Long-term neurodevelopmental outcomes of infants born late preterm: a systematic review

Figures & data

Figure 1 Flowchart of study selection process.

Abbreviation: n, number of studies included in the current review.

Table 1 Description of papers included in the current systematic review

Authors and location	Study design	Ages assessed	Study population	Control	Primary objective
Chyi et al^Citation18 US	Secondary analysis of cohort study Early Childhood Longitudinal Study, Kindergarten cohort (ECLS-K) dataset	5–11 years	Moderate preterm; n=203 Late preterm; n=767*	Full term; n=13,671	To compare the rate of learning difficulties between late preterm and full term infants at school age
Baron et al^Citation17 US	Retrospective cohort study	3–4 years	Complicated late preterm (cLPT); n=60*	Full term; n=35	To compare general cognition, attention, working memory, motor and visuomotor skills, and executive functions between infants born preterm and admitted to NICU, and full term infants as 3-year-olds
Gurka et al^Citation16 US	Prospective cohort study	4–15 years	Late preterm; n=53	Full term; n=1,245	To compare a variety of cognitive, academic, socioemotional, and behavioral outcomes between healthy late preterm infants and full term infants from ages 4–15 years
Romeo et al^Citation25 Italy	Secondary analysis of a prospective cohort study	12 and 18 months	Late preterm; n=61, and normal head ultrasound or Gr 1 IVH	Full term; n=60	To compare the neurodevelopmental performance of low-risk late preterm infants, at 12 and 18 months of corrected and uncorrected age, to those of full term infants
Talge et al^Citation15 US	Secondary analysis of a prospective cohort study	6–7 years	Late preterm; n=168	Full term; n=168	To compare the risk of cognitive and socioemotional problems in middle childhoods of late preterm infants and full term infants
Baron et al^Citation14 US	Retrospective cohort study	3.51–4.19 years	cLPT; n=9* Uncomplicated late preterm; n=28*	Full term; n=100	To compare the cognitive abilities (general conceptual ability, verbal cluster, nonverbal reasoning cluster, and spatial cluster) of children born late preterm and not admitted to NICU, and those born at full term
Lipkind et al^Citation13 US	Retrospective cohort study Longitudinal Study of Early Development data warehouse	8–9 years	Preterm; n=2,332 Late preterm; n=13,207*	Full term; n=199,599	To compare school-age educational outcomes of late preterm infants compared to preterm and full term infants
Nepomnyaschy et al^Citation12 US	Cohort study ECLS-B	2 and 4 years	Late preterm; n=400	Full term; n=5,050	To compare cognitive, motor, and behavioral outcomes of healthy late preterm and healthy full term singleton infants at 2 and 4 years of age
Quigley et al^Citation19 UK	Retrospective cohort study	5 years	Born between 23–31 weeks; n=106 Born between 32–33 weeks; n=99 Born between 34–36 weeks; n=537* Born between 37–38 weeks; n=1,827	Full term; n=6,159	To compare school performance at age 5 years in children born at full term (39–41 weeks) with those born at early term (37–38 weeks), late preterm (34–36 weeks), moderately preterm (32–33 weeks), and very preterm (<32 weeks)
Woythaler et al^Citation11 US	Prospective cohort study ECLS-B	24 months chronological age	Late preterm; n=1,200*	Full term; n=6,300	To compare neurodevelopmental outcomes for late preterm infants and full term infants at 24 months of age
Baron et al^Citation10 US	Retrospective cohort study Fairfax Neonatal Associates PETIT (Prematurity’s Effects on Toddlers, Infants and Teens) study	3 years 0 months to 3 years 11 months	23–33 weeks; n=52 34–36 weeks; n=196*	Full term; n=121	To compare executive functions of extremely low birth weight and late preterm infants to full term infants at preschool age
Odd et al^Citation20 UK	Cohort study Avon Longitudinal Study of Parents and Children (ALSPAC)	8–11 years	Moderate/late preterm; n=741 Late preterm (34–36 weeks); n=6,905* Moderate preterm (32–33 weeks); n=6,655	Full term; n=13,102	To compare cognitive, memory, attention, or school outcomes in children born late preterm to full term infants
Pitcher et al^Citation23 Australia	Cohort study PREMOCODE (Preterm Motor and Cognitive Development) study	12–13 years	Early preterm; n=40 Late preterm; n=65*	Full term; n=46	To determine if atypical excitability in the brain and cortical pathways assessed with transcranial magnetic stimulation and surface electromyography are related to decreased motor development in 10–13-year-old children born at 25–41 weeks gestational age
Morag et al^Citation27 Israel	Prospective cohort	6 and 12 months of chronological age	Late preterm; n=124	Full term; n=33	To compare the developmental outcome of late preterm infants to full term infants from birth to the end of their first year of life
Odd et al^Citation21 Bristol, UK	Cohort study ALSPAC	7 and 8 years	Moderate/late preterm (mean gestation =35 weeks); n=741	Full term; n=13,102	To compare the risk of being diagnosed with cerebral palsy or having poor motor performance between infants born at late or moderate preterm with infants born preterm
Poulsen et al^Citation22 UK: England and Scotland	Cohort study Millennium cohort study	9 months, 3 years, 5 years, and 7 years	<32 weeks; n=225 32–33 weeks; n=192 34–36 weeks; n=1,107* 37–38 weeks; n=3,655	Full term; n=12,540	To determine the relationship between gestational age and cognition in late preterm and early term groups
Baron et al^Citation9 Virginia, US	Cohort study PETIT study, Fairfax Neonatal Associates’ longitudinal study of the outcomes of preterm birth	3–4 years chronological age	cLPT (admitted to NICU); n=278* 34 weeks; n=132*	Full term; n=192	To compare a range of cognitive measures between late preterm infants admitted to NICU and full term infants at 3 years of age
Brown et al^Citation28 Canada	Cohort study National Longitudinal Survey of Children and Youth (NLSCY)	2–3 years and 4–5 years	n=15,099 Late preterm; n=1,103* Early term; n=4,333 n=12,203 Late preterm; n=866* Early term; n=3,478	Full term; n=9,663 Full term; n=7,859	To study the role of gestational age in determining the risk associated with late preterm and early term births
Oros et al^Citation26 Spain	Cross-sectional cohort study	6–8 years	Late preterm; n=6* Late SGA; n=11	Full term; n=96	To investigate the hypothesis that SGA births and late prematurity present a distinct pattern of structural changes with specific cognitive difficulties
Schneider et al^Citation24 Australia	Retrospective cohort study	11–13 years	<32 weeks; early preterm; n=38 33–36 weeks; late preterm; n=63*	Full term; n=44	To investigate the influence of a range of prenatal and post-natal factors on cognitive development in preterm and term-born adolescents

Note:

* The group of interest that was compared with the control group and was included in our interpretation of the results.

Abbreviations: n, the size of the sample included in the current study; NICU, neonatal intensive care unit; SGA, small-for-gestational age; Gr I IVH, grade I intraventricular haemorrhage; ECLS- B, Early Childhood Longitudinal Study-Birth Cohort; ALSPAC, Avon Longitudinal Study of Parents and Children.

Table 2 Summary of results comparison between infants born LPT and Full term of included studies

Outcome domain	Outcome: Definition/Measurement	Group comparisons			Confounders adjusted for	Short synopsis
Cognition
Chyi (2008)^Citation18	Early childhood longitudinal study-kindergarten assessment scores	Risk of poor outcome 34–36 weeks adjusted OR (95% CI)			Adjusted for sex, race, and maternal education level. Only including singletons	Children born LPT in the United states are at an increased risk of having a below average score in first grade even when controlling for social factors and multiple gestations
	Reading T score
	Kindergarten	1.13 (0.97 to 1.33)
	First grade	1.24 (1.06 to 1.45)*
	Third grade	1.03 (0.86 to 1.23)
	Fifth grade	1.03 (0.84 to 1.26)
	Math T score
	Kindergarten	1.15 (0.98 to 1.34)
	First grade	1.22 (1.04 to 1.43)*
	Third grade	0.98 (0.82 to 1.17)
	Fifth grade	1.07 (0.88 to 1.31)
Baron (2009)^Citation17		cLPT compared to term children			None	cLPT have lower cognitive and visual motor outcomes than infants born at term
	DAS-II – general conceptual ability	Student’s t-test 2.16, P=0.033*
	Spatial cluster	Student’s t-test 2.88, P=0.005*
	Pattern construction T score	Student’s t-test 2.72, P=0.008*
	Copying T score	Student’s t-test 2.50, P=0.014*
	Beery Visual Motor Integration	Student’s t-test 2.57, P=0.112*
	Animal fluency total	Student’s t-test 2.41, P=0.018*
	Action- verb fluency total	Student’s t-test 2.27, P=0.026*
Gurka(2010)^Citation16	Woodcock Johnson psycho educational battery revised	No difference in the cognitive and achievement scores through age 15 years			Adjusted for sex, race, maternal education, maternal age, delivery type, maternal health, home environment, maternal depression score, and maternal vocabulary	This study found no significant difference between the LPT and FT infants on cognitive or behavioral outcomes. This was a small sample of 53 LPT infants who were at very low medical and social risk
Romeo (2010)^Citation25	Development quotient at 12 and 18 months	12 months	18 months		None	This study found that LPI have “caught up” to their term peers by 12 or 18 months – meaning when using uncorrected ages they are still delayed
		Mean ± SD	Mean ± SD
	Term	99.8±8.7	97.8±8.1
	LPT corrected age	100.3±8.7	97.0±9.1
	LPT uncorrected age	91.9±9.3	87.9±9.9
	Developmental quotients comparison	Mann Whitney U results
	Full term vs LPT	P<0.01*	P<0.01*
	LPT corrected age vs	P<0.01*	P<0.01*
	LPT uncorrected age
Talge (2010)^Citation15	Wechsler Intelligence scale for children Mean group differences, (95% CI), P-value				Adjusted for residential setting, maternal IQ, maternal education, marital status, and child sex	LPT infants (unknown of health status) are more likely to have a full scale and performance IQ which is 1 SD below the mean than those who were born FT, even though their full scale IQ and verbal IQ were similar to the term infants even after adjusting for social and maternal education factor
	Full scale IQ	1.31, (1.67 to 4.29), Ns
	Verbal IQ	0.15, (2.91 to 3.21), Ns
	Performance IQ	2.49, (0.53 to 5.51), P<0.10*
	Odds of having a delay, (95% CI), P-value
	Full scale IQ	aOR =2.35, (1.20 to 4.61), P<0.05*
	Verbal IQ	aOR =1.52, (0.78 to 2.95), Ns
	Performance IQ	aOR =2.04, (1.09 to 3.82), P<0.05*
Baron (2011)^Citation14	Mean DAS-II standard score				None	Mean DAS-11 General conceptual ability non- verbal reasoning, and spatial clusters of cIPT, but not uLPT, are lower than that of term infants. However, all groups had a mean score within the average range Rate of impairment (being more than 1 SD below the mean) in nonverbal reasoning and spatial cluster was higher in the cLPT, but not uLPT. However there was no difference in general cognitive impairments or composite verbal scores
	General conceptual ability	cLPT < full term: P=0.006*
	Composite verbal score-	Ns differences
	Nonverbal score	cLPT < full term: P=0.022*
	Spatial score	cIPT < full term: P=0.005*
	Rate of Impairment (standard score <85) on DAS-11
	General conceptual ability	Ns differences
	Composite verbal score	Ns differences
	Nonverbal score	cIPT vs full term: RR 7.22 (95% CI; 1.68 to 3 1.13)*
	Spatial score	cLPT vs full term: RR 5.56 (95% CI; 1.25 to 24.68)*
Woythaler (2011)^Citation11	BSF-R	Adjusted odds ratio (95% CI)			Adjusted for gestational age, plurality, maternal race, education, marital status, depression, prenatal care, primary language, infant sex, poverty level, delivery type, fetal growth, and any breast milk feeding	Infant born late preterm had lower mental abilities at 24 months even when adjusting for prematurity and maternal factors So the LPT infants have not caught up resulting in statistically significant differences at 24 months
	Derived MDI	MDI score <70
		1.51 (1.26 to 1.82)*
		MDI score 70–84
		1.43 (1.22 to 1.67)*
Baron (2012)^Citation10	DAS-II general conceptual ability	t(366) =−2.96, P<0.01*			Mother’s educational level Age	LPT group had reduced cognitive scores on the DAS and had lower executive function scores on 3 out of 8 measures used. Thus only a minor difference in executive function and lower general cognitive scores
	Executive function
	Preschool Continuous Performance Test
		F-test, P-value
	Commission	F(2,354)=5.93, Ns
	Omission	F(2,354)=17.57. P < 0.01*
	Reaction time	F(2,354)=0.74, Ns
	Go/No-Go test
	Comissions	F(2,354) = 11.92, Ns
	Omission	F(2,354) = 10.38, P<0.01*
	Reaction time	F(2,354) = 3.85, Ns
	Boy-Girl stroop test
	Correct	F(2,354) = 1.63, Ns
	Time	F(2,354) = 19.32, Ns
	Jack’s boxes test
	Within-error	F(2,354) =3.15, NS
	Between error	F(2,354) =6.14, P<0.01*
	Digit repetition	F(2,354) =3.83, Ns
Nepomnyaschy (2012)^Citation12	Association between late preterm birth and developmental outcomes at ages 2 and 4 years				Adjusted for race/ethnicity, age, education, marital birth, father co- residence, household below poverty, and complications of labor and delivery	The LPT group showed significant differences in math ability at 4 years of age when compared to the full term group Literacy and vocabulary are the only impairments seen in this national sample of LPT infants at 2 and 4 years when controlling for social and labor and delivers complications
	At 4 year outcome	Adjusted ordinary least squares, (95% CI), P-value
	Math ability	−0.99, (−1.78 to −0.19), P<0.05*
	Score > 1 SD below sample means
	Math ability	1.18, (0.85 to 1.65), Ns
	At 2 year outcomes
	Bayley mental score	−0.35, (−1.53 to 0.83), Ns
	Vocabulary	−0.72,(−2.24 to 0.79), Ns
	Language use	−0.25, (−0.47 to −0.03), P<0.05*
	At 4 years
	Literacy	−1.05, (−1.75 to −0.35), P<0.01 *
	Receptive language	−0.17, (−0.37 to 0.03), Ns
	Expressive language	−0.05, (−0.15 to 0.06), Ns
	Color knowledge	−0.15, (−0.41 to 0.12), Ns
	Vocabulary	0.56, (−1.33 to 0.21), Ns
	Language use	0.04, (−0.36 to 0.44), Ns
	Receptive language	−0.17, (−0.37 to 0.03), P<0.10*
	Expressive language	−0.05, (−0.15 to 0.06), Ns
	Odds ratio of having a score > 1 (95% CI), P-value	SD below sample means,
	At 2 year outcomes
	Bayley mental score	1.07, (0.76 to 1.50), Ns
	Vocabulary	1.22, (0.85 to 1.74), Ns
	Language use	1.17, (0.85 to 1.60), Ns
	At 4 years
	Literacy	0.89, (0.59 to 1.32), Ns
	Receptive language	0.98, (0.67 to 1.44), Ns
	Expressive language	1.04, (0.68 to 1.57), Ns
	Color knowledge	1.15, (0.83 to 1.61), Ns
	Vocabulary	1.33, (1.00 to 1.77), P<0.05*
	Language use	1.03, (0.73 to 1.43), Ns
	Receptive language	0.98, (0.67 to 1.44), Ns
	Expressive Language	1.04, (0.68 to 1.57), Ns
Odd (2012)^Citation20	Wechsler scale for moderate/LP compared with term infants.				Adjusted for ethnicity, housing, crowding, maternal education, socio-economic group, car ownership, age, sex, weight, length and head circumference at birth, mode of delivery, and maternal hypertension and pyrexia	As a group moderate and late preterm (mean age 35 weeks) infants combined together are at higher risk of mild cognitive issues. When controlling for social and medical risk factors these infants still show mild difficulty in reading accuracy, but in other areas are less significant. They also get more special education support in school but this could be related to a higher rate of identification in infants born preterm compared to the FT with cognitive issues
	Adjusted difference in mean, (95% CI), P-value
	Verbal subtest
	Information	−0.29, (−0.63 to 0.04), Ns
	Arithmetic	−0.22, (−0.67 to 0.24), Ns
	Vocabulary	−0.04, (−0.50 to 0.42), Ns
	Comprehension	0.13, (−0.28 to 0.54), Ns
	Similarities	0.18, (−0.25 to 0.61), Ns
	Performance subtest
	Picture completion	0.26, (−0.14 to 0.67), Ns
	Coding	−0.22, (0.55 to 0.10), Ns
	Picture arrangement	0.00, (0.53 to 0.53), Ns
	Block design	−0.03, (−0.45 to 0.38), Ns
	Object assembly	−0.12, (−0.55 to 0.31), Ns
	Summary scores
	Verbal IQ	−0.33, (−2.06 to 1.40), Ns
	Performance IQ	−0.12, (−1.96 to 1.73), Ns
	Summary IQ	0.18, (−1.88 to 1.52), Ns
	Linear regression difference for moderate/Late preterm compared with term infants
		Fully adjusted mean difference, (95% CI), P-value
	Test of memory
	No word repetition	1.55, (−3.18 to 0.09), Ns
	Span score	1.04, (−2.77 to 0.68), Ns
	Test of attention
	Sky search Attention	1.29, (−3.00 to 0.42), Ns
	Dual Attention Score	1.12, (−3.03 to 0.79), Ns
	Test of reading
	Accuracy	1.97, (−3.61 to −0.32), P=0.019*
	Read per minute	1.18, (−2.84 to 0.47), Ns
	Comprehension	0.98, (−2.58 to 0.61), Ns
Morag (2013)^Citation27	Griffith mental development scale - at 12 month chronological age				Adjusted to corrected Age	Similar to the Romeo study this study suggests that the LPT infant are not “catching up” by 12 months of age and appear delayed if tested without correction. But with correction are similar to full term infants
		LPT	Control	P-value
		Mean (SD)	Mean (SD)
	Personal-Social	112 (10)	117 (8)	0.001*
	Performance	84 (10)	95 (19)	0.001*
	Griffith mental development scale - at 12 month adjusted age
		LPT	Control	P-value
		Mean (SD)	Mean (SD)
	Personal-Social	123 (11)	117 (8)	Ns
	Performance	95 (12)	95 (19)	Ns
Poulsen (2013)^Citation22	Mean differences LPT vs term; Adjusted z score (95% CI)				Adjusted for mother’s education, mother’s SES based on occupation, mother’s age at birth, mother’s marital status, first-born status, child’s ethnic group, smoking and alcohol use during pregnancy	Infant born LPT have lower mean scores and are at higher risk of having a mild cognitive delays in some cognitive domains between 3 and 7 years of age even when controlling for maternal and social risk factors
	British ability scale II
	Naming vocabulary subscale	At age 3 yr: −0.1 (−0.2 to 0.01) At age 5 yr: 0.03 (−0.05 to 0.1)
	Picture similarities subscale	At age 5 yr: −0.02 (−0.1 to 0.1)
	Pattern construction measures	At age 5 yr: −0.1 (−0.2 to −0.1)* At age 7 yr: −0.1 (−0.2 to 0.02)
	Word reading subscale	At age 7 yr: −0.1 (−0.2 to −0.03)*
	Bracken school readiness assessment	At age 3 yr, −0.1 (−0.2 to −0.04)*
	Mathematics assessment numeracy skills	At age 7 yr, −0.04 (−0.1 to 0.04)
	Risk ratio of scoring > 1 SD below the mean (95% CI)
	British ability scale II
	Naming vocabulary subscale	At age 3 yr-aRR =1.1 (0.9 to 1.3)
	Picture similarities subscale	At age 5 yr-aRR = 1.0 (0.8 to 1.2)
	Pattern construction measures	At age 5 yr-aRR = 1.2 (1.0 to 1.3)*
	Word reading subscale	At age 5 yr-aRR =1.4 (1.1 to 1.6)* At age 7 yr-aRR = 1.05 (0.8 to 1.3)
	Bracken School readiness assessment	At age 7 yr-aRR = 1.4 (1.2 to 1.6)*
	Mathematics assessment numeracy skills	At age 3 yr, aRR =1.3 (1.1 to 1.5)* At age 7 yr, aRR = 1.05 (0.8 to 1.3)
Brown (2014)^Citation28	Motor and social development scale developed by the US National Center for Health Statistics	Adjusted Risk Ratio (95% CI) 1.06 (0.79 to 1.43) 1.13 (0.90 to 1.42)			Adjusted for perinatal variables (smoking during pregnancy, alcohol use during pregnancy, placental ischemia and other hypoxia [maternal hypertension, small for gestational age], other biological determinants of preterm family resources (family income adequacy, maternal education, maternal age, maternal health, maternal mental health), and family functioning and other covariates (child sex)	Motor/Social development is decreased in infants born LPT (compared to term infants). However, this decrease disappears when you control of social factors, lower maternal education level, financial instability, negative style or inconsistent parenting. Vocabulary is not delayed in infants born LPT, and continues to be unrelated to LPT birth status when you control for social factors
Baron (2014)^Citation9	At 3–4 years	ANOVA results			Adjusted for medical variables and demographic variables (sex, maternal education)	This study suggests that both cLPT and cLPT infant have cognitive impairments at preschool age when adjusting for medical and social factors
		cLPT < Term	uLPT < Term
		Cohen’s d, P-value	Cohen’s d, P-value
	General conceptual ability	−0.511, P<0.05*	−0.452, P<0.05*
	Verbal cluster	−0.302, P<0.05*	−0.329, P<0.05*
	Non verbal	−0.386, P<0.05*	−0.325, P<0.05*
	Spatial cluster	−0.491, P<0.05*	−0.395, P<0.05*
	Picture similarities	−0.279, P<0.05*	−0.311, P<0.05*
	Pattern construction	−0.418, P<0.05*	−0.271, Ns
	Copying	−0.422, P<0.05*	−0.422, P<0.05*
	Beery Visual Motor Integration	−0.398, P<0.05*	−0.319, Ns
	BASC- 2 adaptability	−0.352, P<0.05*	−0.417, P<0.05*
Oros (2014)^Citation26	Abnormal Children’s Bender Visual Motor Gestalt Test	Proportion of LPT and FT 16.7% and 6.2% (P=0.32)			None	There was no difference between LPT and FT controls on percent of children with abnormal visual motor function
Schneider (2014)^Citation24	Woodcock Johnson III Tests of cognitive abilities	There was not significant difference between the LPT and FT group on any cognitive domain (no specific data provided to support this statement)			Head circumference, body length at birth, Apgar score, multiple birth, parity, maternal age, maternal BMI, child height, weight and % of body fat, and laterality quotient	This study compares the cognitive abilities of Early preterm, late preterm, and full term infants between groups and others factors which may contribute to cognitive development. No data is presented on the comparison on LPT to term other than a statement the models were not significant
	Verbal ability
	Thinking ability
	Cognitive efficiency
	Auditory processing
	Phonemic awareness
	Working memory
	Global intelligence composite score
School/Academic performance
Chyi (2008)^Citation18	Teacher academic rating scales, 34–36 weeks adjusted				Adjusted for sex, race, and maternal education level, and only including singletons	Significant differences were found in the school based outcomes between late preterms and full terms where late preterms had lower scores in reading abilities at K grade. The teacher assessment scale showed that LPT infants were less proficient in reading and math abilities than FT. Late preterms are at a higher need for individualized education program than FT. However, these risk decreased by 3-5 grade
	OR (95% CI)
	Math
	Kindergarten	1.30 (1.07 to 1.59)*
	First grade	1.28 (1.06 to 1.54)*
	Third grade	1.28 (1.01 to 1.61)*
	Fifth grade	1.31 (1.05 to 1.65)*
	Reading
	Kindergarten	1.25 (1.05 to 1.49)*
	First grade	1.19 (0.99 to 1.43)
	Third grade	1.18 (0.86 to 1.62)
	Fifth grade	0.99 (0.71 to 1.37)
	Individualized Education Program
	Kindergarten	2.10 (1.47 to 3.00)*
	First grade	1.56 (1.10 to 2.21)*
	Third grade	1.27 (0.92 to 1.74)
	Fifth grade	1.29 (0.92 to 1.82) 34–36 weeks adjusted OR (95% CI)
	Special education
	Kindergarten	1.38 (1.00 to 1.89)*
	First grade	1.44 (1.08 to 1.91)*
	Third grade	1.13 (0.85 to 1.49)
	Fifth grade	1.10 (0.80 to 1.50)
	Individualized Education Program
	Kindergarten	2.13 (1.56 to 2.90)*
	First grade	1.44 (1.04 to 1.98)*
	Third grade	1.22 (0.92 to 1.63)*
	Fifth grade	1.28 (0.95 to 1.74)*
Quigley (2011)^Citation19	Foundation Stage profile	Adjusted Risk Ratios for not working securely in foundation stage profile scales (95% CI)			Adjusted for multiple birth, child’s sex, ethnicity, whether first born, breastfeeding duration, month of birth (age within the school year) and mother’s age, marital status, education, social class, and whether languages other than English were spoken at home	The findings suggests that there was a 12% increased risk of poorer academic achievement in late preterm children compared to full term infants
	Not good level of overall achievement	1.12, (1.04 to 1.22)*
	Not working securely in all three scales of personal, social, and emotional development	1.14, (0.99 to 1.32)
	Not work securely in all scales of communication, language, and literacy	1.16, (1.00 to 1.34)*
	Not working securely in the knowledge and understanding of the world scale	1.30, (1.08 to 1.56)*
	Not working securely in the physical development scale	1.27, (0.92 to 1.74)
	Not working securely in the creative development	1.46, (0.94 to 2.27)
Odd (2012)^Citation20	Teacher completed questionnaire: ‘Has this child ever been recognized as having special educational needs?’	Fully adjusted odds ratio, (95% CI), P-value 1.56, (1.18 to 2.07), 0.002*			Adjusted for ethnicity, housing, crowding, maternal education, socio-economic group, car ownership, age, sex, parity, weight, length and head circumference at birth, mode of delivery, and maternal hypertension and pyrexia	While this study found that there was little cognitive difference between groups, moderate to late preterm infants required more special education services than full term infants
Lipkind (2013)^Citation13		Adjusted SD%, (95% CI), P-value			Adjusted for child sex, maternal age, maternal race/ethnicity, insurance status, parity, low Apgar score, medical risk factors, complications of pregnancy, neonatal intensive care admission, days absent in third grade, and small for gestational age < 10th percentile	LPT infants in 3rd grade in New York city demonstrated impaired language arts and math performance on standardized school assessment and received more special education services even when the risks are controlled by social factors and medical risk factors. This was a fairly sick group of LPT infants while the analysis should have controlled for this It is possible that some factors related to the medical fragility could have not been adjusted and impacted the outcomes
	Standard 3rd grade English	4.0%, (−5.7 to −2.3), P<0.001*
	Language Arts Assessments
	Standardized 3rd grade Math	6.7%, (−8.4 to −5.1), P<0.001*
	Assessment
		Adjusted OR (95% CI)
	Individualized Education Program	1.34, (1.29 to 1.40)*
Language
Morag (2013)^Citation27	Hearing and Language	LPI	Control	P-value		This study found significant difference in the means of the hearing and language scores at 12 months of chronological age between LPT and FT group. No differences were seen between the groups when corrected age was used
		Mean ± SD	Mean ± SD		Adjusted for corrected age
	At 12 month chronological age	87±14	96±14	0.001*
	At 12 month corrected age	96±15	96±14	Ns
Motor development
Woythaler (2011)^Citation11	BSF-R				Gestational age, plurality, maternal race, education, marital status, depression, prenatal care, primary language, infant sex, poverty level, delivery type, fetal growth, and any breast milk feeding	Infants born late preterm have an increased risk of motor delays at 24 months even when adjusted for prematurity and social factors
	Derived PDI	Adjusted odds ratio of PDI score <70 (95% CI)
		1.56 (1.29 to 1.88)*
		Adjusted odds ratio PDI score
		70–84 (95% CI)
		1.58 (1.37 to 1.83)*
Nepomnyaschy (2012)^Citation12	Adjusted Ordinary Least Squares	(95% CI)			Adjusted for race/ethnicity, age, education, marital birth, father co-residence, household below poverty, and complications of labor and delivery	Infants born LPT are similar to infant born full in their motor development in the first 2-4 years of life
	At 2 years
	Derived Bayley Motor score	−0.33, (−1.58 to 0.91)*
	At 4 years
	Gross motor ability	−0.10, (−0.39 to 0.18), Ns
	Fine motor ability-copying forms	0.13, (−0.33 to 0.07), Ns
	Fine motor-building w/blocks	−0.02, (−0.11 to 0.07), Ns
	Adjusted ordinary least squares of having a score > 1 SD below sample mean (95% CI), P-value
	At 2 years
	Bayley motor score	1.00, (0.71 to 1.42), Ns
	At 4 years
	Gross motor ability	1.08, (0.73 to 1.58), Ns
	Fine motor ability-copying forms	1.18, (0.75 to 1.87), Ns
	Fine motor-building w/blocks	1.23, (0.87 to 1.73), Ns
Pitcher (2012)^Citation23		Mean percentile score for MABC ± SD			Adjusted for sex, GA, BW %, and corticomotor excitability	The study suggests there are no groups differences in the motor abilities of children about 12 months when assessed on the M-ABC
		LPT	Term	P-value
	Manual dexterity
	Males	34.4±22.3	41.6±24.3	Ns
	Females	53.1±27.4	42.0±25.5	Ns
	Aiming and catching
	Males	74.5±23.8	70.5±28.2	Ns
	Females	60.0±27.1	63.4±28.3	Ns
	Balance
	Males	45.5±30.6	62.7±26.7	Ns
	Females	67.6±31.2	71.4±28.5	Ns
	Total Score
	Males	50.4±26.0	59.8±23.8	Ns
	Females	59.4±29.9	60.8±26.8	Ns
	Total score	54.3±27.9	60.2±25.0	Ns
Baron(2014)^Citation9	Purdue dominant hand, raw				Adjusted for medical variables and demographic variables (sex, maternal education)	At 3 years of age, children who were born LPT as a groups have some fine motor delays regardless of their medical course at birth
		cLPT < Term	uLPT< Term
		Cohen’s d, P-value	Cohen’s d, P-value
		−0.294, P<0.05*	−0.451, P<0.05*
Morag (2013)^Citation27	Griffiths Mental Development Scales				Adjusted for corrected age	Infant born LPT have a not “caught up” from their PT birth by 12 months, but with correction for prematuritiy their motor skills are appropriate at 12 months
		LPT	Control	P-value
		Mean ± SD	Mean ± SD
	At 12 month chronologic age
	Locomotor	90±11	97±12	0.001*
	Eye hand Coordination	97±8	104±11	0.001*
	At 12 month corrected age
	Locomotor	100±12	97±12	Ns
	Eye hand Coordination	107±9	104±11	Ns
Odd (2013)^Citation21	Avon Longitudinal Study of Parents and Children coordination test	Association between moderate/late preterm gestation and risk of poor movements scores/outcomes			Adjusted for ethnicity, housing, crowding, and maternal education, socio-economic group, car ownership, and age Sex, parity, weight, length and head circumference at birth Mode of delivery, maternal hypertension, pyrexia, and need for resuscitation at birth	Infant born moderate/late preterm have an increased risk of fine motor impairments as well as movement impairments and CP. However, it is unclear how much of this risk is associated with the moderately preterm vs the late preterm.
		Fully adjusted differences, (95% CI), P-value
	Heel-to-toe score	1.27, (0.98 to 1.63), Ns
	Bean-bag score	1.17, (0.91 to 1.50), Ns
	Peg score	1.40, (1.08 to 1.81), 0.011*
	Summary score	1.39, (1.12 to 1.72), 0.003*
	Movement disorders
	Cerebral palsy	6.38, (2.28 to 17.76), P<0.001*
	Poor coordination score or cerebral palsy	1.56, (1.01 to 2.42), 0.045*
Brown (2014)^Citation28	Motor and Social Development Scale developed by the US National Center for Health Statistics	Adjusted risk ratio, (95% CI) 1.13; (0.90 to 1.42)			Adjusted for perinatal variables (smoking during pregnancy, alcohol use during pregnancy, placental ischemia and other hypoxia [maternal hypertension, small for gestational age], other biological determinants of preterm birth [maternal diabetes, other medical conditions during pregnancy], delivery mode); social context as described in terms of family structure (maternal partnership status, number of siblings), family resources (family income adequacy, maternal education, maternal age, maternal health, maternal mental health), and family functioning and other covariates (child sex)	Children born LPT are at an elevated risk for developmental delay when compared to those born full term when not adjusted for any of the medical and social factors. However, non significant group differences were seen once adjusted for medical and social factors.

Notes: All results presented are adjusted if presented by the authors as adjusted for confounders.

* results which were statistically significant P<0.05 or RR did not include 1 or OR did not include 0.

Abbreviations: LPT, late preterm; cLPT, complicated late preterm; FT, full term; SD, Standard deviation; CI, confidence interval; Ns, not statistically significant; RR, risk ratio; OR, odds ratio; aRR, adjusted relative risks; DAS-II, Differential Ability Scale; GCA, General Conceptual ability; BSF-R, Bayley Short Form-Research Edition; BASC-2, Behavior Assessment System for Children – Second Edition; MDI, Mental Development Index; PDI, Psychomotor Developmental Index; MABC, Movement Assessment Battery for Children; yr, year; uLPT, uncomplicated late preterms; aOR, adjusted odds ratio; GA, gestational age; BW, body weight; CP, Cerebral Palsy; SES, socioeconomic status.

Table 3 Summary of Critical Appraisal Skills Program (CASP) results

Reference	Did the study address a clearly focused issue?	Was the cohort recruited in an acceptable way?	Was the exposure accurately measured to minimize bias?	Was the outcome accurately measured to minimize bias?	Have the authors identified all important confounding factors?	Have the authors taken into account the confounding factors in the design and/or analysis	Was the follow-up of subjects complete enough?	Was the follow-up of subjects long enough?
Chyi et al^Citation18	Yes	Yes	No	Not clear	No	Yes	Yes	Yes
Baron et al^Citation17	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes
Gurka et al^Citation16	Yes	Yes	No	Not clear	Yes	Yes	Yes	Yes
Romeo et al^Citation25	Yes	Yes	Yes	Not clear	Not clear	Yes	Not clear	Yes
Talge et al^Citation15	Yes	Yes	Not clear	Not clear	No	Yes	Yes	Yes
Baron et al^Citation14	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes
Lipkind et al^Citation13	Yes	No	Yes	Yes	Yes	Yes	Yes	Yes
Nepomnyaschy et al^Citation12	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Quigley et al^Citation19	Yes	Yes	No	Yes	No	Yes	No	Yes
Woythaler et al^Citation11	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes
Baron et al^Citation10	Yes	Yes	Yes	No	Yes	No	Not clear	No
Odd et al^Citation20	Yes	Yes	Yes	Not clear	Yes	Yes	No	Yes
Pitcher et al^Citation23	Yes	Yes	Yes	Not clear	Yes	Yes	Yes	Yes
Morag et al^Citation27	Yes	Yes	Yes	Not clear	Yes	Yes	Yes	Yes
Odd et al^Citation21	Yes	Yes	Yes	Not clear	Yes	Yes	Not clear	Yes
Poulsen et al^Citation22	Yes	Yes	No	Not clear	No	Yes	Yes	Yes
Baron et al^Citation9	Yes	Yes	Yes	Not clear	Yes	Yes	Yes	Yes
Brown et al^Citation28	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Oros et al^Citation26	Yes	Yes	Yes	Not clear	No	Yes	Yes	Yes
Schneider et al^Citation24	Yes	Yes	Yes	Yes	No	Yes	No	Yes

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