Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 2014
To evaluate the accuracy of sonographic classification of chorionicity in a large cohort of twins... more To evaluate the accuracy of sonographic classification of chorionicity in a large cohort of twins and investigate which factors may be associated with sonographic accuracy. We conducted a secondary analysis of a randomized trial of preterm birth prevention in twins. Sonographic classification of chorionicity was compared with pathologic examination of the placenta. Maternal (age, body mass index, diabetes, and hypertension), obstetric (prior cesarean delivery, gestational age at the first sonographic examination, and antepartum bleeding), and sonographic (oligohydramnios, polyhydramnios, and twin-twin transfusion syndrome) factors were assessed for their possible association with accuracy. A total of 545 twin sets in which chorionicity was classified by sonography before 20 weeks' gestation were included; 455 were dichorionic and 90 were monochorionic based on pathologic examination. Sonography misclassified 35 of 545 twin pregnancies (6.4%): 18 of 455 dichorionic twins (4.0%) a...
American Journal of Obstetrics and Gynecology, 2015
The primary aim of the &a... more The primary aim of the "Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be" is to determine maternal characteristics, which include genetic, physiologic response to pregnancy, and environmental factors that predict adverse pregnancy outcomes. Nulliparous women in the first trimester of pregnancy were recruited into an observational cohort study. Participants were seen at 3 study visits during pregnancy and again at delivery. We collected data from in-clinic interviews, take-home surveys, clinical measurements, ultrasound studies, and chart abstractions. Maternal biospecimens (serum, plasma, urine, cervicovaginal fluid) at antepartum study visits and delivery specimens (placenta, umbilical cord, cord blood) were collected, processed, and stored. The primary outcome of the study was defined as pregnancy ending at <37+0 weeks' gestation. Key study hypotheses involve adverse pregnancy outcomes of spontaneous preterm birth, preeclampsia, and fetal growth restriction. We recruited 10,037 women to the study. Basic characteristics of the cohort at screening are reported. The "Nulliparous Pregnancy Outcomes Study: monitoring…
Objective The aim of the study was to evaluate associations between fetal growth and weight at 2 ... more Objective The aim of the study was to evaluate associations between fetal growth and weight at 2 years in infants born preterm using a customized approach for birth weight. Study Design This is a secondary analysis of a multicenter trial that included a 2-year follow-up of children born prematurely. Customized birth weight percentiles were calculated using the Gardosi model for a U.S. population, and the relation between customized percentile and weight and height at 2 years (adjusted for gender using z-score) was determined using regression analysis and by comparing z-scores for children with birth weight <10th versus ≥10th percentile. Results Weight z-score at 2 years was significantly lower in the <10th than in the ≥10th percentile group (median [interquartile range, IQR]: -0.66 [-1.58, -0.01] vs. -0.23 [-1.05, 0.55]; p < 0.001), and remained after adjusting for maternal education (p < 0.001). A similar relationship was noted for height z-score between groups (median [IQR]: -0.56 [-1.29, 0.19] vs. -0.24 [-0.99, 0.37]; p < 0.001). Positive relationships between customized birth weight percentile and weight and height at 2 years were noted (p < 0.001 for both), but were not strong (R (2) = 0.04 and 0.02, respectively). Conclusion Customized birth weight percentile is a minor determinant of weight at 2 years among children born preterm.
American Journal of Obstetrics and Gynecology, 2000
Objective:This study was undertaken to determine the relationship among cervical lactoferrin conc... more Objective:This study was undertaken to determine the relationship among cervical lactoferrin concentration, other cervical markers potentially related to infection, and spontaneous preterm birth.
American Journal of Obstetrics and Gynecology, 1995
OBJECTIVE: Our purpose was to determine the effect of ceftizoxime in the prolongation of pregnanc... more OBJECTIVE: Our purpose was to determine the effect of ceftizoxime in the prolongation of pregnancies receiving tocolysis for preterm labor.STUDY DESIGN: A prospective, randomized, double-blinded, placebo-controlled trial was conducted in patients with preterm labor between 24 and 35 weeks' gestation. A total of 545 patients with intact membranes and without chorioamnionitis who were receiving magnesium sulfate were screened. Exclusions were
American Journal of Obstetrics and Gynecology, 2015
OBJECTIVE: We sought to evaluate whether the presence of conditionspecific obstetric protocols wi... more OBJECTIVE: We sought to evaluate whether the presence of conditionspecific obstetric protocols within a hospital was associated with better maternal and neonatal outcomes.
American Journal of Obstetrics and Gynecology, 2015
The purpose of this study was to compare maternal and neonatal outcomes in nulliparous women with... more The purpose of this study was to compare maternal and neonatal outcomes in nulliparous women with nonmedically indicated inductions at term vs those expectantly treated. Data were obtained from maternal and neonatal charts for all deliveries on randomly selected days across 25 US hospitals over a 3-year period. A low-risk subset of nulliparous women with vertex nonanomalous singleton gestations who delivered 38 0/7 to 41 6/7 weeks were selected. Maternal and neonatal outcomes for nonmedically indicated induction within each week were compared with women who did not undergo nonmedically indicated induction during that week. Multivariable analysis was used to adjust for hospital, maternal age, race/ethnicity, body mass index, cigarette use, and insurance status. We found 31,169 women who met our criteria. Neonatal complications were either less frequent with nonmedically indicated induction or no different between groups. Nonmedically indicated induction was associated with less frequent peripartum infections (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.16-0.98) at 38 weeks of gestation and less frequent third- and fourth-degree lacerations (OR, 0.60; 95% CI, 0.42-0.86) and less frequent peripartum infections (OR, 0.66; 95% CI, 0.49-0.90) at 39 weeks of gestation. Nonmedically indicated induction was associated with a longer admission-to-delivery time by approximately 3-4 hours and increased odds of cesarean delivery at 38 (OR, 1.50; 95% CI, 1.08-2.08) and 40 weeks (OR, 1.30; 95% CI, 1.15-1.46) of gestation. At 39 weeks of gestation, nonmedically indicated induction is associated with lower maternal and neonatal morbidity than women who are expectantly treated.
This paper is the first in a three-part series on preterm birth, which is the leading cause of pe... more This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks' gestational age after: (1) spontaneous labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12-13% in the USA and 5-9% in many other developed countries; however, the rate of preterm birth has increased in many locations, predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple pregnancies. Common reasons for indicated preterm births include pre-eclampsia or eclampsia, and intrauterine growth restriction. Births that follow spontaneous preterm labour and PPROM-together called spontaneous preterm births-are regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race, periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.
Preterm birth has been difficult to study and prevent because of its complex syndromic nature. To... more Preterm birth has been difficult to study and prevent because of its complex syndromic nature. To identify phenotypes of preterm delivery syndrome in the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. A population-based, multiethnic, cross-sectional study conducted at 8 geographically demarcated sites in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States. A total of 60 058 births over a 12-month fixed period between April 27, 2009, and March 2, 2014. Of these, 53 871 had an ultrasonography estimate of gestational age, among which 5828 were preterm births (10.8%). Pregnancies were prospectively studied using a standardized data collection and online data management system. Newborns had anthropometric and clinical examinations using standardized methods and identical equipment and were followed up until hospital discharge. The main study outcomes were clusters of preterm phenotypes and for each cluster, we analyzed signs of presentation at hospital admission, admission rates for neonatal intensive care for 7 days or more, and neonatal mortality rates. Twelve preterm birth clusters were identified using our conceptual framework. Eleven consisted of combinations of conditions known to be associated with preterm birth, 10 of which were dominated by a single condition. However, the most common single cluster (30.0% of the total preterm cases; n = 1747) was not associated with any severe maternal, fetal, or placental condition that was clinically detectable based on the information available; within this cluster, many cases were caregiver initiated. Only 22% (n = 1284) of all the preterm births occurred spontaneously without any of these severe conditions. Maternal presentation on hospital admission, newborn anthropometry, and risk for death before hospital discharge or admission for 7 or more days to a neonatal intensive care unit, none of which were used to construct the clusters, also differed according to the identified phenotypes. The prevalence of preterm birth ranged from 8.2% in Muscat, Oman, and Oxford, England, to 16.6% in Seattle, Washington. We identified 12 preterm birth phenotypes associated with different patterns of neonatal outcomes. In 22% of all preterm births, parturition started spontaneously and was not associated with any of the phenotypic conditions considered. We believe these results contribute to an improved understanding of this complex syndrome and provide an empirical basis to focus research on a more homogenous set of phenotypes.
To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent c... more To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD). Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) < 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences. Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI. Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD.
This study aims to evaluate whether magnesium sulfate administration for neuroprotection prolongs... more This study aims to evaluate whether magnesium sulfate administration for neuroprotection prolongs latency in women with preterm premature rupture of membranes (PPROM) between 24 and 31(6/7) weeks' gestation. This is a secondary analysis of a randomized controlled trial of magnesium sulfate for prevention of cerebral palsy. Gravid women with a singleton pregnancy between 24 and 31(6/7) weeks' gestation with PPROM without evidence of labor were randomized to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour up to 12 hours, or placebo. Maternal outcomes for this analysis were delivery in less than 48 hours and in less than 7 days from randomization. Neonatal outcomes included a composite of respiratory distress syndrome, interventricular hemorrhage grades 3 or 4, periventricular leukomalacia, sepsis, necrotizing enterocolitis, retinopathy of prematurity, or death. A total of 1,259 women were included. The rate of delivery < 48 hours was not different in the magnesium sulfate and the placebo groups (22.2 and 20.7%, p = 0.51). Delivery < 7 days was similar between groups (55.4 and 51.4%, p = 0.16). Median latency was also similar between groups (median [interquartile range], 6.0 days [range, 2.4-13.8 days] and 6.6 days [range, 2.4-15.1 days], p = 0.29). Composite neonatal outcomes did not differ between groups. Magnesium sulfate administration given for neuroprotection in women with a singleton gestation with PPROM and without labor before 32 weeks does not impact latency.
American Journal of Obstetrics and Gynecology, 1997
Objectives: Our purpose was to investigate the relationship between expression of cyclooxygenase-... more Objectives: Our purpose was to investigate the relationship between expression of cyclooxygenase-2 and inducible nitric oxide synthase genes after labor induction with bacterial lipopolysaccharide in a murine model of preterm parturition. Study Design: Pregnant C57Bl/6 mice were given Escherichia coli lipopolysaccharide (20 μg per mouse) by intraperitoneal injection on day 16 of gestation, and the animals were followed up for
Journal of Maternal-Fetal and Neonatal Medicine, 2006
Objective. Antibiotic administration has become part of the standard of care for patients with pr... more Objective. Antibiotic administration has become part of the standard of care for patients with preterm premature rupture of membranes (PROM). Yet, the natural history of intrauterine infection/inflammation during antibiotic therapy remains largely unknown. This study was conducted to determine if antibiotic administration to the mother eradicates intra-amniotic infection and/or reduces the frequency of intra-amniotic inflammation, a risk factor for impending preterm labor/delivery and adverse neonatal outcome. Methods. A subset of patients with preterm PROM admitted to our institution underwent amniocenteses before and after antibiotic administration in order to guide clinical management. Amniotic fluid analysis consisted of a Gram stain, culture for aerobic and anaerobic bacteria as well as genital mycoplasmas, and amniotic fluid white blood cell (WBC) count. Microbial invasion of the amniotic cavity (MIAC) was defined as a positive amniotic fluid culture. Intra-amniotic inflammation was defined as an amniotic fluid WBC count 100/mm 3 . Patients were given antibiotics and steroids after the 24 th week of gestation. Antibiotic treatment consisted of ampicillin and erythromycin for 7 days for patients without evidence of intra-amniotic inflammation or MIAC, and ceftriaxone, clindamycin and erythromycin for 10-14 days for those with intra-amniotic inflammation or MIAC. Results. Forty-six patients with preterm PROM whose first amniocentesis was performed between 18 and 32 weeks (median 27.4 weeks) were included in the study. The overall prevalence of intra-amniotic inflammation in the first amniocentesis was 39% (18/46). Seven had a positive amniotic fluid culture for microorganisms. At the time of the second amniocentesis, six of the seven patients with a positive amniotic fluid culture had microorganisms. Of 18 patients with intra-amniotic inflammation at admission, only three showed no evidence of inflammation after antibiotic treatment. Among patients with no evidence of intra-amniotic inflammation at admission, 32% (9/28) developed inflammation despite therapy. Five of these nine patients had positive amniotic fluid cultures.
Group B streptococcal infection is the most common cause of neonatal sepsis and is responsible fo... more Group B streptococcal infection is the most common cause of neonatal sepsis and is responsible for significant neonatal morbidity and mortality. Group B streptococcus is also the causative agent in 50,000 maternal infections per year. Approximately 30% of women have asymptomatic group B streptococcal colonization at some time during pregnancy, but the neonatal attack rate is only about 2 per 1,000 deliveries. Maternal and neonatal risk factors contribute to the rates of vertical transmission and symptomatic neonatal disease. Options that have been investigated for prevention of neonatal group B streptococcal disease include identification of at-risk pregnancies as well as antenatal, intrapartum, and neonatal treatment. The intrapartum treatment of women at risk for vertical transmission of group B streptococcus to their neonates unequivocally has been shown to decrease the rate of neonatal colonization. Practitioners should implement one of two strategies that incorporate intrapartum prophylaxis for prevention of perinatal group B disease.
When extremely preterm birth is anticipated, a reliable estimate of neonatal outcome is essential... more When extremely preterm birth is anticipated, a reliable estimate of neonatal outcome is essential for the parents and health care providers who face difficult management decisions. Estimates of birth weight and gestational age are most commonly used for this purpose. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (NICHD MFMU) Network performed an observational study of data available before delivery of infants with birth weights <1000 g. Ultrasonographic variables (estimated fetal weight, obstetrically estimated gestational age, femur length, and biparietal diameter) and clinical variables (maternal race, antenatal care, substance abuse, medical treatment, reason for delivery, fetal gender, and presentation) were studied as predictors of intrapartum stillbirth, neonatal death, survival to 120 days after birth or to discharge, and with markers of "serious" morbidity (high-grade intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, oxygen dependence at discharge or 120 days, and seizures). Survival without serious morbidity was considered "intact." Logistic regression was used to evaluate the influence of the obstetrician's opinion of viability and willingness to perform cesarean delivery for fetal distress, birth weight, growth, gender, presentation, and ethnicity on outcomes. Fetal femur length and estimated gestational age predicted survival better than did biparietal diameter or estimated fetal weight. Antenatal ultrasound and clinical data did not distinguish those infants who would suffer serious morbidity or be considered intact. Willingness to perform cesarean delivery was associated with increased likelihood of both survival and intact survival by virtually eliminating intrapartum stillbirth and reducing neonatal mortality. However, such practice was associated with an increased chance of serious morbidity among survivors below 800 g or 26 weeks'. Although obstetricians were willing to intervene for fetal indications in most cases by 24 weeks', willingness to perform cesarean delivery was associated with twice the risk for serious morbidity in survivors at that gestational age.
The Preterm Prediction Study conducted by the Maternal Fetal Medicine Network between 1993 and 19... more The Preterm Prediction Study conducted by the Maternal Fetal Medicine Network between 1993 and 1996 studied a large number of risk factors for preterm birth in more than 3,000 women at 10 centers. The goals of the study were to better understand the strength of one risk factor versus another and to explore interactions among the predictors looking for combinations of factors that were more predictive of preterm birth than any single factor used alone. The most potent factors that were associated with spontaneous preterm birth at <32 weeks were a positive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) and <10 th percentile cervical length (odds ratio, 5.8), and in serum, >90 th percentiles of ␣-fetoprotein (odds ratio, 8.3) and alkaline phosphatase (odds ratio, 6.8), and >75 th percentile of granulocyte colony-stimulating factor (odds ratio, 5.5). Results for spontaneous preterm birth at <35 weeks were generally similar but not as strong. The overlap among the strongest biologic markers for predicting spontaneous preterm birth was small. This suggests that the use of tests such as maternal ␣-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor as a group or adding their results to fetal fibronectin and cervical length test results may enhance our ability to predict spontaneous preterm birth and that the development of a multiple-marker test for spontaneous preterm birth is feasible.
The objectives of this study were to test the hypotheses that antibiotic therapy will alter the h... more The objectives of this study were to test the hypotheses that antibiotic therapy will alter the histologic appearance of fetal membranes in preterm premature rupture of membranes (pPROM), and that the membrane histology will demonstrate distinct differences between term and preterm rupture of membranes. We also wished to test interobserver variability of pathologists. Placental membranes were sampled from 268 women participating in a randomized placebo-controlled trial of antibiotic therapy for pPROM at 24-32 weeks of gestation (cases) and from 4 control groups who were not in the randomized trial: (1) preterm labor without pPROM (n = 21), (2) term labor (n = 65), (3) term PROM (n = 21), and (4) term cesarean section (n = 27). The cases and controls were scored for 40 histologic features by pathologists blinded to the identity of each sample (case or control). pPROM histology of samples from patients receiving antibiotics and those receiving placebo was compared using a chi-squared test and with control groups using logistic regression. There were no histological differences between pPROM cases treated with antibiotic and those receiving placebo, nor with respect to duration of membrane rupture greater or less than 48 h. Concordance among pathologists was low for features other than acute inflammation. Logistic regression analysis controlled for race and pathologist, and demonstrated that all of the control groups had significantly fewer common markers of acute inflammation when compared with the pPROM cases. This study suggests that histopathologic evidence of infection is seen more frequently with pPROM than in preterm or term controls. The histologic features used in this study cannot be used to determine the effectiveness of antibiotic therapy.
To estimate whether antibiotic treatment of asymptomatic women with a positive cervical or vagina... more To estimate whether antibiotic treatment of asymptomatic women with a positive cervical or vaginal fetal fibronectin test in the second trimester would reduce the risk of spontaneous preterm delivery.
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 2014
To evaluate the accuracy of sonographic classification of chorionicity in a large cohort of twins... more To evaluate the accuracy of sonographic classification of chorionicity in a large cohort of twins and investigate which factors may be associated with sonographic accuracy. We conducted a secondary analysis of a randomized trial of preterm birth prevention in twins. Sonographic classification of chorionicity was compared with pathologic examination of the placenta. Maternal (age, body mass index, diabetes, and hypertension), obstetric (prior cesarean delivery, gestational age at the first sonographic examination, and antepartum bleeding), and sonographic (oligohydramnios, polyhydramnios, and twin-twin transfusion syndrome) factors were assessed for their possible association with accuracy. A total of 545 twin sets in which chorionicity was classified by sonography before 20 weeks' gestation were included; 455 were dichorionic and 90 were monochorionic based on pathologic examination. Sonography misclassified 35 of 545 twin pregnancies (6.4%): 18 of 455 dichorionic twins (4.0%) a...
American Journal of Obstetrics and Gynecology, 2015
The primary aim of the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more The primary aim of the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; is to determine maternal characteristics, which include genetic, physiologic response to pregnancy, and environmental factors that predict adverse pregnancy outcomes. Nulliparous women in the first trimester of pregnancy were recruited into an observational cohort study. Participants were seen at 3 study visits during pregnancy and again at delivery. We collected data from in-clinic interviews, take-home surveys, clinical measurements, ultrasound studies, and chart abstractions. Maternal biospecimens (serum, plasma, urine, cervicovaginal fluid) at antepartum study visits and delivery specimens (placenta, umbilical cord, cord blood) were collected, processed, and stored. The primary outcome of the study was defined as pregnancy ending at &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;37+0 weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation. Key study hypotheses involve adverse pregnancy outcomes of spontaneous preterm birth, preeclampsia, and fetal growth restriction. We recruited 10,037 women to the study. Basic characteristics of the cohort at screening are reported. The &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Nulliparous Pregnancy Outcomes Study: monitoring…
Objective The aim of the study was to evaluate associations between fetal growth and weight at 2 ... more Objective The aim of the study was to evaluate associations between fetal growth and weight at 2 years in infants born preterm using a customized approach for birth weight. Study Design This is a secondary analysis of a multicenter trial that included a 2-year follow-up of children born prematurely. Customized birth weight percentiles were calculated using the Gardosi model for a U.S. population, and the relation between customized percentile and weight and height at 2 years (adjusted for gender using z-score) was determined using regression analysis and by comparing z-scores for children with birth weight &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10th versus ≥10th percentile. Results Weight z-score at 2 years was significantly lower in the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10th than in the ≥10th percentile group (median [interquartile range, IQR]: -0.66 [-1.58, -0.01] vs. -0.23 [-1.05, 0.55]; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), and remained after adjusting for maternal education (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). A similar relationship was noted for height z-score between groups (median [IQR]: -0.56 [-1.29, 0.19] vs. -0.24 [-0.99, 0.37]; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Positive relationships between customized birth weight percentile and weight and height at 2 years were noted (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001 for both), but were not strong (R (2) = 0.04 and 0.02, respectively). Conclusion Customized birth weight percentile is a minor determinant of weight at 2 years among children born preterm.
American Journal of Obstetrics and Gynecology, 2000
Objective:This study was undertaken to determine the relationship among cervical lactoferrin conc... more Objective:This study was undertaken to determine the relationship among cervical lactoferrin concentration, other cervical markers potentially related to infection, and spontaneous preterm birth.
American Journal of Obstetrics and Gynecology, 1995
OBJECTIVE: Our purpose was to determine the effect of ceftizoxime in the prolongation of pregnanc... more OBJECTIVE: Our purpose was to determine the effect of ceftizoxime in the prolongation of pregnancies receiving tocolysis for preterm labor.STUDY DESIGN: A prospective, randomized, double-blinded, placebo-controlled trial was conducted in patients with preterm labor between 24 and 35 weeks' gestation. A total of 545 patients with intact membranes and without chorioamnionitis who were receiving magnesium sulfate were screened. Exclusions were
American Journal of Obstetrics and Gynecology, 2015
OBJECTIVE: We sought to evaluate whether the presence of conditionspecific obstetric protocols wi... more OBJECTIVE: We sought to evaluate whether the presence of conditionspecific obstetric protocols within a hospital was associated with better maternal and neonatal outcomes.
American Journal of Obstetrics and Gynecology, 2015
The purpose of this study was to compare maternal and neonatal outcomes in nulliparous women with... more The purpose of this study was to compare maternal and neonatal outcomes in nulliparous women with nonmedically indicated inductions at term vs those expectantly treated. Data were obtained from maternal and neonatal charts for all deliveries on randomly selected days across 25 US hospitals over a 3-year period. A low-risk subset of nulliparous women with vertex nonanomalous singleton gestations who delivered 38 0/7 to 41 6/7 weeks were selected. Maternal and neonatal outcomes for nonmedically indicated induction within each week were compared with women who did not undergo nonmedically indicated induction during that week. Multivariable analysis was used to adjust for hospital, maternal age, race/ethnicity, body mass index, cigarette use, and insurance status. We found 31,169 women who met our criteria. Neonatal complications were either less frequent with nonmedically indicated induction or no different between groups. Nonmedically indicated induction was associated with less frequent peripartum infections (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.16-0.98) at 38 weeks of gestation and less frequent third- and fourth-degree lacerations (OR, 0.60; 95% CI, 0.42-0.86) and less frequent peripartum infections (OR, 0.66; 95% CI, 0.49-0.90) at 39 weeks of gestation. Nonmedically indicated induction was associated with a longer admission-to-delivery time by approximately 3-4 hours and increased odds of cesarean delivery at 38 (OR, 1.50; 95% CI, 1.08-2.08) and 40 weeks (OR, 1.30; 95% CI, 1.15-1.46) of gestation. At 39 weeks of gestation, nonmedically indicated induction is associated with lower maternal and neonatal morbidity than women who are expectantly treated.
This paper is the first in a three-part series on preterm birth, which is the leading cause of pe... more This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestational age after: (1) spontaneous labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12-13% in the USA and 5-9% in many other developed countries; however, the rate of preterm birth has increased in many locations, predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple pregnancies. Common reasons for indicated preterm births include pre-eclampsia or eclampsia, and intrauterine growth restriction. Births that follow spontaneous preterm labour and PPROM-together called spontaneous preterm births-are regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race, periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.
Preterm birth has been difficult to study and prevent because of its complex syndromic nature. To... more Preterm birth has been difficult to study and prevent because of its complex syndromic nature. To identify phenotypes of preterm delivery syndrome in the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. A population-based, multiethnic, cross-sectional study conducted at 8 geographically demarcated sites in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States. A total of 60 058 births over a 12-month fixed period between April 27, 2009, and March 2, 2014. Of these, 53 871 had an ultrasonography estimate of gestational age, among which 5828 were preterm births (10.8%). Pregnancies were prospectively studied using a standardized data collection and online data management system. Newborns had anthropometric and clinical examinations using standardized methods and identical equipment and were followed up until hospital discharge. The main study outcomes were clusters of preterm phenotypes and for each cluster, we analyzed signs of presentation at hospital admission, admission rates for neonatal intensive care for 7 days or more, and neonatal mortality rates. Twelve preterm birth clusters were identified using our conceptual framework. Eleven consisted of combinations of conditions known to be associated with preterm birth, 10 of which were dominated by a single condition. However, the most common single cluster (30.0% of the total preterm cases; n = 1747) was not associated with any severe maternal, fetal, or placental condition that was clinically detectable based on the information available; within this cluster, many cases were caregiver initiated. Only 22% (n = 1284) of all the preterm births occurred spontaneously without any of these severe conditions. Maternal presentation on hospital admission, newborn anthropometry, and risk for death before hospital discharge or admission for 7 or more days to a neonatal intensive care unit, none of which were used to construct the clusters, also differed according to the identified phenotypes. The prevalence of preterm birth ranged from 8.2% in Muscat, Oman, and Oxford, England, to 16.6% in Seattle, Washington. We identified 12 preterm birth phenotypes associated with different patterns of neonatal outcomes. In 22% of all preterm births, parturition started spontaneously and was not associated with any of the phenotypic conditions considered. We believe these results contribute to an improved understanding of this complex syndrome and provide an empirical basis to focus research on a more homogenous set of phenotypes.
To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent c... more To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD). Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences. Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI. Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD.
This study aims to evaluate whether magnesium sulfate administration for neuroprotection prolongs... more This study aims to evaluate whether magnesium sulfate administration for neuroprotection prolongs latency in women with preterm premature rupture of membranes (PPROM) between 24 and 31(6/7) weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation. This is a secondary analysis of a randomized controlled trial of magnesium sulfate for prevention of cerebral palsy. Gravid women with a singleton pregnancy between 24 and 31(6/7) weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation with PPROM without evidence of labor were randomized to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour up to 12 hours, or placebo. Maternal outcomes for this analysis were delivery in less than 48 hours and in less than 7 days from randomization. Neonatal outcomes included a composite of respiratory distress syndrome, interventricular hemorrhage grades 3 or 4, periventricular leukomalacia, sepsis, necrotizing enterocolitis, retinopathy of prematurity, or death. A total of 1,259 women were included. The rate of delivery &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 48 hours was not different in the magnesium sulfate and the placebo groups (22.2 and 20.7%, p = 0.51). Delivery &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 7 days was similar between groups (55.4 and 51.4%, p = 0.16). Median latency was also similar between groups (median [interquartile range], 6.0 days [range, 2.4-13.8 days] and 6.6 days [range, 2.4-15.1 days], p = 0.29). Composite neonatal outcomes did not differ between groups. Magnesium sulfate administration given for neuroprotection in women with a singleton gestation with PPROM and without labor before 32 weeks does not impact latency.
American Journal of Obstetrics and Gynecology, 1997
Objectives: Our purpose was to investigate the relationship between expression of cyclooxygenase-... more Objectives: Our purpose was to investigate the relationship between expression of cyclooxygenase-2 and inducible nitric oxide synthase genes after labor induction with bacterial lipopolysaccharide in a murine model of preterm parturition. Study Design: Pregnant C57Bl/6 mice were given Escherichia coli lipopolysaccharide (20 μg per mouse) by intraperitoneal injection on day 16 of gestation, and the animals were followed up for
Journal of Maternal-Fetal and Neonatal Medicine, 2006
Objective. Antibiotic administration has become part of the standard of care for patients with pr... more Objective. Antibiotic administration has become part of the standard of care for patients with preterm premature rupture of membranes (PROM). Yet, the natural history of intrauterine infection/inflammation during antibiotic therapy remains largely unknown. This study was conducted to determine if antibiotic administration to the mother eradicates intra-amniotic infection and/or reduces the frequency of intra-amniotic inflammation, a risk factor for impending preterm labor/delivery and adverse neonatal outcome. Methods. A subset of patients with preterm PROM admitted to our institution underwent amniocenteses before and after antibiotic administration in order to guide clinical management. Amniotic fluid analysis consisted of a Gram stain, culture for aerobic and anaerobic bacteria as well as genital mycoplasmas, and amniotic fluid white blood cell (WBC) count. Microbial invasion of the amniotic cavity (MIAC) was defined as a positive amniotic fluid culture. Intra-amniotic inflammation was defined as an amniotic fluid WBC count 100/mm 3 . Patients were given antibiotics and steroids after the 24 th week of gestation. Antibiotic treatment consisted of ampicillin and erythromycin for 7 days for patients without evidence of intra-amniotic inflammation or MIAC, and ceftriaxone, clindamycin and erythromycin for 10-14 days for those with intra-amniotic inflammation or MIAC. Results. Forty-six patients with preterm PROM whose first amniocentesis was performed between 18 and 32 weeks (median 27.4 weeks) were included in the study. The overall prevalence of intra-amniotic inflammation in the first amniocentesis was 39% (18/46). Seven had a positive amniotic fluid culture for microorganisms. At the time of the second amniocentesis, six of the seven patients with a positive amniotic fluid culture had microorganisms. Of 18 patients with intra-amniotic inflammation at admission, only three showed no evidence of inflammation after antibiotic treatment. Among patients with no evidence of intra-amniotic inflammation at admission, 32% (9/28) developed inflammation despite therapy. Five of these nine patients had positive amniotic fluid cultures.
Group B streptococcal infection is the most common cause of neonatal sepsis and is responsible fo... more Group B streptococcal infection is the most common cause of neonatal sepsis and is responsible for significant neonatal morbidity and mortality. Group B streptococcus is also the causative agent in 50,000 maternal infections per year. Approximately 30% of women have asymptomatic group B streptococcal colonization at some time during pregnancy, but the neonatal attack rate is only about 2 per 1,000 deliveries. Maternal and neonatal risk factors contribute to the rates of vertical transmission and symptomatic neonatal disease. Options that have been investigated for prevention of neonatal group B streptococcal disease include identification of at-risk pregnancies as well as antenatal, intrapartum, and neonatal treatment. The intrapartum treatment of women at risk for vertical transmission of group B streptococcus to their neonates unequivocally has been shown to decrease the rate of neonatal colonization. Practitioners should implement one of two strategies that incorporate intrapartum prophylaxis for prevention of perinatal group B disease.
When extremely preterm birth is anticipated, a reliable estimate of neonatal outcome is essential... more When extremely preterm birth is anticipated, a reliable estimate of neonatal outcome is essential for the parents and health care providers who face difficult management decisions. Estimates of birth weight and gestational age are most commonly used for this purpose. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (NICHD MFMU) Network performed an observational study of data available before delivery of infants with birth weights <1000 g. Ultrasonographic variables (estimated fetal weight, obstetrically estimated gestational age, femur length, and biparietal diameter) and clinical variables (maternal race, antenatal care, substance abuse, medical treatment, reason for delivery, fetal gender, and presentation) were studied as predictors of intrapartum stillbirth, neonatal death, survival to 120 days after birth or to discharge, and with markers of "serious" morbidity (high-grade intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, oxygen dependence at discharge or 120 days, and seizures). Survival without serious morbidity was considered "intact." Logistic regression was used to evaluate the influence of the obstetrician's opinion of viability and willingness to perform cesarean delivery for fetal distress, birth weight, growth, gender, presentation, and ethnicity on outcomes. Fetal femur length and estimated gestational age predicted survival better than did biparietal diameter or estimated fetal weight. Antenatal ultrasound and clinical data did not distinguish those infants who would suffer serious morbidity or be considered intact. Willingness to perform cesarean delivery was associated with increased likelihood of both survival and intact survival by virtually eliminating intrapartum stillbirth and reducing neonatal mortality. However, such practice was associated with an increased chance of serious morbidity among survivors below 800 g or 26 weeks'. Although obstetricians were willing to intervene for fetal indications in most cases by 24 weeks', willingness to perform cesarean delivery was associated with twice the risk for serious morbidity in survivors at that gestational age.
The Preterm Prediction Study conducted by the Maternal Fetal Medicine Network between 1993 and 19... more The Preterm Prediction Study conducted by the Maternal Fetal Medicine Network between 1993 and 1996 studied a large number of risk factors for preterm birth in more than 3,000 women at 10 centers. The goals of the study were to better understand the strength of one risk factor versus another and to explore interactions among the predictors looking for combinations of factors that were more predictive of preterm birth than any single factor used alone. The most potent factors that were associated with spontaneous preterm birth at <32 weeks were a positive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) and <10 th percentile cervical length (odds ratio, 5.8), and in serum, >90 th percentiles of ␣-fetoprotein (odds ratio, 8.3) and alkaline phosphatase (odds ratio, 6.8), and >75 th percentile of granulocyte colony-stimulating factor (odds ratio, 5.5). Results for spontaneous preterm birth at <35 weeks were generally similar but not as strong. The overlap among the strongest biologic markers for predicting spontaneous preterm birth was small. This suggests that the use of tests such as maternal ␣-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor as a group or adding their results to fetal fibronectin and cervical length test results may enhance our ability to predict spontaneous preterm birth and that the development of a multiple-marker test for spontaneous preterm birth is feasible.
The objectives of this study were to test the hypotheses that antibiotic therapy will alter the h... more The objectives of this study were to test the hypotheses that antibiotic therapy will alter the histologic appearance of fetal membranes in preterm premature rupture of membranes (pPROM), and that the membrane histology will demonstrate distinct differences between term and preterm rupture of membranes. We also wished to test interobserver variability of pathologists. Placental membranes were sampled from 268 women participating in a randomized placebo-controlled trial of antibiotic therapy for pPROM at 24-32 weeks of gestation (cases) and from 4 control groups who were not in the randomized trial: (1) preterm labor without pPROM (n = 21), (2) term labor (n = 65), (3) term PROM (n = 21), and (4) term cesarean section (n = 27). The cases and controls were scored for 40 histologic features by pathologists blinded to the identity of each sample (case or control). pPROM histology of samples from patients receiving antibiotics and those receiving placebo was compared using a chi-squared test and with control groups using logistic regression. There were no histological differences between pPROM cases treated with antibiotic and those receiving placebo, nor with respect to duration of membrane rupture greater or less than 48 h. Concordance among pathologists was low for features other than acute inflammation. Logistic regression analysis controlled for race and pathologist, and demonstrated that all of the control groups had significantly fewer common markers of acute inflammation when compared with the pPROM cases. This study suggests that histopathologic evidence of infection is seen more frequently with pPROM than in preterm or term controls. The histologic features used in this study cannot be used to determine the effectiveness of antibiotic therapy.
To estimate whether antibiotic treatment of asymptomatic women with a positive cervical or vagina... more To estimate whether antibiotic treatment of asymptomatic women with a positive cervical or vaginal fetal fibronectin test in the second trimester would reduce the risk of spontaneous preterm delivery.
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