Cyclic vomiting syndrome: contribution to dysphagic infant death.

Vomiting involves the simultaneous violent contraction of abdominal and diaphragm muscles to produce a high pressure on the stomach. The heart right atrium forms a through path from IVC to SVC, so the high intra-abdominal pressure will drive blood from abdominal contents into the head. Normally internal viscous drags in organs will limit the volume leaving them during a single vomiting event. However, repetitive vomiting such as occurs in cyclic vomiting syndrome (CVS) may drive sufficient blood into head veins to produce extreme venous hypertension. Dysphagic infant death is essentially a head vein hypertension malady, some features of which match those that are postulated for Shaken Baby Syndrome. CVS was described by Gee in 1882 but is still poorly understood. Recently a consensus statement has been released by the North American Society for Pediatric Gastroenterology Hepatology and Nutrition setting out key issues to be addressed. Understanding CVS may therefore have important implications beyond its gastroenterological aspects. A case demonstrating a sequence of features suggesting CVS and the effects of increasing abdominal muscle strength with age is presented. It showed (1) swallowing dysfunction, (2) grunting and apnoea (surfactant poisoning), (3) reflux, (4) diarrhoea, (5) apparently unprovoked prolonged screaming fits (migraine?), (6) petechiae (local capillary rupture), (7) skull growth abnormalities (hydrocephalus) and (8) unconscious "blank staring spells " (from which the infant would auto-resuscitate). Repetitive vomiting may also sensitise the epiglottis thus increasing the risk of laryngospasm, and making attempts at intubation hazardous, possibly leading to hypoxic brain death.

Shaken baby syndrome: does it exist?

UNLABELLED: The original (1993) definition of Shaken Baby Syndrome (SBS) specifies a group of infants with a history of dysphagia, presenting in a comatose state with respiratory difficulty progressing to apnoea or bradycardia requiring cardiopulmonary resuscitation. It is stated that retinal and vitreous haemorrhages are characteristic of SBS, and that subdural haemorrhage caused by shearing forces disrupting small bridging veins is a common result of shaking, but visible cerebral contusions are unusual. COMMENT: Experimental studies of whiplash injuries in primates in the 1960s showed that when coma was induced cerebral contusions were usually visible, but where the impulse was insufficient to induce coma no damage of any sort was found. Two modes of injury were established, having different impulse thresholds. At the lower threshold it was possible to study injury to axons, e.g. compare the effect of varying the plane of rotation, without inducing subdural bleeding. Contusions were usually observed in this mode, which was considered to be due to separation of the pia mater from the cortex due to trabecular tension. Subdural bleeding could be added by raising the impulse above the second threshold. Thus contusions can occur without subdural bleeding but not vice versa in whiplash injury. HYPOTHESIS: The SBS definition is internally inconsistent. By specifying that contusions are rarely seen it seems to rule out whiplash on which the concept of Shaken Baby Syndrome is based. The definition is consistent with dysphagic accidents leading to aspiration, a Dysphagic Infant Death Syndrome in which the carer plays no part.

Paroxysmal coughing, subdural and retinal bleeding: a computer modelling approach.

Unexplained subdural and retinal haemorrhages in an infant are commonly attributed to 'shaking', the mechanism of which is believed to be traumatic venous rupture. However, the haemorrhagic retinopathy reported as a result of Valsalva manoeuvres and the subdural bleeding that is a rare complication of pertussis together demonstrate that if a sustained rise in intrathoracic pressure is transmitted to cerebral and retinal vessels, it may result in bleeding, similar to that reported in inflicted injury. Such haemorrhages would be expected to occur whenever severe paroxysmal coughing were induced, whatever the cause. This study used a computer modelling approach to investigate feeding accidents as the trigger for bleeding. A dynamic circulatory model of a 3-month-old infant was induced to 'cough', and the response to changes in physiological variables monitored. It showed that coughing causes intracranial pressures to build up exponentially to approach a maximum, proportional to the amount of pressure the musculature of the thorax can produce, as venous return is impeded. They do not have time to become dangerous during individual coughs, as blood quickly returns after the cough is over, reestablishing normal pressures. Paroxysmal coughing, however, does not allow blood to return between coughs, with the result that very high luminal pressures may be generated, sufficient to damage veins. A history of coughing, vomiting or choking is not uncommon in otherwise normal infants with retinal and subdural bleeding. Our findings suggest that paroxysmal coughing could account for such bleeding in some cases.

Dysphagia as a risk factor for sudden unexplained death in infancy.

The TRIAD of encephalopathy, subdural haemorrhages, and retinal haemorrhages is commonly considered diagnostic of Shaken Baby Syndrome, but the original paper describes a statistically linked QUADRAD of features, the fourth of which is a previous history of feeding difficulties (dysphagia). Recent reviews of giving pacifiers (dummies) to infants during sleeping periods have found a significant reduction in the incidence of Sudden Infant Death Syndrome. Stimulation of swallowing is a possible connection with dysphagia, which is examined here, illustrated by a well documented case. Although amniotic fluid passes freely through the larynx of fetal mammals during fetal breathing, application of pure water to the laryngeal epithelium in infants causes choking and laryngeal closure. "Water sensors" in the surface respond to lack of chloride ions and adapt very slowly or not at all. Others have found in puppies that following application of pure water only 32% resume breathing in less than 30-40s. The rest needed at least one saline flush, and some required artificial ventilation in addition. These receptors also respond to high potassium concentrations and acid or alkaline solutions. Normally, airway closure during swallowing or vomiting prevents entry of feed or oesophageal reflux, but in some forms of dysphagia leakage can occur, causing paroxysmal coughing, reflex laryngeal closure, and so prolonged apnoea. Recently, it has been realised that the TRIAD injuries can also result from high intracranial vascular pressures transmitted from intra-thoracic pressure surges during paroxysmal coughing, choking, etc. Triggering of such pressure surges by dysphagic accidents provides a physiological link to injuries commonly considered diagnostic of Shaken Baby Syndrome, completing the statistically identified QUADRAD of features. Further dysphagic research might reveal predictive factors, and preventative measures such as feeds of optimal pH.

The 'Sutured Skull' and intracranial bleeding in infants.

It is known that retinal haemorrhages can result in adults when elevated intrathoracic pressures due to coughing, cardiopulmonary resuscitation, etc., force blood into the head. In infants under one year of age retinal and intracranial haemorrhage commonly occur together, but the same is not true for the older child and adult. The role of the elasticity of the infant skull (resulting from suture and fontanelle stretching) compared to the rigid mature skull, was investigated in a computer aided method. This showed that although in the event of Valsalva-like situations very high lumen pressures may be present in both groups, in the rigid adult skull an immediate corresponding increase in intracranial pressure is produced which surrounds and supports vascular walls leaving transmural pressures little changed. No such support is provided in the eye, and retinal vessels may rupture. Within the skull there may be drastic effects on brain circulation, but since changes in vascular transmural pressure are minimal vessel distension is not induced. In the infant skull the sutures stretch as pressure rises. Since vascular volume is only about 5% of intracranial volume each 1% increase in skull volume permits a 20% increase in vascular volume. Quite small skull expansions will allow dangerous vascular distension and risk of wall damage. Until skull bones fuse, intra-cranial bleeding will be expected in the soft infant skull in any situation where retinal haemorrhage alone is known to occur in the adult or child.

Paroxysmal cough injury, vascular rupture and 'shaken baby syndrome'.

It is widely assumed that subdural and retinal haemorrhage in infants can only result from traumatic rupture of vulnerable blood vessels. An alternative aetiology, that of vascular rupture resulting from excessive intraluminal pressure, is presented in three disease conditions. (1) Perlman et al., studying premature neonates requiring mechanical ventilation for respiratory distress syndrome, observed "cough-like" fluctuations in oesophageal pressure greater than 18 cms H2O, whose timing matched fluctuations in anterior cerebral artery flow. When 14 out of 24 neonates were paralysed (to prevent abdominal muscle activity) intraventricular haemorrhage developed in all 10 controls but in only one of the paralysed group during paralysis. (2) New analysis of pressure data extracted from a previous study of prolonged expiratory apnoea showed alveolar collapse induced 100 mmHg intrathoracic cough pressure surges. Superior vena cava pressures up to 50 mmHg were implied, and radial artery systolic pressures over 180 mmHg recorded. (3) Bordetella pertussis bacteria attach to cilia in the airways, but do not invade the underlying tissue. The irritation causes the powerful coughing paroxysms of whooping cough. Brain haemorrhages and retinal detachment have been observed to result from the high intravascular pressures produced. The data suggest that any source of intense airway irritation not easily removed (laryngeal infection, inhalation of regurgitated feed, fluff, smoke etc.) could induce similar bleeding, a paroxysmal cough injury (PCI). Additional objective evidence of inflicted trauma is necessary to distinguish between 'shaken baby syndrome' and PCI.

Spiral artery associated restricted growth (SPAARG): a computer model of pathophysiology resulting from low intervillous pressure having fetal programming implications.

Failure of adequate trophoblastic conversion of maternal spiral arteries is associated with intrauterine growth restriction (IUGR). In addition to poor oxygen delivery, raised spiral artery resistance reduces placental intervillous pressure. An iterative type computer model was formed by linking an existing model of the fetus and a new nine cotyledon placental model. Simulation of compression cuffing of the spiral arteries to progressively restrict uteroplacental flow was performed, while observing various fetal and placental variables. Water moved to the fetus in the cotyledonary core villi, and to the mother in the outer villous layers. While the fetus could match villous capillary pressure to changes in intervillous pressure, net transplacental water movement was minimal, but when spiral artery resistance was increased sufficiently to cause mean intervillous pressure to fall below that which the fetus could match, a net flow to the mother appeared. That continued until the resulting fetal blood hemoconcentration produced a sufficient increase in colloid osmotic pressure to restrict further loss. All cells within the fetal-placental unit are then required to operate in an abnormal ionic environment, which may significantly affect systems such as the renin-angiotensin set-point, with implications for post-natal homeostasis such as control of adult blood pressure. Furthermore, in vivo, cells of the feto-placental unit respond to the increased intravascular osmotic pressure by production of intracellular osmolytes in order to match intracellular and vascular/interstitial osmotic pressures. This may explain the observed effects on postnatal water balance in growth restricted infants and could also provide a possible mechanism for the association of the systemic maternal complications associated with impaired placentation and reduced intervillus flow.

The pulmonary vein Doppler flow velocity waveform: feature analysis by comparison of in vivo pressures and flows with those in a computerized fetal physiological model.

OBJECTIVES: Doppler flow velocity waveforms (FVW) in fetal veins that discharge into the atria show fluctuations related to atrial events. Pulmonary veins are of particular interest because both ends (atrial and collecting venule) are within the intrathoracic pressure environment reducing fetal breathing artifacts. Indices, such as pulsatility index for veins (PIV), have been suggested to classify FVWs and relate them to fetal well being. We wished to examine the relationship between function and FVW in circumstances which cannot ethically be examined in vivo, by studying the mechanisms which produced altered 'flows' in a detailed fetal computer model. We then related these findings to current flow indices. METHODS: A computer model of the feto-placental unit, responding to changes in organ oxygenation and regional flow is briefly described. In vivo intracardiac pressures and FVWs obtained from other studies were used to extend detail in the model until matching 'pressures' and 'flows' resulted. The effects of flow redistribution in the hypoxic fetus on pulmonary vein 'Doppler' flow velocity waveforms were then studied. RESULTS AND CONCLUSIONS: Flow reversal in pulmonary veins during atrial contraction indicates hypoxia, but change of shape of the FVW envelope reflects the changes in the pressure waveform of the left atrium. Of the major veins the pulmonary vein Doppler FVW gave the truest representation of atrial pressure response to both intracardiac and systemic vascular status. Although current indices indicate general fetal condition, more specific indices are needed if pulmonary venous flow is to be used as an end-point. A pulmonary vein pressure gradient index is suggested.

Audible in utero sound caused by the ultrasonic radiation force from a real-time scanner.

While investigating in utero sound levels during vibro-acoustic stimulation on the maternal abdomen it was noticed that noise level increased when the real-time ultrasonic scanner beam was directed at the sensing hydrophone. The noise was recorded and later analysed for frequency content and waveform. It appeared related to the scanning and frame rate frequencies of the scanner used. Sounds may originate from radiation pressure produced when the ultrasound beam is absorbed by tissue or reflected from bone or the metal hydrophone. This implies that although ultrasound cannot be heard per se, any modulation of its intensity will produce vibrations in the maternal tissues or reflecting structures such as skull bone, and especially stapes, malleus and incus, that would be heard as sound by the fetus. The intensity of the sound produced varied with orientation of the transducer beam and this may itself produce a stimulation. Based on our recordings (Fig. 1), it was calculated (please see Appendix) that the fetus would hear a sound corresponding to 84dB noise pressure level in air.

Hydrostatic and osmotic pressure gradients produce manifestations of fetofetal transfusion syndrome in a computerized model of monochorial twin pregnancy.

OBJECTIVE: In spite of recent advances in the assessment and treatment of fetofetal transfusion syndrome, its underlying mechanism remains controversial. We aimed to determine whether the clinical features of fetofetal transfusion syndrome could be explained by unidirectional or bidirectional intertwin transfusion along placental vascular anastomoses. STUDY DESIGN: We constructed a dynamic computerized model of monochorial twin fetoplacental units on the basis of numerous interrelated hemodynamic, osmotic, and metabolic physiologic variables. The circulations were then linked by various combinations of direction and number of arteriovenous anastomoses. RESULTS: With unidirectional anastomoses disease severity, characterized by disparity in blood solids, depended on donor arterial pressure but not on the number of anastomoses. In the chronic state water movement resulting from raised osmotic pressure in the recipient and reduction in the donor produced hydroosmotic pressure equilibrium, reducing anastomotic flow to near zero. Atrial natriuretic peptide-driven urine production was markedly increased in the recipient because of the raised vascular hydrostatic pressure component. With bidirectional anastomoses recirculation between twins reduced discordancy in colloids and hematocrit, and the clinical picture was determined by the degree of asymmetry in the number of connections. CONCLUSIONS: Severe manifestations of fetofetal transfusion syndrome can be explained by unidirectional intertwin transfusion and lesser degrees by asymmetric bidirectional transfusion.

Uterine flow velocity waveform shape as an indicator of maternal and placental development failure mechanisms: a model-based synthesizing approach.

High pulsatility indices (PIs) and/or notches on the Doppler flow velocity waveforms of the uterine artery have been interpreted as indications of high placental flow impedance, and are known to be associated with poor fetal outcome. A software model of the uteroplacental blood path and its use to investigate possible interactions within the uteroplacental unit in more detail are described. Increasing transcotyledonary resistance to represent intervillous obstruction raised the cotyledonary core pressure and spiral artery PI. Increased spiral artery flow resistance, representing failed spiral artery invasion, reduced the cotyledonary core pressure and reduced the spiral artery PI. In vivo, such changes in cotyledonary core pressure would modify the transplacental water balance, promoting oligohydramnios for spiral artery invasion failure and polyhydramnios for villous obstruction. Both mechanisms increased the uterine and arcuate PI, but failed to produce a notch. It was found that notch formation depended on terms representing increased compliance (distensibility) of the uterine and/or arcuate artery walls, which have no direct effect on uteroplacental mean flow. The same mechanism steepened and increased uterine artery peak systolic flow, contributing to increased PI. The notch phenomenon seems to be an indicator of abnormal maternal artery wall status, independent of placental obstructive mechanisms, which can mask obstructive PI changes. Computer analysis of the frequency index profile should allow separation.

Uterine artery blood flow response to correction of amniotic fluid volume.

OBJECTIVE: Our purpose was to investigate whether acute alterations of amniotic fluid volume affect uteroplacental perfusion. STUDY DESIGN: Three groups of patients of comparable gestational age were studied in a fetal medicine referral unit: (1) eight pregnancies with severe polyhydramnios because of twin-twin transfusion syndrome undergoing therapeutic amnioreduction, (2) seven with severe oligohydramnios undergoing diagnostic amnioinfusion, and (3) six control women having invasive procedures of similar duration without manipulation of amniotic fluid volume. Color Doppler imaging was used to measure uterine artery impedance index values and quantitative blood flow before and within 15 minutes of the end of the procedure. RESULTS: Quantitative flow measurements increased after amnioreduction (74% median increase of volume flow, range 22% to 329%, p < 0.01) and decreased after amnioinfusion (33% median decrease of volume flow, range 17% to 51%, p < 0.05). Impedance index values increased after amnioinfusion (25% median increase in pulsatility index, range 4% to 71%, p < 0.05) and did not alter with amnioreduction. There were no significant changes in the control group. CONCLUSION: Acute changes in amniotic fluid volume alter uteroplacental perfusion. In twin-twin transfusion syndrome amelioration in uterine flow may improve fetal condition and explain in part the success of serial amnioreduction therapy.

Needle modifications for invasive fetal procedures.

OBJECTIVE: To investigate the effect of needle size and siliconization on fetal blood sampling, transfusion, and electrocardiography. METHODS: Standard needles were modified by increasing the internal (but not the external) diameter and either siliconization of the bore or external Teflon coating. The siliconized needles were subjected to a series of flow experiments with either blood or saline at various driving pressures, and assessed in clinical use during fetal transfusion and fetal blood sampling. The Teflon-coated needles were used for fetal transfusion to try and facilitate the fetal electrocardiogram (ECG). RESULTS: Under conditions simulating fetal transfusion, the siliconized needle allowed a 93% increase in flow rate compared to the standard needle (P < .05). Samples obtained after fetal transfusion with the siliconized needles were free of clots, whereas 50% of the post-transfusion samples with the standard needle had clots present. Similarly, samples taken for fetal platelet count were free of platelet clumping and clots with siliconized needles, but not with standard needles. Fetal ECG recordings were recorded successfully when Teflon-coated needles were used to access the fetal circulation via the intrahepatic vein. CONCLUSIONS: Modifications to standard needles improved blood flow and reduced the activation of coagulation during both fetal intravascular transfusion and platelet count measurement. Direct fetal ECG recording was facilitated by Teflon coating the external surface of the needle, insulating the fetal signal from maternal electrical signals.

Changes in hemorheology with fetal intravascular transfusion.

OBJECTIVE: Our aim was to determine the changes in fetal hemorheologic parameters caused by fetal intravascular transfusion for alloimmune anemia. STUDY DESIGN: Fetal blood samples were collected before and after 95 fetal transfusions in 31 women. Fetal hematocrit, whole-blood viscosity at a variety of shear rates, plasma viscosity, fetal fibrinogen, and fetal plasma proteins were measured. RESULTS: Fetal whole-blood viscosity increased, sometimes massively, with transfusion. The rise in viscosity was principally dependent on the rise in hematocrit, with a linear rise in hematocrit producing a linear rise in the logarithm of whole-blood viscosity, but was also affected by the amount of adult plasma proteins present in the donor blood. CONCLUSIONS: Rises in fetal whole-blood viscosity during transfusion can be minimized by using donor blood that has been serum depleted to a high hematocrit (> 90%) and by restricting the end hematocrit to 50% to 55%.

Fetal breathing movements in oligohydramnios are not increased by aminoinfusion.

OBJECTIVE: To determine whether fetal breathing movements (FBM) in pregnancies with oligohydramnios change with restoration of amniotic fluid volume. DESIGN: A prospective experimental study. SETTING: Fetal Medicine Unit, tertiary referral hospital. SUBJECTS: 16 women with singleton pregnancies complicated by severe oligohydramnios. INTERVENTIONS: Restoration of amniotic fluid volume by transabdominal amnioinfusion. Controls comprised pregnancies in which infused fluid leaked vaginally, so that oligohydramnios was not corrected. MAIN OUTCOME MEASURES: Change in total breathing movements, change in FBM incidence derived from 40 min recordings immediately before and after amnioinfusion. RESULTS: There was no significant difference in the change in total breathing movements or in the change in incidence of FBM between the 10 pregnancies in which amniotic fluid volume was restored, and the other six in which fluid leaked after infusion and volume was not restored. In both groups, there was no significant change with infusion in number of FBM (mean change -72, 95% CI -218 to +74 in the fluid-retained group and -64, 95% CI -273 to +145 in the fluid-leaked group) and incidence of FBM (median change -2.5%, range -27 to +10 in the fluid retained group and -4.5%, range -34 to +15 in the fluid-leaked group). CONCLUSIONS: This study suggests that restitution of amniotic fluid volume in human pregnancies complicated by severe oligohydramnios does not acutely alter the incidence of FBM. These data support an increasing literature suggesting that impairment of fetal breathing is not the mechanism for oligohydramnios-related pulmonary hypoplasia.