Hyperparathyroidism in Pregnancy: A Review of the Literature.

IMPORTANCE: Maternal hyperparathyroidism can be associated with significant maternal and fetal morbidity and fetal mortality. Because the maternal symptoms are typically nonspecific, the disorder may not be recognized leading to adverse pregnancy outcomes. OBJECTIVE: The aim of this study was to review the literature on the etiology/prevalence, pathophysiology, diagnosis, management (medical and surgical), and the maternal/neonatal complications associated with pregnancies complicated by hyperparathyroidism. EVIDENCE ACQUISITION: A literature search was undertaken by our university librarian using the search engines PubMed and Web of Science. Search terms used included "hyperparathyroidism" AND "pregnancy" OR "pregnancy complications" OR "maternal." The number of years searched was not limited, but the abstracts had to be in English. RESULTS: There were 309 abstracts identified, 164 of which are the basis of this review. This includes 137 articles of the 269 individual case reports in the literature since the first case report in 1947. The articles and case reports reviewed the etiology, risk factors, diagnosis, management, complications, and maternal/fetal outcomes of pregnancies complicated by hyperparathyroidism. CONCLUSIONS AND RELEVANCE: Undiagnosed maternal hyperparathyroidism can result in critical maternal and fetal outcomes during pregnancy. This review highlights what is currently known about hyperparathyroidism during pregnancy to increase the awareness of this serious pregnancy disorder.

Placental changes in diabetic pregnancies and the contribution of hypertension.

OBJECTIVE: To evaluate placental abnormalities in pregnancies affected by diabetes compared to unaffected pregnancies from a single academic center. METHODS: This is a retrospective cohort study of women with singleton gestations delivered at the University of Arkansas for Medical Sciences from 2007 to 2016. Pathologic examination of placentas from pregestational and gestational diabetic pregnancies were compared to placentas from patients without diabetes using 12 histologic elements. Maternal and neonatal outcomes were extracted from the medical record and compared between groups. Findings were adjusted for hypertensive disorders of pregnancy. Placental lesions were also correlated with diabetic control. RESULTS: Pathology reports of 590 placentas along with corresponding medical records were reviewed. The diabetic group (N = 484) consisted of 188 patients with pregestational diabetes and 296 patients with gestational diabetes. The nondiabetic group consisted of 106 patients. The diabetic group was older, had a higher average BMI, and more hypertensive disorders (p < .0001). Out of the 12 histologic elements investigated, accelerated villous maturation (aOR = 8.45, 95%CI (1.13-62.95)) and increased placental weight (aOR = 3.131, 95% CI (1.558-6.293)) were noted to be significantly increased in placentas from diabetic pregnancies after controlling for hypertension. Intervillous thrombi were not significantly increased in pregnancies affected by diabetes. Neonates of the diabetic group were more likely to be large for gestational age (p < .0001) and had a higher rate of preterm delivery (p < .0001). CONCLUSIONS: Accelerated villous maturation was found to be more frequent in pregnancies complicated by pregestational diabetes, even after controlling for hypertension. In pregnancies complicated by gestational diabetes, the placental findings were not significant after controlling for hypertension. In contrast with prior studies, there was no increase in thrombotic lesions of the placenta in patients with diabetes.

Fetal intracranial hemorrhage associated with maternal coagulopathy and vitamin K deficiency after biliary drain placement: A case report and literature review.

INTRODUCTION: Fetal intracranial hemorrhage (ICH) is a rare but serious prenatal diagnosis. Predisposing factors include maternal trauma and fetal coagulation dysfunction. Maternal vitamin K deficiency has been described as an etiology. We present a case of maternal vitamin K deficiency associated with fetal ICH after percutaneous biliary drain (PBD) placement in a complicated cholecystectomy with injury to the common bile duct. CASE PRESENTATION: A 21-year-old woman, G2P1, presented at 23 weeks and 3 days of gestation with epigastric pain, nausea and vomiting. Right upper quadrant ultrasound diagnosed cholelithiasis. The patient was managed conservatively and discharged. She returned four days later, at 24 weeks of gestation, with worsening symptoms and ultrasound showing acute cholecystitis. She underwent laparoscopic cholecystectomy. Increasing bilirubin and imaging showed a transected biliary duct that required percutaneous biliary drain (PBD) placement. The patient was discharged and followed up at a high-risk obstetric clinic. Prenatal ultrasound showed bilateral ventriculomegaly with features of ICH. Maternal vitamin K deficiency was confirmed with PIVKA-II testing. The patient received vitamin K supplementation with normalization of the coagulopathy. Delivery occurred at 36 weeks of gestation via cesarean delivery after preterm premature rupture of membranes for fetal macrocrania. The neonate was discharged to a hospice. DISCUSSION: Maternal and neonatal etiologies for ICH include malabsorption and coagulopathy. Maternal vitamin K deficiency should be considered when coagulopathy is present. This case highlights that maternal vitamin K deficiency due to biliary diversion and malabsorption increases the risk of fetal ICH, which impacts pregnancy and neonatal outcomes.

Knowledge, Attitudes, Beliefs, and Treatment Burden Related to the Use of Levothyroxine in Hypothyroid Pregnant Women in the United States.

Background: The use of prescribed medications during pregnancy is a challenge and an underestimated source of treatment burden. Levothyroxine (LT4) for the treatment of overt and subclinical hypothyroidism is extensively prescribed during pregnancy. To this end, we aimed to explore the patients' perceived benefits and risks, knowledge, beliefs, attitudes, and related burden of LT4 therapy during pregnancy. Methods: In this cross-sectional study, we surveyed pregnant women who were treated with LT4 during pregnancy from January 1, 2019, to December 31, 2019, in a tertiary academic medical center of the United States. The anonymous online survey included questions to gather demographic data and multiple-choice questions regarding the benefits and risks, knowledge, beliefs, attitudes, and burden related to LT4 use during pregnancy. Results: Sixty-four pregnant women (mean age 31.5 years) completed the study survey (response rate: 96%): 62% were diagnosed with hypothyroidism more than 12 months before pregnancy, 16% less than or about 12 months before pregnancy, and 22% during pregnancy. We found that one-third of pregnant women using LT4 had a feeling of uneasiness/anxiety due to their hypothyroidism diagnosis. About half of the respondents (45%) reported that they did not receive an explanation by their clinician regarding the maternal/fetal risks of uncontrolled hypothyroidism or the benefits of adequate control. Finally, two in three patients expressed various concerns of LT4-related treatment burden. Conclusions: Our findings support the need for increased effective communication and tailored counseling to address fears, anxiety, and uncertainties about the benefits and risks of LT4 use in pregnancy. For patients with clear benefits from LT4 treatment in pregnancy, it could help to overcome their concerns, promote adherence, and decrease adverse maternal/fetal outcomes. For patients with no clear benefits established, clinicians need to be aware of LT4-related treatment burden in pregnancy and implement patient-centered approaches in their clinical practices.

Parental adiposity differentially associates with newborn body composition.

BACKGROUND: Maternal obesity increases offspring's obesity risk. However, studies have not often considered maternal metabolic and exercise patterns as well as paternal adiposity as potential covariates. OBJECTIVE: To assess the relationship between parental and newborn adiposity. METHODS: Participants were mother-child pairs (n = 209) and mother-father-offspring triads (n = 136). Parental (during gestation) and offspring (2 weeks old) percent fat mass (FM) were obtained using air displacement plethysmography. Maternal race, age, resting energy expenditure (indirect calorimetry), physical activity (accelerometry), gestational weight gain (GWG), gestational age (GA), delivery mode, infant's sex and infant feeding method were incorporated in multiple linear regression analyses. The association between parental FM and offspring insulin-like growth factor 1 (IGF-1) was assessed at age 2 years. RESULTS: Maternal adiposity was positively-associated with male (ß = 0.11, P = .015) and female (ß = 0.13, P = .008) infant FM, whereas paternal adiposity was negatively-associated with male newborn adiposity (ß = -0.09, P = .014). Breastfeeding, female sex, GA and GWG positively associated with newborn adiposity. Vaginal and C-section delivery methods associated with greater adiposity than vaginal induced delivery method. Plasma IGF-1 of 2-year-old boys and girls positively associated with their respective fathers' and mothers' FM. CONCLUSIONS: Maternal and paternal adiposity differentially associate with newborn adiposity. The mechanisms of this finding remain to be determined.

The Third Stage of Labour in the Extremely Obese Parturient.

BACKGROUND: Maternal obesity has been associated with an increased risk for an abnormal progression of labour; however, less is known about the length of the third stage of labour and its relation to maternal obesity. OBJECTIVE: To determine if the length of the third stage of labour is increased in extremely obese women and its possible correlation with an increased risk for postpartum hemorrhage. STUDY DESIGN: This was a retrospective cohort study of deliveries from January 2008 to December 2015 at our university hospital. Women with a BMI ≥40 and a vaginal delivery were compared with the next vaginal delivery of a woman with a BMI <30. There were 147 women with a BMI ≥40 compared with 157 with a BMI <30. Outcomes evaluated the length of the third stage of labour and the risk for postpartum hemorrhage and included antepartum, intrapartum, and perinatal complications. RESULTS: Subjects in the extreme obese group were more likely to be African American, older, diabetic (pregestational and gestational), hypertensive, pre-eclamptic, had a preterm delivery, and underwent an induction of labour. The overall length of the third stage of labour was significantly longer in the extreme obese group, 5 minutes (3, 8 [25th and 75th percentiles]) compared with 4 minutes (3,7) (P = 0.0374) in the non-obese group. Postpartum hemorrhage occurred more often in the extreme obese group (N = 16/147; 11%) compared with the non-obese group (N = 5/157; 3%) (P = 0.01). There were no differences between groups in respect to the following: gravidity, parity, length of the second stage of labour, birth weight, GA at delivery, Apgar score, cord blood gases, hematocrit change, need for postpartum transfusion, operative delivery, and development of chorioamnionitis. After an adjustment for ethnicity, maternal age, diabetes, preeclampsia, preterm labour, hypertension, and induction/augmentation, the analysis failed to show a significant difference in estimated blood loss and postpartum hemorrhage between the groups. CONCLUSIONS: The length of the third stage of labour is longer in the extreme obese parturient. Postpartum hemorrhage also occurs more often, but after adjustments for confounding variables, it is no longer significant.

Discrepancy in Insulin Regulation between Gestational Diabetes Mellitus (GDM) Platelets and Placenta.

Earlier findings have identified the requirement of insulin signaling on maturation and the translocation of serotonin (5-HT) transporter, SERT to the plasma membrane of the trophoblast in placenta. Because of the defect on insulin receptor (IR) in the trophoblast of the gestational diabetes mellitus (GDM)-associated placenta, SERT is found entrapped in the cytoplasm of the GDM-trophoblast. SERT is encoded by the same gene expressed in trophoblast and platelets. Additionally, alteration in plasma 5-HT levels and the 5-HT uptake rates are associated with the aggregation rates of platelets. Therefore, here, we investigated a novel hypothesis that GDM-associated defects in platelet IR should change their 5-HT uptake rates, and this should be a leading factor for thrombosis in GDM maternal blood. The maternal blood and the placentas were obtained at the time of cesarean section from the GDM and non-diabetic subjects (n = 6 for each group), and the platelets and trophoblasts were isolated to determine the IR activity, surface level of SERT, and their 5-HT uptake rates.Interestingly, no significant differences were evident in IR tyrosine phosphorylation or the downstream elements, AKT and S6K in platelets and their aggregation rates in both groups. Furthermore, insulin stimulation up-regulated 5-HT uptake rates of GDM-platelets as it does in the control group. However, the phosphorylation of IR and the downstream elements were significantly lower in GDM-trophoblast and showed no response to the insulin stimulation while they showed 4-fold increase to insulin stimulation in control group. Similarly, the 5-HT uptake rates of GDM-trophoblast and the SERT expression on their surface were severalfold lower compared with control subjects. IR is expressed in all tissues, but it is not known if diabetes affects IR in all tissues equally. Here, for the first time, our findings with clinical samples show that in GDM-associated defect on IR is tissue type-dependent. While IR is impaired in GDM-placenta, it is unaffected in GDM-platelet.

Legionella Infection in Pregnancy: The Forgotten Pathogen in Septic Shock.

BACKGROUND: Of eight cases of Legionella infection in pregnancy reported over 35 years, there was one case of maternal septic shock with poor outcome, one recovery with good outcome, and six with poor outcome. CASE: A 30-year-old woman, gravida 2 para 1, at 28 weeks of gestation presented with a high fever, cough, nausea, and vomiting. She deteriorated despite treatment for presumed urosepsis, was transferred to the intensive care unit, and remained intubated for 10 days receiving cardiovascular support, antivirals, antifungals, and multiple wide-spectrum antibiotics. Legionella infection antigen testing was performed on hospital day 1 and returned as positive. Azithromycin, started before the testing results became available, was continued for 14 days. The patient recovered, and the pregnancy progressed uneventfully to term. CONCLUSION: Legionella infection should be considered with maternal deterioration despite broad-spectrum antibiotic coverage. A favorable outcome is possible with early diagnosis and treatment.

Correlation of ultrasound estimated with dye-determined or directly measured amniotic fluid volume revisited.

BACKGROUND/AIMS: To examine the relationship of the amniotic fluid index (AFI) and single deepest pocket (SDP) with an AFV as modelled by Brace or Magann. METHODS: AFI and SDP were evaluated for their correlation with an actual AFV using the Spearman correlation coefficient. RESULTS: 482 AFI and 468 SDP pregnancies were evaluated. There was a significant association between the AFI and SDP and an actual AFV (p < 0.0001). The AFI range of 5.1-20 was better correlated than 5.1-24 for normal AFVs Brace (κ = 0.175) and Magann (κ = 0.356) versus 5.1-24 (κ = 0.150 and κ = 0.319), respectively. The agreement level t for the AFI (κ = 0.175) and SDP (κ = 0.126) using Brace was slight and for the AFI (κ = 0.356) and SDP (κ = 0.295) using Magann was fair. CONCLUSIONS: Both the AFI and SDP were correlated with actual AFV using both models. AFI of 5.1-20 better categorizes normal volumes. Although the Magann model correlates AFI/SDP and AFV better, the superiority is minimal.

Antenatal management of at-risk pregnancies from a distance.

This study was undertaken to determine whether antenatal care can be achieved in women with at-risk pregnancies residing in rural areas with limited access to antenatal care and maternal fetal medicine (MFM) specialists. Over a period of 15 months, 156 women with high-risk pregnancies (diabetes, hypertensive disorders, suspected fetal anomalies, prior caesarean complications) from six different healthcare units had 350 visits managed by telemedicine.

GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake.

Serotonin (5-HT) transporter (SERT) regulates the level of 5-HT in placenta. Initially, we found that in gestational diabetes mellitus (GDM), whereas free plasma 5-HT levels were elevated, the 5-HT uptake rates of trophoblast were significantly down-regulated, due to impairment in the translocation of SERT molecules to the cell surface. We sought to determine the factors mediating the down-regulation of SERT in GDM trophoblast. We previously reported that an endoplasmic reticulum chaperone, ERp44, binds to Cys200 and Cys209 residues of SERT to build a disulfide bond. Following this posttranslational modification, before trafficking to the plasma membrane, SERT must be dissociated from ERp44; and this process is facilitated by insulin signaling and reversed by the insulin receptor blocker AGL2263. However, the GDM-associated defect in insulin signaling hampers the dissociation of ERp44 from SERT. Furthermore, whereas ERp44 constitutively occupies Cys200/Cys209 residues, one of the SERT glycosylation sites, Asp208 located between the two Cys residues, cannot undergo proper glycosylation, which plays an important role in the uptake efficiency of SERT. Herein, we show that the decrease in 5-HT uptake rates of GDM trophoblast is the consequence of defective insulin signaling, which entraps SERT with ERp44 and impairs its glycosylation. In this regard, restoring the normal expression of SERT on the trophoblast surface may represent a novel approach to alleviating some GDM-associated complications.

Complications of shoulder dystocia.

Complications of shoulder dystocia are divided into fetal and maternal. Fetal brachial plexus injury (BPI) is the most common fetal complication occurring in 4-40% of cases. BPI has also been reported in abdominal deliveries and in deliveries not complicated by shoulder dystocia. Fractures of the fetal humerus and clavicle occur in about 10.6% of cases of shoulder dystocia and usually heal with no sequel. Hypoxic ischemic brain injury is reported in 0.5-23% of cases of shoulder dystocia. The risk correlates with the duration of head-to-body delivery and is especially increased when the duration is >5 min. Fetal death is rare and is reported in 0.4% of cases. Maternal complications of shoulder dystocia include post-partum hemorrhage, vaginal lacerations, anal tears, and uterine rupture. The psychological stress impact of shoulder dystocia is under-recognized and deserves counseling prior to home discharge.

Antiemetic medications in pregnancy: a prospective investigation of obstetric and neurobehavioral outcomes.

OBJECTIVE: The study goal was to examine the impact of commonly prescribed antiemetic medications in pregnancy on neurobehavioral and obstetric outcomes. STUDY DESIGN: Five hundred thirty-three women accounting for 550 live births (17 multiple gestations) enrolled before 16 weeks' gestation participating in an observational longitudinal study of stress and pharmacologic exposure in pregnancy at Emory Women's Mental Health Program were included in this study. Maternal report of exposure to medications was documented by weeks of use. Obstetric and neonatal data were obtained from medical records. The Neonatal Behavioral Assessment Scale was completed by certified raters at age 7 days. The Child Behavior Checklist (CBCL) was completed by the mother between 17 and 66 months of age. Comparison of groups was conducted using χ(2) and Wilcoxon rank-sum tests. Spearman correlation analysis was used for CBCL percentile scores to evaluate duration of exposure. RESULTS: The exposed group (n = 143) was comprised of children whose mothers received promethazine or ondansetron during pregnancy. Unexposed children (n = 407) were used for comparison. Neonatal Behavioral Assessment Scale data 7 days (range, 2-77) was available on 345 infants (exposed n = 102; unexposed n = 243), and a total of 247 CBCLs (exposed n = 51; unexposed n = 196) at 29 (range, 17-66) months of age. No significant differences were seen using Neonatal Behavioral Assessment Scale and CBCL. Statistically significant differences were seen in gestational age at delivery (0.3 weeks) and birthweight (110 g). CONCLUSION: No clinically significant adverse neurobehavioral effects or obstetric outcomes were identified. This is reassuring as promethazine and ondansetron are commonly prescribed during pregnancy.

Role of serial MRI assessment in the management of an abdominal pregnancy.

A 33-year-old woman was admitted to the hospital with an abdominal pregnancy at a gestational age of 20 weeks. An initial MRI mapping of fetal location and placental vascular invasion was obtained. The patient refused surgical intervention until fetal survival would be possible. Serial MRIs were essential in timing delivery and avoiding an emergency surgical situation. The baby was delivered at 24 weeks with the assistance of a multidisciplinary surgical team. The mother as well as the baby survived. This case report highlights the role of serial MRI evaluations in the diagnosis and expectant management of an abdominal pregnancy. It also highlights the importance of interdisciplinary communication for a successful outcome.

Depression and diabetes: Establishing the pharmacist's role in detecting comorbidity in pregnant women.

OBJECTIVES: To determine the prevalence of depression in women with diabetes receiving prenatal care and to determine whether pregnant women with comorbid depression and diabetes are receiving adequate care for depression. SETTING: Little Rock, AR, between June and August 2007. PRACTICE DESCRIPTION: At a women's health clinic providing obstetrical services to local and statewide patients, the clinical pharmacist functions as a diabetes educator, provides treatment recommendations for the OB/GYN medical residents, and precepts fourth-year student pharmacists. PRACTICE INNOVATION: The pharmacist and student pharmacists screened patients with diabetes for depression using the Beck Depression Inventory, 2nd ed. (BDI-II). MAIN OUTCOME MEASURES: Patient demographics, including obstetrical history, type of diabetes, depression history, and current treatments. RESULTS: 50 patients were screened in this pilot study. Of participants, 42% reported scores that indicated clinical depression. Among patients with clinical depression, only 19% were receiving treatment for depression. Obstetrical history (number of pregnancies) showed a positive correlation with the BDI-II total scores (P = 0.0078). CONCLUSION: This population had a high prevalence of depressive symptoms, but very few women were receiving treatment for depression. Depression screenings should be integrated into routine prenatal care, offering adequate treatment when needed. This study implies that pharmacists can assist with screening for depression in diabetes and thus ensure that at-risk patients receive the attention needed to better manage their illnesses.

Prolonged morphine exposure in utero causes fetal and placental vasoconstriction: a case report.

Vasoconstriction was observed in the fetal middle cerebral and umbilical arteries by Doppler assessment at 27 weeks gestation in a patient requiring continuous morphine infusion for pain control. Fetal heart tracings were also concerning. Fetal status improved after a change to fentanyl infusion, a shorter acting opioid. Caution is recommended when long-term chronic narcotic infusion is used in pregnancy.

Prenatal diagnosis of congenital cardiac anomalies: a practical approach using two basic views.

Structural cardiac anomalies are estimated to occur in 8 of every 1,000 live births. Cardiovascular anomalies are frequently associated with other congenital anomalies because the heart is among the last organs to develop completely in the embryo. The guidelines for routine prenatal evaluation of both the American College of Radiology and the American Institute of Ultrasound in Medicine require evaluation of the fetal heart. The ultrasonographic (US) view that is most commonly used is the four-chamber view, which allows assessment of abnormalities involving the atria and the ventricles. However, this view is not adequate for demonstrating the outflow tracts of the aorta and pulmonary artery. A base view that demonstrates the crossing of the great vessels can be obtained just superior to the four-chamber view. Addition of the base view to routine US evaluation with the four-chamber view increases not only the sensitivity for detection of cardiac anomalies but also the accuracy of diagnosis.