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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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The risk of pregnancy complications increases as the mother's age increases. Risks associated with childbearing over the age of 50 include an increased incidence of gestational diabetes, hypertension, delivery by caesarean section, miscarriage, preeclampsia, and placenta previa. In comparison to mothers between 20 and 29 years of age, mothers over 50 are at almost three times the risk of low birth weight, premature birth, and extremely premature birth; their risk of extremely low birth weight, small size for gestational age, and fetal mortality was almost double.
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.
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.
Facts about the conception of pregnancies in this age group can be difficult to determine, but they are nearly always due to the use of IVF with donor eggs.
Advanced maternal age is associated with adverse outcomes in the perinatal period, which may be caused by detrimental effects on decidual and placental development.
The risk of the mother dying before the child becomes an adult increases by more advanced maternal age, such as can be demonstrated by the following data from France in 2007:
Advanced maternal age continues to be associated with a range of adverse pregnancy outcomes including low birth weight, pre-term birth, stillbirth, unexplained fetal death, and increased rates of Caesarean section.
On the other hand, advanced maternal age is associated with a more stable family environment, higher socio-economic position, higher income and better living conditions, as well as better parenting practices, but it is more or less uncertain whether these entities are "effects" of advanced maternal age, are "contributors" to advanced maternal age, or common effects of a certain state such as personality type.
Kalberer et al. have shown that despite the older maternal age at birth of the first child, the time span between the birth of the first and the second child (= interpregnancy interval) decreased over the last decades. If purely biological factors were at work, it could be argued that interpregnancy interval should have increased, as fertility declines with age, which would make it harder for the woman to get a second child after postponed birth of the first one. This not being the case shows that sociologic factors (see above) prime over biological factors in determining interpregnancy interval.
With technology developments cases of post-menopausal pregnancies have occurred, and there are several known cases of older women carrying a pregnancy to term, usually with in vitro fertilization of a donor egg. A 61-year-old Brazilian woman with implantation of a donor egg expected gave birth to twins in October 2011..
Intrauterine exposure to environmental toxins in pregnancy has the potential to cause adverse effects on the development of the embryo/fetus and to cause pregnancy complications. Air pollution has been associated with low birth weight infants. Conditions of particular severity in pregnancy include mercury poisoning and lead poisoning. To minimize exposure to environmental toxins, the "American College of Nurse-Midwives" recommends: checking whether the home has lead paint, washing all fresh fruits and vegetables thoroughly and buying organic produce, and avoiding cleaning products labeled "toxic" or any product with a warning on the label.
Pregnant women can also be exposed to toxins in the workplace, including airborne particles. The effects of wearing N95 filtering facepiece respirators are similar for pregnant women as non-pregnant women, and wearing a respirator for one hour does not affect the fetal heart rate.
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.
A study of a population of French women from 1670 and 1789 shows that those who married at age 20–24 had 7.0 children on average and 3.7% remained childless. Women who married at age 25–29 years had a mean of 5.7 children and 5.0% remained childless. Women who married at 30–34 years had a mean of 4.0 children and 8.2% remained childless. The average age at last birth in natural fertility populations that have been studied is around 40.
In 1957, a study was done on a large population (American Hutterites) that never used birth control. The investigators measured the relationship between the age of the female partner and fertility. (Infertility rates today are believed to be higher in the general population than for the population in this study from the 1950s.)
This 1957 study found that:
- By age 30, 7% of couples were infertile
- By age 35, 11% of couples were infertile
- By age 40, 33% of couples were infertile
- At age 45, 87% of couples were infertile
The inverse correlation between age and female fertility in later reproductive life is argued to motivate family planning well before having reached 35 years of age. Mapping of a woman's ovarian reserve, follicular dynamics and associated biomarkers can give an individual prognosis about future chances of pregnancy, facilitating an informed choice of when to have children. Notably, a higher level of anti-Müllerian hormone when tested in women in the general population has been found to have a positive correlation with natural fertility in women aged 30–44 aiming to conceive spontaneously, even after adjusting for age. Thus, AMH measurement is helpful to determine which women may need to conceive at an earlier age, and which women can potentially wait.
Fertility following ectopic pregnancy depends upon several factors, the most important of which is a prior history of infertility. The treatment choice does not play a major role; A randomized study in 2013 concluded that the rates of intrauterine pregnancy 2 years after treatment of ectopic pregnancy are approximately 64% with radical surgery, 67% with medication, and 70% with conservative surgery. In comparison, the cumulative pregnancy rate of women under 40 years of age in the general population over 2 years is over 90%.
Twelve percent of all infertility cases are a result of a woman either being underweight or overweight. Fat cells produce estrogen, in addition to the primary sex organs. Too much body fat causes production of too much estrogen and the body begins to react as if it is on birth control, limiting the odds of getting pregnant. Too little body fat causes insufficient production of estrogen and disruption of the menstrual cycle. Both under and overweight women have irregular cycles in which ovulation does not occur or is inadequate. Proper nutrition in early life is also a major factor for later fertility.
A study in the US indicated that approximately 20% of infertile women had a past or current eating disorder, which is five times higher than the general lifetime prevalence rate.
A review from 2010 concluded that overweight and obese subfertile women have a reduced probability of successful fertility treatment and their pregnancies are associated with more complications and higher costs. In hypothetical groups of 1000 women undergoing fertility care, the study counted approximately 800 live births for normal weight and 690 live births for overweight and obese anovulatory women. For ovulatory women, the study counted approximately 700 live births for normal weight, 550 live births for overweight and 530 live births for obese women. The increase in cost per live birth in anovulatory overweight and obese women were, respectively, 54 and 100% higher than their normal weight counterparts, for ovulatory women they were 44 and 70% higher, respectively.
Factors that can cause male as well as female infertility are:
- DNA damage
- DNA damage reduces fertility in female ovocytes, as caused by smoking, other xenobiotic DNA damaging agents (such as radiation or chemotherapy) or accumulation of the oxidative DNA damage 8-hydroxy-deoxyguanosine
- DNA damage reduces fertility in male sperm, as caused by oxidative DNA damage, smoking, other xenobiotic DNA damaging agents (such as drugs or chemotherapy) or other DNA damaging agents including reactive oxygen species, fever or high testicular temperature
- General factors
- Diabetes mellitus, thyroid disorders, undiagnosed and untreated coeliac disease, adrenal disease
- Hypothalamic-pituitary factors
- Hyperprolactinemia
- Hypopituitarism
- The presence of anti-thyroid antibodies is associated with an increased risk of unexplained subfertility with an odds ratio of 1.5 and 95% confidence interval of 1.1–2.0.
- Environmental factors
- Toxins such as glues, volatile organic solvents or silicones, physical agents, chemical dusts, and pesticides. Tobacco smokers are 60% more likely to be infertile than non-smokers.
German scientists have reported that a virus called Adeno-associated virus might have a role in male infertility, though it is otherwise not harmful. Other diseases such as chlamydia, and gonorrhea can also cause infertility, due to internal scarring (fallopian tube obstruction).
When ectopic pregnancies are treated, the prognosis for the mother is very good in Western countries; maternal death is rare, but most fetuses die or are aborted. For instance, in the UK, between 2003 and 2005 there were 32,100 ectopic pregnancies resulting in 10 maternal deaths (meaning that 1 in 3,210 women with an ectopic pregnancy died).
In the developing world, however, especially in Africa, the death rate is very high, and ectopic pregnancies are a major cause of death among women of childbearing age.
Sexually transmitted infections are a leading cause of infertility. They often display few, if any visible symptoms, with the risk of failing to seek proper treatment in time to prevent decreased fertility.
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).
Antisperm antibodies (ASA) have been considered as infertility cause in around 10–30% of infertile couples. In both men and women, ASA production are directed against surface antigens on sperm, which can interfere with sperm motility and transport through the female reproductive tract, inhibiting capacitation and acrosome reaction, impaired fertilization, influence on the implantation process, and impaired growth and development of the embryo. Factors contributing to the formation of antisperm antibodies in women are disturbance of normal immunoregulatory mechanisms, infection, violation of the integrity of the mucous membranes, accidental rape and unprotected oral or anal sex. Risk factors for the formation of antisperm antibodies in men include the breakdown of the blood‑testis barrier, trauma and surgery, orchitis, varicocele, infections, prostatitis, testicular cancer, failure of immunosuppression and unprotected passive anal or oral sex with men.
There are various explanations, none of which is universally accepted because of the complex involvement of cortical, hypothalamic, endocrine, and psychogenic factors. Proposed mechanisms include the effect of stress on the hypothalamo-pituitary-adrenal axis, constipation, weight gain, and the movement of intestinal gas.
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.
Although it is very uncommon, women undergoing surgical abortion after 18 weeks gestation sometimes give birth to a fetus that may survive briefly. Longer term survival is possible after 22 weeks.
If medical staff observe signs of life, they may be required to provide care: emergency medical care if the child has a good chance of survival and palliative care if not. Induced fetal demise before termination of pregnancy after 20–21 weeks gestation is recommended to avoid this.
Death following live birth caused by abortion is given the ; data are identified as either fetus or newborn. Between 1999 and 2013, in the U.S., the CDC recorded 531 such deaths for newborns, approximately 4 per 100,000 abortions.
The rate of pseudocyesis in the United States has declined significantly in the past century. In the 1940s there was one occurrence for approximately every 250 pregnancies. This rate has since dropped to between one and six occurrences for every 22,000 births. The average age of the affected woman is 33, though cases have been reported for girls as young as 6 and women as old as 79. More than two-thirds of women who experience pseudocyesis are married, and about one-third have been pregnant at least once.
The rate of cancer during pregnancy is 0.02–1%, and in many cases, cancer of the mother leads to consideration of abortion to protect the life of the mother, or in response to the potential damage that may occur to the fetus during treatment. This is particularly true for cervical cancer, the most common type of which occurs in 1 of every 2,000–13,000 pregnancies, for which initiation of treatment "cannot co-exist with preservation of fetal life (unless neoadjuvant chemotherapy is chosen)". Very early stage cervical cancers (I and IIa) may be treated by radical hysterectomy and pelvic lymph node dissection, radiation therapy, or both, while later stages are treated by radiotherapy. Chemotherapy may be used simultaneously. Treatment of breast cancer during pregnancy also involves fetal considerations, because lumpectomy is discouraged in favor of modified radical mastectomy unless late-term pregnancy allows follow-up radiation therapy to be administered after the birth.
Exposure to a single chemotherapy drug is estimated to cause a 7.5–17% risk of teratogenic effects on the fetus, with higher risks for multiple drug treatments. Treatment with more than 40 Gy of radiation usually causes spontaneous abortion. Exposure to much lower doses during the first trimester, especially 8 to 15 weeks of development, can cause intellectual disability or microcephaly, and exposure at this or subsequent stages can cause reduced intrauterine growth and birth weight. Exposures above 0.005–0.025 Gy cause a dose-dependent reduction in IQ. It is possible to greatly reduce exposure to radiation with abdominal shielding, depending on how far the area to be irradiated is from the fetus.
The process of birth itself may also put the mother at risk. "Vaginal delivery may result in dissemination of neoplastic cells into lymphovascular channels, haemorrhage, cervical laceration and implantation of malignant cells in the episiotomy site, while abdominal delivery may delay the initiation of non-surgical treatment."
Sporadic OHSS is very rare, and may have a genetic component. Clomifene citrate therapy can occasionally lead to OHSS, but the vast majority of cases develop after use of gonadotropin therapy (with administration of FSH), such as Pergonal, and administration of hCG to induce final oocyte maturation and/or trigger oocyte release, often in conjunction with IVF. The frequency varies and depends on a woman's risk factors, management, and methods of surveillance. About 5% of treated women may encounter moderate to severe OHSS. Risk factors include young age, the development of many ovarian follicles under stimulation, extreme elevated serum estradiol concentrations, the use of hCG for final oocyte maturation and/or release, the continued use of hCG for luteal support, and the occurrence of a pregnancy (resulting in hCG production).
Mortality is low, but several fatal cases have been reported.
The risk of a repeat GTD is approximately 1 in 100, compared with approximately 1 in 1000 risk in the general population. Especially women whose hCG levels remain significantly elevated are at risk of developing a repeat GTD.