Seven-month developmental outcomes of very low birth weight infants enrolled in a randomized controlled trial of delayed versus immediate cord clamping

Objective: The results from our previous trial revealed that infants with delayed cord clamping (DCC) had significantly lesser intraventricular hemorrhage (IVH) and late-onset sepsis (LOS) than infants with immediate cord clamping (ICC). A priori, we hypothesized that infants with DCC would have better motor function by 7 months corrected age. Study Design: Infants between 24 and 31 weeks were randomized to ICC or DCC and follow-up evaluation was completed at 7 months corrected age. Result: We found no differences in the Bayley Scales of Infant Development (BSID) scores between the DCC and ICC groups. However, a regression model of effects of DCC on motor scores controlling for gestational age, IVH, bronchopulmonary dysplasia, sepsis and male gender suggested higher motor scores of male infants with DCC. Conclusion: DCC at birth seems to be protective of very low birth weight male infants against motor disability at 7 months corrected age

Delayed Cord Clamping in Very Preterm Infants Reduces the Incidence of Intraventricular Hemorrhage and Late-Onset Sepsis: A Randomized, Controlled Trial

Objective: This study compared the effects of immediate (ICC) and delayed (DCC) cord clamping on very low birth weight (VLBW) infants on 2 primary variables: bronchopulmonary dysplasia (BPD) and suspected necrotizing enterocolitis (SNEC). Other outcome variables were late-onset sepsis (LOS) and intraventricular hemorrhage (IVH). Study Design: This was a randomized, controlled unmasked trial in which women in labor with singleton fetuses \u3c32 weeks’ gestation were randomly assigned to ICC (cord clamped at 5–10 seconds) or DCC (30–45 seconds) groups. Women were excluded for the following reasons: their obstetrician refused to participate, major congenital anomalies, multiple gestations, intent to withhold care, severe maternal illnesses, placenta abruption or previa, or rapid delivery after admission. Results: Seventy-two mother/infant pairs were randomized. Infants in the ICC and DCC groups weighed 1151 and 1175 g, and mean gestational ages were 28.2 and 28.3 weeks, respectively. Analyses revealed no difference in maternal and infant demographic, clinical, and safety variables. There were no differences in the incidence of our primary outcomes (BPD and suspected NEC). However, significant differences were found between the ICC and DCC groups in the rates of IVH and LOS. Two of the 23 male infants in the DCC group had IVH versus 8 of the 19 in the ICC group. No cases of sepsis occurred in the 23 boys in the DCC group, whereas 6 of the 19 boys in the ICC group had confirmed sepsis. There was a trend toward higher initial hematocrit in the infants in the DCC group. Conclusions: Delayed cord clamping seems to protect VLBW infants from IVH and LOS, especially for male infants

Language at rest: A longitudinal study of intrinsic functional connectivity in preterm children

AbstractBackgroundPreterm (PT) children show early cognitive and language deficits and display altered cortical connectivity for language compared to term (T) children. Developmentally, functional connectivity networks become more segregated and integrated, through the weakening of short-range and strengthening of long-range connections.MethodsLongitudinal intrinsic connectivity distribution (ICD) values were assessed in PT (n=13) compared to T children (n=12) at ages 8 vs. 16 using a Linear Mixed Effects model. Connectivity values in regions generated by the group×age interaction analysis were then correlated to scores on full IQ (FSIQ), verbal IQ (VIQ), verbal comprehension IQ (VCIQ), performance IQ (PIQ), Peabody picture vocabulary test—revised (PPVT­R), and Rapid Naming Composite (RDRL_Cmp).ResultsNine regions were generated by the group×age interaction analysis. PT connectivity significantly increased over time in all but two regions, and they ultimately displayed greater relative connectivity at age 16 than Ts in all areas except the left occipito-temporal cortex (OTC). PTs underwent significant connectivity reductions in the left OTC, which corresponded with worse performance on FSIQ, VIQ, and PIQ. These findings differed from Ts, who did not undergo any significant changes in connectivity over time.ConclusionsThese findings suggest that the developmental alterations in connectivity in PT children at adolescence are both pervasive and widespread. The persistent and worsening cognitive and language deficits noted in the PT subjects may be attributed to the loss of connections in the left OTC

Effects of Placental Transfusion on Neonatal and 18 Month Outcomes in Preterm Infants: A Randomized Controlled Trial

Objective: To assess the effect of delayed cord clamping (DCC) vs immediate cord clamping (ICC) on intraventricular hemorrhage (IVH), late onset sepsis (LOS), and 18-month motor outcomes in preterm infants. Study Design: Women (n = 208) in labor with singleton fetuses (\u3c32 weeks gestation) were randomized to either DCC (30-45 seconds) or ICC (\u3c10 seconds). The primary outcomes were IVH, LOS, and motor outcomes at 18-22 months corrected age. Intention-to-treat was used for primary analyses. Results: Cord clamping time was 32 ± 16 (DCC) vs 6.6 ± 6 (ICC) seconds. Infants in the DCC and ICC groups weighed 1203 ± 352 and 1136 ± 350 g and mean gestational age was 28.3 ± 2 and 28.4 ± 2 weeks, respectively. There were no differences in rates of IVH or LOS between groups. At 18-22 months, DCC was protective against motor scores below 85 on the Bayley Scales of Infant Development, Third Edition (OR 0.32, 95% CI 0.10-0.90, P = .03). There were more women with preeclampsia in the ICC group (37% vs 22%, P = .02) and more women in the DCC group with premature rupture of membranes/preterm labor (54% vs 75%, P = .002). Preeclampsia halved the risk of IVH (OR 0.50, 95% CI 0.2-1.0) and premature rupture of membranes/preterm labor doubled the risk of IVH (OR 2.0, 95% CI 1.2-4.3). Conclusions: Although DCC did not alter the incidence of IVH or LOS in preterm infants, it improved motor function at 18-22 months corrected age

Developmental Outcomes of Very Preterm Infants with Tracheostomies

Objectives To evaluate the neurodevelopmental outcomes of very preterm (<30 weeks) infants who underwent tracheostomy. Study design Retrospective cohort study from 16 centers of the NICHD Neonatal Research Network over 10 years (2001-2011). Infants who survived to at least 36 weeks (N=8,683), including 304 infants with tracheostomies, were studied. Primary outcome was death or neurodevelopmental impairment (NDI, a composite of one or more of: developmental delay, neurologic impairment, profound hearing loss, severe visual impairment) at a corrected age of 18-22 months. Outcomes were compared using multiple logistic regression. We assessed impact of timing, by comparing outcomes of infants who underwent tracheostomy before and after 120 days of life. Results Tracheostomies were associated with all neonatal morbidities examined, and with most adverse neurodevelopmental outcomes. Death or NDI occurred in 83% of infants with tracheostomies and 40% of those without [odds ratio (OR) adjusted for center 7.0 (95%CI, 5.2-9.5)]. After adjustment for potential confounders, odds of death or NDI remained higher [OR 3.3 (95%CI, 2.4-4.6)], but odds of death alone were lower [OR 0.4 (95%CI, 0.3-0.7)], among infants with tracheostomies. Death or NDI was lower in infants who received their tracheostomies before, rather than after, 120 days of life [adjusted OR 0.5 (95%CI, 0.3-0.9)]. Conclusions Tracheostomy in preterm infants is associated with adverse developmental outcomes, and cannot mitigate the significant risk associated with many complications of prematurity. These data may inform counseling about tracheostomy in this vulnerable population

Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P\u3c0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. CONCLUSIONS: Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.

Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants

Background: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia. Methods: We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity. Results: A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively. Conclusions: In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

Amygdala functional connectivity is associated with social impairments in preterm born young adults

Survivors of preterm birth experience long-lasting behavioral problems characterized by increased risk of depression, anxiety, and impairments in social functioning. The amygdala is a key region for social functioning and alterations in amygdala structure and connectivity are thought to underlie social functioning deficits in many disorders, including preterm birth. However, functional connectivity of the amygdala and its association with social impairments is not well-studied in preterm participants (PTs). In a group of late adolescents born very PT (600–1250 g birth weight), measures of social and emotional development were examined using the Child Behavior Checklist (CBCL) administered at age 16 (66 term and 161 preterm participants), the Youth Self Report (YSR) administered at age 16 (56 term and 45 preterm participants), and the Vineland Adaptive Behavior Scales (VABS) administered at age 18 (71 term and 190 preterm participants). Amygdala functional connectivity was also examined using resting-state functional magnetic resonance imaging at age 20 (17 term and 19 preterm participants). By parent report, preterm-born adolescents demonstrate increased social impairment compared to their term-born peers. Amygdala connectivity is altered for those prematurely-born, and markers of social functioning correlate with altered amygdala-PCC connectivity. These findings add to knowledge regarding the developmental trajectory of amygdala connectivity in PT and suggest a possible neural underpinning for the well-characterized social impairment experienced by prematurely-born individuals. Keywords: Amygdala, Magnetic resonance imaging, Resting-state, Social development, Preterm birt