Maternal serum fructosamine levels and stillbirth: a case-control study of the Stillbirth Collaborative Research Network.

OBJECTIVE: To evaluate the association between maternal fructosamine levels at the time of delivery and stillbirth. DESIGN: Secondary analysis of a case-control study. SETTING: Multicentre study of five geographic catchment areas in the USA. POPULATION: All singleton stillbirths with known diabetes status and fructosamine measurement, and representative live birth controls. MAIN OUTCOME MEASURES: Fructosamine levels in stillbirths and live births among groups were adjusted for potential confounding factors, including diabetes. Optimal thresholds of fructosamine to discriminate stillbirth and live birth. RESULTS: A total of 529 women with a stillbirth and 1499 women with a live birth were included in the analysis. Mean fructosamine levels were significantly higher in women with a stillbirth than in women with a live birth after adjustment (177 ± 3.05 versus 165 ± 2.89 µmol/L, P < 0.001). The difference in fructosamine levels between stillbirths and live births was greater among women with diabetes (194 ± 8.54 versus 162 ± 3.21 µmol/L), compared with women without diabetes (171 ± 2.50 versus 162 ± 2.56 µmol/L). The area under the curve (AUC) for fructosamine level and stillbirth was 0.634 (0.605-0.663) overall, 0.713 (0.624-0.802) with diabetes and 0.625 (0.595-0.656) with no diabetes. CONCLUSIONS: Maternal fructosamine levels at the time of delivery were higher in women with stillbirth compared with women with live birth. Differences were substantial in women with diabetes, suggesting a potential benefit of glycaemic control in women with diabetes during pregnancy. The small differences noted in women without diabetes are not likely to justify routine screening in all cases of stillbirth. TWEETABLE ABSTRACT: Maternal serum fructosamine levels are higher in women with stillbirth than in women with live birth, especially in women with diabetes.

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.

Customized vs population-based growth charts to identify neonates at risk of adverse outcome: systematic review and Bayesian meta-analysis of observational studies.

OBJECTIVE: To compare the effectiveness of customized vs population-based growth charts for the prediction of adverse pregnancy outcomes. METHODS: MEDLINE, ClinicalTrials.gov and The Cochrane Library were searched up to 31 May 2016 to identify interventional and observational studies comparing adverse outcomes among large- (LGA) and small- (SGA) for-gestational-age neonates, when classified according to customized vs population-based growth charts. Perinatal mortality and admission to the neonatal intensive care unit (NICU) of both SGA and LGA neonates, intrauterine fetal demise (IUFD) and neonatal mortality of SGA neonates, and neonatal shoulder dystocia and hypoglycemia as well as maternal third- and fourth-degree perineal lacerations in LGA pregnancies were evaluated. RESULTS: The electronic search identified 237 records that were examined based on title and abstract, of which 27 full-text articles were examined for eligibility. After excluding seven articles, 20 observational studies were included in a Bayesian meta-analysis. Neonates classified as SGA according to customized growth charts had higher risks of IUFD (odds ratio (OR), 7.8 (95% CI, 4.2-12.3)), neonatal death (OR, 3.5 (95% CI, 1.1-8.0)), perinatal death (OR, 5.8 (95% CI, 3.8-7.8)) and NICU admission (OR, 3.6 (95% CI, 2.0-5.5)) than did non-SGA cases. Neonates classified as SGA according to population-based growth charts also had increased risk for adverse outcomes, albeit the point estimates of the pooled ORs were smaller: IUFD (OR, 3.3 (95% CI, 1.9-5.0)), neonatal death (OR, 2.9 (95% CI, 1.2-4.5)), perinatal death (OR, 4.0 (95% CI, 2.8-5.1)) and NICU admission (OR, 2.4 (95% CI, 1.7-3.2)). For LGA vs non-LGA, there were no differences in pooled ORs for perinatal death, NICU admission, hypoglycemia and maternal third- and fourth-degree perineal lacerations when classified according to either the customized or the population-based approach. In contrast, both approaches indicated that LGA neonates are at increased risk for shoulder dystocia than are non-LGA ones (OR, 7.4 (95% CI, 4.9-9.8) using customized charts; OR, 8.0 (95% CI, 5.3-10.1) using population-based charts). CONCLUSIONS: Both customized and population-based growth charts can identify SGA neonates at risk for adverse outcomes. Although the point estimates of the pooled ORs may differ for some outcomes, the overlapping CIs and lack of direct comparisons prevent conclusions from being drawn on the superiority of one method. Future clinical trials should compare directly the two approaches in the management of fetuses of abnormal size. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Reconsidering the switch from low-molecular-weight heparin to unfractionated heparin during pregnancy.

Venous thromboembolic disease accounts for 9% of all maternal deaths in the United States. In patients at risk for thrombosis, common practice is to start prophylactic doses of low-molecular-weight heparin and transition to unfractionated heparin during the third trimester, with the perception that administration of neuraxial anesthesia will be safer while on unfractionated heparin, as spinal/epidural hematomas have been associated with recent use of low-molecular-weight heparin. In patients receiving prophylactic doses of unfractionated heparin, neuraxial anesthesia may be placed, provided the dose used is 5,000 units twice a day. The American Society of Regional Anesthesia and Pain Medicine guidelines recognize that the safety of neuraxial anesthesia in patients receiving more than 10,000 units per day or more than 2 doses per day is unknown, limiting the theoretical benefit of unfractionated heparin at doses higher than 5,000 units twice a day.

Aging of intrauterine tissues in spontaneous preterm birth and preterm premature rupture of the membranes: A systematic review of the literature.

BACKGROUND: Many adverse pregnancy outcomes (APOs), including spontaneous preterm birth (PTB), are associated with placental dysfunction. Recent clinical and experimental evidences suggest that premature aging of the placenta may be involved in these events. Although placental aging is a well-known concept, the mechanisms of aging during normal pregnancy and premature aging in APOs are still unclear. This review was conducted to assess the knowledge on placental aging related biochemical changes leading to placental dysfunction in PTB and/or preterm premature rupture of membranes (pPROM). METHODS: We performed a systematic review of studies published over the last 50 years in two electronic databases (Pubmed and Embase) on placental aging and PTB or pPROM. RESULTS: The search yielded 554 citations, 30 relevant studies were selected for full-text review and three were included in the review. Only one study reported oxidative stress-related aging and degenerative changes in human placental membranes and telomere length reduction in fetal cells as part of PTB and/or pPROM mechanisms. Similarly, two animal studies reported findings of decidual senescence and referred to PTB mechanisms. CONCLUSION: Placental and fetal membrane oxidative damage and telomere reduction are linked to premature aging in PTB and pPROM but the risk factors and biomolecular pathways causing this phenomenon are not established in the literature. However, no biomarkers or clinical indicators of premature aging as a pathology of PTB and pPROM have been reported. We document major knowledge gaps and propose several areas for future research to improve our understanding of premature aging linked to placental dysfunction.

Nitric oxide and its role during pregnancy: from ovulation to delivery.

Nitric oxide (NO) is a major paracrine mediator and important regulatory agent in various female reproductive processes, such as ovulation, implantation, pregnancy maintenance, labor and delivery. Ovulation: Circulating NO-products are increased during follicle development and decreased right after ovulation. INOS-inhibition results in a 50% reduction of ovulation, an effect completely reversed by an NO. Endometrium/Implantation: NO also regulates endometrial functions such as endometrial receptivity, implantation and menstruation. NO-donors may be useful for promoting fertility, while NO-inhibitors might be used for contraception. Uterine contractility: Throughout gestation myometrial NO-production is upregulated thus contributing to achieve uterine quiescence. Close to term, NO-production decreases promoting effective contractions resulting in labor. Clinical trials have demonstrated that NO-donors are effective tocolytics. Cervical ripening: In contrast to the myometrium, NO-production in the cervix is low during gestation and becomes upregulated once pregnancy advances to term. NO-donors are effective and safe cervical ripening agents. This finding from animal studies has been confirmed by several clinical trials. Vasoreactivity: In blood vessels, NO is a potent vasodilator and platelet-aggregation-inhibitor. Lack of NO during gestation was related to the development of pregnancy-induced hypertension and preeclampsia. In conclusion, NO-donors and NOS-inhibitors may provide novel, effective, safe, and inexpensive drugs to regulate and steer various functions in female reproductive life. The benefits reach from contraception to preventing possibly lethal pregnancy complications such as preeclampsia. Introducing NO-donors as tocolytics and cervical ripening agents may contribute to a reduction of fetal and maternal perinatal morbidity and mortality.

Citrulline does not relax isolated rat and rabbit vessels.

The study was prompted by the report of Ruiz E. & Tejerina T., 1998 describing endothelium-independent relaxation by L-citrulline via activation of particulate guanylate cyclase. We compared the effects of L-citrulline and L-arginine in isolated aortic rings of rats and in isolated aortic, carotid and femoral artery rings of rabbits. No significant relaxation to either L-citrulline or L-arginine was found in the concentration range of 10(-12) to 10(-3) M, while 3-morpholinosydnonimine hydrochloride (SIN-1, 10(-6) M) relaxed vascular tissues. This study does not support the conclusion that L-citrulline has direct vasorelaxing action on vascular smooth muscle.

Methods and devices for the management of term and preterm labor.

In this review, we outline studies showing that the uterus (myometrium) and cervix pass through a conditioning step in preparation for labor. This step is not easily identifiable with present methods designed to assess the uterus or cervix. In the uterus, this seemingly irreversible step consists of changes in the electrical properties that make muscle more excitable and responsive and produce forceful contractions. In the cervix, the step consists of softening of the connective tissue components. Progesterone and nitric oxide appear to have important roles in these processes. The progress of labor can be assessed noninvasively using electromyographic (EMG) signals from the uterus (the driving force for contractility) recorded from the abdominal surface. Uterine EMG bursts detected in this manner characterize uterine contractile events during human and animal pregnancy. A low uterine EMG activity, measured transabdominally throughout most of pregnancy, rises dramatically during labor. EMG activity also increases substantially during preterm labor in humans and rats and may be predictive of preterm labor. A quantitative method for assessing the cervix is also described. A collascope estimates cervical collagen content from a fluorescent signal generated when collagen crosslinks are illuminated with an excitation light of about 340 nm. The system has proved useful in rats and humans at various stages of pregnancy and indicates that cervical softening occurs progressively in the last one-third of pregnancy. In rats, collascope readings correlate with resistance measurements made in the isolated cervix, which may help to assess cervical function during pregnancy and indicate controls and treatments.

Use of the World Wide Web in research: randomization in a multicenter clinical trial of treatment for twin-twin transfusion syndrome.

OBJECTIVE: To describe the process involved in using the World Wide Web to coordinate a randomized, multicenter international trial of treatment for twin-twin transfusion syndrome. METHOD: A Web site was designed by members of the research team, a Web consultant, and a senior computer programmer. The original intent was to provide patient randomization only, but the Web site later was designed so that centers could download a data collection form. Data could be entered directly into the Web site and subsequently imported into a database at the coordinating center. EXPERIENCE: The Web site has been active for 3 years, with 13 participating centers and 31 patients enrolled. COMMENT: Use of the World Wide Web to coordinate an international, multicenter trial is an efficient method. Although there are many benefits, the most obvious is the capability to initiate and conduct a large international trial at minimal cost.

Successful urokinase treatment of massive pulmonary embolism in pregnancy.

BACKGROUND: Thrombolytic agents have been used successfully to treat patients with massive pulmonary embolism and cardiorespiratory insufficiency, but experience with these drugs in pregnancy is limited. CASE: A 20-year-old woman at 21 weeks' gestation was admitted with a massive pulmonary embolism. She was initially given intravenous heparin therapy but because of worsening clinical condition, urokinase was used. After two 12-hour periods of therapy, the urokinase was discontinued and the heparin restarted. She remained on subcutaneous heparin therapy for the remainder of her pregnancy, which was otherwise uncomplicated. She delivered a healthy male infant at term without complications and was discharged on warfarin therapy. CONCLUSION: Thrombolytic therapy can be life-saving and should be considered in the treatment of hemodynamically significant pulmonary embolism in pregnancy.

Fetal platelet counts correlate with the severity of the anemia in red-cell alloimmunization.

OBJECTIVE: To determine whether fetal anemia secondary to maternal red-cell alloimmunization is associated with thrombocytopenia. METHODS: The records of 78 patients undergoing intrauterine transfusion for red-cell alloimmunization were reviewed. Pre-transfusion fetal platelet counts were compared between hydropic and nonhydropic fetuses. A regression analysis was performed between the fetal platelet counts and the fetal bilirubin levels, hematocrits, and reticulocyte counts taken at the initial transfusion. The hematocrits, reticulocyte counts, and bilirubin levels were adjusted for gestational age by calculating the number of standard deviations (SDs) from the mean for that age or the multiples of the mean (MOM). Student t test, Pearson coefficient, and contingency table randomization test were used to analyze the data. P < .05 was considered significant. RESULTS: Thirty-seven fetuses were hydropic and 41 were nonhydropic. Hydropic fetuses had a significantly lower platelet count than nonhydropic fetuses (197.5 +/- 86.4 versus 252.6 +/- 73.7 x 10(3)/microL; P < .01). Platelet counts correlated negatively with the reticulocyte count MOM (r = -0.652; P < .01) and the hematocrit SDs below the mean (r = -0.659; P < .01), but did not correlate with the bilirubin MOM (r = -0.183; P = .2). CONCLUSION: Hydropic and severely anemic fetuses are at increased risk for thrombocytopenia. We suggest that increased erythropoiesis diverts the hematopoietic stem cell away from thrombopoiesis.

The effect of intrauterine transfusion on fetal bilirubin in red cell alloimmunization.

OBJECTIVE: To evaluate the change in fetal serum bilirubin levels in response to intrauterine transfusion for red cell alloimmunization. METHODS: The records of 37 patients who underwent more than one intrauterine transfusion were reviewed. The following indices were extracted: pre- and post-transfusion fetal hematocrit, total and direct serum bilirubin, reticulocyte count, Kleihauer-Betke test results, volumes of intravascular and intraperitoneal transfusions, and the source used for transfusion. The data were compared for interval 1 (transfusion 1 to 2) and interval 2 (transfusion 2 to 3). The rates of change in bilirubin, reticulocyte count, and percent fetal cells on the Kleihauer-Betke test were defined as the differences between the initial values of one transfusion and the initial values of the next transfusion divided by the number of days between transfusions. Analysis of variance, sign-rank test, and linear regression analysis were used when appropriate. P < .05 was significant. RESULTS: The median number of intrauterine transfusions for each patient was 3 (range 2-8). Gestational ages ranged from 22 to 37 weeks. Total bilirubin remained above the 97.5 percentile for gestational age in all but five patients. There was a significant decrease in reticulocyte count and fetal cells on the Kleihauer-Betke test, and an increase in hematocrit with serial intrauterine transfusions. Bilirubin increased significantly after the first intrauterine transfusion (3.9 versus 5.0 mg/dL) and remained elevated thereafter. CONCLUSION: Fetal total serum bilirubin remains elevated with repeated intrauterine transfusions in fetal alloimmunization. Total bilirubin should not be used to evaluate fetal hematologic responses to the transfusions.

In vitro comparison of four tocolytic agents, alone and in combination.

OBJECTIVE: To compare the tocolytic effects of magnesium sulfate, ritodrine, terbutaline, and nifedipine on human myometrial strips. METHODS: Myometrial strips were suspended in organ chambers for isotonic measurements and contracted with KCI. STrips from nonpregnant patients were used to obtain concentration-response curves. Myometrial strips from pregnant uteri were then exposed to the molar concentrations causing 50% relaxation in the nonpregnant tissues. RESULTS: In strips from nonpregnant patients, nifedipine was found to be the most potent tocolytic. Using strips from nonlaboring patients, nifedipine caused relaxation similar to ritodrine, and both were more effective than magnesium sulfate or terbutaline. Combinations were more effective than single agents. These agents were found to be equally less effective in myometrial strips from laboring patients. CONCLUSIONS: Nifedipine, alone or in combination, relaxes myometrial strips more effectively than the other agents studied. Myometrial strips from laboring patients are more resistant to inhibition, with none of the agents being superior.

The relation between magnesium sulfate therapy and fetal heart rate variability.

OBJECTIVE: To determine the relation between magnesium sulfate therapy and fetal heart rate (FHR) variability. METHODS: Twelve women diagnosed with preeclampsia who were to receive magnesium sulfate for seizure prophylaxis were recruited. Exclusion criteria included delivery anticipated within 2 hours, gestational age less than 28 weeks, abnormal fetal testing, fetal growth retardation, and use of illicit drugs or medications. Six grams of magnesium sulfate in 100 mL 0.9% saline was administered intravenously over 20 minutes, followed by a continuous infusion of 2 g/hour. A cardiotocogram analysis computer system was used to analyze various elements of the FHR pattern before, during, immediately after, and 60 minutes following magnesium sulfate loading. For each time interval, the basal heart rate, number of accelerations and decelerations, number of minutes of high and low variability, mean minute range variation, and the short-term (3.75-second interval) variability were measured. RESULTS: There was a statistically significant decrease in short-term variability 60 minutes after initiation of therapy (6.7 +/- 2.0 versus 9.8 +/- 3.3 milliseconds; P = .003). Long- and medium-term variability did not change significantly after magnesium sulfate was administered. CONCLUSION: Although magnesium sulfate therapy was associated with an objectively measured, statistically significant decrease in short-term variability, the decrease was not clinically significant; furthermore, it was not associated with a decrease in long-term variability or in the number of accelerations measured.

Cerebrovascular reactivity in normal pregnancy and preeclampsia.

OBJECTIVE: To compare cerebrovascular reactivity in normotensive and preeclamptic pregnant women. METHODS: Transcranial Doppler ultrasound was used to measure peak, end-diastolic, and mean velocities in the middle cerebral arteries of 45 normotensive and 36 preeclamptic women in the third trimester. All measurements were done in the left lateral position at baseline, during 5% carbon dioxide (CO2) inhalation, and during an isometric hand-grip test. Blood pressure (BP), heart rate, oxygen (O2) saturation, and end-tidal partial pressure of carbon dioxide (pCO2) were recorded with each Doppler measurement. The mean pulsatility index (PI), resistance index (RI), and cerebral perfusion pressure at each time was compared using two-way repeated measures analysis of variance. Cerebrovascular reactivity, calculated as the percentage change in response to each maneuver, was also compared using analysis of covariance. A post hoc power analysis was performed to evaluate the primary measures of the study (middle cerebral artery PI and RI). Using alpha error of 5%, the statistical power to identify a difference in PI and RI in women with preeclampsia compared with normotensive women was 90% and 67%, respectively. The statistical power to identify a difference in PI and RI in response to the two maneuvers was 69% and 53%, respectively. Statistical significance was set at P <.05. RESULTS: Preeclamptic women had higher baseline cerebral perfusion pressure (90.4 compared with 61.9 mmHg, P <.05) and lower PI (0.64 compared with 0.76, P <.05) and RI (0.46 compared with 0.51, P <.05) than normotensive pregnant women. In normotensive patients, both 5% CO2 inhalation and isometric hand-grip test caused a significant decrease in PI (-9.5% and -6.1%, respectively) and RI (-6.5% and -4.2%, respectively). In contrast, in preeclamptic patients there was no change in any of the middle cerebral artery parameters in response to either maneuver. CONCLUSION: Normotensive pregnant women had normal middle cerebral artery responses to both 5% CO2 inhalation and isometric hand-grip test. Preeclamptic patients had elevated baseline cerebral perfusion pressure and reduced vasodilatory responses to both tests. These findings are consistent with a state of vasoconstriction in preeclamptic women that is unresponsive to stimuli that under normal circumstances result in vasodilation.

Calcitonin gene-related peptide dilates the pregnant rat uterine vascular bed via guanylate cyclase, ATP- and Ca-sensitive potassium channels and gap junctions.

We studied the mechanism of calcitonin gene-related peptide (CGRP)-induced vasorelaxation in isolated uterine vascular beds of pregnant rats. The vascular beds were perfused in situ with Krebs buffer containing dextran and indomethacin, an inhibitor of cyclooxygenase. Baseline perfusion pressure was maintained with norepinephrine. When applied as a bolus, CGRP caused a decreased perfusion pressure in uterine vascular beds that was dose-dependent and equal in both mid-pregnant and late-pregnant rats. The non-selective inhibitor of nitric oxide synthase (NOS), Nomega-nitro-L-arginine methyl ester (L-NAME), did not significantly affect CGRP-induced vasodilatation in vascular beds of either group. CGRP-induced vasodilatation was not influenced by preincubation with the inhibitors of adenylate cyclase (SQ 22536 or MDL 12330A), but was significantly attenuated by the selective inhibitor of soluble guanylate cyclase (ODQ). The vasorelaxant effect of CGRP was not significantly influenced by the inhibitor of voltage-gated potassium (KV) channels (4-aminopyridin), but was significantly attenuated by an inhibitor of calcium-regulated potassium (KCa) channels (tetraethylammonium) and by an inhibitor of adenosine triphosphate-sensitive potassium (KATP) channels (glibenclamide). The gap junction uncoupling agent (carbenoxolone) also significantly attenuated the CGRP-induced decrease in perfusion pressure. We conclude that vasorelaxation induced by CGRP in the pregnant rat uterine vascular bed is not dependent on endothelial nitric oxide. In the uterine circulation of late-pregnant rats, the CGRP effect involves activation of soluble guanylate cyclase, but not adenylate cyclase, and does involve KCa and KATP channels and gap junctions.

Human immunodeficiency virus (HIV)-related pulmonary complications in pregnancy.

With changes in the demographics of human immunodeficiency virus (HIV) infection, women and children are becoming the fastest growing group of newly infected patients. With longer survival after HIV infection, more women infected with HIV are becoming pregnant. Pulmonary disease is one of the most common presenting conditions in an AIDS-defining illness. Pneumocystis carini pneumonia and tuberculosis are the most common disorders that herald the onset of AIDS. They are also the most frequently encountered HIV-related pulmonary complications during pregnancy. Others have been rarely reported during pregnancy and include fungal infections (Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitus), bacterial infections (Haemophilus influenzae and Streptococcus pneumoniae along with Pseudomona aeruginosa), viral infections (CMV), opportunistic neoplasms (Kaposi's sarcoma, lymphoma) and miscellaneous conditions peculiar to HIV-infected individuals (nonspecific interstitial pneumonitis, lymphoid interstitial pneumonitis, isolated pulmonary hypertension, and pulmonary edema secondary to cardiac disease or drug abuse). Most of the data regarding the pulmonary complications of HIV infection come from studies in nonpregnant patients. The extent to which pregnancy affects the course of respiratory disease in HIV infection and vice versa is not well documented. Clinical presentation is usually not altered by pregnancy. Except for minor modifications mainly related to potential fetal effects, the diagnostic work-up and management are similar to those in the nonpregnant patient. The most important effect of pregnancy on these conditions remains the delay in diagnosis and treatment. A high index of suspicion should, therefore, be maintained. In addition, most prophylactic measures recommended in nonpregnant HIV-infected individuals also apply to pregnant women.

New developments in the management of preterm labor.

Current management of preterm labor has not changed the incidence of preterm delivery; therefore, significant research effort has been concentrated on the search for new methods of management. New tocolytics like inhibitors of cyclooxygenase 2 and nitric oxide donors have been tested in animal models and in preliminary clinical trials with promising results. Inhibition of cervical ripening may be one alternative to tocolysis. This new approach has a potential to be a valuable method of management of preterm labor if human studies confirm the promising results reported in animals. Growing evidence suggests that premature delivery may be associated with infection or fetal growth abnormalities, with dire consequences to the fetus. If these associations are to be included in risk and benefit assessment, then inhibition of preterm labor may prove to be detrimental to the fetus.

Vascular reactivity in preeclampsia.

It has long been known that vascular reactivity is altered in preeclamptic patients compared with normal pregnant women. This change even occurs weeks earlier than any clinical manifestation of the disease. Many investigators believe that the conditions for the development of preeclampsia are set as early as the first trimester. These changes in vascular reactivity appear to be independent of the blood pressure because they also occur in chronic hypertensive women destined to have preeclampsia. This review focuses on these changes in vascular reactivity reported in preeclampsia. Increased reactivity of the blood vessels in preeclampsia has been described in most, but not all, studies. The cause for the differences in reactivity between vessels from preeclamptic and normal pregnant women is not known. However, it cannot be attributed solely and with certainty to abnormalities in endothelium-dependent relaxation or the nitric oxide system because the study results published to date remain contradictory. In addition to functional differences, vessels from normal pregnant and preeclamptic women show distinct mechanical properties.