Clara L. Rodríguez-Bernal

Circulating 25-Hydroxyvitamin D3 in Pregnancy and Infant Neuropsychological Development

OBJECTIVE: To investigate whether circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration in pregnancy is associated with neuropsychological development in infants. METHODS: 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)D3 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)D3 were calculated by using linear regression analysis. RESULTS: The median plasma value of 25(OH)D3 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)D3 concentrations in pregnancy and mental and psychomotor scores in the offspring. After adjustment for potential confounders, infants of mothers with 25(OH)D3 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)D3 concentrations <20 ng/mL. CONCLUSIONS: Higher circulating concentration of maternal 25(OH)D3 in pregnancy was associated with improved mental and psychomotor development in infants.

Diet quality in early pregnancy and its effects on fetal growth outcomes: the Infancia y Medio Ambiente (Childhood and Environment) Mother and Child Cohort Study in Spain

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.

Maternal pre-pregnancy overweight and obesity, and child neuropsychological development: two Southern European birth cohort studies

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Associations of maternal circulating 25‐hydroxyvitamin D3 concentration with pregnancy and birth outcomes

To investigate the association of maternal circulating 25‐hydroxyvitamin D3 [25(OH)D3] concentration with pregnancy and birth outcomes.

Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms

Background 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. Methods 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), Conners Kiddie Continuous Performance Test (K-CPT) and ADHD-DSM-IV form list. Regression models were adjusted for social determinants and co-morbidities. Results 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). Conclusions 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.

Vitamin D in Pregnancy and Attention Deficit Hyperactivity Disorder-like Symptoms in Childhood.

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.

Dietary intake in pregnant women in a Spanish Mediterranean area: as good as it is supposed to be?

OBJECTIVE To assess food and nutrient intakes and compliance with nutritional recommendations in pregnant women according to selected sociodemographic characteristics. DESIGN Cross-sectional study based on data from the INMA-Valencia cohort (Spain), which recruited pregnant women between 2004 and 2005. Information on maternal sociodemographics and anthropometry was collected. Dietary intake was assessed through an FFQ. Intakes of foods were compared with Spanish food-based dietary guidelines. Intake inadequacy for nutrients was assessed using the Dietary Reference Intakes of the US Institute of Medicine. SETTING Valencia, Spain. SUBJECTS We studied 822 pregnant women who had information on dietary intake during their first trimester of pregnancy. RESULTS More than 50% of pregnant women did not meet the guidelines for cereals and legumes; reported intakes of carbohydrates, n-3 and n-6 fatty acids were below recommendations and exceeded the total fat intake according to dietary references. Dietary inadequacy for folate, Fe and vitamin E ranged from 99% to 68%. Vegetable intake was related to age only. Younger and less educated women showed lower intakes of protein and n-3 fatty acids and higher intakes of trans-fatty acids as well as greater inadequacy for micronutrients. Spanish women reported lower intakes of fruit and carbohydrates and higher intakes of protein, total fat, SFA, MUFA and n-3 fatty acids compared with their foreign-born counterparts. CONCLUSIONS Women in the studied area have inadequate intakes of several nutrients relevant during pregnancy. Age, education and country of origin are factors significantly related to dietary intake and adequacy.

Long-Term Diet Quality Is Associated with Lower Obesity Risk in Young African American Women with Normal BMI at Baseline

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 Womens 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.

Oral Anticoagulants Initiation in Patients with Atrial Fibrillation: Real-World Data from a Population-Based Cohort

Objective: Little is known about initial prescription of currently used oral anticoagulants (OAC), and correlated characteristics in real-world practice. We aimed to assess patterns of initiation of Vitamin K antagonists (VKA) and non-VKA oral anticoagulants (NOAC) in naive patients with non-valvular atrial fibrillation and the factors associated with starting treatment with NOAC. Methods: Population-based retrospective cohort study of all patients with NVAF who had a first prescription of OAC from November 2011 to February 2014 in the Valencia region, Spain (n = 21,881). Temporal trends of OAC initiation are described for the whole population and by type of OAC and therapeutic agent. Factors associated with starting treatment with NOAC (vs. VKA) were identified using logistic multivariate regression models. Results: Among the patients initiating OAC, 25% started with NOAC 2 years after market release. Regarding temporal trends, prescription of NOAC doubled during the study period. VKA prescription also increased (by around 13%), resulting in a 30% rise in total treatment initiation with OAC during 2011–2014. NOAC initiation (vs. VKA) was associated with a lower baseline risk of thromboembolism and higher income. Conclusions: In this Spanish population-based cohort, initiation of OAC therapy saw a rapid increase, mainly but not exclusively, due to a two-fold rise in the use of NOAC. Initiation with NOAC was associated with a lower baseline risk of thromboembolism and higher income, which opposes the indications of NOAC use and reflects disparities in care. Inadequate prescription patterns might threaten the effectiveness and safety of these therapies, thus monitoring OAC prescription is necessary and should be setting-specific.

Overuse and Underuse of Antiosteoporotic Treatments According to Highly Influential Osteoporosis Guidelines: A Population-Based Cross-Sectional Study in Spain

Inappropriate prescribing of antiosteoporotic medications has been observed; however, the joint study of both overuse and underuse has barely been attempted. Spain, with its high utilization rates, constitutes a good example to assess differences in over and under use according to diverse highly-influential osteoporosis guidelines (HIOG) worldwide. We used data of a population-based cross-sectional study including 824 post-menopausal women ≥50 years old living in the city of Valencia, Spain and aimed to estimate the percentage of women eligible for treatment, and the proportion of overuse and underuse of antiosteoporotic treatment according to HIOG. The prevalence of antiosteoporotic treatment in postmenopausal women ≥ 50 in Valencia was 20.9% (95%CI:17.6–24.4). The type of antiosteoporotic drugs prescribed varied greatly depending on the medical specialty responsible of the initial prescription. When applying the HIOG, the percentage of women 50 and over who should be treated varied from less than 9% to over 44%. In real terms, from the approximately eight million women of 50 years old and over in Spain, the number eligible for treatment would range from 0.7 to 3.8 million, depending on the guideline used. A huge proportion of inappropriate treatments was found when applying these guidelines to the Spanish population, combining a high overuse (42–78% depending on the guideline used) and underuse (7–41%). In conclusion, we found that the pharmacological management of osteoporosis in women of 50 and over in this population combines an important overuse and, to a lesser extent, underuse, although the level of inappropriateness varied strikingly depending on the CPG used. It seems urgent to reduce treatment overuse without neglecting underuse, as is urgent an attempt to reach wider agreement worldwide regarding osteoporosis management, in order to facilitate appropriate treatment and development of policies to reduce effectively treatment inappropriateness.