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.

Placental Cadmium Levels Are Associated with Increased Preeclampsia Risk.

Environmental exposure to heavy metals is a potentially modifiable risk factor for preeclampsia (PE). Toxicologically, there are known interactions between the toxic metal cadmium (Cd) and essential metals such as selenium (Se) and zinc (Zn), as these metals can protect against the toxicity of Cd. As they relate to preeclampsia, the interaction between Cd and these essential metals is unknown. The aims of the present study were to measure placental levels of Cd, Se, and Zn in a cohort of 172 pregnant women from across the southeast US and to examine associations of metals levels with the odds of PE in a nested case-control design. Logistic regressions were performed to assess odds ratios (OR) for PE with exposure to Cd controlling for confounders, as well as interactive models with Se or Zn. The mean placental Cd level was 3.6 ng/g, ranging from 0.52 to 14.5 ng/g. There was an increased odds ratio for PE in relationship to placental levels of Cd (OR = 1.5; 95% CI: 1.1-2.2). The Cd-associated OR for PE increased when analyzed in relationship to lower placental Se levels (OR = 2.0; 95% CI: 1.1-3.5) and decreased with higher placental Se levels (OR = 0.98; 95% CI: 0.5-1.9). Similarly, under conditions of lower placental Zn, the Cd-associated OR for PE was elevated (OR = 1.8; 95% CI: 0.8-3.9), whereas with higher placental Zn it was reduced (OR = 1.3; 95% CI: 0.8-2.0). Data from this pilot study suggest that essential metals may play an important role in reducing the odds of Cd-associated preeclampsia and that replication in a larger cohort is warranted.

Implementing a prenatal oral health program through interprofessional collaboration.

Interprofessional collaboration has become a critical component of accreditation standards in dentistry and medicine. This article reports on implementation in an academic setting of a prenatal oral health program (pOHP) that addresses coordinated care, accreditation standards, and new clinical practice guidelines. The pOHP is an educational intervention for third-year medical students, residents, and faculty members to deliver preventive oral health information and referral to a dental home for pregnant women. At the same time, senior dental students and faculty members are introduced to prenatal oral health principles and delivery of comprehensive oral health care to pregnant women. A systems-based approach was used to guide the pOHP implementation during the 2012-13 academic year. Participants were 96 third-year medical students (50% of the total in an obstetrics and gynecology clerkship) and all 81 fourth-year dental students. During that academic year, 126 dental referrals were made to the School of Dentistry, and 55 women presented for care, resulting in 50% (n=40) of dental students participating in the clinical experience and delivery of simple to complex oral health procedures. The prenatal period is a frequently missed opportunity to address oral health care. The pOHP is an interprofessional collaboration model designed to educate dental and medical providers and provide a system of referral for comprehensive clinical care of pregnant patients, including educating women about their oral health and that of their children. Such programs can help meet interprofessional accreditation standards and encourage implementation of practice guidelines.

Society for maternal-fetal medicine (SMFM) special report: the maternal-fetal medicine subspecialists' role within a health care system.

A maternal-fetal medicine (MFM) subspecialist has advanced knowledge of the medical, surgical, obstetrical, fetal, and genetic complications of pregnancy and their effects on both the mother and fetus. MFM subspecialists are complementary to obstetric care providers in providing consultations, co-management, or transfer of care for complicated patients before, during, and after pregnancy. The MFM subspecialist provides peer and patient education and performs research concerning the most recent approaches and treatments for obstetrical problems, thus promoting risk-appropriate care for these complicated pregnancies. The relationship between the obstetric care provider and the MFM subspecialist depends on the acuity of the maternal and/or fetal condition and the local resources. To achieve the goal of promoting early access and sustained adequate prenatal care for all pregnant women, we encourage collaboration with obstetricians, family physicians, certified midwives, and others, and we also encourage providing preconception, prenatal, and postpartum care counseling and coordination. Effective communication between all obstetric care team members is imperative. This special report was written with the intent that it would be broad in scope and appeal to a diverse readership, including administrators, allowing it to be applied to various systems of care both horizontally and vertically. We understand that these relationships are often complex and there are more models of care than could be addressed in this document. However, we aimed to promote the development of a highly effective team approach to the care of the high-risk pregnancy that will be useful in the most common models for obstetric care in the United States. The MFM subspecialist functions most effectively within a fully integrated and collaborative health care environment. This document defines the various roles that the MFM subspecialist can fulfill within different heath care systems through consultation, co-management, and transfer of care, as well as education, research, and leadership.

Influence of neonatal practice variation on outcomes of late preterm birth.

OBJECTIVE: Examine variation in short-term outcomes of late preterm births (34(0/7)-36(6/7) weeks) between a university teaching hospital, teaching community hospital, and nonteaching community hospital. STUDY DESIGN: Review of maternal and newborn data from a random sample of late preterm births at three hospitals in North Carolina from 2008 to 2009. Outcomes included length of stay, neonatal intensive care unit (NICU) admission, respiratory support, antibiotic exposure, phototherapy exposure, and hypoglycemia. RESULTS: We analyzed data from 331 singleton late preterm newborns: 93 (28.1%) from a university teaching hospital, 110 (33.2%) from a teaching community hospital, and 128 (38.7%) from a nonteaching community hospital. Mean gestational age did not vary between hospitals. NICU admission, exposure to antibiotics, and phototherapy were more common at the university teaching hospital after controlling for risk factors, yet length of stay was shortest at the university teaching hospital and longest at the teaching community hospital after adjustment. CONCLUSION: Practice variation contributes to differences in length of stay, NICU admission, and exposure to antibiotics and phototherapy among late preterm newborns. Differences in practice during the birth hospitalization may affect outcomes and health care utilization (e.g., readmission) after discharge.

Vitamin D status and periodontal disease among pregnant women.

BACKGROUND: Maternal periodontal disease is found in < or = 40% of pregnant women and is associated with adverse pregnancy outcomes. Vitamin D deficiency may play a role in periodontal disease and tooth loss, and insufficient vitamin D status is common among pregnant women. The objective of this study is to examine the relationship between maternal vitamin D status and periodontal disease. METHODS: A case-control study was conducted. Cases were defined as pregnant women with clinical moderate to severe periodontal disease; controls were pregnant women who were periodontally healthy. Maternal data were chart abstracted and serum was collected between 14 and 26 weeks of gestation. Serum 25-hydroxyvitamin D (25[OH]D) levels were measured using liquid chromatography-tandem mass spectrometry. Median serum 25(OH)D levels and prevalence of vitamin D insufficiency (defined as <75 nmol/l) were compared between cases and controls. The odds ratio and 95% confidence interval for moderate to severe periodontal disease among women with vitamin D insufficiency was calculated using multivariable logistic regression, adjusting for maternal race, season of blood draw, and other potential confounders. RESULTS: A total of 117 cases were compared to 118 controls. Cases had lower median 25(OH)D levels than controls (59 versus 100 nmol/l; P <0.001) and were more likely to have vitamin D insufficiency (65% versus 29%; P <0.001). The adjusted odds ratio (95% confidence interval) for moderate to severe periodontal disease among women with vitamin D insufficiency was 2.1 (0.99 to 4.5). CONCLUSIONS: Vitamin D insufficiency (serum 25[OH]D <75 nmol/l) is associated with maternal periodontal disease during pregnancy. Vitamin D supplementation represents a potential therapeutic strategy to improve maternal oral health.