Birthweight Extremes and Neonatal and Childhood Outcomes after Preterm Premature Rupture of Membranes

Objective To determine the association between birthweight extremes and risk of adverse neonatal and childhood outcomes following preterm premature rupture of membranes (PPROM). Study Design This is a secondary analysis of data from the Beneficial Effects of Antenatal Magnesium Sulfate Trial. Women with nonanomalous singletons and PPROM delivering ≥24.0 weeks were included. Birthweight was classified as small for gestational age (SGA), appropriate for gestational age (AGA), or large for gestational age (LGA). Composite severe neonatal morbidity and childhood outcomes at age 2, were compared between these groups. Results One thousand five hundred and ninety-eight infants were included (58 SGA, 1,354 AGA, and 186 LGA). There was an inverse relationship between birthweight and rate of composite major neonatal morbidity (55.2% of SGA, 31.5% of AGA, 18.3% of LGA, p < 0.001). Former-SGA children were more likely to be diagnosed with major composite childhood morbidity at age 2 (25.9% of SGA, 8.3% of AGA, 5.9% of LGA, p < 0.001). In multivariate models, LGA infants had improved initial neonatal outcomes compared with AGA infants (adjusted odds ratio [aOR], 0.44; 95% confidence interval [CI], 0.28-0.71; p = 0.001). Conclusion Among infants delivered following PPROM, those who were LGA at delivery had improved composite adverse neonatal outcomes. SGA increases the risk of severe neonatal morbidity, early childhood death, and moderate/severe cerebral palsy at age 2

Maternal lipid levels during pregnancy and child weight status at 3 years of age

Background: The intrauterine environment is critical in the development of child obesity. Objective: To investigate the association between maternal lipid levels during pregnancy and child weight status. Methods: Maternal lipid levels (total cholesterol, high-density and low-density lipoprotein cholesterol, triglycerides) collected from fasting blood samples collected at less than 20 and 24–29 weeks' gestation and child weight status at age 3 were examined prospectively among 183 mother-child dyads enrolled in the Pregnancy, Infection, and Nutrition. Measured height and weight at 3 years were used to calculate age- and sex-specific body mass index z-scores. Child risk of overweight/obesity was defined as body mass index greater than or equal to 85th percentile for age and sex. Regression models estimated the association between maternal lipid levels and child body mass index z-score and risk of being affected by overweight/obesity, respectively. Results: Higher triglyceride levels at less than 20 and 24–29 weeks of pregnancy were associated with higher body mass index z-scores (β = 0.23; 95% CI: 0.07-0.38 and β = 0.15; 95% CI: 0.01-0.29; respectively) after adjusting for confounders. There was no evidence of an association between total or low-density lipoprotein cholesterol and child weight status at age 3. Conclusions: Early childhood body mass index may be influenced by maternal triglyceride levels during pregnancy

The neuroimmunology of chronic pain: from rodents to humans

Chronic pain, encompassing conditions, such as low back pain, arthritis, persistent post-surgical pain, fibromyalgia, and neuropathic pain disorders, is highly prevalent but remains poorly treated. The vast majority of therapeutics are directed solely at neurons, despite the fact that signaling between immune cells, glia, and neurons is now recognized as indispensable for the initiation and maintenance of chronic pain. This review highlights recent advances in understanding fundamental neuroimmune signaling mechanisms and novel therapeutic targets in rodent models of chronic pain. We further discuss new technological developments to study, diagnose, and quantify neuroimmune contributions to chronic pain in patient populations.Peter M. Grace, Vivianne L. Tawfik, Camilla I. Svensson, Michael D. Burton, Marco L. Loggia and Mark R. Hutchinso

Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice

Objective This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice. Study Design Pregnant friend virus B (FVB)-strain mice were allocated on embryonic day (e) 0.5 to one of four groups; group 1: control diet (CD, 10% fat) + control treatment (CT), group 2: CD + metformin treatment (MT), group 3: high-fat diet (HFD, 60% fat) + CT, and group 4: HFD + MT. Metformin (2.5 mg/mL) was provided in water; CT mice received water. Fetuses and placentas were collected. Western blot measured placental p-Akt and p-S6 expression. Results 20 dams (five/group) and 192 fetuses were studied. Compared with CD-fed, HFD-fed dams had higher placental p-Akt protein expression (p < 0.0001). Among HFD-dams, placental p-Akt was higher in metformin-treated compared with control-treated (p < 0.001). Among CD-fed dams, there was no significant difference in placental p-S6 expression in MT versus CT groups. Among HFD-fed dams placental p-S6 expression was lower in those exposed to metformin-treated versus controls (p = 0.001). Conclusion Increased placental mTOR signaling and metformin inhibition of placental mTOR signaling only occurred in the presence of an HFD exposure. These findings suggest that metformin may modulate placental mTOR signaling in the presence of metabolic exposures during pregnancy

Risk Factors for Postpartum Septic Pelvic Thrombophlebitis: A Multicenter Cohort

Objective The objective of this study was to identify risk factors associated with the development of septic pelvic thrombophlebitis (SPT). Study Design This is a secondary case-control study of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit Network Cesarean Registry. SPT was defined as suspected infectious thrombosis of the pelvic veins, often persistent febrile illness in the setting of antibiotic therapy for endometritis. Women with SPT were compared with those without SPT using descriptive statistics. Logistic regression models estimated the association between selected risk factors and SPT. Results Of 73,087 women in the cohort, 89 (0.1%) developed SPT. Women with SPT were more likely to be < 20 years old (33.7 vs. 10.6%, p < 0.001), black race (58.4 vs. 29.1%, p < 0.001), and nulliparous (51.1 vs. 23.3%, p < 0.001). Hypertensive disorders of pregnancy (32.6 vs. 11.8%, p < 0.001) and multiple gestation (12.5 vs. 7.4%, p = 0.03) were also more common in women with SPT. In the multivariable regression model, maternal age < 20, black race, multiple gestation, and preeclampsia were all significantly associated with increased odds of SPT (adjusted odds ratio [aOR]: 1.96, 95% confidence interval [CI]: 1.22, 3.14; aOR: 2.6, 95% CI: 1.68, 4.02; aOR: 2.10, 95% CI: 1.13, 3.88; aOR: 2.91, 95% CI: 1.86, 4.57). Conclusion SPT is a rare pregnancy complication. Our analysis confirmed known risk factors (e.g., infections, cesarean delivery), and identified novel ones, including black race, young age, preeclampsia, and multiple gestation

Lipoprotein particle concentration measured by nuclear magnetic resonance spectroscopy is associated with gestational age at delivery: a prospective cohort study

Objective: To estimate the association between lipoprotein particle concentrations in pregnancy and gestational age at delivery. Design: Prospective cohort study. Setting: The study was conducted in the USA at the University of North Carolina. Population: We assessed 715 women enrolled in the Pregnancy, Infection, and Nutrition study from 2001 to 2005. Methods: Fasting blood was collected at two time points (&lt;20 and 24–29 weeks of gestation). Nuclear magnetic resonance (NMR) quantified lipoprotein particle concentrations [low-density lipoprotein (LDL), high-density lipoprotein (HDL), very-low density lipoprotein (VLDL)] and 10 subclasses of lipoproteins. Concentrations were assessed as continuous measures, with the exception of medium HDL which was classified as any or no detectable level, given its distribution. Cox proportional hazards models estimated hazard ratios (HR) for gestational age at delivery adjusting for covariates. Main outcome measures: Gestational age at delivery, preterm birth (&lt;37 weeks of gestation), and spontaneous preterm birth. Results: At &lt;20 weeks of gestation, three lipoproteins were associated with later gestational ages at delivery [large LDL NMR (HR 0.78, 95% CI 0.64–0.96), total VLDL NMR (HR 0.77, 95% CI 0.61–0.98), and small VLDL NMR (HR 0.78, 95% CI 0.62–0.98], whereas large VLDL NMR (HR 1.19, 95% CI 1.01–1.41) was associated with a greater hazard of earlier delivery. At 24–28 weeks of gestation, average VLDL NMR (HR 1.25, 95% CI 1.03–1.51) and a detectable level of medium HDL NMR (HR 1.90, 95% CI 1.19–3.02) were associated with earlier gestational ages at delivery. Conclusion: In this sample of pregnant women, particle concentrations of VLDL NMR , LDL NMR , IDL NMR , and HDL NMR were each independently associated with gestational age at delivery for all deliveries or spontaneous deliveries &lt;37 weeks of gestation. These findings may help formulate hypotheses for future studies of the complex relationship between maternal lipoproteins and preterm birth. Tweetable abstract: Nuclear magnetic resonance spectroscopy may identify lipoprotein particles associated with preterm delivery

Maternal Morbidity after Previable Prelabor Rupture of Membranes

OBJECTIVE: To identify risk factors for maternal morbidity after previable prelabor rupture of membranes (PROM). METHODS: We conducted a case-control study of singleton and twin pregnancies complicated by previable PROM (14.0-22.9 weeks of gestation) at a single tertiary care referral institution, 2000-2015. Pregnancies complicated by fetal anomalies, previable PROM within 2 weeks of chorionic villus sampling or amniocentesis, and those with contraindications to expectant management (eg, chorioamnionitis) were excluded. Cases were women with the primary outcome of composite maternal morbidity (defined as having at one or more of the following: sepsis, intensive care unit admission, acute renal insufficiency, uterine curettage, hysterectomy, deep vein thrombosis, pulmonary embolus, blood transfusion, readmission, or maternal death). Controls were women without the primary composite morbidity. Bivariate analysis compared demographic, clinical, and management characteristics of women in the case group and those in the control group. Multivariable logistic regression models were developed to quantify the association between maternal characteristics and composite severe maternal morbidity. RESULTS: During the study period, 174 women presented with by previable PROM and were candidates for expectant management. Sixty-five (37%) women opted for immediate delivery; 109 (63%) elected expectant management. Twenty-five of 174 (14%) experienced one or more components of the composite maternal morbidity (cases) and were compared with 149 (86%) women in the control group. Women in the case group were more not more likely to elect expectant management (68% compared with 59%, P=.40), but were more likely to be aged 35 years or older (40% compared with 14%, P=.002) or to be carrying twins (52% compared with 16%, P<.01). In the regression model, twin gestation and age 35 years or older were both significantly associated with increased odds of composite maternal morbidity (odds ratio [OR] 5.62, 95% confidence interval [CI] 2.21-14.3 and OR 4.00, 95% CI 1.48-10.8, respectively). CONCLUSION: Antenatal counseling of women with previable PROM should include that one in seven women experience significant morbidity. Although expectant management was not associated with increased risk in this cohort, women with twins or those aged 35 years or older were at substantially increased risk