The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry.

Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = -0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs.

Impact of earlier gestational diabetes screening for pregnant people with obesity on maternal and perinatal outcomes.

OBJECTIVES: Gestational diabetes (GDM) screening at 24-28 weeks' gestation reduces risk of adverse maternal and perinatal outcomes. While experts recommend first-trimester screening for high-risk patients, including those with obesity, data supporting this recommendation is limited. METHODS: We implemented a systematic population intervention to encourage first-trimester GDM screening by oral glucose tolerance testing in a cohort of pregnant people with obesity in two integrated health systems from 2009 to 2013, and compared outcomes to the same population pre-intervention (2006-2009). Up to five years of postpartum glucose testing results (through 2018) were assessed among GDM cases in the post-intervention group. Primary outcomes were large-for-gestational-age birthweight (LGA); macrosomia; a perinatal composite outcome; gestational hypertension/preeclampsia; cesarean delivery; and medication treatment of GDM. RESULTS: A total of 40,206 patients (9,156 with obesity) were screened for GDM; 2,672 (6.6%) were diagnosed with GDM. Overall, multivariate adjusted risk for LGA and cesarean delivery were lower following the intervention (LGA: aOR 0.89 [0.82, 0.96]; cesarean delivery: 0.89 [0.85, 0.93]). This difference was more pronounced in patients diagnosed with GDM (LGA: aOR 0.52 [0.39, 0.70]; cesarean delivery 0.78 [0.65, 0.94]); insulin/oral hypoglycemic treatment rates for GDM were also higher post-intervention than pre-intervention (22 vs. 29%; p<0.0001). There were no differences for the other primary outcomes. Only 20% of patients diagnosed with GDM early in pregnancy who had postpartum testing had results in the overt diabetes range, suggesting a spectrum of diabetes detected early in pregnancy. CONCLUSIONS: First trimester GDM screening for pregnant people with obesity may improve GDM-associated outcomes.

A Pragmatic, Randomized Clinical Trial of Gestational Diabetes Screening.

BACKGROUND: Gestational diabetes mellitus is common and is associated with an increased risk of adverse maternal and perinatal outcomes. Although experts recommend universal screening for gestational diabetes, consensus is lacking about which of two recommended screening approaches should be used. METHODS: We performed a pragmatic, randomized trial comparing one-step screening (i.e., a glucose-tolerance test in which the blood glucose level was obtained after the oral administration of a 75-g glucose load in the fasting state) with two-step screening (a glucose challenge test in which the blood glucose level was obtained after the oral administration of a 50-g glucose load in the nonfasting state, followed, if positive, by an oral glucose-tolerance test with a 100-g glucose load in the fasting state) in all pregnant women who received care in two health systems. Guidelines for the treatment of gestational diabetes were consistent with the two screening approaches. The primary outcomes were a diagnosis of gestational diabetes, large-for-gestational-age infants, a perinatal composite outcome (stillbirth, neonatal death, shoulder dystocia, bone fracture, or any arm or hand nerve palsy related to birth injury), gestational hypertension or preeclampsia, and primary cesarean section. RESULTS: A total of 23,792 women underwent randomization; women with more than one pregnancy during the trial could have been assigned to more than one type of screening. A total of 66% of the women in the one-step group and 92% of those in the two-step group adhered to the assigned screening. Gestational diabetes was diagnosed in 16.5% of the women assigned to the one-step approach and in 8.5% of those assigned to the two-step approach (unadjusted relative risk, 1.94; 97.5% confidence interval [CI], 1.79 to 2.11). In intention-to-treat analyses, the respective incidences of the other primary outcomes were as follows: large-for-gestational-age infants, 8.9% and 9.2% (relative risk, 0.95; 97.5% CI, 0.87 to 1.05); perinatal composite outcome, 3.1% and 3.0% (relative risk, 1.04; 97.5% CI, 0.88 to 1.23); gestational hypertension or preeclampsia, 13.6% and 13.5% (relative risk, 1.00; 97.5% CI, 0.93 to 1.08); and primary cesarean section, 24.0% and 24.6% (relative risk, 0.98; 97.5% CI, 0.93 to 1.02). The results were materially unchanged in intention-to-treat analyses with inverse probability weighting to account for differential adherence to the screening approaches. CONCLUSIONS: Despite more diagnoses of gestational diabetes with the one-step approach than with the two-step approach, there were no significant between-group differences in the risks of the primary outcomes relating to perinatal and maternal complications. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ScreenR2GDM ClinicalTrials.gov number, NCT02266758.).

Prolonged interpregnancy interval: how does it impact the length of second stage of labor?

Objectives Short interpregnancy intervals (IPI) have been linked to multiple adverse maternal and neonatal outcomes, but less is known about prolonged IPI, including its relationship with labor progression. The objective of the study was to investigate whether prolonged IPIs are associated with longer second stages of labor. Methods A perinatal database from Kaiser Permanente Hawaii was used to identify 442 women with a prolonged IPI ≥60 months. Four hundred forty two nulliparous and 442 multiparous women with an IPI 18-59 months were selected as comparison groups. The primary outcome was second stage of labor duration. Perinatal outcomes were compared between these groups. Results The median (IQR) second stage of labor duration was 76 (38-141) min in nulliparous women, 15 (9-28) min in multiparous women, and 18 (10-38) min in women with a prolonged IPI (p<0.0001). Pairwise comparisons revealed significantly different second stage duration in the nulliparous group compared to both the multiparous and prolonged IPI groups, but no difference between the multiparous and prolonged IPI groups. There was a significant association with the length of the IPI; median duration 30 (12-61) min for IPI ≥120 months vs. 15 (9-27) min for IPI 18-59 months and 16 (9-31) min for IPI 60-119 months (p=0.0014). Conclusions The second stage of labor did not differ in women with a prolonged IPI compared to normal multiparous women. Women with an IPI ≥120 months had a significantly longer second stage vs. those with a shorter IPI. These findings provide a better understanding of labor progression in pregnancies with a prolonged IPI.

Timing of Gestational Diabetes Diagnosis by Maternal Obesity Status: Impact on Gestational Weight Gain in a Diverse Population.

Background: We hypothesized that earlier gestational diabetes mellitus (GDM) diagnosis and treatment of high-risk women would reduce gestational weight gain (GWG) in the first trimester and overall. Materials and Methods: We evaluated timing of GDM diagnosis among 5,391 pregnant women who delivered singleton births 2010-2013 in a large diverse health maintenance organization (HMO). All GDM screening was by the same oral glucose tolerance testing protocol; GDM treatment protocols were also consistent irrespective of timing of diagnosis. Women without risk factors were universally screened at 24-28 weeks gestation (Usual). Early screening was recommended in obese and other high-risk women at the first prenatal visit; those who screened negative Early were rescreened at 24-28 weeks (Early+Usual). Results: Average GWG for all women was 12.8 kg; 10.7% of women were diagnosed with GDM. Average GWG for all women diagnosed with GDM was 10.7 kg, adjusted for gestational age. Women with EarlyGDM averaged 2.4 kg less GWG than women diagnosed with UsualGDM (p < 0.0001). Among obese women, only women diagnosed with EarlyGDM averaged overall GWG within Institute of Medicine (IOM) weight guidelines (mean 8.1 kg) and were weight neutral in the first trimester (-0.2 kg). Overall, 43% of all pregnant women exceeded IOM GWG guidelines (gained more total weight than recommended); 60% of obese women exceeded guidelines. Obese women diagnosed with GDM were less likely to exceed IOM guidelines if diagnosed earlier in pregnancy (35% EarlyGDM vs. 59% UsualGDM exceeded guidelines, p < 0.0001). Conclusion: Our results suggest that EarlyGDM diagnosis (and thus treatment) in high-risk women is beneficial for optimizing GWG.

A randomized pragmatic clinical trial of gestational diabetes screening (ScreenR2GDM): Study design, baseline characteristics, and protocol adherence.

BACKGROUND: ScreenR2GDM is a pragmatic randomized clinical trial designed to investigate if one of two gestational diabetes (GDM) screening and treatment protocols results in improved outcomes in the context of standard clinical care. METHODS: Pregnant women are randomized to one of two GDM screening strategies: 1-step: 2-h, 75 g, oral glucose tolerance test (OGTT) or 2-step: 1-h, 50 g glucose challenge test (GCT) followed by 3-h, 100 g OGTT if GCT-positive. Providers are prompted within the electronic medical record to order the assigned test but were given the option to order the alternate test. Collected data include maternal and pregnancy characteristics, GDM testing, and outcomes for mother and newborn. We describe the study design and baseline characteristics and evaluate characteristics associated with adhering to the randomized protocol. RESULTS: Baseline characteristics of the 23,792 randomized pregnancies were comparable between the two groups. Adherence to assigned test differed between the two strategies: 66.1% for 1-step and 91.7% for 2-step (p < .0001). 27% of the women randomized to receive the 1-step completed the 2-step test vs 2% randomized to the 2-step who completed the 1-step (p < .0001). Patient characteristics related to adherence included obesity, age, prior GDM, Medicaid insurance, race and nulliparity. Clinician characteristics related to adherence included provider type, age and gender. CONCLUSIONS: Both patient and provider characteristics were related to adherence to the randomized GDM screening protocol. Analytical techniques that incorporate these findings into the formal evaluation of the two protocols on GDM-associated outcomes will be necessary to account for potential biases introduced by non-adherence.

Impact of Maternal Glucose and Gestational Weight Gain on Child Obesity over the First Decade of Life in Normal Birth Weight Infants.

Objective To determine, among children with normal birth weight, if maternal hyperglycemia and weight gain independently increase childhood obesity risk in a very large diverse population. Methods Study population was 24,141 individuals (mothers and their normal birth weight offspring, born 1995-2003) among a diverse population with universal GDM screening [50-g glucose-challenge test (GCT); 3 h. 100 g oral glucose tolerance test (OGTT) if GCT+]. Among the 13,037 full-term offspring with normal birth weight (2500-4000 g), annual measured height/weight was ascertained between ages 2 and 10 years to calculate gender-specific BMI-for-age percentiles using USA norms (1960-1995 standard). Results Among children who began life with normal birth weight, we found a significant trend for developing both childhood overweight (>85 %ile) and obesity (>95 %ile) during the first decade of life with both maternal hyperglycemia (normal GCT, GCT+ but no GDM, GDM) and excessive gestational weight gain [>40 pounds (18.1 kg)]; p < 0.0001 for both trends. These maternal glucose and/or weight gain effects to imprint for childhood obesity in the first decade remained after adjustment for potential confounders including maternal age, parity, as well as pre-pregnancy BMI. The attributable risk (%) for childhood obesity was 28.5 % (95 % CI 15.9-41.1) for GDM and 16.4 % (95 % CI 9.4-23.2) for excessive gestational weight gain. Conclusions for Practice Both maternal hyperglycemia and excessive weight gain have independent effects to increase childhood obesity risk. Future research should focus on prevention efforts during pregnancy as a potential window of opportunity to reduce childhood obesity.

Markedly different rates of incident insulin treatment based on universal gestational diabetes mellitus screening in a diverse HMO population.

OBJECTIVE: We sought to evaluate population gestational diabetes mellitus (GDM) screening results and risk for incident insulin treatment. STUDY DESIGN: Among 64,687 pregnant women universally screened for GDM from 1995 through 2010 in 2 regions of a large US health plan, we stratified women requiring insulin treatment during their pregnancy by GDM screening results (50-g glucose challenge test [GCT]), followed by a 3-hour, 100-g oral glucose tolerance test if GCT was positive. Women with GCT >200 mg/dL were evaluated separately. RESULTS: Overall, 2% of all pregnant women required insulin treatment, ranging from 0.1% (normal GCT) to 49.9% (GCT >200 mg/dL; P for trend < .0001). Women with GCT >200 mg/dL had a much higher rate of insulin treatment than women with GDM (odds ratio, 3.7; 95% confidence interval, 3.1-4.4). Risk factors for higher insulin treatment rates with GDM or GCT >200 mg/dL included obesity, race/ethnicity, and diagnosed ≤16 weeks' gestation. CONCLUSION: Our results indicate women with GCT >200 mg/dL could be reasonably treated as GDM without requiring additional oral glucose tolerance test for diagnosis.

Acute chorioamnionitis at term caused by the oral pathogen Fusobacterium nucleatum.

Fusobacterium nucleatum is an oral pathogen associated with preterm birth. Presented is a case of acute chorioamnionitis that progressed to maternal sepsis in a term patient with intact membranes. In addition to its role in periodontal disease and preterm birth, our case demonstrates that intrauterine infection with Fusobacterium nucleatum can result in severe disease at term.

Variation in fetal ultrasound biometry based on differences in fetal ethnicity.

OBJECTIVE: The objective of the study was to evaluate whether fetal ultrasound biometry is affected by variation in fetal ethnicity compared with white controls. STUDY DESIGN: This was a retrospective observational study of ultrasound biometry in pregnant women with accurate gestational age. RESULTS: Three hundred five white, 370 Asian, 895 part Hawaiian, 76 Pacific Islander, and 311 white Asian fetuses were analyzed. At 18 weeks gestation femur length was significantly shorter in Asian and white Asian. Humerus length was significantly shorter in Asian, part Hawaiian, and white Asian. White genetic sonogram was positive 14% for femur and 15% for humerus. The following was found: Asian 29% femur (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.70-3.92), 25% humerus (OR, 1.86; 95% CI, 1.23-2.82); part Hawaiian 21% femur (OR, 1.67; 95% CI, 1.14-2.45), 23% humerus (OR, 1.64; 95% CI, 1.13-2.38); Pacific Islander 27% femur (OR, 2.37; 95% CI, 1.23-4.54), 33% humerus (OR, 2.76; 95% CI, 1.47-5.14); and white Asian 20% femur (OR, 1.56; 95% CI, 1.01-2.46), 22% humerus (OR, 1.56; 95% CI, 1.01-2.42). CONCLUSION: Genetic sonogram was screen positive more frequently because of shorter long bone measurements in all nonwhite ethnicities.