Increased Rat Placental Fatty Acid, but Decreased Amino Acid and Glucose Transporters Potentially Modify Intrauterine Programming.

Regulation of placental nutrient transport significantly affects fetal development and may modify intrauterine growth restriction (IUGR) and fetal programming. We hypothesized that placental nutrient transporters are differentially affected both by utero-placental insufficiency and prenatal surgical stress. Pregnant rats underwent bilateral uterine artery and vein ligation (LIG), sham operation (SOP) or no operation (controls, C) on gestational day E19. Placentas were obtained by caesarean section 4 h (LIG, n=20 placentas; SOP, n=24; C, n=12), 24 h (LIG, n=28; SOP, n=20; C, n=12) and 72 h (LIG, n=20; SOP, n=20; C, n=24) after surgery. Gene and protein expression of placental nutrient transporters for fatty acids (h-FABP, CD36), amino acids (SNAT1, SNAT2) and glucose (GLUT-1, Connexin 26) were examined by qRT-PCR, western blot and immunohistochemistry. Interestingly, the mean protein expression of h-FABP was doubled in placentas of LIG and SOP animals 4, 24 (SOP significant) and 72 h (SOP significant) after surgery. CD36 protein was significantly increased in LIG after 72 h. SNAT1 and SNAT2 protein and gene expressions were significantly reduced in LIG and SOP after 24 h. Further significantly reduced proteins were GLUT-1 in LIG (4 h, 72 h) and SOP (24 h), and Connexin 26 in LIG (72 h). In conclusion, placental nutrient transporters are differentially affected both by reduced blood flow and stress, probably modifying the already disturbed intrauterine milieu and contributing to IUGR and fetal programming. Increased fatty acid transport capacity may affect energy metabolism and could be a compensatory reaction with positive effects on brain development. J. Cell. Biochem. 117: 1594-1603, 2016. © 2015 Wiley Periodicals, Inc.

Neonatal Outcome After Preeclampsia and HELLP Syndrome: A Population-Based Cohort Study in Germany.

Aim: To analyze short term outcomes of very low birth weight infants (VLBWI) born preterm after maternal preeclampsia and HELLP syndrome within the German Neonatal Network. Methods: The German Neonatal Network is a large population-based cohort study enrolling VLBWI since 2009. Two thousand six hundred and fifty two infants below 32 weeks of gestation born after maternal preeclampsia or HELLP syndrome and 13,383 infants born prematurely for other causes between 2009 and 2018 were included in our analysis. Descriptive statistics and multinomial regression models including preeclampsia and HELLP syndrome were performed for short-term outcome measures such as intracerebral hemorrhage, necrotizing enterocolitis requiring surgery, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, persistent ductus arteriosus requiring surgery, blood culture positive sepsis and death. Results: After adjustment for confounding variables, preterm birth due to preeclampsia or HELLP syndrome was associated with a reduced risk for intracerebral hemorrhage (OR 0.73, 95% CI 0.60-0.89), necrotizing enterocolitis requiring surgery (OR 0.35 95% CI 0.15-0.82), periventricular leukomalacia (OR 0.61 95% CI 0.40-0.92), and death (OR 0.72 95% CI 0.55-0.96) as compared to other causes of preterm birth. Conclusions: The indication for preterm birth has an impact on neonatal outcome in preterm infants born below 32 weeks. This notion should be included when counseling the families.

Genetic predisposition for vitamin D deficiency is not associated with adverse outcome of very low birth weight infants: A cohort study from the German Neonatal Network.

OBJECTIVE: Postnatal vitamin D supplementation is standard of care in neonates and preterm infants. Despite routine supplementation of vitamin D, a wide range of complications related to vitamin D deficiency has been described in the literature. Since standard vitamin D supplementation might be not sufficient in preterm infants with a genetic predisposition for vitamin D deficiency, we investigated the outcome of preterm infants with regard to their genetic estimated vitamin D levels. METHODS: Preterm infants with a birth weight below 1500 grams were included in the German Neonatal Network at the time of their birth and tested at the age of five. The vitamin D level was genetically calculated based on three single nucleotide polymorphisms (SNPs: rs12794714, rs7944926 and rs2282679) which alter vitamin D synthesis pathways. Specific alleles of these polymorphisms are validated markers for low plasma vitamin D levels. Outcome data were based on baseline data at the time of birth, typical complications of prematurity, body measurements at the age of five and occurrence of bone fractures. T-test and Fisher's exact test were used for statistical comparison. RESULTS: According to their genetic predisposition, 1,924 preterm infants were divided into groups of low (gsVitD < 20. Percentile), intermediate and high vitamin D level estimates. Low genetic vitamin D level estimates could not be shown to be associated with any adverse outcome measures examined. The analyses covered data on aforementioned determinants. CONCLUSION: Low genetic vitamin D level estimates could not be shown to be associated with previously described adverse outcome in preterm infants.

Surgical necrotizing enterocolitis but not spontaneous intestinal perforation is associated with adverse neurological outcome at school age.

Gastrointestinal complications during the neonatal period, i.e. necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP), are associated with adverse short-term outcome in very-low-birthweight infants (VLBWI, <1500 g birth weight). However, little is known about the neurological outcome of survivors at school age. We analysed data of 2241 infants followed-up at the age of 6 years. To determine the effect of NEC and SIP on cognitive outcome in consideration of other important confounding factors, we used multivariable logistic regression models. In addition, infants with surgical diagnosis of NEC (n = 43) or SIP (n = 41) were compared to NEC (n = 43) or SIP (n = 41) negative controls using Mahalanobis distance matching. Infants with a history for NEC had a three times increased risk (RR 3.0 [1.8-4.2], p < 0.001) to develop IQ scores <85 while history of surgical SIP did not increase the relative risk for lower IQs at school age (RR 1.0 [0.4-2.1], p = 1.000). In a matched-cohort analysis, we confirmed that infants with surgical NEC had lower mean IQ results than unaffected controls (±SD) (85±17 vs. 94±14, p = 0.023) while no differences were found for history of SIP. Our results reflect that the different aetiology and inflammatory extent of NEC and SIP may lead to disparate neurodevelopment trajectories. Hence, our data suggest a potential role of early gut-brain axis distortion in infants with NEC which needs to be further explored.