Cervical funneling or intra-amniotic debris and preterm birth in nulliparous women with midtrimester cervical length less than 30 mm.

OBJECTIVE: To evaluate whether the presence of cervical funneling or intra-amniotic debris identified in the second trimester is associated with a higher rate of preterm birth (PTB) in asymptomatic nulliparous pregnant women with a midtrimester cervical length (CL) less than 30 mm (i.e. below the 10th percentile). METHODS: This was a secondary cohort analysis of data from a multicenter trial in nulliparous women between 16 and 22 weeks' gestation with a singleton gestation and CL less than 30 mm on transvaginal ultrasound, randomized to treatment with either 17-alpha-hydroxyprogesterone caproate or placebo. Sonographers were centrally certified in CL measurement, as well as in identification of intra-amniotic debris and cervical funneling. Univariable and multivariable analysis was performed to assess the associations of cervical funneling and intra-amniotic debris with PTB. RESULTS: Of the 657 women randomized, 112 (17%) had cervical funneling only, 33 (5%) had intra-amniotic debris only and 45 (7%) had both on second-trimester ultrasound. Women with either of these findings had a shorter median CL than those without (21.0 mm vs 26.4 mm; P < 0.001). PTB prior to 37 weeks was more likely in women with cervical funneling (37% vs 21%; odds ratio (OR), 2.2 (95% CI, 1.5-3.3)) or intra-amniotic debris (35% vs 23%; OR, 1.7 (95% CI, 1.1-2.9)). Results were similar for PTB before 34 and before 32 weeks' gestation. After multivariable adjustment that included CL, PTB < 34 and < 32 weeks continued to be associated with the presence of intra-amniotic debris (adjusted OR (aOR), 1.85 (95% CI, 1.00-3.44) and aOR, 2.78 (95% CI, 1.42-5.45), respectively), but not cervical funneling (aOR, 1.17 (95% CI, 0.63-2.17) and aOR, 1.45 (95% CI, 0.71-2.96), respectively). CONCLUSIONS: Among asymptomatic nulliparous women with midtrimester CL less than 30 mm, the presence of intra-amniotic debris, but not cervical funneling, is associated with an increased risk for PTB before 34 and 32 weeks' gestation, independently of CL. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth: a case-control study.

OBJECTIVE: To determine whether ß2 -adrenoceptor (ß2 AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester. DESIGN: A case-control ancillary study to a multicentre randomised controlled trial. SETTING: Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. POPULATION: Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length. METHODS: Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. ß2 AR genotype was determined at positions encoding for amino acid residues 16 and 27. MAIN OUTCOME MEASURES: Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks. RESULTS: Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited. CONCLUSIONS: ß2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with ß2 AR genotype do not appear to involve a short cervix pathway.

Prenatal vitamin C and E supplementation in smokers is associated with reduced placental abruption and preterm birth: a secondary analysis.

OBJECTIVE: Smoking and pre-eclampsia (PE) are associated with increases in preterm birth, placental abruption and low birthweight. We evaluated the relationship between prenatal vitamin C and E (C/E) supplementation and perinatal outcomes by maternal self-reported smoking status focusing on outcomes known to be impacted by maternal smoking. DESIGN/SETTING/POPULATION: A secondary analysis of a multi-centre trial of vitamin C/E supplementation starting at 9-16 weeks in low-risk nulliparous women with singleton gestations. METHODS: We examined the effect of vitamin C/E by smoking status at randomisation using the Breslow-Day test for interaction. MAIN OUTCOME MEASURES: The trial's primary outcomes were PE and a composite outcome of pregnancy-associated hypertension (PAH) with serious adverse outcomes. Perinatal outcomes included preterm birth and abruption. RESULTS: There were no differences in baseline characteristics within subgroups (smokers versus nonsmokers) by vitamin supplementation status. The effect of prenatal vitamin C/E on the risk of PE (P = 0.66) or PAH composite outcome (P = 0.86) did not differ by smoking status. Vitamin C/E was protective for placental abruption in smokers (relative risk [RR] 0.09; 95% CI 0.00-0.87], but not in nonsmokers (RR 0.92; 95% CI 0.52-1.62) (P = 0.01), and for preterm birth in smokers (RR 0.76; 95% CI 0.58-0.99) but not in nonsmokers (RR 1.03; 95% CI 0.90-1.17) (P = 0.046). CONCLUSION: In this cohort of women, smoking was not associated with a reduction in PE or the composite outcome of PAH. Vitamin C/E supplementation appears to be associated with a reduction in placental abruption and preterm birth among smokers.

Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids.

OBJECTIVE: The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. STUDY DESIGN: This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. RESULTS: CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. CONCLUSION: Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.

Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population?

OBJECTIVE: To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. DESIGN: A nested case-control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. SETTING: A multicentre study in 16 academic medical centres in the USA. POPULATION: Low-risk nulliparous women. METHODS: Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. MAIN OUTCOME MEASURES: Change in PlGF, sFlt-1 and sEng. RESULTS: Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. CONCLUSION: Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia.

Vitamin D status and recurrent preterm birth: a nested case-control study in high-risk women.

OBJECTIVE: To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption. DESIGN: A nested case-control study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. SETTING: Fourteen academic health centres in the USA. POPULATION: Women with prior spontaneous preterm birth. METHODS: In 131 cases (preterm delivery at <35 weeks of gestation) and 134 term controls, we measured serum 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) from samples collected at baseline (16-22 weeks of gestation). Logistic regression models controlled for study centre, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment. MAIN OUTCOME MEASURES: Recurrent preterm birth at <37 and <32 weeks of gestation. RESULTS: The median mid-gestation serum 25(OH)D concentration was 67 nmol/l, and 27% had concentrations of <50 nmol/l. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR 1.33; 95% CI 0.48-3.70 for lowest versus highest quartiles). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/l, or higher, with those with <50 nmol/l generated an odds ratio of 0.80 (95% CI 0.38-1.69). Contrary to our expectation, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (-0.18, P < 0.01). CONCLUSIONS: In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth.

Differential expression of fibulin family proteins in the para-cervical weak zone and other areas of human fetal membranes.

OBJECTIVE: Human fetal membranes (FM) at term have been shown to contain a weak zone in the region overlying the cervix which exhibits characteristics of increased collagen remodeling and apoptosis. It has been hypothesized that the FM rupture initiation site is within this weak zone. Although the FM weak zone has been partially characterized, it is unclear what structural differences in the extracellular matrix result in its decreased rupture strength. A screen for differentially expressed proteins in the amnion of the weak zone versus other FM areas demonstrated that fibulin 1 was decreased. We investigated potential regional differences in all fibulin protein family members. METHODS: FM fibulins were localized by immunohistochemistry. Detected fibulins were screened by Western blot for differences in abundance in the amnion of the weak zone versus non-weak zone FM regions. Amnion epithelial and mesenchymal cells were also screened for fibulin production. RESULTS: Fibulins 1 and 5 were detected in the cytoplasm of and in a pericellular pattern surrounding all FM cells, and in a dense extracellular pattern in the amniotic compact zone. Fibulin 3 was detected within the cytoplasm of amnion epithelial and chorion trophoblast cells. Fibulins 2 and 4 were not detected. Fibulins 1, 3 and 5 demonstrated decreased abundance of 33%, 63% and 58% (all P<0.01) in amnion of the weak zone relative to other FM regions. Amnion cells produced all three detected fibulins. Furthermore, TNF inhibited amnion cell fibulin production in a dose dependent manner. CONCLUSION: Fibulins 1, 3 and 5 were localized coincident with major microfibrillar networks in amnion. Each showed decreased abundance in the amnion component of the FM weak zone. Amnion epithelial and mesenchymal cells produced all three fibulins and their abundance was inhibited by TNF. We speculate that the amnion microfibrillar layer undergoes significant remodeling with the development of the FM weak zone.

Preterm prediction study: comparison of the cervical score and Bishop score for prediction of spontaneous preterm delivery.

OBJECTIVE: To prospectively compare digital cervical score with Bishop score as a predictor of spontaneous preterm delivery before 35 weeks of gestation. METHODS: Data from a cohort of 2,916 singleton pregnancies enrolled in a multicenter preterm prediction study were available. Patients underwent digital cervical examinations at 22-24 and 26-29 weeks of gestation for calculation of Bishop score and cervical score. Relationships between Bishop score, cervical score, and spontaneous preterm delivery were assessed with multivariable logistic regression analysis, McNemar test, and receiver operating characteristic (ROC) curves to identify appropriate diagnostic thresholds and predictive capability. RESULTS: One hundred twenty-seven of 2,916 patients (4.4%) undergoing cervical examination at 22-24 weeks had a spontaneous preterm delivery before 35 weeks. Eighty-four of the 2,538 (3.3%) reexamined at 26-29 weeks also had spontaneous preterm delivery. Receiver operating characteristic curves indicated that optimal diagnostic thresholds for Bishop score were at least 4 at 22-24 weeks, at least 5 at 26-29 weeks, and less than 1.5 at both examinations for cervical score. At 22-24 weeks, areas under the ROC curve favored Bishop score. At 26-29 weeks, there was no significant difference in areas under the ROC curve; however, a cervical score less than 1.5 (sensitivity 35.7%, false positive rate 4.8%) was superior to a Bishop score of 5 or more (P<.001). CONCLUSION: Both cervical evaluations are associated with spontaneous preterm delivery in a singleton population; however, predictive capabilities for spontaneous preterm delivery were modest among women with low event prevalence. Although Bishop score performed better in the mid trimester, by 26-29 weeks a cervical score less than 1.5 was a better predictor of spontaneous preterm delivery before 35 weeks than a Bishop score of at least 5.

The physiology of fetal membrane rupture: insight gained from the determination of physical properties.

Premature rupture of the fetal membranes is a major cause of preterm birth and its associated infant morbidity and mortality. Recently, it has become clear that rupture of the fetal membranes, term or preterm, is not merely the result of the stretch and shear forces of uterine contractions, but is, in significant part, the consequence of a programmed weakening process. Work in the rat model has demonstrated that collagen remodeling, with activation of matrix metalloproteinases (MMPs), and apoptosis increase markedly in the amnion at end-gestation, suggesting that these processes are involved in fetal membrane weakening. We have developed fetal membrane strength testing equipment and a systematic tissue sampling methodology that has allowed us to demonstrate that term, non-labored, fetal membranes have a zone of weakness overlying the cervix, which contains biochemical markers of both collagen remodeling and apoptosis. These findings provide strong support for the concept of programmed fetal membrane weakening prior to labor. Our model has also been used to establish the physical properties of individual fetal membrane components (amnion, chorion), determine the sequence of events during the fetal membrane rupture process, and demonstrate that treatment of fetal membranes with TNF or IL-1beta, in vitro, induces weakness and the identical biochemical markers of collagen remodeling and apoptosis seen in the physiological weak zone. The ability to simultaneously correlate macroscopic physical properties with histological and biochemical fetal membrane characteristics, presents a unique perspective on the physiology of fetal membrane rupture.

Fetal startle response observed under ultrasonography: a good predictor of a reassuring biophysical profile.

OBJECTIVE: To correlate the vibroacoustic stimulus-evoked fetal startle response observed under ultrasonography with the subsequent biophysical profile (BPP) score. METHODS: Vibroacoustic stimulation was applied under ultrasound observation to gravidas who had a nonreactive fetal heart rate in the first 10 minutes of monitoring. Fetal startle response was defined as a sudden movement of fetal extremities in the 2 seconds following stimulus. Subsequently, nonstress testing was completed and a BPP performed on all women who required vibroacoustic stimulation. The presence or absence of a fetal startle response was compared with the observed BPP score. RESULTS: Two hundred tests were performed at 35.3 +/- 3.7 weeks. After the vibroacoustic stimulation, 70% of the nonreactive tracings became reactive. Mothers perceived the fetal startle response after vibroacoustic stimulus in 93% of cases. All cases with a fetal startle response after a vibroacoustic stimulation had a subsequent BPP score of 8 or more (negative predictive value of 100%). In addition, all patients with a nonreassuring BPP score were in the group of patients with absent fetal startle response. However, the positive predictive value of an absent fetal startle response for a subsequent BPP score of 6 or less was only 10%. CONCLUSION: This preliminary study suggests that the fetal startle response predicts a BPP score equal to or greater than 8. After the availability of larger studies supporting these findings, this test could be used as a rapid antepartum test to predict fetal well-being.

Obstetric antecedents to apparent stillbirth (Apgar score zero at 1 minute only).

OBJECTIVE: To identify antecedent risk factors for the delivery of an infant with an Apgar score of 0 at 1 minute who is subsequently successfully resuscitated. METHODS: Infants born between January 1986 and February 1999 with 1-minute Apgar score of 0 followed by 5-minute Apgar score above 0 were studied. Each eligible infant was randomly matched with two control infants, born in the same year, with 1-minute Apgar score greater than 0. Hospital records of their mothers were reviewed. The variables were compared between the groups by univariate analysis. Those factors demonstrating significant differences were then analyzed by logistic regression. P <.05 was considered statistically significant. RESULTS: Seventy-four of 81,603 infants (0.9:1000 births) born with an Apgar score of 0 at 1 minute only were compared with 148 control babies. Univariate analysis revealed significant differences between study and control group regarding: gestational age, abruptio placentae, preterm premature rupture of membranes, chorioamnionitis, preeclampsia, small-for-gestational age, male gender, bradycardia, and abnormal fetal heart rate (FHR) other than bradycardia, respectively. Logistic regression of these factors found gestational age, bradycardia, and abnormal FHR to be independent risk factors for the delivery of an apparent stillborn infant. After exclusion of FHR criteria, logistic regression found gestational age (odds ratio [OR] 0.8 per week), male gender (OR 2.5), preeclampsia (OR 3.9), and abruptio placentae (OR 13.6) to be independent risk factors for the delivery of an apparent stillborn infant. CONCLUSION: Preterm birth, male gender, preeclampsia, and abruptio placentae are independently associated with an increased risk of apparent stillbirth.

Risk factors for meconium aspiration syndrome.

OBJECTIVE: To identify potential predictors of meconium aspiration syndrome (MAS) in pregnancies complicated by moderate or thick meconium-stained amniotic fluid (AF). METHODS: In the period 1990-1993, 937 vertex singleton pregnancies with moderate or thick meconium-stained AF were delivered; of these, 39 neonates developed MAS and 898 did not. The two groups were compared retrospectively according to maternal findings, pregnancy outcome, and neonatal complications, using univariate analysis (P < .05 considered significant) and stepwise multiple logistic regression analysis to identify independent significant factors for prediction of MAS and to calculate odds ratios (OR) and 95% confidence intervals. RESULTS: The two groups had a similar mean gestational age at delivery and birth weight. They also had similar incidences of post-dates pregnancies, small and large for gestational age infants, and amnioinfusion use. Univariate analysis identified significant differences between the two groups in 13 variables, two of which were excluded from logistic analysis because of inadequate data. Logistic regression analysis identified only six variables with independent, statistically significant effects on MAS: admission for induction with nonreassuring fetal heart tracing (OR 6.9), need for endotracheal intubation and suctioning below the vocal cords (OR 4.9), 1-minute Apgar score of 4 or less (OR 3.1), present cesarean delivery (OR 3.0), and previous cesarean delivery (OR 2.5). Cigarette smoking was associated with a lower risk for MAS (OR 0.07). The presence of at least one of the five risk factors had a sensitivity of 92%, a specificity of 56%, a positive predictive value of 8%, and a negative predictive value of 99% for MAS. CONCLUSION: Considering the high negative predictive value of the test, infants without any risk factors will not develop MAS and thus can be safely allowed to room with their mothers. Furthermore, this model helps to identify infants who may benefit from 24-hour observation and in counseling women about the neonatal risk for developing MAS.

Evaluation of two rapid group B streptococcal antigen tests in labor and delivery patients.

Two rapid group B streptococcal antigen tests were compared with nonselective blood agar culture in 1062 unselected patients admitted to labor and delivery. Vaginal specimens taken from each patient on admission were used to perform each of two rapid tests and corresponding cultures. The rapid tests were the Streptex latex agglutination assay and the Equate Strep B test, which uses a solid-phase immunoassay. Overall, 105 patients (9.9%) had at least one positive culture. The sensitivities for the rapid tests were 15.1% for Streptex and 21.5% for Equate. Specificities were 99.3 and 98.7%, respectively. Sensitivity was minimally increased in the setting of ruptured membranes for both tests. Likewise, use of separate swabs for streaking the culture plate and performing the rapid test increased the sensitivity, but this was not significant for either test. In control experiments, the limit of sensitivity of both rapid tests was 5 x 10(6) colony-forming units. We conclude that at present, these tests are not sensitive enough for routine use in this type of clinical setting.

Obstetric characteristics among nulliparas under age 15.

OBJECTIVE: To describe and analyze the obstetric characteristics of adolescent women under 15 years of age. METHODS: A matched cohort design was used. The pregnancies of 261 nulliparous women under age 15 delivered at our institution between January 1990 and December 1992 were compared to 261 nulliparous controls aged 20-29, matched for race, infant gender, and year of delivery. Multiple gestation and delivery immediately after hospital admission were exclusion criteria. RESULTS: The number of antepartum admissions was identical (n = 35 in each group). There were no significant differences between the study and control groups in cervical dilatation at admission, frequency of labor induction (12.6% for each), epidural anesthesia (44.4 versus 49.4%), mean birth weight (2918 +/- 661 versus 2979 +/- 753 g), or preterm birth (24.1 versus 20.3%). Use of oxytocin was less common and magnesium sulfate more common in the adolescent group. Nevertheless, the duration of the active phase of labor and the rate of cesarean delivery were significantly lower in the adolescent group (4.5 +/- 2.7 versus 5.2 +/- 2.4 hours, P = .02; and 13.8 versus 25.3%, P = .001, respectively). The incidence of operative vaginal delivery was not different between the groups. Analysis of the data after controlling for fetal presentation, marital status, and insurance status did not alter these findings. Postpartum complications were similar. CONCLUSION: Pregnancy at the lower limit of reproductive age in an urban American population is not associated with an abnormal labor course, as is commonly believed.

The preterm prediction study: fetal fibronectin testing and spontaneous preterm birth. NICHD Maternal Fetal Medicine Units Network.

OBJECTIVE: To evaluate the presence of fetal fibronectin in the cervix and vagina as a screening test for spontaneous preterm birth. METHODS: Two thousand nine hundred twenty-nine women at ten centers were routinely screened every 2 weeks from 22-24 to 30 weeks for cervical and vaginal fetal fibronectin. A positive test was defined as a value equal to or greater than 50 ng/mL. The relation between a positive test at four gestational ages and spontaneous preterm birth at various intervals after the test was determined. RESULTS: In each testing period, 3-4% of the fetal fibronectin tests were positive. The correlation between cervical and vaginal fetal fibronectin at the same visit was always approximately 0.7 (P < .001), and that between cervical or vaginal fetal fibronectin in consecutive visits was between 0.17 and 0.25 (P < .001). The sensitivity of fetal fibronectin at 22-24 weeks to predict spontaneous preterm birth at less than 28 weeks was 0.63, and the relative risk for a positive versus negative test was 59. The specificity was always 96-98%, whereas the positive predictive value rose from 13% to 36% as the upper limit of the definition of preterm birth was increased from less than 28 to less than 37 weeks. The relative risk for spontaneous preterm birth after a positive fetal fibronectin test compared with a negative fetal fibronectin test varied substantially by testing period and by the definition of spontaneous preterm birth, but always remained greater than 4 and statistically significant. CONCLUSION: A positive cervical or vaginal fetal fibronectin test at 22-24 weeks predicted more than half of the spontaneous preterm births at less than 28 weeks (sensitivity 0.63). As the definition of spontaneous preterm birth was extended to include later gestational ages or when the fetal fibronectin test was performed later in pregnancy, the level of association between a positive fetal fibronectin test and spontaneous preterm birth, while remaining highly significant, tended to decrease. Although fetal fibronectin is an excellent test for predicting spontaneous preterm birth, we present no evidence that the use of this test will result in a reduction in spontaneous preterm birth.

Amniotic fluid index in hospitalized hypertensive patients managed expectantly.

OBJECTIVE: To determine the relationship between low amniotic fluid (AF) index and fetal growth retardation (FGR), fetal distress, and cesarean delivery in patients hospitalized for hypertensive disease, and to describe changes in AF status in relation to the severity of maternal disease. METHODS: The AF index in 142 hospitalized hypertensive patients was followed per an inpatient protocol with semi-weekly testing; medical records were reviewed to obtain delivery data. RESULTS: Fetal growth retardation was significantly associated with an AF index of 5.0 cm or less or 7.0 cm or less (P < .001) at initial assessment, with positive predictive values of 86 and 52%, respectively. However, the sensitivity of an AF index of 5.0 cm or less or 7.0 cm or less to detect FGR was limited (21 and 46%, respectively). Fetal distress and cesarean delivery were not associated with an AF index of 5.0 cm or less or 7.0 cm or less throughout observation in this cohort. Based upon a definition of oligohydramnios as an AF index of 7.0 cm or less, the AF status worsened from an initial normal value in 39% of patients whose final diagnosis was severe preeclampsia, versus only 14% of patients who were diagnosed as having mild disease. The AF index also normalized in ten patients who were originally diagnosed with oligohydramnios and admitted for expectant management. Only one of these women was diagnosed with severe preeclampsia. CONCLUSIONS: 1) Depending on the definition, the incidence of oligohydramnios ranges from 10-30% in hypertensive patients requiring hospitalization; 2) an AF index of 5.0 cm or less at initial evaluation predicts FGR but lacks sensitivity; 3) the AF status frequently changes with serial assessment, and these changes appear to be related to the severity of hypertensive disease; and 4) the frequency of the obstetric complications studied depends more upon the severity of hypertensive disease than on its potential effect of inducing oligohydramnios.

The impact of a policy of amnioinfusion for meconium-stained amniotic fluid.

OBJECTIVE: To evaluate the impact of an amnioinfusion (AI) policy for thick or moderate meconium-stained amniotic fluid (AF) on neonatal outcome, specifically meconium-aspiration syndrome and its complications. METHODS: We reviewed maternal and neonatal charts of 937 vertex, singleton pregnancies complicated by moderate or thick meconium-stained AF during a 3-year period. The patients were divided into groups according to whether AI was performed. Demographic characteristics, risk factors, mode of delivery, pregnancy outcome, and neonatal complications, including meconium-aspiration syndrome, were analyzed. RESULTS: Four hundred forty patients (47%) received AI (AI group); 497 (53%) did not, for the following reasons: imminent delivery (310 patients), occult meconium (141), or emergency cesarean delivery (46) (no-AI group). Our study did not show any reduction in the incidence of 5-minute Apgar scores of 7 or less (8 versus 7%), meconium below the vocal cords (28 versus 29%), meconium aspiration syndrome (4.5 versus 3.8%), ventilation requirement (4.3 versus 2.4%), or neonatal death (0.7 versus 0.2%) in the AI and no-AI groups, respectively. The AI group had a higher incidence of fetal heart rate abnormalities in labor (48 versus 31%, P < .05), instrumental delivery (15 versus 8%, P < .05), cesarean delivery (28 versus 17%, P < .001), and endometritis (21 versus 13%, P = .004). CONCLUSIONS: With the policy of routine AI for moderate or thick meconium-stained AF, AI was not clinically feasible in 53% of the cases. We were unable to demonstrate any improvement in neonatal outcome in those who received AI for moderate or thick meconium.

Preterm labor and preterm premature rupture of the membranes. Diagnosis and management.

Preterm delivery due to preterm labor and pPROM is responsible for most infant morbidity and mortality in the United States. The patient who presents with suspicious symptoms should undergo a thorough evaluation to confirm the diagnosis of either entity and identify a treatable cause. Determination of gestational age, fetal well-being, and the presence of intrauterine infection is a crucial step in subsequent management. Corticosteroid therapy has been demonstrated to be one of the most effective antenatal interventions to reduce infant morbidity and should be administered to patients with preterm labor, if feasible, when fetal pulmonary maturity is absent or undocumented. We recommend a similar protocol regarding gravidas with pPROM remote from term but recognize the need for further study in this area. Acute tocolytic therapy has been demonstrated to offer short-term benefit to enhance corticosteroid effect. However, all of the available tocolytic agents carry significant risks to the mother and fetus. As such, administration of these agents should be given only when the potential benefits outweigh the risks of administration. Evaluation for fetal pulmonary maturity and intrauterine infection, in concert with evaluation of gestational age-dependent risks of prematurity, may be helpful in determining whether tocolysis should be attempted. Adjunctive antibiotic administration has not been shown to reduce maternal or infant morbidity in the face of preterm labor. However, such treatment offers a reduction of chorioamnionitis, prolongation of latency, and a possible reduction of neonatal infectious and gestational age-dependent morbidity in the setting of pPROM remote from term. Finally, current guidelines recommend the administration of intrapartum GBS prophylaxis when preterm birth or prolonged membrane rupture is anticipated if GBS carrier status is unknown or positive. Intrapartum treatment with intravenous penicillin or ampicillin is appropriate.

Midtrimester premature rupture of the membranes.

Midtrimester premature rupture of the membranes is an uncommon adverse complication of pregnancy with an occurrence of approximately 0.65%. Significant perinatal and maternal morbidity includes pulmonary hypoplasia, restriction deformities, and sequelae of prematurity as well as maternal chorioamnionitis and endometritis. Moreover, 31% of survivors are affected by long-term complications such as chronic lung disease, neurological and developmental abnormalities. Fetal survival is evident with increasing latency and good residual amniotic fluid (largest vertical pocket > or = 2 cm). In this article, we review the relevant literature regarding prognosis, counseling, and management of the patient with membrane rupture in the midtrimester.

Antibiotic therapy for preterm premature rupture of the membranes.

Amniotic fluid studies and placental histopathological evaluation have confirmed the association between intrauterine infection and preterm premature rupture of the membranes (pPROM). This association is increasingly strong with pPROM at early gestational ages. The organisms associated with pPROM include a broad spectrum of aerobic and anaerobic gram-positive and gram-negative bacteria. In many cases, the patient presenting with pPROM will have overt intrauterine infection necessitating delivery. For those amenable to expectant management, the clinical course is usually of brief latency between membrane rupture and delivery. A number of well-designed prospective clinical trials have evaluated the utility of antibiotic treatment during the expectant management of pPROM. Taken together, these studies suggest broad spectrum antibiotic treatment of this population to enhance pregnancy prolongation, and to reduce maternal and neonatal infectious morbidity. There are some data suggesting the potential for a reduction in neonatal gestational age-dependent morbidity. We recommend aggressive adjunctive antibiotic treatment to prolong pregnancy and reduce morbidity in patients with pPROM, at gestations remote from term, when a significant improvement in neonatal outcome can anticipated with expectant management.