Severe Fetal Growth Restriction Research Articles

A case study of multiple placental cysts complicated by severe fetal growth restriction

A case study of multiple placental cysts complicated by severe fetal growth restriction

A case of Breus’ mole that was diagnosed with sequential ultrasound observation after finding severe fetal growth restriction.

A case of Breus’ mole that was diagnosed with sequential ultrasound observation after finding severe fetal growth restriction.

Pregnancy Outcome in Pregnancies Complicated by Fetal Growth Restriction and Severe Preeclampsia

Abstract Background common pathophysiological feature favors parallel occurrence of severe pre-eclampsia (PET) and fetal growth restriction. Objective To identify pregnancy and neonatal outcome differences between early-onset and late-onset preeclampsia, in relation to fetal growth restriction (FGR) Methods this retrospective study included 50 singleton pregnancies with FGR and severe PET who were admitted in Ain Shams University Maternity Hospital. Fetal growth restriction was defined as EFW and/or AC < 10th percentile. Preeclampsia with severe features included patients with systolic BP ≥ 160 mmHg, diastolic BP ≥ 110 mmHg, elevated liver transaminases twice the normal values, elevated serum creatinine twice the normal levels, or > 1.1mg/dl, HELLP syndrome, features of impending eclampsia, pulmonary edema, and/or thrombocytopenia with platelets level < 100 x 109/L. obstetric and neonatal outcomes were compared in early and late onset PET. Results The current study revealed that there was no difference between early and late onset PET in fetal and pregnancy outcomes while there was significant difference in neonatal outcomes. Conclusion the current study showed that risk of adverse neonatal outcomes as respiratory distress syndrome and neonatal death were higher in cases with early onset PET.

Neurodevelopmental outcomes at 2 years in children who received sildenafil therapy in utero: The STRIDER randomised controlled trial.

Severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains vasoactive responsiveness but is susceptible to treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, which may improve perinatal outcomes. Superiority, double-blind randomised controlled trial. A total of 20 UK fetal medicine units. Pregnancies affected by FGR, defined as an abdominal circumference below the tenth centile with absent end-diastolic flow in the umbilical artery between 22+0 and 29+6 weeks of gestation. Treatment with sildenafil (25 mg three times/day) or placebo until delivery or 32 weeks of gestation. All infants alive at hospital discharge were assessed for cardiovascular function and cognitive, speech/language and neuromotor impairment at 2 years of age. The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley-III composite score of >85. In total, 135 women were randomised between November 2014 and July 2016 (70 to sildenafil and 65 to placebo). We previously published that there was no improvement in time to delivery or perinatal outcomes with sildenafil. In all, 75 babies (55.5%) were discharged alive, with 61 infants eligible for follow-up (32 sildenafil and 29 placebo). One infant died (placebo), three mothers declined and ten mothers were uncontactable. There was no difference in neurodevelopment or blood pressure following treatment with sildenafil. Infants who received sildenafil had a larger head circumference at 2 years of age (median difference 49.2 cm, IQR 46.4-50.3, vs 47.2 cm, 95% CI 44.7-48.9 cm). Sildenafil therapy did not prolong pregnancy or improve perinatal outcomes and did not improve infant neurodevelopment in FGR survivors. Therefore, sildenafil should not be prescribed for this condition.

Initiation of metformin in early pregnancy results in fetal bioaccumulation, growth restriction, and renal dysmorphology in a primate model

BackgroundIn recent years, pragmatic metformin use in pregnancy has stretched to include prediabetes, type 2 diabetes, gestational diabetes and (most recently) pre-eclampsia. With its expanded use, however, concerns of unintended harm have been raised. ObjectiveWe developed an experimental primate model and applied triple-quadruple pole LC mass spectrometry (UHPLC-QQQ) for direct quantitation of maternal and fetal tissue metformin levels with detailed fetal biometry and histopathology. Study designWithin 30 days of confirmed conception (defined as early pregnancy), n=13 time-bred (TMB) Rhesus dams with gestations designated for fetal necropsy were initiated on twice daily human dose-equivalent 10 mg/kg metformin or vehicle control. Pregnant dams were maintained as pairs and fed either a control chow or 36% fat Western-style diet (WSD). Metformin or placebo vehicle control were delivered in a variety of treats while animals were separated via a slide. A Cesarean was performed at G145, and amniotic fluid and blood were collected and the fetus and placenta were delivered. The fetus was immediately necropsied by trained primate center personnel. All fetal organs were dissected, measured, sectioned, and processed per clinical standards. Fluid and tissue metformin levels were assayed using validated UHPLC-QQQ in SRM against standard curves. ResultsAmong the n=13 G145 pregnancies with fetal necropsy, n=1 dam and its fetal tissues had detectable metformin levels despite being allocated to the vehicle control group (>1 μM metformin/kg maternal weight or fetal/placental tissue), while a second fetus allocated to the vehicle control group had severe fetal growth restriction (birthweight 248.32 g, <1%) and was suspected of having a fetal congenital condition. After excluding these two fetal gestations from further analyses, 11 fetuses from dams initiated on either vehicle control (n=4, 3 female, 1 male fetuses) or 10 mg/kg metformin (n=7, 5 female, 2 male fetuses) were available for analyses. Among dams initiated on metformin by G30 (regardless of maternal diet), we observed significant bioaccumulation within the fetal kidney (0.78-6.06 μmol/kg, mean 2.48 μmol/kg) , liver (0.16-0.73 μmol/kg, mean 0.38 μmol/kg), fetal gut (0.28-1.22 μmol/kg, mean 0.70 μmol/kg), amniotic fluid (0.43-3.33 μmol/L, mean 1.88 μmol/L), placenta (0.16-1.0 μmol/kg , mean 0.50 μmol/kg) and fetal serum (0 -0.66 μmol/L , mean 0.23 μmol/L ), and fetal urine (4.1-174.1 μmol/L mean 38.5 μmol/L ), with fetal levels near biomolar equivalent to maternal levels (maternal serum 0.18-0.86 μmol/L , mean 0.46 μmol/L; maternal urine 42.6-254.0 μmol/L , mean 149.3 μmol/L). WSD feeding neither accelerated nor reduced metformin bioaccumulations in maternal or fetal serum, urine, amniotic fluid, placenta nor fetal tissues. In these 11 animals, fetal bioaccumulation of metformin was associated with less fetal skeletal muscle (57% lower cross-sectional area of gastrocnemius) and decreased liver, heart, and retroperitoneal fat masses (p<0.05), collectively driving lower delivery weight (p<0.0001) without changing the crown-rump length. Sagittal sections of fetal kidneys demonstrated delayed maturation, with disorganized glomerular generations and increased cortical thickness; this renal dysmorphology was not accompanied by structural nor functional changes indicative of renal insufficiency. ConclusionsWe demonstrate fetal bioaccumulation of metformin with associated fetal growth restriction and renal dysmorphology following maternal initiation of the drug within 30 days of conception in primates. Given these results and the prevalence of metformin use during pregnancy, additional investigation of any potential immediate and enduring effects of prenatal metformin use is warranted.

Prediction of severe preeclampsia and intrauterine growth restriction based on serum placental exosome miR-520a-5p levels during the first-trimester.

To assess the predictive capabilities of serum exosomal levels of micro-RNA-520a-5p (miR-520a-5p) concerning the occurrence of severe preeclampsia (sPE) and fetal growth restriction (FGR) during the first trimester of pregnancy. During the period spanning from October 2020 to October 2021, serum samples were procured from the first trimester and subsequently preserved by freezing at -80 ℃. These samples were obtained from 105 pregnant women in a nested case-control study. This cohort consisted of individuals who later developed sPE (sPE group, n = 35) and FGR (FGR group, n = 35) during the third trimester. Additionally, 35 women with normal blood pressure were denoted as normal pregnancy group. Serum samples from the first trimester were retrieved from all groups for further analysis after thawing. Exosomes were extracted from the serum samples collected during the first trimester and examined using transmission electron microscopy, western blot, and nanoparticle tracking analysis. Additionally, the determination of their placental origin was also established during the course of the study. Exosome miR-520a-5p levels were measured using real-time quantitative polymerase chain reaction assays, primarily involving quantitative reverse transcription polymerase chain reactions. Fetal placental tissues from the 3 groups were collected shortly after birth, and miR-520a-5p expression was measured using real-time quantitative polymerase chain reaction. Serum placental exosomes and fetal placental tissues were compared for miR-520a-5p levels. Placental trophoblasts were identified as the source of serum exosomes in all 3 groups. It was found that serum placental exosomes exhibited lower levels of miR-520a-5p in both the sPE and FGR groups when compared to the normal pregnancy group. This finding was consistent with observations made in postpartum placental tissues. The predictive accuracy for sPE using miR-520a-5p levels in serum placental exosomes during the first trimester was notably higher (area under the receiver operating characteristic curve = 0.806, P <.05) compared to the prediction of FGR (area under the receiver operating characteristic curve = 0.628, P <.05). Placenta-derived exosomes can be extracted from maternal serum during the first trimester of pregnancy and miR-520a-5p detected from the exosomes. The downregulation of miR-520a-5p serves as a more predictive indicator for the subsequent development of sPE compared to predicting FGR.

Obstetric Outcomes After Chemotherapy in Pregnancy [ID 2683556

INTRODUCTION: Cancer affects approximately 1 in 1,000 pregnancies; limited data exist to guide clinical decision making and counseling regarding chemotherapy. We investigated the obstetric outcomes of patients who received chemotherapy for cancer in pregnancy at a large county hospital. METHODS: In this retrospective IRB-approved study, patients diagnosed with cancer prior to or during pregnancy from May 2009 to May 2023 were identified. Those who received chemotherapy in pregnancy were included. Type of cancer, chemotherapeutic agents, and obstetric outcomes were obtained from the electronic medical record. RESULTS: Of 22 patients who initiated or continued chemotherapy, seven had a cancer diagnosis prior to pregnancy. Fifteen were diagnosed in pregnancy, at an average gestational age of 15.5 weeks. Average maternal age was 30.5 years. Hematologic (36%) and breast (32%) cancers were most common. Four terminated pregnancy and 18 continued pregnancy. Chemotherapy initiation occurred at an average of 21.2 weeks. Most patients received alkylating agents or antitumor antibiotics, and only one required antepartum admission for chemotherapy-related complications. Patients delivered at an average of 35.6±3.0 (29–41) weeks and 9/18 (50%) patients delivered prior to 37 weeks. Severe fetal growth restriction (less than third percentile) occurred in 6/18 (33%) patients; one had a history of fetal growth restriction in a prior pregnancy. There were no neonatal deaths or congenital malformations. CONCLUSION: While high rates of fetal growth restriction and preterm birth were observed, chemotherapy was well tolerated in pregnancy and all non-terminated pregnancies delivered viable infants in the third trimester. Chemotherapy can be administered in pregnancy with counseling regarding neonatal risks.

Prediction of adverse neonatal adaptation in fetuses with severe fetal growth restriction after 34 weeks of gestation

ObjectiveTo establish a predictive model for adverse immediate neonatal adaptation (INA) in fetuses with suspected severe fetal growth restriction (FGR) after 34 gestational weeks (GW). Methods. We conducted a retrospective observational study at the University Hospitals of Strasbourg between 2000 and 2020, including 1,220 women with a singleton pregnancy and suspicion of severe FGR who delivered from 34 GW. The primary outcome (composite) was INA defined as Apgar 5-minute score <7, arterial pH <7.10, immediate transfer to pediatrics, or the need for resuscitation at birth. We developed and tested a logistic regression predictive model. Results. Adverse INA occurred in 316 deliveries. The model included six features available before labor: parity, gestational age, diabetes, middle cerebral artery Doppler, cerebral-placental inversion, onset of labor. The model could predict individual risk of adverse INA with confidence interval at 95 %. Taking an optimal cutoff threshold of 32 %, performances were: sensitivity 66 %; specificity 83 %; positive and negative predictive values 60 % and 87 % respectively, and area under the curve 78 %. Discussion. The predictive model showed good performances and a proof of concept that INA could be predicted with pre-labor characteristics, and needs to be investigated further.

Neonatal Outcomes among Fetuses with an Abdominal Circumference

Fetal growth restriction (FGR) is defined as an estimated fetal weight (EFW) or abdominal circumference (AC) <10th percentile (%ile) for gestational age (GA). An EFW <3rd %ile for GA is considered severe FGR (sFGR). It remains unknown if fetuses with isolated AC <3rd %ile should be considered sFGR. Our primary objective was to assess composite neonatal outcomes in fetuses with an AC <3rd %ile and overall EFW 3rd to 9th %ile compared with those with an EFW <3rd %ile. This retrospective cohort study was undertaken at a tertiary academic center from January 2016 to December 2021. Inclusion criteria were singleton fetuses with an EFW <3rd %ile (Group 1) or AC <3rd %ile with EFW 3rd to 9th %ile (Group 2) at 28 weeks' gestation or greater. Exclusion criteria were multiple gestations, presence of a major fetal anomaly, resolution of FGR, genetic syndrome, or infection. Composite neonatal outcome was defined by any of the following: neonatal intensive care unit admission >48 hours, necrotizing enterocolitis, sepsis, respiratory distress syndrome, mechanical ventilation, retinopathy of prematurity, seizures, intraventricular hemorrhage, stillbirth, or death before discharge. Small for gestational age (SGA) was defined as birth weight <10th %ile for GA. A total of 743 patients fulfilled our study criteria, with 489 in Group 1 and 254 in Group 2. The composite neonatal outcome occurred in 281 (57.5%) neonates in Group 1 and 53 (20.9%) in Group 2 (p < 0.01). The rates of SGA at birth were 94.9 and 75.6% for Group 1 and Group 2, respectively (OR 5.99, 95% confidence interval 3.65-9.82). Although AC <3rd %ile with EFW 3rd to 9th %ile is associated with a lower frequency of SGA and neonatal morbidity than EFW <3 %ile, fetuses with AC <3 %ile still exhibited moderate rates of these adverse perinatal outcomes. Consideration should be given to inclusion of an AC <3rd %ile with EFW 3rd to 9th %ile as a criterion for sFGR. However, prospective studies comparing delivery at 37 versus 38 to 39 weeks' gestation are needed to ensure improved outcomes before widespread adaptation in clinical practice. · The composite neonatal outcome occurred in 57.5% of fetuses with an overall EFW <3rd %ile and 20.9% of fetuses with an AC <3rd %ile but EFW 3rd to 9th %ile.. · Both groups demonstrated a high positive predictive value for SGA birth weight.. · Consideration should be given to inclusion of an AC <3rd %ile as a criterion for sFGR..

Prenatal Features of MIRAGE Syndrome-Case Report and Review of the Literature.

MIRAGE syndrome is a recently described congenital condition characterized genetically by heterozygous gain-of-function missense mutations in the growth repressor sterile alpha domain containing 9 (SAMD9) located on the arm of chromosome 7 (7q21.2). The syndrome is rare and is usually diagnosed in newborns and children with myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy, hence the acronym MIRAGE. The aims of this paper are (1) to present fetal ultrasound features in a case where MIRAGE syndrome was diagnosed prenatally and (2) to review the existing literature records on prenatal manifestations of MIRAGE syndrome. In our case, the fetus had severe early fetal growth restriction (FGR) with normal Doppler studies, atypical genitalia, oligohydramnios, and hyperechogenic bowel at the routine mid-gestation anomaly scan. Amniocentesis excluded infections and numeric or structural chromosomal abnormalities while whole exome sequencing (WES) of the fetal genetic material identified the specific mutation. Targeted testing in parents was negative, suggesting the "de novo" mutation in the fetus. We could not identify other specific case reports in the literature on the prenatal diagnosis of MIRAGE syndrome. In cases reported in the literature where the diagnosis of MIRAGE syndrome was achieved postnatally, there are mentions related to the marked FGR on prenatal ultrasound. Severe early-onset FGR with no other apparent cause seems to be a central prenatal feature in these babies, and WES should be offered, especially if there are other structural abnormalities. Prenatal diagnosis of MIRAGE syndrome is possible, allowing for reproductive choices, improved counseling of parents, and better preparation of neonatal care.

Point-of-care ultrasound, today, tomorrow, and the future – the place for task sharing

Background: Maternal and neonatal morbidity and mortality remain public health concerns. A study onmortality in Kenyan hospitals found that neonates comprise two-thirds of deaths in the pediatric agegroup (0–13 years). These deaths are caused by preventable conditions or those, which can bemanaged better if diagnosed early, such as placenta insufficiency, placenta previa, severe fetal growthrestriction, congenital abnormalities, multiple pregnancies, and breech presentation; these can all beidentified using point-of-care ultrasound (POCUS). Obstetrical ultrasound availability is limited to level 4and higher facilities, yet most women access lower levels of health care. Implementation of POCUS iscurrently limited because of a lack of appropriate training, limited scope of practice for frontline workers,and legal framework.Objective: The POCUS project is being undertaken to develop national guidelines to facilitate the roll outand scale-up of obstetrical POCUS.Methods: A collaborative participatory approach is planned for the development of the national POCUSguidelines. The key in this process is the identification of suitable frontline workers who, with adjustmentto their scope of practice, appropriate training, implementation of a supervision/referral system, canundertake obstetrical POCUS and gain buy-in from regulatory bodies, the inclusion of voices of relevantstakeholders, and leadership from government. A landscape and stakeholders analysis will also beundertaken as part of the process of the guideline development.Results: Narrative literature review shows that the WHO recommends effective and reliable antenatalultrasound services to be available to all pregnant women to optimize maternal and newborn healthoutcomes and at least one ultrasound scan up to 24 weeks of pregnancy. That there are deliberateefforts in Kenya to introduce POCUS with pilot training and implementation. Where obstetrical POCUS isimplemented, it is useful in diagnosing fetal malpresentation, placenta previa, congenital malformations,or multiple pregnancies. Appropriate interventions, such as reduction of cesarean delivery, induction oflabor, reduction of small for gestational age, low birthweight, preterm birth, and stillbirths, can improve thehealth outcome of the mother and neonate. There is a need to develop national POCUS guidelines.Conclusions: Implementation of POCUS may be riddled with difficulties, particularly where frontlineworkers’ current scope of practice may not allow them to perform such procedures, regulatoryframework, lack of knowledge, awareness, negative attitude, or behavior. The proposed guidelines willaddress these barriers.

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 one or both diagnoses are present. Quantification of placental villous structures in each of these settings may identify distinct differences in developmental pathways. To determine how quantity and surface area of placental villi and vessels differ between severe, early-onset fetal growth restriction with absent/reversed umbilical artery Doppler indices, hypertensive disorders of pregnancy, and the two conditions combined among subjects with disease severity warranting early preterm delivery. We hypothesize that trajectories of placental morphogenesis diverge after a common initiating insult of deep defective placentation. Specifically, we postulate 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 four groups: [1] Severe fetal growth restriction with absent/reversed umbilical artery end-diastolic velocities and hypertensive disorders of pregnancy, [2] Severe fetal growth restriction with absent/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. 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 with linear regression. Placentas from pregnancies complicated by hypertensive disorders of pregnancy exhibited significantly fewer stem villi (-282 stem villi, 95% CI: [-467, -98], p<0.01), smaller stem villous area (-4.3 mm2, 95% CI: [-7.3, -1.2], p<0.01), and fewer stem villous vessels (-4967 stem villous vessels, 95% CI [-8501, -1433], p<0.01), with no difference in total vascular area. In contrast, placental abnormalities in severe growth restriction were limited to terminal villi, with global decreases in number of villi (-873 terminal villi, 95% CI: [-1501, -246], p<0.01), villous area (-1.5 mm2, 95% CI: [-2.7, -0.4], p<0.01), number of blood vessels (-5165 terminal villous vessels, 95% CI: [-8201, -2128], p<0.01), and vascular area (-0.6 mm2, 95% CI: [-1.1, -0.1], p=0.02). 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/reversed umbilical artery end-diastolic velocities were limited to the terminal villi. There were no significant statistical interactions with the combination of growth restriction and hypertension, suggesting that distinct pathophysiologic pathways downstream of the initial insult of defective placentation are involved in each entity and do not synergize to result in more severe pathologic consequences. Delineating mechanisms underlying the divergence in placental development after a common inciting event of defective deep placentation may shed light on new targets for prevention or treatment.

Rate of deterioration of umbilical artery Doppler indices in fetuses with severe early-onset fetal growth restriction

ObjectiveTo examine risk factors for the development of absent or reversed end-diastolic velocity (A/REDV) and the time intervals of deterioration from normal UA EDV by S/D, PI or RI to decreased and A/REDV in fetuses with early-onset severe FGR. Study DesignRetrospective cohort study performed from 2005 to 2020. All singleton pregnancies with severe (estimated fetal weight [EFW] or abdominal circumference [AC] below the 3rd percentile) and early-onset (diagnosed between 20 0/7 to 31 6/7 weeks of gestation) were included. Fetal genetic or structural anomalies, suspected congenital infections, A/REDV at diagnosis, poor pregnancy dating and absence of follow-up ultrasounds were excluded. EFW, AC and Doppler indices were reviewed longitudinally from diagnosis to delivery. To examine risk factors for A/REDV, we performed backward stepwise logistic regression and calculated odds ratio with 95% confidence interval (CI). Kaplan-Meier curves were compared using log-rank test. ResultsA total of 985 patients met the inclusion criteria and 79 (8%) progressed to A/REDV. Factors associated with development of A/REDV included gestational age at diagnosis (AOR 4.88 [2.55 – 9.37, 95% CI] at 20 0/7 to 23 6/7 weeks and AOR 1.56 [0.86-2.82, 95%CI] at 24 0/7 to 27 6/7 weeks compared to 28 0/7 to 31 6/7 weeks) and presence of chronic hypertension (CHTN) with AOR 2.37 (1.33 – 4.23, 95% CI). Rates of progression from diagnosis of FGR with normal UA Doppler to A/REDV were significant after 4 weeks from diagnosis (5.84% [4.50 – 7.57, 95% CI]). Regarding the Doppler indices, the progression from normal values to abnormal indices was similar in 1 and 2 weeks however the progression from normal to abnormal S/D ratio compared to PI or RI were higher at 4 and 6 weeks. Deterioration from abnormal indices to A/REDV was shorter with abnormal RI and PI when compared to S/D ratio at 2, 4 and 6 weeks after diagnosis and at 6 weeks, respectively. ConclusionEarlier gestational age at diagnosis and CHTN are considered risk factors for Doppler deterioration and development of A/REDV in the UA. With normal Doppler indices, significant deterioration and progression to A/REDV is unlikely until 4 weeks after diagnosis. Abnormal S/D ratio seems to be appear first. However, abnormal PI or RI was associated with A/REDV.

Placental mesenchymal dysplasia associated with severe fetal growth restriction: A case report

Placental mesenchymal dysplasia associated with severe fetal growth restriction: A case report

1068 Pregnancy Outcomes in Severe Early-Onset Fetal Growth Restriction: Results from the Multicenter PERIMETER Study

1068 Pregnancy Outcomes in Severe Early-Onset Fetal Growth Restriction: Results from the Multicenter PERIMETER Study

452 Evaluating updated guidelines for delivery management of severe fetal growth restriction

452 Evaluating updated guidelines for delivery management of severe fetal growth restriction

Systemic Oxidative Stress in Severe Early-Onset Fetal Growth Restriction Associates with Concomitant Pre-Eclampsia, Not with Severity of Fetal Growth Restriction.

Placental insufficiency is an important mechanism underlying early-onset fetal growth restriction (eoFGR). Reduced placental function causes impaired metabolic and gaseous exchange. This unfavorable placental environment is among other processes characterized by increased oxidative stress. Systemic free thiols (FT) are known for their reactive oxygen species scavenging capacity, and higher plasma levels of FT are associated with a better outcome in a multitude of ischemic and inflammatory diseases. We aimed to investigate the relationships between systemic FT levels and maternal and perinatal clinical characteristics and outcomes. In a post hoc analysis of the Dutch Strider study, a cohort of women with eoFGR, we investigated the association between the maternal redox status (FT) levels at study inclusion, placental biomarkers, and maternal and neonatal outcomes in 108 patients. FT were significantly lower in pregnancies complicated with eoFGR with concurrent maternal hypertensive disorders (pregnancy-induced hypertension; ρ = -0.281 p = 0.004, pre-eclampsia; ρ = -0.505 p = 0.000). In addition, lower FT levels were significantly associated with higher systolic (ρ = -0.348 p = 0.001) and diastolic blood pressure (ρ = -0.266 p = 0.014), but not with the severity of eoFGR. FT levels were inversely associated with sFlt (ρ = -0.366, p < 0.001). A strong relation between systemic FT levels and PlGF levels was observed in women with pre-eclampsia at delivery (ρ = 0.452, p = 0.002), which was not found in women without hypertensive disorders (ρ = 0.008, p = 0.958). In women with pregnancies complicated with eoFGR, FT levels reflect the severity of maternal disease related to the underlying placental insufficiency rather than the severity of the placental dysfunction as reflected in eoFGR or perinatal outcomes.

Importance of prenatally diagnosed portosystemic vascular shunts in clinical outcomes

To report two cases of prenatal diagnosis of portosystemic vascular shunts and review the importance of this rare pathology in its neonatal and pediatric evolution. Case 1: pregnancy with fetal growth restriction, 2nd percentile, polyhydramnios, without fetal malformations and abnormal patterns on fetal Doppler. Abnormal blood flow through the ductus venous and abnormal venous communication in the liver were identified. Normal genetic study. Male newborn (NB) delivered at 36 weeks, because of severe fetal growth restriction, by emergency cesarean section. He evolved asymptomatic, with normal liver function, and did not continue follow-up. Case 2: pregnancy with fetal growth restriction < percentile 1. Agenesis of the ductus venous and abnormal communication between the portal vein and the left suprahepatic vein were identified with no other malformations or signs of heart failure. Severe SGA newborn was delivered by induction of labor at 35 weeks. He evolved asymptomatic. Normal complementary study. A home check-up at 2 months showed persistent vascular anomaly without systemic involvement. Even though in the cases presented there were no neonatal complications, this kind of malformations require a high index of suspicion in cases with fetal growth restriction, as well as a long-term multidisciplinary follow-up.

Small for gestational age at preterm birth identifies adverse neonatal outcomes more reliably than antenatal suspicion of fetal growth restriction

Background Fetal growth restriction (FGR) is an important reason for premature delivery and a leading cause of perinatal morbidity and mortality. We aimed to evaluate whether classification as small for gestational age (SGA; <10th centile) at birth or antenatal suspicion of FGR was more strongly associated with neonatal morbidity and mortality in preterm infants. Methods A retrospective audit of infants born between 24 + 0 and 32 + 6 weeks of gestation from 2012–2019 and admitted to the Neonatal Unit at Mercy Hospital for Women (MHW). Infants were categorized according to whether FGR was listed as an antenatal complication in the medical records and whether they were SGA (<10th centile on Fenton chart) or appropriate for gestational age (AGA) at birth, and comparisons for neonatal outcomes were made. Results 371/2126 preterm infants (17.5%) had antenatal suspicion of FGR, and 166 (7.8%) were SGA at birth. No differences in any neonatal outcomes were found between infants with or without suspected FGR, except decreased intraventricular hemorrhage (IVH) in the FGR group. SGA classification was associated with increased rates of all morbidities other than IVH, including bronchopulmonary dysplasia, retinopathy of prematurity, and necrotizing enterocolitis, compared with the AGA group. Death was significantly higher in the SGA group (7.2%) compared with the AGA group (3.5%). Conclusion SGA by Fenton chart more reliably identified neonates at risk of adverse neonatal outcomes than antenatal suspicion of FGR, suggesting it is a reasonable clinical proxy. This most likely reflects the much lower tenth centile weight cutoffs on the Fenton charts compared to in-utero charts used antenatally to diagnose FGR based on ultrasound estimated fetal weight. SGA classification by Fenton approximately equates to <3rd centile on in-utero charts at our institution, therefore identifying the most severe FGR cases.

Novel approach to prenatal predictors of outcomes for fetuses with severe Ebstein anomaly

Objective Ebstein anomaly (EA) is a cardiac malformation with highly variable presentation and severity with limited perinatal management options. We present incorporation of fetal lung measurements into a multidisciplinary evaluation for counseling and predicting postnatal outcomes in patients with severe EA. Methods Five fetuses with severe fetal EA were reviewed. Third trimester sonographic observed/expected total lung area (O/E TLA) and lung to head ratio (O/E LHR), fetal MRI total fetal lung volume ratio (O/E-TFLV), echocardiographic cardio-thoracic ratio (CT ratio), sonographic estimated fetal weight (EFW) by Hadlock formula and presence of hydrops, were used to guide perinatal management. Results Three of five had appropriate fetal growth, were delivered at term in a cardiac operative suite, and underwent immediate intervention with good neonatal outcomes. Two had severe fetal growth restriction (FGR), CT ratios > 0.8 and O/E LHR and TLA < 25%. One of which delivered prematurely with neonatal demise and one suffered in utero demise at 34 weeks. Conclusions FGR, hydrops, increased CT ratio and reduced O/E LHR and TFLV are potential prognosticators of poor outcomes in severe EA, and should be validated in larger cohorts that would allow for a statistical analysis of the predictive utility of these measurements.