Effects of intrauterine latent iron deficiency on auditory neural maturation in full-term newborns

Pallone, Leticia Valerio; Jesus, Felipe Alves de; Gonçalves, Gleice Aline; Navarra, Laura Carvalho; Melo, Débora Gusmão; Ferreira, Rodrigo Alves; Germano, Carla Maria Ramos

doi:10.1016/j.jped.2018.08.007

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Original articles • J. Pediatr. (Rio J.) 96 (2) • Mar-Apr 2020 • https://doi.org/10.1016/j.jped.2018.08.007 copy

Effects of intrauterine latent iron deficiency on auditory neural maturation in full-term newborns^☆ ☆ Please cite this article as: Pallone LV, Jesus FA, Gonçalves GA, Navarra LC, Melo DG, Ferreira RA, et al. Effects of intrauterine latent iron deficiency on auditory neural maturation in full-term newborns. J Pediatr (Rio J). 2020;96:202-9. , ^☆☆ ☆ Como citar este artigo: Pallone LV, Jesus FA, Gonçalves GA, Navarra LC, Melo DG, Ferreira RA, et al. Effects of intrauterine latent iron deficiency on auditory neural maturation in full-term newborns. J Pediatr (Rio J). 2020;96:202-9.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective:

This study analyzed the relationship between latent iron deficiency evaluated by ferritin, and the myelination of the central nervous system evaluated through the brainstem evoked response audiometry test.

Method:

A total of 109 full-term newborns, born without anemia and risk factor for hearing deficiency, were enrolled. After delivery, umbilical cord blood was collected to determine ferritin and hematocrit levels. The brainstem evoked response audiometry test was carried out in the first 28 days of life. Analysis was performed between the control group (n = 71) with ferritin greater than 75 ng/mL, and the latent iron deficiency group (n = 38) with ferritin between 11 and 75 ng/mL. Results were presented as mean ± standard deviation. Statistical analysis was performed using GraphPad prism7 and SPSS with a significance level of 5%.

Results:

A significant higher V-wave (p = 0.02) and interpeak intervals I-III (p = 0.014), I-V (p = 0.0003), and III-V (p = 0.0002) latencies were found in the latent iron deficiency group, as well as a significant inversely proportional correlation between ferritin and the same wave and intervals (p = 0.003, p = 0.0013, p = 0.0002, p = 0.009, respectively). Multiple correlation analysis showed a significant correlation of latent iron deficiency with all interpeak intervals, even taking into account newborn gestational age.

Conclusion:

Iron deficiency anemia is a prevalent pathology; this study showed auditory delayed maturation associated to intrauterine iron deficiency, even in its latent form. This reinforces the importance of adopting effective measures, on a global scale, to prevent and treat this pathology in different life periods, especially in the most vulnerable population.

KEYWORDS
BERA; Ferritin; Newborn; Latent iron deficiency

	Control group (n = 71)	LID group (n = 38)	p-Value
Maternal age (mean ± SD)	30.6 ± 5.8	32.0 ± 6.1	0.28^a a Nonparametric t-test (Mann-Whitney).
Supplemental health care (%)	56.3	50	0.55^b b Fisher's exact test.
Public health care (%)	43.7	50	0.55^b b Fisher's exact test.
Number of pregnancies median (min-max)	2 (1-4)	2 (1-6)	0.59^a a Nonparametric t-test (Mann-Whitney).
Number of abortions median (min-max)	0 (0-3)	0 (0-4)	0.98^a a Nonparametric t-test (Mann-Whitney).
Number of prenatal visits median (min-max)	10 (4-15)	10 (7-15)	0.36^a a Nonparametric t-test (Mann-Whitney).
Maternal DM or/and hypertension (%)	7	21.1	0.06^b b Fisher's exact test.
Fagerström test (%)	Smoker 4 Non-smoker 96	Smoker 0 Non-smoker 100	0.55^b b Fisher's exact test.
T-ACE score median (min-max)	0 (0-1)	0 (0-1)	0.59^a a Nonparametric t-test (Mann-Whitney).
Apgar score 1' median (min-max)	9 (7-10)	9 (7-10)	0.51^a a Nonparametric t-test (Mann-Whitney).
Apgar score 5' median (min-max)	10 (9-10)	10 (9-10)	0.80^a a Nonparametric t-test (Mann-Whitney).
Birth weight (g) mean ± SD	3273 ± 343.9	3573 ± 374.7	<0.0001^a a Nonparametric t-test (Mann-Whitney). ,^c c Differences between groups were significant at p < 0.05.
Birth length (cm) mean ± SD	48.3 ± 2.6	48.9 ± 2.1	0.12^a a Nonparametric t-test (Mann-Whitney).
Female (%)	46.5	34.2	0.23^b b Fisher's exact test.
Male (%)	53.5	65.8	0.23^b b Fisher's exact test.
Gestational age (days) mean ± SD	274.5 ± 5.9	272.1 ± 6.5	0.04^a a Nonparametric t-test (Mann-Whitney). ,^c c Differences between groups were significant at p < 0.05.
Gestational age test (days) mean ± SD	289.1 ± 8.1	287.3 ± 7.1	0.21^a a Nonparametric t-test (Mann-Whitney).
Postnatal age test (days) mean ± SD	14.6 ± 5.9	15.3 ± 5.7	0.40^a a Nonparametric t-test (Mann-Whitney).
TSH (mUI/L) mean ± SD	5.1 ± 2.7	4.8 ± 2.5	0.68^a a Nonparametric t-test (Mann-Whitney).

	Control (n = 71)	LID (n = 38)	p-Value
I-Wave mean ± SD (median)	1.8 ± 0.1 (1.7)	1.7 ± 0.1 (1.7)	0.33^a a Nonparametric t-test (Mann-Whitney).
III-Wave mean ± SD (median)	4.4 ± 0.1 (4.4)	4.4 ± 0.2 (4.4)	0.59^a a Nonparametric t-test (Mann-Whitney).
V-wave mean ± SD (median)	6.9 ± 0.1 (6.9)	7.0 ± 0.2 (7.0)	0.02 ^a a Nonparametric t-test (Mann-Whitney). ,^b b Differences between groups were significant at p < 0.05.
Interval I-III mean ± SD (median)	2.6 ± 0.1 (2.6)	2.7 ± 0.1 (2.7)	0.01^a a Nonparametric t-test (Mann-Whitney). ,^b b Differences between groups were significant at p < 0.05.
Interval I-V mean ± SD (median)	5.1 ± 0.1 (5.1)	5.2 ± 0.2 (5.2)	0.0003^a a Nonparametric t-test (Mann-Whitney). ,^b b Differences between groups were significant at p < 0.05.
Interval III-V mean ± SD (median)	2.4 ± 0.1 (2.4)	2.5 ± 0.1 (2.5)	0.002^a a Nonparametric t-test (Mann-Whitney). ,^b b Differences between groups were significant at p < 0.05.

	V-wave		Interval I-III		Interval I-V		Interval III-V
	r	p	r	p	r	p	r	p
Maternal age	-0.047	0.629	-0.134	0.165	-0.042	0.668	0.049	0.612
Number of pregnancies	0.009	0.924	-0.150	0.120	0.072	0.459	0.163	0.091
Number of abortions	-0.002	0.981	-0.067	0.490	0.025	0.793	0.150	0.120
Number of prenatal visits	0.214	0.025 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.020	0.839	0.165	0.087	0.079	0.412
Patho	0.084	0.385	0.124	0.198	0.150	0.120	0.136	0.159
Gestational age (days)	-0.246	0.010 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	-0.033	0.731	-0.221	0.021 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	-0.150	0.118
Birth weight (g)	0.034	0.729	0.043	0.657	0.117	0.224	0.219	0.022 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.
Birth length (cm)	-0.016	0.871	0.089	0.358	0.042	0.664	0.114	0.238
Apgar score 1'	-0.177	0.066	0.040	0.677	-0.217	0.023 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	-0.262	0.006 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.
Apgar score 5'	0.040	0.682	0.125	0.196	0.052	0.590	-0.058	0.546
Hematocrit (%)	-0.056	0.562	-0.113	0.244	0.071	0.461	0.174	0.070
Ferritin (ng/mL)	-0.287	0.003 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	-0.237	0.013 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	-0.351	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	-0.249	0.009 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.
LID	0.240	0.012 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.265	0.005 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.365	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.294	0.002 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.
Gestational age test (days)	-0.316	0.001 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	-0.039	0.687	-0.294	0.002 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	-0.151	0.116
Postnatal age test (days)	-0.193	0.045 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.018	0.849	-0.170	0.077	-0.059	0.541
I-Wave	0.575	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	-0.106	0.272	-0.006	0.954	0.018	0.849
III-Wave	0.730	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.595	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.388	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.018	0.853
V-Wave	1	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.324	0.001 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.743	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.491	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.
Interval I-III	0.324	0.001 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	1	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.485	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	-0.065	0.500
Interval I-V	0.743	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.485	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	1	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	0.626	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.
Interval III-V	0.491	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	-0.065	0.500	0.626	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.	1	0.000 ^a a Variables that presented significant simple correlation (row × column) at p < 0.05.

Variable	Multiples correlations Significant independent variables			Multiples correlations Stepwise
		Standardized β coefficient	p-Value	Predictors of the variable
		Standardized β coefficient	p-Value	Standardized β coefficient	p-Value
V-Wave	Number of prenatal visits	0.141	0.143
	Birth weight	0.66	0.531
	Ferritin	-0.047	0.676
	LID	0.125	0.300
	Gestational age test	-0.226	0.073 ^b b Independent variables that presented significant correlation with the dependent variable (first column) at p < 0.1.	-0.255	0.007 ^a a Independent variables that presented significant correlation with the dependent variable (first column) at p < 0.05.
	Postnatal age test	-0.003	0.979
Interval I-III	Birth weight	-0.059	0.563
	Ferritin	-0.012	0.916
	LID	0.249	0.042 ^a a Independent variables that presented significant correlation with the dependent variable (first column) at p < 0.05.	0.233	0.015 ^a a Independent variables that presented significant correlation with the dependent variable (first column) at p < 0.05.
Interval I-V	Birth weight	0.087	0.394
	Apgar score 1'	-0.191	0.041 ^a a Independent variables that presented significant correlation with the dependent variable (first column) at p < 0.05.	-0.206	0.027 ^a a Independent variables that presented significant correlation with the dependent variable (first column) at p < 0.05.
	Ferritin	0.017	0.879
	LID	0.206	0.084 ^b b Independent variables that presented significant correlation with the dependent variable (first column) at p < 0.1.	0.249	0.008 ^a a Independent variables that presented significant correlation with the dependent variable (first column) at p < 0.05.
	Gestational age	-0.027	0.829
	Gestational age test	-0.175	0.164
Interval III-V	Birth weight	0.189	0.061 ^b b Independent variables that presented significant correlation with the dependent variable (first column) at p < 0.1.
	Apgar score 1'	-0.255	0.006 ^a a Independent variables that presented significant correlation with the dependent variable (first column) at p < 0.05.	-0.263	0.005 ^a a Independent variables that presented significant correlation with the dependent variable (first column) at p < 0.05.
	Ferritin	0.087	0.430
	LID	0.185	0.114	0.229	0.013 ^a a Independent variables that presented significant correlation with the dependent variable (first column) at p < 0.05.
	Gestational age	-0.123	0.196

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[1] * Corresponding author. E-mails:cgermano@ufscar.br, carlavictor@uol.com.br (C.M. Germano).