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Fetal hypoxia due to placental dysfunction is the hallmark of fetal growth restriction (FGR). Preferential perfusion of the brain (brain-sparing effect), as a part of physiological placental cardiovascular compensatory mechanisms to hypoxia, in FGR was reported. Therefore, the correlation between vascular endothelial growth factor A (VEGF-A) protein expression in the FGR placentas and newborns' early neurological outcome was examined. This study included 50 women with FGR complicated pregnancies and 30 uneventful pregnancies. Fetal hemodynamic parameters, neonatal acid–base status after delivery, placental pathohistology and VEGF-A expression were followed. Early neonatal morphological brain evaluation by ultrasound and functional evaluation of neurological status by Amiel – Tison Neurological Assessment at Term (ATNAT) were performed. VEGF-A protein expression level was significantly higher in the FGR placentas than normal term placentas (Fisher–Freeman–Halton's test, p≤0.001). No statistically significant correlation between placental VEGF-A expression and different prenatal and postnatal parameters was noticed. Whereas the alteration of an early neurological status assessed by ATNAT was found in 58 % of FGR newborns, morphological brain changes evaluated by UZV was noticed in 48 % of cases. No association between the level of placental VEGF-A expression and the early neurological deficits was found. As far as we know this is the first study of a possible connection between VEGF-A protein expression in the FGR placentas and neonates' early neurological outcomes. The lack of correlation between the FGR placental VEGF-A expression and neonates' neurological outcome could indicate that optimal early neurodevelopment may take place due to compensatory mechanism not related to placental VEGF-A expression. [ABSTRACT FROM AUTHOR]

Customized birthweight centiles have improved the detection of small for gestational age (SGA) and large for gestational age (LGA) babies compared to existing population standards. This study used perinatal registry data to derive coefficients for developing customized growth charts for Qatar.The PEARL registry data on women delivering in Qatar (2017–2018) was used to develop a multivariable linear regression model predicting optimal birthweight. Physiological variables included gestational age, maternal height, weight, ethnicity, parity, and sex of the baby. Pathological variables such as hypertension, preexisting and gestational diabetes and smoking were calculated and excluded to derive the optimal weight at term.The regression model found a term optimal birthweight of 3,235 g for a Qatari nationality mother with median height (159 cm), booking weight (72 kg), parity (1) and gestation at birth (276 days) at the end of an uncomplicated pregnancy. Constitutional coefficients significantly affecting birthweight were gestational age, height, weight, and parity. The main pathological factors were preexisting diabetes (increase by +175.7 g) and smoking (decrease by −190.9 g). The SGA and LGA rates in the entire cohort after applying the population-specific customized centiles were 11.1 and 12.2 %, respectively (contrasting with the Hadlock standard: SGA-26.3 % and LGA-1.8 %, and Fenton standard: SGA-12.9 % and LGA-4.0 %).Constitutional and pathological variations in fetal growth and birthweight apply in the maternity population in Qatar and have been quantified to allow the generation of customised charts for better identification of pregnancies with abnormal growth. Currently in-use population standards may misdiagnose many SGA and LGA babies. [ABSTRACT FROM AUTHOR]

Atenolol is a commonly used beta bloscker in non-pregnant women. Many providers are hesitant in prescribing atenolol in pregnancy because of a possible association with poor fetal growth. We aimed to assess the association between atenolol and the occurrence of small for gestational age neonates compared to other beta blockers, as described in the existing literature.We used the meta-analytic method to generate a forest plot for risk ratios (RR) of small for gestational age in patients who used atenolol vs. other beta blockers. Statistical heterogeneity was assessed with the I2 statistic.Two studies were included, with a resultant RR of 1.94 [95 % confidence interval (CI) 1.60; 2.35]. A study by Duan et al. in 2018 noted the following rate of small for gestational age for each beta blocker use: 112/638 atenolol, 590/3,357 labetalol, 35/324 metoprolol, and 50/489 propranolol. A study by Tanaka et al. in 2016 noted the following rate of small for gestational age: 8/22 for propranolol, 2/12 for metoprolol, 2/6 for atenolol, 0/5 for bisoprolol. Heterogeneity (I2) was 0 %.Our results suggested an elevated risk of small for gestational age associated with atenolol use in comparison to other beta blockers, specifically labetalol, propranolol, bisoprolol, and metoprolol. [ABSTRACT FROM AUTHOR]

The failure of a fetus to develop to its full potential due to maternal or placental factors is known as intrauterine growth restriction (IUGR). Fetal head growth is usually preserved in that situation producing a potential discordance between head and body size. Our goal is to discover if IUGR has an impact on the prenatal ultrasound measurements taken to assess pulmonary development in congenital diaphragmatic hernia (CDH). A retrospective chart review (IRB#2017-6361) was performed on all prenatally diagnosed CDH patients from 2007 to 2016. Patient demographics, fetal and neonatal anthropometric measurements, and fetal lung parameters were the main subjects of the data that were gathered. Fetal growth was assessed by the curves based on US data by Olsen et al. and by Peleg et al. Of 147 CDH patients, 19 (12.9 %) patients were diagnosed with IUGR before the 30th gestational week while there were 20 (13.6 %) patients after the 30th gestational week. Patients with IUGR and the observed-to-expected lung-to-head ratio (O/E LHR) less than 25 % had better survival rates both to discharge and date compared to non IUGR group (p=0.226, OR 2.25 95 % CI 0.60–1.08 and p=0.175, OR 2.40 95 % CI 0.66–1.17, respectively). Moreover, the ECMO need of the patients who had IUGR and O/E LHR less than 25 % was significantly less than the patients without IUGR (38.5 vs. 80.0 %, p=0.005). This study confirms that the intrauterine measurements to predict pulmonary hypoplasia in CDH patients are misleading in the presence of IUGR and cause an overestimation. [ABSTRACT FROM AUTHOR]

To investigate midbrain growth, including corpus callusum (CC) and cerebellar vermis (CV) and cortical development in late fetal growth restricted (FGR) subclassified according to the umbilical vein blood flow (UVBF) values. This was a prospective study on singleton fetuses late FGR with abnormal placental cerebral ratio (PCR). FGR fetuses were further subdivided into normal (≥fifth centile) and abnormal (

Although the relationship between maternal viral infections and fetal growth restriction (FGR) is well established, the association between SARS-CoV-2 infection in pregnancy and FGR remains unclear. We investigated the association between SARS-CoV-2 infection in pregnancy and FGR at a single county hospital. We performed a prospective cohort study with cohorts matched by gestational age and month of SARS-CoV-2 PCR testing between April 2020 and July 2022. Individuals were included if they had a SARS-CoV-2 PCR testing up to 32 weeks of gestation and had a third trimester ultrasound. Primary outcome was a diagnosis of FGR, while secondary outcomes were rates of preeclampsia, small for gestational age (SGA) and birthweight. Univariate analyses, chi-square test and logistic regression were used for analysis. Our cohorts constituted of 102 pregnant individuals with a positive SARS-CoV-2 PCR test result and 103 pregnant individuals with a negative SARS-CoV-2 PCR test result in pregnancy. FGR rates were 17.8 % and 19.42 % among positive and negative SARS-CoV-2 cohorts respectively. While a statistical difference in preeclampsia rates was noted (34.31 % vs. 21.36 %, p=0.038) between cohorts, odds of getting preeclampsia based on SARS-CoV-2 test result was not significant (aOR 1.01, CI=0.97–1.01, p=0.75). No statistical difference was noted in demographics, FGR and SGA rates, and birthweight. Our findings suggest no association between SARS-CoV-2 infection in pregnancy and FGR at a single institution. Our results validate emerging data that additional fetal growth ultrasonographic assessment is not indicated solely based on SARS-CoV-2 infection status. [ABSTRACT FROM AUTHOR]

This study aims to evaluate if low levels of serum maternal pregnancy associated plasma protein-A (PAPP-A) during the first trimester are related to increased umbilical artery pulsatility index (UA PI) later in pregnancy, in cases of estimated fetal weight between the 3rd and 10th percentiles, in order to establish PAPP-A as a predictor of this particular cases of fetal growth restriction (FGR). An observational, retrospective cohort study, conducted at a tertiary University Hospital located in Oporto, Portugal. Pregnant women who did the first trimester combined screening, between May 2013 and June 2020 and gave birth in the same hospital, with an estimated fetal weight (EFW) between the 3rd and 10th percentiles were included. The primary outcome is the difference in increased UA PI prevalence between two groups: PAPP-A<0.45 MoM and PAPP-A≥0.45 MoM. As secondary outcomes were evaluated differences in neonatal weight, gestational age at delivery, cesarean delivery, neonatal intensive care unit hospitalization, 5-min Apgar score below 7 and live birth rate between the same two groups. We included 664 pregnancies: 110 cases of PAPP-A<0.45 MoM and 554 cases with PAPP-A≥0.45 MoM. Increased UA PI prevalence, which was the primary outcome of this study, was significantly different between the two groups (p=0.005), as the PAPP-A<0.45 MoM group presents a higher prevalence (12.7 %) when compared to the PAPP-A≥0.45 MoM group (5.4 %). The secondary outcome cesarean delivery rate was significantly different between the groups (p=0.014), as the PAPP-A<0.45 MoM group presents a higher prevalence (42.7 %) than the PAPP-A≥0.45 MoM group (30.1 %). No other secondary outcomes showed differences between the two groups. There is an association of low serum maternal PAPP-A (<0.45 MoM) during the first trimester and increased UA PI (>95th percentile) later in pregnancy, in cases of EFW between the 3rd and 10th percentiles. However, this association is not strong enough alone for low PAPP-A to be a reliable predictor of increased UA PI in this population. [ABSTRACT FROM AUTHOR]

To systematically identify and critically assess the quality of clinical practice guidelines (CPGs) on management fetal growth restriction (FGR). Medline, Embase, Google Scholar, Scopus and ISI Web of Science databases were searched to identify all relevant CPGs on FGR. Diagnostic criteria of FGR, recommended growth charts, recommendation for detailed anatomical assessment and invasive testing, frequency of fetal growth scans, fetal monitoring, hospital admission, drugs administrations, timing at delivery, induction of labor, postnatal assessment and placental histopathological were assessed. Quality assessment was evaluated by AGREE II tool. Twelve CPGs were included. Twenty-five percent (3/12) of CPS adopted the recently published Delphi consensus, 58.3% (7/12) an estimated fetal weight (EFW)/abdominal circumference (AC) EFW/AC <10th percentile, 8.3% (1/12) an EFW/AC <5th percentile while one CPG defined FGR as an arrest of growth or a shift in its rate measured longitudinally. Fifty percent (6/12) of CPGs recommended the use of customized growth charts to assess fetal growth. Regarding the frequency of Doppler assessment, in case of absent or reversed end-diastolic flow in the umbilical artery 8.3% (1/12) CPGs recommended assessment every 24–48, 16.7% (2/12) every 48–72 h, 1 CPG generically recommended assessment 1–2 times per week, while 25 (3/12) did not specifically report the frequency of assessment. Only 3 CPGs reported recommendation on the type of Induction of Labor to adopt. The AGREE II standardized domain scores for the first overall assessment (OA1) had a mean of 50%. There is significant heterogeneity in the management of pregnancies complicated by FGR in published CPGs. [ABSTRACT FROM AUTHOR]

To compare short term variation (STV) and phase rectified signal averaging (PRSA) and their association with fetal outcome in early onset fetal growth restriction (FGR). Data were used from a retrospective cohort study of women who were admitted for FGR and/or pre-eclampsia and who were delivered by pre-labor Cesarean section or had a fetal death before 32 weeks' gestation. Computerized cardiotocography (cCTG) registrations of the 5 days before delivery or fetal death were used for calculation of STV and PRSA. PRSA was expressed as the average acceleration capacity (AAC) and average deceleration capacity (ADC). FHR decelerations were classified visually as absent, 1–2 per hour or recurrent. Abnormality of STV and of PRSA was either analyzed as a single parameter or in combination with recurrent decelerations. Endpoints were defined as composite adverse condition at birth consisting of fetal death, low Apgar score, low umbilical pH, the need for resuscitation after birth and as major neonatal morbidity or neonatal death. Included were 367 pregnancies of which 20 resulted in fetal death. An abnormal cCTG with either recurrent decelerations and/or low STV or recurrent decelerations and/or low PRSA were similarly associated with composite adverse condition at birth (n=99), but neither with major neonatal morbidity. PRSA and STV have similar efficacy for measuring fetal heart rate variation in early onset FGR. An increased risk of a composite adverse condition at birth is indicated by a low value of either parameter and/or the presence of recurrent decelerations. [ABSTRACT FROM AUTHOR]

To develop a nomogram for fetal left brachiocephalic vein (LBCV) diameters during a healthy pregnancy and to assess LBCV values in fetuses with fetal growth restriction (FGR). This prospective observational study included 31 FGR pregnancies and 438 low-risk pregnancies. The low-risk group was used to determine the 5th, mean, and 95th percentiles for the LBCV between 12 and 39 weeks of gestation based on gestational age. On growth charts, LBCV measurements of FGR fetuses were displayed, and those above the gestational age 95th percentile were considered wide vein. Cerebroplacental ratio (CPR) and umbilical artery (UA), middle cerebral artery (MCA), and ductus venosus (DV) Doppler parameters were evaluated in FGR fetuses. LBCV diameter increased significantly with advancing gestational age. The LBCV diameters were above the 95th percentile in 23 of the 31 FGR fetuses (74.2%). All fetuses (15/15, 100%) with early-onset (EO)-FGR and 8 fetuses (8/16, 50%) with the late-onset (LO)-FGR had LBCV values above the 95th percentile (p<0.01). UA-PI was significantly higher and MCA-PI and CPR were significantly lower in LO-FGR fetuses with LBCV diameters above the 95th percentile (p<0.05). LBCV diameters of fetuses with FGR were significantly wider than the normal population. In the LO-FGR group, there was a good correlation between LBCV diameter and CPR. [ABSTRACT FROM AUTHOR]

We aim to investigate the utility of middle cerebral artery peak systolic velocity (MCA PSV) Doppler in determining the perinatal mortality and morbidity in serial Doppler measurements from the time of diagnosis to the delivery of complicated cases with fetal growth restriction (FGR). At 24–38 weeks of gestation, 65 pregnant women diagnosed with FGR were included in the study. The fetal biometry measurements, MCA pulsatility index (PI), and MCA PSV Doppler evaluation of the cases formed at the diagnosis and the delivery were recorded. Gestational weeks, birth weights, APGAR scores, cord pH values, NICU (neonatal intensive care unit) admission, NICU duration of stay, and perinatal morbidity parameters such as RDS (respiratory distress syndrome), BPD (bronchopulmonary dysplasia), NEC (necrotizing enterocolitis), sepsis and perinatal mortality were compared. The patients were divided into two groups: early and late-onset fetal growth restriction. Perinatal morbidity and mortality were accepted as adverse perinatal outcomes. MCA PSV above the 95th percentile at the diagnosis and delivery time was seen at a significantly higher rate with adverse perinatal outcomes. This study shows that evaluating MCA PSV with Doppler can be a helpful diagnostic method for early diagnosis of restriction and hypoxic fetuses. Also, it may be used in clinics as a noninvasive method to predict neonatal prognosis. [ABSTRACT FROM AUTHOR]

This study aims to evaluate sonographic measurements of fetal adrenal gland size and middle adrenal artery Doppler in pregnancies with fetal growth restriction (FGR) and in a healthy control group. This prospective study included 107 singleton pregnancies with FGR between 24 and 42 weeks of gestation and 107 pregnancies with fetuses whose growth was appropriate for gestational age (AGA). Adrenal gland size and Doppler parameters of the adrenal artery were measured and the values and obstetric outcomes were compared between the study and control groups. In the study group, the Z-scores of total adrenal width-length and height, fetal zone width-length and middle adrenal artery-peak systolic velocity (MAA-PSV) were significantly higher than those in the control group (p<0.05). The Z-scores of middle adrenal artery-pulsatility index (MAA-PI) were significantly lower in the study group than in the control group (p<0.05). The rate of neonatal intensive care unit admission in fetuses with high adrenal artery PI scores was higher in the FGR group (p<0.05). In the present study, we observed decreased adrenal artery PI, increased adrenal blood flow, and increased fetal adrenal volume in fetuses diagnosed with fetal growth restriction, most likely in response to placental insufficiency and chronic hypoxia. [ABSTRACT FROM AUTHOR]

To compare maternal serum midkine (MK) level in pregnant women with idiopathic fetal growth restriction (FGR) and healthy. In addition, we assessed the value of maternal serum MK level in predicting neonatal intensive care unit (NICU) admission. A total of 144 pregnant women were included, 72 with idiopathic FGR and 72 healthy in this study. The control group was matched for the mother's age, parity, gestational age, and pre-pregnancy body mass index (BMI) with the idiopathic FGR group at the time of recruitment into the study and sample collection. Serum MK level is higher in the idiopathic FGR than the control group (0.24 ng/mL (0.19–0.32) vs. 0.18 ng/mL (0.14–0.23), p<0.001). In addition, we compared the maternal serum MK level of those with and without NICU admission in the FGR group (0.25 ng/mL (0.19–0.37) vs. 0.21 ng/mL (0.18–0.28), p=0.014). We performed ROC curve analysis to serum MK level predicting NICU admission in the FGR group (AUC: 0.668, %95 CI [0.550, 0.785], p=0.014). A sensitivity of 63% and a specificity of 62% for the serum MK level were achieved with a cut-off value of 0.22 for NICU admission. To the best of our knowledge, this study is the first to compare maternal serum MK level in pregnant women with idiopathic FGR and healthy. We showed that maternal serum MK level was significantly elevated in pregnant women with FGR than healthy. [ABSTRACT FROM AUTHOR]

Many stillbirths are associated with fetal growth restriction, and are hence potentially avoidable. The Growth Assessment Protocol (GAP) is a multidisciplinary program with an evidence based care pathway, training in risk assessment, fetal growth surveillance with customised charts and rolling audit. Antenatal detection of small for gestational age (SGA) has become an indicator of quality of care. Evaluation is essential to understand the impact of such a prevention program. Randomised trials will not be effective if they cannot ensure proper implementation before assessment. Observational studies have allowed realistic evaluation in practice, with other factors excluded that may have influenced the outcome. An award winning 10 year study of stillbirth data in England has been able to assess the effect of GAP in isolation, and found a strong, causal association with improved antenatal detection of SGA babies, and the sustained decline in national stillbirth rates. The challenge now is to apply this program more widely in low and middle income settings where the main global burden of stillbirth is, and to adapt it to local needs and resources. [ABSTRACT FROM AUTHOR]

The article focuses on the study to analyze umbilical artery (UA) Doppler velocimetry and its possible role in placenta-mediated fetal growth restriction (FGR) in second- and third-trimester fetuses with trisomy 18 and 13. It mentions that high prevalence of abnormal UA Doppler velocimetry was found in second- and third-trimester fetuses with trisomy 18 and 13, which further increased with gestational age.

The article focuses on the study to evaluate subclinical signs of fetal cardiac remodeling in late-onset small-for-gestational-age (SGA) and growth restricted fetuses using two-dimensional speckle tracking echocardiography (2D-STE). It mentions that Cardiovascular disease (CVD) is one of the greatest challenges for our healthcare system and is one of the main causes of death worldwide.

Smoking during pregnancy is a leading and modifiable risk factor for fetal growth restriction (FGR) and low birthweight (<10th centile). We studied the effects of smoking in the development of early and late FGR or low birthweight, as well as in uteroplacental and fetoplacental hemodynamics of growth-restricted fetuses. Retrospective cohort study of 5,537 consecutive singleton pregnancies delivered at ≤34 + 0 ("early delivery" group, n=95) and >34 + 0 ("late delivery" group, n=5,442) weeks of gestation. Each group was divided into smokers and non-smokers. Prenatal diagnosis of FGR was based on customized fetal growth standards and fetal Doppler, and postnatal birthweight was assessed using the Olsen newborn chart. There were 15/95 (15.8%) and 602/5,442 (11.1%) smokers in the early and late delivery groups, respectively. In early deliveries, FGR was diagnosed in 3/15 (20%) of smokers and in 20/80 (25%) of non-smokers (p=0.68). We also found no differences in birthweights and hemodynamics. In late deliveres, FGR was detected in 30/602 (5%) smokers and 64/4,840 (1.3%) non-smokers (p<0.001). Birthweights <3rd centile and <10th centile were more common in smokers vs. non-smokers: 38/602 (6.3%) vs. 87/4,840 (1.8%) and 89/602 (14.8%) vs. 288/4,840 (6%), respectively (all p<0.01). Fetal Doppler of late FGR showed slightly higher umbilical artery resistances in smokers. Smoking in pregnancy is associated with FGR, low birthweight and higher umbilical artery Doppler resistances after 34 weeks of gestation, but we could not confirm this association in earlier deliveries. [ABSTRACT FROM AUTHOR]

Gestational IDA has been linked to adverse maternal and neonatal outcomes, but the impact of iron supplementation on outcome measures remains unclear. Our objective was to assess the effects of gestational IDA on pregnancy outcomes and compare outcomes in pregnancies treated with either oral or intravenous iron supplementation. We evaluated maternal and neonatal outcomes in 215 pregnancies complicated with gestational IDA (Hb<100 g/L) and delivered in our tertiary unit between January 2016 and October 2018. All pregnancies from the same period served as a reference group (n=11,545). 163 anemic mothers received oral iron supplementation, and 52 mothers received intravenous iron supplementation. Gestational IDA was associated with an increased risk of preterm birth (10.2% vs. 6.1%, p=0.009) and fetal growth restriction (FGR) (1.9% vs. 0.3%, p=0.006). The gestational IDA group that received intravenous iron supplementation had a greater increase in Hb levels compared to those who received oral medication (18.0 g/L vs. 10.0 g/L, p<0.001), but no statistically significant differences in maternal and neonatal outcomes were detected. Compared to the reference group, prematurity, FGR, postpartum infections, and extended hospital stays were more common among mothers with gestational IDA, causing an additional burden on the families and the healthcare system. [ABSTRACT FROM AUTHOR]

Our primary aim was to evaluate the ability of various cerebroplacental ratio (CPR) reference values suggested by the Fetal Medicine Foundation to predict adverse neonatal outcomes in term fetuses exhibiting late-onset fetal growth restriction (LOFGR). Our secondary aim was to evaluate the effectiveness of other obstetric Doppler parameters used to assess fetal well-being in terms of predicting adverse neonatal outcomes. This was a retrospective cohort study of 317 pregnant women diagnosed with LOFGR at 37–40 weeks of gestation between January 1, 2016, and September 1, 2019. Receiver operating characteristic (ROC) curves were drawn to determine the predictive performance of CPR <1, CPR <5th or <10th percentile, and umbilical artery pulsatility (PI) >95th percentile in terms of predicting adverse neonatal outcomes. Pregnant women exhibiting LOFGR who gave birth in our clinic during the study period at a mean of 38 gestational weeks (minimum 37+0; maximum 40+6 weeks); the median CPR was 1.51 [interquartile range (IQR) 1.12–1.95] and median birthweight 2,350 g (IQR 2,125–2,575 g). The CPR <5th percentile best predicted adverse neonatal outcomes [area under the curve (AUC) 0.762, 95% confidence interval (CI) 0.672–0.853, p<0.0001] and CPR <1 was the worst predictor (AUC 0.630, 95% CI 0.515–0.745, p=0.021). Of other Doppler parameters, neither the umbilical artery systole/diastole ratio nor the mid-cerebral artery to peak systolic velocity ratio (MCA–PSV) predicted adverse neonatal outcomes (AUC 0.598, 95% CI 0.480–0.598, p=0.104; AUC 0.521, 95% CI 0.396–0.521, p=0.744 respectively). The CPR values below the 5th percentile better predicted adverse neonatal outcomes in pregnancies complicated by LOFGR than the UA PI and CPR <1 by using Fetal Medicine Foundation reference ranges. [ABSTRACT FROM AUTHOR]

The maternal body size affects birth weight. The impact on birth weight percentiles is unknown. The objective of the study was to develop birth weight percentiles based on maternal height and weight. This observational study analyzed 2.2 million singletons from the German Perinatal Survey. Data were stratified into 18 maternal height and weight groups. Sex-specific birth weight percentiles were calculated from 31 to 42 weeks and compared to percentiles from the complete dataset using the GAMLSS package for R statistics. Birth weight percentiles not considering maternal size showed 22% incidence of small for gestational age (SGA) and 2% incidence of large for gestational age (LGA) for the subgroup of newborns from petite mothers, compared to a 4% SGA and 26% LGA newborns from big mothers. The novel percentiles based on 18 groups stratified by maternal height and weight for both sexes showed significant differences between identical original percentiles. The differences were up to almost 800 g between identical percentiles for petite and big mothers. The 97th and 50th percentile from the group of petite mothers almost overlap with the 50th and 3rd percentile from the group of big mothers. There is a clinically significant difference in birth weight percentiles when stratified by maternal height and weight. It could be hypothesized that birth weight charts stratified by maternal anthropometry could provide higher specificity and more individual prediction of perinatal risks. The new percentiles may be used to evaluate estimated fetal as well as birth weight. [ABSTRACT FROM AUTHOR]

Objectives: To compare a birth weight-derived (Brenner) and multiple ultrasound-derived [Hadlock, National Institute of Child Health and Human Development (NICHD), International Fetal and Newborn Growth Consortium (INTERGROWTH)] classification systems' frequency of assigning an antenatal estimated fetal weight (EFW) <10% and subsequent detection rate for abnormal umbilical artery Doppler (UAD). Methods: We analyzed 569 consecutive non-anomalous singleton gestations identified by ultrasound with either an abdominal circumference (AC) <3% or EFW <10% at a tertiary medical center between 1/2012 and 12/2016. The biometric measurements were exported for all serial ultrasounds and the sensitivity, specificity, positive and negative predictive values, and area under the curve (AUC) were calculated for the diagnosis of any abnormal UAD, absent or reversed end-diastolic flow (AREDF), and small for gestational age (SGA) for each classification method. Results: Brenner classified less patients with EFW <10% (49.7%) vs. the comparison methods (range: 84.2–85.0%; P < 0.001). The sensitivity was highest using Hadlock for detection of any abnormal UAD [96.6%; confidence interval (CI) 92.8–98.8%], AREDF (100%; CI 95.1–100%), and SGA (89.0%; CI 85.4–91.6%). However, there was minimal variation between the Hadlock, NICHD, and INTERGROWTH methods for detection of the studied outcomes. The AUCs for any abnormal UAD, AREDF, and SGA were highest for the Brenner method, but there were a substantial number of false-negative results with lower overall detection rates. Conclusions: Use of a birth weight-derived method to assign a fetal weight <10% as the threshold to initiate UAD surveillance has a lower detection rate for abnormal UAD when compared to ultrasound-derived methods. Despite substantial methodological differences in the creation of the Hadlock, NICHD, and INTERGROWTH methods, there were no differences in the detection rates of abnormal UAD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the possible predictive value of fetal fraction in the cell-free DNA (cfDNA) test in pregnancies with early- and late-onset fetal growth restriction (FGR). Methods: This retrospective study comprised 247 women who were screened using the cfDNA test for aneuploidies during the first or second trimester and had deliveries at our institution from January 2016 to December 2019. The fetal fractions of women with early- (n = 14) and late-onset (n = 83) FGR and those with uncomplicated pregnancies (n = 150) were compared. Results: The median fetal fractions for the early-onset FGR, late-onset FGR, and control groups were 5.7 [interquartile range (IQR) 2.65], 7 (IQR 5), and 7.35 (IQR 3.65), respectively. The fetal fractions were significantly lower in the early-onset FGR group than in the late-onset FGR and control groups (P = 0.047 and P = 0.037, respectively). There was no difference in fetal fractions between the late-onset FGR and control groups (P = 1.00). Conclusion: As a placenta-related disease, early-onset FGR had lower fetal fractions in the cfDNA test than uncomplicated pregnancies. For clinical use, lower fetal fractions can contribute as a biomarker for screening asymptomatic women for possible placenta-related diseases, such as early-onset FGR. However, more studies are needed to define the "lower" limit. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare transabdominal and transcervical chorionic villus sampling (CVS) as well as amniocentesis (AC) with respect to their rates of premature delivery and fetal growth restriction. Methods: We retrospectively evaluated the mentioned procedures of invasive prenatal testing performed in a single center between 2001 and 2016. Seven hundred and ninety-nine cases of AC and 719 cases of CVS were included, of which 400 were performed transvaginally. Only singleton pregnancies with a normal karyotype and delivery after 24 + 0 weeks of gestation were included. Fetal growth restriction was defined as birth weight below the 10th percentile. Premature delivery was defined as delivery before 37 + 0 weeks of gestation. Data were compared to a control group without an invasive procedure. Results: The frequency of premature delivery was 8.5% after transabdominal CVS, 6.3% after transcervical CVS and 10.5% after AC as compared to 10.8% in the control group. The frequency of fetal growth restriction was 8.2% after transabdominal CVS 6.8% after transcervical CVS and 8.4% after AC as compared to 9.7% in the control group. Conclusion: Our study supports that the three different methods of invasive prenatal testing do not lead to a higher risk of either premature delivery or fetal growth restriction when compared to controls. We found no difference in risk profile among the three techniques. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate if low levels of serum maternal pregnancy associated plasma protein-A (PAPP-A) during the first trimester are related to increased umbilical artery pulsatility index (UA PI) later in pregnancy, in cases of estimated fetal weight between the 3rd and 10th percentiles, in order to establish PAPP-A as a predictor of this particular cases of fetal growth restriction (FGR)., Methods: An observational, retrospective cohort study, conducted at a tertiary University Hospital located in Oporto, Portugal. Pregnant women who did the first trimester combined screening, between May 2013 and June 2020 and gave birth in the same hospital, with an estimated fetal weight (EFW) between the 3rd and 10th percentiles were included. The primary outcome is the difference in increased UA PI prevalence between two groups: PAPP-A<0.45 MoM and PAPP-A≥0.45 MoM. As secondary outcomes were evaluated differences in neonatal weight, gestational age at delivery, cesarean delivery, neonatal intensive care unit hospitalization, 5-min Apgar score below 7 and live birth rate between the same two groups., Results: We included 664 pregnancies: 110 cases of PAPP-A<0.45 MoM and 554 cases with PAPP-A≥0.45 MoM. Increased UA PI prevalence, which was the primary outcome of this study, was significantly different between the two groups (p=0.005), as the PAPP-A<0.45 MoM group presents a higher prevalence (12.7 %) when compared to the PAPP-A≥0.45 MoM group (5.4 %). The secondary outcome cesarean delivery rate was significantly different between the groups (p=0.014), as the PAPP-A<0.45 MoM group presents a higher prevalence (42.7 %) than the PAPP-A≥0.45 MoM group (30.1 %). No other secondary outcomes showed differences between the two groups., Conclusions: There is an association of low serum maternal PAPP-A (<0.45 MoM) during the first trimester and increased UA PI (>95th percentile) later in pregnancy, in cases of EFW between the 3rd and 10th percentiles. However, this association is not strong enough alone for low PAPP-A to be a reliable predictor of increased UA PI in this population., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Whether placental location confers specific neonatal risks is controversial. In particular, whether placenta previa is associated with intra-uterine growth restriction (IUGR)/small for gestational age (SGA) remains a matter of debate. Methods: We searched Medline, EMBASE, Google Scholar, Scopus, ISI Web of Science and Cochrane database search, as well as PubMed (www.pubmed.gov) until the end of December 2018 to conduct a systematic review and meta-analysis to determine the risk of IUGR/SGA in cases of placenta previa. We defined IUGR/SGA as birth weight below the 10th percentile, regardless of the terminology used in individual studies. Risk of bias was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. We used odds ratios (OR) and a fixed effects (FE) model to calculate weighted estimates in a forest plot. Statistical homogeneity was checked with the I2 statistic using Review Manager 5.3.5 (The Cochrane Collaboration, 2014). Results: We obtained 357 records, of which 13 met the inclusion criteria. All study designs were retrospective in nature, and included 11 cohort and two case-control studies. A total of 1,593,226 singleton pregnancies were included, of which 10,575 had a placenta previa. The incidence of growth abnormalities was 8.7/100 births in cases of placenta previa vs. 5.8/100 births among controls. Relative to cases with alternative placental location, pregnancies with placenta previa were associated with a mild increase in the risk of IUGR/SGA, with a pooled OR [95% confidence interval (CI)] of 1.19 (1.10–1.27). Statistical heterogeneity was high with an I2 = 94%. Conclusion: Neonates from pregnancies with placenta previa have a mild increase in the risk of IUGR/SGA. [ABSTRACT FROM AUTHOR]

Background: We developed an open-source software for the computerized analysis of antenatal fetal cardiotocography (CTG) without limitation of duration of the registration, enabling batch processing and adaptation to any digital storage system. Methods: STVcalc was developed based on literature about the FetalCare system (Huntleigh Healthcare Ltd, Cardiff, UK). For comparison with FetalCare, we selected the CTGs of all women who delivered in 2011 a small-for-gestational-age (SGA) fetus between 24 and 31 weeks by cesarean section (CS) for fetal distress, or had fetal death, before labor onset. Results: In 471 CTGs from 39 women, the agreement was 99% for a short-term variation (STV) cut-off of 2.6 ms below 29 weeks and 3.0 ms thereafter, and 95% for 3.5 and 4.0 ms, respectively. In 18 (4%) cases, the proportional difference in STV between FetalCare and STVcalc was more than 10%. Conclusion: As only slight differences were observed between the proposed feature-rich application and the FetalCare system, it can be considered valuable for clinical practice and research purposes. [ABSTRACT FROM AUTHOR]

Background: There is little available data on fetal monocyte phenotype and function. A prospective cross-sectional pilot study was conducted to describe the cord blood monocyte subset phenotype in preeclampsia (PE) and fetal growth restriction (FGR) as compared to normal pregnancy and maternal circulation. Methods: Maternal and cord blood samples from 27 pregnancies were collected at delivery from normal pregnancy, PE, FGR and PE + FGR. The distribution of fetal monocyte subtypes was characterized by CD14 and CD16 expression using flow cytometry and compared for each clinical group using a classification of classical, intermediate and non-classical subsets. Results: The intermediate monocytes were the dominant monocyte subset in the cord blood of PE and PE + FGR with an increase in the combined inflammatory monocyte subsets intermediate and non-classical in PE compared to normal pregnancy. The non-classical monocyte subset proportion was elevated in all pathological groups PE, FGR and PE + FGR. A significant reduction in the non-classical monocyte subset was observed in the cord blood of the normal pregnancy group as compared to the maternal circulation. Conclusion: This study describes for the first time in the fetal circulation, dominant monocyte intermediate subsets and increased inflammatory subsets in PE as well as increased non-classical subsets in PE and FGR compared to normal pregnancy. [ABSTRACT FROM AUTHOR]

Background: As conflicting results have been reported about the association of reversed flow on the aortic isthmus (AoI) and adverse perinatal results in fetal growth restriction (FGR), we aim to compare perinatal outcomes (including tolerance to labor induction) of late-onset FGR between those with anterograde and reversed AoI flow. Methods: This was an observational retrospective cohort study on 148 singleton gestations diagnosed with late-onset FGR (diagnosis ≥32+0 weeks), with an estimated fetal weight (EFW) <10th centile and mild fetal Doppler alteration: umbilical artery (UA) pulsatility index (PI) >95th centile, middle cerebral artery (MCA)-PI <5th centile or cerebral-placental ratio <5th centile. Anterograde AoI flow was present in n=79 and reversed AoI flow in n=69. Delivery was recommended from 37 weeks in both groups. Perinatal results were compared between the groups. Results: The global percentage of vaginal delivery of fetuses with anterograde and reversed blood flow was 55.7% vs. 66.7% (P=0.18) and the percentage of cesarean section (C-section) for non-reassuring fetal status was 12.7% vs. 15.9% (P=0.29), respectively. When evaluating those that underwent labor induction, the vaginal delivery rate was 67.9% vs. 77.2% (P=0.17), respectively. There were no significant differences regarding any other perinatal variables and there were no cases of severe morbidity or mortality. Conclusion: We observed that the presence of reversed AoI flow does not worsen perinatal outcomes on fetuses with late-onset growth restriction with mild Doppler alterations. Attempt of labor induction is feasible in these fetuses regardless of the direction of AoI flow. [ABSTRACT FROM AUTHOR]

Objective: To clarify and compare if the neurological outcomes of fetal growth restriction (FGR) cases with abnormal cord insertion (CI) are associated with a higher risk of a poor neurological outcome in subjects aged 3 years or less versus those with normal CI. Methods: A multicenter retrospective cohort study was conducted among patients with a birth weight lower than the 3rd percentile, based on the standard reference values for Japanese subjects after 22 weeks' gestation, who were treated at a consortium of nine perinatal centers in Japan between June 2005 and March 2011. Patients whose birth weights were less than the 3rd percentile and whose neurological outcomes from birth to 3 years of age could be checked from their medical records were analyzed. The relationship between abnormal CI and neurological outcomes was analyzed. Univariate and multivariate models of multivariate logistic regression were employed to estimate the raw and odds ratio (OR) with 95% confidence intervals comparing marginal (MCI) and velamentous cord insertion (VCI) to normal CI. Results: Among 365 neonates, 63 cases of MCI and 14 cases of VCI were observed. After excluding 24 cases with neonatal or infant death from the total FGR population, the assessment of the outcomes of the infants aged 3 years or younger showed the following rates of neurological complications: 7.3% (n=25) for cerebral palsy, 8.8% (n=30) for developmental disorders, 16.7% (n=57) for small-for-gestational-age short stature (SGA), 0.6% (n=2) for impaired hearing, 0.9% (n=3) for epilepsy, 1.2% (n=4). The ORs (95% confidence intervals) based on multivariate analysis were as follows: cerebral palsy=10.1 (2.4–41.5) in the VCI group and 4.3 (1.6–11.9) in the MCI group, developmental disorders=6.7 (1.7–26) in the VCI group and 3.9 (1.1–14.2) in the single umbilical artery (SUA) group, 5.1 (1.4–18.7) for birth weight <1000 g and 2.8 (1.2–6.7) for placental weight <200 g. Conclusions: The present results indicate that growth-restricted fetuses diagnosed with a birth weight below the 3rd percentile exhibiting abnormal umbilical CI are at a high risk for poor neurological outcomes, including cerebral palsy and/or developmental disorders. [ABSTRACT FROM AUTHOR]

Objective: To compare the adrenal gland size of fetal growth restricted (FGR) and normal control fetuses. Study design: In this prospective study the adrenal gland size of 63 FGR fetuses and 343 normal controls was measured between 20 and 41 weeks of gestation. The total width and the medulla width were measured in a new standardized transversal plane. The cortex width and a calculated ratio of the total and medulla width (adrenal gland ratio) were compared between both groups. Results: The mean cortex width and the adrenal gland ratio in FGR fetuses were higher in comparison to the controls (P<0.001; P=0.036, respectively). The cortex width correlated positively with the gestational age (control group: P<0.001; FGR group: P=0.089) whilst the adrenal gland ratio showed no association with the gestational age (control group: P=0.153; FGR group: P=0.314). Conclusion: The adrenal gland cortex width and the adrenal gland ratio were increased in FGR fetuses compared to normal fetuses. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate when in pregnancy to stop the administration of low dose aspirin (150 mg/daily) so as to prevent fetal growth restriction (FGR) A randomised, placebo-controlled study was designed. The patients were all screened positive using the Fetal Medicine Foundation (FMF) early pregnancy screening test for preeclampsia (PE) and FGR prediction. One hundred and fifty patients were enrolled and divided equally into three groups: A – the controls who received placebo treatment; B – those who received aspirin till 32 weeks of gestation and C – those who received aspirin till 36 weeks of gestation. The mean gestational age at enrollment was similar for all the groups (12.4 weeks). The growth curves, fetal and maternal Doppler measurements and amniotic fluid index (AFI) were monitored every 4 weeks. Also, the outcome of the pregnancy was noted and all the results were compared between the groups. FGR was defined as a fetal weight below the 10th centile for gestational age. In group C, there were less cases of FGR compared with the other groups: 6% vs. 10% in group B vs. 24% in controls. Also, there was a significant birth weight improvement in this group with a median of 3180 g compared with 2950 g in group B and 2760 g in group A (P=0.01). The gestational age at delivery was similar in all the groups (39 weeks in group C/39.2 weeks in group B/38.6 weeks in group A). In conclusion, low dose aspirin improves the outcome in the selected population and should be offered for prevention of FGR from 12 to 36 weeks. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate longitudinal mechanical dyssynchrony in normally grown fetuses by speckle tracking echocardiography (STE) and to compare longitudinal mechanical dyssynchrony in fetal growth restriction (FGR) with normal controls. Materials and methods: A prospective study was performed on 30 FGR and 62 normally grown fetuses, including 30 controls matched by gestational age, using STE and a transversal four-chamber view. Data analysis was carried out with a high frame rate of about 175 frames/s. Dyssynchrony was analyzed offline with QLab 9 (Philips Medical Systems, Andover, MA, USA) as time differences between peaks in strain of both ventricles and the septum. Inter- and intraventricular and intraseptal dyssynchrony were obtained and inter- and intraobserver reliability was analyzed. Results: Longitudinal mechanical dyssynchrony was feasible in all cases, with high inter- and intraobserver reliability. Levels of inter- and intraventricular dyssynchrony were higher in the FGR than in the control group. Conclusion: Speckle tracking echocardiography (STE) is a reliable technique for cardiac function assessment in the fetal heart. Interventricular dyssynchrony could be a potential parameter for early detection of subclinical myocardial dysfunction before other parameters demand intervention. The future clinical role of longitudinal mechanical dyssynchrony needs to be verified in larger studies and with a technique customized for prenatal echocardiography. [ABSTRACT FROM AUTHOR]

Aims: Severe preterm fetal growth restriction (FGR) remote from term is problematic. We aimed to investigate the effect of maternally-administered antithrombin on maternal and neonatal outcomes. A prospective, one-arm, pilot study was performed in 14 women with severe FGR (≤ 5th centile) at < 28 weeks of gestation, without hypertensive disorders. Maternal plasma concentrations of soluble Feline McDonough Sarcoma (FMS)-like trypsin kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured and categorized into three groups: group 1; low sFlt-1 and high PlGF, group 2; moderate sFlt-1 and low PlGF, and group 3; high sFlt-1 and low PlGF. Antithrombin was administered for 3 days. The incidence of perinatal mortality, infant morbidity, and the period of pregnancy prolongation were compared. Results: In group 1 (n = 4), their pregnancies were extended for longer periods and the maternal and infant outcomes were good. The prolongation periods were shorter in groups 2 (n = 3) and 3 (n = 7), which resulted in poor maternal [severe preeclampsia or hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome] and infant outcomes. Conclusions: The evaluation of the maternal sFlt-1 and PlGF at 21-27 weeks of gestation is useful in the managements of severe FGR. Antithrombin treatment could prolong the pregnancies with low sFlt-1 and high PlGF without negatively affecting maternal or fetal health. [ABSTRACT FROM AUTHOR]

The article discusses the study that determined the potential role of recombinant vascular endothelial growth factor (VEGF)121 (rVEGF121) injection in preventing fetal growth restriction in a preeclampsia (PE) mouse model (Mus musculus). Topics discussed include conclusion that rVEGF121 injection has potential of preventing fetal growth restriction in newly proposed PE mouse model, and possibility of fetal growth restriction with endothelial damage inhibition.

The article discusses the study that determined whether neonatal outcome of severe growth restricted human fetuses (IUGR) can be improved by intrauterine intraumbilical supplementation with amino acids (AA) and glucose. Topics discussed include pregnancy with severe placental insufficiency and brain sparing can be prolonger for many weeks by intravascular treatment of IUGR with fetal nutrition, and enhanced AA imbalance observed in IUGR fetuses after supplementation.

Aims: Fetuses with gastroschisis are at increased risk of intrauterine growth restriction (IUGR). However, there is a tendency for underestimation of fetal abdominal circumference and hence fetal weight, leading to overdiagnosis of IUGR. Our objective was to evaluate the accuracy of ultrasound for the prediction of being small for gestational age (SGA) at birth in these cases. Methods: A retrospective study of prenatally diagnosed cases of gastroschisis was conducted at a tertiary center. Fetal weight was estimated using the formula of Hadlock. IUGR was defined as an estimated fetal weight ≤ 10th percentile for gestational age. SGA at the time of birth was defined as a birth weight ≤ 10th percentile for gestational age. The incidence of IUGR on last ultrasound and that of SGA at birth were calculated, and the precision of ultrasound in predicting SGA was determined. Results: IUGR was reported on the last ultrasound prior to delivery in 9/25 cases (36%). Postnatally, 13/25 newborns (52%) were SGA. All sonographically suspected cases of IUGR based on the last ultrasound were SGA at birth. The positive predictive value of the last ultrasound in identifying SGA was 100%. Conclusions: At least half of the infants affected by gastroschisis were SGA at birth. Sonographic estimation of fetal weight within 1 month of birth reliably predicted SGA in infants with gastroschisis. [ABSTRACT FROM AUTHOR]

Objectives: To develop a nomogram for fetal left brachiocephalic vein (LBCV) diameters during a healthy pregnancy and to assess LBCV values in fetuses with fetal growth restriction (FGR)., Methods: This prospective observational study included 31 FGR pregnancies and 438 low-risk pregnancies. The low-risk group was used to determine the 5th, mean, and 95th percentiles for the LBCV between 12 and 39 weeks of gestation based on gestational age. On growth charts, LBCV measurements of FGR fetuses were displayed, and those above the gestational age 95th percentile were considered wide vein. Cerebroplacental ratio (CPR) and umbilical artery (UA), middle cerebral artery (MCA), and ductus venosus (DV) Doppler parameters were evaluated in FGR fetuses., Results: LBCV diameter increased significantly with advancing gestational age. The LBCV diameters were above the 95th percentile in 23 of the 31 FGR fetuses (74.2%). All fetuses (15/15, 100%) with early-onset (EO)-FGR and 8 fetuses (8/16, 50%) with the late-onset (LO)-FGR had LBCV values above the 95th percentile (p<0.01). UA-PI was significantly higher and MCA-PI and CPR were significantly lower in LO-FGR fetuses with LBCV diameters above the 95th percentile (p<0.05)., Conclusions: LBCV diameters of fetuses with FGR were significantly wider than the normal population. In the LO-FGR group, there was a good correlation between LBCV diameter and CPR., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: To compare short term variation (STV) and phase rectified signal averaging (PRSA) and their association with fetal outcome in early onset fetal growth restriction (FGR)., Methods: Data were used from a retrospective cohort study of women who were admitted for FGR and/or pre-eclampsia and who were delivered by pre-labor Cesarean section or had a fetal death before 32 weeks' gestation. Computerized cardiotocography (cCTG) registrations of the 5 days before delivery or fetal death were used for calculation of STV and PRSA. PRSA was expressed as the average acceleration capacity (AAC) and average deceleration capacity (ADC). FHR decelerations were classified visually as absent, 1-2 per hour or recurrent. Abnormality of STV and of PRSA was either analyzed as a single parameter or in combination with recurrent decelerations. Endpoints were defined as composite adverse condition at birth consisting of fetal death, low Apgar score, low umbilical pH, the need for resuscitation after birth and as major neonatal morbidity or neonatal death., Results: Included were 367 pregnancies of which 20 resulted in fetal death. An abnormal cCTG with either recurrent decelerations and/or low STV or recurrent decelerations and/or low PRSA were similarly associated with composite adverse condition at birth (n=99), but neither with major neonatal morbidity., Conclusions: PRSA and STV have similar efficacy for measuring fetal heart rate variation in early onset FGR. An increased risk of a composite adverse condition at birth is indicated by a low value of either parameter and/or the presence of recurrent decelerations., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)

Objectives: We aim to investigate the utility of middle cerebral artery peak systolic velocity (MCA PSV) Doppler in determining the perinatal mortality and morbidity in serial Doppler measurements from the time of diagnosis to the delivery of complicated cases with fetal growth restriction (FGR)., Methods: At 24-38 weeks of gestation, 65 pregnant women diagnosed with FGR were included in the study. The fetal biometry measurements, MCA pulsatility index (PI), and MCA PSV Doppler evaluation of the cases formed at the diagnosis and the delivery were recorded. Gestational weeks, birth weights, APGAR scores, cord pH values, NICU (neonatal intensive care unit) admission, NICU duration of stay, and perinatal morbidity parameters such as RDS (respiratory distress syndrome), BPD (bronchopulmonary dysplasia), NEC (necrotizing enterocolitis), sepsis and perinatal mortality were compared. The patients were divided into two groups: early and late-onset fetal growth restriction. Perinatal morbidity and mortality were accepted as adverse perinatal outcomes., Results: MCA PSV above the 95th percentile at the diagnosis and delivery time was seen at a significantly higher rate with adverse perinatal outcomes., Conclusions: This study shows that evaluating MCA PSV with Doppler can be a helpful diagnostic method for early diagnosis of restriction and hypoxic fetuses. Also, it may be used in clinics as a noninvasive method to predict neonatal prognosis., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: To correlate placental pathologic lesions, as defined by the Society for Pediatric Pathology, to the severity of the ratio of the pulsatility Doppler index (PI) of the fetal middle cerebral artery to that of the umbilical artery (cerebroplacental ratio, CPR). Study design: A cohort-study of 176 singleton pregnancies complicated by fetal growth restriction (FGR). Results: The mean values of gestational age, birth weight and CPR of the entire cohort were 33.9±3.6 weeks, 1552±561 g, and 1.33±0.68, respectively. In ordered logistic regression analysis, after adjustment for potential confounders, muscularised arteries (Odds Ratio [OR]=3.14; 95% confidence intervals [CI]=1.58-6.28, P=0.001), mural hypertrophy (OR=2.35; 95% CI=1.26-4.4, P=0.008), immature intermediate trophoblast (OR=2.0; 95% CI=1.07-3.71, P=0.03) and maternal vascular underperfusion (OR=2.32; 95% CI=1.25-4.23, P=0.007) were the only parameters associated with severity of CPR. Conclusions: The correlation between placental histological findings indicating maternal underperfusion and placental occlusion suggest that forced centralization of fetal circulation in FGR could be at least partially attributable to the hemodynamic consequences of increased placental vascular resistance. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate sonographic measurements of fetal adrenal gland size and middle adrenal artery Doppler in pregnancies with fetal growth restriction (FGR) and in a healthy control group., Methods: This prospective study included 107 singleton pregnancies with FGR between 24 and 42 weeks of gestation and 107 pregnancies with fetuses whose growth was appropriate for gestational age (AGA). Adrenal gland size and Doppler parameters of the adrenal artery were measured and the values and obstetric outcomes were compared between the study and control groups., Results: In the study group, the Z-scores of total adrenal width-length and height, fetal zone width-length and middle adrenal artery-peak systolic velocity (MAA-PSV) were significantly higher than those in the control group (p<0.05). The Z-scores of middle adrenal artery-pulsatility index (MAA-PI) were significantly lower in the study group than in the control group (p<0.05). The rate of neonatal intensive care unit admission in fetuses with high adrenal artery PI scores was higher in the FGR group (p<0.05)., Conclusions: In the present study, we observed decreased adrenal artery PI, increased adrenal blood flow, and increased fetal adrenal volume in fetuses diagnosed with fetal growth restriction, most likely in response to placental insufficiency and chronic hypoxia., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: To compare maternal serum midkine (MK) level in pregnant women with idiopathic fetal growth restriction (FGR) and healthy. In addition, we assessed the value of maternal serum MK level in predicting neonatal intensive care unit (NICU) admission., Methods: A total of 144 pregnant women were included, 72 with idiopathic FGR and 72 healthy in this study. The control group was matched for the mother's age, parity, gestational age, and pre-pregnancy body mass index (BMI) with the idiopathic FGR group at the time of recruitment into the study and sample collection., Results: Serum MK level is higher in the idiopathic FGR than the control group (0.24 ng/mL (0.19-0.32) vs. 0.18 ng/mL (0.14-0.23), p<0.001). In addition, we compared the maternal serum MK level of those with and without NICU admission in the FGR group (0.25 ng/mL (0.19-0.37) vs. 0.21 ng/mL (0.18-0.28), p=0.014). We performed ROC curve analysis to serum MK level predicting NICU admission in the FGR group (AUC: 0.668, %95 CI [0.550, 0.785], p=0.014). A sensitivity of 63% and a specificity of 62% for the serum MK level were achieved with a cut-off value of 0.22 for NICU admission., Conclusions: To the best of our knowledge, this study is the first to compare maternal serum MK level in pregnant women with idiopathic FGR and healthy. We showed that maternal serum MK level was significantly elevated in pregnant women with FGR than healthy., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Aims: The expression of the anti-inflammatory glycoprotein progranulin and the hypoxia-induced transcription factor 1α (HIF-1α) in the villous trophoblast was compared between placentae from patients with preeclampsia (PE), fetal growth restriction (FGR), and normal controls. Study design: Matched pairs analysis of third trimester placentae specimens (mean gestational age 36+2) was performed by semiquantitative measurements of the immunohistochemical staining intensities for progranulin and HIF-1α expression (PE n=13, FGR n=9 and controls n=11). Further, placental progranulin mRNA expression was analyzed by qRT-PCR on term placentae (n=3 for each group). Results: Compared to controls, villous trophoblast revealed a significantly higher expression of progranulin in cases of PE (P<0.05) and FGR (P<0.01). Similar results were shown for HIF-1α expression (P<0.01 for PE and <0.05 for FGR). The increase of the progranulin protein was not accompanied by an increase of the progranulin mRNA in term placentae. Conclusions: Increased expression of progranulin protein in villous trophoblast cells in cases of PE and FGR may result from disturbed placental development and, therefore, may be of pathogenetic importance. The increase was correlated to HIF-1α expression. Further evaluation of this potential mechanism of regulation is required. [ABSTRACT FROM AUTHOR]

Objective: To investigate the outcome of pregnancy after detection of chromosomal mosaicism and to determine the correlation between human chorionic gonadotropin (free β-HCG) and pregnancy-associated plasma protein-A (PAPP-A) levels from first-trimester-screening with pregnancy outcome. Methods: In a single-center, retrospective survey of the results of prenatal diagnostics performed between January 2000 and March 2011, we identified a total of 40 pregnancies with chromosomal mosaicism. Clinical characteristics and results of first-trimester screening, as well as the outcome of these cases, are described. Results: Out of 40 cases, 21 were defined as confined placental mosaicism, 10 classified as true mosaicism and nine were not classifiable cases. Nuchal translucency (NT) was ≥2.5 mm in 8/30 cases with respective measurements. PAPP-A levels were ≤0.4 MoM in 9/26 cases, with respective measurements, two of them being newborns with growth restriction. Remarkably, in pregnancies of all four children born with severe growth retardation, <3rd percentile PAPP-A levels were below 0.52 MoM. Conclusions: Our observations show mosaic pregnancy outcomes to be very heterogeneous. Nevertheless, a combination of low PAPP-A and interpretation of chromosomal mosaicism might identify pregnancies at particular risk for fetal growth restriction. [ABSTRACT FROM AUTHOR]

Objective: To estimate the influence of fetal growth restriction (FGR) on neonatal morbidity and mortality among premature discordant twin neonates. Study design: Our medical records (2002-2007) of preterm twins born at 24-37 weeks' gestation were reviewed. Significant discordance was defined as >15% difference in birth weight. Small for gestational age (SGA) was defined as birth weight <10th percentile, and appropriate for gestational age (AGA) was between the 10th and 90th percentile, according to a twin and sex-adjusted gestational age nomogram. The SGA/AGA group comprised of one SGA twin and its AGA pair (30 pairs). Another group of non-SGA discordant twins was also evaluated (n=40 pairs, AGA/AGA). The morbidity and mortality rates were compared between the groups. Results: Of the selected outcome variables, the only ones in which the incidence was significantly lower for SGA neonates than their AGA pairs were respiratory distress syndrome (5 vs. 11, P=0.014), apnea (1 vs. 9, P=0.004) and the need for respiratory support (5 vs. 14, P=0.002). Anemia, erythropoietin therapy and hyperbilirubinemia were significantly higher in the SGA twin. All selected outcome variables had similar rates within the AGA/AGA pairs. Conclusion: FGR among premature discordant twin pairs is associated with significantly lower rates of respiratory morbidity and higher anemia and erythropoietin therapy rates. Overall morbidity is similar for discordant non-FGR twin pairs. [ABSTRACT FROM AUTHOR]

Aim: To determine the independent effect of prenatal tobacco smoke exposure on fetal growth using customized birthweight norms. Methods: Demographic characteristics and data on exposure to tobacco smoke during pregnancy were obtained from singleton neonates ≥34 weeks' gestation. Centile Calculator software v62.2 (www.gestation.net) was used for calculating customized birthweight percentiles. Results: Of the 3227 neonates studied, 30.9% were exposed to maternal smoking during pregnancy, whereas involuntary maternal exposure was reported in 20.1%. Growth restriction was noted in 350 (10.8%). The odds ratio (OR) for fetal growth restriction was 1.49 (1.10-1.91) in passive smokers, and 2.34 (1.81-2.96) in smokers. A decrease in birthweight and an increase in the prevalence of growth restriction with the increasing number of cigarette consumption was observed. This effect was evident even in cases of a 'minimal' consumption of 1-5 cigarettes per day. Conclusion: An essential adverse effect of tobacco smoke exposure on fetal growth in pregnancies exposed to passive smoking, as well as in those with 'minimal' maternal cigarette consumption, was found. Since approximately 30% of growth restricted neonates could be independently attributed to active or passive maternal exposure, these findings reinforce the need for smoking preventive strategies in pregnant women and their environment. [ABSTRACT FROM AUTHOR]

Aim: The association between the growth deficit and the occurrence of adverse outcome was analyzed in a cohort of small-for-gestational age fetuses delivered at term. Methods: A cohort of consecutive singleton fetuses suspected of being SGA during the late third trimester and delivered beyond 37 weeks was selected. Growth deficit area was calculated as that between the individual 10th centile curve of the customized optimal fetal weight and the individual fetal growth curve. Results: A total of 55 women were included. Of these, 16 had 28 adverse events: eight cases of umbilical artery pH<7.15, 9 cases of caesarean section for fetal distress and 11 cases of admission to neonatal intensive care unit. Whereas the mean area of growth deficit was 8.8 kg×week units (SD 7.6) for cases with normal outcomes, it was 13.9 (SD 8.04) for cases with adverse outcomes (P=0.03). A growth area deficit >10 units, predicted the occurrence of adverse outcome with a sensitivity and specificity of 62% and 68%, respectively. Conclusion: In term growth restricted fetuses the degree of growth deficit from the optimal customized growth may be used to identify a subgroup of fetuses at high-risk for adverse outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Smoking during pregnancy is a leading and modifiable risk factor for fetal growth restriction (FGR) and low birthweight (<10th centile). We studied the effects of smoking in the development of early and late FGR or low birthweight, as well as in uteroplacental and fetoplacental hemodynamics of growth-restricted fetuses., Methods: Retrospective cohort study of 5,537 consecutive singleton pregnancies delivered at ≤34 + 0 ("early delivery" group, n=95) and >34 + 0 ("late delivery" group, n=5,442) weeks of gestation. Each group was divided into smokers and non-smokers. Prenatal diagnosis of FGR was based on customized fetal growth standards and fetal Doppler, and postnatal birthweight was assessed using the Olsen newborn chart., Results: There were 15/95 (15.8%) and 602/5,442 (11.1%) smokers in the early and late delivery groups, respectively. In early deliveries, FGR was diagnosed in 3/15 (20%) of smokers and in 20/80 (25%) of non-smokers (p=0.68). We also found no differences in birthweights and hemodynamics. In late deliveres, FGR was detected in 30/602 (5%) smokers and 64/4,840 (1.3%) non-smokers (p<0.001). Birthweights <3rd centile and <10th centile were more common in smokers vs. non-smokers: 38/602 (6.3%) vs. 87/4,840 (1.8%) and 89/602 (14.8%) vs. 288/4,840 (6%), respectively (all p<0.01). Fetal Doppler of late FGR showed slightly higher umbilical artery resistances in smokers., Conclusions: Smoking in pregnancy is associated with FGR, low birthweight and higher umbilical artery Doppler resistances after 34 weeks of gestation, but we could not confirm this association in earlier deliveries., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: To analyze umbilical artery (UA) Doppler velocimetry and its possible role in placenta-mediated fetal growth restriction (FGR) in second- and third-trimester fetuses with trisomy 18 and 13., Methods: UA pulsatility index (PI) and half-peak systolic velocity deceleration time (hPSV-DT) were measured in fetuses with trisomy 18 and 13. Correlation with gestational age, birthweight, and perinatal outcome was analyzed., Results: A total of 80 measurements were taken from 33 fetuses with trisomy 18 and 19 with trisomy 13. Overall, there was a high prevalence of abnormal UA Doppler velocimetry. In fetuses with trisomy 18, 54% (27/50) of the UA PI values and 58% (29/50) of the UA hPSV-DT values were abnormal. In fetuses with trisomy 13, 80% (24/30) of the UA PI values and 87% (26/30) of the UA hPSV-DT values were abnormal. The prevalence of abnormal UA Doppler velocimetry increased with gestational age in both types of aneuploidy. However, this trend was only significant for trisomy 13 (p<0.05). All fetuses with trisomy 18 and 86% of fetuses with trisomy 13 were classified at birth as FGR. There were no perinatal survivors in this series., Conclusions: A high prevalence of abnormal UA Doppler velocimetry was found in second- and third-trimester fetuses with trisomy 18 and 13, which further increased with gestational age. These results may well correlate with alterations described previously in the placenta, suggesting placental insufficiency has an important role in the development of FGR in these autosomal aneuploid fetuses., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)