Choosing the Optimal Rat Stock as a Model for Research into Pharmacological Correction of Male Sexual Dysfunction.

The aim of the study is to identify the mechanisms mediating differences in sexual behavior between Sprague Dawley and Wistar rats, in order to choose the optimal stock for research into pharmacological correction of male sexual dysfunction. Materials and Methods: The experiments were carried out on sexually mature male rats of two stocks (Sprague Dawley and Wistar) weighing 350-450 g and aged 3 to 6 months. The comparative study of animal behavior was performed using standard tests for social interaction, locomotor activity, and anxiety level, as well as male mating behavior patterns. In order to determine the role of hypothalamic glycine receptors in the male sexual behavior, pharmacological manipulations of glycine receptor activity during mating with receptive females were conducted via bilateral intracerebral microcannulas implanted in the medial preoptic area (mPOA) of the male rat anterior hypothalamus. Results: The obtained results revealed statistically significant inter-stock differences in sexual behavior at the final consummatory stage of both intact animals and those after pharmacological activation of glycine receptors in the mPOA. The number of anxiety-related grooming patterns in the Open Field test significantly differed between the stocks for both intact animals and those after pharmacological activation of glycine receptors; the observed differences disappeared after the mPOA glycine receptors were blocked. In the Crowley test of social interaction, no significant difference was found between the stocks.Thus, the revealed difference in sexual behavior between Sprague Dawley and Wistar male rats is likely due to the difference in the level of anxiety, which, in turn, may be associated with difference in the mechanisms of glycinergic neurotransmission in the hypothalamic mPOAs of these rats. Conclusion: To study the relationship between the level of anxiety and sexual behavior, the choice of the Wistar rat stock is optimal since the male sexual behavior in this stock is more sensitive to stress than that in Sprague Dawley rats. However, to model male sexual dysfunction not associated with anxiety, the use of Sprague Dawley male rats should be preferred as these animals show more stable sexual behavior, which is less dependent on the level of anxiety.

Effects of Glycine Receptors of the Medial Preoptic Nucleus on Sexual Behavior of Male Wistar Rats.

We studied the effect of bilateral microinjections of selective pharmacological agents modulating glycine receptor activity into the medial preoptic nucleus on sexual behavior of male Wistar rats. Application of the glycine receptor blocker strychnine (20 µM, 2 µl) led to a significant inhibition of both appetitive and consummatory components of sexual behavior, whereas stimulation with glycine (1 mM and 50 µM, 2 µl) had no significant effect.

Preterm birth phenotypes in women with autoimmune rheumatic diseases: a population-based cohort study.

OBJECTIVE: To investigate preterm birth (PTB) phenotypes in women with different autoimmune rheumatic diseases in a large population-based cohort. DESIGN: Retrospective cohort study. SETTING: California, USA. POPULATION: All live singleton births in California between 2007 and 2011 were analysed. Patients with autoimmune disease at delivery were identified by International Classification of Diseases, Ninth Revision , Clinical Modification (ICD-9-CM), codes for systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis/dermatomyositis (DM/PM), and juvenile idiopathic arthritis (JIA). METHODS: Maternally linked hospital and birth certificate records of 2 481 516 deliveries were assessed (SLE n = 2272, RA n = 1501, SSc n = 88, JIA n = 187, DM/PM n = 38). Multivariable Poisson regression models estimated the risk ratios (RRs) for different PTB phenotypes (relative to term deliveries) for each autoimmune disease compared with the general obstetric population, adjusting for maternal age, race/ethnicity, body mass index, smoking, education, payer, parity, and prenatal care. MAIN OUTCOME MEASURES: Preterm birth (PTB) was assessed overall (20-36 weeks of gestation) and by subphenotype: preterm prelabour rupture of membranes (PPROM), spontaneous birth, or medically indicated PTB. The risk of PTB overall and for each phenotype was partitioned by gestational age: early (20-31 weeks of gestation) and late (32-36 weeks of gestation). RESULTS: Risks for PTB were elevated for each autoimmune disease evaluated: SLE (RR 3.27, 95% CI 3.01-3.56), RA (RR 2.04, 95% CI 1.79-2.33), SSc (RR 3.74, 95% CI 2.51-5.58), JIA (RR 2.23, 95% CI 1.54-3.23), and DM/PM (RR 5.26, 95% CI 3.12-8.89). These elevated risks were observed for the majority of PTB phenotypes as well. CONCLUSIONS: Women with systemic autoimmune diseases appear to have an elevated risk of various PTB phenotypes. Therefore, preconception counselling and close monitoring during pregnancy is crucial. TWEETABLE ABSTRACT: This study found that women with systemic autoimmune diseases have an elevated risk of preterm birth phenotypes.

Development and validation of a machine-learning model for prediction of shoulder dystocia.

OBJECTIVES: To develop a machine-learning (ML) model for prediction of shoulder dystocia (ShD) and to externally validate the model's predictive accuracy and potential clinical efficacy in optimizing the use of Cesarean delivery in the context of suspected macrosomia. METHODS: We used electronic health records (EHR) from the Sheba Medical Center in Israel to develop the model (derivation cohort) and EHR from the University of California San Francisco Medical Center to validate the model's accuracy and clinical efficacy (validation cohort). Subsequent to application of inclusion and exclusion criteria, the derivation cohort included 686 singleton vaginal deliveries, of which 131 were complicated by ShD, and the validation cohort included 2584 deliveries, of which 31 were complicated by ShD. For each of these deliveries, we collected maternal and neonatal delivery outcomes coupled with maternal demographics, obstetric clinical data and sonographic fetal biometry. Biometric measurements and their derived estimated fetal weight were adjusted (aEFW) according to gestational age at delivery. A ML pipeline was utilized to develop the model. RESULTS: In the derivation cohort, the ML model provided significantly better prediction than did the current clinical paradigm based on fetal weight and maternal diabetes: using nested cross-validation, the area under the receiver-operating-characteristics curve (AUC) of the model was 0.793 ± 0.041, outperforming aEFW combined with diabetes (AUC = 0.745 ± 0.044, P = 1e-16 ). The following risk modifiers had a positive beta that was > 0.02, i.e. they increased the risk of ShD: aEFW (beta = 0.164), pregestational diabetes (beta = 0.047), prior ShD (beta = 0.04), female fetal sex (beta = 0.04) and adjusted abdominal circumference (beta = 0.03). The following risk modifiers had a negative beta that was < -0.02, i.e. they were protective of ShD: adjusted biparietal diameter (beta = -0.08) and maternal height (beta = -0.03). In the validation cohort, the model outperformed aEFW combined with diabetes (AUC = 0.866 vs 0.784, P = 0.00007). Additionally, in the validation cohort, among the subgroup of 273 women carrying a fetus with aEFW ≥ 4000 g, the aEFW had no predictive power (AUC = 0.548), and the model performed significantly better (0.775, P = 0.0002). A risk-score threshold of 0.5 stratified 42.9% of deliveries to the high-risk group, which included 90.9% of ShD cases and all cases accompanied by maternal or newborn complications. A more specific threshold of 0.7 stratified only 27.5% of the deliveries to the high-risk group, which included 63.6% of ShD cases and all those accompanied by newborn complications. CONCLUSION: We developed a ML model for prediction of ShD and, in a different cohort, externally validated its performance. The model predicted ShD better than did estimated fetal weight either alone or combined with maternal diabetes, and was able to stratify the risk of ShD and neonatal injury in the context of suspected macrosomia. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Out-of-hospital births in California 1991-2011.

OBJECTIVE: We investigated the frequencies and characteristics of out-of-hospital births in a 20-year period in California, where 1 of every 7 births in the United States occurs. STUDY DESIGN: Birth certificate records of deliveries in California between 1991 and 2011 were analyzed. Out-of-hospital births were assessed by year, parity, gestational age and maternal race/ethnicity. RESULTS: In the 20-year period there were 10 593,904 deliveries, of which 46 243 occurred out of hospital (0.44%). Out-of-hospital births decreased from 0.54 to 0.38% per year between 1991 and 2004, and increased from 0.41% in 2005 to 0.61% in 2011. In contrast, preterm out-of-hospital births declined from 7.2% in 2006 to 5.0% in 2011. The frequency of vaginal birth after cesarean in the out-of-hospital birth cohort increased from 1.2% (n=19) in 1996 to 4.2% (n=82) in 2011. CONCLUSION: California birth records from a 20-year period show an increase in out-of-hospital births from years 2005 to 2011, following a period of decline from 1991 to 2004.

Opportunities for maternal transport for delivery of very low birth weight infants.

OBJECTIVE: To assess frequency of very low birth weight (VLBW) births at non-level III hospitals. STUDY DESIGN: Retrospective cohort study using linked California birth certificate and discharge data of 2008 to 2010 for deliveries of singleton or first-born infant of multiple gestations with birth weight 400 to 1500 g. Delivery rates by neonatal level of care were obtained. Risk of delivery at non-level III centers was estimated in univariable and multivariable models. RESULTS: Of the 1 508 143 births, 13 919 (9.2%) were VLBW; birth rate at non-level III centers was 14.9% (8.4% in level I and 6.5% in level II). Median rate of VLBW births was 0.3% (range 0 to 4.7%) annually at level I and 0.5% (range 0 to 1.6%) at level II hospitals. Antepartum stay for >24 h occurred in 14.0% and 26.9% of VLBW births in level I and level II hospitals, respectively. CONCLUSION: Further improvement is possible in reducing VLBW infant delivery at suboptimal sites, given the window of opportunity for many patients.

Maternal characteristics and mid-pregnancy serum biomarkers as risk factors for subtypes of preterm birth.

OBJECTIVE: To examine the relationship between maternal characteristics, serum biomarkers and preterm birth (PTB) by spontaneous and medically indicated subtypes. DESIGN: Population-based cohort. SETTING: California, United States of America. POPULATION: From a total population of 1 004 039 live singleton births in 2009 and 2010, 841 665 pregnancies with linked birth certificate and hospital discharge records were included. METHODS: Characteristics were compared for term and preterm deliveries by PTB subtype using logistic regression and odds ratios adjusted for maternal characteristics and obstetric factors present in final stepwise models and 95% confidence intervals. First-trimester and second-trimester serum marker levels were analysed in a subset of 125 202 pregnancies with available first-trimester and second-trimester serum biomarker results. MAIN OUTCOME MEASURE: PTB by subtype. RESULTS: In fully adjusted models, ten characteristics and three serum biomarkers were associated with increased risk in each PTB subtype (Black race/ethnicity, pre-existing hypertension with and without pre-eclampsia, gestational hypertension with pre-eclampsia, pre-existing diabetes, anaemia, previous PTB, one or two or more previous caesarean section(s), interpregnancy interval ≥ 60 months, low first-trimester pregnancy-associated plasma protein A, high second-trimester α-fetoprotein, and high second-trimester dimeric inhibin A). These risks occurred in 51.6-86.2% of all pregnancies ending in PTB depending on subtype. The highest risk observed was for medically indicated PTB <32 weeks in women with pre-existing hypertension and pre-eclampsia (adjusted odds ratio 89.7, 95% CI 27.3-111.2). CONCLUSIONS: Our findings suggest a shared aetiology across PTB subtypes. These commonalities point to targets for further study and exploration of risk reduction strategies. TWEETABLE ABSTRACT: Findings suggest a shared aetiology across preterm birth subtypes. Patterns may inform risk reduction efforts.

Maternal serum markers, characteristics and morbidly adherent placenta in women with previa.

OBJECTIVE: To examine associations with morbidly adherent placenta (MAP) among women with placenta previa. STUDY DESIGN: Women with MAP (cases) and previa alone (controls) were identified from a cohort of 236,714 singleton pregnancies with both first and second trimester prenatal screening, and live birth and hospital discharge records; pregnancies with aneuploidies and neural tube or abdominal wall defects were excluded. Logistic binomial regression was used to compare cases with controls. RESULT: In all, 37 cases with MAP and 699 controls with previa alone were included. Risk for MAP was increased among multiparous women with pregnancy-associated plasma protein-A (PAPP-A) ⩾95th percentile (⩾2.63 multiple of the median (MoM); adjusted OR (aOR) 8.7, 95% confidence interval (CI) 2.8 to 27.4), maternal-serum alpha fetoprotein (MS-AFP) ⩾95th percentile (⩾1.79 MoM; aOR 2.8, 95% CI 1.0 to 8.0), and 1 and ⩾2 prior cesarean deliveries (CDs; aORs 4.4, 95% CI 1.5 to 13.6 and 18.4, 95% CI 5.9 to 57.5, respectively). CONCLUSION: Elevated PAPP-A, elevated MS-AFP and prior CDs are associated with MAP among women with previa.

Response times for emergency cesarean delivery: use of simulation drills to assess and improve obstetric team performance.

OBJECTIVE: We documented time to key milestones and determined reasons for transport-related delays during simulated emergency cesarean. STUDY DESIGN: Prospective, observational investigation of delivery of care processes by multidisciplinary teams of obstetric providers on the labor and delivery unit at Lucile Packard Children's Hospital, Stanford, CA, USA, during 14 simulated uterine rupture scenarios. The primary outcome measure was the total time from recognition of the emergency (time zero) to that of surgical incision. RESULT: The median (interquartile range) from time zero until incision was 9 min 27 s (8:55 to 10:27 min:s). CONCLUSION: In this series of emergency cesarean drills, our teams required approximately nine and a half minutes to move from the labor room to the nearby operating room (OR) and make the surgical incision. Multiple barriers to efficient transport were identified. This study demonstrates the utility of simulation to identify and correct institution-specific barriers that delay transport to the OR and initiation of emergency cesarean delivery.

Transdisciplinary translational science and the case of preterm birth.

Medical researchers have called for new forms of translational science that can solve complex medical problems. Mainstream science has made complementary calls for heterogeneous teams of collaborators who conduct transdisciplinary research so as to solve complex social problems. Is transdisciplinary translational science what the medical community needs? What challenges must the medical community overcome to successfully implement this new form of translational science? This article makes several contributions. First, it clarifies the concept of transdisciplinary research and distinguishes it from other forms of collaboration. Second, it presents an example of a complex medical problem and a concrete effort to solve it through transdisciplinary collaboration: for example, the problem of preterm birth and the March of Dimes effort to form a transdisciplinary research center that synthesizes knowledge on it. The presentation of this example grounds discussion on new medical research models and reveals potential means by which they can be judged and evaluated. Third, this article identifies the challenges to forming transdisciplines and the practices that overcome them. Departments, universities and disciplines tend to form intellectual silos and adopt reductionist approaches. Forming a more integrated (or 'constructionist'), problem-based science reflective of transdisciplinary research requires the adoption of novel practices to overcome these obstacles.

Postpartum hemorrhage treated with a massive transfusion protocol at a tertiary obstetric center: a retrospective study.

BACKGROUND: A massive transfusion protocol may offer major advantages for management of postpartum hemorrhage. The etiology of postpartum hemorrhage, transfusion outcomes and laboratory indices in obstetric cases requiring the massive transfusion protocol were retrospectively evaluated in a tertiary obstetric center. METHODS: We reviewed medical records of obstetric patients requiring the massive transfusion protocol over a 31-month period. Demographic, obstetric, transfusion, laboratory data and adverse maternal outcomes were abstracted. RESULTS: Massive transfusion protocol activation occurred in 31 patients (0.26% of deliveries): 19 patients (61%) had cesarean delivery, 10 patients (32%) had vaginal delivery, and 2 patients (7%) had dilation and evacuation. Twenty-six patients (84%) were transfused with blood products from the massive transfusion protocol. The protocol was activated within 2h of delivery for 17 patients (58%). Median [IQR] total estimated blood loss value was 2842 [800-8000]mL. Median [IQR] number of units of red blood cells, plasma and platelets from the massive transfusion protocol were: 3 [1.75-7], 3 [1.5-5.5], and 1 [0-2.5] units, respectively. Mean (SD) post-resuscitation hematologic indices were: hemoglobin 10.3 (2.4)g/dL, platelet count 126 (44)×10(9)/L, and fibrinogen 325 (125)mg/dL. The incidence of intensive care admission and peripartum hysterectomy was 61% and 19%, respectively. CONCLUSIONS: Our massive transfusion protocol provides early access to red blood cells, plasma and platelets for patients experiencing unanticipated or severe postpartum hemorrhage. Favorable hematologic indices were observed post resuscitation. Future outcomes-based studies are needed to compare massive transfusion protocol and non-protocol based transfusion strategies for the management of hemorrhage.

Serum relaxin levels and kidney function in late pregnancy with or without preeclampsia.

OBJECTIVE: Relaxin, a potent pregnancy-related hormone, has been proposed to be a major mediator of renal physiology in normal pregnancy. We wished to test relaxin levels in pregnancy and preeclampsia. METHODS: We performed precise physiologic measurements of kidney function in 38 normal peripartum women and 58 women with preeclampsia. We measured serum relaxin levels prior to delivery and over the first 4 postpartum weeks utilizing a modern, validated ELISA. Results were compared to those of 18 normal women of childbearing age. RESULTS: Relaxin levels were substantially elevated in women prior to delivery (364 ± 268 vs. 15 ± 16 pg/ml) and fell rapidly over the first postpartum week reaching normal non pregnant levels by Week 2 (32 ± 64 vs. 15 ± 16 pg/ml). No differences were seen between relaxin levels in normal pregnancy as compared to preeclampsia (364 ± 268 vs. 376 ± 241 pg/ml) despite substantial and persistent abnormalities in GFR (149 ± 33 vs. 89 ± 25 ml/min), albuminuria (14 vs. 687 mg/g) and mean arterial pressure (80 ± 8 vs. 111 ± 18). Furthermore no correlation could be established between physiologic measures (GFR, MAP, RBF, RVR) and relaxin levels (p > 0.3), either in the overall population or any of the subgroups. CONCLUSION: Relaxin is indeed significantly elevated in the serum of women during late pregnancy and the early puerperium. However, serum relaxin does not appear to influence BP, renal vascular resistance, renal blood flow or GFR in late pregnancy or in women with preeclampsia.

Urinalysis vs urine protein-creatinine ratio to predict significant proteinuria in pregnancy.

OBJECTIVE: To compare the urine protein-creatinine ratio with urinalysis to predict significant proteinuria (>or=300 mg per day). STUDY DESIGN: A total of 116 paired spot urine samples and 24-h urine collections were obtained prospectively from women at risk for preeclampsia. Urine protein-creatinine ratio and urinalysis were compared to the 24-h urine collection. RESULT: The urine protein-creatinine ratio had better discriminatory power than urinalysis: the receiver operating characteristic curve had a greater area under the curve, 0.89 (95% confidence interval (CI) 0.83 to 0.95) vs 0.71 (95% CI 0.64 to 0.77, P<0.001). When matched for clinically relevant specificity, urine protein-creatinine ratio (cutoff >or=0.28) is more sensitive than urinalysis (cutoff >or=1+): 66 vs 41%, P=0.001 (with 95 and 100% specificity, respectively). Furthermore, the urine protein-creatinine ratio predicted the absence or presence of proteinuria in 64% of patients; urinalysis predicted this in only 19%. CONCLUSION: The urine protein-creatinine ratio is a better screening test. It provides early information for more patients.

Course of preeclamptic glomerular injury after delivery.

We evaluated the early postpartum recovery of glomerular function over 4 wk in 57 women with preeclampsia. We used physiological techniques to measure glomerular filtration rate (GFR), renal plasma flow, and oncotic pressure (pi(A)) and computed a value for the two-kidney ultrafiltration coefficient (K(f)). Compared with healthy, postpartum controls, GFR was depressed by 40% on postpartum day 1, but by only 19% and 8% in the second and fourth postpartum weeks, respectively. Hypofiltration was attributable solely to depression, at corresponding postpartum times, of K(f) by 55%, 30%, and 18%, respectively. Improvement in glomerular filtration capacity was accompanied by recovery of hypertension to near-normal levels and significant improvement in albuminuria. We conclude that the functional manifestations of the glomerular endothelial injury of preeclampsia largely resolve within the first postpartum month.

Outcome of pregnancies complicated by systemic sclerosis and mixed connective tissue disease.

Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are rare autoimmune diseases which share the common feature of non-inflammatory vasculopathy. Studies evaluating pregnancy outcomes in these patients have yielded conflicting results. We sought to describe the outcomes of pregnancies associated with SSc and MCTD followed at our center utilizing a retrospective review of all pregnant women with SSc and MCTD followed at Stanford University from 1993 to 2003. We identified 20 pregnancies occurring in 13 women with SSc or MCTD. Twelve pregnancies occurred in seven women with SSc and eight pregnancies occurred in six women with MCTD. The overall preterm delivery rate was 39% and small for gestational age infants occurred in 50% and 63% of pregnancies associated with SSc and MCTD, respectively. Fetal loss complicated two pregnancies in women with severe diffuse SSc and the antiphospholipid antibody syndrome. There were no cases of congenital heartblock among infants, and only one case of pre-eclampsia was observed. Maternal flares of disease during pregnancy were generally mild. Most pregnancies in women with SSc and MCTD in this cohort were uncomplicated. The high rates of prematurity and small for gestational age infants underscore the risk for growth restriction consistent with the vasculopathy associated with these diseases.

Effect of L-arginine therapy on the glomerular injury of preeclampsia: a randomized controlled trial.

OBJECTIVE: To assess the benefit of l-arginine, the precursor to nitric oxide, on blood pressure and recovery of the glomerular lesion in preeclampsia. METHODS: Forty-five women with preeclampsia were randomized to receive either l-arginine or placebo until day 10 postpartum. Primary outcome measures including mean arterial pressure, glomerular filtration rate, and proteinuria were assessed on the third and 10th days postpartum by inulin clearance and albumin-to-creatinine ratio. Nitric oxide, cyclic guanosine 3'5' monophosphate, endothelin-1, and asymmetric-dimethyl-arginine and arginine levels were assayed before delivery and on the third and 10th days postpartum. Healthy gravid women provided control values. Assuming a standard deviation of 10 mm Hg, the study was powered to detect a 10-mm Hg difference in mean arterial pressure (alpha .05, beta .20) between the study groups. RESULTS: No significant differences existed between the groups with preeclampsia before randomization. Compared with the gravid control group, women with preeclampsia exhibited significantly increased serum levels of endothelin-1, cyclic guanosine 3'5' monophosphate, and asymmetric-dimethyl-arginine before delivery. Despite a significant increase in postpartum serum arginine levels due to treatment, no differences were found in the corresponding levels of nitric oxide, endothelin-1, cyclic guanosine 3'5' monophosphate, or asymmetric-dimethyl-arginine between the two groups with preeclampsia. Further, there were no significant differences in any of the primary outcome measures with both groups demonstrating similar levels in glomerular filtration rate and equivalent improvements in both blood pressure and proteinuria. CONCLUSION: Blood pressure and kidney function improve markedly in preeclampsia by the 10th day postpartum. Supplementation with l-arginine does not hasten this recovery. LEVEL OF EVIDENCE: I.

Neonatal chest wall rigidity following the use of remifentanil for cesarean delivery in a patient with autoimmune hepatitis and thrombocytopenia.

Remifentanil is a useful adjunct in general anesthesia for high-risk obstetric patients. It provides effective blunting of the rapid hemodynamic changes that may be associated with airway manipulation and surgical stimulation. There have been no previous reports of opioid-related rigidity in the neonate delivered by a parturient receiving intraoperative remifentanil. We present a case of short-lived neonatal rigidity and respiratory depression following remifentanil administration during cesarean section to a parturient with autoimmune hepatitis complicated by cirrhosis, esophageal varices and thrombocytopenia.

The dynamics of glomerular filtration in the puerperium.

We evaluated the glomerular filtration rate (GFR) during the second postpartum week in 22 healthy women who had completed an uncomplicated pregnancy. We used physiological techniques to measure GFR, renal plasma flow, and oncotic pressure and computed a value for the two-kidney ultrafiltration coefficient (K(f)). We compared these findings with those in pregnant women previously studied on the first postpartum day as well as nongravid women of reproductive age. Healthy female transplant donors of reproductive age permitted the morphometric analysis of glomeruli and computation of the single-nephron K(f). The aforementioned physiological and morphometric measurements were utilized to estimate transcapillary hydraulic pressure (Delta P) from a mathematical model of glomerular ultrafiltration. We conclude that postpartum day 1 is associated with marked glomerular hyperfiltration (+41%). A theoretical analysis of GFR determinants suggests that depression of glomerular capillary oncotic pressure, the force opposing the formation of filtrate, is the predominant determinant of early elevation of postpartum GFR. A reversal of the gestational hypervolemia and hemodilution, still evident on postpartum day 1, eventuates by postpartum week 2. An elevation of oncotic pressure in the plasma that flows axially along the glomerular capillaries to supernormal levels ensues; however, GFR remains modestly elevated (+20%) above nongravid levels. An analysis of filtration dynamics at this time suggests that a significant increase in Delta P by up to 16%, an approximately 50% increase in K(f), or a combination of smaller increments in both must be invoked to account for the persistent hyperfiltration.

Central nervous system lupus and pregnancy: 11-year experience at a single center.

OBJECTIVE: To describe the pregnancy outcomes in women with central nervous system (CNS) manifestations of lupus. METHODS: Between 1991 and 2002, the outcome of five pregnancies in four patients with CNS lupus were retrospectively reviewed. All patients had an established history of systemic lupus erythematosus (SLE), and either a history of CNS lupus or active CNS lupus. Pregnancy outcomes assessed included term and preterm birth, intrauterine growth restriction, abnormal antepartum testing, perinatal mortality, pre-eclampsia and other maternal morbidities. RESULTS: Evidence of active CNS lupus symptoms developed in three of the five pregnancies. Two pregnancies were complicated by early onset pre-eclampsia, abnormal antepartum testing and extreme prematurity, with one subsequent neonatal death. The remaining three pregnancies had good neonatal outcomes, but were complicated by severe maternal post-pregnancy exacerbations, and the eventual death of one patient. CONCLUSIONS: CNS lupus in pregnancy represents an especially severe manifestation of SLE, and may involve great maternal and fetal risks.

A longitudinal analysis of maternal serum insulin-like growth factor I (IGF-I) and total and nonphosphorylated IGF-binding protein-1 in human pregnancies complicated by intrauterine growth restriction.

In cord blood and late gestation maternal serum, IGF-I is positively correlated with birth weight, whereas IGF-binding protein-1 (IGFBP-1) is inversely correlated with birth weight. Our goal was to determine whether maternal serum or amniotic fluid concentrations of IGF-I, IGFBP-1, or nonphosphorylated IGFBP-1 (npIGFBP-1) in early gestation predict later fetal growth abnormalities. Maternal serum was collected prospectively across gestation (5-40 wk) from 749 pregnant subjects. Amniotic fluid was collected after amniocentesis during wk 15-26 from 207 subjects. We compared median serum concentrations of IGF-I, IGFBP-1, and npIGFBP-1 in 38 subjects who delivered growth-restricted infants with the control group of 236 subjects with normal weight infants for each gestational age grouping, wk 5-12, 13-23, and 24-34. In the control group median IGF-I concentrations were 14.8, 11, and 15.6 nmol/liter for wk 5-12, 13-23, and 24-34, respectively, compared with 13.7, 14.3, and 10.6 nmol/liter in the intrauterine growth restriction (IUGR) group. Median IGFBP-1 concentrations were 8.5, 30.4, and 24.4 nmol/liter, respectively, in controls, compared with 11.4, 28.6, and 25.5 nmol/liter in the IUGR group. Median npIGFBP-1 concentrations were 6.9, 22, and 17.4 nmol/liter, respectively, in controls, compared with 5.0, 32.1, and 24.2 nmol/liter in the IUGR group. In the control group the median amniotic fluid IGFBP-1 level was 13,160 nmol/liter, and the median npIGFBP-1 level was 15,970 nmol/liter; in the IUGR group these levels were 13,440 and 18,440 nmol/liter, respectively. No clinically useful differences were found between the IUGR and control groups. Our results do not support the use of maternal serum IGF-I or IGFBP-1 or amniotic fluid IGFBP-1 or npIGFBP-1 early in gestation to predict later fetal growth restriction.