Early developmental intervention programmes provided post hospital discharge to prevent motor and cognitive impairment in preterm infants.

BACKGROUND: Infants born preterm are at increased risk of cognitive and motor impairments compared with infants born at term. Early developmental interventions for preterm infants are targeted at the infant or the parent-infant relationship, or both, and may focus on different aspects of early development. They aim to improve developmental outcomes for these infants, but the long-term benefits remain unclear. This is an update of a Cochrane review first published in 2007 and updated in 2012 and 2015. OBJECTIVES: Primary objective To assess the effect of early developmental interventions compared with standard care in prevention of motor or cognitive impairment for preterm infants in infancy (zero to < three years), preschool age (three to < five years), and school age (five to < 18 years). Secondary objective To assess the effect of early developmental interventions compared with standard care on motor or cognitive impairment for subgroups of preterm infants, including groups based on gestational age, birthweight, brain injury, timing or focus of intervention and study quality. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and trial registries in July 2023. We cross-referenced relevant literature, including identified trials and existing review articles. SELECTION CRITERIA: Studies included randomised, quasi-randomised controlled trials (RCTs) or cluster-randomised trials of early developmental intervention programmes that began within the first 12 months of life for infants born before 37 weeks' gestational age (GA). Interventions could commence as an inpatient but had to include a post discharge component for inclusion in this review. Outcome measures were not prespecified, other than that they had to assess cognitive outcomes, motor outcomes or both. The control groups in the studies could receive standard care that would normally be provided. DATA COLLECTION AND ANALYSIS: Data were extracted from the included studies regarding study and participant characteristics, timing and focus of interventions and cognitive and motor outcomes. Meta-analysis using RevMan was carried out to determine the effects of early developmental interventions at each age range: infancy (zero to < three years), preschool age (three to < five years) and school age (five to < 18 years) on cognitive and motor outcomes. Subgroup analyses focused on GA, birthweight, brain injury, time of commencement of the intervention, focus of the intervention and study quality. We used standard methodological procedures expected by Cochrane to collect data and evaluate bias. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Forty-four studies met the inclusion criteria (5051 randomly assigned participants). There were 19 new studies identified in this update (600 participants) and a further 17 studies awaiting outcomes. Three previously included studies had new data. There was variability in the focus and intensity of the interventions, participant characteristics, and length of follow-up. All included studies were either single or multicentre trials and the number of participants varied from fewer than 20 to up to 915 in one study. The trials included in this review were mainly undertaken in middle- or high-income countries. The majority of studies commenced in the hospital, with fewer commencing once the infant was home. The focus of the intervention programmes for new included studies was increasingly targeted at both the infant and the parent-infant relationship. The intensity and dosages of interventions varied between studies, which is important when considering the applicability of any programme in a clinical setting. Meta-analysis demonstrated that early developmental intervention may improve cognitive outcomes in infancy (developmental quotient (DQ): standardised mean difference (SMD) 0.27 standard deviations (SDs), 95% confidence interval (CI) 0.15 to 0.40; P < 0.001; 25 studies; 3132 participants, low-certainty evidence), and improves cognitive outcomes at preschool age (intelligence quotient (IQ); SMD 0.39 SD, 95% CI 0.29 to 0.50; P < 0.001; 9 studies; 1524 participants, high-certainty evidence). However, early developmental intervention may not improve cognitive outcomes at school age (IQ: SMD 0.16 SD, 95% CI -0.06 to 0.38; P = 0.15; 6 studies; 1453 participants, low-certainty evidence). Heterogeneity between studies for cognitive outcomes in infancy and preschool age was moderate and at school age was substantial. Regarding motor function, meta-analysis of 23 studies showed that early developmental interventions may improve motor outcomes in infancy (motor scale DQ: SMD 0.12 SD, 95% CI 0.04 to 0.19; P = 0.003; 23 studies; 2737 participants, low-certainty evidence). At preschool age, the intervention probably did not improve motor outcomes (motor scale: SMD 0.08 SD, 95% CI -0.16 to 0.32; P = 0.53; 3 studies; 264 participants, moderate-certainty evidence). The evidence at school age for both continuous (motor scale: SMD -0.06 SD, 95% CI -0.31 to 0.18; P = 0.61; three studies; 265 participants, low-certainty evidence) and dichotomous outcome measures (low score on Movement Assessment Battery for Children (ABC) : RR 1.04, 95% CI 0.82 to 1.32; P = 0.74; 3 studies; 413 participants, low-certainty evidence) suggests that intervention may not improve motor outcome. The main source of bias was performance bias, where there was a lack of blinding of participants and personnel, which was unavoidable in this type of intervention study. Other biases in some studies included attrition bias where the outcome data were incomplete, and inadequate allocation concealment or selection bias. The GRADE assessment identified a lower certainty of evidence in the cognitive and motor outcomes at school age. Cognitive outcomes at preschool age demonstrated a high certainty due to more consistency and a larger treatment effect. AUTHORS' CONCLUSIONS: Early developmental intervention programmes for preterm infants probably improve cognitive and motor outcomes during infancy (low-certainty evidence) while, at preschool age, intervention is shown to improve cognitive outcomes (high-certainty evidence). Considerable heterogeneity exists between studies due to variations in aspects of the intervention programmes, the population and outcome measures utilised. Further research is needed to determine which types of early developmental interventions are most effective in improving cognitive and motor outcomes, and in particular to discern whether there is a longer-term benefit from these programmes.

Early developmental intervention programmes provided post hospital discharge to prevent motor and cognitive impairment in preterm infants.

BACKGROUND: Infants born preterm are at increased risk of developing cognitive and motor impairment compared with infants born at term. Early developmental interventions have been provided in the clinical setting with the aim of improving overall functional outcomes for these infants. Long-term benefits of these programmes remain unclear. OBJECTIVES: Primary objective To compare the effectiveness of early developmental intervention programmes provided post hospital discharge to prevent motor or cognitive impairment in preterm (< 37 weeks) infants versus standard medical follow-up of preterm infants at infancy (zero to < three years), preschool age (three to < five years), school age (five to < 18 years) and adulthood (≥ 18 years). Secondary objectives To perform subgroup analyses to determine the following.• Effects of gestational age, birth weight and brain injury (periventricular leukomalacia (PVL)/intraventricular haemorrhage (IVH)) on cognitive and motor outcomes when early intervention is compared with standard follow-up. ∘ Gestational age: < 28 weeks, 28 to < 32 weeks, 32 to < 37 weeks. ∘ Birth weight: < 1000 grams, 1000 to < 1500 grams, 1500 to < 2500 grams. ∘ Brain injury: absence or presence of grade III or grade IV IVH or cystic PVL (or both) or an abnormal ultrasound/magnetic resonance image (MRI) before initiation of the intervention.• Effects of interventions started during inpatient stay with a post-discharge component versus standard follow-up care.• Effects of interventions focused on the parent-infant relationship, infant development or both compared with standard follow-up care.To perform sensitivity analysis to identify the following.• Effects on motor and cognitive impairment when early developmental interventions are provided within high-quality randomised trials with low risk of bias for sequence generation, allocation concealment, blinding of outcome measures and selective reporting bias. SEARCH METHODS: The search strategy of the Cochrane Neonatal Review Group was used to identify randomised and quasi-randomised controlled trials of early developmental interventions provided post hospital discharge. Two review authors independently searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Advanced, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and EMBASE (1966 to August 2015). SELECTION CRITERIA: Studies included had to be randomised or quasi-randomised controlled trials of early developmental intervention programmes that began within the first 12 months of life for infants born before 37 weeks' gestational age. Interventions could commence on an inpatient basis but had to include a post-discharge component for inclusion in this review. Outcome measures were not prespecified, other than that they had to assess cognitive outcomes, motor outcomes or both. Rates of cerebral palsy were documented. DATA COLLECTION AND ANALYSIS: Two independent review authors extracted and entered data. Cognitive and motor outcomes were pooled by four age groups: infancy (zero to < three years), preschool age (three to < five years), school age (five to < 18 years) and adulthood (≥ 18 years). Meta-analysis using RevMan 5.1 was carried out to determine the effects of early developmental interventions at each age range. Subgroup analyses focused on gestational age, birth weight, brain injury, commencement of the intervention, focus of the intervention and study quality. MAIN RESULTS: Twenty-five studies met the inclusion criteria (3615 randomly assigned participants). Only 12 of these studies were randomised controlled trials with appropriate allocation concealment. Variability was evident with regard to focus and intensity of the intervention, participant characteristics and length of follow-up. Meta-analysis led to the conclusion that intervention improved cognitive outcomes at infancy (developmental quotient (DQ): standardised mean difference (SMD) 0.32 standard deviations (SDs), 95% confidence interval (CI) 0.16 to 0.47; P value < 0.001; 16 studies; 2372 participants) and at preschool age (intelligence quotient (IQ); SMD 0.43 SDs, 95% CI 0.32 to 0.54; P value < 0.001; eight studies; 1436 participants). However, this effect was not sustained at school age (IQ: SMD 0.18 SDs, 95% CI -0.08 to 0.43; P value = 0.17; five studies; 1372 participants). Heterogeneity between studies for cognitive outcomes at infancy and at school age was significant. With regards to motor outcomes, meta-analysis of 12 studies showed a significant effect in favour of early developmental interventions at infancy only; however, this effect was small (motor scale DQ: SMD 0.10 SDs, 95% CI 0.01 to 0.19; P value = 0.03; 12 studies; 1895 participants). No effect was noted on the rate of cerebral palsy among survivors (risk ratio (RR) 0.82, 95% CI 0.52 to 1.27; seven studies; 985 participants). Little evidence showed a positive effect on motor outcomes in the long term, but only five included studies reported outcomes at preschool age (n = 3) or at school age (n = 2). AUTHORS' CONCLUSIONS: Early intervention programmes for preterm infants have a positive influence on cognitive and motor outcomes during infancy, with cognitive benefits persisting into preschool age. A great deal of heterogeneity between studies was due to the variety of early developmental intervention programmes tested and to gestational ages of included preterm infants; thus, comparisons of intervention programmes were limited. Further research is needed to determine which early developmental interventions are most effective in improving cognitive and motor outcomes, and to discern the longer-term effects of these programmes.

Assessment of uterus position as a surrogate for high-risk clinical target volume with respect to the applicator position for multiple fractions of brachytherapy in cervical cancer.

AIM: Hybrid magnetic resonance imaging/computerized tomography (MRI/CT) planning for high-dose-rate (HDR) brachytherapy in cervical cancer with MR/CT fusion for the first fraction followed by CT for fraction 2 and 3 is used at our center. The aim of this study is to evaluate the position of applicator intrauterine tube (IU) in relation to uterine serosa with each fraction of intracavitary high-dose-rate brachytherapy. METHODS: Position of the applicator relative to uterus was measured from tip of the applicator (IU) to the top of uterus in the plane of IU and perpendicular to IU in anterior, posterior, left and right directions at the tip of IU, mid-point of the IU and 1 cm from the surface of vaginal ring. The mean absolute difference (±95 % confidence interval) between these positions at fraction 2 and 3 was calculated with fraction one as reference. RESULTS: The mean absolute difference (±95 %) of the applicator relative to uterus was 2.7 ± 0.5 mm at the tip, 1.5 ± 4 mm at mid-point and 1.1 ± 0.3 mm at 1 cm from the surface of the ring. CONCLUSION: This study shows that there is consistency in inter-fraction applicator position relative to uterus apart from at the tip and, therefore, in situations where high-risk clinical target volume (HRCTV) extends towards uterine fundus, MRI should be used for each fraction of brachytherapy planning to accurately define HRCTV.

Early developmental intervention programmes post-hospital discharge to prevent motor and cognitive impairments in preterm infants.

BACKGROUND: Infants born preterm are at increased risk of developing cognitive and motor impairments compared with infants born at term. Early developmental interventions have been used in the clinical setting with the aim of improving the overall functional outcome for these infants. However, the long-term benefit of these programmes remains unclear. OBJECTIVES: To review the effectiveness of early developmental intervention post-discharge from hospital for preterm (< 37 weeks) infants on motor or cognitive development. SEARCH METHODS: The Cochrane Neonatal Review group search strategy was used to identify randomised and quasi-randomised controlled trials of early developmental interventions post hospital discharge. Two review authors independently searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE Advanced, CINAHL, PsycINFO and EMBASE (1966 through to October 2012). SELECTION CRITERIA: Studies included had to be randomised or quasi-randomised controlled trials of early developmental intervention programmes that began within the first 12 months of life for infants born at < 37 weeks with no major congenital abnormalities. Intervention could commence as an inpatient; however, a post-discharge component was necessary to be included in this review. The outcome measures were not pre-specified other than that they had to assess cognitive ability, motor ability or both. The rates of cerebral palsy were also documented. DATA COLLECTION AND ANALYSIS: Data were extracted and entered by two independent review authors. Cognitive and motor outcomes were pooled in four age groups - infancy (zero to < three years), pre-school age (three to < five years), school age (five to 17 years) and adulthood (≥ 18 years). Meta-analysis was carried out using RevMan 5.1 to determine the effects of early developmental intervention at each age range. Subgroup analysis was carried out in relation to gestational age, birthweight, brain injury, commencement of intervention and focus of intervention. MAIN RESULTS: Twenty-one studies met the inclusion criteria (3133 randomised patients). Only 10 of these studies were RCTs with appropriate allocation concealment. There was variability with regard to the focus and intensity of the intervention, subject characteristics and in length of follow-up. Meta-analysis concluded that intervention improved cognitive outcomes at infant age (developmental quotient (DQ): standardised mean difference (SMD) 0.31 standard deviations (SD); 95% confidence interval (CI) 0.13 to 0.50; P < 0.001; 13 studies; 2147 patients), and pre-school age (intelligence quotient (IQ); SMD 0.45 SD; 95% CI 0.34 to 0.57; P < 0.001; six studies; 1276 patients). However, this effect was not sustained at school age (IQ: SMD 0.25 SD; 95% CI -0.10 to 0.61; P = 0.16; five studies; 1242 patients). There was significant heterogeneity between studies for cognitive outcomes at infant and school ages. In regards to motor outcomes, meta-analysis of 10 studies showed a significant effect in favour of early developmental interventions; however, the effect was small (motor scale developmental quotient (DQ): SMD 0.10 SD; 95% CI 0.00 to 0.19; P = 0.04; 10 studies; 1745 patients). There was no effect on the rate of cerebral palsy in survivors; risk ratio (RR) 0.89; 95% CI 0.55 to 1.44; five studies; 737 patients). There was little evidence for a positive effect on motor outcomes in the long term, with only five of the included studies reporting outcomes at pre-school or school age. AUTHORS' CONCLUSIONS: Early intervention programmes for preterm infants have a positive influence on cognitive and motor outcomes during infancy, with the cognitive benefits persisting into pre-school age. There is a great deal of heterogeneity between studies due to the variety of early developmental intervention programmes trialled and gestational ages of the preterm infants included, which limits the comparisons of intervention programmes. Further research is needed to determine which early developmental interventions are the most effective at improving cognitive and motor outcomes, and on the longer-term effects of these programmes.

Do early intervention programmes improve cognitive and motor outcomes for preterm infants after discharge? A systematic review.

AIM: The aim of this study was to review the effects of early developmental intervention after discharge from hospital on motor and cognitive development in preterm infants. METHOD: Randomized controlled trials (RCTs) or quasi-RCTs of early developmental intervention programmes for preterm infants in which motor or cognitive outcomes were reported and in which the intervention commenced before or after discharge were included. A systematic review and meta-analysis of studies grouped by intervention, age of outcome, and study quality was undertaken. Databases searched (up to January 2009) included the Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, PsycINFO, and Embase. RESULTS: Eighteen studies met the inclusion criteria (2686 patients randomized), but only 11 studies had data suitable for meta-analysis. Early developmental intervention improved cognitive outcomes at infant age (developmental quotient: standardized mean difference [SMD] 0.42, 95% confidence interval [CI] 0.33-0.52; p<0.001), and at preschool age (IQ: SMD 0.46, 95% CI 0.33-0.59; p<0.001). However, the benefit was not sustained at school age (IQ: SMD 0.02, 95% CI -0.10 to 0.14; p=0.71). Early intervention had little effect on motor outcome at infant or school age, and there was no study reporting motor outcome at preschool age. INTERPRETATION: Current evidence suggests that the benefits of developmental intervention postdischarge are restricted to short-term gains in cognitive outcome.

Improving the outcome of infants born at <30 weeks' gestation--a randomized controlled trial of preventative care at home.

BACKGROUND: Early developmental interventions to prevent the high rate of neurodevelopmental problems in very preterm children, including cognitive, motor and behavioral impairments, are urgently needed. These interventions should be multi-faceted and include modules for caregivers given their high rates of mental health problems. METHODS/DESIGN: We have designed a randomized controlled trial to assess the effectiveness of a preventative care program delivered at home over the first 12 months of life for infants born very preterm (<30 weeks of gestational age) and their families, compared with standard medical follow-up. The aim of the program, delivered over nine sessions by a team comprising a physiotherapist and psychologist, is to improve infant development (cognitive, motor and language), behavioral regulation, caregiver-child interactions and caregiver mental health at 24 months' corrected age. The infants will be stratified by severity of brain white matter injury (assessed by magnetic resonance imaging) at term equivalent age, and then randomized. At 12 months' corrected age interim outcome measures will include motor development assessed using the Alberta Infant Motor Scale and the Neurological Sensory Motor Developmental Assessment. Caregivers will also complete a questionnaire at this time to obtain information on behavior, parenting, caregiver mental health, and social support. The primary outcomes are at 24 months' corrected age and include cognitive, motor and language development assessed with the Bayley Scales of Infant and Toddler Development (Bayley-III). Secondary outcomes at 24 months include caregiver-child interaction measured using an observational task, and infant behavior, parenting, caregiver mental health and social support measured via standardized parental questionnaires. DISCUSSION: This paper presents the background, study design and protocol for a randomized controlled trial in very preterm infants utilizing a preventative care program in the first year after discharge home designed to improve cognitive, motor and behavioral outcomes of very preterm children and caregiver mental health at two-years' corrected age. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12605000492651.

NICU Graduates: The Role of the Allied Health Team in Follow-Up.

Infants who graduate from the neonatal intensive care unit, including those infants born preterm and/or with brain injury, are at increased risk of long-term neurodevelopmental impairments. The developmental allied health team, consisting of physical therapy, occupational therapy, and speech pathology, is crucial in early evaluation of gross motor, fine motor, feeding, and language development. Surveillance of neurodevelopment in the first year of life is essential to ensure early detection of specific developmental delays and impairments, and to ensure timely referral for early intervention. Early intervention is not only important in optimizing long-term outcomes for the child, but it also plays an important role in enhancing the parent-child relationship and parental well-being. In this review, we discuss the role of the developmental allied health team in the follow-up of high-risk infants, identify key assessment tools used in early neurodevelopmental surveillance, and provide recommendations regarding referral to intervention programs to optimize child and family outcomes. [Pediatr Ann. 2018;47(4):e165-e171.].

Hybrid (CT/MRI based) vs. MRI only based image-guided brachytherapy in cervical cancer: Dosimetry comparisons and clinical outcome.

PURPOSE: Limited access to MRI has restricted implementation of MRI-based image-guided brachytherapy (IGBT) in line with GEC-ESTRO guidelines in many centers. This work reports our experience using an alternative CT/MRI based (hybrid) approach for IGBT, dosimetry comparisons, and its impact on long-term clinical outcome and major toxicity. METHODS AND MATERIALS: Seventy-six patients diagnosed with locally advanced cervical cancer between May 2008 and May 2012 treated with IGBT were analyzed. The hybrid approach is the default IGBT approach during this study period. Forty-nine had hybrid approach and 27 patients had "3-fraction conformal MRI" approach (17 within EMBRACE study). Treatment consisted of 48 Gy in 24 fractions of conformally planned external beam radiotherapy with weekly cisplatin followed by three weekly fractions of brachytherapy to high-risk clinical target volume (HR-CTV). All patients have a prebrachytherapy MRI 4 days before treatment and with the applicators in place on Fraction 1. MRI only or CT is used for subsequent fractions. Using image registration techniques and the assumption that the HR-CTV is fixed with respect to the applicator, the HR-CTV from MRI at Fraction 1 is transferred onto subsequent fraction CT image sets for the hybrid approach. RESULTS: Median follow-up was 41 months (range, 23-71 months). Excellent 3-year local control, overall progression-free survival, and overall survival of 92.6%, 78.8%, and 77.7% were seen with the hybrid approach and 92.2%, 66.3%, and 69.6% with a 3-fraction conformal MRI approach, respectively. Dosimetry achieved and late toxicity rates were comparable in the two groups. CONCLUSIONS: Hybrid IGBT in locally advanced cervical cancer offers an alternative approach when access to MRI restricts implementation of IGBT.

Challenges of neurodevelopmental follow-up for extremely preterm infants at two years.

AIM: This study examined the rates of follow-up for a cohort of extremely preterm (EP -<28weeks gestation) and/or extremely low birthweight (ELBW -<1000g) children at two years with related perinatal and geographical factors. The secondary aim was to determine the rates of developmental delay and disability. METHODS: A retrospective review of two year follow-up data for all EP and/or ELBW infants born in a large tertiary neonatal hospital over a two year period was undertaken. Neurodevelopmental outcome was assessed using the Bayley Scales of Infant and Toddler Development Scale - 3rd edition (Bayley-III) and neurosensory disability was assessed by a paediatrician using a standard proforma. Rates of delay (composite score≥1SD below mean) were determined using the Bayley-III test norms and a local cohort normative group. Attrition rates and reasons for loss to follow-up were determined. RESULTS: Only 50% (109/219) of eligible children participated in the follow-up. The follow-up rate for children engaged in an ongoing research project was excellent at 98% (58/59), however it was only 32% (51/160) for children following the clinical pathway. The main reason for not attending the follow-up was loss of contact. Factors associated with attendance included a lower gestation, sepsis and living in the metropolitan areas. The rates of delay in this cohort were greater with reference to local cohort normative data compared to Bayley-III test norms with an overall rate of delay of 72% (95%CI, 63% to 81%) compared to 38% (95%CI, 29% to 50%). CONCLUSIONS: Follow-up of EP/ELBW infants to two years is an important part of clinical care, however the high rate of attrition in routine clinical follow-up and consequent difficulty in accurately determining rates of delay highlight challenges for centres providing ongoing care.

Cerebral palsy and developmental coordination disorder in children born preterm.

Children born early (<37 weeks of gestation) are at high risk of a range of motor impairments due to a variety of biological and environmental risk factors. Cerebral palsy occurs more frequently in those children born preterm, with the risk increasing with decreasing gestational age. Mild and moderate motor impairments, consistent with developmental coordination disorder, occur in almost half of those children born preterm and include difficulties with balance, manual dexterity and ball skills. All forms of motor impairment are associated with comorbidities, which may have a greater effect on quality of life, academic achievement and participation in extracurricular activities than the motor impairment itself. Infants at risk of motor impairment can be identified in early infancy with a combination of clinical assessment tools and perinatal risk factors. However, the reliable diagnosis of motor impairment requires follow-up into early childhood and it is important to ensure that the appropriate intervention is implemented.

Preventive care at home for very preterm infants improves infant and caregiver outcomes at 2 years.

OBJECTIVE: The objective of this study was to determine the effects of preventive care at home on child development and primary caregiver mental health at 2 years of age. METHODS: A total of 120 very preterm infants (<30 weeks) were assigned randomly to intervention (n = 61) or control (n = 59) groups. The intervention group received the preventive care program (9 home visits over the first year from a physiotherapist and a psychologist, focusing on the parent-infant relationship, the parents' mental health, and the infant's development); and the control group received standard care. At corrected age of 2 years, developmental outcomes were assessed, and primary caregivers completed the Infant-Toddler Social and Emotional Assessment. The mental health of the primary caregivers was assessed with the Hospital Anxiety and Depression Scale. RESULTS: At 2 years of age, 115 children (96%) were assessed with the Bayley Scales of Infant and Toddler Development III and 100 children (83%) with the Infant-Toddler Social and Emotional Assessment; and 91 (86%) of 106 caregivers completed the Hospital Anxiety and Depression Scale. There were no statistically significant differences in cognitive, language, or motor composite scores between the treatment groups. However, children in the intervention group were reported by their primary caregivers to exhibit less externalizing and dysregulation behaviors and increased competence, compared with control subjects. Primary caregivers in the intervention group reported less anxiety and depression. CONCLUSION: A preventive care program for very preterm infants and their families improved behavioral outcomes for infants and reduced anxiety and depression for primary caregivers.