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Preterm birth

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Preterm birth

Preterm birth
Intubated preterm baby in an incubator
Classification and external resources
Specialty Obstetrics, pediatrics
ICD-10 O60.1, P07.3
ICD-9-CM 644, 765
DiseasesDB 10589
MedlinePlus 001562
eMedicine ped/1889
MeSH D047928

Preterm birth, also known as premature birth, is the birth of a baby at less than 37 weeks gestational age.[1] These babies are known as preemies or premmies.[1] Symptoms of preterm labor include uterine contractions which occur more often than every ten minutes or the leaking of fluid from the vagina.[2] Premature infants are at greater risk for cerebral palsy, delays in development, hearing problems, and problems seeing. These risks are greater the earlier a baby is born.[1] The cause of preterm birth is often not known.[3] Risk factors include diabetes, high blood pressure, being pregnant with more than one baby, being either obese or underweight, a number of vaginal infections, tobacco smoking, and psychological stress, among others.[3][4] It is recommended that labor not be medically induced before 39 weeks unless required for other medical reasons. The same recommendation applies to cesarean section.[3] Medical reasons for early delivery include preeclampsia.[5] In those at risk, the hormone progesterone, if taken during pregnancy, may prevent preterm birth. Evidence does not support the usefulness of bed rest.[6][7] It is estimated that at least 75% of preterm infants would survive with appropriate treatment.[3] In women who might deliver between 24 and 34 weeks corticosteroids improve outcomes.[8] A number of medications including nifedipine may delay delivery so that a mother can be moved to where more medical care is available and the corticosteroids have a greater chance to work.[9] Once the baby is born care includes keeping the baby warm through skin to skin contact, supporting breastfeeding, treating infections, and supporting breathing.[3] Preterm birth is the most common cause of death among infants worldwide.[1] About 15 million babies are preterm each year (5% to 18% of all deliveries). In many countries rates of premature births have increased between the 1990s and 2010s.[3] Complications from preterm births resulted in 0.74 million deaths in 2013 down from 1.57 million in 1990.[10] The chance of survival at less than 23 weeks is close to zero, while at 23 weeks it is 15%, 24 weeks 55% and 25 weeks about 80%.[11] The chances of survival without long term difficulties is less.[12]

Contents

  • Classification 1
  • Signs and symptoms 2
    • Complications 2.1
      • Mortality and morbidity 2.1.1
      • Specific risks for the preterm neonate 2.1.2
  • Risk factors 3
    • Maternal background 3.1
    • Factors during pregnancy 3.2
      • Infection 3.2.1
  • Diagnosis 4
    • Placental alpha microglobulin-1 4.1
    • Fetal fibronectin 4.2
    • Ultrasound 4.3
  • Prevention 5
    • Before pregnancy 5.1
    • During pregnancy 5.2
      • Screening of low risk women 5.2.1
      • Self-care 5.2.2
    • Secondary (reducing existing risks) 5.3
      • :During pregnancy 5.3.1
        • Reducing indicated preterm birth 5.3.1.1
        • Reducing spontaneous preterm birth 5.3.1.2
  • Management 6
    • Glucocorticosteroids 6.1
    • Tocolysis 6.2
    • Neonatal care 6.3
  • Prognosis 7
  • Epidemiology 8
  • Society and culture 9
    • Economics 9.1
    • Notable cases 9.2
    • Etymology 9.3
  • Ethics 10
  • References 11
  • External links 12

Classification

Stages in prenatal development, with weeks and months numbered from last menstruation.

In humans the usual definition of preterm birth is birth before a ventilator. Therefore, a significant overlap exists between preterm birth and prematurity. Generally, preterm babies are premature and term babies are mature. Preterm babies born near 37 weeks often have no problems relating to prematurity if their lungs have developed adequate surfactant, which allows the lungs to remain expanded between breaths. Sequelae of 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

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

Preterm birth causes a range of problems.[14]

The main categories of causes of preterm birth are preterm labor induction and spontaneous preterm labor. Signs and symptoms of preterm labor include four or more uterine contractions in one hour. In contrast to false labor, true labor is accompanied by cervical dilatation and effacement. Also, vaginal bleeding in the third trimester, heavy pressure in the pelvis, or abdominal or back pain could be indicators that a preterm birth is about to occur. A watery discharge from the vagina may indicate premature rupture of the membranes that surround the baby. While the rupture of the membranes may not be followed by labor, usually delivery is indicated as infection (chorioamnionitis) is a serious threat to both fetus and mother. In some cases the cervix dilates prematurely without pain or perceived contractions, so that the mother may not have warning signs until very late in the birthing process.

Complications

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 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.[15] 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%.[16] Prematurely born infants are also at greater risk for having subsequent serious chronic health problems as discussed below.

The earliest [18] although rare survivors have been documented as early as 21 weeks.[19] 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.[20] 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.[21]

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.

Children born preterm are more likely to have white matter brain abnormalities early on causing higher risks of cognitive dysfunction.[24] White matter connectivity between the frontal and posterior brain regions are critical in learning to identify patterns in language.[24] Preterm children are at a greater risk for having poor connectivity between these areas leading to learning disabilities.[25]

Cardiovascular complications may arise from the failure of the ductus arteriosus to close after birth: patent ductus arteriosus (PDA).

A study of 241 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.[26][27]

Risk factors

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 (placental abruption), decidual bleeding, and intrauterine inflammation/infection.[28] Activation of one or more of these pathways may happen gradually over weeks, even months.[28] 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

Risk factor Relative risk
or odds ratio[29]
95% confidence
interval
[29]
Black ethnicity/race 2.0 1.8–2.2
Filipino ancestry[30] 1.7 1.5-2.1
High or low BMI 0.96 0.66–1.4
Large or small pregnancy weight gain 1.8 1.5–2.3
Short maternal height 1.8 1.3–2.5
History of spontaneous preterm birth 3.6 3.2–4.0
Being single/unmarried[31] 1.2 1.03-1.28
Bacterial vaginosis 2.2 1.5–3.1
Asymptomatic bacteriuria 1.1 0.8–1.5
Periodontitis 1.6 1.1–2.3
Low socio-economic status 1.9 1.7–2.2
Short cervical length 2.9 2.1–3.9
Fetal fibronectin 4.0 2.9–5.5
Chlamydia 2.2 1.0–4.8
Celiac disease 1.4[32] 1.2–1.6[32]

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[33] or less than 18 years of age.[34] Maternal height and weight can play a role.[35]

Further, in the US and the UK, black women have preterm birth rates of 15–18%, more than double than that of the white population. Filipinos are also at high risk of premature birth, and it is believed that nearly 11-15% of Filipinos born in the U.S. (compared to other Asians at 7.6% and whites at 7.8%) are premature.[36] Filipinos being a big risk factor is evidenced with the Philippines being the 8th highest ranking in the world for preterm births, the only non-African country in the top 10.[37] This discrepancy is not seen in comparison to other Asian groups or Hispanic immigrants and remains unexplained.[34]

Pregnancy interval makes a difference as women with a six-month span or less between pregnancies have a two-fold increase in preterm birth.[38] 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.[34]

A history of spontaneous (i.e., miscarriage) or surgical abortion has been associated with a small increase in the risk of preterm birth, with an increased risk with increased number of abortions, although it is unclear whether the increase is caused by the abortion or by confounding risk factors (e.g., socioeconomic status).[39] Increased risk has not been shown in women who terminated their pregnancies medically.[40] Pregnancies that are unwanted or unintended are also a risk factor for preterm birth.[41]

Adequate maternal nutrition is important. Women with a low BMI are at increased risk for preterm birth.[42] Further, women with poor nutrition status may also be deficient in vitamins and minerals. Adequate nutrition is critical for fetal development and a diet low in saturated fat and cholesterol may help reduce the risk of a preterm delivery.[43] Obesity does not directly lead to preterm birth; however, it is associated with diabetes and hypertension which are risk factors by themselves.[34] 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.[44] 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).[31] Pregnancy outside of marriage was associated overall with a 20% increase in total adverse outcomes, even at a time when Finland provided free maternity care. A study in Quebec of 720,586 births from 1990 to 1997 revealed less risk of preterm birth for infants with legally married mothers compared with those with common-law wed or unwed parents.[45]

Genetic make-up is a factor in the causality of preterm birth. Genetics has been a big factor into why Filipinos have a high risk of premature birth as the Filipinos have a large prevalence of mutations that helps them be predisposed to premature births.[36] An intra- and transgenerational increase in the risk of preterm delivery has been demonstrated.[46][47][48] No single gene has been identified. It appears with the complexity of the labor initiation that numerous polymorphic genetic interactions are possible.

[49]

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.[50] 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. Often labor has to be induced for medical reasons; such conditions include high blood pressure,[51] pre-eclampsia,[52] maternal diabetes,[53] asthma, thyroid disease, and heart disease.

In a number of women anatomical issues prevent the baby from being carried to term. Some women have a weak or short cervix[51] (the strongest predictor of premature birth)[54][55][56] 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.[57] Women with vaginal bleeding during pregnancy are at higher risk for preterm birth. While bleeding in the third trimester may be a sign of placenta previa or placental abruption – conditions that occur frequently preterm – even earlier bleeding that is not caused by these conditions is linked to a higher preterm birth rate.[58] Women with abnormal amounts of amniotic fluid, whether too much (polyhydramnios) or too little (oligohydramnios), are also at risk.[34] The mental status of the women is of significance. Anxiety[59] and depression have been linked to preterm birth.[34]

Finally, the use of tobacco, cocaine, and excessive alcohol during pregnancy increases the chance of preterm delivery. Tobacco is the most commonly abused drug during pregnancy and contributes significantly to low birth weight delivery.[60][61] Babies with birth defects are at higher risk of being born preterm.[62]

  • read more about 34 weeks pregnant


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References

As a result of this decision, when Sarah Capewell gave live birth at 21 weeks 5 days gestation, her son was denied treatment, and died within two hours of birth. According to the mother, he was breathing unaided, had a strong heartbeat, and was moving his arms and legs. If he had been born two days later he might have received treatment. This took place at James Paget Hospital in Gorleston, Norfolk, in October 2008. [145]

In the UK, the debate regarding resuscitation of babies born at 23 weeks was highlighted by Dr Daphne Austin, an NHS official who advised local health authorities on how to spend their budgets in 2011. She argued that babies born at 23 weeks should not be resuscitated because their chances of surviving are so slim and that there is sufficient evidence that keeping the babies alive can, according to her view, do more harm than good. [143] UK practice follows the Nuffield council on bioethics guidance on neonatal medicine. It states that medics should not attempt to resuscitate babies born before 22 weeks, as it would not be in the best interests of the child. From 22 to 23 weeks standard practice should be not to resuscitate the baby for the same reason. From 24 weeks babies should be offered full intensive care and support from birth. From 23 to 24 weeks is a grey area and individual circumstances make it difficult to apply generalised standards, resuscitation may or may not be appropriate.[144]

This is discussed at great length in a report "Critical care decisions in fetal and neonatal medicine: ethical issues"[142] produced by the London-based Nuffield Council for Bioethics.

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.

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, though possibly with severe disabilities. As a consequence, families and health professionals have to make complex decisions about how much intervention is necessary or justifiable.

Ethics

Preterm birth in Latin: partus praetemporaneus or partus praematurus.

Etymology

Historical figures who were born prematurely include Johannes Kepler (born in 1571 at 7 months gestation), Isaac Newton (born in 1642, 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).[141]

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.[140]

The record for the smallest premature baby to survive was held for a considerable amount of time by Madeline Mann, who was born at 26 weeks weighing 9.9 oz (280 g) and 9.5 inches (24.1 cm) long.[137] This record was broken in September 2004 by Rumaisa Rahman, who was born in the same hospital[138] 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).[139] Generally healthy, the twins had to undergo laser eye surgery to correct vision problems, a common occurrence among premature babies.

Amillia Taylor is also often cited as the most premature baby.[135] She was born on 24 October 2006 in Miami, Florida, at 21 weeks and 6 days gestation.[136] 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.[124] At birth, she was 9 inches (22.9 cm) long and weighed 10 ounces (283 grams).[135] She suffered digestive and respiratory problems, together with a brain hemorrhage. She was discharged from the Baptist Children's Hospital on 20 February 2007.[135]

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.[133][134]

Notable cases

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.[130] The 2007 Institute of Medicine report Preterm Birth [131] 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.[132]

Economics

Society and culture

Complications from preterm births resulted in 0.74 million deaths in 2013 down from 1.57 million in 1990.[10]

As weight is easier to determine than gestational age, the birth weight (< 2,500 grams), which occurred in 16.5 percent of births in less developed regions in 2000.[128] 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.[129] Almost all neonates in these latter two groups are born preterm.

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.[34] 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).[34]

Disability-adjusted life year for prematurity and low birth weight per 100,000 inhabitants in 2004.[127]
  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

Epidemiology

Some children will adjust well during childhood and adolescence,[122] although disability is more likely nearer the limits of viability. A large study followed children born between 22 and 25 weeks until the age of 6 years old. Of these children, 46 percent had moderate to severe disabilities such as cerebral palsy, vision or hearing loss and learning disabilities, 34 percent had mild disabilities, and 20 percent had no disabilities. 12 percent had disabling cerebral palsy.[27] 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.[122] 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, intellectual disability, disorders of psychological development, behavior, and emotion, disabilities of vision and hearing, and epilepsy.[123] 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.[27] It is also shown that higher levels of education were less likely to be obtained with decreasing gestational age at birth.[123] People born prematurely may be more susceptible to developing depression as teenagers.[124] 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.[125] Studies of people born premature and investigated later with MRI brain imaging, demonstrate qualitative anomalies of brain structure and grey matter deficits within temporal lobe structures and the cerebellum that persist into adolescence.[126] Throughout life they are more likely to require services provided by physical therapists, occupational therapists, or speech therapists.[122]

The chance of survival at less than 23 weeks is close to zero, while at 23 weeks it is 15%, 24 weeks 55% and 25 weeks about 80%.[11] The chances of survival without long term difficulties is less.[12]

Prognosis

In a 2012 policy statement, the American Academy of Pediatrics recommended feeding preterm infants human milk, finding "significant short- and long-term beneficial effects," including lower rates of necrotizing enterocolitis (NEC). [121]

Water should be carefully provided to prevent dehydration but no so much to increase risks of side effects.[120]

After delivery, plastic wraps or warm mattresses are useful to keep the infant warm on their way to the NICU.[119] 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).

Neonatal care

The routine use of cesarean section for early delivery of infants expected to have very low birth weight is controversial,[85] and a decision concerning the route and time of delivery probably needs to be made on a case by case basis.

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.[118] Because of concern about necrotizing enterocolitis, amoxicillin or erythromycin has been recommended, but not amoxicillin + clavulanic acid (co-amoxiclav).[118]

A number of medications may be useful to delay delivery including: β2-agonist drugs delay by 48 hours but carry more side effects.[85][116] Magnesium sulfate does not appear to be useful and may be harmful when used for this purpose.[117]

Tocolysis

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.[114]

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.[109] 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.[110] Other side effects of corticosteroids are diabetes mellitus, osteoporosis, inhibition of growth, hypertension, cognitive problems, anxiety, depression, gastritis, and colitis. Finally, a single study on animals has shown that a single exposure to these same drugs during brain development causes rapid brain degeneration.[111][112] Despite these concerns, there is a consensus that the benefits of a single regimen of prenatal glucocorticosteroids vastly outweigh the potential risks.[113]

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 complications are reduced by the use of glucocorticosteroids, namely intraventricular haemorrhage, necrotising enterocolitis, and patent ductus arteriosus.[108]

Glucocorticosteroids

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.[107] 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. In a hospital setting women are hydrated via intravenous infusion (as dehydration can lead to premature uterine contractions).

Management

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.[104][106] 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.[85]

Cervical cerclage

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 reduction in the risk of preterm birth in women with recurrent preterm birth by 40–55%.[102][103] Progesterone supplementation also reduces the frequency of preterm birth in pregnancies where there is a short cervix.[104] However, progesterone is not effective in all populations, as a study involving twin gestations failed to see any benefit.[105]

Progesterone

Studies examining the use of antibiotics have provided mixed results; a Cochrane review of 15 trials shows no major benefit,[100] in contrast a review by Lamont suggested that treatment of bacterial vaginosis if initiated prior to 20 w gestation is beneficial.[101] It has been suggested that chronic chorioamnionitis is not sufficiently treated by antibiotics alone (and therefore they cannot ameliorate the need for preterm delivery in this condition).[85]

Antibiotics

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.[98] 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,[99] and further studies are in the making.

Reducing spontaneous 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-dose aspirin was used.[85] Interestingly, even if agents such as calcium or antioxidants were able to reduce preeclampsia, a resulting decrease in preterm birth was not observed.[85]

Reducing indicated preterm birth

:During pregnancy

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 therapies prior to conception, be it for asthma, diabetes, hypertension and others.

Secondary (reducing existing risks)

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.[96][97]

Self-care

Screening for asymptomatic bacteriuria followed by appropriate treatment reduces pyelonephritis and reduces the risk of preterm birth.[95] 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.[85] 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.[85] Screening for the presence of fibronectin in vaginal secretions is not recommended at this time in women at low risk.

Screening of low risk women

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.[85] Calcium supplementation as well as supplemental intake of C and E vitamins could not be shown to reduce preterm birth rates.[93][94] 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.[85] While periodontal infection has been linked with preterm birth, randomized trials have not shown that periodontal care during pregnancy reduces preterm birth rates.[85]

During pregnancy

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.[85] 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).[87] Also, night work has been linked to preterm birth.[88] Health policies that take these findings into account can be expected to reduce the rate of preterm birth.[85] 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,[89] 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.[90][91][92] Reducing smoking is expected to benefit pregnant women and their offspring.[85]

Before pregnancy

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.[85] Smoking bans are effective in decreasing preterm births.[86]

Prevention

Obstetric ultrasound has become useful in the assessment of the cervix in women at risk for premature delivery. A short cervix preterm is undesirable: A cervical length of less than 25 mm at or before 24 weeks of gestational age is the most common definition of cervical incompetence.[82] Further, the shorter the cervix the greater the risk.[83] 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.[84]

Ultrasound

Fetal fibronectin (fFN) has become an 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.[34] 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.[81]

Fetal fibronectin

Placental alpha microglobulin-1 (PAMG-1) has been the subject of several investigations evaluating its ability to predict imminent spontaneous preterm birth in women with signs, symptoms, or complaints suggestive of preterm labor.[73][74][75][76][77][78][79] In one investigation comparing this test to fetal fibronectin testing and cervical length measurement via transvaginal ultrasound, the test for PAMG-1 (commercially known as the PartoSure test) has been reported to be the single best predictor of imminent spontaneous delivery within 7 days of a patient presenting with signs, symptoms, or complaints of preterm labor. Specifically, the PPV, or positive predictive value, of the tests were 76%, 29%, and 30% for PAMG-1, fFN and CL, respectively (P < 0.01).[80]

Placental alpha microglobulin-1

A helpful clinical test should predict a high risk for preterm birth during the early and middle part of the third trimester, when their impact is significant. Many women experience false labor (not leading to cervical shortening and effacement) and are falsely labeled to be in preterm labor. The study of preterm birth has been hampered by the difficulty in distinguishing between "true" preterm labor and false labor.[28] These new tests are used to identify women at risk for preterm birth.

Diagnosis

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.[71][72] In contrast, viral infections, unless accompanied by a significant febrile response, are considered not to be a major factor in relation to preterm birth.[34]

It has been reported that asymptomatic Bacterial vaginosis has been linked to preterm birth raising the risk by a factor of 1.5 – 3.[70] 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 these populations. It is opined that bacterial vaginosis before or during pregnancy may affect the decidual inflammatory response that leads to preterm birth.[34]

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 the fetus. A chorioamnionitis also may lead to sepsis of the mother. Fetal infection is linked to preterm birth and to significant long-term handicap including cerebral palsy.[34]

Infections play a major role in the genesis of preterm birth and may account for 25–40% of events.[68] The frequency of infection in preterm birth is inversely related to the gestational age.[34] cytokines stimulate deciduas responses including the release of prostaglandins which may stimulate uterine contractions. Further, the decidual response may include release of matrix-degrading enzymes that weaken fetal membranes leading to premature rupture.[68] Intrauterine infection appears to be a chronic process.[68] Mycoplasma genitalium infection is associated with increased risk of preterm birth, and spontaneous abortion.[69]

Infection

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.[66] 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.[67]

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.[65]

Presence of anti-thyroid antibodies is associated with an increased risk preterm birth with an odds ratio of 1.9 and 95% confidence interval of 1.1–3.5.[64]

[63]

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