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Little is known about the association between hypospadias and small fetuses, as well as the pathological implications of fetal growth restriction (FGR). Thus, we aimed to investigate the association between hypospadias and small fetuses using a database of fetal ultrasound and obstetric events.A cohort of male singleton infants delivered after 22 weeks of gestation at Keio University Hospital between 2013 and 2019 was retrospectively reviewed. FGR was defined according to the Delphi criteria. Logistic regression analysis was performed to identify the significant predictors of hypospadias. Placental pathology was reviewed in cases with hypospadias.Of the 2,040 male infants included in the present study, 23 had hypospadias. The prevalences of a single umbilical artery (SUA), small for gestational age, maternal hypertensive disorders of pregnancy, and a small placenta, were significantly higher in infants with hypospadias. Multiple logistic regression analysis revealed that FGR (odds ratio [OR] = 9.39; 95% confidence interval [CI], 2.50-35.3) and the presence of a SUA (OR = 33.4; 95% CI, 8.00-139.5) were independently and significantly associated with hypospadias. When FGR was stratified by the time of onset, its association with hypospadias was significant regardless of the time of onset. Moreover, placental histological findings suggested that fetal vascular malperfusion might play a role in hypospadias.FGR and SUAs are independent prenatal predictors of the development of hypospadias, and fetal vascular malperfusion of the placenta may be involved in the etiology of hypospadias.

OBJECTIVE: Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy. The incidence of GDM is increasing worldwide and 5-25% of pregnancies are diagnosed with GDM depending on screening strategies and diagnostic criteria. GDM may lead to obstetric complications and increases the risk of adult metabolic disease in the offspring. Timely identification of GDM allows for regulation of maternal glucose levels which may reduce the obstetric complications considerably. The aim of this study is to investigate the association between second trimester ultrasound biometrics and GDM.STUDY DESIGN: This is a retrospective cohort study including 2697 singleton pregnancies attending second trimester ultrasound scan at 20 + 0 to 20 + 6 weeks' gestation and giving birth at Aalborg University Hospital in the year 2020. Ultrasound measurements included head circumference (HC), abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW) by Hadlock's formula. Women with pregestational diabetes were excluded. GDM screening was performed on indication using oral-glucose-tolerance-test (OGTT) including 75 g glucose and a 2-hour serum glucose value ≥ 9 mmol/L was considered diagnostic. The association between fetal biometrics and GDM was investigated by logistic regression.RESULTS: A total of 174 (6.5 %) were diagnosed with GDM. The incidence of GDM in pregnancies with biometrics above the 90th centile was; FL: 10.5 %, HC: 8.8 %, AC: 7.6 %, EFW: 9.3 %. Fetal biometrics above the 90th centile was significantly associated with GDM; ORFL = 2.07, p = 0.001; ORHC = 1.89, p = 0.001; ORAC = 1.63, p = 0.033; OREFW = 1.64, p = 0.036. This association remained significant for HC and FL when adjusted for maternal obesity (Body Mass Index ≥ 27): ORHC(adj)=1.56, p = 0.019; ORFL(adj) = 1.57, p = 0.049.CONCLUSION: At the second trimester scan, fetal biometrics above the 90th centile increase the risk of GDM. In pregnancies that are later diagnosed with GDM fetal growth is increased already at the second trimester scan. Such knowledge underlines the importance of early identification of GDM.

Objective To investigate the association of the maternal serum albumin (MAlb) level with fetal growth and fetal growth restriction (FGR) risk in term-born singletons. Design Prospective cohort study. Setting Four hospital maternity units of the Tongji Maternal and Child Health Cohort study initiated from September 2013 to April 2016 at Wuhan City, in central China. Patient(s) A total of 3,065 mother–offspring pairs. Intervention(s) None. Main Outcome Measure(s) Fetal growth was evaluated by birth weight (BW) and birth length. Fetal growth restriction was defined as BW below the 10th percentile. Result(s) All MAlb levels were within the upper limit of normal. After adjustment for liver function parameters, inflammatory indicators, and others, a reverse U-shaped relationship between MAlb and fetal growth was observed. Specifically, BW increased significantly with an increasing MAlb level when the MAlb level was 36.1 g/L (per g/L: β = −15.1; 95% CI, −21.2, −8.9). There was a similar association between MAlb and birth length. Furthermore, the adjusted odd ratios of FGR across increasing tertiles of the MAlb levels were 1.0 (reference), 1.1 (0.7, 1.8), and 1.7 (1.0, 2.6). Conclusion(s) There was a reverse U-shaped association between MAlb and fetal growth. A higher MAlb level was associated with an increased risk of FGR. Clinical Trial Registration Number NCT03099837.

First trimester circulating ADAM12 is reduced in fetal growth restriction (FGR) and preeclampsia. We measured plasma ADAM12 at 36 weeks' gestation preceding diagnosis of term preeclampsia or delivery of a small for gestational age (SGA; birthweight10th centile) infant in two independent cohorts (Cohort 1 90 SGA, 41 preeclampsia, 862 controls; Cohort 2121 SGA 23 preeclampsia; 190 controls). ADAM12 was reduced with SGA in both cohorts (p = 0.0015 and 0.011 respectively), and further reduced with birthweight5th centile (p = 0.0013 and 0.0058 respectively). This validates ADAM12 as an SGA biomarker near term. Circulating ADAM12 preceding preeclampsia was not consistently altered.

Background: Hypertensive disorders of pregnancy and fetal growth restriction share common etiopathological origins and could be caused by maternal hemodynamic maladaptation to pregnancy. Objective: The aim of our study is to evaluate if there is a correlation between maternal hemodynamic detected by UltraSonic Cardiac Output Monitor (USCOM®) during the first trimester and the pregnancy outcome. Study design: We recruited a nonconsecutive series of women in the first trimester of pregnancy with no previous history of hypertensive disorders. We measured the pulsatility index uterine arteries and performed a hemodynamic evaluation by USCOM® device. After delivery, we reported the development of hypertensive disorders or intrauterine fetal growth restriction later during gestation. Results: A total of 187 women were enrolled during the first trimester; 17 (9%) developed gestational hypertension or preeclampsia while 11 (6%) delivered a restricted growth fetus. Mean uterine artery pulsatility index above the 95th percentile was significantly more frequent in both women who developed hypertension and those with fetal growth restriction compared to controls. Hemodynamic parameters (reduced cardiac output and increased total vascular resistance) were significantly different in the group that developed hypertensive disorders, compared to uncomplicated pregnancy. ROC curves demonstrated the usefulness of uterine artery pulsatility index in the prediction of fetal growth restriction, while hemodynamic parameters were significantly associated to the development of hypertensive disorders. Conclusions: Hemodynamic maladaptation to pregnancy may predispose to the development of hypertension, while we demonstrated a significative relationship between growth restriction and mean uterine pulsatility index. Further studies are needed to assess the value of hemodynamics evaluation in screening protocols of preeclampsia.

Background It is important to examine perinatal deaths as part of a national mortality audit to identify risk factors. Implementing and re-evaluating recommendations from perinatal mortality audits completes the audit cycle, preventing similar deaths in the future. Lack of implementation results in recommendations recurring. Objectives In this study we examine national perinatal mortality audits’ methodology in four high-income countries (United Kingdom, New Zealand, Ireland, Netherlands) to highlight different approaches taken. We compare the recommendations made in these audits’ reports over the last five years, as well as review national initiatives and programmes addressing them. Study Design This study is an integrative review where two comprehensive literature searches were completed: on established national perinatal mortality audits in high-income countries; and on national initiatives addressing recommendations from these audits. Content analysis of the audits’ recommendations was performed organising them into themes according to topics these focused on. Results Though the methodology of the national perinatal mortality audits varied, all four were state-funded and had standardised online data collection forms to report deaths. The recommendations themes included: Raising public awareness of perinatal mortality risk factors, Detection of fetal growth restriction, Prevention of preterm birth, Resources for data collection and review. Only the UK had various initiatives addressing perinatal mortality risk factors directly. New Zealand included stakeholders in the audit recommendations’ development and provided updates on their implementation. The Netherlands developed a programme for audit recommendation implementation. Ireland created a group which is progressing some recommendations from the audit. Conclusions National perinatal mortality audits are important in identifying contributory factors and making recommendations to address these. Recurring recommendations suggest a failure to resolve the identified issues. This study shows how some challenges are common to high-income countries’ audits, highlighting the need for shared learning of successful initiatives.

Placental mesenchymal dysplasia (PMD) is a rare placental abnormality that is closely related to severe pregnancy complications. A 27-year-old woman with fetal growth restriction and placenta previa was referred to a university hospital at 22 gestational weeks (GW). She was suspected of having a twin pregnancy with a complete or partial hydatidiform mole and coexisting normal live fetus, because two separate placentas, an enlarged one with multiple cystic lesions and a normal one, were shown on ultrasound examinations. At 27 GW, she experienced a sudden intrauterine fetal death (IUFD) after bleeding due to placenta previa, despite confirmation of fetal well-being at 2 h before bleeding. After delivery, histopathological examination confirmed the diagnosis of PMD. This is the first documented case of a woman with PMD and placenta previa who had a sudden IUFD after bleeding. Patients with both PMD and placenta previa should be considered at extremely high risk for IUFD.

To evaluate perinatal outcomes in fetuses with severe late-onset fetal growth restriction.This was a retrospective and observational cohort study in which pregnant women diagnosed with late-onset fetal growth restriction assisted at perinatal maternity birth from 2010 to 2017 were included. The outcomes were intensive care unit (ICU) admission and perinatal complications, such as neonatal death, intraventricular hemorrhage, periventricular leukomalacia, hypoxic-ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, and sepsis.We selected 277 pregnant women, of whom 124 newborns (44.76%) went to the ICU. The chance of a newborn needing ICU decreases by 62, 7, and 9% according to an increase of one gestational week, 1 cm of the abdominal circumference, or 1 cm of the amniotic fluid index, respectively. Oligohydramnios increases the risk of going to the ICU by 2.13 times. The increase in the umbilical artery pulsatility index (PI) Doppler increases the chance of ICU admission by 7.9 times. The normal middle cerebral artery PI Doppler and the normal cerebroplacental ratio reduce the risk of ICU admission.The estimated fetal weight, abdominal circumference, and amniotic fluid index diagnosed severe late-onset fetal growth restriction. With the decrease in middle cerebral artery PI Doppler, there is a greater probability of admission to the ICU, with the most common complications being intraventricular hemorrhage and necrotizing enterocolitis.

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Resume Objectifs Les recommandations pour la pratique clinique (RPC) sur le retard de croissance intra-uterin (RCIU) ont ete publiees en decembre 2013. Il nous est apparu interessant de realiser un etat des lieux sur la prise en charge du RCIU dans les centres hospitalo-universitaires (CHU) et maternites de type III. Materiel et methodes Nous avons realise une enquete retrospective sur l’annee universitaire 2020/2021. Tous les CHU et maternite de type III de France metropolitaine ont ete contactes (n = 67). Le questionnaire portait sur les courbes de croissance utilisees, bilan etiologique realise, rythme et modalites de surveillance en antenatal ainsi que les criteres indiquant une naissance. Resultats Le taux de reponse etait de 76 %. Les courbes du CFEF sont utilisees en depistage dans 78,4 % des cas et en cas de RCIU dans 39,2 % d’entre eux. Le bilan etiologique comprend une echographie referente dans 62,7 % des cas et une amniocentese est proposee dans 74,5 % des centres en cas de RCIU severe et precoce. Tous les centres utilisent le Doppler ombilical en cas de RCIU. Le rythme cardiaque fœtal est surveille entre une fois par semaine a trois fois par jour en cas de redistribution cerebro-placentaire. En cas de reverse flow la naissance est provoquee a partir de 28 SA pour certaines equipes tandis que d’autres poursuivent la grossesse jusqu’a 39 SA. En cas d’arret de la croissance fœtale les termes de naissance envisages sont compris entre 28 et 38 SA. Conclusion Il existe une grande heterogeneite de la prise en charge des RCIU notamment au niveau de la surveillance antenatale et du terme de naissance envisage.

Fetal growth restriction (FGR) is associated with an increased risk of adverse perinatal outcomes. The cerebroplacental ratio (CPR) represents the interaction of alterations in blood flow to the fetal brain and placenta. CPR has been utilized as a superior reflection of fetal hypoxia/acidemia and therefore a better predictor of fetal morbidity. We sought to determine the role of the CPR as an adjunctive tool to identify fetuses at increased risk of adverse perinatal outcomes in a study population of marijuana (MJ) exposed FGR fetuses.This was a retrospective cohort study of high-risk singleton pregnancies over a 4-year period. Self-identified daily MJ users with FGR fetuses in the 3rd trimester were isolated. Fetal biometry, amniotic fluid indices, and CPRs were calculated. A CPR1 was considered abnormal. FGR fetuses with normal and abnormal CPRs were then compared.26/192 (13.5%) of MJ exposed fetuses were diagnosed with FGR in the 3rd trimester. 12/26 (46%) had an abnormal CPR and 14 had a normal CPR (mean CPR 0.60 vs 1.57,Approximately half of the MJ exposed FGR fetuses had an abnormal CPR. In this subset of patients,90% had severe FGR, a higher proportion had absence/reversal of end diastolic flow in the UA, and a higher proportion had oligohydramnios. This demonstrates that an abnormal CPR identifies a group of FGR fetuses at a greater risk of adverse perinatal outcomes.

Aim. To assess the relationship of rs5918 ITGB3, rs1126643 ITGA2 and rs5985 F13A1 polymorphic loci with the risk for preeclampsia (PE) in pregnant women with fetal growth retardation (FGR). Materials and methods. The study included 272 pregnant women, of which 76 had a combination of PE and FGR and 196 had FGR. In the studied groups, genetic testing was carried out for three polymorphic loci of candidate genes for hereditary thrombophilia (rs5918 ITGB3, rs1126643 ITGA2, and rs5985 F13A1). Results. The rs5918 genetic variant in the ITGB3 gene is associated with the development of PE in pregnant women with FGR: C allele of rs5918 ITGB3 increases the risk for this complication of pregnancy by 1,8 times (OR 1.761.77, p0.036, pperm0.038). The rs5918 polymorphism determines an increase in the affinity of DNA motifs for seven transcription factors (BDP1, ELF1, IRF, NRSF, Pax-5, Sp1, and Zfx), is a missense mutation and causes the Leu59Pro amino acid substitution in the 3 subunit of integrin, is multidirectionally associated with the expression of five genes (EFCAB13, TBKBP1, NPEPPS, MRPL45P2, THCAT158) and alternative splicing of two genes (EFCAB13, MRPL45P2), is located in the region of functionally important DNA regions (promoters and enhancers) in cell cultures and organs which are pathogenetically important for the formation of PE and FGR. Conclusion. The rs5918 polymorphism in the ITGB3 gene increases the risk for PE in pregnant women with FGR.

OBJECTIVE To evaluate left myocardial performance index (MPI) and its time intervals in monochorionic diamniotic (MCDA) twin pairs complicated by selective fetal growth restriction (sFGR) with abnormal (persistent -type II- or intermittent -type III- absent or reversed end-diastolic flow) umbilical artery Doppler. METHODS Retrospective study including 16 MCDA twin pairs with sFGR type II, 26 MCDA twin pairs with sFGR type III and 42 gestational age-matched uncomplicated MCDA twin pairs in a single tertiary center. Left isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) were measured and MPI calculated by conventional Doppler at diagnosis of sFGR. RESULTS In sFGR type II, the smaller twin had shorter ET and prolonged IRT and MPI, while the larger twin showed prolonged ICT and MPI as compared to uncomplicated MCDA twins. In sFGR type III, the smaller twin had shorter ICT and ET, while the larger twin showed prolonged ICT, IRT, and MPI in comparison to controls. CONCLUSION A differential pattern of MPI time intervals could be observed in MCDA twins with sFGR type II and III. All twins had echocardiographic signs of pressure/volume overload, except the smaller twin type III with shorter systolic times probably reflecting reduced volume load.

Catastrophic antiphospholipid syndrome (CAPS) is an uncommon and the most severe form of antiphospholipid syndrome (APS). A 33-week pregnant patient with Klippel-Trenaunay syndrome, past SARS-CoV-2 infection and type I fetal growth restriction with shortening of the fetal long bone was diagnosed in our center with a probable CAPS. Cesarean section was performed four days after the diagnosis due to the torpid evolution of the patient. Clinical improvement was noted a few days later and the mother and baby were discharged within a week. We review the current literature on CAPS during pregnancy and provide an updated view.

Background Fetal Growth restriction (FGR) is the pathological failure of a fetus to reach its biologically determined growth potential. Detection of FGR fetuses is a universally agreed key objective of antenatal care. Antenatal detection of FGR has undeniable benefits, juggling between intensive fetal surveillance and optimized timing of delivery; it reduces adverse perinatal outcomes by up to four-fold. However, FGR is still widely underdiagnosed. We aimed to identify the prevalence of FGR diagnosis in our wards and study the impact of the 2013 published French guidelines on the detection rate of FGR. The secondary objective aimed to highlight the factors of suboptimal screening in the population of non-diagnosed FGR fetuses and emphasize the screening method that led to antenatal diagnosis of FGR. Materials and methods We conducted a retrospective study at a single tertiary maternity center in Lyon-France, the Femme Mere Enfant Hospital, including the exhaustive population of FGR born after 24 + 0 weeks of gestation from 1 January 2011 to 31 December 2017. FGR was defined combining the neonatal and antenatal consensus-based definitions for early and late FGR in absence of congenital anomalies, excluding small for gestational age fetuses. For all FGR fetuses, we compared the antenatal detection rate of FGR during 2011-2013 to 2015-2017, since the French guidelines were published in December 2013. When FGR fetuses underwent an antenatal diagnosis of FGR, we retrospectively collected the characteristics that led to the diagnosis. When fetuses were not diagnosed as FGR, we retrospectively reviewed the implementation of the recommended screening method, enabling to evaluate whether screening was optimal or not. Statistical analysis was performed in July 2018, and statistical significance was regarded as a p-value Results Over the seven-year period, and among 31,052 newborns, 1020 (3.3%) infants were identified as FGR and met the inclusion criteria. The detection rate of FGR was similar before and after publication of the French Guidelines related to FGR in 2013. Indeed, 50.8% (201/395) FGR were diagnosed between 2011 and 2013 versus 52.6% (245/465) between 2015 and 2017 (p = .59). In the population of non-diagnosed FGR infants, screening was suboptimal in 80%. Symphysis-fundal height (SFH) was not measured in 10.7%, with no difference before and after 2014 (7.3 versus 11.8% p = .11). Ultrasound examination for fetal biometry had not been prescribed in spite of abnormal SFH in 47.7% of undiagnosed FGR infants. Diagnosis has been missed in 11.5% of infants because of misinterpretation of the estimated fetal weight's centile. Conclusion FGR is widely underdiagnosed. However, the limited performances can partially be explained by the regular misuse of screening method in clinical practice. Despite the systematic third trimester ultrasound screening, the detection rate of FGR was similar to the one reported in the medical literature. The timing of routine third trimester ultrasound in low-risk women may be rethought.

Both transverse relaxation time (T2*) and intravoxel incoherent motion (IVIM) on magnetic resonance imaging (MRI) are promising for discriminating fetal growth restriction (FGR). We aimed to compare the utility of these two parameters and their combination in the same cohort.Twenty-seven FGR and 24 control pregnancies after 28 weeks of gestation in which both T2* and IVIM scans were performed on a 3.0 T MRI were recruited. We compared the T2* Z-score, perfusion fraction (f), diffusion coefficient (D) and pseudodiffusion coefficient (D*) between groups. Binary logistic regression analysis and areas under the curve (AUCs) with receiver operating characteristic (ROC) curve were used to evaluate the diagnostic efficacy of these parameters and their combination.Compared with normal pregnancies, T2* Z-score (0.036 ± 0.95 vs. -2.479 ± 1.56, p 0.001), f (0.2753 ± 0.035 vs. 0.3304 ± 0.035, p 0.001), D* (48279.82 ± 7497.36 μm2/s vs. 56167.92 ± 8549.87 μm2/s, p = 0.001) and D (1664.32 ± 288.53 μm2/s vs. 1887.15 ± 204.08 μm2/s, p = 0.002) were significantly decreased in FGR pregnancies. However, only AUC(T2* Z-score) (0.903) and AUC(f) (0.873) were good predictors of FGR. The AUC(T2* Z-score-IVIM) (0.937), calculated with the combination of T2* Z-score and f, was similar to AUC(T2* Z-score) and ACU(f).Both T2* and f were effective in discriminating FGR. However, the combination of the two parameters did not further improve diagnostic efficacy. We suggest that T2* might be more suitable for evaluating placental dysfunction, as it is fast to obtain and easy to measure.

Placental growth factor (PlGF) has shown promise in identification of placental fetal growth restriction (FGR). We aimed to investigate the association between PlGF and sonographic markers of placental dysfunction and assess its ability to diagnose FGR secondary to maternal vascular malperfusion (MVM).A retrospective study of singleton pregnancies with small for gestational age (SGA) fetuses, who had PlGF testing at 16-36 weeks. Fetuses with major chromosomal and/or structural anomalies and pregnancies with missing outcomes were excluded. Sonographic characteristics, perinatal outcomes and placental histopathology were compared between pregnancies with normal and low PlGF (10th percentile for gestational age). The diagnostic accuracy of PlGF for prediction of MVM was calculated.130 fetuses met inclusion criteria. Compared to normal PlGF (n = 65), pregnancies with low PlGF (n = 65) were associated with an estimated fetal weight 5th centile (73.8% (48) vs 53% (35), respectively, p = 0.01), abnormal uterine, umbilical and MCA Dopplers (p = 0.001 for all), fetal demise (18.8% (12) vs 0% respectively, p = 0.01) and preterm delivery (100% (65) vs 39% (59), respectively, p 0.001) . Low PlGF had a 70.1% (58.6-80.0) sensitivity and a 79.6% (64.7-90.2) specificity for identifying MVM, with an AUC of 0.73 (0.63-0.84). Positive and negative predictive values were 85.7% (76.8-91.2) and 60.3% (51.2-68.9), respectively. PlGF outperformed other parameters of placental FGR (uterine, umbilical artery, middle cerebral artery and abdominal circumference 5th centile), in isolation and when combined.PlGF is a useful tool to aid in the diagnosis of placental FGR secondary to MVM.

To compare Doppler alterations and perinatal outcomes in pregnant women who evolved with early- and late-onset fetal growth restriction (FGR).A retrospective, observational cohort study with pregnant women who evolved with FGR treated between January 2018 and April 2019, in which all live births from singleton pregnancies, over 24 weeks, with FGR ultrasound diagnosis and under 2700 g weight were included in the study.Pregnancies with early-onset FGR were more associated with hypertensive disorders (Early-onset FGR had a lower prevalence but was associated with higher maternal and fetal morbidity and mortality than late-onset FGR.

Prenatal ultrasound (US) has been shown to overestimate the incidence of suspected fetal growth restriction (FGR) in gastroschisis cases. This is largely because of altered sonographic abdominal circumference (AC) measurements when comparing gastroschisis cases with population nomograms. Individualized Growth Assessment (IGA) evaluates fetal growth using serial US measurements that allow consideration of the growth potential for a given case. Our goal was to assess the utility of IGA for distinguishing normal and pathological fetal growth in gastroschisis cases.Pregnancies with prenatally diagnosed fetal gastroschisis were managed and delivered at a single academic medical center. US fetal biometry including head circumference (HC), abdominal circumference (AC), and femur diaphysis length (FDL), and neonatal measurements including birthweight and HC were collected and analyzed for 32 consecutive fetal gastroschisis cases with at least two 2nd and two 3rd trimester measurements. Second trimester growth velocities were compared to a group of 118 non-anomalous fetuses with normal neonatal growth outcomes. Gastroschisis cases were classified into groups based on fetal growth pathology score (FGPS9) patterns. Agreement between IGA (FGPS9) and serial conventional estimated fetal weight (EFW) measurements for determining growth pathology was evaluated. Neonatal size outcomes were compared between conventional birthweight classifications for determining small for gestational age (SGA) and IGA Growth Potential Realization Index (GPRI) for weight and head circumference measurements.Fetal growth pathology score (FGPS9) measurements identified three in-utero growth patterns: no growth pathology, growth restriction and recovery, and progressive growth restriction. In the no growth pathology group (We present the first study using IGA to evaluate normal and pathological fetal growth in prenatally diagnosed gastroschisis cases. IGA was able to delineate two 3rd trimester growth pathology patterns - one with persistent growth restriction and another with in-utero growth recovery. Further validation of these initial findings with larger cohorts is warranted.

Abnormal fetal growth (growth restriction and overgrowth) is associated with perinatal morbidity, mortality, and lifelong risks to health. To describe abnormal growth, "small for gestational age" and "large for gestational age" are commonly used terms. However, both are statistical definitions of fetal size below or above a certain threshold related to a reference population, rather than referring to an abnormal condition. Fetuses can be constitutionally small or large and thus healthy, whereas fetuses with seemingly normal size can be growth restricted or overgrown. Although golden standards to detect abnormal growth are lacking, understanding of both pathologic conditions has improved significantly.

Three modern cohort studies have an advantage over historical fetal growth references because they included diverse populations. Despite similar inclusion criteria, estimated fetal weight percentiles for gestational age varied among studies, which result in different proportions of fetuses as being classified below or above a cutoff point. A universal reference would make comparison of fetal growth simpler for clinical use and for comparison across populations but may misclassify small-for-gestational-age or large-for-gestational-age fetuses. It is important to know how a growth reference performs in a local population in relation to fetal morbidity and mortality when implementing in clinical practice.

Multifetal gestation pregnancies present a clinical challenge due to unique complications including growth issues, prematurity, maternal risk, and pathologic processes, such as selective intrauterine growth restriction (sIUGR), twin-to-twin transfusion syndrome (TTTS), and twin anemia-polycythemia sequence. If sIUGR is found, then management may involve some combination of increased surveillance, fetal procedures, and/or delivery. The combination of sIUGR with TTTS or other comorbidities increases the risk of pregnancy complications. Multifetal pregnancy reduction is an option when a problem is confined to a single fetus or when weighing the risks and benefits of a multifetal gestation in comparison to a singleton pregnancy.

Fetal growth restriction (FGR) is a common clinical manifestation of placental insufficiency. As such, FGR is a risk factor for stillbirth. This association has been demonstrated in numerous studies but is prone to overestimation because of the possibility of prolonged in utero retention before the recognition of the fetal death. Stillbirth risk reduction by optimizing maternal medical conditions and exposures and appropriate antenatal testing and delivery timing are essential to pregnancies affected by FGR. It is important to evaluate stillbirths with FGR with fetal autopsy, placental pathology, genetic testing, and assessment of antiphospholipid antibodies and fetal-maternal hemorrhage.

Fetal growth restriction (FGR) is a common obstetric complication that predisposes to mortality across the lifespan. Women with a prior pregnancy affected by FGR have a 20% to 30% risk of recurrence, but effective preventive strategies are lacking. Pharmacologic interventions to prevent FGR are lacking. Low-dose aspirin may be somewhat effective, but low-molecular-weight heparin and sildenafil are not. Surveillance in a subsequent pregnancy may consist of serial ultrasonography with timing and frequency determined by the clinical severity in the index pregnancy. Once FGR is diagnosed, the principal management strategy consists of close surveillance and carefully timed delivery.

Background We determined the effect of fetal sex on birth/placental weight and umbilical vein and artery oxygen values with implications for placental efficiency and regulatory mechanisms underlying fetal–placental growth differences. Methods A hospital database was used to obtain birth/placental weight, cord PO2 and other information on patients delivering between Jan 1, 1990 and Jun 15, 2011 with GA > 34 weeks (N = 69,836). Oxygen saturation was calculated from the cord PO2 and pH data, while fractional O2 extraction was calculated from the oxygen saturation data. The effect of fetal sex on birth/placental weight, cord PO2, O2 saturation, and fractional O2 extraction was examined in all patients adjusting for pregnancy and labor/delivery covariates, and in a subset of low-risk patients. Results Birth/placental weights were lower in females indicating decreased placental efficiency. Umbilical vein oxygen values were higher in females attributed to increased uterine blood flow, while artery oxygen values were lower in females attributed to decreased hemoglobin and umbilical blood flow, and increased oxygen consumption. Fetal O2 extraction was increased in females confirming increased O2 consumption relative to delivery. Conclusions Sex-related differences in uterine/umbilical blood flows, placental development, and fetal O2 consumption can be linked to the differences observed in cord oxygen. The lower umbilical artery oxygen in females as a measure of systemic oxygenation signaling growth could account for their decreased birth weights, while slower development in female placentae could account for their lower placental weights, which could be differentially effected contributing to their lower birth/placental weights.

To investigate fetal epicardial fat thickness (EFT) value in fetal growth restriction (FGR) and its relationship with clinical parameters, fetal modified myocardial index (Mod-MPI), and the Doppler parameters.Eighty-five pregnant women, with 30 diagnosed with FGR and 55 healthy pregnant women as control group participated in this prospective case-control study. FGR group was divided into 2 subgroups as early (EFT value was found statistically lower in the early and late FGR groups than the control group (Our study showed that the measurement of EFT may contribute to predicting the diagnosis of FGR. Moreover, lower EFT values can be related to the severity of FGR. Future randomized control studies are needed to understand the effects and pathways of fetal EFT on fetal cardiac function.

To improve identification of fetal growth restriction (FGR) by means of umbilical venous flow (QUV) and maternal hemodynamics, including systemic vascular resistance (SVR) and cardiac output (CO), in order to distinguish between FGR and SGA.We enrolled 68 pregnancies (36 SGA, 8 early FGR and 24 late FGR) who underwent a complete fetal hemodynamic examination including QUV and a noninvasive maternal hemodynamics assessment by means of USCOM.In comparison with SGA, QUV and corrected for estimated fetal weight QUV (cQUV) were significantly lower in early and late-FGR. In addition, maternal CO was lower in early and late-FGR, while SVR was lower only in early-onset FGR. According to ROC analysis, cQUV centile (AUC 0.92, 0.72) was the best parameter for the prediction of SGA before and after 32 weeks, followed by SVR and CO. For all parameters, the prediction was always better in the case of early-onset FGR32 weeks.UV flow and maternal hemodynamics examination are useful tools to accurately discern between SGA and FGR.

Third trimester ultrasound has long been in obstetrics a topic of debate. This issue is framed in a historical debate on the effectiveness of routine obstetrical ultrasound and two opposing trends originated in America and Europe, respectively. Primary function of this ultrasound has been to detect fetal growth restriction, but no study has shown evidence of improving perinatal outcomes. Other secondary functions are detection of fetal abnormalities or evaluation of fetal presentation, and they have also shown no evidence. Despite the continuous appearance of works in this regard, health policies of both american and european trends have not been modified. Future seems to show a prolongation of the stalemate. Those health systems with a universal third trimester policy should propose an optimization of the test, in order to improve the benefits and obtain data for future studies that could resolve this longstanding debate.

Background Increasing the detection of fetal growth restriction (FGR), while reducing stillbirth, also leads to unnecessary early intervention, and associated morbidity, for normally grown babies who are incorrectly suspected of FGR. Aims We sought to design a balance measure that addresses the specificity of FGR detection. Methods A retrospective cohort study on all singleton births ≥32 weeks gestation in 2016 and 2017 in Victoria. We compared two balance measures for the detection of FGR, defined as the proportion of all babies iatrogenically delivered before 39 weeks gestation for suspected FGR that had a birthweight ≥10th centile (balance measure 1) or ≥25th centile (balance measure 2). Hospital level performance on each balance measure was derived and compared to an existing performance measure for severe FGR detection in Victoria. Results Of the 38 hospitals analysed, 12 (32%) had a favourable performance on an existing indicator of FGR detection, seven (18%) hospitals had a favourable performance on balance measure 1, and 15 (39%) had a favourable performance on balance measure 2. There was a moderate correlation between hospital performance on the existing indicator and on balance measure 1 (r = 0.447, P = 0.005) but not balance measure 2 (r = -0.063, P = 0.71). There was no difference in perinatal mortality between high performing hospitals and low performing hospitals. Conclusion Introducing a balance measure into routine reporting may bring greater awareness to the unintended harm associated with increased detection of FGR.

Introduction Our objective was to compare the fetal growth velocity and fetal hemodynamics in pregnancies complicated and in those not complicated by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Material and methods Prospective case‐control study of consecutive pregnancies complicated by SARS‐CoV‐2 infection during the second half of pregnancy matched with unaffected women. The z scores of head circumference, abdominal circumference, femur length, and estimated fetal weight were compared between the two groups. Fetal growth was assessed by analyzing the growth velocity of head circumference, abdominal circumference, femur length, and estimated fetal weight between the second‐ and third‐trimester scans. Similarly, changes in the pulsatility index of uterine, umbilical, and middle cerebral arteries, and their ratios were compared between the two study groups. Results Forty‐nine consecutive pregnancies complicated, and 98 not complicated, by SARS‐CoV‐2 infection were included. General baseline and pregnancy characteristics were similar between pregnant women with and those without SARS‐CoV‐2 infection. There was no difference in head circumference, abdominal circumference, femur length, and estimated fetal weight z scores between pregnancies complicated and those not complicated by SARS‐CoV‐2 infection at both the second‐ and third‐trimester scans. Likewise, there was no difference in the growth velocity of all these body parameters between the two study groups. Finally, there was no difference in the pulsatility index of both maternal and fetal Doppler scans throughout gestation between the two groups. Conclusions Pregnancies complicated by SARS‐CoV‐2 infection are not at higher risk of developing fetal growth restriction through impaired placental function. The findings from this study do not support a policy of increased fetal surveillance in these women.

Introduction. Multifetal pregnancy is associated with an increased risk of perinatal morbidity and mortality. Type of placentation and discordant fetal growth may be risk factors of adverse pregnancy outcomes.Aim: to compare an impact of dichorionic and monochorionic twin pregnancies with symmetric and discordant fetal growth on perinatal outcomes, as well as morbidity and mortality.Materials and Methods. There was conducted a retrospective study of 485 pregnant women and paired 959 newborns. Depending on the type of chorionicity, subjects were stratified into two study groups being further subdivided into based on describing fetal weight discordance. The antenatal period and the neonatal outcome of newborns in groups and subgroups were compared.Results. We analyzed 308 dichorionic and 177 monochorionic twin pregnancies. It was found that neonate discordant growth was observed in 5.4 % and 13.4 % (p < 0.001), respectively. The incidence of assisted reproductive technologies was higher in dichorionic than in monochorionic twins comprising 66.5 and 40.7 % (р < 0.001). Antenatal mortality in monochorionic vs. dichorionic twins was by 8-fold higher. The preterm birth rate in monochorionic vs. dichorionic twins was 74.6 and 62.7% (p = 0.009), respectively. Neonate body weight in monochorionic vs. dichorionic twins was lowered comprising 1991 and 2430 gr. (р < 0.001), respectively. Low Apgar scores were more common for monochorionic twins with discordant body weight. The rate of early neonatal mortality in monochorionic vs. dichorionic twins was 4.4 % vs. 1.5 % (p = 0.009), whereas in dichorionic vs. monochorionic twins with weight discordance it was up to 5.8 and 10.5% (р < 0.001), respectively.Conclusion. Monochorionic twin pregnancy complicated with growth discordance is associated with a higher risk of adverse antenatal period as well as neonatal morbidity and mortality compared to symmetric DCDA twins. Chorionicity and growth discordancy represent important predictors for outcome of twin pregnancy.

Background Rates of induction of labour have been increasing globally to up to one in three pregnancies in many high-income countries. Although guidelines around induction, and strength of the underlying evidence, vary considerably by indication, shared decision-making is increasingly recognised as key. The aim of this study was to identify women’s mode of birth preferences and experiences of shared decision-making for induction of labour. Method An antenatal survey of women booked for an induction at eight Sydney hospitals was conducted. A bespoke questionnaire was created assessing women’s demographics, indication for induction, pregnancy model of care, initial birth preferences, and their experience of the decision-making process. Results Of 189 survey respondents (58% nulliparous), major reported reasons for induction included prolonged pregnancy (38%), diabetes (25%), and suspected fetal growth restriction (8%). Most respondents (72%) had hoped to labour spontaneously. Major findings included 19% of women not feeling like they had a choice about induction of labour, 26% not feeling adequately informed (or uncertain if informed), 17% not being given alternatives, and 30% not receiving any written information on induction of labour. Qualitative responses highlight a desire of women to be more actively involved in decision-making. Conclusion A substantial minority of women did not feel adequately informed or prepared, and indicated they were not given alternatives to induction. Suggested improvements include for face-to-face discussions to be supplemented with written information, and for shared decision-making interventions, such as the introduction of decision aids and training, to be implemented and evaluated.

Objectives The primary objective was the identification of sub-standard care in antepartum stillbirths in Emilia-Romagna Region (Italy), hence the number of potentially preventable cases. Secondly, we seek to evaluate any association between inadequate care and either risk factors for stillbirth or causes of death. Study Design This study was based on prospectively-collected data in an institutional stillbirth audit project, involving all 29 hospital with a maternity unit in Emilia-Romagna Region. For each stillbirth occurred in the area from 2014 to the first semester of 2019 the same diagnostic workup was performed and a clinical record with data about mother and stillborn was completed. Every case was discussed in a multidisciplinary local audit to assess both the cause of death and the quality of care. Two aspects of care quality were evaluated: clinical management and women’s access to care. Data were then reviewed by the Regional Audit Group. Results Elements of inadequate care were identified in 56 out of 524 (10.7 %) fetal deaths. Non-Italian women and pregnancies with fetal growth restriction had double the risk of having received inadequate care during pregnancy, compared to Italian women (aOR 2.0, 95 % CI 1.1–3.6) and a normally developing fetus (aOR 2.0, 95 % CI 1.1–4.1), respectively. Women whose stillbirth was caused by maternal disorders were at higher risk for inadequate care compared to women who had stillbirth explained by other cause (aOR 5.89, 95 %CI 2.2–15.4). Sub-optimal clinical management and barriers to access to care were observed to equal extents. Inappropriate ultrasound monitoring was the most frequent suboptimal care element. Conclusions About one out of ten stillbirths was potentially preventable. Interventions to reduce stillbirth occurrence in our high-resource setting should focus on appropriate diagnosis and management of maternal disorders and fetal growth restriction, as well as improving access to antenatal care.

IGF-1 deficiency in prenatal period is known to be a definite pathophysiology of retinopathy of prematurity(ROP), which is more frequent in infants with fetal growth restriction(FGR). Of note, recent reports demonstrated intra-amniotic inflammation(IAI) closely linked to acute histologic chorioamnionitis(acute-HCA) is associated with a decrease in intact-form of IGFBP-1, ultimately rising the probability of an increase in IGF-1. Therefore, we hypothesized ROP in preterm-infants without FGR would be decreased with the progression of acute-HCA.The frequency of ROP was examined in 85 singleton preterm-infants(24.5weeks ≤ gestational-age[GA] at delivery30weeks) due to either preterm-labor and intact-membranes(PTL) or preterm premature rupture of membranes(preterm-PROM) without FGR(birth-weight5th percentile for GA). Patients were divided according to the progression of inflammation in extra-placental membranes(EPM) and the progression of inflammation in chorionic-vessel(CV) and umbilical-cord(UC).1) ROP was present in 40%(34/85) of study-population; 2) Of note, there was a significant stepwise-decrease in ROP with the progression of inflammation in EPM(inflammation-free EPM vs. inflammation restricted to CD vs. amnionitis; 55.6%[15/27]vs.39.5%[17/43]vs.13.3%[2/15]) and the progression of inflammation in CV and UC(inflammation-free CV and UC vs. inflammation restricted to CV and umbilical vessels vs. inflammation in Wharton's jelly[WJ]; 49.2%[29/59]vs.25.0%[3/12]vs.14.3%[2/14])(each-for P 0.05, Chi-square test and each-for P 0.01, linear-by-linear association); 3) Multiple logistic-regression analysis demonstrated amnionitis(Odds-Ratio 0.120, 95%Confidence-Interval 0.022-0.654, P = 0.014) and inflammation in WJ(Odds-Ratio 0.124, 95%Confidence-Interval 0.022-0.694, P = 0.018) were independent protective-factors against ROP.ROP in preterm-infants due to PTL or preterm-PROM without FGR is decreased with the progression of acute-HCA. This finding may be an evidence to suggest the progression of acute-HCA is closely associated with reducing the pathophysiology of ROP.

Introduction: This paper aimed to assess the knowledge of healthcare professionals (obstetric and gynecology residents, specialists, and midwives) in the field of perinatal medicine regarding fetal growth diagnosis and management. Methods: A questionnaire was created consisting of a set of questions regarding demographic data, methods of growth assessment, and management. It was a handout survey. The results were analyzed with the use of descriptive statistics and χ2 analysis using the program Statistica. Results: 190 medical professionals have participated in the questionnaire. 86.3% of respondents agreed that pregnancy dating should be modified based on first-trimester ultrasound. 90.9% agreed that III trimester ultrasound has a ±15% margin of error. When asked which growth charts are best fit for assessing growth in a studied population, 10.7% marked standard, 37.4% reference, 26.2% customized, and 26.2% did not know the difference between the three choices. 60.3% stated that they use a growth chart to assess growth and qualify fetuses for monitoring. 70.2% used the 10th centile as a cutoff, 20.1% 5th centile, and 9.7% 3rd centile. Only 40.9% would diagnose fetal growth restriction based on fetal weight only. 28.7% using the 10th centile cutoff, 16.1% 5th centile, and 54.0% 3rd centile. Only a quarter of the respondents were able to name the growth chart or tool that they use for assessment. The most common responses were Yudkin, Hadlock, and online calculators of Fetal Medicina Barcelona and the Fetal Medicine Foundation. Discussion: A lot of confusion is observed primarily in the aspect of cutoff values for identification, subsequent monitoring, and management of fetal growth restriction. There is a need for extensive training and education in this field and uniform national recommendations.

This study is an analysis of literary sources devoted to the use of transverse cerebellar diameter (TCD) and its relation to fetal abdominal circumference in the diagnosis of fetal growth restriction and determination of gestational age. All available research works on this subject were reviewed and a summary table with the results of the twenty-five most significant of them was compiled. The relevance of transferring TCD from the category of additional fetometry parameters to the category of standard fetometry parameters was indicated. Key words: fetal growth restriction, fetal growth retardation, transverse cerebellar diameter, gestational age, fetometry