"A Warning From The Cradle?"

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"A Warning From The Cradle?"

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"A Warning From The Cradle?"
© 2002 PFPC

This was the title of an editorial which appeared in the Journal of the Canadian Medical Association (CMAJ) in 1997, commenting on the problem of low birth weight and infant mortality. Because they may signal a deterioration in the nation's health, trends in infant mortality and low birth weight are of utmost importance (Chance, 1998). An increase in low birth-weight babies may reflect the declining health of many mothers. The proportion of low birthweight reflects the health and nutritional status of the mother (UNICEF, 1992). Low birth weight is a public health problem of the first rank (Paneth, 1995).

Neonatal (first month) mortality accounts for about three-quarters of infant (first-year) mortality in the US and Canada.

Low birth weight is so directly related to neonatal mortality that the relative position of each state's neonatal mortality rate can be predicted with reasonable accuracy from the proportion of low birth weight infants (those weighing less than 2,500 grams, or 5 pounds, 8 ounces, at birth) among live births (Paneth, 1995).

Low birth weight babies are seven times more likely than other babies to die of respiratory infections and three times more likely to die of diarrhea (WHO, 1990). In the 1980s, nearly 1 of every 10 babies in Latin America had low birth weight which was a factor in 78 percent of early neonatal deaths. (PAHO, 1990).

Preterm Delivery

The principal determinant of low birth weight in the US is preterm delivery. Preterm delivery is more common in the US than in many other industrialized nations, and is the factor most responsible for the relatively high infant mortality rate in the US. A U.S. study of 349 neonatal deaths found that 83% of deaths were associated with delivery <37 weeks and 66% with delivery <29 weeks. Therefore, the immediate outcome of pregnancy determines infant mortality, and the chief indicator of how pregnancy has progressed is the infant's birth weight (Paneth, 1995).

Preterm delivery is usually referring to birth prior to 37 completed weeks of gestation.

It is preterm delivery that underlies most low birth weight in the United States.

Preterm delivery and like low birth weight are closely related to low thyroid function.

Gestational Age and Thyroid

Paul et al (1998), in a study investigating the relationship between thyroid function and neonatal outcome, reported T4 values strongly correlated with gestational age (r = .56). Overall, 289 (85%) of 342 infants had transient hypothyroxenimia (hypothyroidism). After controlling for potential confounding variables, T4 value remained associated with an increased odds of mortality (odds ratio: 2.3; 95% confidence interval 1.6 to 3.4).

The importance of maternal thyroid hormone is supported by clear evidence of the placental transfer of maternal thyroxine to the fetus (Vulsma et al, 1989; Morreale de Escobar et al, 1989).

Although inserts of Synthroid and other levo-thyroxine products claim that thyroid hormones do not cross the placenta, it has clearly been shown otherwise. It is of utmost importance that pregnant mothers who are on any anti-thyroid medications for hypothyroidism become aware that their dose might need adjustment to compensate for this, as even sub-clinical thyroid deficiency in the mother has shown to be of great effect on the offspring.

Rooman (1996) and Reuss (1997) also found that, in preterm infants, values for serum thyroxine and free thyroxine in the first days of life vary directly with gestation. [FLUORIDE -> A similar relationship for gestation for fluoride levels was shown by Caldera (1986).] In addition, the levels of T4 and free T4 found in premature infants are lower than those seen in the normal fetus at similar gestational ages (Ballabio et al. 1989; Thorpe-Beetson et al. 1989; Radunovic et al.1991).

Recent Taiwanese studies on a total of one-hundred VLBW infants showed transient hypothyroxinemia (low thyroid) in forty-one (46.1 percent) of the survivors. Again, the authors found a correlation between low T4 and free T4 values and mortality and neonatal illness, clearly showing that an under-functioning thyroid was associated with critical illness (Hsu et al, 1999).


Ballabio M, Nicolini U, Jowett T, Ruiz de Elvira MC, Ekins RP, Rodeck CH - "Maturation of thyroid function in normal human fetuses" Clin Endocrinol 31:565-71 (1989)

Bergman I, Hirsch RP, Fria TJ et al - "Causes of hearing loss in the high-risk premature infant" Journal of Pediatrics 106:95-101 (1985)

Caldera R, Chavinie J, Laurent AM, Fermanian J, Tortrat D - "Preliminary study on transplacental transfer of fluoride. Apropos of 41 mother-infant couples" Gynecol Obstet Biol Reprod (Paris)15(6):731-5 (1986)

Hsu CH, Chang JH, Lee YJ, Hung HY, Kao HA, Huang FY - "Thyroid function in the sick very low-birth-weight infants" Chung Hua Min Kuo Hsiao Erh Ko I Hsueh Hui Tsa Chih 40(4):237-42 (1999)

Morreale de Escobar G, Ruiz de Ona C, Obregon MJ, Escobar del Rey F -"Models of fetal iodine deficiency" In: DeLong GR, Robbins J, Condliffe PG, eds. Iodine and the brain. New York: Plenum Press,187-201(1989)

Paneth, NS - "The Problem of Low Birth Weight" The Future of Children Vol. 5 No. 1 (1995)

Paneth, NS - "Recent trends in preterm delivery rates in the United States" INSERM Colloque: Prevention of Preterm Birth 138:15-30 (1986)

Paul DA, Leef KH, Stefano JL, Bartoshesky L - "Low serum thyroxine on initial newborn screening is associated with intraventricular hemorrhage and death in very low birth weight infants" Pediatrics 101(5):903-7 (1998)

Radunovic N, Dumez Y, Nastic D, Mandelbrot L, Dommergues M -"Thyroid function in fetus and mother during the second half of normal pregnancy" Biol Neonate 59:139-48 (1991)

Reuss ML, Paneth N, Pinto-Martin JA, Lorenz JM, Susser M -"The relation of transient hypothyroxinemia in preterm infants to neurologic development at two years of age" N Engl J Med 1334:821-7 (1996)

Reuss ML, Leviton A, Paneth N, Susser M -"Thyroxine values from newborn screening of 919 infants born before 29 weeks' gestation" Am J Public Health 87:1693-7.(1997)

Rooman RP, Du Caju MVL, Op De Beeck, Docx M, Van Acker -"Low thyroxinaemia occurs in the majority of very preterm newborns. Eur J Pediatr 55:211-5 (1996)

Thorpe-Beetson JG, Nicolaides KH, Felton CV, Butler J, McGregor AM -"Maturation of the secretion of thyroid hormone and thyroid stimulating hormone in the fetus" N Engl J Med 324:532-6 (1991)

Vulsma T, Gons MH, de Vijlder JJM -"Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis" N Engl J Med 321:13-6 (1989)

Riedel F, Burckhard von Stockhausen H, Ball P - "Diagnosis of thyroid function in premature infants in intensive care" Padiatr Padol 22(3):236-44 (1987)
"In 47 neonates (54%) T4 and fT4 were found to be low, including all infants under 30 weeks of gestational age and all ventilated infants. Screening TSH was not elevated but in some cases with iodine contamination."

Rooman RP, Du Caju MV, De Beeck LO, Docx M, Van Reempts P, Van Acker KJ - "Low thyroxinaemia occurs in the majority of very preterm newborns" Eur J Pediatr 155(3):211-5 (1996)
"In 13 infants (5%), transient hypothyroidism (low FT4 and TSH >20 mU/l on day 14) was found. In the remaining 250 patients FT4 on days 1 and 14 but not TSH correlated positively with GA. In neonates with a GA of 35-41 weeks, FT4 increased postnatally to levels within or above the normal adult range. In contrast, in the very preterm group (26-31 weeks) the already low FT4 levels declined to values significantly below the range observed in term neonates. A significant proportion of these neonates had FT4 levels within the hypothyroid range. There was no difference in thyroid function between neonates treated with povidone-iodine or chlorhexidine. CONCLUSION: Very preterm neonates have FT4 levels on day 14 that are much lower than is generally assumed while TSH remains in the normal range. We therefore propose to measure FT4 in all preterms with a GA below 33 weeks, during the 2nd week of life."

Mahachoklertwattana P, Sriphrapradang A, Supapannachart S, Pongsuwan A, Choubtum L, Rajatanavin R - "Thyroid function in healthy Thai neonates" J Med Assoc Thai 82 Suppl 1:S22-6 (1999)
"RESULTS: Mean serum T4 and FT4 levels rapidly increased after delivery to the maximum level at 1-3 days of age. Thereafter, they declined to a steady state level within 2-4 weeks. Mean serum T3 level was very low at birth. The concentration increased 3-5 times and reached a steady state levels within 1 week. In contrast, mean serum TSH declined from birth and the level at 1-3 days of agewas slightly less than that of the cord blood. It changed little after 3 days of age. Previous studies have shown a transient TSH surge in the first 24-48 hour of life. TSH surge was not apparent in our study because samples were not obtained from infants < 24 hours old. Therefore, if TSH is measured for screening of congenital hypothyroidism, samples should be obtained from umbilical cord or infants aged > 48 hours."

Smith C, Thomsett M, Choong C, Rodda C, McIntyre HD, Cotterill AM - "Congenital thyrotoxicosis in premature infants" Clin Endocrinol (Oxf) 54(3):371-6 (2001)
"Antenatal prediction of affected infants is imprecise; however, maternal history, coupled with a high maternal serum TSH receptor binding immunoglobulin index (TBII) predict adverse neonatal outcome. Mortality is reported to be as high as 25% in affected infants and wouldtherefore be expected to be higher in premature infants. This study illustrates that in sick, premature, extreme low birth weight (ELBW) or intrauterine growth retarded (IUGR) infants, the diagnosis maybe overlooked especially in the absence of antenatal risk assessment and management of thyrotoxicosis in this setting is complex..."
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