Iodine is a trace element which is essential for the synthesis of thyroid hormones. Premature babies need >30 µg I / kg /day (International Council for the Control of Iodine Deficiency Disorders recommendations ICCIDD) (1)
The thyroid hormones, thyroxine (T4) and 3,5,3´-triiodothyronine (T3), are necessary for adequate growth and development throughout fetal and extra-uterine life during the first years of life.
Their effects of on the central nervous system are mediated by the regulation of the expression of genes that synthesize proteins implicated in: cerebral neurogenesis, neuronal migration and differentiation, axonal out-growth, dendritic ontogeny and synaptogenesis, cerebellar neurogenesis, gliogenesis and myelinogenesis. Iodine deficiency may contribute to hypothyroxinemia and is recognised as cause of preventable mental retardation (2,3,4)
Neonates and preterm infants are a population at risk of suffering the consequences of iodine deficiency, because of the effects of the resulting neonatal hypothyroxinemia on brain development.
Transient hypothyroxinemia of prematurity (THOP) is characterized by low levels of serum thyroxine (T4) and tri-iodothyronine (T3), but normal thyroid stimulating hormone (TSH) levels until up to 6 weeks (wk) (evident in 41% of infants under 27 weeks gestation and in 23% of infants between 28-30 weeks gestation) (5,6,7,8,9).
The ethyology of transient hypothyroxinaemia may have contributions from the withdrawal of maternal-placental thyroxine transfer, hypothalamic-pituitary-thyroid immaturity, developmental constraints on the synthesis and peripheral metabolism of iodothyronines, iodine deficiency, and non-thyroidal illness.
The studies realized in the previous years in premature babies of 27-36 weeks of gestacional age, in the Neonatal Unit of La Paz revealed clearly that these infants have very low levels of free thyroxin (FT4) and of tri-yodo-thyronin (T3), compared with those of term newborns. The mental development has been studied at the age of 4 of age, being low in those children who had lower concentrations during the postnatal period, especially if this situation extended during the first two months of life. A subsequent study was performed in premature babies of minor gestacional age (<30 weeks), but fed on formulae with higher iodine content. The mental development has been studied at the age of 6, 12, 18 and 24 months of age. A preliminary evaluation of the results indicates that the children with more problems of development keep on being those who had a lower iodione intake (10-23).
Parenteral nutrition is used in the clinical practice in all the immature newborn babies immediately in the first hours of life. At present the preparations used for the feeding parenteral in newborn babies present a content of iodine of 1 microgram for ml. (24) and the recommendations of administration of iodine by route parenteral were established a few years ago in 1 microgram/kg/day, being these quantities lower than the recommendations for oral route, possibly being based on the possibility of toxicity of the iodine by parenteral route. In absence of other sources of iodine, the newborn babies who are fed on parenteral nutrition present a deficiency of this micronutrient.
In pilot studies it has been described that the parenteral supplementation with quantities of iodine of 30 microgr/KG/day produces positive balance in the newborn baby, these are sure quantities and they do not produce side effects (9,25). There are not at present preparations with iodine content higher than 1 microgr/ml. The parenteral supplementation of iodine needs an intravenous route, adds the maintenance of the sterility, there is more risk of infection and needs more sanitary personnel for maintenance.
These factors lead us to think that the administration of supplements by enteral route (oral drops) is effective, easier to administer, it is cheaper and does not exhibit the patient to major risks. The enteral supplementation of iodine has theoretically many advantages. Prevention of iodine deficiency and follow-up is recognized as a priority. The number of extremely low birth weight (ELBW) infants is high. Correction of their iodine deficiency and hypothyroxinemia and its consequences appears, to be an intervention with promising possibilities. Future research would be facilitated if preterm babies were followed during their stay in intensive care units with respect to their iodine nutrition and thyroid function as carefully as they are followed for other organ functions. Our aim is to determine, through a randomized controlled trial, whether nutritional supplementation with iodine solution via oral route (as a drop in the mouth) enables extreme preterm infants to achieve a positive iodine balance.
STUDY DESING:
We conducted a study of thyroid hormones in infants under 1500 g of birth weight. The study was designed as a longitudinal clinical trial, one group of infants with iodine supplements and a control group. Enrollment period: January 2007 - December 2009. 47 subjects were enrolled in the Control group (no supplements). 47 subjects were enrolled in the Iodine supplemented group (30 µg /kg/day of Potassium Iodine (SSKI) in oral drops). Treatment period: All treatments start within 24 hours after birth. Every study subject receives the supplement during hospitalization until discharge. Parental written consent was obtained for each study subject. Parents and clinicians were not blind from treatment assignment throughout the entire study period. The study was approved by the Ethics Committee and by the Institutional Review Boards of the enrolment center (University Hospital LA PAZ, Madrid, Spain). Excluded were mothers less than 18 years old, mothers with thyroid disease or reported substance abuse (i.e., alcoholism or use of heroin or methadone, as these substances can interfere with hormone transport in serum) and newborns with major congenital malformations or if death was expected within 48 hours.
Intervention
We used Potasium Iodine in oral drops (Babyodo 30 ™. Dietetic food, watery solution of contained iodine 30 mcg for 0,5 ml. Babyodo 90 ™: Dietetic food, watery solution of contained iodine 90 mcg for 1,5 ml. LITAPHAR Labs Pharmaceuticals).
Randomization was done by a web-based computer program, which balanced gestational age and sex. The iodine drops were administered from postnatal day 1 to postnatal day at discharge. We delivered either as oral drops or in oral submucosa. All infants in the supplemented group received a dose of 30 microgr/Kg/day, independently of iodine intake received by milk or parenteral solutions.
During hospitalization, a daily evaluation of the intake was done.