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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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In low-risk pregnancies, the association between cigarette smoking and a reduced risk of pre-eclampsia has been consistent and reproducible across epidemiologic studies. High-risk pregnancies (those with pregestational diabetes, chronic hypertension, history of pre-eclampsia in a previous pregnancy, or multifetal gestation) showed no significant protective effect. The reason for this discrepancy is not definitively known; research supports speculation that the underlying pathology increases the risk of preeclampsia to such a degree that any measurable reduction of risk due to smoking is masked. However, the damaging effects of smoking on overall health and pregnancy outcomes outweighs the benefits in decreasing the incidence of preeclampsia. It is recommended that smoking be stopped prior to, during and after pregnancy.
Studies suggest that marijuana use in the months prior to or during the early stages of pregnancy may interfere with normal placental development and consequently increase the risk of preeclampsia.
There is also an increased risk for cardiovascular complications, including hypertension and ischemic heart disease, and kidney disease. Other risks include stroke and venous thromboembolism. It seems pre-eclampsia does not increase the risk of cancer.
Lowered blood supply to the fetus in pre-eclampsia causes lowered nutrient supply, which could result in intrauterine growth restriction (IUGR) and low birth weight. The fetal origins hypothesis states that fetal undernutrition is linked with coronary heart disease later in adult life due to disproportionate growth.
Because preeclampsia leads to a mismatch between the maternal energy supply and fetal energy demands, pre-eclampsia can lead to IUGR in the developing fetus. Infants suffering from IUGR are prone to suffer from poor neuronal development and in increased risk for adult disease according to the Barker hypothesis. Associated adult diseases of the fetus due to IUGR include, but are not limited to, coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), cancer, osteoporosis, and various psychiatric illnesses.
The risk of pre-eclampsia and development of placental dysfunction has also been shown to be recurrent cross-generationally on the maternal side and most likely on the paternal side. Fetuses born to mothers that were born small for gestational age (SGA) were 50% more likely to develop preeclampsia while fetuses born to both SGA parents were three-fold more likely to develop preeclampsia in future pregnancies.
Factors increasing the risk (to either the woman, the fetus/es, or both) of pregnancy complications beyond the normal level of risk may be present in a woman's medical profile either before she becomes pregnant or during the pregnancy. These pre-existing factors may relate to physical and/or mental health, and/or to social issues, or a combination.
Some common risk factors include:
- Age of either parent
- Adolescent parents
- Older parents
- Exposure to environmental toxins in pregnancy
- Exposure to recreational drugs in pregnancy:
- Ethanol during pregnancy can cause fetal alcohol syndrome and fetal alcohol spectrum disorder.
- Tobacco smoking and pregnancy, when combined, causes twice the risk of premature rupture of membranes, placental abruption and placenta previa. Also, it causes 30% higher odds of the baby being born prematurely.
- Prenatal cocaine exposure is associated with, for example, premature birth, birth defects and attention deficit disorder.
- Prenatal methamphetamine exposure can cause premature birth and congenital abnormalities. Other investigations have revealed short-term neonatal outcomes to include small deficits in infant neurobehavioral function and growth restriction when compared to control infants. Also, prenatal methamphetamine use is believed to have long-term effects in terms of brain development, which may last for many years.
- Cannabis in pregnancy is possibly associated with adverse effects on the child later in life.
- Exposure to Pharmaceutical drugs in pregnancy. Anti-depressants, for example, may increase risks of such outcomes as preterm delivery.
- Ionizing radiation
- Risks arising from previous pregnancies:
- Complications experienced during a previous pregnancy are more likely to recur.
- Many previous pregnancies. Women who have had five previous pregnancies face increased risks of very rapid labor and excessive bleeding after delivery.
- Multiple previous fetuses. Women who have had more than one fetus in a previous pregnancy face increased risk of mislocated placenta.
- Multiple pregnancy, that is, having more than one fetus in a single pregnancy.
- Social and socioeconomic factors. Generally speaking, unmarried women and those in lower socioeconomic groups experience an increased level of risk in pregnancy, due at least in part to lack of access to appropriate prenatal care.
- Unintended pregnancy. Unintended pregnancies preclude preconception care and delays prenatal care. They preclude other preventive care, may disrupt life plans and on average have worse health and psychological outcomes for the mother and, if birth occurs, the child.
- Height. Pregnancy in women whose height is less than 1.5 meters (5 feet) correlates with higher incidences of preterm birth and underweight babies. Also, these women are more likely to have a small pelvis, which can result in such complications during childbirth as shoulder dystocia.
- Weight
- Low weight: Women whose pre-pregnancy weight is less than 45.5 kilograms (100 pounds) are more likely to have underweight babies.
- Obese women are more likely to have very large babies, potentially increasing difficulties in childbirth. Obesity also increases the chances of developing gestational diabetes, high blood pressure, preeclampsia, experiencing postterm pregnancy and/or requiring a cesarean delivery.
- Intercurrent disease in pregnancy, that is, a disease and condition not necessarily directly caused by the pregnancy, such as diabetes mellitus in pregnancy, SLE in pregnancy or thyroid disease in pregnancy.
Some women have a greater risk of developing hypertension during pregnancy. These are:
- Women with chronic hypertension (high blood pressure before becoming pregnant).
- Women who developed high blood pressure or preeclampsia during a previous pregnancy, especially if these conditions occurred early in the pregnancy.
- Women who are obese prior to pregnancy.
- Pregnant women under the age of 20 or over the age of 40.
- Women who are pregnant with more than one baby.
- Women with diabetes, kidney disease, rheumatoid arthritis, lupus, or scleroderma.
A number of factors have been identified that are linked to a higher risk of a preterm birth such as being less than 18 years of age. Maternal height and weight can play a role.
Further, in the US and the UK, black women have preterm birth rates of 15–18%, more than double than that of the white population. Filipinos are also at high risk of premature birth, and it is believed that nearly 11-15% of Filipinos born in the U.S. (compared to other Asians at 7.6% and whites at 7.8%) are premature. Filipinos being a big risk factor is evidenced with the Philippines being the 8th highest ranking in the world for preterm births, the only non-African country in the top 10. This discrepancy is not seen in comparison to other Asian groups or Hispanic immigrants and remains unexplained.
Pregnancy interval makes a difference as women with a six-month span or less between pregnancies have a two-fold increase in preterm birth. Studies on type of work and physical activity have given conflicting results, but it is opined that stressful conditions, hard labor, and long hours are probably linked to preterm birth.
A history of spontaneous (i.e., miscarriage) or surgical abortion has been associated with a small increase in the risk of preterm birth, with an increased risk with increased number of abortions, although it is unclear whether the increase is caused by the abortion or by confounding risk factors (e.g., socioeconomic status). Increased risk has not been shown in women who terminated their pregnancies medically. Pregnancies that are unwanted or unintended are also a risk factor for preterm birth.
Adequate maternal nutrition is important. Women with a low BMI are at increased risk for preterm birth. Further, women with poor nutrition status may also be deficient in vitamins and minerals. Adequate nutrition is critical for fetal development and a diet low in saturated fat and cholesterol may help reduce the risk of a preterm delivery. Obesity does not directly lead to preterm birth; however, it is associated with diabetes and hypertension which are risk factors by themselves. To some degree those individuals may have underlying conditions (i.e., uterine malformation, hypertension, diabetes) that persist.
Women with celiac disease have an increased risk of the development of preterm birth. The risk of preterm birth is more elevated when celiac disease remains undiagnosed and untreated.
Marital status is associated with risk for preterm birth. A study of 25,373 pregnancies in Finland revealed that unmarried mothers had more preterm deliveries than married mothers (P=0.001). Pregnancy outside of marriage was associated overall with a 20% increase in total adverse outcomes, even at a time when Finland provided free maternity care. A study in Quebec of 720,586 births from 1990 to 1997 revealed less risk of preterm birth for infants with legally married mothers compared with those with common-law wed or unwed parents.
Genetic make-up is a factor in the causality of preterm birth. Genetics has been a big factor into why Filipinos have a high risk of premature birth as the Filipinos have a large prevalence of mutations that help them be predisposed to premature births. An intra- and transgenerational increase in the risk of preterm delivery has been demonstrated. No single gene has been identified.
Subfertility is associated with preterm birth. Couples who have tried more than 1 year versus those who have tried less than 1 year before achieving a spontaneous conception have an adjusted odds ratio of 1.35 (95% confidence interval 1.22-1.50) of preterm birth. Pregnancies after IVF confers a greater risk of preterm birth than spontaneous conceptions after more than 1 year of trying, with an adjusted odds ratio of 1.55 (95% CI 1.30-1.85).
Some disorders and conditions can mean that pregnancy is considered high-risk (about 6-8% of pregnancies in the USA) and in extreme cases may be contraindicated. High-risk pregnancies are the main focus of doctors specialising in maternal-fetal medicine.
Serious pre-existing disorders which can reduce a woman's physical ability to survive pregnancy include a range of congenital defects (that is, conditions with which the woman herself was born, for example, those of the heart or , some of which are listed above) and diseases acquired at any time during the woman's life.
Gestational hypertension is one of the most common disorders seen in human pregnancies. Though relatively benign on its own, in roughly half of the cases of gestational hypertension the disorder progresses into preeclampsia, a dangerous condition that can prove fatal to expectant mothers. However, gestational hypertension is a condition that is fairly rare to see in other animals. For years, it has been the belief of the scientific community that gestational hypertension and preeclampsia were relatively unique to humans, although there has been some recent evidence that other primates can also suffer from similar conditions, albeit due to different underlying mechanisms. The underlying cause of gestational hypertension in humans is commonly believed to be an improperly implanted placenta. Humans have evolved to have a very invasive placenta to facilitate better oxygen transfer from the mother to the fetus, to support the growth of its large brain.
The use of fertility medication that stimulates the ovary to release multiple eggs and of IVF with embryo transfer of multiple embryos has been implicated as an important factor in preterm birth. Maternal medical conditions increase the risk of preterm birth. Often labor has to be induced for medical reasons; such conditions include high blood pressure, pre-eclampsia, maternal diabetes, asthma, thyroid disease, and heart disease.
In a number of women anatomical issues prevent the baby from being carried to term. Some women have a weak or short cervix (the strongest predictor of premature birth) Women with vaginal bleeding during pregnancy are at higher risk for preterm birth. While bleeding in the third trimester may be a sign of placenta previa or placental abruption – conditions that occur frequently preterm – even earlier bleeding that is not caused by these conditions is linked to a higher preterm birth rate. Women with abnormal amounts of amniotic fluid, whether too much (polyhydramnios) or too little (oligohydramnios), are also at risk.
The mental status of the women is of significance. Anxiety and depression have been linked to preterm birth.
Finally, the use of tobacco, cocaine, and excessive alcohol during pregnancy increases the chance of preterm delivery. Tobacco is the most commonly abused drug during pregnancy and contributes significantly to low birth weight delivery. Babies with birth defects are at higher risk of being born preterm.
Passive smoking and/or smoking before the pregnancy influences the probability of a preterm birth. The World Health Organization published an international study in March 2014.
Presence of anti-thyroid antibodies is associated with an increased risk preterm birth with an odds ratio of 1.9 and 95% confidence interval of 1.1–3.5.
A 2004 systematic review of 30 studies on the association between intimate partner violence and birth outcomes concluded that preterm birth and other adverse outcomes, including death, are higher among abused pregnant women than among non-abused women.
The Nigerian cultural method of abdominal massage has been shown to result in 19% preterm birth among women in Nigeria, plus many other adverse outcomes for the mother and baby. This ought not be confused with massage conducted by a fully trained and licensed massage therapist or by significant others trained to provide massage during pregnancy, which has been shown to have numerous positive results during pregnancy, including the reduction of preterm birth, less depression, lower cortisol, and reduced anxiety.
Despite these risks for gestational hypertension, the hemochorial placenta has been favored because of its advantages in the way that it aids in diffusion from mother to fetus later in pregnancy. The bipedal posture that has allowed humans to walk upright has also led to a reduced cardiac output, and it has been suggested that this is what necessitated humans’ aggressive early placental structures. Increased maternal blood pressure can attempt to make up for lower cardiac output, ensuring that the fetus’s growing brain receives enough oxygen and nutrients. The benefits of being able to walk upright and run on land have outweighed the disadvantages that come from bipedalism, including the placental diseases of pregnancy, such as gestational hypertension. Similarly, the advantages of having a large brain size have outweighed the deleterious effects of having a placenta that does not always convert the spiral arteries effectively, leaving humans vulnerable to contracting gestational hypertension. It is speculated that this was not the case with Neanderthals, and that they died out because their cranial capacity increased too much, and their placentae were not equipped to handle the fetal brain development, leading to widespread preeclampsia and maternal and fetal death.
Gestational hypertension in the early stages of pregnancy (trimester 1) has been shown to improve the health of the child both in its first year of life, and its later life. However, when the disease develops later in the pregnancy (subsequent trimesters), or turns into preeclampsia, there begin to be detrimental health effects for the fetus, including low birth-weight. It has been proposed that fetal genes designed to increase the mother’s blood pressure are so beneficial that they outweigh the potential negative effects that can come from preeclampsia. It has also been suggested that gestational hypertension and preeclampsia have remained active traits due to the cultural capacity of humans, and the tendency for midwives or helpers to aid in delivering babies.
Preeclampsia is a condition that typically starts after the 20th week of pregnancy and is related to increased blood pressure and protein in the mother's urine (as a result of kidney problems). Preeclampsia affects the placenta, and it can affect the mother's kidney, liver, and brain. When preeclampsia causes seizures, the condition is known as eclampsia--the second leading cause of maternal death in the U.S. Preeclampsia is also a leading cause of fetal complications, which include low birth weight, premature birth, and stillbirth.
There is no proven way to prevent preeclampsia. Most women who develop signs of preeclampsia, however, are closely monitored to lessen or avoid related problems. The only way to "cure" preeclampsia is to deliver the baby.
Hypercoagulability in pregnancy is the propensity of pregnant women to develop thrombosis (blood clots). Pregnancy itself is a factor of hypercoagulability (pregnancy-induced hypercoagulability), as a physiologically adaptive mechanism to prevent "post partum" bleeding. However, when combined with an additional underlying hypercoagulable states, the risk of thrombosis or embolism may become substantial.
Not only is obesity associated with miscarriage, it can result in sub-fertility and other adverse pregnancy outcomes. Recurrent miscarriage is also related to obesity. Women with bulimia nervosa and anorexia nervosa may have a greater risk for miscarriage. Nutrient deficiencies have not been found to impact miscarriage rates but hyperemesis gravidarum sometimes precedes a miscarriage.
Caffeine consumption also has been correlated to miscarriage rates, at least at higher levels of intake. However, such higher rates have been found to be statistically significant only in certain circumstances.
Vitamin supplementation has generally not shown to be effective in preventing miscarriage. Chinese traditional medicine has not been found to prevent miscarriage.
Being pregnant decreases the risk of relapse in multiple sclerosis; however, during the first months after delivery the risk increases. Overall, pregnancy does not seem to influence long-term disability. Multiple sclerosis does not increase the risk of congenital abnormality or miscarriage.
A study by the Agency for Healthcare Research and Quality (AHRQ) found that of the 3.8 million births that occurred in the United States in 2011, approximately 6.1% (231,900) were diagnosed with low birth weight (<2,500 g). Approximately 49,300 newborns (1.3%) weighed less than 1,500 grams (VLBW). Infants born at low birth weight are at a higher risk for developing neonatal infection.
LBW is closely associated with fetal and Perinatal mortality and Morbidity, inhibited growth and cognitive development, and chronic diseases later in life. At the population level, the proportion of babies with a LBW is an indicator of a multifaceted public-health problem that includes long-term maternal malnutrition, ill health, hard work and poor health care in pregnancy. On an individual basis, LBW is an important predictor of newborn health and survival and is associated with higher risk of infant and childhood mortality.
Low birth weight constitutes as sixty to eighty percent of the infant mortality rate in developing countries. Infant mortality due to low birth weight is usually directly causal, stemming from other medical complications such as preterm birth, poor maternal nutritional status, lack of prenatal care, maternal sickness during pregnancy, and an unhygienic home environment. According to an analysis by University of Oregon, reduced brain volume in children is also tied to low birth-weight.
The age of the pregnant woman is a significant risk factor. Miscarriage rates increase steadily with age, with more substantial increases after age 35. In those under the age of 35 the risk is about 10% while it is about 45% in those over the age of 40. Risk begins to increase around the age of 30. Paternal age is associated with increased risk.
PROM occurring before 37 weeks (PPROM) is one of the leading causes of preterm birth. 30-35% of all preterm births are caused by PPROM. This puts the fetus at risk for the many complications associated with prematurity such as respiratory distress, brain bleeds, infection, necrotizing enterocolitis (death of the fetal bowels), brain injury, muscle dysfunction, and death. Prematurity from any cause leads to 75% of perinatal mortality and about 50% of all long-term morbidity. PROM is responsible for 20% of all fetal deaths between 24 and 34 weeks gestation.
The use of recreational drugs in pregnancy can cause various pregnancy complications.
- Ethanol during pregnancy can cause fetal alcohol syndrome and fetal alcohol spectrum disorder. Studies have shown that light to moderate drinking during pregnancy might not pose a risk to the fetus, although no amount of alcohol during pregnancy can be guaranteed to be absolutely safe.
- Tobacco smoking during pregnancy can cause a wide range of behavioral, neurological, and physical difficulties. Smoking during pregnancy causes twice the risk of premature rupture of membranes, placental abruption and placenta previa. Smoking is associated with 30% higher odds of preterm birth.
- Prenatal cocaine exposure is associated with premature birth, birth defects and attention deficit disorder.
- Prenatal methamphetamine exposure can cause premature birth and congenital abnormalities. Short-term neonatal outcomes show small deficits in infant neurobehavioral function and growth restriction. Long-term effects in terms of impaired brain development may also be caused by methamphetamine use.
- Cannabis in pregnancy has been shown to be teratogenic in large doses in animals, but has not shown any teratogenic effects in humans.
The prognosis of this complication depends on whether treatment is received by the patient, on the quality of treatment, and on the severity of the abruption. Outcomes for the baby also depend on the gestational age.
In the Western world, maternal deaths due to placental abruption are rare. The fetal prognosis is worse than the maternal prognosis; approximately 12% of fetuses affected by placental abruption die. 77% of fetuses that die from placental abruption die before birth; the remainder die due to complications of preterm birth.
Without any form of medical intervention, as often happens in many parts of the world, placental abruption has a high maternal mortality rate.
Although the risk of placental abruption cannot be eliminated, it can be reduced. Avoiding tobacco, alcohol and cocaine during pregnancy decreases the risk. Staying away from activities which have a high risk of physical trauma is also important. Women who have high blood pressure or who have had a previous placental abruption and want to conceive must be closely supervised by a doctor.
The risk of placental abruption can be reduced by maintaining a good diet including taking folic acid, regular sleep patterns and correction of pregnancy-induced hypertension.
It is crucial for women to be made aware of the signs of placental abruption, such as vaginal bleeding, and that if they experience such symptoms they must get into contact with their health care provider/the hospital "without any delay".
A pregnant woman may have intercurrent diseases, defined as disease not directly caused by the pregnancy, but that may become worse or be a potential risk to the pregnancy.
- Diabetes mellitus and pregnancy deals with the interactions of diabetes mellitus (not restricted to gestational diabetes) and pregnancy. Risks for the child include miscarriage, growth restriction, growth acceleration, fetal obesity (macrosomia), polyhydramnios (too much amniotic fluid), and birth defects.
- Thyroid disease in pregnancy can, if uncorrected, cause adverse effects on fetal and maternal well-being. The deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neurointellectual development in the early life of the child. Demand for thyroid hormones is increased during pregnancy which may cause a previously unnoticed thyroid disorder to worsen.
- Untreated celiac disease can cause spontaneous abortion (miscarriage), intrauterine growth restriction, small for gestational age, low birthweight and preterm birth. Often reproductive disorders are the only manifestation of undiagnosed celiac disease and most cases are not recognized. Complications or failures of pregnancy cannot be explained simply by malabsorption, but by the autoimmune response elicited by the exposure to gluten, which causes damage to the placenta. The gluten-free diet avoids or reduces the risk of developing reproductive disorders in pregnant women with celiac disease. Also, pregnancy can be a trigger for the development of celiac disease in genetically susceptible women who are consuming gluten.
- Systemic lupus erythematosus in pregnancy confers an increased rate of fetal death "in utero," spontaneous abortion, and of neonatal lupus.
- Hypercoagulability in pregnancy is the propensity of pregnant women to develop thrombosis (blood clots). Pregnancy itself is a factor of hypercoagulability (pregnancy-induced hypercoagulability), as a physiologically adaptive mechanism to prevent "post partum" bleeding. However, in combination with an underlying hypercoagulable states, the risk of thrombosis or embolism may become substantial.
In sheep, intrauterine growth restriction can be caused by heat stress in early to mid pregnancy. The effect is attributed to reduced placental development causing reduced fetal growth. Hormonal effects appear implicated in the reduced placental development. Although early reduction of placental development is not accompanied by concurrent reduction of fetal growth; it tends to limit fetal growth later in gestation. Normally, ovine placental mass increases until about day 70 of gestation, but high demand on the placenta for fetal growth occurs later. (For example, research results suggest that a normal average singleton Suffolk x Targhee sheep fetus has a mass of about 0.15 kg at day 70, and growth rates of about 31 g/day at day 80, 129 g/day at day 120 and 199 g/day at day 140 of gestation, reaching a mass of about 6.21 kg at day 140, a few days before parturition.)
In adolescent ewes (i.e. ewe hoggets), overfeeding during pregnancy can also cause intrauterine growth restriction, by altering nutrient partitioning between dam and conceptus. Fetal growth restriction in adolescent ewes overnourished during early to mid pregnancy is not avoided by switching to lower nutrient intake after day 90 of gestation; whereas such switching at day 50 does result in greater placental growth and enhanced pregnancy outcome. Practical implications include the importance of estimating a threshold for "overnutrition" in management of pregnant ewe hoggets. In a study of Romney and Coopworth ewe hoggets bred to Perendale rams, feeding to approximate a conceptus-free live mass gain of 0.15 kg/day (i.e. in addition to conceptus mass), commencing 13 days after the midpoint of a synchronized breeding period, yielded no reduction in lamb birth mass, where compared with feeding treatments yielding conceptus-free live mass gains of about 0 and 0.075 kg/day.
In both of the above models of IUGR in sheep, the absolute magnitude of uterine blood flow is reduced. Evidence of substantial reduction of placental glucose transport capacity has been observed in pregnant ewes that had been heat-stressed during placental development.
Before 24 weeks the fetus is still developing its organs, and the amniotic fluid is important for protecting the fetus against infection, physical impact, and for preventing the umbilical cord from becoming compressed. It also allows for fetal movement and breathing that is necessary for the development of the lungs, chest, and bones. Low levels of amniotic fluid due to mid-trimester or previable PPROM (before 24 weeks) can result in fetal deformity (ex: Potter-like facies), limb contractures, pulmonary hypoplasia (underdeveloped lungs), infection (especially if the mother is colonized by group B streptococcus or bacterial vaginosis), prolapsed umbilical cord or compression, and placental abruption.
Eclampsia, like pre-eclampsia, tends to occur more commonly in first pregnancies. Women who have long term high blood pressure before becoming pregnant have a greater risk of pre-eclampsia. Furthermore, women with other pre-existing vascular diseases (diabetes or nephropathy) or thrombophilic diseases such as the antiphospholipid syndrome are at higher risk to develop pre-eclampsia and eclampsia. Having a large placenta (multiple gestation, hydatidiform mole) also predisposes women to eclampsia. In addition, there is a genetic component: a woman whose mother or sister had the condition is at higher risk than otherwise. Women who have experienced eclampsia are at increased risk for pre-eclampsia/eclampsia in a later pregnancy.
IUGR affects 3-10% of pregnancies. 20% of stillborn infants have IUGR. Perinatal mortality rates are 4-8 times higher for infants with IUGR, and morbidity is present in 50% of surviving infants.
According to the theory of thrifty phenotype, intrauterine growth restriction triggers epigenetic responses in the fetus that are otherwise activated in times of chronic food shortage. If the offspring actually develops in an environment rich in food it may be more prone to metabolic disorders, such as obesity and type II diabetes.