Neonatal Birth Weight With Daily Compared With Every-Other-Day Glucose Monitoring in Gestational Diabetes Mellitus: A Randomized Controlled Trial.

OBJECTIVE: To assess whether universal use of every-other-day glucose monitoring in patients with gestational diabetes mellitus (GDM) resulted in similar birth weights and medication use and was preferred by the patient compared with traditional daily glucose monitoring. METHODS: This was a noninferiority randomized controlled trial conducted at a single New York City hospital between April 2021 and May 2022. Patients with singleton pregnancies who were diagnosed with GDM after 20 weeks of gestation and had a minimum of 7 days of previous daily blood glucose testing were randomly assigned to test blood glucose values daily or every other day. The primary outcome was neonatal birth weight. We calculated a total sample size of 196 participants needed for noninferiority to be tested, assuming the mean birth weight in the every-other-day group, compared with the daily group, was no higher than the predefined noninferiority margin of 200 g (80% power and one-sided alpha of 0.05). Postrandomization characteristics, including blood glucose values and medication initiation and timing, were recorded. Satisfaction with treatment group was assessed using the validated Oxford Maternity Diabetes Treatment Satisfaction Questionnaire. RESULTS: A total of 197 patients were randomized: 98 in the daily group and 99 in the every-other-day group. Baseline characteristics were similar between groups. The mean neonatal birth weight was similar between groups (mean±SD 3,090±418 g among newborns in the daily group compared with 3,181±482 g among newborns in the every-other-day group). For the primary outcome, the every-other-day group was found to be noninferior to the daily group with an upper confidence limit for the mean difference in mean birth weight of 197 g, which was below the noninferiority margin of 200 g (P=.046). Postrandomization, there were no significant differences in the number of patients who required medication, the gestational age at which medication was started, or the type of medication used. Average fasting and postprandial glucose values were similar between groups. There was an increase in adherence to treatment group in those randomized to every-other-day blood sugars, but no difference in patient satisfaction. CONCLUSION: In patients with GDM, testing blood glucose values every other day was as effective as testing daily, without apparent effects on birth weight, medication initiation, or glucose control. Reduced frequency of blood glucose monitoring might help decrease the emotional, physical, and financial burden experienced by patients with GDM. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04857073.

Barriers to completion of expanded carrier screening in an inner city population.

PURPOSE: The American College of Medical Genetics and Genomics emphasizes a "consistent and equitable approach for offering carrier screening." At our academic center, publicly insured prenatal patients underwent universal expanded carrier screening (ECS) to promote equitable care. The aim of the study was to evaluate rates, time, and barriers to complete ECS. This was defined as post-test counseling and partner testing after a patient was found heterozygous for a pathogenic variant. METHODS: In this descriptive retrospective cohort study from 2018 to 2021, patients were offered ECS, consisting of 283 recessive and X-linked genes. Heterozygotes were contacted by genetic counselors (≤5 attempts) for education and partner testing. Rates of counseling, partner testing, diagnostic procedures, follow-up times, and barriers to completion were assessed. RESULTS: During this time, 643 women underwent ECS. Of these 643 women, 462 were heterozygotes and 326 of 462 had undergone counseling. Two hundred twenty-two of 462 partners obtained testing, with a median of 32 days from patient to partner result. Approximately 21 couples were heterozygous for the same pathogenic variant. One patient pursued diagnostic testing. CONCLUSION: ECS offers useful information; however, this study highlights significant barriers to completion. There was suboptimal patient follow-up and low partner screening, perhaps from insufficient time to educate and counsel. Future directions include implementing quality measures to ensure optimal completion.

Opening Pandora's box: abnormal genetic carrier screening and need for lifetime follow-up.

OBJECTIVE: Expanded carrier screening (ECS) is rising in popularity because of its application in a diverse population, its decreasing cost, and efficiency.1 However, it has traditionally been used to assess fetal risk. The next generation sequencing ECS panel offered at our academic medical center consists of 283 genes associated with hereditary disorders. Of those, 20 (7.1%) are autosomal recessive conditions, notable for variable expression of the clinical phenotype in heterozygous carriers, which may increase maternal risk for malignancy, bleeding, cardiovascular, or rheumatologic disease. Another 21 (7.4%) are X-linked conditions. We aimed to evaluate the prevalence of variants that have a potential for maternal phenotypic expression and whether identification of specific variants prompted patients to pursue further care in our health system, namely comprehensive genetic counseling and further healthcare consults when recommended. STUDY DESIGN: An institutional review board-approved descriptive retrospective cohort study was performed in a New York City academic medical center at which reproductive aged women were offered universal ECS from 2018 to 2021 by their provider, inclusive of obstetrician-gynecologists, maternal-fetal medicine physicians, and genetic counselors. Pretest counseling was performed by the ordering provider. Patients found to carry mutations with the potential for maternal phenotypic expression were contacted by genetic counselors regarding their clinical risks. In addition, patients who were carriers for factor XI deficiency, Bernard Soulier syndrome, ataxia telangectesia, fumarase deficiency, Nijmegen breakage syndrome, Duchenne muscular dystrophy, and familial hypercholesterolemia were advised to seek specialized healthcare pertaining to their clinical risk. The genetic counseling summary was placed in the electronic medical records (EMRs) so that the primary provider could view the findings. Through our EMRs, we evaluated the rates of healthcare uptake among these patients for at least 1 year after delivery. RESULTS: In total, 168 of 1184 (14.2%) patients were identified as carriers of mutations with a potential for maternal phenotypic expression. Of these, 156 (93%) were pregnant and 12 (7%) were preconception. Of those patients, 143 (85%) were carriers of autosomal recessive traits (Figure 1), whereas 22 of 168 (13%) patients were carriers of X-linked conditions (Figure 2) and 3 of 168 (2%) patients carried both autosomal recessive traits and X-linked conditions. Of these carriers, 132 of 168 (78.6%) patients underwent genetic counseling. The most common heterozygous mutations were sickle cell trait (25.6%), thalassemia (alpha and/or beta) trait (14.2%), factor XI deficiency (4.7%), dystrophic epidermolysis bullosa (4.2%), and Alport syndrome (4.1%). Two patients were diagnosed as homozygous carriers of nonclassical congenital adrenal hyperplasia. During the study period, 23 of 168 (13.6%) patients were heterozygous for specific pathogenic variants (inclusive of factor XI, Bernard Soulier syndrome, ataxia telangectesia, fumarase deficiency, Nijmegen breakage syndrome, Duchenne muscular dystrophy, and familial hypercholesterolemia) and were advised to seek specialized healthcare pertaining to these findings. Of these, 20 (87.0%) received genetic counseling with standardized recommendations, however, only 4 of 23 (17%) patients pursued the recommended referrals during our study period. CONCLUSION: This study described the follow-up rates among patients identified as carriers of conditions with the potential for maternal phenotypic expression using ECS. We observed that 14.2% of patients who underwent ECS were identified as carriers of genetic mutations with the potential for maternal phenotypic expression, and of the 23 who were recommended specific care because a pathogenic variant was identified, only 17.4% of patients followed the recommendations. We believe that as ECS implementation becomes widespread, more maternal carriers with clinical risk to themselves will be identified. Therefore, as we open this Pandora's box, the burden of counseling and follow-up must be addressed.

A Case of Markedly Elevated Isolated Alkaline Phosphatase in the Third Trimester of Pregnancy.

Background: Alkaline phosphatase (ALP) is an enzyme produced by the liver, small intestine, bone, and kidneys as well as the placenta during pregnancy. ALP levels may increase up to twice the normal limit during pregnancy secondary to placental release and fetal bone growth. Rare case reports of extremely elevated levels of ALP during pregnancy have demonstrated possible association with adverse pregnancy outcomes. Case: The patient is a 36-year-old G2P1001 who was found to have extremely elevated ALP levels during pregnancy after presenting with bilateral lower leg swelling and rash after receiving the Pfizer COVID-19 vaccine. She subsequently developed intrahepatic cholestasis of pregnancy and preeclampsia. ALP peaked at 2,601 U/L immediately prior to delivery at 36 weeks 1 day. She was followed postpartum, and her ALP levels had nearly normalized by 15 weeks postpartum. Conclusion: Our case demonstrates a rare report of an extremely elevated level of ALP in the setting of multiple adverse pregnancy outcomes, including preterm delivery, preeclampsia without severe features, and intrahepatic cholestasis of pregnancy.

Maternal Parvovirus B19 Infection Causing First-Trimester Increased Nuchal Translucency and Fetal Hydrops.

This is a case report of a 31-year-old primigravida who was diagnosed with an asymptomatic acute parvovirus B19 infection in the second trimester of pregnancy and its suspected association with an increased nuchal translucency (NT) measurement. Parvovirus B19 is a single-stranded DNA virus that is cytotoxic to erythroid progenitor cells, causing inhibition of erythropoiesis. While maternal disease is usually mild, fetal infection can result in spontaneous abortion, aplastic anemia, nonimmune fetal hydrops, and fetal demise. This fetus had an increased NT of 3.2 mm at 11 weeks' gestation with a normal male karyotype and microarray analysis on chorionic villi sampling, in addition to a normal fetal echocardiogram at 15 weeks' gestation. The anatomy scan at 20 weeks' and 1-day gestation revealed fetal ascites, pleural effusion, and increased middle cerebral artery peak systolic velocity suspicious for fetal anemia. At this time, maternal serology for parvovirus was positive for IgM and IgG. Amniocentesis, cordocentesis, and intrauterine transfusion were performed. The amniocentesis revealed elevated parvovirus B19 DNA, quantitative PCR (2,589,801 copies/mL, reference range <100 copies/mL). The patient delivered a viable male fetus at 37 weeks' and 6-day gestation, without sequelae of the previously noted hydrops. Parvovirus B19 infection should be a consideration when evaluating increased NT and hydrops fetalis. It warrants close antepartum surveillance and possible intrauterine fetal transfusions. With prompt recognition, proper treatment, and surveillance, these patients can go on to achieve healthy term deliveries. Long-term outcomes of delivered infants require further study.