Inger F. Bocca-Tjeertes

Neonatal Morbidities and Developmental Delay in Moderately Preterm-Born Children

BACKGROUND AND OBJECTIVE: Children born moderately preterm (32–356/7 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 childs 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.

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.

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]: 32–3567 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.

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

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 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 childrens 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 childrens 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.

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.

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, ie, 0.7 SD) than that of AGA PT and also higher (0.6 points, ie, 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.

Risk of developmental delay increases exponentially as gestational age of preterm infants decreases: a cohort study at age 4 years: Decreasing Gestational Age and Exponential Risk of Developmental Delay

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.