The association of exercise during pregnancy with trimester-specific and postpartum quality of life and depressive symptoms in a cohort of healthy pregnant women.

Few published studies have examined the relationship between exercise during pregnancy, quality of life (QOL), and postpartum depressive symptoms in healthy pregnant women. A prospective cohort of 578 healthy pregnant women were followed during their pregnancy through 6 months postpartum. Levels of self-reported exercise and QOL before, during, and following pregnancy were assessed using standardized questionnaires during each trimester of pregnancy and 6 months postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) at 28 weeks gestation and 6 weeks postpartum. Participants were classified as having "sufficient exercise" if they achieved at least 150 min of exercise per week. Sufficient exercisers reported significantly higher ratings on most domains of QOL during each trimester of pregnancy and in the postpartum follow-up, compared with insufficient exercisers. There were no significant between-group differences in depressive symptoms. In examining the impact of exercise during each trimester, active women who became sedentary during their third trimester demonstrated a decline in their QOL. Achieving recommended levels of exercise during pregnancy was associated with higher QOL during pregnancy and the postpartum in healthy pregnant women. Decreasing the amount of exercise during pregnancy was associated with reduced QOL. These results suggest that it may be important for health care professionals to counsel healthy pregnant women about both the benefits of being physically active during pregnancy, and to provide guidance on how to remain physically active during a healthy pregnancy.

The Current State of Ultrasound Training in Obstetrics and Gynecology Residency Programs.

OBJECTIVES: We evaluated the current state of ultrasound training in obstetrics and gynecology (OB-GYN) residency programs across the United States. METHODS: An electronic survey was sent to OB-GYN residency program directors and OB-GYN residents. Responses were obtained in September 2016. Program directors and residents were asked to reflect on their current ultrasound curriculum. RESULTS: A total of 93 program directors and 437 residents responded. Respondents were mostly from university programs located in tertiary centers. Ultrasound curricula varied: 11% of program directors and 23% of residents did not have any ultrasound-related didactics; of those who did, 27% of program directors and 40% of residents had it yearly or less. Three-quarters had mandatory ultrasound rotations, and few offered ultrasound electives (program directors, 52%; residents, 28%). Most residents were required to perform ultrasound examinations daily or weekly (98%). Most stated that the main focus of the rotation was OB only. Skill was evaluated mainly subjectively by direct observation. Although most program directors stated that residents were satisfactory/excellent in ultrasound, 22% would not treat patients on the basis of ultrasound examinations performed by their senior residents. Similarly, of all postgraduate year 4 respondents (n = 86), 76% stated that they will require additional training to be able to perform or read ultrasound examinations independently, and 43% would not treat a patient on the basis of their own ultrasound examinations without further confirmation. Residents believed that the biggest obstacle in ultrasound training is lack of dedicated faculty time (41%). CONCLUSIONS: Recognizing the lack of clearly defined milestones in ultrasound training in OB-GYN residency, this study confirms the substantial heterogeneity in curricula between programs, highlighting a need for a standardized ultrasound curriculum.

Longitudinal characterization of renal proximal tubular markers in normotensive and preeclamptic pregnancies.

Glomerular damage is common in preeclampsia (PE), but the extent and etiology of tubular injury are not well understood. The aim of this study was to evaluate tubular injury in patients with PE and to assess whether it predates clinical disease. We performed a prospective cohort study of 315 pregnant women who provided urine samples at the end of the second trimester and at delivery. This analysis included women who developed PE (n = 15), gestational hypertension (GH; n = 14), and normotensive controls (NC; n = 44). Urinary markers of tubular injury, α1-microglobulin (A1M), retinol-binding protein (RBP), kidney-injury molecule-1 (KIM1), complement C5b-9, tissue inhibitor metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein-7 (IGFBP-7) were measured by enzyme-linked immunosorbent assay (ELISA) and reported in relation to urine creatinine concentration. Second-trimester concentrations of all markers were similar among groups. At delivery, A1M concentrations were higher in the PE group than in the GH and NC groups as an A1M/creatinine ratio >13 (66.7, 8.3, and 35%, respectively, P = 0.01). Concentrations of C5b-9 were higher in the PE group than in the GH and NC groups (medians 9.85, 0.05, and 0.28 ng/mg, respectively, P = 0.003). KIM1, RBP, TIMP-2, and IGFBP-7 concentrations did not differ among groups at delivery. In conclusion, proximal tubular dysfunction, as assessed by A1M and C5b-9, developed during the interval between the end of the second trimester and delivery in patients with PE. However, this was not matched by abnormalities in markers previously associated with tubular cell injury (KIM-1, IGFBP-7, and TIMP-2).

Antepartum nonobstetrical surgery at ≥23 weeks' gestation and risk for preterm delivery.

OBJECTIVE: We sought to describe the influence of antepartum nonobstetrical surgical procedures performed at viable fetal gestational ages (GAs) on incidence of preterm delivery. STUDY DESIGN: This was a retrospective case series of patients requiring nonobstetrical surgery at ≥23 weeks' gestation at the Mayo Clinic during the interval 1992 through 2014. Data were abstracted for maternal demographic variables, operative procedure, anesthetic type, whether intraoperative fetal monitoring was employed, and both GA and method of delivery. RESULTS: In all, 111 patients underwent 121 operative procedures at a mean GA of 29.2 weeks (range, 23-37 weeks). The majority of procedures were completed under general anesthesia (88/121, 73%), with intraoperative fetal monitoring performed in 14 cases (14/121, 12%); fetal loss occurred during a single unmonitored procedure. Outcome data were available for the majority of patients (86/111, 78%) with preterm delivery occurring in 41% (35/86) at a mean GA of 36.9 weeks (range, 25-41 weeks). Mean interval from procedure to delivery was 7.7 weeks, with 9 patients (9/86, 10%) delivering within 1 week of surgery. Neither procedures requiring entry into the abdominal cavity (P = .65) nor GA at time of procedure (P = 1.0) statistically influenced the risk of preterm delivery. CONCLUSION: Nonobstetrical surgical procedures performed at or beyond fetal viability increased the incidence of preterm delivery regardless of surgical site or timing of procedure, however the risk of intraoperative or immediate postoperative obstetrical complications was relatively low.

Combined elevated midpregnancy tumor necrosis factor alpha and hyperlipidemia in pregnancies resulting in early preterm birth.

OBJECTIVE: The objective of the study was to determine whether pregnancies resulting in early preterm birth (PTB) (<30 weeks) were more likely than term pregnancies to have elevated midtrimester serum tumor necrosis factor alpha (TNF-α) levels combined with lipid patterns suggestive of hyperlipidemia. STUDY DESIGN: In 2 nested case-control samples drawn from California and Iowa cohorts, we examined the frequency of elevated midpregnancy serum TNF-α levels (in the fourth quartile [4Q]) and lipid patterns suggestive of hyperlipidemia (eg, total cholesterol, low-density-lipoproteins, or triglycerides in the 4Q, high-density lipoproteins in the first quartile) (considered independently and by co-occurrence) in pregnancies resulting in early PTB compared with those resulting in term birth (n = 108 in California and n = 734 in Iowa). Odds ratios (ORs) and 95% confidence intervals (CIs) estimated in logistic regression models were used for comparisons. RESULTS: Early preterm pregnancies were 2-4 times more likely than term pregnancies to have a TNF-α level in the 4Q co-occurring with indicators of hyperlipidemia (37.5% vs 13.9% in the California sample (adjusted OR, 4.0; 95% CI, 1.1-16.3) and 26.3% vs 14.9% in the Iowa sample (adjusted OR, 2.7; 95% CI, 1.1-6.3). No differences between early preterm and term pregnancies were observed when TNF-α or target lipid abnormalities occurred in isolation. Observed differences were not explicable to any maternal or infant characteristics. CONCLUSION: Pregnancies resulting in early PTB were more likely than term pregnancies to have elevated midpregnancy TNF-α levels in combination with lipid patterns suggestive of hyperlipidemia.

A proposed method to predict preterm birth using clinical data, standard maternal serum screening, and cholesterol.

OBJECTIVE: The objective of the study was to create a predictive model for preterm birth (PTB) from available clinical data and serum analytes. STUDY DESIGN: Serum analytes and routine pregnancy screening plus cholesterol and corresponding health information were linked to birth certificate data for a cohort of 2699 Iowa women with serum sampled in the first and second trimester. Stepwise logistic regression was used to select the best predictive model for PTB. RESULTS: Serum screening markers remained significant predictors of PTB, even after controlling for maternal characteristics. The best predictive model included maternal characteristics, first-trimester total cholesterol, total cholesterol change between trimesters, and second-trimester alpha-fetoprotein and inhibin A. The model showed better discriminatory ability than PTB history alone and performed similarly in subgroups of women without past PTB. CONCLUSION: Using clinical and serum screening data, a potentially useful predictor of PTB was constructed. Validation and replication in other populations, and incorporation of other measures that identify PTB risk, like cervical length, can be a step toward identifying additional women who may benefit from new or currently available interventions.

Variations in CRHR1 are associated with persistent pulmonary hypertension of the newborn.

INTRODUCTION: Persistent pulmonary hypertension of the newborn (PPHN) is associated with substantial infant morbidity and mortality. Recently, genetic associations have been found in idiopathic pulmonary arterial hypertension. RESULTS: PPHN was significantly (P < 0.05) associated with genetic variants in corticotropin-releasing hormone (CRH) receptor 1, CRHR1 and CRH-binding protein, CRHBP. Association with CRHR1 rs4458044 passed the Bonferroni threshold for significance. No mutations were found in the bone morphogenetic protein receptor type II (BMPR2) gene. DISCUSSION: We describe previously unreported genetic associations between PPHN and CRHR1 and CRHBP. These findings may have implications for further understanding the pathophysiology of PPHN and treatment. METHODS: We performed a family-based candidate gene study to examine a genetic association with PPHN and sequenced the BMPR2 gene in 72 individuals. We enrolled 110 families with infants diagnosed with PPHN based on inclusion criteria. After medical chart review, 22 subjects were excluded based on predefined criteria, and DNA samples from 88 affected infants and at least one parent per infant were collected and genotyped. Thirty-two single-nucleotide polymorphisms in 12 genes involved in vasoconstriction/vasodilation, lung development, surfactant regulation, or vascular endothelial cell function were investigated using family-based association tests.

Amphetamine-Dextroamphetamine and Pregnancy: Neonatal Outcomes After Prenatal Prescription Mixed Amphetamine Exposure.

Objective: A retrospective cohort study was performed to evaluate whether birthweight was less among infants of women taking amphetamine-dextroamphetamine during pregnancy at our academic institution. Method: We identified mother-infant pairs with documented exposure to amphetamine-dextroamphetamine in pregnancy from 2005 through 2015. Patients were matched 2:1 with unexposed controls. Charts were reviewed for known causes of intrauterine growth restriction. Analysis of birthweight used generalized estimating equation blocking on matching. Medical histories were analyzed with χ2 test or Fisher's exact test. Results: We identified 53 exposed mother-infant pairs. The difference in mean birthweight of infants exposed to amphetamine-dextroamphetamine versus those not exposed was 26.9 g, which is not significant (95% confidence interval [CI] = [-141, 195 g]; p = .75). A significant difference was noted for exposed versus unexposed mothers for comorbid psychiatric illness and history of substance abuse (p < .001). Conclusion: With a limited sample size, our study suggests no significant difference in birthweight.

Perceived Barriers to Exercise in the First Trimester of Pregnancy.

Regular physical activity has been shown to improve pregnancy outcomes. We sought to identify barriers to exercise during the first trimester of pregnancy. Five hundred forty-nine pregnant women in their first trimester rated barriers to exercise on a scale of 1 (not a barrier) to 5 (a huge barrier) and recorded physical activity (minutes/week). Women were placed into one of three classifications, nonexercisers (zero exercise), infrequent exercisers (<150 minutes/week), or exercisers (≥150 minutes/week). The greatest barriers (mean) were nausea/fatigue (3.0) and lack of time (2.6). Exercisers reported significantly lower barrier levels. Nausea/fatigue was a greater barrier for nonexercisers compared to exercisers (3.6 vs 2.8, p < .001). Focusing education and interventions on these barriers may help pregnant women achieve healthy exercise levels.

Pregnancy-Related Changes of Amino Acid and Acylcarnitine Concentrations: The Impact of Obesity.

Objective Our primary objective was to assess the difference in amino and fatty acid biomarkers throughout pregnancy in women with and without obesity. Interactions between biomarkers and obesity status for associations with maternal and fetal metabolic measures were secondarily analyzed. Methods Overall 39 women (15 cases, 24 controls) were enrolled in this study during their 15- to 20-weeks' visit at the University of Iowa Hospitals and Clinics. We analyzed 32 amino acid and acylcarnitine concentrations with tandem mass spectrometry for differences throughout pregnancy as well as among women with and without obesity (body mass index [BMI] ≥ 35, BMI < 25). Results There were substantial changes in amino acids and acylcarnitine metabolites between the second and third trimesters (nonfasting state) of pregnancy that were significant after correcting for multiple testing (p < 0.002). Examining differences by maternal obesity, C8:1 (second trimester) and C2, C4-OH, C18:1 (third trimester) were higher in women with obesity compared with women without obesity. Several metabolites were marginally (0.002 < p < 0.05) correlated with birth weight, maternal glucose, and maternal weight gain stratified by obesity status and trimester. Conclusions Understanding maternal metabolism throughout pregnancy and the influence of obesity is a critical step in identifying potential mechanisms that may contribute to adverse outcomes in pregnancies complicated by obesity.

Preeclampsia/Eclampsia candidate genes show altered methylation in maternal leukocytes of preeclamptic women at the time of delivery.

OBJECTIVE: To analyze methylation profiles of known preeclampsia/eclampsia (PE) candidate genes in normal (NL) and preeclamptic (PE) women at delivery. METHODS: A matched case-control study comparing methylation in 79 CpG sites/33 genes from an independent gene set in maternal leukocyte DNA in PE and NL (n = 14 each) on an Illumina BeadChip platform. Replication performed on second cohort (PE = 12; NL = 32). RESULTS: PE demonstrates differential methylation in POMC, AGT, CALCA, and DDAH1 compared with NL. CONCLUSION: Differential methylation in four genes associated with PE may represent a potential biomarker or an epigenetic pathophysiologic mechanism altering gene transcription.

False Negative Cell-Free DNA Screening Result in a Newborn with Trisomy 13.

Background. Noninvasive prenatal screening (NIPS) is revolutionizing prenatal screening as a result of its increased sensitivity, specificity. NIPS analyzes cell-free fetal DNA (cffDNA) circulating in maternal plasma to detect fetal chromosome abnormalities. However, cffDNA originates from apoptotic placental trophoblast; therefore cffDNA is not always representative of the fetus. Although the published data for NIPS testing states that the current technique ensures high sensitivity and specificity for aneuploidy detection, false positives are possible due to isolated placental mosaicism, vanishing twin or cotwin demise, and maternal chromosome abnormalities or malignancy. Results. We report a case of false negative cell-free DNA (cfDNA) screening due to fetoplacental mosaicism. An infant male with negative cfDNA screening result was born with multiple congenital abnormalities. Postnatal chromosome and FISH studies on a blood specimen revealed trisomy 13 in 20/20 metaphases and 100% interphase nuclei, respectively. FISH analysis on tissues collected after delivery revealed extraembryonic mosaicism. Conclusions. Extraembryonic tissue mosaicism is likely responsible for the false negative cfDNA screening result. This case illustrates that a negative result does not rule out the possibility of a fetus affected with a trisomy, as cffDNA is derived from the placenta and therefore may not accurately represent the fetal genetic information.

Persistent Notochord in a Fetus with COL2A1 Mutation.

Multiple anomalies including micromelia, poor mineralization of the vertebrae, and a persistent notochord were identified on second trimester ultrasound in a fetus with a COL2A1 mutation. To our knowledge, this represents the first case of a persistent notochord associated with a COL2A1 mutation in humans. In this case report, we describe ultrasound and postmortem findings and review the pathogenesis associated with a persistent notochord.

Pregnancy Complications and the Risk of Metabolic Syndrome for the Offspring.

Metabolic syndrome is a growing problem globally, and is a contributor to non-communicable diseases such as type II diabetes and cardiovascular disease. The risk of developing specific components of the metabolic syndrome such as obesity, hyperlipidemia, hypertension, and elevated fasting blood sugar has been largely attributed to environmental stressors including poor nutrition, lack of exercise, and smoking. However, large epidemiologic cohorts and experimental animal models support the "developmental origins of adult disease" hypothesis, which posits that a significant portion of the risk for adult metabolic conditions is determined by exposures occurring in the perinatal period. Maternal obesity and the rate of complications during pregnancy such as preterm birth, preeclampsia, and gestational diabetes continue to rise. As our ability to reduce perinatal morbidity and mortality improves the long-term metabolic consequences remain uncertain, pointing to the need for further research in this area.

Mutations in the cyclin family member FAM58A cause an X-linked dominant disorder characterized by syndactyly, telecanthus and anogenital and renal malformations.

We identified four girls with a consistent constellation of facial dysmorphism and malformations previously reported in a single mother-daughter pair. Toe syndactyly, telecanthus and anogenital and renal malformations were present in all affected individuals; thus, we propose the name 'STAR syndrome' for this disorder. Using array CGH, qPCR and sequence analysis, we found causative mutations in FAM58A on Xq28 in all affected individuals, suggesting an X-linked dominant inheritance pattern for this recognizable syndrome.