preterm labor reformatted

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CHAPTER I - INTRODUCTION

I.I. Overview

Preterm labor is defined as the presence of uterine contractions of sufficient frequency and intensity to effect progressive effacement and dilation of the cervix prior to term gestation (between 20 and 37 wk). Preterm labor precedes almost half of preterm births and preterm birth occurs in approximately 12% of pregnancies and is the leading cause of neonatal mortality in Asia. In addition, preterm birth accounts for 70% of neonatal morbidity, mortality, and health care dollars spent on the neonate, largely due to the 2% of Average women delivering very premature infants (< 32 wk).

Successful reduction of perinatal morbidity and mortality associated with prematurity may require the implementation of effective risk identification and behavioral modification programs for the prevention of preterm labor; these in turn require both an improved understanding of the psychosocial risk factors, etiology, and mechanisms of preterm labor and programs for accurate identification of pregnant women at risk for premature labor and delivery. In fact, recent evidence suggests that early identification of at-risk gravidas with timely referral for subspecialized obstetrical care may help identify women at risk for preterm labor and delivery and decrease the extreme prematurity (< 32 wk) rate, thereby reducing the morbidity, mortality, and expense associated with prematurity.

I.II. Goals of management

The focus of this article is the prevention, diagnosis, and treatment of preterm labor with intact membranes. The management of preterm labor associated with ruptured membranes is reviewed in Premature Rupture of Membranes; however, the overall goals of both management schemes are similar.

Goals of obstetric patient management of preterm labor should include:

Early identification of risk factors associated with preterm birth. Timely diagnosis of preterm labor. Identifying the etiology of preterm labor. Evaluating fetal well-being. Providing prophylactic pharmacologic therapy to prolong gestation and reduce the

incidence of respiratory distress syndrome (RDS) and intra-amniotic infection (IAI). Initiating tocolytic therapy when indicated. Establishing a plan of maternal and fetal surveillance with patient/provider education

to improve neonatal outcome.

Medical Papers (Referat) – Preterm Labor – RSUD Ciawi – Aditiawan & Fitriyani (FK UNTAR)

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CHAPTER II - DISCUSSION

II.I. Definition

Preterm or premature births are terms used to define neonates who are born too early (before 37 completed weeks, that is, < 8 months). This definition was based on a statistical analysis of gestasional age distribution at birth (Steer, 2005). Infants born before term can be small or large for gestational age but still fit the definition of preterm. Low birthweight refers to neonates weighing 1500 to 2500 g; very low birthweight refers to those between 1000 and 1500 g; and extremely low birthweight refers to those between 500 and 1000 g.

It lacks a specific functional basis and should be clearly distinguished from the concept of prematurity. Prematurity represents incomplete development of various organ systems at birth. The lungs are particularly affected, leading to the respiratory distress syndrome.

Beginning, in 2005, in recognition that infants born between 34 weeks and 37 weeks experience morbidities and mortality characteristic of premature infants, preterm births were subdivided. Those before 34 weeks are labeled – early preterm, and those occurring between 34 and 36 completed weeks – late preterm.

Table 42-1 suggest that optimal pregnancy outcomes vis-a-vis prematurity are achived at 39 weeks’ gestation. These example suggest that shortened human gestation with regard to prematurity is birth before 37 weeks rather than before 39 weeks.


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II.II. Risk Factors

The exact mechanism(s) of preterm labor is largely unknown but is believed to include decidual hemorrhage, (eg, abruption, mechanical factors such as uterine overdistension from multiple gestation or polyhydramnios), cervical incompetence (eg, trauma, cone biopsy), uterine distortion (eg, müllerian duct abnormalities, fibroid uterus), cervical inflammation (eg, resulting from bacterial vaginosis [BV], trichomonas), maternal inflammation/fever (eg, urinary tract infection), hormonal changes (eg, mediated by maternal or fetal stress), and uteroplacental insufficiency (eg, hypertension, insulin-dependent diabetes, drug abuse, smoking, alcohol consumption).

Although prediction of preterm delivery remains inexact, a variety of maternal and obstetric characteristics are known to increase the risk, presumably via one of these mechanisms. Finally, the fetus plays a role in the initiation of labor. In a simplistic sense, the fetus recognizes a hostile intrauterine environment and precipitates labor by premature activation of a fetal-placental parturition pathway.

Risk factors for preterm birth include demographic characteristics, behavioral factors, and aspects of obstetric history such as previous preterm birth. Demographic factors for preterm labor include nonwhite race, extremes of maternal age (< 17 y or >35 y), low socioeconomic status, and low prepregnancy weight. Preterm labor and birth can be associated with stressful life situations (eg, domestic violence; close family death; insecurity over food, home, or partner; work and home environment) either indirectly by associated risk behaviors or directly by mechanisms not completely understood. Many risk factors may manifest in the same gravida.

Methods used for predicting preterm birth include home uterine activity monitoring (HUAM), assessments of salivary estriol, fetal fibronectin (FFN), the presence of BV, and cervical length assessment.

While hospital tocodynamometry has been effective for monitoring uterine contractions to evaluate preterm labor, HUAM has not been proven valuable in detecting or preventing preterm birth and is not currently recommended for use.

The proposed use of salivary estriol measurements in detecting preterm labor was based on the belief that the adrenal gland production of dehydroepiandrosterone increases before the onset of labor, which results in an increase of maternal estriol. Unfortunately, maternal estriol levels show diurnal variation, peaking at night, and are suppressed by betamethasone administration, thereby decreasing the predictive value of salivary estriol in the detection of preterm delivery risk.

FFN is a basement membrane protein that helps bind placental membranes to the decidua. While a negative FFN is helpful in predicting women who are not destined to deliver preterm, a positive FFN has limited value in predicting women who will deliver preterm. Nevertheless, FFN has a predictive value in identifying patients who will or will not deliver within the subsequent 1-2 weeks.


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While the presence of BV has been associated with the risk of preterm delivery, prospective treatment trials eradicating asymptomatic BV failed to reduce the risk of preterm delivery.

Longer term prediction of the risk of preterm delivery is achieved by cervical length measurements. A short cervical length in the early or late second trimester has been associated with a markedly increased risk of preterm labor and delivery. The prediction of preterm delivery may potentially be improved by combining FFN testing with measurements of cervical length.

Preconceptual evaluation

While the risk for preterm birth in nulliparous patients is hard to determine, past obstetric experience and personal behavior may provide significant insight into future pregnancy


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outcome in multiparous women. Identifying at-risk patients preconceptually may allow additional treatment options. Women who seek birth control have a 30% chance of becoming pregnant in the next 2 years, suggesting that these women represent one potential opportunity for intervention. The presence of the following risk factors should be addressed prior to pregnancy.

Cervical trauma

The most common etiologies for cervical injury are elective abortion, surgeries to treat cervical dysplasia, and injury occurring at delivery. A single uncomplicated elective abortion at less than 10 weeks’ gestation does not increase the risk of midtrimester loss or preterm birth unless the cervix has been forcibly dilated to more than 10 mm at the time of the abortion. However, patients with a history of multiple first-trimester elective terminations or one or more second-trimester elective abortions may be at increased risk for preterm delivery. Cervical dilatation with laminaria or cervical ripening agents, such as misoprostol, appears to be less traumatizing to the cervix than mechanical dilation.

Cervical dysplasia should be treated appropriately whenever diagnosed. However the incidence of preterm birth and cervical incompetence may be increased 200-300% after preconceptual surgical treatment (eg, cold knife cone, cryoconization, laser cone, LEEP) of cervical intraepithelial neoplasia (CIN). The risk of subsequent preterm delivery may be proportional to the amount of cervical tissue removed during surgery. Surprisingly, the ease of performing LEEP for relatively minor abnormalities may have paradoxically led to more cervical injury than was observed with the relatively more invasive cone biopsy.

Obstetric trauma may be underestimated as a risk for midtrimester loss or preterm birth. While women may relate a history of cervical laceration, often they are unaware of the injury and the obstetric records of the previous delivery may be misleading as to the extent of the cervical injury. Therefore, visual inspection of the cervix is important to assess the degree of injury and risk. Defects that involve more than 50% of the cervical length may indicate a higher risk for midtrimester loss. The accuracy of transvaginal ultrasonic measurements to determine risk of cervical incompetence, specifically in the presence of a history of cervical trauma, has yet to be determined.

Genital tract infection

The young gynecology patient diagnosed with gonorrhea, chlamydia, or trichomoniasis has an approximate 25% risk of reinfection during the subsequent 12 months, but a clear association between these organisms and preterm delivery has not been established. BV is a vaginal syndrome associated with an alteration of the normal vaginal flora rather than an infection specific to any one organism and a lack of vaginal inflammation is evident when


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compared with vaginitis. The diagnosis of BV should be suspected with a positive Gram stain result or the presence of 3 of 4 traditional diagnostic signs (homogenous gray-white discharge, >20% clue cells on saline wet smear, positive whiff test, and a vaginal pH >4.50) Patients should be treated per the US Centers for Disease Control and Prevention guidelines, with test-of-cure sampling and subsequent treatment if necessary.

Preterm labor/birth history

A history of prior preterm deliveries places the patient in the high-risk category. Of the predictors of preterm birth, past obstetric history may be one of the strongest predictors of recurrent preterm birth. Given a baseline risk of 10-12%, the risk of recurrent preterm birth after 1, 2, and 3 consecutive preterm births may be increased to approximately 15%, 30%, and 45%, respectively. Preconceptual counseling should help encourage patients to make informed decisions concerning future pregnancy in light of prematurity risk in the presence of previous preterm delivery. Often the best time to counsel the patient is at her 4- to 6-week postpartum check after a preterm delivery.

Lykke et al found that spontaneous preterm delivery, preeclampsia, or fetal growth deviation in a first singleton pregnancy predisposes women to those complications in their second pregnancy, especially if the complications were severe.

The optimal method of preterm birth in multiple gestations has yet to be proven. Cervical cerclage, prophylactic bed rest, and empiric use of tocolytics have not been successful. Most recently, a randomized controlled trial by Lim et al suggests that the use of 17α-hydroxyprogesterone caproate does not prevent neonatal morbidity or preterm birth in multiple pregnancies.

Midtrimester loss

Midtrimester loss has many etiologies, including infection (eg, syphilis), antiphospholipid syndrome, diabetes, substance abuse, genetic disorders, congenital müllerian abnormalities, cervical trauma, and cervical incompetence. Unfortunately, many midtrimester losses remain unexplained. A complete workup (see History of midtrimester loss) may be of value in selected patients following a midtrimester loss.

II.III. Etiology

Pathway to Preterm Labor

Pregnancy with intact fetal membranes and spontaneous preterm labor must be distinguished from those complicated by preterm prematurely ruptured membranes. Even so, those with spontaneous preterm labor do not constitute a homogeneous group characterized singularly


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by early initiation of parturition (American College of Obstetricians and Gynecologists, 2012b). This certainly is one reason why preventative therapies and clinical tools to assess the risks for preterm birth have been difficult to identify. Among the more common associated findings are multifetal pregnancy, intrauterine infection, bleeding, placental infarction, premature cervical dilatation, cervical insufficiency, hydramnions, uterine fundal abnormalities, and fetal anomalies. Severe maternal illness as a resullt of infections, autoimmune diseases, and gestational hypertension also increases preterm labor risks.

Although there are unique aspects to each cause of preterm labor, these diverse processes culminate in a common end point, which is premature cervical dilatation and effacement and premature activation of uterine contractions. It seems important to emphasize that actual process of preterm labor should be considered a final step – one that results from progressive or acute changes that could be initiated days or even weeks before labor onset. Indeed many forms of spontaneous preterm labor that result from premature initiation of phase 2 of parturition.

Diverse pathways to instigate parturition exist and are dependent on the etiology of preterm birth. Identification of both common and uncommon factors has begun to explain the physiological processes of human parturition at term and preterm.

Four major causes of spontaneous preterm labor, include:

Uterine distention Maternal – fetal stress Premature cervical changes Infection

There are four main direct reasons for preterm births, these include:

Spontaneous unexplained preterm labor with intact membranes Idiopathic preterm prematur rupture of membrane (PPROM) Delivery for maternal or fetal indications Twins and higher – order multifetalbirths

Of all preterm births, 30 to 35 percent are indicated, 40 to 45 percent are due to spontaneous preterm labor, and 30 to 35 percent follow preterm membrane rupture (Goldenberg, 2008). Reasons for preterm birth have multiple, of interacting, antecedents and contributing factors.

II.IV. Diagnosis

Contractions of sufficient frequency and intensity to effect progressive effacement and dilation of the cervix at 24-37 weeks’ gestation are indicative of active preterm labor. If the diagnosis of preterm labor is suspected, but not confirmed, it may be prudent to first obtain a vaginal fetal fibronectin (FFN) sample before pelvic cervical examination. If the diagnosis of preterm labor becomes obvious after the pelvic examination, the FFN specimen can be


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subsequently discarded. However, if the diagnosis remains in doubt, the FFN specimen can be sent to the lab for analysis.

Criteria that indicate consideration of tocolytic therapy include more than 6 contractions per hour resulting in a demonstrated cervical change or presumed prior cervical change (transvaginal cervical length < 2.5 cm, >50% cervical effacement, or cervical dilation ≥2 cm). If contractions are present without cervical change, management options include continued observation or therapeutic sleep (eg, morphine sulphate 10-15 mg subcutaneous).

When using strict criteria in women at 24 0/7 to 33 6/7 weeks’ gestation for “false preterm labor” (one contraction or less in 10 min, cervical dilation < 2 cm, and no evidence of cervical change over 2 h of observation), Chao et al demonstrated that these patients had a greater incidence of late preterm (34-36 weeks’ gestation) but not early preterm delivery (< 34 weeks’ gestation), compared with a control obstetric population. However, those patients with cervical dilation of 1 cm were more likely to delivery prior to 34 weeks’ gestation. Although this study provides some guidance as to management, a negative FFN result and/or evidence of abated contractions may be of additional value in discharging patients with false preterm labor. In addition, measures of absolute or change in cervical length (effacement), in addition to dilation, may be of value in discriminating true versus false preterm labor.

Symptoms

Early differentiation between true and false labor is difficult before there is demonstrable cervical effacement and dilatation. Uterine activity alone can be misleading because of Braxton Hicks contractions. These contractions, described as irregular, no rhythmical, and either painful or painless, can cause considerable confusion in the diagnosis of true preterm labor. Not infrequently, women who deliver before term have uterine activity that is attributed to Braxton Hicks contractions, prompting an incorrect diagnosis of false labor.

Accordingly, the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists (2012) define preterm labor to be regular contractions before 37 weeks that are associated with cervical change. In addition to painful or painless uterine contractions, symptoms such as pelvic pressure, menstrual-like cramps, watery vaginal discharge, and lower back pain have been empirically associated with impending preterm birth. Iams and coworkers (1994) found that the signs and symptoms signaling preterm labor, including uterine contractions, appeared only within 24 hours of preterm labor.

Signs

Asymptomatic cervical dilatation after midpregnancy is suspected to be a risk factor for preterm delivery, although some clinicians consider it to be a normal anatomical variant. Moreover, study results have suggested that parity alone is not sufficient to explain cervical dilation discovered early in the third trimester. Cook (1996) longitudinally evaluated cervical


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status with transvaginal sonography between 18 and 30 weeks in both nulliparous and parous women who all subsequently gave birth at term. Cervical length and diameter were identical in both groups throughout these critical weeks. In a study from Parkland Hospital, routine digital cervical examinations were performed between 26 and 30 weeks in 185 women. Approximately 25 percent of women whose cervix was dilated 2 or 3 cm delivered before 34 weeks.

Knowledge of antenatal cervical dilatation did not affect any pregnancy outcome related to preterm birth or the frequency of interventions for preterm labor. The investigators also reported that cervical examination were not related to preterm membrane rupture. At this time, it seems that prenatal cervical examinations are neither beneficial nor harmful.

Iams and associates (2002) analyzed data from almost 35.000 hours of daily home monitoring and verifed that no contraction pattern efficiently predicted preterm birth. The American College of Obstetricians and Gynecologists (2012a) does not recommend home monitoring uterine activity monitoring.

Lockwood (1991) reported that fibronectin detection in cervicovaginal secretions before membrane rupture was a possible marker for impending preterm labor. Values exceeding 50 ng/ml are considered positive. Sample contamination by amniotic fluid and maternal blood should be avoided. Interventional studies based on the use of fetal fibronectin screening in asymptomatic women have not demonstrated improved perinatal outcomes (Andrews, 2003; Grobman, 2004). The American College of Obstetricians and Gynecologists (2012b) does not recommend screening with fetal fibronectin tests.

II.V. Prevention

Prevention of preterm birth has been an elusive goal. Recent reports, however, suggest that prevention in selected populations may be achieveable.

Cervical cerclage, indication:- History of recurrent midtrimester losses and who are diagnosed with cervical

insufficiency- Women that identified during sonographic examination to have a short cervix


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- “rescue” cerclage, done emergently when cervical incompetence is recognized in women with threatened preterm labor.

Cerclage for sonographically detected short cervix alone has not been found to be beneficial. In contrast, women with a very short cervix, that is, < 15 mm, and a history of prior preterm birth may be benefit.

Progestin compundsProgesterone level in most mammals fall rapidly before the onset of labor. This is termed progesterone withdrawal and is considered to be a parturition-triggering event. During human parturition , however, maternal, fetal, and amnionic fluid progesterone levels remain elevated with no decline. It has been proposed that human parturition involves functional progesterone withdrawal mediated by decreased progesterone activity of progesterone receptors (Ziyan, 2010). It follows conceptually that the administration of progesterone to maintain uterine quiscence may block preterm labor.

II.VI. Management

Preterm labor may be difficult to diagnose and a potential exists for overtreatment of uterine irritability. Tocolytic agents, while generally safe in appropriate dosages with proper clinical monitoring, have potential morbidity and should only be used after consideration of the risks and benefits of such use. Neonatal morbidity and mortality are greatly affected by gestational age, especially when the pregnancy is less than 28 weeks’ gestation. Tocolysis should be used with caution when the fetus is previable because the expected prolongation of the pregnancy is limited, and the neonate has a minimal chance of survival at less than 23 weeks. The likelihood of survival is further reduced in the presence of significant medical complications, such as intra-amniotic infection (IAI) at these ages.


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On the other hand, the risk of neonatal mortality and morbidity is low after 34 completed weeks of gestation; although a trial of acute tocolysis may be initiated, aggressive tocolytic therapy is generally not recommended beyond 34 weeks, due to potential maternal complications. Between 24 and 33 weeks’ gestation, benefits of tocolytic therapy are generally accepted to outweigh the risk of maternal and/or fetal complications and these agents should be initiated provided no contraindications exist. Although aggressive tocolysis is not typically used beyond 34 weeks’ gestation, clinicians are advised not to deliver patients at this gestation without indication because of a higher risk of neonatal morbidity in infants born at 34-36 weeks’ gestation compared with deliveries at 37-40 weeks’ gestation.

Preterm prematurely ruptured membranes

A history of vaginal leakage of fluid, either as a continuous stream or as a gush, should prompt a speculum examination to visualize gross vaginal pooling of amnionic fluid, clear fluid from the cervical canal, or both. Confirmation of ruptured membranes is usually accompanied by sonographic examinationto assess amnionic fluid volume, to identify the presenting part, and if not previously determined, to estimate gestational age. Amnionic fluid is slightly alkaline (pH 7,1 – 7,3) compared with vaginal secretions (pH 4,5 – 6,0). This is the basis of frequently used pH testing for ruptured membranes. Blood, semen, antiseptics, or bacterial vaginosis, however, are all also alkaline and can give false positive results.


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Preterm labor with intact membranes

Women with sign and symptoms of preterm labor with intact membranes are managed much the same as described above for those with preterm ruptured membranes. If possible, delivery before 34 weeks is delayed. Drugs used to abate or suppress preterm uterine contractions are subsequently discussed.

Assessment prior to tocolytic therapy

One should always attempt to determine gestational age by first identifying the first day of the last menstrual period (LMP) and confirming it by one or more of the following:

Positive pregnancy test (home or clinic) prior to the expected date of the second missed period

Uterine size determined by bimanual examination prior to 12 weeks' gestation Doppler fetal heart tones noted prior to 12 weeks' gestation Ultrasonographic estimation of gestational age (ie, first trimester within 1 wk, second

trimester within 2 wk, and third trimester within 3 wk)

When the LMP is not reliable, the gestational age is determined by the first ultrasonography. Following gestational age determination, assessment of fetal well-being, fetal growth, and evaluation of congenital anomaly should be conducted. Subspecialist consultation (MFM) is


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recommended in the presence of suspected fetal anomalies because tocolytics are generally contraindicated for any congenital anomaly incompatible with life. Tocolytics are not indicated in patients with either suspected or confirmed IAI. Use of tocolytics is relatively contraindicated when evidence of a hostile intrauterine environment exists, such as the following:

Oligohydramnios Nonreactive nonstress test results Positive contraction stress test results Absent or reversed diastolic flow upon Doppler examination of umbilical blood flow Repetitive severe variable decelerations Significant vaginal bleeding consistent with abruption, unless patient is stable and

fetal well being established

Evaluate for the presence of genital tract infection

Tocolytics are contraindicated in the presence of symptomatic IAI. The definition of IAI infection (ie, chorioamnionitis) includes a temperature greater than 38.0°C (100.0°F) and 2 of the 5 following signs:

WBC count greater than 15,000 cells/mm 3 Maternal tachycardia greater than 100 beats per minute (bpm) Fetal tachycardia greater than 160 bpm Tender uterus Foul-smelling discharge

In situations in which the diagnosis remains unclear, an amniocentesis for fluid culture (aerobic/anaerobic bacteria), Gram stain (bacteria present if Gram stain is positive or if WBC count is >50 cells/mm3), glucose level (positive if < 15 mg/dL), or leukocyte esterase evaluation may be considered. However, amniocentesis may result in a false-positive FFN test result if the FFN is performed after amniocentesis.

A study by Romero et al indicated that IAI can be quickly and accurately diagnosed with polymerase chain reaction assay with electrospray ionization time-of-flight mass spectrometry (PCR/ESI-MS). In the study, amniotic fluid from 142 women with preterm labor with intact membranes underwent culturing and PCR/ESI-MS testing. Standard culturing techniques detected microbial invasion of the amniotic cavity in 7% of these patients, while PCR/ESI-MS detected it in 12% of them. Compared with women in whom both tests were negative, those patients who had negative cultures but positive PCR/ESI-MS results had a significantly greater incidence of intra-amniotic inflammation and acute histologic chorioamnionitis, as well as a shorter time to delivery and offspring with a greater perinatal mortality risk.[23]


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Patients with preterm labor may be assessed for the presence or absence of lower genital tract infection, such as:

Sterile speculum examination for ruptured membranes Endocervical sampling for gonorrhea and chlamydia Vaginal fluid pH Wet smear for BV and trichomonal infection if indicated GBS culture Urinalysis and culture

Positive results are treated with appropriate antibiotics.

Assess for medical contraindications to tocolysis

Tocolytics should be used with considerable caution in pregnant patients with cardiac disease, especially those who require medication or have a history of congestive heart failure, cardiac surgery, significant pulmonary disease, renal failure, or maternal infection (ie, pneumonia, appendicitis, pyelonephritis). In these cases, it may be prudent to consult with an MFM specialist.

Specific tocolytic agents should not be used whenever known allergies exist. Indomethacin is contraindicated in the presence of aspirin-induced asthma, coagulopathy, or significant liver disease. Magnesium sulfate should not be used in conjunction with select medications, such as calcium channel blockers, or when myasthenia gravis or neuromuscular disorders exist. Beta-mimetics (eg, terbutaline) may be contraindicated in the presence of cardiac arrhythmia, valvular disease, and ischemic heart disease and may alter glucose homeostasis in patients with diabetes.

Fetal therapy

The administration of glucocorticoids is recommended in the absence of clinical infection whenever the gestational age is between 24 and 34 weeks. An attempt should be made to delay delivery for a minimum of 12 hours to obtain the maximum benefits of antenatal steroids. However, a randomized clinical trial by Porto et al showed that treatment with corticosteroids at 34-36 weeks of pregnancy does not reduce the incidence of respiratory disorders in newborn infants.

The recommended dosage of betamethasone consists of two 12 mg doses 24 hours apart while four doses of 6 mg of dexamethasone should be administered at 6-hour intervals. Whenever the following clinical conditions exist, the glucocorticoid regimen may require modification:

In the presence of insulin-dependent or gestational diabetes, the provider should be prepared for control of blood sugars.


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In the event of an acutely distressed fetus, indicative of fetal hypoxia, the use of prophylactic steroids should not delay the delivery of an acutely distressed fetus.

Although the use of repeated doses of glucocorticoids remains controversial, a meta-analysis concluded that repeated doses of prenatal corticosteroids in women who remained at risk for preterm birth 7 or more days after an initial course reduced the risk of their infants developing respiratory distress syndrome and reduced serious infant outcomes (relative risk 0.83 and 0.84, respectively). Treatment with repeat doses was associated with a reduction in mean birthweight of approximately 76 g; however, no differences in growth assessments or disabilities at early childhood were noted in follow-up. In view of these conclusions, the authors suggest that the clinician consider use of a single repeated dose of glucocorticoids if the patient remains at significant risk for preterm delivery within the next 7 days, at a gestational age less 34 weeks.

Group B streptococci prophylaxis

All patients in preterm labor should be considered at high risk for neonatal GBS sepsis. Patients in preterm labor with the potential to deliver should receive prophylactic antibiotics against GBS, unless GBS culture is negative. Prophylactic antibiotics should be administered when the diagnosis of preterm labor is made and should be continued until delivery or for a minimum of 72 hours. Patients should be re-treated if preterm labor recurs or when the patient enters labor at term depending upon culture results.

Tocolytic Agents

The most common tocolytic agents used for the treatment of preterm labor are magnesium sulfate (MgSO4), indomethacin, and nifedipine. In the past, beta-mimetic agents, such as terbutaline or ritodrine, were the agents of choice, but in recent years their use has been significantly curtailed due to maternal and fetal side effects, such as maternal tachycardia, hyperglycemia, and palpitations The use of these agents can lead to pulmonary edema, myocardial ischemia, and cardiac arrhythmia.

Tocolytic agents have not proven to be efficacious in preventing preterm birth or reducing neonatal mortality or morbidity. The primary purpose of tocolytic therapy today is to delay delivery for 48 hours to allow the maximum benefit of glucocorticoids to decrease the incidence of RDS. While tocolytics can be successful for 48 hours when membranes are intact, some clinical studies suggest that the effectiveness of tocolytics is only slightly better than bedrest and hydration, both of which have fewer adverse effects than tocolytic therapy.


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Magnesium sulfate

Magnesium sulfate is widely used as the primary tocolytic agent because it has similar efficacy to terbutaline with far better tolerance. Common maternal side effects include flushing, nausea, headache, drowsiness, and blurred vision. The mother should be monitored for toxic effects, such as respiratory depression or even cardiac arrest that can occur at supratherapeutic levels. In addition, magnesium sulfate readily crosses the placenta and may lead to respiratory and motor depression of the neonate.

Indomethacin

Indomethacin is an appropriate first-line tocolytic for the pregnant patient in early preterm labor (< 30 wk) or preterm labor associated with polyhydramnios. A more significant inflammatory response in the membranes and decidua is observed at gestational ages less than 30 weeks compared with 30-36 weeks. Indomethacin reduces prostaglandin synthesis from decidual macrophages. The fetal renal effects of indomethacin may be beneficial to reduce polyhydramnios.

Nifedipine

Nifedipine, a calcium channel blocker, is commonly used to treat high blood pressure and heart disease because of its ability to inhibit contractility in smooth muscle cells by reducing calcium influx into cells. Consequently, nifedipine has emerged as an effective and safe alternative tocolytic agent for the management of preterm labor. Despite its unlabeled status, several randomized studies have shown that the use of nifedipine in comparison with other tocolytics is associated with a more frequent successful prolongation of pregnancy, resulting in significantly fewer admissions of newborns to the neonatal intensive care unit, and may be associated with a lower incidence of RDS, necrotizing enterocolitis, and intraventricular hemorrhage.

II.VII. Complications

The following table depicts survival, major short-term morbidity, and intact long-term survival by gestational age.


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On shorts we can pull a red string that the older we can deliver the newborn, better outcome will ensure to follow.

REFERENCES

F. Gary C, Kenneth J, Steven L, et all. Williams Obstetrics, 24th ED. McGraw-Hill Education. United States of America. 2014.D. Keith E, Saruna A, Adam B, et all. Dewhurst’s Textbook of Obstetrics & Gynaecology, 7th ED. Blackwell Publishing. United States of America. 2007.American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Assessment of risk factors for preterm birth. Clinical management guidelines for obstetrician-gynecologists. Number 31, October 2001. Obstet Gynecol. Oct 2001;98(4):709-16.ACOG practice bulletin. Management of preterm labor. Number 43, May 2003. Int J Gynaecol Obstet. Jul 2003;82(1):127-35.RCOG. Tocolysis for Women in Preterm Labour. No. Ib, February 2911. Gree-top Guideline. Feb 2011.Goldenberg R, Culhune J, Iams J, Romero R. Epidemiology and causes of preterm birth. Lancet 2008;371:75–84.


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Chao TT, Bloom SL, Mitchell JS, McIntire DD, Leveno KJ. The diagnosis and natural history of false preterm labor. Obstet Gynecol. Dec 2011;118(6):1301-8.Cheng Y, Kaimal A, Bruckner T, Hallaron D, Caughey A. Perinatal morbidity associated with late preterm deliveries compared with deliveries between 37 and 40 weeks of gestation. BJOG. Nov 2011;118(12):1446-1454.Porto AM, Coutinho IC, Correia JB, Amorim MM. Effectiveness of antenatal corticosteroids in reducing respiratory disorders in late preterm infants: randomised clinical trial. BMJ. Apr 12 2011;342:d1696.


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