Umbilical Flow Research Articles

Impact of fetal haemodynamics on surgical and neurodevelopmental outcomes in patients with Ebstein anomaly and tricuspid valve dysplasia.

To evaluate the impact of fetal haemodynamics on surgical and neurodevelopmental outcomes in severe Ebstein anomaly and tricuspid valve dysplasia. Thirty-four fetuses with Ebstein anomaly/tricuspid valve dysplasia were referred from 2013 to 2019 for fetal echocardiography and clinical management. Nineteen fetuses with Ebstein anomaly/tricuspid valve dysplasia and 30 controls underwent cardiovascular magnetic resonance to quantify the fetal blood flow and to calculate cerebral oxygen delivery (cDO2) and consumption (cVO2). The 3D steady-state free precession acquisition was used to measure fetal brain volume. Surgical outcome, brain MRI, and neurodevelopmental follow-up were reviewed. Twenty-six fetuses were live born (76%) and survival (65%) at a mean follow-up of 4 years. Nine fetuses had a brain MRI before discharge, and all had clinically silent injuries and volume loss. At 18 months, five single-ventricle patients had a neurodevelopmental delay in cognition and language (mean percentile: 11th), with gross-motor skills more affected than fine-motor skills (mean percentiles: 4th and 34th). Fetuses with Ebstein anomaly/tricuspid valve dysplasia had smaller brains, lower combined ventricular output, ascending aorta, superior caval vien and umbilical vein flows, lower oxygen saturation in ascending aorta and superior caval vien, lower cDO2 and cVO2 (p < 0.05). Superior caval vien/combined ventricular output and descending aorta/combined ventricular output ratios were lower in fetuses with circular shunt (p < 0.05). Fetuses requiring the Starnes procedure tended to have smaller brains, lower combined ventricular output, superior caval vien, descending aorta, and umbilical vein flows. All patients with Ebstein anomaly/tricuspid valve dysplasia are at high risk of neurodevelopmental delay and warrant follow-up. Fetal cardiovascular magnetic resonance revealed impaired brain growth with diminished cerebral blood flow and cDO2, the extenting dependent on the severity of the haemodynamic compromise.

The Role of The Doppler Study (Umbilical, Middle, Cerebral Arteries and Ductus Venosus) to Predict General Adverse Pregnancy Outcomes in Patients With Hypertensive Diseases in The Third Trimester

Background: The hypertensive pregnancies complicated by preeclampsia show an increase in maternal and perinatal morbidity and mortality.Color Doppler ultrasound has been employed for fetal surveillance. Objective: To evaluate the role of Doppler study in the prediction of adverse pregnancy outcomes in hypertensive pregnant women at the third trimester of pregnancy. Patients and Methods: A clinical prospective follow up study conducted in Outpatient Ultrasound Clinic at Al-Imamein Kadhimein Medical City, Baghdad, Iraq from 1st July, 2018 till 31st of July 2019 included 50 pregnant women with hypertensive disorder of pregnancy at the third trimester. The fetal and neonatal outcome was reported poor when intrauterine fetal death occurs during follow-up of pregnant women or more than two of the reported neonatal complications were poor. Results: Means of the middle cerebral artery and umbilical artery-resistance and pulasatility indices ratio were significantly decreased among pregnant women with poor neonatal outcomes. Similarly, the umbilical artery end-diastolic flow and Ductus Venousu waveforms were Conclusion: The middle cerebral artery and umbilical artery indices of pregnant women with hypertensive disorders are good predictors for neonatal outcomes. Keywords: Hypertensive disorder, Middle cerebral artery, Umbilical artery, Ductus venosus

Umbilical artery Doppler changes in fetal growth restriction with intermittently absent umbilical artery end-diastolic flow

Absent or reversed end-diastolic flow (A/REDF) are umbilical artery Doppler (UAD) velocimetry abnormalities associated with increased risk of perinatal demise and neonatal morbidity in pregnancies with fetal growth restriction (FGR). However, the clinical implications of intermittent (iAEDF) versus persistent (pAEDF) absent end-diastolic flow are unclear. This study compared changes in UAD velocimetry and latency to delivery in FGR pregnancies with iAEDF versus pAEDF at diagnosis.

Umbilical Vein Pulse Wave Spectral Analysis: A Possible Method for Placental Assessment Through Evaluation of Maternal and Fetal Flow Components.

Placental blood flow analysis is complicated by having both maternal and fetal flow components. Using the Fast Fourier Transform (FFT) of the umbilical venous pulse wave spectra (PW) envelope, we could simultaneously assess maternal/fetal blood flow in the placenta and investigate if normal and intrauterine growth restriction (IUGR)/pre-eclamptic pregnancies could be distinguished. This retrospective study included normal gestations (N=11) and gestations with IUGR, pre-eclampsia, or both (N=13). Umbilical vein PW were acquired and spectral envelopes were identified as a function of time and analyzed by FFT. Base-10 logarithms of the ratios of the maternal/fetal spectral peaks (LRSP) were compared in normal and IUGR/pre-eclamptic populations (two-tailed t-test). Body mass index (BMI), gestational age at scan time, placental position, and weight-normalized umbilical vein blood volume flow (two-tailed t-test, analysis of variance [ANOVA] analysis) were tested. P < .05 was considered significant. The LRSP for normal and IUGR/pre-eclamptic pregnancies were 0.141 ± 0.180 and -0.072 ± 0.262 (mean ± standard deviation), respectively (P=.033). We detected differences between normal gestations and combinations of LRSP and weight-normalized umbilical venous blood flows. Placental effects based on LRSPs and blood flow may act synergistically in cases with both pre-eclampsia and IUGR (P=.014). No other significant associations were seen. In this preliminary study, we showed that umbilical venous flow contains markers related to placental maternal/fetal blood flow, which can be used to assess IUGR and pre-eclampsia. When coupled with umbilical cord blood flow, this new marker may potentially identify the primary causes of the two conditions.

MRI characterization of hemodynamic patterns of human fetuses with cyanotic congenital heart disease.

To characterize, using magnetic resonance imaging (MRI), the distribution of blood flow and oxygen transport in human fetuses with subtypes of congenital heart disease (CHD) that present with neonatal cyanosis. Blood flow was measured in the major vessels of 152 late-gestation human fetuses with CHD and 40 gestational-age-matched normal fetuses, using cine phase-contrast MRI. Oxygen saturation (SaO2 ) was measured in the major vessels of 57 fetuses with CHD and 40 controls. Compared with controls, we found lower combined ventricular output in fetuses with single-ventricle physiology, with the lowest being observed in fetuses with severe forms of Ebstein's anomaly. Obstructive lesions of the left or right heart were associated with increased flow across the contralateral side. Pulmonary blood flow was reduced in fetuses with Ebstein's anomaly, while those with Ebstein's anomaly and tricuspid atresia had reduced umbilical flow. Flow in the superior vena cava was elevated in fetuses with transposition of the great arteries, normal in fetuses with hypoplastic left heart, tetralogy of Fallot or tricuspid atresia and reduced in fetuses with Ebstein's anomaly. Umbilical vein SaO2 was reduced in fetuses with hypoplastic left heart or tetralogy of Fallot. Ascending aorta and superior vena cava SaO2 were reduced in nearly all CHD subtypes. Fetuses with cyanotic CHD exhibit profound changes in the distribution of blood flow and oxygen transport, which result in changes in cerebral, pulmonary and placental blood flow and oxygenation. These alterations of fetal circulatory physiology may influence the neonatal course and help account for abnormalities of prenatal growth and development that have been described in newborns with cyanotic CHD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Computing Z‐Score Equations for Clinical Use to Measure Fetal Umbilical Vein Size and Flow Using Six Independent Variables of Age and Size

Measurements of the umbilical vein diameter (UVD) and blood flow (mL/min) (UVF) have been demonstrated to be decreased in fetuses with growth restriction (FGR) using gestational age (GA) as the independent variable. However, no previous studies have used the biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), and the estimated fetal weight (EFW) to create equations to be used for z-score computations when evaluating fetuses at risk foran abnormal UVD and UVF. Two hundred and forty normal fetuses between 20 and 40 weeks of gestation were examined in which the UVD and time averaged maximal velocity (TAMX) were measured from which the UVF, UVF/HC, UVF/AC, and UVF/kg were computed. Fractional polynomial regression analysis was used to compute z-score equations using the above independent variables. Thirty-six fetuses with abnormal growth of the AC were examined to test the validity of the equations. The UVD, TAMX, UVF, UVF/HC, and UVF/AC all increased with gestatonal age and fetal growth except for the UVF/kg, which decreased with age and growth. From the regression equations, two z-score calculators were created using an Excel spreadsheet that can be used in clinical practice. Abnormal measurements of the UVD, UVF, UVF/HC, UVF/AC, and UVF/kg were observed in the 36 study fetuses, 21 with an AC < 10th centile and 15 with an AC > 90th centile. Using the equations generated from this study and the z-score calculators provides a clinical tool to measure the size and flow of the umbilical vein that may have clinical implications.

Abstract 12589: Fetoscopic Selective Laser Photocoagulation of Placental Anastomoses Leads to Early Reduction of Cardiovascular Burden in the Twin-Twin Transfusion Syndrome

Background: Twin-twin transfusion syndrome (TTTS) occurs with an incidence of 10-15% in monochorionic pregnancies. The Children’s Hospital of Philadelphia (CHOP) TTTS Cardiovascular Score (CVS) is a 20-point scale and encompasses evaluation of five domains: Recipient (R) abnormalities of 1) ventricular hypertrophy/systolic dysfunction, 2) atrioventricular valve insufficiency, 3) diastolic ventricular inflow, ductus venosus and umbilical vein flow patterns and 4) right ventricular outflow/pulmonary obstruction; Donor (D) abnormalities of 5) umbilical arterial (UA) flow. We explore the early impact of selective fetoscopic laser photocoagulation (SLPC) of placental anastomoses on fetal cardiovascular (CV) burden. Methods: Fetal echocardiograms performed prior to and one week post SLPC from 11/2012 to 6/2018 were reviewed. Pulsatility indices (PI) of the UA and middle cerebral artery (MCA), cerebroplacental ratio (CPR) and CHOP CVS elements were analyzed pre and post SLPC using paired t-tests. Results: SLPC was performed in 198 subjects; 17 excluded due to one twin demise post SLPC. Of the 181 analyzed, mean gestational age at SLPC was 19.8 (95% CI: ±0.3) weeks. Following SLPC, R demonstrated an increase in MCA PI and decrease in UA PI, with increase in CPR. D demonstrated a similar magnitude decrease in both MCA PI and UA PI, yielding no change in CPR. Following SLPC, mean CHOP CVS decreased. CHOP pre SLPC CVS was ≥6 in 62 (34%). The magnitude of change was greater in the subgroup with greater pre SLPC CV burden (CVS &gt; 6). Most common elements to improve were systolic dysfunction, tricuspid inflow, ductus venosus and umbilical vein flow patterns; least likely to improve was ventricular hypertrophy. Conclusions: Improvement in CV burden is seen as early as 1 week post SLPC, which supports acute alteration of loading conditions as contributing to the disease. Further study of the trajectory of CV alterations may provide insight into the complex mechanisms underlying TTTS.

Abstract 16932: Primary Hyperaldosteronism And Resistant Hypertension In Pregnancy

Case Presentation: A 42-year-old woman with history of primary hyperaldosteronism (PA), IDDM and chronic kidney disease stage 3b (baseline Cr 2.5 mg/dl) presented at 10 weeks gestation with uncontrolled hypertension during pregnancy. Given prior difficulties conceiving and lack of discussions surrounding pregnancy risks, preconception counseling had not been done. She was taking carvedilol, spironolactone, and furosemide at pregnancy diagnosis. Given unclear safety profile in pregnancy, her spironolactone was discontinued. Her regimen was uptitrated to nifedipine 90 mmHg, carvedilol 50mg BID, hydralazine 50mg TID and furosemide 80mg BID. At 18 weeks gestation, she was readmitted with severe range hypertension and fluid overload unresponsive to escalating diuretic dosing. Due to poor urine output and creatinine to 5.5 mg/dl, she was initiated on dialysis. Her fetus was diagnosed with severe intrauterine growth restriction (IUGR) and umbilical doppler noted reversal of umbilical artery end-diastolic flow indicating severely elevated arterial resistance (Figure). During admission, she developed resistant hypertension requiring nicardipine and esmolol drips and severe headache, concerning for superimposed preeclampsia (SIPE). At 25 weeks gestation, she was taken for urgent c-section. Given extreme prematurity and growth restriction, her newborn baby passed away shortly after delivery. Discussion: This case highlights complications which arise from PA and antepartum persistent hypertension including progression of kidney disease, heart failure, IUGR, SIPE, and preterm delivery. It further highlights unique challenges using targeted therapies of mineralocorticoid receptor antagonists in PA in pregnancy. This information is crucial as PA is an increasingly recognized cause of resistant hypertension in young adults. Both PA and preeclampsia involve pathophysiologic mechanisms in the RAAS pathway and deserve further attention and research.

Abstract 11766: Late Gestation Fetal Oxygenation is Associated With Birthweight and Head Circumference in Patients With Cyanotic Congenital Heart Disease

Introduction: Abnormal fetal growth and development are evident in patients with cyanotic congenital heart disease (cCHD). However, the relationship between growth and fetal oxygenation is unknown. We sought to investigate the relationship between fetal hemodynamics and fetal growth in cCHD using fetal cardiovascular Magnetic Resonance Imaging (MRI). Hypothesis: The impaired fetal oxygenation would be associated with diminished fetal brain and body growth in cCHD. Methods: We performed a prospective observational study in fetuses diagnosed with cCHD at our institution from June 2010 to January 2020. Late-gestational fetal cardiovascular MRI was performed in 152 fetuses with cCHD to assess fetal blood flow (phase-contrast MRI) and oxygen saturation (T2 oximetry) in the major fetal vessels to calculate oxygen delivery to the brain and body according to our previously published techniques. Results are provided as medians with IQR and compared with 30 gestational age-matched normal controls using Mann-Whitney U test. A Pearson’s correlation was used to examine the relationships between variables. Results: Compared with normal controls, fetuses with cCHD had significantly reduced birth weight Z-scores [-0.41 (-0.29, 0.84) vs. -0.19 (-0.46, 0.37), p = 0.03], and neonatal head circumference Z-scores [0.1 (-1.75, 0.95) vs. 0.69 (0.1, 1.79), p = 0.003]. As a combined cohort, birthweight Z-score was correlated with fetal oxygen delivery (r = 0.33, p = 0.003), umbilical vein flow (r = 0.2, p = 0.006) and oxygen saturation (r = 0.25, p = 0.02). Birth head circumference Z-score was correlated with fetal cerebral oxygen delivery (r = 0.33, p = 0.01) and ascending aorta oxygen saturation (r = 0.33, p = 0.009). We also found an inverse relationship between ascending aorta oxygen saturation and superior vena cava flow (r = -0.24, p = 0.036). Conclusions: In conclusion, we observed associations between placental function in late gestation and birthweight, as well as cerebral oxygen delivery in utero and head circumference at birth. Our findings are in keeping with the concept that cCHD impacts fetal development through abnormal circulatory physiology and placental function.

Preeclampsia Falling into the Spectrum of Mirror Syndrome

Mirror syndrome, by definition, is maternal edema with fetal hydrops. Majority of the pregnancies in developing countries are complicated by preeclampsia and intrauterine growth retardation. Fetal ascites, on the other hand, is a part of spectrum of the condition under hydrops fetalis. Abnormal umbilical artery Doppler is an indicator of fetal growth retardation and not many cases are found with such diversely intermixed conditions. A 26-year-old primigravida with 36 weeks gestation by the last menstrual cycle and 34 weeks by ultrasound presented to our hospital with a history of decreased fetal movements, headache, fever, weakness, dizziness, and new-onset raised blood pressure. Her blood pressure was 164/118 and 3+ proteinuria on the urinary dipstick test. A diagnosis of preeclampsia was made. An antenatal ultrasound was performed, which showed fetal ascites, mild thickening of fetal skin, oligohydramnios with reversed umbilical artery flow but normal uterine arteries, and middle cerebral arteries. The blood pressure was controlled and she later delivered a low-birth weight baby that needed neonatal intensive care unit stay for fetal distress and abdominal distention. The baby did not survive the coming few days and died due to increasing fluid in the body cavity. The mother continued to have raised blood pressure in the postpartum period. Mirror syndrome is when the maternal pathology mirrors that of the fetus. Preeclampsia, fetal hydrops, and placental edema are the conditions lead to suspicion of it. In the case, we present, the mother had preeclampsia, and there was fetal ascites and reversed umbilical flow. The fetal and maternal outcome was in the form of intrauterine growth retardation, impending hydrops fetalis and chronic hypertension, respectively.

Association of Adverse Outcomes with Abnormal Umbilical Artery Waveform in Intrauterine Growth Restricted Pregnancies

Background: Intrauterine growth restriction refers to a fetus with a fetal weight in the 10th percentile on ultrasonography who has not reached its biologically set growth potential due to a pathologic condition. Aim: To determine the association of adverse outcome with abnormal umbilical artery waveform groups in intrauterine growth restricted pregnancies. Methods: This Cohort Study was conducted from February 2019 to 12 February 2020 at Gynae &amp; Obs Department, Imran Idrees Teaching Hospital Sialkot, Sialkot Medical College, Sialkot 120 pregnant females, attending Department of Gynae &amp; Obs were recruited into the study after 28 weeks of gestation. The women were divided into two groups depending on their Doppler findings. One group (exposed) comprised of women with intrauterine growth restriction, with absent or reversed diastolic flow in the umbilical artery. The control (unexposed) group included women with small-for-date fetuses, with normal umbilical artery Doppler flow. Results: The mean age of females was 27.40 ± 4.77 years. The mean gestational age was 30.69 ± 2.19 weeks. The mean birth weight of neonates was 2.37 ± 0.90 kg. The mean AGPAR score of neonates was 6.60 ± 1.70. It was observed that there was significant association between groups and low birth weight with p-value = 0.002. Admissions to NICU were significantly lower in normal Doppler wave form group having p-value = 0.001. Conclusion: The percentage of NICU admission was 46.7% and the percentage of low birth weight was 46.7% in intrauterine growth restriction. The mean birth weight was significantly lower in exposed group and the mean APGAR score was also significantly lower in exposed group. Keywords: Apgar score, neonatal intensive care unit, Intrauterine Growth Restriction, Doppler ultrasound,

Evaluation of umbilical venous flow volume measured using ultrasound compared to circuit flow volume in the EXTra-uterine Environment for Neonatal Development (EXTEND) system in fetal sheep.

To compare and validate umbilical venous flow volume (UVFV) measured at the intra-abdominal portion using ultrasound with actual flow volume of umbilical vein (UV) in fetal sheep sustained on the EXTrauterine Environment for Neonatal Development (EXTEND) system. Circuit flow volume through the oxygenator was obtained using sensors. Ultrasound derived UVFV (ml/min) was calculated as (UV diameter [cm]/2)2 3.14 maximum velocity (cm/s) 0.5 60, measured at approximately the mid portion between its abdominal insertion and the origin of the ductus venosus. UVFV was measured by ultrasound once daily and was compared to the average of daily circuit flow volume directly measured. UVFV was measured 168 times in 15 fetal sheep. The ratio of circuit flow volume to combined cardiac output remained stable within the anticipated physiological range throughout. UVFV measured by ultrasound showed good correlation to directly measured circuit flow (r=0.72). Interclass correlation coefficients for intra-observer variability was 0.991 (95% confidence interval [CI], 0.979-0.996). UVFV measured at the intra-abdominal portion using ultrasound shows a good correlation with directly measured circuit flow volume in UV of fetal sheep on the EXTEND system. Regular incorporation of such validated UVFV measures into clinical use may offer opportunities to better understand conditions of placental dysfunction.

Acute fetal response to high-intensity interval training in the second and third trimesters of pregnancy.

The majority of women do not meet the recommended levels of exercise during their pregnancies, frequently due to a lack of time. High-intensity interval training offers a potential solution, providing an effective, time-efficient exercise modality. This exercise modality has not been studied in pregnancy therefore, the objective of this study was to evaluate fetal response to a high-intensity interval training resistance circuit in the late second and early third trimesters of pregnancy. Fourteen active, healthy women with uncomplicated, singleton pregnancies participated in a high-intensity interval training resistance circuit between 28 + 0/7 and 32 + 0/7 weeks. A Borg rating of perceived exertion of 15-17/20 and an estimated heart rate of 80%-90% of maternal heart-rate maximum was targeted. Fetal well-being was evaluated continuously with fetal heart-rate tracings and umbilical artery Doppler velocimetry conducted pre-and post-exercise. Fetal heart rate tracings were normal throughout the exercise circuit. Post-exercise, umbilical artery end-diastolic flow was normal and significant decreases were observed in the mean systolic/diastolic ratios, pulsatility indexes and resistance indexes. Therefore, in a small cohort of active pregnant women, a high-intensity interval training resistance circuit in the late second and early third trimesters of pregnancy appears to be a safe exercise modality with no acute, adverse fetal effects but further study is required. Novelty: High-intensity interval training, at an intensity in excess of current recommendations, does not appear to be associated with any adverse fetal effects in previously active pregnant women. High-intensity interval training is an enjoyable and effective exercise modality in previously active pregnant women.

Early neonatal outcome of preterm babies with absent or reverse end diastolic flow in antenatal doppler velocimetry

Background: Preterm babies with abnormal doppler velocimetry during second and third trimesters of pregnancy pose various early neonatal morbidities like recurrent hypoglycaemia, feed intolerance and prolonged hospital stay. In our study we compared the incidence of hypoglycaemia, feed intolerance, risk of necrotising enterocolitis (NEC) and length of hospital stay among preterm babies with abnormal doppler flow to the gestational age matched preterm babies with normal umbilical artery doppler flow velocimetry.Methods: 30 preterm babies who had abnormal umbilical artery flow during their last antenatal doppler scan were included as study group and gestational age matched 30 preterm babies who had normal doppler study had been taken as controls. The incidence of hypoglycaemia, feed intolerance, NEC, length of hospital stay had been compared between two groups.Results: The case group with abnormal umbilical artery doppler had increased incidence of hypoglycaemia (15 of 30 babies in case versus 5 of 30 babies in control) which was statistically significant. Feed intolerance, necrotizing enterocolitis and length of hospital stay were all significantly increased in preterm babies with abnormal umbilical artery doppler when compared to preterm babies with normal umbilical artery doppler flow.Conclusions: Preterm babies with abnormal umbilical artery doppler were at increased risk of hypoglycaemia, feed intolerance, NEC and prolonged hospital stay. Knowledge on this is important to monitor closely for hypoglycaemia, gradually increase feeds and explain parents about expected morbidities which can increase the length of hospital stay in neonatal intensive care unit (NICU).

Pre-gestational diabetes: Maternal body mass index and gestational weight gain are associated with augmented umbilical venous flow, fetal liver perfusion, and thus birthweight.

To assess how maternal body mass index and gestational weight gain are related to on fetal venous liver flow and birthweight in pregnancies with pre-gestational diabetes mellitus. In a longitudinal observational study, 49 women with pre-gestational diabetes mellitus were included for monthly assessments (gestational weeks 24-36). According to the Institute Of Medicine criteria, body mass index was categorized to underweight, normal, overweight, and obese, while gestational weight gain was classified as insufficient, appropriate or excessive. Fetal size, portal flow, umbilical venous flow and distribution to the fetal liver or ductus venosus were determined using ultrasound techniques. The impact of fetal venous liver perfusion on birthweight and how body mass index and gestational weight gain modified this effect, was compared with a reference population (n = 160). The positive association between umbilical flow to liver and birthweight was more pronounced in pregnancies with pre-gestational diabetes mellitus than in the reference population. Overweight and excessive gestational weight gain were associated with higher birthweights in women with pre-gestational diabetes mellitus, but not in the reference population. Fetuses of overweight women with pre-gestational diabetes mellitus had higher umbilical (p = 0.02) and total venous liver flows (p = 0.02), and a lower portal flow fraction (p = 0.04) than in the reference population. In pre-gestational diabetes mellitus pregnancies with excessive gestational weight gain, the umbilical flow to liver was higher than in those with appropriate weight gain (p = 0.02). The results support the hypothesis that umbilical flow to the fetal liver is a key determinant for fetal growth and birthweight modifiable by maternal factors. Maternal pre-gestational diabetes mellitus seems to augment this influence as shown with body mass index and gestational weight gain.

Macronutrient analysis of human milk and factors associated with its composition in mothers of preterm infants ≤ 32 weeks.

We conducted an exploratory longitudinal study to evaluate the macronutrient composition of human milk in mothers delivering very preterm infants ≤ 32 weeks over the first 4 weeks of lactation and the association of human milk composition with maternal and neonatal factors A total of 213 human milk samples collected in the morning between 8 am and 12 pm from 60 eligible mothers were analyzed on 7 (n = 60), 14 (n = 60), 21 (n = 52), and 28 (n = 41) days of lactation by infrared transmission spectroscopy. The true protein content decreased significantly over 4 weeks (mean difference (95% confidence interval)) (MD (95% CI)) week 1 and week 4 = 0.2 g (0.037 to 0.363, P = 0.009)). On the contrary, the mean fat and calorie content showed significant increase over time (MD (95% CI)) = - 1.03 g (- 1.719 to - 0.343, P = 0.001) and - 9.0 kcal/dl (- 15.170 to - 2.830, P = 0.001), respectively). There was no difference in the carbohydrate content of human milk over 4 weeks. Macronutrient composition was independent of maternal parity, mode of delivery, pre-pregnancy body mass index, umbilical artery Doppler flows, previous breast feeding experience, neonatal centile status, gestation, and infant's weight at birth. Multiple regression analysis of human milk composition with mother's dietary components showed no significant association. CONCLUSION : We conclude that in mothers who deliver very preterm infants ≤ 32 weeks, true protein content decreased, fat and calorie content increased, and carbohydrate content remained stable in human milk during first 4 weeks of lactation. Human milk macronutrient composition was independent of various maternal and neonatal factors including maternal body mass index and dietary intake. TRIAL REGISTRATION : CTRI/2017/02/007895 What is Known: • Preterm human milk has high temporal and inter-individual variation in the macronutrient composition. What is New: • In mothers who deliver very preterm infants < 32 weeks, true protein content decreases, fat and calorie content increases, and carbohydrate content remains stable in human milk during first 4 weeks of lactation. • Human milk macronutrient composition is independent of various maternal and neonatal factors including maternal body mass index and dietary intake.

Diagnosis and management of fetal growth restriction: the ISUOG guideline and comparison with the SMFM guideline.

Diagnosis and management of fetal growth restriction: the ISUOG guideline and comparison with the SMFM guideline.

Perinatal outcome of monochorionic diamniotic twin pregnancy complicated by selective intrauterine growth restriction according to umbilical artery Doppler flow pattern: single-center study using strict fetal surveillance protocol.

To determine the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by selective intrauterine growth restriction (sIUGR), which were classified according to the umbilical artery (UA) Doppler flow pattern of the IUGR twin. This was a retrospective cohort study of all MCDA twin pregnancies diagnosed with sIUGR and managed at a single tertiary referral center between 2012 and 2018. Cases were classified according to the UA Doppler flow pattern of the IUGR twin as Type I (positive end-diastolic flow), Type II (persistently absent/reversed end-diastolic flow) or Type III (intermittently absent/reversed end-diastolic flow). Patients with Type-II or -III sIUGR were hospitalized at 26-28 weeks of gestation for increased fetal surveillance. Perinatal and immediate and long-term neurodevelopmental outcomes were stratified according to the UA Doppler flow pattern at the final examination. Intact survival rate was defined as the number of infants surviving without neurological impairment, divided by the total number of fetuses. Composite adverse outcome, defined as any mortality, presence of severe brain lesions on postnatal transcranial ultrasound or severe neurological morbidity, was also assessed. Of 88 MCDA twin pregnancies with sIUGR included in the study, 28 underwent selective termination by cord occlusion using radiofrequency ablation, resulting in a perinatal survival rate of 89.3% and a median gestational age (GA) at delivery of 33.8 (interquartile range (IQR), 28.8-38.2) weeks for the large cotwin. Expectant management was employed in 60 cases. In 26 (43.3%) cases in the expectant-management group, the classification according to the UA Doppler flow pattern changed during gestation, resulting in 26 (43.3%) cases of Type-I, 22 (36.7%) cases of Type-II and 12 (20.0%) cases of Type-III sIUGR at the final examination. The perinatal survival rate of both twins with sIUGR Types I, II and III at the final examination was 100%, 81.8% and 75.0%, respectively (P = 0.04). Two cases of double fetal death and one case of single fetal death occurred 1-4 weeks after the Doppler pattern had changed from Type I or Type II to Type III. The median GA at delivery was 34.8 (IQR, 33.1-35.7) weeks in Type I, 30.3 (IQR, 28.6-32.1) weeks in Type II and 32.0 (IQR, 31.3-32.6) weeks in Type III (P < 0.01). The total intact survival rate was 100% for Type I, 77.3% for Type II and 75.0% for Type III (P < 0.001). Multivariate analysis demonstrated that early GA at diagnosis (odds ratio (OR), 0.83 (95% CI, 0.69-0.99); P = 0.04) and the presence of Type II or III vs Type I at the last examination (OR, 13.16 (95% CI, 1.53-113.32); P = 0.02) were associated with preterm birth < 32 weeks' gestation. Early GA at diagnosis was also associated with the composite adverse outcome (OR, 0.60 (95% CI, 0.36-0.99); P = 0.04). The classification system of MCDA pregnancy complicated by sIUGR, according to the UA Doppler flow pattern of the IUGR twin at final examination, is associated with perinatal outcome. Importantly, the UA Doppler flow pattern can change during gestation, which has an impact on the risk of fetal death. Nevertheless, under strict fetal surveillance, the perinatal outcome of these pregnancies is favorable. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Distinction between SGA and FGR by means of fetal umbilical vein flow and maternal hemodynamics

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

Cardiac function in fetal growth restriction.

Fetal growth restriction (FGR) is defined as the inability of the fetus to reach its growth potential. According to the onset of the disease is defined early (<32 weeks) or late (≥32 weeks). FGR is associated with an increased risk of adverse short- and long-term outcomes, including hypoxemic events and neurodevelopmental delay compared to normally grown fetuses and increased risk of complications in the infanthood and adulthood. The underlying cause of FGR is placental insufficiency leading to chronic fetal hypoxia that affects cardiac hemodynamic with different mechanism in early and late onset growth restriction. In early onset FGR adaptive mechanisms involve the diversion of the cardiac output preferentially in favor of the brain and the heart, while abnormal arterial and venous flow manifest in the case of further worsening of fetal hypoxia. In late FGR the fetal heart shows a remodeling of its shape and function mainly related to a reduction of umbilical vein flow. In this review we discuss the modifications occurring at the level of the fetal cardiac hemodynamic in fetuses with early and late FGR.