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.

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.

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.

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.

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.

Risk of developmental delay increases exponentially as gestational age of preterm infants decreases: a cohort study at age 4 years.

AIM: The aim of the study was to assess the influence of decreasing gestational age on the risk of developmental delay in various domains at age 4 years among children born at a wide range of gestational ages. METHOD: In a community-based cohort, the parents of 1439 preterm-born children (24 0/7 to 35 6/7 wks) and 544 term-born children (38 0/7 to 41 6/7 wks') born in 2002 and 2003 completed the Ages and Stages Questionnaire (ASQ) when their child was 3 years 7 months to 4 years 1 month old. The prevalence rates of abnormal scores on the ASQ-total problems scale were compared in preterm and term-born children and the resulting odds ratios for gestational age groups were calculated and adjusted for social and biological covariates. RESULTS: The prevalence rates of abnormal scores on the ASQ-total problems scale increased with decreasing gestational age: from 4.2% among term-born children to 37.5% among children born at 24-25 weeks' gestation (p<0.001). The risk of an abnormal ASQ-total score increased exponentially with decreasing gestational age compared with children born at term (odds ratio per week of gestation 1.14, 95% confidence interval 1.09-1.19). A similar exponential pattern was seen on all underlying ASQ domains, both before and after adjustment. INTERPRETATION: The risk of developmental delay increases exponentially with decreasing gestational age below 36 weeks' gestation on all developmental domains of the ASQ. Adjustment for covariates did not alter the pattern of exponential increase in developmental risk with decreasing gestational age. We speculate that both direct perinatal cerebral injuries and tropic and maturational brain disturbances are involved.

Neonatal morbidities and developmental delay in moderately preterm-born children.

BACKGROUND AND OBJECTIVE: Children born moderately preterm (32-35(6/7) weeks' gestation) are at increased risk of both neonatal morbidities and developmental delays in early childhood. It is unknown whether neonatal morbidities contribute to the increased risk of developmental delay. The objective of this study was to determine the effect of neonatal morbidities after moderately preterm birth on development at preschool age. METHODS: In a community-based, stratified cohort, parents of 832 moderately preterm children born in 2002 or 2003 completed the Ages and Stage Questionnaire when their child was 43 to 49 months old. Data on Apgar scores, asphyxia, tertiary NICU admission, hospital transfer, circulatory insufficiency, hypoglycemia, septicemia, mechanical ventilation, continuous positive airway pressure, apneas, caffeine treatment, and hyperbilirubinemia were obtained from medical records. We assessed associations of neonatal characteristics with developmental delay, adjusted for gender, small-for-gestational-age status, gestational age, and maternal education. RESULTS: Hypoglycemia and asphyxia were associated with developmental delay; odds ratios (ORs) were 2.42 (95% confidence interval [CI]: 1.23-4.77) and 3.18 (95% CI: 1.01-10.0), respectively. Tertiary NICU admission and hyperbilirubinemia had positive but statistically borderline nonsignificant associations with developmental delay: ORs were 1.74 (95% CI: 0.96-3.15) and 1.52 (95% CI: 0.94-2.46), respectively. No other neonatal morbidities were associated with developmental delay. In multivariate analyses, only hypoglycemia was associated with developmental delay (OR: 2.19; 95% CI: 1.08-4.46). CONCLUSIONS: In moderately preterm-born children, only hypoglycemia increased the risk of developmental delay at preschool age. A concerted effort to prevent hypoglycemia might enhance developmental outcome in this group.

Growth of preterm and full-term children aged 0-4 years: integrating median growth and variability in growth charts.

OBJECTIVES: To assess the distribution of height, weight, and head circumference (HC) in preterm infants for ages 0-4 years, by gestational age (GA) and sex, and to construct growth reference charts for preterm-born children, again by GA and sex, for monitoring growth in clinical practice. STUDY DESIGN: The community-based cohort study covered a quarter of The Netherlands. 1690 preterm infants (GA, 25-35(+6) weeks) and a random sample of 634 full-term control infants (GA 38-41(+6)), who were followed from birth to 4 years of age. Height, weight, and HC were regularly assessed during routine well-child visits and data were retrospectively collected. RESULTS: At all ages, the median height and weight of preterm children were lower compared with full-term children. Growth depended on the child's GA. Increase in HC showed an early catch-up and was similar to full-term children by the age of 1. Height, weight, and HC were more variable in boys, particularly in the very preterm children. CONCLUSIONS: At 0 to 4 years, the growth of preterm children differed from that of full-term children and depended on their GA. The greater variability of growth in boys suggests that they are more vulnerable to the complications of preterm birth that influence growth. These growth charts are the most precise tools currently available for monitoring growth in preterm children.

Growth and predictors of growth restraint in moderately preterm children aged 0 to 4 years.

OBJECTIVE: To describe growth in moderately preterm-born children, determine the prevalence of growth restraint at the age of 4, and identify predictors of growth restraint. We hypothesized that growth in moderately preterm-born children differs from growth in term-born children and that growth restraint is more prevalent in those born prematurely. PATIENTS AND METHODS: This was a community-based cohort study of 1123 children born moderately prematurely (gestational age [GA]: 32-35 6/7 weeks) between January 2002 and June 2003. RESULTS: On average, we found that moderately preterm-born children were shorter and weighed less at each assessment during the first 4 years of life than their term-born counterparts. Thirty-two boys (5.6%) and 18 girls (3.8%) were growth-restricted in height, and 21 boys (3.4%) and 27 girls (5.8%) were growth-restricted in weight. Their growth in head circumference was normal compared with term-born children. In addition, growth restraint was associated with being small for GA at birth (odds ratio [OR] for height: 7.7 [95% confidence interval (CI): 2.9-20.4]; OR for weight: 9.5 [95% CI: 3.9-23.1]) and maternal height below -1 SD (OR for height: 4.9 [95% CI: 2.6-10.2]; OR for weight: 2.6 [95% CI: 1.3-5.2]). Poor head-circumference growth was associated with a low level of maternal education (OR: 5.3 [95% CI: 1.4-20.8]). CONCLUSIONS: Growth in moderately preterm-born children significantly differs from that of term-born children. Predictors at birth are being small for GA, maternal height below -1 SD, and a low level of maternal education. The fact that growth in moderately preterm-born children may lag warrants close monitoring during routine practice. Additional research on prevention of growth restraint is needed.

Developmental delay in moderately preterm-born children at school entry.

OBJECTIVE: To determine the prevalence and nature of developmental delay at preschool age in infants born moderately preterm compared with those born full-term and early preterm. STUDY DESIGN: Parents of 927 moderate preterm infants (32-35(+6) weeks gestation), 512 early preterm infants (<32 weeks gestation) and 544 full-term infants (38-41(+6) weeks gestation) completed the Ages and Stages Questionnaire (ASQ) when the child was aged 43-49 months. We analyzed rates of abnormal ASQ scores and odds ratios for abnormal ASQ scores in both preterm groups compared with the full-term group. We repeated the analyses after adjustment for socioeconomic status, sex, being part of a multiple birth, and small for gestational age status. RESULTS: Abnormal (ie, >2 SDs below the mean) ASQ total scores were noted in 8.3% of moderate preterm infants, in 4.2% of full-term infants, and in 14.9% of early preterm infants. ORs of abnormal ASQ total scores were 2.1 (95% CI, 1.3-3.4) for moderate preterm infants and 4.0 (95% CI, 2.4-6.5) for early preterm infants. Both moderate and early preterm infants had more frequent problems with fine motor, communication, and personal-social functioning compared with full-term infants. Compared with full-term infants, moderate preterm infants did not have a greater prevalence of problems with gross motor functioning and problem solving, whereas early preterms did. Socioeconomic status, small for gestational age status, and sex were associated with abnormal ASQ scores in moderate preterm infants. CONCLUSIONS: At preschool age, the prevalence of developmental delay in moderate preterm infants was 2-fold of that in full-term infants and one-half of that in early preterm infants.

Staged bilateral lung volume reduction surgery - the benefits of a patient-led strategy.

OBJECTIVE: Lung volume reduction surgery (LVRS) is conventionally a one-staged bilateral operation. We hypothesised that a more conservative staged bilateral approach determined by the patient not the surgeon would reduce operative risk and prolong the overall benefit. METHODS: In a population of 114 consecutive patients who were identified as suitable for bilateral LVRS an initial cohort of 26 patients (15 male; 11 female, median age: 58 years) underwent one-staged bilateral surgery: 18 by median sternotomy and eight by video-assisted thoracoscopic surgery (VATS) (group OB). A subsequent cohort of 88 patients had unilateral VATS LVRS with the contralateral operation not scheduled until the patient requested this. Longitudinal follow-up included analysis of lung function, health status (SF 36) and survival. RESULTS: At a median follow-up of 2.8 (range: 0-9.9) years, staged bilateral LVRS was performed in 16 patients (10 male; 6 female, median age: 59 years) (group SB) at a median interval of 3.9 (range: 0.7-5.9) years after the first operation. Unilateral LVRS has been performed in 73 patients (43 male; 30 female, median age: 60 years) (group U). There were significant improvements in forced expiratory volume in 1s (FEV1) for 6 months in groups OB and U; in group SB there was a second improvement at 4 years (p<0.05). There were significant reductions in residual volume (RV) and total lung capacity (TLC) in groups OB and U for 2 years; in group SB there was a further significant reduction lasting up to 6 years in TLC (p<0.05) and RV (p<0.01). There were significant improvements in health status lasting up to 1 year in groups OB and U. However, in group SB these improvements lasted for 4 years in the domain of physical functioning and 6 years in the domains of social functioning and energy/vitality. There was no significant difference (p=0.07) in 30-day mortality among groups OB (7.7%), SB (13%) and U (4.1%). Similarly, there was no difference between groups OB and SB/U in 3-year survival (81% vs 77%) or 5-year survival (54% vs 66%). CONCLUSION: A staged bilateral approach to LVRS dictated by patients' perception of their condition appears to lead to a more prolonged overall benefit than one-staged LVRS without compromising survival.

Latissimus dorsi myoclonus after video assisted thoracoscopic lung volume reduction.

Myoclonus as a sequel to thoracotomy has been reported, and its treatment can be challenging to both the patient and the surgeon. We describe a 43-year-old patient with chest wall pain and latissimus dorsi muscle contractions (myoclonus) after video-assisted thoracoscopic lung volume reduction. His symptoms remained refractory to benzodiazepines, nerve blockage, and botulinum toxin injection due to either poor compliance or lack of response to therapy. These symptoms started to resolve spontaneously 18 months after the procedure.

A prospective analysis of the inter-relationship between lung volume reduction surgery and body mass index.

OBJECTIVES: LVRS is thought to result in significant improvements in BMI. Patients with a higher BMI at the time of diagnosis of COPD are known to have better survival, and those with a low BMI prior to LVRS have significantly worse perioperative morbidity. We aimed to assess the influence of BMI on the outcome of LVRS in our own experience. METHODS: Complete preoperative BMI data was available in 114 of 131 consecutive patients who have undergone LVRS since 1995. These patients were arbitrarily classified into three categories: underweight (BMI26 kg/m2). The in-hospital course and perioperative change in BMI at 3, 6, 12, 24 and 36 months were prospectively recorded for each category and compared. RESULTS: There were no significant differences in preoperative variables except BMI. There were significantly more postoperative ITU admissions among the lowest two BMI groups (12/29, 18/58 and 3/27 patients, respectively, p=0.02), and significantly shorter hospital stay in overweight patients [16 days (5-79) vs 18 days (6-111) vs 13 days (6-25), respectively, p=0.005, expressed as median (range)]. However, there was no difference in survival between the three groups (p=0.21). Postoperative physiological improvements in the first year were related to preoperative BMI for both FEV1 (r=0.29, p=0.02) and DLCO (r=0.33, p=0.02). Postoperative BMI significantly increased in the underweight yet significantly decreased in the overweight at all time points. CONCLUSIONS: The perioperative course of LVRS and its physiological benefits are influenced by preoperative BMI. Whilst the treatment of the underweight is more complicated, LVRS may be the only way of increasing their BMI. Future work is needed to explore the roles of changing energy requirements and body composition following LVRS.

Pseudo tumors of the lung after lung volume reduction surgery.

We describe 2 patients who underwent lung volume reduction surgery, who postoperatively had computed tomographic scans that showed symptomatic mass lesions suggestive of malignancy and an inhaled foreign body. Investigations excluded these conditions with the remaining likely diagnosis of pseudotumor secondary to buttressing material. These potential sequelae of lung volume reduction surgery should be recognized in follow-up investigations.

The increase in body mass index observed after lung volume reduction may act as surrogate marker of improved health status.

OBJECTIVE: To assess the effects of lung volume reduction surgery (LVRS) on body mass index (BMI). METHODS: Prospective data was collected on a series of 63 patients undergoing LVRS (bilateral in 22 patients, unilateral in 41 patients). Median age was 58 (41-70) years. The peri-operative effects of LVRS on BMI, lung function and health status (assessed by SF 36 questionnaire) were recorded at 3, 6, 12 and 24 months. RESULTS: We found an overall increase in BMI after LVRS, which was significant up to 2 years. These changes correlated with the changes in FEV1 (R = 0.3, P < 0.01 6 months after LVRS) and diffusing capacity for carbon monoxide (DLCO) (R = 0.5, P < 0.01 6 months after LVRS). At 6 months, when the best results in health status were found, the patients were divided in a responders group (improved SF 36 score) and a non-responders group (same or worse SF 36 score) for each of the 8 domains of the SF 36. In 6 domains the non-responders showed no increase in BMI. In 6 domains the responders showed a significant increase in BMI. CONCLUSION: LVRS significantly improves postoperative BMI, which correlates with improvements in DLCO and reflects changes in health status.

The long-term health status improvements seen after lung volume reduction surgery.

OBJECTIVES: To correlate the long-term changes in respiratory physiology, body mass index (BMI) and health status after lung volume reduction surgery (LVRS). PATIENTS/METHODS: From 1995 to 2002 77 patients; 48 male: 29 female, median age 59 (41-72) years, have undergone LVRS (simultaneous bilateral in 27; staged bilateral in 3; unilateral in 47). FEV(1), total lung capacity (TLC), residual volume (RV) and RV/TLC ratio were measured preoperatively and at 3 months, 6 months, 1 year, 2 years, 3 years and 4 years post surgery. At the same time interval health status was assessed by Euroquol and Short Form 36 (SF 36) questionnaires. Seventeen patients have died within 4 years of their operation (30 day mortality 5%). RESULTS: The changes in FEV(1) are only significantly improved for 1 year post LVRS, while the improvements in TLC and RV remain significant up to 3 years postoperatively. The improvements in BMI also persist for 3 years. The best scores in Euroquol and SF 36 are obtained 6 months after LVRS but are only significantly improved up to 1 year. CONCLUSION: The physiological effects of volume LVRS are lasting but initial improvements in health status decline more rapidly.