Preterm birth

Preterm birth
Classification and external resources

Intubated preterm baby in an incubator
ICD-10 O60.1, P07.3
ICD-9 644, 765
DiseasesDB 10589
MedlinePlus 001562
eMedicine ped/1889
MeSH D047928

In humans, preterm birth refers to the birth of a baby of less than 37 weeks gestational age. The cause for 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, commonly used as a synonym for preterm birth, refers to the birth of a baby before its organs mature enough to allow normal postnatal survival, and growth and development as a child. 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 by far the most common cause of prematurity, and is the major cause of neonatal mortality in developed countries. Premature children may commonly be referred to throughout their life as being born a "preemie" or "preemie baby".

Contents

Classification

In that they continue developing after birth, most animals are not born mature. At birth, a normal human infant is less mature than infants of some other primate species, possibly to allow the disproportionately large head to fit through a pelvis adapted for walking on two legs.

In humans, whereas the usual definition of preterm birth is birth before 37 weeks gestation,[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; such signs consists of four or more uterine contractions in one hour before 37 weeks' gestation. In contrast to false labor, true labor is accompanied by cervical shortening 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 real 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,[5][6] although rare survivors have been documented as early as 21 weeks.[1] This date is controversial as gestation in this case was measured from the date of conception rather than the date of the mother's last menstrual period. Gestation appears 2 weeks less than if calculated by the more common method.[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.

Specific risks for the preterm neonate

Preterm infants usually show physical signs of prematurity in reverse proportion to the gestational age. As a result they are at risk for numerous medical problems affecting different organ systems.

A large study on children born between 22 and 25 weeks who were currently at school age found that 46 percent had severe or moderate disabilities such as cerebral palsy, vision or hearing loss and learning problems. 34 percent were mildly disabled and 20 percent had no disabilities. While 12 percent had disabling cerebral palsy.[10]

A new mother holds her premature baby at Kapiolani Medical Center NICU in Honolulu, Hawaii

Causes

As the cause of labor still remains elusive, the exact cause of preterm birth is also unsolved. 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.[11] Activation of one or more of these pathways may happen gradually over weeks, even months.[11] 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[12] or less than 18 years of age.[1] Further, in the US and the UK Afro-American and Afro-Caribbean women have preterm birth rates of 15–18%, 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.[13] 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).[14] The preterm birth link has not been shown in women who terminated their pregnancies medically with pills such as RU-486.[15] Adequate maternal nutrition is important. Women with a low BMI are at increased risk for preterm birth.[16] 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.[17] 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 15–50% depending on number of previous events and their timing.[18] 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)[19]. 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[20].

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.[21][22][23] 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.[24] 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,[25] pre-eclampsia,[26] maternal diabetes,[27] 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[25] (the strongest predictor of premature birth)[28][29][30] 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.[31] 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.[32] 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[33] 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.[34][35] Babies with birth defects are at higher risk of being born preterm.[36]

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[37].

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[38]. 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[39].

Infection

Infections play a major role in the genesis of preterm birth and may account for 25–40% of events.[40] The frequency of infection in preterm birth is inversely related to the gestational age.[1] Endotoxins released by microorganisms and cytokines stimulate deciduasl 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.[40] Intrauterine infection appears to be a chronic process.[40] 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 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.[41] 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.[42] 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

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 labelled 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.[11] These new test are used to identify women at risk for preterm birth.

Fetal fibronectin

Fetal fibronectin has become the most important biomarker—the 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.[43]

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.[44] 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.[45]

Prevention

Historically efforts have been primarily aimed to improve survival and health of preterm infants (tertiary intervention). Such efforts, however, have not reduced the incidence of preterm birth. Increasingly primary interventions that are directed at all women, and secondary intervention that reduce existing risks are looked upon as measures that need to be developed and implemented to prevent the health problems of premature infants and children.[46]

Preconceptional

Raising public and professional awareness about the scope of the problem and its significance as the major contributor to infant mortality is a beginning to reduce avoidable risk factor. Among them is the need to reduce repeated uterine instrumentation (i.e. repeated surgical abortions)[47] and to avoid risky choices in infertility treatments. Adoption of specific professional policies can immediately reduce risk of preterm birth as the experience in assisted reproduction has shown when the number of embryos during embryo transfer were limited.[46] Many countries have established specific programs to protect pregnant women from hazardous and night-shift work, and to provide them with time for prenatal visits and paid pregnancy-leave. The EUROPOP study showed that preterm birth is not related to type of employment, but to prolonged work (>42 h per week) or prolonged standing (>6 h per day).[48] Also, night work has been linked to preterm birth.[49] Health policies that take these findings into account can be expected to reduce the rate of preterm birth.[46] Avoidance of weight extremes and good nutritional support are important. Although a study failed to show that multivitamin preparation taken prior to conception reduces the risk of preterm birth,[50] preconceptional intake of folic acid is recommended to reduce birth defects. There is significant evidence that long term (> one year) use of folic acid supplement preconceptionally may reduce premature birth.[51][52][53] Reducing smoking is expected to benefit pregnant women and their offspring.[46]

During pregnancy

Interventions that should have been initiated prior to pregnancy, can still be instituted during pregnancy including nutritional adjustments, use of vitamin supplements, and smoking cessation.[46] Calcium supplementation as well as supplemental intake of C and E vitamins could not be shown to reduce preterm birth rates.[54][55] Different strategies are used in the administration of prenatal care, and future studies need to determine if the focus should be on screening for high risk women, or widened support for low-risk women, or to what degree these approaches should be merged.[46] While periodontal infection has been linked with preterm birth, randomized trials have not shown that periodontal care during pregnancy reduces preterm birth rates.[46]

Screening of low risk women

Screening for asymptomatic bacteriuria followed by appropriate treatment reduces pyelonephritis and reduces the risk of preterm birth.[56] Extensive studies have been carried out to determine if other forms of screening in low-risk women followed by appropriate intervention are beneficial, including: Screening for and treatment of Ureaplasma urealyticum, group B streptococcus, Trichomonas vaginalis, and bacterial vaginosis did not reduce the rate of preterm birth.[46] Routine ultrasound examination of the length of the cervix identifies patients at risk, but cerclage is not proven useful, and the application of a progesterone is under study.[46] Screening for the presence of fibronectin in vaginal secretions is not recommended at this time in women at low risk.

Self-care

Self-care methods to reduce the risk of preterm birth include proper nutrition, avoiding stress, seeking appropriate medical care, avoiding infections, and the control of preterm birth risk factors (e.g. working long hours while standing on feet, carbon monoxide exposure, domestic abuse, and other factors). Self-monitoring vaginal pH followed by yogurt treatment or clindamycin treatment if the pH was too high all seem to be effective at reducing the risk of preterm birth.[57][58]

Secondary (reducing existing risks)

Women are identified to be at increased risk for preterm birth on the basis of their past obstetrical history or the presence of known risk factors. Preconception intervention can be helpful in selected patients in a number of ways. Patients with certain uterine anomalies may have a surgical correction (i.e. removal of a uterine septum), and those with certain medical problems can be helped by optimizing medical prior to conception, be it for asthma, diabetes, hypertension and others.

During pregnancy

Reducing indicated preterm birth

A number of agents have been studied for secondary prevention of indicated preterm birth. Trials using low-dose aspirin, fish oil, vitamin C and E, and calcium to reduce preeclampsia demonstrated some reduction in preterm birth only when low-aspirin was used.[46] Interestingly, even if agents such as calcium or antioxidants were able to reduce preeclampsia, a resulting decrease in preterm birth was not observed.[46]

Reducing spontaneous preterm birth

Reduction in maternal activity – pelvic rest, limited work, bed rest – is frequently recommended although there is no clear proof of its efficacy. Also, increasing medical care by more frequent visits and more education has not shown a reduction in preterm birth rates.[59] Use of nutritional supplements such as omega-3 polyunsaturated fatty acids is based on the observation that populations who have a high intake of such agents are at low risk for preterm birth, presumably as these agents inhibit production of proinflammatory cytokines. A randomized trial showed a significant decline in preterm birth rates,[60] and further studies are in the making.

Antibiotics

Studies examining the use of antibiotics have provided mixed results; a Cochrane review of 15 trials shows no major benefit,[61] in contrast a review by Lamont suggested that treatment of bacterial vaginosis if initiated prior to 20 w gestation is beneficial.[62] It has been suggested that the presence of a chronic chorioamnionitis may not be amenable to antibiotics, thus the difficulty to demonstrate their effectiveness.[46]

Progesterone

Progesterone, often given in the form of 17-hydroxyprogesterone caproate, relaxes the uterine musculature, maintains cervical length, and has anti-inflammatory properties, and thus exerts activities expected to be beneficial in reducing preterm birth. Two meta-analyses demonstrated a deduction in the risk of preterm birth in women with recurrent preterm birth by 40–55%.[63][64] However, progesterone is not effective in all populations, as a study involving twin gestations failed to see any benefit.[65]

Cervical cerclage

In preparation for childbirth, the woman's cervix shortens. Preterm cervical shortening is linked to preterm birth and can be detected by ultrasonography. Cervical cerclage is a surgical intervention that places a suture around the cervix to prevent its shortening and widening. Numerous studies have been performed to assess the value of cervical cerclage and the procedure appears helpful primarily for women with a short cervix and a history of preterm birth.[66] Instead of a prophylactic cerclage, women at risk can be monitored during pregnancy by sonography, and when shortening of the cervix is observed, the cerclage can be performed. Women with a short cervix but no history of preterm birth, and women with twin gestation, do not benefit from a cerclage.[46]

Management

Tertiary interventions are aimed at women who are about to go into preterm labor, or rupture the membranes or bleed preterm. The use of the fibronectin test and ultrasonography improves the diagnostic accuracy and reduces false-positive diagnosis. While treatments to arrest early labor where there is progressive cervical dilatation and effacement will not be effective to gain sufficient time to allow the fetus to grow and mature further, it may defer delivery sufficiently to allow the mother to be brought to a specialized center that is equipped and staffed to handle preterm deliveries.[67] Centers for the care of women with preterm delivery are usually staffed by maternal-fetal specialists and highly trained staff and linked to neonatal intensive care units (vi). In a hospital setting women are hydrated via intravenous infusion as dehydration can lead to premature uterine contractions.

Glucocorticosteroids

Severely premature infants may have underdeveloped lungs, because they are not yet producing their own surfactant. This can lead directly to respiratory distress syndrome, also called hyaline membrane disease, in the neonate. To try to reduce the risk of this outcome, pregnant mothers with threatened premature delivery prior to 34 weeks are often administered at least one course of glucocorticoids, a steroid that crosses the placental barrier and stimulates the production of surfactant in the lungs of the fetus. Typical glucocorticoids that would be administered in this context are betamethasone or dexamethasone, often when the fetus has reached viability at 23 weeks. In cases where premature birth is imminent, a second "rescue" course of steroids may be administered 12 to 24 hours before the anticipated birth. There is no research consensus on the efficacy and side-effects of a second course of steroids, but the consequences of RDS are so severe that a second course is often viewed as worth the risk. Beside reducing respiratory distress, other neonatal complication are reduced by the use of glucocorticosteroids, namely intraventricular haemorrhage, necrotising enterocolitis, and patent ductus arteriosus.[68]

Despite being used for over 50 years to treat respiratory distress syndrome, glucocorticosteroid therapy is still controversial. Much of this concern is based on when these steroids should be administered (i.e. prenatally or postnatally) or for how long (i.e. acutely or chronically). For instance, recent clinical research has shown that the postnatal administration of dexamethasone can lead to permanent neuromotor and cognitive deficits.[69] This has led to a drastic reduction in the postnatal use of glucocorticosteroids in prematurely born infants. In addition, a recent large scale study has found that a second “rescue” dose of betamethasone prenatally does not improve preterm birth outcomes and leads to decreased weight, length, and head circumference.[70] Finally, while glucocorticosteroid exposure in the adult is considered safe, recent animal research has shown that a single exposure to these same drugs during brain development causes rapid brain degeneration.[71][72] Despite these concerns, there is a consensus that the benefits of a single regimen of prenatal glucocorticosteroids vastly outweigh the potential risks.[73]

The routine administration of antibiotics to all women with threatened preterm labor reduces the risk of the baby to get infected with group B streptococcus and has been shown to reduce related mortality rates.[74]

Research reported at the 2008 conference of the Society for Maternal-Fetal Medicine suggests that administration of magnesium sulfate (Epsom salt) to women just before premature birth can cut the rate of cerebral palsy in half. While the compound is cheap and safe, it may make mothers and infants groggy, and details are pending scientific publication.[52]

Tocolysis

Anti-contraction medications (tocolytics), such as Beta2-agonist drugs (ritodrine, terbutaline, fenoterol), calcium-channel blockers nifedipine and oxytocin antagonists (atosiban) appear only to have a temporary effect in delaying delivery. Tocolysis has not fulfilled its promise as it is rarely successful beyond 24–48 hours because current medication do not alter the fundamentals of labor activation.[11] However, just gaining 48 hours is sufficient to allow the pregnant women to be transferred to a center specialized for management of preterm deliveries and give administered corticosteroids the possibility to reduce neonatal organ immaturity. Meta-analyses indicate that calcium-channel blockers and an oxytocin antagonist can delay delivery by 2–7 days, and β2-agonist drugs delay by 48 hours but carry more side effects. [75][46] Meta-analyses of magnesium sulfate failed to support it as a tocolytic agent.[11]

When membranes rupture prematurely, obstetrical management looks for development of labor and signs of infection. Administration of corticosteroids is indicated prior to 32 weeks gestation. Prophylactic antibiotic administration has been shown to prolong pregnancy and reduced neonatal morbidity with rupture of membranes at less than 34 weeks.[76] Because of concern about necrotizing enterocolitis, amoxicillin or erythromycin has been recommended, but not amoxicillin + clavulanic acid (co-amoxiclav).[76]

The routine use of cesarean section for early delivery of infants expected to have very low birth weight is controversial,[46] and a decision concerning the route and time of delivery probably needs to be made on a case by case basis.

Neonatal care

In developed countries premature infants are usually cared for in a neonatal intensive care unit (NICU). The physicians who specialize in the care of very sick or premature babies are known as neonatologists. In the NICU, premature babies are kept under radiant warmers or in incubators (also called isolettes), which are bassinets enclosed in plastic with climate control equipment designed to keep them warm and limit their exposure to germs. Modern neonatal intensive care involves sophisticated measurement of temperature, respiration, cardiac function, oxygenation, and brain activity. Treatments may include fluids and nutrition through intravenous catheters, oxygen supplementation, mechanical ventilation support, and medications. In developing countries where advanced equipment and even electricity may not be available or reliable, simple measures such as kangaroo care (skin to skin warming), encouraging breastfeeding, and basic infection control measures can significantly reduce preterm morbidity and mortality. Bili lights may also be used to treat newborn jaundice (hyperbilirubinemia).

Prognosis

Most children even if born very preterm adjust very well during childhood and adolescence.[77] As survival has improved, the focus of interventions directed at the newborn has shifted to reduce long-term disabilities, particularly those related to brain injury.[77] Some of the complications related to prematurity may not be apparent until years after the birth. A long-term study demonstrated that the risks of medical and social disabilities extend into adulthood and are higher with decreasing gestational age at birth and include cerebral palsy, mental retardation, disorders of psychological development, behavior, and emotion, disabilities of vision and hearing, and epilepsy.[78] Also it was shown that higher levels of education were less likely to be obtained with decreasing gestational age at birth.[78] People born prematurely may be more susceptible to developing depression as teenagers.[79] Some of these problems can be described as being within the executive domain and have been speculated to arise due to decreased myelinization of the frontal lobes.[80] Throughout life they are more likely to require services provided by physical therapists, occupational therapists, or speech therapists. Further long-term studies are needed to get a better picture about the sequalae of preterm birth.[77]

Epidemiology

Disability-adjusted life year for prematurity and low birth weight per 100,000 inhabitants in 2004.[81]
     no data      less than 120      120-240      240-360      360-480      480-600      600-720      720-840      840-960      960-1080      1080-1200      1200-1500      more than 1500

In Europe and many developed countries the preterm birth rate is generally 5–9%, and in the USA it has even risen to 12–13% in the last decades.[1] Three obstetric events precede preterm birth: spontaneous preterm births are the 40–45% preterm births that follow preterm labor and the 25–30% preterm births after premature rupture of membranes. The remainder (30–35%) are preterm births that are induced for obstetrical reasons; obstetricians may have to deliver the baby preterm because of a deteriorating intrauterine environment (i.e. infection, intrauterine growth retardation) or significant endangerment of the maternal health (i.e. preeclampsia, cancer). By gestational age, 5% of preterm births occur at less than 28 weeks (extreme prematurity), 15% at 28–31 weeks (severe prematurity), 20% at 32–33 weeks (moderate prematurity), and 60–70% at 34–36 weeks (late preterm).[1]

As weight is easier to determine than gestational age, the World Health Organization tracks rates of low birth weight (< 2,500 grams), which occurred in 16.5 percent of births in less developed regions in 2000.[82] It is estimated that one-third of these low birth weight deliveries are due to preterm delivery. Weight generally correlates to gestational age, however, infants may be underweight for other reasons than a preterm delivery. Neonates of low birth weight (LBW) have a birth weight of less than 2500 g (5 lb 8 oz) and are mostly but not exclusively preterm babies as they also include small for gestational age (SGA) babies. Weight-based classification further recognizes Very Low Birth Weight (VLBW) which is less than 1500 g, and Extremely Low Birth Weight (ELBW) which is less than 1000 g.[83] Almost all neonates in these latter two groups are born preterm.

Preterm birth is a significant cost factor in healthcare, not even considering the expenses of long-term care for individuals with disabilities due to preterm birth. A 2003 study in the US determined neonatal costs to be $224,400 for a newborn at 500–700 g versus $1,000 at over 3,000 g. The costs increase exponentially with decreasing gestational age and weight.[84] The 2007 Institute of Medicine report Preterm Birth [85] found that the 550,000 preemies born each year in the U.S. run up about $26 billion in annual costs, mostly related to care in NICUs, but the real tab may top $50 billion.[86]

Society and culture

Notable preterm births

James Elgin Gill (born on 20 May 1987 in Ottawa, Canada) was the earliest premature baby in the world. He was 128 days premature (21 weeks and 5 days gestation) and weighed 1 pound 6 ounces (624 g). He survived and is quite healthy.[87][88]

Amillia Taylor is also often cited as the most-premature baby.[89] She was born on 24 October 2006 in Miami, Florida, at 21 weeks and 6 days gestation.[90] This report has created some confusion as her gestation was measured from the date of conception (through in-vitro fertilization) rather than the date of her mother's last menstrual period making her appear 2 weeks younger than if gestation was calculated by the more common method.[79] At birth, she was 9 inches (22.86 cm) long and weighed 10 ounces (283 grams).[89] She suffered digestive and respiratory problems, together with a brain hemorrhage. She was discharged from the Baptist Children's Hospital on 20 February 2007.[89]

The record for the smallest premature baby to survive was held for some time by Madeline Mann, who was born at 26 weeks weighing 9.9 oz (280 g) and 9.5 inches (24.13 cm) long.[91] This record was broken in September 2004 by Rumaisa Rahman, who was born in the same hospital[92] at 25 weeks gestation. At birth, she was eight inches (20 cm) long and weighed 244 grams (8.6 ounces). Her twin sister was also a small baby, weighing 563 grams (1 pound 4 ounces) at birth. During pregnancy their mother had suffered from pre-eclampsia, which causes dangerously high blood pressure putting the baby into distress and requiring birth by caesarean section. The larger twin left the hospital at the end of December, while the smaller remained there until 10 February 2005 by which time her weight had increased to 1.18 kg (2.6 lb).[93] Generally healthy, the twins had to undergo laser eye surgery to correct vision problems, a common occurrence among premature babies.

The autistic savant Derek Paravicini was born at 25 weeks. The oxygen therapy given during his time in a neonatal intensive care unit rendered him blind and affected his developing brain, resulting in his severe learning disability. Furthermore Paravicini developed autism. However, he also has absolute pitch and his musical abilities developed to genius levels.

The world's smallest premature boy to survive was born in February 2009 at Children's Hospitals and Clinics of Minnesota in Minneapolis, Minnesota. Jonathon Whitehill was born at 25 weeks gestation with a weight of 310 grams (10.9 ounces). He was hospitalized in the Neonatal Intensive Care Unit for five months, and then discharged. [94]

Historical figures who were born prematurely include Johannes Kepler (born in 1571 at 7 months gestation), Isaac Newton (born in 1643, small enough to fit into a quart mug, according to his mother), Winston Churchill (born in 1874 at 7 months gestation), and Anna Pavlova (born in 1885 at 7 months gestation).[95]

References

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  7. ↑ James SD (2007). "Life at 21 weeks:Immature Lungs and a Handful of Fragile Skin and Pain". ABC News. http://abcnews.go.com/Health/story?id=2890242&page=1. Retrieved 2008-12-16. 
  8. ↑ 8.0 8.1 March of Dimes --> Neonatal Death Retrieved on September 2, 2009
  9. ↑ Berbel P, Navarro D, Ausó E, Varea E, Rodríguez AE, Ballesta JJ, Salinas M, Flores E, Faura CC, de Escobar GM. (2010). Role of late maternal thyroid hormones in cerebral cortex development: an experimental model for human prematurity. Cereb Cortex. 20(6):1462-75. PMID: 19812240.
  10. ↑ {{cite web|url=http://www.msnbc.msn.com/id/6790571/ns/health-kids_and_parenting/ | title=Extreme preemies face long-term disabilities
  11. ↑ 11.0 11.1 11.2 11.3 11.4 Simhan HN, Caritis SN (2007). "Prevention of Preterm Delivery". New England Journal of Medicine 357: 477–487. doi:10.1056/NEJMra050435. PMID 17671256. 
  12. ↑ Martius JA, Steck T, Oehler MK, Wulf KH (1998). "Risk factors associated with preterm (<37+0 weeks) and early preterm birth (<32+0 weeks): univariate and multivariate analysis of 106 345 singleton births from the 1994 statewide perinatal survey of Bavaria". European Journal of Obstetrics & Gynecology and Reproductive Biology 80 (2): 183–189. doi:10.1016/S0301-2115(98)00130-4. PMID 9846665. 
  13. ↑ Smith GC, Pell JP, Dobbie R (2003). "Interpregnancy interval and risk of preterm birth and neonatal death: retrospective cohort study". British Medical Journal 327: 313. doi:10.1136/bmj.327.7410.313. PMID 12907483. 
  14. ↑ Moreau, Caroline (2005). "Previous Induced Abortions and the Risk of Very Preterm Delivery: Results of the EPIPHAGE Study". Obstetrical and Gynecological Survey 60: 627–628. PMID 16186764. 
  15. ↑ Virk J, Zhang J, Olsen J (2007). "Medical Abortion and the Risk of Subsequent Adverse Pregnancy Outcomes". New England Journal of Medicine 357: 648–653. doi:10.1056/NEJMoa070445. PMID 17699814. 
  16. ↑ Hendler I, Goldenberg RL, Mercer BM, et al. (2005). "The preterm prediction study: association between maternal body mass index (BMI) and spontaneous preterm birth". American Journal of Obstetrics & Gynecology 192: 882–886. doi:10.1016/j.ajog.2004.09.021. PMID 15746686. 
  17. ↑ "Cholesterol Lowering Diet for Pregnant Women May Help Prevent Preterm Birth". British Medical Journal 331: 1093. 2005. doi:10.1136/bmj.331.7525.0-e. 
  18. ↑ Mercer BM, Goldenberg RL, Moawad AH, et al. (1999). "The preterm prediction study: effect of gestational age and cause of preterm birth on subsequent obstetric outcome". American Journal of Obstetrics & Gynecology 181: 1216–1221. doi:10.1016/S0002-9378(99)70111-0. PMID 10561648. 
  19. ↑ Raatikainen K, Heiskanen N, Heinonen S (2005). "Marriage still protects pregnancy". BJOG 112: 1411–6. 
  20. ↑ Luo ZC, Wilkins R, Kramer MS (2004). "Disparities in pregnancy outcomes according to marital status and cohabitation status". Obstetrics and Gynecology 103: 1300–7. 
  21. ↑ Winkvist A, Mogren I, Hogberg U (1998). "Familial patterns in birth characteristics: impact on individual and population risks". International Journal of Epidemiology 27: 248–254. doi:10.1093/ije/27.2.248. PMID 9602406. 
  22. ↑ Porter TF, Fraser AM, Hunter CY, Ward RH, Varner WM (1997). "The risk of preterm birth across generations". Obstetrics & Gynecology 90: 63–67. doi:10.1016/S0029-7844(97)00215-9. PMID 9207815. 
  23. ↑ doi:10.1097/AOG.0b013e3181dffcdb
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  24. ↑ Gardner MO, Goldenberg RL, Cliver SP, Tucker JM, Nelson KG, Copper RL (1995). "The origin and outcome of preterm twin pregnancies". Obstetrics & Gynecology 85 (4): 553–557. doi:10.1016/0029-7844(94)00455-M. PMID 7898832. 
  25. ↑ 25.0 25.1 Goldenberg RL, Iams JD, Mercer BM, et al. (1998). "The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. NICHD MFMU Network". American Journal of Public Health 88 (2): 233–238. doi:10.2105/AJPH.88.2.233. PMID 9491013. 
  26. ↑ Bánhidy F, Acs N, Puhó EH, Czeizel AE (2007). "Pregnancy complications and birth outcomes of pregnant women with urinary tract infections and related drug treatments". Scandinavian Journal of Infectious Diseases 39 (5): 390–397. doi:10.1080/00365540601087566. PMID 17464860. 
  27. ↑ Rosenberg TJ, Garbers S, Lipkind H, Chiasson MA (2005). "Maternal obesity and diabetes as risk factors for adverse pregnancy outcomes: differences among 4 racial/ethnic groups". American Journal of Public Health 95 (9): 1545–1551. doi:10.2105/AJPH.2005.065680. PMID 16118366. 
  28. ↑ To MS, Skentou CA, Royston P, Yu CKH, Nicolaides KH (2006). "Prediction of patient-specific risk of early preterm delivery using maternal history and sonographic measurement of cervical length: a population-based prospective study". Ultrasound in Obstetrics & Gynecology 27: 362–367. doi:10.1002/uog.2773. PMID 16565989. 
  29. ↑ Fonseca EB, Celik E, Parra M, Singh M, Nikolaides KH, Fetal Medicine Foundation Second Trimester Screening Group (2007). "Progesterone and the risk of preterm birth among women with a short cervix". New England Journal of Medicine 357 (5): 462–469. doi:10.1056/NEJMoa067815. PMID 17671254. 
  30. ↑ Romero R (2007). "Prevention of sponatneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment". Ultrasound in Obstetrics & Gynecology 30: 675–686. doi:10.1002/uog.5174. PMID 17899585. http://www3.interscience.wiley.com/journal/99020267/home. 
  31. ↑ Acien P (1993). "Reproductive performance of women with uterine malformations". Human Reproduction 8: 122–126. PMID 8458914. 
  32. ↑ Krupa FG, Faltin D, Cecatti JG, Surita FG, Souza JP (2006). "Predictors of preterm birth". International Journal of Gynecology & Obstetrics 94: 5–11. doi:10.1016/j.ijgo.2006.03.022. PMID 16730012. 
  33. ↑ Dole N, Savitz DA, Hertz-Picciotto I, Siega-Riz AM, McMahon MJ, Buekens P (2003). "Maternal stress and preterm birth". American Journal of Epidemiology 157 (1): 14–24. doi:10.1093/aje/kwf176. PMID 12505886. http://171.66.121.65/cgi/reprint/157/1/14. 
  34. ↑ Shiono PH, Klebanoff MA, Nugent RP, Cotch MF, Wilkins DG, Rollins DE, Carey CJ, Behrman RE (1995). "Fetus-Placenta-Newborn: the Impact of Cocaine and Marijuana Use on Low Birth Weight and Preterm Birth: a Multicenter Study". American Journal of Obstetrics & Gynecology 172: 19–27. doi:10.1016/0002-9378(95)90078-0. PMID 7847533. 
  35. ↑ Parazzini F, Chatenoud L, Surace M, Tozzi L, Salerio B, Bettoni G, Benzi G (2003). "Moderate Alcohol Drinking and Risk of Preterm Birth". European Journal of Clinical Nutrition 57: 1345. doi:10.1038/sj.ejcn.1601690. PMID 14506499. 
  36. ↑ Dola SM, Gross SJ, Merkatz IR, et al. (2007). "The Contribution of Birth Defects to Preterm Birth and Low Birth Weight". Obstetrics & Gynecology 110: 318–324. 
  37. ↑ Boy A, Salihu HM (2004). "Intimate partner violence and birth outcomes: a systematic review". Int J Fertil Womens Med 49 (4): 159–64. 
  38. ↑ Ugboma HA, Akani CL (2004). "Abdominal massage: another cause of maternal mortality". Niger J Med 13 (3): 259–62. 
  39. ↑ Field T, Deeds O, Diego M, Hernandez-Reif M, Gauler A, Sullivan S, Wilson D, Nearing G (2009). "Benefits of combining massage therapy with group interpersonal psychtherapy in prenatally depressed women". J Bodyw Mov Ther 13 (4): 297=303. 
  40. ↑ 40.0 40.1 40.2 Goldenberg RL, Hauth JC, Andrews WW (2000). "Intrauterine infection and preterm delivery". New England Journal of Medicine 342: 1500–1507. doi:10.1056/NEJM200005183422007. PMID 10816189. 
  41. ↑ Hillier SL, Nugent RP, Eschenbach DA, et al. (1995). "Association between bacterial vaginosis and preterm delivery of a low-birthweight infant. The vaginal infections and prematurity study group". New England Journal of Medicine 333: 1737–1742. doi:10.1056/NEJM199512283332604. PMID 7491137. 
  42. ↑ Jeffcoat MK, Geurs NC, Reddy MS, Cliver SC, Goldenberg RL, Hauth JC (2001). "Periodontal Infection and Preterm Birth". Journal of the American Dental Association 132 (7): 875–880. PMID 11480640. 
  43. ↑ Lu GC, Goldenberg RL, Cliver SP, Kreaden US, Andrews WW (2001). "Vaginal fetal fibronectin levels and spontaneous preterm birth in symptomatic women". Obstetrics & Gynecology 97: 225–228. doi:10.1016/S0029-7844(00)01130-3. PMID 11165589. 
  44. ↑ Iams JD, Goldenberg RL, Meis PJ, et al. (1996). "The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network". New England Journal of Medicine 334 (9): 567–572. doi:10.1056/NEJM199602293340904. PMID 8569824. 
  45. ↑ Leitich H, Brunbauer M, Kaider A, Egarter C, Husslein P (1999). "Cervical length and dilatation of the internal cervical os detected by vaginal ultrasonography as markers for preterm delivery: A systematic review". American Journal of Obstetrics & Gynecology 181 (6): 1465–1472. doi:10.1016/S0002-9378(99)70407-2. PMID 10601930. 
  46. ↑ 46.00 46.01 46.02 46.03 46.04 46.05 46.06 46.07 46.08 46.09 46.10 46.11 46.12 46.13 46.14 Iams JD, Romero R, Culhane JF, Goldenberg RL (2008). "Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth". The Lancet 371 (9607): 164–175. doi:10.1016/S0140-6736(08)60108-7. PMID 18191687. 
  47. ↑ Ancel PY, Lelong N, Papiernik E, et al. and for EUROPOP (2004). "History of induced abortion as a risk factor for preterm birth in European countries: results of the EUROPOP survey". Human Reproduction 19: 734–740. doi:10.1093/humrep/deh107. PMID 14998979. 
  48. ↑ Saurel-Cubizolles MJ, Zeitlin J, Lelong N, et al. and for the Europop Group (2004). "Employment, working conditions, and preterm birth: results from the Europop case-control survey". Journal of Epidemiology and Community Health 58: 395–401. doi:10.1136/jech.2003.008029. PMID 15082738. 
  49. ↑ Other Complications include: -Jaundice Of Prematurity -Atrial Septal Defects commonly seen in babies with bronchopulmonary dysplasia because their lungs are so fragile. -GER Gastroesophgeal reflux -Patent Ductus Arterosis - Seizures - Immature GI System so feeding from a (NG) tube or Nasogastric tube may help make feeding easier on the babiesx tummy. Also theirs TPN feeding or Total Parentral Nutrition its made up of lipids,calories,good fats calsuim,magnesium salfate and other vitamins including B and C. Neonatalologists work with the family as a whole instead of just the neonate or baby whose systems are to immature to actually swallow food so babies between 23-28 weeks are fed through a neonatal gastric tube from the babies nose to the stomach. In some neonates there are disabilites from varying conditions of the baby this depends on the gestational age the babies delivered at usually women with severe enough Preeclampsia will deliver earlier than normal and those mothers worry greatly because of all of their rumours about NICUs and babies needing wheelchairs glasses and also needing medicines for seizures and ADD/ADHD, Borderline Personality Disorder,Anxeity Disorders. Pompeii LA, Savitz DA, Evenson KR, Rogers B, McMahon M (2005). "Physical exertion at work and the risk of preterm delivery and small-for-gestational-age birth". Obstetrics & Gynecology 106: 1279–1288. PMID 16319253. 
  50. ↑ Czeizel AE, Dudas I, Metnecki J (1994). "Pregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation. Final report". Archives of Gynecology and Obstetrics 255: 131–139. doi:10.1007/BF02390940. PMID 7979565. 
  51. ↑ Bukowski R, Malone FD, Porter FT, Nyberg DA, Comstock CH, Hankins GDV, Eddleman K, Gross SJ, Dugoff L, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, D'Alton ME (2009). "Preconceptional folate supplementation and the risk of spontaneous preterm birth: a cohort study". PLoS Med 6 (5): e1000061. doi:10.1371/journal.pmed.1000061. 
  52. ↑ 52.0 52.1 Associated Press (8 February 2008). "Study: Giving moms magnesium sulfate cuts risk of cerebral palsy in preemies". Press release. http://www.nctimes.com/articles/2008/02/10/health/16_51_232_8_08.txt. Retrieved 2008-12-16. 
  53. ↑ Engel SM, Olshan AF, Siega-Riz AM, Savitz DA, Chanock SJ (2006). "Polymorphisms in folate metabolizing genes and risk for spontaneous preterm and small-for-gestational age birth". American Journal of Obstetrics & Gynecology 195 (5): 1231.e1–11. doi:10.1016/j.ajog.2006.07.024. PMID 17074544. 
  54. ↑ Hofmeyr GJ, Atallah AN, Duley L (2006). "Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems". Cochrane Database Systematic Reviews 3: CD001059. PMID 16855957. 
  55. ↑ Rumbold AR, Crowther CA, Haslam RR, et al. (2006). "Vitamins C and E and the risks of preeclampsia and perinatal complications". New England Journal of Medicine 354: 1796–1806. doi:10.1056/NEJMoa054186. PMID 16641396. 
  56. ↑ Romero R, Oyarzun E, Mazor M, Sirtori M, Hobbins JC, Bracken M (1989). "Meta-analysis of the relationship between asymptomatic bacteriuria and preterm delivery/low birth weight". Obstetrics & Gynecology 73: 576–582. PMID 2927852. 
  57. ↑ Lamont RF, Jaggat AN (2007). "Emerging drug therapies for preventing spontaneous preterm labor and preterm birth". Expert Opinion on Investigational Drugs 16: 337–345. doi:10.1517/13543784.16.3.337. PMID 17302528. 
  58. ↑ Hoyme UB, Saling E (2004). "Efficient prematurity prevention is possible by pH-self measurement and immediate therapy of threatening ascending infection". European Journal of Obstetrics & Gynecology and Reproductive Biology 115: 148–153. doi:10.1016/j.ejogrb.2004.02.038. PMID 15262346. 
  59. ↑ Hodnett ED, Fredericks S (2003). "Support during pregnancy for women at increased risk of low birth weight babies". Cochrane Database Systematic Reviews 3: CD000198. doi:10.1002/14651858.CD000198. PMID 12917888. 
  60. ↑ Olsen SF, Secher SJ, Tabor A, et al. (2000). "Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trial In Pregnancy (FOTIP) Team". British Journal of Obstetrics & Gynaecology 107: 382–395. doi:10.1111/j.1471-0528.2000.tb13235.x. PMID 10740336. 
  61. ↑ McDonald HM, Brocklehurst P, Gordon A (2007). Cochrane Database Systematic Reviews. 1. pp. CD000262. PMID 17253447. 
  62. ↑ Lamont RF (2005). "Can antibiotics prevent preterm birth–the pro and con debate". British Journal of Obstetrics & Gynaecology 112 (Suppl 1): 67–73. doi:10.1111/j.1471-0528.2005.00589.x. PMID 15715599. 
  63. ↑ Dodd JM, Flenady V, Cincotta R, Crowther CA (2006). "Prenatal administration of progesterone for preventing preterm birth". Cochrane Database Systematic Reviews 1: CD004947. PMID 18591318. 
  64. ↑ Mackenzie R, Walker M, Armson A, Hannah ME (2006). "Progesterone for the prevention of preterm birth among women at increased. A systematic review and meta-analysis of randomized controlled trials.". American Journal of Obstetrics & Gynecology 194: 1234–1242. doi:10.1016/j.ajog.2005.06.049. PMID 16647905. 
  65. ↑ Caritis S, Rouse D (2006). "A randomized controlled trial of 17-hydroxyprogesterone caproate (17-OHPC) for the prevention of preterm birth in twins". American Journal of Obstetrics & Gynecology 195: S2. doi:10.1016/j.ajog.2006.10.003. 
  66. ↑ Berghella V, Odibo AO, To MS, Rust O, Althuisius SM (2005). "Cerclage for short cervix on ultrasonography; meta-analysis of trials using individual patient data". Obstetrics & Gynecology 106: 181–189. PMID 15994635. 
  67. ↑ Phibbs CS, Baker LC, Caughey AB, et al. (2007). "Level and volume of neonatal intensive care and mortality in very-low-birth-weight infants". New England Journal of Medicine 356: 2165–2175. doi:10.1056/NEJMsa065029. PMID 17522400. 
  68. ↑ Roberts D, Dalziel S (2006). "Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth". Cochrane Database Systematic Reviews 3: CD004454. PMID 16856047. 
  69. ↑ Yeh TF, Lin YJ, Lin HC, et al. (2004). "Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity". New England Journal of Medicine 350: 1304–1313. doi:10.1056/NEJMoa032089. PMID 15044641. 
  70. ↑ Murphy KE, Hannah ME, Willan AR, et al. (2008). "Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial". The Lancet 372: 2143–2151. doi:10.1016/S0140-6736(08)61929-7. PMID 19101390. 
  71. ↑ Noguchi KK, Walls KC, Wozniak DF, et al. (2008). "Acute neonatal glucocorticoid exposure produces selective and rapid cerebellar neural progenitor cell apoptotic death". Cell Death & Differentiation 15: 1582–1592. doi:10.1038/cdd.2008.97. PMID 18600230. 
  72. ↑ "Steroids used in preemies may kill brain cells". USA Today. 2008-11-17. http://www.usatoday.com/printedition/life/20081118/bl_bottomstrip18.art.htm. Retrieved 2010-05-22. 
  73. ↑ http://consensus.nih.gov/1994/1994AntenatalSteroidPerinatal095html.htm
  74. ↑ Schrag S, Gorwitz R, Kultz-Butts K, Schuchat K (2002). "Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC". MMWR: Recommendations and Reports 51: 1–22. PMID 12211284. 
  75. ↑ Li X, Zhang Y, Shi Z. Ritodrine in the treatment of preterm labour: a meta-analysis.Indian J Med Res. 2005 Feb;121(2):120-7.PMID: 15756046
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  77. ↑ 77.0 77.1 77.2 Saigal S, Doyle LW (2008). "An overview of mortality and sequelae of preterm birth from infancy to adulthood.". The Lancet 371 (9608): 261–269. doi:10.1016/S0140-6736(08)60136-1. PMID 18207020. 
  78. ↑ 78.0 78.1 Moster D, Lie RT, Markestad T (2008). "Long-Term Medical and Social Consequences of Preterm Birth". New England Journal of Medicine 359 (3): 262–273. doi:10.1056/NEJMoa0706475. PMID 18635431. 
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  80. ↑ Böhm, Katz-Salamon, Institute, Smedler, Lagercrantz, Forssberg (2002). "Developmental Risks and Protective Factors for Influencing cognitive outcome at 5,5 years of age in very-low-birthweight children". Developmental Medicine & Child Neurology 44: 508–516. doi:10.1017/S001216220100247X. PMID 12206615. 
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  82. ↑ "Data and statistics". World Health Organisation. http://www.who.int/research/en/. 
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  84. ↑ Gilbert WM, Nesbitt TS, Danielsen B (2003). "The Cost of Prematurity: Quantification by Gestational Age and Birth Weight". Obstetrics & Gynecology 102: 488–492. doi:10.1016/S0029-7844(03)00617-3. PMID 12962929. 
  85. ↑ Richard E. Behrman, Adrienne Stith Butler, Editors, Committee on Understanding Premature Birth and Assuring Healthy Outcomes. Preterm Birth: Causes, Consequences, and Prevention. Institute of Medicine. The National Academies Press, 2007. Retrieved 2010-1-14.
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Pathology of pregnancy, childbirth and the puerperium (O, 630-679)
Pregnancy
Pregnancy with
abortive outcome
Ectopic pregnancy (Abdominal pregnancy, Cervical pregnancy, Ovarian pregnancy, Interstitial pregnancy) · Hydatidiform mole · Miscarriage
Oedema, proteinuria and
hypertensive disorders
Gestational hypertension (Pre-eclampsia, Eclampsia, HELLP syndrome) · Gestational diabetes
Other, predominantly
related to pregnancy
Hyperemesis gravidarum · Intrahepatic cholestasis of pregnancy · Acute fatty liver of pregnancy · Hepatitis E
Integumentary system/
dermatoses of pregnancy

PUPPP · Gestational pemphigoid

Impetigo herpetiformis · Intrahepatic cholestasis of pregnancy · Linea nigra · Prurigo gestationis · Pruritic folliculitis of pregnancy · Striae gravidarum
Chorea gravidarum
Gestational thrombocytopenia · Pregnancy-induced hypercoagulability
Maternal care related to the
fetus and amniotic cavity
amniotic fluid (Polyhydramnios, Oligohydramnios) · chorion/amnion (Chorioamnionitis, Chorionic hematoma, Premature rupture of membranes, Amniotic band syndrome, Monoamniotic twins) · placenta (Placenta praevia, Placental abruption, Monochorionic twins, Twin-to-twin transfusion syndrome, Circumvallate placenta) · Braxton Hicks contractions · Hemorrhage (Antepartum)
Labor
Preterm birth · Postmature birth · Cephalopelvic disproportion · Dystocia (Shoulder dystocia) · Fetal distress · Vasa praevia · Uterine rupture · Hemorrhage (Postpartum) · placenta (Placenta accreta) · Umbilical cord prolapse · Amniotic fluid embolism
Puerperal
Puerperal fever · Peripartum cardiomyopathy · Postpartum thyroiditis · Puerperal mastitis · Breastfeeding difficulties (Agalactia, Galactorrhea) · Postpartum depression · Diastasis symphysis pubis
Other
Maternal death

: OBS

phys/devp

mthr/fetu/infc,

proc, drug(2A/G2C)
Certain conditions originating in the perinatal period / fetal disease (P, 760-779)
Maternal factors and
complications of pregnancy,
labour and delivery

placenta: Placenta praevia · Placental insufficiency · Twin-to-twin transfusion syndrome

chorion/amnion: Chorioamnionitis

umbilical cord: Umbilical cord prolapse · Nuchal cord · Single umbilical artery
Length of gestation
and fetal growth
Small for gestational age/Large for gestational age · Preterm birth/Postmature birth · Intrauterine growth restriction
Birth trauma
scalp (Cephalhematoma, Chignon, Caput succedaneum, Subgaleal hemorrhage) · Brachial plexus lesion (Erb's palsy, Klumpke paralysis)
By system
Respiratory
Intrauterine hypoxia · Infant respiratory distress syndrome · Transient tachypnea of the newborn · Meconium aspiration syndrome · pleural disease (Pneumothorax, Pneumomediastinum) · Wilson-Mikity syndrome · Bronchopulmonary dysplasia
Pneumopericardium · Persistent fetal circulation
Haemorrhagic and
hematologic disease

Vitamin K deficiency (Haemorrhagic disease of the newborn)

HDN (ABO • Anti-Kell • Rh c • Rh D • Rh E) · Hydrops fetalis · Hyperbilirubinemia (Kernicterus, Neonatal jaundice)

Velamentous cord insertion

Intraventricular hemorrhage (Germinal matrix hemorrhage)

Anemia of prematurity
Digestive
Ileus · Necrotizing enterocolitis · Meconium peritonitis
Erythema toxicum · Sclerema neonatorum
Nervous system
Periventricular leukomalacia
Musculoskeletal
Gray baby syndrome · muscle tone (Congenital hypertonia, Congenital hypotonia)
Infectious
Perinatal infection (Congenital rubella syndrome, Neonatal herpes simplex) · Omphalitis · Neonatal sepsis (Group B streptococcal infection) · Neonatal conjunctivitis
Other
Perinatal mortality (Stillbirth, Infant mortality) · Neonatal withdrawal

: OBS

phys/devp

mthr/fetu/infc,

proc, drug(2A/G2C)