A history of prior preeclampsia as a risk factor for preterm birth.

OBJECTIVE: The objectives of this study are to evaluate the frequency and type of preterm birth (PTB) in women with prior preeclampsia and to compare neonatal outcomes between spontaneous PTB (SPTB) and medically indicated PTB (IPTB) groups. STUDY DESIGN: A secondary analysis of data in women with prior preeclampsia enrolled in a multicenter randomized trial for preeclampsia prevention. Delivery indications were categorized as SPTB and IPTB. Primary outcomes were rates of SPTB and IPTB by gestational age (GA). The rates of composite respiratory morbidity and neonatal intensive care unit (NICU) admission were compared between the PTB groups. RESULTS: Of the 606 pregnancies studied, 142 (23%) pregnancies were delivered at < 37 weeks: 67 (47%) pregnancies were caused by SPTB and 75 (53%) pregnancies were caused by IPTB. Of those who delivered preterm, 89 (63%) were in the late preterm period. The overall rate of the composite neonatal morbidity was 23%. The rates of composite neonatal morbidity, NICU admission, and perinatal death were not different between the groups. The frequency of small for gestational age (SGA) infants was higher in the IPTB group as compared with the SPTB group (21.3 vs. 1.4%, p = 0.01). CONCLUSION: Women with prior preeclampsia are at high risk for PTB (SPTB and IPTB), particularly late PTB, as well as increased risk for SGA.

Corticosteroids effect on caspase 3 expression in an in-vitro model of hypoxic brain cells.

OBJECTIVE: Effects of corticosteroids (CS) in the brain of growth-restricted fetus remain largely unstudied. We investigated if dexamethasone (DXM) exposure contributes to neuronal injury in an in-vitro model of neuronal cells under hypoxic conditions (surrogate for fetal growth restriction). STUDY DESIGN: U87 glioblastoma cells exposed to hypoxic or normoxic conditions for 10 h were incubated in the absence or presence of DXM for 48 h. Apoptosis as possible indicator of neurotoxicity was determined using a caspase-3-specific activity assay and western blotting. Caspase-3 was calculated as percentage of mean caspase-3 cleavage. Each experiment was performed in triplicate (n = 48). Caspase 3 activity in cell culture media was also measured by ELISA. RESULTS: Pro-caspase-3 (32 kDa) was expressed in culture, but activated 17 Kd caspase 3 was not expressed in cell lysate. There was no difference in ratio of caspase 3 activation when U87 cells were exposed to 10 v of hypoxia as compared to normoxia (0.46 ± 0.44 versus 0.37 ± 0.37). The pro-apoptotic effects of DXM were not increased by pre-exposure to hypoxia: (0.37 ± 0.37 versus 0.47 ± 0.40). CONCLUSION: The addition of DXM to hypoxic U87 cells had no additive or synergistic effects on the activation of caspase 3. Therefore, we speculate that the administration of CS in the setting of fetal growth restriction would not lead to increased apoptosis with potential neuronal injury.

The impact of medically indicated and spontaneous preterm birth among hypertensive women.

OBJECTIVE: To (1) describe the frequency of spontaneous preterm birth (SPTB) and medically indicated preterm birth (PTB) among women with chronic hypertension (CHTN) and (2) to evaluate differences in neonatal outcomes according to SPTB or medically indicated PTB. STUDY DESIGN: Retrospective analysis of a previously conducted multicenter randomized trial. Deliveries were categorized as SPTB or medically indicated and stratified by gestational ages (<37 weeks, 34 to 366/7 weeks, 30 to 336/7 weeks, < 30 weeks). Rates of neonatal intensive care unit admission, composite respiratory morbidity, perinatal mortality, and small for gestational age (SGA) were evaluated. RESULTS: Of 765 women, 32.2% (n = 246) delivered at < 37 weeks, of which 10.5% (n = 80) were SPTB and 21.6% (n = 166) were medically indicated. Fifty-nine percent of PTBs occurred in the late preterm period (n = 146). SGA was significantly more frequent among those with medically indicated PTB at < 30 weeks (p = 0.03). There were no other differences in adverse neonatal outcomes between medically indicated versus SPTB at any gestational age (p > 0.05). CONCLUSION: Nearly one-third of women with CHTN delivered preterm. The majority of PTBs were medically indicated and late preterm, but approximately one-third were due to SPTB.

Customized estimated fetal weight: a novel antenatal tool to diagnose abnormal fetal growth.

OBJECTIVE: We sought to apply customized standards to ultrasound-derived estimated fetal weight (EFW), and assess the frequency of abnormal growth when compared to population-based standards. We also evaluated association with adverse perinatal outcomes. STUDY DESIGN: This was a historical cohort using prenatal ultrasound examination data at ≥24 weeks over a 1-year period. Ultrasound-derived EFW and growth percentile (population-based EFW [popEFW]) were reported and compared to a customized EFW (custEFW). RESULTS: In all, 782 women met inclusion criteria. More fetuses were identified as small for gestational age (SGA) (15.1% vs 3.8%; P < .0001) and large for gestational age (LGA) (6.8% vs 1.7%; P < .0001) using custEFW, and adverse perinatal outcomes were more frequent among those identified by the custEFW compared to the popEFW. Both SGA and LGA diagnosed by custEFW were predictive of a neonatal SGA (positive likelihood ratio, 8.64) and LGA (positive likelihood ratio, 15.4). CONCLUSION: CustEFW was a better predictor of abnormal birthweight and adverse outcomes compared to traditional popEFW standards.

Relationship between fetal station and successful vaginal delivery in nulliparous women.

OBJECTIVE: To study the relationship between fetal station and successful vaginal delivery in nulliparous women. STUDY DESIGN: This was a secondary analysis from a previously reported trial of pulse oximetry. Vaginal delivery rates were evaluated and compared with respect to the fetal station. Spontaneous labor and induction of labor groups were evaluated separately. Multivariable logistic regression analysis was performed to adjust for confounding factors. RESULTS: Successful vaginal delivery was more frequent with an engaged vertex for spontaneous labor (86.2% versus 78.6%; p = 0.01) and induced labor (87.7% versus 66.1%; p < 0.01). After adjustment, engaged fetal vertex was not associated with vaginal delivery for spontaneous labor (odds ratio [OR] 1.5; 95% confidence interval [CI] 0.95 to 2.3; p = 0.08) or for women with induced labor (OR 2.2; 95% CI 0.96 to 5.1; p = 0.06). CONCLUSION: Among nulliparous women enrolled in the FOX randomized trial in spontaneous labor or for labor induction, an engaged fetal vertex does not affect their vaginal delivery rate.

Excessive early gestational weight gain and risk of gestational diabetes mellitus in nulliparous women.

OBJECTIVE: To estimate whether there is an association between excessive early gestational weight gain and the development of gestational diabetes mellitus (GDM) and excessive fetal growth. METHODS: This is a secondary analysis of a randomized controlled trial of vitamins C and E in nulliparous low-risk women. Maternal weight gain from prepregnancy (self-reported) to 15-18 weeks of gestation was measured, and expected gestational weight gain was determined using the Institute of Medicine 2009 guidelines for each prepregnancy body mass index category. Excessive early gestational weight gain was defined as gestational weight gain greater than the upper range of the Institute of Medicine guidelines. Rates of GDM, birth weight greater than 4,000 g, and large for gestational age (LGA, birth weight 90 percentile or higher) were calculated and compared between women with excessive early gestational weight gain and early nonexcessive gestational weight gain (within or below Institute of Medicine guidelines). RESULTS: A total of 7,985 women were studied. Excessive early gestational weight gain occurred in 47.5% of women. Ninety-three percent of women with excessive early gestational weight gain had total gestational weight gain greater than Institute of Medicine guidelines. In contrast, only 55% of women with nonexcessive early gestational weight gain had total gestational weight gain greater than Institute of Medicine guidelines (P<.001). Rates of GDM, LGA, and birth weight greater than 4,000 g were higher in women with excessive early gestational weight gain. CONCLUSION: In our population, excessive early gestational weight gain occurred in 93% of women who had total gestational weight gain greater than the Institute of Medicine guidelines. In low-risk nulliparous women, excessive early gestational weight gain is associated with the development of GDM and excessive fetal growth. LEVEL OF EVIDENCE: II.

The frequency of prior antenatal corticosteroid therapy in late preterm birth pregnancies.

We sought to quantify how often women with late preterm birth (LPTB) receive antenatal corticosteroid (ACS) therapy prior to 34 weeks and to determine its effects on neonatal respiratory morbidity. LPTBs (34 (0)/ (7) to 36 (6)/ (7) weeks) over a 1-year period at a single tertiary care hospital were studied. A composite neonatal respiratory outcome was defined as mechanical ventilation, continuous positive airway pressure with fraction of inspired oxygen (F IO(2)) >40% for >2 hours or F IO(2) >40% for >4 hours within the first 72 hours of life. Multivariate logistic regression analysis was used to evaluate the association between ACS therapy and neonatal respiratory morbidity. Over the study period, 503 LPTBs met the study criteria and 6.8% ( N = 34) had ACS therapy <34 weeks. Most had exposure >7 days prior to delivery (64.7%). Almost one-half of those receiving prior ACS therapy delivered between 34 and 35 weeks. There was no difference in the rate of prior ACS therapy based on LPTB indication for delivery. After adjusting for confounding factors, prior ACS therapy was not associated with lower respiratory morbidity (odds ratio [OR] 2.0, 95% confidence interval [CI] 0.2 to 16.3, P = 0.53). Advancing gestational age was the only variable associated with respiratory morbidity (OR 0.50, 95% CI 0.26 to .94, P = 0.03). In our population, prior ACS therapy was infrequent and was not associated with improvements in neonatal respiratory morbidity following LPTB.

Approximately one-third of medically indicated late preterm births are complicated by fetal growth restriction.

OBJECTIVE: The purpose of this study was to report the frequency of fetal growth restriction (FGR) based on indication for late preterm birth (LPTB). STUDY DESIGN: Singleton live born pregnancies that were delivered from 34-36 weeks 6 days of gestation over a 1-year period at a tertiary care medical center were studied. Indications for delivery were categorized as spontaneous (spontaneous preterm birth or premature rupture of membranes), medically indicated, or elective. A customized birthweight percentile was calculated for each pregnancy; the rate of FGR was compared based on indication for LPTB. RESULTS: There were 482 LPTBs that met all criteria. Customized birthweight percentiles (median; interquartile range) were different among groups (spontaneous, 45.5%; 20.8-73.5%; medically indicated, 26.9%; 4.1-63.6%; elective, 45.9%; 22.2-78.3%; P = .001). The rate of FGR was also different among groups (spontaneous, 13%; medically indicated, 32%; elective, 21%; P = .001). CONCLUSION: With the use of customized birthweight standards, we found that FGR complicated approximately one-third of all cases of medically indicated LPTB.

Engineering input/output nodes in prokaryotic regulatory circuits.

A large number of prokaryotic regulatory elements have been interfaced artificially with biological circuits that execute specific expression programs. Engineering such circuits involves the association of input/output components that perform discrete signal-transfer steps in an autonomous fashion while connected to the rest of the network with a defined topology. Each of these nodes includes a signal-recognition component for the detection of the relevant physicochemical or biological stimulus, a molecular device able to translate the signal-sensing event into a defined output and a genetic module capable of understanding such an output as an input for the next component of the circuit. The final outcome of the process can be recorded by means of a reporter product. This review addresses three such aspects of forward engineering of signal-responding genetic parts. We first recap natural and non-natural regulatory assets for designing gene expression in response to predetermined signals - chemical or otherwise. These include transcriptional regulators developed by in vitro evolution (or designed from scratch), and synthetic riboswitches derived from in vitro selection of aptamers. Then we examine recent progress on reporter genes, whose expression allows the quantification and parametrization of signal-responding circuits in their entirety. Finally, we critically examine recent work on other reporters that confer bacteria with gross organoleptic properties (e.g. distinct odour) and the interfacing of signal-sensing devices with determinants of community behaviour.

Overestimation of fetal weight by ultrasound: does it influence the likelihood of cesarean delivery for labor arrest?

OBJECTIVE: We sought to determine whether the overestimation of ultrasound-derived estimated fetal weight (EFW) is associated with increased diagnosis of labor arrest. STUDY DESIGN: This is a historical cohort study of nulliparous women with term pregnancies who underwent bedside ultrasound examination for EFW before labor induction. Labor outcomes of women with EFW overestimation > 15% the actual birthweight were compared with those with EFW not overestimated. RESULTS: Overestimation of EFW occurred in 9.5% of cases (23/241). The rate of cesarean delivery (CD) for labor arrest was higher for those with EFW overestimation (34.8% vs 13.3%; P = .01) even though there were no differences in length of the induction duration. After adjusting for confounding factors, EFW overestimation remained associated with CD for labor arrest (odds ratio, 4.8; 95% confidence interval, 1.5-15.2). CONCLUSION: Our finding suggests that an overestimation of EFW may be associated with a lower threshold for CD for labor arrest.

Stable implantation of orthogonal sensor circuits in Gram-negative bacteria for environmental release.

A broad host range, orthogonal genetic platform has been developed to format sensor circuits in the chromosome of Gram-negative microorganisms destined for environmental release as bioindicators of toxic or perilous compounds (e.g. explosives) in soil. The genetic scheme includes the generation of a genomic landing pad for the sensor module with a Tn5-mini-transposon bearing an optimal attTn7 sequence and a choice of reporter systems with optical and enzymatic outputs. The array of functional elements thereby inserted in the chromosome match that of a cognate plasmid vector which delivers the transcription factors and the promoters to a frame that places the regulatory parts in front of the reporters. Site-specific recombination sites allow the deletion of antibiotic resistances and enables reporter output prior to deliberate release. The system thus allows the production and maintenance of cells in a pre-release state and its intentional conversion in deliverable strains that fulfil all safety, stability and performance criteria. The combination of such a genetic platform with a variant of the transcriptional regulator XylR of Pseudomonas putida that responds to 2,4-dinitrotoluene has been the basis for the production of strains that emit light upon exposure to residues of explosives in a soil microcosm.

Relationship between meconium staining and amniotic fluid volume in term pregnancies.

OBJECTIVE: Our purpose was to evaluate the relationship between meconium-stained amniotic fluid (MEC-AF) and amniotic fluid volume (AFV) and their impact on the risk of cesarean delivery for fetal indications in term pregnancies. METHODS: 1,655 live-born singleton gestations delivering at > or = 37 weeks within 7 days of sonographic assessment of the amniotic fluid index (AFI) were studied. AFI was categorized as: oligohydramnios (< or = 5.0 cm); decreased (5.1-8.0 cm); normal (8.1-18.0 cm); increased (18.1-23.9 cm), and polyhydramnios (> or = 24.0 cm). Frequencies of MEC-AF for each AFV category were stratified by gestational age (GA) and rates of cesarean delivery for fetal indications compared between patients with clear amniotic fluid and those with MEC-AF. Stepwise logistic regression analyses were performed for determinants of MEC-AF and the need for cesarean delivery for fetal indications. RESULTS: The frequency of MEC-AF at birth in term pregnancies was not related to AFV: oligohydramnios (16.7%); decreased (16.7%); normal (20.1%); increased (24.4%), and polyhydramnios (22.1%). The only factor associated with the occurrence of MEC-AF was increasing GA at delivery (p < 0.01). Both MEC-AF (p < 0.02) and decreasing neonatal ponderal index (p < 0.02) were independently associated with cesarean delivery for fetal distress. CONCLUSIONS: MEC-AF does not appear to be related to AFV in term pregnancies, and its presence increases the risk of cesarean delivery for fetal distress independent of AFV and neonatal ponderal index.