Gestational vitamin D deficiency and autism-related traits: the Generation R Study.

There is intense interest in identifying modifiable risk factors associated with autism-spectrum disorders (ASD). Autism-related traits, which can be assessed in a continuous fashion, share risk factors with ASD, and thus can serve as informative phenotypes in population-based cohort studies. Based on the growing body of research linking gestational vitamin D deficiency with altered brain development, this common exposure is a candidate modifiable risk factor for ASD and autism-related traits. The association between gestational vitamin D deficiency and a continuous measure of autism-related traits at ~6 years (Social Responsiveness Scale; SRS) was determined in a large population-based cohort of mothers and their children (n=4229). 25-hydroxyvitamin D (25OHD) was assessed from maternal mid-gestation sera and from neonatal sera (collected from cord blood). Vitamin D deficiency was defined as 25OHD concentrations less than 25 nmol l-1. Compared with the 25OHD sufficient group (25OHD>50 nmol l-1), those who were 25OHD deficient had significantly higher (more abnormal) SRS scores (mid-gestation n=2866, ß=0.06, P<0.001; cord blood n=1712, ß=0.03, P=0.01). The findings persisted (a) when we restricted the models to offspring with European ancestry, (b) when we adjusted for sample structure using genetic data, (c) when 25OHD was entered as a continuous measure in the models and (d) when we corrected for the effect of season of blood sampling. Gestational vitamin D deficiency was associated with autism-related traits in a large population-based sample. Because gestational vitamin D deficiency is readily preventable with safe, cheap and accessible supplements, this candidate risk factor warrants closer scrutiny.

Maternal anthropometrics are associated with fetal size in different periods of pregnancy and at birth. The Generation R Study.

OBJECTIVE: We aimed to examine the associations of maternal anthropometrics with fetal weight measured in different periods of pregnancy and with birth outcomes. DESIGN: Population-based birth cohort study. SETTING: Data of pregnant women and their children in Rotterdam, the Netherlands. POPULATION: In 8541 mothers, height, prepregnancy body mass index (BMI) and gestational weight gain were available. METHODS: Fetal growth was measured by ultrasound in mid- and late pregnancy. Regression analyses were used to assess the impact of maternal anthropometrics on fetal weight and birth outcomes. MAIN OUTCOME MEASURES: Fetal weight and birth outcomes: weight (grams) and the risks of small (<5th percentile) and large (>95th percentile) size for gestational age at birth. RESULTS: Maternal BMI in pregnancy was positively associated with estimated fetal weight during pregnancy. The effect estimates increased with advancing gestational age. All maternal anthropometrics were positively associated with fetal size (P-values for trend <0.01). Mothers with both their prepregnancy BMI and gestational weight gain quartile in the lowest and highest quartiles showed the highest risks of having a small and large size for gestational age child at birth, respectively. The effect of prepregnancy BMI was strongly modified by gestational weight gain. CONCLUSIONS: Fetal growth is positively affected by maternal BMI during pregnancy. Maternal height, prepregnancy BMI and gestational weight gain are all associated with increased risks of small and large size for gestational age at birth in the offspring, with an increased effect when combined.

Improved control of oral anticoagulant dosing: a randomized controlled trial comparing two computer algorithms.

BACKGROUND: Efforts to improve dosing quality in oral anticoagulant control include the use of computer algorithms. As current algorithms are simplistic and give dosage proposals in a small fraction of patients, we developed an algorithm based on principles of system and control engineering that gives proposals in nearly all patients. OBJECTIVE: To evaluate the new algorithm in clinical practice. PATIENTS AND METHODS: We conducted a double-blind randomized controlled trial among 712 patients with an indication for long-term anticoagulant treatment at the Leiden Anticoagulation Clinic. We compared oral anticoagulant dosing supported by the new algorithm (ICAD) with the standard algorithm (TRODIS). RESULTS: The percentage of time spent in the therapeutic range was similar for the new and standard algorithm groups, 79.8% vs. 80.2% (difference 0.4%, 95% CI: -1.7-2.6%). The new algorithm produced a dosage proposal in 97.5% of visits, and the standard algorithm in 60.8% (difference 36.7%, 95% CI: 35.4-38.0%). Of proposals of the new algorithm, 79.3% were accepted by the physician vs. 90.9% for the standard algorithm (difference 11.6%, 95% CI: 10.2-13.0%). This implies that the new algorithm gave an acceptable proposal in 77.4% of all patient visits vs. 55.3% for the standard algorithm (difference 22.1%, 95% CI 20.4-23.8%). CONCLUSIONS: Substantially more dosage proposals were generated and accepted with the new than with the standard algorithm, and the new algorithm will therefore improve the efficiency of anticoagulant monitoring without loss of quality.

Infant weight growth velocity patterns and general and abdominal adiposity in school-age children. The Generation R Study.

BACKGROUND/OBJECTIVES: The objective of this study was to examine the association of individually derived infant weight growth velocity patterns with general and abdominal adiposity measures in childhood. SUBJECTS/METHODS: In a population-based prospective cohort study among 5126 children, we used repeated growth measurements between 0 and 3 years of age to derive peak weight velocity (PWV), age at adiposity peak (AGEAP) and body mass index at adiposity peak (BMIAP). At the median age of 6.0 years (95% range 5.7, 6.8), we estimated body mass index (BMI), body fat percentage, android/gynoid fat mass ratio and pre-peritoneal abdominal fat area by using dual-energy X-ray absorptiometry and abdominal ultrasound. RESULTS: Higher infant PWV and BMIAP were associated with higher childhood BMI, body fat percentage, android/gynoid fat mass ratio and pre-peritoneal abdominal fat area (all P-values<0.05), with the strongest effect estimates for BMI (differences in BMI: 0.37 standard deviation (s.d.), 95% confidence interval (CI): 0.34, 0.39 and 0.45 s.d. (95% CI: 0.43, 0.48) per 1-s.d. increase in infant PWV and BMIAP, respectively). Infant AGEAP in the highest tertile (>0.75 years) was associated with higher general and abdominal adiposity among girls at the age of 6 years (all P-values<0.05). Similarly, a 1-s.d. higher infant PWV and BMIAP were associated with increased risks of childhood overweight (odds ratios (95% CI): 2.1 (1.9, 2.3) and 2.5 (2.2, 2.8), respectively). These associations were independent of gestational age and size at birth and tended to be stronger among girls. CONCLUSIONS: Higher infant PWV and BMIAP are associated with adverse general and abdominal fat distribution profiles and increased risks of overweight at school age. Whether infant growth patterns add to the prediction of later overweight should be further studied.

A model-based algorithm for the monitoring of long-term anticoagulation therapy.

It has been shown that computerized algorithms for the prescription of coumarin derivates can improve the quality of long-term anticoagulation treatment. These algorithms are usually based on an empiric relationship between dosage and International Normalized Ratio and do not quantify the delaying effect of the drug's pharmacokinetics or the effect of alternating doses that are used to approximate a certain average dosage. Our objective was to develop a mathematical model that takes into account these effects and to develop a new algorithm based on this model that can be used to further optimize the quality of long-term anticoagulation treatment. We simplified a general model structure that was proposed by Holford in 1986 so that the parameters can be estimated using data that are available during long-term anticoagulation treatment. The constant parameters in the model were estimated separately for phenprocoumon and acenocoumarol using data from 1279 treatment courses from three different anticoagulation clinics in the Netherlands. The only variable parameter in the model is the sensitivity of the patient, which is estimated during the course of each treatment. A total of 194 dosage and appointment intervals that were proposed by the new algorithm were scored as 'good', 'acceptable', or 'bad' by two dosing experts. One hundred and seventy-eight (91.8%) proposals were considered good by at least one expert and bad by none. In 39 cases the experts disagreed. We believe that this algorithm will allow further improvement of anticoagulation treatments.