Does Delayed Cord Clamping Improve Long-Term (≥4 Months) Neurodevelopment in Term Babies? A Systematic Review and a Meta-Analysis of Randomized Clinical Trials

Abstract

Background: Recently, the literature suggested that placental transfusion facilitated by delayed cord clamping (DCC), besides having benefits on hematological parameters, might improve the infants' brain development.Objective: The present review primarily evaluates the Ages and Stages Questionnaire (ASQ) total score mean difference (MD) at long-term follow-up (≥4 months) comparing DCC (>90 or >180 s) to early cord clamping (ECC). Secondary aims consisted of evaluating the ASQ domains' MD and the results obtained from other methods adopted to evaluate the infants' neurodevelopment.Methods: MEDLINE, Scopus, Cochrane, and ClinicalTrials.gov databases were searched (up to 2nd November 2020) for systematic review and meta-analysis. All randomized controlled trials (RCTs) of term singleton gestations received DCC or ECC. Multiple pregnancies, pre-term delivery, non-randomized studies, and articles in languages other than English were excluded. The included studies were assessed for bias and quality. ASQ data were pooled stratified by time to follow up.Results: This meta-analysis of 4 articles from 3 RCTs includes 765 infants with four-month follow-up and 672 with 12 months follow-up. Primary aim (ASQ total score) pooled analysis was possible only for 12 months follow-up, and no differences were found between DCC and ECC (MD 1.1; CI 95: −5.1; 7.3). DCC approach significantly improves infants' communication domains (MD 0.6; CI 95: 0.1; 1.1) and personal-social assessed (MD 1.0; CI 95: 0.3; 1.6) through ASQ at 12 months follow-up. Surprisingly, the four-month ASQ personal social domain (MD −1.6; CI 95: −2.8; −0.4) seems to be significantly lower in the DCC group than in the ECC group.Conclusions: DCC, a simple, non-interventional, and cost-effective approach, might improve the long-term infants' neurological outcome. Single-blinding and limited studies number were the main limitations. Further research should be performed to confirm these observations, ideally with RCTs adopting standard methods to assess infants' neurodevelopment.Trial registration: NCT01245296, NCT01581489, NCT02222805, NCT01620008, IRCT201702066807N19, and NCT02727517

Umbilical cord blood acid–base analysis at birth and long‐term neurodevelopmental outcomes in children: a systematic review and meta‐analysis

“…46,47 Further, delayed cord clamping per se is associated with some long-term benefits, making interpretation of long-term follow-up results that include populations with both early and delayed cord clamping difficult. [48][49][50] Another explanation for the BSID test result may be confounding factors, as discussed under the study's limitations.…”

“…Delayed cord clamping may result in artificial lowered cord artery pH and in better outcomes for the babies, as late clamping prevents hypovolaemia and increases the oxygen‐carrying capacity in the blood 46,47 . Further, delayed cord clamping per se is associated with some long‐term benefits, making interpretation of long‐term follow‐up results that include populations with both early and delayed cord clamping difficult 48–50 . Another explanation for the BSID test result may be confounding factors, as discussed under the study's limitations.…”

Toward greater nuance in delayed cord clamping

“…Term infants receiving DCC (5 min) vs. ECC showed increased myelin content in regions of the brain notable for motor function, visual and spatial skills, and sensory processing at 4 and 12 months of age [11 && ,12]. There was no difference in developmental assessments between the groups; however, higher Ages and Stages Questionnaires (ASQ) scores in the subdomains of communication and personal-social skills have been identified among 12-month-old term and near-term infants who received DCC, despite no differences in total ASQ scores [13]. The strength of neurodevelopmental studies has been limited due to challenges including protocol violations, loss to follow-up, a variety of assessment tools, and shifting outcomes across age groups [14,15].…”

Hemoglobin differences in twins are related to the time of cord clamping, not intertwin transfusion – a prospective cohort study

“…Al. DCC was found to improve the long-term infants' neurological outcome [8]. In 2015, the International Liaison Committee on Resuscitation suggested performing DCC for over 30 s for preterm infants not requiring immediate resuscitation after birth, however it was a weak recommendation with very low-quality evidence [9].…”