Fetal Growth Restriction Cases Research Articles

Pravastatin Improves Angiogenic Factors and Feto- Placental Doppler in Pregnancy with Early Severe Fetal Growth Restriction: A Case Report

Early fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. No therapeutic strategies have proved to be effective in improving fetal and neonatal outcomes either in growth restricted fetuses or any placenta-related disorder such as preeclampsia. Delivery of the fetus and placenta is the only definitive cure. However, recent studies suggest that pravastatin appears to be safe in pregnancy, improves placental perfusion and fetal growth and prevents angiogenic imbalance. Angiogenic (PlGF) and antiangiogenic (sFlt-1) factors and feto-maternal Doppler evaluation are strongly associated with fetal growth restriction prognosis and severity. Thus, pravastatin has been proposed as a promising therapeutic drug for fetal growth restriction. We report the findings of a case of early-onset FGR treated with pravastatin 40mg daily until delivery. During this time, feto-maternal Doppler and angiogenic profile evolution were recorded. Fetal and placental perfusion observed on Doppler and angiogenic imbalance improved after pravastatin was started. sFlt-1 down-regulation was more marked than PlGF up-regulation. The patient developed severe preeclampsia (PE) at 27+6 weeks of gestation, necessitating immediate fetal extraction owing to hypertension refractory to adequate treatment. This report supports further investigation on the use of pravastatin to improve angiogenic profile and feto-maternal circulation in FGR fetuses.

Successful management of early onset fetal growth restriction: A case report

FGR (Fetal Growth Restriction) is a condition in which a fetus fails to attend its predetermined biological genetic growth potential. Growth-restricted fetuses are at increased risk of perinatal mortality and morbidity. Growth restricted babies also have poor long term outcomes of cardiovascular, neurological, cognitive or neurological system. The present case of Early FGR where patient presented to us at at 29+6 weeks of gestation with lag in fetal growth of 3 weeks & an Amniotic fluid Index of 3.2 cm and her pregnancy could be successfully prolonged up to 35+2 two weeks of gestation. The protocol for management of the fetus was as per Delphi consensus and ISUOG guidelines, and we could prolong pregnancy to the maximum possible gestation and delivered a low birth weight fetus with good Apgar score and who did not require Neonatal Intensive Care Unit admission. Tools for diagnosis and follow up of FGR fetus are customized growth charts, sequential ultrasound measurements focusing on declining/crossing growth centiles, functional parameters such as Doppler waveform analysis (umbilical artery (UA), fetal middle cerebral artery, and ductus venosus), Biophysical profile scoring, Cardio tocography and serum biomarkers.

Considering evidence in the management of fetal growth restriction.

Considering evidence in the management of fetal growth restriction.

Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood, Placental Size, and Risk for Fetal Growth Restriction: A Nested Case-control Study

ObjectiveTo explore the effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on placental size and birth outcomes. MethodsBased on the perspective Wenzhou Birth Cohort, this nested case-control study included 101 fetal growth restriction (FGR) and 101 healthy newborns. Maternal serum samples were collected during the third trimester and measured for PBDEs by gas chromatography tandem mass spectrometry. The basic information of mother-newborn pairs was collected from questionnaires, whereas the placental size and birth outcomes of newborns were obtained from hospital records. ResultsA total of 19 brominated diphenyle ether (BDE) congeners were detected in maternal serum samples. Higher concentrations of BDE-207, -208, -209, and ∑19PBDEs were detected in FGR cases than in controls. Increased BDE-207, -208, -209, and ∑19PBDEs levels in maternal serum were related to decreased placental length, breadth, surface area, birth weight, birth length, gestational age, and Quetelet index of newborns. After adjusting for confounders, BDE-207 and ∑19PBDE concentrations in maternal serum were significantly associated with an increased risk of FGR. ConclusionA negative association was found between PBDE levels in maternal serum and placental size and birth outcomes. Prenatal PBDE exposure may be associated with elevated risk of the incidence of FGR birth.

Validation of Delphi procedure consensus criteria for defining fetal growth restriction.

Recently, a Delphi procedure was used to establish new criteria for defining fetal growth restriction (FGR). These criteria require clinical validation. We sought to validate the Delphi consensus criteria by comparing their performance with that of our current definition (estimated fetal weight (EFW) < 10th percentile) in predicting adverse neonatal outcome (ANO). This was a secondary analysis of data from a prospective cohort study of women referred for fetal growth assessment between 26 and 36 weeks' gestation. The current standard definition of FGR used in our clinical practice is EFW < 10th percentile using Hadlock's fetal growth standard. The Delphi consensus criteria for FGR include either a very small fetus (abdominal circumference (AC) or EFW < 3rd percentile) or a small fetus (AC or EFW < 10th percentile) with additional abnormal Doppler findings or a decrease in AC or EFW by two quartiles or more. The primary outcome was the prediction of a composite of ANO including one or more of: admission to the neonatal intensive care unit, cord pH < 7.1, 5-min Apgar score < 7, respiratory distress syndrome, intraventricular hemorrhage, neonatal seizures or neonatal death. The discriminatory capacities of the two definitions of FGR for composite ANO and delivery of a small-for-gestational-age (SGA) neonate, defined as birth weight < 10th percentile, were compared using area under the receiver-operating-characteristics curve (AUC). The sensitivity, specificity and predictive values of the methods were also compared. Of 1055 pregnancies included in the study, composite ANO occurred in 139 (13.2%). There were only two cases of early FGR (before 32 weeks); therefore, the study focused on late FGR. Our current FGR diagnostic criterion of EFW < 10th percentile was not associated significantly with composite ANO (relative risk (RR), 1.1 (95% CI, 0.6-1.8)), while the Delphi FGR criteria were (RR, 2.0 (95% CI, 1.2-3.3)). Our current definition of FGR showed higher discriminatory ability in the prediction of a SGA neonate (AUC, 0.69 (95% CI, 0.65-0.73)) than did the Delphi definition (AUC, 0.64 (95% CI, 0.60-0.67)) (P = 0.001). The AUCs of both definitions were poor for the prediction of composite ANO, despite slightly improved performance using the Delphi consensus definition of FGR (AUC, 0.53 (95% CI, 0.50-0.55)) compared with that of our current definition (AUC, 0.50 (95% CI, 0.48-0.53)) (P = 0.02). The newly postulated criteria for defining FGR based on a Delphi procedure detects fewer cases of neonatal SGA than does our current definition of EFW < 10th percentile, but is associated with a slight improvement in predicting ANO. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

A pilot study on investigating the role of Salvia miltiorrhiza in fetal growth restriction.

To date there is no effective treatment for pregnancies complicated by fetal growth restriction (FGR). Salvia miltiorrhiza, a traditional Chinese herb has been shown to promote blood flow and improve microcirculatory disturbance. In this pilot study, we evaluated whether S. miltiorrhiza can potentially become a possible therapy for FGR. Nineteen pregnant women with FGR were treated with S. miltiorrhiza and ATP supplementation for an average of 7 days, and 17 cases received ATP supplementation as controls. The estimated fetal weights (EFWs) were measured by ultrasound after treatment, and the birthweights were recorded after birth. After treatment with S. miltiorrhiza, 7 (37%) FGR cases showed an increase in EFW to above the 10th percentile, compared with 4 (23%) FGR cases in controls (odds ratio: 1.896, 95% confidence limits (CLs): 0.44–8.144). At delivery, 10 (53%) FGR cases in the treatment group delivered babies with a birthweight above the 10th percentile, compared with 6 (35%) FGR cases in the control group (odds ratio: 2.037, 95% CL: 0.532–7.793); 80 or 64% FGR cases in the treatment group showed an increase in fetal abdominal circumference (AC) or biparietal diameter (BPD) above the 10th percentile before delivery. While 44 or 30% FGR cases in the control group showed an increase in AC or BPD. No improvement of head circumference (HC) or femur length (FL) was seen. These pilot data suggest the need for multicenter randomized clinical trials on the potential of S. miltiorrhiza to improve perinatal outcome in pregnant women complicated by FGR.

Non-invasive prediction of fetal growth restriction by whole-genome promoter profiling of maternal plasma DNA: a nested case-control study.

ObjectiveTo predict fetal growth restriction (FGR) by whole‐genome promoter profiling of maternal plasma.DesignNested case–control study.SettingHospital‐based.Population or Sample810 pregnancies: 162 FGR cases and 648 controls.MethodsWe identified gene promoters with a nucleosome footprint that differed between FGR cases and controls based on maternal plasma cell‐free DNA (cfDNA) nucleosome profiling. Optimal classifiers were developed using support vector machine (SVM) and logistic regression (LR) models.Main outcome measuresGenes with differential coverages in promoter regions through the low‐coverage whole‐genome sequencing data analysis among FGR cases and controls. Receiver operating characteristic (ROC) analysis (area under the curve [AUC], accuracy, sensitivity and specificity) was used to evaluate the performance of classifiers.ResultsThrough the low‐coverage whole‐genome sequencing data analysis of FGR cases and controls, genes with significantly differential DNA coverage at promoter regions (−1000 to +1000 bp of transcription start sites) were identified. The non‐invasive ‘FGR classifier 1’ (CFGR1) had the highest classification performance (AUC, 0.803; 95% CI 0.767–0.839; accuracy, 83.2%) was developed based on 14 genes with differential promoter coverage using a support vector machine.ConclusionsA promising FGR prediction method was successfully developed for assessing the risk of FGR at an early gestational age based on maternal plasma cfDNA nucleosome profiling.Tweetable abstractA promising FGR prediction method was successfully developed, based on maternal plasma cfDNA nucleosome profiling.

Association between fetal growth restriction and maternal exposure to polybrominated diphenyl ethers.

Humans are exposed to polybrominated diphenyl ethers (PBDEs) via ingestion of food, dust inhalation, and dermal absorption. Exposure to PBDEs via the placenta and breast milk is a special and important pathway in infants. This nested case-control study aimed to investigate the levels of PBDEs in maternal serum and colostrum, and to assess the association between the occurrence of fetal growth restriction (FGR) and prenatal exposure to PBDEs. We recruited 293 mother-newborn pairs, including 98 FGR cases and 195 healthy controls in Wenzhou, China. Maternal serum and colostrum samples were collected during pregnancy and after delivery, respectively, and the levels of PBDEs were measured by gas chromatography-tandem mass spectrometry. The total levels of PBDEs in maternal serum and colostrum were found to be in equilibrium, but congener profiles of PBDEs in these matrices were different. Increased BDE-207, BDE-209, ∑BDE196-209 and ∑PBDEs levels in maternal serum and BDE-99, ∑BDE17-154 and ∑PBDEs levels in colostrum were correlated with decreased birth weight Z score. Increased concentrations of higher brominated BDEs in maternal serum (odds ratio (OR)=1.010, 95%CI=1.003-1.018) and low-to moderately brominated BDEs in colostrum (OR=1.004, 95%CI=1.000-1.009) were associated with increased risk of FGR, which showed an exposure-response relationship. In addition, infants with FGR were more exposed to PBDEs in colostrum after birth than healthy infants. Longitudinal birth cohort studies are needed to determine the prolonged effect of PBDEs exposure on the growth of FGR infants in the future.

Placental pathology in pregnancies complicated by fetal growth restriction: recurrence vs. new onset.

In an attempt to shed new light on the pathogenesis of fetal growth restriction (FGR), we aimed to study pregnancy characteristics, neonatal outcomes, and placental histopathological lesions of FGR pregnancies in two different subgroups: when developed after appropriate for gestational age (AGA) pregnancy and when developed after previous pregnancy with FGR. Pregnancy and placental reports of all singleton pregnancies complicated by FGR (defined as actual birthweight below the 10th percentile according to local birthweight nomograms) between 2008 and 2018 were reviewed. Included were only cases with previous delivery. Maternal background, neonatal outcomes, and placental histopathology were compared between FGR that occurred after FGR (recurrent FGR group) and FGR that occurred after an AGA pregnancy (FGR after AGA group). Placental lesions were classified according to the current "Amsterdam" criteria. Continuous variables were compared using the Student's t test or the Mann-Whitney test as appropriate. Categorical variables were compared using Chi-square or Fisher's exact test as appropriate. A total of 334 FGR cases with a previous delivery were included in the study. Of them, 111 cases constituted the recurrent FGR group and 223 constituted the FGR after AGA group. The recurrent FGR group was characterized by higher rates of maternal diabetes during pregnancy and hypertensive diseases (9% versus 2.7%, p = 0.01 and 19.8% versus 11.6%, p = 0.04). The FGR after AGA group was characterized by a higher rate of fetal vascular malperfusion (FVM) lesions (29.6% versus 18.0%, p = 0.02), and by lower mean birthweight (1842 ± 424.9 versus 1977.4 ± 412.2, p = 0.005), as compared to the recurrent FGR group. Recurrent FGR was associated with maternal background morbidities during pregnancy which represents a chronic repeated insult, while "new" FGR cases (those followed an AGA pregnancy) were characterized by a higher rate of FVM lesions and lower birthweight which probably represent an "accident" in placentation. These findings may suggest that different mechanisms of placental dysfunction exist in the two subgroups of FGR.

Twelve Weeks of Reversed Umbilical Flow in a Fetal Growth Restriction Case Associated with Severe Periconceptional Maternal Anemia

We present a case of a patient diagnosed with severe intrauterine growth restriction and periconceptional severe anemia, where the fetal well-being features, including reversal of umbilical artery end-diastolic flow and abnormal cerebroplacental ratio, remained stationary for 12 weeks. We are not aware of reports with similar findings, and the professionals should take into consideration the possibility of a "frozen" fetal well-being for a long time. Possibly, in our case, the evolution may be due to the prompt correction of the chronic severe maternal anemia. This approach may offer the opportunity to prolong the pregnancy, even in cases with apparently imminent delivery, as the association of reversal of umbilical artery end-diastolic flow.

Non-targeted urinary metabolomics in pregnancy and associations with fetal growth restriction

Our objective was to identify metabolites associated with fetal growth restriction (FGR) by examining early and late pregnancy differences in non-targeted urinary metabolites among FGR cases and non-FGR controls. An exploratory case-control study within LIFECODES birth cohort was performed. FGR cases (N = 30), defined as birthweight below the 10th percentile, were matched with controls (N = 30) based on maternal age, race, pre-pregnancy body mass index, and gestational age at delivery. Gas chromatography/electron-ionization mass spectrometry was performed on urine samples collected at 10 and 26 weeks of gestation. Differences in urinary metabolite levels in cases and controls at each time point and between the two time points were calculated and then changes compared across pregnancy. 137 unique urinary metabolites were annotated, and several identified that were higher in cases compared to controls. For example, urinary concentrations of benzoic acid were higher in cases compared to controls at both study visits (3.01-fold higher in cases at visit 1, p < 0.01; 3.10-fold higher in cases at visit 3, p = 0.05). However, these findings from our exploratory analysis were not robust to false-discovery-rate adjustment. In conclusion, using a high-resolution, non-targeted approach, we found specific urinary organic acids differed over pregnancy by FGR case status.

Cytokine profiles in maternal serum are candidates for predicting an optimal timing for the delivery in early-onset fetal growth restriction.

We examined whether maternal serum cytokine profiles of mothers with early-onset fetal growth restriction (FGR) were associated with delivery within 2 weeks after sampling during the third trimester. This exploratory prospective cross-sectional study included a total of 20 singleton fetuses with early-onset FGR and 31 healthy controls. Maternal serum samples during the early third trimester were analyzed for 23 cytokines. Of 20 fetuses with early-onset FGR, 14 had delivery within 2 weeks after sampling. Multivariate analysis revealed that maternal serum concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and soluble CD40 ligand (sCD40L) were independently associated with delivery within 2 weeks in early-onset FGR. Among cases of early-onset FGR, concentrations of almost all maternal serum cytokines were similar. Maternal serum sVEGFR-1 concentrations were high when delivery occurred within 2 weeks. Maternal serum sCD40L concentrations were elicited only in cases in which delivery within 2 weeks occurred due to fetal deterioration. We identified two biomarkers, one specific for FGR and the other dependent on severity, that were significant components of angiogenic activities and inflammation factors. Imbalances in serum protein expression may have a substantial effect on the pathogenesis of FGR.

A maternal serum metabolite ratio predicts fetal growth restriction at term.

Fetal growth restriction (FGR) is the major single cause of stillbirth1 and is also associated with neonatal morbidity and mortality2,3, impaired health and educational achievement in childhood4,5 and with a range of diseases in later life6. Effective screening and intervention for FGR is an unmet clinical need. Here, we performed ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) metabolomics on maternal serum at 12, 20 and 28 weeks of gestational age (wkGA) using 175 cases of term FGR and 299 controls from the Pregnancy Outcome Prediction (POP) study, conducted in Cambridge, UK, to identify predictive metabolites. Internal validation using 36 wkGA samples demonstrated that a ratio of the products of the relative concentrations of two positively associated metabolites (1-(1-enyl-stearoyl)-2-oleoyl-GPC (P-18:0/18:1) and 1,5-anhydroglucitol) to the product of the relative concentrations of two negatively associated metabolites (5α-androstan-3α,17α-diol disulfate and N1,N12-diacetylspermine) predicted FGR at term. The ratio had approximately double the discrimination as compared to a previously developed angiogenic biomarker7, the soluble fms-like tyrosine kinase 1:placental growth factor (sFLT1:PlGF) ratio (AUC 0.78 versus 0.64, P = 0.0001). We validated the predictive performance of the metabolite ratio in two sub-samples of a demographically dissimilar cohort, Born in Bradford (BiB), conducted in Bradford, UK (P = 0.0002). Screening and intervention using this metabolite ratio in conjunction with ultrasonic imaging at around 36 wkGA could plausibly prevent adverse events through enhanced fetal monitoring and targeted induction of labor.

Reproductive Outcomes following Use of Barbed Suture during Laparoscopic Myomectomy

To review pregnancy outcomes after laparoscopic myomectomy with the use of barbed suture. Retrospective cohort study and follow-up survey. Single, large academic medical center. Patients who underwent laparoscopic myomectomy with the use of barbed suture for myometrial closure between 2008 and 2016. Laparoscopic myomectomy and a follow-up survey regarding pregnancy outcome. A total of 486 patients met inclusion criteria and underwent a laparoscopic myomectomy between 2008 and 2016. Of the 428 with viable contact information, 240 agreed to participate (56%). Of those who responded to the survey, 101 (42%) attempted to get pregnant, and there were 4 unplanned pregnancies. There were 110 pregnancies among 76 survey respondents. In total, of the women attempting a postoperative pregnancy, 71% had at least 1 pregnancy. Comparing the women who did and did not conceive postoperatively, the group who got pregnant was on average younger, 33.8 ± 4.5 years vs 37.5 ± 6.5 years (p = .001); had fewer myomas removed, median = 2 (range 1-9) vs median = 2 (range 1-16) myomas (p = .038); and had a longer follow-up period, 30 months ( vs 30 (11-93 months) ± 20 (p <.001). The mean time to first postoperative pregnancy was 18.0 months (range 2-72 months). Of the 110 reported postoperative pregnancies, there were 60 live births (55%), 90% by means of cesarean section. The mean gestational age at birth was 37.8 weeks. In the cohort, there were 8 preterm births, 3 cases of abnormal placentation, 2 cases of fetal growth restriction, 3 cases of hypertensive disorders of pregnancy, and 2 cases of myoma degeneration requiring hospitalization for pain control. There were no uterine ruptures reported. According to our findings, pregnancy outcomes after laparoscopic myomectomy with barbed suture are comparable with available literature on pregnancy outcomes with conventional smooth suture.

Etiology and perinatal outcome of periviable fetal growth restriction associated with structural or genetic anomaly.

To investigate the etiology and perinatal outcome of periviable fetal growth restriction (FGR) associated with a structural defect or genetic anomaly. This was a retrospective study of singleton pregnancies seen at a referral fetal medicine unit between 2005 and 2018, in which FGR (defined as fetal abdominal circumference ≤ 3rd percentile for gestational age) was diagnosed between 22 + 0 and 25 + 6 weeks of gestation. The study group included pregnancies with periviable FGR associated with a genetic or structural anomaly (anomalous FGR), while the control group consisted of structurally and genetically normal pregnancies with periviable FGR (non-anomalous FGR). Results of genetic testing, TORCH screen and postmortem examination, as well as perinatal outcome, were investigated. Of 255 pregnancies complicated by periviable FGR, 188 were eligible; of which 52 (28%) had anomalous FGR and 136 (72%) had non-anomalous FGR. A confirmed genetic abnormality accounted for 17/52 cases (33%) of anomalous FGR, with trisomy 18 constituting over 50% (9/17; 53%). The most common structural defects associated with FGR were central nervous system abnormalities (13/35; 37%). Overall, 12 (23%) cases of anomalous FGR survived the neonatal period. No differences were found in terms of perinatal survival between pregnancies with anomalous and those with non-anomalous FGR. Most pregnancies complicated by anomalous FGR were associated with a structural defect. The presence of an associated genetic defect was invariably lethal, while those with a structural defect, in the absence of a confirmed genetic abnormality, survived into infancy in over 90% of cases, with an overall one in three chance of perinatal survival. These data can be used for counseling prospective parents. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Metabolomic identification of placental alterations in fetal growth restriction

Introduction Fetal growth restriction (FGR), viz., birth weight <10th percentile is a common pregnancy complication which increases the risk of adverse fetal and newborn outcomes. The placenta is the key organ for fetal growth as it controls oxygen and nutrient availability. This study aims to elucidate the mechanisms of and identify putative placental biomarkers for FGR using high-resolution metabolomics. Methods Placenta samples from 19 FGR cases and 30 controls were analyzed using proton magnetic resonance (1H NMR) spectroscopy and direct flow injection mass spectrometry with reverse-phase liquid-chromatography mass spectrometry (DI-LC-MS/MS). Significant concentration differences (p-value <.05) in 179 of the 220 metabolites were measured. Results Of the 179 metabolites, 176 (98.3%) had reduced placental levels in FGR cases. The best performing metabolite model: 3-hydroxybutyrate, glycine and PCaaC42:0 achieved an AUC (95% CI) = 0.912 (0.814–1.000) with a sensitivity of 86.7% and specificity of 84.2% for FGR detection. Metabolite set enrichment analysis (MSEA) revealed significant (p < .05) perturbation of multiple placental metabolite pathways including urea metabolism, ammonia recycling, porphyrin metabolism, bile acid biosynthesis, galactose metabolism and perturbed protein biosynthesis. Conclusion The placental metabolic pathway analysis revealed abnormalities that are consistent with fetal hepatic dysfunction in FGR. Near global reduction of metabolite concentrations was found in the placenta from FGR cases and metabolites demonstrated excellent diagnostic accuracy for FGR detection.

Risk evaluation of fetal growth restriction by combined screening in early and mid-pregnancy.

Objectives:To assess risk of fetal growth restriction (FGR) by combined screening in early and mid-pregnancy.Methods:Pregnant women who received prenatal examinations and delivered in our hospital from January 2015 to January 2019 were selected and retrospectively analyzed. All women completed two ultrasonographic examinations during pregnancy, i.e. Down’s screening during early pregnancy (11-13 + 6 weeks) and prenatal color Doppler screening during mid-pregnancy (20-24 weeks). A total of 33 FGR cases were screened out, and there were 1,507 normal pregnant women. The clinical, ultrasonographic and serological indices in early and mid-pregnancy were recorded. When the false positive rate was 5%, logistic regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the influencing factors and predictive values of individual and combined indices for FGR in corresponding gestational weeks. The sensitivity and specificity of the optimal cutoff value of each index as well as the combination of optimal predictive indices were found by the area under ROC curve (AUC).Results:When the false positive rate was 5% in the single-index screening during early pregnancy, the parity, BPD, AC, HC, and FL had statistical significances. Multivariate analysis showed that the parity and BPD had statistical significances. During mid-pregnancy, univariate analysis revealed that the parity, BMI, BPD, AC, HC, FL, UTA-PI, UTA-RI, UA-PI and UA-RI had statistical significances. BMI, AC, UTA-PI, UTA-RI, UA-PI and UA-RI had statistical significances in multivariate analysis. BMI, UTA-PI and UA-PI were risk factors for FGR, with UTA-PI being most dangerous. AUC for combined screening exceeded those for individual screenings. The best combined screening program was BPD in early pregnancy + BMI + AC + UTA-PI + UTA-RI + UA-PI + UA-RI in mid-pregnancy. The optimal cutoff value was 0.015, with the sensitivity of 83.1% and the specificity of 61.3%.Conclusion:The predictive efficiency of combined FGR screening in early and mid-pregnancy surpasses that of simple mid-pregnancy screening. It is recommended to use the integrated screening program in early and mid-pregnancy to predict FGR.

734: Which fetal growth curve best predicts a small for gestational age infant in obese women?

To determine if prediction of small for gestational age (SGA) infants using standardized ultrasound growth curves (GC) is affected by maternal obesity and which GC performs best in obese women. Retrospective cohort study from 6/1/18 to 6/1/19 of all growth ultrasounds performed from 30+0 to 32+6 weeks at a single institution. Multifetal gestations and intrauterine fetal demises were excluded. We determined the estimated fetal weight (EFW) for all patients using four clinically utilized GCs (Hadlock, Brenner, Hadlock abdominal circumference (AC) alone, and Brenner plus AC (B + AC)). We defined fetal growth restriction (FGR) as EFW < 10th percentile for Hadlock and Brenner or AC < 5th percentile for AC. SGA was defined as birthweight < 10th percentile by WHO or Fenton GCs. The primary outcome was the impact of maternal obesity (BMI ≥30 kg/m2) on the ability of each GC to predict SGA and to determine which GC performs best in obese women. Predictive characteristics were calculated for each GC and the area under the receiver operating characteristic curve (AUC) was compared between non-obese and obese patients. Within the obese patients, the AUC was compared between all four GCs. Of 763 patients included, 77 infants (10.3%) were SGA. Obese women were significantly less likely to deliver an SGA infant (p< 0.01). Maternal obesity significantly decreased the ability of Hadlock to predict SGA compared to non-obese patients (AUC 0.58 (95%CI 0.48-0.69) vs AUC 0.73 (95%CI 0.66-0.79), p=0.02) (Fig 1). There was no significant difference in the ability of the other GCs to predict SGA between obese and non-obese women. In obese patients, there was no significant difference between ability of the GCs to predict SGA (p=0.41) (Fig 2). Brenner identified no cases of FGR in obese patients. In non-obese women, Hadlock outperformed the other three GCs (p< 0.01) (Fig 2). Maternal obesity decreases the ability of the Hadlock GC to predict SGA infants. Among obese women, no GC is significantly more predictive of SGA infants. All performed poorly in the obese population.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Role of sFlt-1 and PlGF in the screening of small-for-gestational age neonates during pregnancy: A systematic review.

Background Fetal growth restriction, i.e. the restriction of genetically predetermined growth potential due to placental dysfunction, is a major cause of neonatal morbidity and mortality. The consequences of inadequate fetal growth can be life-long, but the risks can be reduced substantially if the condition is identified prenatally. Currently, screening strategies are based on ultrasound detection of a small-for-gestational age fetus and do not take into account the underlying vascular pathology in the placenta. Measurement of maternal circulating angiogenic biomarkers placental growth factor, sFlt-1 (soluble FMS-like tyrosine kinase-1) are increasingly used in studies on fetal growth restriction as they reflect the pathophysiological process in the placenta. However, interpretation of the role of angiogenic biomarkers in prediction of fetal growth restriction is hampered by the varying design, population, timing, assay technique and cut-off values used in these studies. Methods We conducted a systematic-review in PubMed (MEDLINE), EMBASE (Ovid) and Cochrane to explore the predictive performance of maternal concentrations of placental growth factor, sFlt-1 and their ratio for fetal growth restriction and small-for-gestational age, at different gestational ages, and describe the longitudinal changes in biomarker concentrations and optimal discriminatory cut-off values. Results We included 26 studies with 2514 cases with small-for-gestational age, 27 cases of fetal growth restriction, 582 cases mixed small-for-gestational age/fetal growth restriction and 29,374 reference. The largest mean differences for the two biomarkers and their ratio were found after 26 weeks of gestational age and not in the first trimester. The ROC-AUC varied between 0.60 and 0.89 with sensitivity and specificity matching the different cut-off values or a preset false-positive rate of 10%. Conclusions Most of the studies did not make a distinction between small-for-gestational age and fetal growth restriction, and therefore the small-for-gestational age group consists of fetuses with growth restriction and fetuses that are constitutionally normal. The biomarkers can be a valuable screening tool for small-for-gestational age pregnancies, but unfortunately, there is not yet a clear cut-off value to use for screening. More research is needed to see if these biomarkers are sufficiently able to differentiate growth restriction on their own and how these biomarkers in combination with other relevant clinical and ultrasound parameters can be used in clinical routine diagnostics.

Associations between PBDEs exposure during pregnancy, fetal growth and aberrant DNA methylation of human placenta

TPS 711: The exposome, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Aim: To evaluated the association between in utero PBDEs exposure and fetal growth and examined the potential role of altered DNA methylation of growth regulatory genes in these associations. Methods: A total of 249 mother-newborn pairs comprised of 124 fetal growth restriction (FGR) cases and 125 controls within the Wenzhou Birth Cohort were enrolled in this nested case–control study. In utero exposure of 19 PBDEs congeners, including thirteen lower PBDE congeners (BDE-17~190) and six higher brominate BDE congeners (BDE-196~209), were determined by gas chromatography tandem mass spectrometry in umbilical cord blood. Placental DNA methylation of LINE1, HSD11B2 and IGF2 was measured by quantitative polymerase chain reaction-pyrosequencing at differentially methylated regions (DMRs). Multiple linear regression and logistic regressions models were used to examine associations among PBDEs exposure, fetal growth indicators and DMR methylation fractions. Results: Concentrations of BDE-49, BDE-206, BDE-209, BDE-17~190 and ∑19PBDEs were significantly higher in FGR cases than those in normal controls. Meanwhile, DNA methylation of IGF2 and HSD11B2 showed significant differences between FGR group and control group, respectively. BDE-206 (OR: 1.569, 95% CIs: 1.053-2.338), BDE-17~190 (OR: 2.860, 95% CIs: 1.233-6.634), BDE-196~209 (OR: 1.688, 95% CIs: 1.024-2.783) and ∑19PBDEs (OR: 2.387, 95% CIs: 1.220-4.668) concentrations were associated with increased risk of FGR. Being FGR birth were also associated with increasing DNA methylation of HSD11B2 (OR: 1.145, 95% CIs: 1.032-1.270) and decreasing DNA methylation of IGF2 (OR: 0.892, 95% CIs: 0.845, 0.941). In addition, BDE-17~190 showed significant associations with placental DNA methylation of HSD11B2 and IGF2 (β: 1.127, 95% CIs: 0.069-2.186; β: -3.452, 95% CIs: -5.512--1.392). These results were consistent with the expected direction relating PBDEs exposure, fetal growth and placental DNA methylation. Conclusion: We report an inverse association between in utero exposures to PBDEs and fetal growth and provide evidence supporting epigenetic gene plasticity in these associations.