Frequent first-trimester pregnancy loss in rhesus macaques infected with African-lineage Zika virus.

In the 2016 Zika virus (ZIKV) pandemic, a previously unrecognized risk of birth defects surfaced in babies whose mothers were infected with Asian-lineage ZIKV during pregnancy. Less is known about the impacts of gestational African-lineage ZIKV infections. Given high human immunodeficiency virus (HIV) burdens in regions where African-lineage ZIKV circulates, we evaluated whether pregnant rhesus macaques infected with simian immunodeficiency virus (SIV) have a higher risk of African-lineage ZIKV-associated birth defects. Remarkably, in both SIV+ and SIV- animals, ZIKV infection early in the first trimester caused a high incidence (78%) of spontaneous pregnancy loss within 20 days. These findings suggest a significant risk for early pregnancy loss associated with African-lineage ZIKV infection and provide the first consistent ZIKV-associated phenotype in macaques for testing medical countermeasures.

Cotyledon-Specific Flow Evaluation of Rhesus Macaque Placental Injury Using Ferumoxytol Dynamic Contrast-Enhanced MRI.

BACKGROUND: Recently, dynamic contrast-enhanced (DCE) MRI with ferumoxytol as contrast agent has recently been introduced for the noninvasive assessment of placental structure and function throughout. However, it has not been demonstrated under pathological conditions. PURPOSE: To measure cotyledon-specific rhesus macaque maternal placental blood flow using ferumoxytol DCE MRI in a novel animal model for local placental injury. STUDY TYPE: Prospective animal model. SUBJECTS: Placental injections of Tisseel (three with 0.5 mL and two with 1.5 mL), monocyte chemoattractant protein 1 (three with 100 µg), and three with saline as controls were performed in a total of 11 rhesus macaque pregnancies at approximate gestational day (GD 101). DCE MRI scans were performed prior (GD 100) and after (GD 115 and GD 145) the injection (term = GD 165). FIELD STRENGTH/SEQUENCE: 3 T, T1-weighted spoiled gradient echo sequence (product sequence, DISCO). ASSESSMENT: Source images were inspected for motion artefacts from the mother or fetus. Placenta segmentation and DCE processing were performed for the dynamic image series to measure cotyledon specific volume, flow, and normalized flow. Overall placental histopathology was conducted for controls, Tisseel, and MCP-1 animals and regions of tissue infarctions and necrosis were documented. Visual inspections for potential necrotic tissue were conducted for the two Tisseelx3 animals. STATISTICAL TESTS: Wilcoxon rank sum test, significance level P < 0.05. RESULTS: No motion artefacts were observed. For the group treated with 1.5 mL of Tisseel, significantly lower cotyledon volume, flow, and normalized flow per cotyledon were observed for the third gestational time point of imaging (day ~145), with mean normalized flow of 0.53 minute-1. Preliminary histopathological analysis shows areas of tissue necrosis from a selected cotyledon in one Tisseel-treated (single dose) animal and both Tisseelx3 (triple dose) animals. DATA CONCLUSION: This study demonstrates the feasibility of cotyledon-specific functional analysis at multiple gestational time points and injury detection in a placental rhesus macaque model through ferumoxytol-enhanced DCE MRI. LEVEL OF EVIDENCE: NA TECHNICAL EFFICACY: Stage 2.

Management of twin reversed arterial perfusion (TRAP) sequence with microwave ablation: A case report and review of the literature.

Twin reversed arterial perfusion (TRAP) sequence carries a high mortality risk to the "pump twin." Management involves disrupting blood flow to the acardiac mass. In this case, the pregnant patient presented at 20 weeks 6 days with Stage IIb TRAP Sequence and underwent percutaneous ultrasound-guided microwave ablation (MWA) of the acardiac mass at 21 weeks 0 days. The probe traversed the thorax of the acardiac mass and ablated the confluence of the umbilical vessels. A healthy child was delivered at 33 weeks 5 days gestation. This report demonstrates the utility of MWA in TRAP sequence and describes a novel approach.

Continuous positive airway pressure treatment of obstructive sleep apnea and hypertensive complications in high-risk pregnancy.

PURPOSE: To evaluate whether or not continuous positive airway pressure (CPAP) treatment in pregnancies complicated by obstructive sleep apnea (OSA) is associated with a decrease in hypertensive disorders of pregnancy. METHODS: This was a retrospective cohort study of perinatal outcomes in women who underwent objective OSA testing and treatment as part of routine clinical care during pregnancy. Where diagnostic criteria for OSA were reached (respiratory event index (REI) ≥ 5 events per hour), patients were offered CPAP therapy. Obstetrical outcomes were compared between the control group (no OSA), the group with untreated OSA (OSA diagnosed, not CPAP compliant), and the group with treated OSA (OSA diagnosed and CPAP compliant), with CPAP compliance defined as CPAP use ≥ 4 h, 70% of the time or greater. A composite hypertension outcome combined diagnoses of gestational hypertension (gHTN) and preeclampsia (PreE) of any severity. RESULTS: The study comprised outcomes from 177 completed pregnancies. Our cohort was characterized by obesity, with average body mass indices > 35 kg/m2, and average maternal age > 30 years old. CPAP was initiated at an average gestational age of 23 weeks (12.1-35.3 weeks), and average CPAP use was 5.9 h (4-8.5 h). The composite hypertension outcome occurred in 43% of those without OSA (N = 77), 64% of those with untreated OSA (N = 77), and 57% of those with treated OSA, compliant with CPAP (N = 23) (p = 0.034). CONCLUSION: Real-world data in this small study suggest that CPAP therapy may modulate the increased risk of hypertensive complications in pregnancies complicated by OSA.

Does Daily Self-Weighing Contribute to Postpartum Weight Loss? A Secondary Analysis of Daily Postpartum Weights among Women with Hypertensive Disorders of Pregnancy.

OBJECTIVE: This study was aimed to examine the impact of daily self-weighing via remote monitoring on postpartum weight loss. STUDY DESIGN: This was a secondary analysis of a nonrandomized controlled trial comprised of postpartum women with diagnosed hypertensive-related disorders in pregnancy who received a tablet device linked to Bluetooth-enabled equipment including a scale and blood pressure cuff. In addition to blood pressure monitoring, participants were instructed to perform daily self-weighing. The primary outcome of this study was to determine whether postpartum women who performed daily self-weighing lost more weight than those who did not, with a 42-day endpoint based on a 6-week postpartum visit weight. RESULTS: Overall, 214 women participated in this program and 214 received usual care. Median weight loss for women participating in the remote blood pressure monitoring system was 23.0 (interquartile range [IQR]: 17-30) pounds versus 23.0 (IQR: 17-29) pounds among controls. Weight loss did not vary by prepregnancy obesity (median: 20 pounds [IQR: 17-28 pounds] for nonobese and 23 [IQR: 17-30] pounds for women with obesity, p = 0.16). Women who weighed themselves more than half of follow-up days lost a median of 24 pounds (IQR: 17-30 pounds) compared with 20.5 pounds (IQR: 14-29 pounds), p = 0.06. Women who weighed themselves more than half of follow-up days lost a mean of 11.4% (standard deviation [SD] = 0.41%) of body weight compared with 9.1% (SD = 0.74%; p = 0.01). The amount of weight loss in the telehealth group was correlated with the number of daily weights performed (Pearson's correlation coefficient 0.164, p = 0.025). Postpartum weight loss for daily self-weighing participants was most notable in the first 2 weeks with ongoing weight loss up to the 42-day (6-week) endpoint of this secondary analysis. CONCLUSION: Daily self-weighing alone may be insufficient to promote postpartum weight loss. However, there was a slight trend toward more weight loss with more frequent weighing. KEY POINTS: · Daily self-weighing is insufficient for postpartum weight loss.. · Women who weighed themselves more lost slightly more weight.. · Weight loss was the most notable in the first 2 weeks.. · Its use as one part of a program may be worth studying..

SERUM GLP-2 is Increased in Association with Excess Gestational Weight Gain.

OBJECTIVE: Obesity in pregnancy bears unique maternal and fetal risks. Obesity has also been associated with chronic inflammation, including elevated serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Higher serum lipopolysaccharide (LPS) levels have been implicated in driving this inflammation, a phenomenon called metabolic endotoxemia (ME). GLP-2, a proglucagon-derived peptide, is believed to be integral in maintaining the integrity of the intestine in the face of LPS-mediated endotoxemia. We hypothesized that obesity and/or excess weight gain in pregnancy would be associated with an increase in maternal and neonatal markers of ME, as well as GLP-2. STUDY DESIGN: Paired maternal and neonatal (cord blood) serum samples (n = 159) were obtained from our pregnancy biobank repository. Serum levels of LPS, endotoxin core antibody-immunoglobulin M (EndoCAb-IgM), and GLP-2 were measured by ELISA. IL-6 and TNF-α were measured using a Milliplex assay. Results were stratified by maternal body mass index (BMI), maternal diabetes, and gestational weight gain (GWG). RESULTS: Maternal IL-6 is significantly decreased in the obese, diabetic cohort compared with the nonobese, nondiabetic cohorts (95.28 vs. 99.48 pg/mL, p = 0.047), whereas GLP-2 is significantly increased (1.92 vs. 2.89 ng/mL, p = 0.026). Neonatal TNF-α is significantly decreased in the obese cohort compared with the nonobese cohort (12.43 vs. 13.93 pg/mL, p = 0.044). Maternal GLP-2 is significantly increased in women with excess GWG compared with those with normal GWG (2.27 vs. 1.48 ng/mL, p = 0.014). We further found that neonatal IL-6 and TNF-α are negatively correlated with maternal BMI (-0.186, p = 0.036 and -0.179, p = 0.044, respectively) and that maternal and neonatal IL-6 showed a positive correlation (0.348, p < 0.001). CONCLUSION: Although we observed altered levels of markers of inflammation (IL-6 and TNF-α) with maternal obesity and diabetes, no changes in LPS or endoCAb-IgM were observed. We hypothesize that the increased GLP-2 levels in maternal serum in association with excess GWG may protect against ME in pregnancy. KEY POINTS: · Maternal serum levels of GLP-2, a proglucagon-derived peptide, are increased in obese, diabetic gravidae.. · Maternal serum GLP-2 levels are also increased in association with excess gestational weight gain compared with normal gestational weight gain.. · GLP-2 may be increased in association with obesity and weight gain to protect against metabolic endotoxemia in pregnancy..

African-Lineage Zika Virus Replication Dynamics and Maternal-Fetal Interface Infection in Pregnant Rhesus Macaques.

Following the Zika virus (ZIKV) outbreak in the Americas, ZIKV was causally associated with microcephaly and a range of neurological and developmental symptoms, termed congenital Zika syndrome (CZS). The viruses responsible for this outbreak belonged to the Asian lineage of ZIKV. However, in vitro and in vivo studies assessing the pathogenesis of African-lineage ZIKV demonstrated that African-lineage isolates often replicated to high titers and caused more-severe pathology than Asian-lineage isolates. To date, the pathogenesis of African-lineage ZIKV in a translational model, particularly during pregnancy, has not been rigorously characterized. Here, we infected four pregnant rhesus macaques with a low-passage-number strain of African-lineage ZIKV and compared its pathogenesis to those for a cohort of four pregnant rhesus macaques infected with an Asian-lineage isolate and a cohort of mock-inoculated controls. The viral replication kinetics for the two experimental groups were not significantly different, and both groups developed robust neutralizing antibody titers above levels considered to be protective. There was no evidence of significant fetal head growth restriction or gross fetal harm at delivery (1 to 1.5 weeks prior to full term) in either group. However, a significantly higher burden of ZIKV viral RNA (vRNA) was found in the maternal-fetal interface tissues of the macaques exposed to an African-lineage isolate. Our findings suggest that ZIKV of any genetic lineage poses a threat to pregnant individuals and their infants. IMPORTANCE ZIKV was first identified in 1947 in Africa, but most of our knowledge of ZIKV is based on studies of the distinct Asian genetic lineage, which caused the outbreak in the Americas in 2015 to 2016. In its most recent update, the WHO stated that improved understanding of African-lineage ZIKV pathogenesis during pregnancy must be a priority. The recent detection of African-lineage isolates in Brazil underscores the need to understand the impact of these viruses. Here, we provide the first comprehensive assessment of African-lineage ZIKV infection during pregnancy in a translational nonhuman primate model. We show that African-lineage isolates replicate with kinetics similar to those of Asian-lineage isolates and can infect the placenta. However, there was no evidence of more-severe outcomes with African-lineage isolates. Our results highlight both the threat that African-lineage ZIKV poses to pregnant individuals and their infants and the need for epidemiological and translational in vivo studies with African-lineage ZIKV.

Documented ß-Lactam Allergy and Risk for Cesarean Surgical Site Infection.

Objective: To examine the relationship between documented ß-lactam allergy and cesarean delivery (CD) surgical site infection (SSI). Study Design. We conducted a retrospective cohort analysis of women who underwent CD at Ben Taub Hospital and Texas Children's Pavilion for Women (Houston, TX) from August 1, 2011, to December 31, 2019. The primary exposure was a documented ß-lactam allergy, and the second exposure of interest was the type of perioperative antibiotic received. The primary outcome was the prevalence of SSI. Maternal characteristics were stratified by the presence or absence of a documented ß-lactam allergy, and significance was evaluated using Pearson's chi-squared test for categorical variables and t-test for continuous variables. A logistic regression model estimated odds of SSI after adjusting for possible confounders. Results: Of the 12,954 women included, 929 (7.2%) had a documented ß-lactam allergy while 12,025 (92.8%) did not. Among the 929 women with a ß-lactam allergy, 495 (53.3%) received non-ß-lactam perioperative prophylaxis. SSI occurred in 38 (4.1%) of women who had a ß-lactam allergy versus 238 (2.0%) who did not (p ≤ 0.001). ß-Lactam allergy was associated with higher odds of SSI compared to no allergy (adjusted odds ratio (aOR) = 1.97; 95%confidence interval (CI) = 1.24-3.14; p = 0.004) after controlling for age, race, ethnicity, insurance status, delivery body mass index (BMI), tobacco use, intra-amniotic infection in labor, duration of membrane rupture, preterm delivery, delivery indication, diabetes, hypertension, group B Streptococcus colonization, and type of perioperative antibiotic received. Conclusion: The presence of a ß-lactam allergy is associated with increased odds of developing a CD SSI after controlling for possible confounders, including the type of perioperative antibiotic received.

Prenatal care experiences among pregnant women with obesity in Wisconsin, United States: a qualitative quality improvement assessment.

BACKGROUND: Stigma and bias experienced during prenatal care can affect quality of care and, ultimately, the health of pregnant women with obesity and their infants. We sought to 1) better understand the bias and stigma that women with BMIs ≥40 kg/m2 experience while receiving prenatal care, 2) gauge women's interest in group prenatal education for women with obesity, and 3) gather feedback about their preferred weight-related terminology. METHODS: We conducted and thematically content-analyzed 30 semi-structured interviews of women with BMIs ≥40 kg/m2 who received prenatal care at a university-affiliated teaching hospital in the Midwest region of the United States. RESULTS: All women recalled positive experiences during their perinatal care during which they felt listened to and respected by providers. However, many also described a fear of weight-related bias or recalled weight-based discrimination. Women reacted favorably to a proposed group prenatal care option for pregnant women with obesity that focused on nutrition, physical activity, and weight management. Women rated "weight" and "BMI" as the most desirable terms for describing weight, while "large size" and "obesity" were rated least desirable. CONCLUSIONS: Many pregnant women with BMIs ≥40 kg/m2 experience bias in the prenatal care setting. Potential steps to mitigate bias towards weight include improving provider awareness of the experiences and perspectives of this population, expanding prenatal care options targeted towards women with high BMIs, including group care, and using patient-preferred weight-related terminology. Through the remainder of this manuscript, wherever possible, the term "high BMI" will be used in place of the term "obesity" to describe women with BMI ≥ 30 kg/m2 in order to respect the preferred terminology of the women we interviewed.

A Matter of Time: Does Gestational Age Affect the Duration of the Fetal Anatomic Survey?

OBJECTIVE: To assess the average duration of detailed fetal anatomic surveys in pregnancy in relation to gestational age (GA) and the maternal body mass index (BMI) to determine optimal timing of the examination. METHODS: This was a retrospective cohort study of gravidae presenting for detailed fetal anatomic examinations between January 1, 2010, and June 30, 2017. After excluding examinations expected to have longer duration (ie, multifetal, major fetal anomalies), there were a total of 6522 examinations performed between GAs of 18 weeks 0 days and 22 weeks 0 days. Women were grouped by BMI, and results were analyzed by logistic regression. RESULTS: Gravidae of normal weight (BMI, 18.5-24.9 kg/m2 ) had a decrease of 47.47 seconds of the examination time with each increasing week of gestation (P = .036). Overweight (BMI, 25-29.9 kg/m2 ) gravidae similarly had a decrease of 66.31 seconds of the examination time with each additional week of gestation (P = .017). Underweight (BMI, 8.5 kg/m2 ) and obese (BMI, ≥30 kg/m2 ) gravidae did not have differences in the examination time with increasing GA. Increases in suboptimal examinations were noted with an increasing BMI (P < .001). There was a decreased frequency of suboptimal examinations in obese gravidae with a BMI of 40 kg/m2 or higher with increasing GA (P = .037). CONCLUSIONS: The duration of detailed fetal anatomic examinations decreased with increasing GA in normal-weight and overweight gravidae but not in obese gravidae. Performing the anatomy scan earlier in class I and II obese gravidae (BMI, 30-40 kg/m2 ) may enable improved pregnancy management options without increasing the examination duration or likelihood of a suboptimal evaluation.

Maternal Metabolic Biomarkers are Associated with Obesity and Excess Gestational Weight Gain.

OBJECTIVE: The purpose of this study was to evaluate the independent contribution of maternal obesity and gestational weight gain (GWG) in excess of the Institute of Medicine's guidelines on levels of maternal serum inflammatory and metabolic measures. STUDY DESIGN: Banked maternal serum samples from 120 subjects with documented prepregnancy or first trimester body mass index (BMI) were utilized for analyte analyses. Validated, BMI-specific formulas were utilized to categorize GWG as either insufficient, at goal or excess based on the Institute of Medicine guidelines with gestational age adjustments. Serum was analyzed for known inflammatory or metabolic pathway intermediates using the Luminex xMap system with the MILLIPLEX Human Metabolic Hormone Magnetic Bead Panel. Measured analytes included interleukin-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α and metabolic markers amylin, c-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, pancreatic polypeptide, and peptide YY. Kruskal-Wallis ANOVA and Pearson's correlation coefficients were calculated for each marker. RESULTS: C-peptide, insulin, and leptin all varied significantly with both obesity and GWG while glucagon-like peptide-1 varied by BMI but not GWG. These analytes covaried with other metabolic analytes, but not with inflammatory analytes. CONCLUSION: Maternal metabolic biomarkers at delivery vary significantly with both obesity and GWG. Taken together, these findings suggest that GWG (with and without comorbid obesity) is an important mediator of measurable metabolites in pregnancy but is not necessarily accompanied by inflammatory measures in serum. These findings are consistent with GWG being an independent risk factor for metabolic disturbances during pregnancy.

Metformin Exposure and Risk of Hypertensive Disorders of Pregnancy in Patients with Type 2 Diabetes.

OBJECTIVE: Metformin has been found to have a role in promoting vascular remodeling and angiogenesis which may reduce the risk of developing preeclampsia. Prior studies have shown a decrease in the incidence of hypertensive disorders of pregnancy in patients with type 2 and gestational diabetes taking metformin. We hypothesize metformin exposure decreases the risk of developing hypertension in patients with type 2 diabetes. STUDY DESIGN: Retrospective cohort study from 2009 to 2019 of singleton pregnancies was complicated by type 2 diabetes. We compared patients who received metformin throughout pregnancy to those with no metformin exposure. The primary outcome was a hypertension composite defined as gestational hypertension, preeclampsia with or without severe features, HELLP syndrome, or eclampsia. Individual hypertensive outcomes and neonatal outcomes were secondarily evaluated. Logistic regression was used to adjust for confounding variables. RESULTS: A total of 254 pregnancies were included. Women exposed to metformin were significantly less likely to develop hypertension composite compared with nonexposed women (22.7 vs. 33.1%, aOR 0.53, 95% CI 0.29-0.96). The incidence of preeclampsia with severe features was also significantly lower in those who received metformin compared with those who did not (12.1 vs. 20.7%, aOR 0.38, 95% CI 0.18-0.81). There were no differences in preterm birth prior to 34 or 37 weeks, fetal growth restriction, or birth weight between the study groups. A subgroup analysis of women without chronic hypertension also had a significantly lower risk of developing preeclampsia with severe features (7.6 vs. 17.8%, aOR 0.35, 95% CI 0.13-0.94). CONCLUSION: Metformin exposure was associated with a decreased risk of composite hypertensive disorders of pregnancy in patients with pregestational type 2 diabetes. These data suggest that there may be benefit to metformin administration beyond glycemic control in this patient population. KEY POINTS: · Metformin use showed a decreased risk of a hypertension composite.. · Results were consistent in patients without chronic hypertension.. · Metformin may show benefit beyond glycemic control in women with type 2 diabetes..

Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques.

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10-12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated.

Travel During Pregnancy: Results From an Ultrasound Unit-Based Questionnaire.

BACKGROUND: The frequency of domestic and international travel among women residing in the United States, and specifically Wisconsin, during pregnancy is not known. Given the recent epidemic of Zika virus disease, clinicians should be aware of the frequency of travel during pregnancy and should inquire about travel by pregnant women, women of reproductive age, and their sexual partners. METHODS: Due to the Zika epidemic, our obstetric ultrasound center added questions about international and domestic travel to a general health form that is routinely distributed to all patients presenting for anatomic ultrasounds. The forms were then collected and recorded in order to provide an estimate of the frequency of travel during the first half of pregnancy. RESULTS: Of 1,256 women screened, 64 (5.1%) traveled internationally and 498 (39.6%) traveled domestically prior to their anatomic ultrasound. Additionally, 77 (6.1%) women screened reported international travel by their sexual partner. Among international travelers, 20 (28.1%) traveled to destinations with active ongoing transmission of Zika virus disease, and 16 (25%) traveled after the Centers for Disease Control and Prevention (CDC) issued a travel alert for the area. Among domestic travelers, Florida was the sixth most common destination, and Texas was the 10th most common. CONCLUSIONS: In the population of women screened by this questionnaire, 5.1% traveled internationally and 39.6% traveled domestically prior to their anatomic ultrasound. Notably, Florida and Texas are common travel destinations among women at this clinic, and both have had active local transmission of Zika virus.

Increasing maternal obesity is associated with alterations in both maternal and neonatal thyroid hormone levels.

OBJECTIVE: Obesity is associated with alterations in thyroid hormone (TH) levels in obese, pregnant individuals. The maintenance of TH levels throughout gestation is important for proper foetal development. The aim of this study was to measure levels of fT3, fT4 and TSH in maternal and matched cord blood serum from normal weight, overweight and obese gravidae to determine alterations in maternal and neonatal TH levels by virtue of maternal obesity. DESIGN, SETTING, SUBJECTS, OUTCOME MEASURES: ELISA was utilized to measure fT3, fT4 and TSH levels from banked, matched maternal and neonatal (cord blood) serum (N = 205 matched pairs). Data were stratified according to prepregnancy or first trimester BMI. RESULTS: Both maternal and neonatal fT3 levels consistently increased with increasing maternal obesity, and maternal and neonatal fT3 were significantly correlated (r = 0·422, P < 0·001). Maternal and neonatal fT3 were also significantly associated with birthweight (ß = 0·155, P = 0·027 and ß = 0·171, P = 0·018, respectively). Both the maternal and neonatal fT3 to fT4 ratio significantly increased with increasing maternal obesity. We further found that excess gestational weight gain was associated with a decrease in maternal fT4 compared with gravidae who had insufficient gestational weight gain (0·86 ± 0·17 vs 0·95 ± 0·22, P < 0·01). CONCLUSION: Maternal obesity is not only associated with maternal alterations in TH, but with accompanying neonatal changes. Because both maternal obesity and alterations in TH levels are associated with childhood obesity, based on these findings and our prior analyses in a nonhuman primate model, we propose that changes in fT3 levels in the offspring of obese mothers may be a potential molecular mediator of foetal overgrowth and childhood obesity.

Marijuana use and its effects in pregnancy.

BACKGROUND: It is generally assumed that marijuana is one of the more widely used controlled substances during pregnancy. However, there remains a general paucity of population-based data regarding its use and subsequent perinatal morbidity. We hypothesized that direct patient query during pregnancy regarding marijuana, tobacco, and nicotine use would provide crucial initial population-based data on perinatal risk. OBJECTIVE: Our study sought to examine maternal and neonatal outcomes in pregnancies with reported marijuana exposure, in isolation or in combination with maternal cigarette smoking. STUDY DESIGN: We applied a retrospective cohort study design to subjects (n = 12,069) with available information on marijuana use and pregnancy outcomes. Since 2011, we have routinely and directly questioned all gravidae regarding use of marijuana, tobacco, and nicotine-containing products. We examined perinatal outcomes in marijuana smokers vs nonsmokers, as well as patients reporting both marijuana and cigarette smoking. Multivariate analysis enabled determination of adjusted odds ratios for maternal and fetal outcomes, adjusting for confounders. Significance was determined with Mann-Whitney U, χ(2), and Fischer exact tests (as appropriate). RESULTS: In all, 106/12,069 reported marijuana use (0.88%), with 48/12,069 (0.4%; or 48/106, 45%) concurrently using cigarettes and marijuana. After controlling for potential confounding variables, while marijuana use alone was not associated with significant adverse outcomes, use in combination with cigarette smoking was significantly associated with increased risk of multiple adverse perinatal outcomes (increased occurrence of maternal asthma [adjusted odds ratio, 2.4; 95% confidence interval, 1.0-5.9]; preterm birth [adjusted odds ratio, 2.6; 95% confidence interval, 1.3-4.9]; decreased [<25th percentile] head circumference [adjusted odds ratio, 2.8; 95% confidence interval, 1.3-4.3]; and decreased [<25th percentile] birthweight [adjusted odds ratio, 2.8; 95% confidence interval, 1.6-5.0]). Maternal pregnancy-related hypertension was not increased in marijuana smokers (adjusted odds ratio, 1.30; 95% confidence interval, 0.681-2.498), or in cigarette smokers (adjusted odds ratio, 1.4; 95%, confidence interval, 0.9-1.9). However, co-users had elevated rates of preeclampsia compared to nonusers (adjusted odds ratio, 2.5; 95% confidence interval, 1.4-5.0). CONCLUSION: In our initial cohort analysis, after controlling for potential confounders, while marijuana exposure alone was not associated with significant perinatal adverse outcomes, co-use with cigarette smoking rendered increased risk over either alone. Due to observed prevalence of concurrent cigarette and marijuana use, it is of likely importance to counsel patients regarding use in pregnancy.

The preterm placental microbiome varies in association with excess maternal gestational weight gain.

OBJECTIVE: Although a higher maternal body mass index is associated with preterm birth, it is unclear whether excess gestational weight gain (GWG) or obesity drives increased risk. We and others have shown that the placenta harbors microbiota, which is significantly different among preterm births. Our aim in this study was to investigate whether the preterm placental microbiome varies by virtue of obesity or alternately by excess GWG. STUDY DESIGN: Placentas (n=320) were collected from term and preterm pregnancies. Genomic DNA was extracted and subjected to metagenomic sequencing. Data were analyzed by clinical covariates that included the 2009 Institute of Medicine's GWG guideline and obesity. RESULTS: Analysis of 16S recombinant RNA-based metagenomics revealed no clustering of the microbiome by virtue of obesity (P=.161). Among women who spontaneously delivered preterm, there was again no clustering by obesity (P=.480), but there was significant clustering by excess GWG (P=.022). Moreover, among preterm births, detailed analysis identified microbial genera (family and genus level) and bacterial metabolic gene pathways that varied among pregnancies with excess GWG. Notably, excess GWG was associated with decreased microbial folate biosynthesis pathways and decreased butanoate metabolism (linear discriminate analysis, >3.0-fold). CONCLUSION: Although there were no significant alterations in the microbiome by virtue of obesity per se, excess GWG was associated with an altered microbiome and its metabolic profile among those women who experienced a preterm birth.

Role of Maternal Serum Alpha-Fetoprotein and Ultrasonography in Contemporary Detection of Spina Bifida.

OBJECTIVE: Midtrimester maternal serum alpha-fetoprotein (MSAFP) and sonographic evaluation have been used to screen for spina bifida. With the increased uptake of cell-free DNA (cfDNA) and first trimester screening, MSAFP levels may no longer be obtained routinely. Our aim was to evaluate a pediatric neurosurgical referral center database of spina bifida cases to determine the antenatal detection rate and means of diagnosis. STUDY DESIGN: Nested case series of all spina bifida cases referred postnatally from 2007 to 2013. Data were abstracted from the maternal record and rates of antenatal detection with MSAFP and sonographic screening were determined. RESULTS: Of the 105 postnatally referred cases, 11.4% (12/105) were not identified until delivery. Overall, 39% of the cases had MSAFP screening. The odds ratio for sonogram-based detection of spina bifida was 4.9 (95% confidence interval, 2-11.9). Of the neonatally detected cases, 100% had prenatal care and 91.6% (11 of the 12 cases) had documented sonography. CONCLUSION: We have found that 11.4% of the spina bifida cases were not detected before delivery. Nine out of the 12 cases of antenatally missed spina bifida were not screened using MSAFP. Our findings support the approach of midtrimester MSAFP screening combined with sonographic evaluation. We speculate that prenatal screening with MSAFP is underutilized.

Establishing thromboelastography with platelet-function analyzer reference ranges and other measures in healthy term pregnant women.

OBJECTIVE: The diagnosis of coagulopathy cannot always be performed at point of care. Thromboelastography (TEG) and the platelet-function analyzer (PFA-100), have emerged as reliable means for coagulation analysis. However, their reliable utility in pregnancy remains to be determined. We sought to establish reference values with concomitant determination of other known coagulation measures in nonlaboring gravidae in an effort to report the mean and variance of multiple testing modalities. STUDY DESIGN: Fifty-nine term, nonlaboring, pregnant women without comorbidities were enrolled, either at presentation for scheduled delivery or at presentation to triage for a non-labor-related indication. TEG, PFA-100, and complete coagulation measures of the overall hemostatic function (including prothrombin time, activated partial thromboplastin time, fibrinogen, protein C, protein S, von Willebrand factor antigen, ristocetin cofactor activity, and ADAMTS-13) were performed. Prior investigations of TEG and PFA-100 parameters in normal gravidae were reviewed, and pooled means and standard deviations (as a measure of variance) were calculated. RESULTS: TEG and PFA-100 parameters were significantly different among pregnant gravidae compared with nonpregnant reference ranges, and varied in association with other measures of the coagulation system. Our results and the pooled results reflect a hypercoagulable state. CONCLUSION: Our data suggest that TEG values are significantly different in term, nonlaboring, healthy gravidae compared with nonpregnant reference values. Pooled means and standard deviations shown here may be considered for reference.

Surgical transversus abdominis plane block with liposomal bupivacaine at cesarean: a pilot randomized trial.

BACKGROUND: Postcesarean pain control is challenging. In addition to intrathecal morphine, recent studies have shown that liposomal bupivacaine administered via conventional transversus abdominis plane block reduces postcesarean opioid use. However, whether the administration of liposomal bupivacaine via a surgical approach also reduces opioid use is unknown. OBJECTIVE: This study aimed to investigate whether the administration of liposomal bupivacaine via surgical transversus abdominis plane block (TAP block) reduces the cumulative dose of opioids administered in the first 48 hours after cesarean delivery among participants who also receive intrathecal morphine. STUDY DESIGN: This was a pilot single-blind randomized controlled trial of 60 parturients undergoing cesarean delivery at a community tertiary referral hospital staffed by academic physicians. Immediately before fascial closure during cesarean delivery, a total of 80 mL of dilute bupivacaine plus liposomal bupivacaine or dilute bupivacaine alone was administered via surgical transversus abdominis plane block (40 mL on each side). The primary outcome was a median cumulative opioid dose received within the first 48 hours after cesarean delivery measured in morphine milligram equivalents. In addition, opioid use at other time points, pain scores, and participant satisfaction were assessed. A sample size of 60 was determined to be adequate to inform a potential future adequately powered randomized trial. The primary outcome of morphine milligram equivalents and pain scores were compared using a Wilcoxon rank-sum test. RESULTS: Between October 11, 2021, and August 29, 2022, 60 participants were randomized and analyzed: 31 were allocated to liposomal bupivacaine plus regular bupivacaine (intervention group), and 29 were allocated to regular bupivacaine alone (control group). Participants allocated to the intervention group used a median cumulative dose of 2 morphine milligram equivalents of opioids (interquartile range, 0-24) in the first 48 hours compared with 8 morphine milligram equivalents (interquartile range, 0-40) among participants allocated to the control group (P=.236). The percentage of participants who used ≤15 morphine milligram equivalents of opioids was 61% in the intervention arm and 41% in the control arm (P=.123), and the percentage who used zero opioids was 45% in the intervention arm and 34% in the control arm (P=.399). The total number of opioid pills prescribed at discharge was fewer in the intervention arm than in the control arm (P=.029). Patient satisfaction with the intervention group and control group was similar. CONCLUSION: Our pilot study suggests that liposomal bupivacaine administered via surgical transversus abdominis plane block is worth critical evaluation as an adjunctive analgesic modality in an adequately powered randomized trial.