Pregnancy in a Patient with Idiopathic Pulmonary Fibrosis: A Case Report.

Idiopathic pulmonary fibrosis (IPF) is a progressive restrictive lung disease. Data on the impact of pregnancy on IPF and maternal outcome is extremely limited. We present the case of a 35-year-old woman, gravida 1 para 0 with familial IPF with no oxygen requirement prior to pregnancy. The patient demonstrated significant deterioration in her lung function beginning at 22 weeks' gestation and underwent hospitalization at 27 2/7 weeks gestation due to acute on chronic hypoxic respiratory failure, ultimately requiring delivery at 28 weeks' gestation. The patient has not regained her baseline pulmonary function and remains oxygen dependent at 5 months postpartum. Based on limited available data, significant maternal morbidity and mortality is reported for women with IPF who become pregnant. Key Points Pregnancy outcomes in IPF are more severe than chronic interstitial lung disease due to connective tissue disorders.Deterioration in lung function amongst pregnant women with IPF occurs predominantly in the late second trimester, and lung function does not appear to recover postpartum.Significant maternal morbidity and mortality (40% at 1 year postpartum) is reported for women with IPF who become pregnant.

A Novel, Cardiac-Derived Algorithm for Uterine Activity Monitoring in a Wearable Remote Device.

Background: Uterine activity (UA) monitoring is an essential element of pregnancy management. The gold-standard intrauterine pressure catheter (IUPC) is invasive and requires ruptured membranes, while the standard-of-care, external tocodynamometry (TOCO)'s accuracy is hampered by obesity, maternal movements, and belt positioning. There is an urgent need to develop telehealth tools enabling patients to remotely access care. Here, we describe and demonstrate a novel algorithm enabling remote, non-invasive detection and monitoring of UA by analyzing the modulation of the maternal electrocardiographic and phonocardiographic signals. The algorithm was designed and implemented as part of a wireless, FDA-cleared device designed for remote pregnancy monitoring. Two separate prospective, comparative, open-label, multi-center studies were conducted to test this algorithm. Methods: In the intrapartum study, 41 laboring women were simultaneously monitored with IUPC and the remote pregnancy monitoring device. Ten patients were also monitored with TOCO. In the antepartum study, 147 pregnant women were simultaneously monitored with TOCO and the remote pregnancy monitoring device. Results: In the intrapartum study, the remote pregnancy monitoring device and TOCO had sensitivities of 89.8 and 38.5%, respectively, and false discovery rates (FDRs) of 8.6 and 1.9%, respectively. In the antepartum study, a direct comparison of the remote pregnancy monitoring device to TOCO yielded a sensitivity of 94% and FDR of 31.1%. This high FDR is likely related to the low sensitivity of TOCO. Conclusion: UA monitoring via the new algorithm embedded in the remote pregnancy monitoring device is accurate and reliable and more precise than TOCO standard of care. Together with the previously reported remote fetal heart rate monitoring capabilities, this novel method for UA detection expands the remote pregnancy monitoring device's capabilities to include surveillance, such as non-stress tests, greatly benefiting women and providers seeking telehealth solutions for pregnancy care.

Wireless, remote solution for home fetal and maternal heart rate monitoring.

BACKGROUND: Access to prenatal care can be challenging due to physician shortages and rural geography. The multiple prenatal visits performed to collect basic fetal measurements lead to significant patient burden as well. The standard of care tools for fetal monitoring, external fetal heart rate monitoring with cardiotocography, as used today, must be applied by a medical professional in a healthcare setting. Novel tools to enable a remote and self-administered fetal monitoring solution would significantly alleviate some of the current barriers to care. OBJECTIVE: To compare maternal and fetal heart rate monitoring data obtained by 'Invu system' (a wireless, wearable, self-administered, fixed-location device containing passive electrical and acoustic sensors) to cardiotocography, toward a true remote fetal monitoring solution. MATERIALS AND METHODS: A prospective, open-label, multicenter study evaluated concurrent use of Invu and cardiotocography in pregnant women, aged 18 to 50 years, with singleton pregnancies ≥32+0 weeks' gestation (NCT03504189). Simultaneous recording sessions from Invu and cardiotocography lasted for ≥30 minutes. Data from the 8 electrical sensors and 4 acoustic sensors in the Invu belt were acquired, digitized, and sent wirelessly for analysis by an algorithm on cloud-based servers. The algorithm validates the data, preprocesses the data to remove noise, detects heartbeats independently from the two data sources (electrical and acoustic), and fuses the detected heartbeat arrays to calculate fetal heart rate (FHR) and maternal heart rate (MHR). The primary performance endpoint was Invu FHR limit of agreement within ± 10 beats per minute (bpm) of FHR measured with cardiotocography. RESULTS: A total of 147 women were included in the study analysis. The mean (SD) maternal age was 31.8 ±6.9 years, and the mean gestational age was 37.7 ±2.3 weeks. There was a highly significant correlation between FHR measurements from Invu and cardiotocography (r = 0.92; P<0.0001). The 95% limits of agreement for the difference, the range within which most differences between the two measurements will lie, were -8.84 bpm to 8.24 bpm. Invu measurements of MHR were also very similar to cardiotocography and were highly significantly correlated (r = 0.97; P<0.0001). No adverse events were reported during the study. CONCLUSION: Although captured by very different methods, the FHR and MHR outputs wirelessly obtained by the Invu system through passive methods were very similar to those obtained by the current standard of care. The limits of agreement for FHR measured by Invu were within a clinically acceptable ± 8 bpm of cardiotocography FHR. The Invu device uses passive technology to allow for safe, non-invasive and convenient monitoring of patients in the clinic and remotely. Further work should investigate how remote perinatal monitoring could best address some of the recent challenges seen with prenatal care and maternal and fetal outcomes. CLINICAL TRIAL INFORMATION: Registration date: April 20, 2018; First participant enrollment: February 28, 2018; ClinicalTrials.gov registration NCT03504189; https://clinicaltrials.gov/ct2/show/NCT03504189.

Benefits and Pitfalls of Ultrasound in Obstetrics and Gynecology.

Diagnostic ultrasound is a powerful tool in obstetrics/gynecology. It has multiple applications, but for every use there are potential pitfalls that can have significant deleterious effects. Guidelines and certifications have been implemented to enhance the safety of this technique.

A randomized clinical trial of knotless barbed suture vs conventional suture for closure of the uterine incision at cesarean delivery.

BACKGROUND: Knotless barbed sutures are monofilament sutures with barbs cut into them. These sutures self-anchor, maintaining tissue approximation without the need for surgical knots. OBJECTIVE: The hypothesis of this study was that knotless barbed suture could be used on the myometrium to close the hysterotomy at cesarean delivery. The objective was to compare uterine closure time, need for additional sutures, and blood loss between this and a conventional suture. STUDY DESIGN: This was a prospective, unblinded, randomized controlled trial conducted at the Ziv Medical Center, Zefat, Israel. The primary outcome was the length of time needed to close the uterine incision, which was measured from the start of the first suture on the uterus until obtaining uterine hemostasis. To minimize provider bias, women were randomized by sealed envelopes that were opened in the operating room just prior to uterine closure with either a bidirectional knotless barbed suture or conventional suture. Secondary outcomes included the number of additional hemostatic sutures needed and blood loss during incision closure. RESULTS: Patients were enrolled from August 2016 until March 2017. One hundred two women were randomized. Fifty-one had uterine closure with knotless barbed suture and 51 with conventional suture. The groups were similar for demographics as well as number of previous cesarean deliveries. Uterine closure time using the knotless barbed suture was significantly shorter than the conventional suture by a mean of 1 minute 43 seconds (P < .001, 95% confidence interval, 67.69-138.47 seconds). Knotless barbed sutures were associated with a lower need for hemostatic sutures (median 0 vs 1, P < .001), and blood loss measured during incision closure was significantly lower (mean 221 mL vs 268 mL, P < .005). CONCLUSION: The use of a knotless barbed suture is a reasonable alternative to conventional sutures because it reduced the closure time of the uterine incision. There was also less need for additional hemostatic sutures and slightly reduced estimated blood loss.

Modifying Risk of Aneuploidy with a Positive Cell-Free Fetal DNA Result.

Noninvasive genomic assessments of the fetus while in utero have been made possible by the analysis of cell-free fetal DNA fragments from the serum of pregnant women, as part of a noninvasive prenatal testing screening strategy. Between 7% and 10% of total cell-free DNA in the maternal blood comes from placental trophoblasts, allowing for identification of the DNA associated with the fetal component of the placenta. Using simple venipuncture in the outpatient setting, this cell-free, extracellular fetal DNA can be isolated in the maternal serum from a single blood draw as early as the seventh week of gestation.

Early wound dressing removal after scheduled cesarean delivery: a randomized controlled trial.

BACKGROUND: Following cesarean delivery, wound dressings are typically left over the incision for 24-48 hours. OBJECTIVE: The objective of this study was to determine if early removal of the wound dressing at 6 hours postsurgery has any effect on wound complications. STUDY DESIGN: This was a randomized, controlled study from August 2013 through January 2015 in which 320 low-risk women aged 18-44 years having scheduled primary, first repeat, or second repeat cesarean delivery were randomized for wound dressing removal at either 6 or 24 hours postsurgery. Skin closure was with staples in all cases. The primary outcome was postoperative wound complications, defined as infection, disruption (skin dehiscence or deeper), or seroma/hematoma. Also examined was patient satisfaction with timing of their ability to wash or shower after wound dressing removal. A sample size of 160 women in each group was needed to show a 100% increase in the wound complication incidence from 12-24%. RESULTS: A total of 320 women were randomized, 160 in the 6-hour group and 160 in the 24-hour group. The proportion of primary and repeat cesarean deliveries was similar. The incidence of wound complications was not significantly different between the groups, 13.8% in the 6-hour group and 12.5% in the 24-hour group (odds ratio, 1.16; 95% confidence interval, 0.58-2.14). More women were pleased and satisfied with their ability to wash or shower soon after wound dressing removal in the 6-hour group (75.6%) compared to the 24-hour group (56.9%; odds ratio, 2.35; 95% confidence interval, 1.46-3.79). CONCLUSION: Early removal of the wound dressing at 6 hours following cesarean delivery has no detrimental effect on incision healing. Early removal permits the woman to attend to personal hygiene earlier, making her more satisfied with her postoperative recovery.

The effect of chart speed on fetal monitor interpretation.

OBJECTIVE: Electronic fetal heart monitor chart speeds vary between countries, and it is unclear whether differing chart speeds affect physician tracing interpretation. METHODS: Twenty-minute segments of 19 tracings were displayed on both 1 and 3 cm/min strips and interpreted by 14 physicians at the particular speed they were accustomed to reading. Interpretations of tracing characteristics were compared between groups using free margin kappa, a measure of interobserver agreement. RESULTS: Compared to 3 cm/min tracings, 1 cm/min tracings were significantly more often identified as having absent than minimal variability, and minimal than moderate variability. Accelerations were significantly more often identified in 1 versus 3 cm/min strips. There were no significant differences between groups with respect to baseline fetal heart rate, prolonged or repetitive decelerations, or American College of Obstetricians and Gynecologists tracing category. Neither chart speed had substantial interobserver agreement in tracing variables; however, agreement was consistently higher in 3 versus 1 cm/min tracings (all p < 0.05). CONCLUSIONS: Tracing interpretation is significantly affected by fetal monitor chart speed with regards to variability, acceleration and deceleration. Further studies are required to determine if differences in chart speed interpretation affect clinical management.

Use of the Combined First-Trimester Screen in High- and Low-Risk Patient Populations After Introduction of Noninvasive Prenatal Testing.

OBJECTIVES: To report changes in the use of the combined first-trimester screen (FTS) in patients classified as high and low risk for fetal aneuploidy, including after introduction of noninvasive prenatal testing (NIPT). METHODS: A prospectively collected database was reviewed to investigate changes in FTS use before and after American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 77 (Obstet Gynecol 2007; 109:217-227), which recommended that all patients be offered aneuploidy screening, and after NIPT introduction. High-risk patients were classified as 35 years or older at the estimated time of delivery or those with an abnormal prior screen, abnormal ultrasound findings, or family history of aneuploidy. Data were normalized per 100 morphologic ultrasound examinations to account for changes in patient number over time. Statistical significance was defined as P < .05. RESULTS: A total of 10,125 FTSs were recorded during the 88-month study period, including 2962 in high-risk patients and 7163 in low-risk patients. The total number of FTSs performed per 100 morphologic ultrasound examinations significantly increased after ACOG Practice Bulletin No. 77 and significantly decreased after NIPT introduction. In high-risk patients, the total number of FTSs performed per 100 morphologic ultrasound examinations significantly increased after ACOG Practice Bulletin No. 77 but significantly decreased after NIPT introduction. In contrast, in low-risk patients, the total number of FTSs performed per 100 morphologic ultrasound examinations significantly increased after ACOG Practice Bulletin No.77 but was not statistically different after NIPT introduction. CONCLUSIONS: American College of Obstetricians and Gynecologists Practice Bulletin No. 77 significantly increased patient use of FTS. The introduction of NIPT significantly decreased FTS use in the high-risk population but not in the low-risk population.

Overview of the impact of noninvasive prenatal testing on diagnostic procedures.

Noninvasive prenatal testing (NIPT) has had a profound influence in the field of prenatal diagnosis since the 1997 discovery of cell-free fetal DNA in maternal blood. Research has progressed rapidly, with clinical data supporting laboratory studies showing that NIPT is highly sensitive and specific for fetal aneuploidy, resulting in marked uptake in the high-risk patient population. The superior accuracy of NIPT compared with conventional screening methods has led to significant decreases in the number of invasive diagnostic procedures, in addition to a concomitant decrease in the number of procedure-related fetal losses. Yet, NIPT has been described as a 'disruptive innovation' due to the considerable changes the technology has commanded on current prenatal screening and diagnostic practices. This review summarizes both institutional and global experience with NIPT uptake, its effect on reducing diagnostic invasive procedures, and the unique challenges that reduced procedural volume may have on physician and trainee proficiency, cytogenetic laboratories, and neonatal outcome.

Counseling for fetal macrosomia: an estimated fetal weight of 4,000 g is excessively low.

OBJECTIVE: Because of the known complications of fetal macrosomia, our hospital's policy has been to discuss the risks of shoulder dystocia and cesarean section (CS) in mothers with a sonographic estimated fetal weight (SEFW) ≥ 4,000 g at term. The present study was performed to determine the effect of this policy on CS rates and pregnancy outcome. STUDY DESIGN: We examined the pregnancy outcomes of the macrosomic (≥ 4,000 g) neonates in two cohorts of nondiabetic low risk women at term without preexisting indications for cesarean: (1) SEFW ≥ 4,000 g (correctly suspected macrosomia) and (2) SEFW < 4,000 g (unsuspected macrosomia). RESULTS: There were 238 neonates in the correctly suspected group and 205 neonates in the unsuspected macrosomia group, respectively. Vaginal delivery was accomplished in 52.1% of the suspected group and 90.7% of the unsuspected group, respectively, p < 0.001. There was no difference in the rates of shoulder dystocia. The odds ratio for CS was 9.0 (95% confidence interval, 5.3-15.4) when macrosomia was correctly suspected. CONCLUSION: The policy of discussing the risk of macrosomia with SEFW ≥ 4,000 g to women is not justified. A higher SEFW to trigger counseling for shoulder dystocia and CS, more consistent with American College of Obstetrics and Gynecology (ACOG) guidelines, should be considered.

Uptake of noninvasive prenatal testing at a large academic referral center.

OBJECTIVE: Noninvasive prenatal testing (NIPT) is a recently developed risk-assessment technique with high sensitivity and specificity for fetal aneuploidy. The effect NIPT has had on traditional screening and diagnostic testing has not been clearly demonstrated. In this study, NIPT uptake and subsequent changes in the utilization of first-trimester screen (FTS), chorionic villus sampling (CVS), and amniocentesis in a single referral center is reported. STUDY DESIGN: Monthly numbers of NIPT (in high-risk patients), FTS, CVS, and amniocentesis were compared between a 35-month baseline period (April 2009 through February 2012) before introduction of NIPT, and the initial 16 months following NIPT introduction divided in 4-month quarters beginning in March 2012 through June 2013. RESULTS: A total of 1265 NIPT, 6637 FTS, 251 CVS, and 1134 amniocentesis were recorded over the 51-month study period in singleton pregnancies of women who desired prenatal screening and diagnostic testing. NIPT became the predominant FTS method by the second quarter following its introduction, increasing by 55.0% over the course of the study period. Total first-trimester risk assessments (NIPT+FTS) were not statistically different following NIPT (P = .312), but average monthly FTS procedures significantly decreased following NIPT introduction, decreasing by 48.7% over the course of the study period. Average monthly CVS and amniocentesis procedures significantly decreased following NIPT introduction, representing a 77.2% and 52.5% decrease in testing, respectively. Screening and testing per 100 morphological ultrasounds followed a similar trend. CONCLUSION: NIPT was quickly adopted by our high-risk patient population, and significantly decreased alternate prenatal screening and diagnostic testing in a short period of time.

Association of combined first-trimester screen and noninvasive prenatal testing on diagnostic procedures.

OBJECTIVE: To describe the changes over a 9-year period in the number and rate of diagnostic testing after the introduction of the combined first-trimester screen and subsequent noninvasive prenatal testing. METHODS: The number of prenatal screening and diagnostic tests was recorded over a 9-year period from billing records. Three time intervals were considered: 1) 20 months before a combined first-trimester screen was offered; 2) 72 months after a combined first-trimester screen was offered; and 3) 16 months after noninvasive prenatal testing introduction. Prenatal testing was compared per year, per time interval, and per 100 morphologic ultrasonograms to account for fluctuations in patient number. RESULTS: A total of 15,418 prenatal tests was recorded during the study period, consisting of 9,780 combined first-trimester screen, 1,265 noninvasive prenatal testing, 608 chorionic villus sampling (CVS), and 3,765 amniocenteses. Combined first-trimester screen peaked at 1,836 in 2009-2010 but declined by 48.1% after noninvasive prenatal testing was introduced. Combined first-trimester screen per 100 morphologic ultrasonograms also significantly decreased (P<.05) after noninvasive prenatal testing introduction. Chorionic villus sampling peaked after combined first-trimester screen introduction in 2007-2008 with 100 procedures, representing an 81.8% increase from prefirst-trimester screen. After the introduction of noninvasive prenatal testing, CVS declined by 68.6% during 2012-2013. Chorionic villus sampling per 100 morphologic ultrasonograms followed the same trend. Amniocentesis declined every year of the study period (78.8% overall), including 60.3% after combined first-trimester screen and a further 46.7% after noninvasive prenatal testing. Monthly amniocentesis procedures per 100 morphologic ultrasonograms significantly decreased (P<.05) after introduction of a combined first-trimester screen and noninvasive prenatal testing. CONCLUSION: The introduction of combined first-trimester screen was associated with an increase in CVS and a decrease in amniocentesis testing. Noninvasive prenatal testing was associated with a subsequent decrease in CVS and further decrease in amniocentesis. LEVEL OF EVIEDENCE: III.

Impact of noninvasive prenatal testing in regionally dispersed medical centers in the United States.

OBJECTIVE: Noninvasive prenatal testing using cell-free DNA is a new alternative to screen for common fetal aneuploidies. It is not known what impact regional location may play on noninvasive prenatal testing implementation and downstream invasive prenatal procedure use in the United States. STUDY DESIGN: Six different regionally based centers collected data on noninvasive prenatal testing indication and results between February and November 2012, as well as their invasive prenatal procedure rates before and after offering noninvasive prenatal testing. Statistical analyses were performed using the 2-proportion Z-test. RESULTS: Of 1477 patients who underwent noninvasive prenatal testing; 693 (47%) were from centers in the West; 522 (35.3%) from centers in the East; and 262 (17.7%) from 1 center in the Midwest. Statistically significant differences were observed between West Coast and nonWest Coast sites for gestational age (14.1 weeks; P ≤ .0001). Advanced maternal age (AMA-only) was the most frequent indication in 5 of 6 sites (range, 21.8-62.9%) A total of 98 invasive prenatal procedures performed on 94 (6.4%) patients of which 64 (65.3%) were performed at centers in the West. More invasive procedures were performed following negative noninvasive prenatal testing results (n = 61) than abnormal noninvasive prenatal testing results (n = 30). The overall rate of patients undergoing invasive procedure after an abnormal noninvasive prenatal testing result was 32.6% (30 of 92). All 6 centers reported a decrease in invasive procedure volume after noninvasive prenatal testing introduction. CONCLUSION: This study demonstrates differences in clinical implementation of noninvasive prenatal testing across regionally dispersed centers in the United States, suggesting patient demographics and views toward prenatal testing influence use as well as downstream management.

Fetal biometry: relevance in obstetrical practice.

Fetal biometry is the measurement of the fetus and various segments of the fetal anatomy. Every part of the fetal anatomy may be imaged, but fetal head, abdomen, and femur measurements are the most commonly used, as well as the crown-rump length in early gestation. These biometric measurements can be used to estimate gestational age and fetal weight, evaluate interval fetal growth, and identify fetuses who are either growth restricted or macrosomic. These measurements may influence antepartum and intrapartum management and may be used to predict peripartum outcomes. Biometry is therefore an integral and valuable element of obstetrical practice.

Optimization of transrenal DNA analysis: detection of fetal DNA in maternal urine.

BACKGROUND: Fragments of DNA from cells dying throughout the body are detectable in urine (transrenal DNA, or Tr-DNA). Our goal was the optimization of Tr-DNA isolation and detection techniques, using as a model the analysis of fetal DNA in maternal urine. METHODS: We isolated urinary DNA using a traditional silica-based method and using a new technique based on adsorption of cell-free nucleic acids on Q-Sepharose resin. The presence of Y chromosome-specific SRY (sex-determining region Y) sequences in urine of pregnant women was detected by conventional and real-time PCR using primers/probe sets designed for 25-, 39-, 65-, and 88-bp PCR targets. RESULTS: Method of DNA isolation and PCR target size affected fetal Tr-DNA detection. Assay diagnostic sensitivity increases as the PCR target is shortened. Shorter DNA fragments (50-150 bp) could be isolated by Q-resin-based technique, which also facilitated fetal Tr-DNA analysis. Using DNA isolated by Q-resin-based method and an "ultrashort" DNA target, we successfully detected SRY sequences in 78 of 82 urine samples from women pregnant with male fetuses (positive predictive value 87.6%). Eleven of 91 urine samples from women pregnant with female fetuses produced SRY false-positive results (negative predictive value 95.2%). CONCLUSIONS: Single-copy fetal DNA sequences can be successfully detected in the urine of pregnant women when adequate methods for DNA isolation and analysis are applied. Strong precautions against sample contamination with male cells and DNA are necessary to avoid false-positive results.