Late effects of caffeine use on sleep of infants born prematurely

This study aimed to evaluate whether the therapeutic use of caffeine for premature newborns is associated with changes in sleep habits and the presence of obstructive sleep apnea in childhood.

Methods:

This is a cross-sectional single-center study in which the caretakers of 87 children aged 5–10 years, born full-term or preterm, treated or not with caffeine in the neonatal period, answered questionnaires to screen for obstructive sleep apnea (Pediatric Obstructive Sleep Apnea Screening Tool [PosaST]) and to characterize the sleep habits (Children's Sleep Habits Questionnaire [CSHQ]) of their children. ANOVA and linear regression tests were performed to verify possible differences between the groups.

Results:

Children born prematurely who were treated with caffeine woke up significantly later on weekdays than those born at term (09h±00h58 and 07h43±1h15, respectively, p=0.022) and had longer total daily sleep time also compared to those born at term (10h24±1h08 and 09h29±1h08, respectively, p<0.001). There was no significant difference between the three groups in overall PosaST and CSHQ scores.

Conclusions:

Caffeine use in the neonatal period did not impair sleep habits later in life and did not lead to increased obstructive sleep apnea scores in prematurely born children compared to those born at term.

Keywords:
Sleep; Preterm infants; Caffeine; Obstructive sleep apnea; Sleep habits

Variables		PCG (n=22; 25%)	PNCG (n=20; 23%)	TG (n=45; 52%)	p-value
Demographic data
	Sex: female	12 (54.54)	15 (75)	25 (55.56)	0.285
	Age, years^* * Mean±standard deviation. Statistical analysis of the categorical variables was performed by using Qui-squared test. The post hoc adjusted residual analysis identified significant associations between term gestation and single pregnancies, preterm birth and antenatal corticosteroid administration, SGA and PNCG, TG and least indication of resuscitation in the delivery room, IGR and PNCG, TG, and the absence of hypertensive disorder of pregnancy. Continuous variables were compared by Kruskal-Wallis test that identified differences in the GA (TG>PNCG>PCG), birth weight (TG>PNCG>PCG), birth stature (TG>PNCG>PCG), first minute (TG>PNCG=PCG), and fifth minute (TG>PNCG=PCG) Apgar scores.	7.36±1.62	6.8±1.40	7.00±1.51	0.486
Clinical data
	Multiple gestation	3 (13.64)	2 (10)	0 (0)	0.029
	Antenatal corticosteroid	12 (54.54)	7 (35)	2 (4.45)	<0.001
	Cesarean section	16 (72.73)	15 (75)	31 (68.89)	0.868
	Gestational age considered (days)	205±16	234±10	281±8	<0.001
	Weight, g	1117±288	1633±273	3260±427	<0.001
	Length, cm	36±3.13	40±2.07	49.00±2.17	<0.001
Weight adjustment					<0.001
	SGA	3 (13.64)	11 (55)	4 (8.89)
	AGA	19 (86.36)	9 (45)	34 (75.56)
	LGA	0 (0)	0 (0)	7 (15.56)
	APGAR 1st min	6.68±1.67	7.75±1.52	8.90±1.14	<0.001
	APGAR 5th min	8.68±1.09	9±0.79	9.79±0.41	<0.001
	Resuscitation in the delivery room	10 (45.45)	5 (25)	0 (0)	<0.001
Maternal medical history
	Systemic arterial hypertension	4 (18.18)	0 (0)	1 (2.22)	0.014
	Diabetes mellitus	1 (4.54)	0 (0)	0 (0)	0.224
	Cardiopathy	0 (0)	0 (0)	0 (0)	–
	Pneumopathy	0 (0)	0 (0)	2 (4.45)	1.0
Obstetric complications
	Intrauterine growth restriction	1 (4.54)	6 (30)	2 (4.45)	0.007
	Hypertensive disorder of pregnancy	13 (59.09)	7 (35)	3 (6.67)	<0.001
	Gestational diabetes	3 (13.64)	2 (10)	5 (11.11)	0.607
	Chorioamnionitis	0 (0)	0 (0)	0 (0)	–

Variables		PCG (n=22; 52%)	PNCG (n=20; 48%)
Respiratory distress syndrome		21 (95.45)	14 (70)
Bronchopulmonary dysplasia		7 (31.82)	1 (5)
Apnea of prematurity		21 (95.45)	1 (5)
Persistent ductus arteriosus		6 (27.27)	1 (5)
Sepsis		7 (31.82)	2 (10)
Meningitis		1 (4.54)	0 (0)
Necrotizing enterocolitis		1 (4.54)	1 (5)
Periventricular hemorrhage		8 (36.36)	2 (10)
Leukomalacia		0 (0)	0 (0)
Retinopathy of prematurity		5 (22.73)	0 (0)
Metabolic bone disease		0 (0)	0 (0)
Mechanical ventilation		17 (77.27)	3 (15)
	Days on mechanical ventilation	14.8±16.7	9±13
Corticosteroid		4 (18.18)	1 (5)
	Days of corticosteroids	5±4	13±0
Diuretics		7 (31.82)	1 (5)
	Days of diuretics	26.4±23.7	–
Caffeine		22 (100)	0 (0)
	Days of caffeine	29.9±14.3	0 (0)
Parenteral nutrition		19 (86.36)	7 (35)
	Days of parenteral nutrition	21.5±30.8	11.9±9.28
Full enteral nutrition, days		16.5±5.72	10.5±3.54
Weight loss, %		-8.32±4.78	-7.95±4.55
Day for weight recovery		10.3±5.81	8.88±3.82
Lemght of hospital stay in days		67.6±39.2	42.6±48.7
Corrected gestational age at hospital discharge in weeks		39 2/7±5 2/7	39 2/7±6 3/7

Groups	Total number of individuals	Number (%) above the cutoff point in CSHQ	Number (%) above the cutoff point in PosaST
PNCG	20	14 (70)	5 (25)
PCG	22	15 (68)	2 (9)
TG	45	34 (75)	3 (6.6)

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[1] *Corresponding author. E-mail: ac.oliveira@unifesp.br (A. C. Oliveira)