Objectives To determine whether the single-family room (SFR)-neonatal intensive care unit (NICU) is associated with improved 18-month neurodevelopmental outcome, especially in infants of mothers with ...high maternal involvement. Study Design An 18-month follow-up was undertaken that compared infants born <30 weeks gestational age; 123 from a SFR-NICU vs 93 from an open-bay NICU. Infants were divided into high vs low maternal involvement based on days/week of kangaroo care, breast/bottle feeding, and maternal care. Infants with high vs low maternal involvement in the SFR and open-bay NICUs were compared on the Bayley Cognitive, Language, and Motor scores and Pervasive Developmental Disorders autism screen. Results There were more mothers in the high maternal involvement SFR than in the high maternal involvement open-bay group ( P = .002). Infants with high maternal involvement in both NICUs had greater Cognitive ( P = .029) and Language ( P < .000) scores than infants with low maternal involvement. Effect sizes within NICU were moderate to large in the SFR-NICU for Language scores and moderate for the Language composite in the open-bay NICU. The number of days of maternal involvement was greater in the SFR than open-bay NICU ( P < .000), and length of stay was shorter in the high maternal involvement SFR than high maternal involvement open-bay NICU ( P = .024). Kangaroo and maternal care predicted Cognitive (kangaroo, P = .003) and Language scores ( P = .015, P = .032, respectively). Infants with ≥1 symptom of autism were more likely to be in the open-bay low maternal involvement group vs the SFR high maternal involvement group (OR = 4.91, 95% CI = 2.2-11.1). Conclusions High maternal involvement is associated with improved 18-month neurodevelopmental outcome, especially in infants cared for in a SFR-NICU.
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 (<32 weeks gestation) were randomized to either DCC (30-45 seconds) or ICC (<10 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. Clinical trial registration ClinicalTrials.gov : NCT00818220 and NCT01426698.
Objective In this study, we aimed to investigate relationships between maternal prepregnancy obesity and gestational diabetes mellitus and placental leptin DNA methylation. Study Design This study ...comprises data on 535 mother-infant dyads enrolled in the Rhode Island Child Health Study, a prospective cohort study of healthy term pregnancies. Prepregnancy body mass index was calculated from self-reported anthropometric measures and gestational diabetes mellitus diagnoses gathered from inpatient medical records. DNA methylation of the leptin promoter region was assessed in placental tissue collected at birth using quantitative bisulfite pyrosequencing. Results In a multivariable regression analysis adjusted for confounders, infants exposed to gestational diabetes mellitus had higher placental leptin methylation (β = 1.89, P = .04), as did those demonstrating prepregnancy obesity (β = 1.17, P = .06). Using a structural equations model, we observed that gestational diabetes mellitus is a mediator of the effects of prepregnancy obesity on placental leptin DNA methylation (β = 0.81, 95% confidence interval, 0.27–2.71). Conclusion Our results suggest that the maternal metabolic status before and during pregnancy can alter placental DNA methylation profile at birth and potentially contribute to metabolic programming of obesity and related conditions.
Objective The purpose of this study was to determine in a mouse model whether uterine natural killer (uNK) cell cytotoxic activation induces infection/inflammation-associated preterm labor and ...delivery. Study Design Wild type or interleukin (IL)-10–/– mice were injected intraperitoneally with lipopolysaccharide on gestational day 14. Mice were either killed for collection of uteroplacental tissue, spleen, and serum or allowed to deliver. Uteroplacental tissue was used for histology and characterization of uNK cells. Results Low-dose lipopolysaccharide treatment triggered preterm labor and delivery in IL-10–/– , but not wild type mice, in a manner independent of progesterone levels. Preterm labor and delivery in IL-10–/– mice was associated with an increased number and placental infiltration of cytotoxic uNK cells and placental cell death. Depletion of NK cells or tumor necrosis factor (TNF)-α neutralization in these mice restored term delivery. Furthermore, TNF-α neutralization prevented uNK cell infiltration and placental cell apoptosis. Conclusion The uNK cell-TNF-α–IL-10 axis plays an important role in the genesis of infection/inflammation-induced preterm labor/delivery.
Objectives To compare inter-alpha inhibitor protein (IaIp) levels in neonates with proven necrotizing enterocolitis (NEC) and neonates with other, nonspecific abdominal disorders. Study design This ...was a prospective observational study of neonates in the neonatal intensive care unit. NEC was diagnosed according to Bell's staging criteria. The nNeonates in the control group had a nonspecific abdominal disorder, but no radiographic evidence of NEC and no disease progression. All neonates with radiographically confirmed NEC were included. Plasma IaIp levels were quantitated by enzyme-linked immunosorbent assay. Results Seventeen neonates had confirmed NEC, and 34 neonates had nonspecific abdominal disorders that improved rapidly. Gestational age, postnatal age, weight, sex, maternal obstetric variables, rupture of membranes, and mode of delivery did not differ between the two groups. Mean IaIp level was significantly lower in the NEC group compared with the control group (137 ± 38 mg/L; 95% confidence interval CI, 118-157 mg/L vs 258 ± 53 mg/L; 95% CI, 238-277 mg/L; P <.0001). Conclusions The finding of significantly lower IaIp levels in neonates with NEC suggests that IaIp might be a useful, sensitive biomarker, allowing initiation of appropriate therapy and reducing antibiotic overuse in neonates with suspected but unproven NEC. Administration of IaIp may significantly reduce the severity of systemic inflammation and associated tissue injury.
We evaluated Inter-alpha inhibitor proteins (IaIp) as a diagnostic marker in neonatal sepsis. Samples were collected from 573 neonates who were examined for suspected sepsis. IaIp level was ...significantly lower in the septic group (121 ± 71 mg/L) than in the non-septic group (322 ± 91 mg/L). The optimal cutoff value with the receiver operating characteristic curve was ≤177 mg/L (sensitivity, 89.5%; specificity, 99%; positive predictive value, 95%; negative predictive value, 98%) with area under the curve of 0.94. IaIp is a more reliable diagnostic marker for neonatal sepsis than other available tests.