Normal Umbilical Artery Research Articles

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).

Reference Values of Umbilical Artery Doppler Indices in Healthy Uncomplicated Pregnancy from 18-40 Week Gestation

Background: Doppler ultrasound in second and third trimesters is non invasive method to assess fetal wellbeing and monitoring fetoplacental unit. Normal umbilical artery Doppler indices reference values have been established in Western countries but there is paucity of studies conducted in Pakistan regarding normal umbilical artery Doppler indices reference values. Objective: To evaluate the Doppler indices in the umbilical arteries of healthy pregnant women from 18-40 wks gestation. Material and Methods: A cross sectional study was conducted in Radiology department of Hayatabad Medical Complex from July 2018 to Dec 2018.Total 260 normal singleton pregnancies with gestational age ranging from 18--40 weeks were included. Doppler parameters; Resistive Index (RI), Pulsatility Index (PI) and the systolic to diastolic ratio(S/D) were recorded. Results: The normal umbilical artery Doppler indices at different gestational ages in healthy pregnant women were analyzed. Percentile values were calculated for these indices. Median values for the pulsatility index were 1.23 at 18-20 wks which reduced to 0.86 at 39-40 wks, for the resistivity index median values were 0.70 at 18-20 wks and 0.52 at 39-40 wks. Systolic/diastolic ratio was 4.16 at 18-20 wks and 2.21 at 39-40 wks. Conclusion: In normal healthy pregnancies, doppler ultrasound should be used to evaluate the degree of feto-placental blood flow in order to detect the risk of pregnancy complications. Our study results can form a baseline for Doppler indices in second and third trimester which can further help in abnormal values in high risk patients. Keywords: Doppler ultrasound, Doppler indices, Normal pregnancy, Umbilical artery;

Influence of Cerebral Vasodilation on Blood Reelin Levels in Growth Restricted Fetuses.

Fetal growth restriction (FGR) is one of the most important obstetric pathologies. It is frequently caused by placental insufficiency. Previous studies have shown a relationship between FGR and impaired new-born neurodevelopment, although the molecular mechanisms involved in this association have not yet been completely clarified. Reelin is an extracellular matrix glycoprotein involved in development of neocortex, hippocampus, cerebellum and spinal cord. Reelin has been demonstrated to play a key role in regulating perinatal neurodevelopment and to contribute to the emergence and development of various psychiatric pathologies, and its levels are highly influenced by pathological conditions of hypoxia. The purpose of this article is to study whether reelin levels in new-borns vary as a function of severity of fetal growth restriction by gestational age and sex. We sub-grouped fetuses in: normal weight group (Group 1, n = 17), FGR group with normal umbilical artery Doppler and cerebral redistribution at middle cerebral artery Doppler (Group 2, n = 9), and FGR with abnormal umbilical artery Doppler (Group 3, n = 8). Our results show a significant association of elevated Reelin levels in FGR fetuses with cerebral blood redistribution compared to the normal weight group and the FGR with abnormal umbilical artery group. Future research should focus on further expanding the knowledge of the relationship of reelin and its regulated products with neurodevelopment impairment in new-borns with FGR and should include larger and more homogeneous samples and the combined use of different in vivo techniques in neonates with impaired growth during their different adaptive phases.

Forthcoming Issues

Fetuses with an estimated fetal weight below the 10th centile have an increased risk of adverse perinatal and long-term outcomes as well as increased rates of cardiac dysfunction, which often alters cardiac size and shape of the 4-chamber view and the individual ventricles. As a result, a simple method has emerged to screen for potential cardiac dysfunction in fetuses with estimated fetal weights <10th centile by measuring the size and shape of the 4-chamber view and the size of the ventricles.To determine the number of fetuses with an abnormal size and shape of the 4-chamber view and size of the ventricles in fetuses with an estimated fetal weight <10th centile.This was a retrospective study of 50 fetuses between 25 and 37 weeks of gestation with an estimated fetal weight <10th centile. Data from their last examination were analyzed. From an end-diastolic image of the 4-chamber view, the largest basal–apical length and transverse width were measured from their corresponding epicardial borders. This allowed the 4-chamber view area and global sphericity index (4-chamber view length/4-chamber view width) to be computed. In addition, tracing along the endocardial borders with speckle tracking software enabled measurements of the right and left ventricular chamber areas and the right ventricle/left ventricle area ratios to be computed. Doppler waveform pulsatility indices from the umbilical (umbilical artery pulsatility index) and middle cerebral arteries (middle cerebral artery pulsatility index) were analyzed, and the cerebroplacental ratio (middle cerebral artery pulsatility index/umbilical artery pulsatility index) computed. Umbilical artery pulsatility indices >90th and cerebroplacental ratios <10th centile were considered abnormal. Using data from the control fetuses, the centile for each of the cardiac measurements was categorized by whether it was <10th or >90th centile, depending upon the measurement.Of the 50 fetuses with estimated fetal weight <10th centile, 50% (n = 25) had a normal umbilical artery pulsatility index and cerebroplacental ratio. These fetuses had significantly more (P < 0.02 to <0.0001) abnormalities of the size and shape of the 4-chamber view than controls. In all, 44% had a 4-chamber view area >90th centile, 32% had a 4-chamber view global sphericity index <10th centile, 56% had a 4-chamber view width >90th centile, and 80% had 1 or more abnormalities of size and/or shape. The remaining 50% of fetuses (n = 25) had abnormalities of 1 or both for the umbilical artery pulsatility index and/or cerebroplacental ratio. These fetuses had significantly higher rates of abnormalities (P <0.05 to <0.0001) than controls for the following 4-chamber view measurements: 36% had a 4-chamber view area >90th centile; 28% had a 4-chamber view global sphericity index <10th centile; and 68% had a 4-chamber view width >90th centile. Only those fetuses with an abnormal umbilical artery pulsatility index had significant changes in ventricular size; 56% had a left ventricular area <10th centile; 28% had a right ventricular area <10th centile; 36% had right ventricular/left ventricular area ratio >90th centile. One or more of the above abnormal measurements were present in 92% of the fetuses.Higher rates of abnormalities of cardiac size and shape of the 4-chamber view were found in fetuses with an estimated fetal weight <10th centile, regardless of their umbilical artery pulsatility index and cerebroplacental ratio measurements. Those with a normal umbilical artery pulsatility index and an abnormal cerebroplacental ratio had larger and wider measurements of the 4-chamber view. In addition, the shape of the 4-chamber view was more globular or round than in controls. These fetuses may have an increased risk of perinatal complications and childhood and/or adult cardiovascular disease. Screening tools derived from the 4-chamber view, acting as surrogates for ventricular dysfunction, may identify fetuses who could benefit from further comprehensive testing and future preventive interventions.

Doppler studies of placental function

Placental-associated diseases account for most cases of adverse perinatal outcome in developing countries. Doppler evaluation has been incorporated as a predictive parameter at early pregnancy for high-risk placental disease, in the diagnosis and management of those fetuses with impaired intrauterine growth and for the evaluation of fetal wellbeing in those high-risk pregnancies.Uterine Doppler at second trimester predicts most instances of early-onset preeclampsia and intrauterine growth restriction. However, the growing evidence of an effective early propylactic strategy, has turned Uterine Doppler an essential parameter to be included in first trimester predictive algorithms. Umbilical artery Doppler helps in the identification of small-for-gestational-age fetuses at higher risk, and is one of the essential vessels in the assessment of fetal hypoxia impairment, especially in the early cases. It helps in the decision timing for ending the pregnancy improving thus perinatal outcomes. Moreover, in high-risk pregnancies, umbilical artery Doppler has demonstrated to reduce the risk of perinatal deaths and the risk of obstetric interventions. On the other hand, middle cerebral artery Doppler reflects fetal adaptation to hypoxia, and with the cerebroplacental ratio, they improve the detection of fetuses a high risk of adverse perinatal outcome, mostly of those late small fetuses, where most instances of adverse outcome occur in fetuses with normal umbilical artery. Ductus venosous Doppler waveform is a surrogate parameter of the fetal base-acid status. Its use has demonstrated to improve perinatal outcomes, mainly reducing the risk of fetal intrauterine death. Alone or in combination with computerized CTG, it helps tailoring the best moment to end the pregnancy among early cases.

FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction.

Fetal growth restriction (FGR) is defined as the failure of the fetus to meet its growth potential due to a pathological factor, most commonly placental dysfunction. Worldwide, FGR is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Ongoing advances in clinical care, especially in definitions, diagnosis, and management of FGR, require efforts to effectively translate these changes to the wide range of obstetric care providers. This article highlights agreements based on current research in the diagnosis and management of FGR, and the areas that need more research to provide further clarification of recommendations. The purpose of this article is to provide a comprehensive summary of available evidence along with practical recommendations concerning the care of pregnancies at risk of or complicated by FGR, with the overall goal to decrease the risk of stillbirth and neonatal mortality and morbidity associated with this condition. To achieve these goals, FIGO (the International Federation of Gynecology and Obstetrics) brought together international experts to review and summarize current knowledge of FGR. This summary is directed at multiple stakeholders, including healthcare providers, healthcare delivery organizations and providers, FIGO member societies, and professional organizations. Recognizing the variation in the resources and expertise available for the management of FGR in different countries or regions, this article attempts to take into consideration the unique aspects of antenatal care in low-resource settings (labelled “LRS” in the recommendations). This was achieved by collaboration with authors and FIGO member societies from low-resource settings such as India, Sub-Saharan Africa, the Middle East, and Latin America.

Fetal Outcomes Associated with the Sequence of Doppler Deterioration in Severely Growth-Restricted Fetuses.

Various patterns of Doppler deterioration exist in fetal growth restriction (FGR). However, the factors that differentiate these patterns are still unknown. The purpose of this study was to clarify the perinatal outcomes and factors to determine the pattern of Doppler deterioration in severe FGR. We conducted a retrospective cohort study of preterm severe FGR with Doppler abnormality, wherein the clinical features, including maternal characteristics, medical history, and sonographic findings, were compared between the patterns of Doppler deterioration. We used the multivariable logistic regression analyses to identify the factors associated with the pattern of Doppler deterioration. Of 322 eligible fetuses, 143 had Doppler abnormalities. Fetuses with Doppler deterioration from ductus venosus uniquely featured fetal and placental-umbilical abnormalities detected after birth. Gestational age (GA) at diagnosis of FGR and at the first diagnosis of Doppler abnormality in fetuses with Doppler deterioration from middle cerebral artery (MCA) were later than those from umbilical artery. In addition, the factor associated with Doppler deterioration from MCA was 31-week GA at the first diagnosis of Doppler abnormality (adjusted odds ratio [aOR]: 26.7; 95% CI: 8.35-103), not GA at diagnosis of FGR (aOR: 1.82; 95% CI: 0.50-5.96). Characteristics of each Doppler deterioration pattern might reflect FGR etiology. Undetectable anomalies and umbilical-placental abnormalities were found in fetuses with Doppler deterioration from the ductus venosus. Doppler deterioration from the MCA was observed after 31 weeks of gestation not only in the late-onset FGR but also in the early-onset FGR with normal umbilical artery Doppler findings.

Prevalence of Antenatal Depression Among Pregnant Women; A Cross Sectional Study in Tertiary Care Hospital Islamabad, Pakistan

Background: Doppler ultrasound in second and third trimesters is non invasive method to assess fetal wellbeing and monitoring fetoplacental unit. Normal umbilical artery Doppler indices reference values have been established in Western countries but there is paucity of studies conducted in Pakistan regarding normal umbilical artery Doppler indices reference values. Objective: To evaluate the Doppler indices in the umbilical arteries of healthy pregnant women from 18-40 wks gestation. Material and Methods: A cross sectional study was conducted in Radiology department of Hayatabad Medical Complex from July 2018 to Dec 2018.Total 260 normal singleton pregnancies with gestational age ranging from 18--40 weeks were included. Doppler parameters; Resistive Index (RI), Pulsatility Index (PI) and the systolic to diastolic ratio(S/D) were recorded. Results: The normal umbilical artery Doppler indices at different gestational ages in healthy pregnant women were analyzed. Percentile values were calculated for these indices. Median values for the pulsatility index were 1.23 at 18-20 wks which reduced to 0.86 at 39-40 wks, for the resistivity index median values were 0.70 at 18-20 wks and 0.52 at 39-40 wks. Systolic/diastolic ratio was 4.16 at 18-20 wks and 2.21 at 39-40 wks. Conclusion: In normal healthy pregnancies, doppler ultrasound should be used to evaluate the degree of feto-placental blood flow in order to detect the risk of pregnancy complications. Our study results can form a baseline for Doppler indices in second and third trimester which can further help in abnormal values in high risk patients. Keywords: Doppler ultrasound, Doppler indices, Normal pregnancy, Umbilical artery;

Considering evidence in the management of fetal growth restriction.

Considering evidence in the management of fetal growth restriction.

Inhibition of mechanistic target of rapamycin signaling decreases levels of O-GlcNAc transferase and increases serotonin release in the human placenta.

Changes in placental function, in particular down-regulation of placental O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) in response to maternal stress and increased placental secretion of serotonin into the fetal circulation following maternal infection, have been mechanistically linked to adverse neurodevelopment in mice. We hypothesized that mechanistic target of rapamycin (mTOR) signaling is a key regulator of trophoblast serotonin synthesis and OGT protein expression and that serotonin is secreted by the human placenta into the fetal circulation. Placental homogenates (n=46) from elective terminations at 8-22 weeks of gestation and from healthy-term women were sexed and the protein levels of OGT and enzymes involved in serotonin synthesis was determined. Primary human trophoblast (PHT) cells were isolated from normal term placenta (n=27), cultured and transfected (n=8) with siRNA targeting a scramble sequence (control), raptor (inhibits mTOR Complex 1 (mTORC1)), or rictor (inhibits mTOR Complex 2 (mTORC2)). Subsequently, conditioned media and PHT cell lysates were collected. Free serotonin concentration was measured using ELISA in cell culture media and in platelet-depleted normal term umbilical vein and artery plasma (n=38). Both mTORC1 and mTORC2 inhibition down-regulated OGT levels in PHT cells. The level of serotonin synthesis enzyme tryptophan hydroxylase (TPH-1) was higher in early gestation female placentas and at term serotonin concentration was three-fold higher in the umbilical vein than in the umbilical artery. Inhibition of mTORC2, but not mTORC1, increased cultured PHT cell serotonin secretion. Our data are consistent with the model that mTOR signaling is a key regulator of trophoblast serotonin synthesis and OGT protein expression.

Normal Umbilical Artery Doppler Assessment in Second and Third Trimester Singleton Gestation of Healthy Pregnant Women in Port Harcourt, Nigeria

Normal Umbilical Artery Doppler Assessment in Second and Third Trimester Singleton Gestation of Healthy Pregnant Women in Port Harcourt, Nigeria

Perinatal outcome of growth restricted fetuses with abnormal umbilical artery Doppler waveforms compared to growth restricted fetuses with normal umbilical artery Doppler waveforms at a tertiary referral hospital in urban Ethiopia.

Intrauterine growth restriction is defined as a fetal weight below the 10th percentile for a given gestational age and can be identified using umbilical artery Doppler velocimetry which is a non-invasive technique. The objective of this study was to determine the perinatal outcome of growth-restricted fetuses with abnormal umbilical artery Doppler study compared to those with normal umbilical artery Doppler waveforms at a tertiary referral hospital in Ethiopia. A prospective cohort study was conducted among pregnant mothers with fetal growth restriction admitted for labour and delivery from September 2018-February 2019. The data were entered and analyzed using SPSS version 23. After conducting descriptive analysis, exploring the entire data, and checking for, statistical associations between abnormal umbilical artery Doppler and outcome variables, multiple logistic regression was conducted to control for confounders. A total of 170 pregnant mothers complicated with growth-restricted fetuses were included in the study, among which 133 were with normal umbilical artery Doppler studies and 37 were with abnormal umbilical artery Doppler studies. Four (3%) of normal and 9(24.3%) of abnormal umbilical artery Doppler studies ended in perinatal death-value = 0.001. Twenty (15%) of normal and 24(64.9%) of abnormal umbilical artery Doppler study neonates required neonatal intensive care admission-value = 0.002. Growth restricted fetuses complicated with abnormal Doppler were two times more likely to require neonatal intensive care unit admissions compared to growth-restricted fetuses with normal umbilical artery Doppler flow, P-value 0.002, (OR = 2.059,95%CI 1.449-2.926). Growth restricted fetuses complicated with abnormal Doppler were four times more likely to end in early neonatal death compared to growth-restricted fetuses with normal umbilical artery Doppler flow, P-value 0.001, (OR = 4.136, 95%CI 3.423-4.998). However, the study is unmatched and there is a possibility of gestational age confounding the result and should be seen with the context of preterm morbidity and mortality. The abnormal umbilical artery Doppler waveform is associated with cesarean section delivery, neonatal intensive care unit admission, respiratory distress syndrome, neonatal sepsis, neonatal hyperbilirubinemia, and early neonatal death compared to normal umbilical artery Doppler flow.

Perioperative fetal hemodynamic changes in twin-twin transfusion syndrome and neurodevelopmental outcome at two years of age.

ObjectiveTo investigate whether perioperative fetal hemodynamic changes in twin‐to‐twin transfusion syndrome (TTTS) are associated with neurodevelopmental impairment (NDI) at two years.MethodsDoppler parameters of three sonograms (day before, first day after and 1 week after laser surgery for TTTS) were assessed for correlation with neurodevelopmental outcome at two years (2008‐2016). NDI was defined as: cerebral palsy, deafness, blindness, and/or a Bayley‐III cognitive/motor developmental test‐score > 2SD below the mean.ResultsLong‐term outcome was assessed in 492 TTTS survivors. NDI was present in 5% (24/492). After adjustment for severe cerebral injury (present in 4%), associated with NDI were: middle cerebral artery peak systolic velocity (MCA‐PSV) >1.5 multiples of the median (MoM) 1 day after surgery (odds ratio [OR] 4.96; 95% confidence interval [CI]: 1.17‐21.05, P = .03), a change from normal umbilical artery pulsatility index (UA‐PI) presurgery to UA‐PI >p95 postsurgery (OR 4.19; 95% CI: 1.04‐16.87, P = .04), a change from normal to MCA‐PSV >1.5MoM (OR 4.75; 95% CI: 1.43‐15.77, P = .01).ConclusionPerioperative fetal hemodynamic changes in TTTS pregnancies treated with laser are associated with poor neurodevelopmental outcome. Prospective research on the cerebrovascular response to altered hemodynamic conditions is necessary to further understand the cerebral autoregulatory capacity of the fetus in relation to neurodevelopmental outcome.

Misdiagnosis of a twin pregnancy with double-corner uterine rupture following salpingectomy and protrusion of the amniotic sac as an adnexal cyst: a case report

BackgroundSalpingectomy-associated uterine rupture during intrauterine pregnancy is rare in the clinic. We report a case of pregnancy with bilateral rupture of the uterine horns after bilateral salpingectomy.Case presentationA 30-year-old woman of Han ethnicity presented with right epigastric pain at 28 weeks and 6 days of gestation. Examination by colour Doppler ultrasound showed the following: “Twin live births with normal foetal umbilical artery blood flow indexes and a 183 mm × 112 mm anechoic zone in the right front of the uterus”. Initially, we made an incorrect judgement wherein we considered the amniotic sac that was protruding into the abdominal cavity to be an adnexal cyst. Fortunately, the diagnosis of uterine rupture was confirmed before the protruded amniotic sac broke. The mother did not bleed much, and the twin foetuses survived in our case.ConclusionA previous history of salpingectomy via laparoscopy could be a risk factor for uterine rupture in pregnant women. Attention should be paid to rare complications of pregnancy. To avoid adverse events, we should pay special attention to women with a history of laparoscopic salpingectomy who complain about abdominal discomfort and offer them a relevant ultrasound examination.

Abnormal Umblical Artery Doppler is Utilized for Fetuses with Intrauterine Growth Restriction Birth at 280/7–336/7 Gestational Weeks

Purpose: To compare short-term perinatal outcomes in preterm infants with intrauterine growth restriction (IUGR) in those with absent or reversed end-diastolic umbilical artery blood flow (AREDF) to those with normal end-diastolic umbilical artery blood flow (NEDF). Methods: This study included preterm births (280/7–336/7 gestational weeks) with IUGR with AREDF (n = 86) or NEDF (n = 27). Results: There were lower mean gestational weeks, birth weights, and a higher ratio of corticosteroid application in the AREDF group (p < 0.05). The mean length of neonatal intensive care unit stay of the AREDF group was significantly longer (p < 0.001). Sepsis and feeding intolerance ratios in the AREDF group were also significantly higher (p = 0.041 and p < 0.001 respectively). Conclusions: Patients with IUGR and umbilical Doppler abnormalities have longer neonatal intensive care unit stays.

289: The effect of chronic hypertension on deterioration of umbilical artery Dopplers in fetal growth restriction

Chronic hypertension (cHTN) can impair placental implantation possibly contributing to later dysfunction. We sought to examine how the presence of chronic hypertension affects the rate of progression of Doppler waveform abnormalities in pregnancies affected by fetal growth restriction (FGR). This retrospective cohort study of women with and without cHTN included non-anomalous, singleton pregnancies with FGR at a single center with an estimated due date from 1/1/2016 to 12/31/2018. Those with other medical conditions associated with placental dysfunction were excluded. Those with normal umbilical artery (UA) Dopplers had weekly ultrasounds and those with abnormal flow had twice weekly. Patients with Absent (AEDF) and reversed end diastolic flow (REDF) were evaluated and delivered at 34 and 32 weeks respectively. The primary outcome was time to progression to AEDF. Secondary outcomes included time to (i) elevated SD ratios (≥95%ile) and (ii) REDF. Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) adjusted for race, insurance type and BMI. Among the 450 women with FGR, 238 women met study criteria with 18 women (8%) with cHTN. Both groups were similar in race, BMI, insurance type and gestational age at diagnosis of FGR. Onset of elevated SD ratios was not significantly different for patients with or without chronic hypertension. Deterioration to AEDF occurred significantly sooner for patients with chronic hypertension (Figure). Deterioration to REDF was not significantly different. Infants born to mothers with hypertension were born two weeks earlier (p< 0.0007) and weighed 510 grams less (p< 0.003) than those without. Among those with FGR and cHTN, progression to REDF occurred sooner compared to normotensive patients. As there is little data on how cHTN affects outcomes in the setting FGR, this study could aid in prognostication of adverse outcomes. View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The use of 5-azacytidine in pregnant patient with Acute Myeloid Leukemia (AML): a case report

BackgroundThe management of Acute Myeloid Leukemia (AML) during pregnancy remains challenging as both the maternal and fetal outcomes should be considered. Several reports suggested that chemotherapy can be administered safely during the second and third trimester of pregnancy. However, the use of 5-azacytidine presents limitation due to lack of data.Case presentationA 28-years-old woman in the 26th week of gestation diagnosed with FLT3/ITD-mutated AML, complete remission was induced by Daunorubicin and Cytarabine, and subsequently with 5-azacytidine (75 mg/m2 daily for 7 days) with no fetal hematological or toxicity issues. Fetal ultrasound showed no aberrant morphology. Fetal size below the 5th percentile with normal umbilical artery dopplers, normal middle cerebral artery dopplers and ductus venosus doppler.Three weeks post 5-azacytidine, the team determined the most appropriate time for delivery after balancing the risks of prematurity and prevention of disease relapse since patient in hematological remission. The patient underwent elective lower segment caesarian section and had a baby girl delivered at 35 weeks of gestation weighing 1670 g without apparent anomalies.ConclusionTreatment using 5-azacytadine during last trimester of pregnancy resulted in no major fetal and maternal complications. These findings concluded that 5-azacytadine during the third trimester of pregnancy seems to be safe however, potential risks of this agent should be considered.

Antenatal hemodynamic findings and heart rate variability in early school-age children born with fetal growth restriction

Background According to epidemiological studies, impaired intrauterine growth increases the risk for cardiovascular morbidity and mortality in adulthood. Heart rate variability (HRV), which reflects the autonomic nervous system function, has been used for risk assessment in adults while its dysfunction has been linked to poor cardiovascular outcome. Objective We hypothesized that children who were born with fetal growth restriction (FGR) and antenatal blood flow redistribution have decreased HRV at early school age compared to their gestational age matched peers with normal intrauterine growth. Study design A prospectively collected cohort of children born with FGR (birth weight <10th percentile and/or abnormal umbilical artery flow, n = 28) underwent a 24-hour Holter monitoring at the mean age of 9 years and gestational age matched children with birth weight appropriate for gestational age (AGA, n = 19) served as controls. Time- and frequency domain HRV indices were measured and their associations with antenatal hemodynamic changes were analyzed. Results Time- and frequency domain HRV parameters (standard deviation of R–R intervals, SDNN; low frequency, LF; high frequency, HF; LF/HF; very low frequency, VLF) did not differ significantly between FGR and AGA groups born between 24 and 40 weeks. Neither did they differ between children born with FGR and normal umbilical artery pulsatility or increased umbilical artery pulsatility. In total, 56% of the FGR children demonstrated blood flow redistribution (cerebroplacental ratio, CPR < −2 SD) during fetal life and their SDNN (p = .01), HF (p = .03) and VLF (p = .03) values were significantly lower than in FGR children with CPR ≥ −2SD. Conclusions Early school age children born with FGR and intrauterine blood flow redistribution demonstrated altered heart rate variability. These prenatal and postnatal findings may be helpful in targeting preventive cardiovascular measures in FGR.

Size and shape of the four-chamber view of the fetal heart in fetuses with an estimated fetal weight less than the tenth centile

Fetuses with an estimated fetal weight below the 10th centile have an increased risk of adverse perinatal and long-term outcomes as well as increased rates of cardiac dysfunction, which often alters cardiac size and shape of the 4-chamber view and the individual ventricles. As a result, a simple method has emerged to screen for potential cardiac dysfunction in fetuses with estimated fetal weights <10th centile by measuring the size and shape of the 4-chamber view and the size of the ventricles. To determine the number of fetuses with an abnormal size and shape of the 4-chamber view and size of the ventricles in fetuses with an estimated fetal weight <10th centile. This was a retrospective study of 50 fetuses between 25 and 37 weeks of gestation with an estimated fetal weight <10th centile. Data from their last examination were analyzed. From an end-diastolic image of the 4-chamber view, the largest basal-apical length and transverse width were measured from their corresponding epicardial borders. This allowed the 4-chamber view area and global sphericity index (4-chamber view length/4-chamber view width) to be computed. In addition, tracing along the endocardial borders with speckle tracking software enabled measurements of the right and left ventricular chamber areas and the right ventricle/left ventricle area ratios to be computed. Doppler waveform pulsatility indices from the umbilical (umbilical artery pulsatility index) and middle cerebral arteries (middle cerebral artery pulsatility index) were analyzed, and the cerebroplacental ratio (middle cerebral artery pulsatility index/umbilical artery pulsatility index) computed. Umbilical artery pulsatility indices >90th and cerebroplacental ratios <10th centile were considered abnormal. Using data from the control fetuses, the centile for each of the cardiac measurements was categorized by whether it was <10th or >90th centile, depending upon the measurement. Of the 50 fetuses with estimated fetal weight <10th centile, 50% (n= 25) had a normal umbilical artery pulsatility index and cerebroplacental ratio. These fetuses had significantly more (P < 0.02 to <0.0001) abnormalities of the size and shape of the 4-chamber view than controls. In all, 44% had a 4-chamber view area >90th centile, 32% had a 4-chamber view global sphericity index <10th centile, 56% had a 4-chamber view width >90th centile, and 80% had 1 or more abnormalities of size and/or shape. The remaining 50% of fetuses (n= 25) had abnormalities of 1 or both for the umbilical artery pulsatility index and/or cerebroplacental ratio. These fetuses had significantly higher rates of abnormalities (P <0.05 to <0.0001) than controls for the following 4-chamber view measurements: 36% had a 4-chamber view area >90th centile; 28% had a 4-chamber view global sphericity index <10th centile; and 68% had a 4-chamber view width >90th centile. Only those fetuses with an abnormal umbilical artery pulsatility index had significant changes in ventricular size; 56% had a left ventricular area <10th centile; 28% had a right ventricular area <10th centile; 36% had right ventricular/left ventricular area ratio >90th centile. One or more of the above abnormal measurements were present in 92% of the fetuses. Higher rates of abnormalities of cardiac size and shape of the 4-chamber view were found in fetuses with an estimated fetal weight <10th centile, regardless of their umbilical artery pulsatility index and cerebroplacental ratio measurements. Those with a normal umbilical artery pulsatility index and an abnormal cerebroplacental ratio had larger and wider measurements of the 4-chamber view. In addition, the shape of the 4-chamber view was more globular or round than in controls. These fetuses may have an increased risk of perinatal complications and childhood and/or adult cardiovascular disease. Screening tools derived from the 4-chamber view, acting as surrogates for ventricular dysfunction, may identify fetuses who could benefit from further comprehensive testing and future preventive interventions.

Perinatal outcomes after intrauterine growth restriction and intermittently elevated umbilical artery Doppler

Intermittently elevated umbilical artery pulsatility index has been identified among pregnancies with intrauterine growth restriction but has unclear clinical significance. The purpose of this study was to analyze perinatal morbidity and stillbirth after intrauterine growth restriction with an intermittently elevated umbilical artery pulsatility index. This retrospective cohort study included nonanomalous singleton, intrauterine growth-restricted pregnancies that received umbilical artery pulsatility index testing at a tertiary-care prenatal diagnostic center from 2010-2016. Women with persistently elevated umbilical artery pulsatility index, absent or reversed end-diastolic blood flow on umbilical artery pulsatility index, or only 1 umbilical artery pulsatility index result were excluded. Intermittently elevated umbilical artery pulsatility index was defined as ≥1 elevated umbilical artery pulsatility index (>95%) and ≥1 normal umbilical artery pulsatility index (≤95%). Women with an intermittently elevated umbilical artery pulsatility index were matched 1:3 by gestational age at intrauterine growth restriction diagnosis to those with a normal umbilical artery pulsatility index. The primary outcome was composite neonatal morbidity and deaths (stillbirth, mechanical ventilation, sepsis, intraventricular hemorrhage, and necrotizing enterocolitis). Secondary outcomes included 5-minute Apgar score, umbilical artery pH, delivery type, and interval from intrauterine growth restriction diagnosis to delivery. We compared outcomes after intermittently elevated umbilical artery pulsatility index with those after normal umbilical artery pulsatility index with multivariable logistic regression, adjusting for gestational age at delivery, betamethasone use, and maternal factors. Of 1893 women, 143 (7.6%) had an intermittently elevated umbilical artery pulsatility index and were matched to 429 control subjects. Among the 143 women with an intermittently elevated umbilical artery pulsatility index, 78 (54.5%), 52 (36.4%), and 13 (0.9%) women had elevated umbilical artery pulsatility index for 1-24%, 25-49%, and 50-74% of recorded Doppler measurements, respectively. None of the women had an elevated umbilical artery pulsatility index for 75-99% of recorded umbilical artery pulsatility index measurements. The last recorded umbilical artery pulsatility index was elevated for 37 women with an intermittently elevated umbilical artery pulsatility index (25.9%). Overall, the odds of composite neonatal morbidity was similar among intrauterine growth-restricted pregnancies with an intermittently elevated vs a normal umbilical artery pulsatility index (adjusted odds ratio, 1.05; 95% confidence interval, 0.59-1.87); there were no stillbirths. There was no difference in 5-minute Apgar scores, umbilical artery pH, rate of cesarean delivery for fetal distress, or interval from intrauterine growth restriction diagnosis to delivery between the 2 groups. Similarly, sensitivity analyses that stratified the population of intermittently elevated umbilical artery pulsatility index by the proportion of elevated umbilical artery pulsatility index to overall umbilical artery pulsatility index measurements and by whether the last umbilical artery pulsatility index recorded was normal or elevated showed no difference in neonatal morbidity or obstetric outcomes between the comparator groups. Among intrauterine growth-restricted pregnancies, an intermittently elevated umbilical artery pulsatility index is neither uncommon nor associated with an increased risk of neonatal morbidity, stillbirth, or cesarean delivery. These findings suggest intrauterine growth-restricted pregnancies with intermittently elevated umbilical artery pulsatility index could be managed clinically as are those with normal umbilical artery pulsatility index.