Abstract

Although reports suggest that baby mortality is increased during iodine deficiency, the effect of iodine supplementation on infant mortality is unknown. A double-masked, randomized, placebo-controlled, clinical trial of oral iodized oil was conducted in Subang, West Coffee, Indonesia to evaluate the effect of iodine supplementation on infant mortality. Infants were allocated to receive placebo or oral iodized oil (100 mg) at about six wk of age and were followed to half dozen mo of age. Six hundred seventeen infants were enrolled in the study. Infant survival was plainly improved, as indicated past a 72% reduction in the gamble of expiry during the outset 2 mo of follow-up (P < 0.05) and a delay in the hateful time to death amid infants who died in the iodized oil group compared with infants who died in the placebo group (48 days vs. 17.5 d, P = 0.06). Other infant characteristics associated with reduced risk of death included weight-for-age at base line, consumption of solid foods, female gender and recent history of maternal iodine supplementation. Oral iodized oil supplementation had a stronger effect on the bloodshed of males compared with females. This study suggests that oral iodized oil supplementation of infants may reduce infant bloodshed in populations at adventure for iodine deficiency.

Approximately 1.6 billion people worldwide may consume inadequate daily amounts of iodine (UNICEF 1995) and are at risk for iodine deficiency disorders (IDD)4 (Hetzel and Pandav 1994), which include enlargement of the thyroid (goiter) and a wide spectrum of mental, psychomotor and growth abnormalities (Delange 1994). Currently, in that location are an estimated 655 million cases of endemic goiter and 26 million cases of preventable mental deficiency, including five.seven million cases of cretinism worldwide (Hetzel and Pandav 1994, WHO 1991b). Seventy-v percent of people with goiter live in developing countries (Gaitan et al. 1991). In areas with a high prevalence of IDD, maternal and fetal iodine deficiency has been associated with increased rates of stillbirth, abortion, congenital anomaly, and infant mortality (Pharoah et al. 1976, Thilly et al. 1980). Iodine supplementation of women before conception or during pregnancy seems to reduce abortions, stillbirths and infant bloodshed (Chaouki and Benmiloud 1994, Fierro-Benitez et al. 1988, Glinoer et al. 1995, Hetzel 1983, Pharoah and Connolly 1987, Pharoah et al. 1971 and 1972, Potter et al. 1979). Although these studies suggest that iodized oil supplementation of infants might improve their survival, this has not been shown definitively.

Oral iodized oil supplementation might influence infant survival through its effect on thyroid status and immunity. Thyroid hormones exert a powerful modulating event on the immune organization (Fabris 1973), including furnishings on B prison cell differentiation (Paavonen 1982), antibody responses (Keast and Ayre 1980), lymphoproliferation to mitogen (Keast and Taylor 1982) and T cell subsets (Ohashi and Itoh 1994). Although the human relationship between thyroid illness and autoimmunity is well documented (Mooij and Drexhage 1992), less is known regarding IDD and immune function in humans. Thyroid status and vitamin A status may also potentially interact to modulate immune responses. Both an active metabolite of vitamin A, 9-cis retinoic acid, and thyroid hormone can demark to retinoid X receptor (Leng et al. 1994) and command factor transcription.

SUBJECTS AND METHODS

The study population consisted of mothers and their infants from 28 villages in an area of mild-to-severe IDD in Subang, Westward Java, Indonesia. Eligible infants were 6–x wk old, clinically euthyroid, and built-in in the report villages. The fourth dimension of supplementation of 6–10 wk of age was based upon the possible programmatic integration of oral iodized oil supplementation with the first visit of the Expanded Programme on Immunization (EPI) (Bruning et al. 1993, WHO 1987, 1990 and 1991a) at which fourth dimension infants received oral poliovirus and diphtheria-pertussis-tetanus vaccines. The written report design was a randomized, double-masked, placebo-controlled, clinical trial. Infants were allocated past random number table in blocks of ten to receive oral iodized oil or placebo, which was given at the beginning EPI visit. Upon enrollment, infants were assigned sequential identification numbers. An envelope labeled with the identification number contained identically actualization capsules of either oral iodized oil in poppyseed oil (100 mg) or poppyseed oil placebo (Lipiodol, Laboratoire Guerbet, Aulnay-sous-bois, French republic). The code was unknown to the investigators and report squad until after the completion of the study. The capsules were administered immediately subsequently the commencement dose of oral polio vaccine. Infants in the clinical trial so completed the immunization schedule of the EPI with visits at 10 and xiv wk of age, and a last follow-up evaluation at six mo of age.

A 7-d morbidity history was obtained at each visit. Height, weight, mid-upper arm circumference and head circumference were assessed at the first, third and last visits using standard procedures. At each visit, mothers were asked whether their infants were being breast-fed and/or given solid food or other liquids besides breastmilk, how many times a day they were breast-fed and/or fed other foods, and the list of other foods given. Community health workers visited the homes of participants on a monthly basis and monitored the written report population for deaths, including those amidst infants who dropped out of the study but remained in their villages. Probable causes of death were determined by the pediatrician afterward interviewing relatives of the deceased infant using verbal dissection techniques adapted from other pediatric studies (Dowell et al. 1993, Kalter et al. 1990).

Base-line and follow-upwards comparisons between treatment groups were fabricated using Pupil'southward t test for comparison of two means and Fisher's exact test for comparison between proportions, with statistical significance at a 2-tailed P value of 0.05 or less. Absolute and gender-stratified relative adventure, bloodshed rates and Kaplan-Meier survival curves were calculated and compared betwixt resource allotment groups (Armitage and Berry 1987). Adapted survival analyses were conducted using Cox regression models (Kleinbaum et al. 1982). Written informed consent was obtained from parents or guardians. The study was approved by the institutional review lath at the Johns Hopkins School of Medicine and by the ethical committees of the Hasan Sadikin Hospital, University Pajajaran and the Ministry of Health, Government of Republic of indonesia.

RESULTS

From June to October 1994, 617 infants were recruited to participate in the written report. Of the 617 participants, 307 (49.8%) infants received oral iodized oil and 310 (fifty.ii%) received placebo; 311 (50.4%) infants were males and 306 (49.6%) were females. The treatment groups were similar past maternal goiter status, maternal historic period, babe gender, socioeconomic status, utilize of iodized salt and all other characteristics at base of operations line, some of which are displayed on Tabular array 1. Five hundred seven infants completed follow-up to 6 mo, 255 of 307 in the iodized oil group (83%), and 252 of 310 (81%) in the placebo group. There was no differential loss to follow-up by handling group or gender. Eighty-eight infants dropped out of the study before 6 mo of age. Their base-line characteristics were similar to those who remained in the study (data not shown). A total of 22 infants died, 15 (68.2%) in the placebo group and 7 (31.eight%) in the iodized oil group. Of those who died, xiv (63.half dozen%) were male and eight were female (36.four%).

Tabular array one

Selected base of operations-line characteristics by resource allotment group

Placebo n = 310 n (%) Iodized oil n = 307 n (%) P-value
Maternal characteristics
Goiter form 1
00 275 (89.half dozen) 267 (87.6) 0.54
1A twenty (6.v) 26 (8.5)
1B 7 (2.3) 8 (2.6)
02 three (ane.0) 4 (i.3)
03 two (0.6) 0 (0.0)
Previous maternal iodine supplementation 52 (sixteen.8) 47 (15.three) 0.66
Utilize of vitamin and mineral supplements during pregnancy 259 (84.6) 261 (85.6) 0.82
Mean historic period, ane , two y 25.four ± 0.32 25.7 ± 0.32 0.61
Pregnancies, n ii.3 ± 0.09 2.3 ± 0.08 0.69
Deliveries, north ii.2 ± 0.09 2.2 ± 0.08 0.76
Live births, n 2.2 ± 0.09 2.ii ± 0.08 0.69
Children live, due north 2.i ± 0.08 2.1 ± 0.07 0.98
Maternal education, y vii.one ± 0.15 vii.four ± 0.16 0.32
Maternal occupation: housewife 272 (94.1) 266 (90.5) 0.32
Infant gender, age at base line, and delivery history
Gender
Male 157 (50.6) 154 (50.ii) 0.90
Female person 153 (49.3) 153 (49.8)
Identify of delivery
Abode 269 (86.8) 272 (89.2) 0.66
Midwife'southward house 16 (5.i) 11 (3.half-dozen)
Hospital 17 (five.v) 17 (5.half-dozen)
Clinic eight (2.6) v (i.6)
Delivery assisted past
Traditional nativity bellboy 235 (76.1) 237 (77.5) 0.38
Midwife 65 (21.0) 65 (21.ii)
Doctor ix (2.9) 4 (1.3)
Mean nascence weight, kg 1 iii.twenty ± 0.03 3.20 ± 0.03 0.74
Hateful age, mo 1.82 ± 0.02 1.80 ± 0.02 0.54
Placebo n = 310 n (%) Iodized oil due north = 307 n (%) P-value
Maternal characteristics
Goiter grade one
00 275 (89.half-dozen) 267 (87.6) 0.54
1A twenty (half dozen.5) 26 (8.v)
1B 7 (2.3) 8 (2.six)
02 3 (i.0) 4 (ane.iii)
03 two (0.vi) 0 (0.0)
Previous maternal iodine supplementation 52 (16.viii) 47 (15.3) 0.66
Apply of vitamin and mineral supplements during pregnancy 259 (84.half dozen) 261 (85.six) 0.82
Mean age, ane , two y 25.iv ± 0.32 25.7 ± 0.32 0.61
Pregnancies, n ii.3 ± 0.09 2.three ± 0.08 0.69
Deliveries, northward ii.2 ± 0.09 2.2 ± 0.08 0.76
Live births, n 2.2 ± 0.09 2.2 ± 0.08 0.69
Children alive, n 2.1 ± 0.08 2.1 ± 0.07 0.98
Maternal education, y vii.ane ± 0.fifteen 7.4 ± 0.sixteen 0.32
Maternal occupation: housewife 272 (94.i) 266 (90.5) 0.32
Infant gender, age at base line, and delivery history
Gender
Male 157 (fifty.6) 154 (50.2) 0.90
Female person 153 (49.3) 153 (49.8)
Place of commitment
Home 269 (86.8) 272 (89.2) 0.66
Midwife's firm xvi (5.1) 11 (3.half-dozen)
Hospital 17 (five.5) 17 (5.6)
Clinic 8 (2.vi) 5 (i.6)
Commitment assisted by
Traditional nascency bellboy 235 (76.i) 237 (77.5) 0.38
Midwife 65 (21.0) 65 (21.2)
Doctor ix (ii.nine) four (1.3)
Mean nativity weight, kg 1 3.20 ± 0.03 3.20 ± 0.03 0.74
Mean historic period, mo one.82 ± 0.02 1.80 ± 0.02 0.54

ane

Data from placebo group (n = 307), iodized oil grouping (northward = 305).

ii

Hateful ± SEM.

Table i

Selected base-line characteristics past allocation grouping

Placebo n = 310 north (%) Iodized oil n = 307 northward (%) P-value
Maternal characteristics
Goiter grade 1
00 275 (89.half dozen) 267 (87.vi) 0.54
1A twenty (6.v) 26 (8.5)
1B seven (2.three) 8 (2.6)
02 3 (one.0) 4 (1.iii)
03 2 (0.6) 0 (0.0)
Previous maternal iodine supplementation 52 (16.8) 47 (15.iii) 0.66
Use of vitamin and mineral supplements during pregnancy 259 (84.6) 261 (85.6) 0.82
Mean age, 1 , 2 y 25.4 ± 0.32 25.7 ± 0.32 0.61
Pregnancies, n 2.3 ± 0.09 2.3 ± 0.08 0.69
Deliveries, northward 2.two ± 0.09 ii.2 ± 0.08 0.76
Live births, northward 2.ii ± 0.09 ii.ii ± 0.08 0.69
Children alive, n 2.1 ± 0.08 2.1 ± 0.07 0.98
Maternal instruction, y 7.1 ± 0.15 vii.4 ± 0.16 0.32
Maternal occupation: housewife 272 (94.i) 266 (xc.5) 0.32
Infant gender, age at base line, and delivery history
Gender
Male 157 (50.6) 154 (l.ii) 0.90
Female 153 (49.3) 153 (49.8)
Place of delivery
Home 269 (86.8) 272 (89.ii) 0.66
Midwife's house xvi (5.1) 11 (three.6)
Hospital 17 (five.five) 17 (5.half-dozen)
Clinic eight (2.6) v (one.6)
Delivery assisted by
Traditional birth attendant 235 (76.1) 237 (77.five) 0.38
Midwife 65 (21.0) 65 (21.ii)
Medico 9 (2.9) four (i.3)
Mean nascency weight, kg 1 three.20 ± 0.03 3.20 ± 0.03 0.74
Mean age, mo 1.82 ± 0.02 ane.80 ± 0.02 0.54
Placebo north = 310 n (%) Iodized oil due north = 307 north (%) P-value
Maternal characteristics
Goiter grade 1
00 275 (89.half-dozen) 267 (87.6) 0.54
1A 20 (6.v) 26 (8.5)
1B 7 (ii.iii) 8 (ii.6)
02 3 (one.0) four (1.3)
03 2 (0.6) 0 (0.0)
Previous maternal iodine supplementation 52 (sixteen.eight) 47 (15.3) 0.66
Employ of vitamin and mineral supplements during pregnancy 259 (84.vi) 261 (85.6) 0.82
Mean historic period, 1 , two y 25.4 ± 0.32 25.7 ± 0.32 0.61
Pregnancies, n two.3 ± 0.09 two.3 ± 0.08 0.69
Deliveries, north 2.two ± 0.09 2.ii ± 0.08 0.76
Live births, northward ii.two ± 0.09 ii.2 ± 0.08 0.69
Children live, n 2.1 ± 0.08 2.1 ± 0.07 0.98
Maternal educational activity, y 7.i ± 0.fifteen seven.4 ± 0.16 0.32
Maternal occupation: housewife 272 (94.one) 266 (90.5) 0.32
Baby gender, age at base line, and delivery history
Gender
Male person 157 (50.six) 154 (50.2) 0.90
Female person 153 (49.3) 153 (49.8)
Place of delivery
Dwelling 269 (86.viii) 272 (89.ii) 0.66
Midwife's house xvi (5.1) 11 (3.6)
Hospital 17 (five.5) 17 (v.half dozen)
Clinic eight (2.6) 5 (ane.vi)
Delivery assisted by
Traditional birth attendant 235 (76.one) 237 (77.5) 0.38
Midwife 65 (21.0) 65 (21.2)
Doctor 9 (ii.9) 4 (1.3)
Mean nativity weight, kg 1 iii.20 ± 0.03 iii.xx ± 0.03 0.74
Mean age, mo 1.82 ± 0.02 i.80 ± 0.02 0.54

one

Data from placebo group (north = 307), iodized oil grouping (n = 305).

2

Mean ± SEM.

Infants who died before six mo of age were significantly lighter and had smaller head and arm circumferences at written report entry than the infants who survived to 6 mo of age. Their mean weight-for-age was besides significantly lower, indicating that they were malnourished at base line in comparing with the surviving infants (Table 2). None of the mothers whose infants died had a history of iodized oil supplementation in comparing with 86 (17%) of the 507 mothers whose infants survived to 6 mo of age (P = 0.034). Supplemented mothers had received oral iodized oil on average 120 d earlier the beginning of the study. No other base of operations-line differences were observed betwixt those who survived to six mo of historic period and those who did non. The percentage of mothers who had been supplemented in the by and the fourth dimension elapsed between maternal and infant supplementation were similar in the iodized and placebo groups.

Tabular array two

Birth weight and base-line age and anthropometry by infant vital condition

Dead due north = 22 Alive n = 507 P-value
Birthweight, 1 , two kg  3.0 ± 0.xi  3.two ± 0.02 0.ten
Historic period at base line, mo  1.7 ± 0.07  1.8 ± 0.01 0.32
Weight, kg  iv.5 ± 0.14  4.8 ± 0.03 0.03
Length, cm  55.0 ± 0.49  55.8 ± 0.11 0.12
Head circumference, cm  37.ii ± 0.24  37.9 ± 0.06 0.01
Arm circumference, cm  11.9 ± 0.21  12.5 ± 0.05 0.02
Weight-for-age Z-score −0.43 ± 0.17  0.03 ± 0.04 0.01
Height-for-age Z-score −0.lxx ± 0.twenty −0.38 ± 0.04 0.09
Weight-for-height Z-score  0.sixteen ± 0.17  0.40 ± 0.03 0.11
Dead n = 22 Alive north = 507 P-value
Birthweight, 1 , ii kg  3.0 ± 0.xi  three.2 ± 0.02 0.10
Age at base line, mo  ane.7 ± 0.07  1.8 ± 0.01 0.32
Weight, kg  four.five ± 0.14  4.8 ± 0.03 0.03
Length, cm  55.0 ± 0.49  55.8 ± 0.xi 0.12
Head circumference, cm  37.2 ± 0.24  37.9 ± 0.06 0.01
Arm circumference, cm  11.9 ± 0.21  12.5 ± 0.05 0.02
Weight-for-age Z-score −0.43 ± 0.17  0.03 ± 0.04 0.01
Height-for-historic period Z-score −0.lxx ± 0.20 −0.38 ± 0.04 0.09
Weight-for-summit Z-score  0.16 ± 0.17  0.40 ± 0.03 0.11

1

Mean ± SEM.

2

For birthweights, those who died (n = 17), those alive (n = 331).

Table two

Birth weight and base-line historic period and anthropometry by babe vital status

Dead n = 22 Alive n = 507 P-value
Birthweight, 1 , ii kg  3.0 ± 0.xi  3.2 ± 0.02 0.10
Age at base line, mo  i.vii ± 0.07  1.8 ± 0.01 0.32
Weight, kg  4.5 ± 0.14  4.8 ± 0.03 0.03
Length, cm  55.0 ± 0.49  55.eight ± 0.11 0.12
Head circumference, cm  37.2 ± 0.24  37.9 ± 0.06 0.01
Arm circumference, cm  11.9 ± 0.21  12.five ± 0.05 0.02
Weight-for-age Z-score −0.43 ± 0.17  0.03 ± 0.04 0.01
Height-for-historic period Z-score −0.70 ± 0.20 −0.38 ± 0.04 0.09
Weight-for-height Z-score  0.16 ± 0.17  0.40 ± 0.03 0.11
Dead n = 22 Alive n = 507 P-value
Birthweight, ane , 2 kg  3.0 ± 0.11  3.2 ± 0.02 0.x
Age at base line, mo  1.7 ± 0.07  i.8 ± 0.01 0.32
Weight, kg  4.5 ± 0.14  four.viii ± 0.03 0.03
Length, cm  55.0 ± 0.49  55.viii ± 0.xi 0.12
Head circumference, cm  37.2 ± 0.24  37.ix ± 0.06 0.01
Arm circumference, cm  eleven.nine ± 0.21  12.5 ± 0.05 0.02
Weight-for-age Z-score −0.43 ± 0.17  0.03 ± 0.04 0.01
Tiptop-for-age Z-score −0.70 ± 0.20 −0.38 ± 0.04 0.09
Weight-for-height Z-score  0.16 ± 0.17  0.40 ± 0.03 0.11

1

Mean ± SEM.

two

For birthweights, those who died (n = 17), those alive (due north = 331).

Deaths in the iodized oil group occurred on average 48 d (± 13.one) subsequently the intervention, whereas in the placebo group, deaths occurred on average 17.5 d (± four.0) later on the initial visit (P = 0.06). There were thirteen deaths (65%) due to pneumonia or bronchopneumonia, 1 decease (five%) due to meningoencephalitis, 1 death (5%) due to asphyxia, and two deaths with unspecified diagnoses (allergic reaction and shock of undetermined nature). 5 deaths were not investigated through verbal autopsies. The unadjusted relative risk of death in the iodized oil group in comparing with the placebo group during the first ane, 2 and four mo of follow-upward were 0.19 (95%CI 0.04–0.85, P = 0.021); 0.28 (95%CI 0.09–0.82, P = 0.018); and 0.48 (95%CI 0.20–ane.15, P = 0.126), respectively. Figure ane shows the Kaplan-Meier survival curves according to treatment group. At the end of iv mo of follow-up, the overall mortality experience in the iodized oil grouping was nevertheless considerably lower than that of the placebo group, respective to a 52% reduction in mortality in the supplemented grouping. The final mortality departure at 6 mo of age, however, failed to reach statistical significance, peradventure due to the pocket-size sample size studied. The ability to detect a deviation such as the one observed at 6 mo of age was approximately 32%.

Effigy 1

Survival of infants in the oral iodized oil and placebo groups from time of supplementation through 120 d of follow-up. Age at base line was 6 wk.

Survival of infants in the oral iodized oil and placebo groups from time of supplementation through 120 d of follow-up. Historic period at base line was six wk.

Figure ane

Survival of infants in the oral iodized oil and placebo groups from time of supplementation through 120 d of follow-up. Age at base line was 6 wk.

Survival of infants in the oral iodized oil and placebo groups from time of supplementation through 120 d of follow-up. Historic period at base line was 6 wk.

Multivariable Cox regression assay was used to measure the effect of other independent variables on survival, to control for potential confounding and to test for interactions. Variables analyzed included gender, infant's nutrition at base line (breastfeeding and/or introduction of solid foods), diarrhea or acute respiratory infection (coughing, difficult breathing, or fast breathing) at base line, history of maternal iodized oil supplementation, anthropometry at base line, and interaction among handling, gender and other variables showing clan with survival. Iodine supplementation, consumption of solid foods or liquids at base line, female gender, weight, weight-for-age Z-score (WAZ), and head and arm circumference were independently associated with improved survival. WAZ was selected for the terminal model on the ground of the magnitude and statistical significance of the beneficial effect on survival and multicolinearity betwixt anthropometric parameters. Table 3 presents the results of the multivariable Cox survival analysis with the effect of iodine supplementation adjusted for gender, WAZ and consumption of solid foods at base line. Handling event was non confounded and did non interact with the effect of solid foods and anthropometry at base line. Sex-stratified assay of handling effect indicated that male survival at 6 mo of age in the iodized oil group was significantly better than that of male person infants in the placebo group (22.ix per k vs. 84.6 per k, P = 0.03). The P-value for the interaction between treatment and sexual practice in the Cox regression model was 0.15. Because the deviation in bloodshed occurred soon later enrollment, there were express data regarding time-dependent variables such as anthropometry and diet for the infants who died; therefore, the Cox regression analysis was limited to base of operations-line variables merely.

Table three

Relative take a chance (RR) of death and 95% confidence interval (CI) at 1, 2 and 4 mo subsequently study entry co-ordinate to iodine supplementation adjusted for gender, weight-for-age Z-score and consumption of solid foods at base line

Variable 1 mo two mo 4 mo
RR (95% CI; P) RR (95% CI; P) RR (95% CI; P)
Iodized oil vs. control 0.20 (0.04–0.91; 0.04) 0.xxx (0.x–0.90; 0.03) 0.52 (0.21–1.28; 0.15)
Solid food vs. no solid food 0.41 (0.12–ane.35; 0.14) 0.41 (0.15–1.09; 0.08) 0.41 (0.17–1.01; 0.05)
Female vs. male 0.54 (0.eighteen–1.68; 0.29) 0.39 (0.15–1.04; 0.06) 0.49 (0.20–ane.18; 0.11)
Weight-for-age Z-score at base line 0.58 (0.30–1.13; 0.xi) 0.53 (0.30–0.92; 0.02) 0.55 (0.33–0.91; 0.02)
Variable 1 mo 2 mo 4 mo
RR (95% CI; P) RR (95% CI; P) RR (95% CI; P)
Iodized oil vs. control 0.20 (0.04–0.91; 0.04) 0.30 (0.x–0.90; 0.03) 0.52 (0.21–1.28; 0.15)
Solid food vs. no solid food 0.41 (0.12–1.35; 0.xiv) 0.41 (0.xv–1.09; 0.08) 0.41 (0.17–1.01; 0.05)
Female person vs. male person 0.54 (0.18–one.68; 0.29) 0.39 (0.15–1.04; 0.06) 0.49 (0.20–1.18; 0.xi)
Weight-for-age Z-score at base of operations line 0.58 (0.30–1.13; 0.11) 0.53 (0.30–0.92; 0.02) 0.55 (0.33–0.91; 0.02)

Table iii

Relative run a risk (RR) of decease and 95% confidence interval (CI) at 1, ii and 4 mo after study entry according to iodine supplementation adjusted for gender, weight-for-historic period Z-score and consumption of solid foods at base of operations line

Variable 1 mo 2 mo iv mo
RR (95% CI; P) RR (95% CI; P) RR (95% CI; P)
Iodized oil vs. control 0.xx (0.04–0.91; 0.04) 0.30 (0.10–0.xc; 0.03) 0.52 (0.21–1.28; 0.xv)
Solid food vs. no solid food 0.41 (0.12–i.35; 0.14) 0.41 (0.15–1.09; 0.08) 0.41 (0.17–1.01; 0.05)
Female vs. male 0.54 (0.xviii–1.68; 0.29) 0.39 (0.15–i.04; 0.06) 0.49 (0.xx–i.18; 0.11)
Weight-for-age Z-score at base of operations line 0.58 (0.30–1.13; 0.eleven) 0.53 (0.30–0.92; 0.02) 0.55 (0.33–0.91; 0.02)
Variable 1 mo 2 mo 4 mo
RR (95% CI; P) RR (95% CI; P) RR (95% CI; P)
Iodized oil vs. control 0.20 (0.04–0.91; 0.04) 0.30 (0.10–0.90; 0.03) 0.52 (0.21–one.28; 0.15)
Solid food vs. no solid nutrient 0.41 (0.12–one.35; 0.xiv) 0.41 (0.15–ane.09; 0.08) 0.41 (0.17–1.01; 0.05)
Female vs. male 0.54 (0.eighteen–i.68; 0.29) 0.39 (0.fifteen–1.04; 0.06) 0.49 (0.20–i.18; 0.xi)
Weight-for-historic period Z-score at base line 0.58 (0.30–1.13; 0.11) 0.53 (0.xxx–0.92; 0.02) 0.55 (0.33–0.91; 0.02)

Among 326 infants whose base of operations-line diets included foods or liquids, 164 (50.0%), 126 (38.4%), 35 (11.3%) and 1 (0.3%) were fed solid foods or liquids ane, 2, 3 and four times/d, respectively. Other liquids consisted of water, tea with saccharide or love, or fruit juice. Solid or mushy foods included premasticated rice (bubur), mashed bananas, biscuits, industrialized infant food (east.grand., Promina and Farley) and infant formulas (e.g., Lactogen, SNN and SGN). The proportion of infants breast-fed at base line was lower, but not significantly and so, amid infants who received supplements (95.7 vs. 97.nine%, P = 0.125). Infants who received solid foods or liquids supplements at base line were slightly, but significantly older at written report entry than infants who did not receive supplements (1.ix vs. 1.8 mo, P < 0.0001). They were too heavier and taller (iv.9 vs. iv.vii kg, P = 0.0041; 56.2 vs. 55.5 cm, P = 0.0003), had slightly greater head and arm circumference (38.0 vs. 37.7 cm, P = 0.002; and 12.five vs. 12.4 cm, P = 0.05), merely like age adjusted Z-scores (WAZ 0.03 vs. −0.03, P = 0.371; elevation-for-age Z-score −0.34 vs. −0.45, P = 0.109; weight-for-peak Z-score 0.37 vs. 0.39, P = 0.622). Infants who did not receive solid foods were more likely to have a improve socioeconomic status as indicated, for example, by the significantly higher percentage living in houses with electricity and college mean years of parental schooling (information not shown). The result of supplemental foods/liquids on survival did not alter when controlled for age, socioeconomic status, iodine supplementation, WAZ or gender.

DISCUSSION

This study suggests that iodine (100 mg) given at 6 wk of historic period may reduce the run a risk of death amongst infants in a geographical area of iodine deficiency. The absence of deaths amongst infants whose mothers received iodine supplementation in the recent past was another finding in this study that too supports the potentially benign function of iodine in reducing mortality. To our knowledge, this is the outset study to demonstrate that infant oral iodine supplementation tin can reduce infant mortality. This finding is corroborated past previous studies that suggest that babe survival is improved among infants born to women whose iodine deficiency was corrected before or during pregnancy. In People's democratic republic of algeria, the rates of abortion, stillbirth and prematurity were significantly lower amongst women treated with oral iodized oil 1–3 mo before conception or during pregnancy than amongst untreated women (Chaouki and Benmiloud 1994). Infant mortality was lower amid infants built-in to women who received intramuscular iodized oil supplementation at around 28 wk of pregnancy compared with infants built-in to controls in a clinical trial from Zaire (Thilly et al. 1980). Studies in Papua New Guinea indicated an inverse relationship between levels of maternal thyroxine during pregnancy and expiry rates among the offspring (Pharoah et al. 1976), and an improved long-term survival amongst children built-in to women whose iodine deficiencies were corrected during or presently before pregnancy (Pharoah and Connolly 1987). A mayhap related finding is a recent report of significantly reduced mortality among immature sheep in villages receiving iodine in irrigation water compared with control villages in Prc (Cao et al. 1994).

This study suggests that there may be a possible differential upshot of treatment co-ordinate to gender. Nutritional and immunological differences between boys and girls may influence response to infections and survival. For instance, boys are more susceptible to vitamin A deficiency than girls, which is a consequent observation in different countries (Sommer 1982). Differences in immunologic condition (Leon et al. 1993), responses to vaccination (Garenne et al. 1991) and micronutrient supplementation (Sazawal et al. 1996) are known between boys and girls. It is unknown whether boys are at higher risk of iodine deficiency or whether there is a gender difference in response to iodine supplementation. A handling effect may non have been observed in girls because of their already loftier survival rate of 97%.

It is possible that infants receiving solid foods were exposed to commercial products which potentially provided them with additional sources of iodine. However, the report did not use systematic methodologies carefully designed for the evaluation of dietary practices or for adequate assessment of iodine content of foods. The finding of improved survival among infants having solid foods in the diet at study entry should be investigated farther past means of a more precise dietary cess. This study is limited in that biochemical indicators of iodine and thyroid status were non bachelor. However, detailed anthropometric evaluation and clinical cess of maternal goiter suggest that the observed differences in mortality were not due to base-line imbalances in the handling group.

Traditionally, the primary focus in the prevention of IDD has been to eliminate the ensuing mental impairment, cretinism and goiter. Ideally, adequate iodine levels should be fabricated available from the outset of fetal development in utero by adequate supplementation of women of childbearing age and pregnant women. The EPI may serve as an additional commitment system for providing supplementation to mothers and infants who missed before opportunities. The duration for which one 100-mg dose of iodine will right iodine deficiency in a half dozen-wk-quondam infant is unknown; notwithstanding, WHO (1991) estimates that a 240-mg dose of iodine administered once in the kickoff year of life will right iodine deficiency for upward to 2 y. Infant iodine supplementation may be a potential intervention that could reduce baby mortality in iodine-deficient areas by fifty%; further study is required to approve these findings with a larger sample size. Iodine supplementation may exist an important strategy for child survival, and this study suggests that the infrastructure to deliver supplements could be provided by the Expanded Programme on Immunization.

ACKOWLEDGMENT

The authors thank Dr. Nicholas Cohen for his encouragement and support.

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Abbreviations

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    Expanded Plan on Immunization

  • IDD

    iodine deficiency disorders

  • WAZ

Footnotes

ane

Supported past the Thrasher Enquiry Fund and the World Health Organization.

two

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© 1997 American Society for Nutritional Sciences