Preterm birth

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. Preterm birth is among the top causes of death in infants worldwide.

Classification
In humans whereas the usual definition of preterm birth is birth before 37 complete weeks of gestational age,[2] a "premature" infant is one that has not yet reached the level of fetal development that generally allows life outside the womb. In the normal human fetus, several organ systems mature between 34 and 37 weeks, and the fetus reaches adequate maturity by the end of this period. One of the main organs greatly affected by premature birth is the lungs. The lungs are one of the last organs to develop in the womb; because of this, premature babies typically spend the first days/weeks of their life on a ventilator. Therefore, a significant overlap exists between preterm birth and prematurity. Generally, preterm babies are premature and term babies are mature. Prematurity can be reduced to a small extent by using drugs to accelerate maturation of the fetus, and to a greater extent by preventing preterm birth.

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. Chorioamnionitis is an inflammation of the fetal membranes (amnion and chorion) due to a bacterial infection. It typically results from bacteria ascending into the uterus from the vagina and is most often associated with prolonged labor. The risk of developing chorioamnionitis increases with each vaginal examination that is performed in the final month of pregnancy, including during labor.[3]

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.

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, the amniotic 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 including cerebral 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 microorganism 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, asymptomatic bacteriuria, 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]

Diagnosis
A helpful clinical test should predict a high risk for preterm birth during the early and middle part of the third trimester, when their impact is significant. Many women experience false labor (not leading to cervical shortening and effacement) and are falsely labeled to be in preterm labor. The study of preterm birth has been hampered by the difficulty in distinguishing between "true" preterm labor and false labor.[13] These new tests are used to identify women at risk for preterm birth.

Fetal fibronectin

Fetal fibronectin has become the most important biomarkerthe presence of this glycoprotein in the cervical or vaginal secretions indicates that the border between the chorion and deciduas has been disrupted. A positive test indicates an increased risk of preterm birth, and a negative test has a high predictive value.[1] It has been shown that only 1% of women in questionable cases of preterm labor delivered within the next week when the test was negative. Fetal fibronectin "leaks" into the vagina if a preterm delivery is likely to occur and can be measured in a diagnostic test.[1] When the fFN test is positive, it is an inconclusive result. A positive result can indicate that a woman will go into preterm labor soon, but she may not go into labor for weeks. When the fFN test is negative, the result is a better predictor. A negative result means that there is little possibility of preterm labour within the next 7 to 10 days, and the test can be repeated weekly for women who remain at high risk. A negative fetal fibronectin test gives a more than 95% likelihood of remaining undelivered for the next 2 weeks.[2] A systematic review of the medical literature found that fetal fibronectin is a good predictor of spontaneous preterm birth before cervical dilation.[3] The test may be run on patients between 22 and 35 weeks gestation. The test is easily performed and is usually painless. A specimen is collected from the patient using a vaginal swab. The swab is placed in a transport tube and sent to a laboratory for testing. Most labs can easily produce a result in less than one hour. A false positive fetal fibronectin result can occur if the test is performed after digital examination of the cervix or after having had intercourse. It is important that the swab be taken before a digital vaginal exam is performed.

Ultrasonography of the cervix

Obstetric ultrasound has become useful in the assessment of the cervix in women at risk for premature delivery. A short cervix preterm is undesirable: At 24 weeks gestation a cervix length of less than 25 mm defines a risk group for preterm birth. Further, the shorter the cervix the greater the risk.[48] It also has been helpful to use ultrasonography in women with preterm contractions, as those whose cervix length exceeds 30 mm are unlikely to deliver within the next week.[49] Traditional obstetric sonograms are done by placing a transducer on the abdomen of the pregnant woman. One variant, a transvaginal sonography, is done with a probe placed in the woman's vagina. Transvaginal scans usually provide clearer pictures during early pregnancy and in obese women. Also used is Doppler sonography which detects the heartbeat of the fetus. Doppler sonography can be used to evaluate the pulsations in the fetal heart and bloods vessels for signs of abnormalities.

Signs of Premature Labor Call your practitioner if you have any of the following:

Contractions or cramps, more than 5 in one hour Bright red blood from your vagina Pain during urination, possible urinary tract, bladder or kidney infection Sudden gush of clear, watery fluid from your vagina Low, dull backache Intense pelvic pressure

Management of Preterm Labor There are a lot of variables to managing preterm labor, both in medical options and in terms of what is going on with you and/or your baby. Here are some of the things that you may deal with when in preterm labor.

Hydration (Oral or IV) Bedrest (Home or Hospital), usually left side lying Medications to stop labor (Magnesium sulfate, brethine, terbutaline, etc.) - Magnesium sulfate is sometimes used as a tocolytic medicine to slow uterine contractions during preterm labor. But studies show it does not stop preterm labor and it may cause complications for both mother and baby.1Magnesium sulfate is usually given through a vein (intravenously) until contractions have slowed and the mother's cervix has stopped thinning (effacing) or opening (dilating).
Preterm labor can be delayed with the use of terbutaline, since the medication can cause muscles in the uterus to relax.

Medication to help prevent infection (More likely if your membranes have ruptured or if the contractions are caused by infection) Evaluation of your baby (Biophysical profile, non-stress or stress tests, amniotic fluid volume index (AFI), ultrasound, etc.) Medications to help your baby's lung develop more quickly (Usually if preterm birth in inevitable)

Biophysical profile

-This test can be done in the later stages of pregnancy. It is more frequently used in cases
where the mother is going past her assigned due date to ensure fetal well-being. In some cases it is done as a precaution after problems in a previous pregnancy or because of high risk factors such as previous pregnancy loss in the second half of pregnancy, high blood pressure, diabetes,

How the test is done: This test is usually done in your practitioner's office. One of the major parts of the BPP is a detailed ultrasound. During the ultrasound the technician is looking for movements of your baby's arms and legs (muscle tone), movements of the body, breathing movements (moving chest muscles), and the measurement of amniotic fluid. The second portion of the test consists of a non-stress test. When the test is done: This test is most frequently done between weeks 38 and 42, however, it can be used as early as the beginning of the third trimester. How the results are given: Your baby will be scored on five things during the test. A score of 0 (abnormal) or 2 (normal) will be given in each of these categories:

muscle tone body movements breathing movements amniotic fluid levels heart rate

A score of below 6 is worrisome and action will probably be taken, which may include induction or cesarean section. 6 is considered borderline. The test may be repeated as often as daily until the baby is born, though most often it is a one time event or a weekly event depending on the reason for the biophysical profile.

Non-stress
Why the test is done: This test can be done in the later stages of pregnancy. It is more frequently used in cases where the mother is going past her assigned due date to ensure fetal well-being. In some

cases it is done as a precaution after problems in a previous pregnancy or because of high risk factors such as diabetes, intrauterine growth retardation (IUGR), etc. How the test is done: This test is usually done in your practitioner's office. You will sit in a chair or lie on a table with fetal monitoring equipment hooked to your belly. The monitor will record your baby's heart rate in conjunction with any uterine activity. More frequently than not you are asked to press a button when the baby moves so that the heart rate can be seen in relationship to that movement.

When the test is done: This test is most frequently done between weeks 38 and 42, however, it can be used as early as the beginning of the third trimester. How the results are given: Reactive and non-reactive are usually the way the results are give. Sometimes little ones don't cooperate during the testing and move. So the mother is offered a drink of something usually containing sugar or bubbles to perk the baby up. If this doesn't cause the baby to move sometimes a loud sound will be used to startle the baby into moving. Remember babies can and do sleep in utero.

- Stress tests
Why the test is done: This test is done to see how well the baby will respond to the stress of contractions during labor. How the test is done: Usually an injection of Pitocin will be given and you will be monitored to see how your baby responds to the contractions via the electronic fetal monitor. When the test is done: This test is usually done at the very end of pregnancy, prior to an induction. How the results are given:

Pass or fail. Risks involved: May start labor, may cause fetal distress. Alternatives: Non-stress testing or biophysical profile. Where do you go from here? If the baby passes you may either be left alone for other testing and to wait until natural labor starts. You may be induced, or a cesarean birth may be decided upon if your baby does not appear to deal well with contractions.

- Amniotic fluid volume index (AFI)

Why the test is done: This test can be done in the later stages of pregnancy. It is more frequently used in cases where the mother is going past her assigned due date to ensure fetal well-being. In some cases it is done as a precaution after problems in a previous pregnancy or because of high risk factors such as previous pregnancy loss in the second half of pregnancy, high blood pressure, diabetes, intrauterine growth retardation (IUGR), etc. How the test is done: This test is usually done in your practitioner's office. One of the major parts of the BPP is a detailed ultrasound. During the ultrasound the technician is looking for movements of your baby's arms and legs (muscle tone), movements of the body, breathing movements (moving chest muscles), and the measurement of amniotic fluid. The second portion of the test consists of a non-stress test. When the test is done: This test is most frequently done between weeks 38 and 42, however, it can be used as early as the beginning of the third trimester. How the results are given: Your baby will be scored on five things during the test. A score of 0 (abnormal) or 2 (normal) will be given in each of these categories:

muscle tone body movements

breathing movements amniotic fluid levels heart rate

A score of below 6 is worrisome and action will probably be taken, which may include induction or cesarean section. 6 is considered borderline. The test may be repeated as often as daily until the baby is born, though most often it is a one time event or a weekly event depending on the reason for the biophysical profile.

- Ultrasound
Why the test is done: This is a very simple test in a lot of ways and can give your practitioners a lot of valuable information. However, it is important to note that the routine use of ultrasound is questioned, even by the American College of Obstetricians and Gynecologists in healthy, low risk pregnancies. The most frequent reasons for its use are:

Dating of the pregnancy Rule out ectopic pregnancy (tubal pregnancy) Check for fetal viability, particularly after bleeding or other complication Screening for certain genetic defects or anomalies Assist in certain genetic testing procedures like Amniocentesis and CVS

How the test is done: This test can be done with an abdominal or vaginal probe depending on the stage of the pregnancy and what they are looking for. The transducer or probe sends out high frequency sound waves which are sent into the body. As they pass through they bounce off different objects and are sent back as electrical signals, which are then processed and displayed as the image on the screen. You may be asked to have a full bladder for better viewing of the baby and uterus. For the abdominal ultrasound you will usually slip your pants down to the top of your thighs and a cold gel will be applied to aid in the visualization of the baby. The transducer is moved slowly over your abdomen and the signals are sent back to the machine which will project the images of your baby. Vaginal ultrasound is used earlier on in pregnancy, also known as transvaginal ultrasound. You will remove your pants and the vaginal probe will be inserted into your vagina for a better view. When the test is done: This test can be done at any point in pregnancy depending on the results that they wish to obtain. It is nearly impossible to see anything prior to the hCG levels of pregnancy reaching 1,500 -

2,000 mIU. Many women will have an ultrasound between 18-22 weeks known as a fetal anatomy survey. How the results are given: Depends on the use of the test. Usually your practitioner will explain the results to you.

Prevention of Preterm Labor While not all cases of preterm labor can be prevented there are a lot of women who will have contractions that can be prevented by simple measures. One of the first things that your practitioner will tell you to do if you are having contractions is staying very well hydrated. We definitely see the preterm labor rates go up in the summer months. What happens with dehydration is that the blood volume decreases, therefore increasing the concentration of oxytocin (hormone that causes uterine contractions) to rise. Hydrating yourself will increase the blood volume. Others things that you can do would be to pay attention to signs and symptoms of infections (bladder, yeast, etc.) because they can also cause infections. Keeping all of your appointments with your practitioner and calling whenever you have questions or symptoms. A lot of women are afraid of "crying wolf," but it is much better to be incorrect than to be in preterm labor and not being treated. Bed rest and medications that relax the muscles in the uterus are also commonly used to try to stop preterm labor.

Who is at risk for preterm labor and birth?

Health care providers currently have no way of knowing which women will experience preterm labor or deliver their babies preterm. But there are factors that place a woman at higher risk for preterm labor or birth:

Certain infections, such as bacterial vaginosis and trichomoniasis Shortened cervix Previously given birth preterm

Bacterial vaginosis

What is bacterial vaginosis? Bacterial vaginosis is an infection of the vagina. It occurs when there are too many bacteria that are normally present in the vagina. It is the most common vaginal infection in women of reproductive age. What are the symptoms of bacterial vaginosis? Bacterial vaginosis often causes a thin, milky discharge from the vagina that is described as having a fishy odor. This odor may be more noticeable after sexual intercourse. Redness or itching of the vagina is not common. In fact, some women with bacterial vaginosis have no symptoms at all. In addition, having bacterial vaginosis increases the risk of getting other sexually transmitted diseases. The condition has also been associated with pelvic inflammatory disease. Bacterial vaginosis is thought to be associated with preterm labor and preterm birth. What are the treatments for bacterial vaginosis? A health care provider can prescribe an antibiotic to treat bacterial vaginosis. The medication will bring the level of bacteria in the vagina back into a healthy range. There are no over-thecounter treatments for bacterial vaginosis.

Trichomoniasis

What is vaginitis? Vaginitis is a term for any infection or inflammation of the vagina. What are the symptoms of vaginitis? In general, vaginitis may cause itching, irritation, or abnormal vaginal discharge. There are a several different kinds of vaginitis, each with their own causes and symptoms:

Candida or yeast infections Yeast infections of the vagina are probably the most familiar form of vaginitis. They occur when too much of the fungus Candida grows in the vagina. Yeast infections produce a thick, white discharge from the vagina that can look like cottage cheese. The discharge can be watery and often has no smell. Yeast infections usually cause the vagina and vulva (the area outside the vagina) to become itchy and red.

Bacterial vaginosis Bacterial vaginosis is the most common vaginal infection in women of reproductive age. It is caused by an overgrowth of bacteria that are usually present in the vagina.

Bacterial vaginosis will often cause a thin, milky discharge from the vagina that may have a fishy odor. Many women with bacterial vaginosis have no symptoms and only discover they have it during a routine gynecologic exam.

Trichomoniasis Trichomoniasis is a sexually transmitted disease that is caused by a single-cell parasite. It can cause vaginal itching, burning, and soreness of the vagina and vulva, as well as burning during urination. Many women with trichomoniasis do not develop any symptoms. Non-infectious vaginitis This form of vaginitis is usually caused by an allergic reaction or irritation from vaginal sprays, douches, spermicidal products, soaps, detergents, or fabric softeners. It can cause burning, itching, or vaginal discharge even if there is no infection.

What are the treatments for vaginitis? The key to treating vaginitis is knowing which kind you have. The treatment must be specific to the type of vaginitis present.

Yeast infections are usually treated with an anti-yeast cream or suppository placed inside the vagina. A health care provider can write a prescription for most yeast infection treatments. Although you can also buy medicine to treat yeast infections over-the-counter, it is a good idea to see a health care provider the first time you have symptoms of a yeast infection. Because this medicine will not cure other types of vaginitis, it is important to be sure you actually have a yeast infection before using these treatments.

Bacterial vaginosis is treated with an antibiotic that gets rid of the bad bacteria and leaves the good bacteria. There is no over-the-counter treatment for bacterial vaginosis, so it is important to see your health care provider for a prescription. Sexually transmitted forms of vaginitis need to be treated by a health care provider right away. It is important to avoid sexual contact until you have been treated to prevent spreading the infection. A womans sexual partner(s) will need treatment as well. Trichomoniasis and Chlamydia are both treated by antibiotics. Neither genital herpes nor HPV can be cured, but both can be controlled with the help of your health care provider and medications.

Non-infectious vaginitis can be treated by stopping the use of the product that caused the allergic reaction or irritation. Your health care provider may also be able to provide medicated cream to help reduce the symptoms until the reaction goes away.

It is important to remember that each type of vaginitis has a different treatment. Therefore it is very important to see a health care provider to be sure you are using the right treatment for your condition. Also, some kinds of vaginitis have no symptoms so it is important to have regular gynecologic exams.

Can I prevent vaginitis? There are some things you can do to lower your chances of getting vaginitis.

If you often get yeast infections, you may want to avoid clothes that hold in heat and moisture, such as panty hose without a cotton lining, nylon panties, or tight jeans. Avoid douches and vaginal sprays because they can kill good bacteria or cause irritation. Practicing safe sex can help protect against sexually transmitted forms of vaginitis.

Preventing preterm labor and birth

You can help prevent preterm birth by learning the symptoms of preterm labor and following some simple instructions. The first thing to do is to get medical care both before and during pregnancy. If you do have preterm labor, get medical help quickly. This will improve the chances that you and your baby will do well. Medications sometimes slow or stop labor if they are given early enough. Drugs called corticosteroids, if given 24 hours before birth, can help the baby's lungs and brain mature. This can prevent some of the worst health problems a preterm baby has. Only if a woman receives medical care quickly can drugs be helpful. Knowing what to look for is essential. Treatment with a form of the hormone progesterone may help prevent premature birth in some women who have already had a premature baby. Symptoms of preterm labor Remember, preterm labor is any labor that occurs between 20 weeks and 37 weeks of pregnancy. Here are the symptoms:

Contractions (your abdomen tightens like a fist) every 10 minutes or more often Change in vaginal discharge (leaking fluid or bleeding from your vagina) Pelvic pressurethe feeling that your baby is pushing down Low, dull backache Cramps that feel like your period Abdominal cramps with or without diarrhea

If you start to have any of these symptoms between 20 weeks and 37 weeks of pregnancy, follow the instructions in the section below "What to do if you have symptoms of preterm labor." Don't let anyone tell you that these symptoms are "normal discomforts of pregnancy"! If any of them (you don't need to have all of them) happen before your 37th week of pregnancy, you need to do something about it.

What to do if you have symptoms of preterm labor? Call your health care provider or go to the hospital right away if you think you are having preterm labor. Your provider may tell you to:

Come to the office or go to the hospital for evaluation. Stop what you are doing and rest on your left side for one hour. Drink 23 glasses of water or juice (not coffee or soda).

If the symptoms get worse, or don't go away after one hour, call your health care provider again or go to the hospital. If the symptoms go away, take it easy for the rest of the day. If the symptoms stop but come back, call your health care provider again or go to the hospital. When you call your provider, be sure to tell the person on the phone that you are concerned about the possibility of preterm labor. The only way your provider can know if preterm labor is starting is by doing an internal examination of your cervix (the bottom of your uterus). If your cervix is opening up (dilating), preterm labor could be beginning. You and your health care provider are a team, working together to have a healthy pregnancy and healthy baby. Your team works best when both of you participate fully, so your knowledge about preterm labor can be essential in helping to prevent a preterm birth. Talk to your health care provider about all of this, and be sure to keep all of your prenatal care appointments. Preterm birth is one of the complications of pregnancy that health care providers are working hard to eliminate. Your participation in this effort is just as important as theirs!

Mortality and Morbidity

Mortality is the rate of death or the number of premature babies admitted to an NCIU who do not survive compared to those who do. As noted above, the mortality rate of premature babies has dramatically improved over the last 20 years or so. The overwhelming majority of babies with access to the modern technology and medical techniques available in the NICU now survive. At the same time, there are limits to the medical technology and techniques available in the NICU; some babies who are born too soon are too small to either save at all or save without serious disability or morbidity. Morbidity is the number of babies who survive but with lasting complications, compared to the number who survive with no lasting complications. In other words, the morbidity rate is the number of premature babies who grow up with medical, developmental, or psychological problems compared to those who grow up without any of these issues. Although many premature babies go on to live normal, healthy lives, the success rate in this regard is not as overwhelming as the dramatic improvement in mortality. In fact, the two statistics are related: medicine has become very successful at keeping premature babies alive, especially the extremely premature, who tend to have more complications than other premature babies.

STATISTICS
Of all early neonatal deaths (deaths within the first 7 days of life) that are not related to congenital malformations, 28% are due to preterm birth.7 Preterm birth rates have been reported to range from 5% to 7% of live births in some developed countries, but are estimated to be substantially higher in developing countries.8 These figures appear to be on the rise.9 Events leading to preterm birth are still not completely understood, although the etiology is thought to be multifactorial. It is, however, unclear whether preterm birth results from the interaction of several pathways or the independent effect of each pathway. Causal factors linked to preterm birth include medical conditions of the mother or fetus, genetic influences, environmental exposure, infertility treatments, behavioural and socioeconomic factors and iatrogenic prematurity.9 Approximately 4550% of preterm births are idiopathic, 30% are related to preterm rupture of membranes (PROM) and another 1520% are attributed to medically indicated or elective preterm deliveries.10,11 Estimation of preterm birth rates and, ideally, their proper categorization (e.g. spontaneous versus indicated) are essential for accurate determination of global incidence in order to inform policy and programmes on interventions to reduce the risk of premature labour and delivery. No data have been published on the global incidence of preterm birth. Preterm birth rates available from some developed countries, such as the United Kingdom, the United States and the Scandinavian countries, show a dramatic rise over the past 20 years.6,12 Factors possibly contributing to but not completely explaining this upward trend include increasing rates of multiple births, greater use of assisted reproduction techniques, increases in the proportion of births among women over 34 years of age and changes in clinical practices, such as greater use of elective Caesarean section. For example, the increasing use of ultrasonography rather than the date of the last menstrual period to estimate gestational age may have resulted in larger numbers of births being classified as preterm. Changes in the definitions of fetal loss, stillbirth and early neonatal death may also have contributed to the substantial increases in preterm birth rates recorded in developed countries in the past two decades.13,14 In developing countries, accurate and complete population data and medical records usually do not exist. Furthermore, estimates of the rate of preterm birth in developing countries are influenced by a range of factors including varying procedures used to determine gestational age, national differences in birth registration processes, heterogeneous definitions used for preterm birth, differences in perceptions of the viability of preterm infants and variations in religious practices such as local burial customs, which can discourage the registering of preterm births.15 These issues make measurement of preterm birth and comparisons across and between developing countries difficult. The World Health Organization (WHO) conducted a systematic review of the worldwide incidence/prevalence of maternal mortality and morbidity in the period 19972002 to contribute to the knowledge base in this area.16,17 Data extracted for that review and relevant to the estimation of preterm birth rates are used for this study, along with data from a supplementary search carried out for the years 20032007 to bring the estimates up to date. This manuscript

presents an analysis of preterm birth rates worldwide in an effort to understand the global extent of this public health problem, gain insight into existing assessment strategies and map