Introduction Preterm birth (Latin: partus praetemporaneus or partus praematurus) is the birth of a baby of less than 37 weeks gestational

age. The cause of preterm birth is in many situations elusive and unknown; many factors appear to be associated with the development of preterm birth, making the reduction of preterm birth a challenging proposition. Premature birth is defined either as the same as preterm birth, or the birth of a baby before the developing organs are mature enough to allow normal postnatal survival. Premature infants are at greater risk for short and long term complications, including disabilities and impediments in growth and mental development. Significant progress has been made in the care of premature infants, but not in reducing the prevalence of preterm birth.[1]Preterm birth is among the top causes of death in infants worldwide Signs and Symptoms Symptoms of imminent spontaneous preterm birth, are signs of premature labor; one sign is four or more uterine contractions in one hour. In contrast to false labor, true labor is accompanied by cervical dilatation and effacement. Also, vaginal bleeding in the third trimester, heavy pressure in the pelvis, or abdominal or back pain could be indicators that a preterm birth is about to occur. A watery discharge from the vagina may indicate premature rupture of the membranes that surround the baby. While the rupture of the membranes may not be followed by labor, usually delivery is indicated as infection (chorioamnionitis) is a serious threat to both fetus and mother. In some cases the cervix dilates prematurely without pain or perceived contractions, so that the mother may not have warning signs until very late in the birthing process. Mortality and morbidity The shorter the term of pregnancy, the greater the risks of mortality and morbidity for the baby primarily due to the related prematurity. Preterm-premature babies ("preemies" or "premmies") have an increased risk of death in the first year of life (infant mortality), with most of that occurring in the first month of life (neonatal mortality). Worldwide, prematurity accounts for 10% of neonatal mortality, or around 500,000 deaths per year.[3] In the U.S. where many infections and other causes of neonatal death have been markedly reduced, prematurity is the leading cause of neonatal mortality at 25%.[4] Prematurely born infants are also at greater risk for having subsequent serious chronic health problems as discussed below. The earliest gestational age at which the infant has at least a 50% chance of survival is referred to as the limit of viability. As NICU care has improved over the last 40 years, viability has reduced to approximately 24 weeks, although rare survivors have been documented as early as 21 weeks.This date is controversial, as gestation in the case reported was measured from the known date of conception (by IVF) rather than, as usual, the date of the mother's last menstrual period, making gestation appear two weeks less than if calculated by the conventional method in this case.[7] As risk of brain damage and developmental delay is significant at that threshold even if the infant survives, there are ethical controversies over the aggressiveness of the care rendered to such infants. The limit of viability has also become a factor in the abortion debate.

CAUSES As the cause of labor still remains elusive, the exact cause of preterm birth is also unsolved. In fact, the cause of 50% of preterm births is never determined. Labor is a complex process involving many factors. Four different pathways have been identified that can result in preterm birth and have considerable evidence: precocious fetal endocrine activation, uterine overdistension, decidual bleeding, and intrauterine inflammation/infection.[13]Activation of one or more of these pathways may happen gradually over weeks, even months.[13] From a practical point a number of factors have been identified that are associated with preterm birth, however, an association does not establish causality. Maternal background A number of factors have been identified that are linked to a higher risk of a preterm birth: age at the upper and lower end of the reproductive years, be it more than 35[14] or less than 18 years of age.[1] Maternal height and weight can also play a role.[15] Further, in the US and the UK, black women have preterm birth rates of 1518%, more than double than that of the white population. This discrepancy is not seen in comparison to Asian or Hispanic immigrants and remains unexplained.[1] Pregnancy interval makes a difference as women with a 6 months span or less between pregnancies have a two-fold increase in preterm birth.[16] 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.[1] Women who have undergone previous surgically induced abortions have been shown to have a higher risk of preterm birth (less than 37 weeks), as well as extreme preterm birth (less than 28 weeks).[17] The preterm birth link has not been shown in women who terminated their pregnancies medically with pills such as RU486.[18] Adequate maternal nutrition is important. Women with a low BMI are at increased risk for preterm birth.[19]Further, women with poor nutritional 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.[20] Obesity does not directly lead to preterm birth; however, it is associated with diabetes and hypertension which are risk factors by themselves.[1]Women with a previous preterm birth are at higher risk for a recurrence at a rate of 1550% depending on number of previous events and their timing.[21] To some degree those individuals may have underlying conditions (i.e. uterine malformation, hypertension, diabetes) that persist. 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).[22]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 1990-97 revealed less risk of preterm birth for infants with legally married mothers, compared with those with common law wed or unwed parents.[23] Genetic make-up is a factor in the causality of preterm birth. An intra- and transgenerational increase in the risk of preterm delivery has been demonstrated.[24][25][26] No single gene has been identified, and it appears with the complexity of the labor initiation, that numerous polymorphic genetic interactions are possible.

Factors during pregnancy Multiple pregnancies (twins, triplets, etc.) are a significant factor in preterm birth. The March of Dimes Multicenter Prematurity and Prevention Study found that 54% of twins were delivered preterm vs. 9.6% of singleton births.[27] Triplets and more are even more endangered. 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, and often labor has to be induced for medical reasons; such conditions include high blood pressure,[28] pre-eclampsia,[29] maternal diabetes,[30] asthma, thyroid disease, and heart disease. In a number of women anatomical issues prevent that the baby is carried to term. Some women have a weak or short cervix[28] (the strongest predictor of premature birth)[31][32][33] The cervix may also have been compromised by previous cervical conization or loop excision. In women with uterine malformations the capacity of the uterus to hold the growing pregnancy may be limited and preterm labor ensues.[34] 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 two conditions is linked to a higher preterm birth rate.[35] Women with abnormal amounts of amniotic fluid, too much (polyhydramnios) or too little (oligohydramnios) are also at risk.[1] The mental status of the women is of significance. Anxiety[36] and depression have been linked to preterm birth.[1] Finally, the use of tobacco, cocaine, and excessive alcohol during pregnancy also increases the chance of preterm delivery. Tobacco is the most commonly abused drug during pregnancy and also contributes significantly to low birth weight delivery.[37][38] Babies with birth defects are at higher risk of being born preterm.[39] 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 1.13.5.[40] 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.[41] 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.[42] 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.[43] Infection Infections play a major role in the genesis of preterm birth and may account for 2540% of events.[44] The frequency of infection in preterm birth is inversely related to the gestational age.[1]Endotoxins released by microorganisms and cytokines stimulate deciduas responses including the release of prostaglandins which may stimulate uterine contractions. Further the decidual response may include release of matrix-degrading enzymes that weaken fetal membranes leading to premature rupture.[44] Intrauterine infection appears to be a chronic process.[44] Typical organisms identified in the uterus before rupture of the membranes are genital Mycoplasma spp and specifically Ureaplasma urealyticum. Micro-organisms may reach

the decidua in a number of ways, ascending, hematogeneous, iatrogenic by a procedure, or retrograde through the fallopian tubes. From the deciduas they may reach the space between the amnion and chorion, theamniotic fluid, and finally the fetus. A chorioamnionitis also may lead to sepsis of the mother. Fetal infection not only is linked to preterm birth but to significant long-term handicap includingcerebral palsy.[1] It has been reported that asymptomatic colonization of the decidua occurs in up to 70% of women at term using a DNA probe suggesting that the presence of micro-organism alone may be insufficient to initiate the infectious response. Bacterial vaginosis has been linked to preterm birth raising the risk by a factor of 1.5 3.[45] As the condition is more prevalent in black women in the US and the UK, it has been suggested to be an explanation for the higher rate of preterm birth in this population. It is opined that bacterial vaginosis before or during pregnancy may affect the decidual inflammatory response that leads to preterm birth.[1] A number of maternal bacterial infections are associated with preterm birth including pyelonephritis, asymptomaticbacteriuria, pneumonia, and appendicitis. Also periodontal disease has been shown repeatedly to be linked to preterm birth.[46] In contrast, viral infections, unless accompanied by a significant febrile response, are considered not to be a major factor in relation to preterm birth.[1]