Serum from pregnant donors induces human beta cell proliferation.

Pancreatic beta cells are among the slowest replicating cells in the human body and have not been observed to increase in number except during the fetal and neonatal period, in cases of obesity, during puberty, as well as during pregnancy. Pregnancy is associated with increased beta cell mass to meet heightened insulin demands. This phenomenon raises the intriguing possibility that factors present in the serum of pregnant individuals may stimulate beta cell proliferation and offer insights into expansion of the beta cell mass for treatment and prevention of diabetes. The primary objective of this study was to test the hypothesis that serum from pregnant donors contains bioactive factors capable of inducing human beta cell proliferation. An immortalized human beta cell line with protracted replication (EndoC-ßH1) was cultured in media supplemented with serum from pregnant and non-pregnant female and male donors and assessed for differences in proliferation. This experiment was followed by assessment of proliferation of primary human beta cells. Sera from five out of six pregnant donors induced a significant increase in the proliferation rate of EndoC-ßH1 cells. Pooled serum from the cohort of pregnant donors also increased the rate of proliferation in primary human beta cells. This study demonstrates that serum from pregnant donors stimulates human beta cell proliferation. These findings suggest the existence of pregnancy-associated factors that can offer novel avenues for beta cell regeneration and diabetes prevention strategies. Further research is warranted to elucidate the specific factors responsible for this effect.

Serum from pregnant donors induces human beta cell proliferation and insulin secretion.

Pancreatic beta cells are among the slowest replicating cells in the human body. Human beta cells usually do not increase in number with exceptions being during the neonatal period, in cases of obesity, and during pregnancy. This project explored maternal serum for stimulatory potential on human beta cell proliferation and insulin output. Gravid, full-term women who were scheduled to undergo cesarean delivery were recruited for this study. A human beta cell line was cultured in media supplemented with serum from pregnant and non-pregnant donors and assessed for differences in proliferation and insulin secretion. A subset of pregnant donor sera induced significant increases in beta cell proliferation and insulin secretion. Pooled serum from pregnant donors also increased proliferation in primary human beta cells but not primary human hepatocytes indicating a cell-type specific effect. This study suggests stimulatory factors in human serum during pregnancy could provide a novel approach for human beta cell expansion.

Outcomes of pregnancies at high-risk for placenta accreta spectrum following negative diagnostic imaging.

OBJECTIVES: To assess the pretest and negative post-test probability for placenta accreta spectrum (PAS) in a group of patients with high-risk clinical factors. METHODS: We included patients with suspected and/or confirmed PAS at our institution over 8 years. Sonography performed by maternal-fetal medicine specialists, and selected patients underwent MRI. Imaging was considered positive if either sonography or MRI suggested PAS. Histopathology was the gold standard for diagnosis of PAS. We assessed the pretest and negative imaging-test probability, and resources required. RESULTS: We identified 82 high-risk patients with the following: (1) a history of ≥1 cesarean section and/or intrauterine gynecologic procedure and placenta previa in the index pregnancy; (2) a history of >3 cesarean deliveries and/or gynecologic procedures regardless of placental location; (3) prior PAS disorder, or retained placenta requiring manual extraction and/or curettage, complicated by postpartum hemorrhage; and (4) suspected cesarean section scar pregnancy. Histopathology confirmed PAS in 52 patients, with pretest probability of 63%. Imaging correctly identified 44/50 cases with PAS, and excluded this condition in 24/30 cases. Thus, the positive and negative post-test probability for PAS following negative imaging was 88 and 20%, respectively. Of the six patients with false-negative imaging, all had either surgical complications or required care beyond that for routine cesarean section. CONCLUSIONS: Although diagnostic imaging is sensitive, the negative posttest probability remains high in women with high pretest probability for PAS. Therefore, women at high risk for PAS should be managed in experienced centers by a multidisciplinary team even if imaging is negative.

Improved management of placenta accreta spectrum disorders: experience from a single institution.

OBJECTIVES: To assess the applicability of a standardized multidisciplinary protocol for managing placenta accreta spectrum (PAS) disorders and its impact on the outcomes. METHODS: We compared patients with PAS manage by a standardized multidisciplinary protocol (T2) to historic controls managed on a case-by-case basis by individual physicians between (T1). The primary outcome is composite maternal morbidity. Secondary outcomes were the rates of surgical complications, estimated blood loss, number of blood products transfused, intensive care unit admissions, ventilator use, and birth weight. Multivariate logistic analysis was used to identify independent predictors of composite maternal morbidity. RESULTS: During T1 and T2, we managed 39 and 36 patients with confirmed PAS, respectively. During T2, the protocol could be implemented in 21 cases (58%). Compared to T1, patients managed during T2 had 70% less composite maternal morbidity (95% CI: 0.11-0.82) and lower blood loss (median, 2,000 vs. 1,100 mL, p=0.008). Also, they were 68% less likely to require transfusion of blood products (95% CI: 0.12-0.81; p=0.01), including fewer units of packed red blood cells (median, 2 vs. 0, p=0.02). Management following the protocol was the only independent factor associated with lower composite maternal morbidity (OR: 0.22; 95% CI: 0.05-0.95; p=0.04). Selected maternal and neonatal outcomes were not different among 12 and 15 patients with suspected but unconfirmed PAS disorders managed during T1 and T2, respectively. CONCLUSIONS: Most patients can be managed under a standardized multidisciplinary protocol for PAS disorders, leading to improved outcomes.

Fetal sex discordance between noninvasive prenatal screening results and sonography: A single institution's experience and review of the literature.

BACKGROUND: With the increasing availability of noninvasive prenatal screening (NIPS) and high-resolution ultrasound, more cases of sex discordance are being identified in routine clinical practice. This can be a source of much concern for families and clinicians. Knowledge about the limitations of NIPS and reasons for discordant results are critical for counseling parents. AIMS: Here, we present three cases from a single tertiary care referral center. We also review the literature to address potential limitations of NIPS in correctly identifying fetal sex chromosomes. MATERIALS AND METHODS: After Institutional Review Board approval, cases of discordant fetal sex were identified using ICD-9 and ICD-10 codes. In addition, departmental counseling database and cytogenetics laboratory logbooks were reviewed. RESULTS: In our first case, a 37-year-old G4 P2012 underwent NIPS at 11 weeks gestation and Monosomy X (associated with Turner syndrome) was identified. Morphological sonographic assessment at 20 weeks gestation was consistent with a female fetus following an amniocentesis at 16 weeks that revealed normal 46, XX karyotype. During the third trimester, the patient was diagnosed with Stage IV invasive ductal carcinoma of the breast. Postnatal follow-up of the neonate was consistent with a phenotypic female. In the second case, a 22-year-old G2 P1001 obese female underwent NIPS at 14 weeks gestation and normal 46, XY karyotype was identified. Morphological sonographic assessment at 20 weeks was not consistent with a male fetus. The patient declined invasive testing. Postnatally, the karyotype was 46, XX and the neonate was phenotypically female. The reason for the discordant results was not identified. In the third case, a 25-year-old G1 P0 obese female underwent NIPS at 13 weeks gestation and normal 46, XY karyotype was identified. Morphological sonographic assessment at 20 weeks was indeterminate; however, follow-up at 24 weeks was consistent with a female fetus. The patient declined invasive prenatal testing. Postnatally, the karyotype was 46, XX, and the neonate was phenotypically female with uterus present on ultrasound. The reason for the discordant results was not identified. DISCUSSION: Our cases demonstrate possible limitations of NIPS in correctly identifying sex chromosomes. CONCLUSIONS: Providers and patients need to be aware of these limitations, and invasive diagnostic prenatal testing should be offered in cases of discordance between NIPS and sonographic sex assessment.

Evidence for Use of Tenofovir in Pregnancy to Prevent Perinatal Transmission of Hepatitis B Infection.

Perinatal transmission of hepatitis B virus continues to be a serious global public health concern. Transmission failures are related to high maternal viremia. Several antiviral therapies reduce maternal viremia around the time of delivery and decrease maternal-to-child-transmission. This chapter is a review of current studies that, ultimately, have provided strong evidence for the efficacy and safety of 3 antiviral drugs in pregnancy-lamivudine, telbivudine and tenofovir. The latter drug is the particular focus of this chapter which will show that tenofovir is the preferred antiviral therapy in pregnant women because of its potency, safety profile, and low risk of resistance.