Date Published: February 12, 2018
Publisher: Public Library of Science
Author(s): Deodata Tijsseling, Maike ter Wolbeek, Jan B. Derks, Willem B. de Vries, Cobi J. Heijnen, Frank van Bel, Eduard J. H. Mulder, Olivier Baud.
Although postnatal corticosteroid (CS) therapy has well established beneficial effects on pulmonary function, it may also result in growth restriction during treatment. The course of early childhood growth is believed to predict cardiovascular and metabolic diseases in adulthood. Therefore, we determined the effects of postnatal dexamethasone (DEX) or hydrocortisone (HC) treatment on patterns of postnatal growth until approximately four years of age.
In an observational cohort study of children born prematurely (<32 weeks of gestation), we compared growth patterns for body weight, height, and head circumference from birth to age four years, of children who received DEX (boys: N = 30, girls: N = 14), HC (boys: N = 33, girls: N = 28) to a reference group that had not received postnatal CSs (boys: N = 52, girls: N = 53) using linear mixed-effects modeling. Growth velocity curves of CS-treated neonates showed a shift to the right, representing a delay in time. They had decreased absolute growth velocities during and shortly after treatment, followed by an increase in growth velocity thereafter. A shift to the right was also seen for the age at which maximal growth velocity of weight/height was reached in boys and girls. Fractional growth rates of weight, height, and head circumference were generally reduced in the CS-treated groups during the first two months of age, with catch-up growth in the following months. In DEX-treated infants these changes were more pronounced than in HC-treated infants. These data suggest that postnatal growth patterns of preterm born infants are affected by CS-treatment, more by DEX than by HC. Effects were observed mainly on growth velocities. This observation may have impact on health in later life for those individuals treated with CSs in the neonatal period. A definitive conclusion would require a randomized trial of these therapies.
Chronic lung disease (CLD) is a significant problem in preterm infants carrying a high risk of mortality and long-term morbidity . Corticosteroids (CS), especially dexamethasone (DEX) and less frequently hydrocortisone (HC), are used to prevent and reduce CLD. Short-term benefits of neonatal CS-therapy to enhance pulmonary development are well-established with the use of either drug [2–5]. However, follow-up studies of children treated with DEX in the neonatal period have reported on increased rates of cerebral palsy and long-term motor deficits and neuropsychological impairments [6–11]. HC is considered to be safer [12–14], although impairment in neurodevelopment at school age has been described in a small follow-up study .
Participant characteristics are summarized in Table 1 and can also be found in the S1 File. Compared to the untreated group, infants in the treated groups were born earlier, weighed less at birth, and were less frequently a twin member (significant for DEX group). However, the group differences in birth weight disappeared after adjustment for gestational age at birth and gender, as evidenced by the birth weight SD scores. In the neonatal period, CS-treated infants had a higher prevalence of Infant Respiratory Distress Syndrome (IRDS) (grades 1–4) and severe IRDS (grades 3–4) and needed more often artificial ventilation and for a longer period of time than untreated infants. The onset of CS-therapy occurred significantly earlier in the HC group than in the DEX group, however this had no contribution to the model. Duration of CS therapy was not significantly different between both groups and duration was therefore not considered a covariable in the analyses of growth.
The current findings suggest that neonatal intervention with DEX and HC affects growth patterns for weight, height, and head circumference of preterm born males and females in their first 48 months, as compared to growth parameters of a preterm born reference group that was not CS-treated. Effects of DEX and HC treatment were observed mainly on growth velocities. Compared to untreated infants, the growth velocity curves of treated neonates showed a shift to the right, representing a delay in time. They presented as decreased absolute growth velocities during and shortly after treatment, followed by an increase in growth velocity. A shift to the right was also seen for the age at which maximal growth velocity of weight/size was reached in boys and girls. FGRs of weight, height, and head circumference were generally reduced in the treated groups during the first two months of age, with catch-up growth in the following months. In DEX-treated infants these changes were more pronounced than in HC-treated infants.