The value of angiogenetic biomarkers in the detection of early onset fetal growth restriction.

OBJECTIVE: The identification of fetal growth restriction (FGR) due to uteroplacental insufficiency is important to improve perinatal outcomes. To distinguish FGR from small for gestational age (SGA), FGR consensus definition is currently based on biometry and/or additional biophysical parameters. This study aims to verify if this definition might be modified by including circulating angiogenic factors. STUDY DESIGN: This historical cohort study included singleton pregnancies with SGA fetuses after 20 weeks. All patients underwent detailed ultrasound and measurements of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) at first assessment. ISUOG criteria for FGR were applied. Total PlGF was calculated using free PlGF, sFlt-1 and a receptor pharmacology model, and multiple of the median (MoM) values for sFlt-1, free PlGF, total PlGF and sFlt-1/PlGF ratio were calculated to adjust for gestational age. RESULTS: 72 pregnancies with SGA were first evaluated at median (IQR) of 28+5 (26+2 -31+3) weeks' gestation, and 51 fetuses (70.8 %) satisfied the FGR consensus definition. Pregnancies with FGR showed significantly lower levels of free and total PlGF MoM (0.12, 95 % IQR: 0.07-0.36 vs 0.32, 95 % IQR: 0.20-0.53, p = 0.008) and 0.26, 95 % CI: 0.16-0.55 vs 0.43, 95 % IQR: 0.23-0.53, p = 0.028) respectively; and higher sFlt-1 MoM (4.62, 95 % IQR: 1.80-7.30 vs 1.74, 95 % IQR:1.11-3.61, p = 0.014) than pregnancies not classified as FGR. Free and total PlGF MoM correlated significantly with gestational age at delivery (r = 0.776, p < 0.001 and r = 0.707, p < 0.001, respectively). sFlt-1 MoM and sFlt-1/PlGF ratio MoM also correlated with gestational age at delivery (r = -0.681, p < 0.001 and r = -0.823, p < 0.001). Six cases identified as FGR at first ultrasound were not confirmed at birth showing significantly higher levels of free PlGF MoM (0.77, 95 % IQR: 0.27-3.07 vs 0.17, 95 % IQR: 0.08-0.43, p = 0.022). CONCLUSION: These findings show that total as well as free PlGF levels are lower in pregnancies affected with placental growth restriction. Angiogenic biomarkers might improve the differentiation between placental growth restriction and constitutional smallness. Further studies are needed to determine how to integrate them into the current definitions of FGR.

Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA.

Altered epigenetic mechanisms have been previously reported in growth restricted offspring whose mothers experienced environmental insults during pregnancy in both human and rodent studies. We previously reported changes in the expression of the DNA methyltransferase Dnmt3a and the imprinted genes Cdkn1c (Cyclin-dependent kinase inhibitor 1C) and Kcnq1 (Potassium voltage-gated channel subfamily Q member 1) in the kidney tissue of growth restricted rats whose mothers had uteroplacental insufficiency induced on day 18 of gestation, at both embryonic day 20 (E20) and postnatal day 1 (PN1). To determine the mechanisms responsible for changes in the expression of these imprinted genes, we investigated DNA methylation of KvDMR1, an imprinting control region (ICR) that includes the promoter of the antisense long non-coding RNA Kcnq1ot1 (Kcnq1 opposite strand/antisense transcript 1). Kcnq1ot1 expression decreased by 51% in growth restricted offspring compared to sham at PN1. Interestingly, there was a negative correlation between Kcnq1ot1 and Kcnq1 in the E20 growth restricted group (Spearman's ρ = 0.014). No correlation was observed between Kcnq1ot1 and Cdkn1c expression in either group at any time point. Additionally, there was a 11.25% decrease in the methylation level at one CpG site within KvDMR1 ICR. This study, together with others in the literature, supports that long non-coding RNAs may mediate changes seen in tissues of growth restricted offspring.

Intrauterine growth restriction alters kidney metabolism at the end of nephrogenesis.

BACKGROUND: This study investigated the effect of uteroplacental insufficiency (UPI) on renal development by detecting metabolic alterations in the kidneys of rats with intrauterine growth restriction (IUGR). METHODS: On gestational day 17, pregnant Sprague Dawley rats were selected and allocated randomly to either the IUGR group or the control group. The IUGR group received a protocol involving the closure of bilateral uterine vessels, while the control group underwent a sham surgery. The rat pups were delivered on gestational day 22 by natural means. Pups were randomly recruited from both the control and IUGR groups on the seventh day after birth. The kidneys were surgically removed to conduct Western blot and metabolomic analyses. RESULTS: IUGR was produced by UPI, as evidenced by the significantly lower body weights of the pups with IUGR compared to the control pups on postnatal day 7. UPI significantly increased the levels of cleaved caspase-3 (p < 0.05) and BAX/Bcl-2 (p < 0.01) in the pups with IUGR. Ten metabolites exhibited statistically significant differences between the groups (q < 0.05). Metabolic pathway enrichment analysis demonstrated statistically significant variations between the groups in the metabolism related to fructose and mannose, amino and nucleotide sugars, and inositol phosphate. CONCLUSIONS: UPI alters kidney metabolism in growth-restricted newborn rats and induces renal apoptosis. The results of our study have the potential to provide new insights into biomarkers and metabolic pathways that are involved in the kidney changes generated by IUGR.

Effects of uteroplacental insufficiency on cardiac development in growth-restricted newborn rats.

Fetal growth restriction (FGR) is associated with reduced cardiac function in neonates. Uteroplacental insufficiency (UPI) is the most common cause of FGR. The mechanisms underlying these alterations remain unknown. We hypothesized that UPI would influence cardiac development in offspring rats. Through this study, we evaluated the effects of UPI during pregnancy on heart histology and pulmonary hypertension in growth-restricted newborn rats. On gestation Day 18, either UPI was induced through bilateral uterine vessel ligation (FGR group) or sham surgery (control group) was performed. The right middle lobe of the lung and the heart were harvested for histological and immunohistochemical evaluation on postnatal days 0 and 7. The FGR group exhibited significantly lower body weight, hypertrophy and degeneration of cardiomyocytes, increased intercellular spaces between the cardiomyocytes and collagen deposition, and decreased glycogen deposition and HNK-1 expression compared with the control group on postnatal days 0 and 7. These results suggest that neonates with FGR may have inadequate myocardial reserves, which may cause subsequent cardiovascular compromise in future life. Further studies are required to evaluate the hemodynamic changes in these growth-restricted neonates.

Preeclampsia and diabetes mellitus.

OBJECTIVE: The purpose of this paper is to provide a review of recent research on the relationship between preeclampsia and diabetes mellitus in pregnancy. METHODOLOGY: A structured search for literary sources in PubMed and ScienceDirect databases using keywords, followed by a selection of papers based on solid methodology. RESULTS: Preeclampsia is a serious condition, which complicates 2-7% of pregnancies. It causes maternal complications (organ dysfunction) and fetal complications (pathological haemodynamic parameters of the uteroplacental unit and fetal growth restriction). Pregnant women with pregestational diabetes have a 2- and 4-times higher risk of developing preeclampsia and the ones with gestational diabetes have 1.3-times higher risk. The main identified risk factors are inadequate compensation of diabetes, diabetic nephropathy, retinopathy and the duration of diabetes. To minimalize the risk of developing preeclampsia, a composite screening has been implemented. With a positive result a preventive use of acetylsalicylic acid from at the latest 16 and up until the 36th week is advised. Preeclampsia is also a risk factor for developing diabetes mellitus and other cardiovascular diseases later in life. For that reason, a long-term dispensary of women who had preeclampsia in pregnancy is recommended.

Determination of the ideal timing of delivery among growth- restricted fetuses at less than 32 weeks age of gestation using a stage-based doppler protocol for admitted patients at the Philippine Children’s Medical Center

OBJECTIVES@#Early onset fetal growth restriction substantially contributes to neonatal mor-bidities and mortalities. The main dilemma lies on the timing of delivery, especially for pre- and peri-viable fetuses, due to the challenge in creating an ideal balance of minimized in-utero hy- poxia-induced fetal injury or death versus the risks of iatrogenic preterm delivery. We wished to determine the ideal timing of delivery among growth-restricted fetuses <32 weeks gestation us- ing a stage-based doppler protocol.@*MATERIALS AND METHODS@#A retrospective-cohort study of 67 singleton-pregnant wom- en with growth restriction at <32 weeks gestation and hospitalized from January 2010 to Sep- tember 2021 was conducted. Medical records were reviewed, and the outcomes were extracted. The primary outcomes were arterial pH at birth and mortality, while secondary outcomes includ- ed neonatal morbidities.@*RESULTS@#Fetal growth restriction progressed by an average of 3 stages (41.79%) within a 2- to 3.5-week period. More than half had arterial pH <7.20, which was lowest at Stage II FGR (50.00%). The prevalence of neonatal mortality was 16.42% and was lowest at Stage I (8.70%) and Stage II FGR (18.75%).@*CONCLUSION@#Doppler studies may be conducted weekly for Stage I, biweekly for Stage II, every 1-2 days for Stage III and every 12 hours for Stage IV. Delivery is ideal at Stage II as this resulted in the least number of acidosis and neonatal mortalities.

Uteroplacental Insufficiency Causes Microbiota Disruption and Lung Development Impairment in Growth-Restricted Newborn Rats.

Preclinical studies have demonstrated that intrauterine growth retardation (IUGR) is associated with reduced lung development during the neonatal period and infancy. Uteroplacental insufficiency (UPI), affecting approximately 10% of human pregnancies, is the most common cause of IUGR. This study investigated the effects of UPI on lung development and the intestinal microbiota and correlations in newborn rats with IUGR, using bilateral uterine artery ligation to induce UPI. Maternal fecal samples were collected on postnatal day 0. On postnatal days 0 and 7, lung and intestinal microbiota samples were collected from the left lung and the lower gastrointestinal tract. The right lung was harvested for histological assessment and Western blot analysis. Results showed that UPI through bilateral uterine artery ligation did not alter the maternal gut microbiota. IUGR impaired lung development and angiogenesis in newborn rats. Moreover, on postnatal day 0, the presence of Acinetobacter and Delftia in the lungs and Acinetobacter and Nevskia in the gastrointestinal tract was negatively correlated with lung development. Bacteroides in the lungs and Rodentibacter and Romboutsia in the gastrointestinal tract were negatively correlated with lung development on day 7. UPI may have regulated lung development and angiogenesis through the modulation of the newborn rats' intestinal and lung microbiota.

Effects of uteroplacental insufficiency on growth-restricted rats with altered lung development: A metabolomic analysis.

Background: Intrauterine growth restriction (IUGR) is among the most challenging problems in antenatal care. Several factors implicated in the pathophysiology of IUGR have been identified. We aimed to investigate the effect of UPI on lung development by identifying metabolic changes during the first seven days of postnatal life. Materials and methods: On gestation day 17, four time-dated pregnant Sprague Dawley rats were randomized to a IUGR group or a control group, which underwent an IUGR protocol comprising bilateral uterine vessel ligation and sham surgery, respectively. On gestation day 22, 39 control and 26 IUGR pups were naturally delivered. The rat pups were randomly selected from the control and IUGR group on postnatal day 7. The pups' lungs were excised for histological, Western blot, and metabolomic analyses. Liquid chromatography mass spectrometry was performed for metabolomic analyses. Results: UPI induced IUGR, as evidenced by the IUGR rat pups having a significantly lower average body weight than the control rat pups on postnatal day 7. The control rats exhibited healthy endothelial cell healthy and vascular development, and the IUGR rats had a significantly lower average radial alveolar count than the control rats. The mean birth weight of the 26 IUGR rats (5.89 ± 0.74 g) was significantly lower than that of the 39 control rats (6.36 ± 0.55 g; p < 0.01). UPI decreased the levels of platelet-derived growth factor-A (PDGF-A) and PDGF-B in the IUGR newborn rats. One-way analysis of variance revealed 345 features in the pathway, 14 of which were significant. Regarding major differential metabolites, 10 of the 65 metabolites examined differed significantly between the groups (p < 0.05). Metabolite pathway enrichment analysis revealed significant between-group differences in the metabolism of glutathione, arginine-proline, thiamine, taurine-hypotaurine, pantothenate, alanine-aspartate-glutamate, cysteine-methionine, glycine-serine-threonine, glycerophospholipid, and purine as well as in the biosynthesis of aminoacyl-tRNA, pantothenate, and CoA. Conclusions: UPI alters lung development and metabolomics in growth-restricted newborn rats. Our findings may elucidate new metabolic mechanisms underlying IUGR-induced altered lung development and serve as a reference for the development of prevention and treatment strategies for IUGR-induced altered lung development.

Patterns of Brain Sparing in a Fetal Growth Restriction Cohort.

Objective: Our objective was to compare differences in Doppler blood flow in four fetal intracranial blood vessels in fetuses with late-onset fetal growth restriction (FGR) vs. those with small for gestational age (SGA). Methods: Fetuses with estimated fetal weight (EFW) <10th percentile were divided into SGA (n = 30) and FGR (n = 51) via Delphi criteria and had Doppler waveforms obtained from the middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), and vertebral artery (VA). A pulsatility index (PI) <5th centile was considered "abnormal". Outcomes included birth metrics and neonatal intensive care unit (NICU) admission. Results: There were more abnormal cerebral vessel PIs in the FGR group versus the SGA group (36 vs. 4; p = 0.055). In FGR, ACA + MCA vessel abnormalities outnumbered PCA + VA abnormalities. All 8 fetuses with abnormal VA PIs had at least one other abnormal vessel. Fetuses with abnormal VA PIs had lower BW (1712 vs. 2500 g; p < 0.0001), delivered earlier (35.22 vs. 37.89 wks; p = 0.0052), and had more admissions to the NICU (71.43% vs. 24.44%; p = 0.023). Conclusions: There were more anterior vessels showing vasodilation than posterior vessels, but when the VA was abnormal, the fetuses were more severely affected clinically than those showing normal VA PIs.

Epigenetic Mechanisms Responsible for the Transgenerational Inheritance of Intrauterine Growth Restriction Phenotypes.

A poorly functioning placenta results in impaired exchanges of oxygen, nutrition, wastes and hormones between the mother and her fetus. This can lead to restriction of fetal growth. These growth restricted babies are at increased risk of developing chronic diseases, such as type-2 diabetes, hypertension, and kidney disease, later in life. Animal studies have shown that growth restricted phenotypes are sex-dependent and can be transmitted to subsequent generations through both the paternal and maternal lineages. Altered epigenetic mechanisms, specifically changes in DNA methylation, histone modifications, and non-coding RNAs that regulate expression of genes that are important for fetal development have been shown to be associated with the transmission pattern of growth restricted phenotypes. This review will discuss the subsequent health outcomes in the offspring after growth restriction and the transmission patterns of these diseases. Evidence of altered epigenetic mechanisms in association with fetal growth restriction will also be reviewed.

The effect of combined spinal epidural versus epidural analgesia on fetal heart rate in laboring patients at risk for uteroplacental insufficiency.

BACKGROUND: The effects of neuraxial analgesia on fetal heart tracings have been studied in "healthy" pregnancies. Our objective was to compare the impact of intrapartum epidural analgesia (EA) versus combined spinal epidural analgesia (CSE) on fetal heart rate changes in pregnancies at risk for uteroplacental insufficiency (UPI). METHODS: Singleton pregnancies diagnosed with chronic hypertension, gestational hypertension and/or preeclampsia, and/or fetal growth restriction (FGR) and receiving neuraxial analgesia intrapartum from 2012 to 2015 were studied retrospectively. The primary outcome was change in fetal heart rate (FHR) category following neuraxial analgesia. Manual review of all FHR tracings was performed and classified by the National Institute of Child Health and Human Development (NICHD) categories. Data collection included maternal demographics, blood pressure, uterine tachysystole, uterine hypertonus, mode of delivery, interventions for FHR abnormalities and neonatal outcomes. RESULTS: Of laboring patients at risk for UPI, 110 patients received EA and 127 patients received CSE. The rate and change in FHR categories and abnormalities following neuraxial analgesia were the same in both groups. Both EA and CSE resulted in a significant increase in NICHD FHR category II, from 27.3 to 65.5% for EA and 20.9 to 64.3% for CSE. The occurrence of maternal hypotension, uterine tachysystole, interventions for FHR abnormalities, and uterine hypertonus following neuraxial analgesia was not found to be significantly different between the two groups. When compared to the EA group, CSE had a higher rate of NICU admission (29.5 versus 16.4%, p = .021). CONCLUSIONS: FHR category increased following both CSE and EA. The side effects of maternal hypotension and need for fetal interventions was not different between CSE and EA.

Epigenetic mechanisms involved in intrauterine growth restriction and aberrant kidney development and function.

Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency results in a placenta that is unable to provide adequate nutrients and oxygen to the fetus. These growth-restricted babies have an increased risk of hypertension and chronic kidney disease later in life. In rats, both male and female growth-restricted offspring have nephron deficits but only males develop kidney dysfunction and high blood pressure. In addition, there is transgenerational transmission of nephron deficits and hypertension risk. Therefore, epigenetic mechanisms may explain the sex-specific programming and multigenerational transmission of IUGR-related phenotypes. Expression of DNA methyltransferases (Dnmt1and Dnmt3a) and imprinted genes (Peg3, Snrpn, Kcnq1, and Cdkn1c) were investigated in kidney tissues of sham and IUGR rats in F1 (embryonic day 20 (E20) and postnatal day 1 (PN1)) and F2 (6 and 12 months of age, paternal and maternal lines) generations (n = 6-13/group). In comparison to sham offspring, F1 IUGR rats had a 19% decrease in Dnmt3a expression at E20 (P < 0.05), with decreased Cdkn1c (19%, P < 0.05) and increased Kcnq1 (1.6-fold, P < 0.01) at PN1. There was a sex-specific difference in Cdkn1c and Snrpn expression at E20, with 29% and 34% higher expression in IUGR males compared to females, respectively (P < 0.05). Peg3 sex-specific expression was lost in the F2 IUGR offspring, only in the maternal line. These findings suggest that epigenetic mechanisms may be altered in renal embryonic and/or fetal development in growth-restricted offspring, which could alter kidney function, predisposing these offspring to kidney disease later in life.

In vivo: maternal betaine supplementation normalized fetal growth in diabetic pregnancy.

PURPOSE: Diabetes alters maternal metabolism and can lead to aberrant fetal growth. In addition to insulin treatment, nutritional diet interventions are recommended for promoting fetal health against diabetes-induced adverse effects. Therefore, we conducted an in vivo study to investigate betaine efficacy on fetal development against maternal diabetes. METHODS: Thirty-two dams were divided into four equal groups: control (C), betaine supplementation (BS), diabetic pregnancy (DP) and diabetic pregnancy plus betaine supplementation (DP + BS). Fasting blood sugar (FBS) and body weight (BW) were monitored during pregnancy. After physiological delivery, dams glycated hemoglobin (HbA1c) concentrations were measured, followed by fetal development indices including litter size (LS), neonatal weight (NW) and crown-rump (CR). Also, maternal oxidative status was assessed by evaluating glutathione (GSH) content, glutathione peroxidase (GSH-Px) and catalase (CAT) activities, and malondialdehyde (MDA) concentration in the erythrocytes. RESULTS: Betaine supplementation significantly alleviated FBS and tended to recover BW loss. It also significantly decreased HbA1c values in dams of DP + BS compared to DP group. Normalized fetal indices such as LS, NW and CR under betaine supplementation were associated with a significant increase in GSH content and GSH-Px activity, as well as decreased MDA concentrations in erythrocytes of dams in the DP + BS versus the DP group, indicating improved redox balance in the dams. CONCLUSION: We indicated for the first time that betaine supplementation improved the maternal glucose metabolism and redox balance associated with normalized fetal growth. Nevertheless, further studies are required to investigate the mechanisms through which betaine protects fetal growth in diabetic pregnancy.

Electronic cigarettes and obstetric outcomes: a prospective observational study.

OBJECTIVE: To compare the obstetric outcomes and socio-demographic factors in electronic cigarette (EC) users with cigarette smokers and non-smokers in pregnancy. DESIGN: Prospective observational cohort study. SETTING: A large urban maternity hospital delivering almost 8500 infants per year. POPULATION: Pregnant women attending for antenatal care. METHODS: Electronic cigarette users at time of booking history were prospectively identified. Maternal and neonatal outcomes were compared with those of pregnant smokers and non-smokers. Multiple logistic regression analysis was performed to estimate the association between the explanatory variables and birthweight. MAIN OUTCOMES MEASURES: Infant birthweight, gestation at delivery, incidence of low birthweight. RESULTS: A total of 218 women with exclusive EC use and 195 women with dual use of both cigarettes and EC, had a live birth during the study period. EC users were of higher socio-economic status than smokers. Infants born to EC users had a mean birthweight of 3470 g (± 555 g), which was similar to that of non-smokers (3471 ± 504 g, P = 0.97) and significantly greater than that of smokers (3166 ± 502 g, P < 0.001). The mean birth centile of EC users was similar to non-smokers (51st centile versus 47th centile, P = 0.28) and significantly greater than that of smokers (27th centile, P < 0.001). Dual users had a mean birthweight and birth centile similar to that of smokers. CONCLUSION: The birthweight of infants born to EC users is similar to that of non-smokers, and significantly greater than cigarette smokers. Dual users of both cigarettes and EC have a birthweight similar to that of smokers. TWEETABLE EXTRACT: Birthweight of infants born to electronic cigarette users appears to be similar to that of non-smokers.

Do Doppler Changes Reflect Pathology of Placental Vascular Lesions in IUGR Pregnancies?

OBJECTIVES: Doppler assessment of uteroplacental (UP) and fetoplacental (FP) circulation detects abnormal waveforms in intrauterine growth-restricted (IUGR) pregnancies. Similarly, histopathology also reveals lesions of vascular compromise in IUGR placenta. We evaluated an association between Doppler and histopathological (HP) assessment of the maternal and fetal circulation in IUGR. METHODS: IUGR cases with both Doppler and histopathology assessment were selected from our database. Doppler patterns recorded UP and FP insufficiency. The HP vascular lesions were classified as maternal vascular underperfusion and fetal thrombotic vasculopathy (FTV). IUGRs were grouped based on (i) presence of preeclampsia (PE), (ii) clinical onset (early vs late) of IUGR (early onset [EO]/late onset), and (iii) gestational age (term, T/preterm, PT). RESULTS: Abnormal Doppler waveforms were present in 69 of the total 88 IUGR cases (78.4%). The most frequent pattern was fetoplacental insufficiency (FPI) (66%) which was combined with uteroplacental insufficiency (UPI) in 49%. HP showed vascular lesions in 52.3% and most frequent was FTV (38%). PE-associated IUGR (n = 49) had higher UPI pattern (75.5% vs 43.6%, P = .004), while normotensive IUGR had higher FPI pattern (28.2% vs 8.2%, P = .01). EO-IUGR (n = 55) and PT-IUGR (n = 52) had significant abnormal Doppler waveforms (P < .05) with higher combined patterns and brain sparing. Doppler was more sensitive for fetal vascular lesions than maternal (75.8% vs 66.7%). However, 42% of cases with normal Doppler findings showed HP vascular lesions. CONCLUSION: IUGR pregnancies harbor significant vascular compromise. Fetal circulatory lesions were more common in IUGR pregnancies. In a significant number of cases with normal Doppler report, vascular lesions were identified on histopathology, emphasizing placental examination in all cases of IUGR.

Decoding stillbirths using the Relevant Condition at Death classification: Study from the developing world

Objective: To determine the stillbirth rate in 2017 at Christian Medical College, a tertiary care perinatal center in South India, and to identify causes for the various stillbirths that occurred using the Relevant Condition at Death (ReCoDe) classification. Material and Methods: Medical records of the women with stillbirths between January 1st, to December 31st, 2017, were retrieved and analyzed using the SPSS software (IBM, version 23). The study was approved by the institutional review board (minute no: 11273, retro dated: 28/3/2018). Results: Of the total 14696 deliveries between January 1st, 2017, to December 31st, 2017, there were 247 stillbirths, a rate of 16.8 per 1000 births. Maternal factors: 156 (64.2%) women were booked and the rest were un-booked. Hypertensive disorders of pregnancy were detected in 27.5% (n=67). A greater number of un-booked women had gestational hypertension as compared with booked women (41% vs 24%, p=0.005). Fetal characteristics: still births secondary to lethal congenital anomalies were seen in 18.2% (n=45). Lethal congenital anomalies were diagnosed 10 times more in the booked patients than un-booked ones (24.7% vs 2.3%, p=0.001). Obstetric factors: one or two previous miscarriages were seen in 29.5% cases. Seventeen women (6.9%) had a prior stillbirth. ReCoDe Classification: we were able to successfully classify 84.2% of the stillbirths, leaving 15.78% unclassified. Fetal growth restriction secondary to uteroplacental insufficiency was found in 25.9% cases. Of the placental causes, abruption accounted for 10.9% of cases. Medical co-morbidities were seen in 46.5% pregnancies. Conclusion: The ReCoDe method of classifying stillbirths is useful in the developing world. It helped to elucidate the cause for stillbirths in 84.2% of cases. The majority of cases in our set were due to fetal growth restriction, hypertensive disorders of pregnancy, and uteroplacental insufficiency. Stillbirths can be prevented by a comprehensive antenatal care system, early recognition, and close monitoring of high-risk pregnancies.

Early Accreta and Uterine Rupture in the Second Trimester.

The differential diagnosis of third trimester bleeding can range from placenta abruptia to placenta previa to uterine rupture and the placenta accreta spectrum (PAS). However, patients with risk factors such as multiple cesarean sections (c-sections), advanced maternal age (AMA), grand multiparity, and single-layer uterine closure are at greater risk of developing these complications earlier than we would traditionally expect. This case recounts a 38-year-old gravida 6 preterm 3 term 1 abortus 1 live 4 (G6P3114) at 23 weeks and five days gestational age (GA) with a past medical history of preterm pregnancy, pre-eclampsia, chronic abruptia, three previous c-sections, and low-lying placenta who presented to the emergency department (ED) with vaginal bleeding. Initial workup revealed placenta accreta and possible percreta. The patient was placed on intramuscular (IM) corticosteroids in anticipation of preterm delivery. As soon as the patient was stable, she was discharged home. She presented to a different hospital the next day with the same complaints. Imaging was consistent with accreta and her presentation with abruption. During the hospital stay, the patient went into threatened preterm labor (PTL). At first, we suspected preterm premature rupture of membranes (PPROM) due to apparent pooling of amniotic fluid in the vaginal canal. Upon further work up, the diagnosis was consistent with chronic abruption oligohydramnios sequence (CAOS). Before this could be investigated, her hospital course was complicated by acute abruption and Category III/nonreassuring fetal heart rate (FHR) tracing. The patient underwent an emergency c-section at 26 weeks GA as well as a planned supracervical hysterectomy for desired permanent sterilization. During the operation, the patient suffered a postpartum hemorrhage (PPH) of 4500 mL. She was later discharged home on postoperative day (POD) eight.

Restricción de crecimiento fetal y factores angiogénicos: un nuevo horizonte: a new horizon / Fetal growth restriction and angiogenic factors

Fetal growth restriction is intimately linked to the placental function due to its failure of adequately nurture and oxygenate the fetus, with consequences in the short and long term. The search for the best definition and best diagnostic biomarkers has currently led to angiogenic factors closely related to the placenta formation and development. Placenta hypoperfusion has been linked to alterations in the levels of angiogenic factors, and it is proposed that these could help to differentiate the fetuses truly affected by chronic hypoxia even before the late adaptive hemodynamic changes are evident by Doppler ultrasound. This could have implications not only in the definition of growth restriction but also in the potential prediction of the event.

La restricción de crecimiento fetal está íntimamente ligada a la función placentaria por el fracaso de la adecuada nutrición y oxigenación del feto, con múltiples consecuencias a corto y largo plazo. La búsqueda de la mejor definición y de los mejores biomarcadores diagnósticos actualmente se dirige a los factores angiogénicos. Estos factores se relacionan estrechamente con la formación y desarrollo placentario. En la hipoperfusión placentaria se ha hallado alteraciones en los niveles de los factores angiogénicos, por lo que estos factores podrían ayudar a diferenciar a los fetos verdaderamente afectados por hipoxia crónica aún antes que los cambios hemodinámicos adaptativos tardíos sean evidenciables en la ultrasonografía Doppler. Esto podría tener implicancias no solo en la definición de restricción de crecimiento sino también en la potencial predicción del evento.