988368

1. Introduction 
The modern era of neonatal care is characterized by significant technological advances in mechanical ventilation and medicinal therapies [1, 2]. Such advances have dramatically increased the survival rate for the youngest and smallest preterm infants [3, 4]. Approximately 90% of neonates born prematurely require highly specialized neonatal care. Although such care and technology save lives, medical and developmental sequelae (e.g., cognitive delays, neurodevelopmental and behavior problems) related to immaturity remain of concern [5]. The challenge of healthcare professionals who support preterm neonates and their parents is not only ensuring neonates’ survival but also optimizing infant development [6]. 
The stressful environment that premature neonates face, negatively impacts brain development and neurobehavioral outcomes in the future [7]. Exposure to loud or sharp sounds and constant light are the sources of stress for preterm neonates that may lead to physiological and behavioral stress [8]. Infants demonstrate physiological and psychological stability during Neonatal Intensive Care Unit (NICU) hospitalization, a critical period for neurodevelopment when protected from excessive light and noise [9, 10, 11, 12].
The preemies lack the muscle tone and strength to control normal posture and movements, so their extremities tend to lie extended rather than flexed. This long-term abnormal position can lead to abnormal posture and deformities with consequent delay in acquiring developmental motor skills and disturbs oral-motor abilities [13]. According to the literature, therapeutic positioning is a major early neurodevelopmental intervention in the NICU that promotes the normal position of newborns and supports neuromuscular development and behavioral organization [11, 14, 15]. These high-risk infants should usually be followed up with developmental screening for early detection and start early intervention to decrease adverse outcomes.
Enabling participation in everyday occupations and life activities as a critical factor in an infant’s development has become an important outcome for occupational therapy services [16]. Facilitation of mother-infant bonding is an important key in caring for at-risk infants, so healthcare professionals have emphasized family-centered care and parent training that support optimal brain development and provides various benefits to both mother and infant [17, 18]. 
Literature review shows that most studies on the effectiveness of developmental care are based on trials performed during the hospitalization period and do not have follow-ups. Many scientific studies have been performed about developmental care and parent training, but they concentrated on one strategy [19, 20].
Performance of training programs such as COPE (Creating Opportunities for Parent Empowerment) utilizes these strategies and interventions. COPE is a comprehensive educational program used for preterm neonates and their parents [21]. A review of previous studies reveals that the COPE program can decrease stress level that interferes with caring tasks. By increasing parents’ knowledge and changing their opinions on preterm neonates, their parental roles will change [22, 23]. This study has concentrated on ways to improve the care and environment of the NICU for neonates and their parents through the use of developmental care programs. This study aims to empower mothers by gradually training and facilitating the responsibility for meeting every need of their infants; consequently, an empowered mother can promote developmental outcomes of premature infants.
2. Methods 
The influence of the COPE program on developmental outcomes was analyzed through a randomized, double-blind clinical trial, which included a sample of 40 preterm infants. The criteria for including preterm neonates were 1) weight 1000 to 2500 g at birth, 2) GA lower than 37 weeks, 3) 5-minute Apgar score 7 and more, 4) no considerable brain ultrasound abnormalities (grade III or IV Intraventricular Hemorrhage [IVH]), 5) no neuromuscular disorders and congenital anomalies, and 6) hospitalization in NICU for at least 7 to 30 days. Neonates were excluded from the study if they had the disease or neonatal death during the study, or the parents tended to exclude their infants from the study for any reason and at any time despite their initial satisfaction.
The randomization process was done using a randomized block design, and neonates were assigned randomly to the intervention (n=20) and control (n=20) groups. Parents of infants in the intervention group received a COPE schedule in a set of CDs in conjunction with written instruction and supplemented activities (guidebook). COPE schedule was performed in 5 steps: step I, 2-4 days following the entrance of the infant to the NICU; step II, 2-4 days after implementing the first step; step III, 1-4 days before the infant leaves the NICU; step IV, about one week after discharge; and step V, about 2 months old of corrected age. Neonates in the control group received routine services and interventions, and the research therapist performed no additional interventions.
Outcome measurements
A detailed history and new Ballard examination were made for all neonates at the time of enrollment, followed by administration of Ages and Stages Questionnaire (ASQ) by an occupational therapist, double-blinded for the study, to any of the available parents (mostly mothers) at 6 months of corrected age (Figure 1). Statistical analysis
Data analysis was performed using the SPSS software v. 18. All values were tabulated as Mean±SD. The independent t test was used to analyze the difference between groups. The significance level for the statistical test was considered to be 0.05, and the confidence interval was 95%. 
All ethical considerations were observed according to the Research Ethics Committee of Rehabilitation College of Iran University of Medical Sciences. This research was performed at the NICU of two University Hospitals in Tehran City, Iran, from March 2015 to February 2016. All parents gave their free and informed consent to participate in the study.
3. Results
The Mean±SD gestational age of the neonates was 31.80±2.50 weeks in the control group; range: 26-36 weeks and 33.05±1.39 weeks in the intervention group; range: 32-35 weeks. As shown in Table 1, neonates in both groups were matched in terms of gestational age, birth weight, birth height, head circumference at birth, Apgar scores (1 min, 5 min), prematurity, and new Ballard score.


So, there was no significant difference between them at the baseline. The results showed (Table 2) more maturity in “communication”, “gross motor”, “problem-solving”, and “personal-social” in the intervention group, and the differences between the 2 groups in these outcomes were significant (P<0.05). 


4. Discussion
The present study investigated the developmental areas of premature infants during the first months of life using the ASQ scales. Many studies have been done to investigate parent training about the development of their premature neonate. The Mother-Infant Transaction Program (MITP) is an intervention program designed to enhance parent sensitivity to their own hospitalized premature neonates. It uses tactile stimulation activities such as touch or skin-to-skin care [24]. The MITP highlights the transactional nature of development and, with its intervention program, attempts to sensitize the parents to their infant’s cues, especially those that are a sign of stimulus overload, distress, and readiness for interaction [25]. In a trial of MITP, parents were trained to recognize and minimize stress responses in their preterm infants. At 6 months of corrected age, the infants in the intervention group scored better than the control group on the communication and symbolic behavior scales developmental profile infant-toddler checklist [26].
Another commonly used intervention is the Newborn Individualized Developmental Care and Assessment Program (NIDCAP). It is developmental-related supportive care and early intervention that starts quickly after birth. The long-time effectiveness of NIDCAP in improving behavior and mother-child interaction has already been shown [27]. The Infant Behavioral Assessment and Intervention Program (IBAIP) is an intervention that delivers post-discharge and yields sustainable consequences on raising children’s locomotion in routine activities [28]. However, benefits in behavior and cognition found at 6 months were not lasting through to preschool age [29, 30].
The latest systematic review has focused on the cognitive and motor skills of premature infants [31, 32, 33]. Spittle et al. [31] and Orton et al. [30], in their Cochrane review, mentioned that there are good consequences on cognitive development in preschool-age that were not lasting to school age. No motor maturity consequences were shown at any age. Vanderveen et al. [32] reviewed Randomized Controlled Trials (RCTs) or quasi-RCTs published up to 2008 that investigated early interventions on preterm infants and their parents. Interventions covered training sessions for parents, visiting infants at home, utilizing appropriate stimuli, and routine intervention in NICU. With meta-analysis, significant positive changes are seen in the intervention group in 12 months. At 24 months, positive changes have stayed for cognitive scores only. By ages 3 and 5 years, no significant changes have stayed.
The COPE intervention provides a unique approach to helping mother–preterm infant establishes positive interaction patterns. However, systematic reviews suggest that evidence for improved over-lasting developmental consequences is not conclusive [34, 35].
5. Conclusion
In conclusion, our study result is consistent with previous research and showed that interventions emphasizing parent-infant interactions and stress reduction might positively affect some fundamental development indicators for preterm infants. This finding is in line with the relevance development of preterm brain and stress confronted and with evidence of advancements in the early brain development after appropriate intervention in NICU.

Ethical Considerations
Compliance with ethical guidelines
This research has been registered at www.irct.ir (code: IRCT2015040521613N1) and approved by the Research Ethics Committee of Rehabilitation College of Iran University of Medical Sciences. After obtaining written consent from the parents, the participants were entered into the study protocol.

Funding
This study was extracted from the project at the Department of Occupational Therapy, School of Rehabilitation Sciences, Iran University of Medical Sciences (No.: 5536/105/D/93).

Authors' contributions
Conceptualization and Supervision: Narges Shafaroodi, Reihaneh Askary Kachoosangy, and Mohammad Heidarzadeh; Methodology: Mostafa Qorbani, Narges Shafaroodi, and Reihaneh Askary Kachoosangy; Data collection: Seyede Zeinab Beheshti and Reihaneh Askary Kachoosangy; Data analysis: Mostafa Qorbani; Investigation, Writing-original draft, and Writing-review & editing: All authors.

Conflict of interest
The authors declared no conflict of interest.

Acknowledgments
The authors would like to thank the parents and their infants for participating in this study. We also thank the attending physicians and nurses of two University Hospitals, Akbar-abadi and Mahdieh in Tehran.


References

1. Stoelhorst GM, Rijken M, Martens SE, Brand R, Den Ouden AL, Wit J-M, et al. Changes in neonatology: Comparison of two cohorts of very preterm infants (gestational Age< 32 weeks): The project on preterm and small for gestational age infants 1983 and the Leiden follow-up project on prematurity 1996-1997. Pediatrics. 2005; 115(2):396-405. [DOI:10.1542/peds.2004-1497] [PMID]
2. Askary Kachoosangy RA, Aliabadi F. Effect of tactile-kinesthetic stimulation on motor development of low birth weight neonates. Iranian Rehabilitation Journal. 2011; 10(13):16-8. https://www.sid.ir/en/Journal/ViewPaper.aspx?ID=321589
3. Wilson-Costello D, Friedman H, Minich N, Fanaroff AA, Hack M. Improved survival rates with increased neurodevelopmental disability for extremely low birth weight infants in the 1990s. Pediatrics. 2005; 115(4):997-1003. [DOI:10.1542/peds.2004-0221] [PMID]
4. Aliabadi F, Askary RK. Effects of tactile-kinesthetic stimulation on low birth weight neonates. Iranian Journal of Pediatrics. 2013; 23(3):289-94. [PMCID]
5. McGrath JM, Braescu AVB. State of the science: Feeding readiness in the preterm infant. The Journal of Perinatal & Neonatal Nursing. 2004; 18(4):353-68. [DOI:10.1097/00005237-200410000-00006] [PMID]
6. Als H. Program guide: Newborn individualized developmental care and assessment program (NIDCAP): An education and training program for health care professionals. Boston, MA: Children’s Medical Center Corporation. 2002. http://nidcap.org/wp-content/uploads/2014/09/Program-Guide-Rev-22Sep2014.pdf
7. Milgrom J, Newnham C, Anderson PJ, Doyle LW, Gemmill AW, Lee K, et al. Early sensitivity training for parents of preterm infants: Impact on the developing brain. Pediatric Research. 2010; 67(3):330-5. [DOI:10.1203/PDR.0b013e3181cb8e2f] [PMID]
8. Nair M, Gupta G, Jatana S. NICU environment: Can we be ignorant? Medical Journal Armed Forces India. 2003; 59(2):93-5. [DOI:10.1016/S0377-1237(03)80046-1]
9. Santos J, Pearce SE, Stroustrup A. Impact of hospital-based environmental exposures on neurodevelopmental outcomes of preterm infants. Current Opinion in Pediatrics. 2015; 27(2):254-60. [DOI:10.1097/MOP.0000000000000190] [PMID] [PMCID]
10. Venkataraman R, Kamaluddeen M, Amin H, Lodha A. Is less noise, light and parental/caregiver stress in the neonatal intensive care unit better for neonates? Indian Pediatrics. 2018; 55(1):17-21. [DOI:10.1007/s13312-018-1220-9] [PMID]
11. Almadhoob A, Ohlsson A. Sound reduction management in the neonatal intensive care unit for preterm or very low birth weight infants. The Cochrane Database of Systematic Reviews. 2015; 1:CD010333. [DOI:10.1002/14651858.CD010333.pub2] [PMID]
12. Turk CA, Williams AL, Lasky RE. A randomized clinical trial evaluating silicone earplugs for very low birth weight newborns in intensive care. Journal of Perinatology. 2009; 29(5):358-63. [DOI:10.1038/jp.2008.236] [PMID] [PMCID]
13. Madlinger-Lewis L, Reynolds L, Zarem C, Crapnell T, Inder T, Pineda R. The effects of alternative positioning on preterm infants in the neonatal intensive care unit: A randomized clinical trial. Research in Developmental Disabilities. 2014; 35(2):490-7. [DOI:10.1016/j.ridd.2013.11.019] [PMID] [PMCID]
14. Waitzman KA. The importance of positioning the near-term infant for sleep, play, and development. Newborn and Infant Nursing Reviews. 2007; 7(2):76-81. [DOI:10.1053/j.nainr.2007.05.004]
15. Siddicky SF, Bumpass DB, Krishnan A, Tackett SA, McCarthy RE, Mannen EM. Positioning and baby devices impact infant spinal muscle activity. J Biomech. 2020; 104:109741. [DOI:10.1016/j.jbiomech.2020.109741] [PMID] [PMCID]
16. Pashazadeh Azari Z, Hosseini SA, Rassafiani M, Samadi SA, Hoseinzadeh S, Dunn W. Contextual intervention adapted for autism spectrum disorder: An RCT of a parenting program with parents of children diagnosed with Autism Spectrum Disorder (ASD). Iranian Journal of Child Neurology. 2019; 13(4):19-35. [PMCID]
17. Conde-Agudelo A, Díaz-Rossello JL. Kangaroo mother care to reduce morbidity and mortality in low birthweight infants. Cochrane Database of Systematic Reviews. 2016; 2016(8):CD002771. [DOI:10.1002/14651858.CD002771.pub4]
18. Harrison LL, Williams AK, Berbaum ML, Stem JT, Leeper J. Physiologic and behavioral effects of gentle human touch on preterm infants. Research in Nursing & Health. 2000; 23(6):435-46. [DOI:10.1002/1098-240X(200012)23:63.0.CO;2-P]
19. Pineda R, Bender J, Hall B, Shabosky L, Annecca A, Smith J. Parent participation in the neonatal intensive care unit: Predictors and relationships to neurobehavior and developmental outcomes. Early Human Development. 2018; 117:32-8. [DOI:10.1016/j.earlhumdev.2017.12.008] [PMID] [PMCID]
20. Umberger E, Canvasser J, Hall SL. Enhancing NICU parent engagement and empowerment. Seminars in Pediatric Surgery; 2018; 27(1):19-24. [DOI:10.1053/j.sempedsurg.2017.11.004] [PMID]
21. Melnyk BM, Feinstein NF, Alpert-Gillis L, Fairbanks E, Crean HF, Sinkin RA, et al. Reducing premature infants’ length of stay and improving parents’ mental health outcomes with the Creating Opportunities for Parent Empowerment (COPE) neonatal intensive care unit program: A randomized, controlled trial. Pediatrics. 2006; 118(5):e1414-27. [DOI:10.1542/peds.2005-2580] [PMID]
22. Melnyk BM, Alpert-Gillis L, Feinstein NF, Crean HF, Johnson J, Fairbanks E, et al. Creating opportunities for parent empowerment: Program effects on the mental health/coping outcomes of critically ill young children and their mothers. Pediatrics. 2004; 113(6):e597-607. [DOI:10.1542/peds.113.6.e597] [PMID]
23. Melnyk BM, Alpert‐Gillis L, Feinstein NF, Fairbanks E, Schultz‐Czarniak J, Hust D, et al. Improving cognitive development of low-birth-weight premature infants with the COPE program: A pilot study of the benefit of early NICU intervention with mothers. Research in Nursing & Health. 2001; 24(5):373-89. [DOI:10.1002/nur.1038] [PMID]
24. Rauh VA, Nurcombe B, Achenbach T, Howell C. The mother-infant transaction program: The content and implications of an intervention for the mothers of low-birthweight infants. Clinics in Perinatology. 1990; 17(1):31-45. [DOI:10.1016/S0095-5108(18)30586-4]
25. Sameroff AJ, Fiese BH. Transactional regulation: The developmental ecology of early intervention. In: Shonkoff JP, Meisels SJ, ediotrs. Handbook of early childhood intervention. United Kingdom: Cambridge University Press; 2000. [DOI:10.1017/CBO9780511529320.009]
26. Kleberg A, Westrup B, Stjernqvist K. Developmental outcome, child behaviour and mother-child interaction at 3 years of age following Newborn Individualized Developmental Care and Intervention Program (NIDCAP) intervention. Early Human Development. 2000; 60(2):123-35. [DOI:10.1016/S0378-3782(00)00114-6]
27. Verkerk G, Jeukens-Visser M, Koldewijn K, van Wassenaer A, Houtzager B, Kok J, et al. Infant behavioral assessment and intervention program in very low birth weight infants improves independency in mobility at preschool age. The Journal of Pediatrics. 2011; 159(6):933-8.e1. [DOI:10.1016/j.jpeds.2011.05.035] [PMID]

28. Koldewijn K, Wolf M-J, Van Wassenaer A, Beelen A, De Groot IJ, Hedlund R. The Infant Behavioral Assessment and Intervention Program to support preterm infants after hospital discharge: A pilot study. Developmental Medicine and Child Neurology. 2005; 47(2):105-12. [DOI:10.1111/j.1469-8749.2005.tb01098.x] [PMID]
29. Verkerk G, Jeukens-Visser M, Houtzager B, Koldewijn K, van Wassenaer A, Nollet F, et al. The infant behavioral assessment and intervention program in very low birth weight infants; Outcome on executive functioning, behaviour and cognition at preschool age. Early Human Development. 2012; 88(8):699-705. [DOI:10.1016/j.earlhumdev.2012.02.004] [PMID]
30. Orton J, Spittle A, Doyle L, Anderson P, Boyd R. Do early intervention programmes improve cognitive and motor outcomes for preterm infants after discharge? A systematic review. Developmental Medicine & Child Neurology. 2009; 51(11):851-9. [DOI:10.1111/j.1469-8749.2009.03414.x] [PMID]
31. Spittle AJ, Ferretti C, Anderson PJ, Orton J, Eeles A, Bates L, et al. Improving the outcome of infants born at< 30 weeks’ gestation-a randomized controlled trial of preventative care at home. BMC Pediatrics. 2009; 9:73. [DOI:10.1186/1471-2431-9-73] [PMID] [PMCID]
32. Vanderveen J, Bassler D, Robertson C, Kirpalani H. Early interventions involving parents to improve neurodevelopmental outcomes of premature infants: A meta-analysis. Journal of Perinatology. 2009; 29(5):343-51. [DOI:10.1038/jp.2008.229] [PMID]
33. Spittle A, Orton J, Doyle L, Boyd R. Early developmental intervention programs post hospital discharge to prevent motor and cognitive impairments in preterm infants. Cochrane Database of Systematic Reviews. 2007; (2):CD005495. [DOI:10.1002/14651858.CD005495.pub2] [PMCID]
34. Symington AJ, Pinelli J. Developmental care for promoting development and preventing morbidity in preterm infants. Cochrane Database of Systematic Reviews. 2006; (2):CD001814. [DOI:10.1002/14651858.CD001814.pub2] [PMID]
35. Guralnick MJ. Preventive interventions for preterm children: Effectiveness and developmental mechanisms. Journal of Developmental and Behavioral Pediatrics. 2012; 33(4):352-64. [DOI:10.1097/DBP.0b013e31824eaa3c] [PMID] [PMCID]