Maternal Hyperoxygenation Research Articles

In vivo MRI assessment of placental and foetal oxygenation changes in a rat model of growth restriction using blood oxygen level-dependent (BOLD) magnetic resonance imaging

To evaluate whether changes in BOLD signal intensities following hyperoxygenation are related to intrauterine growth restriction (IUGR) in a rat model. IUGR was induced in pregnant rats by ligating the left vascular uterine pedicle at day 16 of gestation. BOLD MR imaging using a balanced steady-state free-precession (balanced-SSFP) sequence on a 1.5-T system was performed on day 19. Signal intensities (SI) before and after maternal hyperoxygenation were compared in the maternal liver and in control and growth-restricted foetoplacental units (FPUs). Maternal hyperoxygenation resulted in a significant increase in SI in all regions of interest (P < 0.05) in the 18 rats. In the control group, the SI (mean ± SD) increased by 21 % ± 15 in placentas (n = 74) and 13 % ± 8.5 in foetuses (n = 53). In the IUGR group, the increase was significantly lower: 6.5 % ± 4 in placentas (n = 36) and 7 %± 5.5 in foetuses (n = 34) (P < 0.05). BOLD MRI allows non-invasive assessment of the foetoplacental response to maternal hyperoxygenation in the rat and demonstrates its alteration in an IUGR model. This imaging method may provide a useful adjunct for the early diagnosis, evaluation, and management of human IUGR. • Intra-uterine growth restriction is an important cause of perinatal morbidity and mortality. • Blood oxygen level-dependent MRI non-invasively assesses foetoplacental response to maternal hyperoxygenation. • In the rat, foetoplacental response to maternal hyperoxygenation is altered in IUGR. • Functional MRI may help to assess human IUGR.

Use of Intravoxel Incoherent Motion MR Imaging to Assess Placental Perfusion in a Murine Model of Placental Insufficiency

The objectives of this study were to evaluate the potential of intravoxel incoherent motion (IVIM) magnetic resonance imaging at 4.7 T to distinguish decreased placental perfusion from normal perfusion in a controlled murine model and to determine the effect of transient maternal hyperoxygenation on placental microvascularization. The study was approved by our animal care committee. Ten pregnant rats underwent ligation of the left uterine vascular pedicle on the 17th embryonic day (E17). A multishot diffusion-weighted spin-echo echo-planar imaging sequence, using 14 b values (b10 to b800), was performed on the 19th embryonic day (E19) under room air and during maternal hyperoxygenation. For each placenta and its 2 layers, the signal intensity decay curve according to the b values was obtained. The following IVIM parameters were calculated using biexponential fitting: the diffusion coefficient (D), the pseudodiffusion coefficient (D*), and the perfusion fraction (f). Mixed regression modeling was used to analyze the effect of ligation status, oxygenation, and the placental layer on IVIM parameters. Seventy-three placentas were examined: 23 in the ligated horn and 50 in the nonligated control horn. The IVIM parameters were obtained for 67% of the placentas. In the control horn, the mean (SD) values on room air were 28% (13%), 9.6 (9) ×10(-3) mm(2)/s, and 0.88 (0.36) ×10(-3) mm(2)/s for the perfusion fraction, the pseudodiffusion coefficient, and the diffusion coefficient, respectively. The perfusion fraction was significantly decreased in the ligated horn (-6.7% [1.9%]; P = 0.001) and during maternal hyperoxygenation (-3.3 [1.64%]; P = 0.047). The diffusion coefficient increased significantly during the hyperoxygenation (0.26 [0.04] × 10(-3) mm(2)/s; P = 0.0001) and in the inner placental layer (0.21 [0.05] ×10(-3) mm(2)/s; P = 0.0001). The perfusion fraction is a sensitive marker of decreased placental perfusion. The perfusion fraction and the diffusion coefficient are modified during the hyperoxygenation. Our IVIM-based approach may help in the investigation and early diagnosis of vascular diseases during pregnancy.

394: Effects of maternal hyperoxygenation on fetal pulmonary circulation and on blood flow patterns in the middle cerebral artery, in normal and high-risk pregnancies

394: Effects of maternal hyperoxygenation on fetal pulmonary circulation and on blood flow patterns in the middle cerebral artery, in normal and high-risk pregnancies

Prediction of pulmonary hypoplasia in mid‐trimester preterm prelabor rupture of membranes: research or clinical practice?

Prediction of pulmonary hypoplasia in mid‐trimester preterm prelabor rupture of membranes: research or clinical practice?

394: Effects of maternal hyperoxygenation on fetal pulmonary circulation and on blood flow patterns in the ductus venosus in normal third-trimester fetuses

394: Effects of maternal hyperoxygenation on fetal pulmonary circulation and on blood flow patterns in the ductus venosus in normal third-trimester fetuses

Maternal hyperoxygenation test in fetuses undergoing FETO for severe isolated congenital diaphragmatic hernia

To predict neonatal survival and pulmonary hypertension by measurement of fetal pulmonary artery reactivity to maternal hyperoxygenation in fetuses with severe congenital diaphragmatic hernia treated by fetoscopic endoluminal tracheal occlusion (FETO). Thirty-eight fetuses underwent FETO at around 28 weeks' gestation and the balloon was removed at 34 weeks in most cases. We performed a hyperoxygenation test and measured the lung-to-head ratio of each fetus before and after each procedure. Outcome measures were neonatal survival, occurrence of pulmonary hypertension and its response to inhaled nitric oxide (iNO). Fetuses that survived had a larger increase in lung size and decrease of resistance in the first branch of the main pulmonary artery than did those that died. Both measures were also predictive of pulmonary hypertension unresponsive to iNO. The hyperoxygenation test and lung-to-head ratio were both best predictive for neonatal survival when measured following removal of the balloon (P < 0.002). Discriminant analysis confirmed that these two parameters are independent predictors of outcome. In fetuses undergoing FETO, pulmonary vascular reactivity in relation to oxygen and lung size are independent predictors of neonatal survival and pulmonary hypertension. The hyperoxygenation test merits further study in expectantly managed cases.

Fetal Ventricular Diastolic Filling Characteristics in a Primate Model: The Role of Fetal Heart Rate and Pulmonary Vascular Impedance

We hypothesized that fetal ventricular diastolic filling characteristics are related to fetal heart rate (FHR) and pulmonary vascular impedance. Rhesus monkeys underwent Doppler ultrasonography at near-term gestation. Tricuspid (TV) and mitral valve (MV) blood velocity waveforms were used to calculate maximum velocity (V-max) and velocity time integral (VTI) E/A ratios (early filling/ventricular filling during atrial contraction) at baseline and during maternal hyperoxygenation. Right pulmonary artery (RPA) pulsatility indices (PIs) and FHR were measured. Hyperoxgenation significantly decreased FHR and RPA PI. The TV V-max and the MV VTI E/A ratios increased significantly and correlated with a decrease in FHR but not with a decrease in RPA PI. The TV and MV A-wave V-max decreased during hyperoxygenation and their decrease correlated significantly with a drop in FHR. Fetal ventricular diastolic filling characteristics are related to FHR but not to pulmonary vascular impedance.

Vasoreactive Response to Maternal Hyperoxygenation in the Fetus With Hypoplastic Left Heart Syndrome

Cardiopulmonary interactions play an important role in the pathophysiology of hypoplastic left heart syndrome (HLHS). Pulmonary vasculopathy has been identified, especially in those with restrictive/intact atrial septum. Responsiveness of the pulmonary vasculature to maternal hyperoxygenation (MH) may provide a tool to assess the degree of pulmonary vasculopathy present before birth. Doppler echocardiography was performed in 27 normal and 43 HLHS fetuses. In HLHS, sampling was repeated after 10 minutes of MH with 60% FiO(2) and after 5 minutes of recovery. Sampling was performed in the proximal, midportion, and distal branch pulmonary artery (PA). Pulsatility index (PI) was used as a measure of vascular impedance. Of the HLHS fetuses, 34 had an open interatrial septum and 9 had a restrictive/intact atrial septum. At birth, 5 fetuses underwent immediate intervention on the interatrial septum. Middle cerebral artery PI was lower in HLHS versus normal fetuses (P<0.001). There was no difference in UA, DA, or branch PA PI between normal fetuses and those with HLHS. MH led to a significant decrease in PI at each of the PA sites sampled in fetuses with an open atrial septum (P<0.001); however, there no was significant change in the PI in fetuses that required immediate intervention on the atrial septum at birth. Using a cutoff value of <10% vasoreactivity, the sensitivity of MH testing for determining need for immediate intervention at birth is 100% (0.46 to 1.0); specificity, 94% (0.78 to 0.99); positive predictive value, 71% (0.30 to 0.95); and negative predictive value, 100% (0.86 to 1.0). No untoward effects were seen with MH. PA vasoreactivity to MH occurs in the fetus with HLHS. MH testing accurately identifies fetuses requiring urgent postnatal intervention at birth and may be used to select candidates for fetal atrial septoplasty.

OC01.01: Maternal hyperoxygenation test in fetuses with congenital diaphragmatic hernia as a predictor of neonatal outcome

Objective: To predict neonatal outcome and unresponsive pulmonary hypertension (PHT) in fetuses with isolated congenital diaphragmatic hernia (iCDH) by fetal pulmonary arterial reactivity after maternal hyperoxygenation. Methods: 59 fetuses with iCDH were assessed ≥ 30 wks, either expectantly managed (n=27) or following removal of tracheal occlusion (n=32). Doppler measurements of pulsatility index (PI) in the 1st branch of the contralateral pulmonary artery were performed before and after maternal administration of 60% O2 by mask. Outcome measures included the decrease in PI after O2 (deltaPI), observed/expected lung-to-head-ratio (O/E LHR), neonatal survival at discharge, and unresponsive PHT, defined on the presence of a pre-/postductal O2 saturation gradient of > 20mmHg that did not respond to therapy. Results: Oxygen test was performed at 33.6 ± 1.6. Delivery took place at 37.1 ± 2.1 wks. In 25% we could not obtain echocardiography data, hence not assess severity of PHT. 36 (61%) neonates survived until discharge. Their O/E LHR and deltaPI values where significantly different from those who died. Only one of the survivors (2%) and 20/23 (87%) of those who eventually died after birth had unresponsive PHT, with different O/E LHR and delta PI as compared to those without or responsive PHT. Discriminant analysis shows that both prenatal measurements independently predict outcome. Conclusion: O/E LHR and Delta PI in the third trimester are both predictive parameters for neonatal survival and occurrence of severe PHT in CDH.

OP09.11: Maternal hyperoxygenation test in fetuses treated prenatally for severe isolated congenital diaphragmatic hernia

Aim: Pulmonary hypoplasia and hypertension (PHT) are key problems of newborns with isolated congenital diaphragmatic hernia (CDH). Lung size to head ratio (O/E LHR) and liver position are related to the degree of pulmonary hypoplasia. Prenatal evaluation of the lung vasculature can be either through anatomical measurements, flow patterns, or by measuring vascular reactivity. We evaluated the course and predictive value of the fetal pulmonary artery reactivity to maternal hyperoxygenation (HPVR) in selected fetuses with severe CDH prior to and following fetoscopic endoluminal tracheal occlusion (FETO). Methods: 38 fetuses underwent FETO around 28 wks and the balloon was removed at 34 weeks. We performed a HPVR test and measured O/E LHR within 2 days before (T1,T3) and after (T2,T4) each procedure. Outcomes included neonatal survival, occurrence of PHT unresponsive to inhaled-NO (iNO). Results: The HPVR-test and O/E LHR follow different courses around the time of FETO. They are best predictive when HPVR is measured following balloon removal (T4; p<0.002). Fetuses who survive have a larger increase in O/E LHR and decrease of resistance in the first branch of the main pulmonary artery than those who died. Both are also predictive of PHT unresponsive to iNO. Discriminant analysis confirms that the LHR and HPVR independently predict outcome. Conclusions: In fetuses undergoing FETO pulmonary vascular reactivity to oxygen and lung size are independent predictors of neonatal survival and pulmonary hypertension. The hyperoxygenation test merits further study in expectantly managed cases.

OC01.03: Intrapartum levator common and occult trauma visualization by translabial 3D ultrasound

Objective: To predict neonatal outcome and unresponsive pulmonary hypertension (PHT) in fetuses with isolated congenital diaphragmatic hernia (iCDH) by fetal pulmonary arterial reactivity after maternal hyperoxygenation. Methods: 59 fetuses with iCDH were assessed ≥ 30 wks, either expectantly managed (n=27) or following removal of tracheal occlusion (n=32). Doppler measurements of pulsatility index (PI) in the 1st branch of the contralateral pulmonary artery were performed before and after maternal administration of 60% O2 by mask. Outcome measures included the decrease in PI after O2 (deltaPI), observed/expected lung-to-head-ratio (O/E LHR), neonatal survival at discharge, and unresponsive PHT, defined on the presence of a pre-/postductal O2 saturation gradient of > 20mmHg that did not respond to therapy. Results: Oxygen test was performed at 33.6 ± 1.6. Delivery took place at 37.1 ± 2.1 wks. In 25% we could not obtain echocardiography data, hence not assess severity of PHT. 36 (61%) neonates survived until discharge. Their O/E LHR and deltaPI values where significantly different from those who died. Only one of the survivors (2%) and 20/23 (87%) of those who eventually died after birth had unresponsive PHT, with different O/E LHR and delta PI as compared to those without or responsive PHT. Discriminant analysis shows that both prenatal measurements independently predict outcome. Conclusion: O/E LHR and Delta PI in the third trimester are both predictive parameters for neonatal survival and occurrence of severe PHT in CDH.

OC01.02: What measurements are needed to classify pregnancies of unknown location?

Objective: To predict neonatal outcome and unresponsive pulmonary hypertension (PHT) in fetuses with isolated congenital diaphragmatic hernia (iCDH) by fetal pulmonary arterial reactivity after maternal hyperoxygenation. Methods: 59 fetuses with iCDH were assessed ≥ 30 wks, either expectantly managed (n=27) or following removal of tracheal occlusion (n=32). Doppler measurements of pulsatility index (PI) in the 1st branch of the contralateral pulmonary artery were performed before and after maternal administration of 60% O2 by mask. Outcome measures included the decrease in PI after O2 (deltaPI), observed/expected lung-to-head-ratio (O/E LHR), neonatal survival at discharge, and unresponsive PHT, defined on the presence of a pre-/postductal O2 saturation gradient of > 20mmHg that did not respond to therapy. Results: Oxygen test was performed at 33.6 ± 1.6. Delivery took place at 37.1 ± 2.1 wks. In 25% we could not obtain echocardiography data, hence not assess severity of PHT. 36 (61%) neonates survived until discharge. Their O/E LHR and deltaPI values where significantly different from those who died. Only one of the survivors (2%) and 20/23 (87%) of those who eventually died after birth had unresponsive PHT, with different O/E LHR and delta PI as compared to those without or responsive PHT. Discriminant analysis shows that both prenatal measurements independently predict outcome. Conclusion: O/E LHR and Delta PI in the third trimester are both predictive parameters for neonatal survival and occurrence of severe PHT in CDH.

OP10.01: The influence of maternal demographic features on fetal size in the first trimester

Aim: Pulmonary hypoplasia and hypertension (PHT) are key problems of newborns with isolated congenital diaphragmatic hernia (CDH). Lung size to head ratio (O/E LHR) and liver position are related to the degree of pulmonary hypoplasia. Prenatal evaluation of the lung vasculature can be either through anatomical measurements, flow patterns, or by measuring vascular reactivity. We evaluated the course and predictive value of the fetal pulmonary artery reactivity to maternal hyperoxygenation (HPVR) in selected fetuses with severe CDH prior to and following fetoscopic endoluminal tracheal occlusion (FETO). Methods: 38 fetuses underwent FETO around 28 wks and the balloon was removed at 34 weeks. We performed a HPVR test and measured O/E LHR within 2 days before (T1,T3) and after (T2,T4) each procedure. Outcomes included neonatal survival, occurrence of PHT unresponsive to inhaled-NO (iNO). Results: The HPVR-test and O/E LHR follow different courses around the time of FETO. They are best predictive when HPVR is measured following balloon removal (T4; p<0.002). Fetuses who survive have a larger increase in O/E LHR and decrease of resistance in the first branch of the main pulmonary artery than those who died. Both are also predictive of PHT unresponsive to iNO. Discriminant analysis confirms that the LHR and HPVR independently predict outcome. Conclusions: In fetuses undergoing FETO pulmonary vascular reactivity to oxygen and lung size are independent predictors of neonatal survival and pulmonary hypertension. The hyperoxygenation test merits further study in expectantly managed cases.

OP10.02: The influence of body mass index on first trimester fetal growth

Aim: Pulmonary hypoplasia and hypertension (PHT) are key problems of newborns with isolated congenital diaphragmatic hernia (CDH). Lung size to head ratio (O/E LHR) and liver position are related to the degree of pulmonary hypoplasia. Prenatal evaluation of the lung vasculature can be either through anatomical measurements, flow patterns, or by measuring vascular reactivity. We evaluated the course and predictive value of the fetal pulmonary artery reactivity to maternal hyperoxygenation (HPVR) in selected fetuses with severe CDH prior to and following fetoscopic endoluminal tracheal occlusion (FETO). Methods: 38 fetuses underwent FETO around 28 wks and the balloon was removed at 34 weeks. We performed a HPVR test and measured O/E LHR within 2 days before (T1,T3) and after (T2,T4) each procedure. Outcomes included neonatal survival, occurrence of PHT unresponsive to inhaled-NO (iNO). Results: The HPVR-test and O/E LHR follow different courses around the time of FETO. They are best predictive when HPVR is measured following balloon removal (T4; p<0.002). Fetuses who survive have a larger increase in O/E LHR and decrease of resistance in the first branch of the main pulmonary artery than those who died. Both are also predictive of PHT unresponsive to iNO. Discriminant analysis confirms that the LHR and HPVR independently predict outcome. Conclusions: In fetuses undergoing FETO pulmonary vascular reactivity to oxygen and lung size are independent predictors of neonatal survival and pulmonary hypertension. The hyperoxygenation test merits further study in expectantly managed cases.

Reducing stillbirths: interventions during labour.

BackgroundApproximately one million stillbirths occur annually during labour; most of these stillbirths occur in low and middle-income countries and are associated with absent, inadequate, or delayed obstetric care. The low proportion of intrapartum stillbirths in high-income countries suggests that intrapartum stillbirths are largely preventable with quality intrapartum care, including prompt recognition and management of intrapartum complications. The evidence for impact of intrapartum interventions on stillbirth and perinatal mortality outcomes has not yet been systematically examined.MethodsWe undertook a systematic review of the published literature, searching PubMed and the Cochrane Library, of trials and reviews (N = 230) that reported stillbirth or perinatal mortality outcomes for eight interventions delivered during labour. Where eligible randomised controlled trials had been published after the most recent Cochrane review on any given intervention, we incorporated these new trial findings into a new meta-analysis with the Cochrane included studies.ResultsWe found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality, especially on stillbirths. Available evidence suggests that operative delivery, especially Caesarean section, contributes to decreased stillbirth rates. Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact, though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour. Planned Caesarean section for term breech presentation has been shown in a large randomised trial to reduce stillbirths, but the feasibility and consequences of implementing this intervention routinely in low-/middle-income countries add caveats to recommending its use. Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures, but studies have not demonstrated impact on perinatal mortality. There was limited evidence of impact for maternal hyperoxygenation, and concerns remain about maternal safety. Transcervical amnioinfusion for meconium staining appears promising for low/middle income-country application according to the findings of many small studies, but a large randomised trial of the intervention had no significant impact on perinatal mortality, suggesting that further studies are needed.ConclusionAlthough the global appeal to prioritise access to emergency obstetric care, especially vacuum extraction and Caesarean section, rests largely on observational and population-based data, these interventions are clearly life-saving in many cases of fetal compromise. Safe, comprehensive essential and emergency obstetric care is particularly needed, and can make the greatest impact on stillbirth rates, in low-resource settings. Other advanced interventions such as amnioinfusion and hyperoxygenation may reduce perinatal mortality, but concerns about safety and effectiveness require further study before they can be routinely included in programs.

OP14.16: Cardiovascular changes and neonatal outcome in IUGR fetuses born to normotensive and preeclamptic mothers

Objectives: To compare the effects of maternal hyperoxygenation on the Doppler waveforms in twin pregnancies where one fetus has IUGR and absent or reversed end diastolic flow (ARED) in room air. Methods: Women with monochorionic diamniotic twin pregnancies with one IUGR fetus with ARED in room air between 2006 and 2008 who were hospitalized after 24 weeks gestation for close surveillance and bed rest were included in the study. All fetuses had structurally normal hearts. None had evidence of twin-twin transfusion syndrome. Measurements of Doppler flow pattern in middle cerebral artery (MCA), free loop of umbilical artery (FLUA) and ductus venosus (DV) were made in room air and then after breathing 60% oxygen by face mask for twenty minutes. Results: Seven twin pregnancies were included. The normal cotwin in each case had normal Doppler waveforms in room air and oxygen. All seven IUGR fetuses had ARED in room air and dilated DV size. In five patients, the FLUA normalized (PI < 1.75) after breathing 60% oxygen (mean PI = 3.21 in room air versus mean PI = 1.65 in oxygen). These five patients who had positive change with oxygen delivered an average of 5 weeks (range 3–14 weeks) after hospitalization. The other two patients who had no change in FLUA with oxygen and had abnormal MCA and DV in room air were delivered for obstetric indications within one day of the test. Conclusions: Maternal hyperoxygenation may be associated with normalization of the FLUA in fetuses with ARED after 24 weeks of gestation. A positive maternal hyperoxygenation test can select IUGR fetuses who have an abnormal FLUA in room air with a better prognosis and may be useful in postponing delivery in these fetuses with ARED.

OP14.15: The effects of the maternal hyperoxygenation test on twin pregnancies with one intrauterine growth restricted (IUGR) fetus

Objectives: To compare the effects of maternal hyperoxygenation on the Doppler waveforms in twin pregnancies where one fetus has IUGR and absent or reversed end diastolic flow (ARED) in room air. Methods: Women with monochorionic diamniotic twin pregnancies with one IUGR fetus with ARED in room air between 2006 and 2008 who were hospitalized after 24 weeks gestation for close surveillance and bed rest were included in the study. All fetuses had structurally normal hearts. None had evidence of twin-twin transfusion syndrome. Measurements of Doppler flow pattern in middle cerebral artery (MCA), free loop of umbilical artery (FLUA) and ductus venosus (DV) were made in room air and then after breathing 60% oxygen by face mask for twenty minutes. Results: Seven twin pregnancies were included. The normal cotwin in each case had normal Doppler waveforms in room air and oxygen. All seven IUGR fetuses had ARED in room air and dilated DV size. In five patients, the FLUA normalized (PI < 1.75) after breathing 60% oxygen (mean PI = 3.21 in room air versus mean PI = 1.65 in oxygen). These five patients who had positive change with oxygen delivered an average of 5 weeks (range 3–14 weeks) after hospitalization. The other two patients who had no change in FLUA with oxygen and had abnormal MCA and DV in room air were delivered for obstetric indications within one day of the test. Conclusions: Maternal hyperoxygenation may be associated with normalization of the FLUA in fetuses with ARED after 24 weeks of gestation. A positive maternal hyperoxygenation test can select IUGR fetuses who have an abnormal FLUA in room air with a better prognosis and may be useful in postponing delivery in these fetuses with ARED.

Maternal hyperoxygenation in late gestation promotes rapid increase of cardiac dimensions in fetuses with hypoplastic left hearts with intrinsically normal or slightly abnormal aortic and mitral valves

Maternal hyperoxygenation in late gestation promotes rapid increase of cardiac dimensions in fetuses with hypoplastic left hearts with intrinsically normal or slightly abnormal aortic and mitral valves

Is it time to add aortic isthmus evaluation to the repertoire of Doppler investigations for placental insufficiency?

Is it time to add aortic isthmus evaluation to the repertoire of Doppler investigations for placental insufficiency?

728: Maternal hyperoxygenation in the fetus with hypoplastic left heart syndrome (HLHS): A tool for assessment of the pulmonary vasculature

Cardio-pulmonary interactions play an important role in the pathophysiology of HLHS. Pulmonary vasculopathy has been identified at birth, especially in fetuses with a restrictive atrial communication. Responsiveness of the pulmonary vasculature to maternal hyperoxygenation (MH) may provide a tool to assess the degree of fetal pulmonary vasculopathy.