BACKGROUND:Vitamin D status during prenatal brain development may influence risk of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood. However, there are no prospective ...studies addressing this hypothesis. We aimed to examine whether maternal vitamin D status in pregnancy is associated with risk of ADHD-like symptoms in offspring.
METHODS:We conducted a prospective study analyzing data from 1,650 mother–child pairs from five birth cohorts embedded in the INMA Project (Spain, 1997–2008). Maternal vitamin D status in pregnancy was estimated by measuring plasma concentration of 25-hydroxyvitamin D3 25(OH)D3 at 13 weeks of gestation. Children were assessed by teachers for ADHD-like symptoms at ages 4–5 years using the Diagnostic and Statistical Manual of Mental Disorders ADHD form list.
RESULTS:After adjustment, the number of total ADHD-like symptoms in children decreased by 11% per 10 ng/ml increment of maternal 25(OH)D3 concentration (incidence rate ratio IRR = 0.89; 95% confidence interval CI = 0.80, 0.98). Similarly, the number of symptoms in the ADHD subscales decreased in relation to higher maternal 25(OH)D3 concentration (IRR per 10 ng/ml increment = 0.89; 95% CI = 0.79, 0.99 for the inattention scale; and IRR = 0.88; 95% CI = 0.78, 0.99 for the hyperactivity–impulsivity scale). Using diagnostic criteria, we found an association of increasing maternal 25(OH)D3 with a lower risk of ADHD DSM-IV (relative risk ratio per 10 ng/ml increment = 0.87; 95% CI = 0.72, 1.06) and ICD-10 hyperkinetic disorder (relative risk ratio = 0.72; 95% CI = 0.49, 1.04) in children.
CONCLUSION:Higher maternal circulating levels of 25(OH)D3 in pregnancy are associated with lower risk of developing ADHD-like symptoms in childhood.
To investigate whether circulating 25-hydroxyvitamin D(3) 25(OH)D(3) concentration in pregnancy is associated with neuropsychological development in infants.
The Spanish population-based cohort study ...INfancia y Medio Ambiente Project recruited pregnant women during the first trimester of pregnancy between November 2003 and February 2008. Completed data on 1820 mother-infant pairs were used. Maternal plasma 25(OH)D(3) concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.5 ± 2.1 weeks of gestation). Offspring mental and psychomotor scores were assessed by trained psychologists at age 14 months (range, 11-23) by using the Bayley Scales of Infant Development. β-Coefficients with 95% confidence intervals (CIs) of mental and psychomotor scores associated with continuous or categorical concentrations of maternal plasma 25(OH)D(3) were calculated by using linear regression analysis.
The median plasma value of 25(OH)D(3) in pregnancy was 29.6 ng/mL (interquartile range, 21.8-37.3). A positive linear relationship was found between circulating concentrations of maternal 25(OH)D(3) concentrations in pregnancy and mental and psychomotor scores in the offspring. After adjustment for potential confounders, infants of mothers with 25(OH)D(3) concentrations in pregnancy >30 ng/mL showed higher mental score (β = 2.60; 95% CI 0.63-4.56) and higher psychomotor score (β = 2.32; 95% CI 0.36-4.28) in comparison with those of mothers with 25(OH)D(3) concentrations <20 ng/mL.
Higher circulating concentration of maternal 25(OH)D(3) in pregnancy was associated with improved mental and psychomotor development in infants.
BACKGROUND: Maternal diet has been associated with fetal growth outcomes; however, evidence is scarce on the role of dietary quality. OBJECTIVE: The objective was to assess the effect of diet quality ...during the first trimester of pregnancy, as measured by the Alternate Healthy Eating Index (AHEI) adapted for pregnancy, on fetal growth. DESIGN: We studied 787 women and their newborns from a Spanish cohort study. Diet quality was assessed by using a modification of the AHEI. Adjusted birth weight, birth length, and head circumference were used as continuous outcomes. We used a customized model to define fetal growth restriction in weight, length, and head circumference. RESULTS: After adjustment of multivariate models, a positive association was observed between diet quality and adjusted birth weight and adjusted birth length. The greatest differences were found between the fourth and first quintiles of the AHEI. Newborns of women in the fourth quintile were on average 126.3 g (95% CI: 38.5, 213.9 g) heavier and 0.47 cm (95% CI: 0.08, 0.86 cm) longer than those in the lowest quintile (P for trend = 0.009 and 0.013, respectively). Women with the highest AHEI scores had a significantly lower risk of delivering a fetal growth-restricted infant for weight (odds ratio: 0.24; 95% CI: 0.10, 0.55; P for trend = 0.001) than did women in the lowest quintile, but this was not the case for fetal growth restriction in length (P for trend = 0.538) or head circumference (P for trend = 0.070). CONCLUSION: A high-quality diet in the first trimester of pregnancy is associated with birth size and the risk of fetal growth restriction.
Acetaminophen is extensively used during pregnancy. But there is a lack of population-representative cohort studies evaluating its effects on a range of neuropsychological and behavioural endpoints. ...We aimed to assess whether prenatal exposure to acetaminophen is adversely associated with neurodevelopmental outcomes at 1 and 5 years of age.
This Spanish birth cohort study included 2644 mother-child pairs recruited during pregnancy. The proportion of liveborn participants evaluated at 1 and 5 years was 88.8% and 79.9%, respectively. Use of acetaminophen was evaluated prospectively in two structured interviews. Ever/never use and frequency of use (never, sporadic, persistent) were measured. Main neurodevelopment outcomes were assessed using Childhood Autism Spectrum Test (CAST), Conner's Kiddie Continuous Performance Test (K-CPT) and ADHD-DSM-IV form list. Regression models were adjusted for social determinants and co-morbidities.
Over 40% of mothers reported using acetaminophen. Ever-exposed offspring had higher risks of presenting more hyperactivity/impulsivity symptoms incidence rate ratio (IRR) = 1.41, 95% confidence interval (CI) 1.01-1.98), K-CPT commission errors (IRR = 1.10, 1.03-1.17), and lower detectability scores (coefficient β = -0.75, -0.13--0.02). CAST scores were increased in ever-exposed males (β = 0.63, 0.09-1.18). Increased effect sizes of risks by frequency of use were observed for hyperactivity/impulsivity symptoms (IRR = 2.01, 0.95-4.24) in all children, K-CPT commission errors (IRR = 1.32, 1.05-1.66) and detectability (β = -0.18, -0.36-0.00) in females, and CAST scores in males (β = 1.91, 0.44-3.38).
Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders. These associations seem to be dependent on the frequency of exposure.
Maternal pre-pregnancy obesity may be associated with impaired infant neuropsychological development; however, there are few studies and it is unclear if reported associations are due to intrauterine ...mechanisms.
We assessed whether maternal pre-pregnancy overweight and obesity were associated with cognitive and psychomotor development scores (mean 100 ± 15) of children aged 11-22 months in two birth cohorts: Environment and Childhood (INMA, Spain; n = 1967) and Mother-Child (RHEA, Greece: n = 412). Paternal body mass index (BMI) was used as a negative control exposure.
The percentage of overweight and obese mothers was 18% and 8%, respectively, in INMA and 20% and 11% in RHEA, respectively. Maternal pre-pregnancy obesity was associated with reduced infant cognitive development scores in both INMA (score reduction: -2.72; 95% CI: -5.35, -0.10) and RHEA (score reduction: -3.71; 95% CI: -8.45, 1.02), after adjusting for socioeconomic variables and paternal BMI. There was evidence in both cohorts of a dose-response relationship with continuous maternal BMI. Paternal overweight/obesity was not associated with infant cognitive development. Associations with psychomotor scores were not consistent between cohorts, and were stronger for paternal than maternal BMI in RHEA.
This study in two birth cohorts with moderately high obesity prevalence suggests that maternal pre-pregnancy obesity is associated with reduced child cognitive development at early ages. This association appears more likely to be due to maternal than shared family and social mechanisms, but further research is needed to disentangle a direct intrauterine effect from other maternal confounding factors.
The association between the use of vitamin K antagonists (VKAs) and cancer risk reduction remains unclear. We aimed to assess the association between the use of VKAs or direct oral anticoagulants ...(DOACs) and the incidence of cancer in a large cohort of patients with atrial fibrillation (AF) by means of a population‐based, propensity‐weighted cohort study using population‐wide databases including patients diagnosed with nonvalvular AF (NVAF) followed for up of 5 years (median 2.94 years). We created two cohorts based on the initiation therapy (VKA or DOAC). Initiation with VKA or DOAC was defined as filling a prescription with no previous exposure in the preceding 12 months. Cancer diagnoses of any type and for specific tumors (lung, colon, prostate, bladder, and breast). We included 39,989 patients, 31,200 (78.0%) in the VKA cohort. Incidence rate for any cancer was 12.45 per 1,000 person‐year in the DOAC cohort vs. 14.55 in the VKA cohort (adjusted hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.02–1.32). In secondary outcomes, no differences were found for specific types of cancer, such as lung (HR: 1.28, CI: 0.89–1.83), colon (HR: 0.84, CI: 0.62–1.13), prostate (HR: 1.40, CI: 0.94–2.10), bladder (HR: 1.07, CI: 0.76–1.52), and breast (HR: 1.05, CI: 0.66–1.69). Sensitivity analyses yielded similar results. Subgroup analyses also produced consistent findings, except for men, for whom VKA was associated with a lower risk of colon cancer (HR: 0.68, 95% CI: 0.48–0.96). Our results do not confirm a chemoprotective effect of VKA when compared with DOAC in a large, real‐world cohort of patients with NVAF followed for up to 5 years.
Aims
Acenocoumarol is a vitamin‐K antagonist (VKA) primarily used in certain countries (e.g. India, Netherlands, Spain). The half‐life of acenocoumarol is similar to that of non‐VKA oral ...anticoagulants (NOAC), unlike warfarin, and this could affect comparative effectiveness and safety (CES). However, data on CES for NOAC come almost exclusively from studies using warfarin as the comparator. We aimed to assess outcomes of NOAC and acenocoumarol in people with non‐valvular atrial fibrillation (NVAF) in real‐world clinical practice.
Methods
This is a population‐based retrospective cohort study. All new users of oral anticoagulants from November 2011 to December 2015 with NVAF were included (n = 41,560). Data were obtained by linking several health electronic records of the Valencia region, Spain. Incidence rates were estimated. We used the inverse probability of treatment weighted Cox analysis to control for indication bias when assessing the risk of effectiveness and safety outcomes for each NOAC compared with acenocoumarol. Several sensitivity analyses were performed.
Results
We did not find differences in the risk of mortality, ischaemic stroke or any gastrointestinal bleeding. However, we did find a decreased risk of intracranial haemorrhage for dabigatran (HR: 0.34, 95% CI 0.20–0.56) and rivaroxaban (HR: 0.55, 95% CI 0.35–0.85) as compared to acenocoumarol. In subanalyses, apixaban showed a higher risk of ischaemic stroke in high‐risk persons (≥75 years and CHA2DS2‐VASC score ≥ 2).
Conclusions
No differences in clinical outcomes were found between NOAC and acenocoumarol overall, although dabigatran and rivaroxaban showed a lower risk of intracranial haemorrhage. Findings on the potential inferiority of specific NOAC in high‐risk subgroups should be studied further.
The prevalence of obesity body mass index (BMI) ≥30 kg/m2 is high among African American women, with most weight gain occurring before middle age. We assessed diet quality, as measured by the ...Alternate Healthy Eating Index-2010 (AHEI-2010) and the Dietary Approaches to Stop Hypertension (DASH) diet score in relation to incident obesity in the Black Women's Health Study. Prospective data were collected via biennial questionnaires from 1995 to 2011. AHEI-2010 and DASH scores were calculated from food-frequency questionnaire data collected in 1995 and 2001. We restricted the analysis to 19,885 nonobese women aged 21-39 y at baseline. Multivariable Cox regression was used to estimate HRs and 95% CIs. Among women with consistent diet scores in 1995 and 2001, higher diet quality scores were inversely associated with obesity incidence: the multivariable HRs comparing highest with lowest quintiles of the AHEI-2010 and DASH scores were 0.76 (95% CI: 0.58, 0.98) and 0.68 (95% CI: 0.53, 0.88), respectively, among women with a BMI in the normal range (18.5-24.9 kg/m2) at baseline. There were no significant associations among women who were overweight at baseline. The findings suggest that a high-quality diet that is sustained over time is associated with reduced obesity risk among young African American women with a normal BMI at baseline.
Despite the continuous update of clinical guidelines, little is known about the real-world management of patients with atrial fibrillation (AF) who survived a stroke. We aimed to assess patterns of ...therapeutic management of stroke survivors with AF and clinical outcomes using data from routine practice in a large population-based cohort.
A population-based retrospective cohort study of all patients with AF who survived a stroke, from January 2010 to December 2017 in the Valencia region, Spain (
= 10,986), was carried out. Treatment strategies and mean time to treatment initiation are described. Temporal trends are shown by the management pattern during the study period. Factors associated with each pattern (including no treatment) vs. oral anticoagulant (OAC) treatment were identified using logistic multivariate regression models. Incidence rates of clinical outcomes (mortality, stroke/TIA, GI bleeding, and ACS) were also estimated by the management pattern.
Among stroke survivors with AF, 6% were non-treated, 23% were prescribed antiplatelets (APT), 54% were prescribed OAC, and 17% received OAC + APT at discharge. Time to treatment was 8.0 days (CI 7.6-8.4) for APT, 9.86 (CI 9.52-10.19) for OAC, and 16.47 (CI 15.86-17.09) for OAC + APT. Regarding temporal trends, management with OAC increased by 20%, with a decrease of 50% for APT during the study period. No treatment and OAC + APT remained relatively stable. The strongest predictor of no treatment and APT treatment was having the same management strategy pre-stroke. Those treated with APT had the highest rates of GI bleeding and recurrent stroke/TIA, and untreated patients showed the highest rates of mortality.
In this large population-based cohort using real-world data, nearly 30% of AF patients who suffered a stroke were untreated or treated with APT, which overall is not recommended. Treatment was started within 2 weeks as recommended, except for OAC + APT, which was started later. The strong association of APT treatment or non-treatment with the same treatment strategy before stroke occurrence suggests a strong therapeutic inertia and opposes recommendations. Patients under these two strategies had the highest rates of adverse outcomes. An inadequate prescription poses a great risk on patients with AF and stroke; thus monitoring their management is necessary and should be setting-specific.
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