Neurologic sequelae of severe chikungunya infection in the first 6 months of life: a prospective cohort study 24-months post-infection.

BACKGROUND: Perinatally chikungunya infected neonates have been reported to have high rates of post-infection neurologic sequelae, mainly cognitive problems. In older children and adults chikungunya does not appear to have sequelae, but data on postnatally infected infants are lacking. METHODS: We performed a prospective, non-controlled, observational study of infants infected before the age of 6 months with a severe chikungunya infection during the 2014-2015 epidemic in Curaçao, Dutch Antilles. Two years post-infection cognitive and motor - (BSID-III) and social emotional assessments (ITSEA) were performed. RESULTS: Of twenty-two infected infants, two died and two were lost to follow up. Eighteen children were seen at follow-up and included in the current study. Of these, 13 (72%) had abnormal scores on the BSID-III (cognitive/motor) or ITSEA. CONCLUSION: In the first study aimed at postnatally infected infants, using an uncontrolled design, we observed a very high percentage of developmental problems. Further studies are needed to assess causality, however until these data are available preventive measure during outbreaks should also include young infants. Those that have been infected in early infancy should receive follow up.

Temporizing management vs immediate delivery in early-onset severe preeclampsia between 28 and 34 weeks of gestation (TOTEM study): An open-label randomized controlled trial.

INTRODUCTION: There is little evidence to guide the timing of delivery of women with early-onset severe preeclampsia. We hypothesize that immediate delivery is not inferior for neonatal outcome but reduces maternal complications compared with temporizing management. MATERIAL AND METHODS: This Dutch multicenter open-label randomized clinical trial investigated non-inferiority for neonatal outcome of temporizing management as compared with immediate delivery (TOTEM NTR 2986) in women between 27+5 and 33+5 weeks of gestation admitted for early-onset severe preeclampsia with or without HELLP syndrome. In participants allocated to receive immediate delivery, either induction of labor or cesarean section was initiated at least 48 hours after admission. Primary outcomes were adverse perinatal outcome, defined as a composite of severe respiratory distress syndrome, bronchopulmonary dysplasia, culture proven sepsis, intraventricular hemorrhage grade 3 or worse, periventricular leukomalacia grade 2 or worse, necrotizing enterocolitis stage 2 or worse, and perinatal death. Major maternal complications were secondary outcomes. It was estimated 1130 women needed to be enrolled. Analysis was by intention-to-treat. RESULTS: The trial was halted after 35 months because of slow recruitment. Between February 2011 and December 2013, a total of 56 women were randomized to immediate delivery (n = 26) or temporizing management (n = 30). Median gestational age at randomization was 30 weeks. Median prolongation of pregnancy was 2 days (interquartile range 1-3 days) in the temporizing management group. Mean birthweight was 1435 g after immediate delivery vs 1294 g after temporizing management (P = .14). The adverse perinatal outcome rate was 55% in the immediate delivery group vs 52% in the temporizing management group (relative risk 1.06; 95% confidence interval 0.67-1.70). In both groups there was one neonatal death and no maternal deaths. In the temporizing treatment group, one woman experienced pulmonary edema and one placental abruption. Analyses of only the singleton pregnancies did not result in other outcomes. CONCLUSIONS: Early termination of the trial precluded any conclusions for the main outcomes. We observed that temporizing management resulted in a modest prolongation of pregnancy without changes in perinatal and maternal outcome. Conducting a randomized study for this important research question did not prove feasible.

Executive function training in very preterm children: a randomized controlled trial.

Objective of the current study was to assess whether game-formatted executive function (EF) training, is effective in improving attention, EF and academic performance in very preterm and/or extremely low birthweight children aged 8-12 years. A multi-center, double-blind, placebo- and waitlist controlled randomized trial (NTR5365) in two academic hospitals in The Netherlands was performed. Eighty-five very preterm children with parent-rated attention problems on the Child Behavior Checklist were randomized to one of three treatment conditions: EF training, placebo training or waitlist condition. EF or placebo training was completed at home (6 weeks, 25 sessions of 30-45 min each). At baseline, 2 weeks after training or being on the waitlist, and five months after first follow-up visit, children underwent assessments of primary outcomes (parent and teacher ratings of attention) and secondary outcomes (parent and teacher ratings of daily-life EF, computerized EF tasks and academic performance). Linear mixed model analyses were performed for all outcome measures. There were no significant differences in improvement over time on parent- and teacher ratings of attention, parent- and teacher ratings of daily-life EF, computerized EF tasks, and academic performance (arithmetic and reading) between the EF training, placebo training and waitlist condition. In conclusion, game-formatted EF training does not improve attention, EF or academic performance in very preterm children with parent-rated attention problems.

Development and nationwide implementation of a postdischarge responsive parenting intervention program for very preterm born children: The TOP program.

A previous randomized controlled trial has suggested the effectiveness of a Dutch postdischarge responsive parenting program for very preterm (VPT) infants, indicating that nationwide implementation was justified. This paper describes the development and nationwide implementation of the intervention, known as the TOP program, which consisted of three phases. In the preparation phase (2006-2010), a theory of change and the structure of the TOP program were developed, and funding for phase two, based on a positive Business Case, was obtained. In the pilot implementation phase (2010-2014), intervention strategies were developed for a real-world setting, capacity and adoption were increased, systematic evaluations were incorporated, and sustained funding was obtained. In the full-implementation phase (2014-2019), all Dutch Healthcare Insurers reimbursed the TOP program, enabling VPT infants to participate in the program without charge. By 2018, the number of interventionists that provided the TOP program had increased from 37 to 91, and all level III hospitals and 65% of regional hospitals in the Netherlands referred VPT infants. Currently, the program reaches 70% of the Dutch target population and parental satisfaction with the TOP program is high. After a 12-year implementation period, the TOP program forms part of routine care in the Netherlands.

Un previo ensayo controlado al azar ha sugerido la eficacia de un programa holandés sobre la crianza sensible para infantes muy prematuros (VPT) posterior al momento en que se les dio de alta, indicando que la implementación a lo largo de toda la nación era justificada. Este artículo describe el desarrollo y la implementación a nivel de toda la nación de la intervención, conocida como el programa ToP, el cual consistía de tres fases. En la fase de preparación (2006-2010), se desarrollaron una teoría de cambio y la estructura del programa ToP, y se obtuvieron los fondos para la fase dos, con base en un Caso de Negocios (BC) positivo. En la fase piloto de implementación (2010-2014), se desarrollaron estrategias de intervención para un escenario del mundo real, se aumentaron la capacidad y la adopción, se incorporaron evaluaciones sistemáticas y se obtuvieron fondos para mantener el programa. En la fase de implementación completa (2014-2019), todas las Aseguradoras Holandesas del Sector Salud reembolsaron el costo del programa ToP, permitiéndoles a los infantes VPT participar en el programa sin costo alguno. Para 2018, el número de practicantes de la intervención que prestaban el servicio del programa ToP había aumentado de 37 a 91, y todos los hospitales del nivel III y 65% de los hospitales regionales en Holanda refirieron los infantes VPT al programa. Actualmente, el programa llega a 70% de la población holandesa para la cual está destinado y la satisfacción de los padres con el programa ToP es alta. Después de un período de implementación de 12 años, el programa ToP forma parte del cuidado de salud rutinario en Holanda.

Un essai contrôlé randomisé précédent a suggéré l'efficacité d'un programme hollandais de sensibilité de parentage après la sortie de l'hôpital pour les nourrissons grands prématurés (GP ici en français), indiquant qu'une mise en œuvre au niveau national était justifiée. Cet article décrit le développement et la mise en œuvre au niveau national de l'intervention, connue en tant que ToP program, qui a consisté en trois phases. Dans la phase de préparation (2006-2010), une théorie du changement et la structure du programme ToP a été développée, et le financement pour la phase deux, basée sur une Etude de Cas positive, a été sécurisé. Dans la phase pilote d'implémentation (2010-2014) des stratégies d'intervention ont été développées pour un contexte réel, la capacité et l'adoption ont été augmentées, les évaluations systématiques ont été incorporées, et un financement durable a été sécurisé. Dans la pleine phase de mise en œuvre (2014-1029), tous les Assurances Santé Hollandaises ont remboursé le programme ToP, permettant aux nourrissons GP de participer au programme sans coût. En 2018 le nombre de prestataires qui offraient le programme ToP a augmenté de 37 à 91, et tous les hôpitaux de niveau III ainsi que 65% des hôpitaux régionaux aux Pays Bas ont envoyé les nourrissons GP au programme. En ce moment le programme atteint 70% de la population cible hollandaise et la satisfaction parentale avec le programme ToP est élevée. Après une période de mise en œuvre de 12 ans le programme ToP fait partie des soins de routine aux Pays Bas.

Early-onset fetal growth restriction: A systematic review on mortality and morbidity.

INTRODUCTION: Severe early-onset fetal growth restriction is an obstetric condition with significant risks of perinatal mortality, major and minor neonatal morbidity, and long-term health sequelae. The prognosis of a fetus is influenced by the extent of prematurity and fetal weight. Clinical care is individually adjusted. In literature, survival rates vary and studies often only include live-born neonates with missing rates of antenatal death. This systematic review aims to summarize the literature on mortality and morbidity. MATERIAL AND METHODS: A broad literature search was conducted in OVID MEDLINE from 2000 to 26 April 2019 to identify studies on fetal growth restriction and perinatal death. Studies were excluded when all included children were born before 2000 because (neonatal) health care has considerably improved since this period. Studies were included that described fetal growth restriction diagnosed before 32 weeks of gestation and antenatal mortality and neonatal mortality and/or morbidity as outcome. Quality of evidence was rated with the GRADE instrument. RESULTS: Of the 2604 publications identified, 25 studies, reporting 2895 pregnancies, were included in the systematic review. Overall risk of bias in most studies was judged as low. The quality of evidence was generally rated as very low to moderate, except for 3 large well-designed randomized controlled trials. When combining all data on mortality, in 355 of 2895 pregnancies (12%) the fetus died antenatally, 192 died in the neonatal period (8% of live-born neonates) and 2347 (81% of all pregnancies) children survived. Of the neonatal morbidities recorded, respiratory distress syndrome (34% of the live-born neonates), retinopathy of prematurity (13%) and sepsis (30%) were most common. Of 476 children that underwent neurodevelopmental assessment, 58 (12% of surviving children, 9% of all pregnancies) suffered from cognitive impairment and/or cerebral palsy. CONCLUSIONS: When combining the data of 25 included studies, survival in fetal growth restriction pregnancies, diagnosed before 32 weeks of gestation, was 81%. Neurodevelopmental impairment was assessed in a minority of surviving children. Individual prognostic counseling on the basis of these results is hampered by differences in patient and pregnancy characteristics within the included patient groups.

Eight-year-old very and extremely preterm children showed more difficulties in performance intelligence than verbal intelligence.

AIM: This study determined possible discrepancies between verbal IQ and performance IQ in 8-year-old very preterm (VPT) and extremely preterm (EPT) children, and examined associations between verbal IQ and performance IQ, and sociodemographic factors, perinatal factors, early cognitive outcomes and also with school achievement scores. METHODS: This prospective cohort study included 120 eight-year-old VPT/EPT children. Cognitive development was assessed at the ages of 2, 5 and 8 years. Eight years' school achievement results in arithmetic, reading and spelling were collected. Multiple regression analyses were performed to determine predictors of verbal IQ and performance IQ at the age of 8 years and to determine associations with school achievement scores. RESULTS: Mean performance IQ (89.8) was significantly lower than mean verbal IQ (99.4; Cohen's d = 0.59) at the age of 8 years. Gestational age (GA), small for GA status, and cognitive scores at the ages of 2 and 5 years significantly predicted verbal IQ and performance IQ at the age of 8 years. Performance IQ at age 8 years was an important predictor for arithmetic scores (ß = 0.42). CONCLUSION: Performance IQ was more strongly affected than verbal IQ in 8-year-old VPT/EPT children and was strongly related to mathematical difficulties.

Executive function deficits in children born preterm or at low birthweight: a meta-analysis.

AIM: To investigate the magnitude of executive function deficits and their dependency on gestational age, sex, age at assessment, and year of birth for children born preterm and/or at low birthweight. METHOD: PubMed, PsychINFO, Web of Science, and ERIC were searched for studies reporting on executive functions in children born preterm/low birthweight and term controls born in 1990 and later, assessed at a mean age of 4 years or higher. Studies were included if five or more studies reported on the same executive function measures. RESULTS: Thirty-five studies (3360 children born preterm/low birthweight, 2812 controls) were included. Children born preterm/low birthweight performed 0.5 standardized mean difference (SMD) lower on working memory and cognitive flexibility and 0.4 SMD lower on inhibition. SMDs for these executive functions did not significantly differ from each other. Meta-regression showed that heterogeneity in SMDs for working memory and inhibition could not be explained by study differences in gestational age, sex, age at assessment, or year of birth. INTERPRETATION: Children born preterm/low birthweight since 1990 perform half a SMD below term-born peers on executive function, which does not seem to improve with more recent advances in medical care or with increasing age. WHAT THIS PAPER ADDS: Children born preterm/low birthweight perform below term-born children on core executive functions. Lower gestational age or male sex are not risk factors for poorer executive functions. Executive function difficulties in children born preterm/low birthweight remain stable across childhood. Executive function difficulties are similar for children born recently and children born in earlier eras.

Child outcomes after placement of a cervical pessary in women with a multiple pregnancy: A 4-year follow-up of the ProTWIN trial.

INTRODUCTION: The ProTWIN trial previously showed no beneficial effect of treatment with a cervical pessary vs usual care to prevent preterm birth in women with a multiple pregnancy. However, in women with a midtrimester short cervix (<38 mm), pessary did reduce the composite outcome of neonatal morbidity and mortality. This follow-up study evaluates the long-term outcomes of all children born to mothers who participated in the ProTWIN trial at 4 years of age. MATERIAL AND METHODS: Parents received the Ages and Stages Questionnaire, Strength and Difficulties Questionnaire and a health questionnaire. All questionnaires were reported separately and as a combined outcome (abnormal child outcome). A linear mixed effects model was used to adjust for correlated data in twins and correction for confounders was performed. In exploratory analysis, a composite outcome of death or survival with abnormal child outcome was used by combining extrapolated data on child outcome with survival data. All data were analyzed for the total group and the subgroup of women with midtrimester short cervix. RESULTS: Of the original 813 women of the ProTWIN trial, we approached 579, of whom 258 participated (45%) in follow-up. We received questionnaires of 514 children (281 pessary vs 233 control), with 119 children in the subgroup of women with midtrimester short cervix. An abnormal child outcome was found in 23% in the pessary group vs 16% in the control group (odds ratio 1.58; 95% confidence interval 0.94-2.65). In exploratory analysis with extrapolated data on child outcome (n = 815), no difference in abnormal child outcome was seen between the pessary and control group. In the subgroup of women with a short cervix (n = 268), this composite outcome indicated a favorable outcome for children born to mothers with pessary. CONCLUSIONS: In women with a multiple pregnancy, the use of a cervical pessary did not improve development, behavior or physical outcomes of the surviving children at age 4.

Maternal psychological distress after severe pregnancy hypertension was associated with increased child behavioural problems at the age of 12.

AIM: We examined the association between early maternal psychological distress after severe hypertensive disorders of pregnancy (HDP) and behavioural issues in their 12-year-old offspring. METHODS: This secondary analyses of a prospective mother-child birth cohort focused on 95 women with severe HDP and their singleton offspring. The mothers were recruited during pregnancy from 2000 to 2003 in Amsterdam, the Netherlands. Maternal distress at child term age and three months post-term was measured using the Symptom Checklist-90. The Child Behaviour Checklist for six years to 18 years was used to quantify social and attention problems in their offspring at 12 years of age. Perinatal and neonatal risk factors were also analysed. RESULTS: The children were born at a mean age of just under 32 weeks and 90% weighed below the 10th percentile. High psychological distress (score ≥133) affected 45% of the mothers at term age and 44% three months post-term. Child social problems were significantly associated with maternal distress at three months and were highest in cases of high maternal distress in combination with major neonatal morbidity. Child attention problems were associated with maternal anxiety at three months post-term. CONCLUSION: Early maternal psychological distress after severe maternal HDP was associated with childhood behavioural issues at the age of 12.

Consensus Based Definition of Growth Restriction in the Newborn.

OBJECTIVE: To develop a consensus definition of growth restriction in the newborn that can be used clinically to identify newborn infants at risk and in research to harmonize reporting and definition in the current absence of a gold standard. STUDY DESIGN: An international panel of pediatric leaders in the field of neonatal growth were invited to participate in an electronic Delphi procedure using standardized methods and predefined consensus rules. Responses were fed back at group-level and the list of participants was provided. Nonresponders were excluded from subsequent rounds. In the first round, variables were scored on a 5-point Likert scale; in subsequent rounds, inclusion of variables and cut-offs were determined with a 70% level of agreement. In the final round participants selected the ultimate algorithm. RESULTS: In total, 57 experts participated in the first round; 79% completed the procedure. Consensus was reached on the following definition: birth weight less than the third percentile, or 3 out of the following: birth weight <10th percentile; head circumference <10th percentile; length <10th percentile; prenatal diagnosis of fetal growth restriction; and maternal pregnancy information. CONCLUSIONS: Consensus was reached on a definition for growth restriction in the newborn. This definition recognizes that infants with birth weights <10th percentile may not be growth restricted and that infants with birth weights >10th percentile can be growth restricted. This definition can be adopted in clinical practice and in clinical trials to better focus on newborns at risk, and is complementary to the previously determined definition of fetal growth restriction.

Fetal Growth Restriction with Brain Sparing: Neurocognitive and Behavioral Outcomes at 12 Years of Age.

OBJECTIVE: To study neurocognitive functions and behavior in children with a history of fetal growth restriction (FGR) with brain sparing. We hypothesized that children with FGR would have poorer outcomes on these domains. STUDY DESIGN: Subjects were 12-year-old children with a history of FGR born to mothers with severe early-onset hypertensive pregnancy disorders (n = 96) compared with a normal functioning full term comparison group with a birth weight ≥2500 g (n = 32). Outcome measures were neurocognitive outcomes (ie, intelligence quotient, executive function, attention) and behavior. RESULTS: For the FGR group, the mean ratio of the pulsatility index for the umbilical artery/middle cerebral artery (UC-ratio = severity of brain sparing) was 1.42 ± 0.69. The mean gestational age was 31-6/7 ± 2-2/7 weeks. The mean birth weight was 1341 ± 454 g, and the mean birth weight ratio 0.68 ± 0.12. Neurocognitive outcomes were comparable between groups. Parents of children with FGR reported more social problems (mean T-score 56.6 ± 7.7; comparison 52.3 ± 4.3, P < .001, effect size = 1, 95% CI 0.52-1.46) and attention problems (mean T-score 57.3 ± 6.9; comparison 53.6 ± 4.2, P = .004, effect size = 0.88, 95% CI 0.42-1.33). UC-ratio was not associated with any of the outcomes, but low parental education and lower birth weight ratio were. CONCLUSIONS: In this prospective follow-up study of 12-year-old children with a history of FGR and confirmed brain sparing, neurocognitive functions were comparable with the comparison group, but parent-reported social and attention problem scores were increased.

Consequences of Correcting Intelligence Quotient for Prematurity at Age 5 Years.

OBJECTIVES: To determine the effects of correcting for prematurity on full scale IQ (FSIQ), verbal IQ (VIQ), performance IQ (PIQ), and processing speed quotient (PSQ) scores, and to investigate whether differences between corrected and uncorrected FSIQ are associated with gestational age (GA), FSIQ, and age at assessment. STUDY DESIGN: Single-center consecutive cohort study. Data were analyzed from 275 very preterm children (GA <30 weeks), born between January 2006 and December 2009 and assessed at 5 years corrected age as part of the neonatal long-term follow-up program, at the Emma Children's Hospital in Amsterdam, The Netherlands. Outcome measures were FSIQ, VIQ, PIQ, and PSQ, calculated for uncorrected and corrected age. Paired sample t tests, repeated measures ANOVA, and ANCOVA were performed to explore differences between corrected and uncorrected IQ. RESULTS: Differences between corrected and uncorrected FSIQ, VIQ, PIQ, and PSQ ranged from 0-15 IQ points. All corrected IQ scores were significantly higher than uncorrected IQ scores (all P values <.001). Differences were larger at lower GAs, for higher IQ scores, and if time of assessment lay near the starting point of a 3-month age band of the Wechsler Preschool and Primary Scale of Intelligence-Third Edition-Dutch Version. CONCLUSIONS: Given the great variation observed in differences between corrected and uncorrected IQ scores, an international standard as to what age correction is appropriate should be pursued.

Rethinking preventive post-discharge intervention programmes for very preterm infants and their parents.

Post-discharge preventive intervention programmes with involvement of the parent may support the resilience and developmental outcomes of infants born very preterm. Randomized controlled trials of home-based family-centred intervention programmes in very preterm infants that aimed to improve cognitive outcome, at least at age two, were selected and updated on the basis of a recent systematic review to compare their content and effect over time to form the basis of a narrative review. Six programmes were included in this narrative review. Four of the six programmes led to improved child cognitive and/or motor development. Two programmes, which focused primarily on responsive parenting and development, demonstrated improved cognitive outcome up till 5 years after completion of the programme. The programmes that also focused on maternal anxiety remediation led to improved maternal mental well-being, along with improved child behaviour, in one study - even at 3 years after completion of the programme. The magnitude of the effects was modest. Family-centred preventive intervention programmes that aim at improvement of child development should be continued after discharge home to improve the preterm child's resilience. Programmes may be most effective when they support the evolvement of a responsive parent-infant relationship over time, as well as the parent's well-being.

Effect of socioeconomic status on psychosocial problems in 5- to 6-year-old preterm- and term-born children: the ABCD study.

This study aimed at analysing the association between socioeconomic status (SES) and psychosocial problems in preterm- and term-born children. Scores of mothers and teachers on the Strengths and Difficulties Questionnaire (SDQ) regarding 217 preterm-born children (<37 weeks' gestation, mean 34 weeks) were compared with 4336 term-born children in the Amsterdam Born Children and their Development (ABCD) cohort at age 5-6 years. Associations between SDQ scores and SES (maternal education and perceived income adequacy) were examined with multivariate linear regression analysis. The mean mother-reported total difficulties score was significantly higher for preterm children (6.1 ± 4.7) than for term children (5.2 ± 4.1). After covariate adjustment, this difference was 0.5 (95 % CI 0.0-1.0). For preterm children 16.1 % of the mothers reported psychosocial problems compared with 10.1 % for term children. Lower maternal education and lower income adequacy were significantly related to higher SDQ scores of mothers and teachers. Differences in mothers' SDQ score between preterm and term children were larger in the high-education (Δ0.9, 95 % CI 0.2-1.5) and high-income group (Δ0.9, 95 % CI 0.3-1.6). No significant differences were found between preterm and term children in the SDQ scores reported by teachers. Low level of maternal education and inadequate income showed a much stronger association with psychosocial problems than preterm birth. No combined effect of low SES and preterm birth was found. This study corroborates the evidence for the strength of the disadvantageous effects of low SES on early psychosocial development.

Social variables predict gains in cognitive scores across the preschool years in children with birth weights 500 to 1250 grams.

OBJECTIVE: To determine the extent that social variables influence cognitive development of very low birth weight (VLBW) infants across the preschool years. STUDY DESIGN: Participants were VLBW (500-1250 g) children enrolled in the Caffeine for Apnea of Prematurity randomized trial between 1999 and 2004. We investigated the relationships between 4 potential social advantages: higher maternal education, higher paternal education, caregiver employment, and 2 biologic parents in the same home--and gain in cognitive scores. Cognitive assessments were performed at the corrected ages of 18 months (Mental Development Index score on the Bayley Scales of Infant Development II) and 5 years (Full Scale IQ on the Wechsler Preschool and Primary Scale of Intelligence III). Cognitive gain was computed by subtracting each individual 18-month Mental Development Index score from the corresponding Full Scale IQ at 5 years. RESULTS: Data were available for 1347 children. Mean (SD) cognitive scores were 90.8 (15.7) at 18 months and 98.9 (14.5) at 5 years. Multivariable regression showed that higher maternal education, higher paternal education, and caregiver employment had independent and additive effects of similar size on cognitive gain (P < .001); the mean cognitive gain between 18 months and 5 years increased by 3.6 points in the presence of each of these advantages. When all 3 were present, cognitive scores improved on average by 10.9 points compared with children without any of these advantages. CONCLUSION: In VLBW children, a count of 3 social advantages strongly predicts gains in cognitive scores across the preschool years.

A functional approach to cerebral visual impairments in very preterm/very-low-birth-weight children.

BACKGROUND: Cerebral visual impairment (CVI) is a major cause of visual impairment, with very preterm birth/very low birth weight (VP/VLBW) being a major risk factor. There is no generally accepted definition of CVI. This study aims to investigate the usefulness of an empirically-based functional definition of CVI. METHODS: One-hundred-five VP/VLBW children and 67 controls participated. CVI was defined after comprehensive oculomotor, visual sensory and perceptive assessment, and validated against vision problems in daily life and in terms of intellectual, behavioral, emotional and social functioning, as well as use of therapeutic services. RESULTS: Twenty-four per cent of the VP/VLBW children met criteria for CVI, compared to 7% of controls (P = 0.006, OR: 3.86, 95% CI: 1.40-10.70). VP/VLBW children with CVI had lower performance IQ, but not verbal IQ, than those without CVI. Visual problems in daily life were confirmed in VP/VLBW children classified with CVI. Additionally, difficulties in behavioral and social functioning were most prominent among VP/VLBW children with CVI. CONCLUSION: In VP/VLBW children, CVI defined in terms of visual function deficits is accompanied by intellectual, behavioral, and social impairments, validating our operational definition of CVI. CVI might act as a marker for developmental problems in VP/VLBW children.

The capacity of mid-pregnancy cervical length to predict preterm birth in low-risk women: a national cohort study.

INTRODUCTION: We investigated the predictive capacity of mid-trimester cervical length (CL) measurement for spontaneous and iatrogenic preterm birth. MATERIAL AND METHODS: We performed a prospective observational cohort study in nulliparous women and low-risk multiparous women with a singleton pregnancy between 16(+0) and 21(+6) weeks of gestation. We assessed the prognostic capacity of transvaginally measured mid-trimester CL for spontaneous and iatrogenic preterm birth (<37 weeks) using likelihood ratios (LR) and receiver-operating-characteristic analysis. We calculated numbers needed to screen to prevent one preterm birth assuming different treatment effects. Main outcome measures were preterm birth <32, <34 and <37 weeks. RESULTS: We studied 11,943 women, of whom 666 (5.6%) delivered preterm: 464 (3.9%) spontaneous and 202 (1.7%) iatrogenic. Mean CL was 44.1 mm (SD 7.8 mm). In nulliparous women, the LRs for spontaneous preterm birth varied between 27 (95% CI 7.7-95) for a CL ≤ 20 mm, and 2.0 (95% CI 1.6-2.5) for a CL between 30 and 35 mm. For low-risk multiparous women, these LRs were 37 (95% CI 7.5-182) and 1.5 (95% CI 0.97-2.2), respectively. Using a cut-off for CL ≤ 30 mm, 28 (6.0%) of 464 women with spontaneous preterm birth were identified. The number needed to screen to prevent one case of preterm birth was 618 in nulliparous women and 1417 for low-risk multiparous women (40% treatment effect, cut-off 30 mm). CONCLUSION: In women at low risk of preterm birth, CL predicts spontaneous preterm birth. However, its isolated use as a screening tool has limited value due to low sensitivity.

Preventing Preterm Birth with Progesterone in Women with a Short Cervical Length from a Low-Risk Population: A Multicenter Double-Blind Placebo-Controlled Randomized Trial.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of vaginal progesterone in reducing adverse neonatal outcome due to preterm birth (PTB) in low-risk pregnant women with a short cervical length (CL). STUDY DESIGN: Women with a singleton pregnancy without a history of PTB underwent CL measurement at 18 to 22 weeks. Women with a CL ≤ 30 mm received vaginal progesterone or placebo. Primary outcome was adverse neonatal outcome, defined as a composite of respiratory distress syndrome, bronchopulmonary dysplasia, intracerebral hemorrhage > grade II, necrotizing enterocolitis > stage 1, proven sepsis, or death before discharge. Secondary outcomes included time to delivery, PTB before 32, 34, and 37 weeks of gestation. Analysis was by intention to treat. RESULTS: Between 2009 and 2013, 20,234 women were screened. A CL of 30 mm or less was seen in 375 women (1.8%). In 151 women, a CL ≤ 30 mm was confirmed with a second measurement and 80 of these women agreed to participate in the trial. We randomly allocated 41 women to progesterone and 39 to placebo. Adverse neonatal outcomes occurred in two (5.0%) women in the progesterone and in four (11%) women in the control group (relative risk [RR], 0.47; 95% confidence interval [CI], 0.09-2.4). The use of progesterone resulted in a nonsignificant reduction of PTB < 32 weeks (2.0 vs. 8.0%; RR, 0.33; 95% CI, 0.04-3.0) and < 34 weeks (7.0 vs. 10%; RR, 0.73; 95% CI, 0.18-3.1) but not on PTB < 37 weeks (15 vs. 13%; RR, 1.2; 95% CI, 0.39-3.5). CONCLUSION: In women with a short cervix, who are otherwise low risk, we could not show a significant benefit of progesterone in reducing adverse neonatal outcome and PTB.

Motor impairment in very preterm-born children: links with other developmental deficits at 5 years of age.

AIM: To elucidate the relation between motor impairment and other developmental deficits in very preterm-born children without disabling cerebral palsy and term-born comparison children at 5 years of (corrected) age. METHOD: In a prospective cohort study, 165 children (81 very preterm-born and 84 term-born)were assessed with the Movement Assessment Battery for Children - 2nd edition, Touwen's neurological examination, the Wechsler Preschool and Primary Scale of Intelligence, processing speed and visuomotor coordination tasks of the Amsterdam Neuropsychological Tasks, and the Strengths and Difficulties Questionnaire. RESULTS: Motor impairment (≤15th centile) occurred in 32% of the very preterm-born children compared with 11% of their term-born peers (p=0.001). Of the very preterm-born children with motor impairment, 58% had complex minor neurological dysfunctions, 54% had low IQ, 69% had slow processing speed, 58% had visuomotor coordination problems, and 27%, 50%,and 46% had conduct, emotional, and hyperactivity problems respectively. Neurological outcome (odds ratio [OR]=41.7, 95% confidence intervals [CI] 7.5­232.5) and Full-scale IQ(OR=7.3, 95% CI 1.9­27.3) were significantly and independently associated with motor impairment. Processing speed (OR=4.6, 95% CI 1.8­11.6) and attention (OR=3.2, 95% CI1.3­7.9) were additional variables associated with impaired manual dexterity. These four developmental deficits mediated the relation between preterm birth and motor impairment. INTERPRETATION: Complex minor neurological dysfunctions, low IQ, slow processing speed,and hyperactivity/inattention should be taken into account when very preterm-born children are referred for motor impairment.

Visual sensory and perceptive functioning in 5-year-old very preterm/very-low-birthweight children.

AIM: To examine visual sensory and perceptive functions, study their interrelations, and explore associations between visual dysfunctions and intelligence in very preterm/very-low-birthweight (VP/VLBW) children. METHOD: One-hundred and sixteen VP/VLBW children (57 males, 59 females; mean gestational age 30.1 wks, SD 2.3; mean corrected age 5 y 6 mo, SD 1 mo) and 73 term-born children (40 males, 33 females; mean gestational age 39.9 wks, SD 1.3; mean age 5 y 6 mo, SD 3 mo) completed visual sensory (acuity, visual field, contrast-, color-, and stereovision), perceptive (visual coherence, and Developmental Test of Visual Perception non-motor scale), and intelligence assessments. RESULTS: Compared with term-born children, VP/VLBW children had reduced acuity (d=0.70, p<0.001), inferior visual field (d=0.67, p<0.001), and stereovision (v=0.19, p=0.008). VP/VBLW children showed weaker static coherence (d=0.49, p=0.001) and Position in Space (d=0.41, p=0.006) performance, independent of visual sensory deficits, and showed lower Verbal IQ (VIQ) and Performance IQ (PIQ; p<0.001). Visual perceptive functioning accounted for 13% of variance in VIQ, and for 35% of variance in PIQ. INTERPRETATION: Visual sensory and perceptive dysfunctions are present in VP/VLBW children and occur largely independently of each other. Visual perceptive dysfunctions are moderately associated with PIQ, and weakly with VIQ.