Nitric oxide donor increases umbilical vein blood flow and fetal oxygenation in fetal growth restriction. A pilot study.

INTRODUCTION: To evaluate the maternal and fetal hemodynamic effects of treatment with a nitric oxide donor and oral fluid in pregnancies complicated by fetal growth restriction. METHODS: 30 normotensive participants with early fetal growth restriction were enrolled. 15 participants were treated until delivery with transdermal glyceryl trinitrate and oral fluid intake (Treated group), and 15 comprised the untreated group. All women underwent non-invasive assessment of fetal and maternal hemodynamics and repeat evaluation 2 weeks later. RESULTS: In the treated group, maternal hemodynamics improved significantly after two weeks of therapy compared to untreated participants. Fetal hemodynamics in the treated group showed an increase in umbilical vein diameter by 18.87 % (p < 0.01), in umbilical vein blood flow by 48.16 % (p < 0.01) and in umbilical vein blood flow corrected for estimated fetal weight by 30.03 % (p < 0.01). In the untreated group, the characteristics of the umbilical vein were unchanged compared to baseline. At the same time, the cerebro-placental ratio increased in the treated group, while it was reduced in the untreated group, compared to baseline values. The treated group showed a higher birthweight centile (p = 0.03) and a lower preeclampsia rate (p = 0.04) compared to the untreated group. DISCUSSION: The combined therapeutic approach with nitric oxide donor and oral fluid intake in fetal growth restriction improves maternal hemodynamics, which becomes more hyperdynamic (volume-dominant). At the same time, in the fetal circuit, umbilical vein flow increased and fetal brain sparing improved. Although a modest sample size, there was less preeclampsia and a higher birthweight suggesting beneficial maternal and fetal characteristics of treatment.

Vasa previa in singleton pregnancies: diagnosis and clinical management based on an international expert consensus.

BACKGROUND: There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies. OBJECTIVE: This study aimed to systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions and a Delphi technique. STUDY DESIGN: A 4-round focus group discussion and a 3-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected on the basis of their publication record on vasa previa. First, we convened a focus group discussion panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A 3-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa, which the experts were asked to rate on a 5-point Likert scale (from "strongly disagree"=1 to "strongly agree"=5). Consensus was defined as a median score of 5. Following responses to each round, any statements that had median scores of ≤3 were deemed to have had no consensus and were excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and nonconsensus statements were then aggregated. RESULTS: A total of 68 international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on 5 continents and have contributed to >80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, and 91% for the first, second, and third rounds, respectively, and 71% completed all 3 rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including the following: (1) although there is no agreement on the distance between the fetal vessels and the cervical internal os to define vasa previa, the definition should not be limited to a 2-cm distance; (2) all pregnancies should be screened for vasa previa with routine examination for placental cord insertion and a color Doppler sweep of the region over the cervix at the second-trimester anatomy scan; (3) when a low-lying placenta or placenta previa is found in the second trimester, a transvaginal ultrasound with Doppler should be performed at approximately 32 weeks to rule out vasa previa; (4) outpatient management of asymptomatic patients without risk factors for preterm birth is reasonable; (5) asymptomatic patients with vasa previa should be delivered by scheduled cesarean delivery between 35 and 37 weeks of gestation; and (6) there was no agreement on routine hospitalization, avoidance of intercourse, or use of 3-dimensional ultrasound for diagnosis of vasa previa. CONCLUSION: Through focus group discussion and a Delphi process, an international expert panel reached consensus on the definition, screening, clinical management, and timing of delivery in vasa previa, which could inform the development of new clinical guidelines.

Assessment of the cerebroplacental ratio and uterine arteries in low-risk pregnancies in early labour for the prediction of obstetric and neonatal outcomes.

BACKGROUND: The evidence-based management of human labor includes the antepartum identification of patients at risk for intrapartum hypoxia. However, available evidence has shown that most of the hypoxic-related complications occur among pregnancies classified at low-risk for intrapartum hypoxia, thus suggesting that the current strategy to identify the pregnancies at risk for intrapartum fetal hypoxia has limited accuracy. OBJECTIVE: To evaluate the role of the combined assessment of the cerebroplacental ratio (CPR) and uterine arteries (UtA) Doppler in the prediction of obstetric intervention (OI) for suspected intrapartum fetal compromise (IFC) within a cohort of low-risk singleton term pregnancies in early labor. METHODS: Prospective multicentre observational study conducted across four tertiary Maternity Units between January 2016 and September 2019. Low-risk term pregnancies with spontaneous onset of labor were included. A two-step multivariable model was developed to assess the risk of OI for suspected IFC. The baseline model included antenatal and intrapartum characteristics, while the combined model included antenatal and intrapartum characteristics plus Doppler anomalies such as CPR MoM < 10th percentile and mean UtA Doppler PI MoM ≥ 95th percentile. Predictive performance was determined by receiver-operating characteristics curve analysis. RESULTS: 804 women were included. At logistic regression analysis, CPR MoM < 10th percentile (aOR 1.269, 95 % CI 1.188-1.356, P < 0.001), mean UtA PI MoM ≥ 95th percentile (aOR 1.012, 95 % CI 1.001-1.022, P = 0.04) were independently associated with OI for suspected IFC. At ROC curve analysis, the combined model including antenatal characteristics plus abnormal CPR and mean UtA PI yielded an AUC of 0.78, 95 %CI(0.71-0.85), p < 0.001, which was significantly higher than the baseline model (AUC 0.61, 95 %CI(0.54-0.69), p = 0.007) (p < 0.001). The combined model was associated with a 0.78 (95 % CI 0.67-0.89) sensitivity, 0.68 (95 % CI 0.65-0.72) specificity, 0.15 (95 % CI 0.11-0.19) PPV, and 0.98 (0.96-0.99) NPV, 2.48 (95 % CI 2.07-2.97) LR + and 0.32 (95 % CI 0.19-0.53) LR- for OI due to suspected IFC. CONCLUSIONS: A predictive model including antenatal and intrapartum characteristics combined with abnormal CPR and mean UtA PI has a good capacity to rule out and a moderate capacity to rule in OI due to IFC, albeit with poor predictive value.

Fetal face shape analysis from prenatal 3D ultrasound images.

3D ultrasound imaging of fetal faces has been predominantly confined to qualitative assessment. Many genetic conditions evade diagnosis and identification could assist with parental counselling, pregnancy management and neonatal care planning. We describe a methodology to build a shape model of the third trimester fetal face from 3D ultrasound and show how it can objectively describe morphological features and gestational-age related changes of normal fetal faces. 135 fetal face 3D ultrasound volumes (117 appropriately grown, 18 growth-restricted) of 24-34 weeks gestation were included. A 3D surface model of each face was obtained using a semi-automatic segmentation workflow. Size normalisation and rescaling was performed using a growth model giving the average size at every gestation. The model demonstrated a similar growth rate to standard head circumference reference charts. A landmark-free morphometry model was estimated to characterize shape differences using non-linear deformations of an idealized template face. Advancing gestation is associated with widening/fullness of the cheeks, contraction of the chin and deepening of the eyes. Fetal growth restriction is associated with a smaller average facial size but no morphological differences. This model may eventually be used as a reference to assist in the prenatal diagnosis of congenital anomalies with characteristic facial dysmorphisms.

Beetroot juice, exercise, and cardiovascular function in women planning to conceive.

OBJECTIVE: Prepregnancy optimization of cardiovascular function may reduce the risk of pre-eclampsia. We aimed to assess the feasibility and effect of preconception cardiovascular monitoring, exercise, and beetroot juice on cardiovascular parameters in women planning to conceive. DESIGN AND METHOD: Prospective single-site, open-label, randomized controlled trial. Thirty-two women, aged 18-45 years, were allocated into one of four arms (1 : 1 : 1 : 1): exercise, beetroot juice, exercise plus beetroot juice and no intervention for 12 weeks. Blood pressure (BP) was measured at home daily. Cardiac output ( CO ) and total peripheral resistance (TPR) were assessed via bio-impedance. RESULTS: Twenty-nine out of 32 (91%) participants completed the study. Adherence to daily BP and weight measurements were 81% and 78%, respectively ( n  = 29). Eight out of 15 (53%) of participants did not drink all the provided beetroot juice because of forgetfulness and taste. After 12 weeks, exercise was associated with a reduction in standing TPR (-278 ±â€Š0.272 dynes s cm -5 , P  < 0.05), and an increase in standing CO (+0.88 ±â€Š0.71 l/min, P  < 0.05). Exercise and beetroot juice together was associated with a reduction in standing DBP ( 7 ±â€Š6 mmHg, P  < 0.05), and an increase in standing CO (+0.49 ±â€Š0.66 l/min, P  < 0.05). The control group showed a reduction in standing TPR ( 313 ±â€Š387 dynes s cm -5 ) and standing DBP ( 8 ±â€Š5mmHg). All groups gained weight. CONCLUSION: Exercise and beetroot juice in combination showed a signal towards improving cardiovascular parameters. The control group showed improvements, indicating that home measurement devices and regular recording of parameters are interventions in themselves. Nevertheless, interventions before pregnancy to improve cardiovascular parameters may alter the occurrence of hypertensive conditions during pregnancy and require further investigation in adequately powered studies.

Continuous non-invasive measurement of cardiac output in neonatal intensive care using regional impedance cardiography: a prospective observational study.

OBJECTIVES: To compare agreement between echocardiography and regional impedance cardiography (RIC)-derived cardiac output (CO), and to construct indicative normative ranges of CO for gestational age groups. DESIGN, SETTING AND PARTICIPANTS: Prospective cohort observational study performed in a tertiary centre in London, UK, including neonates born between 25 and 42 weeks' gestational age. EXPOSURES: Neonates on the postnatal ward had 2 hours of RIC monitoring; neonates in intensive care had RIC monitoring for the first 72 hours, then weekly for 2 hours, with concomitant echocardiography measures. MAIN OUTCOMES AND MEASURES: RIC was used to measure CO continuously. Statistical analyses were performed using R (V.4.2.2; R Core Team 2022). RIC-derived CO and echocardiography-derived CO were compared using Pearson's correlations and Bland-Altman analyses. Differences in RIC-derived CO between infants born extremely, very and late preterm were assessed using analyses of variance and mixed-effects modelling. RESULTS: 127 neonates (22 extremely, 46 very, 29 late preterm and 30 term) were included. RIC and echocardiography-measured weight-adjusted CO were correlated (r=0.62, p<0.001) with a Bland-Altman bias of -31 mL/min/kg (limits of agreement -322 to 261 mL/min/kg). The RIC-derived CO fell over 12 hours, then increased until 72 hours after birth. The 72-hour weight-adjusted mean CO was higher in extremely preterm (424±158 mL/min/kg) compared with very (325±131 mL/min/kg, p<0.001) and late preterm (237±81 mL/min/kg, p<0.001) neonates; this difference disappeared by 2-3 weeks of age. CONCLUSIONS: RIC is valid for continuous, non-invasive CO measurement in neonates. Indicative normative CO ranges could help clinicians to make more informed haemodynamic management decisions, which should be explored in future studies. TRIAL REGISTRATION NUMBER: NCT04064177.

Placental syndromes and maternal cardiovascular health.

The placental syndromes gestational hypertension, preeclampsia and intrauterine growth restriction are associated with an increased cardiovascular risk to the mother later in life. In this review, we argue that a woman's pre-conception cardiovascular health drives both the development of placental syndromes and long-term cardiovascular risk but acknowledge that placental syndromes can also contribute to future cardiovascular risk independent of pre-conception health. We describe how preclinical studies in models of preeclampsia inform our understanding of the links with later cardiovascular disease, and how current pre-pregnancy studies may explain relative contributions of both pre-conception factors and the occurrence of placental syndromes to long-term cardiovascular disease.

Do differences in diagnostic criteria for late fetal growth restriction matter?

BACKGROUND: Criteria for diagnosis of fetal growth restriction differ widely according to national and international guidelines, and further heterogeneity arises from the use of different biometric and Doppler reference charts, making the diagnosis of fetal growth restriction highly variable. OBJECTIVE: This study aimed to compare fetal growth restriction definitions between Delphi consensus and Society for Maternal-Fetal Medicine definitions, using different standards/charts for fetal biometry and different reference ranges for Doppler velocimetry parameters. STUDY DESIGN: From the TRUFFLE 2 feasibility study (856 women with singleton pregnancy at 32+0 to 36+6 weeks of gestation and at risk of fetal growth restriction), we selected 564 women with available mid-pregnancy biometry. For the comparison, we used standards/charts for estimated fetal weight and abdominal circumference from Hadlock, INTERGROWTH-21st, and GROW and Chitty. Percentiles for umbilical artery pulsatility index and its ratios with middle cerebral artery pulsatility index were calculated using Arduini and Ebbing reference charts. Sensitivity and specificity for low birthweight and adverse perinatal outcome were evaluated. RESULTS: Different combinations of definitions and reference charts identified substantially different proportions of fetuses within our population as having fetal growth restriction, varying from 38% (with Delphi consensus definition, INTERGROWTH-21st biometric standards, and Arduini Doppler reference ranges) to 93% (with Society for Maternal-Fetal Medicine definition and Hadlock biometric standards). None of the different combinations tested appeared effective, with relative risk for birthweight <10th percentile between 1.4 and 2.1. Birthweight <10th percentile was observed most frequently when selection was made with the GROW/Chitty charts, slightly less with the Hadlock standard, and least frequently with the INTERGROWTH-21st standard. Using the Ebbing Doppler reference ranges resulted in a far higher proportion identified as having fetal growth restriction compared with the Arduini Doppler reference ranges, whereas Delphi consensus definition with Ebbing Doppler reference ranges produced similar results to those of the Society for Maternal-Fetal Medicine definition. Application of Delphi consensus definition with Arduini Doppler reference ranges was significantly associated with adverse perinatal outcome, with any biometric standards/charts. The Society for Maternal-Fetal Medicine definition could not accurately detect adverse perinatal outcome irrespective of estimated fetal weight standard/chart used. CONCLUSION: Different combinations of fetal growth restriction definitions, biometry standards/charts, and Doppler reference ranges identify different proportions of fetuses with fetal growth restriction. The difference in adverse perinatal outcome may be modest, but can have a significant impact in terms of rate of intervention.

The sonopartogram.

The assessment of labor progress from digital vaginal examination has remained largely unchanged for at least a century, despite the current major advances in maternal and perinatal care. Although inconsistently reproducible, the findings from digital vaginal examination are customarily plotted manually on a partogram, which is composed of a graphical representation of labor, together with maternal and fetal observations. The partogram has been developed to aid recognition of failure to labor progress and guide management-specific obstetrical intervention. In the last decade, the use of ultrasound in the delivery room has increased with the advent of more powerful, portable ultrasound machines that have become more readily available for use. Although ultrasound in intrapartum practice is predominantly used for acute management, an ultrasound-based partogram, a sonopartogram, might represent an objective tool for the graphical representation of labor. Demonstrating greater accuracy for fetal head position and more objectivity in the assessment of fetal head station, it could be considered complementary to traditional clinical assessment. The development of the sonopartogram concept would require further undertaking of serial measurements. Advocates of ultrasound will concede that its use has yet to demonstrate a difference in obstetrical and neonatal morbidity in the context of the management of labor and delivery. Taking a step beyond the descriptive graphical representation of labor progress is the question of whether a specific combination of clinical and demographic parameters might be used to inform knowledge of labor outcomes. Intrapartum cesarean deliveries and deliveries assisted by forceps and vacuum are all associated with a heightened risk of maternal and perinatal adverse outcomes. Although these outcomes cannot be precisely predicted, many known risk factors exist. Malposition and high station of the fetal head, short maternal stature, and other factors, such as caput succedaneum, are all implicated in operative delivery; however, the contribution of individual parameters based on clinical and ultrasound assessments has not been quantified. Individualized risk prediction models, including maternal characteristics and ultrasound findings, are increasingly used in women's health-for example, in preeclampsia or trisomy screening. Similarly, intrapartum cesarean delivery models have been developed with good prognostic ability in specifically selected populations. For intrapartum ultrasound to be of prognostic value, robust, externally validated prediction models for labor outcome would inform delivery management and allow shared decision-making with parents.

Impact of perinatal factors on biomarkers of cardiovascular disease risk in preadolescent children.

BACKGROUND: This review aims to summarize associations of the perinatal environment with arterial biophysical properties in childhood, to elucidate possible perinatal origins of adult cardiovascular disease (CVD). METHODS: A systematic search of PubMed database was performed (December 2020). Studies exploring associations of perinatal factors with arterial biophysical properties in children 12 years old or less were included. Properties studied included: pulse wave velocity; arterial stiffness or distensibility; augmentation index; intima-media thickness of aorta (aIMT) or carotids; endothelial function (laser flow Doppler, flow-mediated dilatation). Two reviewers independently performed study selection and data extraction. RESULTS: Fifty-two of 1084 identified records were included. Eleven studies explored associations with prematurity, 14 explored maternal factors during pregnancy, and 27 explored effects of low birth weight, small-for-gestational age and foetal growth restriction (LBW/SGA/FGR). aIMT was consistently higher in offspring affected by LBW/SGA/FGR in all six studies examining this variable. The cause of inconclusive or conflicting associations found with other arterial biophysical properties and perinatal factors may be multifactorial: in particular, measurements and analyses of related properties differed in technique, equipment, anatomical location, and covariates used. CONCLUSION: aIMT was consistently higher in LBW/SGA/FGR offspring, which may relate to increased long-term CVD risk. Larger and longer term cohort studies may help to elucidate clinical significance, particularly in relation to established CVD risk factors. Experimental studies may help to understand whether lifestyle or medical interventions can reverse perinatal changes aIMT. The field could be advanced by validation and standardization of techniques assessing arterial structure and function in children.

Obliterated cavum septi pellucidi: Clinical significance and role of fetal magnetic resonance.

INTRODUCTION: The objective of this study was to describe a cohort of fetuses with an ultrasound prenatal diagnosis of obliterated cavum septi pellucidi (oCSP) with the aim to explore the rate of associated malformations, the progression during pregnancy and the role of fetal magnetic resonance imaging (MRI). MATERIAL AND METHODS: This was a retrospective multicenter international study of fetuses diagnosed with oCSP in the second trimester with available fetal MRI and subsequent ultrasound and/or fetal MRI follow-up in the third trimester. Where available, postnatal data were collected to obtain information on neurodevelopment. RESULTS: We identified 45 fetuses with oCSP at 20.5 weeks (interquartile range 20.1-21.1). oCSP was apparently isolated at ultrasound in 89% (40/45) and fetal MRI found additional findings in 5% (2/40) of cases, including polymicrogyria and microencephaly. In the remaining 38 fetuses, fetal MRI found a variable amount of fluid in CSP in 74% (28/38) and no fluid in 26% (10/38). Ultrasound follow-up at or after 30 weeks confirmed the diagnosis of oCSP in 32% (12/38) while fluid was visible in 68% (26/38). At follow-up MRI, performed in eight pregnancies, there were periventricular cysts and delayed sulcation with persistent oCSP in one case. Among the remaining cases with normal follow-up ultrasound and fetal MRI findings, the postnatal outcome was normal in 89% of cases (33/37) and abnormal in 11% (4/37): two with isolated speech delay, and two with neurodevelopmental delay secondary to postnatal diagnosis of Noonan syndrome at 5 years in one case and microcephaly with delayed cortical maturation at 5 months in the other. CONCLUSIONS: Apparently isolated oCSP at mid-pregnancy is a transient finding with the visualization of the fluid later in pregnancy in up to 70% of cases. At referral, associated defects can be found in around 11% of cases at ultrasound and 8% at fetal MRI indicating the need for a detailed evaluation by expert physicians when oCSP is suspected.

Antenatal detection of large-for-gestational-age fetuses following implementation of the Growth Assessment Protocol: secondary analysis of a randomised control trial.

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP) affects the antenatal detection of large for gestational age (LGA) or maternal and perinatal outcomes amongst LGA babies. DESIGN: Secondary analysis of a pragmatic open randomised cluster control trial comparing the GAP with standard care. SETTING: Eleven UK maternity units. POPULATION: Pregnant women and their LGA babies born at ≥36+0  weeks of gestation. METHODS: Clusters were randomly allocated to GAP implementation or standard care. Data were collected from electronic patient records. Trial arms were compared using summary statistics, with unadjusted and adjusted (two-stage cluster summary approach) differences. MAIN OUTCOME MEASURES: Rate of detection of LGA (estimated fetal weight on ultrasound scan above the 90th centile after 34+0  weeks of gestation, defined by either population or customised growth charts), maternal and perinatal outcomes (e.g. mode of birth, postpartum haemorrhage, severe perineal tears, birthweight and gestational age, neonatal unit admission, perinatal mortality, and neonatal morbidity and mortality). RESULTS: A total of 506 LGA babies were exposed to GAP and 618 babies received standard care. There were no significant differences in the rate of LGA detection (GAP 38.0% vs standard care 48.0%; adjusted effect size -4.9%; 95% CI -20.5, 10.7; p = 0.54), nor in any of the maternal or perinatal outcomes. CONCLUSIONS: The use of GAP did not change the rate of antenatal ultrasound detection of LGA when compared with standard care.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

The cardiac-fetal-placental unit: fetal umbilical vein flow rate is linked to the maternal cardiac profile in fetal growth restriction.

BACKGROUND: The functional maternal-fetal hemodynamic unit includes fetal umbilical vein flow and maternal peripheral vascular resistance. OBJECTIVE: This study investigated the relationships between maternal and fetal hemodynamics in a population with suspected fetal growth restriction. STUDY DESIGN: This was a prospective study of normotensive pregnancies referred to our outpatient clinic for a suspected fetal growth restriction. Maternal hemodynamics measurement was performed, using a noninvasive device (USCOM-1A) and a fetal ultrasound evaluation to assess fetal biometry and velocimetry Doppler parameters. Comparisons among groups were performed with 1-way analysis of variance with Student-Newman-Keuls correction for multiple comparisons and with Kruskal-Wallis test where appropriate. The Spearman rank coefficient was used to assess the correlation between maternal and fetal hemodynamics. Pregnancies were observed until delivery. RESULTS: A total of 182 normotensive pregnancies were included. After the evaluation, 54 fetuses were classified as growth restricted, 42 as small for gestational age, and 86 as adequate for gestational age. The fetus with fetal growth restriction had significantly lower umbilical vein diameter (P<.0001), umbilical vein velocity (P=.02), umbilical vein flow (P<.0001), and umbilical vein flow corrected for fetal weight (P<.01) than adequate-for-gestational-age and small-for-gestational-age fetuses. The maternal hemodynamic profile in fetal growth restriction was characterized by elevated systemic vascular resistance and reduced cardiac output. The umbilical vein diameter was positively correlated to maternal cardiac output (rs=0.261), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.338) and maternal potential energy-to-kinetic energy ratio (rs=-0267). The fetal umbilical vein time averaged max velocity was positively correlated to maternal cardiac output (rs=0.189) and maternal inotropy index (rs=0.162), whereas there was a negative correlation with maternal systemic vascular resistance (rs=-0.264) and maternal potential energy-to-kinetic energy ratio (rs=-0.171). The fetal umbilical vein flow and the flow corrected for estimated fetal weight were positively correlated with maternal cardiac output (rs=0.339 and rs=0.297) and maternal inotropy index (rs=0.217 and r=0.336), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.461 and rs=-0.409) and maternal potential energy-to-kinetic energy ratio (rs=-0.336 and rs=-0.408). CONCLUSION: Maternal and fetal hemodynamic parameters were different in the 3 groups of fetuses: fetal growth restriction, small for gestational age, and adequate for gestational age. Maternal hemodynamic parameters were closely and continuously correlated with fetal hemodynamic features. In particular, a maternal hemodynamic profile with high systemic vascular resistance, low cardiac output, reduced inotropism, and hypodynamic circulation was correlated with a reduced umbilical vein flow and increased umbilical artery pulsatility index. The mother, placenta, and fetus should be considered as a single cardiac-fetal-placental unit. The correlations of systemic vascular resistance, cardiac output, and inotropy index with umbilical artery impedance indicate the key role of these 3 parameters in placental vascular tree development. The umbilical vein flow rate and, therefore, the placental perfusion seems to be influenced not only by these three parameters but also by the maternal cardiovascular kinetic energy.

Reduced fetal growth velocity and weight loss are associated with adverse perinatal outcome in fetuses at risk of growth restriction.

BACKGROUND: Although fetal size is associated with adverse perinatal outcome, the relationship between fetal growth velocity and adverse perinatal outcome is unclear. OBJECTIVE: This study aimed to evaluate the relationship between fetal growth velocity and signs of cerebral blood flow redistribution, and their association with birthweight and adverse perinatal outcome. STUDY DESIGN: This study was a secondary analysis of the TRUFFLE-2 multicenter observational prospective feasibility study of fetuses at risk of fetal growth restriction between 32+0 and 36+6 weeks of gestation (n=856), evaluated by ultrasound biometry and umbilical and middle cerebral artery Doppler. Individual fetal growth velocity was calculated from the difference of birthweight and estimated fetal weight at 3, 2, and 1 week before delivery, and by linear regression of all available estimated fetal weight measurements. Fetal estimated weight and birthweight were expressed as absolute value and as multiple of the median for statistical calculation. The coefficients of the individual linear regression of estimated fetal weight measurements (growth velocity; g/wk) were plotted against the last umbilical-cerebral ratio with subclassification for perinatal outcome. The association of these measurements with adverse perinatal outcome was assessed. The adverse perinatal outcome was a composite of abnormal condition at birth or major neonatal morbidity. RESULTS: Adverse perinatal outcome was more frequent among fetuses whose antenatal growth was <100 g/wk, irrespective of signs of cerebral blood flow redistribution. Infants with birthweight <0.65 multiple of the median were enrolled earlier, had the lowest fetal growth velocity, higher umbilical-cerebral ratio, and were more likely to have adverse perinatal outcome. A decreasing fetal growth velocity was observed in 163 (19%) women in whom the estimated fetal weight multiple of the median regression coefficient was <-0.025, and who had higher umbilical-cerebral ratio values and more frequent adverse perinatal outcome; 67 (41%; 8% of total group) of these women had negative growth velocity. Estimated fetal weight and umbilical-cerebral ratio at admission and fetal growth velocity combined by logistic regression had a higher association with adverse perinatal outcome than any of those parameters separately (relative risk, 3.3; 95% confidence interval, 2.3-4.8). CONCLUSION: In fetuses at risk of late preterm fetal growth restriction, reduced growth velocity is associated with an increased risk of adverse perinatal outcome, irrespective of signs of cerebral blood flow redistribution. Some fetuses showed negative growth velocity, suggesting catabolic metabolism.

Longitudinal Doppler Assessments in Late Preterm Fetal Growth Restriction.

PURPOSE: To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). MATERIALS AND METHODS: A prospective European multicenter observational study included women with a singleton pregnancy, 32+ 0-36+ 6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. RESULTS: 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. CONCLUSION: An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.