Maternal and neonatal outcomes and determinants of iodine deficiency in third trimester of pregnancy in an iodine sufficient area

Numerous physiologic changes in the production of thyroidal hormone during pregnancy can be observed; thus, an increase in the amount of iodine intake should be considered in order to meet the higher demands which are needed for the production of thyroxine (T4), transferring iodine to the fetus, and increasing the clearance of renal iodine by the mother [1‐3]. Due to the elevated production of thyroid hormone, the elevated excretion of renal iodine, and the requirements of fetal iodine, dietary iodine requirements are higher in pregnant adults than non-pregnant ones [4]. Mostly, to determine iodine status in populations, spot urinary iodine values are utilized. Since considerable diurnal and daily variations can be observed in urinary iodine excretion, urinary iodine concentrations (UICs) cannot be applied to detect specific individuals with iodine deficiency [5, 6]. Women enjoying suitable iodine intake before and during pregnancy have suitable intrathyroidal iodine stores, so they can easily adapt to the increased demand for thyroid hormone during pregnancy. Moreover, total-body iodine levels in these women will be constant during pregnancy [7]. Severe shortage of iodine in pregnant women may give rise to the increased rates of pregnancy loss, stillbirth, and increased perinatal and infant mortality or lead to fetal iodine deficiency damaging neurocognitive growth of the growing fetus [8‐11].

Mild to moderate iodine deficiency in pregnant women may expose them to the increased risk of the development of goiter [12] and thyroid disorders [13]. There is a relationship between low maternal UIC in pregnancy and diminished placental weight and neonatal head circumference [14].

The current study was an attempt to assess iodine nutritional status, its determinants and relationship with maternal and neonatal outcomes.

The data from 884 mothers in their third trimester of pregnancy who had attended medical centres to terminate their pregnancies are used in this study. The mean ± standard deviation of the ages of the participants was 29.14 ± 2.5. Besides, the age pregnancy in the attending mothers were 38.4 ± 7.3 weeks gestational age. The median (IQR) urinary iodine concentration in the third trimester was 176 (165–196) micrograms/litre. Table 1 demonstrates the demographic information of the participants.

The results showed that out of 884 participants 838 (94.8%) had a urinary iodine concentration of more than 150 micrograms/litre and 46 (5.2%) showed urinary iodine concentrations less than 150 micrograms/litre. Assessment of the demographic variables of the two groups showed a statistically significance difference regarding the type of pregnancy (Planned vs. unPlanned), the use of dietary complements during pregnancy, the weight gained during pregnancy, the timing between the two most recent pregnancies and mother’s level of education. The results of multivariate logistic regression analysis used to assess the effects of possible variables influencing low urinary iodine concentration in the third trimester of pregnancy are shown in Table 2.

The results of the aforementioned model show that every kilogram of weight gain during pregnancy has led to decreased odds of low urinary concentrations of iodine during the third pregnancy trimester of up to 13%. Moreover, with every one more year added to the time interval between the two most recent pregnancies led to a 20% of decrease of low urinary iodine concentrations. Besides, the odds of urinary iodine concentrations of lower the 150 micrograms/litre was 3.3 times more in those with unplanned pregnancies compared to those who experienced desired pregnancies. When assessed in accordance with the WHO criteria 46 of the participants (5.2%) had insufficient urinary iodine concentrations, 805 (91.06%) had adequate urinary iodine concentrations while 33 (3.73) showed more than adequate levels. There were no participants with urinary iodine concentrations higher than 500 micrograms/litre.

Assessing the neonatal complications showed that out of 884 neonates 29 (3.28%) suffered from severe neonatal hypothyroidism, 202 (22.85) had moderate hypothyroidism and the remainder had no dysfunction of the thyroid gland. The remainder of the maternal and neonatal complications are shown in Table 3.

This table demonstrates meaningful differences between the results of the univariate analyses concerning, preterm birth, NICU admission, neonatal hypothyroidism between the newborns of the mothers with urinary iodine concentrations higher than 150 micrograms/litre and those with lower concentrations. Besides, there was no significant relationship between the APGAR score at birth and urinary iodine concentration (0.11).

Table 4 shows the results of multivariate logistic regression performed to assess the relation of maternal urinary iodine concentrations and neonatal complications, adjusted for interfering variables. No relationship of significance was found between maternal urinary iodine concentrations and other outcomes.

After adjusting the effects of confounding vaiables, the above-mentioned models showed that iodine deficiency in pregnant women has a strong relation with NICU admissions of the neonates and preterm births, so much so that inadequate urinary iodine concentrations led to a 4.6 times increase in NICU admissions and a 3.3 times increase in preterm births (results of full models along with all adjusted variables are available upon the request). The one way analysis of variance (ANOVA) showed that there are no statistical differences (p = 0.47) between the mean maternal urinary iodine concentration in different maternal complications of pregnancy (Fig. 1). Figure 1 showed the differences between the mean level of UIC in different maternal complications.

Our study demonstrated a prevalence of maternal iodine deficiency of 5.2%, as is defined by WHO, with a mean urinary iodine concentration of 131.3 (130–137) micrograms/litre. The main influencing factors on maternal iodine deficiency in this study were weight gain during pregnancy, the interval between the most recent pregnancies, whether or not the pregnancy has been Planned, mother’s level of education, and nutritional complement consumption. The need for a NICU admission, preterm birth and neonatal hypothyroidism were significantly related with maternal iodine deficiency before delivery.

According to WHO, ICCIDD and UNICEF guidelines there is no need for iodine complements in countries that iodinated salt is consistently consumed [17]. However, studies have shown that even in countries with consistent iodinated salt use 50% of pregnant women have urinary iodine concentrations below 150 micrograms/litre [18]. A recent study in Iran showed that the Iranian community has enough iodine intakes and has all of the IDD criteria for optimum control of iodine deficiency [19]. However, the same study showed that nearly 5% of the pregnant women participating in that study suffered from iodine deficiency. The results of a study in 2016 on the third-trimester iodine concentrations in pregnant women showed a 26.4% of urinary iodine concentrations below 150 and 28.7% below 100 micrograms/litre [20]. As this study took place in Tehran and in a specific group of pregnant women (third trimester), the differences in the prevalence can be attributed to the sampling methods and a much wider study environment..

Zimmermann et al. [21] carried out a study in European countries and found that iodine intakes during pregnancy were sufficient in ten countries and in 21 countries were insufficient. The results of a study conducted on 1525 mother-child pairs in the Netherlands revealed that 12.3% pregnant women had UIC < 150 μg/g creatinine in early pregnancy [22]. In another study on pregnant women in the rural area of Bangladesh, the prevalence of inadequate iodine intake was reported to be 6% and excessive iodine intake was 10% [23]. Zoysa et al. [24] in their study depicted that the prevalence of trimester-specific insufficient intake of urinary iodine in line with the World Health Organization criteria were 34.7, 45 and 62.2% in first, second, and third trimesters, respectively. These results were very similar to those of the present study, but the prevalence in the third trimester was less prevalent in the current study. Also, in Rajput et al.’ study [25], the median urinary iodine less than 150 μg/L among euthyroid pregnant women were 43.82, 54.08, and 62.24% in first, second, and third trimesters, respectively. Not only excessive iodine intake but also its deficiency can enhance the risk of goitre; based on a meta-analysis, a U-shaped association between UIC and goitre prevalence among school-age children can be observed [26].

Iodine deficiency during pregnancy has been one of the major problems in public health that affects developed and developing countries [27]. The importance of this issue arises from the fact that it affects the health of the mother and child and increases the financial burden related to this condition worldwide [28]. With effective interventions such as iodinating the dietary salt, educating pregnant women and proper coordination between medical and health departments, this problem can be prevented [29, 30]. Defining the causative chain of iodine deficiency during pregnancy and factors affecting it are necessary in order to prevent maternal iodine deficiency. In our study, there was a 13% decline with every one-kilogram weight gain during pregnancy. It appears that weight gain, as a proxy of proper diet, has protective activity against iodine deficiency [1]. Besides, there were meaningful relations between timing interval between most recent pregnancies, the desirability of the pregnancy, use nutritional micronutrients before and during pregnancy and mother’s level education and urinary iodine concentration. In a study in Ethiopia age, multiparity and mother’s level of education were found to be significantly related to maternal iodine content during pregnancy [31]. In another study in China the type of dietary salt, maternal age, occupation, consumption of complementary micronutrients and seafood were found to affect urinary iodine meaningfully [32]. In another study by Dineva et al. seafood consumption, iodinated salt intake and maternal age were found to be defining factors in urinary iodine concentration of the mother [33]. However, this study did not find any relation of statistical significance between maternal iodine deficiency and maternal complications of the pregnancy. Trolinska et al. did not find a relationship between iodine levels during pregnancy and maternal complications of the pregnancy, however, they proposed a larger study to assess the relationship [34].

The World Health Organization suggested the use of 250 mcg of daily iodine during pregnancy and lactation, and the United States Institute of Medicine (IOM) suggested 220 mcg of daily iodine during pregnancy and 290 mcg of daily iodine during lactation [17, 35]. There are associations between iodine deficiency during pregnancy and some complications including congenital anomalies, stillbirth, abortion, impair neurological development of the fetus, and irreversible fetal brain damage [36‐39]. Geographic area, ethnicity, and different environmental factors affect the pattern of thyroid dysfunction. Thus, taking the importance of iodine in the health of the mother and the child into account, we must verify the urinary iodine status in various conditions.

Using a multivariate logistic regression in this study showed that neonate of mothers with urinary iodine levels below 150 micrograms/litre were 4.6 times more hospitalised in NICU and preterm outcome for the neonates of mothers with UIC below 150 micrograms/litre were 3.3 times more frequent in comparison with referent group. In a recent study in three major cities across the UK, researchers found no relation between iodine deficiency and low birth weight and preterm labour [40]. Walsh et al. did not find any relation between maternal low iodine intake and perinatal mortality and neural development of the neonates of these mothers [41].

Urinary iodine is considered as a non-invasive and efficient index for the population iodine status. Due to the fact that the majority of the absorbed iodine is excreted in the urine, urinary iodine can be regarded as a suitable indicator of recent iodine intake [42]. A single spot urine sample was used in this study. Single spot urine samples were recommended by WHO/UNICEF/ICCIDD for measuring the population iodine status [37]. Single spot urine samples in comparison with 24-h samples or multiple samples are easier in practice and based on a review, the results of spot urine samples are a valid indicator for measuring the population iodine status [43].

While this study with its large sample volume can be a good representation of the urban Tehran women, the existence of different racial minorities and ethnicities has created the need to repeat the study on other populations across the country. On the other hand, this study has focused on third-trimester mothers until delivery, while devising a study that includes the whole length of pregnancy can lead to a better assessment of the effects of maternal iodine concentrations during pregnancy on maternal and neonatal outcomes. Having had the thyroid function tests performed, we could have presented them as a complement to the current results.

This study shows that despite implementation of iodized salt strategies in Iran approximately 5% of the pregnant population suffer from perinatal urinary iodine concentrations below 150 micrograms/litre. Iodine deficiency complication in pregnant women can be decreased by appropriate planning for pregnancy such as the planning for pregnancy, proper time intervals between pregnancies (> 12 months to < 5 years) [44, 45], appropriate nutrition during pregnancy. Besides, controlling maternal urinary iodine concentrations is important to prevent neonatal complications such as preterm delivery and NICU admission. Monitoring of iodine concentration at the population level and iodine replacement may be needed during pregnancy.