الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Prematurity with critical illness, both attenuate hypothalamic-pituitary-thyroid axis response(Cavarzere et al., 2016). Transient hypothyroxinemia of prematurity (THOP) is referred to temporary reduction in thyroid hormones which last for 6−8 weeks with no increase in thyroid-stimulating hormone (TSH) level and is more common with increasing degrees of prematurity (Hollanders et al., 2016). For the etiology of THOP, several factors were postulated including detachment from the placenta, excess or deficiency of iodide, use of drugs that suppress TSH secretion such as glucocorticoid and dopamine, deficiency of hypothalamic TRH in the preterm infants and non-thyroidal illness. Regardless of the cause of low FT4 levels, TSH levels should increase if the HPT axis is properly regulated. Therefore, detachment from the placenta or excess or deficiency of iodide cannot explain the reason for the normal levels of serum TSH (Yamamoto et al., 2015). As preterm infants recover from hypothyroxinemia, some have mild transient serum TSH level elevation before reaching an equilibrium. When followed over time, the TSH returns to normal in most and is considered a normal response to the physiologic hypothyroxinemia seen in healthy preterm infants. Some preterm infants have greater and more persistent delayed TSH elevation. This is either transient or permanent. There do not seem to be any clinical or laboratory characteristics that reliably predict whether the hypothyroidism will be transient or permanent (Woo et al., 2011). For preterm babies with THOP, many studies reported that the low FT4 levels are strongly related to worse neurodevelopmental outcomes and several trials to treat infants with THOP had been carried out but no definite improvement has been reported (Yamamoto et al., 2015) (Yamamoto et al., 2015). However, Hollanders et al stated that there is no association between THOP and neurodevelopmental outcome in young adulthood. Possible explanation for the lack of association is that the total T4 concentration does not always reflect the availability of free T4 in tissues (Hollanders et al., 2016). Many clinical trials were done to find out whether clinical and neurodevelopmental outcome of preterm infants improved by T4 supplementation. In a large randomized trial, van Wassenaer assigned a dose of T4 (8 mg/kg/day) or placebo for 42 days to 100 infants less than 30 weeks gestational age. Van Wassenaer observed an improvement in mental development by Bayley scores at 2 years postnatal age and an improvement in neurological outcome. Based on this trial, the authors have concluded that T4 supplementation may be beneficial in infants born at less than 28 weeks, its role in premature infants of later gestational age is less certain (La Gamma and Paneth, 2012).On the other hand, a Cochrane review in 2017 did not support the use of prophylactic thyroid hormones in preterm infants to reduce neonatal mortality, neonatal morbidity or improve neurodevelopmental outcomes. There is a critical need for specific guidelines as regards the follow-up and reevaluation of transient hypothyroxinemia especially in preterm infants (Kanike et al., 2017). We planned this study to determine transient hypothyroidism in preterm infants and relate it to severity of illness and to other possible risk factors. Also, to assess the impact of thyroid hormone replacement in preterm infants with transient hypothyroidism on short–term neurodevelopmental outcome. We assessed T4 and TSH levels on 3rd-5th day, one month and 3 months of preterm infants’ lives. Our study was performed on 101 preterm infants, 26 of them fulfilled criteria of transient hypothyroxinemia of prematurity with their mean serum T4 level of 4.70±0.98 μg/dl. They were randomized into two groups, 12 infants were assigned to the Treated group where they received L-thyroxine 5μg/ kg daily for 3 months duration (group A) while 14 infants were included in the Untreated group where they received placebo (group B). Nine infants in the Treated group and 10 in the Untreated group were subjected to neurodevelopmental follow-up using Bayley scale (BSID-II) at 3 months of age. We found that the low T4 levels of infants with transient hypothyroxinemia were transient, and that they returned to the normal range, since T4 levels normalized at fourth week of age. We also found THOP was inversely related to gestational age, respiratory distress and need for oxygen therapy, clinical problems as sepsis & PDA, drugs used in NICU and severity of illness. We assessed illness severity using SNAP score for preterm infants included, all infants in the Treated group had mild SNAP score (1-20) while in the Untreated group, 13 infants (92.9%) had mild SNAP score while 1 infant (7.1%) had moderate SNAP score (21-40). No significant difference as regards SNAP score was detected between both groups. In this study, we assessed serum thyroxine (T4) and serum thyroid stimulating hormone (TSH) levels in both Treated (group A) and Untreated (group B) groups of transient hypothyroxinemia at time of recruitment (T4 1st & TSH 1st), at one month (T4 2nd & TSH 2nd) and at three months of age (T4 3rd & TSH 3rd). We found no significant difference in serum thyroxine level at time of recruitment, one month and three months of age when we compared both Treated and Untreated groups. However, within each of the Treated and Untreated groups, serum thyroxine increased significantly between first sample assessed at time of recruitment and one month later. Similarly, it increased significantly between first sample and three months later within each group. However, no significant difference was observed in serum thyroxine between second sample assessed at one month of age and third sample assessed at three months of age within each of the Treated and Untreated groups. We also found no significant difference in serum thyroid stimulating hormone level at time of recruitment and at three months of age when we compared both Treated and Untreated groups. However, a statistically significant difference was observed between both groups when we compared its level at one month of age being significantly higher in the Untreated group. Within the Treated group (group A), no significant difference was observed in serum thyroid stimulating hormone between first sample assessed at time of recruitment and one month later but, within the Untreated group, it was significantly higher at one month than at recruitment. Within the Untreated group, serum thyroid stimulating hormone increased significantly between first sample assessed at time of recruitment and three months later while in the Treated group, it decreased significantly at 3 months compared to a recruitment. Within each of the Treated or Untreated group, no significant difference in serum thyroid stimulating hormone between second sample assessed at one month of age and third sample assessed at three months of age. Our study revealed no significant difference between both Treated and Untreated group in hospitalization duration nor mortality. As we assessed the neurodevelopment among both Treated and Untreated groups using Bayley scale (BSID-II) at 3 months of age, we found no significant difference between both groups indicating no beneficial effect of L-thyroxine supplementation on neurodevelopmental outcome at 3 months of age. As we correlated serum thyroxine and thyroid stimulating hormones levels throughout the study with different clinical parameters included, we found a significant negative correlation between serum T4 at recruitment and SNAP score. At one month of age, serum thyroxine level (T4 2nd) showed significant positive correlation with gestational age, birth weight, length and head circumference. A significant negative correlation was also observed between serum T4 and serum TSH one month of age. A significant positive correlation was observed between serum T4 at one month and serum TSH at three months of age. Till now, transient hypothyroxinemia’s effects on neurodevelopmental outcomes have been controversial, and no obvious effects of thyroid hormone (T4) treatment on clinical and neurodevelopmental outcomes have been established. Consequently, supplemental thyroid hormone (T4) in infants with transient hypothyroxinemia is only recommended if the condition is associated with high TSH levels.