Intrauterine hypoxia | |
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Micrograph of a placental infarct (left of image), a cause of intrauterine hypoxia. H&E stain. | |
Specialty | Pediatrics |
Intrauterine hypoxia (also known as fetal hypoxia) occurs when the fetus is deprived of an adequate supply of oxygen. It may be due to a variety of reasons such as prolapse or occlusion of the umbilical cord, placental infarction, maternal diabetes (prepregnancy or gestational diabetes) [1] and maternal smoking. Intrauterine growth restriction may cause or be the result of hypoxia. Intrauterine hypoxia can cause cellular damage that occurs within the central nervous system (the brain and spinal cord). This results in an increased mortality rate, including an increased risk of sudden infant death syndrome (SIDS). Oxygen deprivation in the fetus and neonate have been implicated as either a primary or as a contributing risk factor in numerous neurological and neuropsychiatric disorders such as epilepsy, attention deficit hyperactivity disorder, eating disorders and cerebral palsy. [2] [3] [4] [5] [6] [7]
Complications arising from intrauterine hypoxia are some of most common causes of preeclampsia. [8] Preeclampsia is a hypertensive disorder that occurs during the second trimester (after the 20th week of pregnancy) resulting from a poorly perfused placenta. [9] The World Health Organization estimates that preeclampsia and eclampsia are responsible for about 14% of maternal deaths globally (around 50,000 to 75,000 deaths annually). [10]
During pregnancy, women with preeclampsia faces serious risk of damage to vital organs such as the kidneys, liver, brain, and the blood system. This hypertensive disorder may also cause damage to the placenta leading to issues such as premature births, miscarriages, placental abruption, or even stillbirths. In some cases, preeclampsia can eventually lead to stroke and organ failure. Untreated, preeclampsia can progress and turn into eclampsia which is much more severe with the addition of seizures. Eclampsia seizures could lead to uncontrollable twitching and a loss of consciousness, which could potentially lead to the death of the mother and or the baby. [11]
Intrauterine hypoxia can be attributed to maternal, placental, or fetal conditions. [12] Kingdom and Kaufmann classifies three categories for the origin of fetal hypoxia: 1) pre-placental (both mother and fetus are hypoxic), 2) utero-placental (mother is normal but placenta and fetus is hypoxic), 3) post-placental (only fetus is hypoxic). [13]
Pre-placental hypoxia is most commonly caused by external hypoxic environments (such as high altitude). It can also be caused by maternal respiratory conditions (such as asthma), cardiovascular conditions (such as heart failure, pulmonary hypertension, and cyanotic heart disease), and hematological conditions (such as anemia). [14] Conditions such as obesity, nutritional deficiencies, infections, chronic inflammations, and stress can also affect the maternal oxygen supply and fetal uptake. [12]
The most preventable cause is maternal smoking. Cigarette smoking by expectant mothers has been shown to have a wide variety of deleterious effects on the developing fetus. [15] Among the negative effects are carbon monoxide induced tissue hypoxia and placental insufficiency which causes a reduction in blood flow from the uterus to the placenta thereby reducing the availability of oxygenated blood to the fetus. Placental insufficiency as a result of smoking has been shown to have a causal effect in the development of pre-eclampsia. While some previous studies have suggested that carbon monoxide from cigarette smoke may have a protective effect against preeclampsia, a recent study conducted by the Genetics of Pre-Eclampsia Consortium in the United Kingdom found that smokers were five times more likely to develop pre-eclampsia. [16] Nicotine alone has been shown to be a teratogen which affects the autonomic nervous system, leading to increased susceptibility to hypoxia-induced brain damage. [16] [17] [18] [19] [20] [21] Maternal anemia in which smoking has also been implicated is another factor associated with IH/BA.[ clarification needed ] Smoking by expectant mothers causes a decrease in maternal nucleated red blood cells, thereby reducing the amount of red blood cells available for oxygen transport. [22] [23] [24]
Utero-placental hypoxia is associated with abnormal placental implantation, impaired vascular remodeling and vascular diseases. [14] It is also associated with pregnancies complicated by gestational hypertension, intrauterine growth restriction, and pre-eclampsia. [25] [26]
Post-placental hypoxia is associated with mechanical obstructions of the umbilical cords, reduced uterine artery flow, progressive fetal cardiac failure, and genetic anomalies. [12] [14]
The perinatal brain injury occurring as a result of birth asphyxia, manifesting within 48 hours of birth, is a form of hypoxic ischemic encephalopathy. [27]
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Treatment of infants with birth asphyxia by lowering the core body temperature is now known to be an effective therapy to reduce mortality and improve neurological outcome in survivors, and hypothermia therapy for neonatal encephalopathy begun within 6 hours of birth significantly increases the chance of normal survival in affected infants. [28]
There has long been a debate over whether newborn infants with birth asphyxia should be resuscitated with 100% oxygen or normal air. [29] It has been demonstrated that high concentrations of oxygen lead to generation of oxygen free radicals, which have a role in reperfusion injury after asphyxia. [30] Research by Ola Didrik Saugstad and others led to new international guidelines on newborn resuscitation in 2010, recommending the use of normal air instead of 100% oxygen. [31] [32] Increasing the oxygen concentration to the mother has shown little effect on the fetus as hyperoxygenated blood does not perfuse the placental exchange site well. [33]
Underlying etiology of intrauterine hypoxia serves as a potential therapeutic target. If maternal preeclampsia [34] is the underlying cause of fetal growth restriction (FGR) antihypertensive therapy and magnesium sulfate are potential therapies. [12] Antihypertensive treatment is used to reduce blood pressure and prevent pulmonary edema and cerebral hemorrhages. An effective course of antihypertensive treatments should reduce blood pressure to below 160/110 mmHg. Magnesium sulfate acts as a vasodilator, reducing vascular resistance and protect the blood-brain barrier (BBB). The goal of these treatments is to prolong pregnancy and increase fetal survival. Each day gained by treatment in utero increases fetal survival and intact survival by 1%–2% up to 28 weeks gestation. [35]
Medical testing and care can be performed in order to prevent intrauterine hypoxia, though can be difficult. These tests don't directly detect hypoxia, but instead detects the general well-being of the baby and ensures that the baby is healthy since hypoxia causes a wide range of responses. These tests can include prenatal testing, such as fetal movement and amniotic fluid levels, Doppler examination, or fetal heart rate. [36] Another risk factor is premature birth in which medical intervention, such as premature birth prevention or C-section delivery, can be used as prevention for intrauterine hypoxia. [37]
Studies have shown a connection between tetrahydrobiopterin (BH4) deficiency and hypoxia-ischemia brain injury, though further studies need to be done. [38] Measuring fetal BH4 levels can be another way to look out for intrauterine hypoxia.[ citation needed ]
During birth, birth asphyxia can occur in which cardiotocograph can be used to monitor the baby's health during labor. [39]
In the United States, intrauterine hypoxia and birth asphyxia were listed together as the tenth leading cause of neonatal death. [40]
IH/BA is also a causative factor in cardiac and circulatory birth defects the sixth most expensive condition, as well as premature birth and low birth weight the second most expensive and it is one of the contributing factors to infant respiratory distress syndrome (RDS) also known as hyaline membrane disease, the most expensive medical condition to treat and the number one cause of infant mortality. [41] [42] [43]
Most expensive medical condition treated in U.S. hospitals. 4 out of 10 linked to intrauterine hypoxia/birth asphxia | Cost | Hospital Charge |
1. Infant respiratory distress syndrome | $45,542 | $138,224 |
2. Premature birth and low birth weight | $44,490 | $119,389 |
6. Cardiac and circulatory birth defects | $35,960 | $101,412 |
9. Intrauterine hypoxia or birth asphyxia | $27,962 | $74,942 |
In the United States the National Practitioner Data Bank 2006 Annual Report obstetrics-related cases accounted for 8.7 percent of all 2006 physician Malpractice Payment Reports and had the highest median payment amounts ($333,334). [44]
Intrauterine growth restriction (IUGR), or fetal growth restriction, refers to poor growth of a fetus while in the womb during pregnancy. IUGR is defined by clinical features of malnutrition and evidence of reduced growth regardless of an infant's birth weight percentile. The causes of IUGR are broad and may involve maternal, fetal, or placental complications.
Eclampsia is the onset of seizures (convulsions) in a woman with pre-eclampsia. Pre-eclampsia is a hypertensive disorder of pregnancy that presents with three main features: new onset of high blood pressure, large amounts of protein in the urine or other organ dysfunction, and edema. If left untreated, pre-eclampsia can result in long-term consequences for the mother, namely increased risk of cardiovascular diseases and associated complications. In more severe cases, it may be fatal for both the mother and the fetus. The diagnostic criteria for pre-eclampsia is high blood pressure occurring after 20 weeks gestation or during the second half of pregnancy. Most often it occurs during the 3rd trimester of pregnancy and may occur before, during, or after delivery. The seizures are of the tonic–clonic type and typically last about a minute. Following the seizure, there is either a period of confusion or coma. Other complications include aspiration pneumonia, cerebral hemorrhage, kidney failure, pulmonary edema, HELLP syndrome, coagulopathy, placental abruption and cardiac arrest.
Pre-eclampsia is a multi-system disorder specific to pregnancy, characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease there may be red blood cell breakdown, a low blood platelet count, impaired liver function, kidney dysfunction, swelling, shortness of breath due to fluid in the lungs, or visual disturbances. Pre-eclampsia increases the risk of undesirable as well as lethal outcomes for both the mother and the fetus including preterm labor. If left untreated, it may result in seizures at which point it is known as eclampsia.
Fetal distress, also known as non-reassuring fetal status, is a condition during pregnancy or labor in which the fetus shows signs of inadequate oxygenation. Due to its imprecision, the term "fetal distress" has fallen out of use in American obstetrics. The term "non-reassuring fetal status" has largely replaced it. It is characterized by changes in fetal movement, growth, heart rate, and presence of meconium stained fluid.
Gestational hypertension or pregnancy-induced hypertension (PIH) is the development of new hypertension in a pregnant woman after 20 weeks' gestation without the presence of protein in the urine or other signs of pre-eclampsia. Gestational hypertension is defined as having a blood pressure greater than 140/90 on two occasions at least 6 hours apart.
Placental abruption is when the placenta separates early from the uterus, in other words separates before childbirth. It occurs most commonly around 25 weeks of pregnancy. Symptoms may include vaginal bleeding, lower abdominal pain, and dangerously low blood pressure. Complications for the mother can include disseminated intravascular coagulopathy and kidney failure. Complications for the baby can include fetal distress, low birthweight, preterm delivery, and stillbirth.
Perinatal asphyxia is the medical condition resulting from deprivation of oxygen to a newborn infant that lasts long enough during the birth process to cause physical harm, usually to the brain. It remains a serious condition which causes significant mortality and morbidity. It is also the inability to establish and sustain adequate or spontaneous respiration upon delivery of the newborn, an emergency condition that requires adequate and quick resuscitation measures. Perinatal asphyxia is also an oxygen deficit from the 28th week of gestation to the first seven days following delivery. It is also an insult to the fetus or newborn due to lack of oxygen or lack of perfusion to various organs and may be associated with a lack of ventilation. In accordance with WHO, perinatal asphyxia is characterised by: profound metabolic acidosis, with a pH less than 7.20 on umbilical cord arterial blood sample, persistence of an Apgar score of 3 at the 5th minute, clinical neurologic sequelae in the immediate neonatal period, or evidence of multiorgan system dysfunction in the immediate neonatal period. Hypoxic damage can occur to most of the infant's organs, but brain damage is of most concern and perhaps the least likely to quickly or completely heal. In more pronounced cases, an infant will survive, but with damage to the brain manifested as either mental, such as developmental delay or intellectual disability, or physical, such as spasticity.
Cerebral hypoxia is a form of hypoxia, specifically involving the brain; when the brain is completely deprived of oxygen, it is called cerebral anoxia. There are four categories of cerebral hypoxia; they are, in order of increasing severity: diffuse cerebral hypoxia (DCH), focal cerebral ischemia, cerebral infarction, and global cerebral ischemia. Prolonged hypoxia induces neuronal cell death via apoptosis, resulting in a hypoxic brain injury.
Complications of pregnancy are health problems that are related to, or arise during pregnancy. Complications that occur primarily during childbirth are termed obstetric labor complications, and problems that occur primarily after childbirth are termed puerperal disorders. While some complications improve or are fully resolved after pregnancy, some may lead to lasting effects, morbidity, or in the most severe cases, maternal or fetal mortality.
Placental insufficiency or utero-placental insufficiency is the failure of the placenta to deliver sufficient nutrients to the fetus during pregnancy, and is often a result of insufficient blood flow to the placenta. The term is also sometimes used to designate late decelerations of fetal heart rate as measured by cardiotocography or an NST, even if there is no other evidence of reduced blood flow to the placenta, normal uterine blood flow rate being 600mL/min.
Velamentous cord insertion is a complication of pregnancy where the umbilical cord is inserted in the fetal membranes. It is a major cause of antepartum hemorrhage that leads to loss of fetal blood and associated with high perinatal mortality. In normal pregnancies, the umbilical cord inserts into the middle of the placental mass and is completely encased by the amniotic sac. The vessels are hence normally protected by Wharton's jelly, which prevents rupture during pregnancy and labor. In velamentous cord insertion, the vessels of the umbilical cord are improperly inserted in the chorioamniotic membrane, and hence the vessels traverse between the amnion and the chorion towards the placenta. Without Wharton's jelly protecting the vessels, the exposed vessels are susceptible to compression and rupture.
A placental disease is any disease, disorder, or pathology of the placenta.
An obstetric labor complication is a difficulty or abnormality that arises during the process of labor or delivery.
Neonatal encephalopathy (NE), previously known as neonatal hypoxic-ischemic encephalopathy, is defined as a encephalopathy syndrome with signs and symptoms of abnormal neurological function, in the first few days of life in an infant born after 35 weeks of gestation. In this condition there is difficulty initiating and maintaining respirations, a subnormal level of consciousness, and associated depression of tone, reflexes, and possibly seizures. Encephalopathy is a nonspecific response of the brain to injury which may occur via multiple methods, but is commonly caused by birth asphyxia, leading to cerebral hypoxia.
Circumvallate placenta is a rare condition affecting about 1-2% of pregnancies, in which the amnion and chorion fetal membranes essentially "double back" on the fetal side around the edges of the placenta. After delivery, a circumvallate placenta has a thick ring of membranes on its fetal surface. Circumvallate placenta is a placental morphological abnormality associated with increased fetal morbidity and mortality due to the restricted availability of nutrients and oxygen to the developing fetus.
Uterine Tachysystole is a condition of excessively frequent uterine contractions during pregnancy. It is most often seen in induced or augmented labor, though it can also occur during spontaneous labor, and this may result in fetal hypoxia and acidosis. This may have serious effects on both the mother and the fetus including hemorrhaging and death. There are still major gaps in understanding treatment as well as clinical outcomes of this condition. Uterine tachysystole is defined as more than 5 contractions in 10 minutes, averaged over a 30-minute period.
Birth injury refers to damage or injury to the child before, during, or just after the birthing process. "Birth trauma" refers specifically to mechanical damage sustained during delivery.
A high-risk pregnancy is one where the mother or the fetus has an increased risk of adverse outcomes compared to uncomplicated pregnancies. No concrete guidelines currently exist for distinguishing “high-risk” pregnancies from “low-risk” pregnancies; however, there are certain studied conditions that have been shown to put the mother or fetus at a higher risk of poor outcomes. These conditions can be classified into three main categories: health problems in the mother that occur before she becomes pregnant, health problems in the mother that occur during pregnancy, and certain health conditions with the fetus.
Fetal programming, also known as prenatal programming, is the theory that environmental cues experienced during fetal development play a seminal role in determining health trajectories across the lifespan.
The Pregnancy Outcome Prediction (POP) Study is a prospective cohort study of 4,512 women who have never given birth, recruited at the Rosie Hospital between January 2008 and July 2012.
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