Placental drainage of fetal blood at cesarean delivery and feto maternal transfusion: a randomized controlled trial.

OBJECTIVE: To assess the efficacy of placental drainage of fetal blood at the time of cesarean delivery on the incidence of feto-maternal transfusion. METHODS: This randomized trial includes 86 gravid women who underwent cesarean delivery. Forty-four women were assigned to the placental drainage group and 42 to the no-drainage group. Placental drainage was accomplished by cutting and milking the umbilical cord until no further blood flow occurred. All placentas were spontaneously expelled. The primary outcome variable, as assessed by preoperative and postoperative Kleihauer-Betke tests, was the amount of fetal blood (greater than or equal to 0.5 mL) in the maternal circulation. RESULTS: The group having placental drainage of fetal blood before placental delivery showed a significantly lower incidence (3 of 44, 6.8%) of feto-maternal transfusion (P=.003) as compared with the undrained group (14 of 42, 33%; relative risk 0.20, 95% confidence interval 0.065-0.65; number needed to treat=4). CONCLUSION: Placental drainage of fetal blood before spontaneous placental delivery at the time of cesarean delivery significantly reduces the incidence of feto-maternal transfusion. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00470899 LEVEL OF EVIDENCE: I.

Association of obesity with pulmonary and nonpulmonary complications of pregnancy in asthmatic women.

OBJECTIVE: To evaluate whether maternal obesity is associated with pulmonary and nonpulmonary pregnancy complications in asthmatic women. METHODS: This is a secondary analysis of the prospective cohort Asthma During Pregnancy Study. Asthma patients were classified as having either mild or moderate to severe disease at the beginning of the study. Rates of pulmonary complications of asthma in asthmatic women and rates of nonpulmonary complications of pregnancy among asthma patients and controls, were compared between obese (body mass index > or = 30 kg/m2) and nonobese women. RESULTS: Maternal body mass index and pregnancy outcome data were available for 1,699 of 1,812 asthmatic women and for 867 of 881 controls. Of the asthma subjects, 30.7% (521) were obese compared with 25.5% of the controls, P = .006. Obese women, regardless of whether they had asthma, were more likely to undergo cesarean delivery (OR 1.6, 95% confidence interval [CI]1.3-2.0) to develop preeclampsia or gestational hypertension (OR 1.7 95% CI 1.3-2.3) and gestational diabetes (OR 4.2, 95% CI 2.8-6.3). There were no differences in the rates of overall asthma improvement (20.6% compared with 23.6%, P = .36) or deterioration (33.3% compared with 28.8%, P = .20) between obese and nonobese asthma patients. After adjustment for confounding variables, obesity, not asthma, was associated with nonpulmonary complications of pregnancy, and obesity was associated with an increase in asthma exacerbations as well (OR 1.3, 95% CI 1.1-1.7). CONCLUSION: Obesity is associated with an increased risk of asthma exacerbations during pregnancy. The increased rate of nonpulmonary complications of pregnancy in asthma patients is associated with obesity in this population and not with asthma status. LEVEL OF EVIDENCE: II-1.

Are women with recurrent spontaneous preterm births different from those without such history?

OBJECTIVE: This study was undertaken to determine whether women with recurrent spontaneous preterm births (rSPBs) have different clinical characteristics or systemic markers than those with isolated preterm (iSPBs) or recurrent term births (rTBs), when assessed remote from delivery. STUDY DESIGN: We compared clinical characteristics and findings (including cervical ultrasound, bacterial vaginosis, fetal fibronectin), maternal plasma markers obtained at 22 to 24 weeks' gestation (inflammatory cytokines, cortisol, and corticotrophin-releasing hormone), between women with rSPBs (2 or 3 consecutive SPBs and no TBs), iSPBs (1 SPB and 1 or 2 TBs), and rTBs (2 or 3 consecutive TBs and no SPBs). RESULTS: A total of 1257 women met our inclusion criteria; 47 rSPBs, 241 iSPBs (80 current and 161 prior iSPBs), and 969 rTBs. Before pregnancy, women with rSPBs had lower weights (P < .0001) and body mass indexes (BMIs) (P < .001), and were more likely to be less than 100 lbs (P = .008) or less than 19.8 kg/m2 BMI (P = .001). At 22 to 24 weeks those with rSPBs remained lighter and leaner, and had more advanced Bishop scores than iSPBs and rTBs. Ultrasound demonstrated progressive decrease in cervical length for those with rTBs, prior iSPBs, current iSPBs, and rSPBs, and also progressively more frequent short cervixes with worsening history (P < .001). Cervical length was shorter for women of lower pregravid weight and BMI, but not with shorter height. At 22 to 24 weeks, women with rSPBs had more common uterine contractions and tocolytic agents, but not more infections or antibiotic therapy. Those with an SPB in the current gestation had higher fetal fibronectin levels and more frequent vaginal bleeding, regardless of prior outcome. Maternal cortisol and corticotrophin-releasing hormone were higher in women with iSPBs and rSPBs than in rTB controls, (P = .001 and .0027), a finding more apparent with SPB in the current pregnancy. However, maternal cytokines were not increased with either iSPBs or rSPBs. CONCLUSION: Women with rSPBs are leaner, contract more, have shorter cervixes, and have more advanced Bishop scores than women with iSPBs or rTBs.

The NICHD-MFMU antibiotic treatment of preterm PROM study: impact of initial amniotic fluid volume on pregnancy outcome.

OBJECTIVE: The purpose of this study was to evaluate the associations between measured amniotic fluid volume and outcome after preterm premature rupture of membranes (PROM). STUDY DESIGN: This was a secondary analysis of 290 women, with singleton pregnancies, who participated in a trial of antibiotic therapy for preterm PROM at 24(0) to 32(0) weeks. Each underwent assessment of the 4 quadrant amniotic fluid index (AFI) and a maximum vertical fluid pocket (MVP) before randomization. The impact of low AFI (< 5.0 cm) and low MVP (< 2.0 cm) on latency, amnionitis, neonatal morbidity, and composite morbidity (any of death, RDS, early sepsis, stage 2-3 necrotizing enterocolitis, and/or grade 3-4 intraventricular hemorrhage) was assessed. Logistic regression controlled for confounding factors including gestational age at randomization, GBS carriage, and antibiotic study group. RESULTS: Low AFI and low MVP were identified in 67.2% and 46.9% of women, respectively. Delivery occurred by 48 hours, 1 and 2 weeks in 32.4%, 63.5% and 81.7% of pregnancies, respectively. Both low AFI and low MVP were associated with shorter latency (P < .001), and with a higher rate of delivery at 48 hours, 1, and 2 weeks (P = .02 for each). However, neither test offered significant additional predictive value over the risk in the total population. Low AFI and low MVP were not associated with increased amnionitis. After controlling for other factors, both low MVP and low AFI were associated with shorter latency (P < or = .002), increased composite morbidity (P = .03), and increased RDS (P < or = .01), but not with increased neonatal sepsis (P = .85) or pneumonia (P = .53). Alternatively, after controlling for fluid volume, gestational age, and GBS carriage, the antibiotic study group had longer latency, and suffered less common primary outcomes and neonatal sepsis. CONCLUSION: Oligohydramnios should not be a consideration in determining which women will be candidates for expectant management or antibiotic treatment when it is identified at initial assessment of preterm PROM remote from term.

Spirometry is related to perinatal outcomes in pregnant women with asthma.

OBJECTIVE: The purpose of this study was to test the hypothesis that maternal asthma symptoms and pulmonary function are related to adverse perinatal outcomes. STUDY DESIGN: Asthmatic patients were recruited from the 16 centers of the Maternal Fetal Medicine Units. Forced expiratory volume in 1 second was obtained at enrollment and at monthly study visits, and the frequency of asthma symptoms was assessed from enrollment to delivery. Perinatal data were obtained at postpartum chart reviews. RESULTS: The final cohort included 2123 participants with asthma. After adjustment for demographic characteristics, smoking, acute asthmatic episodes, and oral corticosteroid use, significant relationships were demonstrated between gestational hypertension and preterm birth and lower maternal gestational forced expiratory volume in 1 second. The data did not show any significant independent relationship between asthma symptom frequency and perinatal outcomes. CONCLUSION: Lower pulmonary function during pregnancy is associated with increased gestational hypertension and prematurity in the pregnancies of women with asthma, which may be due to inadequate asthma control or factors that are associated with increased asthma severity.

The Preterm Prediction Study: association between maternal body mass index and spontaneous and indicated preterm birth.

OBJECTIVE: The purpose of this study was to evaluate the relationship between prepregnancy maternal body mass index and spontaneous preterm birth and indicated preterm birth. STUDY DESIGN: This was a secondary analysis of the Maternal-Fetal Medicine Units Network, Preterm Prediction study. Patients were classified into categories that were based on their body mass index. Rates of indicated and spontaneous preterm birth were compared. RESULTS: Five hundred ninety-seven (20.5%) of 2910 women were obese. Obese women had fewer spontaneous preterm births at < 37 weeks of gestation (6.2% vs 11.2%; P < .001) and at < 34 weeks of gestation (1.5% vs 3.5%; P = .012). Women with a body mass index of < 19 kg/m2 had 16.6% spontaneous preterm birth, with a body mass index of 19 to 24.9 kg/m 2 had 11.3% spontaneous preterm birth, with a body mass index of 25 to 29.9 kg/m2 had 8.1% spontaneous preterm birth, with a body mass index of 30 to 34.9 kg/m2 had 7.1% spontaneous preterm birth, and with a body mass index of > or = 35 kg/m2 had 5.2% spontaneous preterm birth (P < .0001). Indicated delivery was responsible for an increasing proportion of preterm births with increasing body mass index (P = .001). Obese women had lower rates of cervical length < 25 mm (5% vs 8%; P = .012). Multivariable regression analysis confirmed a lower rate of spontaneous preterm birth in obese gravid women (odds ratio, 0.57; 95% CI, 0.39-0.83; P = .003). CONCLUSION: Obesity before pregnancy is associated with a lower rate of spontaneous preterm birth.

Serum homocysteine levels after preterm premature rupture of the membranes.

OBJECTIVE: Preterm premature rupture of the membranes (PPROM) is believed to be caused, in part, by abnormalities of collagen and increased levels of oxidative stress. Elevated homocysteine levels have been shown to induce these same pathophysiologic changes. We tested the hypothesis that serum homocysteine levels would be higher in women with PPROM when compared with matched control women. STUDY DESIGN: A secondary analysis derived from 2 previously completed studies performed in the National Institutes of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. We identified 99 study cases with PPROM (24 to 32 weeks' gestation) and matched them with 99 asymptomatic control women from an observational study of preterm birth prediction. Cases and control women were matched for race, gestational age at sampling, and MFMU Network center. Serum homocysteine levels were determined by immunoassay in batch fashion by personnel masked to study arm and clinical outcomes. Serum homocysteine levels were compared between groups, as were the baseline characteristics of maternal age, cigarette smoking, nulliparity, infections during pregnancy, and body mass index (BMI) <19.8 kg/m 2. Serum homocysteine levels were dichotomized as >75th, 90th, and 95th %ile of control women, and the likelihood of elevated homocysteine levels was determined in women who smoked, had a BMI <19.8 kg/m 2, or who had PPROM. Statistical analyses included the Wilcoxon rank sum, chi-square, and Pearson correlation coefficient, where appropriate. Baseline characteristics were controlled with a logistic regression model. RESULTS: Serum homocysteine levels measured in patients with PPROM were not significantly different from matched control women: median and (25th to 75th %ile): 4.9 (3.5-6.2) vs 4.8 (3.9-6.2 micromol/L), P =.73. In our population, neither the number of cigarettes smoked ( r = -0.08, P =.57), nor BMI ( r = -0.08, P =.24) correlated with serum homocysteine levels. The strongest association was seen in women with PPROM having serum homocysteine levels >95th %ile of control women (odds ratio [OR] 2.7, P =.10). After adjusting for baseline characteristics, no correlation between serum homocysteine level and the presence of PPROM was seen, OR 1.0 (.9-1.1); P =.99. CONCLUSION: Women presenting with PPROM did not have significantly increased serum homocysteine levels when compared with control women.

The relationship of asthma medication use to perinatal outcomes.

BACKGROUND: Maternal asthma has been reported to increase the risk of preeclampsia, preterm deliveries, and lower-birth-weight infants, but the mechanisms of this effect are not defined. OBJECTIVE: We sought to evaluate the relationship between the use of contemporary asthma medications and adverse perinatal outcomes. METHODS: Asthmatic patients were recruited from the 16 centers of the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network from December 1994 through February 2000. Gestational medication use was determined on the basis of patient history at enrollment and at monthly visits during pregnancy. Perinatal data were obtained at postpartum chart reviews. Perinatal outcome variables included gestational hypertension, preterm births, low-birth-weight infants, small-for-gestational-age infants, and major malformations. RESULTS: The final cohort included 2123 asthmatic participants. No significant relationships were found between the use of inhaled beta-agonists (n=1828), inhaled corticosteroids (n=722), or theophylline (n=273) and adverse perinatal outcomes. After adjusting for demographic and asthma severity covariates, oral corticosteroid use was significantly associated with both preterm birth at less than 37 weeks' gestation (odds ratio, 1.54; 95% CI, 1.02-2.33) and low birth weight of less than 2500 g (odds ratio, 1.80; 95% CI, 1.13-2.88). CONCLUSIONS: Use of inhaled beta-agonists, inhaled steroids, and theophylline do not appear to increase perinatal risks in pregnant asthmatic women. The mechanism of the association between maternal oral corticosteroid use and prematurity remains to be determined.

Asthma during pregnancy.

OBJECTIVE: To determine neonatal and maternal outcomes stratified by asthma severity during pregnancy by using the 1993 National Asthma Education Program Working Group on Asthma and Pregnancy definitions of asthma severity. The primary hypothesis was that moderate or severe asthmatics would have an increased incidence of delivery at <32 weeks of gestation compared with nonasthmatic controls. METHODS: This was a multicenter, prospective, observational cohort study conducted over 4 years at 16 university hospital centers. Asthma severity was defined according to the National Asthma Education Program Working Group on Asthma and Pregnancy classification and modified to include medication requirements. This study had 80% power to detect a 2- to 3-fold increase in delivery less than 32 weeks of gestation among the cohort with the moderate or severe asthma compared with controls. Secondary outcome measures included obstetrical and neonatal outcomes. RESULTS: The final analysis included 881 nonasthmatic controls, 873 with mild asthma, 814 with moderate, and 52 with severe asthma. There were no significant differences in the rates of preterm delivery less than 32 weeks (moderate or severe 3.0%, mild 3.4%, controls 3.3%; P =.873) or less than 37 weeks of gestation. There were no significant differences for neonatal outcomes except discharge diagnosis of neonatal sepsis among the mild group compared with controls, adjusted odds ratio 2.9, 95% confidence interval 1.2, 6.8. There were no significant differences for maternal complications except for an increase in overall cesarean delivery rate among the moderate-or-severe group compared with controls (adjusted odds ratio 1.4, 95% confidence interval 1.1, 1.8). CONCLUSION: Asthma was not associated with a significant increase in preterm delivery or other adverse perinatal outcomes other than a discharge diagnosis of neonatal sepsis. Cesarean delivery rate was increased among the cohort with moderate or severe asthma. LEVEL OF EVIDENCE: II-2

Asthma morbidity during pregnancy can be predicted by severity classification.

BACKGROUND: The 1993 National Asthma Education Program Working Group on Asthma and Pregnancy defined asthma severity as mild, moderate, or severe on the basis of symptoms and spirometry, but no studies have evaluated the relationship between this classification system and subsequent asthma morbidity during pregnancy. OBJECTIVE: The objective of this study was to evaluate the relationship between asthma severity classification during pregnancy and gestational asthma exacerbations. METHODS: Asthma severity was defined according to the 1993 classification, adjusted to include medication requirements, in a volunteer sample of 1739 pregnant asthmatic patients who were less than 26 weeks' gestation. RESULTS: Initial asthma classification (mild, moderate, or severe) was significantly related to subsequent asthma morbidity during pregnancy (hospitalizations, unscheduled visits, corticosteroid requirements, and asthma symptoms during labor and delivery). Exacerbations during pregnancy occurred in 12.6% of patients initially classified as mild, 25.7% of patients classified as moderate, and 51.9% of patients classified as severe (P <.001). Asthma morbidity was similar, whether patients were classified as moderate or severe by symptoms and spirometry or by medication requirement. Thirty percent of initially mild patients were reclassified as moderate-severe during pregnancy, and 23% of the initially moderate-severe patients were reclassified as mild later in pregnancy; asthma morbidity in these patients changed accordingly. CONCLUSION: The National Asthma Education Program Working Group on Asthma and Pregnancy classification of asthma severity, adapted to include medication use, predicts subsequent asthma morbidity during pregnancy.

What we have learned regarding antibiotic therapy for the reduction of infant morbidity after preterm premature rupture of the membranes.

Preterm premature rupture of the membranes (pPROM) is responsible for approximately one third of the over 450,000 preterm births occurring in the United States annually. In this manuscript, we summarize the outcomes and analyses related to the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network (NICHD-MFMU) network multicenter trial of antibiotics to reduce infant morbidity after pPROM. Based on evident reduction in gestational age dependent and infectious infant morbidity, we provide the rationale for aggressive intravenous and oral, broad spectrum Ampicillin/Amoxicillin, and Erythromycin therapy during conservative management of pPROM before 32 weeks' gestation. We further review the histopathologic correlates to pPROM, to antibiotic treatment, and to perinatal outcome, and discuss the relationships between maternal and neonatal cytokine levels intercellular adhesion molecule, and other clinical and plasma markers regarding perinatal morbidity. The use and limitations of ultrasound and vaginally collected amniotic fluid pulmonary maturity assessment are discussed.

Frequency of congenital varicella syndrome in a prospective cohort of 347 pregnant women.

OBJECTIVE: To estimate the rate of congenital varicella zoster virus syndrome in neonates born to women developing varicella zoster virus infections during pregnancy. METHODS: Pregnant women with clinical varicella zoster virus infection were enrolled at ten perinatal centers. Maternal and fetal immunoglobulin (Ig) G and IgM by fluorescent antibody confirmed 74.3% of cases. Specialists examined neonates at 0-6 months, 7-18 months, and 19-30 months after delivery to detect abnormalities of their eyes, hearing, and physical and developmental features. A hierarchical set of criteria was used to define congenital varicella syndrome. A jury of four investigators assigned the classification of all findings. RESULTS: In 362 women enrolled from 1993 to 1996, 15 had herpes zoster, and 347 had primary varicella zoster virus infection. Varicella zoster virus affected 140 women (38.7%) in the first trimester, 122 (33.7%) in the second trimester, and 100 (27.6%) in the third trimester. Five twin pairs were included. Only one case (0.4%) of definite congenital varicella syndrome was found, a 3360-g female infant having a left retinal macular lesion with typical skin scars after maternal varicella at 24 weeks. The maternal blood sample at birth was negative for IgG antibodies to toxoplasmosis and cytomegalovirus. Two cases involved fetal death at 20 weeks and fetal hydrops at 17 weeks after maternal varicella at 11 and 5 weeks, respectively. We found no cases of limb hypoplasia, microcephalus, or cataract. CONCLUSION: The frequency of congenital varicella syndrome is very low (0.4%) in a prospectively studied cohort. Eye examinations of exposed infants had a low yield.

The Preterm Prediction Study: the value of serum alkaline phosphatase, alpha-fetoprotein, plasma corticotropin-releasing hormone, and other serum markers for the prediction of spontaneous preterm birth.

OBJECTIVE: High levels of a number of analytes are found in maternal blood; alkaline phosphatase,alpha-fetoprotein, and corticotropin-releasing hormone have been associated with spontaneous preterm birth. We investigated the relationship between 8 potential blood markers and subsequent spontaneous preterm birth in asymptomatic pregnant women. STUDY DESIGN: We performed a nested case control study that involved 127 women who were enrolled in the preterm prediction study and who had a singleton spontaneous preterm birth at <35 weeks and 127 women who had a term birth and served as matched (age, parity, center) controls. Serum that was collected at 24 and 28 weeks was analyzed for alkaline phosphatase, alpha-fetoprotein, corticotropin-releasing hormone, and 5 other analytes. RESULTS: Alkaline phosphatase, alpha-fetoprotein, and corticotropin-releasing hormone, but not other analytes, were significantly elevated in pregnancies that ended in spontaneous preterm birth. For alkaline phosphatase at 24 weeks, the odds ratio for spontaneous preterm birth at <32 weeks was 6.8 (range, 1.4-32.8) and for spontaneous preterm birth at <35 weeks 5.1 (range, 1.7-15.6). Similar results were found at 28 weeks. For alpha-fetoprotein at 24 weeks, the odds ratio for spontaneous preterm birth at <32 weeks was 8.3 (range,2.2-30.9) and for spontaneous preterm birth at <35 weeks was 3.5 (range, 1.8-6.7). The levels at 28 weeks were still predictive but less so than at 24 weeks. Corticotropin-releasing hormone, at 28 weeks but not at 24 weeks, was predictive for spontaneous preterm birth at <35 weeks, with an odds ratio 3.4 (range, 1.0-10.9). CONCLUSION: Elevated alkaline phosphatase and alpha-fetoprotein are associated with subsequent spontaneous preterm birth in asymptomatic pregnant women at 24 and 28 weeks. Elevated corticotropin-releasing hormone levels at 28 weeks are associated with spontaneous preterm birth at <35 weeks.

Risk factors and outcome of varicella-zoster virus pneumonia in pregnant women.

To determine the factors associated with an increased risk of developing varicella-zoster virus (VZV) pneumonia during pregnancy, a case-control analysis was done in which 18 pregnant women with VZV pneumonia were compared with 72 matched control subjects. VZV infection was identified clinically, and VZV pneumonia was diagnosed by dyspnea and findings on chest radiographs. Of 347 pregnant women with VZV infection, 18 (5.2%) had pneumonia treated with acyclovir, and none died. Mean gestational age at rash onset was 25.8 plus minus 8.8 weeks for patients with pneumonia and 17.7 +/- 10.3 weeks for control subjects, which was not significant in the multivariable model. Women with VZV pneumonia were significantly more likely to be current smokers (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.6-16.7) and to have > or = 100 skin lesions (OR, 15.9; 95% CI, 1.9-130.2). Pregnant women with VZV infection may be more likely to develop varicella pneumonia if they are smokers or manifest > or = 100 skin lesions.