Premature birth

Premature birth

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In humans preterm birth refers to the birth
Birth
Birth is the act or process of bearing or bringing forth offspring. The offspring is brought forth from the mother. The time of human birth is defined as the time at which the fetus comes out of the mother's womb into the world...

 of a baby of less than 37 weeks gestational age
Gestational age
Gestational age relates to the age of an embryo or fetus . There is some ambiguity in how it is defined:*In embryology, gestational age is the time elapsed since conception. This interval is also termed fertilisation 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 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
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...

 of preterm birth. Preterm birth is the major cause of neonatal mortality in developed countries.

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
Primate
A primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...

 species, possibly to allow the disproportionately large head to fit through a pelvis adapted for walking on two legs. Furthermore, since the evolution of conscious thought in humans, there is less selective pressure to have more developed infants at birth because of the increased ability to protect human infants.

In humans whereas the usual definition of preterm birth is birth before 37 weeks gestation, 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
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...

; one sign is four or more uterine contraction
Contraction (childbirth)
-Throughout menstrual cycle:The uterus frequently contracts throughout the entire menstrual cycle, and these contractions have been termed endometrial waves or contractile waves. These appear to involve only the sub-endometrial layer of the myometrium...

s 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
Chorioamnionitis
Chorioamnionitis is an inflammation of the fetal membranes due to a bacterial infection. It typically results from bacteria ascending into the uterus from the vagina and is most often associated with prolonged labour...

) is a serious threat to both fetus and mother. In some cases the cervix dilates prematurely without pain or perceived contractions, so that the mother may not have warning signs until very late in the birthing process.

Mortality and morbidity


The shorter the term of pregnancy, the greater the risks of mortality and morbidity for the baby primarily due to the related prematurity. Preterm-premature babies ("preemies" or "premmies") have an increased risk of death in the first year of life (infant mortality
Infant mortality
Infant mortality is defined as the number of infant deaths per 1000 live births. Traditionally, the most common cause worldwide was dehydration from diarrhea. However, the spreading information about Oral Re-hydration Solution to mothers around the world has decreased the rate of children dying...

), 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. 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%. Prematurely born infants are also at greater risk for having subsequent serious chronic health problems as discussed below.

The earliest gestational age
Gestational age
Gestational age relates to the age of an embryo or fetus . There is some ambiguity in how it is defined:*In embryology, gestational age is the time elapsed since conception. This interval is also termed fertilisation age....

 at which the infant has at least a 50% chance of survival is referred to as the limit of viability
Limit of viability
-Scientific thresholds:There is no sharp limit of development, age, or weight at which a fetus automatically becomes viable. According to data years 2003-2005, 20 to 35 percent of babies born at 23 weeks of gestation survive, while 50 to 70 percent of babies born at 24 to 25 weeks, and more than 90...

. As NICU care has improved over the last 40 years, viability has reduced to approximately 24 weeks, although rare survivors have been documented as early as 21 weeks.http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20070220/baby_premature_070219/20070220?hub=CTVNewsAt11 This date is controversial, as gestation in the case reported was measured from the known date of conception (by IVF) rather than, as usual, the date of the mother's last menstrual period, making gestation appear two weeks less than if calculated by the conventional method in this case. As risk of brain damage and developmental delay is significant at that threshold even if the infant survives, there are ethical
Medical ethics
Medical ethics is a system of moral principles that apply values and judgments to the practice of medicine. As a scholarly discipline, medical ethics encompasses its practical application in clinical settings as well as work on its history, philosophy, theology, and sociology.-History:Historically,...

 controversies over the aggressiveness of the care rendered to such infants. The limit of viability has also become a factor in the abortion
Abortion
Abortion is defined as the termination of pregnancy by the removal or expulsion from the uterus of a fetus or embryo prior to viability. An abortion can occur spontaneously, in which case it is usually called a miscarriage, or it can be purposely induced...

 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.
  • Neurological problems include apnea of prematurity
    Apnea of prematurity
    Apnea of prematurity is defined as cessation of breathing by a premature infant that lasts for more than 15 seconds and/or is accompanied by hypoxia or bradycardia. Apnea is traditionally classified as either obstructive, central, or mixed. Obstructive apnea may occur when the infant's neck is...

    , hypoxic-ischemic encephalopathy
    Encephalopathy
    Encephalopathy means disorder or disease of the brain. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of global brain dysfunction; this syndrome can be caused by many different illnesses.-Terminology:...

     (HIE), retinopathy of prematurity
    Retinopathy of prematurity
    Retinopathy of prematurity , previously known as retrolental fibroplasia , is an eye disease that affects prematurely-born babies. It is thought to be caused by disorganized growth of retinal blood vessels which may result in scarring and retinal detachment. ROP can be mild and may resolve...

     (ROP), developmental disability
    Developmental disability
    Developmental disability is a term used in the United States and Canada to describe lifelong disabilities attributable to mental or physical impairments, manifested prior to age 18. It is not synonymous with "developmental delay" which is often a consequence of a temporary illness or trauma during...

    , cerebral palsy
    Cerebral palsy
    Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....

     and intraventricular hemorrhage
    Intraventricular hemorrhage
    An intraventricular hemorrhage , often abbreviated "IVH," is a bleeding into the brain's ventricular system, where the cerebrospinal fluid is produced and circulates through towards the subarachnoid space...

    , the latter affecting 25 percent of babies born preterm, usually before 32 weeks of pregnancy. Mild brain bleeds usually leave no or few lasting complications, but severe bleeds often result in brain damage or even death. Neurodevelopmental problems have been linked to lack of maternal thyroid hormone
    Thyroid hormone
    The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...

    s, at a time when their own thyroid
    Thyroid
    The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...

     is unable to meet postnatal needs.
  • Cardiovascular complications may arise from the failure of the ductus arteriosus to close after birth: patent ductus arteriosus
    Patent ductus arteriosus
    Patent ductus arteriosus is a congenital disorder in the heart wherein a neonate's ductus arteriosus fails to close after birth. Early symptoms are uncommon, but in the first year of life include increased work of breathing and poor weight gain...

     (PDA).
  • Respiratory problems are common, specifically the respiratory distress syndrome
    Infant respiratory distress syndrome
    Infant respiratory distress syndrome , also called neonatal respiratory distress syndrome or respiratory distress syndrome of newborn, previously called hyaline membrane disease, is a syndrome in premature infants caused by developmental insufficiency of surfactant production and structural...

     (RDS or IRDS) (previously called hyaline membrane disease). Another problem can be chronic lung disease
    Bronchopulmonary dysplasia
    Bronchopulmonary dysplasia is a chronic lung disorder that is most common among children who were born prematurely, with low birthweights and who received prolonged mechanical ventilation to treat respiratory distress syndrome...

     (previously called bronchopulmonary dysplasia or BPD).
  • Gastrointestinal and metabolic issues can arise from hypoglycemia, feeding difficulties, rickets
    Rickets
    Rickets is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium , phosphorus or calcium, potentially leading to fractures and deformity. Rickets is among the most frequent childhood diseases in many developing countries...

     of prematurity, hypocalcemia, inguinal hernia
    Inguinal hernia
    An inguinal hernia is a protrusion of abdominal-cavity contents through the inguinal canal. They are very common , and their repair is one of the most frequently performed surgical operations....

    , and necrotizing enterocolitis
    Necrotizing enterocolitis
    Necrotizing enterocolitis is a medical condition primarily seen in premature infants, where portions of the bowel undergo necrosis .-Signs and symptoms:...

     (NEC).
  • Hematologic complications include anemia of prematurity
    Anemia of prematurity
    Anemia of prematurity refers to a form of anemia affecting preterm infants with decreased hematocrit.-Pathophysiology:Preterm infants are often anemic and typically experience heavy blood losses from frequent laboratory testing in the first few weeks of life...

    , thrombocytopenia
    Thrombocytopenia
    Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...

    , and hyperbilirubinemia (jaundice) that can lead to kernicterus
    Kernicterus
    Kernicterus is damage to the brain centers of infants caused by increased levels of unconjugated bilirubin. This may be due to several underlying pathologic processes. Newborn babies are often polycythemic. When they break down the erythrocytes, one of the byproducts is bilirubin, which circulates...

    .
  • Infection, including sepsis
    Sepsis
    Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...

    , pneumonia
    Pneumonia
    Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

    , and urinary tract infection
    Urinary tract infection
    A urinary tract infection is a bacterial infection that affects any part of the urinary tract. Symptoms include frequent feeling and/or need to urinate, pain during urination, and cloudy urine. The main causal agent is Escherichia coli...

     


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.


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. Activation of one or more of these pathways may happen gradually over weeks, even months. 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 or less than 18 years of age. Maternal height
Human height
Human height is the distance from the bottom of the feet to the top of the head in a human body standing erect.When populations share genetic background and environmental factors, average height is frequently characteristic within the group...

 and weight can also play a role. 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.

Pregnancy interval makes a difference as women with a 6 months span or less between pregnancies have a two-fold increase in preterm birth. Studies on type of work and physical activity have given conflicting results, but it is opined that stressful conditions, hard labor, and long hours are probably linked to preterm birth. 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).
The preterm birth link has not been shown in women who terminated their pregnancies medically with pills such as RU-486.
Adequate maternal nutrition
Nutrition
Nutrition is the provision, to cells and organisms, of the materials necessary to support life. Many common health problems can be prevented or alleviated with a healthy diet....

 is important. Women with a low BMI
Body mass index
The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...

 are at increased risk for preterm birth. Further, women with poor nutritional status may also be deficient in vitamin
Vitamin
A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...

s and mineral
Mineral
A mineral is a naturally occurring solid chemical substance formed through biogeochemical processes, having characteristic chemical composition, highly ordered atomic structure, and specific physical properties. By comparison, a rock is an aggregate of minerals and/or mineraloids and does not...

s. Adequate nutrition is critical for fetal development and a diet low in saturated fat
Saturated fat
Saturated fat is fat that consists of triglycerides containing only saturated fatty acids. Saturated fatty acids have no double bonds between the individual carbon atoms of the fatty acid chain. That is, the chain of carbon atoms is fully "saturated" with hydrogen atoms...

 and cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

 may help reduce the risk of a preterm delivery. Obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...

 does not directly lead to preterm birth; however, it is associated with diabetes and hypertension which are risk factors by themselves.
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. 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). 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.

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. 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
TWINS
Two Wide-Angle Imaging Neutral-Atom Spectrometers are a pair of NASA instruments aboard two United States National Reconnaissance Office satellites in Molniya orbits. TWINS was designed to provide stereo images of the Earth's ring current. The first instrument, TWINS-1, was launched aboard USA-184...

, 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. Triplets and more are even more endangered. The use of fertility medication
Fertility medication
Fertility medication are drugs which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary...

 that stimulates the ovary to release multiple eggs and of IVF with embryo transfer
Embryo transfer
Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy...

 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, pre-eclampsia
Pre-eclampsia
Pre-eclampsia or preeclampsia is a medical condition in which hypertension arises in pregnancy in association with significant amounts of protein in the urine....

, maternal diabetes, 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
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...

 (the strongest predictor of premature birth) The cervix
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...

 may also have been compromised by previous cervical conization
Cervical conization
Cervical conization refers to a biopsy of the cervix in which a cone-shaped sample of tissue is removed from the mucous membrane. Conization may be used either for diagnostic purposes, or for therapeutic purposes to remove pre-cancerous cells.Types include:* cold knife conization...

 or loop excision. In women with uterine malformation
Uterine malformation
A uterine malformation is a type of female genital malformation resulting from an abnormal development of the Müllerian duct during embryogenesis...

s the capacity of the uterus to hold the growing pregnancy may be limited and preterm labor ensues.
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
Placental abruption
Placental abruption is a complication of pregnancy, wherein the placental lining has separated from the uterus of the mother. It is the most common pathological cause of late pregnancy bleeding. In humans, it refers to the abnormal separation after 20 weeks of gestation and prior to birth...

 – conditions that occur frequently preterm – even earlier bleeding that is not caused by these two conditions is linked to a higher preterm birth rate. Women with abnormal amounts of amniotic fluid, too much (polyhydramnios
Polyhydramnios
Polyhydramnios is a medical condition describing an excess of amniotic fluid in the amniotic sac. It is seen in 0.2 to 1.6% of pregnancies,,...

) or too little (oligohydramnios
Oligohydramnios
Oligohydramnios is a condition in pregnancy characterized by a deficiency of amniotic fluid. It is the opposite of polyhydramnios.-Diagnosis:Diagnosis is made by ultrasound measurement of the amniotic fluid index...

) are also at risk.
The mental status of the women is of significance. Anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

 and depression have been linked to preterm birth.
Finally, the use of tobacco
Tobacco
Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...

, cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

, and excessive alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

 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. Babies with birth defects are at higher risk of being born preterm.

Presence of anti-thyroid antibodies is associated with an increased risk preterm birth with an odds ratio
Odds ratio
The odds ratio is a measure of effect size, describing the strength of association or non-independence between two binary data values. It is used as a descriptive statistic, and plays an important role in logistic regression...

 of 1.9 and 95% confidence interval
Confidence interval
In statistics, a confidence interval is a particular kind of interval estimate of a population parameter and is used to indicate the reliability of an estimate. It is an observed interval , in principle different from sample to sample, that frequently includes the parameter of interest, if the...

 of 1.1–3.5.

A 2004 systematic review of 30 studies on the association between intimate partner violence and birth outcomes concluded that preterm birth and other adverse outcomes, including death, are higher among abused pregnant women than among non-abused women.

The Nigerian cultural method of abdominal massage has been shown to result in 19% preterm birth among women in Nigeria, plus many other adverse outcomes for the mother and baby. This ought not be confused with massage conducted by a fully trained and licensed massage therapist or by significant others trained to provide massage during pregnancy, which has been shown to have numerous positive results during pregnancy, including the reduction of preterm birth, less depression, lower cortisol, and reduced anxiety.

Infection


Infections play a major role in the genesis of preterm birth and may account for 25–40% of events. The frequency of infection in preterm birth is inversely related to the gestational age. Endotoxin
Endotoxin
Endotoxins are toxins associated with some Gram-negative bacteria. An "endotoxin" is a toxin that is a structural molecule of the bacteria that is recognized by the immune system.-Gram negative:...

s released by microorganisms and cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

s stimulate deciduas responses including the release of prostaglandin
Prostaglandin
A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....

s which may stimulate uterine contractions. Further the decidual response may include release of matrix-degrading enzymes that weaken fetal membranes leading to premature rupture. Intrauterine infection appears to be a chronic process. Typical organisms identified in the uterus before rupture of the membranes are genital Mycoplasma
Mycoplasma
Mycoplasma refers to a genus of bacteria that lack a cell wall. Without a cell wall, they are unaffected by many common antibiotics such as penicillin or other beta-lactam antibiotics that target cell wall synthesis. They can be parasitic or saprotrophic. Several species are pathogenic in humans,...

 spp and specifically Ureaplasma urealyticum
Ureaplasma urealyticum
Ureaplasma urealyticum is a bacterium belonging to the family Mycoplasmataceae. Its type strain is T960.-Clinical significance:U. urealyticum is part of the normal genital flora of both men and women...

. 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
Amnion
The amnion is a membrane building the amniotic sac that surrounds and protects an embryo. It is developed in reptiles, birds, and mammals, which are hence called “Amniota”; but not in amphibians and fish , which are consequently termed “Anamniota”. The primary role of this is the protection of the...

 and chorion
Chorion
The chorion is one of the membranes that exist during pregnancy between the developing fetus and mother. It is formed by extraembryonic mesoderm and the two layers of trophoblast and surrounds the embryo and other membranes...

, the amniotic fluid
Amniotic fluid
Amniotic fluid or liquor amnii is the nourishing and protecting liquid contained by the amniotic sac of a pregnant woman.- Development of amniotic fluid :...

, and finally the fetus. A chorioamnionitis
Chorioamnionitis
Chorioamnionitis is an inflammation of the fetal membranes due to a bacterial infection. It typically results from bacteria ascending into the uterus from the vagina and is most often associated with prolonged labour...

 also may lead to sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...

 of the mother. Fetal infection not only is linked to preterm birth but to significant long-term handicap including cerebral palsy
Cerebral palsy
Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....

.
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
Bacterial vaginosis
Bacterial vaginosis or less commonly vaginal bacteriosis is a disease of the vagina caused by bacteria. The U.S. Centers for Disease Control and Prevention states it is not clear what role sexual activity plays in the development. However, it is known that BV is associated with having a new sex...

 has been linked to preterm birth raising the risk by a factor of 1.5 – 3. 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.
A number of maternal bacterial infections are associated with preterm birth including pyelonephritis
Pyelonephritis
Pyelonephritis is an ascending urinary tract infection that has reached the pyelum or pelvis of the kidney. It is a form of nephritis that is also referred to as pyelitis...

, asymptomatic bacteriuria
Bacteriuria
In medicine, bacteriuria denotes the presence of bacteria in urine not due to contamination from urine sample collection.Urine is normally a sterile bodily fluid when inside the bladder, but can pick up commensals and pathogens when exiting through the urethra...

, pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

, and appendicitis
Appendicitis
Appendicitis is a condition characterized by inflammation of the appendix. It is classified as a medical emergency and many cases require removal of the inflamed appendix, either by laparotomy or laparoscopy. Untreated, mortality is high, mainly because of the risk of rupture leading to...

. Also periodontal disease
Periodontal disease
Periodontitis is a set of inflammatory diseases affecting the periodontium, i.e., the tissues that surround and support the teeth. Periodontitis involves progressive loss of the alveolar bone around the teeth, and if left untreated, can lead to the loosening and subsequent loss of teeth...

  has been shown repeatedly to be linked to preterm birth. In contrast, viral infections, unless accompanied by a significant febrile response, are considered not to be a major factor in relation to preterm birth.

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. These new test are used to identify women at risk for preterm birth.

Fetal fibronectin


Fetal fibronectin
Fetal fibronectin
Fetal fibronectin is a fibronectin protein produced by fetal cells. It is found at the interface of the chorion and the decidua ....

 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. 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.

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. 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.

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.

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) 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.
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 (over 42 hours per week) or prolonged standing (over 6 hours per day). Also, night work has been linked to preterm birth. Health policies that take these findings into account can be expected to reduce the rate of preterm birth.
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, 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. Reducing smoking is expected to benefit pregnant women and their offspring.

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. Calcium supplementation as well as supplemental intake of C and E vitamins could not be shown to reduce preterm birth rates. 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. While periodontal infection has been linked with preterm birth, randomized trials have not shown that periodontal care during pregnancy reduces preterm birth rates.

Screening of low risk women


Screening for asymptomatic bacteriuria followed by appropriate treatment reduces pyelonephritis and reduces the risk of preterm birth. 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. 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. 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.

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
Uterine septum
A uterine septum is a form of a congenital malformation where the uterine cavity is partitioned by a longitudinal septum; the outside of the uterus has a normal typical shape...

), and those with certain medical problems can be helped by optimizing medical prior to conception, be it for asthma, diabetes, hypertension and others.
Reducing indicated preterm birth

A number of agents have been studied for secondary prevention of indicated preterm birth. Trials using low-dose aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

, fish oil
Fish oil
Fish oil is oil derived from the tissues of oily fish. Fish oils contain the omega-3 fatty acids eicosapentaenoic acid , and docosahexaenoic acid , precursors of certain eicosanoids that are known to reduce inflammation throughout the body, and are thought to have many health benefits.Fish do not...

, vitamin C and E, and calcium to reduce preeclampsia demonstrated some reduction in preterm birth only when low-aspirin was used. Interestingly, even if agents such as calcium or antioxidant
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...

s were able to reduce preeclampsia, a resulting decrease in preterm birth was not observed.
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. Use of nutritional supplements such as omega-3 polyunsaturated fatty acid
Polyunsaturated fatty acid
Polyunsaturated fatty acids are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic property....

s 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, 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, in contrast a review by Lamont suggested that treatment of bacterial vaginosis
Bacterial vaginosis
Bacterial vaginosis or less commonly vaginal bacteriosis is a disease of the vagina caused by bacteria. The U.S. Centers for Disease Control and Prevention states it is not clear what role sexual activity plays in the development. However, it is known that BV is associated with having a new sex...

 if initiated prior to 20 w gestation is beneficial. It has been suggested that the presence of a chronic chorioamnionitis may not be amenable to antibiotics, thus the difficulty to demonstrate their effectiveness.

Progesterone
Progesterone, often given in the form of 17-hydroxyprogesterone caproate
17-Hydroxyprogesterone caproate
17α-Hydroxyprogesterone caproate is a synthetic steroid hormone that is similar to medroxyprogesterone acetate and megestrol acetate. It is an ester derivative of 17α-hydroxyprogesterone formed from caproic acid ....

, 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%. However, progesterone is not effective in all populations, as a study involving twin gestations failed to see any benefit.
Cervical cerclage
In preparation for childbirth
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...

, the woman's cervix
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...

 shortens. Preterm cervical shortening is linked to preterm birth and can be detected by ultrasonography. Cervical cerclage
Cervical cerclage
Cervical cerclage , also known as a cervical stitch, is used for the treatment of cervical incompetence , a condition where the cervix has become slightly open and there is a risk of miscarriage because it may not remain closed throughout pregnancy...

 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. 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.

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. 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
Surfactant
Surfactants are compounds that lower the surface tension of a liquid, the interfacial tension between two liquids, or that between a liquid and a solid...

. This can lead directly to respiratory distress syndrome
Infant respiratory distress syndrome
Infant respiratory distress syndrome , also called neonatal respiratory distress syndrome or respiratory distress syndrome of newborn, previously called hyaline membrane disease, is a syndrome in premature infants caused by developmental insufficiency of surfactant production and structural...

, 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
Betamethasone
Betamethasone is a potent glucocorticoid steroid with anti-inflammatory and immunosuppressive properties. Unlike other drugs with these effects, betamethasone does not cause water retention. It is applied as a topical cream, ointment, foam, lotion or gel to treat itching...

 or dexamethasone
Dexamethasone
Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...

, 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
Patent ductus arteriosus
Patent ductus arteriosus is a congenital disorder in the heart wherein a neonate's ductus arteriosus fails to close after birth. Early symptoms are uncommon, but in the first year of life include increased work of breathing and poor weight gain...

.

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, clinical research conducted in 2004 has shown that the postnatal administration of dexamethasone can lead to permanent neuromotor and cognitive deficits. 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. Other side effects of corticosteroids are diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...

, osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...

, inhibition of growth
Growth
Growth refers to an increase in some quantity over time.The quantity can be:*Physical *Abstract ....

, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, cognitive problems, anxiety, depression, gastritis
Gastritis
Gastritis is an inflammation of the lining of the stomach, and has many possible causes. The main acute causes are excessive alcohol consumption or prolonged use of nonsteroidal anti-inflammatory drugs such as aspirin or ibuprofen. Sometimes gastritis develops after major surgery, traumatic...

, colitis
Colitis
In medicine, colitis refers to an inflammation of the colon and is often used to describe an inflammation of the large intestine .Colitides may be acute and self-limited or chronic, i.e...

. Finally, a single study on animals has shown that a single exposure to these same drugs during brain development causes rapid brain degeneration. Despite these concerns, there is a consensus that the benefits of a single regimen of prenatal glucocorticosteroids vastly outweigh the potential risks.

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
Group B Streptococcus
Infection with Group B Streptococcus , also known as 'Streptococcus agalactiae' and more colloquially as Strep B and group B Strep, can cause serious illness and sometimes death, especially in newborn infants, the elderly, and patients with compromised immune systems...

 and has been shown to reduce related mortality rates.

Research reported at the 2008 conference of the Society for Maternal-Fetal Medicine suggests that administration of magnesium sulfate
Magnesium sulfate
Magnesium sulfate is a chemical compound containing magnesium, sulfur and oxygen, with the formula MgSO4. It is often encountered as the heptahydrate epsomite , commonly called Epsom salt, from the town of Epsom in Surrey, England, where the salt was distilled from the springs that arise where the...

 (Epsom salt) to women just before premature birth can cut the rate of cerebral palsy
Cerebral palsy
Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....

 in half. While the compound is cheap and safe, it may make mothers and infants groggy, and details are pending scientific publication.

Tocolysis


Anti-contraction medications (tocolytic
Tocolytic
Tocolytics are medications used to suppress premature labor . They are given when delivery would result in premature birth...

s), such as Beta2-agonist drugs (ritodrine
Ritodrine
Ritodrine is a tocolytic drug, was used to stop premature labor. It is available in oral tablets or as an injection, and is typically used as the hydrochloride salt, ritodrine hydrochloride...

, terbutaline
Terbutaline
Terbutaline is a β2-adrenergic receptor agonist.Terbutaline is currently on the World Anti-Doping Agency's list of prohibited drugs for Olympic athletes, except when administered by inhalation and a Therapeutic Use Exemption has been obtained in advance.Terbutaline is currently used to delay...

, fenoterol
Fenoterol
Fenoterol is an asthma medication designed to open up the airways to the lungs. It is classed as sympathomimetic beta2 agonist.Fenoterol is produced and sold by Boehringer Ingelheim as Berotec N and in combination with ipratropium as Berodual N....

), calcium-channel blockers nifedipine
Nifedipine
Nifedipine is a dihydropyridine calcium channel blocker...

 and oxytocin antagonists (atosiban
Atosiban
Atosiban is an inhibitor of the hormones oxytocin and vasopressin. It is used as an intravenous medication as a labour repressant to halt premature labor. Although initial studies suggested it could be used as a nasal spray and hence would not require hospital admission, it is not used in that form...

) 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. 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. Meta-analyses of magnesium sulfate
Magnesium sulfate
Magnesium sulfate is a chemical compound containing magnesium, sulfur and oxygen, with the formula MgSO4. It is often encountered as the heptahydrate epsomite , commonly called Epsom salt, from the town of Epsom in Surrey, England, where the salt was distilled from the springs that arise where the...

 failed to support it as a tocolytic agent.

When membranes rupture prematurely, obstetrical management looks for development of labor and signs of infection. Administration of corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...

s 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. Because of concern about necrotizing enterocolitis
Necrotizing enterocolitis
Necrotizing enterocolitis is a medical condition primarily seen in premature infants, where portions of the bowel undergo necrosis .-Signs and symptoms:...

, amoxicillin
Amoxicillin
Amoxicillin , formerly amoxycillin , and abbreviated amox, is a moderate-spectrum, bacteriolytic, β-lactam antibiotic used to treat bacterial infections caused by susceptible microorganisms. It is usually the drug of choice within the class because it is better absorbed, following oral...

 or erythromycin
Erythromycin
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...

 has been recommended, but not amoxicillin + clavulanic acid (co-amoxiclav
Co-amoxiclav
Amoxicillin/clavulanic acid or co-amoxiclav is a combination antibiotic consisting of amoxicillin trihydrate, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor...

).

The routine use of cesarean section for early delivery of infants expected to have very low birth weight is controversial, 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
Neonatal intensive care unit
A Neonatal Intensive Care Unit —also called a Special Care Nursery, newborn intensive care unit, intensive care nursery , and special care baby unit —is an intensive care unit specializing in the care of ill or premature newborn infants.The problem of premature and congenitally ill infants is not a...

 (NICU). The physicians who specialize in the care of very sick or premature babies are known as neonatologists
Neonatology
Neonatology is a subspecialty of pediatrics that consists of the medical care of newborn infants, especially the ill or premature newborn infant. It is a hospital-based specialty, and is usually practiced in neonatal intensive care units...

. In the NICU, premature babies are kept under radiant warmers or in incubators (also called isolettes), which are bassinet
Bassinet
A bassinet or bassinette is a bed specifically for babies from birth to about four months, and small enough to provide a "cocoon" that small babies find comforting....

s 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
Oxygenation (medical)
Oxygenation occurs when oxygen molecules enter the tissues of the body. For example, blood is oxygenated in the lungs, where oxygen molecules travel from the air and into the blood...

, and brain activity
Electroencephalography
Electroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...

. Treatments may include fluids and nutrition through intravenous
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...

 catheters, oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

 supplementation, mechanical ventilation
Mechanical ventilation
In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...

 support, and medications. In developing countries where advanced equipment and even electricity may not be available or reliable, simple measures such as kangaroo care
Kangaroo care
Kangaroo care is a technique practiced on newborn, usually preterm, infants wherein the infant is held, skin-to-skin, with an adult. Kangaroo care for pre-term infants may be restricted to a few hours per day, but if they are medically stable that time may be extended. Some parents may keep their...

(skin to skin warming), encouraging breastfeeding
Breastfeeding
Breastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...

, and basic infection control measures can significantly reduce preterm morbidity and mortality. Bili light
Bili light
A bili light is a phototherapy tool to treat newborn jaundice which in higher levels causes brain damage , leading to cerebral palsy, auditory neuropathy, gaze abnormalities and dental enamel hypoplasia. The therapy uses a blue light that converts bilirubin so that it can be excreted in the urine...

s may also be used to treat newborn jaundice (hyperbilirubinemia).

Prognosis


Many children will adjust well during childhood and adolescence, although a large study that followed children born between 22 and 25 weeks found some alarming results. When the children were 6 years old it was 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 while 20 percent had no disabilities.12 percent had disabling cerebral palsy. For the first time this gave a real picture of what happens to children who are at the limits of viability.
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. 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
Cerebral palsy
Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....

, mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...

, disorders of psychological development, behavior, and emotion, disabilities of vision and hearing, and epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...

. Standard intelligence tests showed that 41 percent of children born between 22 and 25 weeks had moderate or severe learning disabilities when compared to the test scores of a group of similar classmates who were born at full-term. It is also shown that higher levels of education were less likely to be obtained with decreasing gestational age at birth. People born prematurely may be more susceptible to developing depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...

 as teenagers.
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. Studies of people born premature and investigated later with MRI brain imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...

, demonstrate qualitative anomalies of brain structure and grey matter deficits within temporal lobe structures and the cerebellum that persist into adolescence. Throughout life they are more likely to require services provided by physical therapists, occupational therapists, or speech therapists.

Epidemiology



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. Three obstetric events precede preterm birth: spontaneous preterm births are the 40–45% preterm births that follow preterm labor
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...

 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
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

, intrauterine growth retardation) or significant endangerment of the maternal health (i.e. preeclampsia, cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

). 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).

As weight is easier to determine than gestational age, the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 tracks rates of low birth weight
Birth weight
Birth weight is the body weight of a baby at its birth.There have been numerous studies that have attempted, with varying degrees of success, to show links between birth weight and later-life conditions, including diabetes, obesity, tobacco smoking and intelligence.-Determinants:There are...

 (< 2,500 grams), which occurred in 16.5 percent of births in less developed regions in 2000. 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
Small for gestational age
Small for gestational age babies are those who are smaller in size than normal for the baby's sex and gestational age, most commonly defined as a weight below the 10th percentile for the gestational age.-Terminology:...

(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. 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.
The 2007 Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...

 report Preterm Birth 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.

Notable preterm births


James Elgin Gill (born on 20 May 1987 in Ottawa
Ottawa
Ottawa is the capital of Canada, the second largest city in the Province of Ontario, and the fourth largest city in the country. The city is located on the south bank of the Ottawa River in the eastern portion of Southern Ontario...

, Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...

) 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.

Amillia Taylor is also often cited as the most-premature baby. She was born on 24 October 2006 in Miami, Florida
Florida
Florida is a state in the southeastern United States, located on the nation's Atlantic and Gulf coasts. It is bordered to the west by the Gulf of Mexico, to the north by Alabama and Georgia and to the east by the Atlantic Ocean. With a population of 18,801,310 as measured by the 2010 census, it...

, at 21 weeks and 6 days gestation. 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. At birth, she was 9 inches (22.86 cm) long and weighed 10 ounces (283 grams). She suffered digestive
Digestion
Digestion is the mechanical and chemical breakdown of food into smaller components that are more easily absorbed into a blood stream, for instance. Digestion is a form of catabolism: a breakdown of large food molecules to smaller ones....

 and respiratory
Respiratory system
The respiratory system is the anatomical system of an organism that introduces respiratory gases to the interior and performs gas exchange. In humans and other mammals, the anatomical features of the respiratory system include airways, lungs, and the respiratory muscles...

 problems, together with a brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

 hemorrhage
Bleeding
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...

. She was discharged from the Baptist Children's Hospital on 20 February 2007.

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 (280.7 g) and 9.5 inches (24.13 cm) long. This record was broken in September 2004 by Rumaisa Rahman, who was born in the same hospital at 25 weeks gestation. At birth, she was eight inches (20 cm) long and weighed 244 gram
Gram
The gram is a metric system unit of mass....

s (8.6 ounce
Ounce
The ounce is a unit of mass with several definitions, the most commonly used of which are equal to approximately 28 grams. The ounce is used in a number of different systems, including various systems of mass that form part of the imperial and United States customary systems...

s). Her twin sister was also a small baby, weighing 563 grams (1 pound 4 ounces) at birth. During pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

 their mother had suffered from pre-eclampsia
Pre-eclampsia
Pre-eclampsia or preeclampsia is a medical condition in which hypertension arises in pregnancy in association with significant amounts of protein in the urine....

, which causes dangerously high blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

 putting the baby into distress and requiring birth by caesarean section
Caesarean section
A Caesarean section, is a surgical procedure in which one or more incisions are made through a mother's abdomen and uterus to deliver one or more babies, or, rarely, to remove a dead fetus...

. 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). 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
Derek Paravicini
Derek Paravicini is a blind English autistic savant and a musical prodigy. He lives in Surrey.-Biography:Paravicini was born extremely prematurely, at 25 weeks . His blindness was caused by oxygen therapy given during his time in a neonatal intensive care unit...

 was born at 25 weeks. The oxygen therapy
Oxygen therapy
Oxygen therapy is the administration of oxygen as a medical intervention, which can be for a variety of purposes in both chronic and acute patient care...

 given during his time in a neonatal intensive care unit
Neonatal intensive care unit
A Neonatal Intensive Care Unit —also called a Special Care Nursery, newborn intensive care unit, intensive care nursery , and special care baby unit —is an intensive care unit specializing in the care of ill or premature newborn infants.The problem of premature and congenitally ill infants is not a...

 rendered him blind and affected his developing brain, resulting in his severe learning disability
Learning disability
Learning disability is a classification including several disorders in which a person has difficulty learning in a typical manner, usually caused by an unknown factor or factors...

. Furthermore Paravicini developed autism. However, he also has absolute pitch
Absolute pitch
Absolute pitch , widely referred to as perfect pitch, is the ability of a person to identify or re-create a given musical note without the benefit of an external reference.-Definition:...

 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
Children's Hospitals and Clinics of Minnesota
Children’s Hospitals and Clinics of Minnesota is one of the largest children’s health care organization in the U.S.A, with 326 staffed beds at its two hospital campuses in St. Paul and Minneapolis...

 in Minneapolis, Minnesota
Minneapolis, Minnesota
Minneapolis , nicknamed "City of Lakes" and the "Mill City," is the county seat of Hennepin County, the largest city in the U.S. state of Minnesota, and the 48th largest in the United States...

. 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
Neonatal intensive care unit
A Neonatal Intensive Care Unit —also called a Special Care Nursery, newborn intensive care unit, intensive care nursery , and special care baby unit —is an intensive care unit specializing in the care of ill or premature newborn infants.The problem of premature and congenitally ill infants is not a...

 for five months, and then discharged.

Historical figures who were born prematurely include Johannes Kepler
Johannes Kepler
Johannes Kepler was a German mathematician, astronomer and astrologer. A key figure in the 17th century scientific revolution, he is best known for his eponymous laws of planetary motion, codified by later astronomers, based on his works Astronomia nova, Harmonices Mundi, and Epitome of Copernican...

 (born in 1571 at 7 months gestation), Isaac Newton
Isaac Newton
Sir Isaac Newton PRS was an English physicist, mathematician, astronomer, natural philosopher, alchemist, and theologian, who has been "considered by many to be the greatest and most influential scientist who ever lived."...

 (born in 1643, small enough to fit into a quart
Quart
The quart is a unit of volume equal to a quarter of a gallon, two pints, or four cups. Since gallons of various sizes have historically been in use, quarts of various sizes have also existed; see gallon for further discussion. Three of these kinds of quarts remain in current use, all approximately...

 mug, according to his mother
Hannah Ayscough
Hannah Ayscough was the mother of Sir Isaac Newton.-Early life:Hannah was born in Market Overton in Rutland in 1623. Her parents were James Ayscough and his wife Margery Blythe.-Motherhood:...

), Winston Churchill
Winston Churchill
Sir Winston Leonard Spencer-Churchill, was a predominantly Conservative British politician and statesman known for his leadership of the United Kingdom during the Second World War. He is widely regarded as one of the greatest wartime leaders of the century and served as Prime Minister twice...

 (born in 1874 at 7 months gestation), and Anna Pavlova (born in 1885 at 7 months gestation).

Ethics


The transformation of medical care means that extremely premature and very ill babies have better chances of survival than ever before. But it is difficult to predict which babies will die and which will live with severe disabilities. As a consequence, families and health professionals have to make complex decisions about how much intervention is necessary or justifiable.

The most difficult decisions are about whether or not to resuscitate a premature baby and admit him or her to neonatal intensive care, or whether to withdraw intensive care and give the child palliative care.

This is discussed at great length in a report "Critical care decisions in fetal and neonatal medicine: ethical issues" produced by the London-based Nuffield Council for Bioethics.

The edge of viability


The gestational age at which a child is born plays a key part in these decisions.

22 weeks: in the UK and France babies are not normally resuscitated.

23 weeks: in Holland babies are not normally resuscitated at this age or below.

24 weeks: in most countries babies at this gestation are resuscitated.

External links