The impact of therapeutic hypothermia on peripheral blood cell in newborns with hypoxic ischemic encephalopathy

Kurt, Abdullah; Zenciroğlu, Ayşegül; Akduman, Hasan

doi:10.1590/s2175-97902022e181053

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Brazilian Journal of Pharmaceutical Sciences

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Article • Braz. J. Pharm. Sci. 58 • 2022 • https://doi.org/10.1590/s2175-97902022e181053 copy

The impact of therapeutic hypothermia on peripheral blood cell in newborns with hypoxic ischemic encephalopathy

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

The effect of hypothermia treatment on white blood cell (WBC), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) values as an indicator of inflammation was evaluated in newborns with hypoxic ischemic encephalopathy (HIE). The study was performed that the before-therapeutic hypothermia (TH) and after-TH WBC, lymphocytes, neutrophils, monocytes and NLR, LMR and PLR values of the complete blood cell count were retrospectively evaluated. The results of the patient group were compared with the results of healthy newborns. A total of 78 patients who underwent TH were evaluated in our study. Mean values before and after TH were NLR3.8/2.7, LMR 5.6/8.6, and PLR 60.3/67.1 respectively. A statistical significance was present for NLR values before and after TH in those with seizure in our study (4.15±2.95/3.01±2.54) but no statistical significance was found for LMR or PLR. In neonates with HIE, effect of TH on complete blood cell count and inflammatory mechanisms (mediated neutrophil and lymphocyte) may be minimal.

Keywords:
Hypoxic ischemic encephalopathy; Inflammation; Newborn

Therapeutic Hypothermia Initiation Criteria (19)
Gestational age ≥35 weeks and ≤6 hours of age
AND Apgar score ≤5 at 10 minutes after birth
OR Continued need for resuscitation at 10 minutes after birth
OR pH<7.00 or base deficit ≥16 mmol/L or more with an umbilical cord blood sample or an arterial or venous blood sample obtained within 60 minutes of birth
AND Moderate or severe encephalopathy on clinical examination
AND Moderately or severely abnormal background of at least 20 minutes’ duration or seizure activity on aEEG after one hour of age

	HIE group (n=78)	Control group (n=38)	p
Gender (n, %)	Female: 30 (38.5)	Female: 21 (55.3)	*p=.065
Gender (n, %)	Male: 48 (61.5)	Male: 17 (44.7)	*p=.065
Form of birth (n, %)	Normal vaginal route: 40 (51.3)	Normal vaginal route: 19 (50)	*p=.527
Form of birth (n, %)	Cesarean section: 38 (48.7)	Cesarean section: 19 (50)	*p=.527
Gestational week (weeks)	38.7±1.6 (35-42)	38.7±1.04 (36-41)	^&p=.807
(Mean±SD) (Min.-Max.)	38.7±1.6 (35-42)	38.7±1.04 (36-41)	^&p=.807
Birth weight (grams)	3058±584 (1850-4300)	3083±493 (2470-4080)	^#p=.703
(Mean±SD) (Min.-Max.)	3058±584 (1850-4300)	3083±493 (2470-4080)	^#p=.703
Age (postnatal day)	0	2.05±1.4 (0-4)	^&p=.000
Hospitalization duration (days)	22.0±30.3 (3-240)	0
(Mean±SD) (Min.-Max.)	22.0±30.3 (3-240)	0
HIE Stage (n, %)	Stage 2: 59 (75.6)	0
(According to Sarnat)	Stage 3: 19 (24.4)	0
Presence of seizures (n, %)	Yes: 39 (50)	0
Presence of seizures (n, %)	No: 39 (50)	0
Mortality (n, %)	Yes: 4 (5.1)	0
Mortality (n, %)	No: 74 (94.9)	0

	Before-TH	After-TH	p value	Control	p value
	n=78	n=78		n=38
	Mean±SD	Mean±SD		Mean±SD
	(Min.-max.)	(Min.-max.)		(Min.-max.)
WBC (×10 ⁹ /L)	20.48±6.99	9.80±4.55	p**<0.001	14.46±6.44	^&p=.000
WBC (×10 ⁹ /L)	(7.26-42.70)	(3.55-33.52)	p**<0.001	(4.70-30.0)	^&p=.000
Lymphocytes (×10 ⁹ /L)	5.04±3.52	2.66±1.74	p*<0.001	4.37±1.55	^&p=.687
Lymphocytes (×10 ⁹ /L)	(1.22-18.86)	(0.93-12.52)	p*<0.001	(1.06-8.11)	^&p=.000
Neutrophils (×10⁹ /L)	13.17±5.55	5.73±4.15	p*<0.001	7.85±5.30	^&p=.000
Neutrophils (×10⁹ /L)	(2.21-30.13)	(0.61-29.15)	p*<0.001	(1.93-20.20)	^#p=.035
Monocytes (×10 ⁹ /L)	1.20 ± 0.59	0.63±0.44	p*<0.001	1.61±0.76	^&p=.002
Monocytes (×10 ⁹ /L)	(0.19-3.58)	(0.04-2.34)	p*<0.001	(0.46-4.06)	^&p=.000
Platelets (×10 ⁹ /L)	204.73±74.37	146.48±66.76	p**<0.001	303.5±92.72	^&p=.000
Platelets (×10 ⁹ /L)	(30-492)	(12-293)	p**<0.001	(163-518)	^&p=.000
NLR	3.82±2.67	2.78±2.44	p*<0.001	1.96±1.44	^&p=.000
NLR	(0.26-15.22)	(0.09-14.22)	p*<0.001	(0.29-6.99)	^#p=.060
LMR	5.62±6.59	8.66±18.67	p*=0.069	2.97±1.07	^&p=.066
LMR	(0.72-47.0)	(0.92-132.25)	p*=0.069	(0.88-5.74)	^&p=.000
PLR	60.35±44.04	67.14±36.56	p**=0.180	79.88±44.32	^&p=.009
PLR	(4.16-246.04)	(3.67-189.34)	p**=0.180	(32.11-244.34)	^#p=.104

	Before-TH (n=78)		After-TH (n=78)			Control
	No seizure	Seizure present	No seizure	Seizure present	p value	Healthy newborn	p value	p value
	n=39	n=39	n=39	n=39		n=38	p value	p value
	Mean±SD	Mean±SD	Mean±SD	Mean±SD		Mean±SD	No seizure-control	Seizure present-control
	(Min.-max.)	(Min.-max.)	(Min.-max.)	(Min.-max.)		(Min.-max.)	No seizure-control	Seizure present-control

WBC	19.39±5.49	21.58±8.14	9.26±3.76	10.34±5.22	p**<0.001 (no seizure)	14.46±6.44	^&p=.000	^&p=.000
(×10 ⁹ /L)	(8.76-33.06)	(7.26-42.7)	(4.3-18.67)	(3.55-33.52)	p**<0.001 (seizure present)	(4.70-30.0)	^&p=.000	^&p=.002

Lymphocytes	5.15±3.38	4.93±3.70	2.57±1.06	2.76±2.24	p**<0.001 (no seizure)	4.37±1.55	^#p=.201	#p=.389
(×10 ⁹ /L)	(1.22-14.28)	(1.33-18.86)	(1.13-5.81)	(0.93-12.52)	p*<0.001 (no seizure)	(1.06-8.11)	^&p=.000	^&p=.000

Neutrophils	12.29±4.59	14.05±6.31	5.43±3.51	6.04±4.73	p**<0.001 (no seizure)	7.85±5.30	^&p=.000	^&p=.000
(×10 ⁹ /L)	(4.17-25.25)	(2.21-30.13)	(0.61-16.82)	(0.70-29.15)	p**<0.001(seizure present)	(1.93-20.20)	^#p=.021	^#p=.119

Monocytes	1.04±0.48	1.36±0.65	0.64±0.49	0.62±0.39	p**<0.001 (no seizure)	1.61±0.76	^&p=.000	^#p=.131
(×10 ⁹ /L)	(0.21-2.74)	(0.19-3.58)	(0.04-2.34)	(0.13-1.82)	p**<0.001 (seizure present)	(0.46-4.06)	^&p=.000	^&p=.000

Platelets	215.71±78.36	193.74±69.42	164.92±64.20	128.05±64.89	p**<0.001 (no seizure)	303.5±92.72	^&p=.000	^&p=.000
(×10 ⁹ /L)	(45.0-492.0)	(30.0-342.0)	(52.0-293.0)	(12.0-280.0)	p**<0.001 (seizure present)	(163-518)	^&p=.000	^&p=.000

NLR	3.49±2.34	4.15±2.95	2.55±2.34	3.01±2.54	p**=0.073 (no seizure)	1.96±1.44	^&p=.001	^&p=.000
NLR	(0.39-10.5)	(0.26-15.22)	(0.10-13.79)	(0.09-14.22)	p**=0.048 (seizure present)	(0.29-6.99)	^#p=.191	^#p=.030

LMR	6.57±7.98	4.68±4.73	9.30±21.2	8.01±16.0	p*=0.426 (no seizure)	2.97±1.07	^#p=.004	^#p=.034
LMR	(0.78-47.0)	(0.72-20.73)	(0.92-132.25	(1.47-96.31)	p*=0.072 (seizure present)	(0.88-5.74)	^&p=.000	^&p=.006

PLR	62.20±42.16	58.49±46.32	72.57±35.18	61.71±37.54	p**=0.216 (no seizure)	79.88±44.32	^#p=.077	^&p=.005
PLR	(4.16-199.18)	(5.25-246.04)	(8.89-189.34)	(3.67-171.78)	p**=0.581 (seizure present)	(32.11-244.34)	^#p=.425	^#p=.056

	Before-TH		After-TH		Control
	Stage 2 HIE	Stage 3 HIE	Stage 2 HIE	Stage 3 HIE	p value	Healthy newborn	p value	p value
	n=59	n=19	n=59	n=19		n=38	p value	p value
	Mean±SD	Mean±SD	Mean±SD	Mean±SD		Mean±SD	Stage	Stage
	(Min.-max.)	(Min.-max.)	(Min.-max.)	(Min.-max.)		(Min.-max.)	2-control	3-control

WBC (×10 ⁹ /L)	19.92±5.36	22.25±10.58	9.91±4.51	9.47±4.80	P**<0.001	14.46±6.44	^&p=.000	^#p=.007
	19.92±5.36	22.25±10.58	9.91±4.51	9.47±4.80	(stage 2)	14.46±6.44	^&p=.000	^#p=.007
	(8.40-33.06)	(7.26-42.7)	4.3-33.52)	(3.55-18.46)	P**<0.001	(4.70-30.0)	^&p=.000	^&p=.003
	(8.40-33.06)	(7.26-42.7)	4.3-33.52)	(3.55-18.46)	(stage 3)	(4.70-30.0)	^&p=.000	^&p=.003

Lymphocytes	4.42±2.75	6.96±4.86	2.52±0.95	3.09±3.13	P*<0.001	4.37±1.55	^&p=.198	^#p=.035
Lymphocytes	4.42±2.75	6.96±4.86	2.52±0.95	3.09±3.13	(stage 2)	4.37±1.55	^&p=.198	^#p=.035
(×10 ⁹ /L)	(1.22-13.63)	(1.33-18.86)	(0.93-5.81)	(1.06-12.52)	p<0.001	(1.06-8.11)	^&p=.000	^&p=.000
(×10 ⁹ /L)	(1.22-13.63)	(1.33-18.86)	(0.93-5.81)	(1.06-12.52)	(stage 3)	(1.06-8.11)	^&p=.000	^&p=.000


Neutrophils	13.5±4.60	12.10±7.89	5.96±4.35	5.05±3.45	P**<0.001	7.85±5.30	^&p=.000	^#p=.019
Neutrophils	13.5±4.60	12.10±7.89	5.96±4.35	5.05±3.45	(stage 2)	7.85±5.30	^&p=.000	^#p=.019
(×10 ⁹ /L)	(4.17-25.25)	(2.21-30.13)	(0.61-29.15)	(1.15-13.09)	P**<0.001	(1.93-20.20)	^#p=.070	^#p=.020
(×10 ⁹ /L)	(4.17-25.25)	(2.21-30.13)	(0.61-29.15)	(1.15-13.09)	(stage 3)	(1.93-20.20)	^#p=.070	^#p=.020


Monocytes	1.17±0.54	1.30±0.73	0.67±0.46	0.50±0.34	P**<0.001	1.61±0.76	^&p=.002	^#p=.154
Monocytes	1.17±0.54	1.30±0.73	0.67±0.46	0.50±0.34	(stage 2)	1.61±0.76	^&p=.002	^#p=.154
(×10 ⁹ /L)	(0.19-2.78)	(0.44-3.58)	(0.04-2.34)	(0.13-1.16)	P**<0.001	(0.46-4.06)	^&p=.000	^&p=.000
(×10 ⁹ /L)	(0.19-2.78)	(0.44-3.58)	(0.04-2.34)	(0.13-1.16)	(stage 3)	(0.46-4.06)	^&p=.000	^&p=.000

Platelets (×10 ⁹ /L)	199.98±68.02	219.47±91.91	155.84±65.27	117.42±64.48	P**<0.001	303.5±92.72	^&p=.000	^&p=.001
	199.98±68.02	219.47±91.91	155.84±65.27	117.42±64.48	(stage 2)	303.5±92.72	^&p=.000	^&p=.001
	(30.0-342)	(89.0-492.0)	(12.0-280.0)	(43.0-293.0)	P**<0.001	(163-518)	^&p=.000	^&p=.000
	(30.0-342)	(89.0-492.0)	(12.0-280.0)	(43.0-293.0)	(stage 3)	(163-518)	^&p=.000	^&p=.000

NLR	4.21±2.69	2.60±2.23	2.80±2.57	2.70±2.05	P*<0.001	1.96±1.44	^&p=.000	^#p=.196
	4.21±2.69	2.60±2.23	2.80±2.57	2.70±2.05	(stage 2)	1.96±1.44	^&p=.000	^#p=.196
	(0.39-15.22)	(0.26-9.12)	(0.10-14.22)	(0.09-6.63)	P**=0.840	(0.29-6.99)	^#p=.069	^#p=.174
	(0.39-15.22)	(0.26-9.12)	(0.10-14.22)	(0.09-6.63)	(stage 3)	(0.29-6.99)	^#p=.069	^#p=.174

LMR	5.27±6.78	6.72±5.96	7.60±17.38	11.93±22.40	P*=0.051	2.97±1.07	^&p=.188	^&p=.023
	5.27±6.78	6.72±5.96	7.60±17.38	11.93±22.40	(stage 2)	2.97±1.07	^&p=.188	^&p=.023
	(0.72-47.0)	(1.67-20.73)	(0.92-132.25)	(1.91-96.31)	p*=0.717	(0.88-5.74)	^&p=.001	^&p=.286
	(0.72-47.0)	(1.67-20.73)	(0.92-132.25)	(1.91-96.31)	(stage 3)	(0.88-5.74)	^&p=.001	^&p=.286

PLR	63.51±45.17	50.52±39.84	68.84±35.72	61.88±39.59	p=0.384	79.88±44.32	^&p=.041	^&p=.004
	63.51±45.17	50.52±39.84	68.84±35.72	61.88±39.59	(stage 2)	79.88±44.32	^&p=.041	^&p=.004
	(4.16-246.04)	(5.25-139.85)	(5.72-189.34)	(3.67-189.34)	p=0.197	(32.11-244.34)	^#p=.180	^#p=.140
	(4.16-246.04)	(5.25-139.85)	(5.72-189.34)	(3.67-189.34)	(stage 3)	(32.11-244.34)	^#p=.180	^#p=.140

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[1] *Correspondence: A. Kurt. Department of Pediatrics Division of Neonatology. Ankara Yıldırım Beyazıt University Yenimahalle Training and Research Hospital. Yeni Batı Mah. 2026 cad. 2367 sokak No:4. Batıkent Yenimahalle Ankara, Turkey. Orcid ID:0000-0002-4430-444X. Phone: +90 312 587 20 00. Phone: 90 533 331 73 29. Fax: +90 312 587 37 75. E-mail: drabdullahkurt@yahoo.com