Cell-Free Total and Fetal DNA in First Trimester Maternal Serum and Subsequent Development of Preeclampsia.

Objective The objective of this study was to assess the relationship between first trimester cell-free total and fetal DNA in maternal plasma and the subsequent development of preeclampsia. Study Design Nested case-control study of patients enrolled in the Combined Antioxidant and Preeclampsia Prediction Studies prediction study of 175 women who did and 175 women who did not develop preeclampsia. The predictive values of cell-free total and fetal DNA and the subsequent development of preeclampsia were measured using receiver operating characteristic curves. Results Cell-free total DNA was higher in African American (median; 25-75%; 6.15; 0.14-28.73; p = 0.02) and Hispanic (4.95; 0.20-26.82; p = 0.037) compared with white women (2.33; 0.03-13.10). Levels of cell-free total DNA were also associated with maternal body mass index (BMI) (p = 0.02). Cell-free total DNA levels were similar between women who later developed preeclampsia (3.52; 0.11-25.3) and controls (3.74; 0.12-21.14, p = 0.96). Conclusion There is no significant difference in levels of cell-free total DNA in the first trimester in women who subsequently develop preeclampsia. Levels of cell-free total DNA in the first trimester are increased in African American and Hispanic compared with white women, and levels increase with increasing BMI.

Waist-to-Hip Ratio versus Body Mass Index as Predictor of Obesity-Related Pregnancy Outcomes.

Objective In nonpregnant populations the waist-to-hip ratio (WHR) is a better predictor of obesity-related outcomes than body mass index (BMI). Our objective was to determine, in pregnancy, the relationship between these measures of obesity, and large-for-gestational age (LGA) and cesarean delivery (CD). Methods This is a secondary analysis of data from the Combined Antioxidant and Preeclampsia Prediction Study. Women with a WHR of ≥ 0.85 and 0.80 to 0.84 at 9 to 16 weeks gestation were compared with those with a WHR < 0.80. Women with early pregnancy BMI ≥ 30.0 kg/m(2) (obese) and 25.0 to 29.9 kg/m(2) (overweight) were compared with those < 25.0 kg/m(2). LGA was defined as > 90% by Alexander nomogram. Univariable analysis, logistic regression, and receiver operating characteristic curves were used. Results Data from 2,276 women were analyzed. After correcting for potential confounders, only BMI ≥ 30 was significantly associated with LGA (adjusted odds ratio [aOR]: 2.07, 1.35-3.16) while BMI 25.0-29.9 (aOR: 1.5, 0.98-2.28), WHR 0.8-0.84 (aOR: 1.33, 0.83-2.13), and WHR ≥ 0.85 (aOR: 1.05, 0.67-1.65) were not. Risk for CD was increased for women with elevated WHR and with higher BMI compared with normal. Conclusion WHR is not associated with LGA. While BMI performed better than WHR, neither was a strong predictor of LGA or need for CD in low-risk nulliparous women.

Relationship of Early Pregnancy Waist-to-Hip Ratio versus Body Mass Index with Gestational Diabetes Mellitus and Insulin Resistance.

OBJECTIVE: To determine the risk of gestational diabetes mellitus (GDM) and insulin resistance (IR) in obesity defined by body mass index (BMI), waist-to-hip ratio (WHR), or both combined. METHODS: Secondary analysis of a randomized multicenter trial of antioxidant supplementation versus placebo in nulliparous low-risk women to prevent pregnancy associated hypertension. Women between 9 and 16 weeks with data for WHR and BMI were analyzed for GDM (n = 2,300). Those with fasting glucose and insulin between 22 and 26 weeks (n = 717) were analyzed for IR by homeostatic model assessment of IR (normal, ≤ 75th percentile). WHR and BMI were categorized as normal (WHR, < 0.80; BMI, < 25 kg/m(2)); overweight (WHR, 0.8-0.84; BMI, 25-29.9 kg/m(2)); and obese (WHR, ≥ 0.85; BMI ≥ 30 kg/m(2)). Receiver operating characteristic curves and logistic regression models were used. RESULTS: Compared with normal, the risks of GDM or IR were higher in obese by BMI or WHR. The subgroup with obesity by WHR but not by BMI had no increased risk of GDM. BMI was a better predictor of IR (area under the curve [AUC]: 0.71 [BMI], 0.65 [WHR], p = 0.03) but similar to WHR for GDM (AUC: 0.68 [BMI], 0.63 [WHR], p = 0.18). CONCLUSION: Increased WHR and BMI in early pregnancy are associated with IR and GDM. BMI is a better predictor of IR compared with WHR. Adding WHR to BMI does not improve its ability to detect GDM or IR.

Is Mid-trimester Insulin Resistance Predictive of Subsequent Puerperal Infection? A Secondary Analysis of Randomized Trial Data.

Objective The objective of this study was to examine whether there is an association between insulin resistance and subsequent development of puerperal infection by measuring insulin resistance in the mid-trimester using the homeostasis model assessment (HOMA:IR). Methods Secondary analysis of low-risk nulliparas enrolled in a multicenter preeclampsia prevention trial. HOMA:IR was measured on fasting plasma glucose and insulin concentrations among low-risk nulliparas between 22 and 26 weeks' gestation. Median HOMA:IR was compared between women who did and did not develop puerperal infection using Wilcoxon rank sum test. Logistic regression was used to control for potential confounders. Results Of 1,180 women with fasting glucose and insulin available, 121 (10.3%) had a puerperal infection. Median HOMA:IR was higher among those with subsequent puerperal infection (4.3 [interquartile, IQR: 2.2-20.5] vs. 2.6 [IQR: 1.5-6.7], p < 0.0001). After controlling for potentially confounding variables HOMA:IR was only marginally associated with an increased risk of development of puerperal infection, adjusted odds ratio: 1.01 (95% confidence interval: 1.00-1.02; p = 0.04) per unit increase. Elevated HOMA:IR performed poorly as a predictor of puerperal infection, with a positive predictive value of 15% and a negative predictive value of 92%. Conclusion Though associated with an increased risk of puerperal infection, insulin resistance, measured by HOMA:IR, is not a clinically useful predictor of puerperal infection.

Quantitative Polymerase Chain Reaction to Assess Response to Treatment of Bacterial Vaginosis and Risk of Preterm Birth.

OBJECTIVE: The aim of this study was to determine whether quantitative polymerase chain reaction (qPCR) bacterial load measurement is a valid method to assess response to treatment of bacterial vaginosis and risk of preterm birth in pregnant women. STUDY DESIGN: Secondary analysis by utilizing stored vaginal samples obtained during a previous randomized controlled trial studying the effect of antibiotics on preterm birth (PTB). All women had risk factors for PTB: (1) positive fetal fibronectin (n=146), (2) bacterial vaginosis (BV) and a prior PTB (n=43), or (3) BV and a prepregnancy weight<50 kg (n=54). Total and several individual BV-related bacteria loads were measured using qPCR for 16S rRNA. Loads were correlated with Nugent scores (Spearman correlation coefficients). Loads were compared pre- and posttreatment with Wilcoxon rank-sum test. Individual patient differences were examined with Wilcoxon signed-rank test. RESULTS: A total of 243 paired vaginal samples were available for analysis: 123 antibiotics and 120 placebo. Groups did not differ by risk factors for PTB. For all samples, bacterial loads were correlated with Nugent score and each of its specific bacterial components (all p<0.01). Baseline total bacterial load did not differ by treatment group (p=0.87). Posttreatment total bacterial load was significantly lower in the antibiotics group than the placebo group (p<0.01). Individual patient total bacterial load decreased significantly posttreatment in the antibiotics group (p<0.01), but not in the placebo group (p=0.12). The rate of PTB did not differ between groups (p=0.24). PTB relative risks calculated for BV positive versus BV negative women and women with the highest quartile total and individual bacterial loads were not statistically significant. CONCLUSION: qPCR correlates with Nugent score and demonstrates decreased bacterial load after antibiotic treatment. Therefore, it is a valid method of vaginal flora assessment in pregnant women who are at high risk for PTB.

Oral health education and therapy reduces gingivitis during pregnancy.

BACKGROUND: Pregnant women demonstrate increases in gingivitis despite similar plaque levels to non-pregnant counterparts. AIM: To evaluate an intensive protocol aimed at reducing gingivitis in pregnant women and provide pilot data for large-scale randomized controlled trials investigating oral hygiene measures to reduce pregnancy gingivitis and alter maternity outcomes. MATERIALS AND METHODS: One hundred and twenty participants between 16 and 24 weeks gestation with Gingival Index (GI) scores ≥2 at ≥50% of tooth sites were enrolled. Plaque index (PI), gingival inflammation (GI), probing depth (PD), and clinical attachment levels (CAL) were recorded at baseline and 8 weeks. Dental prophylaxis was performed at baseline and oral hygiene instructions at baseline, 4 and 8 weeks. Pregnancy outcomes were recorded at parturition. Mixed-model analysis of variance was used to compare clinical measurements at baseline and 8 weeks. RESULTS: Statistically significant reductions in PI, GI, PD, and CAL occurred over the study period. Mean whole mouth PI and GI scores decreased approximately 50% and the percentage of sites with PI and GI ≥2 decreased from 40% to 17% and 53% to 21.8%, respectively. Mean decreases in whole mouth PD and CAL of 0.45 and 0.24 mm, respectively, were seen. CONCLUSIONS: Intensive oral hygiene regimen decreased gingivitis in pregnant patients.

Adverse pregnancy outcomes among women with prior spontaneous or induced abortions.

OBJECTIVE: The aim of the article is to determine whether prior spontaneous abortion (SAB) or induced abortion (IAB), or the interpregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. METHODS: We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios (ORs) for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared with primigravid participants. RESULTS: Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (adj. OR, 1.5; 95% CI, 1.1-2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (PTB) (adj. OR, 2.6, 95% CI, 1.7-4.0), preterm premature rupture of membranes (PROM) (adj. OR, 2.9; 95% CI, 1.6-5.3), and perinatal death (adj. OR, 2.8; 95% CI, 1.5-5.3). Women with one previous IAB had higher rates of spontaneous PTB (adj. OR, 1.4; 95% CI, 1.0-1.9) and preterm PROM (OR, 2.0; 95% CI, 1.4-3.0). An interpregnancy interval less than 6 months after SAB was not associated with adverse outcomes. CONCLUSION: Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes.

Vitamins C and E to prevent complications of pregnancy-associated hypertension.

BACKGROUND: Oxidative stress has been proposed as a mechanism linking the poor placental perfusion characteristic of preeclampsia with the clinical manifestations of the disorder. We assessed the effects of antioxidant supplementation with vitamins C and E, initiated early in pregnancy, on the risk of serious adverse maternal, fetal, and neonatal outcomes related to pregnancy-associated hypertension. METHODS: We conducted a multicenter, randomized, double-blind trial involving nulliparous women who were at low risk for preeclampsia. Women were randomly assigned to begin daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or matching placebo between the 9th and 16th weeks of pregnancy. The primary outcome was severe pregnancy-associated hypertension alone or severe or mild hypertension with elevated liver-enzyme levels, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, medically indicated preterm birth, fetal-growth restriction, or perinatal death. RESULTS: A total of 10,154 women underwent randomization. The two groups were similar with respect to baseline characteristics and adherence to the study drug. Outcome data were available for 9969 women. There was no significant difference between the vitamin and placebo groups in the rates of the primary outcome (6.1% and 5.7%, respectively; relative risk in the vitamin group, 1.07; 95% confidence interval [CI], 0.91 to 1.25) or in the rates of preeclampsia (7.2% and 6.7%, respectively; relative risk, 1.07; 95% CI, 0.93 to 1.24). Rates of adverse perinatal outcomes did not differ significantly between the groups. CONCLUSIONS: Vitamin C and E supplementation initiated in the 9th to 16th week of pregnancy in an unselected cohort of low-risk, nulliparous women did not reduce the rate of adverse maternal or perinatal outcomes related to pregnancy-associated hypertension (ClinicalTrials.gov number, NCT00135707).

Putting the "M" back in maternal-fetal medicine.

Although maternal death remains rare in the United States, the rate has not decreased for 3 decades. The rate of severe maternal morbidity, a more prevalent problem, is also rising. Rise in maternal age, in rates of obesity, and in cesarean deliveries as well as more pregnant women with chronic medical conditions all contribute to maternal mortality and morbidity in the United States. We believe it is the responsibility of maternal-fetal medicine (MFM) subspecialists to lead a national effort to decrease maternal mortality and morbidity. In doing so, we hope to reestablish the vital role of MFM subspecialists to take the lead in the performance and coordination of care in complicated obstetrical cases. This article will summarize our initial recommendations to enhance MFM education and training, to establish national standards to improve maternal care and management, and to address critical research gaps in maternal medicine.

The impact of tobacco use on preterm premature rupture of the membranes.

OBJECTIVE: To determine if tobacco use increases the incidence of preterm premature rupture of the membranes (pPROM) or alters perinatal outcomes after pPROM. STUDY DESIGN: This is a secondary analysis of the databases of three completed Eunice Kennedy Shriver National Institute of Child Health and Human Development-supported Maternal Fetal Medicine Units Network studies. Self-reported tobacco exposure data was obtained. Its relationship with the incidence of pPROM and associated neonatal outcome measures were assessed. RESULTS: There was no difference in the incidence of pPROM when comparing nonsmokers to those using tobacco. Although a trend was seen between the incidence of pPROM and the amount smoked, this did not reach statistical significance. Among the patients with pPROM, the use of tobacco was not associated with an increase in perinatal morbidity. CONCLUSION: Our data do not support a significant relationship between tobacco use and pPROM.

Maternal insulin resistance and preeclampsia.

OBJECTIVE: The purpose of this study was to determine whether mid-trimester insulin resistance is associated with subsequent preeclampsia. STUDY DESIGN: This was a secondary analysis of 10,154 nulliparous women who received vitamin C and E or placebo daily from 9-16 weeks gestation until delivery. Of these, 1187 women had fasting plasma glucose and insulin tested between 22 and 26 weeks gestation. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index. RESULTS: Obese women were twice as likely to have a HOMA-IR result of ≥75th percentile. Hispanic and African American women had a higher percentage at ≥75th percentile for HOMA-IR than white women (42.2%, 27.2%, and 16.9%, respectively; P < .001). A HOMA-IR result of ≥75th percentile was higher among the 85 nulliparous women who subsequently had preeclampsia, compared with women who remained normotensive (40.5% vs 24.8%; adjusted odds ratio, 1.9; 95% confidence interval, 1.1-3.2). Quantitative insulin sensitivity check index results were similar to the HOMA-IR results. CONCLUSION: Midtrimester maternal insulin resistance is associated with subsequent preeclampsia.

Effects of periodontal therapy on rate of preterm delivery: a randomized controlled trial.

OBJECTIVE: To test the effects of maternal periodontal disease treatment on the incidence of preterm birth (delivery before 37 weeks of gestation). METHODS: The Maternal Oral Therapy to Reduce Obstetric Risk Study was a randomized, treatment-masked, controlled clinical trial of pregnant women with periodontal disease who were receiving standard obstetric care. Participants were assigned to either a periodontal treatment arm, consisting of scaling and root planing early in the second trimester, or a delayed treatment arm that provided periodontal care after delivery. Pregnancy and maternal periodontal status were followed to delivery and neonatal outcomes until discharge. The primary outcome (gestational age less than 37 weeks) and the secondary outcome (gestational age less than 35 weeks) were analyzed using a chi test of equality of two proportions. RESULTS: The study randomized 1,806 patients at three performance sites and completed 1,760 evaluable patients. At baseline, there were no differences comparing the treatment and control arms for any of the periodontal or obstetric measures. The rate of preterm delivery for the treatment group was 13.1% and 11.5% for the control group (P=.316). There were no significant differences when comparing women in the treatment group with those in the control group with regard to the adverse event rate or the major obstetric and neonatal outcomes. CONCLUSION: Periodontal therapy did not reduce the incidence of preterm delivery. LEVEL OF EVIDENCE: I.

The frequency and complication rates of hysterectomy accompanying cesarean delivery.

OBJECTIVE: To estimate the frequency, indications, and complications of cesarean hysterectomy. METHODS: This was a prospective, 2-year observational study at 13 academic medical centers conducted between January 1, 1999, and December 31, 2000, on all women who underwent a hysterectomy at the time of cesarean delivery. Data were abstracted from the medical record by study nurses. The outcomes included procedure frequency, indications, and complications. RESULTS: A total of 186 cesarean hysterectomies (0.5%) were performed from a cohort of 39,244 women who underwent cesarean delivery. The leading indications for hysterectomy were placenta accreta (38%) and uterine atony (34%). Of the hysterectomy cases with a diagnosis recorded as accreta, 18% accompanied a primary cesarean delivery, and 82% had a prior procedure (P<.001). Of the hysterectomy cases with atony recorded as a diagnosis, 59% complicated primary cesarean delivery, whereas 41% had a prior cesarean (P<.001). Major maternal complications of cesarean hysterectomy included transfusion of red blood cells (84%) and other blood products (34%), fever (11%), subsequent laparotomy (4%), ureteral injury (3%), and death (1.6%). Accreta hysterectomy cases were more likely than atony hysterectomy cases to require ureteral stents (14% compared with 3%, P=.03) and to instill sterile milk into the bladder (23% compared with 8%, P=.02). CONCLUSION: The rate of cesarean hysterectomy has declined modestly in the past decade. Despite the use of effective therapies and procedures to control hemorrhage at cesarean delivery, a small proportion of women continue to require hysterectomy to control hemorrhage from both uterine atony and placenta accreta. LEVEL OF EVIDENCE: II.

Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length.

OBJECTIVE: The objective of the study was to assess cerclage to prevent recurrent preterm birth in women with short cervix. STUDY DESIGN: Women with prior spontaneous preterm birth less than 34 weeks were screened for short cervix and randomly assigned to cerclage if cervical length was less than 25 mm. RESULTS: Of 1014 women screened, 302 were randomized; 42% of women not assigned and 32% of those assigned to cerclage delivered less than 35 weeks (P = .09). In planned analyses, birth less than 24 weeks (P = .03) and perinatal mortality (P = .046) were less frequent in the cerclage group. There was a significant interaction between cervical length and cerclage. Birth less than 35 weeks (P = .006) was reduced in the less than 15 mm stratum with a null effect in the 15-24 mm stratum. CONCLUSION: In women with a prior spontaneous preterm birth less than 34 weeks and cervical length less than 25 mm, cerclage reduced previable birth and perinatal mortality but did not prevent birth less than 35 weeks, unless cervical length was less than 15 mm.

Decreasing incidence of postcesarean endometritis with extended-spectrum antibiotic prophylaxis.

OBJECTIVE: To describe the effect of an extended-spectrum prophylactic antibiotic regimen on postcesarean endometritis. METHODS: This is a cohort study of trends in postcesarean endometritis using data both from prospective surveillance by the infection control unit and from query of our obstetric computerized database to compare three periods of antibiotic prophylaxis: standard narrow-spectrum with intravenous first- or second-generation cephalosporin (1992-1996), clinical trial of extended-spectrum with addition of intravenous doxycycline and oral azithromycin (1997-1999), and routine use of extended-spectrum with addition of intravenous azithromycin (2001-2006) to standard cephalosporin prophylaxis. RESULTS: A total of 48,913 deliveries at 24 weeks or more of gestation occurred from 1992 to 2006, of which 10,966 (22.4%) were cesarean deliveries. Annual cesarean rates increased from 16% to 27.5%. Trends in the incidence of postcesarean endometritis revealed a biphasic decrease consistent with the phased introduction of extended-spectrum prophylaxis. Incidence (95% confidence interval [CI]) of endometritis by prospective surveillance dropped from 19.9% (95% CI 18.6-21.3%) to 15.4% (95% CI 13.2-17.9%) during the clinical trial period: relative risk (RR) 0.77 (95% CI 0.66-0.91), P=.002; and then to 6.3% (95% CI 5.0-7.9%) during routine use of extended-spectrum prophylaxis: RR 0.41 (95% CI 0.31-0.54), P<.001. Corresponding incidence by database query dropped from 23% (95% CI 21.5-24.4%) to 16% (95% CI 14.4-17.9%): RR 0.69 (95% CI 0.61-0.79), P<.001; and then to 2.1% (95% CI 1.8-2.6%): RR 0.13 (95% CI 0.11-0.16), P<.001. These findings were unchanged after adjusting for potential confounders. CONCLUSION: Extended-spectrum antibiotic prophylaxis involving the addition of azithromycin to standard narrow-spectrum prophylaxis was associated with a significant reduction in postcesarean endometritis. LEVEL OF EVIDENCE: II.

Impact of extended-spectrum antibiotic prophylaxis on incidence of postcesarean surgical wound infection.

OBJECTIVE: We assessed the impact of an extended-spectrum antibiotic prophylaxis regimen (azithromycin in addition to recommended narrow-spectrum cephalosporin) on postcesarean incisional wound infection. STUDY DESIGN: Data from prospective surveillance of surgical site infections at our institution were used to compare incidence in postcesarean incisional wound infection for 3 consecutive time periods of antibiotic prophylaxis: (1) standard (ie, cephalosporin only, 1992-1996); (2) clinical trial of extended spectrum (ie, extended vs cephalosporin only, 1997-1999); and (3) routine use of extended spectrum (2001-2006). RESULTS: The incidence of postcesarean incisional wound infections decreased progressively from 3.1% to 2.4% and then to 1.3% over the 3 consecutive periods (P value for trend < .002). CONCLUSION: Increasing the use of extended-spectrum antibiotic prophylaxis at our institution over 3 time periods was associated with a decreasing trend in postcesarean incisional wound infection.

The Alabama Preterm Birth Study: umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants.

OBJECTIVE: This study was undertaken to evaluate the frequency of umbilical cord blood infections with Ureaplasma urealyticum and Mycoplasma hominis in preterm 23- to 32-week births and to determine their association with various obstetric conditions, markers of placental inflammation, and newborn outcomes. STUDY DESIGN: 351 mother/infant dyads with deliveries between 23 and 32 weeks' gestational age who had cord blood cultures for U. urealyticum and M. hominis had their medical records abstracted, other placental cultures performed, cord interleukin-6 levels determined, placentas evaluated histologically, and infant outcomes determined. RESULTS: U. urealyticum and/or M. hominis were present in 23% of cord blood cultures. Positive cultures were more common in infants of nonwhite women (27.9% vs 16.8%; P = .016), in women less than 20 years of age, in those undergoing a spontaneous compared to an indicated preterm delivery (34.7% vs 3.2%; P = .0001), and in those delivering at earlier gestational ages. Intrauterine infection and inflammation were more common among infants with a positive U. urealyticum and M. hominis culture as evidenced by placental cultures for these and other bacteria, elevated cord blood interleukin-6 levels, and placental histology. Infants with positive cord blood U. urealyticum and M. hominis cultures were more likely to have neonatal systemic inflammatory response syndrome (41.3% vs 25.7%; P = .007; adjusted odds ratio, 1.86; 1.08-3.21) and probably bronchopulmonary dysplasia (26.8% vs 10.1%; P = .0001; adjusted odds ratio 1.99; 0.91-4.37), but were not significantly different for other neonatal outcomes, including respiratory distress syndrome, intraventricular hemorrhage, or death. CONCLUSION: U. urealyticum and M. hominis cord blood infections are far more common in spontaneous vs indicated preterm deliveries and are strongly associated with markers of acute placental inflammation. Positive cultures are associated with neonatal systemic inflammatory response syndrome and probably bronchopulmonary dysplasia.

Early preterm birth: association between in utero exposure to acute inflammation and severe neurodevelopmental disability at 6 years of age.

OBJECTIVE: The purpose of this study was to determine the association between in utero exposure to acute inflammation and long-term major neurodevelopmental disability at age 6 years among children born prior to 32 weeks' gestation. STUDY DESIGN: This was a follow-up investigation of a cohort of maternal-infant dyads delivered between 23 and < 32 weeks' gestation. Surviving infants (and their mothers or caregivers) underwent a battery of psychological and neurodevelopmental tests between 5 and 8 years of age. Pregnancy and neonatal data were analyzed among children with versus those without major neurodevelopmental disability (including IQ < 70 [n = 41], cerebral palsy [CP, n = 11], and a composite major disability [n = 52]). RESULTS: A total of 261 (70%) of the 375 maternal-infant dyads with surviving children were successfully recruited and evaluated at 6.8 +/- 0.7 years. Mean delivery gestational age (GA) and birthweight were 28.8 +/- 2.2 weeks and 1163 +/- 382 g, respectively. Neither surrogate indicators for nor direct markers of in utero exposure to acute inflammation were significantly associated with severe adverse outcomes. Delivery GA was significantly associated with outcome. Logistic regression indicated that each increasing gestational week was associated with a significantly decreased risk of an IQ < 70 (OR 0.75, 95% CI 0.6-0.9). An average 1.9 point increase in IQ at 6 years of age was observed per gestational week gained (23 to 32 weeks). Periventricular leukomalacia was associated with a 9.6 point mean deficit in IQ. The perceptive vocabulary scores (IQ proxy) of primary caregivers were significantly lower among children with an IQ < 70 vs > or = 70 (87.5 +/- 11.5 vs 92.1 +/- 11.2, P = .016). CONCLUSION: Among children born between 23 and 32 weeks' gestation, neonatal complications, GA at delivery, and caregiver IQ, but not in utero exposure to acute inflammation, were associated with increased risk of severe adverse neurodevelopmental outcomes at age 6 years.

Maternal and perinatal outcomes associated with a trial of labor after prior cesarean delivery.

BACKGROUND: The proportion of women who attempt vaginal delivery after prior cesarean delivery has decreased largely because of concern about safety. The absolute and relative risks associated with a trial of labor in women with a history of cesarean delivery, as compared with elective repeated cesarean delivery without labor, are uncertain. METHODS: We conducted a prospective four-year observational study of all women with a singleton gestation and a prior cesarean delivery at 19 academic medical centers. Maternal and perinatal outcomes were compared between women who underwent a trial of labor and women who had an elective repeated cesarean delivery without labor. RESULTS: Vaginal delivery was attempted by 17,898 women, and 15,801 women underwent elective repeated cesarean delivery without labor. Symptomatic uterine rupture occurred in 124 women who underwent a trial of labor (0.7 percent). Hypoxic-ischemic encephalopathy occurred in no infants whose mothers underwent elective repeated cesarean delivery and in 12 infants born at term whose mothers underwent a trial of labor (P<0.001). Seven of these cases of hypoxic-ischemic encephalopathy followed uterine rupture (absolute risk, 0.46 per 1000 women at term undergoing a trial of labor), including two neonatal deaths. The rate of endometritis was higher in women undergoing a trial of labor than in women undergoing repeated elective cesarean delivery (2.9 percent vs. 1.8 percent), as was the rate of blood transfusion (1.7 percent vs. 1.0 percent). The frequency of hysterectomy and of maternal death did not differ significantly between groups (0.2 percent vs. 0.3 percent, and 0.02 percent vs. 0.04 percent, respectively). CONCLUSIONS: A trial of labor after prior cesarean delivery is associated with a greater perinatal risk than is elective repeated cesarean delivery without labor, although absolute risks are low. This information is relevant for counseling women about their choices after a cesarean section.

Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.

BACKGROUND: Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery. METHODS: We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle. RESULTS: Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation (incidence, 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group; relative risk, 0.66 [95 percent confidence interval, 0.54 to 0.81]), delivery at less than 35 weeks of gestation (incidence, 20.6 percent vs. 30.7 percent; relative risk, 0.67 [95 percent confidence interval, 0.48 to 0.93]), and delivery at less than 32 weeks of gestation (11.4 percent vs. 19.6 percent; relative risk, 0.58 [95 percent confidence interval, 0.37 to 0.91]). Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen. CONCLUSIONS: Weekly injections of 17P resulted in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants.