The maternal-fetal medicine units cesarean registry: chorioamnionitis at term and its duration—relationship to outcomes

American Journal of Obstetrics and Gynecology (2004) 191, 211e6

www.elsevier.com/locate/ajog

GENERAL OBSTETRICS AND GYNECOLOGY: OBSTETRICS

The Maternal-Fetal Medicine Units cesarean registry: Chorioamnionitis at term and its durationdrelationship to outcomes Dwight J. Rouse, MD, MSPH,a,* Mark Landon, MD,b Kenneth J. Leveno, MD,c Sharon Leindecker, MS,d Michael W. Varner, MD,e Steve N. Caritis, MD,f Mary Jo O’Sullivan, MD,g Ronald J. Wapner, MD,h Paul J. Meis, MD,i Menachem Miodovnik, MD,j Yoram Sorokin, MD,k Atef H. Moawad, MD,l William Mabie, MD,m Deborah Conway, MD,n Steven G. Gabbe, MD,o Catherine Y. Spong, MD,p and National Institute of Child Health and Human Development, Maternal-Fetal Medicine Units Network Department of Obstetrics and Gynecology, Center for Research in Women’s Health, University of Alabama at Birmingham, Birmingham, Ala,a Department of Obstetrics and Gynecology, Ohio State University, Columbus, Ohio,b University of Texas Southwestern Medical Center, Dallas, Tex,c The Biostatistics Center, George Washington University, Rockville, Md,d Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah,e University of Pittsburgh/Magee-Women’s Hospital, Pittsburgh, Pa,f Department of Obstetrics and Gynecology, University of Miami, Miami, Fla,g Department of Obstetrics and Gynecology, Drexel University, Philadelphia, Pa,h Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC,i Department of Obstetrics and Gynecology, University of Cincinnati, Cincinnati, Ohio,j Department of Obstetrics and Gynecology, Wayne State University, Detroit, Mich,k Department of Obstetrics and Gynecology, University of Chicago, Chicago, Ill,l Department of Obstetrics and Gynecology, University of Tennessee, Memphis, Tenn,m Department of Obstetrics and Gynecology, University of Texas at San Antonio, Tex,n Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, Tenn,o and The National Institute of Child Health and Human Development, Bethesda, Md p Received for publication November 21, 2003; revised March 1, 2004; accepted March 1, 2004

–––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– KEY WORDS Chorioamnionitis Complications Duration

Objective: The purpose of this study was to evaluate the relationship between chorioamnionitis and its duration to adverse maternal, fetal, and neonatal outcomes. Study design: This was a 13-university center, prospective observational study. All women at term carrying a singleton gestation who underwent primary cesarean from January 1, 1999 to Decem-

Supported by grants from the National Institute of Child Health and Human Development: HD27869, HD27915, HD34116, HD36801, HD34208, HD21410, HD34122, HD34136, HD27860, HD27905, HD27917, HD27861, HD21414, HD34210. Presented at the annual meeting of the Society for Maternal-Fetal Medicine, San Francisco, California, February 4-7, 2003. * Reprint requests: Dwight J. Rouse, MD, MSPH, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, 619 19th St South, OHB 457, Birmingham, AL 35249-7333. E-mail: [email protected]

0002-9378/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.03.003

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Rouse et al ber 31, 2000 were eligible. Data abstraction was systematic and performed by trained research nurses. Selected adverse outcomes were compared between pregnancies with, and without, clinically diagnosed chorioamnionitis using relative risks (RRs) and 95% CIs. The duration of chorioamnionitis was stratified into 5 intervals (%3 h,O3-6 h,O6-9 h,O9-12 h, andO12 h), and respective outcomes compared by Mantel-Haenszel test for trend. Additionally, regression analysis was used to compute odds ratios (ORs) and 95% CIs for chorioamnionitis duration length as a continuous explanatory variable. Results: 16,650 pregnancies were analyzed, 1965 (12%) with chorioamnionitis, which was associated with significantly increased risks of maternal blood transfusion, uterine atony, septic pelvic thrombophlebitis, and pelvic abscess (RR 2.3-3.7), as well as 5-minute Apgar %3, neonatal sepsis, and seizures (RR 2.1-2.8). By test of trend, only uterine atony (P ! .01), maternal blood transfusion (P = .03), maternal admission to intensive care unit (P = .02), and 5-minute Apgar %3 (P ! .01) were associated with duration of chorioamnionitis. By logistic analysis, only uterine atony (OR for each hour of chorioamnionitis 1.03, 95% CI 1.00-1.06), 5-minute Apgar %3 (OR 1.09, 95% CI 1.00-1.16), and neonatal mechanical ventilation within 24 hours of birth (OR 1.07, 95% CI 1.01-1.12) were significantly associated with chorioamnionitis duration. Conclusion: Chorioamnionitis was associated with increased rates of morbidity after cesarean at term. The duration of chorioamnionitis, however, was not related to most measures of adverse maternal or fetal-neonatal outcome. Ó 2004 Elsevier Inc. All rights reserved.

––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– Chorioamnionitis is a common infection which poses well-recognized maternal and neonatal risks.1,2 The management of chorioamnionitis consists of broadspectrum antibiotics and delivery. The available data2-4 suggest that neonatal and maternal complications are not related to the time interval between diagnosis of chorioamnionitis and delivery. These data are limited, however, by the overall small number of cases studied (fewer than 350), and the small number of women with diagnosis to delivery intervals of greater than 12 hours (at most 40). This paucity of data raises significant clinical questions. For example, in the common obstetric condition of chorioamnionitis, is there a point in labor beyond which the elevated neonatal risks of continued labor justify cesarean delivery, even though maternal cesarean morbidity is increased in the face of chorioamnionitis? Conversely, do women diagnosed with chorioamnionitis who ultimately undergo cesarean fare worse as the interval between diagnosis and delivery lengthens? To address these questions, the present investigation was undertaken.

Material and methods Subjects were identified as part of a 13-university center, observational study of cesarean delivery. Each center and the data-coordinating center had Institutional Review Board (IRB) approval for this study. All women who underwent primary cesarean delivery with a singleton gestation were identified on a daily basis by dedicated research personnel. Gestational age was assigned based on the best estimate of the local caregivers. Women not at term (!37 wk) were excluded. Maternal

data were abstracted from hospital records and logs onto separate forms for (1) previous pregnancy history, (2) baseline data including demographics, medical history, and current pregnancy history, (3) current pregnancy complications, (4) labor and delivery data, (5) intrapartum and postpartum complications, (6) rare maternal complications, (7) cesarean hysterectomy (if performed), and (8) readmission information through 6 weeks’ postpartum. Infant charts were abstracted until discharge or 120 days of life for (1) basic neonatal data, (2) additional information on any infant admitted to the neonatal intensive care unit, or who died, and (3) data on infants who satisfied criteria indicative of possible hypoxic ischemic encephalopathy. Data without any unique patient identifiers from each of the 13 centers were transmitted weekly by telecommunications link to the data-coordinating center, where they were edited for missing, out of range, and inconsistent values (intraform editing). On a weekly basis, edit reports were transmitted to each center for correction or clarification. Data were also compared across forms (interform editing) at regular intervals, and corrections and clarifications requested from the centers as appropriate. Maternal and neonatal diagnoses (including chorioamnionitis) were made according to the clinical standards of each participating center, with the following exceptions. Chorioamnionitis required an intrapartum temperature of at least 100(F5 and the administration of intrapartum antibiotics for the self-same indication. Deep venous thrombosis and pulmonary embolism required confirmatory imaging studies and treatment with intravenous heparin. Septic pelvic thrombophlebitis required the administration of heparin. Neonatal sepsis

213

Rouse et al Table I

Adverse maternal outcomes in relationship to chorioamnionitis

Outcome

Chorioamnionitis (n = 1965) %

No chorioamnionitis (n = 14,685*) %

Uterine atony Blood transfusion Pelvic abscess Septic pelvic thrombophlebitis Thromboembolic disease Wound complication Necrotizing fasciitis ICU admission Exploratory laparotomy Hysterectomy Death

14.2 4.5 0.3 0.6 0.1 1.5 0.1 0.6 0.3 0.4 0.0

5.7 2.0 0.1 0.2 0.1 1.1 0.0 0.5 0.2 0.3 0.1

RR (95% CI) 2.50 2.25 3.74 2.74 1.49 1.39 2.49 1.03 1.07 1.57 ÿ

(2.20-2.84) (1.78-2.83) (1.28-10.92) (1.38-5.46) (0.33-6.82) (0.95-2.05) (0.26-23.93) (0.55-1.93) (0.42-2.72) (0.74-3.37)

Wound complication is infection, seroma, or hematoma; thromboembolic disease is confirmed deep venous thrombosis or pulmonary embolism. * Outcomes not available for one woman.

required (1) a positive blood, cerebrospinal fluid, or urine culture obtained by catheterization or suprapubic aspiration, or (2) cardiovascular collapse or an unequivocal diagnosis of infection on chest radiograph in an infant who was believed to be clinically septic. If chorioamnionitis was diagnosed, the date and time of diagnosis was abstracted. The analysis was conducted in three stages. First, selected maternal and fetal-neonatal adverse outcomes (or markers thereof) were compared between pregnancies with, and without, chorioamnionitis using relative risks and 95% CIs. Next, in analyses confined to women with chorioamnionitis, the duration of chorioamnionitis was stratified into 5 intervals (%3 h,O3-6 h,O6-9 h,O9-12 h, andO12 h), and the outcomes compared across these intervals using the Mantel-Haenszel test for trend. Finally, the relationship between chorioamnionitis duration and adverse maternal and fetal-neonatal outcomes was assessed using logistic modeling. Outcomes were regressed against the duration of time elapsed between the diagnosis of chorioamnionitis and delivery, and odds ratios (ORs), 95% CIs, and, using the Wald chi-square test, P values calculated for chorioamnionitis duration length as a continuous explanatory variable. All reported P values are two-sided and a P ! .05 was considered significant. SAS software, version 8 (SAS Institute, Inc, Cary, NC), was used for analysis.

Results Data were collected at participating centers for the 2year period January 1, 1999 to December 31, 2000. Over this time period, 21,853 primary cesareans were performed on women carrying singleton gestations, 4989 (23%) of which were preterm. In 44 pregnancies (0.2%), the gestational age could not be reliably established. This left 16,820 women who underwent primary

cesarean delivery at term with a singleton gestation. However, 170 of these women were excluded from the analysis because, although they had been diagnosed with chorioamnionitis, either the date and/or time of the diagnosis was not available or they did not receive intrapartum antibiotics (n = 164), or because their intrapartum temperature was not recorded or they were not categorized as to the presence of chorioamnionitis (n = 6). Thus, 16,650 women met the inclusion criteria (term, singleton, primary cesarean), 1965 (12%) of whom were diagnosed with chorioamnionitis that could be definitively dated and timed. The most common (76%) intrapartum antibiotic regimen for chorioamnionitis was a combination of a penicillin and an aminoglycoside. In the postpartum period, 89% of women who had been diagnosed with chorioamnionitis received intravenous antibiotics (though specific agents were not recorded). The mean maternal age was 27 years. Forty percent were Caucasian, 31% African American, 24% Hispanic, and 5% were other. Most (73%) were nulliparous. Mean weight at delivery was 86 kg. Fifty-six percent had government-funded insurance, and 44% had private insurance. In 24%, gestational age assessment included a first-trimester ultrasound, in 48% a second-trimester ultrasound, and in 11% a third-trimester ultrasound. Mean gestational age at delivery was 40 weeks, and mean birth weight was 3474 g. The predominant cesarean indication was failure to progress; in women with chorioamnionitis it was 69%, whereas it was 35% for women without chorioamnionitis (P ! .001). Women with chorioamnionitis were at significantly increased risk of some adverse outcomes, but not others (Table I). Likewise, the fetus-neonates of women with chorioamnionitis were at increased risk of a 5-minute Apgar score of %3, and some, but not all, adverse outcomes (Table II).

214 Table II

Rouse et al Fetal-neonatal outcomes in relationship to chorioamnionitis

Outcome

Chorioamnionitis (n = 1965) %

No chorioamnionitis (n = 14,685*) %

RR (95% CI)

5-minute Apgar %3 Umbilical artery pH !7 Mechanical ventilation within 24 hours of birth Sepsis Seizures Hypoxic ischemic encephalopathy Death Any of the above

1.0 1.9 3.0 1.3 0.7 0.3 0.2 5.8

0.5 2.2 2.5 0.7 0.3 0.2 0.3 3.9

2.09 0.85 1.20 1.93 2.76 1.21 0.51 1.49

(1.26-3.46) (0.54-1.34) (0.92-1.58) (1.25-2.99) (1.50-5.09) (0.47-3.11) (0.16-1.64) (1.23-1.81)

* O99% ascertainment for all outcomes except for umbilical artery pH !7, for which ascertainment was 57% in the chorioamnionitis group, and 41% in the no chorioamnionitis group.

Table III

Adverse maternal outcomes in relationship to duration of chorioamnionitis Duration of chorioamnionitis in hours

Outcome*

%3 (n = 927) %

O3-6 (n = 593) %

O6-9 (n = 244) %

O9-12 (n = 112) %

O12 (n = 89) %

Uterine atony Blood transfusion Pelvic abscess Septic pelvic thrombophlebitis Thromboembolic disease Wound complication Necrotizing fasciitis ICU admission Exploratory lapartotomy Hysterectomy Death

12.2 3.9 0.2 0.7 0.2 1.6 0.1 0.3 0.4 0.3 0

13.7 4.2 0.5 0.5 0.0 1.5 0.0 0.3 0.2 0.7 0

18.9 5.3 0.0 0.4 0.0 2.5 0.0 1.2 0.0 0.0 0

22.3 8.0 0.0 0.9 0.0 0.0 0.0 0.9 0.0 0.0 0

15.7 6.7 0.0 0.0 0.0 0.0 0.0 2.3 0.0 1.1 0

P value .002 .03 .58 .69 .38 .32 .70 .02 .16 .87 ÿ

Wound complication is infection, seroma, or hematoma; thromboembolic disease is confirmed deep venous thrombosis or pulmonary embolism. * 100% ascertainment for all outcomes.

The duration of chorioamnionitis was %3 hours in 927 (47%) women,O3-6 hours in 593 (30%),O6-9 hours in 244 (12%),O9-12 hours in 112 (6%), andO12 hours in 89 (5%). Of maternal adverse outcomes evaluated, only uterine atony, blood transfusion, and intensive care unit admission were significantly related to the duration of chorioamnionitis, although in terms of increases in absolute rates, the relationships were not dramatic (Table III). The only individual neonatal outcome significantly related to duration of chorioamnionitis was 5-minute Apgar %3 (Table IV). In logistic analyses of individual maternal adverse outcomes evaluated, only uterine atony was significantly related to the duration of chorioamnionitis: for each hour of chorioamnionitis, the log odds ratio increased by 0.03 (Table V). Of individual neonatal outcomes evaluated by logistic regression, only 5-minute Apgar %3 and mechanical ventilation within 24 hours of birth were significantly associated with the duration of chorioamnionitis: for each hour, the odds ratio for the former increased by 0.09, and for the latter by 0.07 (Table VI).

Although our analyses were unadjusted, we did perform 2 simple analyses to assess whether duration of chorioamnionitis was related to one measure of maternal risk (weight) and one measure of neonatal risk (maximum maternal temperature). Although women with shorter durations of chorioamnionitis were significantly heavier (P = .03) than women with longer durations, the differences were not marked. Median maternal weight in the group of women whose chorioamnionitis duration was %3 hours was 82 kg vs 80 kg in the women whose duration was 12 or more hours, and median respective maximal intrapartum temperatures were 38.2(C for both groups. Thus, at least by these measures, women with longer durations of labor were not at substantially lower risk of adverse outcomes. Clearly, however, there may be confounding for which we could not control.

Comment At term, chorioamnionitis is diagnosed in approximately 5% of pregnancies.1 It poses well-recognized

215

Rouse et al Table IV

Fetal-neonatal outcomes in relationship to duration of chorioamnionitis Duration of chorioamnionitis in hours

Outcome* 5-minute Apgar %3 Umbilical artery pH !7 Mechanical ventilation within 24 hours of birth Sepsis Seizures Hypoxic ischemic encephalopathy Death Any of the above

%3 (n = 927) %

O3-6 (n = 593) %

O6-9 (n = 244) %

0.4 1.5 2.5

1.2 2.7 3.4

1.2 2.0 1.7

1.3 0.7 0.2 0.1 4.9

1.4 0.7 0.3 0.3 6.4

0.4 0.0 0.0 0.0 4.1

O12 (n = 89) %

P value

2.7 1.5 5.5

2.3 0.0 5.7

.01 .84 .10

1.8 1.8 0.0 0.0 12.5

2.3 2.3 1.1 0.0 7.9

.78 .22 .54 .83 .03

O9-12 (n = 112) %

* O99% ascertainment for all outcomes except for umbilical artery pH !7, for which ascertainment was 57%.

Table V Logistic analyses: relationship between maternal outcomes and each additional hour of chorioamnionitis

Table VI Logistic analyses: relationship between neonatal outcomes and each additional hour of chorioamnionitis

Outcome

Additional hour (OR [95% CI])

P value

Outcome

Uterine atony Blood transfusion Pelvic abscess Septic pelvic thrombophlebitis Thromboembolic disease Wound complication Necrotizing fasciitis ICU admission Exploratory lapartotomy Hysterectomy

1.03 1.04 0.90 0.91 0.43 0.93 0.34 1.09 0.64 0.98

.04 .15 .52 .39 .11 .26 .11 .07 .13 .85

5-minute Apgar %3 Umbilical artery pH !7 Mechanical ventilation within 24 hours of birth Sepsis Seizures Hypoxic ischemic encephalopathy Death Any of the above

(1.00-1.06) (0.98-1.08) (0.59-1.13) (0.70-1.08) (0.17-1.03) (0.82-1.04) (0.10-1.13) (0.97-1.18) (0.34-1.01) (0.77-1.14)

Additional hour (OR [95% CI])

P value

1.09 (1.00-1.16) .02 0.97 (0.83-1.08) .61 1.07 (1.01-1.12) .01

1.00 1.08 1.07 0.94 1.05

(0.89-1.09) (0.98-1.17) (0.86-1.20) (0.56-1.19) (1.01-1.09)

.97 .07 .41 .75 .02

Wound complication is infection, seroma, or hematoma; thromboembolic disease is confirmed deep venous thrombosis or pulmonary embolism.

maternal6,7 and neonatal risks,1 which our data confirm. However, the relationship between the duration of clinically diagnosed chorioamnionitis and adverse maternal and fetal-neonatal outcomes has been less well investigated.2-4 In stratified analyses, we found that the maternal complications of uterine atony, blood transfusion, and intensive care unit admission were significantly related to the duration of chorioamnionitis, as was the neonatal outcome of 5-minute Apgar score of %3. With logistic analysis, the only maternal complication related to the duration of chorioamnionitis was uterine atony, and the only such related neonatal complications were 5minute Apgar score of %3 and mechanical ventilation within 24 hours of birth. Other maternal and neonatal outcomes were not significantly related to the duration of chorioamnionitis. Our data have both strengths and weaknesses. Strengths include the large number of pregnancies eval-

uated (16,650) and the number of cases of chorioamnionitis (1965). Furthermore, all women categorized as having chorioamnionitis had a temperature of at least 100(F and a clinical diagnosis of chorioamnionitis. Although the percentage of women whose duration of chorioamnionitis exceeded 12 hours was low (5%), the absolute number of cases (89) is substantially more than the 40 cases that we could find in the literature by an English literature search of Medline (from 1966 through August 1, 2003 using the terms ‘‘chorioamnionitis’’ and ‘‘duration’’ or ‘‘length’’) and the retrieved bibliographies. All data for the project were abstracted by trained research nurses shortly after delivery using uniform criteria, and ongoing, systematic procedures for data quality control were employed. Logistic regression analyses were employed for maximum statistical robustness. Weaknesses of these data include both the actual and the theoretical. Only cesarean deliveries were included. However, from a maternal standpoint, this would not seem to invalidate our findings because chorioamnionitis morbidity is increased in the setting of cesarean,6

216 and thus, any relationship of morbidity to chorioamnionitis duration would tend to be amplified by the exclusion of women who were delivered vaginally. From a neonatal standpoint, unless vaginal delivery per se worsens the prognosis for infants delivered in the setting of chorioamnionitis, it should not matter that all infants were delivered by cesarean. An actual weakness of these data, in terms of informing clinical practice, is their observational nature. Discerning clinical biases which may have lead to the foreshortening of labor in some women and its prolongation in others is not possible from our data set. Nor were the data collected in such a way as to allow discrimination among neonates based on their positive culture site (blood, cerebrospinal fluid, or urine). Another weakness of these data is that the data set contained no information on neonatal antibiotic administration. Presumably, some and perhaps most infants born to mothers with chorioamnionitis (and some born to mothers not diagnosed with this infection) received antibiotic therapy. A final limitation of our data is a lack of statistical power to detect relationships between duration of chorioamnionitis and those outcomes that occurred infrequently. For example, our power to find an increase of 0.1 in the 1-hour log OR for the outcomes of maternal blood transfusion, neonatal seizures, and sepsis was, respectively, 15%, 6%, and 7%.8 In summary, we found that chorioamnionitis was associated with increased rates of both maternal and neonatal morbidity after cesarean at term. The duration of chorioamnionitis, however, was not related to most measures of adverse maternal or fetal-neonatal outcome. The rates of those measures of adverse maternal outcome, which were significantly related to chorioamnionitis duration (uterine atony, blood transfusion, and intensive care unit admission), and adverse neonatal outcome (5-minute Apgar score %3 and mechanical ventilation within 24 hours of birth) in absolute terms were low, and did not increase dramatically as duration lengthened. Thus, their increase provides no compelling reason to terminate labor by cesarean, and incur the potential morbidity of cesarean in the setting of chorioamnionitis.

References 1. Alexander JM, McIntire DM, Leveno KJ. Chorioamnionitis and the prognosis for term infants. Obstet Gynecol 1999;94:274-8.

Rouse et al 2. Gibbs RS, Castillo MS, Rodgers PJ. Management of acute chorioamnionitis. Am J Obstet Gynecol 1980;136:709-13. 3. Hauth JC, Gilstrap LC III, Hankins GDV, Connor KD. Term maternal and neonatal complications of acute chorioamnionitis. Obstet Gynecol 1985;66:59-62. 4. Garite TJ, Freeman RK. Chorioamnionitis in the preterm gestation. Obstet Gynecol 1982;59:539-45. 5. Gibbs RS, Dinsmoor MJ, Newton ER, Ramamurthy RS. A randomized trial of intrapartum versus immediate postpartum treatment of women with intra-amniotic infection. Obstet Gynecol 1988;72:823-8. 6. Tran TS, Jamultitrat S, Chongsuvivatwong V, Geater A. Risk factors for postcesarean surgical site infection. Obstet Gynecol 2000;95:367-71. 7. Mark SP, Croughan-Minihan MS, Kilpatrick SJ. Chorioamnionitis and uterine function. Obstet Gynecol 2000;95:909-12. 8. Hsieh FS, Bloch DA, Larsen MD. A simple method of sample size calculation for linear and logistic regression. Stat Med 1998;17: 1623-34.

Appendix Other members of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network are as follows: A. Northen, S. Tate, J. Hauth (University of Alabama at Birmingham), F. Johnson, S. Meadows, H. Walker, J. Iams (Ohio State University), J. McCampbell, D. Bradford, J Alexander, B. Casey, S. Bloom (University of Texas Southwestern Medical Center), E. Thom, H. Juliussen-Stevenson, M. Fischer (George Washington University Biostatistics Center) M. Jensen, K. Anderson, A. Guzman, A. Crowley, K. Jolley, R. Cavaness (University of Utah), M. Cotroneo, D. Fischer, M. B. Luce, K. Lain (University of Pittsburgh/Magee-Women’s Hospital), J. Potter, F. W. Doyle, S. Chandler, G. Burkett, J. Giles (University of Miami), M. M. DiVito, M. Talucci, M. Pollock (Drexel University), M. Swain, C. Moorefield, K. Lanier, L. Steele, M. Harper (Wake Forest University) N. Elder (University of Cincinnati), G. Norman, A. Millinder, C Sudz, B. Steffy, M. Dombrowski (Wayne State University), P. L. Jones, M. Ramos-Brinson, D. Gradishar, M. Moran, G. Mallett, D. Pruitt-Scott, J. Hibbard (University of Chicago), H. How, R. Ramsey (University of Tennessee at Memphis), S. Barker, M. Rodriguez, O. Langer (University of Texas at San Antonio), K. Howell, D. McNellis (National Institute of Child Health and Human Development).