Five-Year Neurodevelopmental Outcome of Children Born Very Preterm Between 2012 and 2018

Abstract

Aim

To analyze neurodevelopmental outcome of children born very preterm (born 2012 to 2018) aged 5 years in Vorarlberg, Austria. To identify medical risk factors and compare with (inter)national data.

Methods

In this population-based study with prospectively collected data very preterm children underwent neurodevelopmental assessment: Kaufman Assessment Battery for Children (KABC-II) for cognitive functioning, Movement Assessment Battery for Children (M-ABC-2) for motor skills, Strengths and Difficulties Questionnaire (SDQ) and Behavior Rating Inventory of Executive Function – Preschool Version (BRIEF-P) for deficits in behavior and executive functions. Risk factors were identified using multiple linear regression.

Results

The study population (n = 114, 46.5% completed follow-up) showed moderate to severe neurodevelopmental disability (KABC-II IQ score <70), mild (KABC-II IQ score 70–84, M-ABC-2 total score <7, SDQ total score >90th percentile or BRIEF-P Global Executive Function score T >65), and no neurodevelopmental disability in 2.9, 31.4, and 65.7% of the children, respectively. Results were more disadvantageous for children born extremely preterm than for very preterm born children. Regarding risk factors, abnormal hearing screening, male gender, and ICH grades 3–4 were associated with poorer cognitive and motor skills.

Conclusion

In our state-wide cohort of very preterm children, we observed a small proportion of moderate to severe neurodevelopmental disabilities of 2.9%, whereby 65.7% had no disability at 5 years. Disadvantageous outcomes are more pronounced in extremely preterm children.

Keywords

very preterm - extremely preterm - neurodevelopmental outcome - preschool age - KABC-II - M-ABC-2

Introduction

In 2020, approximately 13.4 million infants were born preterm worldwide.[1] In Austria, 7% of all live-born infants are born preterm, 1% of those before 32 + 0 weeks of gestational age (GA).[2] [3] In the region of Vorarlberg, a federal state in the western part of Austria, there are around 4,000 live births per year.[4] Preterm births are categorized as moderate to late (32 + 0 to 36 + 6 weeks GA), very preterm (28 + 0 to 31 + 6 weeks GA; VPT), and extremely preterm (<28 weeks GA; EPT).[1]

Preterm-born infants are at great risk for morbidity and mortality.[5] [6] [7] Among the most common morbidities are bronchopulmonary dysplasia (BPD), intracerebral hemorrhage (ICH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), and sepsis.[6] [7] Improved prenatal and neonatal care have led to increasing survival rates and decreasing short-term morbidity.[6] However, no significant improvement in neurodevelopmental outcome has been seen over the past 30 years.[8] Several studies have shown higher rates of neurodevelopmental disabilities in preterm-born children at preschool age.[9] [10] [11] They are especially vulnerable to behavioral problems, deficits in attention, executive functions as well as learning disabilities.[12] [13] Consequently, regularly offered neurodevelopmental assessments are crucial for identifying delay and thus enabling supportive intervention programs. For that reason, national guidelines have been established in Austria describing a minimal consensus of a neurological and an eye examination, a hearing screening during hospital stay, and thorough follow-up assessment at the corrected age of 2 and 5 years.[14] Results regarding mortality and short-term morbidity in preterm-born infants have been published for the national[6] and state-wide[5] population. Also, results for neurodevelopmental outcome at 2 years have been analyzed nation-wide[15] and state-wide.[16] In 2017 we started the 5-year follow-up program.

Aim

The aim of this study is first to analyze the neurodevelopmental outcome of VPT and EPT children at 5 years (chronological age) born in Vorarlberg between 2012 and 2018. Second, the identification of medical risk factors for poor cognitive and motor outcome and third, a comparison with (inter)national data.

Methods

Study Population

This study included all children (a) born between 2012 and 2018 at 23 to 31 + 6 weeks GA in Vorarlberg, who had been admitted to the neonatal intensive care unit at Feldkirch Academic Teaching Hospital and had (b) fully completed cognitive and motor assessment at 5 years. Exclusion criteria were: (a) a GA of >31 + 6 weeks, (b) stillbirths and patients who died in the delivery room, (c) severe congenital malformation or disabilities, and/or (d) incomplete cognitive and motor assessment. Data were prospectively collected and subsequently anonymously entered and stored in a local register and in the national quality assessment program named “Österreichisches Frühgeborenen Outcome Register, ÖFGOR.”[2] The collected data included epidemiological information like GA, birth weight, head circumference at birth, sex, Apgar score at 1/5/10 minutes, pre- and postnatal treatments, hearing screening, and short-term morbidities like BPD, PDA, intracerebral hemorrhage (ICH), and ROP. In accordance with the Austrian consensus of standardized neurodevelopmental follow-up for premature infants born prior to 32 weeks of gestation,[2] [14] each premature infant received a standardized hearing screening before discharge. In the years 2007 to 2012 otoacoustic emissions (OAE) were performed, and then changed to the evaluation of auditory brainstem response (ABR). The results of the recordings were classified as “hearing response present/absent.” The hearing tests were carried out by speech therapists. During the clinical assessment at 5 years, parents were asked about any abnormalities related to their child's hearing performance. Data were analyzed for the whole study group and further divided into two subgroups (<28 + 0 weeks and 28 + 0 ≤ 31 + 6 weeks GA).

Ethics

The study was approved by the Ethics Review Board of the State of Vorarlberg (EK Number EK-2–6/2023), the ÖFGOR registry by the Medical University of Vienna (EK Number 1828/2019) in compliance with the Helsinki Declaration and followed by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines for cohort studies. The authors disclose any potential conflict of interests.

Neurodevelopmental Assessment

Assessment at 5 years included the Kaufman Assessment Battery for Children – Second Edition (KABC-II) for testing cognitive abilities, and the Movement Assessment Battery for Children – Second Edition (M-ABC-2) for motor skills. Testing was performed by trained clinical psychologists (B.F. and V.S.). The child's primary caregiver filled out the Strengths and Difficulties Questionnaire (SDQ) for evaluating behavioral and emotional problems and the Behavior Rating Inventory of Executive Function – Preschool Version (BRIEF-P) for executive functioning.

Cognition

The KABC-II is an individually administered intelligence test for children aged 3 to 18.[17] [18] It measures: “Short-term Memory,” “Long-term Storage and Retrieval,” “Visual Processing and Crystallized Abilities,” and for children above 7 years, “Fluid Reasoning.”[17] [18] A global score, the Fluid-Crystallized Index, was calculated based on all core subtests. The Nonverbal Index was derived for children with language difficulties. Main outcome scores are normed with a mean score of 100 and a standard deviation (SD) of 15. Lower scores indicate a higher degree of impairment. German/Austrian/Swiss normative test values were used.

Motor Skills

The M-ABC-2[19] assesses fine and gross motor skills in children aged 3 to 16 years. It consists of three main domains, namely, “Manual Dexterity,” “Ball Skills,” and “Balance”; a “Total Score” is the calculated sum of all of the eight administered subtests. For each test item a standard score (mean: 10; SD: 3) is derived using age-adjusted norms. In accordance with another study,[20] a conspicuous result was defined as a standard score <7 (below the 16th percentile).

Behavioral and Emotional Problems

The SDQ is a questionnaire that can be used to screen behavior in children aged 4 to 17.[20] [21] It consists of 25 items that correspond to five dimensions: “Emotional Problems,” “Conduct Problems,” “Hyperactivity/Inattention,” “Peer Relationship Problems,” and “Prosocial Behavior.” Each scale has a maximum score of 10; a total score is calculated by adding values from the first four mentioned dimensions. A score between the 80th and 90th percentiles is considered “borderline,” while a score above the 90th percentile is considered “abnormal.”[20] [21]

Executive Functions

The BRIEF-P questionnaire is used to assess executive functions in preschoolers.[22] [23] Its 63 items make up five clinical scales that are grouped into the three index scales “Inhibitory Self-control,” “Flexibility,” and “Emergent Metacognition.” A composite score (“Global Executive Function”) can be calculated. T-scores are normative values; a T-score >65 is considered abnormal.[22] [23]

Classification of Neurodevelopmental Outcome

Neurodevelopmental outcome is often categorized as severe, moderate or mild neurodevelopmental disability, or none.[24] [25] Classification for neurodevelopmental outcome in this study was done based on the literature[9] [11] [25] with some modifications: moderate to severe neurodevelopmental disability was classified as moderate to severe cognitive deficiency (IQ score of > − 2 SD; <70), mild neurodevelopmental disability either as a mild cognitive delay (IQ score of −2 SD to < − 1 SD; 70–84), abnormal results in M-ABC-2 (standard score of <7), or in the parental questionnaires (SDQ: total score >90th percentile or BRIEF-P: GEF: T >65). The definition of neurodevelopmental impairment (NDI) was limited to children with moderate to severe impairment (KABC-II: IQ-score of > − 2 SD; <70) ([Table 1]).

Table 1 Definition of classification of neurodevelopmental outcome at 5 years

Classification of neurodevelopmental outcome at 5 years
Moderate to severe neurodevelopmental disability (NDI)	KABC-II IQ score of > − 2 SD: <70
Mild neurodevelopmental disability	At least one of the following: KABC-II IQ score –2 SD to < − 1 SD (70–84) or abnormal results in M-ABC-2 (standard score <7) or conspicuous SDQ total score >90th percentile or conspicuous BRIEF-P: GEF: T >65
None	No classification as moderate to severe or mild neurodevelopmental disability

Abbreviations: BRIEF-P, Behavior Rating Inventory of Executive Function – Preschool Version; FCI, Fluid Crystallized Index; GEF, Global Executive Function; KABC-II, Kaufman Assessment Battery for Children – Second Edition; M-ABC-2, Movement Assessment Battery for Children – Second Edition; NDI, Neurodevelopmental Impairment; SDQ, Strength and Difficulties Questionnaire.

Note: KABC-II test scores are given in IQ scores (M = 100, SD = 15); M-ABC-2 test scores are given in standard scores (M = 10; SD = 3); SDQ test scores are classified as abnormal with a score above the 90th percentile; BRIEF-P test scores are given in T-scores (M = 50, SD = 10), a score >65 is considered abnormal.

Statistical Analysis

A descriptive analysis of all registered patients meeting the inclusion criteria was performed for sociodemographic and clinical data ([Table 2]). Data were presented as means with standard deviation. To identify risk factors for poor cognitive abilities or poor motor skills, a univariate linear regression model was calculated in a first step. Variables were sex, birth weight, GA, hearing screening at NICU discharge, course of antenatal steroids, Apgar score at 1/5/10 minutes after birth, BPD, PDA, ICH grades 3–4, necrotizing enterocolitis, and ROP. A p-value of <0.1 was considered significant for identification of statistically significant outcome parameters. This level of significance was chosen to generate a robust forecast model since a large number of predictors compromises the strength of the predictive model. In a final step, a multiple linear regression model was calculated to identify risk factors with a p-value of <0.05. A correction for multiple testing was applied in the regression analysis to control for the increased risk of type I error. Descriptive and statistical analyses were conducted using IBM SPSS, Version 29 (Armonk, NY, United States).

Table 2 Sociodemographic data for the total study population (GA < 32 + 0 [n = 114], GA <28 + 0 [n = 35], and GA 28 + 0 ≤ 31 + 6 [n = 79] groups)

	GA <32 + 0				GA <28 + 0 weeks				GA 28 + 0 < 32 + 0
	n	% of total n	Mean	Std. deviation	n	% of total n	Mean	Std. deviation	n	% of total n	Mean	Std. deviation
Sex (male)	59	51.8%			22	62.9%			37	46.8%
Birth weight (g)	114	100.0%	1163.1	340.1	35	100%	839.0	243.8	79	100%	1306.6	271.4
Gestational age (weeks)	114	100.0%	28 + 6	2.2	35	100%	26 + 0	1.3	79	100%	30 + 0	1.0
Steroids antenatal	97	90.7%			30	88.2%			67	91.8%
Apgar minute 1	112		7	2	34		6	2	78		7	2
Apgar minute 5	112		8	2	34		7	2	78		9	1
Apgar minute 10	110		9	1	33		8	1	77		9	1
PDA	28	24.6%			14	40.0%			14	17.7%
BPD	21	18.4%			17	48.6%			4	5.1%
NEC	6	5.3%			4	11.4			2	2.5%
ICH grades 3–4	5	4.4%			4	11.4%			1	1.3%
ROP	21	18.4%			20	57.1%			1	1.3%
Hearing screening conspicuous	2	2.1%			2	5.9%			0	0%

Abbreviations: BPD, bronchopulmonary dysplasia; GA, gestational age; ICH, intracerebral hemorrhage; NEC, necrotizing enterocolitis; PDA, patent ductus arteriosus; ROP, retinopathy of prematurity.

Results

Study Population

The registry included a total of 637 datasets of children born between 2007 and 2022. Of these, 301 were born between 2012 and 2018, 211 before 2012, and 125 after 2018, 52 had a GA >31 + 6, 5 had died, and further 6 had severe disability and couldn't be tested in a standardized way. All children who survived to 5 (n = 238) were invited for follow-up examination and were offered a standardized neurodevelopmental assessment, which was accepted by 131 children. Further 17 had to be excluded due to incomplete follow-up results.

This corresponds to a response rate of 53.5% for participants who attended the assessment and 46.5% for those who completed it fully.

This results in a total study population of 114 participants, who met all inclusion criteria ([Fig. 1]). Although no statistically significant differences were observed across most baseline characteristics in the total cohort, one significant difference was found in a subgroup analysis. Specifically, in the subgroup of children born <32 + 0 weeks of GA, antenatal steroid administration differed significantly between those with and without follow-up (p = 0.01). Similarly, in children born between 28 + 0 and <32 + 0 weeks of GA, antenatal steroids represented the only baseline variable showing a statistically significant difference (p = 0.01) (see [Supplementary Tables S1] and [S2], available in the online version).

Fig. 1 Study population. GA, gestational age.

Neurodevelopmental Results

For the total study population, it was shown that 2.9% (n = 3) of the children had NDI, 31.4% (n = 33) had mild neurodevelopmental disabilities, and 65.7% (n = 69) had no neurodevelopmental disability. For the group of children born at <28 + 0 weeks GA, 9.1% (n = 3) were seen to have NDI, 48.5% (n = 16) had mild neurodevelopmental disabilities, and 42.4% (n = 14) had no neurodevelopmental disability. For the group of children born at 28 + 0 ≤ 31 + 6 weeks GA, no child was reported with NDI, 23.6% (n = 17) showed mild neurodevelopmental disabilities, and 76.4% (n = 55) had no neurodevelopmental disability.

In detail, for the total study group, cognitive results on the KABC-II test showed 2.6% (n = 3) had an IQ score <70, 21.1% (n = 24) had an IQ score of 70 to 84, and 76.3% (n = 87) had an IQ score >84. Regarding motor development in the M-ABC-2 test battery 13.2% (n = 15) showed deficits. Parental evaluation of children's behavior resulted in 9.6% (n = 10) borderline and 3.1% (n = 4) abnormal results on the SDQ and 1.9% (n = 2) on the BRIEF-P questionnaire ([Fig. 2]). Detailed neurodevelopmental outcome results for the entire study group, the groups of children born at <28 + 0 and 28 + 0 ≤ 31 + 6 weeks GA, can be seen in [Table 3].

Fig. 2 Test outcomes calculated and presented as stacked bar charts for KABC-II, M-ABC-2, SDQ, and BRIEF-P for the total study population GA <32 + 0 (n = 114), GA <28 + 0 (n = 35), and GA 28 + 0 ≤ 31 + 6 (n = 79) groups. Please see also Table 1 for a better understanding. Abbreviations and explanations: KABC-II, Kaufman Assessment Battery for Children – Second Edition (M = 100, SD = 15)—“mild”: IQ score 70–84, “moderate to severe”: IQ score <70; M-ABC-2, Movement Assessment Battery for Children – Second Edition, (M = 10; SD = 3)—“mild”: standard score <7; SDQ, Strength and Difficulties Questionnaire—“mild”: score between 80th and 90th percentiles, “moderate to severe”: score above 90th percentile; BRIEF-P, Behavior Rating Inventory of Executive Function – Preschool Version (M = 50, SD = 10)—“mild”: T-score >65.

Table 3 Test results for the total study population GA <32 + 0 (n = 114), GA < 28 + 0 (n = 35), and GA 28 + 0 < 32 + 0 (n = 79) groups

		Total group	GA <28 + 0	GA 28 + 0 < 32 + 0
Moderate to severe neurodevelopmental disability (NDI)		2.9% (n = 3)	9.1% (n = 3)	0% (n = 0)
Mild neurodevelopmental disability		31.4% (n = 33)	48.5% (n = 16)	23.6% (n = 17)
None		65.7% (n = 69)	42.4% (n = 14)	76.4% (n = 55)
KABC-II	n evaluated	114	35	79
	FCI, mean (SD)	96.0 (14.8)	90.9 (15.4)	98.5 (14.0)
	NVI, mean (SD)	99.6 (17.0)	72.0 (0.0)	103.6 (13.9)
	≥85 (n)	76.3% (87)	54.3% (19)	86.1% (68)
	70–84 (n)	21.1% (24)	37.1% (13)	13.9% (11)
	GSM, mean (SD)	95.3 (14.5)	92.0 (15.1)	96.8 (14.0)
	GV, mean (SD)	95.7 (13.9)	93.2 (13.5)	96.9 (14.0)
	GLR, mean (SD)	93.9 (17.1)	88.5 (17.9)	96.4 (16.1)
	GC, mean (SD)	103.4 (14.1)	98.4 (15.5)	105.8 (12.9)
M-ABC-2	n evaluated	114	35	79
	Total standard score, mean (SD)	9.4 (2.7)	9.0 (3.2)	9.6 (2.5)
	<7 (n)	13.2% (15)	25.7% (9)	7.6% (6)
	Manual skills, mean (SD)	7.5 (3.1)	7.0 (3.2)	7.7 (3.0)
	Ball skills, mean (SD)	10.6 (2.8)	10.4 (2.8)	10.7 (2.8)
	Balance skills, mean (SD)	11.2 (2.9)	11.0 (3.3)	11.3 (2.7)
SDQ	n evaluated	104	30	74
	Total score, mean (SD)	7.9 (5.2)	9.3 (5.2)	7.3 (5.2)
	Borderline (n)	9.6% (10)	16.7% (5)	6.8% (5)
	Abnormal (n)	3.8% (4)	6.7% (2)	2.7% (2)
	Emotional problems, mean (SD)	1.5 (1.7)	1.4 (1.4)	1.5 (1.9)
	Conduct problems, mean (SD)	1.9 (1.5)	2.0 (1.3)	1.9 (1.5)
	Hyperactivity, mean (SD)	3.4 (2.4)	3.7 (2.4)	3.3 (2.4)
	Peer relationship problems, mean (SD)	1.3 (1.8)	1.5 (1.9)	1.3 (1.8)
	Prosocial behavior, mean (SD)	8.4 (1.6)	8.6 (1.2)	8.3 (1.7)
BRIEF-P	n evaluated	103	32	71
	Global executive function, mean (SD)	46.5 (7.8)	48.4 (8.0)	45.7 (7.5)
	Not suspicious T ≤65 (n)	98.1% (101)	96.9% (31)	98.6% (70)
	Suspicious T >65 (n)	1.9% (2)	3.1% (1)	1.4% (1)
	Inhibitory self-control, mean (SD)	47.0 (8.6)	49.1 (8.7)	46.1 (8.4)
	Flexibility, mean (SD)	46.1 (8.0)	46.6 (7.9)	45.8 (8.1)
	Emergent metacognition, mean (SD)	47.5 (7.9)	49.3 (9.2)	46.7 (7.2)

Abbreviations: BRIEF-P, Behavior Rating Inventory of Executive Function – Preschool Version; FCI, Fluid Crystallized Index; GC, Crystallized Ability; GEF, Global Executive Function; GLR, Long-Term Storage and Retrieval; GSM, Short Term Memory; GV, Visual Processing; KABC-II, Kaufman Assessment Battery for Children – Second Edition; M-ABC-2, Movement Assessment Battery for Children – Second Edition; NDI, Neurodevelopmental Impairment; NVI, Nonverbal Index; SDQ, Strength and Difficulties Questionnaire.

Note: KABC-II test scores are given in IQ scores (M = 100, SD = 15); M-ABC-2 test scores are given in standard scores (M = 10; SD = 3); SDQ test scores are classified as “borderline” between the 80th and 90th percentiles, abnormal with a score above the 90th percentile; BRIEF-P test scores are given in T-scores (M = 50, SD = 10), a score >65 is considered abnormal.

In the univariate linear regression analysis, the parameters birth weight, GA, ROP, and hearing screening at NICU discharge were identified as statistically significant outcome parameters in the cognitive domain. In the motor domain, the significant parameters were sex, ROP, and ICH grades 3–4. Subsequent multiple linear regression analysis revealed that a negative hearing test result at discharge was associated with a lower IQ score at the age of 5 years. In the motor domain, male sex and ICH grades 3–4 were associated with poorer motor outcomes. An overview for multiple linear regression is given in [Table 4].

Table 4 Results of multiple linear regression for cognition and motor skills

		ẞ	t	P
Cognition (KABC-II)	(Constant)	20.24	0.57	0.57
	Birth weight (g)	0.01	0.01	0.12
	Gestational age (days)	0.07	0.17	0.68
	Hearing screening	24.21	10.28	0.02
	ROP	5.15	1.04	0.30
Motor (M-ABC-2)	(Constant)	7.56	0.78	0.00
	ROP	−0.58	−0.92	0.36
	Sex	1.42	2.95	0.01
	ICH grades 3–4	−2.91	−2.46	0.02

Abbreviations: ICH, intracerebral hemorrhage; KABC-II, Kaufman Assessment Battery for Children – Second Edition; M-ABC-2, Movement Assessment Battery for Children – Second Edition; ẞ, regression coefficient; p, significance; ROP, retinopathy of prematurity.

Note: A p-level of <0.05 indicates a statistically significant result.

Discussion

In this population-based cohort study in very preterm children born at <32 weeks GA between 2012 and 2018 in Vorarlberg, Austria, first, the rate of NDI at 5 years of age was 2.9%, in children born at <28 + 0 weeks GA it was 9.1%; normal results were observed in 65.7 and 42.4%, respectively. A large proportion of infants showed mild neurodevelopmental disabilities, 31.4% in the total and 48.5% in the <28 + 0 weeks GA group. Concerning motor (M-ABC-2), behavioral and emotional (SDQ), and executive functions (BRIEF-P), the results differ between the group of EPT and VPT and are more disadvantageous in the group of EPT.

Second, the proportion of children with cognitive disabilities increased with decreasing GA and male sex as well as with negative hearing test at NICU discharge and is associated with poorer neurodevelopmental outcome. However, the study group of children born at <28 weeks GA includes a large proportion of male patients (62.9%). When analyzed with multiple regression, demographic data and outcome, abnormal hearing screening at discharge, male gender, and ICH grades 3–4 were seen to be associated with poorer long-term 5-year outcomes. Univariate linear regression analysis also highlights the finding that low birth weight, low gestational age, and the occurrence of ROP are associated with poorer results in the 5-year follow-up. This suggests that neurodevelopmental outcome is influenced by a multitude of factors.

Third, when comparing our results regarding neurodevelopmental outcome with (inter)national data, an Austrian study that assessed very preterm-born children aged 5 years showed severe cognitive delay (IQ score less than 70; >  2 SD below the mean) in 5.5% of those children.[26] The finding is similar to our result. Another Austrian study looking at neurodevelopmental outcome in preschool-aged very preterm-born children in connection with the occurrence of BPD showed no neurocognitive disability in 42.9% of children with moderate BPD and in 51.4% of children with no BPD.[27] This rate is comparable to our result for the group born at <28 weeks GA.

The French EPIPAGE-2 cohort study investigated neurodevelopmental outcome (Wechsler Preschool and Primary Scale of Intelligence, 4^th Edition, M-ABC-2, SDQ) in children born EPT and VPT.[9] Results showed higher rates of moderate to severe neurodevelopmental disabilities, namely, in 27.7% of children born between 24 and 26 weeks GA and in 18.7% of children born between 27 and 31 weeks GA. Rates of mild neurodevelopmental disabilities were lower for the children born between 24 and 26 weeks GA, namely, 38.5%, and deficits in motor skills were seen in 18.8% of children born at 24 to 26 weeks GA and in 8.5% of children born at 27 to 31 weeks GA. Emotional and behavioral difficulties were shown in 12.0 and 10.6% of children born at 24 to 26 and 27 to 31 weeks GA, respectively.[9]

The Loire Infant Follow-up Team cohort study of children born very preterm analyzed 1,397 SDQ questionnaires and found that 21% had an abnormal to borderline score higher than in our study (13.4%).[28]

In a prospective cohort study from Taiwan very low birth weight preterm children of <1,500 g (n = 1427, mean GA: 29.02 ± 2.76 weeks) (cognitive functions assessed with the Wechsler preschool and primary scale of intelligence – revised) revealed a rate of moderate to severe cognitive impairment of 8.76% and mild cognitive impairment of 12.1%. These rates are higher than for severe to moderate (2.9%) and lower than for mild cognitive impairment (31.4%) in our study.[29]

In a meta-analytic review,[30] Pascal et al found a delay in motor development in up to 33%[31] and 40%[32] of children born very preterm at around 5 years of age. The percentage of children with motor delay in our study population is much lower and more pronounced in the group of EPT-born children and therefore more comparable with the French EPIPAGE-2 cohort.[9] In our study population we see that even though children perform well according to the M-ABC-2 manual evaluation criteria, qualitative difficulties (e.g., in perception, control of physical muscle power) can be observed. Unfortunately, these difficulties are not reflected in the results. The differences in the results of these studies[9] [28] [29] [30] and our study can be explained by the different definitions of neurodevelopmental impairment used, the different focus of the assessments, the different assessment tools used, and the different times at which the evaluations were conducted.

Regarding executive functions, the percentage of abnormal results seen in parental evaluation of BRIEF-P is very low in our study group. A Danish population-based prospective cohort study with late and very late to moderately late preterm-born children showed that kindergarten teacher assessment resulted in poorer results than did parental evaluation with BRIEF.[10] In our study, only primary caregivers filled out BRIEF-P, and questionnaires were not given to kindergarten teachers.

Strengths and Limitations

Several limitations to our study need to be addressed. Due to the relatively small sample size, the aim of this study is to describe and analyze the data without excessively discussing the results. Also, a comparison with (inter)national literature demands caution, since not only the definition of neurodevelopmental disability differs but also different assessment tests are used, and norm samples are applied. This may explain why in our study the rate of severe to moderate disability is lower and mild disability is higher than reported by other researchers. For this reason, we emphasize the rate of normal results. In addition, our study was not able to include cerebral palsy or neurosensory impairment, which are often included in the categorization of neurodevelopmental impairment.[9] [11] However, one strength of our study is the fact that our sample includes all live-born infants born at <32 weeks GA in the defined region. Data are continuously and prospectively collected over a long period of time and registered in our registry. The 46.5% response rate is fair and children excluded did not differ significantly in sociodemographic data from those included (except for antenatal steroids). Thus, we are convinced that our statements are representative.

Unfortunately, analysis of our study population could not take children's socioeconomic background into account. These parameters are not mandatory for documentation in the ÖFGOR registry. Lower socioeconomic status has been associated with adverse cognitive outcome in children born very preterm.[9] [33] [34] [35] Therefore, it is crucial to view our identified risk factors as indicative rather than definitive. Taking this factor into consideration in this regional study population is certainly important for future research.

In our population-based study it would have been preferable to compare results with a local control group rather than with reference norms given by the test batteries. Also, it would have been better to assess executive functions with a test battery rather than to have primary caregivers fill out a BRIEF-P questionnaire. It has to be emphasized that BRIEF-P questionnaire is a subjective form of assessment, and it may not correlate with objectively measured executive functioning. However, assessing executive functions with a questionnaire gives a first insight into possible difficulties and has been done before.[10]

Conclusion

With our regional population-based study we present for the first time 5-year neurodevelopmental outcome in children born very preterm in this defined region. Altogether, 65.7% of the study children show no neurodevelopmental disabilities and only 2.9% show moderate to severe neurodevelopmental disabilities, which is a promising result. The rate of disabilities is more pronounced in the group of EPT children. The difference in definitions, applied assessment tools, and required adjustments in collected data parameters should be given consideration. This register study of VPT and EPT-born children shows the importance of thorough follow-up assessments at preschool age, as previously proposed in the literature.[14] [36]

Conflict of Interest

The authors declare that they have no conflict of interest.

Acknowledgment

Our special thanks go to Anke Seraphin for keeping the register.

Informed Consent

Patients have been informed that their acquired data are anonymously stored and used for scientific workup.

Contributors' Statement

C.W.: design of the work, acquisition, drafting manuscript, analysis, interpretation of data, approval of final manuscript; V.S.: design of the work, acquisition, drafting manuscript, analysis, interpretation of data, approval of final manuscript; B.F.: acquisition, reviewing, approval of final manuscript; S.G.: acquisition, reviewing, approval of final manuscript; B.S.: conception and design, interpretation of data, reviewing, supervision, approval of final manuscript; K.K.: acquisition, conception and design, interpretation of data, reviewing, supervision, approval of final manuscript.

^‡ These authors contributed equally to this article.

• References

• 1 Ohuma EO, Moller A-B, Bradley E. et al. National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis. Lancet 2023; 402 (10409): 1261-1271
• 2 Konzett K, Kiechl-Kohlendorfer U, Simma B. et al. Frühgeborenennachsorge in Österreich: Etablierung eines nationalen Registers. Monatsschr Kinderheilkd 2022; 170: 1-5
• 3 Statistik Austria. Anteil der Frühgeborenen in Österreich von 1984 bis 2023. Published August 1, 2024. Accessed October 22, 2024 at: https://de.statista.com/statistik/daten/studie/1018502/umfrage/anteil-der-fruehgeborenen-in-oesterreich/#:~:text=Insgesamt%20kamen%20in%20%C3%96sterreich%20im%20Jahr%20von%202023,-%20das%20entspricht%20einer%20Fr%C3%BChgeborenenrate%20von%206%2C8%20Prozent
• 4 Statistik Austria. Anzahl der Geburten in Österreich nach Bundesländern im Jahr 2024. Published February 26, 2025. Accessed June 5, 2025 at: https://de.statista.com/statistik/daten/studie/687273/umfrage/geburten-in-oesterreich-nach-bundeslaendern/
• 5 Konzett K, Riedl D, Blassnig-Ezeh A, Gang S, Simma B. Outcome in very preterm infants: a population-based study from a regional center in Austria. Front Pediatr 2024; 12: 1336469
• 6 Kiechl-Kohlendorfer U, Simma B, Urlesberger B. et al; Austrian Preterm Outcome Study Group. Low mortality and short-term morbidity in very preterm infants in Austria 2011-2016. Acta Paediatr 2019; 108 (08) 1419-1426
• 7 Kong X, Xu F, Wu R. et al. Neonatal mortality and morbidity among infants between 24 to 31 complete weeks: a multicenter survey in China from 2013 to 2014. BMC Pediatr 2016; 16 (01) 174
• 8 Kaempf JW, Guillen U, Litt JS, Zupancic JAF, Kirpalani H. Change in neurodevelopmental outcomes for extremely premature infants over time: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2023; 108 (05) 458-463
• 9 Pierrat V, Marchand-Martin L, Marret S. et al; EPIPAGE-2 writing group. Neurodevelopmental outcomes at age 5 among children born preterm: EPIPAGE-2 cohort study. BMJ 2021; 373 (741) n741
• 10 Sejer EPF, Bruun FJ, Slavensky JA, Mortensen EL, Schiøler Kesmodel U. Impact of gestational age on child intelligence, attention and executive function at age 5: a cohort study. BMJ Open 2019; 9 (09) e028982
• 11 Serenius F, Ewald U, Farooqi A. et al; Extremely Preterm Infants in Sweden Study Group. Neurodevelopmental outcomes among extremely preterm infants 6.5 years after active perinatal care in Sweden. JAMA Pediatr 2016; 170 (10) 954-963
• 12 Aarnoudse-Moens CSH, Weisglas-Kuperus N, van Goudoever JB, Oosterlaan J. Meta-analysis of neurobehavioral outcomes in very preterm and/or very low birth weight children. Pediatrics 2009; 124 (02) 717-728
• 13 Twilhaar ES, de Kieviet JF, Aarnoudse-Moens CS, van Elburg RM, Oosterlaan J. Academic performance of children born preterm: a meta-analysis and meta-regression. Arch Dis Child Fetal Neonatal Ed 2018; 103 (04) F322-F330
• 14 Kiechl-Kohlendorfer U, Brandstetter B, Fuiko R. et al. Standardisierte entwicklungsneurologische Nachuntersuchung von Frühgeborenen mit weniger als 32 Schwangerschaftswochen. Monatsschr Kinderheilkd 2012; 160 (07) 681-683
• 15 Kiechl-Kohlendorfer U, Simma B, Berger A. et al; Austrian Preterm Outcome Study Group. Two-year neurodevelopmental outcome in extremely preterm-born children: the Austrian Preterm Outcome Study Group. Acta Paediatr 2024; 113 (06) 1278-1287
• 16 Jenni F, Konzett K, Gang S, Sparr V, Simma B. Psychomotor and cognitive outcome in very preterm infants in Vorarlberg, Austria, 2007-2019. Neuropediatrics 2024; 55 (02) 90-96
• 17 Melchers P, Melchers M. KABC-II: Kaufman Assessment Battery for Children – II Von Alan S. Kaufman & Nadeen L. Kaufman. Deutschsprachige Fassung. Pearson; 2015
• 18 Renner G, Irblich D, Schroeder A. Factor structure of the KABC-II at ages 5 and 6: is it valid in a clinical sample?. Children (Basel) 2022; 9 (05) 645
• 19 Henderson SE, Sugden DA, Barnett AL, Petermann F, Bös K, Jascenoka J. Movement Assessment Battery for Children-2: (Movement ABC-2): Manual. 4., überarbeitete und erweiterte Auflage. Pearson; 2015
• 20 Niutanen U, Lönnberg P, Wolford E, Metsäranta M, Lano A. Extremely preterm children and relationships of minor neurodevelopmental impairments at 6 years. Front Psychol 2022; 13: 996472
• 21 Goodman R. The Strengths and Difficulties Questionnaire: a research note. J Child Psychol Psychiatry 1997; 38 (05) 581-586
• 22 Gioia GA, Isquith PK. Behavior rating inventory for executive functions. In: Kreutzer JS, DeLuca J, Caplan B. eds. Encyclopedia of Clinical Neuropsychology. New York: Springer; 2011: 372-376
• 23 Duku E, Vaillancourt T. Validation of the BRIEF-P in a sample of Canadian preschool children. Child Neuropsychol 2014; 20 (03) 358-371
• 24 Marlow N, Wolke D, Bracewell MA, Samara M. EPICure Study Group. Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med 2005; 352 (01) 9-19
• 25 van Beek PE, Rijken M, Broeders L. et al. Neurodevelopmental outcome at 5.5 years in Dutch preterm infants born at 24-26 weeks' gestational age: the EPI-DAF study. Arch Dis Child Fetal Neonatal Ed 2024; 109 (03) 272-278
• 26 Neubauer V, Fuchs T, Griesmaier E, Kager K, Pupp-Peglow U, Kiechl-Kohlendorfer U. Poor postdischarge head growth is related to a 10% lower intelligence quotient in very preterm infants at the chronological age of five years. Acta Paediatr 2016; 105 (05) 501-507
• 27 Reiterer F, Scheuchenegger A, Resch B, Maurer-Fellbaum U, Avian A, Urlesberger B. Bronchopulmonary dysplasia in very preterm infants: outcome up to preschool age, in a single center of Austria. Pediatr Int 2019; 61 (04) 381-387
• 28 Robert de Saint Vincent M, Rouger V, Rozé JC, Flamant C, Muller J-B. Assessing behavioral disorders with SDQ in very preterm children at 5 years of age in LIFT cohort. Children (Basel) 2023; 10 (07) 1191
• 29 Lin C-Y, Hsu C-H, Chang J-H. Taiwan Premature Infant Follow-up Network. Neurodevelopmental outcomes at 2 and 5 years of age in very-low-birth-weight preterm infants born between 2002 and 2009: a prospective cohort study in Taiwan. Pediatr Neonatol 2020; 61 (01) 36-44
• 30 Pascal A, Govaert P, Oostra A, Naulaers G, Ortibus E, Van den Broeck C. Neurodevelopmental outcome in very preterm and very-low-birthweight infants born over the past decade: a meta-analytic review. Dev Med Child Neurol 2018; 60 (04) 342-355
• 31 Howe T-H, Sheu C-F, Wang T-N, Hsu Y-W, Wang L-W. Neuromotor outcomes in children with very low birth weight at 5 yrs of age. Am J Phys Med Rehabil 2011; 90 (08) 667-680
• 32 Keunen K, Išgum I, van Kooij BJM. et al. Brain volumes at term-equivalent age in preterm infants: imaging biomarkers for neurodevelopmental outcome through early school age. J Pediatr 2016; 172: 88-95
• 33 Sentenac M, Benhammou V, Aden U. et al. Maternal education and cognitive development in 15 European very-preterm birth cohorts from the RECAP preterm platform. Int J Epidemiol 2022; 50 (06) 1824-1839
• 34 Linsell L, Malouf R, Morris J, Kurinczuk JJ, Marlow N. Prognostic factors for poor cognitive development in children born very preterm or with very low birth weight: a systematic review. JAMA Pediatr 2015; 169 (12) 1162-1172
• 35 Wolke D, Schulz J, Meyer R. Entwicklungslangzeitfolgen bei ehemaligen, sehr unreifen FrühgeborenenBayerische Entwicklungsstudie. Monatsschr Kinderheilkd 2001; 149 (01) S53-S61
• 36 Chin W-C, Wu W-C, Hsu J-F, Tang I, Yao T-C, Huang Y-S. Correlation analysis of attention and intelligence of preterm infants at preschool age: a premature cohort study. Int J Environ Res Public Health 2023; 20 (04) 3357

Publication History

Received: 14 February 2025

Accepted: 25 June 2025

Article published online:
14 July 2025