A home-based, post-discharge early intervention program promotes motor development and physical growth in the early preterm infants: a prospective, randomized controlled trial

In the last two decades, the survival of early preterm infants (EPI) has dramatically improved due to the tremendous progress of neonatal intensive care. However, these survivors’ high incidence of neurodevelopmental impairment is still of great concern to neonatologist and pediatricians [1]. Studies has reported that 53% ~ 72% of EPI experienced learning difficulties and had weaker performance in academics than their term peers, and 15% of them developed cerebral palsy [2, 3]. Currently, to improve the long-term outcome of EPI, particularly the neurodevelopment, is a significant challenge in the pediatric field.

Early intervention (EI) is believed to improve the neurological prognosis of infants born prematurely, who was at high risk for neurodevelopmental impairment [3‐6]. Preterm infants have considerable brain plasticity during the early stage of life, and their nervous system has excellent development potential [7]. Applying EI to preterm infants can provide benign stimulus to the nervous system, modify the immature brain tissue, shape the brain structures, and ultimately improve the infant neurodevelopment [4‐6, 8]. A large body of literature has also demonstrated the effect of EI on promoting the physical growth of infants, including weight, length, and head circumference [9, 10].

Most EI programs are currently carried out in the hospital, follow-up clinics, or community-based medical settings. Implementation of an EI program is laborious, time-consuming, and resource-intensive, limiting its use on a large scale, particularly in some medical resource-limited regions. In 2018, the Chinese Eugenics Association developed a home-based, post-discharge EI program, which aims to promote the global development of preterm infants. It was a revised version of the existing developmental intervention program for infants, which started in 2010 and was universal for either term or preterm infants. The current EI program makes parents the front-line executors of EI under the orientation of medical staff, and it seems to satisfy all requirements for an ideal EI model: flexibility, low-cost, and active involvement of infants and their families [11]. This program provides an innovative approach to carry out EI. To our knowledge, so far, no literature regarding the effectiveness of this EI program has been published internationally. This study was aimed to evaluate the impact of this home-based, post-discharge EI program on neurodevelopment and physical growth in EPI.

A total of 138 infants were eligible for the RCT trial; 65 infants were excluded, resulting in 73 infants being randomly allocated, 37 in the EI-SC group (including one twin), and 36 in the SC-EI group. Besides, 33 infants were retrospectively recruited as the reference group (Fig. 1). No difference was noted among the three groups regarding demographic characteristics. The baseline TIMP, DQ, and anthropometric measures between the EI-SC and SC-EI groups were also comparable (Table 1).

TIMP, the test of infant motor performance; DQ, development quotient, calculated from the Gesell Developmental Schedules assessment; N/A, no neurological assessment for the reference group at baseline (T0).

EI means the intervention should be carried out as soon as possible, commonly started within the first 12 months of life. Post-discharge EI has been widely performed in follow-up clinics or in a community-based setting, which imposes high costs for the health care system. Taking Massachusetts, United States, as an example, the mean cost per infant for EI was 6614 dollars among the infants born at 24 ~ 31 weeks’ gestation, with a total EI cost of 65,910,379 dollars for all infants between 2009 and 2012 [17]. Such a huge number implied that the EI program might not be affordable in all countries, even in some developed countries. Meanwhile, some factors, such as traffic barriers, household overwork, and expensive accommodation cost, limit the parents to access the EI programs. Therefore, exploring a low-cost, family-based, flexible EI program was urgent for the medical providers and some families in need.

Amid this background, Sgandurra et al. developed a technological smart modular system as a tele-rehabilitation tool for EI, which could be implemented by parents at home under the orientation of rehabilitation staff. They demonstrated that this home-based EI significantly improved infant’s motor and visual development [16]. However, drawbacks also were evident; occurrence of technique errors seemed unavoidable for an internet-based system, and getting acquainted with a new system was also a challenge for some parents [18]. In this study, we conducted an innovative approach to carry out the home-based EI program, which was independent of any technological equipment and was free of knowledge gap for parents to perform it. Our study demonstrated that this EI program could promote motor development of EPI, as well as physical growth.

TIMP is the primary outcome measured in this study. Our results of the RCT period showed that the EI program was more effective in improving TIMP score than the standard care, which was consistent with Sgandurra’s study [16]; however, it conflicted with many previous studies, which did not show any significant effect of EI on motor development [4, 6, 19]. Some factors might contribute to the discrepancy. The frequency of EI performed in this study is once daily over 30 days, much higher than other studies which mostly ranged from once weekly to twice weekly [4]. Sgandurra et al. demonstrated that the amount of EI performance could affect the improvement of motor development [16] Meanwhile, our program adopted some promising evidence-based interventions, including body massage and kangaroo care. Body massage has been shown to effectively enhance motor development in various children population, including infants [20, 21]. The effect of kangaroo care on infant development was also well confirmed [22]. Massage and kangaroo care superimposed on basic intervention might generate a synergistic effect. Besides, different assessment tools might also lead to different results. Most previous studies used the Bayley physical development index (BPDI) to assess motor development, whereas our study used the TIMP instead. TIMP was approved to be a reliable and valid measurement of motor development, showing a highly significant correlation with BPDI [23]; TIMP is suitable for assessing infants < 6 months, while six months is the lower age limit for BPDI. Some studies have shown that the effect of EI on motor development was significant in infancy, but has not been noted for a long time. Therefore, a promising result in this study might be partially due to a relatively earlier assessment.

RCT did not show any significant difference in the DQ score between the EI-SC group and SC-EI group. Improvement of motor development demonstrated by TIMP was not present during the GDS assessments, which may be attributed to the structural limitation of the GDS. Each subdomain of GDS only has limited items under each month, scored as “observed” or “unobserved”; some minor changes cannot be specified. Meanwhile, GDS might delay identifying some subtle improvements, even some of which have already been noted by the parents [24]. In terms of physical growth, this EI program generally promoted the growth of weight, length, and HC, which was considered to be the result of a combination of many factors. Body massage has been shown to have the potential to improve gastrointestinal function and ultimately increase physical growth [25]. Literature also indicated that kangaroo care could shape preterm infant sleep behavior and prolong the duration of deep sleep [26]; a longer duration of deep sleep is a good predictor of optimal physical growth [27]. An EI program could also improve the infant’s feeding behavior, increase feeding volume, and positively affect physical growth [28, 29].

We conducted the open phase after the RCT, creditable from the consideration of ethics. No difference was noted between the EI-SC and SC-EI group regarding the improvements in all outcomes, which gave rise to the inference that the 60-day delayed EI had a similar effect to the EI performed at the beginning. Assessment at T2 endpoint also confirmed that no difference in TIMP and physical growth existed between the EI-SC and SC-EI group, but both were much higher than the reference group. It was an encouraging result for some parents who are concerned about the effect of the delayed intervention for their infants due to a variety of causes. However, currently, to carry out an EI program as soon as possible is still in recommendation.

Our study had certain limitations. We did not perform a long-term follow-up, hampering the evaluation of the long-term effect of this EI program. Meanwhile, the parent’s performance should alert the effectiveness of the EI program; however, it was impossible to keep all parents’ performances identical in this study. Fortunately, during the teaching session, our researcher should ensure that every parent had the basic skills to perform EI. In this study, we also cannot completely rule out the situation that some parents performed additional EI beyond the requirements of the study protocol, even the parents have initially signed the consent to comply with the study protocol.

This study introduced a home-based, post-discharge EI program, which was less-cost, particularly suitable in medical source-limited regions. This EI program could significantly promote motor development and physical growth of EPI, at least in a short-term period. However, long-term follow-up is still in need to determine the long-term effect of this program on infant development.