Tocolysis with Beta-2-sympathomimetics Increases the Occurrence of Infantile Hemangiomas in Preterm Born Infants

Ziel: Infantile hemangioma (IH) is the most commonly observed tumor in children. As recently detected, off-label pharmacological treatment of IH with the beta-blocker propranolol induces regression of IH. Based on the fact that IH are more frequently observed in premature babies than in mature babies and the evidence that beta-blocker therapy leads to regression of IH we generated the hypothesis that the use of betamimetics during pregnancy for inhibiting premature labor might increase occurrence of IH in preterm infants.

Methodik: Data of 328 preterm infants (< 32 gestational weeks) or with a birth weight of less than 1500g born between January 2006 and December 2008 were analyzed. Statistics: For subgroup comparison the t-test, Man-Whitney-U-test and Fisher´s exact test were used. Logistic regression was carried out by the forward stepwise method with Wald statistics.

Ergebnis: Fifteen patients died within the 1st month of life and were excluded from analysis, 38 subjects were excluded because of lost to follow up and 6 subjects due to incomplete data. Complete data of 269 preterm infants were retrospectively analyzed (table 1). During the follow up period of median 1.6 years 50 infants developed one or more IH within their first 6 months of life. IH occurred in 40/181 patients with intrauterine exposure to the betamimetic hexoprenaline and in 10/88 without exposure (OR=4.326; 95% CI 1.360–13.763). Antenatal exposure to steroids for induction of lung development reduced occurrence of IH (OR=0.200; 95% CI 0.048–0.833) (table 2).

Schlussfolgerung: Intra-uterine exposure to the beta–2-sympathomimetic hexoprenaline increases the occurence of IH in preterm infants.

Table 1: Subgroupanalysis, variables of patients with infantile hemangioma (IH group, n=50) compared to patients without infantile hemangioma (non-IH group, n=219). Results are given as mean±Standard deviation (SD) or number. Birth weight and birth length were standardized and expressed as SDS (Standard deviation score) using national reference values (Mayer et al 2008).

Variable	IH group	Non-IH group	p-value
Female gender	♀=34/50 (68.0%)	♀=98/219 (44.7%)	0.004
Exposure to hexoprenaline (Primary Endpoint)	40/50 (80.0%)	141/219 (64.4%)	0.044
Hexoprenaline (gestational week)	27.0±2.5	27.0±3.1	0.799
Hexoprenaline (cumulative dose, µg)	1640±1515	1546±1911	0.251
Administration of atosiban	8/50 (16%)	28/219 (12.8%)	0.500
Atosiban (gestatioal week)	27.6±2.0	26.6±2.2	0.288
Prenatal corticosteroids	41/46 (89.1%)	193/209 (92.3%)	0.796
Maternal age (years)	30.5±5.1	30.3±6.0	0.826
Completed gestational weeks	28.9±2.0	29.0±2.5	0.796
Apgar score at 1 minute	6.0±2.2	5.8±2.2	0.469
Apgar score at 5 minutes	7.6±1.5	7.6±1.6	0.814
Cesarean section	33/50 (66.0%)	163/219 (74.4%)	0.224
Twin pregnancy	14/50 (28.0%)	57/219 (26.0%)	0.798
Birth weight (g)	1281±262	1252±411	0.532
Birth weight (SDS)	-0.1±0.7	-0.3±1.4	0.074
Length at birth (cm)	38.2±3.0	38.1±4.1	0.762
Length at birth (SDS)	-0.3±0.8	-0.4±1.0	0.381
Head circumference at birth (cm)	26.9±1.8	26.8±2.8	0.807
Stay in NICU (days)	25±18	32±55	0.852
Total hospital stay (days)	54±26	58±34	0.874
Follow-up times (years)	1.6±1.0	1.6±0.9	0.932

Table 2: Stepwise logistical regression (Wald).

	Odds ratio	95% CI	p-value
Female gender	2.576	1.233–5.383	0.012
Prenatal exposure to hexoprenaline	4.326	1.360–13.763	0.013
Prenatal exposure to corticosteroids	0.200	0.048–0.833	0.027