Moderate-to-Severe Iodine Deficiency in the "First 1000 Days" Causes More Thyroid Hypofunction in Infants Than in Pregnant or Lactating Women.

Background: Iodine deficiency early in the life cycle-the "first 1000 days"-can cause hypothyroidism and irreversibly impair neuromotor development. However, the relative vulnerability among women and infants during this critical period is unclear, making it difficult for country-based programs with limited resources to prioritize their iodine interventions.Objective: Our aim was to determine the prevalence of thyroid hypofunction in women and infants living in an area of moderate-to-severe iodine deficiency.Methods: In a cross-sectional survey in Morocco, we measured urinary iodine concentrations (UICs) and concentrations of thyroid-stimulating hormone (TSH) and total or free thyroxine (TT4 or fT4, respectively) in women of reproductive age (n = 156), pregnant women (n = 245), and lactating women (n = 239) and their young infants (n = 239). We calculated daily iodine intakes and measured iodine concentrations in breast milk and household salt. We compared the incidence of hypothyroidism between the 3 groups of women and with the infants.Results: Women of reproductive age, pregnant women, and lactating women had median (IQR) UICs of 41 (29-63), 32 (17-58), and 35 (19-62) µg/L; and estimated iodine intakes were ∼60%, 22%, and 26% of Recommended Nutrient Intakes (RNIs). The infants' median UIC was 73 (28-157) µg/L, which was greater than for all 3 groups of women (P < 0.001), and their dietary intakes were 27% of the RNI. The prevalence of hypothyroidism was not significantly different between the 4 groups, whereas the prevalence of hypothyroxinemia was higher in infants (40%) than in the 3 groups of women (11-14%) (P < 0.001). The median breast-milk iodine concentration was 42 (26-81) µg/L. Only 6% of salt samples were adequately iodized to a concentration of ≥15 ppm; 54% were inadequately iodized and 40% contained no measurable iodine.Conclusions: In an area of moderate-to-severe iodine deficiency, the prevalence of thyroid hypofunction is ∼4-fold higher in young infants compared with the 3 groups of women, suggesting that, in the "first 1000 days," infants are more vulnerable than their mothers and that programs should prioritize iodine prophylaxis for this group.

Breast Milk Iodine Concentration Is a More Accurate Biomarker of Iodine Status Than Urinary Iodine Concentration in Exclusively Breastfeeding Women.

Background: Iodine status in populations is usually assessed by the median urinary iodine concentration (UIC). However, iodine is also excreted in breast milk during lactation; thus, breast milk iodine concentration (BMIC) may be a promising biomarker of iodine nutrition in lactating women. Whether the mammary gland can vary fractional uptake of circulating iodine in response to changes in dietary intake is unclear.Objective: We evaluated UIC and BMIC as biomarkers for iodine status in lactating women with a wide range of iodine intakes.Methods: We recruited 866 pairs of lactating mothers and exclusively breastfed infants from 3 iodine-sufficient study sites: Linfen, China (n = 386); Tuguegarao, Philippines (n = 371); and Zagreb, Croatia (n = 109). We also recruited iodine-deficient lactating women from Amizmiz, Morocco (n = 117). We collected urine and breast milk samples and measured UIC and BMIC.Results: In the 3 iodine-sufficient sites, a pooled regression analysis of the estimated iodine excretion revealed higher fractional iodine excretion in breast milk than in urine at borderline low iodine intakes. In contrast, in the iodine-deficient site in Morocco, a constant proportion (∼33%) of total iodine was excreted into breast milk.Conclusions: In iodine-sufficient populations, when iodine intake in lactating women is low, there is increased partitioning of iodine into breast milk. For this reason, maternal UIC alone may not reflect iodine status, and BMIC should also be measured to assess iodine status in lactating women. Our data suggest a BMIC reference range (2.5th and 97.5th percentiles) of 60-465 µg/kg in exclusively breastfeeding women. This trial was registered at clinicaltrials.gov as NCT02196337.

Iodine Supplementation Decreases Hypercholesterolemia in Iodine-Deficient, Overweight Women: A Randomized Controlled Trial.

BACKGROUND: In iodine deficiency, thyrotropin (TSH) may increase to stimulate thyroidal iodine uptake. In iodine-sufficient populations, higher TSH predicts higher total cholesterol. Whether higher TSH caused by iodine deficiency affects serum lipids is uncertain. OBJECTIVE: Our aim was to determine if iodine repletion decreases serum TSH and improves the lipid profile. METHODS: In this randomized controlled intervention, iodine-deficient, overweight or obese Moroccan women (n = 163) received 200 µg oral iodine or a placebo daily for 6 mo. Main outcomes were serum TSH and plasma total and LDL cholesterol. Secondary outcomes included thyroid hormones and measures of lipid and glucose metabolism and urinary iodine concentration (UIC). Data were compared by using mixed-model analysis. RESULTS: In the intervention group, median UIC increased from 38 (95% CI: 34, 45) µg/L to 77 (95% CI: 59, 89) µg/L (P < 0.001). After 6 mo of intervention, TSH was 33% lower in the treatment group than in the placebo group (P = 0.024). The triiodothyronine (T3) to thyroxine (T4) ratio and thyroglobulin decreased with treatment [-15% (P = 0.002) and -32% (P < 0.001), respectively], whereas T4 concentrations were higher in the treatment group (P < 0.001). Total cholesterol in subjects with elevated baseline cholesterol (>5 mmol/L) was reduced by 11% after the intervention (P = 0.034). At 6 mo, only 21.5% of treated women remained hypercholesterolemic (total cholesterol >5 mmol/L) vs. 34.8% of controls (baseline: 44.2% in the intervention and 36.8% in the control group; P = 0.015). The reduction in the prevalence of elevated LDL cholesterol (>3 mmol/L) in the intervention group (50.6% to 35.4% compared with 47.4% to 44.9% in the control group) was not significant (P-interaction = 0.23). CONCLUSIONS: Our findings suggest that moderate to severe iodine deficiency in overweight women elevates serum TSH and produces a more atherogenic lipid profile and that iodine supplementation in this group reduces the prevalence of hypercholesterolemia. Thus, iodine prophylaxis may reduce cardiovascular disease risk in overweight adults. This trial was registered at clinicaltrials.gov as NCT01985204.

Neonatal necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a gastrointestinal disease that mostly affects premature infants. It involves infection and inflammation that causes destruction of the bowel. Although it affects only 1 in 2,000 to 4,000 births, or between 1 and 5% of neonatal intensive care unit admissions, NEC is the most common and serious gastrointestinal disorder among hospitalized preterm infants. We present a very representative abdominal X-ray of this disease.

Harlequin ichthyosis.

A 2-hour-old newborn boy hospitalized in the neonatal intensive care unit was examined for unusual cutaneous lesions. He had firm plaques covering his body, with fissures especially in flexural areas. Other remarkable findings included edematous hands and feet, ectropion, eclabium, and contractures (Figure). Topical emollients and etretinate were advised, but the newborn died a few hours later. The parents were first-degree relatives. There was no family history of similar lesions. On the basis of clinical features, the diagnosis of harlequin ichthyosis was made.

Congenital chylothorax.

Although pleural effusion is a rare cause of respiratory distress in newborns, being familiar with this disease is very important because of the generally favorable prognosis when the diagnosis is done early and therapy is prompt. We report a case of a full-term baby diagnosed with respiratory distress after 1 week of life. An X-ray of his chest showed a left pleural effusion. Moreover, a thoracentesis combined with a biochemical study of the pleural fluid confirmed the diagnosis of chylothorax. In our case, the conservative therapy was successful. The baby was followed up for a period of 6 months, with no evidence of recurrence. We have concluded, therefore, that conservative management should be the first line of treatment in chylothorax cases. If it does not work, a surgical approach might be considered.

Effects of wheat-flour biscuits fortified with iron and EDTA, alone and in combination, on blood lead concentration, iron status, and cognition in children: a double-blind randomized controlled trial.

BACKGROUND: Lead is a common neurotoxicant and its absorption may be increased in iron deficiency (ID). Thus, iron fortification to prevent ID in populations is a promising lead mitigation strategy. Two common fortificants are ferrous sulfate (FeSO4) and ferric sodium EDTA (NaFeEDTA). EDTA can chelate iron and lead. OBJECTIVES: Our study objective was to determine the effects of iron and EDTA, alone and in combination, on blood lead (BPb) concentration, iron status, and cognition. DESIGN: In this 2 × 2 factorial, double-blind placebo-controlled trial, 457 lead-exposed Moroccan children were stratified by school and grade and randomly assigned to consume biscuits (6 d/wk at school) containing 1) ∼8 mg Fe as FeSO4, 2) ∼8 mg Fe as NaFeEDTA that contained ∼41 mg EDTA, 3) ∼41 mg EDTA as sodium EDTA (Na2EDTA), or 4) placebo for 28 wk. The primary outcome was BPb concentration; secondary outcomes were iron status and cognitive outcomes from subtests of the Kaufman Assessment Battery for Children and the Hopkins Verbal Learning Test. These outcomes were measured at baseline and endpoint. All data were analyzed by intention-to-treat. RESULTS: The adjusted geometric mean BPb concentration at baseline was 4.3 µg/dL (95% CI: 4.2, 4.3 µg/dL), and at endpoint these values were 3.3 µg/dL (95% CI: 3.1, 3.5 µg/dL) for FeSO4, 2.9 µg/dL (95% CI: 2.7, 3.0 µg/dL) for NaFeEDTA, 3.3 µg/dL (95% CI: 3.1, 3.5 µg/dL) for EDTA, and 3.7 µg/dL (95% CI: 3.5, 3.9 µg/dL) for placebo. We found an effect of iron (P = 0.009) and EDTA (P = 0.012) for reduced BPb concentrations at endpoint, but no iron × EDTA interaction. Iron fortification improved iron status, but there were no positive effects of iron or EDTA on cognitive test scores. CONCLUSIONS: Food fortification with iron and EDTA additively reduces BPb concentrations. Our findings suggest that NaFeEDTA should be the iron fortificant of choice in lead-exposed populations. This trial was registered at clinicaltrials.gov as NCT01573013.

Direct iodine supplementation of infants versus supplementation of their breastfeeding mothers: a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Iodine deficiency in infants can damage the developing brain and increase mortality. Present recommendations state that oral iodised oil should be given to breastfeeding mothers to correct iodine deficiency in infancy when iodised salt is not available, and that direct supplementation should be given to infants who are not being breastfed or receiving iodine-fortified complimentary foods. However, there is little evidence for these recommendations. We aimed to assess the safety and efficacy of direct versus indirect supplementation of the infant. METHODS: We did this double blind, randomised, placebo-controlled trial in Morocco. Healthy breastfeeding mothers and their term newborn babies (aged ≤8 weeks) were block randomised by clinic day to receive either: one dose of 400 mg iodine to the mother and placebo to the infant (indirect infant supplementation), or one dose of about 100 mg iodine to the infant and placebo to the mother (direct infant supplementation). Randomisation was masked to participants and investigators. Coprimary outcomes were: maternal and infant urinary iodine concentrations, breastmilk iodine concentration, maternal and infant thyroid-stimulating hormone (TSH) concentrations, maternal and infant thyroxine (T4) concentrations, and infant growth. These outcomes were measured at baseline, and when infants were aged about 3 months, 6 months, and 9 months, and the two groups were compared using mixed effects models. This study is registered with ClinicalTrials.gov, number NCT01126125. FINDINGS: We recruited 241 mother-infant pairs between Feb 25, and Aug 10, 2010, and completed data collection by Aug 6, 2011. At baseline, median urinary iodine concentration was 35 µg/L (IQR 29-40) in mothers and 73 µg/L (29-237) in infants, suggesting iodine deficiency. During the study, maternal urinary iodine concentration (p=0.011), breastmilk iodine concentration (p<0.0001), and infant urinary iodine concentration (p=0.042) were higher in the indirect infant supplementation group than in the direct supplementation group. Maternal TSH (p=0.276) and T4 (p=0.074) concentrations did not differ between the groups over the course of the study, nor did infant TSH (p=0.597) and T4 (p=0.184) concentrations, but the number of infants with thyroid hypofunction was lower (p=0.023) in the indirect supplementation group than the direct supplementation group. The infant groups did not differ in anthropomorphic measures, except that length-for-age Z score was slightly greater in the direct infant supplementation group (p=0.032). At 3 months and 6 months of age, median infant urinary iodine concentration in the indirect infant supplementation group was sufficient (>100 µg/L), whereas infant urinary iodine concentration was sufficient only at 6 months in the direct supplementation group. There were no serious adverse events in either group. INTERPRETATION: In regions of moderate-to-severe iodine deficiency without effective salt iodisation, lactating women who receive one dose of 400 mg iodine as oral iodised oil soon after delivery can provide adequate iodine to their infants through breastmilk for at least 6 months, enabling the infants to achieve euthyroidism. Direct supplementation is less effective in improving infant iodine status. FUNDING: ETH Zurich, Switzerland; the Medicor Foundation, Vaduz, Lichtenstein.