A randomized open-label controlled trial of chlorhexidine-alcohol vs povidone-iodine for cesarean antisepsis: the CAPICA trial.

BACKGROUND: Identification of optimal surgical site antisepsis preparations may reduce cesarean-related surgical site infections. Two recently published investigations examined efficacy of chlorhexidine-alcohol and iodine-alcohol preparations. No previous randomized controlled trial has compared chlorhexidine-alcohol to povidone-iodine aqueous scrub and paint in reduction of cesarean-related surgical site infection. OBJECTIVE: The purpose of the study was to determine if chlorhexidine-alcohol would result in fewer surgical site infections than povidone-iodine when used as skin antisepsis preparation prior to cesarean delivery. STUDY DESIGN: This study was a single-center pragmatic randomized controlled trial at an urban tertiary care institution to compare chlorhexidine-alcohol 26-mL single-step applicator to povidone-iodine aqueous scrub and paint 236-mL wet skin tray as preoperative skin antiseptic preparation for women undergoing cesarean delivery. Patients were eligible for study participation if they could provide informed consent in English or Spanish, were ≥18 years of age, did not have clinical chorioamnionitis, were unlikely to be lost to follow-up, and had no sensitivities to chlorhexidine, betadine, or iodine. Treatment was assigned by computer-generated simple 1:1 randomization immediately before skin preparation. The primary outcome was surgical site infection occurring within 30 days of cesarean delivery including ≥1 of: superficial or deep surgical site infection, or endometritis, according to Centers for Disease Control and Prevention definitions. Analysis was by intent to treat. Categorical outcomes were compared using Fisher exact test. The Wilcoxon rank-sum test was performed for continuous outcomes. This trial was institutional review board approved and registered at ClinicalTrials.gov (NCT02202577). RESULTS: In all, 932 subjects (461 assigned to chlorhexidine-alcohol, 471 assigned to povidone-iodine) were randomized from February 2013 through May 2016. Rate of follow-up evaluation after 30 days was 99% (455) in the chlorhexidine-alcohol group and 97% (455) in the povidone-iodine group. Surgical site infection occurred in 29 (6.3%) of the chlorhexidine-alcohol group and 33 (7.0%) in the povidone-iodine group (P = .38). The rates of individual components of the primary outcome were as follows: superficial surgical site infection (4.6% v 5.5%; P = .55), deep surgical site infection (0.0% v 0.4%; P = .50), and endometritis (1.7% v 1.1%; P = .42) in chlorhexidine-alcohol vs povidone-iodine arms, respectively. All results were similar in per protocol analysis. CONCLUSION: Preoperative antiseptic skin preparation with chlorhexidine-alcohol 26-mL single-step applicator before cesarean did not result in less frequent surgical site infection when compared with povidone-iodine aqueous scrub and paint 236-mL wet skin preparation tray. Povidone-iodine should still be considered as acceptable for preoperative surgical site antisepsis for cesarean delivery.

Comparison of 2- and 3-Dimensional Sonography for Estimation of Birth Weight and Neonatal Adiposity in the Setting of Suspected Fetal Macrosomia.

OBJECTIVES: To compare the accuracy of 2-dimensional (2D) and 3-dimensional (3D) fetal measurements for prediction of birth weight Z score and neonatal adiposity (percent body fat) in the setting of suspected fetal macrosomia. METHODS: We conducted a prospective observational study of term singleton pregnancies with suspected macrosomia. Patients were enrolled on admission to labor and delivery and underwent sonographic examinations. Within 48 hours of delivery, neonatal anthropometric measurements were obtained. RESULTS: Thirty-four neonates were included in the analysis. Mothers were very obese (mean body mass index ± SD, 39.1 ± 7.8 kg/m(2)); 56.5% were white; and 39.1% had diabetes. Neonates were 38% female and had a mean birth weight of 3940.0 ± 496.8 g, percent body fat of 18.5% ± 4.0%, and Ponderal index of 2.8 ± 0.3 g/cm(3). Mean 2D estimated fetal weight was 3973 ± 443 g; mean 3D estimated fetal weight was 3803 ± 528 g; and mean thigh volume was 102.5 ± 19.6 cm(3). Both 2D and 3D measurements accounted for about half the variance in predicted birth weight (R(2) for 2D = 0.53, 71% within 10% of birth weight; R(2) for 3D = 0.47, 65% within 10% of birth weight). Thigh volume Z score was the prenatal parameter most highly correlated with both birth weight Z score (R(2) = 0.52; r = 0.72; 95% confidence interval, 0.54-0.84; P < .001) and percent body fat (R(2) = 0.22; r = 0.47; 95% confidence interval, 0.17-0.69; P = .04). CONCLUSIONS: In our population of fetuses with suspected macrosomia, fractional thigh volume was the best sonographic estimate of neonatal percent body fat and birth weight Z score. Future research on prediction of neonatal weight and adiposity in macrosomic fetuses should include an estimate of fetal soft tissue given the generalized increase in body fat of these fetuses.

Exercise training and dietary glycemic load may have synergistic effects on insulin resistance in older obese adults.

BACKGROUND/AIMS: The aim of this study was to assess the combined effects of exercise and dietary glycemic load on insulin resistance in older obese adults. METHODS: Eleven men and women (62 +/- 2 years; 97.6 +/- 4.8 kg; body mass index 33.2 +/- 2.0) participated in a 12-week supervised exercise program, 5 days/week, for about 1 h/day, at 80-85% of maximum heart rate. Dietary glycemic load was calculated from dietary intake records. Insulin resistance was determined using the euglycemic (5.0 mM) hyperinsulinemic (40 mU/m(2)/min) clamp. RESULTS: The intervention improved insulin sensitivity (2.37 +/- 0.37 to 3.28 +/- 0.52 mg/kg/min, p < 0.004), increased VO(2max) (p < 0.009), and decreased body weight (p < 0.009). Despite similar caloric intakes (1,816 +/- 128 vs. 1,610 +/- 100 kcal/day), dietary glycemic load trended towards a decrease during the study (140 +/- 10 g before, vs. 115 +/- 8 g during, p < 0.04). The change in insulin sensitivity correlated with the change in glycemic load (r = 0.84, p < 0.009). Four subjects reduced their glycemic load by 61 +/- 8%, and had significantly greater increases in insulin sensitivity (78 +/- 11 vs. 23 +/- 8%, p < 0.003), and decreases in body weight (p < 0.004) and plasma triglycerides (p < 0.04) compared to the rest of the group. CONCLUSION: The data suggest that combining a low-glycemic diet with exercise may provide an alternative and more effective treatment for insulin resistance in older obese adults.

Intrapartum Fetal Heart Rate Tracing Among Small-for-Gestational Age Compared With Appropriate-for-Gestational-Age Neonates.

OBJECTIVE: To compare fetal heart rate (FHR) patterns during the last hour of labor between small-for-gestational-age (SGA; birth weight less than the 10th percentile for gestational age) and appropriate-for-gestational-age (AGA; birth weight at the 10-90th percentile) neonates at 36 weeks of gestation or greater. We also compared the rate of cesarean delivery and composite neonatal morbidity among SGA and AGA newborns. METHODS: This is a secondary analysis of a randomized trial of intrapartum fetal electrocardiographic ST-segment analysis. We excluded women with chorioamnionitis, insufficient duration of FHR tracing in the hour before delivery, and anomalous newborns. Fetal heart rate patterns were categorized by computerized pattern recognition software (PeriCALM Patterns). Composite neonatal morbidity was defined as any of the following: intrapartum fetal death, Apgar score 3 or less at 5 minutes, cord artery pH 7.05 or less, base deficit 12 mmol/L or greater, neonatal seizure, intubation at delivery, neonatal encephalopathy, and neonatal death. Logistic regression was used to evaluate the association between FHR patterns and SGA adjusted for magnesium sulfate exposure and stage of labor. RESULTS: Of the 11,108 women randomized, 85% (n=9,402) met inclusion criteria, of whom 9% were SGA. In the last hour, the likelihood of accelerations was significantly lower among SGA than AGA neonates (72.4% vs 66.8%; P=.001). Variable decelerations lasting greater than 60 seconds, with depth greater than 60 beats per minute (bpm) or nadir less than 60 bpm, were significantly more common with SGA than AGA (all P<.001). The rate of late decelerations, prolonged decelerations, or bradycardia were similar between SGA and AGA (all P>.05). Cesarean delivery for fetal indications was significantly more common with SGA (7.0%) than AGA (4.0%; P<.001). The composite neonatal morbidity was 1.4% among SGA and 1.0% among AGA (odds ratio 1.40, 95% CI 0.74-2.64). CONCLUSION: Although the FHR patterns in the last hour of labor differ among SGA and AGA neonates, as does the rate of cesarean delivery, the composite neonatal morbidity was similar.

The force required to rupture fetal membranes paradoxically increases with acute in vitro repeated stretching.

OBJECTIVE: The purpose of this study was to determine whether acute repetitive stretching causes fetal membranes (FM) weakening. STUDY DESIGN: Cesarean or vaginally delivered FM were repeatedly stretched and thereafter subjected to rupture testing. Rupture strength (RS), work to rupture (WR), and stiffness were determined. Unstretched FM were compared with stretched FM. RESULTS: In the cesarean group, FM stretched to 50% or 75% of the baseline (unstretched) RS for 10-20 cycles of 10 seconds each paradoxically showed increased RS and stiffness. WR decreased compared with baseline. Detailed analysis revealed that even a single stretch cycle initiated these changes to physical properties. Vaginally delivered FM showed similar changes in physical properties, as did separated amnion. CONCLUSION: Acute stretch forces do not directly cause FM weakening.

Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat.

Exercise improves glucose metabolism and delays the onset and/or reverses insulin resistance in the elderly by an unknown mechanism. In the present study, we examined the effects of exercise training on glucose metabolism, abdominal adiposity, and adipocytokines in obese elderly. Sixteen obese men and women (age = 63 +/- 1 yr, body mass index = 33.2 +/- 1.4 kg/m2) participated in a 12-wk supervised exercise program (5 days/wk, 60 min/day, treadmill/cycle ergometry at 85% of heart rate maximum). Visceral fat (VF), subcutaneous fat, and total abdominal fat were measured by computed tomography. Fat mass and fat-free mass were assessed by hydrostatic weighing. An oral glucose tolerance test was used to determine changes in insulin resistance. Exercise training increased maximal oxygen consumption (21.3 +/- 0.8 vs. 24.3 +/- 1.0 ml.kg(-1).min(-1), P < 0.0001), decreased body weight (P < 0.0001) and fat mass (P < 0.001), while fat-free mass was not altered (P > 0.05). VF (176 +/- 20 vs. 136 +/- 17 cm2, P < 0.0001), subcutaneous fat (351 +/- 34 vs. 305 +/- 28 cm2, P < 0.03), and total abdominal fat (525 +/- 40 vs. 443 +/- 34 cm2, P < 0.003) were reduced through training. Circulating leptin was lower (P < 0.003) after training, but total adiponectin and tumor necrosis factor-alpha remained unchanged. Insulin resistance was reversed by exercise (40.1 +/- 7.7 vs. 27.6 +/- 5.6 units, P < 0.01) and correlated with changes in VF (r = 0.66, P < 0.01) and maximal oxygen consumption (r = -0.48, P < 0.05) but not adipocytokines. VF loss after aerobic exercise training improves glucose metabolism and is associated with the reversal of insulin resistance in older obese men and women.

Autoimmune disease as a cause of reproductive failure.

High-risk pregnancy is the most common clinical association with antiphospholipid antibodies; the principal manifestations are pregnancy loss and early preeclampsia. Membership in this family of antibodies is continually growing and includes antibodies against a variety of phospholipids, phospholipid-protein complexes, and phospholipid-binding proteins. The current information in the literature is inadequate to clearly implicate a subgroup of antiphospholipid antibodies or a particular pathophysiologic mechanism as being responsible for poor pregnancy outcomes. It is clear, however, that prevalent diagnostic tests for LA and aCL are extremely useful to identify many of these patients, but are inadequate for diagnosis of all patients with autoimmune pregnancy loss or to elucidate the pathophysiology. Many patients who present clinically with autoimmune-like pregnancy complications currently are negative in tests for LA or aCL, but have antibodies against annexin V, phosphatidylserine, or other relevant antigens. The greatest risk for a complicated pregnancy is conveyed by a subgroup of antibodies that affect the normal function of placental trophoblast. As clinical laboratory tests designed to detect more members of the antiphospholipid antibody family become available, understanding of this complicated disease (APS) will increase.

Neonatal anthropometric measurements to predict birth weight by ultrasound.

OBJECTIVE: To develop a more accurate ultrasound birth weight (BW) model using neonatal anthropometric measurements. STUDY DESIGN: Two hundred thirty-one newborns were evaluated. Measurements included weight; head, chest, and abdominal circumferences (umbilicus and liver), humerus, and femur lengths. Infants were randomly assigned into two groups (G(1) and G(2)). Anthropometric measurements that are obtainable by ultrasound were generated from G(1). Stepwise regression and a bootstrap analysis were used to create the prediction models. The models were validated using G(2). RESULTS: The final stepwise regression model included FL and circumferences of the head, chest, and abdomen. The correlations were: G(1): R(2)=0.91, p<0.001; G(2): R(2)=0.90 p<0.001. There was no difference between derived and actual BW in G(1) (p=0.42) or G(2) (p=0.28). The mean absolute percent error between the prediction model and actual BW was 3.8%. CONCLUSION: Neonatal anthropometric models are strongly predictive of actual BW. This model will be tested prospectively using ultrasound to predict fetal weight.

Fetal membranes from term vaginal deliveries have a zone of weakness exhibiting characteristics of apoptosis and remodeling.

BACKGROUND: Recently we identified a weak zone in term, pre-labor (repeat Cesarean section) human fetal membranes (FM) overlying the cervix with biochemical characteristics suggestive of apoptosis and collagen remodeling. We suggested that this weak zone is the FM rupture initiation site. Vaginally delivered patients have a weak zone in their FM overlying the cervix; a comparable weak zone lies adjacent to the tear line in FM after spontaneous rupture (SROM). METHODS: FM from vaginally delivered patients with artificial rupture (AROM) and SROM were collected. FM of AROM patients were marked per vagina to identify the FM zone overlying the cervix. Postpartum FM were cut, strength tested, and piece strengths were remapped to their former location on a three-dimensional model. A 10-cm diameter zone centered on the marked area (AROM), or defined weak zone (SROM) was compared with the remaining FM. RESULTS: AROM FM exhibit a para-cervical weak zone. SROM FM exhibit a comparable zone on the tear line. The mean rupture strength within weak zones was 60% of the remaining membranes (P <.001). AROM and SROM FM weak zones both exhibit increased matrix metalloproteinase 9, increased poly (ADP-ribose) polymerase I cleavage, decreased tissue inhibitor of metalloproteinase 3 protein, and histology consistent with remodeling and apoptosis. CONCLUSION: Vaginally delivered AROM FM contain a weak zone overlying the cervix. Vaginally delivered SROM FM contain a weak zone adjacent to the tear line that exhibits biochemical and mechanical characteristics suggestive of collagen remodeling and apoptosis comparable to those of the AR FM weak zone.

Proinflammatory cytokines found in amniotic fluid induce collagen remodeling, apoptosis, and biophysical weakening of cultured human fetal membranes.

The mechanisms by which fetal membranes (FM) rupture during the birth process are unknown. We have recently reported that FM weaken, at least in part, because of a developmental process of extracellular matrix remodeling and apoptosis. We now hypothesize that cytokines that normally increase in amniotic fluid at term induce FM collagen remodeling and apoptosis with concomitant weakening. Full-thickness FM fragments were cultured with (0-100 ng/ml) or without tumor necrosis factor (TNF) or interleukin 1, beta (IL1B). Physical properties were then examined with specially adapted industrial rupture strength testing equipment. Cultured FM were also evaluated for evidence of collagen remodeling and apoptosis. Cytokine-treated FM exhibited a dose-dependent decrease in strength and work to rupture. Compared with controls, the highest TNF dose caused maximal decrease in FM rupture strength (13.2 +/- 1.2 N versus 3.8 +/- 1.5 N; P = 0.0003) and work to rupture (0.035 +/- 0.005 J versus 0.005 +/- 0.002 J; P < 0.0001). The highest IL1B dose also decreased rupture strength (12.9 +/- 3.2 versus 4.6 +/- 1.1 N; P = 0.0027) and work to rupture (0.018 +/- 0.005 J versus 0.005 +/- 0.002 J; P < 0.01). Matrix metalloproteinase 9 (MMP9) protein increased, tissue inhibitor of matrix metalloproteinase 3 (TIMP3) protein decreased, and poly (ADP-ribose) polymerase (PARP1) cleavage increased with increasing TNF or IL1B doses (all P < 0.05), suggesting collagen remodeling and apoptosis. TNF and IL1B cause significant weakening of cultured FM. Both cytokines induce biochemical markers in the FM in a manner characteristic of the weak zone of FM overlying the cervix. TNF and or IL1B may be involved in the development of the weak zone of the FM.