Biologic therapies committee. What does it provide?

OBJECTIVE: To assess the general healthcare impact of a Biological  Therapies Commitee (immune-mediated inflammatory diseases) through  prescription habits, pre-biological studies and immunization. METHOD: A quasi-experimental study was conducted on all naïve patients  of legal age who started treatment with a biological agent for an immune- mediated inflammatory disease the year before and the year after the  creation of the Biological Therapies Committee. RESULTS: A total of 31 patients treated in 2016 and 40 patients treated in 2018 were included. Prescriptions of tumor necrosis factor alpha  inhibitor drugs decreased in 2018 (from 80.6% to 45.0%, p < 0.05), while prescriptions of interleukin 12/23 inhibitors increased (from 12.9% to  35.0%, p < 0.05). Tuberculosis screening was statistically different  between the two periods: the number of interferon gamma release assays  performed was higher in 2018 (from 9.7% to 80.0%, p < 0.01) and the  proportion of patients who successfully underwent chemoprophylaxis was  higher in 2018 (from 36.4% to 81.8%, p < 0.05). The proportion of tests  requested for the study of viral pathologies and the number of vaccines  administered were also higher in 2018. CONCLUSIONS: The development of a specific Biological Therapies  Committee allows healthcare improvements, contributing to a deeper  understanding of the medications and to preventing the infection-related  adverse events. It would therefore seem advisable to develop specialized  committees akin to the Biological Therapies Committee in other domains.

Objetivo: Evaluar el impacto general a nivel asistencial de una comisión  de terapias biológicas, en enfermedades inflamatorias inmunomediadas,  mediante los hábitos de prescripción, los estudios prebiológicos y la  inmunización.Método: Se realizó un estudio cuasiexperimental sobre todos los  pacientes naïve mayores de edad que iniciaron tratamiento con un  medicamento biológico por enfermedad inflamatoria inmunomediada el  año anterior y el año posterior a la creación de la comisión de terapias  biológicas.Resultados: Se incluyeron un total de 31 pacientes estudiados en 2016 y  40 pacientes estudiados en 2018. La prescripción de medicamentos inhibidores del factor de necrosis tumoral α se redujo en  2018 (80,6% versus 45,0%; p < 0,05), mientras que la prescripción de  inhibidores de la interleucina 12/23 aumentó (12,9% versus 35,0%; p <  0,05). El cribaje tuberculoso fue estadísticamente diferente entre los  periodos pre y postcomisión de terapias biológicas: la realización del  interferon gamma release assay fue superior en 2018 (9,7% versus  80,0%, p < 0,01) y la proporción de pacientes que realizaron  correctamente la quimioprofilaxis fue superior en 2018 (36,4% versus  81,8%, p < 0,05). La proporción de pruebas solicitadas para estudio de  patologías víricas, así como la administración de vacunas, fueron  superiores en 2018.Conclusiones: El desarrollo de una comisión específica de terapias biológicas aporta mejoras asistenciales en enfermedades  inflamatorias inmunomediadas, al contribuir a un mayor conocimiento  relacionado con los medicamentos y con la prevención de los efectos  adversos de carácter infeccioso, por lo que sería conveniente que se  impulsara el desarrollo de comisiones especializadas como la comisión de  terapias biológicas.

The Effectiveness of Different Doses of Iron Supplementation and the Prenatal Determinants of Maternal Iron Status in Pregnant Spanish Women: ECLIPSES Study.

Iron deficiency (ID), anemia, iron deficiency anemia (IDA) and excess iron (hemoconcentration) harm maternal-fetal health. We evaluated the effectiveness of different doses of iron supplementation adjusted for the initial levels of hemoglobin (Hb) on maternal iron status and described some associated prenatal determinants. The ECLIPSES study included 791 women, randomized into two groups: Stratum 1 (Hb = 110-130g/L, received 40 or 80mg iron daily) and Stratum 2 (Hb > 130g/L, received 20 or 40mg iron daily). Clinical, biochemical, and genetic information was collected during pregnancy, as were lifestyle and sociodemographic characteristics. In Stratum 1, using 80 mg/d instead of 40 mg/d protected against ID on week 36. Only women with ID on week 12 benefited from the protection against anemia and IDA by increasing Hb levels. In Stratum 2, using 20 mg/d instead of 40 mg/d reduced the risk of hemoconcentration in women with initial serum ferritin (SF) ≥ 15 µg/L, while 40 mg/d improved SF levels on week 36 in women with ID in early pregnancy. Mutations in the HFE gene increased the risk of hemoconcentration. Iron supplementation should be adjusted to early pregnancy levels of Hb and iron stores. Mutations of the HFE gene should be evaluated in women with high Hb levels in early pregnancy.

Does the fortified milk with high iron dose improve the neurodevelopment of healthy infants? Randomized controlled trial.

BACKGROUND: Since iron plays an important role in several physiological processes, its deficiency but also overload may harm the development of children. The aim was to assess the effect of iron-fortified milk on the iron biochemical status and the neurodevelopment of children at 12 months of age. METHODS: Randomized controlled trial conducted in 133 Spanish children, allocated in two groups to receive formula milk fortified with 1.2 or 0.4 mg/100 mL of iron between 6 and 12 months of age. Psychomotor (PDI) and Mental (MDI) Development Index were assessed by the Bayley Scales before and after the intervention. Maternal obstetrical and psychosocial variables were recorded. The biochemical iron status of children was measured and data about breastfeeding, anthropometry and infections during the first year of life were registered. RESULTS: Children fortified with 1.2 mg/100 mL of iron, compared with 0.4 mg/100 mL, showed higher serum ferritin (21.5 vs 19.1 µg/L) and lower percentage of both iron deficiency (1.1 to 5.9% vs 3.8 to 16.7%, respectively, from 6 to 12 months) and iron deficiency anemia (4.3 to 1.1% vs 0 to 4.2%, respectively, from 6 to 12 months) at the end of the intervention. No significant differences were found on neurodevelopment from 6 to 12 months between children who received high dose of Fe compared with those who received low dose. CONCLUSION: Despite differences on the iron status were observed, there were no effects on neurodevelopment of well-nourished children in a developed country after iron supplementation with doses within dietary recommendations. Follow-up studies are needed to test for long-term neurodevelopmental improvement. TRIAL REGISTRATION: Retrospectively registered in ClinicalTrials.gov with the ID: NCT02690675.

Excess nutritional risk in infants and toddlers in a Spanish city.

Adequate dietary intake is vital for infants' growth and development. The aim was to analyse food consumption and energy and nutrient intakes in a group of healthy Spanish infants and toddlers. Cross-sectional study. 154 infants were assessed at 6 months, and followed at 12 and 30 months. Clinical history, anthropometry, type of feeding, food consumption and energy and nutrient intakes (24-hours recall) were estimated. Advice about food consumed, estimated average requirements, the prevalence of inadequate intakes and percentage of adequacy of the recommended dietary allowance were applied. Toddlers had an excessive daily consumption of meat (>51.3g/day), milk (>545g/day), fish (>20.8g/day) and free-sugar foods (>30.5g/day). This consumption was related to a very high intake of proteins (>18%) and free sugars (>10%), at 12 and 30 months, as a percentage of daily energy intake. The mean prevalence of inadequacy intakes was above 48% for iron at 6 months, and 68% and 87% for vitamin D at 12 and 30 months, respectively. At 6 months, infants who were breastfed had greater adequacy in energy and nutrients to recommended dietary, while infants fed infant formula had a higher intake (>120% compared with RDA) in vitamins E, C, B1, B2, pantothenic acid, B6, B12 and folic acid. The contribution of micronutrients in infant formula should be reviewed, appropriate protein and free sugars should be provided during complementary feeding, as well as strategies to avoid vitamin D deficiency since childhood; and continue with the promotion of breastfeeding.

Serum hepcidin levels, iron status, and HFE gene alterations during the first year of life in healthy Spanish infants.

The aims of this study were to describe hepcidin levels and to assess their associations with iron status and the main variants in the HFE gene in healthy and full-term newborns during the first year of life, as a longitudinal study conducted on 140 infants. Anthropometric and biochemical parameters, hepcidin, hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), mean corpuscular volume (MCV), and C-reactive protein (CRP), were assessed in 6- and 12-month-olds. Infants were genotyped for the three main HFE variants: C282Y, H63D, and S65C. Hepcidin levels increased from 6 to 12 months of age (43.7 ± 1.5 to 52.0 ± 1.5 ng/mL; p < 0.001), showing higher levels in infants with better iron status compared to those with iron deficiency (ID) (44.8 ± 1.5 vs 37.9 ± 1.3 ng/mL, p < 0.018, and 54.3 ± 1.5 vs 44.0 ± 1.4 ng/mL, p < 0.038, in 6- and 12-month-olds, respectively). In multivariate linear regression models, iron status was found to be associated with hepcidin levels in infants with wild-type HFE gene (p = 0.046 and p = 0.048 in 6- and 12-month-olds, respectively). However, this association was not found in HFE-alteration-carrying infants. Hepcidin levels increased in healthy infants during the first year of life and were positively associated with iron levels only in infants with wild-type HFE gene, a situation that requires further investigation.

Haemoconcentration risk at the end of pregnancy: effects on neonatal behaviour.

OBJECTIVE: To determine the associations between haemoconcentration at the end of pregnancy (third trimester and delivery) and neonatal behaviour in healthy pregnant women supplemented with moderate doses of Fe. DESIGN: A prospective longitudinal study in which obstetric and clinical history, maternal toxic habits, maternal anxiety and Hb levels were recorded at the third trimester and delivery. Neonatal behaviour was assessed at 48-72 h of age using the Neonatal Behavioral Assessment Scale. SETTING: Unit of Obstetrics and Gynaecology of the Sant Joan University Hospital in Reus, Tarragona (Spain). SUBJECTS: A total of 210 healthy and well-nourished pregnant women and their full-term, normal-weight newborns. RESULTS: The results showed that, after adjusting for confounders, in the third trimester the risk of haemoconcentration (6·2 % of pregnant women) was related to decreased neonatal state regulation (B=-1·273, P=0·006) and alertness (B=-1·848, P=0·006) scores. In addition, the risk of haemoconcentration at delivery (12·0 % of pregnant women) was also related to decreased neonatal state regulation (B=-0·796, P=0·021) and poor robustness and endurance (B=-0·921, P=0·005) scores. CONCLUSIONS: Our results show that the risk of haemoconcentration at the end of pregnancy is related to the neonate's neurodevelopment (and self-regulation capabilities), suggesting that Fe supplementation patterns and maternal Fe status during pregnancy are important factors for neurodevelopment which may be carefully controlled.

Adapting iron dose supplementation in pregnancy for greater effectiveness on mother and child health: protocol of the ECLIPSES randomized clinical trial.

BACKGROUND: Currently, there is no consensus regarding iron supplementation dose that is most beneficial for maternal and offspring health during gestation. Recommended iron supplementation dose does not preempt anemia in around 20% of the pregnancies, nor the risk of hemoconcentration in 15%. This deficit, or excess, of iron prejudices the mother-child wellbeing. Therefore the aims of the study are to determine the highest level of effectiveness of iron supplementation adapted to hemoglobin (Hb) levels in early pregnancy, which would be optimum for mother-child health. DESIGN: Randomized Clinical Trial (RCT) triple-blindedSetting: 10 Primary Care Centers from Catalunya (Spain)Study subjects: 878 non-anemic pregnant women at early gestation stage, and their subsequent newborns METHODS: The study is structured as a RCT with 2 strata, depending on the Hb levels before week 12 of gestation. Stratum #1: If Hb from 110 to 130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 80 mg/d. Stratum #2: If Hb >130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 20 mg/d. MEASUREMENTS: In the mother: socio-economic data, clinical history, food item frequency, lifestyle and emotional state, and adherence to iron supplement prescription. Biochemical measurements include: Hb, serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene (C282Y, H63D). In children: ultrasound fetal biometry, anthropometric measurements, and temperament development.Statistical analyses, using the SPSS program for Windows, will include bivariate and multivariate analyses adjusted for variables associated with the relationship under study. DISCUSSION: Should conclusive outcomes be reached, the study would indicate the optimal iron supplementation dose required to promote maternal and infant health. These results would contribute towards developing guidelines for good clinical practice.

Prevalence of iron deficiency states and risk of haemoconcentration during pregnancy according to initial iron stores and iron supplementation.

OBJECTIVE: To describe the prevalence of iron depletion (ID), iron-deficiency anaemia (IDA) and risk of haemoconcentration during pregnancy and at delivery and to assess the influence of initial Fe stores and Fe supplementation on that prevalence. DESIGN: Longitudinal study. SETTING: Hospital Universitari Sant Joan de Reus (Catalonia, Spain). SUBJECTS: Two hundred and eighty-five pregnant women. Serum ferritin and Hb were measured in the first, second and third trimesters and at delivery. Women were classified according to initial Fe stores as ID or no ID (serum ferritin $12mg/l) and according to Fe supplement use as supplemented or nonsupplemented. RESULTS: Initial ID was 16.2%. At delivery, 45.7% had ID, 13.5% IDA and 13.3% had risk of haemoconcentration. Initial ID and non-supplemented groups had significantly higher prevalences of ID and IDA and lower risk of haemoconcentration at delivery than the other groups. In the multiple logistic models, no initial ID and Fe supplementation exerted a protective effect against ID at delivery (adjusted OR50.28; 95% CI 0.13, 0.58 and adjusted OR50.39; 95% CI 0.22, 0.69, respectively). Moderate Fe supplementation did not seem to clearly prevent IDA (adjusted OR50.91; 95% CI 0.42, 1.96) or to enhance the haemoconcentration (adjusted OR51.42; 95% CI 0.58, 3.50). CONCLUSIONS: The prevalence of ID and IDA was high in late pregnancy in healthy pregnant women, particularly in those with initial ID and/or those not taking supplements. Starting pregnancy with no ID and/or taking moderate Fe supplementation decreased the likelihood of ID at delivery. The risk of haemoconcentration was high at delivery, but did not seem to be promoted by Fe supplementation. Further research is necessary to determine the most appropriate nutritional advice for pregnant women.

Effect of different doses of iron supplementation during pregnancy on maternal and infant health.

Currently, there is no consensus regarding the optimum iron supplementation during pregnancy. The aim of this study is to evaluate the effect of different iron supplementation doses (including no supplementation) during pregnancy on the iron status of the mother and on the health of the neonate. A longitudinal study was conducted involving 358 pregnant women and their newborns. Mothers were classified as non-supplemented, low iron supplemented (<60 mg/day), moderate iron supplemented (between 60 and 100 mg/day) or high iron supplemented (>100 mg/day). General clinical and obstetric histories, haemoglobin (Hb), serum ferritin (SF) and transferrin saturation were evaluated in the first, second, third trimesters, and at partum. SF and Hb decreased less sharply in the iron-supplemented groups compared to the non-supplemented group. The higher the doses of iron supplementation, the lower the percentages of iron depletion at partum (p < 0.001), iron deficiency anaemia (p < 0.001) and preterm deliveries (p = 0.009) as well as a higher birth weight of the newborn. However, the group with high supplementation had a greater percentage (27.6 %) of women at risk of haemoconcentration at partum. Our Mediterranean women began gestation with iron stores close to deficit (SF, 28.1 µg/L; 95 % CI 27.9-28.4). With these iron stores, supplementation with iron at daily doses of between 60 and 100 mg appears to be the most beneficial for the health of mother and child. These findings need to be confirmed in further randomised clinical trials.

Efectividad de la pauta de suplementación con hierro recomendada en España a embarazadas sin anemia al inicio de la gestación / Effectivity of the iron supplementation pattern recommended in Spain for pregnant women without anemia at the beginning of pregnancy

Fundamentos: Las autoridades sanitarias españolas aconsejan suplementar con 30 mg/día de hierro de forma temprana a las embarazadas no anémicas. Nuestro objetivo es analizar el porcentaje de éxito en la prevención del déficit de hierro al final del embarazo con la pauta de suplementación recomendada por el Ministerio de Sanidad y Consumo. Métodos: Estudio longitudinal realizado en 120 embarazadas sin anemia inicial, suplementadas con hierro (20-40 mg/día). Se valora: historia clínica y obstétrica. Durante los tres trimestres y parto se determinan: Hemoglobina, Ferritina sérica, Saturación de transferrina. Resultados: El estado en hierro evoluciona negativamente durante la gestación, recuperándose ligeramente al final del embarazo. El 17,9% de las embarazadas inicia la gestación sin reservas de hierro. En el momento del parto, un 53,4% presentó las reservas de hierro exhaustas y un 16,2%, anemia ferropénica. Conclusiones: La pauta de suplementación con hierro aconsejada en España a las mujeres embarazadas sin anemia inicial, no previene los estados carenciales en hierro al final de la gestación en un porcentaje elevado de mujeres de nuestra población. Son necesarias más evidencias que contribuyan a definir la pauta de suplementación con hierro más efectiva para prevenir la anemia en la mujer embarazada (AU)

Background: Health authorities in Spain recommended supplementing the initially non-anemic pregnant women with 30 mg of iron per day from early gestation. The aim of the study was to analyze the rate of success in preventing iron deficiency in late pregnancy with the supplementation pattern recommended by the Spanish Ministery of Health. Methods: Longitudinal study conducted in 120 pregnant women without initial anemia and taking iron supplementation (20-40 mg/day). Clinical and obstetric histories were collected. Blood haemoglobin, serum ferritin and transferrin saturation were measured in each trimester and at delivery. Results: Iron status decreases during pregnancy and recovers slightly in late pregnancy. A 17.9% of pregnant women start pregnancy without iron stores. At the time of delivery, 53.4% had exhausted iron stores and 16.2% presented iron deficiency anemia. Conclusions: The iron supplementation pattern recommended in Spain to pregnant women without initial anemia does not prevent iron-deficiency states at the end of gestation in a high percentage of women in our population. More evidence is needed to help to define the more effective pattern of iron supplementation in order to prevent anemia in pregnant women (AU)

Pre-pregnancy iron reserves, iron supplementation during pregnancy, and birth weight.

BACKGROUND: Early iron supplementation in women with sufficient reserves could provoke iron excess resulting in haemoconcentration and low infant birth weight (IBW). AIM: To clarify the influence of early iron supplementation on maternal iron status and the IBW, taking into account pre-pregnancy iron deposits. STUDY DESIGN: Longitudinal, prospective study. SUBJECTS: Healthy women volunteers (n=82) intending to become pregnant. OUTCOME MEASURES: Women were grouped as a function of their pre-pregnancy (low or present) iron stores (serum ferritin (SF)

Effects of iron deficiency on neonatal behavior at different stages of pregnancy.

Animal and human studies have shown that prenatal and postnatal iron deficiency is a risk factor for behavioral, emotional and cognitive development. The aim of this study was to determine the associations between iron status of pregnant women and the behavior of their newborn, taking into account the timing in which the deficit occurs. This study was conducted in Spain (developed country) where: the general population is well-nourished; during pregnancy routine obstetrical checks are carried out; and pregnant women are systematically iron supplemented. A total of 216 healthy and well-nourished pregnant women and their term, normal weight newborn participated in this study. The neonatal behavior was assessed by the Neonatal Behavior Assessment Scale (NBAS). The results showed that in the first and second trimesters of pregnancy, iron deficiency was a weak and significant predictor of the NBAS autonomous nervous system cluster score, and in the third trimester, this condition predicted the NBAS motor and state organization clusters score and the NBAS robustness and endurance supplementary item. In conclusion, iron deficiency during pregnancy is related to the neonate's general autonomous response, motor performance and self regulation capabilities.