Growth Restricted Pregnancies Research Articles

OPtimal TIming of antenatal COrticosteroid administration in pregnancies complicated by early-onset fetal growth REstriction: results of a large multicenter cohort study (the OPTICORE study).

Early-onset fetal growth restriction as consequence of placental insufficiency frequently requires iatrogenic preterm birth. Administration of antenatal corticosteroids reduces risks of neonatal morbidity and mortality following preterm birth and is most beneficial if the neonate is delivered within 2weeks following treatment. International guidelines on fetal growth restriction pregnancies do not provide directives regarding the timing of antenatal corticosteroids, resulting in practice variation. This study compared the 2 main timing strategies of antenatal corticosteroids administration in the Netherlands for early-onset fetal growth restriction pregnancies: administration when the umbilical artery shows a pulsatility index above the 95th centile with (A) positive end-diastolic flow vs (B) absent or reversed end-diastolic velocity. A multicenter retrospective cohort study was performed in 6 tertiary hospitals in the Netherlands between 2012 and 2021. Three hospitals practiced timing strategy A and 3 strategy B. The primary outcome was defined as a composite of perinatal and in-hospital mortality. Secondary outcomes were in line with the core outcome set for fetal growth restriction. Mixed effects analyses were performed adjusted for birthweight z-score and gestational age at birth to compare the 2 timing strategies. A total of 1453 patients were included, of whom 871 and 582 were treated according to timing strategy A and B, respectively. Corticosteroids were administered at a mean gestational age of 28weeks and 3days (standard deviation 16.0days) in timing strategy A and 28weeks and 4days (standard deviation 15.8days) in timing strategy B. The median birthweights were 1050 (range 795, 1350) and 1060 (range 801, 1339) in timing strategy A and B, respectively. Although not statistically significant, rates of perinatal and in-hospital mortality were increased in timing strategy B infants (7.2% vs 9.8%; adjusted odds ratio 1.47; 95% confidence interval 0.97-2.22, reference A). 52.8% and 53.6% of patients in strategy A and B, respectively, delivered within the corticosteroids therapeutic window of 2 to 14days (P value .663), with a median time between corticosteroid administration and delivery of 6days for strategy A and 6days for strategy B. Timing strategy B was associated with more necrotizing enterocolitis (3.7% vs 7.6%; adjusted odds ratio 2.18; 95% confidence interval 1.29-3.69), but less respiratory distress syndrome (39.6% vs 34.5%; adjusted odds ratio 0.63; 95% confidence interval 0.45-0.88) and bronchopulmonary dysplasia (18.9% vs 17.4%; adjusted odds ratio 0.69; 95% confidence interval 0.50-0.96). Other outcomes were similar between groups. Timing strategy B seemed to be associated with higher rates of the composite of perinatal and in-hospital mortality, which could not be explained by a difference in time intervals between corticosteroid administration and delivery. Importantly, most pregnant women delivered outside the presumed therapeutic corticosteroid window. Future research should focus on the improvement of the timing of antenatal corticosteroids in pregnancies complicated by early-onset fetal growth restriction and the identification of other differences in ante- and/or postnatal management to explain differences in outcomes, given the high risk for neonatal morbidity and mortality in this setting.

TREATMENT OF EARLY-ONSET FETAL GROWTH RESTRICTION WITH LOW MOLECULAR WEIGHT HEPARIN DOES NOT PROLONG GESTATION: A RANDOMIZED CLINICAL TRIAL

Although there is a biological basis for it, there is scarce evidence on the effect of heparin in ameliorating placental insufficiency and maximizing gestational age at delivery among fetal growth restriction (FGR) pregnancies. To explore the effectiveness of treatment using low molecular weight heparin (LMWH) at a prophylactic dose started at the time of diagnosis in prolonging gestation in pregnancies with early-onset fetal growth restriction (FGR). This was a phase III, multicenter, triple-blind, parallel-arm randomized clinical trial conducted in two university hospitals in Spain. Singleton pregnancies qualifying for early-onset placental FGR according to the adapted Delphi consensus (20+0-31+6 weeks at diagnosis with umbilical artery Doppler with absent/reversed diastolic flow; or estimated fetal weight <10th percentile plus pulsatility index (PI) of umbilical artery Doppler >95th percentile; or estimated fetal weight <10th percentile plus mean PI of uterine artery Doppler >95th) were randomized to receive either subcutaneous treatment with bemiparin 3500 IU/0.2 mL/day or a placebo from inclusion at diagnosis to the time of delivery. The primary outcomes were prolongation of pregnancy from inclusion to live birth (days) and gestational age at live birth (days). 49 patients were included (23 in the LMWH group and 26 in the placebo group). In the LMWH group, the median prolongation of pregnancy was 42 days, while in the placebo group it was 41.5 days (median difference 0.5 days [95% CI -22.7 to 6.3] (p=0.667) and in the LMWH group, the median gestational age at delivery was 35.1 weeks, while in the placebo group, it was 34.6 weeks (median difference 0.5 weeks [95% CI -3.4 to 1.2] (p=0.639). The use of prophylactic dose LMWH started at the time of diagnosis does not prolong pregnancy in individuals with early-onset fetal restriction.

The efficacy of sildenafil therapy in dismal prognosis early-onset intrauterine growth restriction: the STRIDER RCT

Background Severe early-onset intrauterine growth restriction is associated with stillbirth, neonatal death and neurodevelopmental impairment. There is no treatment for intrauterine growth restriction with timely delivery being the only management option. Placentas from intrauterine growth restriction pregnancies often show failure to remodel maternal spiral arteries leading to a persistent vasoactive responsiveness. Sildenafil, a phosphodiesterase type 5 inhibitor, potentiates naturally occurring nitrous oxide, encouraging vasodilation of vasoactive vessels. Previous studies in animal models and humans show recovery of placental function and improvement in fetal growth. The STRIDER trial aimed to address whether treatment with sildenafil is beneficial to fetal growth and perinatal and toddler outcomes. Methods The STRIDER trial was a superiority, randomised double-blind placebo-controlled trial that was carried out in 19 fetal medicine units in the United Kingdom. Women with a singleton pregnancy between 22+0 and 29+6 weeks’ gestation, with severe early-onset intrauterine growth restriction, were asked to participate. Women were randomised (1 : 1) to receive either sildenafil 25-mg three times daily or placebo until 31+6 weeks’ gestation or delivery. Women were stratified by site and their gestational age at randomisation (before 26+0 or at 26+0 weeks or later). Severe intrauterine growth restriction was defined as a combination of estimated fetal weight or abdominal circumference below the 10th percentile and absent or reversed end-diastolic blood flow in the umbilical artery on Doppler velocimetry. The primary outcome was the time from randomisation to delivery, measured in days with a 1-week difference deemed to be clinically significant. The phase 2 study followed up all babies alive at discharge to assess for cardiovascular function and neurodevelopment at 2 years of age. Results Between 21 November 2014 and 6 July 2016, a total number of 135 women were recruited to the study, of these 70 were assigned to sildenafil and 65 to the placebo. No difference was found in the median randomisation to delivery interval between sildenafil [17 days (interquartile range 7–24)] and placebo [18 days (8–28), p = 0.23]. Live births [relative risk 1.06, 95% confidence interval 0.84 to 1.33; p = 0.62], fetal deaths (relative risk 0.89, 95% confidence interval 0.54 to 1.45; p = 0.64), neonatal deaths (relative risk 1.33, 95% confidence interval 0.54 to 3.28; p = 0.53), and birthweight [mean difference −14 g (95% confidence interval −100 to 126); p = 0.81] did not differ between the treatment arms and no differences were found for other maternal or perinatal secondary outcomes. Eight serious adverse events were reported during the study (six in the placebo group and two in the sildenafil group); none of these were attributed to sildenafil. Seventy-five babies were discharged alive from the neonatal unit and of those 61 were available for follow-up with 32 treated with sildenafil and 29 with placebo. Of those that did not have a follow-up 1 baby died (placebo) and 3 declined follow-up and 10 were uncontactable. There was no difference in neurodevelopment, or blood pressure for infants treated with sildenafil versus placebo. Infants who received sildenafil had a greater head circumference compared to those who received placebo (median difference 49.25 cm, interquartile range 46.4–50.26 vs. 47.17 cm, 95% confidence interval 44.71 to 48.95). Conclusion Sildenafil did not prolong pregnancy or improve pregnancy outcomes. There was no effect from sildenafil treatment on infant neurodevelopment. Our data show that sildenafil should not be prescribed for fetal growth restriction. Trial registration This trial is registered as ISRCTN39133303. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/62/109) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 18. See the NIHR Funding and Awards website for further award information.

Monitoring of maternal-fetal oxygen transfer in ex vivo full term human placenta from normal and growth restricted pregnancies.

Monitoring of maternal-fetal oxygen transfer in ex vivo full term human placenta from normal and growth restricted pregnancies.

Long-Term Maternal and Neonatal Outcomes Following Birth in Fetal Growth Restricted Pregnancies

Long-Term Maternal and Neonatal Outcomes Following Birth in Fetal Growth Restricted Pregnancies

Prognostic value of angiogenic markers in pregnancy with fetal growth restriction.

Pregnancies with fetal growth restriction (FGR) are at increased risk for pre-eclampsia. Angiogenic markers including soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are altered in pregnancies complicated by FGR, but their utility for predicting pre-eclampsia in growth-restricted pregnancies is uncertain. This study aimed to evaluate the prognostic value of angiogenic markers for predicting the development of pre-eclampsia in pregnancies with FGR and suspected pre-eclampsia. This was a retrospective study of singleton pregnancies with FGR, defined according to Delphi consensus criteria, which underwent sampling of sFlt-1 and PlGF for suspicion of pre-eclampsia at the Medical University of Vienna, Vienna, Austria, between 2013 and 2020. Women with an established diagnosis of pre-eclampsia at sampling were excluded. Cox regression analysis and logistic regression analysis were performed to evaluate the association of angiogenic markers with the development of pre-eclampsia at various timepoints. In this cohort of 93 women, pre-eclampsia was diagnosed in 14 (15.1%) women within 1 week after sampling, 21 (22.6%) within 2 weeks after sampling and 38 (40.9%) at any time after assessment. The sFlt-1/PlGF ratio consistently showed a stronger association with the development of pre-eclampsia compared to sFlt-1 or PlGF alone (pre-eclampsia within 1 week: area under the receiver-operating-characteristics curve, 0.87 vs 0.82 vs 0.72). Models including the sFlt-1/PlGF ratio were associated more strongly with pre-eclampsia hazard compared to models including sFlt-1 or PlGF alone (concordance index, 0.790 vs 0.759 vs 0.755). The risk classification capability of the sFlt-1/PlGF ratio decreased after the 2-week timepoint. The established cut-off value for the sFlt-1/PlGF ratio of < 38 was effective for ruling out pre-eclampsia within 2 weeks, with a negative predictive value of 0.933 and sensitivity of 0.952. Use of the sFlt-1/PlGF ratio is preferrable to the use of PlGF alone for the prediction of pre-eclampsia in pregnancies with FGR. Established cut-offs for ruling out the development of pre-eclampsia in the short term seem to be effective in these patients. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Placental differences between severe fetal growth restriction and hypertensive disorders of pregnancy requiring early preterm delivery: morphometric analysis of the villous tree supported by artificial intelligence

The great obstetrical syndromes of fetal growth restriction and hypertensive disorders of pregnancy can occur individually or be interrelated. Placental pathologic findings often overlap between these conditions, regardless of whether 1 or both diagnoses are present. Quantification of placental villous structures in each of these settings may identify distinct differences in developmental pathways. This study aimed to determine how the quantity and surface area of placental villi and vessels differ between severe, early-onset fetal growth restriction with absent or reversed umbilical artery Doppler indices and hypertensive disorders of pregnancy or the 2 conditions combined among subjects with disease severity that warrant early preterm delivery. We hypothesized that the trajectories of placental morphogenesis diverge after a common initiating insult of deep defective placentation. Specifically, we postulated that only villi are affected in pregnancy-related hypertension, whereas both villous and vascular structures are proportionally diminished in severe fetal growth restriction with no additional effect when hypertension is concomitantly present. In this retrospective cohort study, paraffin-embedded placental tissue was obtained from 4 groups, namely (1) patients with severe fetal growth restriction with absent or reversed umbilical artery end-diastolic velocities and hypertensive disorders of pregnancy, (2) patients with severe fetal growth restriction with absent or reversed umbilical artery Doppler indices and no hypertension, (3) gestational age-matched, appropriately grown pregnancies with hypertensive disease, and (4) gestational age-matched, appropriately grown pregnancies without hypertension. Dual immunohistochemistry for cytokeratin-7 (trophoblast) and CD34 (endothelial cells) was performed, followed by artificial intelligence-driven morphometric analyses. The number of villi, total villous area, number of fetoplacental vessels, and total vascular area across villi within a uniform region of interest were quantified. Quantitative analyses of placental structures were modeled using linear regression. Placentas from pregnancies complicated by hypertensive disorders of pregnancy exhibited significantly fewer stem villi (-282 stem villi; 95% confidence interval,-467 to-98; P<.01), a smaller stem villous area (-4.3 mm2; 95% confidence interval,-7.3 to-1.2; P<.01), and fewer stem villous vessels (-4967 stem villous vessels; 95% confidence interval,-8501 to-1433; P<.01) with no difference in the total vascular area. In contrast, placental abnormalities in cases with severe growth restriction were limited to terminal villi with global decreases in the number of villi (-873 terminal villi; 95% confidence interval,-1501 to-246; P<.01), the villous area (-1.5 mm2; 95% confidence interval,-2.7 to-0.4; P<.01), the number of blood vessels (-5165 terminal villous vessels; 95% confidence interval,-8201 to-2128; P<.01), and the vascular area (-0.6 mm2; 95% confidence interval,-1.1 to-0.1; P=.02). The combination of hypertension and growth restriction had no additional effect beyond the individual impact of each state. Pregnancies complicated by hypertensive disorders of pregnancy exhibited defects in the stem villi only, whereas placental abnormalities in severely growth restricted pregnancies with absent or reversed umbilical artery end-diastolic velocities were limited to the terminal villi. There were no significant statistical interactions in the combination of growth restriction and hypertension, suggesting that distinct pathophysiological pathways downstream of the initial insult of defective placentation are involved in each entity and do not synergize to lead to more severe pathologic consequences. Delineating mechanisms that underly the divergence in placental development after a common inciting event of defective deep placentation may shed light on new targets for prevention or treatment.

Umbilical–portal–systemic venous shunt and intrauterine growth restriction: an inquiry from a prospective study

BackgroundThe investigation of the fetal umbilical-portal venous system is based on the premise that congenital anomalies of this system may be related to adverse perinatal outcomes. Several retrospective small studies have reported a well-established association between umbilical–portal–systemic venous shunts and fetal growth restriction. However, the prevalence of portosystemic shunts in the fetal growth restricted population is yet to be determined. ObjectivesThe aims of this study were:1. To determine the prevalence of fetal umbilical–portal–systemic venous shunts in pregnancies complicated by fetal growth restriction.2. To compare the perinatal and neonatal outcome of fetal growth restriction pregnancies with and without umbilical–portal–systemic venous shunts. Study DesignA prospective cross-sectional study of pregnancies diagnosed with fetal growth restriction, as defined by the Society for Maternal-Fetal Medicine fetal growth restriction guidelines. All participants underwent a detailed anomaly scan supplemented with a targeted scan of the fetal portal system. Venous shunts were diagnosed using color Doppler mode. The perinatal outcomes of fetal growth restriction pregnancies with and without umbilical–portal–systemic venous shunts were compared. ResultsOne hundred and fifty cases of fetal growth restriction were recruited. The prevalence of umbilical–portal–systemic venous shunts in our cohort was 9.3% (n=14). Compared to the control group (fetal growth restriction without umbilical–portal–systemic venous shunts, n=136), the study group had a significantly lower mean gestational age at time of fetal growth restriction diagnosis [29.7 (±5.6) vs. 32.47 (±4.6) weeks of gestation, p=0.036] as well as an earlier gestational week at delivery [33.50 (±6.0) vs. 36.13 (±2.8), p=0.005]. The study group had a higher rate of fetal death (21.4% vs. 0.7%, p<0.001) and accordingly a lower rate of live births (71.4% vs. 95.6%, p=0.001). Associated additional fetal vascular anomalies were significantly more prevalent in the study group compared to controls (35.7% vs. 4.4%, respectively, p=<0.001). The rate of other associated anomalies was similar. The study group had a significantly lower rate of abnormal uterine artery Doppler indices (0% vs. 40.4% p=0.011) and a higher rate of abnormal ductus venosus Doppler indices (64.3% vs. 23% p=0.001). There were no cases of hypertensive disorders of pregnancy in the study group compared to 12.5% in the control group (p=0.16). Other perinatal and neonatal outcomes were comparable. ConclusionsUmbilical–portal–systemic venous shunt is a relatively common finding in growth restricted fetuses. Compared to fetal growth restriction pregnancies with a normal portal system, these pregnancies complicated by FGR and umbilical–portal–systemic venous shunt are associated with different Doppler flow pattern, increased risk for fetal death, earlier presentation of fetal growth restriction, lower gestational age at delivery, additional congenital vascular anomalies and a lower rate of pregnancy induced hypertensive disorders. Meticulous sonographic evaluation of the portal system should be considered in the prenatal workup of fetal growth restriction, as umbilical–portal–systemic venous shunts may have implications on perinatal outcome.

Maternal serum fatty acid binding protein-4 level is upregulated in fetal growth restriction with abnormal Doppler flow patterns.

This study aimed to determine fatty acid binding protein-4 (FABP-4) concentrations in maternal serum of fetal growth restriction (FGR) pregnancies and controls of normal pregnancies. Furthermore, we hypothesized that the alterations in FABP-4 levels might correlate with FGR severity. We performed this prospective case-control study with 83 pregnant women. The study groups included 26 FGR pregnancies without abnormal fetal Doppler flow patterns and 25 pregnancies complicated with FGR accompanied by abnormal fetal Doppler flow patterns. The median serum FABP-4 concentrations were significantly higher in the FGR cases with abnormal Doppler flow pattern group (2.09 ng/mL) than in the FGR cases without abnormal Doppler flow pattern group (1.62 ng/mL) and the control group (1.20 ng/mL, p < 0.001). A significant negative correlation was observed between maternal serum FABP-4 levels and time to birth from blood sample collection (r = -0.356 and p = 0.001), gestational week at birth (r = -0.386 and p < 0.001), and birth weight (r = -0.394 and p < 0.001). A 1.35 ng/mL cut-off value of serum FABP-4 level could be used to discriminate FGR cases with a 78.4% sensitivity and 60.6% specificity. The optimal cut-off value of FABP-4 levels as an indicator for the diagnosis of FGR with abnormal Doppler flow pattern was estimated to be 1.76 ng/mL, which yielded a sensitivity of 84.0% and a specificity of 75.8%. FABP-4 is a crucial biomarker in the diagnosis and determining the severity of pregnancies with restricted fetal growth. We consider that FABP-4 is a powerful, reliable, and unique biomarker to diagnose FGR pregnancies.

EP18.17: Prediction of pre‐eclampsia and fetal growth restriction in pregnancies with systemic lupus erythematosus

EP18.17: Prediction of pre‐eclampsia and fetal growth restriction in pregnancies with systemic lupus erythematosus

OP15_6. Effect of pentaerythrityltetranitrate (PETN) on the development of fetal growth restriction in pregnancies with impaired uteroplacental perfusion at mid gestation – a double blinded randomised multicentre trial

OP15_6. Effect of pentaerythrityltetranitrate (PETN) on the development of fetal growth restriction in pregnancies with impaired uteroplacental perfusion at mid gestation – a double blinded randomised multicentre trial

Silicone breast implants may contribute to early-onset fetal growth restriction.

There are many studies showing that silicone breast implants may affect lactation, but few analyzed whether these implants affect placentation. We observed that many mothers with growth-restricted pregnancies had inflammatory conditions, such as silicone breast implants or giardiasis. This single-center cohort study assessed the prevalence of inflammatory conditions in normotensive growth-restricted singleton pregnancies. Next, we stratified the patients according to the presence or absence of silicone breast implants, to determine whether these implants influence fetal growth restriction onset or severity. Twelve (32%) of the 38 participants underwent cosmetic breast augmentation 4-18years before pregnancy. Half of the patients with and 38% without silicone breast implants had giardiasis. Half of the mothers with and 35% without silicone breast implants had autoantibodies. Silicone breast implants were associated with a 70% increased risk of fetal growth restriction before 32weeks' gestation (95% confidence interval [CI], 1.2-2.5). Fetal growth restriction was diagnosed significantly earlier in mothers with than in those without silicone breast implants, respectively at 27 (95% CI, 25-30) and 30weeks' gestation (95% CI, 29-32). Silicone breast implants also tripled the risk of fetuses being below the third percentile, but the difference was not significant. Our results suggest that the association of inflammatory conditions, such as silicone breast implants, giardiasis, and autoantibodies may contribute to placental insufficiency. Silicone breast implants older than four years increased the risk of early-onset fetal growth restriction. Studies with large samples are needed to validate our findings and define whether silicone-related fetal growth restriction should be included in autoimmune/inflammatory syndrome induced by adjuvants (ASIA) criteria. Key Points • Fetal growth restriction (FGR), responsible for 30% of stillbirths, is the most common cause of prematurity and intrapartum asphyxia. • In this study, including 38 mothers with normotensive FGR, all participants had 2-4 inflammatory conditions, such as giardiasis, sinusitis, candidiasis, dysbiosis, extreme fear or autoantibodies. • Silicone breast implants were associated with a 70% increased risk of fetal growth restriction before 32 weeks' gestation. • FGR was diagnosed at 27 weeks' gestation (95% CI, 25-30) in mothers with and at 30 weeks' gestation (95% CI, 29-32) in mothers without silicone breast implants.

Reduced Endothelial Progenitor Cells: A Possible Biomarker for Idiopathic Fetal Growth Restriction in Human Pregnancies.

Circulating endothelial progenitor cells (EPCs) may be necessary throughout pregnancy by ensuring proper placentation and embryonic growth. The lack of standardized EPC quantification techniques has prevented conclusive proof of an increase in EPC during pregnancy. The purpose of this study was to determine whether EPC levels change for healthy and idiopathic fetal growth restriction (FGR) pregnancies. The study population consisted of 48 healthy pregnant females with no previous history of IUGR (10 in the first trimester, 15 in the second, and 23 in the third), 48 women with pregnancy complicated by idiopathic FGR, and 15 non-pregnant women. By using flow cytometry, EPCs in maternal blood were recognized as CD45dim/CD34/KDR cells. ELISA was used to measure plasmatic cytokines. We ascertained a progressive rise in EPCs in healthy pregnancies that was apparent in the first but more pronounced in the third trimester. At comparable gestational ages, FGR-complicated pregnancies had impaired EPC growth. Placental growth factor and stromal-derived factor-1 levels in the blood were significantly lower in FGR than in healthy pregnancies, which may have contributed to the degradation of the EPCs. The count in EPCs might hold considerable promise toward developing a peculiar authentication marker for observing pregnancies, and could be the focus of cutting-edge tactics for the prognosis and treatment of FGR pregnancies.

Impact of Chorionic Somatomammotropin In Vivo RNA Interference Phenotype on Uteroplacental Expression of the IGF Axis.

While fetal growth is dependent on many factors, optimal placental function is a prerequisite for a normal pregnancy outcome. The majority of fetal growth-restricted (FGR) pregnancies result from placental insufficiency (PI). The insulin-like growth factors (IGF1 and IGF2) stimulate fetal growth and placental development and function. Previously, we demonstrated that in vivo RNA interference (RNAi) of the placental hormone, chorionic somatomammotropin (CSH), resulted in two phenotypes. One phenotype exhibits significant placental and fetal growth restriction (PI-FGR), impaired placental nutrient transport, and significant reductions in umbilical insulin and IGF1. The other phenotype does not exhibit statistically significant changes in placental or fetal growth (non-FGR). It was our objective to further characterize these two phenotypes by determining the impact of CSH RNAi on the placental (maternal caruncle and fetal cotyledon) expression of the IGF axis. The trophectoderm of hatched blastocysts (9 days of gestation, dGA) were infected with a lentivirus expressing either a non-targeting sequence (NTS RNAi) control or CSH-specific shRNA (CSH RNAi) prior to embryo transfer into synchronized recipient ewes. At ≈125 dGA, pregnancies were fitted with vascular catheters to undergo steady-state metabolic studies. Nutrient uptakes were determined, and tissues were harvested at necropsy. In both CSH RNAi non-FGR and PI-FGR pregnancies, uterine blood flow was significantly reduced (p ≤ 0.05), while umbilical blood flow (p ≤ 0.01), both uterine and umbilical glucose and oxygen uptakes (p ≤ 0.05), and umbilical concentrations of insulin and IGF1 (p ≤ 0.05) were reduced in CSH RNAi PI-FGR pregnancies. Fetal cotyledon IGF1 mRNA concentration was reduced (p ≤ 0.05) in CSH RNAi PI-FGR pregnancies, whereas neither IGF1 nor IGF2 mRNA concentrations were impacted in the maternal caruncles, and either placental tissue in the non-FGR pregnancies. Fetal cotyledon IGF1R and IGF2R mRNA concentrations were not impacted for either phenotype, yet IGF2R was increased (p ≤ 0.01) in the maternal caruncles of CSH RNAi PI-FGR pregnancies. For the IGF binding proteins (IGFBP1, IGFBP2, IGFBP3), only IGFBP2 mRNA concentrations were impacted, with elevated IGFBP2 mRNA in both the fetal cotyledon (p ≤ 0.01) and maternal caruncle (p = 0.08) of CSH RNAi non-FGR pregnancies. These data support the importance of IGF1 in placental growth and function but may also implicate IGFBP2 in salvaging placental growth in non-FGR pregnancies.

Determination of maternal serum pro-inflammatory cytokine changes in intrauterine growth restriction.

To evaluate maternal serum inflammatory marker changes in intrauterine growth restriction (IUGR) pregnancies. 50 healthy pregnant women and 50 patients diagnosed with IUGR were enrolled. Maternal serum high sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 levels were measured before delivery and neonatal outcomes were evaluated. Birth weight, Apgar scores, and cord blood gas pH were lower in the IUGR group (p<0.001, p<0.001, p<0.001 and p=0.006, respectively). While the levels of ESR, hsCRP, IL-6, and TNF-α were higher, the IL-10 level was found to be lower in the IUGR group (p<0.001, p=0.033, p<0.001, p=0.004 and p<0.001, respectively). As ESR, hsCRP, and IL-6 levels increased, birth weight, Apgar scores, and cord blood gas pH decreased (p<0.001, p<0.001, p<0.001, p<0.001, p=0.02, p=0.002, p=0.001, p=0.03, p<0.001, p<0.001, p<0.001 and p=0.02, respectively). As TNF-α level increased, only birth weight and Apgar score at the 1st minute decreased (p=0.006 and p=0.048, respectively). As IL-10 level decreased, birth weight, Apgar scores, and cord blood gas pH decreased (p<0.001 for all). IL-6 (>3.2 pg/ml) had a sensitivity of 100%, specificity of 100%, PPV of 100% and NPV of 100%. While birth weight, Apgar score and cord blood pH decreased in IUGR cases, ESR, hsCRP, IL-6 and TNF-α levels increased. Combined measurement of these markers can be used for the diagnosis of IUGR.

A STUDY ON DOPPLER ULTRASOUND PARAMETERS IN FETAL GROWTH RESTRICTED CASES AND ITS RELATION WITH PERINATAL OUTCOME

Introduction - There is signicant maternal and perinatal mortality and morbidity in Fetal Growth Restriction pregnancies. There are chances of increased fetal hypoxia , asphyxia , meconium aspiration syndrome , macrosomia , low birth weight , hypoglycaemia ,still births and even neonatal death. The present study was being conducted in light of the crucial role that doppler examination plays in early detection of FGR cases and possible neonatal morbidity and mortality through prompt management. The present st Aim And Objectives - udy was designed to clinically correlate the ndings of doppler ultrasound in clinically suspected Fetal Growth Restriction cases with perinatal outcome. The objective was to study the doppler parameters in clinically suspected Fetal Growth Restriction cases and to relate with their perinatal outcome. Materials and Method – This study included 80 singleton clinically suspected FGR cases attending Jorhat Medical College and Hospital. It was a hospital based observational Cross sectional study. Flow velocity waveforms, the resistance index (R.I.), pulsatility index (P.I.), systolic/diastolic ratio (S/D) of the above vessels were noted.. Cerebro-placental ratio or MCA/UA P.I. ratio was also noted. The ndings of the last week of delivery were correlated with the perinatal outcomes. In the present study, the ndings of AED Results – F and REDF were associated with signicant morbidity and mortality. All babies with AEDF and REDF had succumbed to death. Considering cerebro-placental ratio is better than UA PI and MCA PI alone. Because CPR incorporates data not only on the placental side but also the fetal response. Additional uterine artery Doppler evaluation is also helpful in predicting adverse pregnancy outcome. Multi vessel colour doppler ultrasound are Conclusion – important monitoring tools in patients with FGR to identify compromised in utero and to take timely appropriate action

ASSOCIATION BETWEEN MATERNAL BASAL GLUCOSE LEVEL AND INTRAUTERINE GROWTH RESTRICTION: A COMPARATIVE CROSS-SECTIONAL STUDY

Background: Intrauterine life is the most pivotal period of development that determines vital outcomes in postnatal life. Diabetes Mellitus may lead to disturbed fetal growth and maternal vasculopathy resulting in placental insufficiency with subsequent development of intrauterine growth restriction (IUGR). This study aims to find an association between hyperglycemia and the risk of IUGR, comparing pregnancies with IUGR with those with adequate for gestational age pregnancies.&#x0D; Methods: This cross sectional study was conducted in Federal Post Graduate Medical Institute (FPGMI) from January 2015 to January 2016, including 106 pregnant women using non-probability convenient sampling technique. Participants were divided into two groups: Group A comprises of pregnant women with adequate for gestational age pregnancies (n=53) and groups B includes pregnant women with intrauterine growth restricted pregnancies (n=53). Random blood sugar level was estimated by glucose/oxidase test and IUGR was confirmed by ultrasonography at 28-35 weeks of gestation. Shapiro-Wilk test was used to examine data normality and independent t-test was used to compare statistically significant difference. A p- value of &lt;0.05 was considered significant.&#x0D; Results: Mean basal sugar level of group A was 98.9 ± 7.1 mg/dL and that of group B was 97.9 ± 6.0mg/dL. This mean difference was not statistically significant (p-value= 0.566).&#x0D; Conclusion: We found no statistically significant association between raised maternal basal glucose level and the occurrence of intrauterine growth restriction at 28-35 weeks of pregnancy.

Comparison of Outcomes of Fetal Growth Restricted Pregnancies by Presence of Proteinuria

Comparison of Outcomes of Fetal Growth Restricted Pregnancies by Presence of Proteinuria

Physician recommendations for physical activity in complicated growth restricted pregnancies

Physician recommendations for physical activity in complicated growth restricted pregnancies

Assessment of Fetal Thymus Size in Small for Gestational Age and Growth Restricted Fetuses

Objective: The purpose of this study was to analyze the fetal thymus size by sonography in healthy, small for gestational age (SGA), and fetal growth restriction (FGR) pregnancies and investigate if there is a difference between healthy fetuses and those with growth restriction. &#x0D; Study Design: The thymic-thoracic ratio (TTR), transverse diameter, and perimeter of the fetal thymus were prospectively measured in SGA and FGR pregnancies between the gestational ages of 20 and 37 weeks and compared with healthy controls. Fetal abdominal circumference (AC) or estimated fetal weight (EFW)