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Doppler ultrasound in the management of fetal growth restriction and IUGR

by Chukwuma Onyeije

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Doppler ultrasound in the management of fetal growth restriction or IUGR

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Leo Voisey Stem cells are “non-specialized” cells that have the potential to form into other types of specific cells, such as blood, muscles or nerves. They are unlike 'differentiated' cells which have already become whatever organ or structure they are in the body. Stem cells are present throughout our body, but more abundant in a fetus.
Medical researchers and scientists believe that stem cell therapy will, in the near future, advance medicine dramatically and change the course of disease treatment. This is because stem cells have the ability to grow into any kind of cell and, if transplanted into the body, will relocate to the damaged tissue, replacing it. For example, neural cells in the spinal cord, brain, optic nerves, or other parts of the central nervous system that have been injured can be replaced by injected stem cells. Various stem cell therapies are already practiced, a popular one being bone marrow transplants that are used to treat leukemia. In theory and in fact, lifeless cells anywhere in the body, no matter what the cause of the disease or injury, can be replaced with vigorous new cells because of the remarkable plasticity of stem cells. Biomed companies predict that with all of the research activity in stem cell therapy currently being directed toward the technology, a wider range of disease types including cancer, diabetes, spinal cord injury, and even multiple sclerosis will be effectively treated in the future. Recently announced trials are now underway to study both safety and efficacy of autologous stem cell transplantation in MS patients because of promising early results from previous trials.
History
Research into stem cells grew out of the findings of two Canadian researchers, Dr’s James Till and Ernest McCulloch at the University of Toronto in 1961. They were the first to publish their experimental results into the existence of stem cells in a scientific journal. Till and McCulloch documented the way in which embryonic stem cells differentiate themselves to become mature cell tissue. Their discovery opened the door for others to develop the first medical use of stem cells in bone marrow transplantation for leukemia. Over the next 50 years their early work has led to our current state of medical practice where modern science believes that new treatments for chronic diseases including MS, diabetes, spinal cord injuries and many more disease conditions are just around the corner.
There are a number of sources of stem cells, namely, adult cells generally extracted from bone marrow, cord cells, extracted during pregnancy and cryogenically stored, and embryonic cells, extracted from an embryo before the cells start to differentiate. As to source and method of acquiring stem cells, harvesting autologous adult cells entails the least risk and controversy.
Autologous stem cells are obtained from the patient’s own body; and since they are the patient’s own, autologous cells are better than both cord and embryonic sources as they perfectly match the patient’s own DNA, meaning that they will never be rejected by the patient’s immune system. Autologous transplantation is now happening therapeutically at several major sites world-wide and more studies on both safety and efficacy are finally being announced. With so many unrealized expectations of stem cell therapy, results to date have been both significant and hopeful, if taking longer than anticipated.
What’s been the Holdup?
Up until recently, there have been intense ethical debates about stem cells and even the studies that researchers have been allowed to do. This is because research methodology was primarily concerned with embryonic stem cells, which until recently required an aborted fetus as a source of stem cells. The topic became very much a moral dilemma and research was held up for many years in the US and Canada while political debates turned into restrictive legislation. Other countries were not as inflexible and many important research studies have been taking place elsewhere. Thankfully embryonic stem cells no longer have to be used as much more advanced and preferred methods have superseded the older technologies. While the length of time that promising research has been on hold has led many to wonder if stem cell therapy will ever be a reality for many disease types, the disputes have led to a number of important improvements in the medical technology that in the end, have satisfied both sides of the ethical issue.
CCSVI Clinic
CCSVI Clinic has been on the leading edge of MS treatment for the past several years. We are the only group facilitating the treatment of MS patients requiring a 10-day patient aftercare protocol following neck venous angioplasty that includes daily ultrasonography and other significant therapeutic features for the period including follow-up surgeries if indicated. There is a strict safety protocol, the results of which are the subject of an approved IRB study. The goal is to derive best practice standards from the data. With the addition of ASC transplantation, our research group has now preparing application for member status in International Cellular Medicine Society (ICMS), the globally-active non-profit organization dedicated to the improvement of cell-based medical therapies through education of physicians and researchers, patient safety, and creating universal standards. For more information please visit http://www.neurosurgeonindia.org/ 1 year ago
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Jessica Forester After 6 months of offering stem cell therapy in combination with the venous angioplasty liberation procedure, patients of CCSVI Clinic have reported excellent health outcomes. Ms. Kasma Gianopoulos of Athens Greece, who was diagnosed with the Relapsing/Remitting form of MS in 1997 called the combination of treatments a “cure”. “I feel I am completely cured” says Ms. Gianopoulos, “my symptoms have disappeared and I have a recovery of many functions, notably my balance and my muscle strength is all coming (back). Even after six months, I feel like there are good changes happening almost every day. Before, my biggest fear was that the changes wouldn’t (hold). I don’t even worry about having a relapse anymore. I’m looking forward to a normal life with my family. I think I would call that a miracle.”
Other recent MS patients who have had Autologous Stem Cell Transplantation (ASCT), or stem cell therapy have posted videos and comments on YouTube. www.youtube.com/watch?v=jFQr2eqm3Cg.
Dr. Avneesh Gupte, the Neurosurgeon at Noble Hospital performing the procedure has been encouraged by results in Cerebral Palsy patients as well. “We are fortunate to be able to offer the treatment because not every hospital is able to perform these types of transplants. You must have the specialized medical equipment and specially trained doctors and nurses”. With regard to MS patients, “We are cautious, but nevertheless excited by what patients are telling us. Suffice to say that the few patients who have had the therapy through us are noticing recovery of neuro deficits beyond what the venous angioplasty only should account for”.
Dr. Unmesh of Noble continues: “These are early days and certainly all evidence that the combination of liberation and stem cell therapies working together at this point is anecdotal. However I am not aware of other medical facilities in the world that offer the synthesis of both to MS patients on an approved basis and it is indeed a rare opportunity for MS patients to take advantage of a treatment that is quite possibly unique in the world”.
Autologous stem cell transplantation is a procedure by which blood-forming stem cells are removed, and later injected back into the patient. All stem cells are taken from the patient themselves and cultured for later injection. In the case of a bone marrow transplant, the HSC are typically removed from the Pelvis through a large needle that can reach into the bone. The technique is referred to as a bone marrow harvest and is performed under a general anesthesia. The incidence of patients experiencing rejection is rare due to the donor and recipient being the same individual.This remains the only approved method of the SCT therapy. 1 year ago
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Because classification of LBW as due to preterm birth or IUGR requires valid estimates of gestational age (GA), attention is required to improving the availability and quality of GA estimates on a population-wide basis in developing countries. This includes, where feasible, recording early in pregnancy the mother's recall of the date her last normal menstrual period began and the training of birth attendants (traditional birth attendants, midwives, nurses, and physicians) in the physical assessment of the newborn (Dubowitz, Ballard, or Capurro scores). In developed countries, early (< 20 weeks) ultrasound examination has improved the validity and reliability of GA assessment, although evidence from randomized trials does not demonstrate improvement in maternal or fetal/infant outcomes with routine early ultrasound. An international fetal growth reference curve should be developed based on pooled data from countries in different geographic regions where fetal growth is believed optimal. Care should be taken to ensure that such a reference fits with the new infant growth reference currently being developed under WHO auspices. Further research is needed to identify those determinants of fetal growth that influence mortality, morbidity, and performance independently of their effects on growth. Although it is quite clear that the use of sex-specific reference curves is justifiable, additional research is needed using large populations and ultrasound confirmation of GA to assess whether infants of different races born at a particular weight for gestational age are at substantially different risks for important health outcomes. Similar research is needed to determine whether infants who are born small because their mothers are primiparous or of short stature or living at high altitude are at the same risk for adverse sequelae as those of equivalent size who are small because, for example, their mothers have pre-eclampsia or smoke cigarettes. Until this information is available, the use of a single, sex-specific international reference has much to recommend it.
Description There are standards or averages in weight for unborn babies according to their age in weeks. When the baby's weight is at or below the 10th percentile for his or her age, it is called intrauterine growth retardation or fetal growth restriction. These babies are smaller than they should be for their age. How much a baby weighs at birth depends not only on how many weeks old it is, but the rate at which it has grown. This growth process is complex and delicate. There are three phases associated with the development of the baby. During the first phase, cells multiply in the baby's organs. This occurs from the beginning of development through the early part of the fourth month. During the second phase, cells continue to multiply and the organs grow. In the third phase (after 32 weeks of development), growth occurs quickly and the baby may gain as much as 7 ounces per week. If the delicate process of development and weight gain is disturbed or interrupted, the baby can suffer from restricted growth.
Application of the international foetal growth reference curve will vary according to its specific clinical and public health uses or purposes. Criteria for diagnosis of foetal growth restriction (e.g., SGA) should be related to evidence of increased risk for perinatal mortality and/or other indices of adverse outcomes. The new reference should provide percentiles [(e.g., 3rd, 5th, 10th, 15th, 25th, 50th (median), 75th, 85th, 90th, 95th, and 97th)] as well as z-scores [(e.g., -3, -2, -1, 0 (mean), 1, 2, and 3 SD)], so that health planners and practitioners can use the most appropriate cut off based on local circumstances. Proportionality at birth may be related to adverse outcomes. Thus there is a need to develop reference data for birth length and head circumference in relation to GA, and for birth weight in relation to birth length. Because the concepts of 'wasting' and 'stunting' have proven useful for categorizing undernourished infants and older children, an attempt should be made to quantify the mortality and morbidity risks associated with 'wasted' and 'stunted' newborns and to develop indicators for their classification.
Most of the evidence on etiologic determinants is based on observational studies and systematic overviews or meta-analyses of such studies. In developing countries, the major determinants of IUGR are nutritional: low gestational weight gain (primarily due to inadequate energy intake), low pre-pregnancy BMI (reflecting chronic maternal undernutrition), and short maternal stature (principally due to undernutrition and infection during childhood). Gastroenteritis, intestinal parasitosis, and respiratory infections are prevalent in developing countries and may also have an important impact. Malaria is a major determinant in countries where that disease is endemic. Cigarette smoking is an increasingly important factor in some settings. In developed countries, cigarette smoking is far and away the most important etiologic determinant, but low gestational weight gain and low pre-pregnancy BMI are also determinants. The etiologic roles of pre-eclampsia, short stature, genetic factors, and alcohol and drug use during pregnancy are well-established but quantitatively less important. Socioeconomic disparities in IUGR risk within developed countries are largely attributable to socioeconomic gradients in smoking, weight gain and maternal stature. In poor urban areas where cocaine abuse is highly prevalent, this may also be important.
The etiologic role of micronutrients in IUGR remains to be clarified. The best evidence concerning their importance derives from randomized trials and from systematic overviews of those trials contained in the Cochrane Collaboration Pregnancy and Childbirth database. Unfortunately, there are few supplementation or fortification trials in developing country settings where deficiencies in these micronutrients are prevalent. Trials are required to define the possible etiologic roles of iron, calcium, vitamin D, and vitamin A, especially in developing countries. The evidence concerning folate, magnesium, and zinc also looks sufficiently promising to justify further investigation. The physiologic and molecular mechanisms by which nutritional or other determinants affect fetal growth are incompletely understood. Growth is determined not only by substrate availability but also by the integrity of physiologic processes necessary to ensure transfer of nutrients and oxygen to the developing fetus. Expansion of maternal plasma volume, maintenance of uterine blood flow, and development of adequate placentation are key physiologic mechanisms required for optimal fetal growth. All substances used by the fetus are transported by the placenta: some (like oxygen and most other gases) by passive diffusion, others by facilitated transport proteins (e.g., Glut 1 for glucose), and still others (e.g., amino acids) by active energy-dependent transport processes. Insulin-like growth factors (IGFs) are important mediators of substrate incorporation into fetal tissue. IGF 1 appears to induce cell differentiation, including (perhaps) oligodendrocyte development in the brain, whereas IGF 2 may function to stimulate mitosis. It remains uncertain whether these physiologic and molecular mechanisms are merely the final common pathways for genetic or environmental determinants of IUGR, or whether they themselves vary (favorably or pathologically) independently of those determinants.
The etiologic role of micronutrients in IUGR remains to be clarified. The best evidence concerning their importance derives from randomized trials and from systematic overviews of those trials contained in the Cochrane Collaboration Pregnancy and Childbirth database. Unfortunately, there are few supplementation or fortification trials in developing country settings where deficiencies in these micronutrients are prevalent. Trials are required to define the possible etiologic roles of iron, calcium, vitamin D, and vitamin A, especially in developing countries. The evidence concerning folate, magnesium, and zinc also looks sufficiently promising to justify further investigation. The physiologic and molecular mechanisms by which nutritional or other determinants affect fetal growth are incompletely understood. Growth is determined not only by substrate availability but also by the integrity of physiologic processes necessary to ensure transfer of nutrients and oxygen to the developing fetus. Expansion of maternal plasma volume, maintenance of uterine blood flow, and development of adequate placentation are key physiologic mechanisms required for optimal fetal growth. All substances used by the fetus are transported by the placenta: some (like oxygen and most other gases) by passive diffusion, others by facilitated transport proteins (e.g., Glut 1 for glucose), and still others (e.g., amino acids) by active energy-dependent transport processes. Insulin-like growth factors (IGFs) are important mediators of substrate incorporation into fetal tissue. IGF 1 appears to induce cell differentiation, including (perhaps) oligodendrocyte development in the brain, whereas IGF 2 may function to stimulate mitosis. It remains uncertain whether these physiologic and molecular mechanisms are merely the final common pathways for genetic or environmental determinants of IUGR, or whether they themselves vary (favorably or pathologically) independently of those determinants.
IUGR can be difficult to diagnose and in many cases doctors are not able to make an exact diagnosis until the baby is born. A mother who has had a growth restricted baby is at risk of having another during a later pregnancy. Such mothers are closely monitored during pregnancy. The length in weeks of the pregnancy must be carefully determined so that the doctor will know if development and weight gain are appropriate. Checking the mother's weight and abdomen measurements can help diagnose cases when there are no other risk factors present. Measuring the girth of the abdomen is often used as a tool for diagnosing IUGR. During pregnancy, the healthcare provider will use a tape measure to record the height of the upper portion of the uterus (the uterine fundal height). As the pregnancy continues and the baby grows, the uterus stretches upward in the direction of the mother's head. Between 18 and 30 weeks of gestation, the uterine fundal height (in cm.) equals the weeks of gestation. If the uterine fundal height is more than 2-3 cm below normal, then IUGR is suspected. Ultrasound is used to evaluate the growth of the baby. Usually, IUGR is diagnosed after week 32 of pregnancy. This is during the phase of rapid growth when the baby should be gaining more weight. IUGR caused by genetic factors or infection may sometimes be detected earlier.
Systematic reviews provide strong evidence of benefit only for the following interventions: balanced protein/energy supplementation, strategies to reduce maternal smoking, and antimalarial prophylaxis. In Jamaica, antibiotic administration to prevent urinary tract infections further reduced an already low prevalence of IUGR. Improvement of maternal nutrition should be a priority, especially in developing countries. Unless maternal undernutrition is severe, the effect of balanced protein/energy supplementation on birth weight is likely to be modest » 100 g). Reduction in maternal smoking should be encouraged, both by individual clinicians (using behavioral modification techniques, for example) and by policy makers (e.g., taxes on cigarettes and other tobacco products). Antimalarial chemoprophylaxis should be provided in endemic areas, particularly to primigravidae, although more research is needed to elucidate the ideal timing of treatment, combination of agents, and safety for the fetus.
This is an example of a foetus at risk for IUGR in which the amniotic fluid index was measured but the nurses and physician did not understand the principles of an abnormal reading. The foetus was allowed to remain in utero and developed cerebral palsy from oxygen deprivation. The family sued the hospital and the physician and was awarded 9.7 million dollars which was the largest malpractice award in the state of Utah This is the amniotic fluid index in the above case. The blue represents the normal range. At 35 weeks the fluid measurement was 16. Four days later it dropped to 6.3. This sudden drop was ignored by the nurses and physician caring for the patient. A few days later the fetus was damaged because the umbilical cord was compressed, resulting in cerebral palsy.
Babies who suffer from IUGR are at an increased risk fordeath, low blood sugar, low body temperature, and abnormal development of the nervous system. These risks increase with the severity of the growth restriction. The growth that occurs after birth cannot be predicted with certainty based on the size of the baby when it is born. Infants with asymmetrical IUGR are more likely to catch up in growth after birth than are infants who suffer from prolonged symmetrical IUGR. However, as of 1998, doctors cannot reliably predict an infant's future progress. Each case is unique. Some infants who have IUGR will develop normally, while others will have complications of the nervous system or intellectual problems like learning disorders. If IUGR is related to a disease or a genetic defect, the future of the infant is related to the severity and the nature of that disorder.

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Doppler ultrasound in the management of fetal growth restriction and IUGR Presentation Transcript

- Intrauterine growth retardation (IUGR)
- Small for Gestational Age:
- Low Birth weight (LBW)
- Multiple gestation
- Drug exposure
- Cardiovascular disease
- Kidney disease
- Chronic infections
- Autoimmune disease
- TORCH infections
- Fetal anomalies
- Aneuploidy
- Skeletal Dysplasia
- Hypoxia
- Uteroplacental insufficiency
- Fetoplacetal insufficiency due to-.
- Difficult diagnosis
- Need to evaluate risk factors
- Serial ultrasounds important
- Dating is important
- Ultrasound signs
- Normal & IUGR Newborn babies
- Normal & IUGR Placentas
- Duration: Until delivery occurs
- Reason : To identify further progression of the disease process that would jeopardize the fetus.
- Modalities : NST, AFI, Doppler, BPP
- Doppler of the Umbilical Artery
- A reduction in perinatal deaths.
- Fewer inductions of labour .
- Fewer admissions to hospital .
- no report of adverse effects .
- No difference was found for fetal distress in labour .
- No difference in caesarean delivery .
- Increased perinatal morbidity and mortality.
- Babies who suffer from IUGR are at an increased risk for death , low blood sugar , low body temperature , and abnormal development of the nervous system. These risks increase with the severity of the growth restriction.
- The growth that occurs after birth cannot be predicted with certainty based on the size of the baby when it is born.
- Infants with asymmetrical IUGR are more likely to catch up in growth after birth than are infants who suffer from prolonged symmetrical IUGR.
- If IUGR is related to a disease or a genetic defect, the future of the infant is related to the severity and the nature of that disorder.
- IUGR infants are more likely to remain small than those of normal birth weight. They will need the special attention of primary health, nutrition and social services during infancy and early childhood.
- Implication of IUGR can be life long affecting:
- It appears to predispose to adult adult-onset, degenerative disease s like maturity onset diabetes and cardiovascular diseases.
- Each case is unique. C an not reliably predict an infant's future progress.

Doppler ultrasound in the management of fetal growth restriction and IUGR

by Chukwuma Onyeije

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Doppler ultrasound in the management of fetal growth restriction and IUGR Presentation Transcript