Associations of parental age at pregnancy with adolescent cognitive development and emotional and behavioural problems: a birth cohort in rural Western China.

BACKGROUND: The relationship between parental age at pregnancy and offspring development in low- and middle-income countries remains unclear. We aimed to examine the associations of parental age at pregnancy with adolescent development in rural China. METHODS: We conducted a prospective birth cohort study of offspring born to pregnant women who participated in an antenatal micronutrient supplementation trial in rural Western China. Adolescent cognitive development and emotional and behavioural problems were assessed by using the Wechsler Intelligence Scale for Children-IV and the Youth Self-Report-2001, respectively. After accounting for the possible nonlinear relationships, we examined the linear associations between parental age (in years) at pregnancy and scores of adolescent cognitive development and emotional and behavioural problems by performing generalized estimating equations. RESULTS: Among 1897 adolescents followed from birth to early adolescence, 59.5% were male with a mean age of 11.8 (standard deviation (SD): 0.8) years. The mean ages of mothers and fathers at pregnancy were 24.6 (SD: 4.4) and 27.9 (SD: 4.1) years old, respectively. All the P values of the nonlinear terms between parental age and adolescent development in all domains were greater than 0.05. Each one-year increase in maternal age at pregnancy was associated with a 0.29-point (95% confidence interval (CI) 0.06, 0.52) increase in the full-scale intelligence quotient in early adolescence. After parental age was categorized into quartiles, the total behavioural problem scores of adolescents with fathers with an age in the fourth quartile (Q4) were 6.71 (95% CI 0.86, 12.57) points higher than those of adolescents with fathers with an age in the first quartile (Q1), with a linear trend P value of 0.01. Similarly, higher scores (worse behavioural problems) were observed for internalizing behavioural problems and other emotional and behavioural symptoms related to anxiety, withdrawal, social problems, thought problems and aggressive behaviour. CONCLUSIONS: At conception, older maternal age was independently linked to better adolescent cognitive development, whereas advanced paternal age was independently associated with a greater risk of adolescent emotional and behavioral problems. These findings suggest that public health policies targeting an optimal parental age at pregnancy should be developed in the context of offspring developmental consequences.

Intake of B vitamins and the risk of developing islet autoimmunity and type 1 diabetes in the TEDDY study.

PURPOSE: The aim was to study the association between dietary intake of B vitamins in childhood and the risk of islet autoimmunity (IA) and progression to type 1 diabetes (T1D) by the age of 10 years. METHODS: We followed 8500 T1D-susceptible children born in the U.S., Finland, Sweden, and Germany in 2004 -2010 from the Environmental Determinants of Diabetes in the Young (TEDDY) study, which is a prospective observational birth cohort. Dietary intake of seven B vitamins was calculated from foods and dietary supplements based on 24-h recall at 3 months and 3-day food records collected regularly from 6 months to 10 years of age. Cox proportional hazard models were adjusted for energy, HLA-genotype, first-degree relative with T1D, sex, and country. RESULTS: A total of 778 (9.2) children developed at least one autoantibody (any IA), and 335 (3.9%) developed multiple autoantibodies. 280 (3.3%) children had IAA and 319 (3.8%) GADA as the first autoantibody. 344 (44%) children with IA progressed to T1D. We observed that higher intake of niacin was associated with a decreased risk of developing multiple autoantibodies (HR 0.95; 95% CI 0.92, 0.98) per 1 mg/1000 kcal in niacin intake. Higher intake of pyridoxine (HR 0.66; 95% CI 0.46, 0.96) and vitamin B12 (HR 0.87; 95% CI 0.77, 0.97) was associated with a decreased risk of IAA-first autoimmunity. Higher intake of riboflavin (HR 1.38; 95% CI 1.05, 1.80) was associated with an increased risk of GADA-first autoimmunity. There were no associations between any of the B vitamins and the outcomes "any IA" and progression from IA to T1D.  CONCLUSION: In this multinational, prospective birth cohort of children with genetic susceptibility to T1D, we observed some direct and inverse associations between different B vitamins and risk of IA.

Adherence to different forms of plant-based diets and pregnancy outcomes in the Danish National Birth Cohort: A prospective observational study.

INTRODUCTION: The number of people adhering to plant-based diets has been increasing dramatically in recent years, fueled by both environmental and animal welfare concerns. Beneficial or possible adverse consequences of such diets, particularly the most restrictive forms during pregnancy, have been minimally explored. The aim of this prospective observational study was to examine associations between different forms of plant-based diets during pregnancy with birth outcomes and pregnancy complications. MATERIAL AND METHODS: The Danish National Birth Cohort included 100 413 pregnancies to 91 381 women in 1996-2002. The population consisted of 66 738 pregnancies, about which sufficient dietary data were available and included in the study. Dietary and supplemental intake was assessed by Food Frequency Questionnaire in gestational week 25 and women were characterized as fish/poultry-vegetarians, lacto/ovo-vegetarians, vegans or omnivorous, based on their self-report in gestational week 30. Main outcome measures were pregnancy and birth complications, birthweight and small for gestational age. RESULTS: A total of 98.7% (n = 65 872) of participants were defined as omnivorous, whereas 1.0% (n = 666), 0.3% (n = 183) and 0.03% (n = 18) identified themselves as fish/poultry vegetarians, lacto/ovo-vegetarians or vegans, respectively. Protein intake was lower among lacto/ovo-vegetarians (13.3%) and vegans (10.4%) than among omnivorous participants (15.4%). Intake of micronutrients was also considerably lower among vegans, but when dietary supplements were taken into consideration, no major differences were observed. Compared with omnivorous mothers, vegans had a higher prevalence of preeclampsia and their offspring had on average -240 g (95% confidence interval -450 to -30) lower birthweight. CONCLUSIONS: The women reporting that they adhered to vegan diets during pregnancy had offspring with lower mean birthweight and higher risk of preeclampsia compared with omnivorous mothers. Low protein intake might be one plausible explanation for the observed association with birthweight.

Association of allergies in children younger than 3 years with levels of maternal intake of n-3 polyunsaturated fatty acids or fish during pregnancy: A nationwide birth cohort study, the Japan Environment and Children's Study.

BACKGROUND: N-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and are expected to prevent the onset of allergies. However, epidemiological studies investigating the relationship between child allergies and maternal intake of n-3 PUFAs or fish have yielded inconsistent results. METHODS: Following exclusions from a dataset comprising 103,057 records from the Japan Environment and Children's Study, 72,105 participants were divided into five groups according to mothers' intake of n-3 PUFAs or fish during pregnancy to assess the risk of their children being diagnosed with allergy by 3 years old. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for child allergies were calculated using multivariable logistic regression analyses with reference to the lowest intake group. RESULTS: Levels of maternal intake of n-3 PUFAs or fish showed inverted associations (i.e., reduced risk) with the incidence of physician-diagnosed allergic rhinoconjunctivitis or parent-reported symptoms of current rhinitis with eye symptoms at different time points and the cumulative incidence from birth to 3 years of age. Inverted associations were also found for current wheeze at 1-<2 years of age and current eczema at 1-<2 and 0-<3 years of age. However, for food allergies, no significant associations were observed in the incidence in each group compared with the lowest intake group at any age. CONCLUSIONS: The findings suggest that n-3 PUFA intake during pregnancy may reduce the risk of developing allergic diseases and symptoms in children. In addition, consumption of n-3 PUFAs or fish is very unlikely to increase the risk of allergy given that the results are from a country with high fish consumption. TRIAL REGISTRATION: UMIN000030786 https://rctportal.niph.go.jp/detail/um?trial_id=UMIN000030786.

Interaction of prenatal maternal selenium and manganese levels on child neurodevelopmental trajectories-the Shanghai birth cohort study.

OBJECTIVE: The fetal brain is particularly plastic, and may be concurrently affected by chemical exposure and malnutritional factors. Selenium is essential for the developing brain, and excess manganese exposure may exert neurotoxic effects. However, few epidemiological studies have evaluated the interaction of manganese and selenium assessed in different prenatal stages on postnatal neurodevelopmental trajectories. METHODS: This study contained 1024 mother-child pairs in the Shanghai-birth-cohort study from 2013 to 2016 recruited since early/before pregnancy with complete data on manganese and selenium levels in different prenatal stages and infant neurodevelopmental trajectories. Whole blood manganese and selenium in early pregnancy and around birth were measured by inductively-coupled-plasma-mass-spectrometry (ICP-MS), children's cognitive development was evaluated at 6, 12, and 24 months of age using Age & Stage-Questionnaire (ASQ)-3 and Bayley-III. Multiple linear regression was used to investigate the interaction of prenatal selenium and manganese on neurodevelopmental trajectories. RESULTS: The prenatal manganese and selenium levels were 1.82 ± 0.98 µg/dL and 13.53 ± 2.70 µg/dL for maternal blood in early pregnancy, and 5.06 ± 1.67 µg/dL and 11.81 ± 3.35 µg/dL for umbilical cord blood, respectively. Higher prenatal Se levels were associated with better neurocognitive performances or the consistently-high-level trajectory (P < 0.05), with more significant associations observed in early pregnancy than around birth. However, such positive relationships became non-significant or even adverse in high (vs. low) manganese status, and the effect differences between low and high manganese were more significant in early pregnancy. CONCLUSIONS: Prenatal Selenium was positively associated with child neurodevelopment, but prenatal high manganese may mitigate such favorable effects. The effects were mainly observed in earlier prenatal stage.

Dietary supplements, guideline alignment and biochemical nutrient status in pregnancy: Findings from the Queensland Family Cohort pilot study.

In high-income nations, multiple micronutrient (MMN) supplementation during pregnancy is a common practice. We aimed to describe maternal characteristics associated with supplement use and daily dose of supplemental nutrients consumed in pregnancy, and whether guideline alignment and nutrient status are related to supplement use. The Queensland Family Cohort is a prospective, Australian observational longitudinal study. Maternal characteristics, nutrient intake from food and supplements, and biochemical nutrient status were assessed in the second trimester (n = 127). Supplement use was reported by 89% of participants, of whom 91% reported taking an MMN supplement. Participants who received private obstetric care, had private health insurance and had greater alignment to meat/vegetarian alternatives recommendations were more likely to report MMN supplement use. Private obstetric care and general practitioner shared care were associated with higher daily dose of supplemental nutrients consumed compared with midwifery group practice. There was high reliance on supplements to meet nutrient reference values for folate, iodine and iron, but only plasma folate concentrations were higher in MMN supplement versus nonsupplement users. Exceeding the upper level of intake for folic acid and iron was more likely among combined MMN and individual supplement/s users, and associated with higher plasma concentrations of the respective nutrients. Given the low alignment with food group recommendations and potential risks associated with high MMN supplement use, whole food diets should be emphasized. This study confirms the need to define effective strategies for optimizing nutrient intake in pregnancy, especially among those most vulnerable where MMN supplement use may be appropriate.

Trimester-Specific Urinary Strontium Concentrations during Pregnancy and Longitudinally Assessed Fetal Growth: Findings from a Prospective Cohort.

BACKGROUND: Studies have claimed that strontium (Sr) is associated with fetal growth, but the research evidence is insufficient. OBJECTIVES: Our study aimed to evaluate associations of trimester-specific urinary Sr concentrations with fetal growth parameters and birth size indicators. METHODS: In this prospective cohort, 9015 urine samples (first trimester: 3561, 2nd trimester: 2756, 3rd trimester: 2698) from 3810 mothers were measured for urinary Sr levels using inductively coupled plasma mass spectrometry (ICP-MS) and adjusted to urine specific gravity. We calculated standard deviation scores (SD-scores) for ultrasound-measured fetal growth parameters (head circumference, abdominal circumference, femur length, and estimated fetal weight) at 16, 24, 31, and 37 wk of gestation and birth size indicators (birth weight, birth length, and Ponderal index). Generalized linear models and generalized estimating equations models were used. Models were adjusted for potential covariates (gestational age, maternal age, body mass index, parity, passive smoking during pregnancy, education, folic acid supplements use, physical activity, maternal and paternal height, and infant sex). RESULTS: Positive associations of naturally logarithm-transformed Sr concentrations with fetal growth parameters and birth size indicators were observed. With each doubling increase in the urinary ln-Sr level in all 3 trimesters resulting in a percent change in SD-scores fetal growth parameters at 24, 31, and 37 wk of gestation and birth size indicators, 5.09%-8.23% in femur length, 7.57%-11.53% in estimated fetal weight, 6.56%-10.42% in abdominal circumference, 6.25% in head circumference, 5.15%-7.85% in birth weight, and 5.71%-9.39% in birth length, respectively. Most of the above statistical results could only be observed in male fetuses. CONCLUSIONS: Our findings suggest a potential association between Sr concentration and increased fetal growth, but these results and underlying mechanisms need further confirmation and clarification.

Mitochondrial DNA copy number variation across three generations: a possible biomarker for assessing perinatal outcomes.

BACKGROUND: Mitochondria have their own circular multi-copy genome (mtDNA), and abnormalities in the copy number are implicated in mitochondrial dysfunction, which contributes to a variety of aging-related pathologies. However, not much is known about the genetic correlation of mtDNA copy number across multiple generations and its physiological significance. METHODS: We measured the mtDNA copy number in cord blood or peripheral blood from 149 three-generation families, specifically the newborns, parents, and grandparents, of 149 families, totaling 1041 individuals. All of the biological specimens and information were provided by the Tohoku Medical Megabank Project in Japan. We also analyzed their maternal factors during pregnancy and neonatal outcomes. RESULTS: While the maternal peripheral blood mtDNA copy number was lower than that of other adult family members, it was negatively correlated with cord blood mtDNA copy number in male infants. Also, cord blood mtDNA copy numbers were negatively correlated with perinatal outcomes, such as gestation age, birth weight, and umbilical cord length, for both male and female neonates. Furthermore, the mtDNA copy number in the infants born to mothers who took folic acid supplements during pregnancy would be lower than in the infants born to mothers who did not take them. CONCLUSIONS: This data-driven study offers the most comprehensive view to date on the genetic and physiological significance of mtDNA copy number in cord blood or peripheral blood taken from three generations, totaling more than 1000 individuals. Our findings indicate that mtDNA copy number would be one of the transgenerational biomarkers for assessing perinatal outcomes, as well as that appropriate medical interventions could improve the outcomes via quantitative changes in mtDNA.

Association Between Maternal Factors in Early Pregnancy and Congenital Heart Defects in Offspring: The Japan Environment and Children's Study.

Background Many prenatal factors are reported to be associated with congenital heart defects (CHD) in offspring. However, these associations have not been adequately examined using large-scale birth cohorts. Methods and Results We evaluated a data set of the Japan Environmental and Children's Study. The primary outcome was a diagnosis of CHD by age 2 years. We defined the following variables as exposures: maternal baseline characteristics, fertilization treatment, maternal history of diseases, socioeconomic status, maternal alcohol intake, smoking, tea consumption, maternal dietary intake, and maternal medications and supplements up to 12 weeks of gestation. We used multivariable logistic regression analysis to assess the associations between various exposures and CHD in offspring. A total of 91 664 singletons were included, among which 1264 (1.38%) had CHD. In multivariable analysis, vitamin A supplements (adjusted odds ratio [aOR], 5.78 [95% CI, 2.30-14.51]), maternal use of valproic acid (aOR, 4.86 [95% CI, 1.51-15.64]), maternal use of antihypertensive agents (aOR, 3.80 [95% CI, 1.74-8.29]), maternal age ≥40 years (aOR, 1.59 [95% CI, 1.14-2.20]), and high maternal hemoglobin concentration in the second trimester (aOR, 1.10 per g/dL [95% CI, 1.03-1.17]) were associated with CHD in offspring. Conclusions Using a Japanese large-scale birth cohort study, we found 6 maternal factors to be associated with CHD in offspring.

Peri-Conceptional Folic Acid Supplementation and Children's Physical Development: A Birth Cohort Study.

BACKGROUND: Maternal lack of folic acid supplementation during pregnancy may increase the risk of low birth weight and preterm delivery. However, little is known about the relationship between folic acid supplementation during pregnancy and the physical development of offspring in the later stage. OBJECTIVE: This study aimed to explore the association between maternal folic acid supplementation status during pregnancy and the physical development of preschool children. METHODS: A total of 3064 mother-child pairs with data on maternal folic acid supplementation status during pregnancy and children's anthropometric measurements were recruited from the Ma'anshan-Anhui Birth Cohort (MABC) in China. Maternal folic acid supplementation status during pregnancy was the main exposure, and the primary outcomes were children's growth development trajectories. Children's growth development trajectories were fitted using group-based trajectory models. The association between maternal folic acid supplementation status during pregnancy and children's growth trajectories was performed using multiple logistic regression models. RESULTS: After adjusting for potential confounders, we found that the absence of maternal folic acid supplementation before pregnancy and in the first trimester was significantly associated with a "high level" trajectory (trajectory 3) and a "high rising level" trajectory (trajectory 4) of BMI-Z scores in children 0 to 6 years of age (OR = 1.423, 95%CI:1.022-1.982; OR = 1.654, 95%CI: 1.024-2.671). In children aged 4 to 6 years old, a "high level" trajectory (trajectory 3) of body fat ratio was substantially related to maternal no folic acid supplementation before pregnancy and in the first trimester (OR = 1.833, 95%CI:1.037-3.240). No significant additional benefits associated with physical developmental indicators in preschool children have been observed with continued folic acid supplementation after the first trimester of gestation. CONCLUSIONS: Maternal non-supplementation with folic acid during pregnancy is associated with a "high level" BMI trajectory and a "high level" body fat ratio trajectory in preschool-aged children.

Phototherapy and risk of developmental delay: the Japan Environment and Children's Study.

This observational cohort study aimed to examine the association between the duration of phototherapy for neonatal jaundice and the risk of developmental delay at 3 years of age using nationwide birth cohort data. Data from 76,897 infants were analyzed. We divided participants into four groups: no phototherapy, short phototherapy (1-24 h), long phototherapy (25-48 h), and very long phototherapy (> 48 h). The Japanese version of the Ages and Stages Questionnaire-3 was used to evaluate the risk of developmental delay at 3 years of age. Logistic regression analysis was performed to assess the impact of phototherapy duration on the prevalence of developmental delay. After adjustment for potential risk factors, a dose-response relationship was identified between the duration of phototherapy and Ages and Stages Questionnaire-3, and the differences were significant in four domains; odds ratio for communication delay was associated with short, long, and very long phototherapy = 1.10 (95% confidence interval 0.97-1.26), 1.32 (1.04-2.66), and 1.48 (1.11-1.98), respectively; for gross motor delay = 1.01 (0.89-1.15), 1.28 (1.03-2.58), and 1.26 (0.96-1.67); for problem solving delay = 1.13 (1.03-1.25), 1.19 (0.99-1.43), and 1.41 (1.11-1.79); and for personal social delay = 1.15 (0.99-1.32), 1.10 (0.84-1.44), and 1.84 (1.38-2.45). CONCLUSION: Longer duration of phototherapy is a predictive factor for developmental delay, making it important to avoid extended periods of phototherapy. However, whether it increases the prevalence of developmental delay remains unclear. WHAT IS KNOWN: • Phototherapy is a common treatment for neonatal jaundice, associated with both short-term and long-term complications. • However, an association between phototherapy and the prevalence of developmental delay has not been revealed in a large cohort study. WHAT IS NEW: • We identified that a long duration of phototherapy was a predictive factor for developmental delay at 3 years of age. • However, whether a long duration of phototherapy increases the prevalence of developmental delay remains unclear.

Associations between life-course household wealth mobility and adolescent physical growth, cognitive development and emotional and behavioral problems: A birth cohort in rural western China.

Background: Parental household wealth has been shown to be associated with offspring health conditions, while inconsistent associations were reported among generally healthy population especially in low- and middle- income countries (LMICs). Whether the household wealth upward mobility in LMICs would confer benefits to child health remains unknown. Methods: We conducted a prospective birth cohort of children born to mothers who participated in a randomized trial of antenatal micronutrient supplementation in rural western China. Household wealth were repeatedly assessed at pregnancy, mid-childhood and early adolescence using principal component analysis for household assets and dwelling characteristics. We used conditional gains and group-based trajectory modeling to assess the quantitative changes between two single-time points and relative mobility of household wealth over life-course, respectively. We performed generalized linear regressions to examine the associations of household wealth mobility indicators with adolescent height- (HAZ) and body mass index-for-age and sex z score (BAZ), scores of full-scale intelligent quotient (FSIQ) and emotional and behavioral problems. Results: A total of 1,188 adolescents were followed, among them 59.9% were male with a mean (SD) age of 11.7 (0.9) years old. Per SD conditional increase of household wealth z score from pregnancy to mid-childhood was associated with 0.11 (95% CI 0.04, 0.17) SD higher HAZ and 1.41 (95% CI 0.68, 2.13) points higher FSIQ at early adolescence. Adolescents from the household wealth Upward trajectory had a 0.25 (95% CI 0.03, 0.47) SD higher HAZ and 4.98 (95% CI 2.59, 7.38) points higher FSIQ than those in the Consistently low subgroup. Conclusion: Household wealth upward mobility particularly during early life has benefits on adolescent HAZ and cognitive development, which argues for government policies to implement social welfare programs to mitigate or reduce the consequences of early-life deprivations. Given the importance of household wealth in child health, it is recommended that socioeconomic circumstances should be routinely documented in the healthcare record in LMICs.

Developing and evaluating Birthing on Country services for First Nations Australians: the Building On Our Strengths (BOOSt) prospective mixed methods birth cohort study protocol.

BACKGROUND: With the impact of over two centuries of colonisation in Australia, First Nations families experience a disproportionate burden of adverse pregnancy and birthing outcomes. First Nations mothers are 3-5 times more likely than other mothers to experience maternal mortality; babies are 2-3 times more likely to be born preterm, low birth weight or not to survive their first year. 'Birthing on Country' incorporates a multiplicity of interpretations but conveys a resumption of maternity services in First Nations Communities with Community governance for the best start to life. Redesigned services offer women and families integrated, holistic care, including carer continuity from primary through tertiary services; services coordination and quality care including safe and supportive spaces. The overall aim of Building On Our Strengths (BOOSt) is to facilitate and assess Birthing on Country expansion into two settings - urban and rural; with scale-up to include First Nations-operated birth centres. This study will build on our team's earlier work - a Birthing on Country service established and evaluated in an urban setting, that reported significant perinatal (and organisational) benefits, including a 37% reduction in preterm births, among other improvements. METHODS: Using community-based, participatory action research, we will collaborate to develop, implement and evaluate new Birthing on Country care models. We will conduct a mixed-methods, prospective birth cohort study in two settings, comparing outcomes for women having First Nations babies with historical controls. Our analysis of feasibility, acceptability, clinical and cultural safety, effectiveness and cost, will use data including (i) women's experiences collected through longitudinal surveys (three timepoints) and yarning interviews; (ii) clinical records; (iii) staff and stakeholder views and experiences; (iv) field notes and meeting minutes; and (v) costs data. The study includes a process, impact and outcome evaluation of this complex health services innovation. DISCUSSION: Birthing on Country applies First Nations governance and cultural safety strategies to support optimum maternal, infant, and family health and wellbeing. Women's experiences, perinatal outcomes, costs and other operational implications will be reported for Communities, service providers, policy advisors, and for future scale-up. TRIAL REGISTRATION: Australia & New Zealand Clinical Trial Registry # ACTRN12620000874910 (2 September 2020).

Vitamin D supplementation and lower respiratory tract infection in infants: a nested case-control study.

PURPOSE: To assess the association between vitamin D (VD) supplementation and the risk of lower respiratory tract infection (LRTI) among infants. METHODS: This is a nested case-control study from an ongoing prospective birth cohort in Wuhan from 2013. Cases were subjects free of neonatal pneumonia but later developed LRTI during infancy, who were matched with five randomly selected controls by infant sex, birth year, and birth season. We included 190 cases and 950 controls in the final analysis. The primary outcome was the first LRTI incident and the exposure was VD supplementation from birth to the index endpoint. The association between VD supplementation and LRTI risk was assessed using the Cox proportional-hazards regression model. RESULTS: Infants taking supplements had a 59% relative reduction in the hazard ratio of LRTI (HR = 0.41; 95% CI 0.26, 0.64) compared to those not supplemented. There was a linear relationship between LRTI risk and VD supplementation within range of 0-603 IU/day: for each 100 IU per day increment in VD supplementation, infants experienced a 21% lower risk of developing LRTI (adjusted HR: 0.79; 95% CI 0.71, 0.89). The linear relationship was stably observed in the sensitivity analyses as well. CONCLUSIONS: VD supplementation was associated with the reduced risk of LRTI throughout infancy, and the optimal supplementation dose for infants may be beyond the current recommendation.

Development of sensitization to peanut and storage proteins and relation to markers of airway and systemic inflammation: A 24-year follow-up.

BACKGROUND: Long-time data of peanut allergy over time is sparse. We aimed to study the longitudinal development of sensitization to peanut extract and storage protein allergen molecules and associations with asthma status, airway and systemic inflammation markers. METHODS: The Swedish birth cohort BAMSE followed 4089 participants with questionnaires, clinical investigations and blood sampling between 0 and 24 years. Information on (i) background factors at 2 months, (ii) peanut allergy symptoms and IgE data (ImmunoCAP) at 4, 8, 16, and 24 years, and (iii) IgE to storage proteins, lung function data including exhaled nitric oxide (FENO) as well as systemic inflammatory markers at 24 years of age were collected. RESULTS: The prevalence of peanut extract sensitization, defined as IgE ≥ 0.35 kUA /L, was 5.4%, 8.0%, 7.5%, and 6.2% at 4, 8, 16, and 24 years of age, respectively. Between 8 and 24 years of age, (33/1565) participants developed IgE-ab to peanut extract (median 1,4, range 0.7-2.6 kUA /L), and among those 85% were also sensitized to birch. Only six individuals developed sensitization to Ara h 2 (≥0.1 kUA /L) between 8 and 24 years of age, of whom three had an IgE-ab level between 0.1-0.12 kUA /L. Storage protein sensitization was associated with elevated FENO, blood eosinophils and type 2 inflammation-related systemic proteins. CONCLUSION: Sensitization to peanut extract after 4 years of age is mainly induced by birch cross-sensitization and IgE to Ara h 2 rarely emerges after eight years of age. Storage protein sensitization is associated with respiratory and systemic inflammation.

Association between the Use of Folic Acid Supplements during Pregnancy and Children's Cognitive Function at 7-9 Years of Age in the INMA Cohort Study.

This study investigated the association between maternal low (<400 µg/day) or high (≥1000 µg/day) folic acid supplements (FAs) use during pregnancy and the attentional function and working memory in boys and girls at age 7-9. A longitudinal analysis based on 1609 mother-child pairs from the Spanish Infancia y Medio Ambiente Project was carried out. Multivariable regression analyses revealed that, compared to the recommended FAs use, a low FAs use during the second period of pregnancy was associated with a lower alertness in all children (ß = 18.70 ms; 95% CI: 7.51; 29.89) and in girls (ß = 30.01 ms; 95% CI: 12.96; 47.01), and with a lower N-back Task performance in boys (d' number 2-back (ß = -0.25; 95% CI: -0.49; 0.01)). A high FAs use throughout the two periods of pregnancy was associated with a better N-back Task performance only in girls (d' number 2-back (ß = 0.28; 95% CI: 0.01; 0.56) and d' number 3-back (ß = 0.32; 95% CI: 0.08; 0.56)). The maternal use of FAs beyond the periconceptional period may affect children's attentional function and working memory at age 7-9 differently for boys and girls.

A multipollutant low-grade exposure regulates the expression of miR-30b, Let-7a and miR-223 in maternal sera: Evidence from the NEHO cohort.

There is growing evidence that environmental pollutants can induce epigenetic modifications altering the balance of miRNAs and inducing the onset of pathological conditions in animals. In this study, we measured the serum concentration of a suite of inorganic and organic pollutants (Cu, Zn, Se, Hg, HCB, p,p'-DDE, PCBs) and their association to serum miR-30b, miR-223 and Let-7a microRNA expression in 68 healthy pregnant women from the NEHO birth cohort sited in a highly industrialized area. The effects of the pollutants on the modulation of circulating miRNAs' expression were first investigated using linear continuous regression models with a single-compound approach showing that miR-223 expression was significantly associated with serum concentration of Se and Zn (pSe = 0.0336; pZn = 0.0225) and miR-30b was associated with Hg levels (pHg = 0.019). Furthermore, when contaminants were categorized into tertiles, miR-223 and miR-30b showed a positive association with higher tertiles of Zn, p,p'-DDE (pZn = 0.023; pDDE = 0.041) and Hg (pHg = 0.008), respectively. Moreover, Let-7a expression was exclusively influenced by medium tertiles levels of Se (low vs medium tertiles, p = 0.001). Simultaneous exposure to multi-pollutant mixture was approached by WQS regression model. Statistical analysis shows a driving effect of Zn, Se, Cu, Hg and HCB on significant increased expression of Let-7a (p = 0.045). Mercury and Se significantly amplified the expression for miR-30b (p = 0.038). Differently, the combined effect of p,p'-DDE, Zn and Se decreased miR-223 expression (p = 0.0001). The documented modified expression of circulating miRNAs in the serum of pregnant women, exposed to low-medium dose contaminants mixtures offers innovative early-warning approaches to human health risk assessment.

Prevalence, predictors of low birth weight and its association with maternal iron status using serum ferritin concentration in rural Eastern Ethiopia: a prospective cohort study.

INTRODUCTION: Low birth weight (LBW) is one of the major predictors of perinatal survival, infant morbidity, and mortality, as well as the risk of developmental disabilities and illnesses in future lives. The effect of the nutritional status of pregnant women on birth outcomes is becoming a common research agenda, but evidence on the level of low birth weight (LBW) and its association with prenatal iron status in Ethiopia, particularly among rural residents, is limited. Thus, this study aimed to assess the prevalence, predictors of LBW, and its association with maternal iron status using serum ferritin concentration in Haramaya district, eastern Ethiopia, 2021. METHODS: A community-based prospective cohort study design was conducted. Of a total of 427 eligible pregnant women followed until birth, 412 (96.48%) were included in the final analysis. Iron status was determined using serum ferritin (SF) concentration from venous blood collected aseptically from the ante-cubital veins analyzed on a fully automated Cobas e411 (German, Japan Cobas 4000 analyzer series) immunoassay analyzer. Iron deficiency(ID) and iron deficiency anemia (IDA) were classified as having SF less than 15 µg/L and SF less than 15 µg/L and Hb level of < 11.0 g/dl during the first or third trimester or < 10.5 g/dl during the second trimester as well, respectively. Birthweight was measured within 72 h of birth and < 2500 g was considered LBW. Birthweight was measured within 72 h of birth and < 2500 g was considered as LBW. A Poisson regression model with robust variance estimation was used to investigate the factors associated with LBW and the association between maternal iron status and LBW. An adjusted prevalence ratio with a 95% confidence interval was reported to show an association using a p-value < 0.05. RESULTS: About 20.2% (95% CI: 16%-24%) of neonates were born with LBW. The prevalence of LBW was 5.04 (95% CI = 2.78-9.14) times higher among women who were iron deficient during pregnancy compared to those who were normal. The neonates of women who were iron deficient during pregnancy had lower birth weight (aPR=5.04; 95% CI = 2.78-9.14) than the neonates of women who were normal. Prevalence of LBW was higher among mothers who were undernourished (MUAC < 23cm) (aPR = 1.92; 95% CI= 1.33-2.27), stunted (height <145cm) (aPR=1.54; 95% CI=1.04-2.27) and among female neonates (aPR=3.70; 95% CI= 2.28-6.00). However, women who were supplemented with iron and folic acid (IFAS) during pregnancy had a 45% decreased chance of delivering low birth weight (aPR= 0.55; 95% CI=0.36-0.84). CONCLUSION: We found that LBW is of public health significance in this predominantly rural setting. ID during pregnancy is found to have a negative effect on birth weight. IFA supplementation, the maternal under-nutrition, height, and sex of neonates were identified as predictors of low weight at birth. To improve maternal nutritional status, health interventions must address targeted strategies promoting desirable food behavior and nutritional practices. These include; promoting the consumption of diversified and rich iron food to improve the maternal nutritional status. A continued effort is needed in enhancing universal access and compliance with IFA supplementation to improve maternal health. Intervention strategies that are complementary and comprehensive across the vulnerable periods for women during pregnancy and their neonates that are based on a life-cycle approach are suggested.

Maternal DHA-rich n-3 PUFAs supplementation interacts with FADS genotypes to influence the profiles of PUFAs in the colostrum among Chinese Han population: a birth cohort study.

BACKGROUND: The single nucleotide polymorphisms (SNPs) in the fatty acid desaturases and elongases might associate with the endogenous synthesis of polyunsaturated fatty acids (PUFAs). However, the related epidemiological evidence is still conflicting. So we aimed to clearly evaluate the interactions between maternal DHA-rich n-3 PUFAs supplementation and the known 26 SNPs on the profiles of PUFAs in the colostrum using a Chinese birth cohort. METHODS: Totally, 1050 healthy mother-infant pairs were enrolled in this study at gestational 6-8 weeks when they established their pregnancy files at Fuxing Hospital affiliated to Capital Medical University in Beijing from January to December 2018. Meanwhile, their venous blood samples were obtained for DNA extraction to detect the genotypes of SNPs in the Fads1, Fads2, Fads3, Elovl2 and Elovl5 using the Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry. Then the colostrum samples were collected to determine the profiles of PUFAs by gas chromatography. RESULTS: Maternal DHA-rich n-3 PUFAs supplementation from the early and middle pregnancy could reduce the infant BMI at birth, and impact the profiles of PUFAs in the colostrum, as higher n-3 PUFAs (EPA, DHA, DHA/ALA and DHA/EPA), lower n-6 PUFAs (AA and AA/LA) and ∑-6/n-3ΣPUFAs. Moreover, there were significant correlations between multiple SNPs and the profiles of n-6 PUFAs (rs76996928 for LA, rs174550, rs174553 and rs174609 for AA, rs174550 and rs76996928 for AA/LA) and n-3 PUFAs in the colostrum (rs174448, rs174537, rs174550, rs174553, rs174598, rs3168072, rs174455 and rs174464 for ALA, rs174550, rs174553 and rs174598 for EPA, rs174455 and rs174464 for DHA, rs174448 and rs3168072 for DHA/EPA) using the multiple linear regressions by adjusting the maternal age, gestational week, mode of delivery, infant sex and BMI at birth, and all these above significant SNPs had the cumulative effects on the profiles of PUFAs. Furthermore, the pairwise comparisons also showed the meaningful interactions between maternal DHA-rich n-3 PUFAs supplementation and related genotypes of SNPs (rs76996928 for LA, rs174598 for EPA, rs174448 for DHA and DHA/EPA) on the contents of PUFAs in the colostrum. CONCLUSIONS: Results from this birth cohort study proved that the pregnant women with the following SNPs such as Fads3 rs174455 T, Fads3 rs174464 A and Fads1 rs174448 G alleles should pay more attention on their exogenous DHA supplementation from the early and middle pregnancy for the blocked endogenous synthesis. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Beijing Pediatric Research Institution, Beijing Children's Hospital affiliated to Capital Medical University (2016-08), which was also registered at the website of http://www.chictr.org.cn/showproj.aspx?proj=4673 (No: ChiCTR-OCH-14004900).

How Parental Predictors Jointly Affect the Risk of Offspring Congenital Heart Disease: A Nationwide Multicenter Study Based on the China Birth Cohort.

Objective: Congenital heart disease (CHD) is complex in its etiology. Its genetic causes have been investigated, whereas the non-genetic factor related studies are still limited. We aimed to identify dominant parental predictors and develop a predictive model and nomogram for the risk of offspring CHD. Methods: This was a retrospective study from November 2017 to December 2021 covering 44,578 participants, of which those from 4 hospitals in eastern China were assigned to the development cohort and those from 5 hospitals in central and western China were used as the external validation cohort. Univariable and multivariable analyses were used to select the dominant predictors of CHD among demographic characteristics, lifestyle behaviors, environmental pollution, maternal disease history, and the current pregnancy information. Multivariable logistic regression analysis was used to construct the model and nomogram using the selected predictors. The predictive model and the nomogram were both validated internally and externally. A web-based nomogram was developed to predict patient-specific probability for CHD. Results: Dominant risk factors for offspring CHD included increased maternal age [odds ratio (OR): 1.14, 95% CI: 1.10-1.19], increased paternal age (1.05, 95% CI: 1.02-1.09), maternal secondhand smoke exposure (2.89, 95% CI: 2.22-3.76), paternal drinking (1.41, 95% CI: 1.08-1.84), maternal pre-pregnancy diabetes (3.39, 95% CI: 1.95-5.87), maternal fever (3.35, 95% CI: 2.49-4.50), assisted reproductive technology (2.89, 95% CI: 2.13-3.94), and environmental pollution (1.61, 95% CI: 1.18-2.20). A higher household annual income (100,000-400,000 CNY: 0.47, 95% CI: 0.34-0.63; > 400,000 CNY: 0.23, 95% CI: 0.15-0.36), higher maternal education level (13-16 years: 0.68, 95% CI: 0.50-0.93; ≥ 17 years: 0.87, 95% CI: 0.55-1.37), maternal folic acid (0.21, 95% CI: 0.16-0.27), and multivitamin supplementation (0.33, 95% CI: 0.26-0.42) were protective factors. The nomogram showed good discrimination in both internal [area under the receiver-operating-characteristic curve (AUC): 0.843] and external validations (development cohort AUC: 0.849, external validation cohort AUC: 0.837). The calibration curves showed good agreement between the nomogram-predicted probability and actual presence of CHD. Conclusion: We revealed dominant parental predictors and presented a web-based nomogram for the risk of offspring CHD, which could be utilized as an effective tool for quantifying the individual risk of CHD and promptly identifying high-risk population.