low and were not associated with neurodevelopment. Fish intake by the mother during pregnancy, and by the infant postnatally, was associated with higher mean developmental scores. For example, the adjusted mean MacArthur comprehension score for children whose mothers consumed fish 4 or more times per week was 72 (95% confidence interval = 71-74), compared with 68 (66-71) among those whose mothers did not consume fish. CONCLUSIONS: When fish is not contaminated, moderate fish intake during pregnancy and infancy may benefit development.     

孕早期使用化妆品对妊娠不良结局和胎儿宫内生长发育的影响

目的探讨孕早期使用化妆品对早产、低出生体质量、小于胎龄儿以及胎儿宫内生长发育的影响。方法选择2014年6月-2016年2月在渠县人民医院进行孕期体检并分娩单胎活产儿的9 219例产妇作为研究对象,分析孕早期化妆品使用情况与不良妊娠结局之间的关系。结果乳液、面霜和眼霜是使用率最高的3种化妆品,每天使用的产妇比例分别为35.77%、23.25%和23.08%,抗皱霜、防晒霜、定型剂和指甲油是使用率最低的品种。孕早期使用化妆品的产妇早产、低出生体质量、小于胎龄儿等3中不良妊娠结局发生率与几乎不使用化妆品的产妇比较,差异无统计学意义(P0.05),Logistic回归分析显示,孕早期是否使用化妆品与早产、低出生体质量、小于胎龄儿无显著统计学关系。孕早期使用化妆品的产妇与几乎不使用化妆品产妇胎儿的出生体质量、胸围、头围和身长等宫内生长发育指标比较,差异无统计学意义(P0.05)。Logistic回归分析显示,孕早期是否使用化妆品与胎儿宫内生长发育指标无相关关系。结论孕早期是否使用化妆品与妊娠不良结局和胎儿宫内生长发育无明显相关性。     

Maternal smoking during pregnancy and subcutaneous fat mass in early childhood. The Generation R Study

Maternal smoking during pregnancy increases the risk of obesity in the offspring. Not much is known about the associations with other measures of body composition. We assessed the associations of maternal smoking during pregnancy with the development of subcutaneous fat mass measured as peripheral and central skinfold thickness measurements in early childhood, in a population-based prospective cohort study from early fetal life onward in the city of Rotterdam, The Netherlands. The study was performed in 907 mothers and their children at the ages of 1.5, 6 and 24 months. As compared to non-smoking mothers, mothers who continued smoking during pregnancy were more likely to have a younger age and a lower educational level. Their children had a lower birth weight, higher risk of small size for gestational age and were breastfed for a shorter duration (P-values <0.01). We did not observe differences in peripheral, central and total subcutaneous fat mass between the offspring of non-smoking mothers, mothers who smoked in first trimester only and mothers who continued smoking during pregnancy (P > 0.05). Also, the reported number of cigarettes smoked by mothers in both first and third trimester of pregnancy were not associated with peripheral, central and total subcutaneous fat mass in the offspring at the ages of 1.5, 6 and 24 months. Our findings suggest that fetal exposure to cigarette smoke during pregnancy does not influence subcutaneous fat mass in early childhood. Follow-up studies are needed in children at older ages and to identify associations of maternal smoking during pregnancy with other measures of body composition.     

孕期宫内血糖暴露对子代器官功能发育的影响

随着孕前糖尿病及妊娠期糖尿病的发生率增高,越来越多的子代在母体孕期暴露于宫内高血糖,造成不良妊娠期结局,并且可能会对子代器官功能及远期器官发育造成负面影响。但是目前针对此类研究还相对较少,该文从眼、耳、牙齿和生殖器官等具体器官功能发育方面总结孕期宫内血糖暴露对子代的不良影响,为临床工作提供参考,并对此类器官发育予以重视并制定提前干预措施。