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Maternal hemoglobin and hematocrit levels during pregnancy and childhood lung function and asthma. The Generation R Study
Abstract
Objective:
To examine the associations of maternal hemoglobin and hematocrit levels during pregnancy with childhood lung function and asthma, and whether adverse pregnancy outcomes and atopic predisposition modify the associations.
Methods:
In a population-based prospective cohort study among 3672 subjects, we measured maternal hemoglobin and hematocrit levels in early pregnancy, and lung function by spirometry and current asthma by questionnaire at age 10 years.
Results:
Higher maternal hematocrit levels, both continuously and categorized into clinical cut-offs, were associated with lower forced expiratory flow at 75% of forced vital capacity (FEF75 ) in children (Z-score (95%CI): -0.04 (-0.07, -0.01), per increase of 1 SDS in hematocrit level; Z-score (95%CI) difference: -0.11 (-0.20, -0.03) compared with normal hematocrit levels, respectively), taking lifestyle and socio-economic factors into account. Adverse pregnancy outcomes and atopic predisposition did not modify the results. No associations of maternal hemoglobin and hematocrit with current asthma were observed.
Conclusion:
Higher maternal hematocrit levels during pregnancy are associated with lower childhood lung function but not with risk of asthma. Adverse pregnancy outcomes and atopic predisposition do not modify these associations. Underlying mechanisms need to be further studied.
... Iron deficiency anemia in pregnancy has been linked to an inadequate oxygen and nutrition supply to the fetus, which increases the risk of preterm birth and low birth weight [8][9][10][11][12][13]. Evidence suggests that preterm birth and low birth weight can affect the offspring's lung function and development of allergic diseases in childhood [9,[14][15][16][17][18][19][20]. In addition, a recent study demonstrated that low iron concentration interferes with interferon (IFN)-γ receptor signaling, which is a key factor for allergy prevention [21]. ...
... Given this situation, low maternal iron status might influence the development of adverse outcomes in children, including allergies. However, to date, few epidemiologic studies have examined the role of maternal iron status on allergic diseases in offspring and the findings have been inconsistent [18,[22][23][24]. ...
... Another analysis in the Generation R study evaluated the associations of maternal hemoglobin and hematocrit levels during pregnancy with lung function measures and asthma among 3672 children. No associations of maternal hemoglobin and hematocrit with current asthma at age 10 years were found [18]. The lack of associations might be explained by the adaptive response of the body. ...
Few epidemiologic studies have examined the role of maternal iron status in allergic diseases in offspring and findings have been inconsistent. We used a large birth cohort in Japan to explore the association of the markers for maternal iron status (maternal hemoglobin, hematocrit and dietary iron intake during pregnancy) with allergy development in offspring during early childhood. We analyzed information on children age 0–3 years from the Japan Environment and Children’s Study (JECS). We used logistic models and generalized estimating equation models to evaluate the effect of maternal hemoglobin and hematocrit levels and dietary iron intake on allergies in children. Models were also fitted with propensity score-matched datasets. Data were collected for a total of 91,247 mother–child pairs. The prevalence (95% confidence interval) of low hemoglobin and hematocrit was 14.0% (13.7–14.2%) and 12.5% (12.3–12.8%), respectively. After adjusting confounders, low hemoglobin and hematocrit during pregnancy were not associated with childhood allergic outcomes. Findings from models with propensity score-matched datasets also indicated that children born to mothers with low hemoglobin or hematocrit levels during pregnancy did not have a higher risk of developing allergic conditions at 3 years old. We found no meaningful associations between low energy adjusted maternal dietary iron intake and allergies in children. In conclusion, using birth cohort data, we found no evidence supporting an association of low maternal hemoglobin, hematocrit and low dietary iron intake with allergy symptoms during early childhood. Further studies with more suitable proxy markers for blood iron status are needed.
... 8 In addition, we previously found a relation of higher maternal hematocrit concentrations during pregnancy with a lower lung function. 9 A randomized control trial showed that, as compared to selective iron supplementation, routine maternal iron supplementation during pregnancy reduced the risk of asthma diagnosis in the children. 10 However, the number of studies on maternal iron status during pregnancy with childhood respiratory and allergy outcomes are scarce, small sample-sized, used genetic variants or hematocrit as a proxy for maternal iron status, or were limited in asthma diagnosis ascertainment. ...
... We previously observed in our cohort that higher maternal hematocrit concentrations in pregnancy were related to a lower FEF 75 in the children at the age of 10 years. 9 Our current results suggest that this association is not driven by maternal iron status. ...
Background:
Iron deficiency during early life could affect the developing lung and immune system, and influence child's respiratory or allergy outcomes in later life.
Objective:
To examine the associations of maternal iron status during early pregnancy with child's lung function, asthma, inhalant allergic sensitization, and physician-diagnosed inhalant allergy at school-age.
Methods:
In a population-based cohort study, among 3825 mother-child pairs, ferritin, transferrin concentrations, and transferrin saturation were measured from maternal venous blood samples during early pregnancy. In children at the age of 10 years, spirometry was used to determine child's lung function, current asthma and physician-diagnosed inhalant allergy were assessed by questionnaires, and inhalant allergic sensitization was measured by skin prick tests. We used multivariable regression models to examine the associations.
Results:
After adjustment for gestational age at maternal iron status measurement and sociodemographic or lifestyle-related confounders, a higher maternal transferrin concentration was associated with a higher risk of physician-diagnosed inhalant allergy (odds ratio [95% confidence interval]: 1.13 [1.01 to1.26]), but not with lung function, asthma, or inhalant allergic sensitization. This association did not attenuate after further adjustment for maternal hemoglobin levels or early growth factors. We observed no consistent association of maternal ferritin concentrations or transferrin saturation with child's respiratory or allergy outcomes.
Conclusion:
Higher maternal transferrin concentrations during pregnancy, reflecting lower serum iron levels, were associated with an increased risk of child's physician-diagnosed inhalant allergy but not lung outcomes. Underlying mechanisms and clinical implications need to be explored.
... Hence, These preterm infants with low HCT levels from birth to the second week of life could have an inadequate supply of oxygen and nutrients, [39] which may adversely impact lung growth and development. [40] Besides, alterations of HCT cause changes in the resistive and elastic properties of the lungs. Low HCT level was verified to decrease elastic properties of the lungs, [41] probably leading to the airway resistance enhancement and may induce occurrence of BPD as it was reported that BPD infants had a significantly higher respiratory system resistance and lower respiratory system compliance than non BPD infants in the first week after birth. ...
To determine hematocrit (HCT) and to identify independent risk factors for predicting bronchopulmonary dysplasia (BPD) in preterm infants with very low birth weight (VLBW) infants. This retrospective study included 296 premature infants with VLBW in the neonatal intensive care unit of the First Affiliated Hospital of the University of Science and Technology of China between January 2015 and December 2019. Maternal pregnant information and clinical information as well as hematological parameters of preterm babies were collected and compared. Then the maximum area under the curve of receiver operating characteristic curve was developed to estimate the predictive indicator in the blood. Finally, differential variables together with the predictive index were screened for multiple logistic regression analysis to determine independent prognostic factors for BPD. Infants were divided into a BPD group (134 cases) and a non-BPD group (162 cases). The area under the curve of HCT at postnatal 1 week was 0.737 with the sensitivity of 52.30 % and the specificity of 86.00%. Birth weight (BW) <1.12 kg, gestational age <28.4 weeks, newborn respiratory distress syndrome, mechanical ventilation ≥ 7 days, ventilation associated pneumonia, patent arterial duct, PaO 2 /FiO 2 <300 mm Hg and HCT <0.455 at postnatal 1 week were risk factors for BPD of VLBW infants. HCT levels below 0.455 at 1 week after birth serve as a valuable indicator for the potential development of BPD.
... 7 We previously demonstrated that a higher maternal hematocrit during pregnancy was associated with a lower forced expiratory flow at 75% of forced vital capacity (FEF 75 ) in children at the age of 10 years. 8 Associations of maternal iron status during pregnancy with other respiratory outcomes such as respiratory tract infections are not fully clear. ...
Background
Maternal hemoglobin and iron status measures during pregnancy might affect the developing fetal respiratory system leading to adverse respiratory conditions. Our aim was to assess the associations of maternal hemoglobin and iron status measures during pregnancy with the risk of respiratory tract infections in children until 10 years of age.
Methods
In a population‐based cohort study among 5134 mother–child pairs, maternal hemoglobin and iron status including ferritin, transferrin, and transferrin saturation were measured during early pregnancy. In children, physician‐attended respiratory tract infections from age 6 months until 10 years were assessed by questionnaires. Confounder‐adjusted generalized estimating equation modeling was applied.
Results
After taking multiple testing into account, high maternal ferritin concentrations and low maternal transferrin saturation during pregnancy were associated with an overall increased risk of upper, not lower, respiratory tract infections until age 10 years of the child [OR (95% CI: 1.23 (1.10, 1.38) and 1.28 (1.12, 1.47), respectively)]. High maternal transferrin saturation during pregnancy was associated with a decreased and increased risk of upper respiratory tract infections at 1 and 6 years, respectively, [OR (95% CI: 0.60 (0.44, 0.83) and 1.54 (1.17, 2.02))]. Observed associations were suggested to be U‐shaped (p‐values for non‐linearity ≤.001). Maternal hemoglobin and iron status measures during pregnancy were not consistently associated with child's gastroenteritis and urinary tract infections, as proxies for general infection effects.
Conclusion
High maternal ferritin and low transferrin saturation concentrations during early pregnancy were most consistently associated with an overall increased risk of child's upper, not lower, respiratory tract infections.
... Mehta et al. [7] indicate that the physiological and anatomical features of the mother's body during pregnancy affect the respiratory system, sometimes changing the presentation of respiratory disorders. Adaptive changes in the respiratory system in pregnant women, emphasized by researchers [9][10][11], begin after fertilization under hormonal stimulation, continue throughout pregnancy and can sometimes mask the pathological process or, conversely, be misinterpreted as a disease. Thus, Mehta et al. (2015) believe that vasodilation due to the action of progesterone results in the development of edema and increased vascularization of mucous membranes, which can cause rhinitis and nosebleeds. ...
Disorders in the fetoplacental complex of pregnant women with chronic respiratory diseases (CRD) is one of the actual problems of modern obstetrics in medical, economic and social aspects. Respiratory diseases in the context of disorders of the fetoplacental complex (FPC) may be a comorbid process, a background to the pathology of pregnancy, or a premorbid condition that contributes to the development of placental dysfunction (PD) or even initiates it; morphophysiological changes characteristic of pregnancy also affect the state of the respiratory system, moderating the course of bronchoobstructive pathology. The presence of respiratory diseases in women, the impact of its treatment and features of the course and medical support of pregnancy in these conditions affect the condition of both the woman and the fetus, and in the future - the physical and neuropsychological development of the child.
... Especially in the perinatal period, an adequate nutrition is pivotal to avoid an atopic predisposition (166,167). A plethora of studies affirm that atopics suffer from numerous micronutrient deficiencies (114,115,(168)(169)(170)(171)(172)(173)(174)(175)(176)(177)(178)(179)(180), such as vitamins A (181), E, (182,183), and D, as well as folic acid and iron (112,162). Although usually widely overlooked, these micronutrients have a profound impact on our genes and our immune system, resulting in many epigenetic changes affecting immune-associated genes (167,184), but, most importantly, being also associated with enhanced inflammatory responses. ...
Although iron is one of the most abundant elements on earth, about a third of the world's population are affected by iron deficiency. Main drivers of iron deficiency are beside the chronic lack of dietary iron, a hampered uptake machinery as a result of immune activation. Macrophages are the principal cells distributing iron in the human body with their iron restriction skewing these cells to a more pro-inflammatory state. Consequently, iron deficiency has a pronounced impact on immune cells, favoring Th2-cell survival, immunoglobulin class switching and primes mast cells for degranulation. Iron deficiency during pregnancy increases the risk of atopic diseases in children, while both children and adults with allergy are more likely to have anemia. In contrast, an improved iron status seems to protect against allergy development. Here, the most important interconnections between iron metabolism and allergies, the effect of iron deprivation on distinct immune cell types, as well as the pathophysiology in atopic diseases are summarized. Although the main focus will be humans, we also compare them with innate defense and iron sequestration strategies of microbes, given, particularly, attention to catechol-siderophores. Similarly, the defense and nutritional strategies in plants with their inducible systemic acquired resistance by salicylic acid, which further leads to synthesis of flavonoids as well as pathogenesis-related proteins, will be elaborated as both are very important for understanding the etiology of allergic diseases. Many allergens, such as lipocalins and the pathogenesis-related proteins, are able to bind iron and either deprive or supply iron to immune cells. Thus, a locally induced iron deficiency will result in immune activation and allergic sensitization. However, the same proteins such as the whey protein beta-lactoglobulin can also transport this precious micronutrient to the host immune cells (holoBLG) and hinder their activation, promoting tolerance and protecting against allergy. Since 2019, several clinical trials have also been conducted in allergic subjects using holoBLG as a food for special medical purposes, leading to a reduction in the allergic symptom burden. Supplementation with nutrient-carrying lipocalin proteins can circumvent the mucosal block and nourish selectively immune cells, therefore representing a new dietary and causative approach to compensate for functional iron deficiency in allergy sufferers.
Background
Studies on the associations between maternal complications during pregnancy and childhood asthma are exclusively conducted in Western countries. The findings are mixed and may not be translated to other populations. We aimed to investigate the associations among the Chinese population and to determine whether the associations were mediated through preterm birth, cesarean delivery, low birth weight, and not breastfeeding in the first 6 months.
Methods
We conducted a retrospective cohort study of 166 772 children in Guangzhou, China. Information on maternal gestational hypertension, gestational diabetes, and gestational anemia during pregnancy was extracted from medical records. Ever diagnosis of asthma in children aged 6–12 years was obtained by questionnaire. Logistic regression models and mediation analyses were used to estimate the adjusted odds ratios (aORs) and 95% confidential intervals (CIs) for childhood asthma.
Results
Gestational hypertension, gestational diabetes, and gestational anemia during pregnancy were associated with an increased risk of ever diagnosed childhood asthma; the aOR was 1.48 (95%CI 1.37–1.60), 1.71 (95%CI 1.65–1.78) and 1.34 (95%CI 1.26–1.45), respectively. A stronger association was observed for 2 or 3 gestational complications (aOR=2.02, 95%CI 1.93–2.16) than 1 gestational complication (aOR=1.64, 95%CI 1.52–1.77). The aOR for three gestational complications was 1.35 (95%CI 1.26–1.45), 1.63 (95%CI 1.58–1.70), and 1.32 (95%CI 1.24–1.43), respectively, after controlling for the mediators, including preterm birth, cesarean delivery, low birth weight, and not breastfeeding in the first 6 months.
Conclusions
Gestational hypertension, diabetes, and anemia during pregnancy were associated with childhood asthma, and the associations were partially explained by the mediation effects.
Pediatric Pulmonology publishes original research, reviews, and case reports related to a wide range of children's respiratory disorders. In our “Year in Review” series, we summarize publications in our major topic areas from 2018, in the context of selected literature in these areas from other journals relevant to our discipline. This review covers selected articles on asthma, physiology/lung function testing, and respiratory infections.
The Generation R Study is a population-based prospective cohort study from fetal life until adulthood. The study is designed to identify early environmental and genetic causes and causal pathways leading to normal and abnormal growth, development and health from fetal life, childhood and young adulthood. This multidisciplinary study focuses on several health outcomes including behaviour and cognition, body composition, eye development, growth, hearing, heart and vascular development, infectious disease and immunity, oral health and facial growth, respiratory health, allergy and skin disorders of children and their parents. Main exposures of interest include environmental, endocrine, genomic (genetic, epigenetic, microbiome), lifestyle related, nutritional and socio-demographic determinants. In total, 9778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. Response at baseline was 61%, and general follow-up rates until the age of 10 years were around 80%. Data collection in children and their parents includes questionnaires, interviews, detailed physical and ultrasound examinations, behavioural observations, lung function, Magnetic Resonance Imaging and biological sampling. Genome and epigenome wide association screens are available. Eventually, results from the Generation R Study contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.
Maternal nutritional status during pregnancy has been reported to be associated with childhood asthma and atopic disease. The Avon Longitudinal Study of Parents and Children has reported associations between reduced umbilical cord Fe status and childhood wheeze and eczema; however, follow-up was short and lung function was not measured. In the present study, the associations between maternal Fe status during pregnancy and childhood outcomes in the first 10 years of life were investigated in a subgroup of 157 mother-child pairs from a birth cohort with complete maternal, fetal ultrasound, blood and child follow-up data. Maternal Fe intake was assessed using FFQ at 32 weeks of gestation and Hb concentrations and serum Fe status (ferritin, soluble transferrin receptor and TfR-F (transferrin receptor:ferritin) index) were measured at 11 weeks of gestation and at delivery. Maternal Fe intake, Hb concentrations and serum Fe status were found to be not associated with fetal or birth measurements. Unit increases in first-trimester maternal serum TfR concentrations (OR 1·44, 95 % CI 1·05, 1·99) and TfR-F index (OR 1·42, 95 % CI 1·10, 1·82) (i.e. decreasing Fe status) were found to be associated with an increased risk of wheeze, while unit increases in serum ferritin concentrations (i.e. increasing Fe status) were found to be associated with increases in standardised mean peak expiratory flow (PEF) (β 0·25, 95 % CI 0·09, 0·42) and forced expiratory volume in the first second (FEV1) (β 0·20, 95 % CI 0·08, 0·32) up to 10 years of age. Increasing maternal serum TfR-F index at delivery was found to be associated with an increased risk of atopic sensitisation (OR 1·35, 95 % CI 1·02, 1·79). The results of the present study suggest that reduced maternal Fe status during pregnancy is adversely associated with childhood wheeze, lung function and atopic sensitisation, justifying further studies on maternal Fe status and childhood asthma and atopic disease.
Abstract Objective. To examine the relationship between maternal haemoglobin concentration (Hb) at 27-29 weeks' gestation and severity of pre-eclampsia (PE). Methods. This was a retrospective study of maternal Hb at 27-29 week in 497 pregnancies that developed PE and 497 healthy controls with normal pregnancy outcomes. Multiple regression analysis was used to examine the association between HB and maternal characteristics and severity of PE classified according to gestation at delivery, birth weight and prevalence of abnormal peripartum maternal creatinine, aspartate transaminase and platelet count. Results. There was no significant difference in median Hb between the PE and control groups. Multiple regression analysis in the PE group showed that significant prediction for Hb was provided by Afro-Caribbean race, gestation at delivery, maternal platelet count <2.5th percentile and birth weight, but not serum creatinine or aspartate transaminase above the 97.5th percentile. Increased Hb was observed in both small and large for gestational age neonates. Conclusion. In PE Hb at 27-29 weeks is influenced by birth weight, maternal characteristics and platelet count.
Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results.
We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years).
First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes.
Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27).
Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.
The Generation R Study is a population-based prospective cohort study from fetal life until adulthood. The study is designed to identify early environmental and genetic causes and causal pathways leading to normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on six areas of research: (1) maternal health; (2) growth and physical development; (3) behavioural and cognitive development; (4) respiratory health and allergies; (5) diseases in childhood; and (6) health and healthcare for children and their parents. Main exposures of interest include environmental, endocrine, genetic and epigenetic, lifestyle related, nutritional and socio-demographic determinants. In total, n = 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. Response at baseline was 61 %, and general follow-up rates until the age of 6 years exceed 80 %. Data collection in mothers, fathers and children include questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome and epigenome wide association screen is available in the participating children. From the age of 5 years, regular detailed hands-on assessments are performed in a dedicated research center including advanced imaging facilities such as Magnetic Resonance Imaging. Eventually, results forthcoming from the Generation R Study contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.
Derive continuous prediction equations and their lower limits of normal for spirometric indices, which are applicable globally.Over 160,000 data points from 72 centres in 33 countries were shared with the European Respiratory Society Global Lung Function Initiative. Eliminating data that could not be used (mostly missing ethnic group, some outliers) left 97,759 records of healthy nonsmokers (55.3% females) aged 2.5-95 years.Lung function data were collated, and prediction equations derived using the LMS (λ, μ, σ) method, which allows simultaneous modelling of the mean (mu), the coefficient of variation (sigma) and skewness (lambda) of a distribution family.After discarding 23,572 records, mostly because they could not be combined with other ethnic or geographic groups, reference equations were derived for healthy individuals from 3-95 years for Caucasians (N=57,395), African Americans (N=3,545), and North (N=4,992) and South East Asians (N=8,255). FEV1 and FVC between ethnic groups differed proportionally from that in Caucasians, such that FEV1/FVC remained virtually independent of ethnic group. For individuals not represented by these four groups, or of mixed ethnic origins, a composite equation taken as the average of the above equations is provided to facilitate interpretation until a more appropriate solution is developed.Spirometric prediction equations for the 3-95 age range are now available that include appropriate age-dependent lower limits of normal. They can be applied globally to different ethnic groups. Additional data from the Indian subcontinent, Arab, Polynesian, Latin American countries, and Africa will further improve these equations in the future.
Previous studies have suggested that asthma, like other common diseases, has at least part of its origin early in life. Low birth weight has been shown to be associated with increased risks of asthma, chronic obstructive airway disease, and impaired lung function in adults, and increased risks of respiratory symptoms in early childhood. The developmental plasticity hypothesis suggests that the associations between low birth weight and diseases in later life are explained by adaptation mechanisms in fetal life and infancy in response to various adverse exposures. Various pathways leading from adverse fetal and infant exposures to growth adaptations and respiratory health outcomes have been studied, including fetal and early infant growth patterns, maternal smoking and diet, children's diet, respiratory tract infections and acetaminophen use, and genetic susceptibility. Still, the specific adverse exposures in fetal and early postnatal life leading to respiratory disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life, and their epigenetic mechanisms may underlie the complex associations of low birth weight with respiratory disease in later life. New well-designed epidemiological studies are needed to identify the specific underlying mechanisms. This review is focused on specific adverse fetal and infant growth patterns and exposures, genetic susceptibility, possible respiratory adaptations and perspectives for new studies.
The aetiology of asthma and allergic disease remains poorly understood, despite considerable research. The International Study of Asthma and Allergies in Childhood (ISAAC), was founded to maximize the value of epidemiological research into asthma and allergic disease, by establishing a standardized methodology and facilitating international collaboration. Its specific aims are: 1) to describe the prevalence and severity of asthma, rhinitis and eczema in children living in different centres, and to make comparisons within and between countries; 2) to obtain baseline measures for assessment of future trends in the prevalence and severity of these diseases; and 3) to provide a framework for further aetiological research into genetic, lifestyle, environmental, and medical care factors affecting these diseases. The ISAAC design comprises three phases. Phase 1 uses core questionnaires designed to assess the prevalence and severity of asthma and allergic disease in defined populations. Phase 2 will investigate possible aetiological factors, particularly those suggested by the findings of Phase 1. Phase 3 will be a repetition of Phase 1 to assess trends in prevalence.
Failure of fetal growth during pregnancy, and preterm birth, are the major causes of stillbirth and early neonatal death. The objective of the study was to determine the association between maternal hemoglobin concentration during pregnancy and perinatal mortality.
The design was prospective, using data on 222,614 first singleton pregnancies in the St Mary's Maternity Information System database in the Northwest Thames region of London.
The association of perinatal mortality with maternal hemoglobin at first antenatal check was not statistically significant (P>.10), but a statistically significant (P<.001) U-shaped pattern was found with lowest recorded maternal hemoglobin concentration. Both early neonatal mortality and stillbirth rates were statistically significantly (P<.005) associated with lowest maternal hemoglobin concentration. The relationship of lowest hemoglobin with early neonatal mortality was largely mediated by the effect of preterm birth, and that between lowest hemoglobin and stillbirth by fetal growth restriction. The lowest perinatal mortality was associated with a lowest recorded maternal hemoglobin concentration of between 9-11 g/dL.
There is an optimal range of lowest hemoglobin concentration in pregnancy, and on either side of this perinatal mortality is increased. The effect of lowest hemoglobin is largely mediated through associations with preterm birth and fetal growth restriction.
The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from fetal life until young adulthood. In total, 9,778 mothers were enrolled in the study. Prenatal and postnatal data collection is conducted by physical examinations, questionnaires, interviews, ultrasound examinations and biological samples. Major efforts have been conducted for collecting biological specimens including DNA, blood for phenotypes and urine samples. In this paper, the collection, processing and storage of these biological specimens are described. Together with detailed phenotype measurements, these biological specimens form a unique resource for epidemiological studies focused on environmental exposures, genetic determinants and their interactions in relation to growth, health and development from fetal life onwards.
Objective:
Vasculogenesis and angiogenesis are crucial for maintaining proper placental perfusion and optimal fetal development. Among other physical and chemical factors, hypoxia is known to stimulate angiogenic processes. Preplacental type of hypoxia is often associated with maternal anemia and is thought to enhance vascularization within the fetoplacental unit. The goal of this study was to establish the correlation between the local expression of vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) receptors (flt-1, flk-1) with maternal hemoglobin (Hb) concentration, hematocrit (Ht) values and the infant birthweight.
Methods:
In total, 43 specimens of term placentas obtained from normal course pregnancies delivered at term were included in the study. The expression of flt-1 and flk-1 receptors was analyzed by immunohistochemical staining. Vascular/extravascular tissular index (V/EVTI) was measured by assessing a total vascular area. Nonparametric Mann-Whitney U-test and Spearman's rank correlation were used to compare the various parameters and their differences between the groups.
Results:
Among the patients with low Hb concentration, nearly 2-fold greater expression of the flt-1 receptor was positively correlated with infants birthweight (p = 0.028).
Conclusions:
Increased placental vascular density (increased flt-1 expression), during a physiological course of gestation, may be an adaptive response to lowered maternal Hb concentration and Ht values encountered during pregnancy.
BACKGROUND: Children born preterm or with a small size for gestational age are at increased risk for childhood asthma.
OBJECTIVE: We sought to assess the hypothesis that these associations are explained by reduced airway patency.
METHODS: We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma.
RESULTS: Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma.
CONCLUSIONS: Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.
Chronic obstructive lung diseases, like asthma and chronic obstructive pulmonary disease, have high prevalences and are a major public health concern. Chronic obstructive lung diseases have at least part of their origins in early life. Exposure to an adverse environment during critical periods in early life might lead to permanent developmental adaptations which results in impaired lung growth with smaller airways and lower lung volume, altered immunological responses and related inflammation, and subsequently to increased risks of chronic obstructive lung diseases throughout the life course. Various pathways leading from early life factors to respiratory health outcomes in later life have been studied, including fetal and early infant growth patterns, preterm birth, maternal obesity, diet and smoking, children's diet, allergen exposure and respiratory tract infections, and genetic susceptibility. Data on potential adverse factors in the embryonic and preconception period and respiratory health outcomes are scarce. Also, the underlying mechanisms how specific adverse exposures in the fetal and early postnatal period lead to chronic obstructive lung diseases in later life are not yet fully understood. Current studies suggest that interactions between early environmental exposures and genetic factors such as changes in DNA-methylation and RNA expression patterns may explain the early development of chronic obstructive lung diseases. New well-designed epidemiological studies are needed to identify specific critical periods and to elucidate the mechanisms underlying the development of chronic obstructive lung disease throughout the life course.
The Generation R Study is a population-based prospective cohort study from fetal life until adulthood. The study is designed to identify early environmental and genetic causes and causal pathways leading to normal and abnormal growth, development and health from fetal life, childhood and young adulthood. In total, 9,778 mothers were enrolled in the study. Data collection in children and their parents include questionnaires, interviews, detailed physical and ultrasound examinations, behavioural observations, Magnetic Resonance Imaging and biological samples. Efforts have been conducted for collecting biological samples including blood, hair, faeces, nasal swabs, saliva and urine samples and generating genomics data on DNA, RNA and microbiome. In this paper, we give an update of the collection, processing and storage of these biological samples and available measures. Together with detailed phenotype measurements, these biological samples provide a unique resource for epidemiological studies focused on environmental exposures, genetic and genomic determinants and their interactions in relation to growth, health and development from fetal life onwards.
Objective:
The objective of this study was to compare different measures of airflow obstruction by spirometry in childhood asthma. The objectives were; (a) to compare sensitivity of large airway tests (FEV1 and PEFR) with tests at low lung volumes (small airways) (FEF25-75, FEF50 and FEF75); (b) compare within each group which individual tests are more sensitive.
Methods:
This was a retrospective analysis of 2307 spirometry tests performed during outpatient visits on 821 doctor-diagnosed asthma patients aged 6-18. Tests were deemed acceptable if they were acceptable and repeatable by American Thoracic Society (ATS) criteria.
Results:
In mild obstruction, FEV1 detected 6.8% abnormal tests while FEF75 detected 33% (p < 0.0001). In more severe obstruction, the difference was more obvious (FEV1 14.8%; FEF75 71%). Tests at low lung volumes (small airway tests) were also more sensitive than PEFR. Within groups, FEV1 was more sensitive than PEFR in the large airway tests and FEF75 was more sensitive than FEF25-75 and FEF50 among the tests at low lung volumes (small airway tests). The FEV1/FVC ratio correlated more closely with tests at low lung volumes (small airway tests), than with large airway tests.
Conclusions:
(1) Tests at low lung volumes (small airway tests) are more sensitive than large airway tests; (2) Within groups, the FEV1 is better than PEFR and FEF75 is better than FEF25-75 or FEF50.
Objective
To assess whether variations in maternal haemoglobin levels during pregnancy are associated with cardio-metabolic risk factors in school age children.DesignPopulation-based prospective cohort study.SettingRotterdam, The Netherlands, 2002–2012.PopulationMothers and children (n = 5002) participating in the Generation R Study.Methods
We obtained maternal haemoglobin levels during early pregnancy (median gestational age 14.6 weeks [95% range 10.3, 25.3]) from venous blood samples. Maternal anaemia and elevated haemoglobin levels were based on World Health Organization criteria. We measured childhood cardio-metabolic risk factors at age 6 years.Main outcome measuresCardio-metabolic risk factors included body mass index, total fat mass percentage, android/gynoid fat mass ratio, systolic and diastolic blood pressure, left ventricular mass, and blood levels of cholesterol, insulin and C-peptide.ResultsMaternal haemoglobin levels were not associated with childhood body mass index, total fat mass percentage, android/gynoid fat mass ratio, systolic blood pressure, cholesterol or insulin levels. Compared with children with normal maternal haemoglobin levels, children from anaemic mothers had slightly higher diastolic blood pressures (difference 0.70 mmHg, 95% CI 0.12, 1.29) and lower C-peptide levels (difference factor 0.93, 95% CI 0.88, 0.98), and children of mothers with elevated haemoglobin levels had lower left ventricular masses (difference −1.08 g, 95% CI −1.88, −0.29). These associations attenuated after adjustment for multiple testing and were not consistent within linear models.Conclusion
These results do not strongly support the hypothesis that variations in maternal haemoglobin levels during pregnancy influence cardio-metabolic risk factors in childhood.
To determine sociodemographic and life style-related risk factors and trimester specific maternal, placental, and fetal consequences of maternal anaemia and elevated haemoglobin levels in pregnancy.
In a population-based prospective cohort study of 7317 mothers, we measured haemoglobin levels in early pregnancy [gestational age median 14.4 weeks (inter-quartile-range 12.5-17.5)]. Anaemia (haemoglobin ≤11 g/dl) and elevated haemoglobin levels (haemoglobin ≥13.2 g/dl) were defined according to the WHO criteria. Maternal blood pressure, placental function and fetal growth were measured in each trimester. Data on gestational hypertensive disorders and birth outcomes was collected from hospitals.
Older maternal age, higher body mass index, primiparity and European descent were associated with higher haemoglobin levels (P < 0.05). Elevated haemoglobin levels were associated with increased systolic and diastolic blood pressure throughout pregnancy (mean differences 5.1 mmHg, 95% confidence interval [CI] 3.8, 6.5 and 4.1 mmHg, 95% CI 3.0, 5.2, respectively) and with a higher risk of third trimester uterine artery notching (RR 1.3, 95% CI 1.0, 1.7). As compared with maternal normal haemoglobin levels, not anaemia, but elevated haemoglobin levels were associated with fetal head circumference, length, and weight growth restriction from third trimester onwards (P < 0.05). Elevated haemoglobin levels were associated with increased risks of gestational hypertensive disorders (RR 1.4, 95% CI 1.1, 1.8) and adverse birth outcomes (RR 1.4, 95% CI 1.1, 1.7).
In a low-risk population, various sociodemographic and life style factors affect haemoglobin levels during pregnancy. Elevated haemoglobin levels are associated with increased risks of maternal, placental, and fetal complications.
Accumulating data suggest that prenatal compromises leading to intrauterine growth restriction (IUGR) increase the risk for respiratory deficiencies after birth. In this respect, a growing body of epidemiological evidence in infants, children and adults indicates that small for gestational (SGA) birth weight can adversely affect lung function, thus questioning the widely accepted concept that IUGR accelerates lung maturation and improves outcome. Although the mechanisms responsible for the relationship between SGA and later lung dysfunction remain poorly documented, animal data indicate that intrauterine lung development can be adversely affected by factors associated with IUGR, namely reduced substrate supply, fetal hypoxemia and hypercortisolemia. Thus, it is suggested that fetal adaptations to intrauterine undernutrition result in permanent changes in lung structure, which in turn lead to chronic airflow obstruction. The purpose of this review is to describe and discuss the effects of IUGR on lung structure and function.
In children unable to perform reliable spirometry, the interrupter resistance (Rint) technique for assessing respiratory resistance is easy to perform. However, few data are available on the possibility to use Rint as a surrogate for spirometry. We aimed at comparing R int and spirometry at baseline and after bronchodilator administration in a large population of asthmatic children. We collected retrospectively Rint and spirometry results measured in 695 children [median age 7.8 (range 4.8-13.9) years] referred to our lab for routine assessment of asthma disease. Correlations between Rint and spirometry were studied using data expressed as z-scores. Receiver operator characteristic curves for the baseline Rint value (z-score) and the bronchodilator effect (percentage predicted value and z-score) were generated to assess diagnostic performance. At baseline, the relationship between raw values of Rint and FEV1 was not linear. Despite a highly significant inverse correlation between Rint and all of the spirometry indices (FEV1, FVC, FEV1/FVC, FEF 25-75%; P < 0.0001), Rint could detect baseline obstruction (FEV1 z-score ≤ -2) with only 42% sensitivity and 95% specificity. Post-bronchodilator changes in R∫ and FEV 1 were inversely correlated (rhô = -0.50, P < 0.0001), and R∫ (a;circyen < 35% predicted value decrease) detected FEV1 reversibility (> 12% baseline increase) with 70% sensitivity and 69% specificity (AUC = 0.79). R∫ measurements fitted a one-compartment model that explained the relationship between flows and airway resistance. We found that R∫ had poor sensitivity to detect baseline obstruction, but fairly good sensitivity and specificity to detect reversibility. However, in order to implement asthma guidelines for children unable to produce reliable spirometry, bronchodilator response measured by R∫ should be systematically studied and further assessed in conjunction with clinical outcomes. Pediatr Pulmonol. 2012. 47:987-993.
This review focuses on genetic and environmental influences that result in long term alterations in lung structure and function. Environmental factors operating during fetal and early postnatal life can have persistent effects on lung development and so influence lung function and respiratory health throughout life. Common factors affecting the quality of the intrauterine environment that can alter lung development include fetal nutrient and oxygen availability leading to intrauterine growth restriction, fetal intrathoracic space, intrauterine infection or inflammation, maternal tobacco smoking and other drug exposures. Similarly, factors that operate during early postnatal life, such as mechanical ventilation and high FiO(2) in the case of preterm birth, undernutrition, exposure to tobacco smoke and respiratory infections, can all lead to persistent alterations in lung structure and function. Greater awareness of the many prenatal and early postnatal factors that can alter lung development will help to improve lung development and hence respiratory health throughout life.
There is convincing evidence that asthma has its origins in early life. We review the epidemiological and biological evidence for fetal exposures that may have a causal role in asthma development. However, those factors that provoke asthma exacerbations are not necessarily the same as those associated with disease induction. Epidemiological studies have identified many potential exposures linked to asthma but these do not confirm causality and have not been replicated by experiment. Asthma is a heterogeneous disease and there are developmental influences on at least two pathways, airway structure and airway inflammation. The fetus is not immunologically naive and intrauterine exposures can act directly to invoke immunological sensitisation leading postnatally to airway inflammation. Other potential mechanisms include indirect effects on airway and lung growth through fetal nutrition and epigenetic modifications of DNA expression by environmental exposures. Identifying the causal factors will provide the targets for interventions to prevent disease.
To determine the effect of maternal anaemia on pregnancy outcome and describe its impact on infant haemoglobin level in the first 18 months of life, we conducted a prospective study of 617 pregnant women and their children in Benin. Prevalence of maternal anaemia at delivery was 39.5%, and 61.1% of newborns were anaemic at birth. Maternal anaemia was not associated with low birth weight [OR = 1.2 (0.6-2.2)] or preterm birth [OR = 1.3 (0.7-2.4)], whereas the newborn's anaemia was related to maternal anaemia [OR = 1.8 (1.2-2.5)]. There was no association between an infant's haemoglobin level until 18 months and maternal anaemia. However, malaria attacks during follow-up, male gender and sickle cell trait were all associated with a lower infant haemoglobin level until 18 months, whereas good infant feeding practices and a polygamous family were positively associated with a higher haemoglobin level during the first 18 months of life.
Multivariate imputation by chained equations (MICE) has emerged as a principled method of dealing with missing data. Despite properties that make MICE particularly useful for large imputation procedures and advances in software development that now make it accessible to many researchers, many psychiatric researchers have not been trained in these methods and few practical resources exist to guide researchers in the implementation of this technique. This paper provides an introduction to the MICE method with a focus on practical aspects and challenges in using this method. A brief review of software programs available to implement MICE and then analyze multiply imputed data is also provided.
Anemia in pregnancy is a global health problem affecting nearly half of all pregnant women worldwide. High fetal demands for iron render iron deficiency the most common cause of anemia of pregnancy, with other micronutrient deficiencies contributing less frequently. In certain geographical populations, human pathogens such as hookworm, malarial parasite and human immunodeficiency virus are important factors in anemia of pregnancy. The hemoglobinopathies, sickle cell disease and thalassemia, represent diverse causes of anemia of pregnancy, requiring specialized care. Aplastic anemia is a rare, morbid cause of anemia of pregnancy and is managed with transfusions until the completion of pregnancy.
Increasing interest has focused on maternal nutrition and micronutrient status during pregnancy and respiratory disease development in the offspring.
To examine the relationship between maternal anemia in pregnancy with wheeze and asthma in early childhood.
The cohort included children of women followed through pregnancy and recontacted when the child was 6 years of age to evaluate respiratory health. Exposure was assessed using maternal anemia diagnosis and hemoglobin (Hgb) < 11 during delivery hospitalization. Study outcomes include wheezing in early childhood; patterns of wheeze from birth to age 6 (early-onset transient wheeze; late-onset wheeze; early-onset persistent wheeze); and diagnosis of childhood asthma.
Maternal anemia was reported by 11.9% of mothers and was associated with recurrent infant wheeze in the first year (adjusted odds ratio [ORa] = 2.17, 95% confidence interval [CI] 1.18, 4.00), wheezing before age 3 (Ora = 2.42, 95% CI 1.38, 4.23), and early-onset transient and early-onset persistent wheeze patterns (Ora = 2.81, 95%CI 1.38, 5.72, and Ora = 2.07, 95% CI 1.02, 4.22), respectively. Among children of mothers with asthma, maternal anemia was associated with recurrent wheeze in year 1 (Ora = 4.22, 95% CI 1.65, 10.80) and wheeze before age 3 (Ora = 2.73, 95% CI 1.17, 6.35). Offspring of mothers with asthma also had increased odds of asthma diagnosis (Ora = 2.53, 95% CI 1.04, 6.17) and current asthma (Ora = 3.46, 95% CI 1.45, 8.26).
Maternal anemia during pregnancy is associated with infant respiratory health outcomes. If this observation is replicated, maternal anemia may be a target for intervention and future research.
We are enthusiastic about the potential for multiple imputation and other methods 14 to improve the validity of medical research results and to reduce the waste of resources caused by missing data. The cost of multiple imputation analyses is small compared with the cost of collecting the data. It would be a pity if the avoidable pitfalls of multiple imputation slowed progress towards the wider use of these methods. It is no longer excusable for missing values and the reason they arose to be swept under the carpet, nor for potentially misleading and inefficient analyses of complete cases to be considered adequate. We hope that the pitfalls and guidelines discussed here will contribute to the appropriate use and reporting of methods to deal with missing data.
The effects of 24 h of reduced maternal uterine blood flow (RUBF) on relative DNA synthesis rates in different tissues and on blood glucose and lactate concentrations were studied in fetal sheep. In six sheep, RUBF was induced for 24 h, whereas in another six sheep (controls), uterine blood flow was not reduced. To estimate DNA synthesis rate, [3H]thymidine (1 mCi/kg) was injected intravenously into each fetus 8 h before the end of the 24-h experimental period. Fetal arterial oxygen saturation decreased from 59.1 +/- 3.3 to 25.7 +/- 5.6% after 1 h of RUBF and remained significantly reduced for the duration of the experiment. Fetal blood lactate concentrations were significantly increased by RUBF from 14.3 +/- 6.5 to 57.8 +/- 12.4 mg/dl at 1 h and remained elevated, whereas fetal blood glucose concentrations were not affected. A 24-h period of RUBF did not significantly alter fetal body weights, tissue weights, tissue-to-body weight ratios, or tissue DNA content. Over the last 8 h of the 24-h experimental period, RUBF was found to significantly reduce the relative rate of DNA synthesis (as assessed by [3H]thymidine incorporation into DNA) in the lung (104.7 +/- 26.6 vs. 17.1 +/- 3.1 dpm/micrograms DNA), quadriceps muscle (92.8 +/- 20.7 vs. 14.4 +/- 5.3 dpm/micrograms DNA), and thymus gland (87.5 +/- 7.1 vs. 32.9 +/- 12.2 dpm/micrograms DNA). Relative DNA synthesis rates in the fetal liver, kidney, small intestine, cerebral cortex, cerebellum, placenta, thyroid gland, and adrenal gland were not significantly affected by RUBF. In this study, we have shown that DNA synthesis was greatly reduced in selected fetal tissues (lung, quadriceps muscle, and thymus gland) by a 24-h period of RUBF, although it is not known why a reduction was only observed in these tissues.
The relation between haemoglobin (Hb) concentrations at antenatal booking and subsequent outcome was examined in 54 382 singleton pregnancies. Both high (greater than 13.2 g/dl) and low (less than 10.4 g/dl) Hb values were associated with an adverse outcome. Mothers with a booking Hb in the intermediate range (10.4-13.2 g/dl) fared best. Significant differences emerged in perinatal mortality between those with high and those with intermediate Hb levels at 13-19 weeks' gestation. The frequencies of perinatal death, low birthweight, and preterm delivery were greater with high than with intermediate Hb. There was a striking relation between booking Hb values and the subsequent frequency of hypertension (p less than 0.001). In primiparas, the frequency of subsequent hypertension ranged from 7% at Hb values under 10.5 g/dl to 42% at Hb concentrations over 14.5 g/dl.
To determine the effects of duration of hypoxia on fetal pulmonary blood flow and vasoreactivity, we studied the response of the fetal pulmonary vascular bed before, during, and after prolonged (2-h) and more brief (30-min) exposures to acute hypoxia in 19 chronically instrumented unanesthetized fetal lambs. Left pulmonary arterial blood flow was measured by an electromagnetic flow transducer. Fetal PO2 was lowered by delivering 10-12% O2 to the ewe. During 2-h periods of hypoxia left pulmonary arterial blood flow decreased, and main pulmonary arterial and pulmonary vascular resistance increased. The increase in pulmonary vascular resistance was sustained throughout the 2-h period of hypoxia. After the return of the ewe to room air breathing, pulmonary vascular resistance remained elevated for at least 1 h despite the rapid correction of hypoxemia and in the absence of acidemia. In contrast, after 30 min of hypoxia, left pulmonary arterial blood flow, pulmonary arterial pressure, and pulmonary vascular resistance returned to base-line values rapidly with the termination of hypoxia. The persistent pulmonary hypoperfusion after 2 h of hypoxia was attenuated by alpha-adrenergic blockade and was characterized by a blunted vasodilatory response to increases in fetal PO2. When fetal PO2 was elevated during the posthypoxia period in the presence of alpha-blockade, pulmonary blood flow still remained unresponsive to increases in fetal PO2. We conclude that 2-h periods of acute hypoxia can decrease fetal pulmonary vasoreactivity, and we speculate that related mechanisms may contribute to the failure of the normal adaptation of the pulmonary circulation at birth.
Pregnancy requires additional maternal absorption of iron. Maternal iron status cannot be assessed simply from hemoglobin concentration because pregnancy produces increases in plasma volume and the hemoglobin concentration decreases accordingly. This decrease is greatest in women with large babies or multiple gestations. However, mean corpuscular volume does not change substantially during pregnancy and a hemoglobin concentration <95 g/L in association with a mean corpuscular volume <84 fL probably indicates iron deficiency. Severe anemia (hemoglobin <80 g/L) is associated with the birth of small babies (from both preterm labor and growth restriction), but so is failure of the plasma volume to expand. Hemoglobin concentrations >120 g/L at the end of the second trimester are associated with a </=3-fold increased risk of preeclampsia and intrauterine growth restriction. The minimum incidence of low birth weight (<2.5 kg) and of preterm labor (<37 completed weeks) occurs in association with a hemoglobin concentration of 95-105 g/L. This is widely regarded as indicating anemia in the pregnant woman but, if associated with a mean corpuscular volume >84 fL, should be considered optimal.
An association between moderate anemia and poor perinatal outcomes has been found through epidemiologic studies, although available evidence cannot establish this relation as causal. Anemia may not be a direct cause of poor pregnancy outcomes, except in the case of maternal mortality resulting directly from severe anemia due to hypoxia and heart failure. Preventing or treating anemia, whether moderate or severe, is desirable. Because iron deficiency is a common cause of maternal anemia, iron supplementation is a common practice to reduce the incidence of maternal anemia. Nevertheless, the effectiveness of large-scale supplementation programs needs to be improved operationally and, where multiple micronutrient deficiencies are common, supplementation beyond iron and folate can be considered. High hemoglobin concentrations are often mistaken as adequate iron status; however, high hemoglobin is independent of iron status and is often associated with poor health outcomes. Very high hemoglobin concentrations cause high blood viscosity, which results in both compromised oxygen delivery to tissues and cerebrovascular complications. Epidemiologic studies have also found an association between high maternal hemoglobin concentrations and an increased risk of poor pregnancy outcomes. Evidence does not suggest that this association is causal; it could be better attributed to hypertensive disorders of pregnancy and to preeclampsia. The pathophysiologic mechanism of these conditions during pregnancy can produce higher hemoglobin concentrations because of reduced normal plasma expansion and cause fetal stress because of reduced placental-fetal perfusion. Accordingly, higher than normal hemoglobin concentrations should be regarded as an indicator of possible pregnancy complications, not necessarily as a sign of adequate iron nutrition, because iron supplementation does not increase hemoglobin higher than the optimal concentration needed for oxygen delivery.
Epidemiological studies show that exposure to factors that restrict fetal growth or lead to low birthweight can alter lung development and have later adverse effects on lung function and respiratory health. The major causal factors include reduced nutrient and oxygen availability, nicotine exposure via maternal tobacco smoking and preterm birth, each of which can affect critical stages of lung development. Experimental studies show that these environmental insults can permanently alter lung structure and hence lung function, increasing the risk of respiratory illness and accelerating the rate of lung aging. Further studies are required that address the molecular and cellular mechanisms by which these factors adversely affect lung development and whether such effects can be blocked or reversed. Ultimately however, a major goal should be to prevent prenatal compromises through clinical monitoring, and in the case of smoking through education, thereby ensuring that each fetus has the best possible environment in which to develop.
The aim of this study was to evaluate the presence and the degree of reversible airflow obstruction as detected by forced expiratory volume in 1 second (FEV1), forced oscillometry (FOT), and interrupter technique (resistance measured by the interrupter technique [Rint]) in mild asthmatic children compared with controls. FOT, Rint, and FEV1 were evaluated before and after albuterol (200 microg) administered by metered-dose inhaler and spacer in 28 asthmatic children (mean age +/-SD, 9.1 +/- 1.9 years) and in 20 healthy children (mean age +/-SD, 8.5 +/- 2.1 years). No correlation was found between FEV1, FOT, and Rint values either before or after albuterol. FOT and Rint values were highly correlated pre- and postbronchodilatation. An improvement in FEV1 > or =12% after albuterol was observed in 11 (39%) asthmatic subjects. As suggested using the cutoff value at R6 > or =29%, significant bronchodilatation was observed in 20 (71%) children with FOT and using a reduction > or = 0.20 kPa or 2 cm of H2O, 22 (78%) subjects showed significant bronchodilatation with Rint. No significant changes were observed after albuterol in controls. FOT and Rint techniques showed a greater sensitivity in detecting reversibility of bronchoconstriction in mild asthmatic patients. Prospective studies are needed to clarify the possible advantages of these findings in mild-moderate asthmatic children.
Relation between maternal haemoglobin concentration and birth weight in different ethnic groups
Standardisation of spirometry