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Item 786 Neonatal outcomes in pregnant women with diagnosis of COVID-19(Elsevier, 2021) Izewski, Joanna; Boudova, Sarah; Rouse, Caroline E.; Ibrahim, Sherrine A.; Shanks, Anthony L.; Reinhardt, Jeff C.; Scifres, Christina; Haas, David M.; Peipert, Jeffrey F.; Tuuli, Methodius G.; Obstetrics and Gynecology, School of MedicineObjective It is unclear whether infection with COVID-19 during pregnancy increases the risk of adverse neonatal outcomes. We tested the hypothesis that a diagnosis of COVID-19 during pregnancy increases the risk of neonatal respiratory morbidity and other adverse neonatal outcomes. Study Design: Retrospective analysis of prospectively collected data from two labor and delivery units with universal COVID-19 testing policy between March 1 and May 31, 2020. Pregnant women with singleton pregnancies who delivered during the study period and underwent testing for COVID-19 at any point in their pregnancy were eligible. The primary outcome was a composite of neonatal respiratory morbidity defined as the occurrence of any one of the following: respiratory distress syndrome, transient tachypnea of the newborn, and need for respiratory support. The risk of neonatal morbidity with and without a COVID-19 diagnosis were compared using univariable and multivariable analyses. Stratified analysis compared the risks of adverse neonatal outcomes in symptomatic and asymptomatic patients with COVID-19 to those without COVID-19. Results: Of 515 subjects meeting inclusion criteria, 55 (10.7%) tested positive for COVID-19; 19 (34.6%) were asymptomatic and 36 (65.4%) were symptomatic. No neonate tested positive for COVID-19. Rates of the primary outcome, composite neonatal respiratory morbidity, were not significantly different in patients with and without COVID-19 (21.8% vs 19.6%, P=0.692). There was no significant difference in the risk of neonatal respiratory morbidity in a Cox regression model accounting for time from diagnosis to delivery, and adjusting for gestational age at delivery, mode of delivery, and maternal diabetes (adjusted hazard ratio: 0.62; 95% CI 0.35, 1.09). There were no significant differences in any of the secondary outcomes in patients with COVID-19 who were asymptomatic or symptomatic (Table). Conclusion: A diagnosis of COVID-19 during pregnancy does not appear to increase the risk of neonatal morbidity. These data may be useful in counseling women diagnosed with COVID-19 during pregnancy.Item 975 ABO blood group, rhesus type and risk of COVID-19 in pregnant women(Elsevier, 2021) Ibrahim, Sherrine A.; Boudova, Sarah; Rouse, Caroline E.; Shanks, Anthony L.; Reinhardt, Jeffrey; Scifres, Christina; Haas, David M.; Peipert, Jeffrey F.; Tuuli, Methodius G.; Obstetrics and Gynecology, School of MedicineObjective: There is controversy regarding the association of ABO blood group, Rhesus (Rh) type and risk of COVID-19. We tested the hypothesis that ABO blood group and Rh type are associated with COVID-19 diagnosis and symptoms during pregnancy. Study Design: Retrospective analysis of prospectively collected data from two labor and delivery units with universal SARS-CoV-2 testing policy between March 1 and May 31, 2020. All pregnant women tested during the study period were eligible. The primary outcome was COVID-19 diagnosis. Secondary outcomes were measures of COVID-19 severity, including symptoms, ICU admission, respiratory support and treatment for COVID-19. Outcomes were compared across ABO blood groups. Women with blood group O or Rh positive blood type were compared with non-O groups and Rh negative, respectively, using univariable and multivariable analyses. Results: Of 586 pregnant women tested, 66 (11.3%) were positive. The most common ABO blood group in the cohort was O (52.2%) and 87.4% were Rh positive. Rates of the primary outcome, COVID-19 diagnosis, were not significantly different across ABO blood groups (P=0.47). There were also no significant differences in measures of COVID-19 severity among blood groups (Table). Compared to other blood groups, the risk of COVID-19 diagnosis was not significantly different in women with group O (13.1% vs 9.3%, adjusted OR 1.43; 95% CI 0.84, 2.4). Rh positive women were at a significantly higher risk of COVID-19 diagnosis (12.3% vs 4.1%, adjusted OR 3.38; 95% CI 1.03, 11.07) and a non-significant increased risk of symptoms (6.8% vs 2.7%, adjusted OR 2.67; 95% CI 0.63, 11.32), after adjusting for ABO blood group (Figure). Conclusion: We found no association between ABO blood group and diagnosis or severity of COVID-19 in pregnant women. However, Rhesus positive women may be at a higher risk of COVID-19.Item A BRCA1+ Patient with Twin Pregnancy of a Complete Mole with Complete Fetus(American Medical Women's Association, 2023-03-23) Yaqub, Amna; Taminack, Hope; Ungureanu, Ilinca; Ganapaneni, Sruthi; Tian, Wendy; Scifres, Christina; Robertson, SharonTitle: A BRCA1+ Patient with Twin Pregnancy of a Complete Mole with Complete Fetus Authors: Yaqub, A., Tominack, H., Ungureanu, I., Ganapaneni, S., Tian, W. MD, Scifres, C. MD, & Robertson, S. MD Background: A complete molar pregnancy is a non-viable pregnancy that results from the implantation of a diploid fertilized egg containing no maternal DNA. Twin pregnancy of a complete mole with complete fetus (CMCF) is a very rare occurrence with an incidence of 1/22,000 to 1/100,000 pregnancies. Continuing a CMCF pregnancy can result in many risks to the health of the mother and fetus. Case: A 35-year-old G3P2 female presented to an obstetric scan at 20 weeks gestation, which was suspicious for both a viable fetus and a molar pregnancy. She had no significant medical history other than being BRCA1+, with two previous uncomplicated pregnancies. Her initial ultrasound at 10 weeks gestation was indeterminate on whether this was a partial mole vs CMCF. The patient was offered the option to terminate the pregnancy due to risk of complications but chose to proceed with the pregnancy. Because she was BRCA1+ with a strong family history of breast and ovarian cancer, she had a planned Cesarean-hysterectomy with bilateral oophorectomy at 34 weeks. Mother and infant were discharged on postoperative day 2, and the pathology report of the placenta confirmed the removal of a complete mole. Serial β-hcg levels were followed after delivery. Clinical Significance: Due to the high risk of complications, pregnancy termination is typically offered to patients in this situation. Patients who choose to continue the pregnancy should be thoroughly informed of potential complications. Risks associated with continuing a CMCF pregnancy include preeclampsia, vaginal bleeding, intrauterine death of the fetus, and the development of gestational trophoblastic disease. This patient was also complicated by being BRCA1+, which impacted surgical planning. Conclusion: CMCF pregnancy is a rare occurrence with many associated risks. In BRCA1+ patients who choose to continue a CMCF pregnancy, extensive counseling is necessary with consideration for risk-reducing surgical management at time of delivery.Item Adequacy of glycemic control in early pregnancy with Type 2 diabetes and perinatal outcomes(2023-02-09) Izewski, Joanna; Tang, Rachel; Crites, Kundai; Campbell, Meredith; Pelton, Sarah; Saiko-Blair, Morgan; Scifres, ChristinaObjective In non-pregnant individuals with type 2 DM (T2DM), an HbA1c target < 7% is recommended. We sought to assess if an HbA1c < 7% in early pregnancy is associated with a lower risk for adverse pregnancy outcomes. Study Design We conducted a retrospective cohort study of individuals with T2DM and a singleton gestation who delivered at 2 health systems between 2018-2020. Demographics, markers of health care utilization, and perinatal outcomes were abstracted from the medical record. Race and ethnicity were self-reported. The primary exposure was levels of glycemic control at less than 20 weeks’ gestation using recommended HbA1c targets in non-pregnant individuals (HbA1c < 7% vs. HbA1c ≥7%). Patients without documentation of HbA1c prior to 20 weeks were excluded. Perinatal outcomes were abstracted from the medical record, and logistic regression was used to adjust for covariates. Results Of the individuals who had a documented HbA1c < 20 weeks of gestation, 128/281 (46%) had a HbA1c < 7%, and 153/281 (54%) had a HbA1c ≥7%. Patients with HbA1c < 7% were more likely to be of White race and have private insurance. They also had the first HbA1c measured earlier in pregnancy, a lower mean HbA1c across gestation, less overall weight gain, and were less likely to require insulin at the time of delivery. There were no significant differences in other demographics or markers of healthcare utilization (Table 1). Outcomes are shown in Table 2. After adjusting for covariates, those with a HbA1c ≥7% were more likely to have a preterm birth < 37 weeks (aOR 2.3, 95% CI 1.3-4.0), cesarean delivery (aOR 1.9, 95% CI 1.1-3.3), and a neonate requiring NICU admission (aOR 2.9, 95% CI 1.7-4.9). Conclusion Adverse perinatal outcomes are common among individuals with T2DM even when early pregnancy HbA1c values are within recommended targets for non-pregnant individuals. Those who present with a HbA1c ≥7% are at even higher risk for several outcomes. We observed important disparities in HbA1c values in early pregnancy that likely represent barriers in accessing medical care prior to pregnancy.Item Assessing Disparities in Care Utilization and Outcomes Among Pregnant Women with T2D Based on Race and Ethnicity(2022-07-29) Pelton, Sarah; Izewski, Joanna; Scifres, ChristinaBackground/Objective: Disparities faced by individuals with type 2 diabetes (T2D) or gestational diabetes mellitus have been identified. However, because less is known about disparities faced by pregnant women with T2D and since the prevalence of T2D is increasing, we sought to investigate this issue. Methods: We performed a retrospective cohort study that included 369 women with singleton gestation and T2D that delivered from 2018-2020. Using maternal self-reported race and ethnicity abstracted from the electronic medical record, we categorized the women as Non-Hispanic White, Non-Hispanic Black, or Hispanic. Demographics, health care utilization, and maternal and neonatal outcomes were also abstracted. One way ANOVA and chi-squared tests were utilized to compare outcomes among the groups, and logistic regression was used to control for co-variates. Results: Non-Hispanic White and Non-Hispanic Black women had a higher BMI at their first prenatal visit and were more likely to be nulliparous. They were also more likely to have a prior caesarean delivery and chronic hypertension. Non-Hispanic Black women were more likely to have ≥12 prenatal visits compared to Non-Hispanic White and Hispanic women (70 vs. 43 vs. 45%, p<0.001), and non-Hispanic Black women had the lowest early pregnancy HbA1c (7.0±1.6 vs. 7.9±2.1 vs. 7.5±1.7%, p<0.001). Additionally, caesarean delivery rates were lowest for Hispanic women compared to Non-Hispanic White and Non-Hispanic Black women (45 vs. 63 vs. 71%, p<0.001); this difference persisted after controlling for co-variates (aOR 0.53, 95% CI 0.30-0.92). Conversely, there were no differences in birth weight category, preterm birth <37 weeks, hypertensive disorders of pregnancy, or NICU admission. Conclusion and Potential Impact: Pregnancies complicated by T2D have an increased risk of poor maternal and neonatal outcomes. For some outcomes, there is a significant difference among Non-Hispanic White, Non-Hispanic Black, and Hispanic women. Future studies are therefore needed to investigate causative factors and potential interventions. Presentation recording available online: https://purl.dlib.indiana.edu/iudl/media/h04d673g6hItem Body Mass Index, Adverse Pregnancy Outcomes, and Cardiovascular Disease Risk(American Heart Association, 2023) Khan, Sadiya S.; Petito, Lucia C.; Huang, Xiaoning; Harrington, Katharine; McNeil, Rebecca B.; Bello, Natalie A.; Bairey Merz, C. N.; Miller, Eliza C.; Ravi, Rupa; Scifres, Christina; Catov, Janet; Pemberton, Victoria; Varagic, Jasmina; Zee, Phyllis C.; Yee, Lynn M.; Ray, Mitali; Kim, Jin Kyung; Lane-Cordova, Abbi; Lewey, Jennifer; Theilen, Lauren H.; Saade, George R.; Greenland, Philip; Grobman, William A.; Obstetrics and Gynecology, School of MedicineBackground: Obesity is a well-established risk factor for both adverse pregnancy outcomes (APOs) and cardiovascular disease (CVD). However, it is not known whether APOs are mediators or markers of the obesity-CVD relationship. This study examined the association between body mass index, APOs, and postpartum CVD risk factors. Methods: The sample included adults from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be) Heart Health Study who were enrolled in their first trimester (6 weeks-13 weeks 6 days gestation) from 8 United States sites. Participants had a follow-up visit at 3.7 years postpartum. APOs, which included hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes, were centrally adjudicated. Mediation analyses estimated the association between early pregnancy body mass index and postpartum CVD risk factors (hypertension, hyperlipidemia, and diabetes) and the proportion mediated by each APO adjusted for demographics and baseline health behaviors, psychosocial stressors, and CVD risk factor levels. Results: Among 4216 participants enrolled, mean±SD maternal age was 27±6 years. Early pregnancy prevalence of overweight was 25%, and obesity was 22%. Hypertensive disorders of pregnancy occurred in 15%, preterm birth in 8%, small-for-gestational-age birth in 11%, and gestational diabetes in 4%. Early pregnancy obesity, compared with normal body mass index, was associated with significantly higher incidence of postpartum hypertension (adjusted odds ratio, 1.14 [95% CI, 1.10-1.18]), hyperlipidemia (1.11 [95% CI, 1.08-1.14]), and diabetes (1.03 [95% CI, 1.01-1.04]) even after adjustment for baseline CVD risk factor levels. APOs were associated with higher incidence of postpartum hypertension (1.97 [95% CI, 1.61-2.40]) and hyperlipidemia (1.31 [95% CI, 1.03-1.67]). Hypertensive disorders of pregnancy mediated a small proportion of the association between obesity and incident hypertension (13% [11%-15%]) and did not mediate associations with incident hyperlipidemia or diabetes. There was no significant mediation by preterm birth or small-for-gestational-age birth. Conclusions: There was heterogeneity across APO subtypes in their association with postpartum CVD risk factors and mediation of the association between early pregnancy obesity and postpartum CVD risk factors. However, only a small or nonsignificant proportion of the association between obesity and CVD risk factors was mediated by any of the APOs, suggesting APOs are a marker of prepregnancy CVD risk and not a predominant cause of postpartum CVD risk.Item Maternal weight gain among individuals with Type 2 diabetes and associated perinatal outcomes(2023-02-10) Izewski, Joanna; Crites, Kundai; Tang, Rachel; Saiko-Blair, Morgan; Campbell, Meredith; Pelton, Sarah; Scifres, ChristinaObjective The prevalence of type 2 Diabetes Mellitus (T2DM) in pregnancy is increasing, and adverse perinatal outcomes are common. We sought to assess whether higher or lower weight gain is associated with adverse perinatal outcomes in T2DM. Study Design This was a retrospective cohort study of patients with T2DM and a singleton gestation who delivered at 2 health systems between 2018-2020. Demographics, markers of health care utilization, and various perinatal outcomes were abstracted from the medical record. Race and ethnicity were self-reported. Our primary exposure was weight gain < 5 kilograms(kg) across gestation compared to those who gained ≥5kg. We excluded patients for whom weight gain could not be calculated. We assessed multiple perinatal outcomes, and we used multinomial logistic regression to adjust for covariates. Results We included 341 individuals with T2DM. There were 216/341 (63%) in the ≥5kg group, and 125/341 (37%) in the < 5kg group. The < 5kg group was more likely to be of Black race. The ≥5kg group initiated prenatal care earlier in gestation, were more likely to have ≥12 total prenatal visits, and be on insulin at the time of delivery. There were no significant differences in other demographics or markers of healthcare utilization (Table 1). Perinatal outcomes are shown in Table 2. Those with < 5kg of weight gain were less likely to develop a hypertensive disorder of pregnancy (aOR 0.3, 95% CI 0.2-0.5), or undergo a cesarean delivery (aOR 0.6, 95% CI 0.4-0.9). Stillbirth was more common among those who gained < 5kg (7 vs. 2%, p=0.02). There was a statistical difference in neonatal birthweight category (AGA vs. SGA vs. LGA) (p=0.04) between the 2 groups that did not persist after adjusting for covariates. Conclusion Weight gain is associated with adverse perinatal outcomes among individuals with T2DM. While weight gain < 5kg is associated with a reduced risk for certain outcomes, the increased risk for stillbirth deserves further study.Item Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial(American Medical Association, 2023) Boggess, Kim A.; Valint, Arielle; Refuerzo, Jerrie S.; Zork, Noelia; Battarbee, Ashley N.; Eichelberger, Kacey; Ramos, Gladys A.; Olson, Gayle; Durnwald, Celeste; Landon, Mark B.; Aagaard, Kjersti M.; Wallace, Kedra; Scifres, Christina; Rosen, Todd; Mulla, Wadia; Valent, Amy; Longo, Sherri; Young, Laura; Marquis, M. Alison; Thomas, Sonia; Britt, Ashley; Berry, Diane; Obstetrics and Gynecology, School of MedicineImportance: 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.Item Treatment of Gestational Diabetes Mellitus and Offspring Early Childhood Growth(Endocrine Society, 2021-04) Feghali, Maisa; Atlass, Jacqueline; Abebe, Kaleab Z.; Comer, Diane; Catov, Janet; Caritis, Steve; Arslanian, Silva; Scifres, Christina; Obstetrics and Gynecology, School of MedicineBackground: Gestational diabetes mellitus (GDM) is associated with fetal overgrowth, and certain treatments are associated with an increased risk of macrosomia. However, there are limited data about the long-term effect of GDM treatment on childhood growth. Methods: Cohort study of 816 women with GDM and their offspring delivered between 2009 and 2012. Childhood height and weight through age 3 were collected from the medical record and z-scores and body mass index (BMI) were calculated. We assessed the association between GDM treatment and childhood growth using linear mixed modeling. Results: Treatment was divided into medical nutritional therapy (MNT) (n = 293), glyburide (n = 421), and insulin (n = 102). At delivery, birthweight, z-score, and BMI were higher in the offspring of women treated with either glyburide or insulin compared to MNT. However, weight, z-score, and BMI were similar among all offspring at 6 months and 1, 2, and 3 years of age. After controlling for covariates, there were differences in the weight z-score (P = 0.01) over the 3-year period by treatment group, but no differences in weight (P = 0.06) or change in BMI (P = 0.28). Pairwise comparisons indicated that insulin was associated with more weight gain compared with MNT (0.69 kg; 95% CI, 0.10-1.28; P = 0.02) and glyburide was associated with a trend toward lower weight z-score compared with MNT (-0.24; 95% CI, -0.47 to 0.003; P = 0.05). Conclusion: Despite growth differences detected at birth, we observed no meaningful differences in childhood growth from 6 months to 3 years among treatment groups, including in the offspring of women with GDM treated with glyburide.