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Objective To assess whether assisted reproductive technology (ART) is associated with increased risk of adverse perinatal outcomes in triplet gestations compared with spontaneous conception. Study Design Secondary analysis of a multicenter randomized trial for the prevention of preterm birth in multiple gestations. Triplets delivered at ≥ 24 weeks were studied. The primary outcome was the rate of composite neonatal morbidity (CNM) that included one or more of the following: bronchopulmonary dysplasia, respiratory distress syndrome, necrotizing enterocolitis, culture proven sepsis, pneumonia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, or perinatal death. Results There were 381 triplets (127 women) of which 89 patients conceived via ART and 38 patients spontaneously. Women with ART were more likely to be older, Caucasian, married, nulliparous, have higher level of education, and develop pre-eclampsia. Spontaneously conceived triplets were more likely to delivery at an earlier gestation (31.2 ± 3.5 vs 32.8 ± 2.7 weeks) (p = 0.009) with a lower birth weight (p Conclusion Triplets conceived by ART had similar perinatal outcomes compared with spontaneously conceived triplets.

Background Although supplemental oxygen (SO2) is routinely administered to laboring gravidas, benefits and harms are not well studied. Objective This article compares strategies of liberal versus indicated SO2 therapy during labor on cesarean delivery (CD) rate and neonatal outcomes. Study Design A controlled, before-and-after trial of laboring women with term, singleton pregnancies. During an initial 8-week period, maternal SO2 was administered at the discretion of the provider followed by an 8-week period where SO2 was to be given only for protocol indications. Results Our study included 844 women. There was no difference in number of women receiving SO2 (53% liberal vs. 50% indicated; p = 0.33). For those receiving SO2, there was no difference in SO2 duration (median, 89 minutes [interquartile range, 42–172] vs. 87 minutes [36–152]; p = 0.42). There were no differences in overall CD rate (20% vs. 17%; p = 0.70), CD for nonreassuring fetal status, or use of intrauterine resuscitative measures. There were more 5-minute APGAR Conclusion Approximately half of women receive SO2 intrapartum regardless of a strategy of liberal or indicated oxygen use. There were no clinically significant differences in outcomes between strategies.

Objective The objective of this study was to compare adverse pregnancy outcomes between fetuses with estimated fetal weight (EFW) 10% in women with preterm preeclampsia (PE) with severe features. Materials and Methods All women with preterm PE with severe features and nonanomalous singletons with EFW were identified at a tertiary center. Women with oligohydramnios or absent/reversed umbilical Doppler velocimetry were excluded. Using multivariable analysis, we compared the composite maternal and neonatal morbidities (CMM and CNM) between those with appropriate for gestational age (AGA) fetal growth, defined as EFW at 10 to 90th versus those with fetal growth restriction (FGR), defined as EFW Results In this study, 165 patients were included; 112 had EFW at 10th to 90th percentile, and 53 had FGR. Of the 53 with FGR, 33 (62%) had EFW at 5 to 9% for GA and 20 (38%) had EFW Conclusion Women with preterm PE with severe features and FGR, when compared with those with AGA, have significantly higher risk of CMM and CNM.

Our goal was to compare composite neonatal and maternal morbidities (composite neonatal morbidity (CNM), composite maternal morbidity (CMM)) among deliveries with small for age (SGA) versus appropriate for gestational age (AGA; birthweight 10-89%) among obese versus non-obese women undergoing repeat cesarean delivery (CD).This is a secondary analysis of a prospective observational study. Women who had elective CD ≥37 weeks were studied. We excluded multiple gestations, fetal anomalies, 1 prior CD, and medical diseases. Patients were divided into BMI ≥30 versus30 kg/mOf 7561 women, we included 65% were obese and 35% were not. SGA rates differed significantly: 8 versus 12% (p .001). Overall, CNM was significantly higher in patients with SGA versus AGA (adjusted odds ratio (aOR) 2.04, 95% CI 1.19-3.49). CMM of SGA in obese versus non-obese was statistically different (aOR 0.11, 95% CI 0.02-0.68). Among obese mothers, SGA neonates had significantly higher CNM compared with AGA ones (aOR 2.17, 95% CI 1.03-4.59).SGA occurred in 8% of low-risk obese women with prior CD. CNM of SGA babies in obese versus non-obese women were similar. Paradoxically, CMM was lower in obese cases, possibly reflecting the caution that obese patients receive preoperatively. Our findings may assist in counseling patients and designing trials.

OBJECTIVE Our objective was to determine if transvaginal cervical length at 16-20 weeks is predictive of preterm birth

To estimate whether nonsteroidal antiinflammatory drugs (NSAIDs) are associated with persistent postpartum hypertension in a cohort of women with preeclampsia and severe features.We conducted a retrospective cohort study at a single, tertiary center from January 2013 to December 2015. All women diagnosed with severe preeclampsia who remained hypertensive for greater than 24 hours after delivery were included. The primary outcome was the rate of persistent postpartum hypertension, defined as systolic blood pressure 150 mm Hg or greater or diastolic 100 mm Hg or greater (or both), on two occasions, at least 4 hours apart. Secondary outcomes included severe maternal morbidity: pulmonary edema, renal dysfunction, stroke, eclampsia, and intensive care unit admission. Additional outcomes included length of postpartum hospital stay, receipt of narcotics, and hospital readmission. Multivariable logistic regression was performed to adjust for confounders. Adjusted odds ratios (ORs) are reported for applicable study outcomes.Of the 399 women with severe preeclampsia, 324 (81%) remained hypertensive 24 hours after delivery. Two hundred forty-three (75%) received NSAIDs (either ibuprofen or ketorolac) and 81 (25%) did not. After multivariable logistic regression, the likelihood of reaching a blood pressure of 150 mm Hg systolic or 100 mm Hg diastolic (or both), on two occasions, at least 4 hours apart, was similar between those who received NSAIDs compared with those who did not (70% compared with 73%; adjusted OR 1.1, 95% CI 0.6-2.0). Similarly, puerperal occurrence of pulmonary edema (3% compared with 10%; OR 4.4, 95% CI 1.5-13.1), renal dysfunction (5% compared with 8%; OR 1.7, 95% CI 0.6-4.8), eclampsia (1% compared with 0%; P=.34), or intensive care unit admission (3% compared with 8%; OR 2.4, 95% CI 0.8-7.1) was similar between the groups. There were no differences in the rate of narcotic use (89% compared with 75%; adjusted OR 0.6 95% CI 0.18-1.70).In this cohort of women with preeclampsia and severe features before delivery, NSAIDs were not associated with increased rates of persistent postpartum hypertension.

Subcapsular liver hematoma is a rare but potentially life-threatening complication of preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. It may present with nonspecific signs and symptoms, none of which are diagnostic, and can mimic pulmonary embolism of cholecystitis. There is no consensus on the management of subcapsular liver hematoma. Unruptured liver hematoma can be conservatively managed. When rupture occurs, surgical, endovascular approaches and, rarely, liver transplantation, may be required. Actual literature is scant and retrospective in nature. Data on follow-up, time to resolution and outcome of subsequent pregnancies are very limited. We here review the diagnosis and management of liver hematoma.

Preeclampsia is a pregnancy-specific hypertensive disorder with multisystem involvement and is a significant cause of obstetric morbidity and mortality worldwide. A major issue in the treatment of preeclampsia stems from its still significant rates of misclassification and misdiagnosis. Angiogenic factors have been speculated as a possible diagnostic modality due to a perceived imbalance in angiogenesis in preeclampsia. Factors currently studied include soluble fms-like protein kinase 1 and placental growth factor. Because of significant mortality associated with preeclampsia it is felt that both early and accurate diagnosis of preeclampsia is imperative if this disease process is to be treated.

Chronic hypertension affects up to 5% of pregnancies. Women can be stratified into low-risk or high-risk chronic hypertension based on baseline laboratory and diagnostic work-up, comorbid conditions, and outcomes in prior pregnancies. Pregnancies complicated by chronic hypertension are at risk for increased adverse maternal and neonatal outcomes including superimposed preeclampsia, fetal growth restriction, placental abruption, and perinatal death. Mainstays of management include blood pressure control, close monitoring for development of superimposed preeclampsia, serial ultrasound assessment of fetal growth, and antenatal testing after 32 weeks.

Aim: To study the contribution of maternal hypertension to autism spectrum disorders’ (ASD) phenotype, and gene expression, in a murine model. Materials & methods: To examine the effects of maternal hypertension, we used a well-described transgenic mouse model lacking functional endothelial nitric oxide synthase (eNOS or NOS3). Behavioral testing was performed on male offspring between 8 and 10 weeks of age. Cerebella underwent shotgun transcriptome RNA sequencing. Differentially expressed genes were examined for Gene Ontology enrichment. 2-way-RM-ANOVA, 1-way-ANOVA and Student's t-test were used for statistical analysis. Results & conclusion: Our findings revealed that a deficit in social behavior, the hallmark of ASD, is differentially present in offspring born to hypertensive mothers. Novel ASD-related genes were differentially expressed in the cerebellum, implicating its possible role in ASD etiology. Condensation: Altered uterine environment resulting from maternal hypertension contributes to ASD phenotype, and modifies expression of novel ASD-related genes in cerebella of eNOS heterozygous offspring.

Objective The American Congress of Obstetricians and Gynecologists (ACOG) task force on hypertension in pregnancy introduced a new definition of superimposed preeclampsia (SIP) adding severe features (SF) as new criteria to define severe disease. They also recommended that those with SIP be delivered ≥ 37 weeks, whereas those with SF be delivered ≤ 34 weeks. Our aim was to investigate the validity of this new definition by comparing adverse pregnancy outcomes in SIP with (SIP-SF) and without SF (SIP). Study Design Women with chronic hypertension (CHTN) enrolled in a multicenter trial were studied. SIP was reclassified according to the new definition to SIP and SIP-SF (persistent systolic blood pressure [BP] > 160 or diastolic BP > 110, platelets 70, creatinine > 1.1, or persistent central nervous system/abdominal symptoms). Composite adverse outcomes including rates of indicated preterm birth, abruptio placentae, postpartum hemorrhage, and maternal death were compared by chi-square. Adjustment was done with a multivariate logistic-regression analysis and all statistical tests were two-sided. Results A total of 216 women (28%) out of 774 with CHTN developed SIP, 87 (11%) had SIP-SF, and 129 (17%) didn't have SF. Baseline characteristics including maternal age, baseline BP, and assignment to low-dose aspirin were similar between groups. Using univariate analysis, the composite adverse outcome was higher among the SIP-SF group (p = 0.04), as well as indicated preterm birth (p = 0.02), cesarean section (p = 0.02), and SGA (p = 0.02). After adjustment, composite adverse outcomes were not significantly different between groups. The rate of SGA, however, was higher among SIP-SF (adjusted odds ratio: 3.12, p = 0.02). Conclusion The rate of SIP-SF in this study was 11% of all women with CHTN. Surprisingly, pregnancy outcomes were not significantly different in those with and without SF. We suggest a prospective observational study to determine the optimal timing for delivery in those with SIP using new ACOG diagnostic criteria.

Diabetes complicates 6 to 7% of all pregnancies in the United States. Poor glycemic control is associated with multiple immediate and long-term adverse effects on both the mother and fetus. Although uniformity exists in the antenatal management of this disease, there is a paucity of evidence-based studies upon which to dictate the optimal time of delivery among affected women. The potential risks of delayed neonatal pulmonary maturation including respiratory distress syndrome and transient tachypnea of the newborn associated with early delivery must be balanced with the increased incidence of fetal demise, overgrowth, and birth injury related to diabetes in late gestations. Even among diabetic women with optimal glycemic control, the risk of stillbirth in the third trimester is considerably higher than their normal counterparts. The current paradigm of delaying delivery to 39 weeks in women with controlled and uncomplicated diabetes has been challenged by recent evidence advocating delivery by 38 weeks to improve perinatal outcomes. However, additional well-designed and adequately powered prospective studies are needed to better understand the short- and long-term implications of the optimal timing of delivery in this high-risk population. This article reviews the most current literature regarding the optimal timing of delivery in pregnancies complicated by diabetes mellitus and gestational diabetes mellitus.

Catastrophic antiphospholipid syndrome (CAPS) is an accelerated form of the antiphospholipid antibody syndrome resulting in multi-organ ischemia and failure. It is a rare and life-threatening condition that can be easily mistaken with hemolysis elevated liver enzymes low platelets syndrome, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome. In order to make a diagnosis, it is required to have multi-organ thrombosis over 1 week affecting at least three organs or systems, and to have positive antiphospholipid antibody on two occasions (6 weeks apart), and histopathologic confirmation of small vessel occlusion. However, due to similarities in clinical and laboratory findings between CAPS and some other obstetric complications, potential misdiagnosis or delay in diagnosis are common, increasing the risk of adverse maternal and perinatal outcomes. In this review we summarized information presented in previous studies, focusing on CAPS related to pregnancy. We reviewed diagnostic criteria, differential diagnosis, and common presentation ranging from malaise, abdominal pain, dyspnea, hypertension, to altered mental status and seizures. We also discussed management in pregnancy and included a detailed algorithm with steps to take. Of note, the most significant reduction in mortality was seen in patients receiving triple therapy which will be discussed in this review.

Objectives Meta-analyses of small to moderate size randomized controlled trials (RCTs) suggested that aspirin started before 17 weeks' gestation reduces the risk of preeclampsia and small-for-gestational-age (SGA) neonates. We evaluated data from large randomized trials originally excluded from meta-analyses. Methods We performed meta-analyses of RCTs including more than 350 participants that compared aspirin to placebo during pregnancy. Corresponding authors were contacted to obtain data according to gestational age. Outcomes included preeclampsia, severe preeclampsia, and SGA. Relative risks (RRs) with their 95% confidence intervals (CIs) were calculated. Results Data for women recruited before 17 weeks' gestation were obtained for three (50%) of the six eligible trials for a total of 11,949 participants including 3,293 recruited before 17 weeks' gestation with available data. We observed no impact of low-dose aspirin (60 mg) started before 17 weeks' gestation on the risk of preeclampsia (RR: 0.93; 95% CI: 0.75–1.15), severe preeclampsia (RR: 0.96; 95% CI: 0.71–1.28), or SGA (RR: 0.84; 95% CI: 0.56–1.26) and it was not statistically different than when started at or after 17 weeks' gestation. Conclusion Data from large randomized trials do not support greater benefits of low-dose aspirin (at 60 mg daily) when started before 17 weeks' gestation for the prevention of preeclampsia or SGA.

Objective The objective of this study was to estimate the effect of low-dose aspirin in multiple gestations to prevent preeclampsia and small for gestational age (SGA) neonates. Methods A systematic review and meta-analysis were performed through electronic database searches. Randomized controlled trials (RCTs) of women with multiple gestations assigned to receive aspirin or placebo or no treatment were included. Outcomes included preeclampsia (mild and severe) and SGA neonates. Relative risks (RR) with their 95% confidence intervals (CI) were calculated. Result Out of 6,853 citations, 6 RCTS, including 898 pregnancies, were included. We observed a significant reduction in the risk of preeclampsia (RR, 0.67; 95% CI, 0.48–0.94) and mild preeclampsia (RR, 0.44; 95% CI, 0.24–0.82) but not severe preeclampsia (RR, 1.02; 95% CI, 0.61–1.72) with low-dose aspirin. The risk of SGA was not changed (RR, 1.09; 95% CI, 0.80–1.47). The reduction of preeclampsia was not different between women randomized before (RR, 0.86; 95% CI, 0.41–1.81) or after 16 weeks' gestation (RR, 0.64; 95% CI, 0.43–0.96) (p = 0.50). Conclusion There is low level of evidence supporting the use of low-dose aspirin for the prevention of preeclampsia and SGA neonates in multiple gestations.

Objective Among uncomplicated pregnancies, serial third-trimester ultrasound examinations identified significantly more cases with a composite of fetal growth or amniotic fluid abnormalities (27%) than did routine fundal height measurements (8%). Methods Women without complications between 24 0/7 and 30 6/7 weeks of gestation were randomized (NCT0270299) to either routine care (control arm) or ultrasound examination every 4 weeks (intervention arm). The primary outcome was a composite of abnormalities of fluid volume and growth: oligohydramnios or polyhydramnios; fetal growth restriction; or large for gestational age. The secondary outcome was the presence of composite maternal or neonatal morbidity among the two groups. A total of 206 participants was needed to have 80% power to detect an increase in the primary composite outcome from 10% in control to 25% in the intervention group (baseline rate 10%; two-tailed; α=0.05; loss to follow-up 5%). All women were included in the intent-to-treat analysis. Fisher exact, χ tests, or two-sample t tests were used to assess group differences. Results From July 11, 2016, to May 24, 2017, 852 women were screened for eligibility and 206 were randomized as follows: 102 in routine care and 104 in serial ultrasound examinations. The two groups were comparable in baseline characteristics. The primary composite outcome was significantly higher among women who were in the ultrasound examination group than the routine care group (27% vs 8%; relative risk 3.43, 95% CI 1.64-7.17); five women (95% CI 3-11) were needed to identify at least one of the composite ultrasound abnormalities. Although we were underpowered to detect a significant difference, the following secondary endpoints occurred with similar frequency in the ultrasound examination group than the routine care group: induction resulting from abnormal ultrasound examination findings (14% vs 6%), cesarean delivery in labor (5% vs 6%), and prespecified composite maternal morbidity (9% in both groups) and composite neonatal morbidity (1% vs 4%). Conclusion Among uncomplicated pregnancies between 24 0/7 and 30 6/7 weeks of gestation, serial third-trimester ultrasound examinations were significantly more likely to identify abnormalities of fetal growth or amniotic fluid than measurements of fundal height and indicated ultrasound examination. No differences in maternal and neonatal outcomes were noted, although we were underpowered for these endpoints. Clinical trial registration ClinicalTrials.gov, NCT02702999.

Chronic hypertension in pregnancy is traditionally classified according to degree of blood pressure (BP) elevation. Alternatively, stratifying women as high or low risk based on the etiology of hypertension, baseline work-up, and comorbid medical conditions will better inform clinicians about thresholds to initiate antihypertensive therapy, target BPs, frequency of antepartum visits, and timing of delivery. Women classified as high-risk chronic hypertension as described here require stricter BP management and more frequent follow-up visits as their associated rates of adverse maternal and/or fetal/neonatal outcomes appear higher than women classified as low-risk chronic hypertension. The latter group can in most cases be managed similarly to the general obstetric population.

Introduction: Computed tomography (CT) imaging should be employed judiciously, given its cost, use of intravenous contrast, and ionizing radiation. The aim of this study was to determine the clinic...

Background: Perinatal death, in particular intrapartum stillbirth and short-term neonatal death, as well as neonatal short-term and long-term morbidity have been associated with the time of day tha...

Since 1989, there have been 24 reported women with Swyer syndrome (SS) achieving successful pregnancies using fresh donor oocyte (FDO) in vitro fertilisation (IVF) (Kalra et al. 2016). Of these, tw...

Objective This study aims to compare neonatal and long-term outcomes among preterm newborns from women with reported versus those who did not report substance abuse. Study Design Secondary analysis of a trial of magnesium sulfate for cerebral palsy prevention. Cases were pregnant women who reported substance abuse, controls were those who denied it. Study outcomes included (1) composite neonatal morbidity, defined as any of the following: Apgar score ≤ 3 at 5 minutes, seizures, culture-proven sepsis, necrotizing enterocolitis grades 2 or 3, intraventricular hemorrhage grades 3 or 4, and/or death before discharge; (2) infant and childhood morbidity, defined as stillbirth or death by 1 year, or moderate/severe cerebral palsy by age of 2. Results Among 1,972 women meeting the inclusion criteria, 197 (10%) reported substance abuse. Composite neonatal, infant, and childhood morbidity rates were similar between cases and controls. However, women reporting substance abuse who delivered between 320/7 and 366/7 weeks had a higher frequency of composite infant and childhood morbidity (6.5 vs. 1.0%; adjusted odds ratio, 6.5; 95% confidence interval, 1.14–36.99). Conclusions Preterm birth was associated with similar composite neonatal morbidity between cases and controls. After 32 weeks, self-reported substance abuse was associated with a sevenfold increase in the rates of stillbirth and long-term infant morbidity.

Accumulation of hypoxia inducible factor-1α (HIF-1α) is commonly an acute and beneficial response to hypoxia, whereas chronically elevated HIF-1α is associated with multiple disease conditions, including preeclampsia, a serious hypertensive disease of pregnancy. However, the molecular basis underlying the persistent elevation of placental HIF-1α in preeclampsia and its role in the pathogenesis of preeclampsia are poorly understood. Here we report that Hif-1α mRNA and HIF-1α protein were elevated in the placentas of pregnant mice infused with angiotensin II type I receptor agonistic autoantibody, a pathogenic factor in preeclampsia. Knockdown of placental Hif-1α mRNA by specific siRNA significantly attenuated hallmark features of preeclampsia induced by angiotensin II type I receptor agonistic autoantibody in pregnant mice, including hypertension, proteinuria, kidney damage, impaired placental vasculature, and elevated maternal circulating soluble fms-like tyrosine kinase-1 levels. Next, we discovered that Hif-1α mRNA levels and HIF-1α protein levels were induced in an independent preeclampsia model with infusion of the inflammatory cytokine tumor necrosis factor superfamily member 14 (LIGHT). SiRNA knockdown experiments also demonstrated that elevated HIF-1α contributed to LIGHT-induced preeclampsia features. Translational studies with human placentas showed that angiotensin II type I receptor agonistic autoantibody or LIGHT is capable of inducing HIF-1α in a hypoxia-independent manner. Moreover, increased HIF-1α was found to be responsible for angiotensin II type I receptor agonistic autoantibody or LIGHT-induced elevation of Flt-1 gene expression and production of soluble fms-like tyrosine kinase-1 in human villous explants. Overall, we demonstrated that hypoxia-independent stimulation of HIF-1α gene expression in the placenta is a common pathogenic mechanism promoting disease progression. Our findings reveal new insight to preeclampsia and highlight novel therapeutic possibilities for the disease.

Objective The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. Study Design This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. Results CRHBP , CRH , and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. Conclusion Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.

The objective of this study was to examine the influence of gestational weight gain on the development of gestational hypertension/preeclampsia (GHTN/PE) in women with an obese prepregnancy body mass index (BMI).Obese women with a singleton pregnancy enrolled at 20 weeks were studied. Data were classified according to reported gestational weight gain (losing weight, under-gaining, within target, and over-gaining) from the recommended range of 11 to 9.7 kg and by obesity class (class 1 = BMI 30-34.9 kg/m(2), class 2 = 35-39.9 kg/m(2), class 3 = 40-49.9 kg/m(2), and class 4 ≥ 50 kg/m(2)). Rates of GHTN/PE were compared by weight gain group overall and within obesity class using Pearson chi-square statistics.For the 27,898 obese women studied, rates of GHTN/PE increased with increasing class of obesity (15.2% for class 1 and 32.0% for class 4). The incidence of GHTN/PE in obese women was not modified with weight loss or weight gain below recommended levels. Overall for obese women, over-gaining weight was associated with higher rates of GHTN/PE compared with those with a target rate for obesity classes 1 to 3 (each p 0.001).Below recommended gestational weight gain did not reduce the risk for GHTN/PE in women with an obese prepregnancy BMI. These data support a gestational weight gain goal ≤ 9.7 kg in obese gravidas.

Postpartum haemorrhage (PPH) is a leading cause of maternal morbidity and mortality worldwide.The most common cause of PPH is uterine atony (80%) of cases, resulting from suboptimal uterine involution and poor contraction of spiral arteries following placental separation. The goal of therapy is timely intervention to prevent haemorrhagic hypovolemic shock, intravascular disseminated coagulopathy, reduced tissue perfusion, and metabolic acidosis. This article is protected by copyright. All rights reserved.

Objective This study sought to determine baseline Caesarean delivery (CD) surgical site infection (SSI) rates in various patient subgroups and to identify potentially modifiable and non-modifiable risk factors for SSI. Methods This is a secondary analysis of a multicentre CD registry. Women who underwent CD were divided into SSI versus no SSI. SSI was defined as an infection that occurred in the part of the body where the surgery took place, within 30 days of surgery. Clinical characteristics and potential risk factors were compared between groups. Results Of 57 182 women, 3696 (6.5%) had SSI. SSI rates were higher in primary versus repeat CD (9.7% vs. 4.2%; P 0.001), and in CD after labour vs. no labour (9.5% vs. 3.8%; P 0.001). After adjustment for confounding factors, low transverse CD (adjusted OR [aOR] 0.7 [0.6–0.9]), CD performed between 7 pm and 7 am (aOR 0.9 [0.83–0.98]), primary CD (aOR 0.5 [0.5–0.6]), and intrapartum antibiotics (aOR 0.3 [0.1–0.4]) were associated with a decreased in the rate of SSI. Black race (aOR 1.9 [1.7–2.1]), tobacco use (aOR 1.4 [1.2–1.6]), increasing American Society of Anesthesiologists category (aOR 1.3 [1.1–1.6]), vertical skin incision (aOR 1.2 [1.1–1.3], emergency CD (aOR 1.3 [1.1–1.5]), and postpartum transfusion (aOR 2.7 [2.1–3.6]) were associated with an increase in the rate of SSI. Conclusion This study estimates the CD SSI rates in different subgroups and serves as a baseline for future trials designed to develop preventive guidelines and protocols.

Hypertensive disorders are associated with maternal and neonatal complications. Though they are more common in women with history of prior preeclampsia, they can occur in uncomplicated pregnancies.To determine the proportion of adverse pregnancy outcomes in deliveries prior to or at ≥39 weeks, in uncomplicated singleton nulliparous women (low-risk), as well as women with history of preeclampsia in a prior gestation (high-risk).This was a secondary analysis from the multicenter trials of low dose aspirin for preeclampsia prevention in low and high-risk pregnancies. The proportion of adverse pregnancy outcomes including hypertensive disorders in pregnancy, small for gestational age, placental abruption, neonatal intensive critical unit admission, and respiratory distress syndrome were evaluated in the two groups. Adverse pregnancy outcomes were stratified by gestational age at delivery (39 weeks and ≥39 weeks). Descriptive statistics were performed, and results reported as percentages.Three thousand twenty-one pregnancies were included in the low risk group, and 600 in the high risk one. In the low risk group 362 (12%) had hypertensive disorders, with 58% occurring at ≥39 weeks. In the low risk group, the rate of small for gestational age was of 5.9%, placental abruption 0.4%, neonatal intensive care unit admission 9%, and respiratory distress syndrome 3.5%. Sixty percent of all small for gestational age, 31% of all placenta abruptions, 44% of all neonatal intensive care unit admissions and 33% of respiratory distress syndrome cases, occurred at ≥39 weeks in the low risk group. In contrast in the high risk group, 197 (33%) patients developed a hypertensive disorder, with 35.5% occurring at ≥39 weeks. The overall rate of small for gestational age was 9.2%, abruption 2%, neonatal intensive care unit admission 15.5%, and respiratory distress syndrome 5%. In this group, 24% of all small for gestational age, 8.3% of all placental abruptions, 16% of all neonatal intensive care unit admissions and 3% of respiratory distress syndrome cases, were at ≥39 weeks.We found that in low-risk women, the majority of hypertensive disorders occur at ≥39 weeks, whereas in women with prior preeclampsia the majority develops at39 weeks. Moreover, a third of all placental abruption occurred at or beyond 39 weeks in the low risk group. Our findings suggest that in low-risk women, a policy of delivery at 39 weeks may prevent most of the adverse outcome that occurs beyond that gestational age cutoff.

Preeclampsia with severe features (SPE) remote from term remains a major cause of maternal morbidity and mortality worldwide. With increasing diagnosis of SPE remote from term and improved methods for monitoring maternal and fetal well-being, several challenges have been made regarding management of preeclampsia. We reviewed the scientific literature of the diagnosis and outcome of SPE before 28 weeks. On the basis of this review, we will present our recommendations on management of SPE before 28 weeks' gestation. In summary, expectant management of SPE at

Hypertensive disorders are the most common medical complication of pregnancy, with an incidence of 5-10%, and a common cause of maternal mortality in the USA. Incidence of pre-eclampsia has increased by 25% in the past two decades. In addition to being among the lethal triad, there are likely up to 100 other women who experience ‘near miss’ significant maternal morbidity that stops short of death for every pre-eclampsia-related mortality. The purpose of this review is to present the new task force statement and novel definitions, as well as management approaches to each of the hypertensive disorders in pregnancy. The increased understanding of the pathophysiology of hypertension in pregnancy, as well as advances in medical therapy to minimize risks of fetal toxicity and teratogenicity, will improve our ability to prevent and treat hypertension in pregnancy. Fetal programming and fetal origins of adult disease theories extrapolate the benefit of such therapy to future generations.

Circulating antiangiogenic factors and proinflammatory cytokines are implicated in the pathogenesis of preeclampsia. This study was performed to test the hypothesis that steroids modify the balance of inflammatory and proangiogenic and antiangiogenic factors that potentially contribute to the patient’s evolving clinical state. Seventy singleton women, admitted for antenatal corticosteroid treatment, were enrolled prospectively. The study group consisted of 45 hypertensive women: chronic hypertension (n=6), severe preeclampsia (n=32), and superimposed preeclampsia (n=7). Normotensive women with shortened cervix (

Pregnancies complicated by diabetic ketoacidosis are associated with increased rates of perinatal morbidity and mortality. A high index of suspicion is required, because diabetic ketoacidosis onset in pregnancy can be insidious, usually at lower glucose levels, and often progresses more rapidly as compared with nonpregnancy. Morbidity and mortality can be reduced with early detection of precipitating factors (ie, infection, intractable vomiting, inadequate insulin management or inappropriate insulin cessation, β-sympathomimetic use, steroid administration for fetal lung maturation), prompt hospitalization, and targeted therapy with intensive monitoring. A multidisciplinary approach including a maternal-fetal medicine physician, medical endocrinology specialists familiar with the physiologic changes in pregnancy, an obstetric anesthesiologist, and skilled nursing is paramount. Management principles include aggressive volume replacement, initiation of intravenous insulin therapy, correction of acidosis, correction of electrolyte abnormalities and management of precipitating factors, as well as monitoring of maternal-fetal response to treatment. When diabetic ketoacidosis occurs after 24 weeks of gestation, fetal status should be continuously monitored given associated fetal hypoxemia and acidosis. The decision for delivery can be challenging and must be based on gestational age as well as maternal-fetal responses to therapy. The natural inclination is to proceed with emergent delivery for nonreassuring fetal status that is frequently present during the acute episode, but it is imperative to correct the maternal metabolic abnormalities first, because both maternal and fetal conditions will likewise improve. Prevention strategies should include education of diabetic pregnant women about the risks of diabetic ketoacidosis, precipitating factors, and the importance of reporting signs and symptoms in a timely fashion.

During the past decade, prophylactic doses of low-molecular-weight heparin (LMWH) have been suggested to decrease the risk of placental-mediated complications. Herein, we review the prospective randomized trials that addressed the usefulness of LMWH in preventing placental-mediated complications in high-risk women. Inclusion criteria and results of these trials are heterogeneous. Unlike older trials (3 of 4 are single center), recent trials (all are multicenter) do not show beneficial effect of LMWH. There is certainly a need of complementary research before stating on the usefulness of LMWH in the prevention of placenta-mediated pregnancy complications in women at high risk.

Women with a prior myomectomy or prior classical cesarean delivery often have early delivery by cesarean because of concern for uterine rupture. Although theoretically at increased risk for placenta accreta, this risk has not been well-quantified. Our objective was to estimate and compare the risks of uterine rupture and placenta accreta in women with prior uterine surgery.Women with prior myomectomy or prior classical cesarean delivery were compared with women with a prior low-segment transverse cesarean delivery to estimate rates of both uterine rupture and placenta accreta.One hundred seventy-six women with a prior myomectomy, 455 with a prior classical cesarean delivery, and 13,273 women with a prior low-segment transverse cesarean delivery were evaluated. Mean gestational age at delivery differed by group (P.001), prior myomectomy (37.3 weeks), prior classical cesarean delivery (35.8 weeks), and low-segment transverse cesarean delivery (38.6 weeks). The frequency of uterine rupture in the prior myomectomy group (P-MMX group) was 0% (95% confidence interval [CI] 0-1.98%). The frequency of uterine rupture in the low-segment transverse cesarean delivery group (LTC group) (0.41%) was not statistically different from the risk in the P-MMX group (P.99) or in the prior classical cesarean delivery group (PC group) (0.88%; P=.13). Placenta accreta occurred in 0% (95% CI 0-1.98%) of the P-MMX group compared with 0.19% in the LTC group (P.99) and 0.88% in the PC group (P=.01 relative to the LTC group). The adjusted odds ratio for the PC group (relative to LTC group) was 3.23 (95% CI 1.11-9.39) for uterine rupture and 2.09 (95% CI 0.69-6.33) for accreta. The frequency of accreta for those with previa was 11.1% for the PC group and 13.6% for the LTC group (P.99).A prior myomectomy is not associated with higher risks of either uterine rupture or placenta accreta. The absolute risks of uterine rupture and accreta after prior myomectomy are low.

Hypertensive disorders have become increasingly prevalent and complicate an increasing number of pregnancies. Therefore it is essential that the medications used to treat these disorders be well understood. Furthermore the management is complicated by special consideration needed for the physiologic changes of pregnancy as well as the consideration for possible adverse fetal effects. Areas covered: We performed a review of the scientific literature of medications used to treat hypertensive disorders in pregnancy. We reviewed the guidelines used by different societies all over the world. We also discussed the pharmacodynamics, pharmacokinetics and possible adverse effects relating to the antihypertensive medications. Finally, we discussed the long-term maternal implications of these diseases. Expert opinion: Overall, we encourage a step-wise approach to treating hypertensive disorders of pregnancy. While making sure to max out the use of one medications prior to shifting to another. Also, it is imperative not to be aggressive with treatment due to risk of compromising utero-placental blood flow. There is research currently involving biomarkers, nano-medicine and the placenta project with hopes of developing new targeted medications with a good fetal safety profile.

Venous thromboembolism, a serious complication comprising deep vein thrombosis and pulmonary embolism, occurs infrequently during pregnancy and the postpartum period, with an estimated incidence of 1–2 per 1,000 deliveries.1 This incidence is substantially higher in women with prior venous thromboem

Background The pathogenesis of essential hypertension is multifactorial with different underlying mechanisms contributing to disease. We have recently shown that TNF superfamily member 14 LIGHT (an acronym for homologous to lymphotoxins, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes, also known as TNFSF 14) induces hypertension when injected into mice. Research reported here was undertaken to examine the role of transglutaminase ( TG ase) in LIGHT ‐induced hypertension. Methods and Results Initial experiments showed that plasma and kidney TG ase activity was induced by LIGHT infusion (13.91±2.92 versus 6.75±1.92 mU/mL and 19.86±3.55 versus 12.00±0.97 mU/10 μg) and was accompanied with hypertension (169±7.16 versus 117.17±11.57 mm Hg at day 14) and renal impairment (proteinuria, 61.33±23.21 versus 20.38±9.01 μg/mg; osmolality, 879.57±93.02 versus 1407.2±308.04 mmol/kg). The increase in renal TG ase activity corresponded to an increase in RNA for the tissue TGase isoform, termed TG 2. Pharmacologically, we showed that LIGHT ‐induced hypertension and renal impairment did not occur in the presence of cystamine, a well‐known competitive inhibitor of TG ase activity. Genetically, we showed that LIGHT ‐mediated induction of TG ase, along with hypertension and renal impairment, was dependent on interleukin‐6 and endothelial hypoxia inducible factor‐1α. We also demonstrated that interleukin‐6, endothelial hypoxia inducible factor‐1α, and TG ase are required for LIGHT ‐induced production of angiotensin receptor agonistic autoantibodies. Conclusions Thus, LIGHT ‐induced hypertension, renal impairment, and production of angiotensin receptor agonistic autoantibodies require TG ase, most likely the TG 2 isoform. Our findings establish TG ase as a critical link between inflammation, hypertension, and autoimmunity.

Objective To compare the effectiveness of intravenous acetaminophen with that of morphine in reducing pain in the first stage of labor. Methods An open-label, randomized controlled trial of women ≥ 34 weeks gestation in the first stage of labor, assigned to either intravenous acetaminophen or morphine. The primary outcome was improved analgesia measured by difference of visual analog scale (VAS) score at 120 minutes from baseline. Secondary outcomes were request for rescue analgesia, maternal side effects, and fetal heart rate changes. Statistical analyses performed were chi-square, Student's t-test, and Kaplan-Meier survival analysis. Results Of 40 women randomized, 18 received acetaminophen (2 did not receive study drug), and 20 received morphine. Because of difficulties in recruitment, the sample size of 88 was not achieved. The primary outcome was similar between groups (p = 0.53). Within 120 minutes of initial treatment, more women receiving intravenous acetaminophen required rescue analgesia (acetaminophen: 52.9% vs. morphine: 17.6%, p Conclusion There was no difference in VAS scores between groups. However, as half of women receiving intravenous acetaminophen required rescue analgesia within 120 minutes of treatment, intravenous acetaminophen may be less effective for analgesia in early labor compared with intravenous morphine.

Background Although rare, trauma in pregnancy can cause uterine rupture. In a periviable pregnancy, uterine rupture can lead to premature delivery and significant morbidity. Case A 29-year-old woman with four prior CSs presented with uterine rupture and a protruding morbidly adherent placenta at 23+4 weeks of gestation. Since the pregnancy was highly desired, the defect was repaired and the decision made to continue with the pregnancy. The patient presented at 29+3 weeks of gestation with preterm labour and subsequently delivered a healthy male infant of 1130 grams. Conclusion Expectant management followed by CS can be beneficial in certain cases of uterine rupture with morbidly adherent placenta following trauma. This is especially the case in a periviable pregnancy, since prolonging the pregnancy will improve neonatal outcomes. We recommend individualized management based on clinical presentation, imaging findings, and the patient's wishes.

BACKGROUND We previously reported that offspring heterozygous mice partially lacking endothelial nitric oxide synthase (eNOS) gene, and born to hypertensive eNOS-/- Knockout mother, are hypertensive. We hypothesized that those offspring when placed on high-fat diet (HFD) will undergo altered metabolic programming increasing their risk for developing metabolic syndrome. METHODS eNOS-/-KO and wild-type mice (eNOS+/+WT) were cross-bred to produce heterozygous offspring: maternal heterozygous (Mat, eNOS-/+), born from hypertensive eNOS-/-KO mothers; and paternal heterozygous (Pat, eNOS-/+), born from normotensive WT mothers. Mat, eNOS-/+ and Pat, eNOS-/+ female were allocated to HFD or control diet (CD) until 8 weeks of age. Then a metabolic profile was obtained: weight, glucose/insulin tolerance test (GTT, ITT), systolic blood pressure (SBP), serum fasting levels of insulin, adiponectin, leptin, and a lipid panel. RESULTS Weight was not different between all offspring within each diet. GTT curve was higher in Mat, eNOS-/+ vs. Pat, eNOS-/+ offspring on both diet (P < 0.001). In ITT, glucose level at 15 minutes was higher in Mat, eNOS-/+ on HFD. Insulin level was increased in Mat, eNOS-/+ vs. Pat, eNOS-/+ on either diet. SBP was elevated in Mat, eNOS-/+ vs. Pat, eNOS-/+ on CD and was further raised in Mat, eNOS-/+ offspring on HFD (P < 0.001). No other differences were seen except for lower high-density lipoprotein levels in Mat, eNOS-/+ fed HFD (P < 0.003). CONCLUSIONS Mat, eNOS-/+ offspring exposed in utero to maternal hypertension and fed HFD postnatally have increased susceptibility for metabolic abnormalities. Thus, maternal HTN is a risk factor for altered fetal metabolic programming.

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.

Pregnancies complicated by severe sepsis and septic shock are associated with increased rates of preterm labor, fetal infection, and preterm delivery. Sepsis onset in pregnancy can be insidious, and patients may appear deceptively well before rapidly deteriorating with the development of septic shock, multiple organ dysfunction syndrome, or death. The outcome and survivability in severe sepsis and septic shock in pregnancy are improved with early detection, prompt recognition of the source of infection, and targeted therapy. This improvement can be achieved by formulating a stepwise approach that consists of early provision of time-sensitive interventions such as: aggressive hydration (20 mL/kg of normal saline over the first hour), initiation of appropriate empiric intravenous antibiotics (gentamicin, clindamycin, and penicillin) within 1 hour of diagnosis, central hemodynamic monitoring, and the involvement of infectious disease specialists and critical care specialists familiar with the physiologic changes in pregnancy. Thorough physical examination and imaging techniques or empiric exploratory laparotomy are suggested to identify the septic source. Even with appropriate antibiotic therapy, patients may continue to deteriorate unless septic foci (ie, abscess, necrotic tissue) are surgically excised. The decision for delivery in the setting of antepartum severe sepsis or septic shock can be challenging but must be based on gestational age, maternal status, and fetal status. The natural inclination is to proceed with emergent delivery for a concerning fetal status, but it is imperative to stabilize the mother first, because in doing so the fetal status will likewise improve. Aggressive [corrected] treatment of sepsis can be expected to reduce the progression to severe sepsis and septic shock and prevention strategies can include preoperative skin preparations and prophylactic antibiotic therapy as well as appropriate immunizations.

To examine pregnancy outcomes of women receiving weekly compounded 17 α-hydroxyprogesterone caproate (17P) injections through a home nursing program compared with those reported in a multicenter trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Network.The study sample was comprised of patients receiving compounded 17P through a home nurse administration care management program. Included were women with current singleton gestation and prior spontaneous preterm birth (SPTB) initiating 17P between 16 and 20 weeks. Maternal characteristics and pregnancy outcomes were compared between study group and NICHD Network trial patients.Women (n = 5493) received a mean of 16.9 ± 4.0 injections. Of the 92,700 injections, 98.4% were administered within the recommended 5- to 9-day interval. Recurrent SPTB occurred in 28.3%. The overall rate of SPTB at37 weeks was similar for black and nonblack women (p = 0.592). Within black or nonblack groups, preterm birth rates at37 weeks were similar regardless of gestational age at start of 17P (p = 0.894 and p = 0.374, respectively). These results were similar to those reported in the multicenter trial. Fetal and neonatal death occurred in 0.8% (46/5493). No significant difference was observed in rate of fetal or neonatal death by gestational age at initiation of 17P (p = 0.478).Home nurse administration of compounded 17P is safe and effective.