Timely onset of labor and delivery has an important role in pregnancy outcome. Both preterm and postterm births are at higher risk for poor outcomes than pregnancies delivered at term.
Preterm labor is the onset of labor before 37 weeks’ gestation. It is the final common pathway for a number of conditions that induce uterine contractions at a time when the uterus is normally quiescent.
Preterm labor complicates 7–10% of all pregnancies and is a very large contributor to perinatal morbidity and mortality. Although over half the cases of preterm labor occur without warning, some factors do carry an identifiable risk: multiple gestation, uterine anomalies, third trimester bleeding, intrauterine infection, excessive amniotic fluid volume, maternal smoking and a history of prior preterm delivery. There have been many unsuccessful attempts to use risk scoring, close clinical observation and home uterine contraction moni toring to predict women at high risk for preterm labor. Several bio chemical markers suggest increased risk of preterm labor: raised salivary estriol, which reflects activation of the fetal hypothalamic pituitary adrenal axis, and cortisol releasing hormone, which is syn thesized by the placenta (Chapters 19 and 22). Fetal fibronectin is normally restricted to the fetal compartment but will appear in vaginal secretions of women who are at risk for preterm delivery. Therefore the absence of fetal fibronectin in maternal vaginal secretions is highly predictive of women who will not experience preterm labor.
Potential mechanisms for preterm labor
The normal mechanisms involved in labor (Chapter 22) predict the pathways for stimuli that start labor prematurely. For instance, intrauterine infection is associated with an elevation in the amniotic fluid levels of the cytokines interleukin-1β, interleukin-6 and tumor necrosis factor α (TNF-α). Products of the cyclo-oxygenase and prostaglandin pathways are also elevated in patients with intrauterine infections. Cytokines and prostaglandins act synergistically to stimulate the myometrium. Their premature elevation with intrauterine infection could activate the uterus prematurely. Recently, thrombin has been shown to be an extremely potent uterotonic agent. The increase in thrombin production that accompanies bleeding in pregnancy may cause preterm labor. Multiple gestations and excessive amniotic fluid excessively stretch the myometrial syncytium. While this may stimulate muscle activity, it is unclear how fiber stretching produces the regular, coordinated contractions of labor.
In some cases of preterm labor, contractions represent an attempt by the uterus to expel the fetus from a hostile intrauterine environment. This may be the goal when premature labor accompanies intrauterine infection. It is usually not prudent to intervene by attempting to stop labor in these clinical situations. When the cause of preterm labor does not independently place the fetus in danger, pharmacologic attempts to stop the premature contractions may be used (Fig. 37.1). Several agents, called tocolytics, are available to inhibit premature uterine contractions. Tocolytics work by interrupting one of four processes: (i) intracellular Ca2+ homeostasis; (ii) myosin phosphorylation; (iii) prostaglandin synthesis; and (iv) oxytocin binding to its receptors (Fig. 37.1). Calcium ions are required for normal myometrial contractions. Magnesium sulfate (MgSO4) acts as a competitive antagonist for Ca2+ and is a commonly used tocolytic. High extracellular magnesium concentrations inhibit Ca2+ entry into myometrial cells via voltage operated channels. In addition, intracellular magnesium competes with Ca2+ for binding sites on calmodulin. Decreased calcium calmodulin binding decreases the activity of myosin light chain kinase and muscle contraction. Nifedipine and nitrendipine are type II (dihydropyridine) calcium channel blockers. They prevent Ca2+ influx through the cell membrane into the myometrial cells via the voltage-operated Ca2+ channels. Beta-adrenergic agonists, such as ritodrine, salbutamol, iso xsuprine and terbutaline, bind to β2-adrenergic receptors on the myo- metrial cell membrane, activate G proteins and increase intracellular cAMP levels. An increase in cAMP levels activates protein kinase A. Activated protein kinase A inhibits myosin light chain phosphoryla- tion. Prostaglandins E and F2α stimulate uterine contractions. The tocolytic, indomethacin, reduces prostaglandin production. It competi tively inhibits cyclo-oxygenases that are necessary for conversion of arachidonic acid to prostaglandins. Oxytocin antagonists bind to the oxytocin receptor but do not activate it. Antagonist-binding blocks activation by the agonist oxytocin. Progesterone prophylaxis has been shown to reduce the rate of preterm birth among women with a history of spontaneous preterm delivery. The mechanism of action of the supplemental progesterone is not known.
Postterm pregnancy refers to a pregnancy that has extended to or beyond 42.0 weeks’ gestation or 294 days from the first day of the last normal menstrual period. About 2% of pregnancies dated by first trimester ultrasound go postterm. The cause of postterm pregnancy is largely unknown. Risk factors include first pregnancy, male fetus, obesity, prior postterm pregnancy and maternal postterm birth. The latter two factors suggest that maternal genetic factors may have a role. Interesting recent data indicate that paternal genes expressed in the fetus may also be involved. Early reports that placental sulfatase deficiency and fetal anencephaly are associated with postterm pregnancy have not been corroborated.
Postterm pregnancy is linked to increased maternal and fetal risk. Labor abnormalities and cesarean deliveries increase because of fetal overgrowth and placental dysfunction. Fetal risks include stillbirth, asphyxia and birth injury from overgrowth. Management of the postterm pregnancy may include induction at 41.0 weeks’ gestation or expectant management with close fetal surveillance.
Placental abruption is defined as premature separation of the placenta prior to delivery of the fetus. Typical symptoms of placen- tal abruption are vaginal bleeding and abdominal pain that are often accompanied by frequent prolonged uterine contractions, uterine tenderness and fetal distress. Placental abruption complicates about 1% of all births. Severe abruptions can result in stillbirth (Chapter 36).
Risk factors for placental abruption that precedes labor include maternal trauma, hypertension, uterine anomalies, inherited and acquired clotting disorders, abruption or pre-eclampsia in a prior pregnancy, poor fetal growth, cocaine use, cigarette smoking and acute intrauterine infection. Rupture of the fetal membranes, either prior to the onset of labor or during labor in the presence of excess amniotic fluid, is also associated with increased risk for placental abruption.
Most commonly, the cause of the placental separation is the rupture of maternal vessels in the decidua basalis next to the placental villi. Rupture of vessels may result from acute trauma, high intravascular pressures or from chronic inflammation and/or necrosis. Maternal blood infiltrates into the decidua and lifts it off of the placenta. The resulting hematoma may stay small or it may enlarge to completely separate the placenta from the uterine wall. Thrombin, an important component of the clotting cascade, is released from the decidua in response to the local hypoxia that accompanies abruption. Thrombin is a very potent uterotonic agent; its release likely produces the exaggerated uterine activity seen with abruption. Thrombin also induces expression of inflammatory cytokines, leading to additional vascular disruption. The detached portion of the placenta cannot exchange gases or deliver nutrients for the duration of the pregnancy. Pregnancy outcome is largely dependent on the size of the separation.
The amount of vaginal bleeding from a placental abruption is not a good indicator of the extent of the separation because some or all of the bleeding can be concealed within the uterus. In cases of abruption severe enough to kill the fetus, maternal disseminated intravascular coagulation can develop due to consumption of available clotting factors by the massive amounts of released thrombin. Management of placental abruption depends on severity and gestational age.
Placenta previa refers to the presence of placental tissue overlying or extremely close to the internal os of the cervix. It occurs in 5–6% of first trimester gestations; however, placental migration away from the cervix results in an incidence of 0.5% in the third trimester. The diagnosis is made by ultrasound examination of the pregnancy within the uterus. Risk factors for placenta previa include prior cesarean delivery and uterine curettage, advancing maternal age and parity, cigarette smoking, multiple gestation and male fetal gender. Conditions associated with placenta previa include placenta accreta, velamentous umbilical cord insertion, vasa previa and abnormal fetal lie. Placenta accreta occurs when the placenta traverses the decidua and invades the myometrium. Velamentous insertion of the umbilical cord occurs when the fetal blood vessels do not insert on the disc of the placenta, presumably as a result of abnormal placental migration. Vasa previa is a rare condition in which the umbilical blood vessels insert onto the fetal membranes instead of the placenta and a fetal vessel lies over the internal os of the cervix.
Placenta previa is thought to occur when an embryo fails to implant in the upper segment of the uterus. Reasons for the abnormal implantation include scarring of the uterus from cesarean deliveries, uterine curettage and prior pregnancies, a need for increased placental surface area to compensate for a reduction in uteroplacental nutrient or oxygen delivery such as occurs with maternal smoking or multiple gestation, and delayed implantation associated with later fertilization in male embryos. An abnormal fetal lie may result from the large volume of placenta in the lower portion of the uterine cavity with a placenta previa.
Abnormal fetal lie and presentation
The term “lie” refers to the orientation of the fetus in the uterus. By far the most common fetal lie is longitudinal. Transverse lie means the fetus is lying sideways in the uterus. Occasionally, the fetal and maternal axes will cross at a 45° angle, forming an oblique lie. Oblique lies are unstable and will usually convert to a longitudinal lie in labor. Only longitudinal lies can safely be delivered vaginally.
Presentation refers to the fetal part that is in closest proximity to the birth canal. The most common fetal presentation is head-down (cephalic or vertex); 95% of fetuses are vertex at term. The second most common presentation is breech, in which the fetal legs or buttocks are just above the cervix. A shoulder typically presents when the fetus is lying transverse.
The major risk factor for abnormal fetal lie and presentation is prematurity. Other risk factors include fetal malformations, congenital neuromuscular disorders, multiple gestation, uterine malformations and high maternal parity (number of prior births).