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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.
Most women with GTD can become pregnant again and can have children again. The risk of a further molar pregnancy is low. More than 98% of women who become pregnant following a molar pregnancy will not have a further hydatidiform mole or be at increased risk of complications.
In the past, it was seen as important not to get pregnant straight away after a GTD. Specialists recommended a waiting period of 6 months after the hCG levels become normal. Recently, this standpoint has been questioned. New medical data suggest that a significantly shorter waiting period after the hCG levels become normal is reasonable for approximately 97% of the patients with hydatidiform mole.
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.
The cause of this condition is not completely understood. Potential risk factors may include defects in the egg, abnormalities within the uterus, or nutritional deficiencies. Women under 20 or over 40 years of age have a higher risk. Other risk factors include diets low in protein, folic acid, and carotene. The diploid set of sperm-only DNA means that all chromosomes have sperm-patterned methylation suppression of genes. This leads to overgrowth of the syncytiotrophoblast whereas dual egg-patterned methylation leads to a devotion of resources to the embryo, with an underdeveloped syncytiotrophoblast. This is considered to be the result of evolutionary competition with male genes driving for high investment into the fetus versus female genes driving for resource restriction to maximise the number of children.
More than 80% of hydatidiform moles are benign. The outcome after treatment is usually excellent. Close follow-up is essential. Highly effective means of contraception are recommended to avoid pregnancy for at least 6 to 12 months.
In 10 to 15% of cases, hydatidiform moles may develop into invasive moles. This condition is named "persistent trophoblastic disease" (PTD). The moles may intrude so far into the uterine wall that hemorrhage or other complications develop. It is for this reason that a post-operative full abdominal and chest x-ray will often be requested.
In 2 to 3% of cases, hydatidiform moles may develop into choriocarcinoma, which is a malignant, rapidly growing, and metastatic (spreading) form of cancer. Despite these factors which normally indicate a poor prognosis, the rate of cure after treatment with chemotherapy is high.
Over 90% of women with malignant, non-spreading cancer are able to survive and retain their ability to conceive and bear children. In those with metastatic (spreading) cancer, remission remains at 75 to 85%, although their childbearing ability is usually lost.
Trophoblastic neoplasms derive from trophoblastic tissue. Examples include:
- Choriocarcinoma
- Hydatidiform mole
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.
Placental site trophoblastic tumor is a form of gestational trophoblastic disease, which is thought to arise from intermediate trophoblast.
It may secrete human placental lactogen (human chorionic somatomammotropin), and result in a false-positive pregnancy test.
Placental site trophoblastic tumor is a monophasic neoplasm of the implantation site intermediate trophoblast, and usually a benign lesion, which comprises less than 2% of all gestational trophoblastic proliferations. Preceding conditions include molar pregnancy (5%). Compared to choriocarcinoma or invasive mole, hemorrhage is less conspicuous and serum β-HCG level is low, making early diagnosis difficult.
Immunohistochemistry: Often stains with hPL, keratin, Mel-CAM, EGFR.
Prognosis: 10–20% of cases metastase leading to death.
Treatment: Because chemotherapy is ineffective; the patient should undergo hysterectomy.
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.
Since gestational choriocarcinoma (which arises from a hydatidiform mole) contains paternal DNA (and thus paternal antigens), it is exquisitely sensitive to chemotherapy. The cure rate, even for metastatic gestational choriocarcinoma, is around 90–95%.
At present, treatment with single-agent methotrexate is recommended for low-risk disease, while intense combination regimens including EMACO (etoposide, methotrexate, actinomycin D, cyclosphosphamide and vincristine (Oncovin) are recommended for intermediate or high-risk disease.
Hysterectomy (surgical removal of the uterus) can also be offered to patients > 40 years of age or those for whom sterilisation is not an obstacle. It may be required for those with severe infection and uncontrolled bleeding.
Choriocarcinoma arising in the testicle is rare, malignant and highly resistant to chemotherapy. The same is true of choriocarcinoma arising in the ovary. Testicular choriocarcinoma has the worst prognosis of all germ-cell cancers.
Choriocarcinoma of the placenta during pregnancy is preceded by:
- hydatidiform mole (50% of cases)
- spontaneous abortion (20% of cases)
- ectopic pregnancy (2% of cases)
- normal term pregnancy (20–30% of cases)
- hyperemesis gravidarum
Rarely, choriocarcinoma occurs in primary locations other than the placenta; very rarely, it occurs in testicles. Although trophoblastic components are common components of mixed germ cell tumors, pure choriocarcinoma of the adult testis is rare. Pure choriocarcinoma of the testis represents the most aggressive pathologic variant of germ cell tumors in adults, characteristically with early hematogenous and lymphatic metastatic spread. Because of early spread and inherent resistance to anticancer drugs, patients have poor prognosis. Elements of choriocarcinoma in a mixed testicular tumor have no prognostic importance.
Choriocarcinomas can also occur in the ovaries.
Trophoblastic neoplasms are neoplasms which derive from trophoblastic tissue.
Examples include:
- choriocarcinoma
- hydatidiform mole
A placental disease is any disease, disorder, or pathology of the placenta. The article also covers placentation abnormalities, which is often used synonymously for placental disease.
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.
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.
Ovarian pregnancies are rare: the vast majority of ectopic pregnancies occur in the fallopian tube; only about 0.15-3% of ectopics occur in the ovary. The incidence has been reported to be about 1:3,000 to 1:7,000 deliveries.
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.
GDM poses a risk to mother and child. This risk is largely related to uncontrolled high blood glucose levels and its consequences. The risk increases with higher blood glucose levels. Treatment resulting in better control of these levels can reduce some of the risks of GDM considerably.
The two main risks GDM imposes on the baby are growth abnormalities and chemical imbalances after birth, which may require admission to a neonatal intensive care unit. Infants born to mothers with GDM are at risk of being both large for gestational age (macrosomic) in unmanaged GDM, and small for gestational age and Intrauterine growth retardation in managed GDM. Macrosomia in turn increases the risk of instrumental deliveries (e.g. forceps, ventouse and caesarean section) or problems during vaginal delivery (such as shoulder dystocia). Macrosomia may affect 12% of normal women compared to 20% of women with GDM. However, the evidence for each of these complications is not equally strong; in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study for example, there was an increased risk for babies to be large but not small for gestational age in women with uncontrolled GDM. Research into complications for GDM is difficult because of the many confounding factors (such as obesity). Labelling a woman as having GDM may in itself increase the risk of having an unnecessary caesarean section.
Neonates born from women with consistently high blood sugar levels are also at an increased risk of low blood glucose (hypoglycemia), jaundice, high red blood cell mass (polycythemia) and low blood calcium (hypocalcemia) and magnesium (hypomagnesemia). Untreated GDM also interferes with maturation, causing dysmature babies prone to respiratory distress syndrome due to incomplete lung maturation and impaired surfactant synthesis.
Unlike pre-gestational diabetes, gestational diabetes has not been clearly shown to be an independent risk factor for birth defects. Birth defects usually originate sometime during the first trimester (before the 13th week) of pregnancy, whereas GDM gradually develops and is least pronounced during the first and early second trimester. Studies have shown that the offspring of women with GDM are at a higher risk for congenital malformations. A large case-control study found that gestational diabetes was linked with a limited group of birth defects, and that this association was generally limited to women with a higher body mass index (≥ 25 kg/m²). It is difficult to make sure that this is not partially due to the inclusion of women with pre-existent type 2 diabetes who were not diagnosed before pregnancy.
Because of conflicting studies, it is unclear at the moment whether women with GDM have a higher risk of preeclampsia. In the HAPO study, the risk of preeclampsia was between 13% and 37% higher, although not all possible confounding factors were corrected.
Placental villous immaturity, also villous immaturity and villous dysmaturity, is chorionic villous development that is inappropriate for the gestational age.
It is associated with diabetes mellitus
and fetal death near term, i.e. intrauterine demise close to the normal gestational period.
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).
Interstitial pregnancies account for 2–4% of all tubal pregnancies, or for 1 in 2,500 to 5,000 live births. About one in fifty women with an interstitial pregnancy dies. Patients with an interstitial pregnancies have a 7-times higher mortality than those with ectopics in general. With the growing use of assisted reproductive technologies, the incidence of interstitial pregnancy is rising.
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.
True cervical pregnancies tend to abort; if, however, the pregnancy is located higher in the canal and the placenta finds support in the uterine cavity it can go past the first trimester. With the placenta being implanted abnormally extensive vaginal bleeding can be expected at time of delivery and placental removal. While early cervical pregnancies may abort spontaneously or can be managed with excision, D&C, suturing, electrocautery, and tamponading, by medication such as methotrexate, and/or by uterine artery embolization, a more advanced pregnancy may require a hysterectomy to control bleeding. The more advanced the pregnancy the higher the risk for a major bleeding necessitating a hysterectomy.
On a very rare occasion, a cervical pregnancy results in the birth of a live baby, typically the pregnancy is in the upper part of the cervical canal and manages to extend into the lower part of the uterine cavity.
A cervical pregnancy can develop together with a normal intrauterine pregnancy; such a heterotopic pregnancy will call for expert management as to not to endanger the intrauterine pregnancy.
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.