Stephen Douglas Sisson, M.D.
https://www.hopkinsmedicine.org/profiles/results/directory/profile/0005225/stephen-sisson
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Dietary changes and exercise reduce weight and rates of the associated metabolic syndrome (Garvey coccyx pain treatment nhs buy anacin 525 mg otc, 2016; Martin, 2016). When used in conjunction with bariatric surgery, glucose control in those with type 2 diabetes is improved (Schauer, 2014). However, both surgical and medical interventions are associated with appreciable long-term failure rates-up to 50 percent in patients with type 2 diabetes undergoing bariatric surgery (Mingrone, 2015). This translates into difficulty in achieving pregnancy, early and recurrent pregnancy loss, preterm delivery, and several obstetrical, medical, and surgical complications with pregnancy, labor, delivery, and the puerperium (American College of Obstetricians and Gynecologists, 2015). Last, infants-and later, adult children-of obese mothers have correspondingly higher morbidity rates (Godfrey, 2017; Reynolds, 2013). Maternal Morbidity For overweight women, higher rates of adverse outcomes complicate pregnancy (Schummers, 2015). Shown in Table 48-2 are results from five studies including more than 1 million singleton pregnancies. Of outcomes, Mariona (2017) reviewed maternal deaths in Michigan and found that the risk of a maternal death was nearly fourfold higher in obese women. Women with super-morbid obesity experience very high rates of maternal and neonatal complications including preeclampsia, fetal overgrowth, and cesarean delivery, with even higher rates of meconium aspiration, ventilator support, and neonatal death (Marshall, 2014; Smid, 2016). As discussed previously, obesity and the metabolic syndrome are characterized by insulin resistance, which causes low-grade inflammation and endothelial activation (Ma, 2016). Similar observations were reported from a large Canadian study and by the Safe Labor Consortium (Kim, 2016; Schummers, 2015). Stewart and colleagues (2016) prospectively studied the effect of obesity on cardiac remodeling in pregnancy among 14 normal and 9 overweight or obese women. Their coexistence with and adverse effects on pregnancy outcomes are discussed in Chapter 57 (pp. Nonalcoholic fatty liver disease is associated with several adverse pregnancy outcomes. In addition to these metabolic complications, quality-of-life measures are also negatively affected by obesity during pregnancy (Amador, 2008; Ruhstaller, 2017). One systematic review found significantly higher risks of depression in overweight and obese women during and after pregnancy (Molyneaux, 2014). Obese women were also significantly more likely to experience anxiety during pregnancy. Perinatal Mortality Stillbirths are more prevalent as the degree of obesity accrues (Ovesen, 2011; Schummers, 2015). In a review of almost 100 studies, obesity was the highest ranking modifiable risk factor for stillbirth (Flenady, 2011). In super-morbidly obese compared with normal-weight gravidas, Yao and associates (2014) found 5.
Syndromes
Folic acid supplementation of 4 mg daily is given orally to sustain erythropoiesis pain management senior dogs buy anacin 525 mg. Women with hereditary spherocytosis cared for at Parkland Hospital had hematocrits ranging from 23 to 41 volumes percent-mean 31 (Maberry, 1992). Infection in four women intensified hemolysis, and three of these required transfusions. Newborns with hereditary spherocytosis may manifest hyperbilirubinemia and anemia shortly after birth. Erythrocyte Enzyme Deficiencies An intraerythrocytic deficiency of enzymes that permit anaerobic glucose metabolism may cause hereditary nonspherocytic anemia. Pyruvate kinase deficiency is associated with variable anemia and hypertensive complications (Wax, 2007). Due to recurrent transfusions in homozygous carriers, iron overload is frequent, and associated myocardial dysfunction should be monitored (Dolan, 2002). The fetus that is homozygous for this mutation may develop hydrops fetalis from anemia and heart failure (Chap. The most common are caused by a base substitution that leads to an amino acid replacement and a broad range of phenotypic severity (Luzzatto, 2015; Puig, 2013). Approximately 2 percent of African-American women are affected, and the heterozygous variant is found in 10 to 15 percent (Mockenhaupt, 2003). In both instances, random X-chromosome inactivation-lyonization-results in variable enzyme activity. Anemia is usually episodic, although some variants induce chronic nonspherocytic hemolysis. Because young erythrocytes contain more enzyme activity, anemia ultimately stabilizes and is corrected soon after the inciting cause is eliminated. Aplastic and Hypoplastic Anemia Aplastic anemia is a grave complication that is characterized by pancytopenia and markedly hypocellular bone marrow (Young, 2015). There are multiple etiologies, and at least one is linked to autoimmune diseases (Stalder, 2009). These include drugs and other chemicals, infection, irradiation, leukemia, immunological disorders, and inherited conditions such as Fanconi anemia and Diamond-Blackfan syndrome (Green, 2009; Lipton, 2009). The functional defect appears to be a marked decrease in committed marrow stem cells. Hematopoietic stem-cell transplantation is optimal therapy in a young patient (Killick, 2016). Immunosuppressive therapy is given, and in some nonresponders, eltrombopag has been successful (Olnes, 2012; Townsley, 2017).
Excessive development of the foetus can usually be traced to prolongation of pregnancy pain medication for dogs advil purchase anacin 525 mg with amex, large size of one or both parents, advancing age, or multiparity of the mother. Whitridge Williams (1903) the concept of excessive or impaired fetal growth was not considered in detail by Williams in his first edition. Abnormally diminished fetal growth was attributed to placental lesions and fetal infections. Currently, fetal-growth disorders at both ends of the spectrum are major problems in obstetrics. Nearly 20 percent of the almost 4 million neonates born in the United States are at the low and high extremes of fetal growth. And, although almost 70 percent of low-birthweight neonates are born preterm, the balance of low-birthweight newborns accounted for approximately 3 percent of term births in 2015 (Martin, 2017). Between 1990 and 2006, the proportion of newborns with birthweights <2500 g grew by more than 20 percent when the rate peaked at 8. In contrast, between 1990 and 2006, the incidence of birthweights >4000 g declined approximately 30 percent to a nadir of 7. This trend away from the upper extreme is difficult to explain because it coincides with the epidemic prevalence of obesity, a known cause of macrosomia (Morisaki, 2013). However, the "obstetrical dilemma" postulates a conflict between the need to walk upright-requiring a narrow pelvis -and the need to think-requiring a large brain, and thus a large head. Some speculate that evolutionary pressures restrict growth late in pregnancy (Mitteroecker, 2016). The initial phase of hyperplasia occurs in the first 16 weeks and is characterized by a rapid increase in cell number. After 32 weeks, fetal mass accrues by cellular hypertrophy, and it is during this phase that most fetal fat and glycogen are accumulated. The precise cellular and molecular mechanisms by which normal fetal growth ensues are incompletely understood. These growth factors are produced by virtually all fetal organs and are potent stimulators of cell division and differentiation. Other hormones implicated in fetal growth have been identified, particularly hormones derived from adipose tissue. These hormones are known broadly as adipokines and include leptin, the protein product of the obesity gene. Fetal leptin concentrations rise during gestation, and they correlate both with birthweight and with neonatal fat mass (Briffa, 2015; Logan, 2017; Simpson, 2017).
Soc Sci Med 83:42 advanced pain treatment center mason ohio discount anacin 525 mg without prescription, 2013 Rabie N, Magann E, Steelman S, et al: Oligohydramnios in complicated and uncomplicated pregnancies: a systematic review and meta-analysis. Ultrasound Obstet Gynecol 49(4):442, 2017 Radaelli T, Lepercq J, Varastehpour A, et al: Differential regulation of genes for fetoplacental lipid pathways in pregnancy with gestational and type 1 diabetes mellitus. Am J Epidemiol 168(10):1145, 2008 Rudzinski E, Gilroy M, Newbill C, et al: Positive C4d immunostaining of placental villous syncytiotrophoblasts supports host-versus-graft rejection in villitis of unknown etiology. J Clin Endocrinol Metab 102(2):499, 2017 Sobhy S, Babiker Z, Zamora J, et al: Maternal and perinatal mortality and morbidity associated with tuberculosis during pregnancy and the postpartum period: a systematic review and meta-analysis. Ultrasound Obstet Gynecol November 11, 2016 [Epub ahead of print] Waldhoer T, Klebermass-Schrehof K: the impact of altitude on birth weight depends on further mother- and infant-related factors: a population-based study in an altitude range up to 1600 m in Austria between 1984 and 2013. Obstet Gynecol 59:624, 1982 Yamamoto R, Ishii K, Shimada M, et al: Significance of maternal screening for toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus infection in cases of fetal growth restriction. Am J Obstet Gynecol 202(6):522, 2010 Zhang J, Mikolajczyk R, Grewal J, et al: Prenatal application of the individualized fetal growth reference. Thus, if at an early period the heart of one embryo is considerably stronger than that of the other, a gradually increasing area of the communicating portion of the placenta is monopolized by the former, so that its heart increases rapidly in size, whilst that of the latter receives less blood and eventually atrophies. These pregnancies may result from two or more fertilization events, from a single fertilization followed by a splitting of the zygote, or from a combination of both. Multifetal gestations were problematic during those times and remain so today for both the mother and her fetuses. For example, in this country, approximately a fourth of very-lowbirthweight neonates-those born weighing <1500 g-are from multifetal gestations (Martin, 2017). Fueled largely by infertility therapy, both the rate and the number of twins and higher-order multifetal births grew dramatically during the 1980s and 1990s in the United States. During the same time, the number of higher-order multifetal births peaked in 1998 at a rate of 1. Since then, however, evolving infertility management has lowered rates of higher-order multifetal births -especially among non-Hispanic white women. For example, the rate of triplets or more declined by more than 50 percent from 1998 to 2015 in this demographic group. These rates of multifetal pregnancies have a direct effect on the rates of preterm birth and its comorbidities. In addition, the risks for congenital malformation and its consequences are greater with multifetal gestations. Importantly, this increased risk applies to each fetus and is not simply the result of more fetuses. In sum, in 2013 in the United States, multifetal births accounted for 3 percent of all live births but for 15 percent of all infant deaths.
Heart 91:e3 back pain treatment for dogs discount anacin 525 mg, 2005 Sliwa K, Blauwet L, Tibazarwa K, et al: Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof-of-concept pilot study. Semin Perinatol 38(5):295, 2014 Stergiopoulos K, Shiang E, Bench T: Pregnancy in patients with pre-existing cardiomyopathies. Obstet Gynecol 126(2):346, 2015 Thorne S, MacGregor A, Nelson-Piercy C: Risks of contraception and pregnancy in heart disease. Heart 92(10):152, 2006 Thurman R, Zaffar N, Sayyer P, et al: Labour profile and outcomes in pregnant women with heart disease. Am J Obstet Gynecol 216:S459, 2017 Trigas V, Nagdyman N, Pildner von Steinburg S, et al: Pregnancy-related obstetric and cardiologic problems in women after atrial switch operation for transposition of the great arteries. Circulation 132(2):132, 2015 Vashisht A, Katakam N, Kausar S, et al: Postnatal diagnosis of maternal congenital heart disease: missed opportunities. Eur J Obstet Gynecol Reprod Biol 56:89, 1994 Vitarelli A, Capotosto L: Role of echocardiography in the assessment and management of adult congenital heart disease in pregnancy. Circ J 79(7):1416, 2015 Watkins H, Ashrafian H, Redwood C: Inherited cardiomyopathies. Circulation 116:1736, 2007 World Health Organization: Medical eligibility for contraceptive use, 4th ed. J Clin Anesth 18:142, 2006 Yang X, Wang H, Wang Z, et al: Alteration and significance of serum cardiac troponin I and cystatin C in preeclampsia. Clin Chim Acta 374:168, 2006 Yu M, Yi K, Zhou L, et al: Pregnancy increases heart rates during paroxysmal supraventricular tachycardia. For the most part, autopsy will reveal the presence of renal changes usually of acute nephritis, though occasionally it may be engrafted upon a chronic process. It is now apparent that chronic hypertension is one of the most common serious complications encountered during pregnancy. The incidence of chronic hypertension complicating pregnancy varies depending on population vicissitudes. In a study of more than 56 million births from the Nationwide Patient Sample, the incidence was 1. Despite this substantive prevalence, optimal management has not been well studied. This is followed by variable behavior later in pregnancy and, importantly, by the unpredictable development of superimposed preeclampsia. The latter carries increased risks for maternal and perinatal morbidity and mortality. This is not a simple task because, like all polygenically determined biological variants, blood pressure norms differ between populations. For example, not only do blood pressures vary between races and genders, but pressures-especially systolic-rise directly with increasing age and weight. Thus, pragmatically, normal adults have a broad range of blood pressures, but so do those with chronic hypertension. After these variables are acknowledged, important considerations for any population are the attendant risks of chronic hypertension.
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The presence of thyroid antibodies has also been associated with preterm birth (Stagnaro-Green upstate pain treatment center cheap 525 mg anacin with amex, 2009). These investigators, however, did find a threefold greater risk of placental abruption in these women. Currently, universal screening for the thyroid autoantibodies is not recommended by any professional organization (De Groot, 2012; Stagnaro-Green, 2011a, 2012a). Iodine Deficiency Decreasing iodide fortification of table salt and bread products in the United States during the past 25 years has led to occasional iodide deficiency (Caldwell, 2005; Hollowell, 1998). Importantly, the most recent National Health and Nutrition Examination Survey indicated that, overall, the United States population remains iodine sufficient (Caldwell, 2011). Even so, experts agree that iodine nutrition in vulnerable populations, such as pregnant women, requires continued monitoring. In 2011, the Office of Dietary Supplements of the National Institutes of Health sponsored a workshop to prioritize iodine research. Participants emphasized the decline in median urinary iodine levels to 125 g/L in pregnant women and the serious potential effects on developing fetuses (Swanson, 2012). Dietary iodine requirements are higher during pregnancy due to augmented thyroid hormone production, increased renal losses, and fetal iodine requirements. Adequate iodine is requisite for fetal neurological development beginning soon after conception, and abnormalities are dependent on the degree of deficiency. Although it is doubtful that mild deficiency causes intellectual impairment, supplementation does prevent fetal goiter (Stagnaro-Green, 2012b). Severe deficiency, on the other hand, is frequently associated with damage typically encountered with endemic cretinism (Delange, 2001). Berbel and associates (2009) began daily supplementation in more than 300 pregnant women with moderate deficiency at three time periods-4 to 6 weeks, 12 to 14 weeks, and after delivery. They found improved neurobehavioral development scores in offspring of women supplemented with 200 g potassium iodide very early in pregnancy. Similarly, Velasco and coworkers (2009) found improved Bayley Psychomotor Development scores in offspring of women supplemented with 300 g of iodine daily in the first trimester. In contrast, Murcia and colleagues (2011) identified lower psychomotor scores in 1-year-old infants whose mothers reported daily supplementation of more than 150 g. To address this, randomized controlled trial of iodine supplementation in mildly to moderately iodine-deficient pregnant women in India and Thailand is nearing completion (Pearce, 2016). Regarding daily iodine intake, the Institute of Medicine (2001) recommends 220 g/d during pregnancy and 290 g/d during lactation (Chap. The Endocrine Society recommends an average iodine intake of 150 g/d in reproductive-aged women, and this should be increased to 250 g during pregnancy and breastfeeding (De Groot, 2012).
Whitridge Williams (1903) Even though Williams only mentions acute hepatic fatty metamorphosis pain treatment journal order anacin 525 mg amex, in practice, disorders of the liver, gallbladder, and pancreas together comprise a formidable list of complications that may arise in pregnancy. The relationships of several of these with pregnancy can be fascinating, intriguing, and challenging. The first includes those specifically related to pregnancy that resolve either spontaneously or following delivery. Examples are intrahepatic cholestasis and acute fatty liver, both discussed in the next sections. Mild hyperbilirubinemia with elevated serum transaminase levels is seen in up to half of affected women requiring hospitalization. Clinical and Laboratory Findings with Acute Liver Diseases in Pregnancy the second category involves acute hepatic disorders that are coincidental to pregnancy, such as acute viral hepatitis. The third category includes chronic liver diseases that predate pregnancy, such as chronic hepatitis, cirrhosis, or esophageal varices. Importantly, several normal pregnancy-induced physiological changes induce appreciable liver-related clinical and laboratory manifestations (Chap. Findings such as elevated serum alkaline phosphatase levels, palmar erythema, and spider angiomas, which might suggest liver disease, are common during normal pregnancy. Metabolism is also affected, due to altered expression of the cytochrome P450 system. This alteration is mediated by higher levels of estrogen, progesterone, and other pregnancy hormones. Importantly, cytochrome enzymes are expressed in many organs besides the liver, most notably the placenta. The net effect is complex and likely influenced by gestational age and organ of expression (Isoherranen, 2013). Despite all of these functional changes, no major hepatic histological changes are induced by normal pregnancy. Intrahepatic Cholestasis of Pregnancy this condition has been called recurrent jaundice of pregnancy, cholestatic hepatosis, and icterus gravidarum and is characterized by pruritus, icterus, or both. It may be more common in multifetal pregnancy, and there is a significant genetic influence (Lausman, 2008; Webb, 2014). For example, cholestasis is infrequent in North America, with an overall incidence approximating 1 case in 500 to 1000 pregnancies. Historically, indigenous women from Chile and Bolivia also have a relatively high incidence. For unknown reasons, this incidence has declined since the 1970s and is now less than 2 percent (Reyes, 2016). In other countries, for example Sweden, China, and Israel, the incidence varies from 0.
Because of the high risk of recurrent hemorrhage from an unresected or inoperable lesion pain treatment herpes zoster discount 525 mg anacin, we favor cesarean delivery. The degenerative diseases are multifactorial and are characterized by progressive neuronal death. The disease affects women twice as often as men, and it usually begins in the 20s and 30s. The demyelinating characteristic of this disorder results predominately from T cell-mediated autoimmune destruction of oligodendrocytes that synthesize myelin. There is a genetic susceptibility and likely an environmental trigger such as exposure to certain bacteria and viruses. Of these, Chlamydophila pneumoniae, human herpesvirus 6, or Epstein-Barr virus are implicated (Frohman, 2006; Goodin, 2009). With it, unpredictable recurrent episodes of focal or multifocal neurological dysfunction usually are followed by full recovery. Similarly, identification of serum antibodies against myelin oligodendrocyte glycoprotein and myelin basic protein is not predictive of recurrent disease activity (Kuhle, 2007). T2-weighted axial image shows bright signal abnormalities in white matter, typical for multiple sclerosis. Relapse risk was reduced 70 percent during pregnancy, but with a significantly greater relapse rate postpartum. This may be related to higher pregnancy-induced numbers of T-helper lymphocytes and an increased T2/T1 ratio (Airas, 2008). Breastfeeding has no apparent effect on postpartum relapses (Hellwig, 2015; Portaccio, 2011). Effects of Multiple Sclerosis on Pregnancy With uncomplicated disease, there are usually no adverse effects on pregnancy outcome (Bove, 2014). Some women may become fatigued more easily, those with bladder dysfunction are predisposed to urinary infection, and women with spinal lesions at or above T6 are at risk for autonomic dysreflexia. In one study of 449 pregnancies in affected women, the labor induction rate was higher, and secondstage labor was longer (Dahl, 2006). The greater induction rate and elective operations contributed to the overall higher cesarean delivery rate. In an analysis of 649 affected women, the mean birthweight was lower but the perinatal mortality rate was similar compared with that of controls (Dahl, 2005). Management in Pregnancy Goals are to arrest acute or initial attacks, employ disease-modifying agents, and provide symptomatic relief. Acute or initial attacks are treated with high-dose intravenous methylprednisolone-500 to 1000 mg daily for 3 to 5 days, followed by oral prednisone for 2 weeks.
This rate can be as high as 90 percent if caused or complicated by sepsis (Phua intractable pain treatment laws and regulations buy anacin 525 mg free shipping, 2009). Although gravidas are younger and usually healthier than the overall population, they still have mortality rates of 25 to 40 percent (Catanzarite, 2001; Cole, 2005). To date, for most interventional studies, a working diagnosis of acute lung injury is made when the PaO2:FiO2 ratio is <300 and is coupled with dyspnea, tachypnea, oxygen desaturation, and radiographic pulmonary infiltrates (Wheeler, 2007). Pyelonephritis, puerperal pelvic infection, and chorioamnionitis are the most frequent causes of sepsis. As discussed on page 917, severe preeclampsia and obstetrical hemorrhage are also commonly associated with permeability edema. Endothelial injury in the lung capillaries releases cytokines that recruit neutrophils to the inflammation site. First, the exudative phase follows widespread injury to microvascular endothelium, including the pulmonary vasculature, and there is also alveolar epithelial injury. These result in increased pulmonary capillary permeability, surfactant loss or inactivation, diminished lung volume, and vascular shunting with resultant arterial hypoxemia. Next, the fibroproliferative phase usually begins 3 to 4 days later and lasts up to day 21. Last, the fibrotic phase results from healing, and despite this, the long-term prognosis for pulmonary function is surprisingly good (Herridge, 2003; Levy, 2015). Clinical Course With pulmonary injury, the clinical condition depends largely on the insult magnitude, the ability to compensate for it, and the disease stage. For example, soon after the initial injury, physical findings are absent except perhaps hyperventilation. With worsening, clinical and radiological evidence for pulmonary edema, decreased lung compliance, and increased intrapulmonary blood shunting become apparent. Progressive alveolar and interstitial edema develop with extravasation of inflammatory cells and erythrocytes. Ideally, pulmonary injury is identified at this early stage, and specific therapy is directed at the underlying insult. Further progression to acute respiratory failure is characterized by marked dyspnea, tachypnea, and hypoxemia. Additional lung volume loss results in worsening of pulmonary compliance and increased shunting. Diffuse abnormalities are heard by auscultation, and a chest radiograph characteristically demonstrates bilateral lung involvement. At this phase, the injury ordinarily would be lethal in the absence of ventilatory support. When shunting exceeds 30 percent, severe refractory hypoxemia develops along with metabolic and respiratory acidosis that can result in myocardial irritability, dysfunction, and cardiac arrest.
If dilatation of the esophagus and medical therapy does not provide relief advanced diagnostic pain treatment center ct order anacin 525 mg without a prescription, myotomy is considered (Torquati, 2006). During pregnancy, normal relaxation of the lower esophageal sphincter in women with achalasia theoretically should not occur. One report of 20 affected pregnant women found no excessive reflux esophagitis (Mayberry, 1987). Khudyak and coworkers (2006) reviewed 35 cases and described most women as symptom free, although esophageal dilatation was needed in a few. With persistent symptoms, other options include nitrates, calcium-channel antagonists, and botulinum toxin A injected locally (Hooft, 2015; Kahrilas, 2015). Balloon dilatation of the sphincter may be necessary, and 85 percent of nonpregnant patients respond to this. Satin (1992) and Fiest (1993) and their associates reported successful use of pneumatic dilatation in pregnancy. One caveat is that esophageal perforation is a serious complication of dilatation. Spiliopoulos and colleagues (2013) described a 29-week pregnant woman with achalasia treated for 10 weeks with parenteral nutrition. Peptic Ulcer Disease the lifetime prevalence of acid peptic disorders in women is 10 percent (Del Valle, 2015). Acid secretion is also important, and thus underlies the efficacy of antisecretory agents (Suerbaum, 2002). Gastroprotection during pregnancy probably originates from physiological changes that include reduced gastric acid secretion, decreased motility, and considerably increased mucus secretion (Hytten, 1991). Despite this, ulcer disease may be underdiagnosed because of frequent treatment for reflux esophagitis (Mehta, 2010). In the past 50 years at Parkland Hospital, during which time we have cared for more than 500,000 pregnant women, we have encountered very few who had proven ulcer disease. Before appropriate therapy was commonplace, Clark (1953) studied 313 pregnancies in 118 women with ulcer disease and noted a clear remission during pregnancy in almost 90 percent. Symptoms recurred in more than half by 3 months postpartum and in almost all by 2 years. Antacids are usually self-prescribed, but first-line therapy is with H2-receptor blockers or proton-pump inhibitors (Del Valle, 2015). Approximately 10 percent of the aluminum salt is absorbed, and it is considered safe for pregnant women (Briggs, 2015). Diagnostic aids include the urea breath test, serological testing, or endoscopic biopsy. If any of these yield positive results, combination antimicrobial and proton-pump inhibitor therapy is indicated.
Stejnar, 43 years: Poorly named, pyogenic granuloma is actually a lobular capillary hemangioma commonly forming on the mouth or hand in response to low-grade local irritation or traumatic injury.
Benito, 37 years: Most require minimal treatment other than management of the fractures and consideration of bisphosphonates to decrease bone loss.
Tangach, 40 years: Placenta 26(6):471, 2005 Derbent A, Simavli S, Gumus I, et al: Nifedipine for the treatment of preterm labor in twin and singleton pregnancies.
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