This study determined the effects of different iodine intake on the maternal and infant health and provide evidence for studying the RNI and UL of iodine in pregnant women.

1. The study of effect on mothers and their infants of the lack of iodine at different gestation in adequate iodine area.

   The purpose of this study was to detect the maternal thyroid function, growth and neuropsychological development of infants in different pregnancy women with diverse iodine intake levels, and to make a clear evaluation for the influence of iodine deficiency during different pregnancy by following up iodine suitable early pregnancy women and mild iodine deficient three pregnancy women as well as their infants.

2. The study of recommended iodine intake (RNI) for healthy pregnant women in three pregnancy.

   Different pregnancy women with different iodine intake levels were recruited and carried out iodine balance experiment in the case of not interfering with their diet. In addition, the iodine intake of the pregnant women when they reached "zero iodine balance" was calculated, that was EAR of iodine in pregnant women. In conclusion, the iodine balance experiment in pregnant women at different pregnancy improved the sample collection methods and evaluation criteria and was more scientific and reasonable than the classic iodine balance experiment.

3. The study of effect of different levels of high iodine exposure on pregnant women, delivery women and their infants.

In this study, we made a prospective study of the early pregnancy women and their infants exposed to different high iodine levels in high water iodine areas. At first we defined the effects of long-term iodine excess exposure on the health of the mother and the infants by combining with the reference index of the normal value of the thyroid function in different maternal and postpartum periods, the level of growth and development of the offspring and the assessment of the level of neuropsychological development. Furthermore the harmful effects of different high levels of iodine exposure on pregnant women was synthetically analyzed. This study obtained the safe intake level of iodine for pregnant women and provided scientific basis for the formulation of iodine UL in pregnant women in China.

1. The relationship between iodine deficiency during pregnancy and maternal offspring health

1. Screening of pregnant women with iodine deficiency:

   A prevalence survey of pregnant women was conducted in iodine-sufficient area, combined with the results of single spot urinary concentration, 24h urinary iodine concentration and thyroglobulin level, screening out pregnant women with iodine deficiency during first, second and third trimester of pregnancy. There are 60 pregnant women in each group. At the same time, 60 pregnant women with iodine-sufficient during early pregnancy were selected, and the total number of the four groups is 240.

2. Effects of iodine deficiency on pregnant women during different pregnancy:

   Pregnant women with iodine deficiency were gived nutritional guidance, and were advised to take iodine supplements. Follow-up with regularly collecting fasting venous blood, dried whole blood and single spot urine was conducted, in order to dynamically grasp the iodine nutritional status and thyroid function of pregnant women during different pregnancy, and clarify the influence of iodine deficiency on pregnant women in each group.

3. Effects of iodine deficiency on offspring during different pregnancy:

   The offspring of follow-up pregnant women were observed, collecting the heel blood at birth for measuring TSH, and performing physical examination. Assessment of neuropsychological development in offspring for two years after delivery was performed , in order to clarify the effects of iodine deficiency on the neuropsychological development of offspring in each group.

4. Statistical analysis:

Normally distributed variables were reported as the mean ± standard deviation, comparison between groups were analyzed with the use of t-test or analysis of variance (ANOVA), and Pearson linear correlation was used for correlation analysis; Urinary iodine level is lognormal distribution, so it was converted into logarithmic form and then analyzed. Non-normally distributed variables were presented as median and interquartile range. The Wilcoxon rank sum test was used for comparison between groups, and correlation analysis was performed using the Spearman rank correlation test. The chi-squared test was adopted for the comparison of enumeration data. P values below 0.05 was considered statistically significant.

2. Study the RNI of iodine on pregnant women during different pregnancy:

1. Screening of pregnant women during different pregnancy:

   A prevalence survey of pregnant women was conducted in iodine-sufficient area, based on 24h urinary iodine concentration, thyroglobulin level, related health check and medical history query results, screening out pregnant women who meet the requirements of this study during first, second and third trimester of pregnancy. Each group has 20 pregnant women, and the total number is 60.

2. Reasearch of the iodine EAR of pregnant women during different pregnancy:

   Iodine balance studies were performed on healthy pregnant women during first, second and third trimester of pregnancy to evaluate the daily iodine intake and excretion, including collecting and testing 24h dietary iodine intake, 24h urinary iodine and fecal iodine excretion of subjects. The daily respiratory iodine intake and excretion of subjects was assessed by measuring the iodine content in the air and exhaled breath. In addition, according to the positive correlation between iodine balance value and iodine intake, a scatter plot was drawn and curve fitting was performed. According to the results of iodine balance experiment, the iodine balance regression curves of first, second and third trimester of pregnancy were established , in order to determine the level of iodine intake when the pregnant women reach the iodine balance, which is the estimated average requirement (EAR) of pregnant women during different pregnancy.

3. Research of iodine RNI on pregnant women during different pregnancy:

Based on the obtained EAR values of iodine for different pregnancy and the 20% coefficient of variation (CV), according to the formula: RNI=EAR+2CV=1.4EAR, the iodine RNI values of pregnant women in different gestation were derived.

3. Study on the relationship between iodine excess and maternal offspring health and iodine UL of pregnant women

1. Prospective study:

   Pregnant women during early pregnancy who were exposed to different excessive water iodine intake were enrolled in a large-scale epidemiological prospective study, in order to assess the levels of iodine intake by collecting and testing random urinary iodine and 24h urinary iodine levels, and to detect the thyroid function indicators under different iodine intake levels to evaluate the health effects and harms of different high iodine intake on pregnant women. At the same time, the growth and development of the offspring and the level of neuropsychological development were evaluated to determine the long-term iodine excess exposure to the health of pregnant women and offspring.

2. Discussion on iodine UL of pregnant women:

   According to the urinary iodine level during pregnancy, the subjects were divided into groups with different iodine intakes, with the TSH abnormal rate of pregnant women > 5% and the increase of FT3/FT4 as the end point, comprehensively determining the harmful effects of different iodine intake on pregnant women and offspring, analyzing the iodine safety intake level suitabled for pregnant women, and exploring the iodine UL of pregnant women.

3. Statistical methods:

Epi-data was used to enter survey data. Univariate statistical analysis was used to analyze the differences in evaluation indicators between different iodine intake levels.. Multivariate statistical analysis methods were used to analyze the safety of each iodine intake level under multiple factors.

Inclusion Criteria:

• 1) aged between 18-35 years old; 2) singleton pregnancy; 3) Living in Tianjin or Shandong at least 5 years; 4) no history of any thyroid diseases; 5) no medication or supplementation of iodine.

Pregnant women were recruited at Tanggu Maternity Hospital and Maternal, Tianjin Child Health Care Service Center and the Maternal and Gaoqing Child Health Hospital, Shandong.