The aetiology of preterm birth and risks of cerebral palsy and cognitive impairment: A systematic review and meta-analysis.

AIM: The associations between the aetiology of preterm birth and later neurodevelopmental outcomes are unclear. A systematic review and meta-analysis examined the existing evidence. METHODS: The PubMed and Embase databases were searched for papers published in English from inception to 16 December 2020. We included original papers on the causes of preterm birth and the risks of cerebral palsy (CP) and suboptimal cognitive development. Two reviewers independently evaluated the studies and extracted the data. RESULTS: The literature search yielded 5472 papers and 13 were selected. The aetiology of preterm birth was classified under spontaneous or medically indicated delivery. A meta-analysis was performed, comprising 104 902 preterm infants from 11 papers on CP. Preterm infants born after a medically indicated delivery had a lower CP risk than infants born after spontaneous delivery, with a pooled odds ratio of 0.59 (95% confidence interval 0.40-0.86). This result was robust in the subgroup and sensitivity analyses. Cognitive development was reported in three papers, which suggested that worse outcomes were associated with medically indicated deliveries. CONCLUSION: The aetiology of preterm delivery may contribute to the risk of CP and cognitive delay. Further research is needed, using individual-level meta-analyses to adjust for possible confounders, notably gestational age.

Associations between the aetiology of preterm birth and mortality and neurodevelopment up to 11 years.

AIM: To investigate how the aetiology of very preterm birth/very low birth weight is associated with mortality and later neurodevelopmental outcomes. METHODS: Very preterm/very low-birth weight singletons were categorised based on the aetiology of preterm birth: spontaneous preterm birth (n = 47, 28.1%), preterm premature rupture of membranes (n = 56, 33.5%) or placental vascular pathology (n = 64, 38.3%). Mortality, cerebral palsy, severe cognitive impairment by 11 years of age (<2SD) and mean full-scale intelligence quotient at 11 years were studied in association with birth aetiology. RESULTS: There was no difference in mortality or rate of cerebral palsy according to birth aetiologies. The rate of severe cognitive impairment was lower (4.9% vs. 15.3%) in the preterm premature rupture of the membrane group in comparison to the placental vascular pathology group (OR 0.2, 95% CI 0.03-0.9, adjusted for gestational age). At 11 years, there was no statistically significant difference in the mean full-scale intelligence quotient. CONCLUSION: Placental vascular pathology, as the aetiology of very preterm birth/very low birth weight, is associated with a higher rate of severe cognitive impairments in comparison to preterm premature rupture of membranes, although there was no difference in the mean full-scale intelligence quotient at 11 years. The aetiology of very preterm birth/very low birth weight was not associated with mortality or the rate of cerebral palsy.

Web-based follow-up tool (ePIPARI) of preterm infants-study protocol for feasibility and performance.

BACKGROUND: Preterm infants have a risk of health and developmental problems emerging after discharge. This indicates the need for a comprehensive follow-up to enable early identification of these problems. In this paper, we introduce a follow-up tool "ePIPARI - web-based follow-up for preterm infants". Our future aim is to investigate whether ePIPARI is a feasible tool in the follow-up of preterm infants and whether it can identify children and parents in need of clinical interventions. METHODS: ePIPARI includes eight assessment points (at term age and at 1, 2, 4, 8, 12, 18, and 24 months of corrected age) when the child´s health and growth, eating and feeding, neurodevelopment, and parental well-being are evaluated. ePIPARI consists of several widely used, standardized questionnaires, in addition to questions typically presented to parents in clinical follow-up visits. It also provides video guidance and written information about age-appropriate neurodevelopment for the parents. Parents of children born before 34 weeks of gestation during years 2019-2022 are being invited to participate in the ePIPARI study, in which web-based follow-up with ePIPARI is compared to clinical follow-up. In addition, the parents of children born before 32 weeks of gestation, who reached the corrected age of two years during 2019-2021 were invited to participate for the assessment point of 24 months of ePIPARI. The parents are asked to fill in the online questionnaires two weeks prior to each clinical follow-up visit. DISCUSSION: The web-based tool, ePIPARI, was developed to acquire a sensitive and specific tool to detect infants and parents in need of further support and clinical interventions. This tool could allow individualized adjustments of the frequency and content of the clinical visits. TRIAL REGISTRATION: ClinicalTrials.cov, NCT05238168 . Registered 11 April 2022 - Retrospectively registered.

Maternal education and cognitive development in 15 European very-preterm birth cohorts from the RECAP Preterm platform.

BACKGROUND: Studies are sparse and inconclusive about the association between maternal education and cognitive development among children born very preterm (VPT). Although this association is well established in the general population, questions remain about its magnitude among children born VPT whose risks of medical and developmental complications are high. We investigated the association of maternal education with cognitive outcomes in European VPT birth cohorts. METHODS: We used harmonized aggregated data from 15 population-based cohorts of children born at <32 weeks of gestational age (GA) or <1500 g from 1985 to 2013 in 13 countries with information on maternal education and assessments of general development at 2-3 years and/or intelligence quotients between 4 and 15 years. Term-born controls (≥37 weeks of GA) were available in eight cohorts. Maternal education was classified as: low (primary/lower secondary); medium (upper secondary/short tertiary); high (bachelor's/higher). Pooled standardized mean differences (SMDs) in cognitive scores were estimated (reference: high educational level) for children assessed at ages 2-3, 4-7 and 8-15 years. RESULTS: The study included 10 145 VPT children from 12 cohorts at 2-3 years, 8829 from 12 cohorts at 4-7 years and 1865 children from 6 cohorts at 8-15 years. Children whose mothers had low, compared with high, educational attainment scored lower on cognitive measures [pooled unadjusted SMDs: 2-3 years = -0.32 (95% confidence intervals: -0.43 to -0.21); 4-7 years = -0.57 (-0.67; -0.47); 8-15 years = -0.54 (-0.72; -0.37)]. Analyses by GA subgroups (<27 vs ≥27 weeks) in children without severe neonatal morbidity and term controls yielded similar results. CONCLUSIONS: Across diverse settings and regardless of the degree of prematurity, low maternal education was associated with lower cognition.

Neurodevelopmental outcome of preterm twins at 5 years of age.

BACKGROUND: Twins are considered to be at an increased risk for perinatal mortality and morbidities, but it is unclear whether preterm twins are at an increased risk for poor developmental outcomes when compared to preterm singletons. Our aim was to compare the neurodevelopmental outcome of preterm twins vs singletons at 5 years of age. METHODS: Very low birth weight and very low gestational age infants (twins n = 66, singletons n = 157) were recruited as a part of the PIPARI project in the Turku University Hospital, covering a regional population. Cognitive development, neuropsychological performance, and neurodevelopmental impairments (including cerebral palsy, hearing deficit, visual impairment, and intellectual disability) were evaluated at 5 years of age. RESULTS: Twins and singletons had otherwise similar perinatal background factors, except for the higher proportion of preterm rupture of membranes in singletons. Twins had cognitive and neuropsychological outcomes that were otherwise comparable with singletons, but they had a slightly lower verbal intelligence quotient (estimate -5.81, 95% CI -11.14 to -0.48, p = 0.03). Being a twin was not a risk for neurodevelopmental impairments. CONCLUSIONS: Our study shows that, contrary to a common hypothesis, the overall neurodevelopment of very preterm twins does not significantly differ from that of preterm singletons.

Prenatal Risk Factors for Adverse Developmental Outcome in Preterm Infants-Systematic Review.

Background: Preterm infants are still at an increased risk for suboptimal neurodevelopmental outcomes when compared with term born infants. The development of a child born preterm can be jeopardized by suboptimal conditions during pregnancy, in addition to the suboptimal growth environment postnatally compared to the normal in utero environment. This review summarizes the literature on the role of chorioamnionitis, placental insufficiency, and maternal smoking on the developmental outcomes of preterm infants. Methods: A systematic database search was performed to identify all original articles published on or before September 12, 2018 that evaluated the impact of clinical or histological chorioamnionitis, abnormal prenatal fetal and placental blood flow, and prenatal smoking exposure on the neuropsychological and cognitive outcomes of preterm infants. We identified a total of 54 studies. Thirty five original articles evaluated the effects of clinical or histological chorioamnionitis; 15 studies evaluated the effects of abnormal blood flow patterns; and four studies evaluated the effects of maternal smoking during pregnancy. Results: The studies on prenatal risk factors showed conflicting results about the impact on the neurodevelopment of preterm infants. The majority of the studies did not show that chorioamnionitis poses a direct risk to the development of preterm infants. The role of abnormal prenatal placental and fetal blood flow on the development of preterm infants remained inconclusive because the sample sizes were often small and methodological problems complicated the interpretation of the data. Maternal smoking during pregnancy was assessed only in one cohort which showed that maternal smoking is a risk for suboptimal cognitive and neuropsychological development in preterm infants. Conclusions: This review summarizes the data on several prenatal risk factors which play a role in the developmental outcomes of preterm infants. To optimize the developmental outcomes, we need to first optimize the fetal wellbeing before birth. More research that extends from the fetal life to long-term developmental outcomes is needed.

Chorioamnionitis and Five-Year Neurodevelopmental Outcome in Preterm Infants.

BACKGROUND: Chorioamnionitis, a risk factor for preterm delivery, has been suggested to be associated with suboptimal neurological development in premature infants. OBJECTIVE: To evaluate the association between chorioamnionitis and neurodevelopment in preterm infants at 5 years of age. Methods Very low birth weight and very low gestational age infants (n = 197) were recruited. Placental samples (n = 117) were evaluated for histological chorioamnionitis. Fetal histological chorioamnionitis was analyzed as a subgroup. The diagnosis of clinical chorioamnionitis was derived from medical records. Neurodevelopmental impairments were evaluated at 2 years of age, and cognitive development (n = 188) and neuropsychological performance (n = 193) were evaluated at 5 years of age. RESULTS: There were no associations between histological or clinical chorioamnionitis and neurodevelopmental impairments at 2 years of age. Clinical chorioamnionitis and fetal histological chorioamnionitis were not associated with cognitive development or neuropsychological performance, but histological chorioamnionitis was associated with poorer cognitive outcome (regression coefficient = -7.22, 95% CI: -14.31 to -0.13) and weaker memory and learning functions (regression coefficient = -1.29, 95% CI: -2.40 to -0.18) at 5 years of age. CONCLUSION: Our study findings do not support clinical chorioamnionitis having a major independent role in the pathogenesis of neurodevelopmental problems in very preterm infants. Histological chorioamnionitis was associated with slightly less optimal performance at 5 years of age, but further studies are needed to verify the clinical significance of these findings.

Is chorioamnionitis harmful for the brain of preterm infants? A clinical overview.

BACKGROUND: Chorioamnionitis is an important risk factor underlying preterm delivery, and it has also been suggested that it is associated with brain lesions and deviant neurological development in prematurely born infants. OBJECTIVE: To evaluate the possible effects of chorioamnionitis on the brain of preterm infants. DESIGN: A systematic review. METHODS: A systematic database search was performed to identify all original articles published until 5 October 2011 evaluating the association between histological and/or clinical chorioamnionitis and brain lesions and/or neurological development in preterm infants. Altogether, 609 potentially relevant articles were identified, of which 84 original articles were included. RESULTS: The majority of the articles do not support the hypothesis that chorioamnionitis poses a direct risk on the central nervous system of preterm infants. The full course of antenatal steroids seems to further reduce the adverse effects of inflammation on the developing nervous system. CONCLUSIONS: It seems that there are both benefits and risks with regard to the effects of chorioamnionitis on the brain development of preterm infants. It is plausible that inflammation enhances maturation of the preterm infant and therefore has protective effects balancing its potential harmful effects. We conclude that chorioamnionitis does not carry higher risks for the brain of preterm infants than other underlying pathologies behind preterm delivery.