Relatively Low ß-Cell Responsiveness Contributes to the Association of BMI with Circulating Glucose Concentrations Measured under Free-Living Conditions among Pregnant African American Women.

BACKGROUND: Body mass index (BMI, in kg/m(2)) is positively associated with plasma glucose in late pregnancy and with risk of adverse obstetric outcomes. Much of the existing research uses single-clinic measures of plasma glucose, which may not accurately reflect circulating glucose under free-living conditions. Furthermore, little is known about circulating glucose concentrations of African American women, who tend to have poorer diet quality and a greater risk of obstetric complications. OBJECTIVE: The objective of the study was to test the hypothesis that the positive association of BMI in early pregnancy with third-trimester circulating glucose concentrations measured under free-living conditions among African American women would be at least partially attributable to lower ß-cell insulin secretion relative to insulin sensitivity [i.e., lower disposition index (DI)]. METHODS: Using a prospective, observational design, 40 pregnant African American women (mean ± SD age: 23.1 ± 4.0 y; mean ± SD BMI: 28.4 ± 7.5) wore continuous glucose monitors and accelerometers for 3 d at 32-35 wk of gestation and concurrently maintained a food diary to report their self-selected meals. The DI was derived from a 75-g oral glucose tolerance test. Linear regression modeling was used to calculate the association of BMI with the 24-h glucose (GLUC24h) and 2-h (GLUC2hPP) postprandial glucose areas under the curve and with the percentage of time the glucose concentrations were >120 mg/dL. RESULTS: The positive associations between BMI and GLUC24h (standardized ß = 0.36, P = 0.03) and the percentage of time glucose concentrations were >120 mg/dL (standardized ß = 0.40, P = 0.02) were independent of total carbohydrate intake and physical activity and were attenuated when DI was added to the model. The positive association of BMI with GLUC2hPP was attenuated when DI was added to the model, and DI itself was independently associated with GLUC2hPP after self-selected breakfast and dinner (standardized ß = -0.33 and -0.42, respectively; P = 0.01). CONCLUSIONS: The association of BMI with high circulating glucose in free-living pregnant African American women is at least partially attributable to lower ß-cell responsiveness.

Association of late-night carbohydrate intake with glucose tolerance among pregnant African American women.

Obesity and late-night food consumption are associated with impaired glucose tolerance. Late-night carbohydrate consumption may be particularly detrimental during late pregnancy because insulin sensitivity declines as pregnancy progresses. Further, women who were obese (Ob) prior to pregnancy have lower insulin sensitivity than do women of normal weight (NW). The aim of this study is to test the hypothesis that night-time carbohydrate consumption is associated with poorer glucose tolerance in late pregnancy and that this association would be exacerbated among Ob women. Forty non-diabetic African American women were recruited based upon early pregnancy body mass index (NW, <25 kg m(-2) ; Ob, ≥30 kg m(-2) ). Third trimester free-living dietary intake was assessed by food diary, and indices of glucose tolerance and insulin action were assessed during a 75-g oral glucose tolerance test. Women in the Ob group reported greater average 24-h energy intake (3055 kcal vs. 2415 kcal, P < 0.05). Across the whole cohort, night-time, but not day-time, carbohydrate intake was positively associated with glucose concentrations after the glucose load and inversely associated with early phase insulin secretion (P < 0.05). Multiple linear regression modelling within each weight group showed that the associations among late-night carbohydrate intake, glucose concentrations and insulin secretion were present only in the Ob group. This is the first study to report an association of night-time carbohydrate intake specifically on glucose tolerance and insulin action during pregnancy. If replicated, these results suggest that late-night carbohydrate intake may be a potential target for intervention to improve metabolic health of Ob women in late pregnancy.

Discordant circulating fetal DNA and subsequent cytogenetics reveal false negative, placental mosaic, and fetal mosaic cfDNA genotypes.

BACKGROUND: The American College of Obstetrics and Gynecology (ACOG) and Maternal Fetal Medicine (MFM) Societies recommended that abnormal cfDNA fetal results should be confirmed by amniocentesis and karyotyping. Our results demonstrate that normal cfDNA results inconsistent with high-resolution abnormal ultrasounds should be confirmed by karyotyping following a substantial frequency of incorrect cfDNA results. METHODS: Historical review of our ~4,000 signed prenatal karyotypes found ~24% of reported abnormalities would not have been detected by cfDNA. Akron Children's Hospital Cytogenetics Laboratory has completed 28 abnormal cfDNA cases among the 112 amniocenteses karyotyped. RESULTS: Following abnormal cfDNA results our karyotypes confirmed only 60% of the cfDNA results were consistent. Our cases found a normal cfDNA test result followed by a 20 weeks anatomical ultrasound detected a false negative trisomy 18 cfDNA result. One cfDNA result that reported trisomy 21 in the fetus was confirmed by karyotyping which also added an originally undetected balanced reciprocal translocation. Another reported karyotyped case followed by a repeated microarray of pure fetal DNA, together revealed one phenotypically normal newborn with a complex mosaic karyotype substantially decreasing the newborn's eventual reproductive fitness. This second case establishes the importance of karyotyping the placenta and cord or peripheral blood when inconsistent or mosaic results are identified following an abnormal cfDNA result with a normal newborn phenotype without a prenatal karyotype. CONCLUSIONS: These Maternal Fetal Medicine referrals demonstrate that positive NIPT results identify an increased abnormal karyotypic frequency as well as a substantial proportion of discordant fetal results. Our results found: (1) a normal NIPT test result followed by a 20 week anatomical ultrasound detected a false negative trisomy 18 NIPT result, (2) a substantial proportion of abnormal NIPT tests identify chromosomal mosaicism that may or may not be confined to the placenta, (3) follow up karyotyping should be completed on the newborn placenta and peripheral blood when the amniocyte karyotype does not confirm the NIPT reported abnormality in order to identify ongoing risk of developing mosaic symptoms, and (4) karyotyping all high risk fetuses tested by amniocentesis defines the 24% of chromosome abnormalities not currently screened by NIPT.

Risk factors for uterine atony/postpartum hemorrhage requiring treatment after vaginal delivery.

OBJECTIVE: We sought to identify risk factors for uterine atony or hemorrhage. STUDY DESIGN: We conducted a secondary analysis of a 3-arm double-blind randomized trial of different dose regimens of oxytocin to prevent uterine atony after vaginal delivery. The primary outcome was uterine atony or hemorrhage requiring treatment. In all, 21 potential risk factors were evaluated. Logistic regression was used to identify independent risk factors using 2 complementary predefined model selection strategies. RESULTS: Among 1798 women randomized to 10, 40, or 80 U of prophylactic oxytocin after vaginal delivery, treated uterine atony occurred in 7%. Hispanic (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.3-3.4), non-Hispanic white (OR, 1.6; 95% CI, 1.0-2.5), preeclampsia (OR, 3.2; 95% CI, 2.0-4.9), and chorioamnionitis (OR, 2.8; 95% CI, 1.6-5.0) were consistent independent risk factors. Other risk factors based on the specified selection strategies were obesity, induction/augmentation of labor, twins, hydramnios, anemia, and arrest of descent. Amnioinfusion appeared to be protective against uterine atony (OR, 0.53; 95% CI, 0.29-0.98). CONCLUSION: Independent risk factors for uterine atony requiring treatment include Hispanic and non-Hispanic white ethnicity, preeclampsia, and chorioamnionitis.

Gestational age at delivery and perinatal outcomes of twin gestations.

OBJECTIVE: The optimal gestational duration for twin gestations is unknown. Epidemiologic studies show that the lowest perinatal mortality rate for twins is at 37-38 weeks, but these studies lack information on pregnancy complications and neonatal morbidities. This study evaluates pregnancy characteristics and perinatal outcomes of twins in order to assess the optimal gestational age for delivery. STUDY DESIGN: This is a retrospective study of twins delivered at ≥36 weeks at our institution from 1991-2009. The composite rate of perinatal morbidity and mortality (including perinatal death, respiratory distress, suspected sepsis, and need for neonatal intensive care) was determined for weekly intervals from 36-39(+) weeks. RESULTS: There were 377 twin gestations included. Of those 83% were dichorionic. Fifty-three percent had spontaneous labor and 48% were delivered by cesarean section. Perinatal outcomes improved as gestational age advanced to 38 weeks. CONCLUSION: Perinatal morbidity and mortality rates suggest that the optimal time for delivery of twins is at 38 weeks or greater.

Midtrimester bacterial vaginosis and cervical length in women at risk for preterm birth.

OBJECTIVE: The purpose of this study was to estimate the effect of bacterial vaginosis on midtrimester cervical length in women at increased risk for recurrent spontaneous preterm birth. STUDY DESIGN: We conducted a secondary analysis of prerandomization data from a multicenter trial of ultrasound-indicated cerclage. Women with previous spontaneous preterm birth at <34 weeks' gestation underwent initial cervical length assessment and vaginal fluid collection at 16-21 weeks 6 days gestation. Gram stains were scored with Nugent criteria. With serial scans, the shortest cervical length was observed. RESULTS: Records for 949 women had complete data. In unadjusted regression models, Nugent score (P = .003) and vaginal fluid pH (P = .008) were related inversely to cervical length. Women with bacterial vaginosis based on Nugent score ≥7 (P = .04) or pH ≥5 (P = .016) had significantly lower cervical length than unaffected women; however, all of these effects were null after covariate adjustment. CONCLUSION: Nugent score, pH level, and bacterial vaginosis are associated inversely with cervical length; however, these relationships become null after adjustment for relevant covariates.

Does midtrimester Nugent score or high vaginal pH predict gestational age at delivery in women at risk for recurrent preterm birth?

OBJECTIVE: To estimate whether bacterial vaginosis, as defined by either Nugent score or vaginal pH, predicts gestational age at delivery in women at risk for recurrent preterm birth. STUDY DESIGN: Planned secondary analysis of a randomized cerclage trial in women with prior spontaneous preterm birth 17°(/)7-336(/)7 weeks. Vaginal Gram stain and pH were collected at the initial study visit. Women not assigned to cerclage, either because they did not experience cervical shortening <25 mm or because they were randomly assigned to no cerclage, were studied. RESULTS: Seven hundred eighty-six women had complete delivery gestational age, Gram stain, and pH results. The diagnosis of bacterial vaginosis by either Nugent score ≥ 7 or by pH ≥ 5 was not associated with earlier birth. CONCLUSION: The presence of bacterial vaginosis at 16-216(/)7 weeks does not predict gestational age at birth in women at risk for recurrent preterm birth.

Cervical funneling: effect on gestational length and ultrasound-indicated cerclage in high-risk women.

OBJECTIVE: The purpose of this study was to assess funnel type and pregnancy duration in women with previous spontaneous preterm birth and cervical length <25 mm. STUDY DESIGN: We performed a secondary analysis of a multicenter randomized trial of cerclage. At the randomization scan that documented short cervix, the presence and type of funnel (U or V) were recorded. RESULTS: One hundred forty-seven of 301 women (49%) had funneling: V-shaped funnel, 99 women; U-shaped funnel, 48 women. U-shaped funnel was associated significantly with preterm birth at <24, <28, <35, and <37 weeks of gestation. In multivariable models that controlled for randomization cervical length and cerclage, women with U-shaped funnel delivered earlier than women with either V-shaped funnel or no funnel. Interaction between cerclage and U-shaped funnel was observed, and analyses that were stratified by cerclage showed that women with a U-shaped funnel and cerclage delivered at a mean of 33.8 +/- 6.6 weeks of gestation, compared with women who did not receive cerclage (28.9 +/- 6.9 weeks of gestation). CONCLUSION: U-shaped funnels in high-risk women with a short cervix are associated with earlier birth.

Cesarean delivery for abnormal labor.

Cesarean delivery is indicated at any stage in the labor process in the presence of nonreassuring fetal status or when conservative measures fail in the setting of abnormal labor. In the absence of maternal or fetal indications for expedited delivery, cesarean delivery is not indicated for latent phase disorders. When to intervene for protracted labor is arguable, but slow rates of labor progress are consistent with safe vaginal delivery. Cesarean delivery in the second stage should be avoided for at least 4 hours if there is progressive fetal descent.

Maternal glucose concentration during pregnancy predicts fat and lean mass of prepubertal offspring.

OBJECTIVE: Intrauterine exposure to high maternal glucose is associated with excess weight gain during childhood, but it is not clear whether the excess weight represents increased fat or lean mass. The purpose of this study was to examine the relationship between maternal glucose concentrations during pregnancy and offspring body composition. A secondary goal was to examine whether the association between maternal glucose and children's body fat was independent of energy intake, energy expenditure, or physical activity. RESEARCH DESIGN AND METHODS: Children aged 5-10 years and their biological mothers (n = 27) were recruited. Maternal glucose concentration 1 h after a 50-g oral glucose load, used to screen for gestational diabetes mellitus at 24-28 weeks gestation, was retrieved from medical records. Children underwent dual-energy X-ray absorptiometry to measure body composition, indirect calorimetry to measure resting energy expenditure (REE), accelerometry to measure physical activity, and three 24-h diet recalls to measure energy intake. RESULTS: Maternal glucose concentration during pregnancy was positively associated with children's lean mass (P < 0.05) and adiposity (fat mass adjusted for lean mass; P < 0.05). The association between maternal glucose and children's adiposity was independent of children's REE, percent of time spent physically active, and energy intake (P < 0.001). CONCLUSIONS: Intrauterine exposure to relatively high maternal glucose is associated with greater lean mass and adiposity among prepubertal offspring. Further research is needed to examine the mechanisms by which maternal glucose concentrations during pregnancy influence children's body composition.

Prevention of preterm birth based on a short cervix: cerclage.

In an attempt to prevent preterm birth, clinicians have recommended cerclage for women with shortened cervical length and other worrisome sonographic cervical features in the mid-trimester, although randomized trials have not supported this practice. Emerging data suggest that preterm birth is a complex and poorly understood syndrome comprising several anatomic and functional components. As a result, preventive efforts have been mostly empiric and generally ineffective. Plausibly, effective preterm birth therapies exist, but matching the effective treatment with the correct patient has been problematic. Mid-trimester cervical changes visualized with vaginal sonography likely represent a pathologic process of premature cervical ripening and not real mechanical disability which has been traditionally treated with suture support. Cerclage may effectively reduce preterm birth in carefully selected women who have experienced a prior early preterm birth and who have shortened mid-trimester cervical length.