Perinatal Morbidity, Mortality, and Neurodevelopmental Outcomes of Neonates with Fetal Growth Restriction

Objective: This study aimed to assess perinatal morbidity, mortality rates, and neurodevelopmental outcomes in the management of fetal growth restriction (FGR) at a single tertiary institute. Methods: Among 2465 deliveries between 2013 and 2019, 109 cases of FGR were reviewed retrospectively for causes, indications for pregnancy termination, perinatal death, overall neonatal outcomes, and long-term prognosis. Results: Excluding FGR due to congenital anomalies (n = 17), the mortality rate was 3.3% (3/92). One neonate delivered at 23 weeks developed cerebral palsy (1.1%). Retinopathy of prematurity occurred in four neonates (4.3%). Neurodevelopmental disorders were present in six neonates (6.5%), all of whom were delivered at 32 - 38 weeks. Significantly lower gestational age at delivery, lower birth weight, and higher umbilical artery resistance indices were observed in neonates with neurodevelopmental disorders. Conclusions: Intact survival before 27 weeks of gestation at delivery with FGR is uncommon. Neurodevelopmental disorders may still develop after delivery at 32 - 38 weeks;consideration should be given to the timing of delivery usingfetal ductus venosus Doppler waveforms measurements to reduce neurodevelopmental disorders.

Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model

Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.

Dietary bile acid supplementation in weaned piglets with intrauterine growth retardation improves colonic microbiota,metabolic activity,and epithelial function

Background Intrauterine growth retardation(IUGR)is one of the major constraints in animal production.Our previ-ous study showed that piglets with IUGR are associated with abnormal bile acid(BA)metabolism.This study explored whether dietary BA supplementation could improve growth performance and colonic development,function,micro-biota,and metabolites in the normal birth weight(NBW)and IUGR piglets.A total of 48 weaned piglets(24 IUGR and 24 NBW)were allocated to four groups(12 piglets per group):(i)NBW group,(ii)NBW+BA group,(iii)IUGR group,and(iv)IUGR+BA group.Samples were collected after 28 days of feeding.Results The results showed that dietary BA supplementation increased the length and weight of the colon and colon weight to body weight ratio,while decreased the plasma diamine oxidase(DAO)concentration in the NBW pig-lets(P<0.05).Dietary BA supplementation to IUGR piglets decreased(P<0.05)the plasma concentrations of D-lactate and endotoxin and colonic DAO and endotoxin,suggesting a beneficial effect on epithelial integrity.Moreover,dietary BA supplementation to NBW and IUGR piglets increased Firmicutes abundance and decreased Bacteroidetes abundance(P<0.05),whereas Lactobacillus was the dominant genus in the colon.Metabolome analysis revealed 65 and 51 differential metabolites in the colon of piglets fed a diet with/without BA,respectively,which was associated with the colonic function of IUGR piglets.Furthermore,dietary BA supplementation to IUGR piglets upregulated the expressions of CAT,GPX,SOD,Nrf1,IL-2,and IFN-γin colonic mucosa(P<0.05).Conclusions Collectively,dietary BA supplementation could improve the colonic function of IUGR piglets,which was associated with increasing proportions of potentially beneficial bacteria and metabolites.Furthermore,BA shows a promising application prospect in improving the intestinal ecosystem and health of animals.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development.AIM To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM patients.METHODS The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively.Among these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis.The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression.RESULTS Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,respectively.The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,respectively.High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent,and their combination can be used as an important index for the early prediction of FGR.

Pterostilbene attenuates intrauterine growth retardation-induced colon inflamm tion in piglets by modulating endoplasmic reticulum stress and autophagy

Background:Endoplasmic reticulum(ER)stress and autophagy are implicated in the pathophysiology of intestinal inflammation;however,their roles in intrauterine growth retardation(IUGR)-induced colon inflammation are unclear.This study explored the protective effects of natural stilbene pterostilbene on colon inflammation using the IUGR piglets and the tumor necrosis factor alpha(TNF-α)-treated human colonic epithelial cells(Caco-2)by targeting ER stress and autophagy.Results:Both the IUGR colon and the TNF-α-treated Caco-2 cells exhibited inflammatory responses,ER stress,and impaired autophagic flux(P<0.05).The ER stress inducer tunicamycin and the autophagy inhibitor 3-methyladenine further augmented inflammatory responses and apoptosis in the TNF-α-treated Caco-2 cells(P<0.05).Conversely,pterostilbene inhibited ER stress and restored autophagic flux in the IUGR colon and the TNF-α-treated cells(P<0.05).Pterostilbene also prevented the release of inflammatory cytokines and nuclear translocation of nuclear factor kappa B p65,reduced intestinal permeability and cell apoptosis,and facilitated the expression of intestinal tight junction proteins in the IUGR colon and the TNF-α-treated cells(P<0.05).Importantly,treatment with tunicamycin or autophagosome-lysosome binding inhibitor chloroquine blocked the positive effects of pterostilbene on inflammatory response,cell apoptosis,and intestinal barrier function in the TNF-α-exposed Caco-2 cells(P<0.05).Conclusion:Pterostilbene mitigates ER stress and promotes autophagic flux,thereby improving colon inflammation and barrier dysfunction in the IUGR piglets and the TNF-α-treated Caco-2 cells.

Intrauterine growth retardation affects liver bile acid metabolism in growing pigs:effects associated with the changes of colonic bile acid derivatives

Background:Intrauterine growth retardation(IUGR)is associated with severely impaired nutrient metabolism and intestinal development of pigs.Our previous study found that IUGR altered intestinal microbiota and metabolites in the colon.However,the consequences of IUGR on bile acid metabolism in pigs remained unclear.The present study aimed to investigate the bile acid metabolism in the liver and the profile of bile acid derivatives in the colon of grow-ing pigs with IUGR using bile acid targeted metabolomics.Furthermore,we determined correlations between colonic microbiota composition and metabolites of IUGR and normal birth weight(NBW)pigs at different growth stages that were 7,21,and 28-day-old,and the average body weight(BW)of 25,50,and 100 kg of the NBW pigs.Results:The results showed that the plasma total bile acid concentration was higher(P<0.05)at the 25 kg BW stage and tended to increase(P=0.08)at 28-day-old in IUGR pigs.The hepatic gene expressions related to bile acid synthe-sis(CYP7A1,CYP27A1,and NTCP)were up-regulated(P<0.05),and the genes related to glucose and lipid metabolism(ATGL,HSL,and PC)were down-regulated(P<0.05)at the 25 kg BW stage in IUGR pigs when compared with the NBW group.Targeted metabolomics analysis showed that 29 bile acids and related compounds were detected in the colon of pigs.The colonic concentrations of dehydrolithocholic acid and apocholic acid were increased(P<0.05),while isodeoxycholic acid and 6,7-diketolithocholic acid were decreased(P<0.05)in IUGR pigs,when compared with the NBW pigs at the 25 kg BW stage.Moreover,Spearman’s correlation analysis revealed that colonic Unclassified_[Mogi-bacteriaceae],Lachnospira,and Slackia abundances were negatively correlated(P<0.05)with dehydrolithocholic acid,as well as the Unclassified_Clostridiaceae abundance with 6,7-diketolithocholic acid at the 25 kg BW stage.Conclusions:These findings suggest that IUGR could affect bile acid and glucolipid metabolism in growing pigs,especially at the 25 kg BW stage,these effects being paralleled by a modification of bile acid derivatives concentra-tions in the colonic content.The plausible links between these modified parameters are discussed.

Helicobacter pylori's virulence and infection persistence define pre-eclampsia complicated by fetal growth retardation

AIM: To better understand the pathogenic role of Helicobacter pylori (H. pylori) in pre-eclampsia (PE), and whether it is associated or not with fetal growth retardation (FGR). METHODS: Maternal blood samples were collected from 62 consecutive pregnant women with a diagnosis of PE and/or FGR, and from 49 women with uneventful pregnancies (controls). Serum samples were evaluated by immunoblot assay for presence of specific antibodies against H. pylori antigens [virulence: cytotoxin-associated antigen A (CagA); ureases; heat shock protein B; flagellin A; persistence: vacuolating cytotoxin A (VacA)]. Maternal complete blood count and liver enzymes levels were assessed at delivery by an automated analyzer. RESULTS: A significantly higher percentage of H. pyloriseropositive women were found among PE cases (85.7%) compared to controls (42.9%, P < 0.001). There were no differences between pregnancies complicated by FGR without maternal hypertension (46.2%) and controls. Importantly, persistent and virulent infections (VacA/ CagA seropositive patients, intermediate leukocyte blood count and aspartate aminotransferase levels) were exclusively associated with pre-eclampsia complicated by FGR, while virulent but acute infections (CagA positive/ VacA negative patients, highest leukocyte blood count and aspartate aminotransferase levels) specifically correlated with PE without FGR. CONCLUSION: Our data strongly indicate that persistent and virulent H. pylori infections cause or contribute to PE complicated by FGR, but not to PE without feto-placental compromise.

The Predictive Value of Plasma Fibronectin Concentration on Fetal Growth Retardation at Earlier Stage of the Third Trimester

In order to evaluate the predictive value of maternal plasma fibronectin (FN) concentration at 24-34 weeks on fetal intrauterine growth retardation (IUGR), a prospective double-blinded study was performed. The maternal plasma FN concentrations were measured by using a rate nephelometric procedure in the 130 initial normal nulliparous pregnant woman at 24-34 gestational weeks. The outcome of pregnancies and birth weight of their infants were followed up. IUGR was defined as that the birth weight was less than the 10th percentile for gestational age. The receiver operating characteristic curves and predictive values of FN predicting on outcome of pregnancy with IUGR were analyzed. The results showed that: (1) In a cohort of 130 initially normal nulliparous pregnant women, IUGR occurred in 14 cases during the follow-up; (2) The plasma FN levels in the women with IUGR (467.58±104.43 mg/L) were significantly higher than in the normal control group (299.44±105.55 mg/L, P<0.01). However, there was no significant difference in the mean maternal age, gravidity, sampling gestational ages, delivering gestational ages between the two groups (P>0.05); (3) The areas under ROC curve for predicting the outcome of pregnancy in IUGR was 0.893; (4) At the cut point of 475 mg/L FN level, the sensitivity, specificity, positive predictive value, negative predictive value and Kappa index for predicting the outcomes of pregnancy in IUGR were 57.14 %, 95.69 %, 61.54 %, 94.87 %, 0.5455 respectively. It was concluded that the maternal plasma FN might be used as an earlier predictor for screening of IUGR.

Color Doppler Monitoring of Changes ofUtero-placental-fetal Circulation in Normal Pregnancy and Intrauterine Growth Retardation

The utero-placental-fetal circulation (UPFC) of 150 subjects duringsecond and third trimester was examined by using color DOppler. Of them 89 were normal woman and 58 were patients with intrauterine growth retardation (IUGR). Our results showed that UPFC was increased gradually during normal pregnant period. In IUGR patients it was revealed that TAV and Q of UmA,UmV and UtA decreased at 20th week of gestation, especially after 30th week.PI, RI and S/D ratio of UmA were increased, but TAV, Q of UmA and UmV were markly reduced, so was UtA. Pl were increased, but the changes of RI,S/D ratio in UtA were not significant. HemodynamicaI findings of UmA,UmV and UtA were abnormal in 92. 53 % of IUGR patients,Only 81. 03% present abnormal S/D ratio of UmA (P<0. 01) and the difference was statistically significant.Maternal serum E,, HPL level in IUGR were significantly lower than that of thenormal. 6KP level was reduced, TXB,/6KP ratio was significantly increased.TXB2/6KP ratio was markedIy related with TAV, Q of UmA, UmV and UtA.Our results suggested that using color doppler ultrasound for examination of hemodynamical changes of UmA, UmV and UtA could revealed UPFC function directly. It is one of the best methods for monitoring IUGR and might be used forearly diagnosis of IUGR. The main pathophysiological changes of IUGR were UPFC obstruction and placental disfunction.

Long-term implications of fetal growth restriction

Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of intrauterine growth velocity in the curve of intrauterine growth.However,the FGR definition is still debated,and there is a lack of a uniform definition in the literature.True IUGR,compared to constitutional smallness,is a pathological condition in which the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus.Infants with IUGR,compared to appropriately grown gestational age infants,have a significantly higher risk of mortality and neonatal complications with long-term consequences.Several studies have demonstrated how suboptimal fetal growth leads to long-lasting physiological alterations for the developing fetus as well as for the newborn and adult in the future.The long-term effects of fetal growth retardation may be adaptations to poor oxygen and nutrient supply that are effective in the fetal period but deleterious in the long term through structural or functional alterations.Epidemiologic studies showed that FGR could be a contributing factor for adult chronic diseases including cardiovascular disease,metabolic syndrome,diabetes,respiratory diseases and impaired lung function,and chronic kidney disease.In this review we discussed pathophysiologic mechanisms of FGR-related complications and potential preventive measures for FGR.

Effect of early nutrition on intestine development of intrauterine growth retardation in rats and its correlation to leptin

AIM：To investigate the intestine and body development of intrauterine growth retardation（IUGR）rats under early different protein diet and to analyze the correlation between leptin and intestine and body development．METHODS：An IUGR rat model was established by food restriction of pregnant female rats．Fifty-six neonatal IUGR rats and 24 neonatal normal rats were randomly divided into normal control group（Cgroup），IUGR model group （scgroup），low protein diet IUGR group（SL group），and high protein diet IUGR group（SH group）．Eight rats were killed per group at wk 0，4，and 12．Serum leptin，body weight（BW），body length（BL），intestinal weight（IW），intestinal length（IL），andintestinal disaccharidase（including lactase，maltase，and saccharase） were detected．RESULTS：BW（4．50±0．41g），BL（5．96±0．40cm），IW（0．05±0．01g），and IL（15.9±2．8cm）in neonatal IUGR rats were much lower than those in Cgroup（6．01±0．55g，6．26±0．44cm，0．10±0．02g，21.8±2．7cm，P〈0．05），while intestinal lactase and maltase activities were higher than those in Cgroup．SH group showed the fastest catch up growth and their BW，BL，IW，and IL reached the Cgroup level at wk 4．SC group showed relatively slower catch up growth than SH group，and their BW，BL，IW did not reach the Cgroup level at wk 4．SL group did not show intestine and body catch up growth．Intestinal maltase [344±33μmol／（min·q）]and saccharase activities[138±32μmol／（min·g）]in SL group were both markedly lower than nose in C group [751±102，258±271μmol／（min·g），P〈0．05]．There were no significant difierences in lactase activities at wk 4 and disaccharidase activities at wk 12 among all groups（P〈0．05）．The leptin level in SL group（0．58±0．12ng／mL） was the highest in all groups，and much lower in SH group（0．21±0．03ng／mL） than that in any other IUGR groups at wk 4（P〈0．05）．Leptin was negatively related to BW （r=-0．556，P=0．001），IW（r=-0．692，P=0．001） and IL（r=-0．738，P=0．000）at wk 4，while no correlation was found at wk 12．CONCLUSION：High protein diet is a reasonable early nutritional mode to IUGR rats in promoting intestine and body catch up growth．

Effect of Dietary Folic Acid Supplementation on Growth Performance and Hepatic Protein Metabolism in Early-Weaned Intrauterine Growth Retardation Piglets

To investigate the effects of dietary supplementation with folic acid on growth performance, hepatic protein metabolism and serum biochemical indices of early-weaned intrauterine growth retardation （IUGR） piglets, 24 male （Durocx （LandracexYorkshire）） weaned （14-d-old） IUGR piglets were randomly divided into 3 treatments with 8 replicates of 1 piglet per replicate. The piglets in each treatment were fed basal diet supplementation with either 0 （control）, 5 and 10 mg kg^-1 folic acid. The trial lasted for 21 d. Dietary folic acid supplementation reduced average daily feed intake （ADFI） （P〈0.05）. In addition, the average daily gain （ADG） in 10 mg kg^-1 folic acid group was significantly decreased （P〈0.01） and the ratio of feed：gain （F/G） increased slightly （P〉0.05）. Serum folic acid concentration increased （P〈0.01） with increasing folic acid inclusion, however, serum homocysteine concentration decreased significantly （P〈0.01）. Enhanced serum urine nitrogen （SUN） and diminished serum total protein （TP） as well as liver TP content were observed in 10 mg kg^-1 folic acid group （/＇〈0.05）. Furthermore, the relative mRNA expressions of insulin-like growth factor 1 （IGF-1） and mammalian target of rapamycin （m-TOR） in liver were respectively tended to reduce （P=0.06） and significantly downregulated （P〈0.05） in 10 mg kg1 group, in compared with 5 mg kg1 group. However, when compared with control group, folic acid supplementation had no significant effect on the mRNA abundance of IGF- 1 and m-TOR. The results indicated that supplementation with 10 mg kg-I folic acid impaired growth performance and hepatic protein metabolism of early-weaned IUGR piglets while 5 mg kg-~ folic acid enriched diet exerted limited positive effects.

Antioxidant capacity and concentration of redox-active trace mineral in fully weaned intra-uterine growth retardation piglets

Background： The redox status of intra-uterine growth retardation（IUGR） piglets post-weaning has been poorly studied.Methods： Newborns from twenty-four sows were weighted, weaned at 21 d and fed a starter diet until sampling.Sampling was done at 14 d post-weaning. A piglet was defined as IUGR when its birth weight was 2 SD below the mean birth weight of the total population. At weaning, eighteen piglets with nearly equal body weight from each category（i.e. IUGR or normal birth weight（NBW） piglets） were selected and then allocated to two treatments,consisted of six replicates with each pen having three piglets.Results： Compared with NBW group, IUGR significantly decreased average daily gain（P 〈 0.001）, average daily feed intake（P = 0.003）, and feed efficiency（P 〈 0.001） of piglets during the first two weeks post-weaning. IUGR decreased the activities of total antioxidant capacity（P = 0.019）, total superoxide dismutase（T-SOD, P = 0.023）,and ceruloplasmin（P = 0.044） but increased the levels of malondialdehyde（P = 0.040） and protein carbonyl（P = 0.010） in plasma. Similarly, the decreased activities of T-SOD（P = 0.005）, copper- and zinc-containing superoxide dismutase（Cu/Zn-SOD, P = 0.002）, and catalase（P = 0.049） was observed in the liver of IUGR piglets than these of NBW piglets. IUGR decreased hepatic Cu/Zn-SOD activity（P = 0.023） per unit of Cu/Zn-SOD protein in piglets when compared with NBW piglets. In addition, IUGR piglets exhibited the decreases in accumulation of copper in both plasma（P = 0.001） and liver（P = 0.014）, as well as the concentrations of iron（P = 0.002） and zinc（P = 0.048） in liver. Compared with NBW, IUGR down-regulated m RNA expression of Cu/Zn-SOD（P = 0.021） in the liver of piglets.Conclusions： The results indicated that IUGR impaired antioxidant capacity and resulted in oxidative damage in fully weaned piglets, which might be associated with the decreased levels of redox-active trace minerals. This study highlights the importance of redox status in IUGR offspring and provides a rationale for alleviating oxidative damage by dietary interventions aiming to supplement trace minerals and to restore redox balance in the future.

EFFECIS OF TEMPERATURE AND OVERLOAD RETARDATION ON CORROSION FATIGUE CRACK GROWTH OF HIGH STRENGTH STEEL

The fatigue crack growth rate (CGR) of ultra high strength steel 30CrMnSiNi2A in distilled water at 18,35 and 55℃ were measured.It was confirmed that the temperature is strongly af- fected on the corrosion fatigue CGR of ultra high strength steel.An expression concerning the effects of Δ K and temperature on the CGR was proposed.The fact that the apparent activation energy (36.6 kJ/mol) resulted from regressive analysis of CGR data was similar to the activation energy of hydrogen diffusion in γ-Fe,strongly supporting the theory of hydrogen-assisted crack growth.The overload retardation effect was greatly reduced in cor- rosion fatigue crack growth,especially at lower frequency,e.g.,0.1 Hz.This phenomenon might be due to the increase of the SCC component of CGR after an overload.

Placental Isoferritin Action in Pathogenesis of Pre-eclampsia and/or Intrauterine Growth Retardation and Its Earlier Predictive Value

In order to investigate the role of placental isoferritin (PLF) in pathogenesis of pre-eclampsia and/or intrauterine growth retardation (IUGR) and its earlier predictive value, a prospective double-blinded study was performed. In 120 initial normal pregnant women at earlier third trimester (from 24 to 34 weeks), plasma placental isoferritin and nitric oxide (NO) metabolites (nitrite/nitrate) (NO 2 -/NO 3 -) were examined by using ELISA and Criess assay respectively. The outcome of pregnancies and birth weight of their infants were followed up. The receiver operating characteristic curves (ROC) and predictive values of PLF predicting the outcome of pregnancy with IUGR, pre-eclampsia were analyzed. Results showed that in 120 initial normal pregnant women, IUGR occurred in 15 pregnant women (IUGR group) and pre-eclampsia in 19 (pre-eclampsia group), and the remaining 86 had normal pregnancy (normal group). The levels of plasma placental isoferritin were significantly decreased in IUGR group (260.01±58.95) μg/ml and pre-eclampsia group (285.31±53.73) μg/ml as compared with those in normal group (775.62±89.32) μg/ml at earlier third trimester (both P<0.01). The levels of plasma NO were significantly increased in IUGR group (61.57±46.22) μmol/L and pre-eclampsia group (58.37±30.52) μmol/L as compared with those in the normal group (35.29±24.46) μmol/L (both P<0.01). There was no significant difference in plasma placental isoferritin and NO levels between IUGR group and pre-eclampsic group (both P>0 05). The plasma placental isoferritin was negatively correlated with NO levels (r=0.329,P<0 01). The areas under ROC of PLF predicting IUGR and pre-eclampsia were 0.977 and 0.905 respectively. At the cut point of 400 μg/ml PLF level, the sensitivity, specificity, positive predictive value, negative predictive value and Kappa index of PLF levels predicting the outcome of pregnancy with pre-eclampsia were 100 %, 85.15 %, 55.88 %, 100 % and 0.645 respectively. At the cut point of 390 μg/ml PLF level, the sensitivity, specificity, positive predictive value, negative predictive value and Kappa index of PLF levels predicting the outcome of pregnancy with IUGR were 100 %, 81.9 %, 44.12 %, 100 % and 0.663 respectively. It was concluded that the decrease of plasma placental isoferritin levels at earlier third trimester was associated with IUGR and/or pre-eclampsia, and the endothelial cell damage may be one of its mechanisms. The plasma PLF level can be used as an earlier predictor for screening of IUGR and/or pre-eclampsia.

Study of the Effects of Glucocorticoid on Growth and Adult Final Height in Children with Primary Nephrotic Syndrome

Objective: To analyze the epidemiological characteristics of growth, as well as factors associated with growth retardation in children with primary nephrotic syndrome (PNS), and to investigate the effect of glucocorticoid (GC) use duration on growth retardation in these children. Methods: Clinical and laboratory data of 353 PNS children treated at our hospital from July 2014 to June 2015 were collected through the medical record management system. Height, weight, and GC usage were recorded. Follow-up assessments were conducted in August 2022 for the original group, recording height, weight, and GC usage. Height and weight were evaluated using standard deviation scores (SDS). Categorical data were analyzed using chi-square test while continuous measurement data were analyzed using t-test or rank-sum test. Linear regression was used to assess the association between two single independent variables, and logistic regression analysis was used to screen for risk factors related to growth retardation in children with PNS. Results: Among the 353 PNS children enrolled in this study, male-to-female ratio of 2.64:1 (256 males vs 97 females). A total of 119 children exhibited growth retardation, incidence rate of 33.71%. The duration of GC usage among those with growth retardation was significantly longer compared to those without it (762.81 ± 934.50 days vs 263.77 ± 420.49 days;p Conclusion: PNS children treated with GC have a high incidence of growth retardation, and a high proportion of short stature in adulthood, especially in children with growth retardation in childhood, most of them have short stature after grown up. Time of GC usage is a risk factor for growth retardation in children with PNS.

EFFECTS OF EARLY NUTRITION INTERVENTION ON IGF1, IGFBP3,INTESTINAL DEVELOPMENT, AND CATCH-UP GROWTH OF INTRAUTERINE GROWTH RETARDATION RATS

To investigate the effects of early nutritional intervention on the serum insulin-like growth factor-1 (IGF1),insulin-like growth factor binding protein 3 (IGFBP3), intestinal development, and catch-up growth of intrauterine growth retardation (IUGR) rats by giving the IUGR new born rats different protein level diet. Methods IUGR rat model was built by starvation of pregnant female rats. Twenty-four IUGR pups and 8 normal pups were divided randomly into 4 groups: normal control group (C group); IUGR control group(S group), IUGR low-protein diet group (SL group), and IUGR high-protein diet group (SH group). Detected the serum IGF1, IGFBP3, body weight, body length, intestinal weight length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT), and disaccharidase at the 4th week. Results (1) The SH group showed the fastest catch-up growth, serum IGF1, IGFBP3, VH, and VSA were significantly higher than those of normal control group and IUGR control group. The intestinal weight and length, and the activities of lactase and saccharase of the SH group also reached the normal control group level. (2) The SL group kept on small size, the serum IGF1, IGFBP3, and most of intestinal histological indexes were all significantly lower than other groups. (3) IGF-1, IGFBP3 were positively correlated to intestinal VH, VSA, saccharase, body weight and length. Conclusions The serum IGF1 was a sensitive index to the catch-up growth. The early nutritional intervention of high-protein diet after birth is helpful for the catch-up growth of IUGR through promoting the intestinal development and the ab-sorption of nutrition

INTRAUTERINE GROWTH RETARDATION AT FULL TERM PREGNANCIES WITH ENDOCRINE FACTORS

Objective To investigate the relationship between intrauterine growth retardation (IUGR) and endocrine parameters so as to assess the effects or the main endocrine ractors on IUGR. The concentrations of growth hormone(GH), insulin, T3, T4 and TSH were measured in umbilical cord blood, amniotic fluid and maternal serum.Methods The samples were collected from 23 pregnant women who were diagnosed as the full term IUGR, 42 normal full term pregnant women with normal infants’ weight were taken as control. Growth hormone and insulin were measured by radioimmunoassay. T3, T4 and TSH were investigated by micro-radioimmunoassay. Results The concentrations of growth hormone, insulin and T4 in umbilical cord blood were lower in IUGR than that in control group(GH4. 63μ/L vs 7. o1μg/L, insulin 1o. 68μIU/ml vs 31. 44μIU/ml, T487. 39nmol/L vs 138. 1onmol/L. P <o. o5, o. o5 and o. o5, respectively). The TSH concentration in umbilical cord blood was higher in IUGR than in control group (1o. 84μmIU/L vs 5. 75μmIU/L, P <o. o1 ). The concentration of growth hormone in maternal serum and the concentration of insulin in amniotic fluid were also lower in IUGR group than in control group(GH 1. 77μg/L vs 2. 74μg/L,P <o. o1, insulin 5. 84μIU/ml vs 15. 64μIU/ml, P <o. o1). Conclusion This study confirms that full term neonates with IUGR are abnormal in endocrine factors. The inadequacy of growth hormone may be one of the causes of IUGR. The relatlve scarcity of growth hormone and insulin seems to be a factor to compromise the fetus’ metabolism. Besides, the early hypothyrosis of infants with IUGR might protect them from unfavorable environment in the uterine.

Effects of dietary Bacillus amyloliquefaciens supplementation on growth performance,intestinal morphology, inflammatory response, and microbiota of intra-uterine growth retarded weanling piglets

Background: The focus of recent research has been directed toward the probiotic potential of Bacillus amyloliquefaciens(BA) on the gut health of animals. However, little is known about BA's effects on piglets with intra-uterine growth retardation(IUGR). Therefore, this study investigated the effects of BA supplementation on the growth performance,intestinal morphology, inflammatory response, and microbiota of IUGR piglets.Methods: Eighteen litters of newborn piglets were selected at birth, with one normal birth weight(NBW) and two IUGR piglets in each litter(i.e., 18 NBW and 36 IUGR piglets in total). At weaning, the NBW piglet and one of the IUGR piglets were assigned to groups fed a control diet(i.e., the NBW-CON and IUGR-CON groups). The other IUGR piglet was assigned to a group fed the control diet supplemented with 2.0 g BA per kg of diet(i.e., IUGR-BA group). The piglets were thus distributed across three groups for a four-week period.Results: IUGR reduced the growth performance of the IUGR-CON piglets compared with the NBW-CON piglets. It was also associated with decreased vil us sizes, increased apoptosis rates, reduced goblet cel numbers, and an imbalance between pro-and anti-inflammatory cytokines in the smal intestine. Supplementation with BA improved the average daily weight gain and the feed efficiency of the IUGR-BA group compared with the IUGR-CON group(P < 0.05). The IUGR-BA group exhibited increases in the ratio of jejunal vil us height to crypt depth, in ileal vil us height, and in ileal goblet cel density. They also exhibited decreases in the numbers of jejunal and ileal apoptotic cel s and ileal proliferative cel s(P < 0.05). Supplementation with BA increased interleukin 10 content, but it decreased tumor necrosis factor alpha level in the smal intestines of the IUGR-BA piglets(P < 0.05). Furthermore, compared with the IUGR-CON piglets, the IUGR-BA piglets had less Escherichia coli in their jejunal digesta, but more Lactobacil us and Bifidobacterium in their ileal digesta(P < 0.05).Conclusions: Dietary supplementation with BA improves morphology, decreases inflammatory response, and regulates microbiota in the smal intestines of IUGR piglets, which may contribute to improved growth performance during early life.

Abnormal adipose tissue-derived microbes drive metabolic disorder and exacerbate postnatal growth retardation in piglet

Postnatal growth retardation(PGR)frequently occurs during early postnatal development of piglets and induces high mortality.To date,the mechanism of PGR remains poorly understood.Adipose tissue-derived microbes have been documented to be associated with several disorders of metabolism and body growth.However,the connection between microbial disturbance of adipose tissue and pig PGR remains unclear.Here,we investigated piglets with PGR and found that the adipose tissue of PGR piglets was charac-terized by metabolism impairment,adipose abnormality,and specific enrichment of culturable bacteria from Proteobacteria.Gavage of Sphingomonas paucimobilis,a species of Sphingomonas genus from the alphaproteobacteria,induced PGR in piglets.Moreover,this bacterium could also lead to metabolic disorders and susceptibility to acute stress,resulting in weight loss in mice.Mechanistically,multi-omics analysis indicated the changes in lipid metabolism as a response of adipose tissue to abnormal microbial composition.Further experimental tests proved that one of the altered lipids phosphatidylethanolamines could rescue the metabolism disorder and growth retardation,thereby suppressing the amount of Sphingomonas in the adipose tissue.Together,these results highlight that the microbe–host crosstalk may regulate the metabolic function of adipose tissue in response to PGR.