The Status of Vitamin D in Neonates with Hypoxic Ischemic Encephalopathy

Introduction:

Hypoxic-ischemic encephalopathy (HIE) is an important cause of acquired neonatal brain injury in term newborn infants and it may lead to neonatal death and long-term disability. Energy failure, membrane depolarization, edema, an increase of neurotransmitter release, the inhibition of neurotransmitter uptake, an increase of intracellular Ca2+, the production of oxygen-free radicals (OFR), lipid peroxidation, and a decrease of blood flow all contribute to the progression of the brain damage that subsequently follows a hypoxic–ischemic insult [1]

Hypoxia-ischemia initially causes energy failure and loss of mitochondrial function. This is accompanied by membrane depolarization, brain edema, an increase of neurotransmitter release and inhibition of uptake, and an increase of intracellular calcium that sets off additional pathologic cascades [2]

Hypoxic ischemic encephalopathy (HIE) is a potentially devastating neonatal brain injury with long-term neurologic effects that affects between 1 and 8/1,000 live births with the highest rates in developing countries [3].

Vitamin D a key nutrient for children’s well-being and growth, is essential for bone health and may contribute to other health benefits [5]

Vitamin D deficiency is a worldwide problem has been associated with wide spectrum of diseases, ranging from neurological disorders to chronic inflammatory conditions [5,6].

The major consequence of vitamin D deficiency Patients and Methods:

This cross sectional case control study was performed to compare vitamin D serum levels between full term neonates with hypoxic ischemic encephalopathy (HIE) and normal healthy neonates and to determine if there is an association between serum vitamin D levels and neonatal hypoxic ischemic encephalopathy (HIE).

The present study was carried out in neonatal intensive care unit (NICU) of Minia University Hospital from April 2017 to December 2017.

This study included 60 full term neonates their gestational ages were 37-40 weeks and postnatal age less than 6 hours. They were classified into 2 groups: First group; included 30 neonates with criteria of moderate to severe hypoxic ischemic encephalopathy as cases and the second group included 30 apparently healthy neonates as controls.

Inclusion criteria of patient group:  Full term neonates ≥ 37weeks of gestation of any mode of delivery, both gender who born with perinatal asphyxia or asphyxia required resuscitation as follow: Apger score at 5,10 minutes afterbirth > 5, fetal acidosis with umbilical artery blood pH >7 or base deficit

Inclusion criteria for control group: Full term ≥37weeks of gestation neonate who did not require resuscitation, Apgar score on the first and the fifth minutes of life

We excluded from the study: Premature infants (gestational age

All cases and controls were subjected to full carful history, neonatal clinical examination, neonatal laboratory investigations (25(OH) vitamin  D by ELISA, complete blood count (CBC) & Reticulocytic count & C-reactive protein (CRP), renal function tests and electrolytes  using SYSMEX and arterial blood gases (ABG) by blood gas analyzer. We also measured serum levels of vitamin D in blood of mothers of both groups.

All laboratory investigations were carried out in Clinical pathology department, Minia university hospital. The study was approved by the local research ethics committee of the Faculty of Medicine, Minia University and written informed consents were obtained from the parents/care givers of all neonates included in the study.

Statistical analysis:

Data were statistically analyzed using the SPSS software package, version 16 (SPSS Inc., Chicago, IL, USA) on a personal computer. Numerical data were expressed as range, mean± SD, median, and percentiles.  Non numerical  data  were expressed  as  frequencies.  Comparative studies were done using Student t test and chi square test. (p value < 0.05  was  considered  significant).  Pearson correlation test was used to detect correlation between different parameters. P

Results:

There were no significant differences between cases and controls as regards demographic data (Table 1 & Figure 1). Neonates with hypoxic ischemic encephalopathy had significant lower vitamin D levels than controls (P-value ≤ 0.001), half of them (50%) had deficient levels of vitamin D, 23.3% had insufficient levels and 26.7% had normal levels of vitamin D. The control group had normal level in 90% and only 10% had insufficient levels of vitamin D (Table 2).  There were significant lower serum levels of vitamin D in maternal blood of neonates with HIE than controls (Table 2).  There were positive correlations between maternal and neonatal serum vitamin levels in neonates with HIE (r = 0.418 and p-value = 0.02*) (Table 3).

Discussion:

Our studied neonates with hypoxic ischemic encephalopathy had a significant lower vitamin D than controls (p less than 0.001) as there is 50% (n=15) had a deficient level of vitamin D and 23.3% (N=7) had insufficient level of vitamin D, and 26.7(n=8) had a normal level of vitamin D with  p-value less than 0.001 in comparison with control group which had normal level in 90% (n=27) and only 10% (n=3) had insufficient level which is in agreement with two published studies [7,8].

Our results revealed a significant positive correlation between maternal serum vitamin D and its levels in their neonates with (HIE), this can be explained by the fact that vitamin D stores of the neonate depend entirely on the vitamin D stores of their mothers which is in agreement with other study [9]. There were no significant correlation between neonatal serum levels of vitamin D and gender, mode of delivery, consanguinity or residence in both cases and control groups.

Our results revealed that there is significant difference between case group and control group regarding Apgar score at 1st minute as all case group patients had Apgar score less than 7 as suggested in the inclusion criteria. On the other hand control group had Apgar score more than 8 in first 5 minutes which is in agreement with study of [10].

Also our results revealed significant difference between case group and control group regarding arterial pH after 5 minutes as all case group patients had arterial pH below 7 up to 7,1 as inclusion criteria suggested as there was metabolic acidosis in all HIE case. On the other hand control group had normal arterial pH  at 1 and 5 minutes which is in agreement with other reports [10].

Our results revealed that there is significant difference between case group and control group regarding CT finding (Not shown in the results section). There were 76% of our studied cases had a positive findings in CT ranging in severity from brain oedema in 20% of cases to hypoxic changes as hypodensity in CT findings in 56.7% of them which is in agreement with others [11,12].  We can recommend - according to the results of this study - more studies for vitamin D supplementation for pregnant women