Iodine status in a large Canadian pregnancy cohort

OBJECTIVE:

Adequate iodine intake in pregnancy is essential for fetal neurodevelopment. Thirty-two percent of non-pregnant Canadian women of childbearing age were reported to have inadequate iodine intake.¹ Because iodine requirements increase during pregnancy, pregnant women in Canada may be at risk for iodine deficiency.

Median urinary iodine concentration (UIC) from spot samples is used to establish overall population iodine status.² UIC from a single spot sample cannot be used to assess the prevalence of inadequate or excessive iodine intake because of the large within-person (day-to-day) variability in iodine intake.² With 2 urine samples from the same individual, iodine intakes (calculated from UIC) can be adjusted for within-person variation. The resulting “usual” iodine intakes can be used to calculate the percentage of the population with intake below the estimated average requirement (EAR) (<160 μg/d in pregnancy, ie, inadequate) and above the tolerable upper intake level (UL) (1100 μg/d, ie, excessive) using the cutpoint method.² Iodine intakes are considered satisfactory when almost all (~97%) of the population falls between the EAR and the UL.² Whereas UIC is a measure of recent iodine intake, thyroglobulin (Tg) is a measure of longer-term iodine status.²

This study assessed iodine status of pregnant women in Canada by using median UIC and plasma Tg, and estimating the prevalence of inadequate or excessive iodine intake with the EAR/UL cut-point method.

STUDY DESIGN:

Pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort were recruited from prenatal clinics in 10 Canadian cities between 2008 and 2011.³ Women were eligible if they were fluent in English or French, aged ≥18 years, planned to deliver locally, and agreed to provide a cord blood sample. Women with multiparous pregnancies, known fetal abnormalities, medical complications, or those using illicit drugs during pregnancy were excluded. Women with UIC measured in trimesters 1 (T1) and 2 (T2) were included in this study (n=1552).

Plasma Tg was measured in T1 and urine iodine and creatinine (Cr) concentrations were measured in T1 and T2. Daily iodine intake was estimated using the following formula that corrects for urine dilution:

$$\begin{array}{l}Iodineintake\left(\frac{\mu g}{day}\right)\\ =UIC/Cr\left(\frac{\mu g}{mg}\right)\times \frac{24-hourCrexcretion\left(\frac{mg}{day}\right)}{0.92}\end{array}$$

Here, 0.92 is the urinary iodine excretion rate.² Predicted 24-hour urine Cr was estimated using an established equation for participants aged ≥18 years¹:

$$\begin{array}{c}24-\text{hour}\text{Cr}\text{excretion}\left(\frac{\text{mg}}{\text{day}}\right)\\ =1.63\times [140-\text{age}(\text{y})]\left[\text{weight}{(\text{kg})}^{1.5}\times \text{height}{(\text{cm})}^{0.5}\right]\\ \times [1+(0.18\times \text{race})]\\ \left[1.429-0.0198\times \text{BMI}\left(\frac{\text{kg}}{{\text{m}}^2}\right)\right]÷1000\end{array}$$

Maternal age, height, weight, and body mass index (BMI) at T1 were used. BMI was calculated using measured weight and height. Maternal self-reported race was coded as Black race=1 and other race=0.

The Simulating Intake of Micronutrients for Policy Learning and Engagement (SIMPLE) macro was used to estimate the prevalence of iodine inadequacy or excess by the EAR/UL cut-point method.⁴ Linear regression was used to examine associations of World Health Organization−informed categorical measures² of UIC and Cr-corrected UIC (UIC/Cr) with Tg, prenatal multivitamin use, and prepregnancy BMI. Logistic regression was used to examine associations between Tg quartiles (low: <9.77 μg/L; low-mid: ≥9.77 to <14.85 μg/L; high-mid: ≥14.85 to <22.38 μg/L; high: ≥22.38 μg/L) and prenatal multivitamin use.

RESULTS:

Women were aged 32.3±5.0 years at enrollment, 86% identi_fied as White, 81% were born in Canada, and 88% reported taking a prenatal multivitamin (Table S1). Table 1 shows median UIC, UIC/Cr, daily iodine intake, and Tg levels. Tg ranged from 3.2 to 56.8 μg/L (2.5th−97.5th percentiles). Median usual iodine intake (adjusted for within-person variation) was 418 μg/d (interquartile range, 323−537), and the percentages of women with usual iodine intake <EAR and >UL were 0.79% and 0.36%, respectively. Higher Tg was observed in women with lower UIC/Cr. Prenatal multivitamin use was more likely in those with higher UIC/Cr, whereas those who did not use multivitamins were more likely to have low UIC or UIC/Cr. Lower and higher prepregnancy BMI was associated with higher and lower UIC/Cr, respectively (Table 2). Women in the lowest, compared with the highest Tg quartile, were more likely to use a prenatal multivitamin (odds ratio, 1.9; 95% confidence interval, 1.1 −3.2).

TABLE 1.

Distribution of unadjusted and creatinine-adjusted urinary iodine concentration, daily iodine intakes, and thyroglobulin by trimester 1 and trimester 2 and averaged across trimesters^a

Iodine status measure	N	Meanb (95% CI)c	SD	25th percentile (95% CI)	50th (median) percentile (95% CI)	75th percentile (95% CI)
UIC (μg/L)
Trimester 1	1552	211 (201–221)	186	75	152	291
Trimester 2	1552	232 (222–242)	202	89	177	316
Average	1552	222 (214–230)	222	108	184d	297
UIC/Cr (μg/g)
Trimester 1	1542	322 (311–334)	228	166	271	432
Trimester 2	1547	377 (360–405)	459	198	311	464
Average	1537	350 (338–367)	272	212	302	431
Iodine intake (μg/d)
Trimester 1	1542	417(402–431)	295	207	342	552
Trimester 2	1547	488 (466–529)	605	256	396	597
Average	1537	452 (438–475)	357	265	391	565
Plasma Tg (μg/L) in Trimester 1e	1147	18.3 (16.5–19.1)	14.6	9.7	14.7	22.3

CI, confidence interval; Cr, creatinine; SD, standard deviation; UIC, urinary iodine concentration; UIC/Cr, urinary iodine concentration adjusted for creatinine.

^aTrimester 1: weeks of gestation=11.6±1.5; trimester 2: weeks of gestation=19.1±2.3

^bArithmetic mean

^cBias corrected and accelerated (BCa method) using 95% CI bootstrapping

^dMedian UIC was within the World Health Organization reference range for adequate population iodine in pregnancy: 150–249 μg/L

^eWomen who were Tg antibody (Ab)- and/or thyroid peroxidase Ab-positive (n=342) were excluded from all Tg analyses.

TABLE 2.

Covariate-adjusted associations between urinary iodine levels and plasma thyroglobulin, prenatal multivitamin use, and prepregnancy body mass index

Categorical urinary iodinea	Plasma Tgb,c			Prenatal multivitamind			Prepregnancy BMIe
	N	B	95% CI	N	aOR	95% CI	n	B	95% CI
UIC (μg/L)
<150	509	−0.018	−0.10 to 0.07	554	0.63f	0.46–0.89f	555	−0.15	−0.73 to 0.43
150–499	466	Ref		762	Ref		762	Ref
≥500	82	−0.048	−0.21 to 0.11	82	1.88	0.74–4.78	82	1.19	−0.03 to 2.41
UIC/Cr (μg/g)
<150	221	0.15f	0.05–0.26f	151	0.36f	0.24–0.54f	151	1.38f	0.47–2.29f
150–499	638	Ref		1006	Ref		1007	Ref
≥500	197	0.013	−0.10 to 0.12	230	2.70f	1.43–5.12f	230	−2.01f	−2.77 to −1.26f

aOR, adjusted odds ratio; B, unstandardized Beta coefficient; BMI, body mass index; CI, confidence interval; Tg, thyroglobulin; UIC, urinary Iodine concentration; UIC/Cr, urinary iodine concentration adjusted for creatinine.

^a<150 μg/L (μg/g)=low iodine range; 150–499 μg/L (μg/g)=mid iodine range; ≥500 μg/L (μg/g)=high iodine range;

^bAssociations between UIC or UIC/Cr with natural log-transformed Tg were examined using trimester 1 data;

^cAssociations adjusted for maternal age, prepregnancy BMI, trimester 1 smoking, and ethnicity (defined as White vs non-White). Women who were Tg antibody (Ab)- and/or thyroid peroxidase Ab-positive (n=342) and had a known thyroid condition (n=69) were removed from the analyses;

^dAssociations adjusted for maternal age, prepregnancy BMI, trimester 1 smoking, and ethnicity, excluding women with a known thyroid condition;

^eAssociations adjusted for maternal age, trimester 1 smoking, and ethnicity, excluding women with a known thyroid condition;

^fSignificant associations (P<.05).

CONCLUSION:

Women in this large Canadian pregnancy cohort had sufficient iodine intakes. In a Michigan pregnancy cohort, 23% of women were reported as having inadequate iodine intakes.⁵ Notably, that study did not adjust for urine dilution or use the appropriate EAR (in μg/d), which likely resulted in an overestimation of the prevalence of deficiency.² The low prevalence of inadequate iodine intake in our cohort is likely explained by the use of prenatal multivitamins containing iodine. Given our large sample size, the reported Tg range informs a normal reference range for pregnant women. Results from this study support a recommendation that women who could become pregnant or who are pregnant take a daily prenatal multivitamin containing iodine.