Neurodevelopmental Outcome at Corrected Age of 2 Years among Children Born Preterm with Operative Vaginal Delivery: A Population-Based Study (LIFT Cohort).

The aim of the study was to determine whether operative vaginal delivery (OVD) was associated with non-optimal neurocognitive development at the corrected age of 2 years for preterm singletons using the Loire Infant Follow-up Team (LIFT) longitudinal cohort, a French regional perinatal network and prospective, population-based cohort of preterm infants. For this study, we included women with cephalic singletons and planned vaginal delivery from 24 to 34 weeks' gestation between 2006 and 2016. The main exposure was the mode of delivery (spontaneous vaginal delivery (SVD), OVD, and cesarean delivery (CS) during labor). The primary outcome was non-optimal neurodevelopmental outcome at the corrected age of 2 years assessed by a physical examination, a neuropsychological test, and/or a parental questionnaire. Secondary outcomes were survival at discharge and survival at discharge without morbidity. We used the multivariate logistic regression and propensity score methods to compare outcomes associated with OVD. The study included 1934 infants born preterm: 1384 (71.6%) with SVD, 87 (4.5%) with OVD, and 463 (23.9%) with CS. Neonates with SVD, OVD, and CS did not differ in survival (97.0%, 97.7%, and 97.8%, respectively; p = 0.79) or in survival without morbidity (82.8%, 86.2%, and 82.7%, respectively; p = 0.71). In survived infants, 1578 (81.6%) were evaluated at age two: 279 (17.7%) were considered to have a non-optimal neurodevelopmental outcome (18.3% after SVD, 18.0% after OVD, and 15.9% after CS; p = 0.57). Propensity score analysis showed that OVD was not associated with non-optimal neurocognitive development at age two, with an adjusted odds ratio (aOR) of 0.86 and a 95% confidence interval (95% CI) of 0.47-1.69, compared with SVD; and an aOR of 0.76 and a 95% CI of 0.31-1.8, compared with CS. Operative vaginal delivery was not associated with non-optimal neurocognitive development at 2 years of corrected age for preterm singletons.

Assessing Behavioral Disorders with SDQ in Very Preterm Children at 5 Years of Age in LIFT Cohort.

BACKGROUND: Preterm-born children are at risk of behavioral disorders and the systematic assessment of these disorders remains a challenge. Questions remain about the accuracy of self-reported parent questionnaires and the real everyday life behavior of the child. AIM: To evaluate the association between SDQ reported by parents in the preterm and behavioral difficulties in the everyday school life environment reported by teacher. METHODS: All children born before 33 weeks and who followed-up in the LIFT (Loire Infant Follow-up team) network were included. The Strengths and Difficulties Parental Questionnaire (SDQ), completed at 5 years, was used to check for behavioral difficulties and identified three groups: "normal", "borderline" and "abnormal". Then, the SDQ results were compared to the Global School Adaptation Score (GSA) at 5 years. RESULTS: Out of the 1825 children followed in the cohort at the age of 5, 1397 questionnaires were analyzed. A total of 11.1% of children had an abnormal score, and 9.7% had a borderline score. Male gender and a lower birth weight z-score were significantly associated with the "abnormal SDQ" group. There is a significant relationship between the probability of being in the "abnormal SDQ" group at 5 years and with difficulty in global school adaptation at 5 years, as well as an SDQ borderline score in the preterm (p < 0.001). CONCLUSIONS: SDQ abnormal and borderline scores are associated with behavioral difficulties in the classroom and everyday life behavior. In preterm children, one should be alerted even by a borderline SDQ score.

Assessing of executive functions in daily life in preterm children aged 3-4 years old from the "Behavior Rating Inventory of Executive Function-Preschool version" questionnaire.

Background: Executive functions (EFs) are a set of neuropsychological skills permitting solving problems in a new situation by regulating action, behavior, and emotional response. As cerebral maturation remains vulnerable in preterm children, a higher risk of developing cognitive disorders including EFs exist compared to term children. Aims: The aim of this study was to estimate the incidence of preschool EF impairments through proxy reports in children born preterm before 34 weeks of gestational age using the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) version. Secondary aims were to report neonatal, child, or socioeconomic factors associated with EF disorders. Results: Parents of 357 children born preterm aged 3-4 years old completed the BRIEF-P version. Impairment in EFs was clinically significant for 13.5% of preterm children (n = 47; 95% CI = 0.10-0.18) compared to 5.1% in term children. A low parental socioeconomic level was significantly associated with impaired parent-rated EF (19.1% vs. 5.3%, p = 0.003). Conclusions: Proxy reports of EF impairment are about twice as frequent as in term children. EF difficulties are not related to neonatal or child severity factors in contrast with the parental socioeconomic level. Using a parent-rated questionnaire may be a useful and easy tool to identify early the daily life impact of EF disorders on clinical follow-up of preterm children.This study was recorded in the Clinical Trials Register under identifier NCT03700463.

A Prospective Observational Study to Assess Attachment Representations With Regard to Neurocognitive and Behavioral Outcomes in Children Born Very Prematurely in the Loire Infant Follow-Up Team (LIFT Cohort).

Context and purpose: Prematurity is a situation that can disrupt parent-child interactions. We hypothesize that establishing relationships with parents in a context of extreme prematurity can alter the development of secure attachment representations in the child. Furthermore, we hypothesize that secure maternal representations and their possible interactions with prematurity factors prevent the development of insecure or disorganized attachment in the child. In addition, maternal representations and their possible interactions with factors related to prematurity may prevent or accentuate the development of an insecure or disorganized attachment in the child. Methods and analysis: This is a longitudinal, prospective, exploratory, and bi-centric study. Children born in the neonatal intensive care units of Angers or Nantes University Hospitals with a gestational age of up to 28 weeks will be included in the study. The main objective is to describe the attachment representations at 3 and 5 years through the Attachment Story Completion Task scales and to analyze them in regard to the children's neurocognitive and behavioral outcomes as well as maternal attachment and mental health. Ethics: The study file received a favorable opinion for the implementation of this research on February 18, 2020 - ID-RCB no. 2019-A03352-55 (File 2-20-007 id6699) 2°HPS. This study has received authorization from the French Data Protection Authority (CNIL) under no. 920229. Discussion: A better understanding of attachment representations in extreme prematurity and their possible associations with children's neurocognitive and behavioral outcomes as well as maternal attachment and mental health could pave the way for individualized care at an early stage, or even interventions during the neonatal period to improve the outcome of these vulnerable newborns. Trial registration: [ClinicalTrials.gov], identifier [NCT04304846].

Relative contributions of prenatal complications, perinatal characteristics, neonatal morbidities and socio-economic conditions of preterm infants on the occurrence of developmental disorders up to 7 years of age.

BACKGROUND: To investigate the relative contributions of prenatal complications, perinatal characteristics, neonatal morbidities and socio-economic conditions on the occurrence of motor, sensory, cognitive, language and psychological disorders in a large longitudinal preterm infant population during the first 7 years after birth. METHODS: The study population comprised 4122 infants born at <35 weeks of gestation who were followed for an average of 74.0 months after birth. Developmental disorders, including motor, sensory, cognitive, language and psychological, were assessed at each follow-up visit from 18 months to 7 years of age. The investigated determinants included prenatal complications (prolonged rupture of membranes >24 hours, intrauterine growth restriction, preterm labour and maternal hypertension), perinatal characteristics (gender, multiple pregnancies, gestational age, birth weight, APGAR score and intubation or ventilation in the delivery room), neonatal complications (low weight gain during hospitalization, respiratory assistance, severe neurological anomalies, nosocomial infections) and socio-economic characteristics (socio-economic level, parental separation, urbanicity). Based on hazard ratios determined using a propensity score matching approach, population-attributable fractions (PAF) were calculated for each of the four types of determinants and for each developmental disorder. RESULTS: The percentages of motor, sensory, cognitive, language and psychological disorders were 17.0, 13.4, 29.1, 25.9 and 26.1%, respectively. The PAF for the perinatal characteristics were the highest and they were similar for the different developmental disorders considered (around 60%). For the neonatal and socio-economic determinants, the PAF varied according to the disorder, with contributions of up to 17% for motor and 27% for language disorders, respectively. Finally, prenatal complications had the lowest contributions (between 6 and 13%). CONCLUSIONS: This study illustrates the heterogeneity of risk factors on the risk of developmental disorder in preterm infants. These results suggest the importance of considering both medical and psycho-social follow-ups of preterm infants and their families.

Neonatal growth velocity of preterm infants: The weight Z-score change versus Patel exponential model.

BACKGROUND: Different methods are used to assess the growth of preterm infants during neonatal hospital stay. The primary objective was to compare two methods for assessing growth velocity: g/kg/d according to the Patel exponential model (EM) and change in weight z-score (ZS) according to Fenton curves. The secondary objective was to highlight factors influencing the level of agreement between the two methods. METHODS: Preterm infants born before 33 weeks were included. Growth velocity was computed by EM and ZS methods and linear regression was used to predict what growth velocity by EM method would be obtained using the ZS method. Differences between EM growth velocity and EM growth velocity predicted by ZS method were then used to assess the level of agreement between the two methods. A difference between -2 and +2 g/kg/day was considered as fair agreement, greater than ± 4 g/kg/day as poor agreement, and as disagreement otherwise. RESULTS: Among the 3954 children included, we observe a fair agreement in 2471 children (62.5%), a poor agreement in 1278 (32.3%) and a disagreement in 205 children (5.2%). Birth weight and gestational age explained 31% and 25%, respectively, of the variance in the difference between the two methods. CONCLUSIONS: In more than a third of enrolled children, the two methods for measuring growth velocity disagreed substantially. As variation of weight Z-score takes into account infant gestational age and gender, it could be more suitable to analyze a population of preterm infants with a wide range of gestational age.

Neonatal and neurodevelopmental outcomes in preterm infants according to maternal body mass index: A prospective cohort study.

OBJECTIVE: Maternal obesity is associated with an increase in maternal, foetal and neonatal morbidity and mortality. The aim of our study was to evaluate the relationships between maternal pre-pregnancy body mass index and (1) neonatal outcome in preterm infants, and (2) neurodevelopmental outcome at 2 years of corrected age. METHOD: We conducted a single-centre cohort study. Infants born between 24+0 and 33+6 weeks of gestation between January 2009 and December 2013, hospitalised in the neonatal intensive care unit of Angers University Hospital, and with available data regarding maternal pre-pregnancy body mass index were eligible. Three groups were defined according to maternal body mass index: normal (n = 418), overweight (n = 136) and obese (n = 89). The primary outcome was neurodevelopment at 2 years of corrected age. Children with a non-optimal neuromotor and/or psychomotor assessment and/or a sensory disability were regarded as having a "non-optimal neurodevelopmental outcome". Neuromotor function was regarded as non-optimal when cerebral palsy was present or when the clinical examination revealed neurological signs of abnormal muscular tone. Psychomotor assessment was regarded as non-optimal if the revised Brunet-Lézine test was < 85 or when the overall score in the parental Ages and Stages Questionnaire (ASQ) was < 185. Finally, sensory disabilities such as blindness and children who required a hearing aid were taken into account. The secondary outcome was the composite criteria of neonatal complications. Multivariable analysis included the following variables: mother's age, gestational age, smoking during pregnancy, magnesium sulphate and steroid treatment during pregnancy, twin status, gender, socioeconomic status and social security benefits for those with low incomes. RESULTS: The study population was composed of 643 preterm infants. Among them, 520 were assessed at 2 years. There was no difference in the proportion of infants with non-optimal neurodevelopmental outcomes between the three groups (16.6% for obese, 13.5% for overweight, 16.9% for normal body mass index mothers; p = 0.73). According to multivariable analysis, being born from an overweight or obese mother was not associated with an increased risk of non-optimal neuro-development at 2 years (adjusted OR = 0.84 [0.40-1.76] for obese, adjusted OR = 0.83 [0.43-1.59] for overweight mothers). There was no difference in the proportion of preterm infants with a non-optimal composite criterion of neonatal complications between the three groups. In the multivariable analysis, being born from an overweight or obese mother was not associated with an increased risk of non-optimal neonatal outcomes (adjusted OR = 0.95 [0.49-1.83] for obese, adjusted OR = 1.18 [0.69-2.01] for overweight mothers). CONCLUSION: In this large prospective cohort of preterm infants born before 34 weeks of gestation, we found no relationship between maternal body mass index and neurodevelopmental outcomes at 2 years of corrected age and no relationship between maternal body mass index and neonatal outcomes. Other prematurity-related factors may be more relevant for neurodevelopmental outcome than the mother's pre-pregnancy BMI.

Impact of parental separation or divorce on school performance in preterm children: A population-based study.

The objective of this study was to quantify the possible decrease in school performance at five years of age in preterm children associated with parental separation or divorce, and to test whether this effect varies according to the child's age at the time of the separation. This study included 3,308 infants delivered at < 35 weeks of gestation born between 2003 and 2011 who were enrolled in the population-based LIFT cohort and who had an optimal neurodevelopmental outcome at two years of age. These infants were evaluated by their teachers to assess their abilities and behavior when they had reached five years of age, using the Global School Adaptation (GSA) questionnaire. The mean GSA score was 50.8 points. Parental separations (assessed as parents either living together or living separately) were associated with a decrease in school performance at five years of age, although this was only the case for children who exhibited difficulties at school (3.7 points, p < 0.01). A decrease in school performance only occurred when parental separations took place between 3 and 5 years after the child's birth. Parental separation was associated with a decrease in these children's levels of motivation, autonomy, and manual dexterity. This study indicates that preterm infants of parents who had separated are particularly at risk of a lower scholar performance.

Impact of preterm birth on parental separation: a French population-based longitudinal study.

OBJECTIVE: The objective of this study was to investigate both the effects of low gestational age and infant's neurodevelopmental outcome at 2 years of age on the risk of parental separation within 7 years of giving birth. DESIGN: Prospective. SETTING: 24 maternity clinics in the Pays-de-la-Loire region. PARTICIPANTS: This study included 5732 infants delivered at <35 weeks of gestation born between 2005 and 2013 who were enrolled in the population-based Loire Infant Follow-up Team cohort and who had a neurodevelopmental evaluation at 2 years. This neurodevelopmental evaluation was based on a physical examination, a psychomotor evaluation and a parent-completed questionnaire. OUTCOME MEASURE: Risk of parental separation (parents living together or parents living separately). RESULTS: Ten percent (572/5732) of the parents reported having undergone separation during the follow-up period. A mediation analysis showed that low gestational age had no direct effect on the risk of parental separation. Moreover, a non-optimal neurodevelopment at 2 years was associated with an increased risk of parental separation corresponding to a HR=1.49(1.23 to 1.80). Finally, the increased risk of parental separation was aggravated by low socioeconomic conditions. CONCLUSIONS: The effect of low gestational age on the risk of parental separation was mediated by the infant's neurodevelopment.

Post-term growth and cognitive development at 5 years of age in preterm children: Evidence from a prospective population-based cohort.

While the effects of growth from birth to expected term on the subsequent development of preterm children has attracted plentiful attention, less is known about the effects of post-term growth. We aimed to delineate distinct patterns of post-term growth and to determine their association with the cognitive development of preterm children. Data from a prospective population-based cohort of 3,850 surviving infants born at less than 35 weeks of gestational age were used. Growth was assessed as the Body Mass Index (BMI) Z-scores at 3, 9, 18, 24, 36, 48, and 60 months. Cognitive development at five years of age was evaluated by the Global School Adaptation score (GSA). Latent class analysis was implemented to identify distinct growth patterns and logistic regressions based on propensity matching were used to evaluate the relationship between identified growth trajectories and cognitive development. Four patterns of post-term growth were identified: a normal group with a Z-score consistently around zero during childhood (n = 2,469; 64%); a group with an early rapid rise in the BMI Z-score, but only up to 2 years of age (n = 195; 5%); a group with a slow yet steady rise in the BMI Z-score during childhood (n = 510; 13%); and a group with a negative Z-score growth until 3 years of age (n = 676; 18%). The group with a slow yet steady rise in the BMI Z-score was significantly associated with low GSA scores. Our findings indicate heterogeneous post-term growth of preterm children, with potential for association with their cognitive development.

Neonatal EEG and neurodevelopmental outcome in preterm infants born before 32†weeks.

OBJECTIVE: To assess the value of neonatal EEG for predicting non-optimal neurodevelopmental outcomes in very preterm infants, using a multimodal strategy of evaluation comprising brain imaging and clinical assessment. DESIGN AND SETTING: Between 2003 and 2009, we performed an observational, population-based study. Out of 2040 eligible preterm infants born before 32 weeks, 1954 were enrolled in the French regional Loire Infant Follow-Up Team (LIFT) cohort. 1744 (89%) of these completed the follow-up. Neonatal EEGs were recorded prospectively as two EEGs during the first 2 weeks of life and then one every 2 weeks up to 33 weeks. MAIN OUTCOME MEASURES: The neurodevelopmental outcome was assessed by physical examination, the Brunet-Lézine Test and/or the Age and Stages Questionnaire at 2 years of corrected age. RESULTS: Of the 1744 infants assessed at 2 years, 422 had a non-optimal outcome. A total of 4804 EEGs were performed, and 1345 infants had at least one EEG. EEG abnormalities were predictive of non-optimal outcomes after controlling for confounding factors such as severe intracranial lesions detected by brain imaging. Transient moderate and severe abnormalities were independent predictors of non-optimal outcomes with an OR and 95% CI of 1.49 (1.08 to 2.04) and 2.38 (1.49 to 3.81), respectively. In the validation group, the predictive risk stratification tree identified severe abnormalities as a factor contributing to the prognosis of two subgroups: infants with severe cranial lesions and infants with a normal examination at discharge and without severe cranial lesions.

The Association of Urbanicity with Cognitive Development at Five Years of Age in Preterm Children.

OBJECTIVE: To determine the association of urbanicity, defined as living in an urban area, with cognitive development at five years of age in preterm children who were free of any disabilities or neurodevelopmental delays. DESIGN: Prospective population-based cohort. SETTING: French regional Loire Infant Follow-up Team (LIFT) network. PARTICIPANTS: Included in the study were 1738 surviving infants born between March 2003 and December 2008 before 35 weeks of gestational age. At two years of age, the children were free of any disabilities and neurodevelopmental delays and were living in the Pays de la Loire region from their birth to five years of age. MAIN OUTCOME MEASURES: The cognitive development at five years of age was evaluated with the Global School Adaptation score (GSA). The urbanicity of the residence for each child was classified into three groups: urban, quasi-rural, and rural area. RESULTS: Quantile regression approaches were used to identify a significant association between urbanicity and the GSA score at five years of age (adjusting for child and family characteristics). We found that the negative impact of urbanicity on the GSA score was more important for the lower quantile of the GSA scores. CONCLUSIONS: Urbanicity was significantly associated with cognitive neurodevelopment at five years of age in preterm children born before 35 weeks of gestation. Complementary results additionally suggest that this relation could be mediated at the residence level by a high socioeconomic deprivation level. If these results are confirmed, more personalized follow-ups could be developed for preterm children. Further studies are needed to finely identify the contextual characteristics of urbanicity that underlie this association.

Predictive value of the parent-completed ASQ for school difficulties in preterm-born children <35 weeks' GA at five years of age.

BACKGROUND: Preterm infants are at greater risk of developmental impairment and require close follow-up for early and optimal care. OBJECTIVES: The objective of the present study was to determine from which age the parental Ages and Stages Questionnaire (ASQ) allows detection of school difficulties in preterm children <35 weeks' gestational age. METHODS: Preterm children from the regional Loire Infant Follow-up Team network were evaluated with the Global School Adaptation (GSA) assessment tool at 5 years of age and at least one parental-completed ASQ at 18, 24, or 36 months. Children belonging to the first decile of the GSA score (<38) were considered to have severe school difficulties. Using overall ASQ scores as continuous variables, receiver operating characteristic (ROC) curves were generated at every age in order to identify preterm children with severe school difficulties. RESULTS: GSA scores were obtained in 1,775 infants at 5 years of age, and at least one ASQ score at 18, 24, or 36 months was completed. Upon ROC analysis, we observed that the 18-, 24-, and 36-month ASQ scores produced respective area under the ROC curve values of 0.66 (0.64-0.69), 0.72 (0.70-0.75), and 0.77 (0.75-0.80) for predicting a GSA score in the first decile. An ASQ cutoff value of 255 at 36 months showed optimal discriminatory power for identifying significant school difficulties at 5 years of age. CONCLUSIONS: The 36-month ASQ is a simple and cost-effective tool that can be employed to help predict future severe school difficulties at 5 years of age in preterm-born children.

Neurological assessment of preterm infants for predicting neuromotor status at 2 years: results from the LIFT cohort.

OBJECTIVE: To develop a predictive risk stratification model for the identification of preterm infants at risk of 2-year suboptimal neuromotor status. DESIGN: Population-based observational study. SETTING: Regional preterm infant follow-up programme (Loire Infant Follow-up Team (LIFT) cohort) implemented in 2003. PARTICIPANTS: 4030 preterm infants were enrolled in the LIFT cohort, and examined by neonatologists using a modified version of the Amiel-Tison neurological assessment tool. MAIN OUTCOME CRITERIA: 2 year neuromotor status based on clinical examinations was conducted by trained paediatricians and parents' responses to the Ages and Stages Questionnaire were reported. RESULTS: At 2 years of corrected age, 3321 preterm infants were examined, and suboptimal neuromotor status was found in 355 (10.7%). The study population was divided into training and validation sets. In the training set, 13 neonatal neurological items were associated with a 2-year suboptimal neuromotor status. Having at least one abnormal item was defined as an abnormal neurological status at term. In the validation set, these data predicted a 2-year suboptimal neuromotor status with a sensitivity of 0.55 (95% CI 0.47 to 0.62) and a specificity of 0.65 (95% CI 0.62 to 0.67). Two predictive risk stratification trees were built using the training set, which were based on the neurological assessment at term along with either gestational age or severe cranial lesions or birth weight. Using the validation set, the first tree identified a subgroup with a relatively low risk of suboptimal neuromotor status (3%), representing 32% of infants, and the second tree identified a subgroup with a risk of 5%, representing 42% of infants. CONCLUSION: A normal neurological assessment at term allows the identification of a subgroup of preterm infants with a lower risk of non-optimal neuromotor development at 2 years.

Usefulness of parent-completed ASQ for neurodevelopmental screening of preterm children at five years of age.

INTRODUCTION: Preterm children are at greater risk of developmental impairment and require close follow-up for early and optimal medical care. Our goal was to examine use of the parent-completed Ages and Stages Questionnaire (ASQ) as a screening tool for neurodevelopmental disabilities in preterm infants at five years of age. PATIENTS AND METHODS: A total of 648 preterm children (<35 weeks gestational age) born between 2003 and 2004 and included in the regional Loire Infant Follow-up network were evaluated at five years of age. ASQ was compared with two validated tools (Intelligence Quotient and Global School Adaptation Score) and the impact of maternal education on the accuracy of this questionnaire was assessed. RESULTS: Overall ASQ scores for predicting full-scale IQ<85 and GSA score produced an area under the receiver operating characteristic curve of 0.73±0.03 and 0.77±0.03, respectively. An ASQ cut-off value of 285 had optimal discriminatory power for identifying children with IQ scores<85 and GSA scores in the first quintile. ASQ values<285 were significantly associated with a higher risk of non-optimal neurologic outcomes (sensitivity of 0.80, specificity of 0.54 for IQ<85). ASQ values>285 were not distinctive for mild delay or normal development. In children with developmental delay, no difference was found when ASQ scores according to maternal education levels were analyzed. CONCLUSIONS: ASQ at five years is a simple and cost-effective tool that can detect severe developmental delay in preterm children regardless of maternal education level, while its capacity to identify children with mild delay appears to be more limited.