Optimal Iodine Nutrition during Pregnancy, Lactation and the Neonatal Period

This Article

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Article Information:


Group: 2004
Subgroup: Volume 2, Issue 1, Winter
Date: March 2004
Type: Review Article
Start Page: 1
End Page: 12

Authors:

  • Delange F
  • International Council for Control of Iodine Deficiency Disorders (ICCIDD), Department of Pediatrics, University of russels, Brussels,

      Correspondence:

      Affiliation: International Council for Control of Iodine Deficiency Disorders (ICCIDD)
      City, Province: Department of Pediatrics, University of russels, Brussels
      Country:
      Tel: Belgium
      Fax:
      E-mail:

Abstract:


Iodine of maternal origin is required for brain development of the progeny during fetal and early postnatal life. Therefore, the iodine requirements of the mother are increased during pregnancy and lactation. This paper reevaluates the iodine requirements during pregnancy, lactation and the neonatal period and formulates original proposals for the median concentrations of urinary iodine indicating optimal iodine nutrition during these three critical periods of life. Based on an extensive and critical review of the literature on thyroid physiopathology during the perinatal period, the following proposals are made: the iodine requirements are 250-300 ug/day during pregnancy, 225-350 ug/day during lactation and 90 ug/day during the neonatal period. The median urinary iodine indicating optimal iodine nutrition during hese three periods should be in the range 150-230 ug/L, These figures are higher than those recommended so far by international agencies.

Keywords: Iodine;Nutrition;Pregnancy;Lactation;Neonatal Period;Median urinary iodine

Manuscript Body:


Introduction

The thyroid economy undergoes a series of metabolic changes during pregnancy and lactation.!" One of the factors involved in these changes is the increased requirement of iodine in the mother due to the transfer of thyroxine (T4) and of iodide from mother to fetus  during pregnancy and to the loss of iodide in breast milk during lactation. These two processes are required in order to ensure normal brain development and prevention of mental retardation in the offspring.5-10
The objectives of this paper are:
1. To review the data from the literature on the iodine requirements during pregnancy, lactation and the neonatal period.
2. To offer practical recommendations regarding the median concentrations of urinary iodine indicating optimal iodine nutrition during these critical periods of life.


Requirement of Iodine During Pregnancy and Lactation
The requirement of iodine is increased during pregnancy because of at least three factors: 1) There is an increased requirement of T4 in order to maintain a normal global metabolism in the mother. 2) There is a transfer of T4 and iodide from the mother to the fetus and 3) There is supposed to be an increased loss of iodide through the kidney due to an increase in the renal clearance of iodide.
Because of these three factors, the recommended dietary intake of iodine during pregnancy is higher than the value of 150 ug/day recommended for non-pregnant adults and adolescents.11, 12 Below this critical threshold of 150 ug/day, the iodine balance is negative during pregnancy.13 WHOfUNICEFIICCIDD recommend an iodine intake of 200 ug/day for pregnant women,11 i.e. a percentage increase of 33% over non-pregnant women.
The Institute of Medicine (10M) of the US Academy of Sciences recommends a higher intake of 220 ug/day, 12 i.e. an increase of some 47%, and other organizations recom- mend 175 to 230 ug/day, 14, 15


Increase in the T4 requirements
The daily requirement of T4 in order to maintain euthyroidism in hypothyroid women increases by 10 to 150% during pregnancy with a median increment of 40_50%.16-18This represents an additional dose of 75 to 150 ug Tz/day, i.e. 50 to 100 ug iodine.


Transfer of T4 and iodide from mother to fetus
The transfer of T4 from mother to fetus, including before the onset of fetal thyroid function, is not quantified but it is has been estimated that up to 40% of the T4 measured on cord at birth is still of maternal origin.8
The transfer of iodide is also difficult to quantify but considering that the iodine content of the fetal thyroid increases progressively from less than 2 ug at 17 weeks of gestation'19 up to 300 ug at term,20-23 that the T4 iodine at term probably averages 500 ~g24 and that the substitutive dose of T4 in hypothyroid neonates is 50-75 ~g/day,25, 26 it can be estimated that the transfer of iodide from mother to fetus represents some 50 ug/day. It has been estimated at 75 ug/day by the IOM.12


Increased renal clearance of iodide
It is often stated that the increase in iodine requirement during pregnancy is largely due to an increased loss of iodide through the kidney because of an increased renal clearance of iodide. This should decrease the serum concentration of plasma inorganic iodide, PII.27 -30 However, Liberman et al."  showed on the contrary that there is no significant decline in the PH during pregnancy. In addition, as shown by the data collected in Table 1 and already by Dworkin et al.,13 almost all studies on urinary iodine during pregnancy showed that, in a given environment, the urinary excretion of iodide is almost similar in pregnant and non-pregnant women and in the general population, irrespective of the status of iodine nutrition in the population. Only the studies conducted by the group of Smyth et a1.32,33in Ireland, the United Kingdom and Sri Lanka, by Kung et al.. in I-long Kong34 and perhaps by Hess et al. in Switzerland" have shown a clear-cut increase in the urinary iodine excretion during pregnancy. The resu lts reported for Switzerland by Brander et a1.36are difficult to interpret because of the surprisingly low value of the urinary iodine in the general population reported in this study as Switzerland is known to be iodine sufficient." On the contrary, some studies showed that urinary iodime decreases durm. g gestatio. n. 38-40It thus appears that the concept of systematically increased urinary loss of iodine during pregnancy is not firmly established.
Finally, it has to be underlined that no data are available on the possible storage and loss of iodide in the placenta itself.
Taking all these variables into consideration, it can be speculated that the additional requirement of iodine during pregnancy is at least 100-150 ug/day, i.e. an increment of almost 100% as compared to non-pregnant adults instead of the 33% proposed by WHOIUNICEF/ICCIDD.11 Consequently, the requirement of iodine during pregnancy is at least 250 ug/day, probably in the range of 250 to 300 ug/day, This figure is still higher than the figure of 220 ug/day proposed by the IOM,12 which did not take into account the increased requirement of T4 during pregnancy.
During lactation, considering that the iodine content of breastmilk in conditions of iodine sufficiency is in the range of 150-180 ug/L 41.42(Table 1) and that the milk production is from 0.5 to 1.1 liter per day up to the age of 6 months, the daily loss of iodine in human milk is estimated at some 75 to 200 ug/day. Consequently, the iodine requirement
during lactation is estimated at 225 to 350 ug/day. The slight difference, if any, as compared to the figure of 290 ug/day recommended by 10Mj?- results +r;rom more recent data on the iodine content of breast milk.41,42

Table 1. Comparison of the median or mean (in bold) urinary iodine (ug/L) in pregnant women and in the general population or in non-pregnant controls (publications 1990-2003)the general population or in non-pregnant controls (publications 1990-2003)

Country

General population or controls

n

S/C

Pregnant women

Country

General population or controls

n

S/C

Pregnant women

 

 

 

 

Trimester

Urinary iodine

 

 

 

 

Trimester

Urinary iodine

Countries with no iodine deficiency

 

 

 

 

 

UK33

73b

-

C

1

125b

Chile31

-

19

S

1

594a

 

 

-

C

2

170

 

 

 

 

2

469

 

 

-

C

3

147

 

 

 

 

3

786

France40

50-80a

306

S

1

50b

 

 

 

 

3 months PP

459

 

 

224

S

3

54

Iran43

193-312b

403

C

1-3

186-338b

Belgium38

50-75a

334

C

1-2

50b

Sweden77

-

51

S

1

180a

 

 

334

C

2-3

45

 

 

51

S

2

170

 

 

136

C

1

56b

 

 

51

S

3

145

 

 

133

C

2

50

Srilanka33

147b

-

C

1

181b

 

 

49

C

3

50

 

 

-

C

2

136

Denmark83

50a

26

S

2

51b

 

 

-

C

3

154

 

 

26

S

3

40

USA78

130

290

C

1-3

148

 

 

26

S

1 week PP

30

Switzerland35 (2000)

115b

511

C

2,3

138b

 

 

26

S

26 weeks PP

50

Scotland79

138b

433

C

 

 

 

 

 

 

 

51

Switzerland36 (1992)

91c

153

C

1-3

205a

Denrnark84

 

-

C

5 days PP

40c

 

 

31

C

1

267

Sudan55

76b

47

S

3

38b

 

 

56

C

2

206

 

 

47

S

3 months PP

51

 

 

66

C

3

172

 

 

47

S

6 months PP

30

 

 

15

S

1

325

 

 

 

 

 

 

 

 

15

S

2

166

 

 

 

 

 

 

 

 

15

S

3

183

 

 

47

S

9 months PP

63

Iodine deficient countries

 

 

 

 

 

New Zealand49

24-47a

35

S

Monthly during pregnancy and 3, 6 and 12 months PP

24-52a

Singapore34,80

98b

253

C

3

124b

 

 

 

 

 

 

 

 

230

S

1

107b

 

 

 

 

 

 

 

 

-

 

2

116

 

 

 

 

 

 

 

 

-

 

3

124

 

 

 

 

 

 

 

 

-

 

6 weeks PP

105

 

 

 

 

 

 

 

 

-

 

3 months PP

104

Italy85 (2002)

Marginal ID

67

C

1,2

74c

Sicily (Italy)54,81

46a

10

S

1,2,3

33a

 

 

 

 

 

 

Turkey82

85a

80

S

1-3

91a

Italy86 (1991)

Marginal ID

18

C

3

50a

Ireland32,33

70b

38

S

1

135b

 

 

 

 

 

 

 

 

38

S

2

125

Germany87

Mild 1D

70

S

1

55c

 

 

38

S

3

122

 

 

70

S

11 days PP

50

 

 

108

C

6 weeks PP

70

Hungary88

Mild 1D

119

C

1,2,3

57c

n: number of subjects; SIC: Sequential (S) or cross-sectional study(C); 1,2,3: Trimesters of pregnancy; PP: Postpartum; 10: Iodine deficiency; 100 ug/L = 0,78 umol/L * ug/day; t ug/L; t ug/g creatinine

 

Level of Urinary Iodine Indicating Optimal Iodine Nutrition During Pregnancy and Lactation
Considering that most (above 90%) of the iodine absorbed in the body eventually appears in the urine, urinary iodine excretion is a good marker of a very recent dietary iodine intake." Therefore, a median urinary iodine in the general population varying from 100 to 199 ug/L is considered as an indicator of an adequate iodine intake and an optimal status of iodine nutrition." As the iodine requirement is increased during pregnancy, the median urinary iodine during pregnancy indicating optimal iodine nutrition needs to be higher than 100 ug/L. Table 2 compares the data available in the literature on urinary iodine in pregnant women and in the general population. In this Table, the countries are arbitrarily listed on the basis of roughly decreasing iodine intake of the general population,  starting with Chile3! which is exposed to iodine excess based on the WHO/UNICEF/ICCIDD criteria,11 down to countries where different degrees of mild to moderate iodine deficiency have been documented. As indicated earlier, there is a striking similarity between the urinary iodine in pregnant women and in the global population except in the reports published by Smyth et a1.32,33in which the values during pregnancy are systematically markedly higher than in non-pregnant controls. Therefore, it appears difficult to derive a reference value for urinary iodine during pregnancy and lactation from the data collected in countries with no  iodine deficiency as this value varies from 800 ug/L in Chile3! to 138 ug/L in Switzerland, where the median urinary iodine in the  general population is barely above the lower limit of normal.35

 

 

Table 2. Selective examples of the iodine content of breastmilk .a

Countries

Medians or means (ug/L)

No iodine deficiency

 

Korea

892

Japan

661

 

33-385

USA

146

 

168

 

124

 

145

 

145

Sweden

93

 

90

 

70

Switzerland

78

Mild to moderate iodine deficiency

 

Germany

93

 

15-150

Belgium

95

France

82

 

77

 

74

 

70

Spain

108

 

77

United Kingdom

 

Hungary

64

Guatemala

60

Philippines

57

Thailand

50

Italy (Sicily)

43

Severe iodine deficiency

 

Marocco

27

Ethiopia

5-16

 

64

Congo

15

 

13

a Compiled from Sernba-Delange 200141 and Dorea 2002,42 where detailed data and references are to be found.

 

 

In Iran, where iodine deficiency has been successfully eliminated,43 themedian urinary iodine in pregnant women in four different cities varies from 186 to 403 ug/L and is almost entirely similar to the values found in the general population in the same cities.44 The values during pregnancy are of the same order of magnitude as the 250-300 ug/day recommended as intake based on metabolic studies. And yet, in spite of these relatively elevated values, Azizi et a1.44 underline that with such medians, some 8% of the values are still below the critical threshold of 100 ug/L for non-pregnant adults. They suggest that the recommended dietary intake of iodine during pregnancy should be still higher. It has to be recognized however, that this figure of 8% corresponds almost exactly to the percentage of values (7.2%) below the cut-off point of 50 ug/L indicating at least moderate iodine deficiency in a general population when the median is between 100 and 200 ~g/L.45 This percentage is considered as acceptable" considering the well documented day to day variability of urinary iodine, including during pregnancy.46.49
From these different considerations, it can be concluded that the recommended median value for urinary iodine during pregnancy and lactation has to be based on theoretical grounds. If, as in non-pregnant adults, the recommended median (100 to 200 ug/L) corresponds to the recommended intake (150 ug/day), the median urinary iodine during pregnancy and lactation should be in the range 225-350 ug/L, If, on the contrary, this recommended median was based on a recommended intake of 225-350 ug/day and a mean daily urinary volume of 1.5 L'day, it should be in the range of 150-230 ug/L, i.e. only slightly higher than the value recommended for non-pregnant adults.
It has to be recognized that thyroid function and volume remained perfectly normal during pregnancy in Iran'" as well as in Chile31 for values still twice higher, which strongly suggests that these values are not excessive and potential sources of side effects.5o,51 On the contrary, in all countries submitted to some degree of iodine deficiency where the point has been investigated, thyroid function is critically impaired during pregnancy and in the neonate even when it remains normal in the general population.52-56 The anomalies include progressive decrease in free T4 and increase in serum Tg and thyroid volume. The alterations are usually still more marked in the neonates than in the mothers.f They are at least partly corrected by iodine supplementation during pregnancy and lactation.57, 58 In summary, it appears that the recommended dietary intake of iodine during pregnancy (250-300 ~g/L) and lactation (225-350 ~g/L) should be higher than what has been proposed earlier, especially by WHOIUNICEF/ICCIDD,11 a nd that a median urinary iodine indicating optimal iodine nutrition during pregnancy and lactation could be in the range 150-230 ug/L.


Requirement of Iodine in Neonates
As underlined by the IOM,12 no functional criteria of iodine status have been demonstrated that reflect response to dietary intake in infants. Consequently, the recommended intake of iodine in neonates reflects the observed mean iodine intake of young infants exclusively fed human milk in iodine replete areas. Up to the late sixties, the iodine content of breast milk in such areas was usually aroun d 50 ug/ILL.41, 42, 59Consi ideerning a daaiilvy imtake of breast milk of some 0,6 to 1 liter in the neonate and young infant, the assumption was that an infant may get 30 to 50 ug/day iodine in milk from an adequately fed mother.60 However, it is well established that the iodine content of breastmilk is critically influenced by the dietary intake of the pregnant and lactating mother and of the general population and that much higher figures have been recorde more recently. 41 ,42 Thus, agam on theoretical grounds, the requirement of io dine in neonates was evaluated from metabolic studies by determining th e value which resulted in a situation of positive iodine balance, which is required in order to insure a progressively increased intrathyroidal iodine pool in the growing young infant. Such iodine balance studies were conducted in healthy preterm and in fullterm infants aged approximately one month in Belgium, a country with mild iodine deficiency." These studies, reported extensively elsewhere.I" indicate that the iodine intake required in order to achieve a positive iodine balance is at least IS ug/kg/day in full terms and 30 ug/kg/day in preterms. This corresponds approximately to 90 ug/day and is consequently twice higher than the 1989 US recommendations of 40-50 ug/day'" but is still a bit lower than the present recommendation of 110 ug/day by the IOM.12


Level of Urinary Iodine Indicating Optimal Iodine Nutrition in Neonates
Table 3 summarizes the data from the literature on the median urinary iodine in neonates in countries or areas with iodine sufficiency and with different degrees of iodine deficiency. There is a large variability in the results even in iodine sufficient countries, where they vary from 736 ug/L in Hokkaido, Japan,63 which is submitted to an extremely high iodine intake?64 to 96 ug/L in Stockholm.65

 

Table 3. Median or mean (in bold) urinary iodine (UI) concentrations (ug/L) in neonates in iodine sufficiency and iodine deficiency

Countries and loca-tion

n

Gestational age

Urinary io-dine (/lg/L)a

Range

Reference

Japan

118

FT Breastfed

736

 

Haradaetal.1994 63

Hokkaido

182

FT Bottlefed

521

 

 

United States

 

 

 

 

 

Boston

?

PT ≤36 weeks

148

16-510

Brown et al. 1997 89

Torrance

50

FT

921

 

Delange et al. 1984 90

Canada

 

 

 

 

 

Toronto

81

FT

148

 

Delange et al. 1986 72

The Netherlands

 

 

 

 

 

Rotterdam

64

FT

162

 

Delange et al. 1986 72

Amesterdam

36

FT

150

 

Bakker et al. 1999 91

Sweden

 

 

 

 

 

Stockholm

39

FT

112

 

Delange et al. 1986 72

Stockholm

61

FT

96

 

Heidemann et al. 1984 65

Mild to moderate iodine deficiency

 

 

 

 

 

Germany

 

 

 

 

 

Nine towns 198

461

FT

12-29

 

Heidemann et al. 1984 65

Berlin West 1985

87

FT

28

 

Delange et al. 1986 72

Kiel1992

50

FT

33

 

Grebe et al 1993 92

Frankfurt 1992

21

FT

37

 

Bohles et al. 1993 93

Berlin West 1994

177

FT

31

 

Gruters et al. 1995 94

Berlin East 1994

213

FT

44

 

Grilters et al. 1995 94

Gottingen 2000

22

FT

50

 

Roth et al. 2001 95

Heidelberg 1999

32

FT

95

 

Klett et al. 1999 96

Belgium

 

 

 

 

 

Brussels 1983

103

PT+FT

35

10-150

Delange et al. 1984 90

Brussels 1985

196

FT

48

 

Delange et al. 1986 72

Brussels 2000

90

FT

86

 

Ciardelli et al. 2001 97

Italy

 

 

 

 

 

Rome 1985

114

FT

47

 

Delange et al. 1986 72

Catania 1985

14

FT

71

 

Delangeetal.1986 72

?towns 1995

195

FT

56

10-950

Rapa er al. 1996 98

Milano 1995

18

PT 30 weeks

123

 

Parra vicini et al. 1996 99

Torino

9

FT

67

10-162

Bono et al 1998 100

France

 

 

 

 

 

Lille 1985

82

FT

58

 

Delange et al. 1986 72

Toulouse 1985

37

FT

29

 

Delange et al. 1986 72

Ireland

 

 

 

 

 

Belfast 1993

?

FT

100

 

Barakat et al. 1994 101

Israel

 

 

 

 

 

Tel Aviv 1996

55

PT 30-31 wks

 

55-100

Linder et al. 1997 102

Czech Republic

 

 

 

 

 

Prague 1998

50

FT

79

 

Hnikova et al. 1999 70

Prisbram 1998

50

PT

78

 

 

Hungary

 

 

 

 

 

Budapest 2002

55

FT

35

 

Peter et al. 2003 103

Gyor 2002

65

FT

57

 

 

Miskole 2002

54

FT

59

 

 

Nyiregyhaza

35

FT

75

 

 

Severe iodine deficiency

 

 

 

 

 

Gottingen 1985

81

FT

15

 

Delange et al. 1986 72

Heidelberg 1985

39

FT

13

 

Delange et al. 1986 72

Freiburg 1985

39

FT

11

 

Delange et al. 1986 72

n: number; FT: Full-term, PT: Pre-term
a Values are medians or means (bold).

 

Therefore, again, the data from the literature do not help substantially in identifying the optimal urinary iodine level and this level has also to be defined on the basis of theoretical considerations. Based on an iodine requirement of 90 ug/day and a volume of urines in neonates of some 0.4 to 0.5 liter/day, 66 the median urinary iodine indicating optimal iodine nutrition in neonates can be evaluated at some 180 to 225 ug/L when ignoring the fact that the iodine balance of the neonate should also be positive in order to constitute the iodine stores of the thyroid. This level, which is higher than the one recommended for schoolchildren and adults, is indeed observed when healthy young infants are supplemented with a daily are supplemented with a daily physiological dose of 90 ug/day.67 It is also the value reported in some parts of the United States suppose d to bee 1i0dmi e suffrcrent.68, 69 0n the other hand, studies reported in the literature in which urinary iodine has been determined simultaneously in mothers at delivery and in neonates duurning the fiirst days 0f life.39, 70, 71in- dicate that these levels are almost similar in mothers and neonates. Therefore, based on the considerations on optimal urinary iodine in pregnant mothers, it can be extrapolated that the level in neonates should be around 150 to 230 ug/L, which is almost similar to the figure derived from the iodine requirements of the neonates.
The data reported from neonates in conditions of mild, moderate and severe iodine deficiency are indeed much lower than normal, down to less than 20 ug/L in Gerrnany72 before the partly successful implementation of a program of voluntary salt iodization.73 It is particularly interesting to observe that this level progressively increased with time in Germany and in Belgium for example following the implementation of programs of iodine supplernentation73, 74 and silent iodine prophylaxis, respectively.75
In summary, the recommended dietary intake of iodine in neonates is 90 ug/day and the median urinary iodine to be expected when this requirement is met is 180 to 225 11g/L , a value almost similar to the one recommended for pregnant women.

Conclusion

Pregnant and lactating women and neonates are the main targets to the effects of iodine deficiency because of the impact of maternal, fetal and neonatal hypothyroxinemia on brain development of the progeny5-10 Therefore, any program of salt iodization in a population should pay special attention to these particular groups. And yet, no firm recommendations are presently available on the level of urinary iodine indicating optimal iodine nutrition in these groups. This paper constitutes an attempt to propose such normative values. It appears that an extensive review of the literature based in particular on the evaluation of urinary iodine in these groups in iodine replete populations does not offer clear answers to the questions because of the variability of individual results even in iodine sufficient countries. One first conclusion of this paper is thus that more accurate data should be collected in iodine sufficient countries, comparing systematically and at the same time the urinary iodine in the general pop ulation, in non-pregnant adults, schoolchildren, pregnant and lactating women and in neonates.
However, based on the data from the literature and on metabolic considerations, it is proposed that the recommended dietary intake of iodine is 250-300 ug/day for pregnant women, 225-350 ug/day for lactating women and 90 ug/day for neonates and young infants. It is proposed that the median level of urinary iodine indicating optimal iodine nutrition during pregnancy and lactation is in the range 150-230 ug/L. Recommendations for neonates are still more difficult not only because of the lack of accurate data but also because the neonate is not in a steady state regarding iodine metabolism and that urinary iodine probably represents a relatively imprecise estimation of the iodine intake. How- ever, based on the data from the literature and on theoretical considerations, it can be concluded that the median urinary iodine indicating optimal iodine nutrition in the neonate should be in the same range of 180-225 ug/L, almost similar to the value recommended for their mothers.
 It has to be emphasized again that these levels are higher than the ones recommended for the general population and are supposed to be potentially responsible for side effects in adolescents and non-pregnant adults.11
Therefore, special attention should be focused on iodine supplementation and monitoring urinary iodine during pregnancy and possibly during the neonatal period in addition to programs of Universal Salt Iodization in countries with iodine deficiency.58 This recommendation is particularly relevant considering that pregnant and lactating women and neonates have usually a limited access to salt in general and, consequently, to iodized salt, and that even in the United States, where the status of iodine nutrition is adequate in the general population (median urinary iodine of 145 ug/L), 6.7% of the pregnant women are still affected by moderate to severe iodine deficiency (urinary iodine below 50 Ilg/L).76 

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