Iodine antiseptics are not harmless

The use of iodine-containing antiseptics is still common in obstetrics and neonatology. Topical iodine given both to the mother before delivery and to the neonate causes iodine overload. The absorption of maternal iodine through the skin is so fast that iodine in the blood of the umbilical cord increases by 50% a few minutes before delivery. Iodine overload also occurs in the mother. Urinary and breast-milk iodine are increased more than 10-fold in the days after delivery if providone-iodine is used in episiotomy. The overload in the neonate is even higher if breast-fed. Particularly in iodine-deficient areas, this overload can produce thyroid blockade with undesirable effects in congenital hypothyroidism screening, raising the number of false positives and its consequences: parental anxiety and screening costs. The potential effects that this thyroid blockade can produce in the neonate are even more serious. Attention should be drawn to the undesirable effects of iodine antiseptics and their use in the perinatal period should be avoided.     

Iodine nutrition in the infant. Committee on Nutrition of the French Society of Pediatrics]

Iodine is a trace element essential for the synthesis of thyroid hormones. It is present in the human body in minute amounts (15-20 mg in adults). The thyroid is very sensitive to iodine deficiency in newborns and infants because of its very low iodine content. Daily iodine requirements in humans vary from 40 micrograms in neonates to 150 micrograms in adults. Iodine deficiency represents the first cause of avoidable mental deficiency in developed countries; it has not yet disappeared in Europe, especially in the East, where it is responsible for a high prevalence of goiter. Iodine deficiency during pregnancy increases the risk of neonatal transient hypothyroidism, with a high recall rate in programs of systematic screening for congenital hypothyroidism. Data available in France suggest that screening for iodine deficiency should be performed during pregnancy, and that the minimal iodine concentration in formula milk should be increased to 10 micrograms/100 kcal for term infants and 20 micrograms/100 kcal for premature infants. Iodine deficiency is ideally prevented by the use of iodized salt. Because of the risk of iodine overexposure and secondary transient hypothyroidism, the use of iodinated antiseptics must be avoided in premature babies and neonates as well as in pregnant and lactating women. The fight against iodine deficiency, associated with oral stable preventive iodine administration, decreases sharply the risk of thyroid cancer in case of nuclear exposure, by diminishing thyroid uptake of iodine radioactive isotopes.     

Update of newborn screening and therapy for congenital hypothyroidism

Unrecognized congenital hypothyroidism leads to mental retardation. Newborn screening and thyroid therapy started within 2 weeks of age can normalize cognitive development. The primary thyroid-stimulating hormone screening has become standard in many parts of the world. However, newborn thyroid screening is not yet universal in some countries. Initial dosage of 10 to 15 microg/kg levothyroxine is recommended. The goals of thyroid hormone therapy should be to maintain frequent evaluations of total thyroxine or free thyroxine in the upper half of the reference range during the first 3 years of life and to normalize the serum thyroid-stimulating hormone concentration to ensure optimal thyroid hormone dosage and compliance. Improvements in screening and therapy have led to improved developmental outcomes in adults with congenital hypothyroidism who are now in their 20s and 30s. Thyroid hormone regimens used today are more aggressive in targeting early correction of thyroid-stimulating hormone than were those used 20 or even 10 years ago. Thus, newborn infants with congenital hypothyroidism today may have an even better intellectual and neurologic prognosis. Efforts are ongoing to establish the optimal therapy that leads to maximum potential for normal development for infants with congenital hypothyroidism. Remaining controversy centers on infants whose abnormality in neonatal thyroid function is transient or mild and on optimal care of very low birth weight or preterm infants. Of note, thyroid-stimulating hormone is not elevated in central hypothyroidism. An algorithm is proposed for diagnosis and management. Physicians must not relinquish their clinical judgment and experience in the face of normal newborn thyroid test results. Hypothyroidism can be acquired after the newborn screening. When clinical symptoms and signs suggest hypothyroidism, regardless of newborn screening results, serum free thyroxine and thyroid-stimulating hormone determinations should be performed.     

Resetting the detection level of cord blood thyroid stimulating hormone (TSH) for the diagnosis of congenital hypothyroidism

An appraisal of a 17-year primary thyroid stimulating hormone (TSH) screening programme for the detection of congenital hypothyroidism was carried out to establish the reference interval of cord blood TSH in unaffected infants; the mean cord blood TSH concentration of affected infants and the incidence of congenital hypothyroidism in the Najran province of Saudi Arabia. Our findings show a reference interval of cord blood TSH of 2.0-16.8 mU/l in unaffected infants; a mean cord blood TSH concentration of 399 mU/l in affected infants; a false positive rate for the diagnosis of at-risk infants of 1.02% and a congenital hypothyroidism incidence rate of 34/100 000 (1 : 2931) live births. These findings suggest that there is a need to reset the cord blood TSH concentration for the detection of at-risk infants. We suggest that the detection level of cord blood TSH for the recognition of at-risk infants can be set at 90 mU/l rather than the recommended level of 30 mU/l. This should reduce the false positive rate for detection of infants at risk of congenital hypothyroidism.     

Newborn screening for congenital hypothyroidism

Most neonates born with congenital hypothyroidism (CH) have normal appearance and no detectable physical signs. Hypothyroidism in the newborn period is almost always overlooked and delayed diagnosis leads to the most severe outcome of CH, mental retardation, emphasizing the importance of neonatal screening. Blood spot T4 or TSH or both can be used in neonatal screening for CH. The latter, which is more sensitive, is not cost effective, so the first two are used in different programs in the world. TSH screening was shown to be more specific in the diagnosis of CH; T4 screening is more sensitive in detecting newborns especially with rare hypothalamic-pituitary hypothyroidism, but less specific with a high frequency of false positives mainly in low birth weight and premature infants. The time at which the sample is taken may vary between centers, with the majority taking blood from a heel prick after 24 hours of age to minimize the false positive high TSH due to the physiological neonatal TSH surge that elevates TSH levels and causes dynamic T4 and T3 changes in the first 1 or 2 days after birth. Early discharge of mothers postpartum has increased the ratio of false positive TSH elevations. Although transient hypothyroidism may occur frequently, all suspected infants should be treated as having CH for the first 3 years of life, taking into account the risks of mental retardation. A reevaluation after 3 years is needed in such patients. The goal of initial therapy in CH is to minimize neonatal central nervous system exposure to hypothyroidism by normalizing thyroid function, as reflected by T4 and TSH levels, as rapidly as possible. Iodine deficiency is the most important cause of CH worldwide. Iodine is essential for thyroid hormone synthesis and is present in soil, water and air. Prevention of iodine deficiency can be by iodized salt, iodized oil, iodized bread or iodine tablets.     

Screening for congenital hypothyroidism with specimen collection at two time periods: results of the Northwest Regional Screening Program

To determine the benefit of collecting two routine specimens to test for congenital hypothyroidism, we examined the results of our newborn screening program during the last 9.5 years. The Northwest Regional Screening Program (NWRSP) performs a primary thyroxine test with thyroid-stimulating hormone determinations on the lowest 10% of dried blood filter paper specimens. An initial specimen is obtained in the newborn period, and a routine second specimen is collected at approximately 4 to 6 weeks of age in all infants born in Oregon and 25% of infants born in Idaho, Montana, Alaska, and Nevada. Between May 1975 and October 1984, 182 infants with primary hypothyroidism were detected from 811,917 infants screened, a prevalence rate of 1:4,461. The routine second specimen led to the diagnosis of 19 infants of 484,604 infants screened, a detection rate of 1:25,505. When infants detected by the second screen were compared with those detected by the first screen, they had higher thyroxine and lower thyroid-stimulating hormone concentrations on filter paper and serum specimens. When thyroid scanning was used, all but one infant detected by the second screen had some residual thyroid tissue, whereas 35% of infants detected by the first screen had thyroid aplasia. Skeletal maturation was more likely to be normal in infants detected by the second screen. These infants appear to have milder hypothyroidism due to a later age of onset or slower evolution of thyroid failure. At a cost of $31,881 per infant detected by the second screen, the NWRSP found it cost-effective to obtain a routine second specimen.     

Increased risk of primary hypothyroidism in preterm infants

Serum levels of thyroid stimulating hormone, thyroxine, triiodothyronine, free T4, thyroxine-binding globulin, reverse T3, and the TSH secretory areas and peak T3 after intravenous injection of 40 micrograms thyrotropin-releasing hormone were determined weekly from day 5 to 6 to 11 weeks of age in 42 unselected full-term and 61 preterm Belgian infants. The results on day 5 indicated a progressive deficit of thyroid function related to the degree of prematurity. In 92 infants this deficit progressively decreased with age and disappeared at 5 to 7 weeks. However, 11 infants developed biochemical evidence of overt but transient hypothyroidism. Belgian neonates are relatively iodine deficient, and this factor affects the constitution of iodine stores within the thyroid gland: (1) the urinary concentrations of iodine in the 103 infants studied in Belgium were markedly lower than in 30 infants from California; and (2) The iodine concentration of the thyroid gland in preterm infants who died during the 10 first days of life was almost three times lower in Brussels than in Toronto. The results indicate that, in Belgium, the effects of relative iodine deficiency on thyroid function are superimposed on and mask the physiologic state of tertiary hypothyroidism in prematurity.     

Incidence of iodine deficiency in Turkish patients with congenital hypothyroidism

Background: Turkey is located in an area of mild to moderate iodine deficiency. The aim of the present study was to investigate the incidence of iodine deficiency in patients with congenital hypothyroidism.
Methods: Twenty five patients with a median age of 12 days (6 days–6 months) at diagnosis and followed for a median time of 7 months (1–60 months) were enrolled in the study. Thyroid function tests, thyroid scintigraphy, ultrasonography and urine iodine measurements of the patients and mothers were performed.
Results and conclusion: Congenital hypothyroidism was diagnosed within postnatal day 13, between days 13 and 30, and after 30 days of age in 68%, 20% and 12% of the patients, respectively. At the time of diagnosis mean serum thyroid-stimulating hormone and total T4 were 85.3 ± 27.6 mIU/L and 3.9 ± 2.8 μg/dL, respectively. Incidence of iodine deficiency was 36% in the patients (median, 110 μg/L) and 88% in the mothers (median, 40 μg/L). Thyroid scintigraphy and ultrasound were normal in all of the patients with iodine deficiency. At scintigraphic evaluation, thyroid gland was not visualized in 28% of patients; in the patients whose thyroid glands were not visualized scintigraphically thyroid ultrasonography indicated agenesis in 57%, and hypoplasia in 43%. In all the patients with thyroid agenesis or hypoplasia iodine levels were normal. In 36% of the patients imaging studies of thyroid gland and urine iodine measurements were normal. Despite salt iodization program, incidence of iodine deficiency is still high in patients with congenital hypothyroidism and mothers. National measures are urgently required for correction of iodine deficiency in Turkey.     

Serum thyroxine and thyroid stimulating hormone concentrations after treatment of congenital hypothyroidism.

Serum thyroid stimulating hormone and thyroxine concentrations were monitored in 42 infants who had been treated for congenital hypothyroidism. Serum thyroid stimulating hormone concentrations were raised in 22 of the infants (52%) at 2 to 4 months, in 16 (38%) at 5 to 11 months, in 14 (33%) at 12 to 18 months, and in eight (19%) at 2 to 4 years. Serum thyroxine and the dose of L-thyroxine/kg/body weight were significantly lower in those infants with raised thyroid stimulating hormone concentrations. Thyroid stimulating hormone was appropriately suppressed when the dose of L-thyroxine was increased, and only one child had delayed maturation of the hypothalamic/pituitary/thyroid axis. We believe it is the infant''s rapid gain in weight in the first two years of life that necessitates this decrease in the dose of L-thyroxine/kg body weight and recommend that the treatment of this age group is reviewed every two to three months.     

Thyroid disorders in neonates: A practical approach to congenital hypothyroidism and thyrotoxicosis

Congenital hypothyroidism is one of the most common causes of preventable intellectual disability in the UK and worldwide. Early diagnosis is critical to allow for early intervention. At present, 1 in 2000 to 1 in 3000 babies born in the UK have congenital hypothyroidism. Of these, most will not display any clinical manifestations or symptoms in the first few weeks of life. In short, babies will develop intellectual disability if they go undiagnosed. It is therefore no surprise that the day 5 blood spot is essential for good outcomes and harm reduction. Diagnosis of thyroid disorder is based on measuring the thyroid hormones and thyroid stimulating hormone levels. The most common cause of congenital hypothyroidism is an abnormality in thyroid gland development (dysgenesis) but it may also be the result of a defect in thyroid hormonogenesis or may be temporary as a result of maternal medications passing through the placenta, maternal blocking antibodies or iodine excess or deficiency. Rarely, it is the result of pituitary or hypothalamic abnormality when it is called central or secondary/tertiary hypothyroidism. This short article offers practical advice on how to diagnose and treat congenital hypothyroidism and how to interpret the results of available biochemical tests.     

Recovery Period of Hypersecretion of Thyroid-Stimulating Hormone in Patients with Congenital Hypothyroidism Treated with Thyroid Hormone

The recovery periods of serum thyroid stimulating hormone (TSH) were studied in patients with congenital hypothyroidism found on neonatal screening. L-T4 was administered at 37.8 ± 15.1 days of age (M ± SD), and serum T4, T3, and TSH concentrations were measured. After L-T4 therapy with 10 µg/kg, the serum TSH levels decreased to below 10 µU/ml in five patients within a week, and in another two patients, within two weeks, and in the total number of 12 patients out of 15 (80%), by one month. These results suggest that the recovery of serum TSH occurs rapidly in hypothyroid infants. Thus, the serum TSH concentration may be a good measurement for assessing the adequacy of thyroid hormone therapy from early infancy in patients with congenital hypothyroidism.     

Congenital hypothyroidism with delayed rise in serum TSH missed on newborn screening

We report on a female patient with congenital hypothyroidism (CH) missed on a newborn screening test. She is now 10 years old with retarded development. The patient was born premature at 34 weeks of gestation with birth-weight of 1515 g, and was judged to be normal in the screening programme of Niigata Prefecture. However, she gradually suffered from poor weight gain and retarded development with stridor at breathing. Serum thyroid stimulating hormone (TSH) levels were rechecked and showed high values with normal T3 and T4 levels. She was referred to our hospital at the age of 13 months. She was diagnosed as having CH (ectopic thyroid) with a delayed rise in blood TSH concentration, probably due to the prematurity of the hypothalamic-pituitary-thyroid axis. l -thyroxine therapy brought a decline in TSH levels with partial improvement of her symptoms. Regardless of the result of newborn screening, infants with elevated serum TSH levels should be carefully examined for possible CH, even when T3, T4 and free T4 values are in the normal range.     

Thyroid function tests in preterm infants born to preeclamptic mothers with placental insufficiency

OBJECTIVE: Since preeclampsia causes placental insufficiency, it can be hypothesized that it decreases placental passage of thyroxine (T4) from mother to infant and thus may deepen the transient hypothyroxinemia seen in preterm infants after birth. The aim of this study was to compare thyroid function tests of preterm infants born to preeclamptic mothers with placental insufficiency with preterm infants born to mothers without placental insufficiency. METHODS: Thirty-one preterm infants born to preeclamptic mothers with placental insufficiency were included in the study (group I) and 31 preterm infants born to mothers without placental insufficiency were included as the control group (group II). Thyroid hormone levels were assayed from blood samples obtained from the women before birth and thereafter from the infants at delivery (cord) and on the 1st, 3rd, 7th, and 21st days of life. RESULTS: Cord blood triiodothyronine (T3), free T3 (FT3) and free thyroxine (FT4) levels in group I were lower than in group II, whereas thyrotropin (TSH) and thyroxine binding globulin (TBG) levels were higher. No statistical difference in hormone levels studied at postnatal 1st, 3rd, 7th, and 21st day was found between the two groups. CONCLUSION: Low levels of thyroid hormones and high level of TSH in cord blood in premature infants born to preeclamptic mothers with placental insufficiency suggest intrauterine hypothyroidism. Increase in TSH and thyroid hormone concentrations after birth reveal that the hypothalamic-pituitary-thyroid axis is intact.     

Newborn screening for congenital hypothyroidism, Victoria, Australia, 1977-1997. Part 1: The screening programme, demography, baseline perinatal data and diagnostic classification.

Clinical, demographic and laboratory data from infants with congenital hypothyroidism (CH) born in the Australian state of Victoria from the commencement of neonatal screening in mid-1977 until December 1988 are reported. These provide a baseline for a 12-year prospective longitudinal study on physical and neuro-psychological outcome until mid-1997, the subject of a second paper. Infants with CH were detected using a primary TT4 screening test. Demographic data were collected prospectively using a clinical assessment protocol. Nearly all affected infants underwent 99mTc pertechnetate scanning at the initial assessment to determine the underlying aetiology of their hypothyroidism. 704,723 infants were screened and 199 with permanent primary hypothyroidism (one in 3,541) were identified. The most common aetiologies were thyroid ectopia (46%), thyroid aplasia (33%), and 'dyshormonogenesis' (11%). The clinical abnormalities classically described in CH were more evident in infants with aplasia, and the striking female preponderance in infants with thyroid dysplasia (syn. dysgenesis) was confirmed. Other features included increased frequencies of 'dyshormonogenesis' in infants of parents of Middle-Eastern origin and of labour induction in infants with dysplasia. A closed posterior fontanelle was not found in any infant with thyroid aplasia.     

Elevated serum creatinine levels in infants with congenital hypothyroidism: reflection of decreased renal function?

The effects of hypothyroid status on renal function have been poorly studied in children. We assessed the renal function of hypothyroid infants detected during neonatal mass screening for congenital hypothyroidism (CH). Eighty hypothyroid infants and 20 age-matched normal infants for controls were enrolled. The 80 patients, aged 1 mo, were divided into two groups based on the initial thyroid stimulating hormone (TSH) and free thyroxine (FT4) values: a mild-moderately hypothyroid (MHT) group (n = 64, 31M and 33F) and a severely hypothyroid (SHT) group (n     

Congenital hypothyroidism. The effect of stopping treatment at 3 years of age

Fifty-six children with congenital hypothyroidism diagnosed by neonatal screening were reviewed at 3 years of age or older. The presence or absence of the thyroid gland was determined by radionuclide scanning prior to treatment in the newborn period. Thyroxine therapy was discontinued in those children who did not have anatomic defects or a secondary rise in their thyrotropin (thyroid-stimulating hormone [TSH]) level once it was suppressed by thyroid hormones. Sixteen of 17 children developed a low thyroxine and an elevated TSH level within three to six weeks. One child was not receiving thyroxine for nine months and was clinically and biochemically euthyroid. We conclude that (1) newborn thyroid scans are useful to determine the cause of hypothyroidism, (2) a secondary rise in the TSH level indicates permanent hypothyroidism, (3) only about one third of infants whose condition is diagnosed by newborn screening will qualify for a trial off therapy at 3 years of age, (4) only 1% to 2% of infants whose condition is diagnosed by newborn screening have transient hypothyroidism, and (5) a three-week period of hormone withdrawal after the age of 3 years seems adequate and safe to confirm permanent hypothyroidism.     

Hypothyroidism secondary to topical iodine treatment in infants with spina bifida

Four infants with spina bifida, who had not undergone surgical closure of a lumbar myelomeningocele, were assessed and investigated for hypothyroidism. From birth, all were treated once daily with an iodine-containing ointment (Betadine) as a local antiseptic applied to the spina defect. All infants showed excess urinary iodine concentration. Two infants, without clinical evidence of hypothyroidism or goitre, showed low serum free thyroxine and high thyroid stimulating hormone concentrations at a mean age of four weeks and were started on thyroxine replacement treatment. Betadine ointment and thyroxine were stopped simultaneously at a mean age of nine months, following which all infants remained euthyroid. Thyroid function tests should be monitored routinely if iodine is applied as a topical antiseptic to infants.     

Persistent hyperthyrotropinaemia since the neonatal period in clinically euthyroid children

We describe three children, now aged between 5 and 6 years, with a persistent mild hyperthyrotropinaemia since the neonatal period and normal levels of thyroid hormones. The increased thyroid stimulating hormone concentration is not artefactual and is not caused by antibody interferences. Their growth and development is normal and none has received thyroid hormone replacement. We believe that they have compensated hypothyroidism, and that before the advent of screening for congenital hypothyroidism these children would have presented in mid-childhood with juvenile hypothyroidism.     

Neonatal seizures

AIMS—To define the aetiology of neonatal transient hypothyroidism (NTH) and recommend preventive measures.METHODS—Maternal and perinatal clinical data on the use of antiseptics, drugs, and contrast agents containing iodine were collected from 40 subjects. Thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), thyroglobulin (TG), TSH receptor antibodies, thyroid peroxidase antibodies and urinary iodine were measured in random neonatal samples. In the mothers with known or suspected thyroid disorders, TSH, FT4, TSH receptor antibodies and thyroid peroxidase antibodies were also measured.RESULTS—The NTH aetiology was identified in 85% of cases. More than 50% of the babies with transient hypothyroidism had been exposed to iodine; maternal transfer of antibodies had occurred in a third of them.CONCLUSIONS—It is suggested that the practice of using iodine containing disinfectants should be withdrawn, and chlorhexidine substituted instead; that pregnant women should be advised of the adverse effects of using iodine products; and that thyroid function should be monitored whenever iodine is used.     

Neonatal hypothyroidism detected by the Northwest Regional Screening Program.

The Northwest Regional Screening Program to detect congenital hypothyroidism in infants born in Oregon, Montana, Alaska, and Idaho (combined birthrate of 69,000/ yr) was added to our ongoing screening program in 1975. The program utilizes dried blood filter paper specimens collected routinely in the first few days of life in all four states and again at about 6 weeks of age in Oregon only. The screening test consist of an initial thyroxine (T4) measurement; a thyroid-stimulating hormore (TSH) determination is performed on those specimens with T4 concentrations in the lowest 3% group. Serum samples obtained by venipuncture are requested for confirmation of the diagnosis. In the first two years of the program, 25 infants with primary hypothyroidism were detected amont 110,667 infants screened, a frequency of 1:4,430. Fourteen cases of thyroxine-binding globulin deficiency were also detected, a frequency of 1:7,900. Using the T4 followed by TSH testing approach, the frequency of request for repeat specimens was 0.4% in Oregon and 0.05% in the other states. The cost per specimen was $1.96. The majority of infants lacked clinical signs or symptoms of hypothyroidism; only one infant was clinically suspected of having hypothyroidism prior to detection. The most common neonatal symptoms were constipation, lethargy, and prolonged jaundice, while the most common physical signs were hypotonia, umbilical hernia, and large fontanels. Thyroid scans showed the most common etiology to be thyroid aplasia, followed by an ectopic gland, hypoplasia, and goiter. Serum T4 concentrations were lowest in those infants with aplasia, intermediate in infants with an ectopic gland or hypoplasia, and normal in the infant with the goiter. Neonatal hypothyroidism varies in degree and has several different causes; the capacity to secrete thyroid hormone, the duration before hypothyroidism becomes clinically manifest, and possibly the eventual prognosis for intellectual function depend on the nature of the underlying cause. While the mean age at treatment was 59 days, the goal of diagnosing congenital hypothyroidism and treating affected infants by 1 month of age seems realistic.