Prenatally detected copy number variants in a national cohort: A postnatal follow-up study.

OBJECTIVE: Belgian genetic centers established a database containing data on all chromosomal microarrays performed in a prenatal context. A study was initiated to evaluate postnatal development in children diagnosed prenatally with a non-benign copy number variant (CNV). METHODS: All children diagnosed with a prenatally detected non-benign CNV in a Belgian genetic center between May 2013 and February 2015 were included in the patient population. The control population consisted of children who had undergone an invasive procedure during pregnancy, with no or only benign CNVs. Child development was evaluated at 36 months using three (3) questionnaires: Ages and Stages Questionnaire Third edition, Ages and Stages Questionnaire Social-Emotional Second Edition and a general questionnaire. RESULTS: A significant difference in communication and personal-social development was detected between children with a reported susceptibility CNV and both children with an unreported susceptibility CNV and the control population. The outcome of children with a particular CNV is discussed in a case-by-case manner. CONCLUSION: Our postnatal follow-up project of children with a prenatally detected non-benign CNV is the first nationwide project of its kind. A higher number of cases for each CNV category is however needed to confirm our findings.

Risk factors for emotional and behavioral problems in moderately-late preterms.

OBJECTIVE: To assess which factors, including maternal, lifestyle, pregnancy- and delivery-related, fetal and neonatal factors adjusted for socio-economic status, are related to emotional and behavioral problems in moderately-late preterm born children (MLPs; gestational age 32.0-35.9 weeks) at 4 years of age. MLPs are at greater risk of emotional and behavioral problems than full-term born children. Especially for MLPs, knowledge about factors that increase or decrease the risk of emotional and behavioral problems is scarce. DESIGN AND SETTING: We assessed emotional and behavioral problems in 809 MLPs between ages 41 and 49 months from the prospective community-based Longitudinal Preterm Outcome Project (LOLLIPOP), using the parent-reported Child Behavior Checklist (CBCL). We collected potential risk factors from hospital records and parental questionnaires. Univariable and multiple logistic regression analyses were applied. MAIN OUTCOME MEASURES: (Sub)clinical CBCL scores. RESULTS: Perinatal infection increased the risk of CBCL total problem scores with an OR 2.22 (p<0.01). Perinatal infection, maternal smoking, and male gender increased the risk of CBCL externalizing problem scores with ORs between 1.64 and 2.46 (all p<0.05). Multiple birth decreased the risk of CBCL internalizing problem scores with an OR 0.63 (p<0.05). CONCLUSIONS: Risk factors for behavioral problems in MLPs are male gender, perinatal infection and maternal smoking, the latter two being potentially modifiable. Multiple birth is a protective factor for emotional problems in MLPs. These results suggest potential factors for targeting preventive intervention in MLPs, comprising the large majority of all preterm born children.

Longitudinal growth and emotional and behavioral problems at age 7 in moderate and late preterms.

OBJECTIVES: Moderately and late preterm children (MLPs, 32.0-36.9 weeks gestational age) have a greater risk of poorer growth. This seems to be associated with poorer neuropsychological functioning. Evidence is limited on whether this also holds for emotional and behavioral (EB) problems. Therefore, we assessed whether longitudinal growth from birth until age 7 was associated with EB problems at age 7 in MLPs. STUDY DESIGN: This study was part of the Longitudinal Preterm Outcome Project, a prospective cohort study. Data on growth (height, weight, head circumference, and extent of catch-up growth) were obtained from assessments from birth until age 7. EB problems were assessed at age 7 with the Child Behavior Checklist. We assessed whether growth and EB problems were associated using logistic regression analyses, adjusting for multiple birth, parity, and socioeconomic status. RESULTS: We included 248 MLPs. Median gestational age was 34 weeks (interquartile range: 33-35 weeks). Mean birth weight was 2.2 kg (standard deviation: 0.5 kg). Postnatal growth measures were below the Dutch reference norm. EB problems were more prevalent in MLPs than in the general Dutch population. Generally, we found no associations between growth and EB problems; odds ratios ranged from 0.20 to 2.72. CONCLUSIONS: In MLPs, postnatal growth from birth until age 7 was not associated with EB problems at age 7. Poorer growth thus seems to relate to neuropsychological problems, but not to EB problems. This suggests that the etiologies of these problems differ at least partially.

Attainment of gross motor milestones by preterm children with normal development upon school entry.

BACKGROUND: Little is known on the motor development of moderately preterm born (MPT) children, in comparison with early preterm born (EPT) children and fullterm born (FT), for children with normal motor outcomes at school entry. AIMS: To compare attainment rates of gross motor milestones reached between ages 1-24 months for MPT, EPT, and FT children, all with normal development upon school entry. STUDY DESIGN: Prospective cohort study. SUBJECTS: We included 1247 preterm (PT) children (gestational age [GA] 24.0-35.6 weeks) and 488 FT children (GA 38.0-41.6 weeks), with normal gross motor development at 4 years according to the Ages and Stages Questionnaire. OUTCOME MEASURES: We assessed 11 gross motor milestones assessed in preventive child healthcare during six standardized visits at calendar age. RESULTS: During the first six months, all PT categories had lower milestone attainment-rates than FTs children (differences 9-60% for PTs compared with FTs children). For all PT categories attainment rates gradually increased during toddlerhood. For PT children with higher GA, differences in attainment rates compared with FTs children were smaller and attainment rates became comparable to FT children at an earlier age. At age 24 months only attainment rates for PT children born <30 weeks GA remained lower than for FTs children (85% versus 95%, P < 0.01). CONCLUSION: Milestone attainment rates are highly dependent on GA during the first two years. Differences between PT and FT children are larger and persist longer with lower GA. For PT children <30 weeks GA, differences still occur at 24 months. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: controlled-trials.com, ISRCTN 80622320.

Stability of Developmental Problems after School Entry of Moderately-Late Preterm and Early Preterm-Born Children.

OBJECTIVE: To assess the stability of developmental problems in moderately-late preterm-born children compared with early preterm and full term-born children before school entry at age 4 years and 1 year after school entry at age 5 years. STUDY DESIGN: We included 376 early preterm, 688 born moderately-late preterm, and 403 full term-born children from the Longitudinal Preterm Outcome Project (LOLLIPOP) cohort study. Developmental problems were assessed by the total score and the 5 domain scores of the Ages and Stages Questionnaire at ages 4 (ASQ-4) and 5 (ASQ-5). From the combinations of normal and abnormal ASQ-4 and ASQ-5 scores we constructed 4 categories: consistently normal, emerging, resolving, and persistent problems. RESULTS: The ASQ-4 total score was abnormal more frequently in moderately-late preterm (7.9%, P = .016) and early preterm-born children (13.0%, P < .001) than in full term-born children (4.1%). Compared with the ASQ-5 total score, moderately-late preterm-born children had persistence and change comparable with full term-born children, and early preterm-born children had significantly greater rates than full term-born children of persistent (8.4% vs 2.2%, P < .001) and emerging problems (7.8% vs 2.7% P = .001). On the underlying domains, both early preterm and moderately-late preterm-born children had mainly emerging motor problems and resolving communication problems, but the changing rates of moderately-late preterm-born children were lower. CONCLUSIONS: After school entry, the overall development of moderately-late preterm-born children had stability patterns comparable with full term-born children, whereas early preterm-born children had greater rates of persistent and emerging problems. On the underlying domains, moderately-late preterm-born children had patterns comparable with early preterm-born children but at lower rates.

Longitudinal Growth and Neuropsychological Functioning at Age 7 in Moderate and Late Preterms.

OBJECTIVE: To determine the association between longitudinal growth measures (height, weight, head circumference, and extent of catch-up growth) and neuropsychological functioning at 7 years in moderately and late preterm children. METHODS: This study was part of a prospective, community-based cohort study. Data on growth were obtained from records on routine assessments in well-child centers until age 4 years and in a research setting at 7 years. Neuropsychological functioning was assessed at age 7 years. We assessed associations of growth with neuropsychological functioning and determined odds ratios for impaired neuropsychological functioning. All analyses were corrected for maternal education. RESULTS: We included 234 children. Median gestational age was 34 weeks (P25-75: 33-35 weeks), and mean birth weight was 2.2 kg (± 0.5 kg). Short stature at all ages was associated with poorer motor, IQ, and attention scores and led to increased risks of impaired motor skills and low IQ. Lower weight at 1 and 4 years was associated with poorer IQ scores. Increased weight gain between age 4 and 7 years was, however, associated with poorer motor, IQ, and attention scores. Decreased head circumference gain in the first year of life was associated with poorer motor and attention scores and led to an increased risk of impaired motor and attention skills. CONCLUSIONS: In moderately and late preterm children, poorer growth in the first 7 years is associated with poorer neuropsychological functioning. Regarding height, short stature was also associated with a higher likelihood of clinically relevant impaired neuropsychological functioning.

Emotional and Behavioral Problems of Preterm and Full-Term Children at School Entry.

BACKGROUND AND OBJECTIVES: Preterm children, compared with term children, are at increased risk of emotional and behavioral problems (EB-problems). Prevalences of EB-problems seem to vary with degree of prematurity and age at assessment. We therefore assessed individual stability of EB-problems in preterm compared with term children first before school entry and again 1 year after school entry, and variation in stability within the preterm group. METHODS: We used data of 401 early preterm (25-31 weeks' gestational age), 653 moderately preterm (32-35 weeks' gestational age), and 389 term children from the Longitudinal Preterm Outcome Project cohort study. We classified EB-problems based on the Child Behavior Checklist at ages 4 and 5; this resulted in 4 categories: consistently normal (2 normal scores), emerging (normal score at age 4 and clinical/subclinical score at age 5), resolving, and persistent EB-problems. RESULTS: All preterm children had higher rates than term children of persistent (7.2% vs 3.6%), emerging (4.3% vs 2.3%), and resolving (7.5% vs 3.6%) EB-problems. Early preterm children had the highest rates of persistent (8.2%) and emerging (5.2%) problems, and moderately preterm children had the highest rates of resolving problems (8.7%). In both preterm and term children, predictive values of normal scores at age 4 for normal scores at age 5 were ∼96%, and of clinical/subclinical scores at age 4 for clinical/subclinical scores at age 5 were ∼50%, except for early preterm children (60%). CONCLUSIONS: Compared with term children, all preterm children are at risk for persistent and changing EB-problems at school entry; individual stability, however, is difficult to predict based solely on the factor of preterm-birth.

Propranolol treatment of infantile hemangioma (IH) is not associated with developmental risk or growth impairment at age 4 years.

BACKGROUND: Long-term adverse effects of propranolol treatment for infantile hemangioma (IH) in young children have been suggested. OBJECTIVE: To compare growth and development in children treated with propranolol for IH with nontreated healthy controls. METHODS: Eighty two (73%) children with IH aged 43 to 51 months treated with propranolol for 6 months or longer, and without other developmental risk factors, were recruited (cases) and matched with 4 twin counterparts and 78 children from a community-based cohort (control subjects). Parents completed the 48-months Ages and Stages Questionnaire (ASQ). Percentages of children with abnormal ASQ results were compared using χ(2) analyses. Mean ASQ scores and growth were compared using Mann-Whitney U tests. RESULTS: Six (7.3%) cases had abnormal ASQ results, compared with 10 (12.2%) controls (P = .292). Mean ASQ total score (25th-75th percentile) was 52.9 (50.8-57.0) for cases and 51.9 (49.0-56.0) for controls (P = .383). Height and weight of cases and controls were comparable. LIMITATIONS: A parent-completed screening instrument was used. The exclusion of children born at gestational age less than 36 weeks and/or children born small for gestational age partly limits generalizability. CONCLUSION: We found no increased developmental risk or growth impairment at age 4 years in patients with IH treated with propranolol.

Co-occurrence of developmental and behavioural problems in moderate to late preterm-born children.

OBJECTIVE: To determine the occurrence of emotional and behavioural problems (EBP) in moderate to late preterm (MLP) and full-term children with developmental delay. DESIGN: Participants were recruited from 13 randomly selected preventive child healthcare (PCH) centres in the Netherlands. We included 903 MLP children of 32-36 weeks' gestation and 538 full-term controls, born between January 2002 and June 2003. Parents completed the Ages and Stages Questionnaire (ASQ) and Child Behaviour Checklist (CBCL) shortly before the scheduled PCH visit at 4 years of age. Co-occurrence was defined as: ASQ total or domain score >2 SDs below the mean and a CBCL score >84th percentile on total problems, internalising (emotional) or externalising (behavioural) problems. RESULTS: EBP were more prevalent among MLP children with abnormal ASQ total problems scores than among full-term children, particularly regarding externalising problems (33.8% vs 23.8%). In MLP children, rates of EBP differed per developmental domain and were highest for the domains problem-solving (36.0% had externalising problems, 95% CI 24.1% to 49.9%) and personal-social skills (38.7% had internalising problems, 95% CI 26.4% to 52.8%). The risk of any type of co-occurrence was higher for MLP than for full-term children (OR 1.86; 95% CI 1.14 to 3.03). Independent risk factors for co-occurrence were male gender, low socioeconomic status and young maternal age. CONCLUSIONS: Up to 39% of 4-year-old MLP children with developmental delay also have EBP, indicating that increased awareness of EBP is warranted in MLP children with developmental delay. Further research is needed to determine whether early detection of co-occurring problems results in better long-term health.

The Ages and Stages Questionnaire and Neurodevelopmental Impairment in Two-Year-Old Preterm-Born Children.

OBJECTIVE: To test the ability of the Ages and Stages Questionnaire, Third Edition (ASQ3) to help identify or exclude neurodevelopmental impairment (NDI) in very preterm-born children at the corrected age of two. METHODS: We studied the test results of 224 children, born at <32 postmenstrual weeks, who had scores on ASQ3 and Bayley Scales of Infant and Toddler Development, Third Edition (BSIDIII) and neurological examination at 22-26 months' corrected age. We defined NDI as a score of <70 on the cognitive--or motor composite scale of BSIDIII, or impairment on neurological examination or audiovisual screening. We compared NDI with abnormal ASQ3 scores, i.e., < -2SDs on any domain, and with ASQ3 total scores. To correct for possible overestimation of BSIDIII, we also analyzed the adjusted BSIDIII thresholds for NDI, i.e., scores <80 and <85. RESULTS: We found 61 (27%) children with abnormal ASQ3 scores, and 10 (4.5%) children who had NDI with original BSIDIII thresholds (<70). Twelve children had NDI at BSIDIII thresholds at <80, and 15 had <85. None of the 163 (73%) children who passed ASQ3 had NDI. The sensitivity of ASQ3 to detect NDI was excellent (100%), its specificity was acceptable (76%), and its negative predictive value (NPV) was 100%. Sensitivity and NPV remained high with the adjusted BSIDIII thresholds. CONCLUSION: The Ages and Stages Questionnaire is a simple, valid and cost-effective screening tool to help identify and exclude NDI in very preterm-born children at the corrected age of two years.

Functional outcomes at age 7 years of moderate preterm and full term children born small for gestational age.

OBJECTIVE: To compare functional outcomes of 7-year-old (school-age) children born small for gestational age (SGA; ie, a birth weight z score ≤ -1 SD), with appropriate for gestational age (AGA) peers, born moderately preterm or full term. STUDY DESIGN: Data were collected as part of the Longitudinal Preterm Outcome Project study, a community-based, prospective cohort study of 336 AGA and 42 SGA born children (median gestational age 35 weeks, range 31-41). Of the SGA children, 32 were moderately preterm, 10 were full term; of the AGA, these numbers were 216 and 120, respectively. At 6.9 years, we assessed intelligence, verbal memory, attention, visuomotor integration, and motor skills and we collected the parent-reported executive functioning. We compared the outcomes of the SGA children with those of their AGA peers. RESULTS: The performance of SGA children was similar to that of their AGA peers, except for attention control which was abnormal more often in SGA children (OR 3.99, 95% CI 1.32-12.12). The IQ of SGA children was 3 points lower, but this difference failed to reach significance. CONCLUSIONS: At school age, children born SGA have a greater risk of abnormal test scores on attention control than children born AGA, independent of gestational age. Their motor and many other cognitive functions are similar. The impact of these outcomes seems limited. Nevertheless, the consequences for school performance deserve attention.

RSV infection among children born moderately preterm in a community-based cohort.

UNLABELLED: We aimed to determine the rates of proven respiratory syncytial virus (RSV) hospitalization and disease severity among children born moderately preterm (MP, gestational age [GA] 32-36 weeks, n = 964), children born full-term (FT, GA 38-42 weeks, n = 572), and children born early preterm (EP, GA <32 weeks, n = 524). Our second aim was to identify risk factors for RSV hospitalization among MP. We extracted data from parental questionnaires and medical records, retrieved from a community-based cohort of children aged 43-49 months. The RSV hospitalization rates of MP were higher than FT (3.9 vs. 1.2 %, relative rate 3.2; 95 % confidence interval (CI) 1.4-7.1) and equal to EP (3.9 vs. 3.2 %, relative rate 1.2; 95 % CI 0.7-2.1). MP were hospitalized at an earlier age than EP. Disease severity (based on the type of treatment and hospitalization length) was equal in all groups. Risk factors for RSV hospitalization in MP were younger age and lower birth weight. In multivariable analyses, shorter GA and passive smoking independently increased the likelihood of RSV hospitalization in MP. CONCLUSION: The rates of hospitalization due to proven RSV infection are higher in MP than FT and not different between MP and EP. No difference in disease severity was observed. Among MP, the rates of RSV hospitalization are higher for lower GA and when exposed to passive smoking.

Behavioural and emotional problems in moderately preterm children with low socioeconomic status: a population-based study.

Moderately preterm (MP) birth is associated with higher rates of behavioural and emotional problems. To determine the extent to which low socioeconomic status (SES) contributes to these higher rates, we assessed independent and joint effects of MP birth and low SES, overall and by gender. Dutch preventive child health care centres provided a population-based sample of 915 MP children (32-36 weeks gestation) and 543 term-born children, born in 2002/2003. In multivariable logistic regression analyses, we determined the risk of behavioural and emotional problems per standard deviation (SD) decrease in gestational age and SES, using standardized measures for both. We also assessed three SES categories, being low (1SD or more below mean of standardized SES), intermediate (mean ± 1SD), and high (greater than mean + 1SD). The Child Behavior Checklist for 1.5-5 years was used to assess behavioural (externalizing), emotional (internalizing), and total problems at age 4 years. MP children with low SES had significantly higher total problem scores than those with high SES (11.3 vs. 5.1%, respectively). Each SD decrease in SES was associated with a 42% higher odds of elevated total problem scores (OR 1.42, 95% CI 1.14-1.77). No joint effects were found, meaning that lower gestational age independently added to the risk of behaviour problems (OR 1.24, 95% CI 1.00-1.56). Effects of MP birth and low SES were more pronounced in girls. In conclusion, MP birth and low SES multiply the risk of behavioural and emotional problems. The combination of risk factors identifies children who could benefit greatly from early intervention.

Symmetrical and asymmetrical growth restriction in preterm-born children.

OBJECTIVE: To determine how symmetric (proportionate; SGR) and asymmetric (disproportionate; AGR) growth restriction influence growth and development in preterms from birth to 4 years. METHODS: This community-based cohort study of 810 children comprised 86 SGR, 61 AGR, and 663 non-growth restricted (NGR) preterms, born in 2002 and 2003. Symmetrical growth restriction was defined as a birth weight below the 16th percentile (-1 SD) compared with full-terms and a head circumference (HC) z score not exceeding the infant's birth weight z score by >1 SD. Asymmetric growth restriction was defined as a HC z score exceeding that for by >1 SD as a proxy of brain sparing. Developmental delay was assessed by the Ages and Stages Questionnaire at 4 years. RESULTS: Longitudinal gains in weight and height were similar for SGR and AGR children and less compared with NGR children. At age 4, z scores for weight were -1.1 for SGR and -0.7 for AGR children vs -0.3 for NGR children. z scores for height were -0.8 and -0.5 vs. -0.2. HC gain were 2 cm more in SGR, but at 1 year, they were -0.2 vs. 0.2 (AGR) and 0.1 (NGR). Developmental delay increased with odds ratios of 2.5 (95% confidence interval 1.1-6.0) for SGR and 2.1 (95% confidence interval 0.7-5.9) for AGR. CONCLUSIONS: Weight and height gains were similar for AGR and SGR children but poorer compared with NGR children. SGR children caught up on HC. Developmental delay was more likely in growth-restricted preterms independent of HC at birth.

Growth patterns of large for gestational age children up to age 4 years.

OBJECTIVE: To determine how growth of large for gestational age (LGA) preterm (PT) children was affected by their PT birth and their LGA status. METHODS: This is a community-based cohort study of 1302 PT and 489 full-term (FT) children, born 2002 and 2003. RESULTS: We found that growth in height, weight, and head circumference of LGA PT children was well balanced during infancy and that only weight gain accelerated during subsequent years. This led to high BMIs comparable to those of LGA FT children. Being born both LGA and PT resulted in a median growth at the age of 4 years that was 0.1 SD lower for weight (P = .44), 0.1 SD lower for height (P = .48), and 0.5 SD lower for head circumference compared with LGA FT counterparts (P = .016), whereas BMI at age 4 years was equal. Compared with appropriate for gestational age (AGA) PT children, these measures for LGA PT children were 0.9 SD, 0.6 SD, and 0.4 SD (all P < .001) higher, respectively. That led to the BMI of LGA PT children at age 4 years being significantly higher (0.9 points, i.e., 0.7 SD) than that of AGA PT and also higher (0.6 points, i.e., 0.4 SD) than that of AGA FT children. CONCLUSIONS: The growth patterns of LGA PT-born children are distinctly different from other PT or FT children. In particular, we found substantially greater weight gains and relatively higher BMIs among them, which added to their already increased metabolic risks based on their gestational age.

Validity and internal consistency of the Ages and Stages Questionnaire 60-month version and the effect of three scoring methods.

BACKGROUND: The Ages and Stages Questionnaire (ASQ) is currently the most used parent-completed developmental screener consisting of different age-specific questionnaires. Psychometric evaluation of the ASQ 60-month version (ASQ-60) is limited. Furthermore, it is unclear which of the available scoring methods of the ASQ is most useful in the identification of children with potential developmental problems. AIM: To evaluate the internal consistency and construct validity of the ASQ-60 with a large sample size, and to assess the effects of three scoring-methods on this validity. STUDY DESIGN: Parents of 394 term-born and 1063 preterm-born children from the prospective cohort-study Lollipop completed the ASQ-60 and a general questionnaire on school-problems. OUTCOME MEASURES: Internal consistency and construct validity of the ASQ-60 were determined using the ASQ total score. Construct validity was also determined using two other types of scoring-methods based on low domain-scores ('ASQ domain score') and parental concerns ('ASQ total score with parental concerns'). RESULTS: Cronbach's alpha for total score was 0.86, confirming internal consistency. Male gender, prematurity, low paternal education, low family income and small-for-gestational-age were associated with low 'ASQ total scores,' confirming construct validity. Regarding construct validity with special education as criterion, sensitivity was best using the 'ASQ domain score' or the 'ASQ total score' with parental concerns (both 0.96). However, the specificity was best (0.93) using the ASQ total score. CONCLUSION: The ASQ-60 has a good internal consistency and validity to screen for developmental problems in the general population. The 'ASQ total score' has the best performance, the 'ASQ domain score' is recommended in case of preferred high sensitivity.

Developmental delay in moderately preterm-born children with low socioeconomic status: risks multiply.

OBJECTIVE: To assess separate and joint effects of low socioeconomic status (SES) and moderate prematurity on preschool developmental delay. STUDY DESIGN: Prospective cohort study with a community-based sample of preterm- and term-born children (Longitudinal Preterm Outcome Project). We assessed SES on the basis of education, occupation, and family income. The Ages and Stages Questionnaire was used to assess developmental delay at age 4 years. We determined scores for overall development, and domains fine motor, gross motor, communication, problem-solving, and personal-social of 926 moderately preterm-born (MP) (32-36 weeks gestation) and 544 term-born children. In multivariable logistic regression analyses, we used standardized values for SES and gestational age (GA). RESULTS: Prevalence rates for overall developmental delay were 12.5%, 7.8%, and 5.6% in MP children with low, intermediate, and high SES, respectively, and 7.2%, 4.0%, and 2.8% in term-born children, respectively. The risk for overall developmental delay increased more with decreasing SES than with decreasing GA, but the difference was not statistically significant: OR (95% CI) for a 1 standard deviation decrease were: 1.62 (1.30-2.03) and 1.34 (1.05-1.69), respectively, after adjustment for sex, number of siblings, and maternal age. No interaction was found except for communication, showing that effects of SES and GA are mostly multiplicative. CONCLUSIONS: Low SES and moderate prematurity are separate risk factors with multiplicative effects on developmental delay. The double jeopardy of MP children with low SES needs special attention in pediatric care.

Maternal and pregnancy-related factors associated with developmental delay in moderately preterm-born children.

OBJECTIVE: To estimate the association between pre-existing maternal and pregnancy-related factors and developmental delay in early childhood in moderately preterm-born children. METHODS: We measured development with the Ages and Stages Questionnaire at age 43-49 months in 834 moderately preterm-born (between 32 0/7 and 35 6/7 weeks of gestation) children born in 2002-2003. We obtained data on preexisting maternal, maternal pregnancy-related, fetal, and delivery-related factors. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) and attributable risks for developmental delay adjusted for sociodemographic and lifestyle variables. RESULTS: Attributable risk for developmental delay for small-for-gestational-age (SGA, as a proxy for intrauterine growth restriction [IUGR]) was 14.2% (SGA 21.9%, no SGA 7.7%, P<.05, adjusted OR 2.75, CI 1.25-6.08), for preexisting maternal obesity 10.5% (obesity 18.0%, no obesity 7.5%, P<.01, adjusted OR 2.73, CI 1.35-5.52), for multiple pregnancy 4.2% (multiple 12.0%, singleton 7.8%, P<.05, adjusted OR 1.86, CI 1.02-3.42), and for male sex 9.3% (male 13.0%, female 3.8%, P<.001, adjusted OR 4.20, CI 2.09-8.46). No other preexisting or pregnancy-related maternal factors or any delivery-related factors were associated with increased risk of developmental delay. CONCLUSIONS: Of all preexisting maternal and pregnancy-related factors studied, SGA, maternal prepregnancy obesity, being one of a multiple, and male sex were associated with the risk of developmental delay in early childhood after moderately preterm birth. Reinforced focus on prevention of IUGR, preconception lifestyle interventions aiming at weight reduction in fertile women, and reinforced efforts to reduce rates of multiple pregnancies in assisted reproduction may all contribute toward more favorable developmental outcomes in moderately preterm-born children. LEVEL OF EVIDENCE: II.

Growth in small-for-gestational-age preterm-born children from 0 to 4 years: the role of both prematurity and SGA status.

BACKGROUND: Fullterm small-for-gestational-age children (SGAs) are known for their ability to catch up on growth. Nevertheless, increased risk of growth restriction remains. Evidence on preterm SGA children's growth is lacking. OBJECTIVE: To determine absolute gains in height and weight, relative growth, and growth restriction in preterm SGAs from 0 to 4 years and how prematurity and SGA status affect these measures. DESIGN/METHODS: Community-based cohort study, n = 1,648 preterm-born (gestational age <36 weeks, 57 SGA) and 605 term-born (12 SGA). We defined SGA as a birth weight less than -2 SD (P 2.3) compared to counterparts matched for gestational age. Height, weight, and head circumference were obtained from medical records and translated to z-scores. We defined growth restriction as height or weight less than -2 SD compared to fullterm appropriate-for-gestational-age children (AGAs). RESULTS: Absolute height and weight gains were similar, but the relative growth of preterms and fullterms differed. Preterm AGAs and fullterm SGAs, although not reaching it, caught up towards the fullterm AGA median (z-scores at 4 years: -0.3 to -1.0). By contrast, preterm SGA children's z-scores were still -1.4 to -1.7. Head circumference growth was less affected by prematurity and SGA birth (z-scores at 1 year: 0.1 to -0.7). Catch-up growth mainly took place during infancy. 30-39% of all preterm SGAs showed growth restriction at 4 years. CONCLUSIONS: Growth in preterm SGAs is affected considerably by the joint effects of preterm birth and SGA status, resulting in a high proportion of growth restriction.