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Background Insulin detemir, being used increasingly during pregnancy, may have pharmacologic benefits compared with neutral protamine Hagedorn. Objective We evaluated the probability that compared with treatment with neutral protamine Hagedorn, treatment with insulin detemir reduces the risk for adverse neonatal outcome among individuals with type 2 or overt type 2 diabetes mellitus (gestational diabetes mellitus diagnosed at Study Design We performed a multiclinic randomized controlled trial (September 2018 to January 2020), which included women with singleton gestation with type 2 or overt type 2 diabetes mellitus who sought obstetrical care at ≤21 weeks’ gestation. Participants were randomized to receive either insulin detemir or neutral protamine Hagedorn by a clinic-stratified scheme. The primary outcome was a composite of adverse neonatal outcomes, including shoulder dystocia, large for gestational age, neonatal intensive care unit admission, respiratory distress (defined as the need of at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life), or hypoglycemia. The secondary neonatal outcomes included gestational age at delivery, small for gestational age, 5-minute Apgar score of 75% probability of any reduction in the primary outcome, assuming 80% power and a hypothesized effect of 33% reduction with insulin detemir. All analyses were intent to treat under a Bayesian framework with neutral priors (a priori assumed a 50:50 likelihood of either intervention being better; National Clinical Trial identifier 03620890). Results There were 108 women randomized in this trial (57 in insulin detemir and 51 in neutral protamine Hagedorn), and 103 women were available for analysis of the primary outcome (n=5 for pregnancy loss before 24 weeks’ gestation). Bayesian analysis indicated an 87% posterior probability of reduced primary outcome with insulin detemir compared with neutral protamine Hagedorn (posterior adjusted relative risk, 0.88; 95% credible interval, 0.61–1.12). Bayesian analyses for secondary outcomes showed consistent findings of lower adverse maternal outcomes with the use of insulin detemir vs neutral protamine Hagedorn: for example, maternal hypoglycemic events (97% probability of benefit; posterior adjusted relative risk, 0.59; 95% credible interval, 0.29–1.08) and hypertensive disorders (88% probability of benefit; posterior adjusted relative risk, 0.81; 95% credible interval, 0.54–1.16). Conclusion In our comparative effectiveness trial involving individuals with type 2 or overt type 2 diabetes mellitus, use of insulin detemir resulted in lower rates of adverse neonatal and maternal outcomes compared with neutral protamine Hagedorn.

Background Inositols (INOs) supplementation during pregnancy, specifically the combination of myo-inositol (MI) and D-chiro-inositol (DCI), has been reported to improve vascular parameters in women with gestational diabetes mellitus. We demonstrated previously that offspring born to pregnant mice lacking the endothelial nitric oxide synthase (eNOS+/–) gene have hypertension (HTN) as adults and, when fed a high-fat diet (HFD), develop a metabolic syndrome (MS) phenotype. Objective Our aim was to evaluate whether INOs treatment in pregnancy complicated by MS improves the vascular and metabolic profile in mice offspring programmed in utero to develop HTN and MS. Materials and Methods Heterozygous eNOS+/– mice fed an HFD manifest a MS phenotype. Female eNOS+/– mice with MS were bred with a wild-type (WT) male. On gestational day 1, pregnant females were randomly allocated to receive either a mixture of INOs (MI/DCI: 7.2/0.18 mg/mL) or water as placebo until delivery. The female offspring obtained were genotyped and categorized as: WT (genetically normal, with eNOS gene) and eNOS+/– offspring (genetically modified, heterozygous for eNOS gene). Both offspring developed in an abnormal uterine environment due to maternal MS. At 9–10 weeks of age, the offspring underwent a glucose tolerance test (GTT) and systolic blood pressure (SBP) measurement. The mice were then sacrificed, and the carotid arteries were isolated for evaluation of vascular responses. Responses to phenylephrine (PE), in the presence and absence of a nonspecific nitric oxide inhibitor (N-nitro-L-arginine methyl ester [L-NAME]), the vasodilator acetylcholine (ACh), and sodium nitroprusside (SNP) were assessed. Results The GTT showed lower glucose levels in both eNOS+/–INOs (P = .03) and WT-INOs (P = .05) offspring born to MS dams on INOs supplementation compared to offspring born to untreated dams. SBP was higher in eNOS+/– offspring compared to WT (169 ± 7 vs 142 ± 9 mm Hg, respectively, P = .04) and INOs treatment decreased SBP in WT-INOs (110 ± 10 mm Hg, P = .01) but not in eNOS+/–INOs offspring. Maximal (%Max) contractile response to PE was higher in eNOS+/– offspring born to MS dams and was decreased in those born to MS dams treated with INOs (%Max, eNOS+/–, 123 ± 7 vs eNOS+/–INOs, 82 ± 11 mm Hg, P = .007). No differences were seen in PE contractile responses in WT offspring born to MS dams treated or not treated with INOs (WT, 92 ± 4 vs WT-INOs, 75 ± 7). The L-NAME response was decreased in eNOS+/–INOs and WT-INOs offspring compared to untreated ones. The ACh vasorelaxation was impaired in eNOS+/– and WT offspring born to MS dams, and maternal INOs treatment improved offspring vascular relaxation in both offspring (P = .01 and P = .03, respectively). No differences were seen in response to SNP. Conclusion Inositols supplementation improved glucose tolerance, SBP, and vascular responses in adult eNOS+/– and WT offspring born to dams with MS. Interestingly, WT born to MS dams show an altered vascular profile similar to eNOS+/– offspring and exhibit an improved response to INOs treatment. Our findings suggest that the benefits of INOs treatment are more pronounced in offspring exposed to environmental factors in utero, and less likely in those due to genetic factors.

Background Myoinositol and D-chiroinositol improve insulin resistance in women with obesity and gestational diabetes and in postmenopausal women with metabolic syndrome. We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase and fed a high-fat diet develop metabolic-like syndrome phenotype. Objective The objective of the study was to investigate the effect of a mixture of myoinositol/D-chiroinositol supplementation during pregnancy on the maternal metabolic profile in pregnancies complicated by the metabolic-like syndrome and obesity using a pregnant mouse model. Study Design Female heterozygous endothelial nitric oxide synthase –/+ mice with moderate hypertension were placed on a high-fat diet for 4 weeks to induce a metabolic-like syndrome phenotype. Similarly, wild-type C57BL/6 mice were placed on a high-fat diet for 4 weeks to induce a murine obesity model. Mice were then bred with wild-type males. On gestational day 1, dams were randomly allocated to receive either a mixture of myoinositol/D-chiroinositol in water (7.2/0.18 mg/mL, respectively) or water as control (placebo). At term (gestational day 18), maternal weights, systolic blood pressure, and a glucose tolerance test were obtained. Dams were then killed; pups and placentas were weighed and maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, gastric inhibitory peptide, glucagon-like peptide 1, glucagon, insulin, leptin, resistin) were measured by a multiplex enzyme-linked immunosorbent assay. Analysis was done comparing metabolic-like syndrome-myoinositol/D-chiroinositol–treated vs metabolic-like syndrome–nontreated mice and obese-myoinositol/D-chiroinositol–treated vs obese nontreated mice. Results Mean systolic blood pressure was lower in metabolic-like syndrome pregnant mice treated with myoinositol/D-chiroinositol compared with placebo ( P = .04), whereas there was no difference in systolic blood pressure between treated and placebo-treated obese pregnant mice. Pregnant metabolic-like syndrome mice treated with myoinositol/D-chiroinositol showed lower glucose values during the glucose tolerance test and in the area under the curve (myoinositol/D-chiroinositol: 17512.5 ± 3984.4 vs placebo: 29687.14 ± 8258.7; P = .003), but no differences were seen in the obese pregnant mice. Leptin serum levels were lower in the metabolic-like syndrome-myoinositol/D-chiroinositol–treated mice compared with the placebo group (myoinositol/D-chiroinositol: 16985 ± 976.4 pg/dL vs placebo: 24181.9 ± 3128.2 pg/dL, P = .045). No other differences were seen in any of the remaining serum metabolic biomarkers studied in metabolic-like syndrome and in obese pregnant mice. Maternal weight gain was not different in the pregnant metabolic-like syndrome dams, whereas it was lower in the obese myoinositol/D-chiroinositol–treated dams compared with the placebo group (myoinositol/D-chiroinositol: 10.9 ± 0.5 g vs 12.6 ± 0.6 g, P = .04). Fetal and placental weights did not differ between myoinositol/D-chiroinositol–treated and nontreated pregnant dams with metabolic-like syndrome and obesity. Conclusion Combined inositol treatment during pregnancy improves blood pressure, glucose levels at the glucose tolerance test, and leptin levels in pregnant dams with metabolic-like syndrome phenotype but not in obese pregnant dams. In addition, inositol treatment was associated with lower gestational weight gain in the obese but not in the metabolic-like syndrome pregnant dams.

Treatment of nonsevere hypertension during pregnancy is controversial. Sildenafil is a phosphodiesterase inhibitor that potentiates nitric oxide by promoting vasodilation. Nitric oxide plays a vital role in mediating the vascular adaptations during pregnancy.The objective of the study was to determine whether treatment with sildenafil during pregnancy would lower maternal systolic blood pressure without adversely affecting fetal growth.Females with nonsevere hypertension (endothelial nitric oxide synthase(+/-)) were cross-bred with normotensive wild-type males. At gestational day 1, pregnant dams were randomized to either sildenafil (0.4 mg/mL per day, comparable dose used in human pregnancy) or water for 3 weeks. Four groups were then generated: wild type (n = 7), wild type-sildenafil (n = 11), endothelial nitric oxide synthase(+/-) (n = 8), and endothelial nitric oxide synthase(+/-)sildenafil (n = 7). On gestational day 18, systolic blood pressure was measured. Dams were killed, fetal and placental weights were obtained, and carotid arteries were dissected to measure in vitro vascular reactivity with a wire-myography system. Responses to phenylephrine, L-NG-nitroarginine methyl ester, acetylcholine, and sodium nitroprusside were studied.Mean systolic blood pressure was elevated in the endothelial nitric oxide synthase(+/-) dams compared with wild-type controls (P = .03). Treatment with sildenafil decreased systolic blood pressure in the endothelial nitric oxide synthase(+/-)-treated dams compared with nontreated endothelial nitric oxide synthase(+/-) dams (P = .03). No differences were seen in the wild-type dams with or without sildenafil (P = .47). Fetuses from endothelial nitric oxide synthase(+/-) dams were smaller compared with wild-type controls (P.001); however, when these endothelial nitric oxide synthase(+/-) dams were treated with sildenafil, fetal weight increased compared with the nontreated endothelial nitric oxide synthase(+/-) group (P.001). No difference were seen in wild-type groups treated or not treated with sildenafil (P = .41). Placental weights were not significantly different among groups (endothelial nitric oxide synthase(+/-)sildenafil vs endothelial nitric oxide synthase(+/-) [P = .48]; wild-type-sildenafil vs wild type [P = .52]). Maximal vascular contraction induced by phenylephrine was blunted in endothelial nitric oxide synthase(+/-) dams treated with sildenafil compared with nontreated endothelial nitric oxide synthase(+/-) dams (P.01). No change in contractile response was seen in wild-type groups treated or not treated (P = .53). When vessels were preincubated with L-NG-nitroarginine methyl ester, the contractile responses were similar among all groups (P = .54). In addition, maximal vascular relaxation induced by acetylcholine was improved in the endothelial nitric oxide synthase(+/-) dams treated with sildenafil compared with endothelial nitric oxide synthase(+/-) nontreated dams (P.01). No change in relaxation response was seen in wild-type groups treated or not treated (P = .62). Sodium nitroprusside did not change the contractile response in any of the groups (P = .31).Pregnant dams deficient in endothelial nitric oxide synthase, a nonsevere hypertensive murine model, treated with sildenafil had lower maternal systolic blood pressure, increased fetal growth, and improvement in vascular reactivity. Treatment with sildenafil may be beneficial in pregnancies complicated by nonsevere hypertension.

Objective Indomethacin (IND) is a prostaglandin production inhibitor that reduces uterine contractions, but crosses the placenta leading to adverse fetal effects. Liposomes (LIP) are nanoscale systems clinically used to preferentially deliver a drug to the tissue of interest and simultaneously prevent distribution to unwanted locations. Our objective was to determine whether LIP could prevent the transfer of IND across the placenta to the fetus while preserving its pharmacological activity. Study Design Multilamellar LIP were designed with a 150- to 200-nm size, fluorescently labeled, and loaded with IND. Timed pregnant CD1 mice (n = 6/group) on gestational day 18 were administered LIP, LIP-IND (1 mg IND/kg), or saline (SAL) via tail vein injection, or IND (1 mg/kg) via oral gavage. After 4 hours, the uterus, placenta, and fetuses were retrieved. LIP levels were visualized using fluorescent microscopy and quantitatively assessed by National Institutes of Health image processing software. LIP brightness values (mean ± SEM) in arbitrary units (AU) were normalized to the autofluorescence of the same tissue (as measured in SAL group). IND and prostaglandin E2 levels were assessed using liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay, respectively. Results The qualitative analysis of LIP distribution revealed that the system was primarily confined within the uterus, minimally detected within the placenta, and absent in the fetus. LIP fluorescence was greater in the uterus compared to placenta and fetus (uterus 15.3 ± 5.4 AU vs placenta 3.0 ± 3.5 AU vs fetus 4.4 ± 2.5 AU; P = .009). LIP-IND resulted in a 7.6-fold reduction in the IND levels in the fetus compared to IND alone (LIP-IND 10.7 ± 17.1 ng/g vs IND 81.3 ± 24.7 ng/g; P = .041). Prostaglandin E2 levels were significantly reduced in the uterus of animals given LIP-IND and IND compared to LIP and SAL. Conclusion LIP localized within the uterus and did not cross the placenta to the fetus. IND within the fetus was reduced 7.6-fold while encapsulated within the LIP and the pharmacologic effects of IND were maintained. Thus, LIP provide a novel therapeutic approach to correct the primary clinical limitation of IND by reducing placental passage to the fetus.

Objective The purpose of this study was to examine the effects of prolonged in utero meconium exposure on adult learning and memory, as measured by the Morris water maze. Study design Timed pregnant Long-Evans rats were studied. On gestational day 20 (term, 21 days of gestation), laparotomy was performed, and each maternal animal received an injection of clear amniotic fluid or meconium-stained amniotic fluid into each gestational sac. The laparotomy incision was closed, and the animals received postoperative monitoring through delivery. On postnatal days 145 to 148, the offspring underwent Morris water maze testing. The mean (±SEM) for the latency time was reported for each day's trial and compared between groups. Results There were significant differences between meconium-stained amniotic fluid group and clear amniotic fluid group in the mean time to platform on day 1 (82.7 ± 1.8 seconds vs 75.9 ± 3.0 seconds; P =.04), day 2 (60.5 ± 3.5 seconds vs 47. 8 ± 4.6 seconds; P =.03), and day 3 (56.5 ± 4.5 seconds vs 34.7 ± 4.4 seconds; P =.001). However, there were no differences on days 4 and 5. There were also no differences between recall and response learning trials that were done after a 12-day retention period. Conclusion In the absence of hypoxia or infection, prolonged in utero meconium exposure is associated with a delay of spatial learning in the adult rat.

Objective: Our purpose was to define twin growth discordance on the basis of perinatal outcome. Study Design: Twins delivered at >23 weeks' gestation between 1995 and 2000 were identified by use of our computerized perinatal database. Birth weight (BW), chorionicity, and the following outcomes were recorded: cesarean delivery for nonreassuring fetal status (NRFS), umbilical artery (UA) pH, 5-minute Apgar score, neonatal intensive care unit (NICU) admission, and stillbirth. Discordance was calculated as 100 ×(Larger BW − Smaller BW)/Larger BW. The distribution of discordance values for the study population was determined. Outcomes were compared for twins with and without discordance at thresholds defined by population percentile. Results: The mean discordance for 346 twins was 11.4% ± 10.5%. The 75th percentile was 16% discordance, the 90th was 23%, and the 95th was 31%. Discordance was independently associated with outcomes. The 95th percentile was the threshold most predictive of cesarean section NRFS, UA pH Conclusion: Defining pathologic discordance as the 95th percentile, or >30% difference, enhances its predictive value. (Am J Obstet Gynecol 2002;187:667-71.)

We sought to compare weight loss in the first 6 weeks postpartum among women with gestational diabetes mellitus (GDM) treated with metformin or placebo, a promising therapy to reduce later risk of progression to diabetes mellitus.We conducted a pilot, randomized trial of metformin vs placebo in postpartum women with GDM. Women with pre-GDM, unable to tolerate metformin, resumed on insulin or oral hypoglycemic agent, delivered34 weeks' gestation, or with a body mass index20 kg/m(2) were excluded. Women were randomized to either metformin 850 mg daily for 7 days, then metformin 850 mg twice a day for the next 5 weeks or placebo prescribed in a similar frequency. The subject, health care provider, and research staff were blinded to the treatment. The primary outcome was weight change from delivery to 6 weeks postpartum. Secondary outcomes included the percentage of women achieving their self-reported prepregnancy weight, reported medication adherence, adverse effects, and satisfaction. Differences in weight change between groups were determined by Wilcoxon rank sum test and in achieving prepregnancy weight by χ(2) test.Of 114 women randomized, 79 (69.3%) completed the 6 weeks; 36 (45.6%) were randomized to metformin and 43 (54.4%) to placebo. Metformin and placebo groups were similar in median weight loss (6.3 kg [range, -0.3 to 19.8] vs 6.5 kg [range, -0.3 to 12.1], P = .988) and percentage of women achieving reported prepregnancy weight (41.7 vs 37.2%, P = .69). Self-reported adherence in taking50% of medication was 75% at 3 weeks and 97% at 6 weeks. Nausea, diarrhea, and hypoglycemia were reported in approximately 11-17% of women and 56-63% reported dissatisfaction with the medication.Women with GDM lost approximately 6 kg by 6 weeks' postpartum. This was similar in both groups and resulted in50% of women achieving their prepregnancy weight. Although the reported adherence and satisfaction with the medication was high, adverse effects were reported with nearly 1 in 5 women including nausea, diarrhea, and hypoglycemia. Contrary to expectation, we found no evidence of benefit from metformin. However, longer treatment periods and larger studies with minimal attrition may be warranted.

Our aim was to compare the clinical characteristics of meconium aspiration syndrome in cases with pHor =7.20 and in those with pH7.20.Medical records of diagnostic codes from the International Classification of Diseases, Ninth Revision, were used to identify neonates with severe meconium aspiration syndrome who had been delivered at our institution from 1994 through 1998. Severe meconium aspiration syndrome was defined as a mechanical ventilator requirement of48 hours. Clinical data including neonatal outcomes of cases of meconium aspiration syndrome associated with umbilical pHor =7.20 at delivery were compared with data on outcomes of cases with pH7.20.During this 4-year study period, 4985 singleton term neonates were delivered through meconium-stained amniotic fluid. Forty-eight cases met all study criteria, and pH values at delivery were as follows: pHor =7.20, n = 29, and pH7.20, n = 19. There were no differences between groups in the incidence of clinical chorioamnionitis, in the presence of meconium below the vocal cords, or in birth weight. Neonates with meconium aspiration syndrome and umbilical pHor =7.20 at delivery developed seizures as often as those with pH7.20 (20.1% vs 21.1%; P = 1.0).Normal acid-base status at delivery is present in many cases of severe meconium aspiration syndrome, which suggests that either a preexisting injury or a nonhypoxic mechanism is often involved.

Objective: This study was undertaken to better define the timing of neurologic insult in neonates with early-onset seizures through evaluation of neonatal nucleated red blood cell levels. Study Design: Medical records and the International Classification of Diseases, Ninth Revision codes were used to identify all term neonates with neonatal convulsions who were delivered at our institution (January 1, 1990–December 31, 1995). Each neonate with early-onset seizures was matched to the next 3 neonates who met the following criteria: gestational age ≥37 weeks, no early-onset seizures, birth weight ≥2800 g, umbilical artery pH ≥7.25, and a 5-minute Apgar score >7. Demographic characteristics, clinical factors, and mean initial nucleated red blood cell counts were compared between groups. Results: During the 6-year study period, there were a total of 36,490 singleton term deliveries of infants who were alive at birth. Forty-five (0.1%) of these neonates had early-onset seizures. Thirty neonates with early-onset seizures met the inclusion criteria. Mean nucleated red blood cell counts (number of nucleated red blood cells per 100 white blood cells) for neonates with early-onset seizures were significantly increased compared with those of control neonates (18.4 ± 22.0 vs 4.6 ± 4.5; P Conclusions: Our findings are suggestive of the hypothesis that neurologic injury leading to early-onset seizures often occurs before the intrapartum period. (Am J Obstet Gynecol 2000;182:1452-7.)

89 The comparative effectiveness of intravenous acetaminophen versus intravenous morphine for pain relief in early labor: a randomized controlled trial Nana-Ama E. Ankumah, Marissa Tsao, Maria Hutchinson, Claudia Pedroza, Jaideep Mehta, Sean Blackwell, Jerrie Refuerzo UT Health University of Texas Medical School at Houston, Houston, TX OBJECTIVE: Intravenous (IV) opioids are common analgesics in early labor, but are limited by marginal pain relief and adverse maternal/fetal effects. Our objective was to compare the effectiveness of IV acetaminophen to IV morphine in reducing pain in early labor. STUDY DESIGN: We conducted an open-label, randomized controlled trial (RCT) of women 34 weeks gestation with regular uterine contractions and cervical dilation 2-6 cm. Women received either IV acetaminophen 1000 mg or IV morphine 2 mg. Women with contraindications to either study drug were excluded. Effectiveness of analgesics was assessed by monitoring the patient’s need for rescue analgesia and by obtaining visual analog scales (VAS) prior and at 15 minutes, 1 hour, 2 hours and 4 hours. VAS scores, rescue analgesics, maternal side effects (nausea, emesis, drowsiness, pruritus, headache, insomnia) and fetal heart rate tracing changes (accelerations, decelerations, baseline change, variability) were compared between groups. An intent-to-treat analysis was performed with chi-square, t-test and logistic regression as appropriate. RESULTS: Of 40 women randomized, 18 received IV acetaminophen (2 did not receive study drug) and 20 received IV morphine. Within 2 hours of analgesics, over half the women who received IV acetaminophen required rescue analgesic demonstrating its minimal effect in pain control (acetaminophen: 52.9 % vs morphine: 17.6%, p1⁄4 0.02). Within 4 hours, there were no differences in rate of rescue analgesics, (acetaminophen: 73.3% vs morphine: 56.3%, p1⁄40.16). VAS scores were similar at each time point for both groups, p>0.05 (Fig 1). Maternal/fetal adverse effects were similar between groups. CONCLUSION: Although overall VAS were comparable between groups across each time interval, over half of women receiving IV acetaminophen required rescue analgesic within 2 hours of treatment. Our findings suggest that IV acetaminophen is less effective for initial pain relief in early labor compared to IV morphine.

Objective Our objective was to describe indications for late preterm birth (LPTB) and estimate the frequency of potentially avoidable LPTB deliveries. Study Design Singleton pregnancies delivered between 34 0/7 –36 6/7 weeks 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) or iatrogenic (elective or medically indicated). Potentially avoidable deliveries were defined as those with elective or medical stable, but high-risk indications. Results During the study period there were 514 LPTB (spontaneous preterm birth 36.2%, preterm premature rupture of membranes 17.7%, medically indicated 37.9%, and elective 8.2%). Potentially avoidable LPTB accounted for 17% of LPTB and were associated with later gestational age (odds ratio [OR], 4.7; 95% confidence interval [CI], 2.5–8.6), nonfaculty physician status (OR, 2.8; 95% CI, 1.5–5.1), and prior cesarean delivery (OR, 1.5; 95% CI, 1.0–2.1). Conclusion At our institution, 80% are clearly unavoidable.

The maternal syndrome of preeclampsia has been attributed to a systemic intravascular inflammatory response and endothelial cell dysfunction. The stimulus responsible for intravascular inflammation in preeclampsia has not been determined. The expression of CD45 isoforms on the surface of human T cells has been used to classify CD4(+) T lymphocytes into naïve cells (CD45RA+) and memory T cells (CD45RO+). An increased percentage of CD45RO+ cells has been interpreted as consistent with previous exposure to microbial products or other antigens. The purpose of this study was to determine whether preeclampsia is associated with a change in the proportion of CD45RA+ and CD45RO+.A prospective study was conducted in patients with preeclampsia (n = 24) and normal pregnancy (n = 75). The percentage of CD45RA+ and CD45RO+ on CD4(+) T lymphocytes in peripheral blood was determined using flow cytometry and monoclonal antibodies. Results were reported as a percentage of CD4(+) lymphocytes. Parametric statistics were used for analysis. A probability value of.05 was considered statistically significant.Patients with preeclampsia had a significantly higher percentage of CD45RO+ than normal pregnant women (P.01). A significantly lower percentage of CD45RA+ was found in patients with preeclampsia than in normal pregnant women (P.01).Preeclampsia is associated with an increase in the percentage of CD45RO+ and a decrease in the CD45RA+ lymphocyte subpopulation. Therefore, patients with preeclampsia have evidence of previous antigenic exposure, the nature of which remains to be established.

Objective: Our aim was to determine whether cocaine use increases neonatal morbidity in patients with preterm premature rupture of membranes. Study Design: We reviewed records of pregnancies that were complicated with preterm premature rupture of membranes between 24 weeks to 34 weeks of gestation. Clinical characteristics and neonatal outcomes of patients who had positive results for cocaine in the urine were compared with patients with negative test results. Results: During the study period, 16.1% (85/528 patients) had a positive result in a urine screen for cocaine use. Patients who used cocaine were older and of higher gravidity and parity. When major neonatal morbidities were compared, there was improvement in morbidities that were linked to neonatal infection in patients with positive test results for cocaine, including pneumonia (3.5% vs 11.7%; P =.012) and sepsis (5.9% vs 14.7%; P =.016). Jointly, neonatal outcomes were significantly worse in the negative cocaine group (χ 2 = 5.143; P =.023). Conclusion: The association of preterm premature rupture of membranes with major neonatal morbidity was unexpectedly and significantly weaker in pregnancies complicated by cocaine use. (Am J Obstet Gynecol 2002;186:1150-4.)

Objective The objective of this study was to determine the fetal drug compartment concentrations when various concentrations of carboplatin cross the placental-trophoblastic barrier and the effect on the fetal kidneys. Study Design An ex vivo human placenta perfusion model was utilized. Term human placentae (n = 9) were collected immediately after delivery and then reperfused with plasma concentrations achieved with carboplatin an area under the curve of 5 (1000 ng/mL), 7.5 (5000 ng/mL), or 11 (11,000 ng/mL). Antipyrine was used as a reference compound. Samples were collected over 2 hours. Placental transfer was evaluated by computation of transport fraction and clearance index. Primary cells isolated by explant culture of 16-18 week old fetal organ tissues were incubated with carboplatin for up to 48 hours with untreated cell as controls. Immunohistochemical, flow cytometry analysis, and immunoblotting were applied for the expression of apoptosis-related proteins. Results Mean transport fractions for carboplatin at low, middle, and high concentrations were 0.05 ± 0.02, 0.04 ± 0.01, and 0.10 ± 0.01, respectively, with clearance indexes of 0.22 ± 0.01, 0.14 ± 0.08, and 0.50 ± 0.07, respectively. The fetal peak concentrations of carboplatin achieved were 61 ± 39 ng/mL (low), 375 ± 248 ng/mL (middle), and 2081 ± 529 ng/mL (high). Fetal kidney cells exposed to carboplatin showed a concentration-dependent increased expression of apoptosis-inducing factor and p53 apoptosis proteins and a time-dependent increase in expression Bax apoptosis protein expression. Apoptosis was confirmed at the high concentration by flow cytometry. Conclusion Doses of carboplatin up to an area under the curve of 7.5 were not associated with significant placental transfer, fetal exposure, or fetal toxic effects. This suggests it might not be necessary to empirically reduce carboplatin doses in pregnant women.

Objective The objective of the study was to examine whether the size of silicon nanovectors (SNVs) inhibits their entrance into the fetal circulation. Study Design Pregnant rats were intravenously administered with SNVs or saline. The SNVs were spherical particles with 3 escalating diameters: 519 nm, 834 nm, and 1000 nm. The maternal and fetal distribution of SNVs was assessed. Results In animals that received 1000 or 834 nm SNV, silicon (Si) levels were significantly higher in the maternal organs vs the saline group, whereas the silicon levels in fetal tissues were similar to controls. However, in animals receiving 519 nm SNVs, fetal silicon levels were significantly higher in the SNV group compared with the saline group (5.93 ± 0.67 μg Si per organ vs 4.80 ± 0.33, P = .01). Conclusion Larger SNVs do not cross the placenta to the fetus and, remaining within the maternal circulation, can serve as carriers for harmful medications in order to prevent fetal exposure.