SemOpenAlex |

SemOpenAlex

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1992472018> ?p ?o ?g. }

Showing items 1 to 100 of ±146 with 100 items per page.

W1992472018 endingPage "1087" @default.
W1992472018 startingPage "1074" @default.
W1992472018 abstract "Pain management practitioners assist with the treatment of pain in a variety of settings. Despite the common occurrence of pain during pregnancy, major textbooks in both pain management and obstetrics lack any concentrated discussion of the topic. In this review, we discuss the potential for fetal toxicity or teratogenic effects of medications often used to treat pain syndromes, as well as the safety of these medications in the breast-feeding mother. We then present an approach to the diagnosis and treatment of several pain management challenges that may present during pregnancy. Teratology and Toxicity of Medications Used in Pain Management The first tenet in the medical management of the pregnant patient is to minimize the use of all medications and to use nonpharmacologic therapies whenever possible. When opting for drug therapy, the clinician should begin by considering any potential for harm to the mother, the fetus, and the course of pregnancy. The degree of protein binding and lipid solubility of the medication, the speed of maternal metabolism, and the molecular weight all have an impact on the placental transfer of medications from the maternal to the fetal circulation. With the exception of large polar molecules (such as heparin and insulin), nearly all medications reach the fetus to some degree. Approximately 3% of newborns have a significant congenital malformation. Only 25% of fetal malformations have a known genetic cause, and only 2%-3% have a clear environmental link [1]. One of the major limitations in evaluating a medication's potential for causing harm to a developing fetus is the degree of species specificity for congenital defects. A classic example of this specificity is the drug thalidomide; nonprimate studies revealed no teratogenic effects, but severe limb deformities occurred in human offspring when thalidomide was prescribed during pregnancy [2]. The most critical period for minimizing maternal drug exposure is during organogenesis-from the 4th through 10th weeks of pregnancy. Drug exposure before organogenesis usually causes an all-or-none effect: the embryo either does not survive or develops without abnormalities. Drug effects later in pregnancy typically lead to multiple-organ involvement, developmental syndromes, or intrauterine growth retardation [1]. Certain medications may not directly influence fetal organ development but may have the potential to adversely influence the physiology of pregnancy. For example, nonsteroidal antiinflammatory drugs (NSAIDs) may delay the onset of labor, decrease amniotic fluid volume, or place a newborn at risk of pulmonary hypertension. The United States Food and Drug Administration (FDA) has developed a five-category labeling system for all drugs approved in the United States (Table 1). This labeling system rates the potential risk for teratogenic or embryotoxic effects based on available scientific and clinical evidence. Our present knowledge about the adverse effects of uncontrolled pain, as well as the risks of administering medications during pregnancy, is incomplete, and the practitioner is left to weight the risks against the benefits of instituting pharmacologic therapy for each individual.Table 1: FDA Pregnancy Risk Classification Categories for Medications Used in Pain ManagementaMedications in the Breast-Feeding Mother High lipid solubility, low molecular weight, minimal protein binding, and the unionized state all facilitate secretion of medications into breast milk. The neonatal dose of most medications obtained through breast feeding is 1%-2% of the maternal dose [3]. Even with minimal exposure via breast milk, neonatal drug allergy and slower infant drug metabolism must be considered. Only small amounts of colostrum are secreted during the first few postpartum days; thus, early breast feeding poses little risk to the infant whose mother received medications during the delivery period [4]. Most breast milk is synthesized and secreted during and immediately after breast feeding. Taking medications after breast feeding or when the infant has the longest interval between feedings, and avoiding long-acting medications minimizes drug transfer via breast milk [4]. However, effective treatment of chronic pain often requires the use of long-acting medications, particularly opioids. The American Academy of Pediatrics has categorized medications in relation to the safety of their ingestion by breast-feeding mothers [3] (Table 2).Table 2: American Academy of Pediatrics (AAP) Classification of Maternal Medication Use During LactationaMedications Often Used in Pain Management Nonsteroidal Antiinflammatory Drugs Aspirin remains the prototypical NSAID and is the most thoroughly studied of this class of medication. The results of the Collaborative Perinatal Project suggest that first-trimester exposure to aspirin does not pose appreciable teratogenic risk [5]. Prostaglandins seem to trigger labor, and the aspirin-induced inhibition of prostaglandin synthesis may result in prolonged gestation and protracted labor [1]. Aspirin also has well known platelet-inhibiting properties and, theoretically, may increase the risk of peripartum hemorrhage. Neonatal platelet function is also inhibited for up to 5 days after delivery in aspirintreated mothers [6]. Although small-dose aspirin therapy (60-80 mg/d) has not been associated with maternal or neonatal complications, larger doses seem to increase the risk of intracranial hemorrhage in neonates born before 35 wk of gestation [7]. Circulating prostaglandins modulate the patency of the fetal ductus arteriosus. NSAIDs have been used therapeutically in neonates with persistent fetal circulation to induce closure of the ductus arteriosus via inhibition of prostaglandin synthesis. In utero, patency of the ductus arteriosus is essential for normal fetal circulation. Indomethacin has shown promise for the treatment of premature labor [8], but its use has been linked to premature antenatal closure of the fetal ductus arteriosus [9]. Ibuprofen has not been linked to congenital defects. The use of ibuprofen during pregnancy may result in reversible oligohydramnios (reflecting diminished fetal urine output) and mild constriction of the fetal ductus arteriosus [10]. Similarly there are no data to support any association between naproxen administration and congenital defects. Because it shares the renal and vascular effects of ibuprofen, naproxen may diminish ductus arteriosus diameter and cause oligohydramnios [7]. Ketorolac is a relatively new NSAID available for both oral and parenteral administration. According to the manufacturer's prescribing information (Syntex Laboratories, Palo Alto, CA, 1997), it did not cause birth defects in the offspring of pregnant rabbits. However, ketorolac administration during labor did lead to dystocia in rodents. Ketorolac shares the platelet-inhibiting properties of other NSAIDs [11]. Although ketorolac has not undergone evaluation for its effects on the fetal ductus arteriosus or renal vasculature, it is likely to have effects similar to those of other NSAIDs. Until more information is available, it may be prudent to choose more extensively studied NSAIDs for use during pregnancy. In breast-feeding women, salicylate transport into breast milk is limited by its highly ionized state and high degree of protein binding. Caution should still be used if more than occasional or short-term aspirin use is contemplated during lactation, because neonates eliminate salicylates very slowly [12]. Both ibuprofen and naproxen are also minimally transported into breast milk and are considered compatible with breast feeding [3]. Indomethacin should be avoided during lactation based on case reports of neonatal seizures and nephrotoxicity [4]. Little information is available on the safety of maternal ketorolac use during lactation. One study found that ketorolac concentrations ranged from 1% to 4% of maternal serum levels in breast milk [13]. Considering the bioavailability of ketorolac after oral administration, this would likely result in neonatal blood levels between 0.16% and 0.40% of the maternal dose. The American Academy of Pediatrics considers ketorolac to be compatible with breast feeding [3]. Because of the antiplatelet properties of NSAIDs, many anesthesiologists are concerned about the risk of epidural hematoma formation as a result of epidural catheter placement. To date, there are no outcome studies on which to base recommendations. There is no evidence that small-dose aspirin therapy or use of other NSAIDs increases the risk of epidural hematoma formation after spinal or epidural placement [14]. As part of our routine history and physical examination of the parturient, we screen for any evidence of bleeding diathesis or easy bruisability and, in their absence, proceed with epidural placement without further laboratory testing. Acetaminophen provides similar analgesia without the antiinflammatory effects of the NSAIDs. It has no known teratogenic properties, does not inhibit prostaglandin synthesis or platelet function, and is hepatotoxic only in extreme overdosage [7]. If persistent pain demands use of a mild analgesic during pregnancy, acetaminophen seems to be a safe and effective first-choice drug. Acetaminophen does enter breast milk, although maximal neonatal ingestion would be less than 2% of a maternal dose [15]. Acetaminophen is considered compatible with breast feeding [5]. Opioid Analgesics Much of our knowledge about the effects of chronic opioid exposure during pregnancy comes from studies of opioid-abusing patients [16-18]. Opioids such as heroin are often adulterated with other substances that pose additional health risks. Bacterial infections (cellulitis, abscess formation, and endocarditis) and viral infections (hepatitis, human immunodeficiency virus) are often associated with intravenous drug abuse. Pregnancy outcomes in studies of drug-abusing mothers must be interpreted with caution when attempting to establish the risks of a prescribed opioid regimen in the pregnant patient with pain. Most studies suggest that methadone maintenance is associated with longer gestation and increased birth weight when compared with outcomes of untreated opioid abusers. However, both methadonemaintained and untreated opioid-abusing pregnant women deliver infants with lower birth weights and smaller head circumference than do drug-free controls [18]. No increase in congenital defects has been observed in the offspring of methadone-consuming patients. The FDA has assigned methadone a risk Category B unless used at large doses near term. Neonatal abstinence syndrome occurs in between 30% and 90% of infants exposed to either heroin or methadone in utero [16,17]. Neonatal withdrawal symptoms may be more frequent if the maternal daily methadone dose exceeds 20 mg [17]. Most infants that have symptomatic opioid withdrawal are symptomatic by 48 h postpartum, but there are reports of withdrawal symptoms beginning 7-14 days postpartum [16]. Neonates with prenatal exposure to opiates for long periods may require very slow weaning (as slow as a 10% reduction every third day) to prevent withdrawal symptoms [16,17]. Methadone levels in breast milk seem sufficient to prevent opioid withdrawal symptoms in the breastfed infant [7]. The American Academy of Pediatrics considers methadone doses of up to 20 mg/d to be compatible with breast feeding [3]. Recognition of infants at risk of neonatal abstinence syndrome and institution of appropriate supportive and medical therapy typically results in little shortterm consequence to the infant [19]. The long-term effects of in utero opioid exposure are unknown. Chasnoff [18] considered both the environmental and socioeconomic factors that influence child development and concluded that there are no definite data demonstrating long-term development sequelae from in utero opioid exposure. There is no evidence to suggest a relationship between exposure to any of the opioid agonists or agonist-antagonists during pregnancy and large categories of major or minor malformations. The Collaborative Perinantal Project monitored 50,282 motherchild pairs, 563 of which had first-trimester exposure to codeine and 686 of which had first-trimester exposure to propoxyphene [5]. No evidence was found for either drug to suggest a relationship to large categories of major or minor malformations. Codeine was associated with six individual defects: respiratory (8 cases), genitourinary (7 cases), Down's syndrome (1 case), tumors (4 cases), umbilical hernia (3 cases), and inguinal hernia (12 cases). Only the association with respiratory malformation was found to be statistically significant. Five possible associations with individual defects after propoxyphene exposure were observed: microcephaly (6 cases), persistent ductus arteriosus (5 cases), benign tumors (12 cases), and clubfoot (18 cases). None of these associations reached statistical significance. Thus, data from large surveillance studies have pointed to possible associations with individual defects, but the incidence is not statistically greater than that of the general population (except for respiratory malformations after codeine). Independent confirmation is needed for all of the findings in this study. Codeine and propoxyphene are rated Risk Category C by the FDA. The Collaborative Perinatal Project reported no congenital anomalies associated with hydrocodone, meperidine, methadone, morphine, or oxycodone use during pregnancy [5]. In the Michigan Medicaid Study, a total of 289 fetal exposures to oxycodone occurred with no evidence of teratogenic effects [5]. There have been no reports linking the use of fentanyl, hydromorphone, oxymorphone, butorphanol, or nalbuphine with congenital defects. However, neither the Collaborative Perinatal Project nor the Michigan Medicaid Study reported exposures to any of these agents. Hydrocodone, meperidine, methadone, morphine, oxycodone, fentanyl, hydromorphone, oxymorphone, butorphanol, and nalbuphine are all rated Risk Category B by the FDA. Fentanyl is one of the most common parenteral opioid analgesics administered during the perioperative period. As with all opioid analgesics, administration of fentanyl to the mother immediately before delivery may lead to respiratory depression in the newborn [20]. Maternal administration of fentanyl or other opioids may also cause loss of the normal variability in fetal heart rate. Loss of fetal heart rate variability can signal fetal hypoxemia; thus, administration of opioids during labor may deprive obstetric caregivers of a useful tool for assessing fetal wellbeing [20]. Meperidine undergoes extensive hepatic metabolism to normeperidine, which has a long elimination half-life (18 h). Repeated dosing can lead to accumulation, especially in patients with renal insufficiency [21]. Normeperidine causes excitation of the central nervous system manifest as tremors, myoclunus, and generalized seizures [21]. Significant accumulation of normeperidine is unlikely in the parturient who receives single or infrequent doses, but meperidine offers no advantages over other parenteral opioids. Although mixed agonist-antagonist opioid analgesics are widely used to provide analgesia during labor, they do not seem to offer any advantage over pure opioid agonists. In a blind, randomized comparison of meperidine and nalbuphine during labor, the two drugs seemed to provide comparable analgesia, as well as neonatal Apgar and neurobehavioral scores [22]. Use of either nalbuphine [23] or pentazocine [24] during pregnancy can lead to neonatal abstinence syndrome. Nalbuphine may also cause a sinusoidal fetal heart rate pattern after maternal administration, thereby complicating fetal assessment [25]. Opioids are excreted into breast milk. Pharmacokinetic analysis has demonstrated that breast milk concentrations of codeine and morphine are equal to or somewhat greater than maternal plasma concentrations [26]. Meperidine use in breast-feeding mothers via patient-controlled analgesia (PCA) resulted in significantly greater neurobehavioral depression of the breast-feeding newborn than equianalgesic doses of morphine [27]. After absorption from the infant's gastrointestinal tract, opioids contained in ingested breast milk undergo significant first-pass metabolism. Morphine undergoes extensive glucuronidation to inactive metabolites. Meperidine undergoes N-demethylation to the active metabolite normeperidine. Normeperidine's half-life is markedly prolonged in the newborn [28] such that regular breast feeding leads to the accumulation of normeperidine and the resultant risks of neurobehavioral depression and seizures. The American Academy of Pediatrics considers use of many opioid analgesics, including codeine, fentanyl, methadone, morphine, and propoxyphene, to be compatible with breast feeding [3]. Postoperative analgesia for most pregnant women undergoing nonobstetric surgery can be readily provided by using opioid analgesics (Table 3). Fentanyl, morphine, and hydromorphone are all safe and effective alternatives when a potent opioid is needed for parenteral administration. There is a range of safe and effective oral analgesics: for mild pain, acetaminophen alone or in combination with hydrocodone is a good alternative; for moderate pain, oxycodone alone or in combination with acetaminophen is effective; more severe pain may require morphine or hydromorphone, both of which are available for oral administration.Table 3: Oral Analgesics for Treating Pain During PregnancyOpioid analgesics can also be administered into the intrathecal or epidural compartments to provide postoperative analgesia. Such neuraxial administration of hydrophilic drugs (such as morphine) greatly reduces total postoperative opioid requirements while providing excellent analgesia [29]. Spinal or epidural delivery of opioids can be used to minimize maternal plasma concentrations of opioids, thereby reducing placental transfer to the fetus or exposure of the breast-feeding infant. Local Anesthetics Few studies have focused on the potential teratogenicity of local anesthetics. Lidocaine and bupivacaine do not seem to pose significant developmental risk to the fetus. In the Collaborative Perinatal Project [5], only mepivacaine had any suggestion of teratogenicity; however, the number of patient exposures was inadequate to draw conclusions. Animal studies have found that continuous exposure to lidocaine throughout pregnancy does not cause congenital anomalies, but it may decrease neonatal birth weight [30]. Neither lidocaine nor bupivacaine appear in measurable quantities in the breast milk after epidural local anesthetic administration during labor [4]. Intravenous infusion of large doses (2-4 mg/min) of lidocaine for suppression of cardiac arrhythmias led to minimal levels in breast milk [31]. Based on these observations, continuous epidural infusion of dilute local anesthetic solutions for postoperative analgesia should result in only small quantities of the drug actually reaching the nursing infant. The American Academy of Pediatrics considers local anesthetics to be safe for use in the nursing mother [3]. Mexilitene is a newer, orally active antiarrhythmic drug with structural and pharmacologic properties similar to lidocaine and has shown promise in the treatment of neuropathic pain. Mexilitene is lipidsoluble and freely crosses the placenta. There are no controlled studies of mixeletene use during pregnancy in humans. Studies in rats, mice, and rabbits using doses up to 4 times the maximal daily dose in humans have demonstrated an increased risk of fetal resorption, but not teratogenicity [32]. Mexilitene seems to be concentrated in breast milk; however, based on expected breast milk concentrations and average daily intake of breast milk, the infant would receive only a small fraction of the usual pediatric maintenance dose of mexilitene [33]. Mexilitine is rated Risk Category C by the FDA and its use should be undertaken cautiously during pregnancy. The American Academy of Pediatrics considers mexilitene use to be compatible with breast feeding [3]. Steroids Most corticosteroids cross the placenta, although prednisone and prednisolone are inactivated by the placenta [1]. Fetal serum concentrations of prednisone are less than 10% of maternal levels. Among 145 patients exposed to corticosteroids during their first trimester of pregnancy, no increase in infant malformations was seen [5]. The use of corticosteroids during a limited trial of epidural steroid therapy in the pregnant patient probably poses minimal fetal risk (see further discussion later in this review). Less than 1% of a maternal prednisone dose appears in the nursing infant over the next 3 days [34]. This amount of steroid exposure is unlikely to have an impact on infant endogenous cortisol secretion [34]. Benzodiazepines Benzodiazepines are among the most frequently prescribed of all drugs and are often used as anxiolytic agents, to treat insomnia, and as skeletal muscle relaxants in patients with chronic pain [35]. First-trimester exposure to benzodiazepines may be associated with an increased risk of congenital malformations. Diazepam may be associated with cleft lip/palate, as well as congenital inguinal hernia [36]. However, epidemiologic evidence has not confirmed the association of diazepam with cleft abnormalities; the incidence of cleft lip and palate remained stable after the introduction and widespread use of diazepam [36]. Epidemiological studies have confirmed the association of diazepam use during pregnancy and congenital inguinal hernia [36]. Benzodiazepine use immediately before delivery also risks fetal hypothermia, hyperbilirubinemia, and respiratory depression [37]. Two other bezodiazepines have been evaluated for teratogenicity. Chlordiazepoxide has been reported to produce a fourfold increase in congenital anomolies, including spastic diplegia, duodenal atresia, and congenital heart disease [38]. However, a study of more than 200,000 Michigan Medicaid recipients did not support these earlier findings [39]. Instead, this study found a high coprevalence of alcohol and ilicit drug use in patients receiving benzodiazepines. Benzodiazepine use alone did not appear to be a risk factor for congenital anomalies. Oxazepam use during pregnancy has also been associated with congenital anomalies, including a syndrome of dysmorphic facial features and central nervous system defects [40]. Aside from the risks of teratogenesis, neonates exposed to benzodiazepines in utero may experience withdrawal symptoms immediately after birth [41]. In the breast-feeding mother, diazepam and its metabolite desmethyldiazepam can be detected in infant serum for up to 10 days after a single maternal dose. This is due to the slower metabolism in neonates compared with adults [42]. Clinically, infants who are nursing from mothers receiving diazepam may show sedation and poor feeding [42]. It seems most prudent to avoid any use of benzodiazepines during organogenesis, near the time of delivery, and during lactation. Antidepressants Antidepressants are often used for the management of migraine headaches, as well as for analgesic and antide-pressant purposes in chronic pain states. Amitriptyline, nortriptyline, and imipramine are all rated Risk Category D by the FDA. The selective serotonin reuptake inhibitors fluoxetine and paroxetine are rated FDA Risk Category B. Desipramine and all other conventional antidepressant medications are Category C [43]. Amitriptyline is teratogenic in hamsters (encephaloceles) and rats (skeletal defects) [7]. Imipramine has been associated with several congenital defects in rabbits, but not in rats, mice, or monkeys [44]. Although there are case reports of human neonatal limb deformities after maternal amitriptyline and imipramine use, large human population studies have not revealed an association with any congenital malformation, with the possible exception of cardiovascular defects after maternal imipramine use [7]. There are no reports linking maternal desipramine use with congenital defects. Withdrawal syndromes have been reported in neonates born to mothers using nortriptyline, imipramine, and desipramine, with symptoms including irritability, colic, tachypnea, and urinary retention [7]. Amitriptyline, nortriptyline, and desipramine are all excreted into human milk. Pharmacokinetic modeling suggests that infants are exposed to approximately 1% of the maternal dose [45]. In a critical review of the literature regarding use of antidepressants during breast feeding, Wisner et al. [45] concluded that amitriptyline, nortriptyline, desipramine, clomipramine, and sertraline were not found in quantifiable amounts in nurslings, and that no adverse effects had been reported. The authors recommend use of these drugs as the antidepressants of choice for breast-feeding women. Fluoxetine is also excreted into human milk and has a milk to plasma ratio of approximately 0.3. No controlled studies are available to guide fluoxetine therapy during lactation [7]; however colic and high infant serum levels have been reported [46]. Maternal doxepin use has also been associated with increased plasma levels of the metabolite N-desmethyldoxepin and respiratory depression in a nursing infant [47]. The American Academy of Pediatrics considers antidepressants to have unknown risk during lactation [3]. Anticonvulsants Most data regarding the risk of major malformation in infants born to women taking anticonvulsants are derived from the treatment of epilepsy. Among one group of epileptic women receiving phenytoin, carbamazepine, or valproic acid, the risk of a congenital defect in their offspring was approximately 5% [48], or twice that of the general population. Neural tube defects predominate in the offspring of women taking carbamazepine and valproic acid [49] and can be detected during routine prenatal screening (elevated alpha-fetoprotein level). Inadequate maternal folate absorption associated with anticonvulsant use during pregnancy may contribute to neural tube defects [49]. The fetal hydantoin syndrome has variable dysmorphic features, including microcephaly, mental deficiency, and craniofacial abnormalities [49]. The appearance of this syndrome may be predicted by either fetal genetic screening or by measuring amniocyte levels of the enzyme responsible for phenytoin metabolism [50]. Although anticonvulsants have a teratogenic risk, epilepsy itself may be partially responsible for fetal malformations [49]. Perhaps pregnant women taking anticonvulsants for chronic pain may have a lower risk of fetal malformations than those taking the same medications for seizure control. Patients contemplating childbearing who are receiving anticonvulsants should have their pharmacologic therapy critically evaluated. Those taking anticonvulsants for neuropathic pain should strongly consider their discontinuation during pregnancy, particularly during the first trimester. Consultation with a perinatologist is recommended if continued use of anticonvulsants during pregnancy is being considered. Frequent monitoring of serum anticonvulsant levels and folate supplementation should be initiated, and maternal alpha-fetoprotein screening may be considered to detect fetal neural tube defects. Gabapentin is a new anticonvulsant that is being used to treat neuropathic pain syndromes. There is very little information about the safety of gabapentin in pregnant women or fetuses. In the prescribing information, the manufacturer (Park Davis, Morris Plains, NJ, 1996) reports a series of nine women who received gabapentin during their pregnancy. Four women elected pregnancy termination and four had normal outcomes; one neonate had pyloric stenosis and an inguinal hernia. The use of anticonvulsants during lactation does not seem to be harmful to infants. Phenytoin, carbamazepine, and valproic acid appear in small amounts in breast milk, but no adverse effects have been noted [7]. There are no data on gabapentin use during lactation. Ergot Alkaloids Ergotamine can have significant therapeutic efficacy in the episodic treatment of migraine headaches. However, even small doses of ergotamines are associated with significant teratogenic risk, whereas larger doses have caused uterine contractions and abortions [43]. During lactation, ergot alkaloids are associated with neonatal convulsions and severe gastrointestinal disturbances [7]. Occasionally, methergonovine is systemically administered to treat uterine atony and maternal hemorrhage immediately after delivery. This brief exposure does not contraindicate breast feeding [51]. Caffeine Caffeine is often used in combination analgesics for the management of vascular headaches. Early studies of caffeine ingestion during pregnancy suggested an increased risk of intrauterine growth retardation, fetal demise, and premature labor. However, these early studies did not control for concomitant alcohol and tobacco use. Subsequent work, which controlled for these confounding factors, found no added risks with moderate caffeine ingestion, although ingestion of more than 300 mg/d was associated with decreased birth weight [52]. Many over-the-counter analgesic formulations contain caffeine (typically in amounts between 30 and 65 mg/dose), and use of these preparations must be considered when determining total caffeine exposure. Moderate ingestion of caffeine during lactation (up to two cups of coffee per day) does not seem to affect the infant. Breast milk usually contains less than 1% of the maternal dose of caffeine, with peak breast milk levels appearing 1 h after maternal ingestion. Excessive caffeine use may cause increased wakefulness and irritability in the infant [53]. Sumatriptan Sumatriptan is a selective serotonin agonist that has achieved wi" @default.
W1992472018 created "2016-06-24" @default.
W1992472018 creator A5030842093 @default.
W1992472018 creator A5042694224 @default.
W1992472018 creator A5071420956 @default.
W1992472018 date "1997-11-01" @default.
W1992472018 modified "2023-10-16" @default.
W1992472018 title "Management of Nonobstetric Pain During Pregnancy and Lactation" @default.
W1992472018 cites W1491528029 @default.
W1992472018 cites W1495974851 @default.
W1992472018 cites W162212974 @default.
W1992472018 cites W1887278174 @default.
W1992472018 cites W195878916 @default.
W1992472018 cites W1968920621 @default.
W1992472018 cites W1974643700 @default.
W1992472018 cites W1975373110 @default.
W1992472018 cites W1976000528 @default.
W1992472018 cites W1976040939 @default.
W1992472018 cites W1978725048 @default.
W1992472018 cites W1980647471 @default.
W1992472018 cites W1981083312 @default.
W1992472018 cites W1986367140 @default.
W1992472018 cites W1988562956 @default.
W1992472018 cites W1991242958 @default.
W1992472018 cites W1992839054 @default.
W1992472018 cites W2004798495 @default.
W1992472018 cites W2006802729 @default.
W1992472018 cites W2008105038 @default.
W1992472018 cites W2010688491 @default.
W1992472018 cites W2016028575 @default.
W1992472018 cites W2018311487 @default.
W1992472018 cites W2019363841 @default.
W1992472018 cites W2019928437 @default.
W1992472018 cites W2029965341 @default.
W1992472018 cites W2032424222 @default.
W1992472018 cites W2032907196 @default.
W1992472018 cites W2034091997 @default.
W1992472018 cites W2037795842 @default.
W1992472018 cites W2042000315 @default.
W1992472018 cites W2046427979 @default.
W1992472018 cites W2055674491 @default.
W1992472018 cites W2055895292 @default.
W1992472018 cites W2059891265 @default.
W1992472018 cites W2060433003 @default.
W1992472018 cites W2063340501 @default.
W1992472018 cites W2066542857 @default.
W1992472018 cites W2067230440 @default.
W1992472018 cites W2068411596 @default.
W1992472018 cites W2074629949 @default.
W1992472018 cites W2076774536 @default.
W1992472018 cites W2078185113 @default.
W1992472018 cites W2082150308 @default.
W1992472018 cites W2083384594 @default.
W1992472018 cites W2084050107 @default.
W1992472018 cites W2085641258 @default.
W1992472018 cites W2090153899 @default.
W1992472018 cites W2099675955 @default.
W1992472018 cites W2112210800 @default.
W1992472018 cites W2132063054 @default.
W1992472018 cites W2139940319 @default.
W1992472018 cites W2145082504 @default.
W1992472018 cites W2152173537 @default.
W1992472018 cites W2158970884 @default.
W1992472018 cites W2172402185 @default.
W1992472018 cites W2234019152 @default.
W1992472018 cites W2261524867 @default.
W1992472018 cites W2304448851 @default.
W1992472018 cites W2312198574 @default.
W1992472018 cites W2317472642 @default.
W1992472018 cites W2320643189 @default.
W1992472018 cites W252905768 @default.
W1992472018 cites W2734697553 @default.
W1992472018 cites W3047826991 @default.
W1992472018 cites W3747616 @default.
W1992472018 cites W4241981892 @default.
W1992472018 cites W4248449558 @default.
W1992472018 cites W4255097306 @default.
W1992472018 cites W55845613 @default.
W1992472018 cites W71201454 @default.
W1992472018 cites W8762804 @default.
W1992472018 doi "https://doi.org/10.1097/00000539-199711000-00021" @default.
W1992472018 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9356103" @default.
W1992472018 hasPublicationYear "1997" @default.
W1992472018 type Work @default.
W1992472018 sameAs 1992472018 @default.
W1992472018 citedByCount "38" @default.
W1992472018 countsByYear W19924720182012 @default.
W1992472018 countsByYear W19924720182013 @default.
W1992472018 countsByYear W19924720182014 @default.
W1992472018 countsByYear W19924720182015 @default.
W1992472018 countsByYear W19924720182016 @default.
W1992472018 countsByYear W19924720182017 @default.
W1992472018 countsByYear W19924720182018 @default.
W1992472018 countsByYear W19924720182019 @default.
W1992472018 countsByYear W19924720182022 @default.
W1992472018 countsByYear W19924720182023 @default.
W1992472018 crossrefType "journal-article" @default.
W1992472018 hasAuthorship W1992472018A5030842093 @default.