Uncomplicated Pregnancies Research Articles

Abstract 4135893: The Importance of Genetic Testing in Diagnosis and Management of Peripartum Cardiomyopathy: A Case Study

Introduction: At least 15% of women diagnosed with peripartum cardiomyopathy (PPCM) are found to have a pathogenic genetic variant associated with dilated cardiomyopathy. We present a patient with PPCM who required orthotopic heart transplantation (OHT) for cardiogenic shock. Her explant pathology and genetic testing played a critical role in identifying the etiology of her cardiomyopathy. Case Description: A 22-year-old primigravid woman with a history of asthma presented in labor and underwent a Cesarean delivery for non-reassuring fetal heart tones. She had noted exertional dyspnea, a dry cough, and orthopnea in her final weeks of pregnancy but had an otherwise uncomplicated pregnancy. Immediately following delivery, she suffered a cardiac arrest with pulseless electrical activity and developed cardiogenic shock. She was found to have severe biventricular systolic dysfunction with a left ventricular (LV) ejection fraction of 10%. She was cannulated on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and transferred to our center. She was transitioned from VA-ECMO to an axillary Impella 5.5 device but continued to require inotropic support without evidence of LV recovery. Therefore, she was listed for and successfully underwent OHT. Explant pathology (Figure 1) revealed arrhythmogenic cardiomyopathy (ACM). Her family history was significant for a maternal grandfather who died of an unspecified arrhythmia at age 57. Genetic testing via a commercial arrhythmia and cardiomyopathy panel revealed a pathogenic desmoplakin ( DSP) truncating variant ( DSP tv) p.Ser1894Leufs*34 in the N-terminal constitutive NMD-competent region, confirming the diagnosis of ACM. The patient had minor cutaneous findings, including curly hair, consistent with the clinical presentation of DSP -mediated ACM. Discussion: This case highlights the importance of genetic testing in all patients with PPCM, as well as attention to the explant pathology in those who undergo OHT. These practices can elucidate the mechanism of cardiomyopathy, inform the risks of disease progression and of relapse with subsequent pregnancy, and allow for cascade testing of family members.

Abstract 4137145: Aortic Stenosis in Pregnancy: A Multidisciplinary Team Approach

Introduction: The hemodynamic adaptations that occur during pregnancy can have significant effects on patients with aortic stenosis (AS). These changes can lead to structural changes identified on echocardiogram even during uncomplicated pregnancies. While some cases can be managed with medical therapy and activity modification, others may require valve intervention in the gestational period. Case: A 29-year-old female with history of congenital bicuspid aortic valve, G1P0 presented at 42+2 weeks of pregnancy and was admitted to cardiac intensive care unit for continuous hemodynamic monitoring via use of arterial line. Her prior aortic valve disease was treated by valve repair with valvotomy, removal of tissue from pseudo raphe, removal of calcified scar tissue from both commissures, and a mitral valve repair for closure of an iatrogenic tear in her anterior leaflet. She followed closely with maternal fetal medicine and cardiology but became symptomatic at week 28 with lightheadedness, shortness of breath and decreased exercise tolerance (NYHA Class II). By week 33 she noticed lower extremity edema. Despite recommendations for planned delivery, she opted to wait until full term for delivery. Surveillance echoes revealed rising velocities yet stable valve area by planimetry. She ultimately underwent an uncomplicated Cesarean delivery of baby boy in week 42. At 6 months post partum she had successful transcatheter aortic valve replacement. Discussion: As the severity of valvular disease worsens there is a higher risk of complications during pregnancy. In our case, aortic valve velocities were elevated due to the expected hemodynamic changes of pregnancy. Thus, echocardiography monitoring should be used to assess the left ventricle’s ability to tolerate and compensate for these changes, while intervening based on symptoms and NYHA classification. We highlight the importance of multidisciplinary collaboration for safe and successful delivery in patients with AS.

Maternal Serum SCUBE-1: A Novel Ischemic Marker in Preeclampsia

Background: SCUBE-1 (Signal peptide-CUB (complement C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor)-domain-containing protein 1) is a novel marker of ischemia, which is a cell surface-secreted protein in the platelets and endothelial cells. The aim of the study is to measure serum SCUBE-1 levels and investigate their association with uteroplacental blood flow in patients with preeclampsia. Methods: The study was conducted on patients with preeclampsia. Maternal serum SCUBE1 and IMA levels were the main outcomes. The control group consisted of gestational-age-matched pregnant women. Fetal umbilical artery (UA) pulsatility index (PI), middle cerebral artery PI, cerebroplacental ratio (CPR), and maternal uterine artery (UtA)-PI were also examined, and correlation analysis was performed to reveal the association between maternal serum SCUBE1 levels and Doppler findings. Results: The study group consisted of thirty-two preeclamptic patients, and the control group consisted of thirty-two uncomplicated singleton pregnancies. Maternal serum SCUBE1 and IMA levels were significantly higher in preeclamptic women compared to the control group (p < 0.000, p < 0.004, respectively). Mean UtA-PI values and fetal UA-PI values were significantly higher in preeclamptic pregnant women compared to the control group (p < 0.05, p < 0.05, respectively). However, the average CPR was significantly lower in pregnant women with preeclampsia (p < 0.05). While no significant correlation was found between maternal serum SCUBE1 levels and UA-PI and CPR (p > 0.05, p > 0.05, respectively), a significant correlation was found between right and left UtA-PI (p < 0.004, p < 0.006, respectively). Conclusions: The maternal serum SCUBE1 level is increased in patients with preeclampsia, and this increase is significantly correlated with the maternal uterine artery pulsatility index.

The prospective associations of fetal growth-related pregnancy complications with subsequent breastfeeding duration and markers of human milk production.

The development of the breast for lactation occurs throughout pregnancy. It is unknown whether pregnancy complications resulting in poor fetal growth can affect breastfeeding success. We examined whether fetal growth-related pregnancy complications were associated with earlier breastfeeding cessation and changes in the concentrations of human milk biomarkers of low milk production. We used data from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) study (n=954). Human milk concentrations of protein, lactose, citrate, sodium, potassium and zinc at 3 weeks postpartum were available for 180 mother-infant dyads. We examined the associations of fetal growth measures, including term infants born small-for-gestational-age (SGA) (<10th percentile), pregnancies complicated by fetal growth deceleration (FGD) (2nd - 3rd trimester fetal growth dropped between major centiles), elevated umbilical artery resistance (UAR) (> 90th percentile) or hypertensive disorders of pregnancy (HDP) with (i) risk of ceasing breastfeeding (Cox regression) and (ii) concentrations of human milk components (weighted linear regression). Adjusting for maternal education, smoking exposure, breastfeeding intentions and pre-pregnancy BMI, individuals who delivered SGA infants, and those with HDP were more likely to breastfeed for a shorter duration when compared to those with uncomplicated pregnancies (adjusted hazard ratio [95% CI]: 1.45 [1.11, 1.89] and 1.61 [1.14, 2.29], respectively); associations were not significant for FGD and UAR. SGA was not associated with concentrations of human milk biomarkers, but compared to participants with uncomplicated pregnancies, milk produced by those with HDP contained lower zinc concentrations (adjusted beta coefficient [95% CI]: -0.56 mg/L [-1.08, -0.04]). Individuals with HDP and those with SGA infants tend to breastfeed for a shorter duration; however, only HDP appeared to be associated with biomarkers of compromised milk production. Further research and support are needed to help individuals with HDP and SGA achieve their breastfeeding goals. This study was registered as NCT01174875, and can be accessed at https://clinicaltrials.gov/study/NCT01174875.

Validation of Fetal Medicine Foundation charts for fetal growth in twins: nationwide Danish cohort study.

To assess the validity of the Fetal Medicine Foundation (FMF) chorionicity-specific models for fetal growth in twin pregnancy. This was an external validation study of the FMF models using a nationwide Danish cohort of twin pregnancies. The cohort included all dichorionic (DC) and monochorionic diamniotic (MCDA) twin pregnancies with an estimated delivery date between 2008 and 2018, which satisfied the following inclusion criteria: two live fetuses at the first-trimester ultrasound scan (11-14 weeks' gestation); biometric measurements available for the calculation of estimated fetal weight (EFW) using the Hadlock-3 formula; and delivery of two liveborn infants. Validation involved assessing the distributional properties of the models and estimating the mean EFW Z-score deviations. Additionally, the models were applied to pregnancies that delivered preterm and attended non-scheduled visits (complicated pregnancies). Overall, 8542 DC and 1675 MCDA twin pregnancies met the inclusion criteria. In DC twins, 17 084 fetuses were evaluated at a total of 95 346 ultrasound scans, of which 44.5% were performed at scheduled visits in pregnancies carried to 37 + 0 weeks or later. The median number of growth scans per DC twin fetus from 20 + 0 weeks onwards was four. The model showed good agreement with the validation cohort for scheduled visits in DC twins delivered at 37 + 0 weeks or later (mean EFW Z-score, -0.14 ± 1.05). In MCDA twins, 3350 fetuses underwent 31 632 eligible ultrasound scans, of which 59.5% were performed at scheduled visits in pregnancies carried to 36 + 0 weeks or later. The median number of growth scans per MCDA twin fetus from 16 + 0 weeks onwards was 10. The model showed favorable agreement with the validation cohort for scheduled visits in MCDA twins delivered at 36 + 0 weeks or later (mean EFW Z-score, -0.09 ± 1.01). Non-scheduled visits and preterm delivery before 37 + 0 weeks for DC twins and before 36 + 0 weeks for MCDA twins corresponded with smaller weight estimates, which was consistent with the study's definition of complicated pregnancy. The FMF models provide a good fit for EFW measurements in our Danish national cohort of uncomplicated twin pregnancies assessed at routine scans. Therefore, the FMF models establish robust criteria for subsequent investigations and potential clinical applications. Future research should focus on exploring the consequences of clinical implementation, particularly regarding the identification of twins that are small-for-gestational age, as they are especially susceptible to adverse perinatal outcome. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cytokine balance in pregnant women with preeclampsia

Studies were conducted to study the levels of pro- (IL-6, IL-18, IL-17A) and anti-inflammatory (IL-4) cytokines in the blood serum of pregnant women at different stages of gestation: 18-20, 28-30, and 33- 38 weeks. The study involved 76 patients at risk of developing preeclampsia. Of these, 34 women developed preeclampsia, making up the main group, and 42 pregnant women had no symptoms of preeclampsia and made up the comparison group. The control group consisted of 28 somatically healthy women with a physiologically normal pregnancy. The average age of the examined patients with preeclampsia was 26.2±4.3 years, and in the group of pregnant women with normal pregnancy it was 25.8±4.7 years. The purpose of the study was to study the levels of cytokines IL-4, IL-6, IL-17A, and IL-18 in women with uncomplicated pregnancy and preeclampsia. These cytokines play an important role in the immune response and may be associated with the development of preeclampsia. The results of the study may help further understand the mechanisms of the disease and develop strategies for its prevention and management. The levels of pro- (IL-6, IL-18, IL-17A) and anti-inflammatory cytokines (IL-4, IL-10) were studied in blood serum by ELISA using test systems of Vector-best JSC (Novosibirsk, Russia) in accordance with the manufacturer’s recommendations. Statistical processing of research results was carried out using variation statistics methods. The results are presented as the sample mean (M) and standard error (m). The significance of the differences in the mean values (P) of the compared indicators was assessed using the Student t test (t). A study conducted by the authors found the following patterns in interleukin (IL) levels in pregnant women at risk of developing preeclampsia (PE). The levels of IL-6, IL-17A, and IL-18 were significantly increased in pregnant women with PE. There was a tendency to decrease the levels of IL-4, and IL-10 in women at risk of developing preeclampsia. These findings may help guide further research and development of strategies to prevent and manage preeclampsia in pregnant women.

Pregnancy care and perinatal outcomes in pregnant women with a shunt for hydrocephalus.

The number of patients with an implanted shunt reaching reproductive age and planning pregnancy is increasing thanks to advances in the treatment of hydrocephalus. Changes in the mother's organism, which are mainly related to the accumulation of water in the organism and the elevation of intra-abdominal pressure, contribute to the increased incidence of complications during pregnancy and childbirth. Therefore, it is necessary to make a preconception exam and specify pregnancy management, a suitable method of childbirth dealing with potential complications. Possible malfunction of the shunt is solved individually according to the current neurological findings and taking into account the patient's overall condition and gestational age. Vaginal delivery is considered safe and preferred by most authors. Primary caesarean section is indicated only in patients with a history of rapidly progressing deterioration of the neurological condition due to shunt malfunction or serious complications related to its impaired shunt function. In an uncomplicated pregnancy with normal values of intracranial pressure, both general and epidural or spinal anesthesia can be used when choosing anesthesia.

Role of C-C chemokine receptor type 5 in pathogenesis of malaria and its severe forms.

Malaria is a mosquito-borne disease caused by Plasmodium parasites, responsible for a significant impact on public health in several tropical and sub-tropical countries. The majority of infection cases are classified as uncomplicated malaria, causing mild symptoms such as fever and headache. However, the disease may progress to severe malaria and death if the infection is not properly treated. Furthermore, malaria poses a major concern for children, pregnant women and immunosuppressed individuals. Exacerbated inflammation is characteristic of severe malaria cases. The C-C chemokine receptor type 5 (CCR5) is an important molecule for leukocyte migration and regulation of inflammation. Although widely known as an HIV-1 co-receptor, CCR5 also affects the susceptibility and progression of autoimmune and inflammatory diseases. There is evidence supporting the participation of CCR5 in malaria manifestations, with the evaluation of CCR5 gene expression levels suggested as a marker to monitor malaria severity. Certain genetic variants in the CCR5 gene affect CCR5 expression, potentially altering CCR5-mediated inflammatory responses during malaria infection. However, the complex influences of CCR5 on malaria remain underexplored. Therefore, this review examines and updates the role of CCR5 in various contexts of malaria infection, including uncomplicated malaria, Plasmodium/HIV co-infection, pregnancy and severe (cerebral) malaria.

Challenging Case: Family Navigation for Autism Spectrum Disorder.

Leo is a 28-month-old boy from a monolingual Spanish-speaking family who was referred to a developmental-behavioral pediatrics (DBP) clinic for concerns regarding autism. His parents migrated to the United States 8 years ago and currently live and work on a farm. He was born in a US hospital after an uncomplicated pregnancy and has been generally healthy. His parents first became concerned about his development when he was 16 months old. He stopped saying mama/dada in Spanish and started lining up random objects. He had frequent temper tantrums and was difficult to console during unexpected changes in his routine. He screened positive on the Modified Checklist for Autism in Toddlers,Revised with Follow-Up (M-CHAT-R/F) at his 18-month well-child visit, and his pediatrician referred him to the local early intervention program. Calls from the early intervention program to his parents were unanswered. At his 24-month well-child visit, he again screened positive on the M-CHAT-R/F, and his pediatrician placed a referral for a DBP consultation. During the DBP visit at 28 months of age, developmental testing indicated his receptive and expressive language skills to be in the extremely low range, with significant scatter in his cognitive and adaptive skills. Behavioral observations were consistent with parental history and showed differences in social communication and interaction, the presence of repetitive behaviors, and extreme distress with transitions. He was diagnosed with autism spectrum disorder. Recommendations, including referral to early intervention, applied behavior analysis therapy, speech and language therapy, audiology evaluation, and genetic testing, were discussed with his parents through an interpreter. An autism packet, written in Spanish, with detailed information about autism and community resources was given to the family. By the time of a follow-up DBP visit 6 months later, Leo had not started on any early intervention or therapeutic services. Where do you go from here?

Associations Between Overweight in Early Pregnancy and Newborn Conditions: A Focus on the SDGs, With Emphasis on SDG 3 for Ensuring Healthy Lives and Well-Being for All Ages

Aim: The aim of this study was to investigate the links between overweight in women giving birth in early pregnancy and the condition of their newborns at the Souissi maternity hospital in Rabat, two factors closely linked to the achievement of the 3rd Sustainable Development Goal, which is based on ensuring healthy lives and promote well-being for all at all ages. Materials and Methods: This was a prospective descriptive study conducted over a 9-month period from March to November 2022, at the Souissi maternity hospital in Rabat. Including mothers of newborns who followed their pregnancy, were either normal weight or overweight at the beginning of pregnancy, and had an uncomplicated pregnancy. Results: A total of 1,145 newborns were recruited. With a response rate of 81.65% and using a mixed questionnaire, the number of newborns surveyed was 935, subdivided into two groups. A group of mothers of normal-bodied newborns (637 cases) and a group of mothers of overweight newborns (298 cases). This study showed the existence of associations between overweight at the start of pregnancy, recorded in the mothers of the newborns surveyed, and the term of delivery (P=0.033), the course of delivery (P=0.031), the mode of delivery (P=0.005), the Apgar score at 5min below 7 (P=0.004) and neonatal complications (P=0.002). Discussion: This study, found that 68.13% of surveyed mothers had a normal BMI, while 31.87% were overweight at the beginning of pregnancy. They were more likely to have overdue deliveries (70.80% vs. 25.27% for normal-weight mothers) and dystocic deliveries (25.50% vs. 4.24%). Overweight status also correlated with higher rates of vaginal delivery (27.18% vs. 0.78% for normal-weight mothers) and poorer Apgar scores (36.58% vs. 12.56%).

Exploring the Associations Between Women's Overweight at the Beginning of Pregnancy and Postpartum Complications in the Context of SDG 3: Ensuring Healthy Lives and Well-Being for All

Aim: The aim of this study was to investigate the associations between overweight recorded in parturient women at the beginning of pregnancy and the occurrence of postpartum complications at the Souissi maternity hospital in Rabat. Materials and Methods: This was a prospective descriptive study conducted over 9-month from March to November 2022, at the Souissi maternity hospital in Rabat. Including women who followed their pregnancy, were either normal or overweight at the beginning of pregnancy and had an uncomplicated pregnancy. Results: A total of 1,145 parturient women were recruited. With a response rate of 81.65% and using a mixed questionnaire, the number of surveyed women was 935, subdivided into two groups. Normal-weight (637 cases) and overweight parturient women (298 cases). This study showed the existence of associations between overweight at the start of pregnancy, recorded in the parturient surveyed, and the term of delivery (P=0.033), the course of delivery (P=0.031), the mode of delivery (P=0.005), the postpartum complications as urinary tract infection (P=0.002), breast engorgement (P=0.001), return of hemorrhagic layers and baby-blues (P=0.005). Discussion: This study found that 68.13% of surveyed women had a normal BMI, while 31.87% were overweight at the beginning of their pregnancy. They were more likely to have overdue deliveries (70.80% vs. 25.27% for normal-weight) and dystocic deliveries (25.50% vs. 4.24%). Overweight status was also correlated with higher rates of urinary tract infection 8.505 and 2.381 time and breast engorgement 16.331 and 3.556 time respectively in the early and last postpartum period.

The Role of Xanthine Oxidase in Pregnancy Complications: A Systematic Review.

Xanthine oxidoreductase (XOR) is an enzyme involved in the oxidation of hypoxanthine and xanthine to uric acid. XOR has two isoforms: xanthine dehydrogenase and xanthine oxidase (XO). XO plays a major role in oxidative stress, causing the formation of reactive oxygen species. In the present study, we aimed to summarize the evidence on the association between XO and pregnancy complications. The PRISMA checklist guided the reporting of the data. We conducted systematic searches in the PubMed and Web of Science databases to identify all human studies investigating XO in pregnancy diseases up to June 2024. A total of 195 references have been identified and 14 studies were included. Most studies focused on women with PE and GD. Overall, all the included studies found a statistically significant increase in maternal, placental, and/or fetal XO levels, activity, or tissue expression in women with pregnancy complications, compared to those with uncomplicated pregnancies. Although promising, the quality and dimension of the included studies do not allow for a definitive answer to the question of whether XO may play a crucial role in pregnancy complications. Future studies are warranted to confirm if XO could represent a prognostic and therapeutic marker in pregnancy complications and their impact on long-term maternal and offspring cardiovascular health.

Meconium as an Analyte for Androgen Exposure: Analysis Through Varying Maternal-Fetal Biomarkers.

Meconium, the first stool produced by neonates, has been used as an analyte for exogenous fetal exposures. However, few studies have investigated the relationship between meconium and androgen exposure in utero. Here, we examine the associations of testosterone and dehydroepiandrosterone (DHEA) across maternal antenatal salivary testosterone, cord blood, meconium, and infant salivary testosterone. A total of 47 women with singleton, uncomplicated pregnancies, and their infants were included in this study. Participants were recruited from an academic obstetric clinic. Maternal saliva was collected at 36-weeks' gestation. Cord blood and meconium were collected at birth. Infant salivary testosterone was collected at 1 and 4 weeks of age. Multivariate model results showed that meconium testosterone was associated with neonatal testosterone at 1 (F=5.62, p=0.029) and 4 weeks (F=4.28, p=0.048) postnatal age; no sex differences were detected. This study suggests meconium is a valuable tool for evaluating endogenous androgen exposure and should be used in future studies to investigate the fetal hormonal milieu.

A Wireless and Wearable Multimodal Sensor to Non-Invasively Monitor Transabdominal Placental Oxygen Saturation and Maternal Physiological Signals.

Poor placental development and placental defects can lead to adverse pregnancy outcomes such as pre-eclampsia, fetal growth restriction, and stillbirth. This study introduces two sensors, which use a near-infrared spectroscopy (NIRS) technique to measure placental oxygen saturation transabdominally. The first one, an NIRS sensor, is a wearable device consisting of multiple NIRS channels. The second one, a Multimodal sensor, which is an upgraded version of the NIRS sensor, is a wireless and wearable device, integrating a motion sensor and multiple NIRS channels. A pilot clinical study was conducted to assess the feasibility of the two sensors in measuring transabdominal placental oxygenation in 36 pregnant women (n = 12 for the NIRS sensor and n = 24 for the Multimodal sensor). Among these subjects, 4 participants had an uncomplicated pregnancy, and 32 patients had either maternal pre-existing conditions/complications, neonatal complications, and/or placental pathologic abnormalities. The study results indicate that the patients with maternal complicated conditions (69.5 ± 5.4%), placental pathologic abnormalities (69.4 ± 4.9%), and neonatal complications (68.0 ± 5.1%) had statistically significantly lower transabdominal placental oxygenation levels than those with an uncomplicated pregnancy (76.0 ± 4.4%) (F (3,104) = 6.6, p = 0.0004). Additionally, this study shows the capability of the Multimodal sensor in detecting the maternal heart rate and respiratory rate, fetal movements, and uterine contractions. These findings demonstrate the feasibility of the two sensors in the real-time continuous monitoring of transabdominal placental oxygenation to detect at-risk pregnancies and guide timely clinical interventions, thereby improving pregnancy outcomes.

Physiological and pathological changes to the eye and vision during and after pregnancy.

Pregnancy introduces a multitude of changes in the body, including hormonal fluctuations and metabolic changes, which can lead to atypical ocular signs and symptoms. Ocular manifestations range from fluctuations in vision, to microstructural changes in the retina and choroid, to dry eye disease. This narrative review highlights the range of pregnancy-related effects on the eye and vision that are likely to present in the context of routine eyecare. Specifically, physiological ocular changes and pathological ocular changes that manifest for the first time, or are exacerbated, in uncomplicated pregnancy are discussed. The literature has evolved from simply noting differences in the eye between pregnant and non-pregnant groups, to refining knowledge of the proposed underlying pathophysiology with the advent of newer technologies in eyecare. A particular focus of this review is navigating when pregnancy changes in the eye occur or peak during the gestational period, and whether the changes are short-lived or might extend past pregnancy. While many pregnancy-associated changes are temporary and resolve post-partum, it is also recognised that some changes persist after pregnancy, with a notable absence of literature on ocular changes with loss or termination of pregnancy. Currently or previously pregnant women (or those planning to become pregnant), and other health professionals, should be educated about the importance of seeking eyecare before, during and after pregnancy.

5104 Ectopic Insulinoma- a Rare Presentation of a Rare Tumor

Abstract Disclosure: O. Lavrynenko: None. A. DeMarsilis: None. C. Jiang: None. R. Middelbeek: None. H. Rosen: None. M.E. Patti: None. Background. Insulinoma is a rare, functioning neuroendocrine tumor (NET) typically localized within the pancreas, that secretes insulin, resulting in hypoglycemia. Ectopic insulinoma is even more rare than pancreatic insulinoma and is more difficult to diagnose. Case report. This 31-year-old previously healthy woman, who had an uncomplicated pregnancy and a healthy baby in October 2021, presented with intermittent hypoglycemia for more than 8 months. She denied any prior use of insulin or antidiabetic medications and was not currently taking any medications at all. There is no history of bariatric or other GI surgery. While nursing her baby in early 2022, she was noted to have a capillary blood glucose (BG) between 20-30 mg/dl, and reported both adrenergic and neuroglycopenic symptoms of hypoglycemia; these usually occurred in the morning or before lunch, especially if lunch was delayed. She wore a Libre CGM which revealed episodic hypoglycemia, which correlated with her timeline of symptoms. She reported weight gain of 8 lbs during this period. Laboratory data obtained after a 10-12 hour fast revealed hypoglycemia (venous glucose 39 mg/dL) with inappropriately high plasma insulin (42.3 mIU/ml), C- peptide (3.78 ng/ml), and proinsulin (99 pmol/L). Beta-hydroxybutyrate was 0.05 mmol/L (reference &amp;lt;0.28) and insulin autoantibody and sulfonylurea screen were negative. Various imaging modalities for localization revealed a solitary omental mass outside the pancreas consistent with extra-pancreatic insulinoma. No pancreatic lesion or other findings were observed with MRCP, CT C/A/P or endoscopic ultrasound. The patient underwent CT-guided biopsy of the omental mass, which confirmed a well-differentiated NET, consistent with insulinoma. Due to persistent hypoglycemia, she was started on corn starch and diazoxide. She subsequently underwent laparoscopic resection of the mass. Postoperative pathology revealed a well-differentiated NET staining positive for insulin, consistent with an extra-pancreatic insulinoma. Following surgical resection of the insulinoma, her hypoglycemia resolved even off corn starch and diazoxide. Conclusion. Ectopic insulinoma is a rare insulin-secreting NET. Only 28 ectopic insulinomas have been described in the literature to date1. We describe a patient with symptomatic hypoglycemia who was found to have an omental neuroendocrine tumor; hypoglycemia completely resolved after laparoscopic enucleation of the ectopic insulinoma. 1Fernando Guerrero-Pérez, Nuria Vialarrasa, Lidia V. Huanuco et. al. Ectopic Insulinoma: a systemic review: Reviews in Endocrine and Metabolic Disorders, 2023 Presentation: 6/1/2024

8532 Circulating Neprilysin in Pregnancy

Abstract Disclosure: A. Kulovic-Sissawo: None. E. Weiss: None. E. Jantscher-Krenn: None. U. Hiden: None. Background: In the complex nature of pregnancy, the female organism undergoes pivotal vascular and metabolic changes orchestrated by a tightly regulated interplay of bioactive regulatory molecules. The neutral endopeptidase, neprilysin, exists both in a membrane-bound and a soluble form (sNEP), of with the latter present in the circulatory system. Neprilysin degrades an exciting range of bioactive peptides involved in glycemic control (insulin B chain, GLP-1) and vascular tone regulation (angiotensin I and II, bradykinin, ANP, BNP), and both of them are altered in pregnancy. Objective: Due to the substrate-specificity of neprilysin and its multifaceted role we hypothesize that neprilysin may be involved in metabolic and vascular adaptions during pregnancy. However, the link between sNEP and maternal metabolism in pregnancy has not yet been investigated. Methodology: Serum sNEP concentration (n=102), longitudinally collected from metabolically healthy women (trial number NTC05496712), was measured at three visits throughout gestation (gestational age: 12.5±0.7; 20±0.8; 33±1.6 weeks) and post-partum (2±1.2 days after delivery) using commercially available sandwich ELISA. In addition, sNEP levels in pregnancy were compared to a cohort of non-pregnant women within reproductive age (n=50). Clinical and anthropometric measurements were determined and the association of sNEP and metabolic characteristics elucidated. Results: Circulating sNEP levels were non-normally distributed (median ± IQR: 2334±232624 pg/ml, n=82, gestational age 12.5±0.7 weeks) and showed high biological variability, with individual levels remaining constant over gestation. After delivery, however, sNEP concentration decreased (median± IQR: 1968±171060 pg/ml n=82, p=0.0001). sNEP showed a positive correlation with systolic blood pressure (Spearman, n=56, r=0.321, p=0.02) at early stages of pregnancy and non-fasting GLP-1 (Spearman, n=98, r=0.309, p=0.002) throughout gestation, but not with blood glucose, insulin resistance or BMI. In the non-pregnant state sNEP concentration (median±IQR: 4322±392152 pg/ml, n=38) positively correlated with body fat percentage (Pearson, n=38, r=0.405, p=0.01), fasting glucose (Pearson, n=43, r=0.301, p=0.05) and body mass index (Spearman, n=38, r=0.369, p=0.02) but did not correlate with systolic blood pressure (Pearson, n=36, r=-0.120, p=0.48). Conclusion: For the first time, the link between sNEP, metabolism and blood pressure during uncomplicated pregnancy was investigated. The decrease in post-partum circulating sNEP as compared to levels throughout pregnancy suggests a particular way of sNEP regulation and release during gestation. Our data indicate that in both, pregnant and non-pregnant state, sNEP may be involved in metabolic and cardiovascular regulation, with circulating sNEP levels showing massive individual differences. Presentation: 6/3/2024

8077 Use of Lovaza for Management of Hypertriglyceridemia in Pregnancy

Abstract Disclosure: J. Segarra-Villafane: None. L.R. Sepulveda-Garcia: None. L. El Musa Penna: None. I.C. Arroyo: None. Z. Maisonet -Feliciano: None. W. Medina-Torres: None. M. Alvarado: None. M. Ramirez: None. L.A. Gonzalez-Rodriguez: None. Severe hypertriglyceridemia in pregnancy increases the risk of health complications to both mother and fetus, including preeclampsia, hyperviscosity syndrome and life-threatening pancreatitis. Several case reports include management of hypertriglyceridemia in pregnancy with medical nutrition therapy, omega fatty acids and gemfibrozil but is controversial. There are no formal clinical guidelines for management of severe hypertriglyceridemia in pregnancy which presents a challenge for physicians. Lovaza is a combination of ethyl esters of omega 3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) indicated as an adjunct to diet to reduce triglycerides (TG) levels in adult patients with severe hypertriglyceridemia. Lovaza is Category C (risk cannot be ruled out) and should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Case of a 40 years old female G3P1A1 with IUP 25 WGA with history of hypothyroidism, dyslipidemia and episode of acute pancreatitis in 2016 due to hypertriglyceridemia, who was referred to clinics due to uncontrolled lipids and thyroid disease. Laboratories included fasting serum triglycerides (TG) 4357mg/dL (40-150mg/dL), total cholesterol 525mg/dL (120-200), HDL 56mg/dL, LDL invalid due to elevated TG. Thyroid function test revealed TSH of 161uIU/mL (0.43-2.91) and FT4 of 0.24ng/dL (0.8-1.8). HbA1c, lipase and amylase within range. Vital signs were normal. Patient was asymptomatic, no abdominal complaints or hypothyroidism-related symptoms, but hospital admission was recommended due to high risk of pancreatitis and uncontrolled hypothyroidism. She was started on Synthroid 220 mcg IV daily for hypothyroidism and was placed NPO until nutritionist evaluation. Triglycerides levels improved with conservative interventions and low-fat diet. However, TG persisted above 2000mg/dL and, after discussing risks and benefits with patient, pharmacological therapy with Lovaza was started to reach goal of TG less than 1000 mg/dL and reduce potential risk of pancreatitis. Patient agreed to start Lovaza 2gm AM and 2gm PM. After initiation of Lovaza, in addition to dietary modifications and hypothyroidism management, laboratories showed significant improvement in TG levels from 3569 down to 1778 mg/dL. Patient was discharged on Lovaza 2gm oral BID and Synthroid 200mcg oral daily. One month later, TG had decreased to 557mg/dL (0-150) and thyroid tests showed TSH at 0.305mIU/mL and FT4 at 1.71ng/dL. Patient tolerated medications well without side effects and had an uncomplicated pregnancy and delivery. This case demonstrates that severe hypertriglyceridemia during pregnancy can be managed effectively and, more importantly, in a safe manner with Lovaza, in addition to dietary fat restriction. However, additional research is needed if its use is to be included in future pregnancy management guidelines. Presentation: 6/2/2024

7988 A Case of Spontaneous Pituitary Hemorrhage in Late Pregnancy

Abstract Disclosure: D. Poudyal: None. G.L. Prince: None. Background: Pituitary apoplexy (PA), caused by hemorrhage into the pituitary gland, is rare. The prevalence in pregnancy is also quite rare, with PA complicating 1 in 10,000 pregnancies. PA usually occurs in patients with pre-existing pituitary adenomas. Spontaneous pituitary hemorrhage (PH) causing PA in the absence of a known adenoma or other precipitating factors is less frequently described. Presenting symptoms of PA are non-specific and can pose diagnostic challenges, yet PA must be managed urgently and decisively due to the risk of life-threatening hormonal deficiencies that can ensue. Physiologic changes in pregnancy pose additional challenges in evaluating and managing patients with possible PA. Here we present a case of spontaneous PH during the third trimester of pregnancy in the absence of pre-existing pituitary pathology or known precipitants. Case presentation: A 31-year-old female, G2P1, with an uncomplicated first pregnancy, presented with acute-onset headache and vision loss at 36 weeks gestation. Her symptoms resolved spontaneously in 45 minutes. MRI brain without contrast showed hemorrhage within the left aspect of the pituitary gland, a mildly displaced infundibulum, but no mass effect on the optic chiasm. MRI brain obtained 1 year prior for headache was unremarkable. Lab work showed an 8AM cortisol of 19 ug/dL (Ref range 3.7 - 19.4 ug/dL), and a total T4 of 11.3 ug/dL (Ref 4.9 - 11.7 ug/dL). Ultimately, interpretation of her cortisol testing was limited by: elevated cortisol-binding globulin in the high-estrogen state of pregnancy, elevated cortisol production by an intact hypothalamic-pituitary-adrenal (HPA) axis during the latter portion of pregnancy, and the lack of validated cutoff values for 8AM serum cortisol levels during pregnancy. In light of these factors and the risk of undiagnosed adrenal insufficiency (AI), she was treated empirically with oral hydrocortisone. Subsequently, she had an uneventful vaginal delivery, supported by stress dosing of her steroids. Postpartum, she had a normal 8AM cortisol level of 14 ug/dL, and she was noted to quickly begin breastfeeding without incident. Conclusion: PA remains a critical diagnosis that cannot be missed in patients presenting with concerning symptoms and signs, in order to identify and treat life-threatening hormonal deficiencies. Pregnancy poses unique challenges in diagnosing hormonal deficiencies such as AI due to normal physiologic changes affecting the HPA axis as well as other pituitary axes. Therefore, the benefit of empiric hydrocortisone treatment likely outweighs any associated treatment risk in cases with consistent symptomatology and radiographic findings. Presentation: 6/2/2024

Is there a relationship between morphokinetic parameters and obstetrical complications? An analysis of singleton live births after single fresh embryo transfer

BackgroundWith the advancement in embryology and the introduction of time-lapse monitoring system, the embryologists' goal might be to find not only the embryo with the highest probability of live birth, but also the embryo with the highest probability to progress to a healthy full-term delivery. Thus, we aimed to investigate the association between morphokinetic time-lapse parameters and obstetrical and perinatal complications.MethodsA cohort study reviewing fertility and delivery files of all singletone births from IVF patients whose embryos were cultured in a time-lapse monitoring system and had a single fresh embryo transfer at our center between 2013–2019. We conducted multiple comparisons between complicated and uncomplicated pregnancies of each perinatal complication, including: gestational diabetes mellitus (GDM); small for gestational age (SGA); pre-eclamptic toxemia (PET); preterm labor < 37 weeks of gestation (PTL); and third stage of labor complications. A comparison between pregnancies with and without a composite outcome of placental complications including GDM, SGA, PET and PTL was also conducted. Baseline characteristics, treatment and morphokinetic parameters in complicated and uncomplicated gestations were compared. Logistic regression analysis was utilized to adjust results for potential confounders.ResultsOne hundred seventy-six single embryo transfers resulted in 176 live births. Morphokinetic time-lapse parameters were similar between the groups, except for a shorter time to full blastulation in the SGA group (tB-tPNf = 75.5 ± 1.3 h vs. 79.5 ± 4.8 in the non-SGA group, p < 0.001), and shorter third cell cycle duration in the PET group (CC3 = 12.4 ± 1.1 h vs. 13.6 ± 2.9 in the non-PET group, p = 0.02). On multivariate regression analysis, none of the morphokinetic parameters were found to be significantly correlated with any of the perinatal complications.ConclusionTime-lapse morphokinetic parameters of the embryo transferred are not associated with adverse obstetric and perinatal outcomes.