Impact of hypertensive disorders of pregnancy and gestational diabetes mellitus on offspring cardiovascular health in early adolescence.

BACKGROUND: Adverse pregnancy outcomes, including hypertensive disorders of pregnancy and gestational diabetes mellitus, influence maternal cardiovascular health long after pregnancy, but their relationship to offspring cardiovascular health following in-utero exposure remains uncertain. OBJECTIVE: To examine associations of hypertensive disorders of pregnancy or gestational diabetes mellitus with offspring cardiovascular health in early adolescence. STUDY DESIGN: This analysis used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome Study from 2000 to 2006 and the Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study from 2013 to 2016. This analysis included 3317 mother-child dyads from 10 field centers, comprising 70.8% of Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study participants. Those with pregestational diabetes and chronic hypertension were excluded. The exposures included having any hypertensive disorders of pregnancy or gestational diabetes mellitus vs not having hypertensive disorders of pregnancy or gestational diabetes mellitus, respectively (reference). The outcome was offspring cardiovascular health when aged 10-14 years, on the basis of 4 metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Each metric was categorized as ideal, intermediate, or poor using a framework provided by the American Heart Association. The primary outcome was defined as having at least 1 cardiovascular health metric that was nonideal vs all ideal (reference), and the second outcome was the number of nonideal cardiovascular health metrics (ie, at least 1 intermediate metric, 1 poor metric, or at least 2 poor metrics vs all ideal [reference]). Modified poisson regression with robust error variance was used and adjusted for covariates at pregnancy enrollment, including field center, parity, age, gestational age, alcohol or tobacco use, child's assigned sex at birth, and child's age at follow-up. RESULTS: Among 3317 maternal-child dyads, the median (interquartile) ages were 30.4 (25.6-33.9) years for pregnant individuals and 11.6 (10.9-12.3) years for children. During pregnancy, 10.4% of individuals developed hypertensive disorders of pregnancy, and 14.6% developed gestational diabetes mellitus. At follow-up, 55.5% of offspring had at least 1 nonideal cardiovascular health metric. In adjusted models, having hypertensive disorders of pregnancy (adjusted risk ratio, 1.14 [95% confidence interval, 1.04-1.25]) or having gestational diabetes mellitus (adjusted risk ratio, 1.10 [95% confidence interval, 1.02-1.19]) was associated with a greater risk that offspring developed less-than-ideal cardiovascular health when aged 10-14 years. The above associations strengthened in magnitude as the severity of adverse cardiovascular health metrics increased (ie, with the outcome measured as ≥1 intermediate, 1 poor, and ≥2 poor adverse metrics), albeit the only statistically significant association was with the "1-poor-metric" exposure. CONCLUSION: In this multinational prospective cohort, pregnant individuals who experienced either hypertensive disorders of pregnancy or gestational diabetes mellitus were at significantly increased risk of having offspring with worse cardiovascular health in early adolescence. Reducing adverse pregnancy outcomes and increasing surveillance with targeted interventions after an adverse pregnancy outcome should be studied as potential avenues to enhance long-term cardiovascular health in the offspring exposed in utero.

A Comparison of Vaginal and Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth.

OBJECTIVE: This study aimed to examine whether vaginal progesterone is noninferior to 17-α hydroxyprogesterone caproate (17OHP-C) in the prevention of recurrent preterm birth (PTB). STUDY DESIGN: This retrospective cohort study included singleton pregnancies among women with a history of spontaneous PTB who received prenatal care at a single tertiary center from 2011 to 2016. Pregnancies were excluded if progesterone was not initiated prior to 24 weeks or the fetus had a major congenital anomaly. The primary outcome was PTB <37 weeks. A priori, noninferiority was to be established if the upper bound of the adjusted two-sided 90% confidence interval (CI) for the difference in PTB fell below 9%. Inverse probability of treatment weighting (IPTW) was used to carefully control for confounding associated with choice of treatment and PTB. Adjusted differences in PTB proportions were estimated via IPTW regression, with standard errors adjustment for multiple pregnancies per woman. Secondary outcomes included PTB <34 and <28 weeks, spontaneous PTB, neonatal intensive care unit admission, and gestational age at delivery. RESULTS: Among 858 pregnancies, 41% (n = 353) received vaginal progesterone and 59% (n = 505) were given 17OHP-C. Vaginal progesterone use was more common later in the study period, and among women who established prenatal care later, had prior PTBs at later gestational ages, and whose race/ethnicity was neither non-Hispanic white nor non-Hispanic Black. Vaginal progesterone did not meet noninferiority criteria compared with 17-OHPC in examining PTB <37 weeks, with an IPTW adjusted difference of 3.4% (90% CI: -3.5, 10.3). For secondary outcomes, IPTW adjusted differences between treatment groups were generally small and CIs were wide. CONCLUSION: We could not conclude noninferiority of vaginal progesterone to 17OHP-C; however, women and providers may be willing to accept a larger difference (>9%) when considering the cost and availability of vaginal progesterone versus 17OHP-C. A well-designed randomized trial is needed. KEY POINTS: · Vaginal progesterone is not noninferior to 17OHP-C.. · PTB risk may be 10% higher with vaginal progesterone.. · Associations did not differ based on obesity status..

Long-Term Maternal Metabolic and Cardiovascular Phenotypes after a Pregnancy Complicated by Mild Gestational Diabetes Mellitus or Obesity.

OBJECTIVE: The aim of this study was to evaluate the association of mild gestational diabetes mellitus (GDM) and obesity with metabolic and cardiovascular markers 5 to 10 years after pregnancy. STUDY DESIGN: This was a secondary analysis of 5- to 10-year follow-up study of a mild GDM treatment trial and concurrent observational cohort of participants ineligible for the trial with abnormal 1-hour glucose challenge test only. Participants with 2-hour glucose tolerance test at follow-up were included. The primary exposures were mild GDM and obesity. The outcomes were insulinogenic index (IGI), 1/homeostatic model assessment of insulin resistance (HOMA-IR), and cardiovascular markers vascular endothelial growth factor, (VEGF), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 40 ligand (CD40L), growth differentiation factor 15 (GDF-15), and suppression of tumorgenesis 2 (ST-2). Multivariable linear regression estimated the association of GDM and obesity with biomarkers. RESULTS: Of 951 participants in the parent study, 642 (68%) were included. Lower 1/HOMA-IR were observed in treated and untreated GDM groups, compared with non-GDM (mean differences, -0.24 and -0.15; 95% confidence intervals [CIs], -0.36 to -0.12 and -0.28 to -0.03, respectively). Lower VCAM-1 (angiogenesis) was observed in treated GDM group (mean difference, -0.11; 95% CI, -0.19 to -0.03). GDM was not associated with IGI or other biomarkers. Obesity was associated with lower 1/HOMA-IR (mean difference, -0.42; 95% CI, -0.52 to -0.32), but not other biomarkers. CONCLUSION: Prior GDM and obesity are associated with more insulin resistance but not insulin secretion or consistent cardiovascular dysfunction 5 to 10 years after delivery. KEY POINTS: · Mild GDM increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Obesity increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Neither mild GDM nor obesity increased the risk of cardiovascular dysfunction 5 to 10 years postpartum..

Outpatient Use of Monoclonal Antibodies in Pregnant Individuals With Mild or Moderate Coronavirus Disease 2019 (COVID-19).

Treatment with monoclonal antibodies has been shown to significantly reduce the risk of hospitalization and disease progression among high-risk patients with coronavirus disease 2019 (COVID-19). Pregnant individuals were excluded from the original trials. In this single-center retrospective cohort study, we evaluated whether monoclonal antibody treatment in pregnant individuals is associated with decreased risk of hospitalization. Outcomes of patients who received the treatment were compared with those who were eligible but did not receive the treatment. Analyses were stratified by vaccination status. Unvaccinated pregnant patients with mild or moderate COVID-19 who received outpatient monoclonal antibodies were less likely to be admitted to the hospital (4.2% vs 15.7%, odds ratio 0.24, 95% CI 0.07-0.74), whereas among vaccinated patients, the treatment was not associated with a lower rate of hospitalization (2.3% vs 0%, P=.99).

Gestational Weight Gain and Adverse Maternal and Neonatal Outcomes for Pregnancies Complicated by Pregestational and Gestational Diabetes.

OBJECTIVE: This study aimed to investigate the association between excess and less than recommended gestational weight gain (GWG) and adverse maternal and neonatal outcomes in women with pregestational and gestational diabetes. STUDY DESIGN: We conducted a secondary analysis of the National Institute of Child Health and Human Development (NICHD) Consortium on Safe Labor (CSL) study. We included deliveries >23 weeks of nonanomalous singletons with either pregestational or gestational diabetes. The exposure was GWG greater than or less than compared with the U.S. Institute of Medicine recommendations for total pregnancy weight gain per prepregnancy body mass index. Consistent with the 2020 Delphi outcome for diabetes in pregnancy, maternal outcomes included cesarean delivery and preeclampsia and neonatal outcomes included small for gestational age (SGA), large for gestational age (LGA), macrosomia >4,000 g, preterm birth <37 weeks, stillbirth, and neonatal death. We modeled both absolute GWG and GWG z-scores, standardized for gestational duration. Multivariable logistic regression with generalized estimating equations was used, adjusting for age, race/ethnicity, parity, prior cesarean delivery, chronic hypertension, tobacco use, U.S. region, and delivery year. RESULTS: Of 8,322 deliveries (n = 8,087 women) complicated by pregestational or gestational diabetes, 47% were in excess, 27% were within, and 26% were less than GWG recommendations. Deliveries with excess absolute GWG were at higher adjusted odds of cesarean delivery, preeclampsia, LGA, and macrosomia, compared with those within recommendations. Similar results were observed when using standardized GWG z-scores, in addition to higher likelihood of preterm birth and neonatal death. Less than recommended GWG was associated with a lower likelihood of these adverse outcomes but higher SGA. Additionally, less GWG by z-score was associated with a lower likelihood of stillbirth. CONCLUSION: Excess GWG increases the risk of adverse maternal and neonatal outcomes for women with pregestational and gestational diabetes. Less GWG than recommended may decrease this risk. KEY POINTS: · Understanding the impact of GWG modeled using both absolute and standardized measures is needed.. · Among pregnant women with diabetes, excess GWG was common and increased the risk of adverse outcomes and less than recommended GWG may decrease the risk of adverse outcomes, including stillbirth.. · Current recommendations may require revision for women with diabetes in pregnancy..

Postoperative complications after non-obstetric surgery among pregnant patients in the National Surgical Quality Improvement Program, 2005-2012.

BACKGROUND: To examine whether pregnant patients have higher risk of major 30-day postoperative complications compared with their non-pregnant counterparts after non-obstetric surgery. METHODS: A secondary analysis of the prospective National Surgical Quality Improvement Program (NSQIP) from 2005 to 2012 of pregnant patients 18-51 years old, without surgery in the preceding 30 days, and who underwent a non-obstetrical operation. The primary outcome was composite 30-day major postoperative complications. We used modified Poisson regression. RESULTS: Among 354,251 assessed patients, 3655 (1%) were pregnant. The overall incidence of 30-day major postoperative complication was 6%, and did not vary by pregnancy status. Pregnant patients were not at higher risk of 30-day major postoperative complications compared to non-pregnant patients following non-obstetric surgery. This held for most procedures, except pregnant patients were at a higher risk of complications with colorectal and hernia surgeries. Secondarily, pregnant patients were at higher risk of transfusion. CONCLUSIONS: Pregnant patients are generally not at higher risk of major postoperative complications following non-obstetric surgery. This information can be used when counseling pregnant patients about the risks versus benefits of non-obstetric surgery.

Racial Disparities in the Risk of Complications After Nonobstetric Surgery in Pregnancy.

OBJECTIVE: To examine whether there are racial and ethnic differences in postoperative complications after nonobstetric surgery during pregnancy in the United States. METHODS: We conducted a secondary analysis of the prospective ACS NSQIP (American College of Surgeons National Surgical Quality Improvement) program from 2005 to 2012. We assessed pregnant women 18-50 years without prior surgery in the preceding 30 days who underwent a nonobstetric surgery. Race and ethnicity were categorized as non-Hispanic Black, Hispanic, and non-Hispanic White (reference). The primary outcome was a composite of 30-day major postoperative complications inclusive of cardiovascular, pulmonary, and infectious complications, reoperation, unplanned readmission, blood transfusion, and death. We used modified Poisson regression to estimate the relative risk of complications. RESULTS: Among 3,093 pregnant women, 18% were non-Hispanic Black, 20% Hispanic, and 62% non-Hispanic White. The most common surgeries were appendectomy (36%) and cholecystectomy (19%). Black women (18%) were more likely to be assigned American Society of Anesthesiologists (ASA) physical status class III or higher than their White (12%) or Hispanic (9%) peers. Non-Hispanic Black pregnant women had a higher risk of 30-day major postoperative complications compared with their White peers (9% vs 6%; adjusted relative risk [aRR] 1.41, 95% CI 1.11-1.99). This difference persisted when limiting the analysis to apparently healthy women (ASA class I or II) (7% vs 4%; aRR 1.64, 95% CI 1.08-2.50), those who underwent appendectomy (10% vs 3%; aRR 2.36, 95% CI 1.13-4.96), and when appendectomy and cholecystectomy were performed by laparoscopy (7% vs 3%; aRR 2.62, 95% CI 1.22-5.58). Hispanic pregnant women were not at an increased risk of complications compared with non-Hispanic pregnant White women. CONCLUSIONS: Pregnant non-Hispanic Black women were at higher risk of major postoperative complications after nonobstetric surgery compared with their White counterparts.

The Accuracy and Cost-Effectiveness of Selective Fetal Echocardiography for the Diagnosis of Congenital Heart Disease in Patients with Pregestational Diabetes Stratified by Hemoglobin A1c.

OBJECTIVE: To evaluate the accuracy of antenatal diagnosis of congenital heart disease (CHD) using screening methods including a combination of elevated hemoglobin A1c, detailed anatomy ultrasound, and fetal echocardiography. STUDY DESIGN: This is a retrospective cohort study of all pregnancies complicated by pregestational diabetes from January 2012 to December 2016. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each screening regimen. The incremental cost-effectiveness ratio (ICER) was calculated for each regimen with effectiveness defined as additional CHD diagnosed. RESULTS: A total of 378 patients met inclusion criteria with an overall prevalence of CHD of 4.0% (n = 15). When compared with a detailed ultrasound, fetal echocardiography had a higher sensitivity (73.3 vs. 40.0%). However, all cases of major CHD were detected by detailed ultrasound (n = 6). Using an elevated early A1c > 7.7% and a detailed ultrasound resulted in a sensitivity and specificity of 60.0 and 99.4%, respectively. The use of selective fetal echocardiography for an A1c > 7.7% or abnormal detailed anatomy ultrasound would result in a 63.3% reduction in cost per each additional minor CHD diagnosed (ICER: $18,290.52 vs. $28,875.67). CONCLUSION: Fetal echocardiography appears to have limited diagnostic value in women with pregestational diabetes. However, these results may not be generalizable outside of a high-volume academic setting.

Clonal and Quantitative In Vivo Assessment of Hematopoietic Stem Cell Differentiation Reveals Strong Erythroid Potential of Multipotent Cells.

Hematopoiesis is arguably one of the best understood stem cell systems; however, significant challenges remain to reach a consensus understanding of the lineage potential, heterogeneity, and relationships of hematopoietic stem and progenitor cell populations. To gain new insights, we performed quantitative analyses of mature cell production from hematopoietic stem cells (HSCs) and multiple hematopoietic progenitor populations. Assessment of the absolute numbers of mature cell types produced by each progenitor cell revealed a striking erythroid dominance of all myeloid-competent progenitors assessed, accompanied by strong platelet reconstitution. All populations with myeloid potential also produced robust numbers of red blood cells and platelets in vivo. Clonal analysis by single-cell transplantation and by spleen colony assays revealed that a significant fraction of HSCs and multipotent progenitors have multilineage potential at the single-cell level. These new insights prompt an erythroid-focused model of hematopoietic differentiation.

Hematopoietic stem cell-specific GFP-expressing transgenic mice generated by genetic excision of a pan-hematopoietic reporter gene.

Selective labeling of specific cell types by expression of green fluorescent protein (GFP) within the hematopoietic system would have great utility in identifying, localizing, and tracking different cell populations in flow cytometry, microscopy, lineage tracing, and transplantation assays. In this report, we describe the generation and characterization of a new transgenic mouse line with specific GFP labeling of all nucleated hematopoietic cells and platelets. This new "Vav-GFP" mouse line labels the vast majority of hematopoietic cells with GFP during both embryonic development and adulthood, with particularly high expression in hematopoietic stem and progenitor cells (HSPCs). With the exception of transient labeling of fetal endothelial cells, GFP expression is highly selective for hematopoietic cells and persists in donor-derived progeny after transplantation of HSPCs. Finally, we also demonstrate that the loxP-flanked reporter allows for specific GFP labeling of different hematopoietic cell subsets when crossed to various Cre reporter lines. By crossing Vav-GFP mice to Flk2-Cre mice, we obtained robust and highly selective GFP expression in hematopoietic stem cells (HSCs). These data describe a new mouse model capable of directing GFP labeling exclusively of hematopoietic cells or exclusively of HSCs.

Inadequate weight gain in overweight and obese pregnant women: what is the effect on fetal growth?

OBJECTIVE: We sought to evaluate inadequate gestational weight gain and fetal growth among overweight and obese women. STUDY DESIGN: We conducted an analysis of prospective singleton term pregnancies in which 1053 overweight and obese women gained >5 kg (14.4 ± 6.2 kg) or 188 who either lost or gained ≤5 kg (1.1 ± 4.4 kg). Birthweight, fat mass, and lean mass were assessed using anthropometry. Small for gestational age (SGA) was defined as ≤10th percentile of a standard US population. Univariable and multivariable analysis evaluated the association between weight change and neonatal morphometry. RESULTS: There was no significant difference in age, race, smoking, parity, or gestational age between groups. Weight loss or gain ≤5 kg was associated with SGA, 18/188 (9.6%) vs 51/1053 (4.9%); (adjusted odds ratio, 2.6; 95% confidence interval, 1.4-4.7; P = .003). Neonates of women who lost or gained ≤5 kg had lower birthweight (3258 ± 443 vs 3467 ± 492 g, P < .0001), fat mass (403 ± 175 vs 471 ± 193 g, P < .0001), and lean mass (2855 ± 321 vs 2995 ± 347 g, P < .0001), and smaller length, percent fat mass, and head circumference. Adjusting for diabetic status, prepregnancy body mass index, smoking, parity, study site, gestational age, and sex, neonates of women who gained ≤5 kg had significantly lower birthweight, lean body mass, fat mass, percent fat mass, head circumference, and length. There were no significant differences in neonatal outcomes between those who lost weight and those who gained ≤5 kg. CONCLUSION: In overweight and obese women weight loss or gain ≤5 kg is associated with increased risk of SGA and decreased neonatal fat mass, lean mass, and head circumference.

Breast-feeding initiation in women with pregestational diabetes mellitus.

OBJECTIVE: To examine feeding practices and factors associated with breast-feeding initiation (BFI) in women with pregestational diabetes mellitus (PGDM) and their infants. METHODS: In all, 392 PGDM (135 late preterm and 257 term) pregnancies were studied. Infant feeding preference was ascertained on admission. RESULTS: After birth, 166 (42%) of the infants received well-baby care, whereas 226 (58%) were admitted to the newborn intensive care unit (NICU). Hypoglycemia (blood glucose <40 mg/dL), which occurred in 128 (33%) of all infants, did not influence BFI. Of 257 women who intended to BF, 55% initiated BF. Also, 5% of 105 women who intended to feed formula and 13% of the 30 undecided later initiated BF. CONCLUSIONS: The BFI rate for women with PGDM is remarkably low even among those who intended to BF. Factors associated with BFI failure in this population were primiparity, African American race, lower education, smoking, lack of intention to BF, and NICU admission.

Risk of uterine rupture and placenta accreta with prior uterine surgery outside of the lower segment.

OBJECTIVE: Women with a prior myomectomy or prior classical cesarean delivery often have early delivery by cesarean because of concern for uterine rupture. Although theoretically at increased risk for placenta accreta, this risk has not been well-quantified. Our objective was to estimate and compare the risks of uterine rupture and placenta accreta in women with prior uterine surgery. METHODS: Women with prior myomectomy or prior classical cesarean delivery were compared with women with a prior low-segment transverse cesarean delivery to estimate rates of both uterine rupture and placenta accreta. RESULTS: One hundred seventy-six women with a prior myomectomy, 455 with a prior classical cesarean delivery, and 13,273 women with a prior low-segment transverse cesarean delivery were evaluated. Mean gestational age at delivery differed by group (P<.001), prior myomectomy (37.3 weeks), prior classical cesarean delivery (35.8 weeks), and low-segment transverse cesarean delivery (38.6 weeks). The frequency of uterine rupture in the prior myomectomy group (P-MMX group) was 0% (95% confidence interval [CI] 0-1.98%). The frequency of uterine rupture in the low-segment transverse cesarean delivery group (LTC group) (0.41%) was not statistically different from the risk in the P-MMX group (P>.99) or in the prior classical cesarean delivery group (PC group) (0.88%; P=.13). Placenta accreta occurred in 0% (95% CI 0-1.98%) of the P-MMX group compared with 0.19% in the LTC group (P>.99) and 0.88% in the PC group (P=.01 relative to the LTC group). The adjusted odds ratio for the PC group (relative to LTC group) was 3.23 (95% CI 1.11-9.39) for uterine rupture and 2.09 (95% CI 0.69-6.33) for accreta. The frequency of accreta for those with previa was 11.1% for the PC group and 13.6% for the LTC group (P>.99). CONCLUSION: A prior myomectomy is not associated with higher risks of either uterine rupture or placenta accreta. The absolute risks of uterine rupture and accreta after prior myomectomy are low.

Perinatal outcomes in Hispanic and non-Hispanic white women with mild gestational diabetes.

OBJECTIVE: To compare perinatal outcomes between self-identified Hispanic and non-Hispanic white women with mild gestational diabetes mellitus (GDM) or glucose intolerance. METHODS: In a secondary analysis of a mild GDM treatment trial, we compared perinatal outcomes by race and ethnicity for 767 women with glucose intolerance (abnormal 50-g 1-hour screen, normal 100-g 3-hour oral glucose tolerance test), 371 women with mild GDM assigned to usual prenatal care, and 397 women with mild GDM assigned to treatment. Outcomes included: composite adverse perinatal outcome (neonatal death, hypoglycemia, hyperbilirubinemia, hyperinsulinemia, stillbirth, birth trauma), gestational age at delivery, birth weight, and hypertensive disorders of pregnancy. Adjusted regression models included: 100-g 3-hour oral glucose tolerance test results, parity, gestational age, body mass index, maternal age at enrollment, and current tobacco use. RESULTS: The sample of 1,535 women was 68.3% Hispanic and 31.7% non-Hispanic white. Among women with glucose intolerance, Hispanic women had more frequent composite outcome (37% compared with 27%, adjusted odds ratio [OR] 1.62, 95% confidence interval [CI] 1.10-2.37) with more neonatal elevated C-cord peptide (19% compared with 13%, adjusted OR 1.79, 95% CI 1.04-3.08) and neonatal hypoglycemia (21% compared with 13%, adjusted OR 2.04, 95% CI 1.18-3.53). Among women with untreated mild GDM, outcomes were similar by race and ethnicity. Among Hispanic women with treated mild GDM, composite outcome was similar to non-Hispanic white women (35% compared with 25%, adjusted OR 1.62, 95% CI 0.92-2.86), but Hispanic neonates had more frequent hyperinsulinemia (21% compared with 10%, adjusted OR 2.96, 95% CI 1.33-6.60). CONCLUSION: Individual components of some neonatal outcomes were more frequent in Hispanic neonates, but most perinatal outcomes were similar between Hispanic and non-Hispanic ethnic groups. LEVEL OF EVIDENCE: II.

Promoting health after gestational diabetes: a National Diabetes Education Program call to action.

The National Diabetes Education Program joins the American College of Obstetricians and Gynecologists (the College) to promote opportunities for obstetrician-gynecologists (ob-gyns) and other primary care providers to better meet the long-term health needs of women with prior gestational diabetes mellitus (GDM) and their children. Up to one third of GDM women may have diabetes or prediabetes postpartum, yet only about half of these women are tested postpartum, and about a quarter are tested 6-12 weeks postpartum. Women with GDM face a lifelong increased risk for subsequent diabetes, primarily type 2 diabetes mellitus. Timely testing for prediabetes may provide an opportunity for ob-gyns to prevent or delay the onset of type 2 diabetes mellitus through diet, physical activity, weight management, and pharmacologic intervention. The College and the American Diabetes Association recommend testing women with a history of GDM at 6-12 weeks postpartum. If the postpartum test is normal, retest every 3 years and at the first prenatal visit in a subsequent pregnancy. If prediabetes is diagnosed, test annually. Because children of GDM pregnancies face an increased risk for obesity and type 2 diabetes mellitus, families need support to develop healthy eating and physical activity behaviors. Current criteria indicate that GDM occurs in 2% to 10% of all pregnancies. If new GDM diagnostic criteria are used, the frequency of GDM may increase to about 18% of pregnancies annually. The projected increase in the number of women with GDM and the potential subsequent associated risks underscore the need for proactive long-term primary care treatment of the mother and her children.

Gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) represents a heterogeneous group of metabolic disorders, which result in varying degrees of maternal hyperglycemia and pregnancy-associated risk. The frequency of GDM is rising globally and may also increase further as less-stringent criteria for the diagnosis are potentially adopted. The additional burden placed on the health care system by increasing cases of GDM requires consideration of diagnostic approaches and currently used treatment strategies. Debate continues to surround both the diagnosis and treatment of GDM despite several recent large-scale studies addressing these controversial issues. As many now have come to reassess their approach to the management of GDM, we provide information in this review to help guide this process. The goal for each health care practitioner should continue to be to provide optimum care for women discovered to have carbohydrate intolerance during pregnancy.

Optimal timing and mode of delivery after cesarean with previous classical incision or myomectomy: a review of the data.

Uterine rupture is an obstetrical emergency that can be catastrophic for the mother and fetus. Previous uterine surgery, including previous cesarean delivery or myomectomy, is an established risk factor, although the exact magnitude of the associated risk remains uncertain. We reviewed the literature related to uterine rupture after previous cesarean delivery with classical incision or myomectomy in an attempt to quantify outcomes associated with various management strategies. Although cesarean delivery with a classical incision is relatively uncommon (representing 0.3%-0.4% of deliveries), it presents a significant risk of rupture in subsequent pregnancies (1%-12% on the basis of published reports). Available data suggest that scheduled cesarean at 36-37 weeks optimizes both maternal and fetal outcomes in these cases. Patients with previous myomectomy are more frequently encountered in the obstetrical population. The risk of uterine rupture in subsequent pregnancies in these women is substantially lower than those with a history of previous classical incision (0.5%-0.7% on the basis of published reports). Although less common, given the potentially devastating consequences of uterine rupture, scheduled delivery at 38 weeks is suggested in those women requiring cesarean delivery. Despite the lack of well-controlled studies, preferred management strategies can be gleaned from previously published data to optimize maternal and fetal outcomes in women with these risk factors.

Soluble fms-Like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies.

BACKGROUND: Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome. METHODS: This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF. RESULTS: The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia. CONCLUSIONS: The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women.

Effect of smoking on circulating angiogenic factors in high risk pregnancies.

OBJECTIVE: Changes in maternal concentrations of the anti-angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng), and the pro-angiogenic placental growth factor (PlGF) precede the development of preeclampsia in healthy women. The risk of preeclampsia is reduced in women who smoke during pregnancy. The objective of this study was to investigate whether smoking affects concentrations of angiogenic factors (sFlt1, PlGF, and sEng) in women at high risk for developing preeclampsia. STUDY DESIGN: We performed a secondary analysis of serum samples from 993 high-risk women (chronic hypertension, diabetes, multifetal gestation, and previous preeclampsia) in a preeclampsia prevention trial. sFlt1, sEng and PlGF were measured in serum samples obtained at study entry, which was prior to initiation of aspirin (median 19.0 weeks' [interquartile range of 16.0-22.6 weeks']). Smoking status was determined by self-report. RESULTS: sFlt1 was not significantly different in smokers from any high-risk groups compared to their nonsmoking counterparts. PlGF was higher among smokers compared to nonsmokers among diabetic women (142.7 [77.4-337.3] vs 95.9 [48.5-180.7] pg/ml, p = 0.005) and women with a history of preeclampsia (252.2 [137.1-486.0] vs 152.2 [73.6-253.7] pg/ml, p = 0.001). sEng was lower in smokers with multifetal gestations (5.8 [4.6-6.5] vs 6.8 [5.5-8.7] ng/ml, p = 0.002) and trended lower among smokers with diabetes (4.9 [3.8-5.6] vs 5.3 [4.3-6.3] ng/ml, p = 0.05). Smoking was not associated with a lower incidence of preeclampsia in any of these groups. CONCLUSIONS: In certain high-risk groups, smoking is associated with changes in the concentrations of these factors towards a pro-angiogenic direction during early pregnancy; however, there was no apparent association between smoking and the development of preeclampsia in our cohort.