Continuous glucose monitoring in pregnancies with type 1 diabetes: small increases in time-in-range improve maternal and perinatal outcomes.

BACKGROUND: Continuous glucose monitors provide detailed information regarding glycemic control in pregnant patients with type 1 diabetes. Little data have been published examining the association between continuous glucose monitor parameters and perinatal outcomes among gravidas with type 1 diabetes using continuous glucose monitors. OBJECTIVE: This study aimed to examine the association between perinatal outcomes and time-in-range as assessed by continuous glucose monitors used in pregnant individuals with type 1 diabetes. We hypothesized that higher time-in-range would be associated with lower risk of adverse perinatal outcomes. STUDY DESIGN: This multicenter retrospective cohort study included all gravidas with type 1 diabetes using continuous glucose monitors who delivered from 2020 to 2022 at 5 University of California sites. Only those with continuous glucose monitor target range set to 70 to 140 mg/dL (±10 mg/dL) were included. Time-in-range (%) was recorded at 12, 16, 20, 24, 28, and 32 weeks. The primary maternal and neonatal outcomes were preeclampsia and large for gestational age, defined as birthweight ≥95th percentile. Kruskal-Wallis tests were used to compare median time-in-range between those with and without the primary outcomes. Log-binomial regression was used to obtain risk ratios, with adjustment for microvascular disease and years with type 1 diabetes. RESULTS: A total of 91 patients were included. Most used an insulin pump (81%) and did not have diabetic microvascular disease (72%). Median time since diagnosis of type 1 diabetes was 16 years, and median periconception hemoglobin A1c was 6.7%. Compared with those with preeclampsia, normotensive gravidas had significantly higher time-in-range at nearly every time point. A similar pattern was observed for those with normal-birthweight infants compared with large-for-gestational-age infants. On adjusted analyses, every 5-unit increase in time-in-range at 12 weeks was associated with 45% and 46% reductions in the risks of preeclampsia and large for gestational age, respectively (preeclampsia: adjusted risk ratio, 0.55; 95% confidence interval, 0.30-0.99; large for gestational age: adjusted risk ratio, 0.54; 95% confidence interval, 0.29-0.99). CONCLUSION: Higher time-in-range is associated with lower risk of preeclampsia and large for gestational age. This association is observed early in gestation, when each 5-unit increase in time-in-range is associated with ∼50% reduction in the risk of these complications. These findings can be used to counsel patients regarding the risk of pregnancy complications at specific time-in-range values, and to encourage patients that even small improvements in time-in-range can have significant impact on pregnancy outcomes. Larger studies are needed to further explore these findings and to identify optimal time-in-range to reduce perinatal complication rates.

Chronic villitis as a distinctive feature of placental injury in maternal SARS-CoV-2 infection.

BACKGROUND: SARS-CoV-2 infection during pregnancy is associated with an increased risk for stillbirth, preeclampsia, and preterm birth. However, this does not seem to be caused by intrauterine fetal infection because vertical transmission is rarely reported. There is a paucity of data regarding the associated placental SARS-CoV-2 histopathology and their relationship with the timing and severity of infection. OBJECTIVE: This study aimed to determine if maternal SARS-CoV-2 infection was associated with specific patterns of placental injury and if these findings differed by gestational age at time of infection or disease severity. STUDY DESIGN: A retrospective cohort study was performed at the University of California San Diego between March 2020 and February 2021. Placentas from pregnancies with a positive SARS-CoV-2 test were matched with 2 sets of controls; 1 set was time-matched by delivery date and sent to pathology for routine clinical indications, and the other was chosen from a cohort of placentas previously collected for research purposes without clinical indications for pathologic examination before the SARS-CoV-2 outbreak. Placental pathologic lesions were defined based on standard criteria and included maternal and fetal vascular malperfusion and acute and chronic inflammatory lesions. A bivariate analysis was performed using the independent Student t test and Pearson chi-square test. A logistic regression was used to control for relevant covariates. Regions of SARS-CoV-2-associated villitis were further investigated using protein-based digital spatial profiling assays on the GeoMx platform, validated by immunohistochemistry, and compared with cases of infectious villitis and villitis of unknown etiology. Differential expression analysis was performed to identify protein expression differences between these groups of villitis. RESULTS: We included 272 SARS-CoV-2 positive cases, 272 time-matched controls, and 272 historic controls. The mean age of SARS-CoV-2 affected subjects was 30.1±5.5 years and the majority were Hispanic (53.7%) and parous (65.7%). SARS-CoV-2 placentas demonstrated a higher frequency of the 4 major patterns of placental injury (all P<.001) than the historic controls. SARS-CoV-2 placentas also showed a higher frequency of chronic villitis and severe chronic villitis (P=.03 for both) than the time-matched controls, which remained significant after controlling for gestational age at delivery (adjusted odds ratio, 1.52; 95% confidence interval, 1.01-2.28; adjusted odds ratio, 2.12; 95% confidence interval, 1.16-3.88, respectively). Digital spatial profiling revealed that programmed death-ligand 1 was increased in villitis-positive regions of the SARS-CoV-2 (logFC, 0.47; adjusted P value =.002) and villitis of unknown etiology (logFC, 0.58; adjusted P value =.003) cases, but it was conversely decreased in villitis-positive regions of the infectious villitis group (log FC, -1.40; adjusted P value <.001). CONCLUSION: Chronic villitis seems to be the most specific histopathologic finding associated with SARS-CoV-2 maternal infection. Chronic villitis involves damage to the vasculosyncytial membrane of the chorionic villi, which are involved in gas and nutrient exchange, suggesting potential mechanisms of placental (and perhaps neonatal) injury, even in the absence of vertical transmission. Surprisingly, changes in protein expression in SARS-CoV-2-associated villitis seem to be more similar to villitis of unknown etiology than to infectious villitis.

Routine screening for gestational diabetes: a review.

PURPOSE OF REVIEW: Rates of gestational diabetes mellitus (GDM) throughout the world continue to increase associated with the increasing rates of obesity. Given this epidemiologic burden, the importance of proper screening, diagnosis, and management cannot be understated. This review focuses on the current screening guidelines utilized throughout the world and new data recently published regarding the most optimal screening techniques and future directions for research. RECENT FINDINGS: Despite unanimous opinion that GDM warrants screening, the optimal screening regimen remains controversial. Notably, in the United States per the consensus recommendation by the American College of Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine, a 2-step screening approach is often used. Recently, there have been multiple studies published that have compared the 1-step and 2-step screening process with respect to GDM incidence and perinatal outcomes. These new findings are summarized below. SUMMARY: Utilization of the 1-step screening as opposed to the 2-step screening results in an increased diagnosis of GDM without significant population level benefit in outcomes. However, these studies remain underpowered to allow for meaningful comparison of outcomes in those diagnosed with GDM.

Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.

Chronic hypertension and risk of preterm delivery: National Longitudinal Study of Adolescents to Adult Health.

BACKGROUND: Chronic hypertension during pregnancy is associated with increased risk of adverse birth outcomes. In 2017, the American College of Cardiology and American Heart Association (ACC/AHA) lowered thresholds to classify hypertension in non-pregnant adults to SBP ≥ 130 mmHg and DBP ≥ 80 mmHg (ie stage I hypertension), resulting in an additional 4.5-million reproductive-aged women meeting criteria for hypertension. Little is known about effects of pre-pregnancy blood pressure (BP) in this range. OBJECTIVES: To examine the effect of pre-pregnancy maternal BP on preterm delivery. METHODS: We analysed the data from two waves of the National Longitudinal Study of Adolescent to Adult Health, including participants that had measured BP at Wave IV (2008-09) and a pregnancy that resulted in a singleton live birth between Waves IV and V (2016-18; n = 2038). We categorised BP using ACC/AHA cut-offs: normal (SBP < 120 mmHg and DBP < 80 mmHg), elevated (SBP 120-129 mmHg and DBP < 80 mmHg), hypertension stage I (SBP 130-139 mmHg or DBP 80-89 mmHg) and hypertension stage II (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg). We estimated risk ratios (RR) with log-binomial regression adjusting for maternal demographics, anthropometrics and medication use. RESULTS: The prevalence of preterm delivery was 12.6%. A standard deviation (SD) increment in SBP (SD = 12.2 mmHg) and DBP (SD = 9.3 mmHg) was associated with a 14% (95% confidence interval [CI] 2, 27) and 20% (95% CI 4, 37) higher risk of preterm delivery. Compared to normotensive controls, stage I (RR 1.33, 95% CI 1.01, 1.74) and stage II (RR 1.34, 95% CI 0.89, 2.00) hypertension were associated with increased risk. CONCLUSIONS: We observed greater risk of preterm delivery among women with higher pre-pregnancy BP. Women with stage I hypertension during pregnancy may benefit from increased BP monitoring. Additional studies on the utility of foetal surveillance in this group are warranted.

Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization: the PASTIME protocol.

BACKGROUND: Multidisciplinary care of placenta accreta spectrum cases improves pregnancy outcomes, but the specific components of such a multidisciplinary collaboration varies between institutions. As experience with placenta accreta spectrum increases, it is crucial to assess new surgical techniques and protocols to help improve maternal outcomes and to advocate for hospital resources. OBJECTIVE: This study aimed to assess a novel multidisciplinary protocol for the treatment of placenta accreta spectrum that comprises cesarean delivery, multivessel uterine embolization, and hysterectomy in a single procedure within a hybrid operative suite. STUDY DESIGN: This was a matched prepost study of placenta accreta spectrum cases managed before (2010-2017) and after implementation of the Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol (2018-2021) at a tertiary medical center. Historical cases were managed with internal iliac artery balloon placement in selected cases with the decision to inflate the balloons intraoperatively at the discretion of the primary surgeon. Intraoperative Embolization cases were compared with historical cases in a 1:2 ratio matched on the basis of placenta accreta spectrum severity and surgical urgency. The primary outcome was a requirement for transfusion with packed red blood cells. Secondary outcomes included estimated surgical blood loss, operative and postoperative complications, procedural time, length of stay, and neonatal outcomes. RESULTS: A total of 15 Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization cases and 30 matched historical cases were included in the analysis. There were no demographic differences noted between the groups. A median (interquartile range) of 0 units (0-2 units) of packed red blood cells were transfused in the Intraoperative Embolization group compared with 2 units (0-4.5 units) in the historical group (P=.045); 5 of 15 (33.3%) Intraoperative Embolization cases required blood transfusions compared with 19 of 30 (63.3%) cases in the historical group (P=.11). The estimated blood loss was significantly less in the Intraoperative Embolization group with a median (interquartile range) of 750 mL (450-1050 mL) compared with 1750 mL (1050-2500 mL) in the historical group (P=.003). There were no cases requiring massive transfusion (≥10 red blood cell units in 24 hours) in the Intraoperative Embolization group compared with 5 of 30 (16.7%) cases in the historical group (P=.15). There were no intraoperative deaths from hemorrhagic shock using the Intraoperative Embolization protocol, whereas this occurred in 2 of the historical cases. The mean duration of the interventional radiology procedure was longer in the Intraoperative Embolization group (67.8 vs 34.1 minutes; P=.002). Intensive care unit admission and postpartum length of stay were similar, and surgical and postoperative complications were not significantly different between the groups. The gestational age and neonatal birthweights were similar; however, the neonatal length of stay was longer in the Intraoperative Embolization group (median duration, 32 days vs 15 days; P=.02) with a trend toward low Apgar scores. Incidence of arterial umbilical cord blood pH <7.2 and respiratory distress syndrome and intubation rates were not statistically different between the groups. CONCLUSION: A multidisciplinary pathway including a single-surgery protocol with multivessel uterine embolization is associated with a decrease in blood transfusion requirements and estimated blood loss with no increase in operative complications. The Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol provides a definitive surgical method that warrants consideration by other centers specializing in placenta accreta spectrum treatment.

Ultrasound and Magnetic Resonance Imaging of Agenesis of the Corpus Callosum in Fetuses: Frontal Horns and Cavum Septi Pellucidi Are Clues to Earlier Diagnosis.

OBJECTIVES: We hypothesized that: (1) fetal frontal horn (FH) morphology and their proximity to the cavum septi pellucidi (CSP) can assist in suspecting complete agenesis of the corpus callosum (cACC) and partial agenesis of the corpus callosum (pACC) earlier than known indirect ultrasound (US) findings; (2) FHs assist in differentiating a true CSP from a pseudocavum; and (3) magnetic resonance imaging (MRI) is useful in learning FH morphology and pseudocavum etiology. METHODS: Thirty-two patients with cACC and 9 with pACC were identified on an Institutional Review Board-approved retrospective review. Of the 41 cases, 40 had prenatal US, and 21 had prenatal MRI; 17 had follow-up neonatal US, and 14 had follow-up neonatal MRI. Variables evaluated retrospectively were the presence of a CSP or a pseudocavum, ventricle size and shape, and FH shape (comma, trident, parallel, golf club, enlarged, or fused). Displacement between the inferior edge of the FH and the midline or cavum/pseudocavum was measured. RESULTS: Fetal FHs had an abnormal shape in 77% ≤20 weeks' gestation, 86% ≤24 weeks, and 90% >24 weeks. Frontal horns were laterally displaced greater than 2 mm in 85% ≤20 weeks, 91% ≤24 weeks, and 95% >24 weeks. The CSP was absent in 100% of cACC cases and 78% of pACC cases, and a pseudocavum was present in 88% of cACC cases and 78% of pACC cases across gestation. Magnetic resonance imaging confirmed US pseudocavums to be focal interhemispheric fluid or an elevated/dilated third ventricle. CONCLUSIONS: Frontal horns assist in assessing ACC ≤24 weeks and throughout gestation. Pseudocavums, often simulating CSPs, are common in ACC. Frontal horn lateral displacement and abnormal morphology, recognized by MRI correlations, are helpful in differentiating a pseudocavum from a true CSP. A normal CSP should not be cleared on screening US unless normally shaped FHs are seen directly adjacent to it.

Obstetrical Unit Response to the COVID-19 Pandemic: OUR Study.

OBJECTIVE: This study aimed to describe the response of labor and delivery (L&D) units in the United States to the novel coronavirus disease 2019 (COVID-19) pandemic and determine how institutional characteristics and regional disease prevalence affect viral testing and personal protective equipment (PPE). STUDY DESIGN: A cross-sectional survey was distributed electronically through the Society for Maternal-Fetal Medicine e-mail database (n = 584 distinct practices) and social media between April 14 and 23, 2020. Participants were recruited through "snowballing." A single representative was asked to respond on behalf of each L&D unit. Data were analyzed using Chi-square and Fisher's exact tests. Multivariable regression was performed to explore characteristics associated with universal testing and PPE usage. RESULTS: A total of 301 surveys (estimated 51.5% response rate) was analyzed representing 48 states and two territories. Obstetrical units included academic (31%), community teaching (45%) and nonteaching hospitals (24%). Sixteen percent of respondents were from states with high prevalence, defined as higher "deaths per million" rates compared with the national average. Universal laboratory testing for admissions was reported for 40% (119/297) of units. After adjusting for covariates, universal testing was more common in academic institutions (adjusted odds ratio [aOR] = 1.73, 95% confidence interval [CI]: 1.23-2.42) and high prevalence states (aOR = 2.68, 95% CI: 1.37-5.28). When delivering asymptomatic patients, full PPE (including N95 mask) was recommended for vaginal deliveries in 33% and for cesarean delivery in 38% of responding institutions. N95 mask use during asymptomatic vaginal deliveries remained more likely in high prevalence states (aOR = 2.56, 95% CI: 1.29-5.09) and less likely in hospitals with universal testing (aOR = 0.42, 95% CI: 0.24-0.73). CONCLUSION: Universal laboratory testing for COVID-19 is more common at academic institutions and in states with high disease prevalence. Centers with universal testing were less likely to recommend N95 masks for asymptomatic vaginal deliveries, suggesting that viral testing can play a role in guiding efficient PPE use. KEY POINTS: · Heterogeneity is seen in institutional recommendations for viral testing and PPE.. · Universal laboratory testing for COVID-19 is more common at academic centers.. · N95 mask use during vaginal deliveries is less likely in places with universal testing..

Prophylactic Internal Iliac Artery Occlusion Balloon Placement to Reduce Operative Blood Loss in Patients with Invasive Placenta.

PURPOSE: To evaluate efficacy and safety of prophylactic internal iliac occlusion balloon placement before cesarean hysterectomy for invasive placenta. MATERIAL AND METHODS: A retrospective analysis was performed of patients with invasive placenta treated with and without occlusion balloon placement. Preoperative occlusion balloons were placed in 90 patients; 61 patients were treated without balloon placement (control group). Baseline demographics, including patient age, gestational age at delivery, gravidity, parity, and number of previous cesarean sections, were not significantly different (P > .05). Of the balloon placement group, 56% had placenta percreta compared with 25% in the control group (P < .001), and 83% had placenta previa compared with 66% in the control group (P = .012). RESULTS: Median blood loss was 2 L (range, 1.5-2.5 L) in the balloon placement group versus 2.5 L (range, 2-4 L) in the control group (P = .002). Patients with occlusion balloons were transfused a median of 2 U (range, 0-5 U) of packed red blood cells versus 5 U (range, 2-8 U) in patients in the control group (P = .002). In the balloon placement group, 34% had large volume blood loss > 2,500 mL versus 61% in the control group (P = .001), and 21% required blood transfusion > 6 U versus 44% in the control group (P = .002). Eight complications (9%) were attributed to occlusion balloon placement. CONCLUSIONS: Prophylactic internal iliac artery occlusion balloon placement reduces operative blood loss and transfusion requirements in patients undergoing hysterectomy for invasive placenta.

Changes in Postpartum Insulin Requirements for Patients with Well-Controlled Type 1 Diabetes.

Objective To compare postpartum with preconception insulin doses in well-controlled (HbA1c ≤ 7.4%) type 1 diabetes mellitus (T1DM) and to characterize differences in postpartum insulin dosing based on infant feeding. Study Design The primary outcome in this retrospective cohort was the change in total daily insulin (TDI) from preconception to postpartum. Insulin administration (continuous subcutaneous insulin infusion [CSII] vs. multiple daily injections [MDI]), HbA1c, body mass index (BMI), and infant feeding were abstracted. Results We identified 44 women with T1DM and HbA1c ≤ 7.4%. Preconception mean BMI was 24.6 ± 3.6 kg/m(2) and median (interquartile range [IQR]) HbA1c was 6.4 (6.0-6.9)%. Of these, 73% used CSII and 27% used MDI. Additionally, 80% of patients reported exclusive breastfeeding, 7% were exclusively formula feeding, and 13% used both breast milk and formula. Median (IQR) preconception TDI was 0.64 (0.49-0.69) U/kg/day, and postpartum: 0.39 (0.30-0.50) U/kg/day. Postpartum TDI was 34% lower than preconception TDI (p = 0.02). There was no difference in the postpartum TDI in patients who were breast versus formula feeding or when comparing CSII with MDI. Conclusion There was a significant decrease in the TDI required postpartum when compared with preconception. Dosages do not seem to be impacted by administration route or breastfeeding. These findings warrant consideration when dosing postpartum insulin in patients with T1DM.

Maternal and fetal capillary malformation-arteriovenous malformation (CM-AVM) due to a novel RASA1 mutation presenting with prenatal non-immune hydrops fetalis.

RASA1 mutations have been shown to cause capillary malformation-arteriovenous malformation (CM-AVM). We describe a patient with CM-AVM and a fetus who presented with non-immune hydrops fetalis during the pregnancy. Sequencing revealed a novel RASA1 mutation in the RASGAP domain that results in a loss of function of p120-RasGap. This report expands our current genetic and clinical understanding of CM-AVM in pregnancy.

Continuous Subcutaneous Insulin Infusion versus Multiple Daily Injections of Insulin for the Management of Type 1 Diabetes Mellitus in Pregnancy: Association with Neonatal Chemical Hypoglycemia.

OBJECTIVE: We hypothesized that patients with type 1 diabetes mellitus (T1DM) who were managed during their pregnancy with a continuous subcutaneous insulin infusion (CSII) would have a lower incidence of neonatal hypoglycemia (NH) than patients managed with multiple daily injections (MDI) of insulin. STUDY DESIGN: This was a retrospective cohort of 95 women with T1DM who delivered singleton, term neonates between 2007 and 2014. The primary outcome was incidence of NH (capillary plasma glucose ≤ 45 mg/dL) in the first 24 hours after birth. RESULTS: The incidence of NH was 66.0% (62/95). The NH rate was significantly higher in women managed with CSII versus MDI (62 vs. 38%, p = 0.024). Neonates with NH had a higher birth weight (3,867 ± 658 vs. 3,414 ± 619 g, p = 0.002). When analyzing intrapartum glucose management, mothers of neonates with NH had significantly less time managed on an insulin infusion (median interquartile range 7 [3.5-30.5] vs. 17.5 [2.0-17.5] hours, p = 0.014). In multivariable analysis, only maternal body mass index (BMI) (p = 0.035) and time on an insulin infusion (p = 0.043) were significantly associated with NH. CONCLUSION: In our population of patients with T1DM, CSII was more prevalent in the NH group; however, when controlling for other factors, intrapartum glucose management and early maternal BMI were the only variables associated with NH.

Diabetic Ketoacidosis and Adverse Outcomes Among Pregnant Individuals With Pregestational Diabetes in the United States, 2010-2020.

OBJECTIVE: To assess the frequency of, risk factors for, and adverse outcomes associated with diabetic ketoacidosis (DKA) at delivery hospitalization among individuals with pregestational diabetes (type 1 and 2 diabetes mellitus) and secondarily to evaluate the frequency of and risk factors for antepartum and postpartum hospitalizations for DKA. METHODS: We conducted a serial, cross-sectional study using the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Readmissions Database from 2010 to 2020 of pregnant individuals with pregestational diabetes hospitalized for delivery. The exposures were 1) sociodemographic and clinical risk factors for DKA and 2) DKA. The outcomes were DKA at delivery hospitalization, maternal morbidity (nontransfusion severe maternal morbidity (SMM), critical care procedures, cardiac complications, acute renal failure, and transfusion), and adverse pregnancy outcomes (preterm birth, hypertensive disorders of pregnancy, and cesarean delivery) and secondarily DKA at antepartum and postpartum hospitalizations. RESULTS: Of 392,796 deliveries in individuals with pregestational diabetes (27.2% type 1 diabetes, 72.8% type 2 diabetes), there were 4,778 cases of DKA at delivery hospitalization (89.1% type 1 diabetes, 10.9% type 2 diabetes). The frequency of DKA at delivery hospitalization was 1.2% (4.0% with type 1 diabetes, 0.2% with type 2 diabetes), and the mean annual percentage change was 10.8% (95% CI, 8.2-13.2%). Diabetic ketoacidosis at delivery hospitalization was significantly more likely among those who had type 1 diabetes compared with those with type 2 diabetes, who were younger in age, who delivered at larger and metropolitan hospitals, and who had Medicaid insurance, lower income, multiple gestations, and prior psychiatric illness. Diabetic ketoacidosis during the delivery hospitalization was associated with an increased risk of nontransfusion SMM (20.8% vs 2.4%, adjusted odds ratio [aOR] 8.18, 95% CI, 7.20-9.29), critical care procedures (7.3% vs 0.4%, aOR 15.83, 95% CI, 12.59-19.90), cardiac complications (7.8% vs 0.8%, aOR 8.87, 95% CI, 7.32-10.76), acute renal failure (12.3% vs 0.7%, aOR 9.78, 95% CI, 8.16-11.72), and transfusion (6.2% vs 2.2%, aOR 2.27, 95% CI, 1.87-2.75), as well as preterm birth (31.9% vs 13.5%, aOR 2.41, 95% CI, 2.17-2.69) and hypertensive disorders of pregnancy (37.4% vs 28.1%, aOR 1.11, 95% CI, 1.00-1.23). In secondary analyses, the overall frequency of antepartum DKA was 3.1%, and the mean annual percentage change was 4.1% (95% CI, 0.3-8.6%); the overall frequency of postpartum DKA was 0.4%, and the mean annual percentage change was 3.5% (95% CI, -1.6% to 9.6%). Of 3,092 antepartum hospitalizations among individuals with DKA, 15.7% (n=485) had a recurrent case of DKA at delivery hospitalization. Of 1,419 postpartum hospitalizations among individuals with DKA, 20.0% (n=285) previously had DKA at delivery hospitalization. The above risk factors for DKA at delivery hospitalization were similar for DKA at antepartum and postpartum hospitalizations. CONCLUSION: The frequency of DKA at delivery hospitalization and antepartum hospitalizations for DKA increased between 2010 and 2020 among deliveries in individuals with pregestational diabetes in the United States. Diabetic ketoacidosis is associated with an increased risk of maternal morbidity and adverse pregnancy outcomes. Risk factors for DKA at delivery were similar to those for DKA during the antepartum and postpartum periods.

Association Between Metformin Use in Early Gestational or Type 2 Diabetes in Pregnancy and Preterm Preeclampsia.

OBJECTIVE: To estimate the association between maternal metformin use for the treatment of early gestational or pre-existing type 2 diabetes and preterm preeclampsia. METHODS: This is a planned secondary analysis of the MOMPOD study (Medical Optimization of Management of Overt Type 2 Diabetes in Pregnancy), a randomized trial comparing the effect of adding metformin with insulin treatment on composite neonatal outcome in singleton pregnancies with early gestational or type 2 diabetes. Participants were randomized at 11-23 weeks of gestation to 1,000 mg metformin twice daily or placebo until delivery. A subset of participants had maternal blood collected at 24-30 weeks of gestation, and serum soluble endoglin, apolipoprotein B, vascular cell adhesion molecule-1, soluble fms-like tyrosine kinase 1, placental growth factor, high-sensitivity C-reactive protein, adiponectin, and vascular endothelial growth factor levels were measured. Our primary outcome was preterm preeclampsia , defined as preeclampsia requiring delivery before 37 weeks of gestation. Secondary outcomes included preterm preeclampsia requiring delivery before 34 weeks of gestation and differences in serum biomarkers. Multivariable regression analysis was used to estimate the associations between metformin use and primary or secondary study outcomes. RESULTS: Of 831 participants, 119 (14.3%) developed preeclampsia requiring delivery before 37 weeks of gestation: 57 of 416 (13.7%) in the placebo group and 62 of 415 (14.9%) in the metformin group. Thirty-seven (4.4%) developed preeclampsia requiring delivery before 34 weeks of gestation: 15 (3.6%) receiving placebo and 22 (5.3%) receiving metformin. Compared with placebo, metformin was not associated with a significant difference in the occurrence of preeclampsia before 37 weeks of gestation (adjusted odds ratio [aOR] 1.04, 95% CI, 0.70-1.56) or before 34 weeks (aOR 1.43, 95% CI, 0.73-2.81). Similarly, there was no association between maternal metformin use and serum biomarker levels. CONCLUSION: Among parturients with early gestational or pre-existing type 2 diabetes, the addition of metformin to insulin was not associated with lower odds of preterm preeclampsia or with serum biomarkers associated with cardiovascular disease risk.

Dicavitary twin pregnancy in patient with bicornuate bicollis uterine anomaly.

Key Clinical Message: Twin pregnancies in uterine didelphys and uterus bicornuate bicollis represent dicavitary twin pregnancies that can be managed using similar principles. Consideration must be given to delivery planning including mode of delivery and uterine incision. Abstract: Dicavitary twin pregnancies present unique challenges for obstetric management. This case demonstrates an approach to management of a bicornuate bicollis twin pregnancy and provides a contemporary review of the literature on dicavitary twin pregnancies.

Associations Between Preconception Glycemia and Preterm Birth: The Potential Role of Health Care Access and Utilization.

Background: Preconception diabetes is strongly associated with adverse birth outcomes. Less is known about the effects of elevated glycemia at levels below clinical cutoffs for diabetes. In this study, we estimated associations between preconception diabetes, prediabetes, and hemoglobin A1c (HbA1c) on the risk of preterm birth, and evaluated whether associations were modified by access to or utilization of health care services. Materials and Methods: We used data from Add Health, a US prospective cohort study with five study waves to date. At Wave IV (ages 24-32), glucose and HbA1c were measured. At Wave V (ages 32-42), women with a live birth reported whether the baby was born preterm. The analytic sample size was 1989. Results: The prevalence of preterm birth was 13%. Before pregnancy, 6.9% of women had diabetes, 23.7% had prediabetes, and 69.4% were normoglycemic. Compared to the normoglycemic group, women with diabetes had 2.1 (confidence interval [95% CI]: 1.5-2.9) times the risk of preterm birth, while women with prediabetes had 1.3 (95% CI: 1.0, 1.7) times the risk of preterm birth. There was a nonlinear relationship between HbA1c and preterm birth such that risk of preterm birth emerged after HbA1c = 5.7%, a standard cutoff for prediabetes. The excess risks of preterm birth associated with elevated HbA1c were four to five times larger among women who reported unstable health care coverage and among women who used the emergency room as usual source of care. Conclusion: Our findings replicate prior research showing strong associations between preconception diabetes and preterm birth, adding that prediabetes is also associated with higher risk. Policies and interventions to enhance access and utilization of health care among women before pregnancy should be examined.

Discovery and verification of extracellular microRNA biomarkers for diagnostic and prognostic assessment of preeclampsia at triage.

We report on the identification of extracellular miRNA (ex-miRNA) biomarkers for early diagnosis and prognosis of preeclampsia (PE). Small RNA sequencing of maternal serum prospectively collected from participants undergoing evaluation for suspected PE revealed distinct patterns of ex-miRNA expression among different categories of hypertensive disorders in pregnancy. Applying an iterative machine learning method identified three bivariate miRNA biomarkers (miR-522-3p/miR-4732-5p, miR-516a-5p/miR-144-3p, and miR-27b-3p/let-7b-5p) that, when applied serially, distinguished between PE cases of different severity and differentiated cases from controls with a sensitivity of 93%, specificity of 79%, positive predictive value (PPV) of 55%, and negative predictive value (NPV) of 89%. In a small independent validation cohort, these ex-miRNA biomarkers had a sensitivity of 91% and specificity of 57%. Combining these ex-miRNA biomarkers with the established sFlt1:PlGF protein biomarker ratio performed better than either set of biomarkers alone (sensitivity of 89.4%, specificity of 91.3%, PPV of 95.5%, and NPV of 80.8%).

Management of diabetes in pregnancy.

The link between diabetes and poor pregnancy outcomes is well established. As in the non-pregnant population, pregnant women with diabetes can experience profound effects on multiple maternal organ systems. In the fetus, morbidities arising from exposure to diabetes in utero include not only increased congenital anomalies, fetal overgrowth, and stillbirth, but metabolic abnormalities that appear to carry on into early life, adolescence, and beyond. This article emphasizes the newest guidelines for diabetes screening in pregnancy while reviewing their potential impact on maternal and neonatal complications that arise in the setting of hyperglycemia in pregnancy.

Insulin pump dosing across gestation in women with well-controlled type 1 diabetes mellitus.

OBJECTIVE: We hypothesized that bolus and basal insulin doses in women with type 1 diabetes mellitus who use insulin pumps would increase 2-fold to maintain hemoglobin A1c <6.5% across gestation. STUDY DESIGN: This was a retrospective study of 9 women with type 1 diabetes mellitus with preconceptional hemoglobin A1c ≤ 7.4% using insulin pumps. The primary outcome was absolute and percentage change of basal and bolus insulin from preconception to delivery. RESULTS: Total daily dose of insulin increased from 33.3 ± 7.8 U/d before conception to 93.5 ± 27.9 U/d at delivery. Basal rates rose modestly (50% increase, from 16.2 ± 6.5 U/d to 24.0 ± 9 U/d); bolus insulin doses quadrupled from 17.1 ± 6.1 U/d to 69.5 ± 29.6 U/d (P = .0001). Bolus insulin increased from approximately 50% of total daily dose of insulin before conception to 75% of total daily dose of insulin at 36 weeks' gestation. CONCLUSION: In well-controlled type 1 diabetes mellitus, insulin requirements increased 3-fold from before conception to 36 weeks' gestation. Most of this requirement was attributed to an increase in bolus rates that are required for control with meals.