Early-life intake of major trace elements, bisphenol A, tetrabromobisphenol A and fatty acids: Comparing human milk and commercial infant formulas.

In the present study, the presence of a wide spectrum of major and trace elements (As, Ag, Al, Ba, Cd, Co, Cr, Cu, Hg, Mn, Ni, Sr, Sb, Se, Sn, Pb, V, and Zn), fatty acids, as well as some pollutants like free and total BPA and tetrabromobisphenol A (TBBPA), was analysed in human milk (n = 53) and infant formula (n = 50) samples. In addition, the infant exposure to these chemicals was assessed. The content of free BPA and several elements (Al, Ca, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Sn, Sr, and Zn) was higher (p < 0.01) in infant formula samples. Furthermore, human milk contained levels of BPA and elements that, in almost all cases, were well below their respective EFSA and/or WHO thresholds, being also independent of the maternal characteristics (e.g., age, BMI or breastfeeding period). The fatty acid profiling also revealed major differences between human milk and infant formulas, which should be taken in account in the development of new formulas as well as in specific recommendations for the diet of breastfeeding mothers. Anyway, the results of this study reinforce that breastfeeding should be always the first feeding option in early life.

Bacteriological, biochemical, and immunological properties of colostrum and mature milk from mothers of extremely preterm infants.

OBJECTIVES: The objective of this work was to elucidate the influence of extremely premature birth (gestational age 24-27 weeks) on the microbiological, biochemical, and immunological composition of colostrum and mature milk. METHODS: A total of 17 colostrum and 34 mature milk samples were provided by the 22 mothers of extremely preterms who participated in this study. Bacterial diversity was assessed by culture-based methods, whereas the concentration of lactose, glucose, and myo-inositol was determined by a gas chromatography procedure. Finally, the concentrations of a wide spectrum of cytokines, chemokines, growth factors, and immunoglobulins were measured using a multiplex system. RESULTS: Bacteria were present in a small percentage of the colostrum and milk samples. Staphylococci, streptococci, and lactobacilli were the main bacterial groups isolated from colostrum, and they could be also isolated, together with enterococci and enterobacteria, from some mature milk samples. The colostrum concentrations of lactose and glucose were significantly lower than those found in mature milk, whereas the contrary was observed in relation to myo-inositol. The concentrations of most cytokines and immunoglobulins in colostrum were higher than in mature milk, and the differences were significant for immunoglobulin G3, immunoglobulin G4, interleukin (IL)-6, interferon-γ, interleukin-4 (IL-4), IL-13, IL-17, macrophage-monocyte chemoattractant protein-1 and macrophage inflammatory protein-1ß. CONCLUSIONS: The bacteriological, biochemical, and immunological content of colostrum and mature milk from mothers of extremely preterm infants is particularly valuable for such infants. Efforts have to be made to try that preterm neonates receive milk from their own mothers or from donors matching, as much as possible, the gestational age of the preterm.

Psychomotor development of children from an iodine-deficient region.

OBJECTIVES: To assess the psychomotor development of the progeny of women from a moderately iodine-deficient area for whom thyroid function during pregnancy was measured. STUDY DESIGN: The development of 86 children was assessed by the Bayley Scale of Infant Development at 12, 18, and 24 months. RESULTS: Maternal serum free thyroxine (FT(4)) levels in the first trimester of pregnancy were the major determinant of psychomotor development at 18 and 24 months. Children born from mothers with FT(4) levels <25th percentile (<10 pg/mL) had an OR of 2.1 for mild-to-severe delay. Furthermore, alterations in behavior were already observed at 12 months and were related to subsequent changes in development. Neonatal thyroid status did not influence development. CONCLUSIONS: This study highlights the need to implement active measures of iodine supplementation periconceptionally and during pregnancy and lactation because the negative effects on development and behavior might be prevented through preemptive action.

Neurodevelopment of preterm infants born at 28 to 36 weeks of gestational age: the role of hypothyroxinemia and long-term outcome at 4 years.

CONTEXT: Hypothyroxinemia in premature neonates may affect long-term neurodevelopment. OBJECTIVE: This study aimed to examine the effects of hypothyroxinemia of the newborn preterm infants born at 28-36 weeks of gestational age (GA) on the neurodevelopment at 4 years of age. PATIENTS: Prospective observational cohort study conducted in Madrid, Spain. Forty-six preterm infants were included in the study. MAIN OUTCOME: The effects of the exposure to neonatal hypothyroxinemia on mental development were examined. RESULTS: Using regression analyses we found that neonatal T4 had a positive association with general cognitive index and Verbal index, and neonatal FT4 with general cognitive and Memory indexes at 4 years of age. CONCLUSIONS: The exposure to hypothyroxinemia during the neonatal period of late preterm infants may play role in neurodevelopmental delays. Higher T4 level means a trend to higher indexes and low T4 level means a lower neurodevelopmental indexes at 4 years of age.

Dietary Habits and Relationship with the Presence of Main and Trace Elements, Bisphenol A, Tetrabromobisphenol A, and the Lipid, Microbiological and Immunological Profiles of Breast Milk.

Breastfeeding is the best way to feed an infant, although it can also be a source of abiotic contaminants such as heavy metals or bisphenol A (BPA). The early life exposure to these compounds can lead to serious toxic effects in both the short and long-term. These substances can reach breast milk through the mother's habits, diet being one of the main routes of exposure. The aim of the present work was to analyse possible associations between the dietary habits of women and the content of major trace elements, BPA, fatty acids and lipids, and the microbiological and immunological profiles of human milk. Possible associations between major trace elements and BPA and the lipid, microbiological and immunological profiles were also analysed. The results of this study support that the microbiological composition of human milk is associated with the dietary habits of the women, and that the consumption of canned drinks is related to the presence of BPA in human milk. Furthermore, some relationships were found between the amount of major trace elements and the microbiological and immunological profile of the milk samples. Finally, the presence of BPA was associated with changes in the immunological profile of human milk.

Iodine nutrition status in Spain Needs for the future. / La nutrición de yodo en España. Necesidades para el futuro.

Although iodine nutrition in Spain has improved in recent years, the problem is not completely resolved. It is necessary that health institutions establish measures to ensure an adequate iodine nutrition of the population, especially among the highest risk groups (children and adolescents, women of childbearing age, pregnant women and nursing mothers). A low salt intake should be advised, but it should be iodized. It is also imperative that food control agencies establish effective control over adequate iodization of salt. Indicators on iodine nutrition should be included in future health surveys. The EUthyroid study and the Krakow Declaration on iodine nutrition provide an opportunity to set up a pan-European plan for the prevention of iodine deficiency that should be considered and used by health authorities.

Neonatal thyroxine supplementation for transient hypothyroxinemia of prematurity : beneficial or detrimental?

Extremely low birth-weight newborns (<1000g) experience low levels of thyroid hormone that vary inversely with the severity of neonatal illness and the extent of developmental immaturity with levels reaching a nadir at approximate, equals7 days after birth; this phenomenon can persist for several weeks. In the absence of transplacental passage, 30-50% of these neonates cannot generate sufficient quantities of thyroid hormone to meet postnatal demands, placing them at an increased risk for developmental delay and cerebral palsy. Population surveys and interventional trials suggest that a therapeutic opening exists during a 'window of opportunity' corresponding to this period of diminished capacity. Variables to consider before intervention focus on the consideration that supplementation of both the substrate thyroxine and the active hormone triiodothyronine may be necessary in quantities that do not suppress thyroid-stimulating hormone release, yet overcome the persistence of increased conversion to 3,3'5'-triodo-L-thyronine, terminal deiodination, and activity of the sulfation inactivation pathways, as well as the diminished capacity of the newborn to accommodate postnatal physiologic changes. Single daily replacement doses may suppress levels of converting enzymes in the brain, suggesting that physiologic 'mimicry' provided by a constant infusion may be the preferred dosing option. Properly powered clinical trials targeting long-term developmental outcomes are needed to discern whether these interventions will do more than simply elevate blood levels of thyroid hormones to the target values of either the fetus or developing neonate. Identifying the appropriate indications for supplementation may alleviate individual pain and distress due to disability for several hundred extremely low birth-weight neonates each year in the US alone, and save society a pro-rated lifetime cost of nearly $US1 million per child.

[Motivations and perceived barriers to initiate or sustain breast- feeding among Spanish women]. / Motivaciones y barreras percibidas por las mujeres Españolas en relación a la lactancia materna.

OBJECTIVE: Breastfeeding for its multiple benefits is the best cost-effective health intervention and should be a public health priority. The aim of this study was to determine motivations and barriers perceived by mothers to initiate or to maintain breastfeeding. METHODS: A cross-sectional, observational study was carried in 2013 out among 569 mothers resident in Spain, with children under the age of 2, who completed a structured questionnaire. A two-stage sampling, stratified by Autonomous Communities and non-probabilistic within each community was used. RESULTS: 88% of the mothers were breastfeeding their children or had breastfed. At the time of the survey 66.6% had stopped breastfeeding, and the average age for weaning was 6.4 (SD 3.8) months. The main reason for stopping breastfeeding was maternal perceptions of insufficient milk supply (29%). The second reason was going back to work (18%). 67% of the mothers said that they made the decision to breastfeed on their own. The main disadvantages reported were: the difficulty to reconcile breastfeeding and work (43%), breastfeeding in public places (39%), more frequent nighttime awakenings (62%) and the reduced weight gain of the baby (29%). Going back to work was the main reason for choosing formula feeding (34%) and also for initiating partial breastfeeding (39%). CONCLUSIONS: The main disadvantages reported were: the difficulty to reconcile breastfeeding and work, breastfeeding in public places, more frequent nighttime awakenings and the reduced weight gain of the baby. Going back to work was the main reason for choosing formula feeding and also for initiating partial breastfeeding.

OBJETIVO: La lactancia materna (LM) por sus múltiples beneficios es la mejor intervención coste-efectiva en salud y debería constituir un objetivo prioritario de salud pública. El objetivo de este estudio fue conocer las motivaciones y barreras percibidas por las madres para iniciar o mantener la LM. METODOS: Estudio observacional transversal con 569 madres residentes en España en 2013, con hijos menores de 2 años que cumplimentaron un cuestionario estructurado. Muestreo bietápico, estratificado por comunidades autónomas y no probabilístico en cada comunidad. RESULTADOS: El 88% de las madres daban LM o lo habían hecho. La edad media del destete fue 6.4 (DE 3.8) meses. El principal motivo para suspender la lactancia fue la sensación de baja producción de leche (29%) seguido de la incorporación al trabajo (18%). El 67% de las madres indicaron que la decisión de amamantar la habían tomado ellas mismas. La dificultad para combinar la LM con la actividad laboral (43%), dar el pecho en lugares públicos (39%), los despertares nocturnos (62%) y el menor aumento de peso del lactante (29%) fueron los inconvenientes más referidos. La incorporación laboral fue el principal motivo para elegir la lactancia artificial (34%) y para iniciar la lactancia parcial (39%). CONCLUSIONES: La dificultad para combinar la LM con la actividad laboral, dar el pecho en lugares públicos, los despertares nocturnos y la menor ganancia de peso del lactante fueron los inconvenientes más referidos. La incorporación laboral fue el principal motivo para elegir la lactancia artificial y para iniciar la lactancia parcial.

[Motivations and Perceived Barriers to Initiate or Sustain Breastfeeding among Spanish Women]. / Motivaciones y barreras percibidas por las mujeres españolas en relación a la lactancia materna.

OBJECTIVE: Breastfeeding for its multiple benefits is the best cost-effective health intervention and should be a public health priority. The aim of this study was to determine motivations and barriers perceived by mothers to initiate or to maintain breastfeeding. METHODS: A cross-sectional, observational study was carried in 2013 out among 569 mothers resident in Spain, with children under the age of 2, who completed a structured questionnaire. A two-stage sampling, stratified by Autonomous Communities and non-probabilistic within each community was used. RESULTS: 88% of the mothers were breastfeeding their children or had breastfed. At the time of the survey 66.6% had stopped breastfeeding, and the average age for weaning was 6.4 (SD 3.8) months. The main reason for stopping breastfeeding was maternal perceptions of insufficient milk supply (29%). The second reason was going back to work (18%). 67% of the mothers said that they made the decision to breastfeed on their own. The main disadvantages reported were: the difficulty to reconcile breastfeeding and work (43%), breastfeeding in public places (39%), more frequent nighttime awakenings (62%) and the reduced weight gain of the baby (29%). Going back to work was the main reason for choosing formula feeding (34%) and also for initiating partial breastfeeding (39%). CONCLUSIONS: The main disadvantages reported were: the difficulty to reconcile breastfeeding and work, breastfeeding in public places, more frequent nighttime awakenings and the reduced weight gain of the baby. Going back to work was the main reason for choosing formula feeding and also for initiating partial breastfeeding.

OBJETIVO: La lactancia materna (LM) por sus múltiples beneficios es la mejor intervención coste-efectiva en salud y debería constituir un objetivo prioritario de salud pública. El objetivo de este estudio fue conocer las motivaciones y barreras percibidas por las madres para iniciar o mantener la LM. METODOS: Estudio observacional transversal con 569 madres residentes en España en 2013, con hijos menores de 2 años que cumplimentaron un cuestionario estructurado. Muestreo bietápico, estratificado por comunidades autónomas y no probabilístico en cada comunidad. RESULTADOS: El 88% de las madres daban LM o lo habían hecho. La edad media del destete fue 6.4 (DE 3.8) meses. El principal motivo para suspender la lactancia fue la sensación de baja producción de leche (29%) seguido de la incorporación al trabajo (18%). El 67% de las madres indicaron que la decisión de amamantar la habían tomado ellas mismas. La dificultad para combinar la LM con la actividad laboral (43%), dar el pecho en lugares públicos (39%), los despertares nocturnos (62%) y el menor aumento de peso del lactante (29%) fueron los inconvenientes más referidos. La incorporación laboral fue el principal motivo para elegir la lactancia artificial (34%) y para iniciar la lactancia parcial (39%). CONCLUSIONES: La dificultad para combinar la LM con la actividad laboral, dar el pecho en lugares públicos, los despertares nocturnos y la menor ganancia de peso del lactante fueron los inconvenientes más referidos. La incorporación laboral fue el principal motivo para elegir la lactancia artificial y para iniciar la lactancia parcial.

Thyroid Function among Breastfed Children with Chronically Excessive Iodine Intakes.

Iodine excess may impair thyroid function and trigger adverse health consequences for children. This study aims to describe iodine status among breastfed infants with high iodine exposure in the Saharawi refugee camps Algeria, and further assess thyroid function and iodine status among the children three years later. In 2010, a cross-sectional study among 111 breastfed children aged 0-6 months was performed (baseline study). In 2013, a second cross-sectional study (follow-up study) was conducted among 289 children; 213 newly selected and 76 children retrieved from baseline. Urinary iodine concentration (UIC) and breast milk iodine concentration (BMIC) were measured at baseline. UIC, thyroid hormones and serum thyroglobulin (Tg) were measured at follow-up. At baseline and follow-up, 88% and 72% had excessive iodine intakes (UIC ≥ 300 µg/L), respectively. At follow-up, 24% had a thyroid hormone disturbance and/or elevated serum Tg, including 9% with subclinical hypothyroidism (SCH), 4% with elevated fT3 and 14% with elevated Tg. Children with SCH had poorer linear growth and were more likely to be underweight than the children without SCH. Excessive iodine intakes and thyroid disturbances were common among children below four years of age in our study. Further, SCH seemed to be associated with poor growth and weight.

Neonatal iodine deficiency: clinical aspects.

Iodine is a trace element which is essential for the synthesis of thyroid hormones. The thyroid hormones, thyroxine (T4) and 3,5,3'-triiodothyronine (T3), are necessary for adequate growth and development throughout fetal and extrauterine life. The iodine intake of newborns is entirely dependent on the iodine content of breast milk and the formula preparations used to feed them. An inadequate iodine supply might be especially dangerous in the case of premature babies. The minimum recommended dietary allowance (RDA) for different age groups has recently been revised. The iodine intake required is at least 15 microg/kg/day in full-term infants and 30 microg/kg/day in preterms. The iodine content of many evaluated preparations for feeding premature infants appears to be inadequate. Premature infants are now in a situation of iodine deficiency, precisely at a stage of psychomotor and neural development which is extremely sensitive to alterations of thyroid function.

Iodine supplementation during pregnancy and lactation. Position statement of the working group on disorders related to iodine deficiency and thyroid dysfunction of the Spanish Society of Endocrinology and Nutrition.

Severe and mild iodine deficiency during pregnancy and lactation affects thyroid function of the mother and neonate as well as the infant's neuropsychological development. Studies performed in Spain confirm that most women are iodine deficient during pregnancy and lactation. Pregnant and breast feeding women and women planning to become pregnant should take iodine supplements.

Thyroid hormone supplementation in preterm infants born before 28 weeks gestational age and neurodevelopmental outcome at age 36 months.

BACKGROUND: Thyroid hormones are required for normal brain maturation, and neonatal plasma thyroid hormone concentrations are low in infants less than 28 weeks gestation. It is not known whether treatment of such infants with thyroid hormone improves neurodevelopmental outcome. METHODS: At three years corrected age, mental, motor, and neurological development was assessed in infants born at less than 28 weeks gestational age who had participated in a phase 1 trial of differing doses and modes of administration of thyroid hormone. The trial's endpoints were thyroid hormone (thyroxine, T4) and thyotropin plasma concentrations in eight study arms: six treated with T4 [4, 8, and 16 µg/(kg · day)], bolus or continuous], one treated with iodine only, and one treated with placebo. Follow-up at three years was not part of the original study goals. Developmental index scores, rates of cerebral palsy (CP), and rates of adverse outcome (death or moderate to severe delay in development and/or disabling CP) were compared between the eight study groups and between groups combined by dosage level, and between infants with and without T4 supplementation. RESULTS: Of 166 randomized infants, 32 (19%) died in the neonatal period. Of the 134 survivors, follow-up results were available for 89 children (66%). Mental and motor development and rates of cerebral palsy did not differ in any of the comparisons made. CONCLUSION: In this study, no differences in neurodevelopment were found in relation to thyroid hormone treatment, but power was insufficient to detect any but very large differences.

Parameters of thyroid function throughout and after pregnancy in an iodine-deficient population.

BACKGROUND: The thyroid hormone milieu is of crucial importance for the developing fetus. Pregnancy induces physiological changes in thyroid homeostasis that are influenced by the iodine status. However, longitudinal studies addressing thyroid function during pregnancy and after delivery are still lacking in mild-to-moderate iodine-deficient populations. Here we characterize the serum parameters of thyroid function throughout pregnancy, and until 1 year after delivery, in a population of pregnant women whom we have previously reported to be iodine deficient (median urinary iodine levels below 75 microg/L). METHODS: One hundred eighteen pregnant women were studied. Clinical data were recorded and serum was collected. Serum total and free thyroxine (T(4)) and triiodothyronine (T(3)), thyroid-stimulating hormone, thyroxine-binding globulin, and thyroglobulin were measured. RESULTS: Mean total T(4) ranged from 159 at the start of gestation to 127 nmol/L at 1 year after delivery, free T(4) from 14.2 to 17.8 pmol/L, total T(3) from 2.4 to 2.1 nmol/L, free T(3) from 6.7 pmol/L to 6.4 pmol/L, thyroid-stimulating hormone from 1.2 to 1.4 mIU/L, T(4)-binding globulin from 62.0 to 26.9 mg/L, and thyroglobulin from 11 to 10 microg/L. CONCLUSION: The pregnant women in this study had an absence of the usual free T(4) spike and a smaller than expected increment in total T(4), described during pregnancy in iodine-sufficient populations. A greater number of women had subclinical hypothyroidism compared with iodine-sufficient populations. This hormonal profile, most likely due to iodine insufficiency, may result in inadequate thyroid hormone supply to the developing fetus. We conclude that care should be taken when reviewing the results of thyroid hormone tests in iodine-insufficient populations and when no gestation-specific reference values have been established. In addition, we recommend iodine supplementation in our population and populations with similar iodine status, particularly during pregnancy and lactation.

Iodine status of pregnant women and their progeny in the Minho Region of Portugal.

BACKGROUND: Iodine sufficiency is particularly necessary throughout pregnancy, given its recognized impact on psychomotor performance of the offspring. There are no recent reports about iodine status or supplementation in Portugal, a country that the International Council for Control of Iodine Deficiency Disorders considered, in 2004, to have probably reached iodine sufficiency. The objective of this study was to evaluate in the Minho region of Portugal the iodine status of women throughout pregnancy and after delivery, and of their offspring. METHODS: Urinary iodine concentration (UI) was determined in 78 nonpregnant premenopausal women, in 140 pregnant women in the three trimesters of pregnancy and after delivery, and in their 142 offspring. Milk iodine concentration was determined at day 3 and 3 months after delivery. The thyroid volume was determined in women in the third trimester of pregnancy and 3 months after delivery and in infants at 3 months of age. RESULTS: Based on the World Health Organization criteria, both nonpregnant and pregnant women had iodine deficiency (ID), as documented by median UI of <75 microg/L and milk iodine concentration of <100 microg/L. Goiter was observed in 14% of the pregnant women. Concordant with the mother's ID, median neonatal UI was low (71 and 97 microg/L at 3 days and 3 months of age). CONCLUSION: Portuguese women of the Minho region have an inadequate iodine intake, which may compromise the potential for full psychomotor development of their progeny. These observations suggest that iodine supplementation should be implemented throughout pregnancy and lactation in Portugal.

Phase 1 trial of 4 thyroid hormone regimens for transient hypothyroxinemia in neonates of <28 weeks' gestation.

BACKGROUND: Transiently low levels of thyroid hormones occur in approximately 50% of neonates born 24-28 weeks' gestation and are associated with higher rates of cerebral palsy and cognitive impairment. Raising hormone levels shows promise for improving neurodevelopmental outcome. OBJECTIVE: To identify whether any of 4 thyroid hormone supplementation regimens could raise T(4) and FT(4) without suppressing TSH (biochemical euthyroidism). METHODS: Eligible subjects had gestational ages between 24 07 and 2767 weeks and were randomized <24 hours of birth to one of six study arms (n = 20-27 per arm): placebo (vehicle: 5% dextrose), potassium iodide (30 microg/kg/d) and continuous or bolus daily infusions of either 4 or 8 microg/kg/d of T(4) for 42 days. T(4) was accompanied by 1 microg/kg/d T(3) during the first 14 postnatal days and infused with 1 mg/mL albumin to prevent adherence to plastic tubing. RESULTS: FT(4) was elevated in the first 7 days in all hormone-treated subjects; however, only the continuous 8 microg/kg/d treatment arm showed a significant elevation in all treatment epochs (P < .002 versus all other groups). TT(4) remained elevated in the first 7 days in all hormone-treated subjects (P < .05 versus placebo or iodine arms). After 14 days, both 8 microg/kg/d arms as well as the continuous 4 microg/kg/d arm produced a sustained elevation of the mean and median TT(4), >7 microg/dL (90 nM/L; P < .002 versus placebo). The least suppression of THS was achieved in the 4 microg/kg/d T(4) continuous infusion arm. Although not pre-hypothesized, the duration of mechanical ventilation was significantly lower in the continuous 4 microg/kg/d T(4) arm and in the 8 microg/kg/d T(4) bolus arm (P < .05 versus remaining arms). ROP was significantly lower in the combined 4 thyroid hormone treatment arms than in the combined placebo and iodine arms (P < .04). NEC was higher in the combined 8 microg/kg/d arms (P < .05 versus other arms). CONCLUSIONS: Elevation of TT(4) with only modest suppression of TSH was associated with trends suggesting clinical benefits using a continuous supplement of low-dose thyroid hormone (4 microg/kg/d) for 42 days. Future trials will be needed to assess the long-term neurodevelopmental effects of such supplementation.

Iodine balance, iatrogenic excess, and thyroid dysfunction in premature newborns.

Iodine is a trace element that is essential for the synthesis of thyroid hormones. The thyroid hormones, thyroxine and 3,5,3'-triiodothyronine, are necessary for adequate growth and development throughout fetal and extrauterine life. The iodine intake of newborns is entirely dependent on the iodine content of breast milk and the formula preparations used to feed them. An inadequate iodine supply (deficiency and excess) might be especially dangerous in the case of premature babies. The minimum recommended dietary allowance is different depending on age groups. The iodine intake required is at least 15 microg/kg/d in full-term infants and 30 microg/kg/d in preterms. Premature infants are in a situation of iodine deficiency, precisely at a stage of psychomotor and neural development that is extremely sensitive to alterations of thyroid function.

The changing role of maternal thyroid hormone in fetal brain development.

This review briefly summarizes: (1) the changes in maternal thyroid function that are imposed by the presence of the fetus and the high concentrations of human chorionic gonadotropin essential for the maintenance of the pregnancy, which result in high first trimester free thyroxine and triiodothyronine, requiring doubling of the iodine intake; (2) the changes in the fetal compartment up to midgestation, which result in increasing concentrations of triiodothyronine in the cerebral cortex generated locally from thyroxine by high activities of type 2 iodothyronine deiodinase; (3) the important role of the maternal contribution of thyroxine to the fetal circulation after onset of secretion of hormones by the fetal thyroid; and (4) the consequences of the interruption of the maternal supply of thyroid hormones that occur with prematurity. Efforts to devise appropriate strategies to avoid or shorten the postnatal hypothyroxinemia of infants born prematurely may well result in fewer and less severe neurodevelopmental deficits.