What is already known on this topic? The introduction of antenatal steroids and surfactant therapy have resulted in a considerable decline in mortality but not in morbidity rates after preterm birth.

Very preterm children born before the introduction of antenatal steroids and surfactant show moderate to severe academic difficulties.

Several perinatal and demographic factors are associated with poor neurodevelopmental outcomes, but the effects on academic performance have not been aggregated across the available studies.

What this study adds? This meta-analysis provides insight in academic performance of the current population of preterm children and moderating effects of perinatal and demographic risk factors.

Preterm children have substantial difficulties in reading, spelling and arithmetic and are almost three times more likely to receive special educational assistance compared with controls.

Bronchopulmonary dysplasia was found to be the most important risk factor for poor academic outcomes.

Since 1990, worldwide preterm birth rates have increased to 11.1% in 2010.1 Since the introduction of antenatal steroids and surfactant in the early 90s, mortality rates of preterm infants (<37 weeks of gestation) have declined considerably.2 However, the decline in mortality is not accompanied by a similar decline in morbidity.3 4 Consequently, absolute numbers of preterm children with neurodevelopmental disabilities have increased and likely continue to increase.2 Providing care, interventions and education fitting the specific needs of these children will therefore place a growing burden on societies.

Academic performance provides an important measure of outcome of preterm children, because it has substantial, causal effects on health, mortality and life chances.5 6 Preterm birth is associated with lower incomes and increased reliance on social security in adulthood, which was predicted by decreased academic abilities.7 More insight into academic difficulties of preterm children may help prevent academic failure and thereby reduce long-term individual burden and societal costs. In a meta-analysis on reading abilities in preterm children at school-age, Kovachy and colleagues8 found worse decoding and reading comprehension abilities in preterm children compared with controls. Furthermore, a meta-analysis by Aarnoudse-Moens and colleagues9 showed moderate to severe difficulties in reading, spelling and arithmetic in very preterm children (<32 weeks of gestation). However, the vast majority of studies included in that meta-analysis comprised cohorts of children born before the introduction of antenatal steroids and surfactant. The present meta-analysis aims to provide insight into academic outcomes of preterm children born in the antenatal steroids and surfactant era.

Outcome data of the current population of preterm children is necessary to help guide medical decision making and parental counselling. In addition, data on perinatal and demographic factors may help to identify those children most at risk for adverse outcomes. This will benefit decision making in the neonatal period and may indicate where interventions should focus on to decrease these risks. For example, preterm children suffering from bronchopulmonary dysplasia (BPD) have increased risks for academic difficulties.10 Other factors predictive of adverse neurodevelopmental outcomes are periventricular leukomalacia (PVL), intraventricular haemorrhage (IVH) and neonatal infectious diseases.11–13 However, the effects on academic performance remain unclear. The current meta-analysis studies arithmetic, reading and spelling performance of preterm children. In addition, potential moderating effects of perinatal and demographic factors on academic performance are explored.

Methods Study selection This meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.14 Inclusion criteria for study selection were (1) the study concerned preterm children (<37 weeks GA); (2) children were born in the antenatal steroids and surfactant era (ie, 1990 or later or earlier studies explicitly reporting antenatal steroids and surfactant use or use confirmed by authors); (3) age at assessment was 5 years or older; (4) academic performance was evaluated using standardised tests; (5) a full-term control group was included; (6) and publication in a peer-reviewed journal. PubMed, Web of Science, ERIC and PsycINFO were searched using combinations of the following terms: premature*, preterm, low birth weight, academic, school, learning, reading, spelling, math*, arithmetic (last search: January 2017). Reference lists of relevant articles were scanned to identify additional relevant studies. The selection process is depicted in figure 1. Retrieved records were screened based on title and abstract to further establish relevance. Subsequently, 173 articles were assessed full-text for eligibility. Seventeen studies met all inclusion criteria. For overlapping cohorts, the study with the longest follow-up interval, most complete data and largest sample was selected. Figure 1 PRISMA flow chart of the study selection procedure. Outcomes and moderators Details of the included studies are presented in table 1. Arithmetic, reading and spelling performance data for preterm children and controls were extracted from the studies. If necessary, authors were contacted for additional data. The academic tests used in the studies are listed in table 1. All tests are widely used, validated, norm-referenced tests and have age-standardised scores with a mean of 100 and a SD of 15. For special educational needs (SEN), percentages of preterm and full-term children receiving any form of special educational assistance were compared. Definitions of SEN per study are provided as online supplementary material. Information on GA, birth weight (BW), age at assessment, IQ, sex, ethnicity, maternal education, small for gestational age (SGA) status, IVH grade I/II, IVH grade III/IV, PVL, BPD, postnatal corticosteroids use and infectious diseases (necrotising enterocolitis (NEC), meningitis and sepsis) was extracted from the studies to create moderator variables. An overview of these details for each study is provided in table 2. Supplementary file 1 [SP1.docx] Table 1 Sample characteristics, tests used to assessment academic achievement, results per academic domain and percentage of children with special educational needs (SEN) Table 2 Demographic and perinatal sample characteristics of the studies included in the meta-analysis Study quality Study quality was assessed using a modified version of the Newcastle-Ottawa Scale for cohort studies.15 Two authors (EST and JFdK) independently rated studies on a 7-point scale with higher scores indicating better quality. Statistical analyses This meta-analysis was performed using Comprehensive Meta-Analysis V.3.0. The standardised mean difference (SMD) in test scores between preterm and full-term children was used as effect size for arithmetic, reading and spelling. The mean difference of each study was weighted by the inverse of its variance. Composite scores were computed for three studies16–18 with more than one subtest per academic domain. Using the reported correlation coefficients between subtest scores, interrelation among outcomes was taken into account.19 Furthermore, combined effects across subgroups were computed for two studies18 20 that reported data for independent subgroups of preterm children. For SEN, the risk ratio (RR) was used as effect size. Random effects meta-analyses were performed to calculate combined effect sizes for arithmetic, reading, spelling and SEN. Dispersion across study effect sizes within each domain was tested using Cochran’s Q. I2 was used to quantify this dispersion. The value of I2 shows the percentage of variation across studies that is due to heterogeneity rather than chance. I2 was interpreted as follows: 30%–60%: moderate; 50%–90%: substantial; and 75%–100%: considerable heterogeneity.21 Publication bias was assessed by visual inspection of funnel plots and Egger’s test. Random effects meta-regressions were performed to explore the predictive role of demographic and perinatal factors for between-study variance in effect sizes. As a rule of thumb, meta-regression is thought only to be meaningful with more than 10 studies included in the analysis.21 Due to the small number of studies with available demographic or perinatal details, meta-regressions were performed irrespective of academic domain to increase the number of available studies. For studies reporting results for more than one academic domain, a composite score was calculated. Composite scores were computed using the correlation between subtests to account for interrelation.19 Sensitivity analyses were performed to compare results of analyses with all studies included and analyses excluding those studies in which also moderately/late preterm children were included.

Results The 17 selected studies included 2390 preterm children and 1549 controls. Arithmetic, reading and spelling performance was evaluated in 12, 15 and 6 studies, respectively. Across studies, GA varied from extremely to late preterm (23–36 weeks), with mean GA ranging from 24.5 to 29.9 weeks. Participants’ ages ranged from 6 to 18 years. Arithmetic, reading, spelling and SEN Meta-analytic results revealed significant differences between preterm and full-term children for all academic domains (see table 3). Arithmetic scores of preterm children were 0.71 SD below scores of full-term peers (z=−7.67, p<0.001), indicating a medium effect. Preterm children scored 0.44 and 0.52 SD lower on reading and spelling, respectively, compared with controls (z=−4.38, p<0.001 and z=−9.53, p<0.001), indicating small-sized and medium-sized effects. Results for arithmetic and reading were highly heterogeneous across studies (Q=60.81, p<0.001, I2 =81.91 and Q=101.97, p<0.001, I2 =86.27), indicating that the pooled effects should be cautiously interpreted. No significant heterogeneity was observed for spelling. Nine studies reported details about SEN for both preterm and full-term children. Based on these studies, preterm children were 2.85 times more likely to receive special educational assistance compared with controls (RR=2.85, 95% CI 2.12 to 3.84, p<0.001). Significant heterogeneity of results was observed (Q=26.19, p=0.001, I2 =69.46), indicating cautious interpretation of the pooled estimate. Forest plots are provided as online supplementary material. Table 3 Individual study and combined effect sizes (SMD) for arithmetic, reading, spelling and SEN (RR) Sensitivity analyses excluding four studies17 20 22 23 in which also moderately/late preterm children were included showed a combined effect of −0.77 for arithmetic (z=−7.79, p<0.001) and −0.55 for reading (z=−7.46, p<0.001). Results for spelling and SEN remained unchanged. Meta-regression Random effects meta-regression analyses were performed to explain heterogeneity in results across studies. GA explained a significant proportion of variance (R2 =0.39, Q(1)=7.49, p=0.006). Regression plots are shown in figure 2. One study,24 with a considerably lower mean GA (24.5 weeks) compared with the other studies, played a key role in this effect (see figure 2). Additional analysis without this study showed non-significant results. The same study reported a much higher incidence of PVL (16%) compared with other studies. Meta-regression showed a significant result for PVL (R2 =0.46, Q(1)=7.33, p=0.007), but additional analysis without this study again was non-significant. BPD explained 44% of the variance in academic performance (Q(1)=7.64, p=0.006) (see figure 2). The difference in intelligence between preterm and controls explained 46% of the variance across studies (Q(1)=8.31, p=0.004). BW, SGA status, IVH grade I/II, IVH grade III/IV, sex, age at assessment, ethnicity, measure of academic performance and study quality were not found to significantly explain heterogeneity. Less than 10 studies reported the incidence of sepsis, meningitis, NEC, postnatal corticosteroids use and maternal education level. The role of these factors could therefore not be assessed. Figure 2 Meta-regression of gestational age (A), bronchopulmonary dysplasia (B) and periventricular leukomalacia (C) on the standardised mean difference in academic performance between preterm and full-term children. The dashed circles in figure B indicate studies also including moderately/late preterm children. Sensitivity analyses without those studies17 20 22 23 also including moderately/late preterm children revealed results highly similar to those obtained in the full sample of studies. Again, intelligence explained a significant proportion of variance across studies (R2 =0.42, Q(1)=6.64, p=0.01). The proportion of variance explained by BPD increased from 44% in the full sample of studies to 78% in this subsample of studies (Q(1)=16.44, p<0.001). Publication bias Inspection of funnel plots did not suggest publication bias, which was confirmed by non-significant Egger’s test (online supplementary material).