Based on recent (2005) US NCHS data, the rate of multiple births is now approximately 3.4% (4,138,349 total births, of which 139,816 were twins or higher-order multiple births).

The majority of identical twins share a common (monochorionic) placenta, and of these approximately 15% go on to develop TTTS.

By extrapolating the number of expected identical twins (about one-third) from annual multiple births, and the number of twins with monochorionic placentae (about two-thirds), and from these the number thought to develop TTTS (about 15%), there are at least 4,500 TTTS cases per year in the U.S. alone: 139,816 X .33 X .66 X .15 = 4,568 cases of TTTS per year in U.S. (involving more than 9,000 babies.)

Since spontaneous pregnancy losses and terminations that occur prior to 20 weeks go uncounted by the C.D.C., this estimate of TTTS cases may be very conservative.

Although infertility treatments have increased the rate of multiple birth, they have not appreciably diluted the expected incidence of identical twins. Studies show a higher rate of identical twins (up to 20 times with IVF) using these treatments versus spontaneous pregnancy rates.

One Australian study, however, noted an occurrence of only 1 in 4,170 pregnancies or 1 in 58 twin gestations. This distinction could be partly explained by the "hidden mortality" associated with MC multifetal pregnancies—instances lost due to premature rupture of membrane (PROM) or intrauterine fetal demise before a thorough diagnosis of TTTS can be made.

Some doctors recommend complete bed-rest for the mother coupled with massive intakes of protein as a therapy to try to counteract the syndrome. Research completed shows these nutritional supplements do work. Diet supplementation was associated with lower overall incidence of TTTS (20/52 versus 8/51, P = 0.02) and with lower prevalence of TTTS at delivery (18/52 versus 6/51, P = 0.012) when compared with no supplementation. Nutritional intervention also significantly prolonged the time between the diagnosis of TTTS and delivery (9.4 ± 3.7 weeks versus 4.6 ± 6.5 weeks; P = 0.014). The earlier nutritional regimen was introduced, the lesser chance of detecting TTTS ( P = 0.001). Although not statistically significant, dietary intervention was also associated with lower Quintero stage, fewer invasive treatments, and lower twin birth weight discordance. Diet supplementation appears to counter maternal metabolic abnormalities in monochorionic twin pregnancies and improve perinatal outcomes in TTTS when combined with the standard therapeutic options. Nutritional therapy appears to be most effective in mitigating cases that are caught in Quintero Stage I, little effect has been observed in those that are beyond Stage I.

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).

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.

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 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.

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.

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.

Causes of increased foetal-maternal haemorrhage are seen as a result of trauma, placental abruption or may be spontaneous with no cause found.

Up to 30 mL of foetal-maternal transfusion may take place with no significant signs or symptoms seen in either mother or foetus. Loss in excess of this may result in significant morbidity and mortality to the fetus. Foetal-maternal haemorrhage is one cause of intrauterine death (IUD).

The following have been identified as risk factors for placenta previa:

- Previous placenta previa (recurrence rate 4–8%), caesarean delivery, myomectomy or endometrium damage caused by D&C.

- Women who are younger than 20 are at higher risk and women older than 35 are at increasing risk as they get older.

- Alcohol use during pregnancy was previous listed as a risk factor, but is discredited by this article.

- Women who have had previous pregnancies ( multiparity ), especially a large number of closely spaced pregnancies, are at higher risk due to uterine damage.

- Smoking during pregnancy; cocaine use during pregnancy

- Women with a large placentae from twins or erythroblastosis are at higher risk.

- Race is a controversial risk factor, with some studies finding that people from Asia and Africa are at higher risk and others finding no difference.

- Placental pathology (Vellamentous insertion, succinturiate lobes, bipartite i.e. bilobed placenta etc.)

- Baby is in an unusual position: breech (buttocks first) or transverse (lying horizontally across the womb).

Placenta previa is itself a risk factor of placenta accreta.

It is estimated that less than 1 mL of foetal blood is lost to the maternal circulation during normal labour in around 96% of normal deliveries. The loss of this small amount of blood may however be a sensitising event and stimulate antibody production to the foetal red blood cells, an example of which is Rhesus disease of the newborn.

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.

Since locked twins are often diagnosed in the late stages of delivery, it is often too late to intervene to save the life of the first twin and thus there is a high rate of stillbirth, estimated to be over 50%.

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.

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".

In rare cases, inherited bleeding disorders, like hemophilia, von Willebrand disease (vWD), or factor IX or XI deficiency, may cause severe postpartum hemorrhage, with an increased risk of death particularly in the postpartum period. The risk of postpartum hemorrhage in patients with vWD and carriers of hemophilia has been found to be 18.5% and 22% respectively. This pathology occurs due to the normal physiological drop in maternal clotting factors after delivery which greatly increases the risk of secondary postpartum hemorrhage.

Another bleeding risk factor is thrombocytopenia, or decreased platelet levels, which is the most common hematological change associated with pregnancy induced hypertension. If platelet counts drop less than 100,000 per microliter the patient will be at a severe risk for inability to clot during and after delivery.

Maternal consequences include the following:

- Itching, which can become intense and debilitating

- Premature labor

- Deranged clotting, which requires Vitamin K

Fetal consequences include:

- Fetal distress

- Meconium ingestion

- Meconium aspiration syndrome

- Stillbirth

Delivery has been recommended in the 38th week when lung maturity has been established.

There are many causes of "fetal distress" including:

- Breathing problems

- Abnormal position and presentation of the fetus

- Multiple births

- Shoulder dystocia

- Umbilical cord prolapse

- Nuchal cord

- Placental abruption

- Premature closure of the fetal ductus arteriosus

- Uterine rupture

- Intrahepatic cholestasis of pregnancy, a liver disorder during pregnancy

In twin pregnancies, it is very common for one or both babies to be in the breech position. Most often twin babies do not have the chance to turn around because they are born prematurely. If both babies are in the breech position and the mother has gone into labour early, a cesarean section may be the best option. About 30-40% of twin pregnancies result in only one baby being in the breech position. If this is the case, the babies can be born vaginally. After the first baby who is not in the breech position is delivered, the baby who is presented in the breech position may turn itself around, if this does not happen another procedure may performed called the breech extraction. The breech extraction is the procedure that involves the obstetrician grabbing the second twin's feet and pulling him/her into the birth canal. This will help with delivering the second twin vaginally. However, if the second twin is larger than the first, complications with delivering the second twin vaginally may arise and a cesarean section should be performed. At times, the first twin (the twin closest to the birth canal) can be in the breech position with the second twin being in the cephalic position (vertical). When this occurs, risks of complications are higher than normal. In particular, a serious complication known as Locked twins. This is when both babies interlock their chins during labour. When this happens a cesarean section should be performed immediately.

According to the theory of thrifty phenotype, placental insufficiency 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.

Fetal microchimerism could have an implication on maternal health. Isolating cells in cultures can alter the properties of the stem cells, but in pregnancy the effects of fetal stem cells can be investigated without in vitro cultures. Once characterized and isolated, fetal cells that are able to cross the blood brain barrier could impact certain procedures. For example, isolating stem cells can be accomplished through taking them from sources like the umbilical cord. These fetal stem cells can be used in intravenous infusion to repair the brain tissue. Hormonal changes in pregnancy alter neurogenesis, which could create favorable environments for fetal cells to respond to injury.

The true function on fetal cells in mothers is not fully known, however, there have been reports of positive and negative health effects. The sharing of genes between the fetus and mother may lead to benefits. Due to not all genes being shared, health complications may arise as a result of resource allocation. During pregnancy, fetal cells are able to manipulate the maternal system to draw resources from the placenta, while the maternal system tries to limit it.

Exact cause of placenta previa is unknown. It is hypothesized to be related to abnormal vascularisation of the endometrium caused by scarring or atrophy from previous trauma, surgery, or infection. These factors may reduce differential growth of lower segment, resulting in less upward shift in placental position as pregnancy advances.

Instead of referring to "fetal distress" current recommendations hold to look for more specific signs and symptoms, assess them, and take the appropriate steps to remedy the situationthrough the implementation of intrauterine resuscitation. Traditionally the diagnosis of "fetal distress" led the obstetrician to recommend rapid delivery by instrumental delivery or by caesarean section if vaginal delivery is not advised.

Fetuses with polyhydramnios are at risk for a number of other problems including cord prolapse, placental abruption, premature birth and perinatal death. At delivery the baby should be checked for congenital abnormalities.