Morgan, Maria A. PhD1; Goldenberg, Robert L. MD2; Schulkin, Jay PhD1
The national preterm delivery rate reached 12.7% in 2005, or one in eight liveborn infants.1 This represents a 33% increase from the 1981 rate of 9.4%. The majority of preterm births, defined as a live birth before 37 weeks of gestation, are the result of spontaneous preterm labor and preterm premature rupture of membranes (PROM).2,3 Several factors have been considered to be predictors of spontaneous preterm birth, such as a history of preterm birth and the presence of bacterial vaginosis.4,5 Several measures can help identify those at increased risk of preterm birth, including vaginal ultrasonography to evaluate cervical length, and vaginal fetal fibronectin screening.6
Efforts to reduce the risk of preterm birth in the population, and to identify and treat those with an increased risk, have not generally been effective in reducing rates of spontaneous preterm birth.2 Preventing preterm labor has proven to be largely unachievable with current techniques. Given the lack of effective methods for preventing preterm birth, access to a newborn intensive care unit (neonatal intensive care unit [NICU]) is crucial for improving neonatal outcome; improved survival of preterm infants in the past 30 years is due largely to such access.2,3 Tocolytic medications can prolong pregnancy for up to a few days but are used primarily to allow for fetal lung maturity through administration of glucocorticoids; the delay itself is not sufficient for improving neonatal outcome.7,8 Brief prolongations can also allow for transport of the patient to a facility with a NICU.
The purpose of this study was to estimate the current practices of obstetrician–gynecologists regarding screening for various preterm birth risk factors, such as infections and other medical indications (eg, previous preterm birth, hypertension), maternal behaviors (eg, smoking), and prior medical interventions (eg, cone biopsy). We also examined the interventions they use when tests and other factors indicate a patient may be at elevated risk for preterm birth, or preterm PROM is already present.
MATERIALS AND METHODS
Questionnaires were mailed in November 2005 to 1,193 Fellows and Junior Fellows in Practice of the American College of Obstetricians and Gynecologists (ACOG). The study was approved by the institutional review board at Drexel University College of Medicine. Of the participants, 593 were members of the Collaborative Ambulatory Research Network (CARN). Members of the CARN are practicing obstetrician–gynecologists who have volunteered to participate in survey studies on a regular basis. The Collaborative Ambulatory Research Network was established to facilitate assessment of clinical practice patterns. The remaining 600 participants consisted of a computer-generated random sample of ACOG Fellows who had not received a survey from ACOG during the previous two years (non-CARN). All nonrespondents received a second mailing of the questionnaire 5 weeks after the first mailing. A final mailing was sent approximately 5 weeks later. Questionnaires returned by April 2006 were included in the study. This protocol has typically resulted in a total sample size of more than 450, which is sufficient to detect differences between groups of less than 0.5 standard deviation with power of 80% and significance at the 0.05 level.9
Survey responses were anonymous and recorded demographic details of physicians and assessed screening and treatment practices regarding preterm birth. The questionnaire contained 50 questions, some multipart, including 12 demographic, 25 practice, 10 knowledge, and three education questions. Question formats included multiple choice, yes/no, a Likert-type response scale, and indicating on a number line ranging from 20 weeks to 36 weeks the gestational ages at which they would perform a particular practice (see, eg, preterm PROM in the Results section). The questions assessing knowledge of preterm birth risk factors and gestational age of viability are addressed elsewhere.10,11
The data were analyzed using a personal computer–based software package (SPSS 15.0, SPSS Inc., Chicago, IL). Descriptive statistics were computed for the measures used in the analyses, which are reported as frequencies and mean±standard error of the mean. Confidence intervals (95%) are provided for various proportions. Student t tests were used to compare group means of continuous variables. Differences on categorical measures were assessed using χ2. Group differences on ordinal measures were assessed using the Mann-Whitney U test. All analyses were tested for significance using an alpha of 0.05.
A total of 715 questionnaires were returned. Data from 17 respondents were invalid (physician retired, returned to sender), resulting in a valid response rate of 59% (698 of 1,176), 420 responses from the CARN members (71% response rate) and 278 from non-CARN members (47% response rate). There were responding physicians from every state of the United States except South Dakota, as well as from the District of Columbia, Puerto Rico, Canada, and overseas military installations. Respondents’ mean age (46.06±0.40 years) closely matched that of the larger population to whom the survey was sent (age 45.56±0.31 years). Females had a higher response rate than males (62% compared with 57%; P=.048). One hundred twenty-one (17%) respondents indicated that they do not practice obstetrics. Because we were interested in practices related to preterm care and delivery, we restricted the remaining analyses to the 577 physicians who see obstetric patients (see Table 1 for physician characteristics). Collaborative Ambulatory Research Network members had been in practice significantly longer than non-CARN members (P<.001). Collaborative Ambulatory Research Network members were more likely to say that they routinely use magnesium sulfate as a tocolytic treatment (97% compared with 91%; P<.01) and to say they would manage a pregnancy seeming to be at very high risk for preterm birth without input from a maternal–fetal medicine specialist (28% compared with 16%; P<.01); data were collapsed across membership group on the remaining variables.
Physicians were asked which of various maternal characteristics, risk factors, and infections potentially related to preterm birth they routinely screen for during pregnancy as risk factors for preterm birth (Table 2, part A). Physicians were most likely to screen routinely for previous preterm birth (98%; 95% confidence interval [CI]±1.14), cone biopsy (95%; 95% CI±1.78), and smoking (92%; 95% CI±2.21). Asked which of various infections they routinely screen for during pregnancy as an attempt to prevent preterm birth, both in asymptomatic women (Table 2, part B) and women with a history of preterm birth (Table 2, part C), respondents were most likely to indicate screening for urinary tract infection. One third (33%; 95% CI±3.83) of respondents did not indicate screening for bacterial vaginosis in women with a history of preterm birth. More than half of respondents indicated screening for group B streptococci (GBS) in an attempt to prevent preterm birth.
Almost all (99.5%) physicians would treat bacterial vaginosis in a pregnant woman with a history of preterm birth who is found to have bacterial vaginosis and would use antibiotics to treat it (99%); presented with the treatment options of metronidazole and clindamycin, the majority would use metronidazole administered orally (64%; 95% CI±3.95), followed by metronidazole vaginally (20%), clindamycin vaginally (8%), and clindamycin orally (2%). Similarly, almost all (98%; 95% CI±1.15) physicians would treat trichomoniasis in a pregnant woman and would use antibiotics to treat it (99.8%); asked if they would use metronidazole, the majority (91%; 95% CI±2.37) would use metronidazole orally, and the remainder would use metronidazole vaginally (8%).
The majority of respondents (54%; 95% CI±4.09) infrequently or never use prenatal progestational agents in an attempt to prevent a preterm birth in women with a history of preterm birth, 22% use them sometimes, and 21% said they use them frequently or always; an additional 13 respondents indicated that they are investigating the use of progestational agents or anticipate using them soon. If a cervical ultrasonogram at 20 weeks of gestation showed a cervical length of 20 mm, 40% (95% CI±4.11) said they would place a cervical cerclage. To evaluate the risk of preterm birth in a twin gestation, respondents most frequently selected repetitive cervical ultrasound measures (69%), followed by repetitive cervical digital exams (48%), vaginal fetal fibronectin screening (36%), home uterine activity monitoring (6%), or none of these choices (16%). Almost one third (31%; 95% CI±3.79) said they routinely recommend bed rest in twin pregnancies.
Almost all (99.5%) respondents routinely observe and do not induce patients with preterm PROM without chorioamnionitis for at least some gestational ages. Twenty weeks gestational age was selected most frequently (47%) as the earliest age and 33 weeks (39%) as the latest gestational age that they would observe and not induce labor. Induction of labor may be offered before 24 weeks so that the mother is protected from infection, and the fetus is delivered previably and not at a time of extremely high risk of major long-term morbidity, whereas induction of labor around 34 weeks or more is often recommended because the risks to the fetus of ascending infection outweigh the risk of preterm birth. Almost all (95%) respondents routinely use antibiotics to prolong the latency period in patients with preterm PROM for at least some gestational ages (earliest: 20 weeks 36%, and 24 weeks 33%; latest: 34 weeks, 30%). Far fewer (60%; 95% CI±4.03) respondents routinely use tocolytic agents in patients with preterm PROM for at least some gestational ages (earliest: 24 weeks 45%; latest: 33 weeks 30%). Most (98%) routinely use tocolytics for women with intact membranes in preterm labor (earliest: 24 weeks 36%; latest: 34 weeks 41%); the tocolytic treatments they routinely use are magnesium sulfate (94%), β-adrenergic agonists (72%), calcium channel blockers (63%), and prostaglandin synthetase inhibitors (51%), as well as hydration (79%) and sedation (32%).
Asked about their practices regarding the use of corticosteroids, almost all (99.5%) physicians said they routinely use them for anticipated preterm births for at least some gestational ages (earliest: 24 weeks 58%; latest: 33 weeks 40%, and 34 weeks 38%). The vast majority of respondents also routinely use corticosteroids in patients with anticipated preterm births who have specific medical conditions: preterm PROM (88%), diabetes (85%), preeclampsia or severe hypertension (88%), and multiple gestation (89%). The corticosteroid regimen most commonly used (94%) was betamethasone, 12 mg every 24 hours for two doses. At 24–26 weeks of gestation with nonlaboring twins, few (17%) routinely use prophylactic corticosteroids. Only 4% of respondents routinely repeat the administration of corticosteroids if the patient has not delivered in one week.
Forty-six respondents self-identified as maternal–fetal medicine specialists. They differed from non-maternal–fetal medicine specialists in some of their screening practices, primarily in that fewer indicated screening for various infections (Table 2). Regarding routine use of tocolytics, maternal–fetal medicine specialists were more likely than non-maternal–fetal medicine specialists to use prostaglandin synthetase inhibitors (72% compared with 50%; P<.01), and less likely to use β-adrenergic agonists (46% compared with 74%; P<.001); they were also less likely to use hydration (63% compared with 80%; P<.01) and sedation (19% compared with 33%; P<.05) to inhibit preterm labor. Finally, maternal–fetal medicine specialists indicated using prenatal progestational agents more frequently to prevent a subsequent preterm birth (P<.05).
Physicians not self-identifying as maternal–fetal medicine specialists were asked the extent to which they would seek maternal–fetal medicine specialist input in two situations. If during prenatal care, a patient seemed to be at exceptionally high risk for preterm birth, 43% said they would consult a maternal–fetal medicine specialist, 31% would comanage the pregnancy with a maternal–fetal medicine specialist, 23% would manage the pregnancy without maternal–fetal medicine specialist input, and 3% would refer the patient to a maternal–fetal medicine specialist for complete care. If a patient experienced spontaneous onset of labor or rupture of fetal membranes at less than 32 weeks of gestation, 27% would consult a maternal–fetal medicine specialist, 27% would refer for complete care, 24% would comanage, and 22% would manage without input.
Almost one quarter (24%) of physicians said there was not a newborn intensive care unit at a hospital where they delivered. These physicians were more likely to get some form of input from a maternal–fetal medicine specialist if a patient were to experience spontaneous onset of labor or rupture of membranes at fewer than 32 weeks of gestation (96% compared with 72%; P<.001), primarily by referring the patient to a maternal–fetal medicine specialist for complete care (79% compared with 9%; P<.001). However, they were not more likely than those with a NICU to get input from a maternal–fetal medicine specialist if a pregnant patient seemed to be at exceptionally high risk for preterm birth (79% compared with 76%; P=.443).
Physicians differed on a number of variables based on the number of years they had been in practice. Years in practice was divided into two groups, those in practice less than or equal to the median of 11 years and those in practice more than 11 years. Those in practice longer were more likely to screen routinely for several things as risk factors for preterm birth, including smoking, alcohol use, and previous first- and second-trimester abortion (Table 2). They were more likely to recommend bed rest routinely in twin pregnancies (46% compared with 18%; P<.001). Those in practice longer were less likely to use corticosteroids routinely in patients with preterm PROM (95% compared with 81%; P<.001), in diabetic patients with anticipated preterm births (88% compared with 81%; P<.05), in patients with preeclampsia or severe hypertension and anticipated preterm births (94% compared with 81%; P<.001), and in patients with multiple gestation pregnancies with anticipated preterm births (93% compared with 86%; P=.013); however, they were more likely to use prophylactic corticosteroids at 24–26 weeks of gestation with twins (11% compared with 23%; P<.001).
This study evaluated obstetrician–gynecologists’ practices regarding screening for various potential preterm birth risk factors and interventions they use when indicators suggest that a patient may be at elevated risk for preterm birth. We found that obstetrician–gynecologists are most frequently screening for preterm birth risk factors with a known increased risk of preterm birth, including previous preterm birth (98%), cone biopsy (95%), and loop electrosurgical excision procedure (91%).3,12,13 One fifth (21%) of respondents did not indicate screening for second-trimester abortion, which, including multiple spontaneous abortion, has been identified as a risk factor for preterm birth.2,14
Obstetrician–gynecologists may be overscreening for certain infections in an attempt to prevent preterm birth, whereas underscreening for other infections. For example, vaginal or rectal GBS is not generally associated with increased risk of preterm birth, and treatment for GBS is likely ineffective toward preventing preterm birth,15 but more than half of respondents indicated screening for it for this indication. Although there may be some association between GBS and preterm birth when the degree of colonization is very high, as indicated by a positive urine culture,16 more recent evidence suggests that even a positive GBS urine culture may not be associated with preterm birth.17 Obstetrician–gynecologists may be confusing this issue with screening for GBS late in pregnancy, or administering intrapartum antibiotic prophylaxis to women with preterm labor, to prevent GBS infection in the newborn.18 Over one quarter of respondents screen for periodontal disease; although there is a positive association between the risk for preterm birth and the severity of periodontal disease,19 there is no clear evidence that its treatment reduces preterm birth.20 On the other hand, screening for and treating asymptomatic urinary tract infection is one of the few interventions that reliable evidence suggests is effective in preventing preterm birth,21,22 yet 21% or more of obstetrician–gynecologists did not indicate screening for this condition.
Respondents were more likely to screen for bacterial vaginosis in women with a history of preterm birth (67%) compared with women without a prior preterm birth (45%), consistent with a 1997 study23 indicating that treatment of bacterial vaginosis was effective in reducing preterm birth in women with a history of preterm birth but not those without a prior preterm birth. A recent review24 concluded that the treatment of bacterial vaginosis only before 20 weeks of gestation may reduce the risk of preterm birth. All but three respondents would treat bacterial vaginosis in women with a history of preterm birth, most typically using metronidazole (84%); another 10% would treat with clindamycin. Some studies support the effectiveness of clindomycin25,26 and metronidazole23 in reducing preterm birth, whereas others indicate an adverse effect of metronidazole on birth outcome.26,27 The lack of consistency in the literature may be reflected in obstetrician–gynecologists’ inconsistency in screening and treatment practices.
Almost one third (31%) of respondents said they routinely recommend bed rest in twin pregnancies, and physicians in practice longer were more likely to use bed rest. A recent review found no evidence in support of the use of bed rest to prevent preterm birth in multiple pregnancies, and bed rest in uncomplicated twin pregnancies may even increase the rate of very preterm delivery.28 On the other hand, although the use of progesterone supplementation during pregnancy may be effective in reducing the risk of preterm birth in women with a history of preterm birth,29 we found that the majority (54%) of responding physicians infrequently or never use prenatal progestational agents for this purpose.
At least one third of preterm births are complicated by preterm PROM, which typically signals that delivery will occur within a week if rupture occurs before 34 weeks of gestation.30,31 When preterm PROM occurs remote from term, antibiotics, tocolytics, and corticosteroids have all been used in an effort to improve pregnancy outcome, with the use of antibiotics and corticosteroids now a part of routine practice. In agreement with findings that broad-spectrum antibiotics may increase the latency to delivery and improve neonatal outcome,32,33 almost all (95%) respondents reported using antibiotics to prolong latency. There is a lack of consensus on the routine use of tocolytics with preterm PROM, and it is not recommended for the prolongation of pregnancy alone.34,35 We found that 60% of respondents routinely use tocolytic agents in women with preterm PROM. Far more (98%) routinely use tocolytics for women with intact membranes in preterm labor, with magnesium sulfate the most commonly used (94%), followed by β-adrenergic agonists (72%). This high usage rate is interesting in view of the probable lack of efficacy of tocolytics in general and of magnesium sulfate in particular,2,36 as well as the potential harm of β-adrenergics to mothers.37 However, tocolytics are commonly used in preterm labor to prolong the pregnancy long enough for the administration of corticosteroids to effectively enhance lung development.2
Nearly 100% of respondents routinely use corticosteroids for anticipated preterm births, largely in accord with the findings of the NIH Consensus Panel.38 Although repeated dosing was a common practice as recently as 2000,39,40 very few (4%) of our respondents said they routinely repeat the doses if delivery has not occurred in 1 week. Current studies on repeated dosing, including an update of the Consensus Panel report, suggest that there is still insufficient evidence to support routine repeat dosing.39 The great majority (85–89%) of respondents indicated routinely using corticosteroids in women with preterm PROM, diabetes, preeclampsia, and multiple gestations, also in correspondence with the findings of the Consensus Panel report.38 It is likely that further improvements in newborn outcomes would be achieved if the remainder of the obstetric practitioners also adopted the routine use of corticosteroids for women with these conditions.
Our study has limitations that should be acknowledged. The response rate was 59%, indicating a potential nonresponse bias. However, this is at the high end of the 35% to 60% rate typical of our survey studies, and responses were derived from diverse geographic locations and practice types. Another limitation concerns those infections screened for “as an attempt to prevent preterm birth”; despite the instruction to respond based on preterm birth prevention, it may be that some respondents indicated screening because they do so as required by law and/or as a routine part of prenatal care, which could have resulted in an overestimation of screening specific to preterm birth.
The findings from this study indicate that more than three fourths of obstetrician–gynecologists would seek some form of input from a maternal–fetal medicine specialist if they were managing a pregnant patient at very high risk for preterm birth, with maternal–fetal medicine specialist input ranging from a consult (43%) to referral for complete obstetric care (3%). In the case of an impending preterm delivery (preterm PROM or labor at fewer than 32 weeks of gestation), a greater proportion of physicians (27%) would refer the patient to a maternal–fetal medicine specialist for complete obstetric care. Improved survival of preterm infants in the past 30 years is due largely to access to a NICU.3 Almost one quarter (24%) of responding physicians did not have access to a NICU, and they were more likely to refer a patient with an impending very preterm delivery to a maternal–fetal medicine specialist for complete obstetric care than were those with NICU access. These results suggest that, when preterm delivery is imminent, physicians often and appropriately seek the most specialized care possible for their patients.
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