Persistent pulmonary hypertension in neonates with perinatal asphyxia and therapeutic hypothermia: a frequent and perilous combination

Figures & data

Table 1. Perinatal, postnatal and outcome data in neonates with and without hypothermia.

	Hypothermia group	Control group	p-Value
	N = 114	N = 70
Male gender (%)	58 (51)	28 (40)	0.15
Gestational age (weeks)†	39.2 (1.7)	39.6 (1.8)	0.14
Birth weight (grams)†	3411 (607)	3350 (637)	0.52
Caesarean delivery (%)	65 (57)	43 (61)	0.56
Apgar score at 5 min^	3 (25^th 1–75^th 4)	5 (25^th 3–75^th 6)
pH†	6.9 (0.2)	6.9 (0.2)	0.50
BE in mmol/L†	−16.7 (7.7)	−16.8 (7.2)	0.94
Lactate in mmol/L†	12.4 (6.0)	9.8 (6.3)	0.006
Sepsis (%)	6 (5)	3 (4)	1.00
MAS (%)	10 (9)	5 (7)	0.70
Inotropes needed (%)	91 (80)	23 (33)	<0.0001
Seizures (%)	82 (72)	48 (69)	0.63
PPHN (%)	26 (23)	8 (11)	0.054
Mortality within one month (%)	36 (32)	17 (24)	0.29

†Mean (standard deviation); ^Median (Interquartile range). BE: base excess, MAS: meconium aspiration syndrome. pH, BE and lactate were collected from the umbilical cord or blood gas within one hour postpartum.

Table 2. Multivariate regression analysis with odds ratios(OR) on developing PPHN in neonates with and without hypothermia.

	Univariate regression analysis		Multivariate regression analysis
	OR (CI)	p-Value	OR (CI)	p-Value
Therapeutic hypothermia	2.290 (0.972–5.392)	0.058	2.534 (1.014–6.327)	0.047
Female gender	2.091 (0.952–4.591)	0.066	2.671 (1.104–6.464)	0.029
Gestational age	0.964 (0.780–1.192)	0.736
Birth weight	1.001 (1.000–1.001)	0.041	1.001 (1.000–1.002)	0.015
Caesarean delivery	1.170 (0.545–2.511)	0.687
Apgar score at 5 min	0.956 (0.789–1.159)	0.647
pH	6.345 (0.813–49.518)	0.078	4.324 (0.489–38.220)	0.188
BE	1.034 (0.982–1.088)	0.204
Lactate	1.045 (0.985–1.110)	0.145
Sepsis	2.323 (0.551–9.795)	0.251
MAS	4.602 (1.540–13.751)	0.006	3.502 (1.103–11.117)	0.033

CI: confidence interval; BE: base excess; MAS: meconium aspiration syndrome. pH, BE, and lactate were collected from the umbilical cord or blood gas within one hour postpartum.

Table 3. Risk factors for PPHN in neonates with therapeutic hypothermia and short-term outcomes.

Hypothermia (n = 114)	PPHN (n = 26)	No PPHN (n = 88)	p-Value
Maternal factors
SSRI use (%) Preeclampsia (%)	0 (0)	1 (1)	1.00
	1 (4)	2 (2)	0.55
Perinatal factors
5 min Apgar score^ pH† BE in mmol/L† Lactate in mmol/L† Sepsis (%) MAS (%)	2 (25^th 1 – 75^th 4)	3 (25^th 1 – 75^th 4)
	6.9 (0.2)	6.9 (0.2)	0.31
	−15.0 (5.0)	−17.3 (8.3)	0.11
	13.6 (6.3)	12.1 (6.0)	0.26
	2 (8)	4 (5)	0.62
	4 (15)	6 (7)	0.23
Respiratory variables
FiO2 before TH > 30% (%) Highest FiO2 before TH† Highest FiO2 during TH† Days mechanical ventilation† HFOV (%) Surfactant (%)	21 (81)	16 (20)	<0.001
	76.0 (33.0)	27.3 (15.1)	<0.001
	84.4 (26.3)	29.7 (12.8)	<0.001
	5.5 (2.3)	4.5 (2.9)	0.11
	17 (65)	1 (1)	<0.001
	16 (62)	7 (8)	<0.001
Circulatory variables
Inotropes before TH (%) Inotropes needed (%) If needed days† If needed number† Hydrocortisone (%)	8 (31)	18 (21)	0.28
	25 (96)	66 (75)	0.018
	4.2 (2.2)	2.6 (2.2)	<0.01
	2.5 (1.1)	1.1 (0.8)	<0.001
	18 (70)	12 (14)	<0.001
Neurological variables
Thompson score^^ Seizures (%) >2 Types of AED (%)	11 (25^th 8–75^th 13)	10 (25^th 8–75^th 13)
	15 (58)	67 (76)	0.066
	7 (27)	31 (35)	0.43
Outcome
Mortality < 28 d (%) Early mortality (<72 h)	7 (27)	29 (33)	0.56
PPHN	3	–
Pulmonary hemorrhage	1	–
Severe brain injury	1	3
Late mortality (>72 h)
Severe brain injury	2	26
Mortality < 28 d and/or severe brain injury on MRI (%)	10 (40)	33 (39)	0.92

†Mean (SD); ^{^}Median. SSRI: selective serotonin reuptake inhibitor; MAS: meconium aspiration syndrome; BE: base excess; FiO2: fraction of inspired oxygen; HFOV: high-frequency oscillation ventilation; AED: anti-epileptic drugs; SD: standard deviation.

pH, BE, and lactate were collected from the umbilical cord or blood gas within one hour postpartum.