Cerclage: A procedure in which the cervical opening is closed with stitches to prevent or delay preterm birth. Cerebral Palsy: A disorder of the nervous system that affects movement, posture, and coordination. This disorder is present at birth. Cervix: The lower, narrow end of the uterus at the top of the vagina. Complications: Diseases or conditions that happen as a result of another disease or condition. An example is pneumonia that occurs as a result of the flu. A complication also can occur as a result of a condition, such as pregnancy. An example of a pregnancy complication is preterm labor. Corticosteroids: Drugs given for arthritis or other medical conditions. These drugs also are given to help fetal lungs mature before birth. Dilation: Widening the opening of the cervix. Effacement: Thinning out of the cervix. Fetal Fibronectin: A protein that is produced by fetal cells. It helps the amniotic sac stay connected to the lining of the uterus. Fetus: The stage of human development beyond 8 completed weeks after fertilization. Gestational Age: How far along a woman is in her pregnancy, usually reported in weeks and days. Hormone: A substance made in the body that controls the function of cells or organs. Magnesium Sulfate: A drug that may help prevent cerebral palsy when it is given to women in preterm labor who may deliver before 32 weeks of pregnancy. Neonatal Intensive Care Unit (NICU): A special part of a hospital in which sick newborns receive medical care. Neonatologist: A doctor who specializes in the diagnosis and treatment of disorders that affect newborn infants. Obstetrician–Gynecologist (Ob-Gyn): A doctor with special training and education in women’s health. Pelvic Exam: A physical examination of a woman’s pelvic organs. Prepregnancy: Before pregnancy. Preterm: Less than 37 weeks of pregnancy. Progesterone: A female hormone that is made in the ovaries and prepares the lining of the uterus for pregnancy. Tocolytics: Drugs used to slow contractions of the uterus. Transvaginal Ultrasound Exam: A type of ultrasound in which the device is placed in your vagina. Ultrasound Exam: A test in which sound waves are used to examine inner parts of the body. During pregnancy, ultrasound can be used to check the fetus. Uterus: A muscular organ in the female pelvis. During pregnancy, this organ holds and nourishes the fetus.
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. 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. [21] The following table depicts survival, major short-term morbidity, and intact long-term survival by gestational age. Table. Neonatal Morbidity and Mortality by Gestational Age (Open Table in a new window)
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. A 2016 clinical study [22] suggested a benefit of late preterm (34 0/7 to 36 6/7 weeks) steroids in women with singleton pregnancies at imminent risk of preterm delivery within 7 days, though tocolysis should not be used in order to delay delivery. The benefits were primarily a reduction in respiratory complications, though there was a marked increase in neonatal hypoglycemia in the treatment cohort. The American Congress of Obstetricians and Gynecologists (ACOG) issued a practice advisory (Practice Advisory: Antenatal Corticosteroid Administration in the Late Preterm Period, 2016) [23] that indicated that “administration of betamethasone may be considered in women with a singleton pregnancy between 34 0/7 and 36 6/7 weeks gestation at imminent risk of preterm birth within 7 days.” ACOG further clarified the bulletin as follows:
A subanalysis of the results indicates that the significant benefit was observed in the patients with a planned late preterm cesarean section. In view of the incidence of neonatal hypoglycemia and the ACOG option to “consider” betamethasone, a reasonable clinical approach may be to limit the administration of late preterm betamethasone to those patients having late preterm planned cesarean sections. 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 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. [24] 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. 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:
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 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:
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:
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. [2] 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. [25] Patients with preterm labor may be assessed for the presence or absence of lower genital tract infection.
Positive results are treated with appropriate antibiotics. 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. In addition, the US Food and Drug Administration (FDA) has warned against extended magnesium sulfate injections in pregnancy. In 2013, the FDA issued a safety alert advising against the off-label administration of magnesium sulfate injections to pregnant women for more than 5-7 days as a means of stopping preterm labor, as this agent can lead to low calcium levels and bone abnormalities in the fetus. [26, 27, 28] The warning was based in part on 18 case reports of skeletal abnormalities in infants whose mothers had received magnesium sulfate injections to stop preterm labor. In these cases, fetuses were exposed to the drug for nearly 10 weeks, on average, with neonates developing transient osteopenia and fractured bones. Epidemiologic evidence also indicates a connection between maternal administration of magnesium sulfate for more than 5-7 days and hypocalcemia and skeletal abnormalities in neonates. [26, 27, 28] 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. 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 clinical benefits of antenatal steroids. Recent data also suggest that glucocorticoids (i.e., betamethasone) may be beneficial in pregnant women at high risk of late preterm birth (within 7 days), between 34 0/7 weeks and 36 6/7 weeks of gestation who have NOT received a prior course of antenatal corticosteroids. [29] Administration of betamethasone led to a significant decrease in respiratory complications and the need for respiratory support, though hypoglycemia was more common in the infants exposed to betamethasone 24.0% versus 14.9% (RR, 1.61; 95% CI, 1.38–1.88). [22] Importantly, administration of late preterm glucocorticoids is not indicated in women with clinical chorioamnionitis, multiple gestations, or pregestational diabetes, and tocolysis should not be used in an attempt to delay delivery in order to administer glucocorticoids in the late preterm period, nor should an indicated late preterm delivery (e.g., preeclampsia with severe features) be postponed for corticosteroid administration. 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:
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. [30] In view of these conclusions, clinicians may consider use of a single repeated dose of glucocorticoids (rescue dose) at least 7-14 days from the initial treatment if the patient remains at significant risk for preterm delivery within the next 7 days, at a gestational age less 34 weeks. 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. |
A nurse is caring for a client who is in preterm labor and has a new prescription for nifedipine
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