John M. Thorp

Frequency of and factors associated with severe maternal morbidity

OBJECTIVE: To estimate the frequency of severe maternal morbidity, assess its underlying etiologies, and develop a scoring system to predict its occurrence. Supplemental Digital Content is Available in the Text. METHODS: This was a secondary analysis of a Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network cohort of 115,502 women and their neonates born in 25 hospitals across the United States over a 3-year period. Women were classified as having severe maternal morbidity according to a scoring system that takes into account the occurrence of red blood cell transfusion (more than three units), intubation, unanticipated surgical intervention, organ failure, and intensive care unit admission. The frequency of severe maternal morbidity was calculated and the underlying etiologies determined. Multivariable analysis identified patient factors present on admission that were independently associated with severe maternal morbidity; these were used to develop a prediction model for severe maternal morbidity. RESULTS: Among 115,502 women who delivered during the study period, 332 (2.9/1,000 births, 95% confidence interval 2.6–3.2) experienced severe maternal morbidity. Postpartum hemorrhage was responsible for approximately half of severe maternal morbidity. Multiple patient factors were found to be independently associated with severe maternal morbidity and were used to develop a predictive model with an area under the receiver operating characteristic curve of 0.80. CONCLUSION: Severe maternal morbidity occurs in approximately 2.9 per 1,000 births, is most commonly the result of postpartum hemorrhage, and occurs more commonly in association with several identifiable patient characteristics. LEVEL OF EVIDENCE: II

Activity restriction among women with a short cervix.

OBJECTIVE: To estimate determinants of and outcomes associated with activity restriction among women with a short cervix. METHODS: This was a secondary analysis of a randomized trial of 17-&agr; hydroxyprogesterone caproate for prevention of preterm birth among nulliparous women with singleton gestations and cervices less than 30 mm by midtrimester ultrasonography. Women were asked weekly whether they had been placed on pelvic, work, or nonwork rest. “Any activity restriction” was defined as being placed on any type of rest. Factors associated with any activity restriction were determined and the association between preterm birth and activity restriction was estimated with multivariable logistic regression. RESULTS: Of the 657 women in the trial, 646 (98%) responded to questions regarding activity restriction. Two hundred fifty-two (39.0%) were placed on any activity restriction at a median of 23.9 weeks (interquartile range 22.6–27.9 weeks). Women on activity restriction were older, more likely to have private insurance, less likely to be Hispanic, had a shorter cervical length, and were more likely to have funneling and intra-amniotic debris. Preterm birth at less than 37 weeks of gestation was more common among women placed on activity restriction (37% compared with 17%, P<.001). After controlling for potential confounding factors, preterm birth remained more common among those placed on activity restriction (adjusted odds ratio 2.37, 95% confidence interval 1.60–3.53). Results were similar for preterm birth at less than 34 weeks of gestation. CONCLUSION: Activity restriction did not reduce the rate of preterm birth in asymptomatic nulliparous women with a short cervix. LEVEL OF EVIDENCE: II

Relationship between 1-hour glucose challenge test results and perinatal outcomes

OBJECTIVE: To estimate the relationship between 1-hour 50 g glucose challenge test values and perinatal outcomes. METHODS: This was a secondary analysis of data from a multicenter treatment trial of mild gestational diabetes mellitus. Women with glucose challenge test values of 135–199 mg/dL completed a 3-hour oral glucose tolerance test. Mild gestational diabetes mellitus was defined as fasting glucose less than 95 mg/dL and two or more abnormal oral glucose tolerance test values: 1-hour 180 mg/dL or more; 2-hour 155 mg/dL or more; and 3-hour 140 mg/dL or more. Our study included untreated women with glucose challenge test values of 135–139 mg/dL and 140–199 mg/dL and a comparison group with values less than 120 mg/dL. Primary outcomes included a perinatal composite (stillbirth, neonatal death, hypoglycemia, hyperbilirubinemia, neonatal hyperinsulinemia, and birth trauma), large for gestational age (LGA, birth weight above the 90th percentile based on sex-specific and race-specific norms), and macrosomia (greater than 4,000 g). RESULTS: There were 436 women with glucose challenge test values less than 120 mg/dL and 1,403 with values of 135 mg/dL or more (135–139, n=135; 140–199, n=1,268). The composite perinatal outcome occurred in 25.6% of those with glucose challenge test values less than 120 mg/dL compared with 21.1% for values of 135–139 mg/dL and 35.3% for values of 140–199 mg/dL. Rates of LGA by group were 6.6%, 6.8%, and 12.4%, respectively. Rates of macrosomia by group were 7.8%, 6.1%, and 12.1%, respectively. Compared with glucose challenge test values less than 120 mg/dL, the adjusted odds ratios (ORs) (95% confidence intervals [CIs]) for values of 140–199 mg/dL were 1.48 (1.14–1.93) for the composite outcome, 1.97 (1.29–3.11) for LGA, and 1.61 (1.07–2.49) for macrosomia. For glucose challenge test values of 135–139 mg/dL, adjusted ORs and 95% CIs were 0.75 (0.45–1.21), 1.04 (0.44–2.24), and 0.75 (0.30–1.66), respectively. The subcategories with glucose challenge test values of 140–144 mg/dL and 145–149 mg/dL also were associated with an increase in selected outcomes when compared with those with values less than 120 mg/dL. CONCLUSIONS: Glucose challenge test values of 135–139 mg/dL were not associated with adverse outcomes compared with values less than 120 mg/dL; however, glucose challenge test values of 140 mg/dL or more were associated with an increase in odds of the composite perinatal outcome, LGA, and macrosomia. LEVEL OF EVIDENCE: II

Laboratory abnormalities in pregnancy-associated hypertension: frequency and association with pregnancy outcomes

OBJECTIVE: To estimate the frequency of abnormal laboratory test results in pregnancy-associated hypertension and the relationship with pregnancy outcomes. METHODS: This was a secondary analysis of a multicenter trial of vitamin C and E for prevention of pregnancy-associated hypertension in low-risk nulliparous women. Laboratory abnormalities included: platelets less than 100,000/mm3, aspartate aminotransferase 100 units/L or greater, creatinine 1.5 mg/dL or greater, lactate dehydrogenase 600 units/L or greater, total bilirubin 1.2 mg/dL or greater, or evidence of hemolysis on peripheral smear. Mild pregnancy-associated hypertension was defined as blood pressure 140–159/90–109 mm Hg. Severe pregnancy-associated hypertension was defined as persistent blood pressure 160/110 mm Hg or greater, acute antihypertensive treatment, or any blood pressure elevation associated with clinical signs of end-organ dysfunction (one or more of headache, epigastric pain, blurred vision, pulmonary edema, eclampsia, or oliguria). Pregnancy outcomes were compared across four groups: I, mild hypertension alone; II, mild hypertension+abnormal laboratory values; III, severe pregnancy-associated hypertension alone; and IV, severe pregnancy-associated hypertension+abnormal laboratory values. RESULTS: Of 9,969 women, 2,752 (27.9%) developed pregnancy-associated hypertension and of these, laboratory abnormalities occurred in 7.3%. Laboratory abnormalities increased with severity of hypertension: mild hypertension alone (4.9%), severe hypertension alone (8.9%), and mild or severe hypertension with clinical signs of end-organ dysfunction (12.2%) (P for trend<.001). Compared with women with mild hypertension alone, the adjusted odds for the perinatal composite (2-fold to 4.8-fold in Category III–IV), preterm birth (2.1-fold to 7.8-fold in Category II–IV), and other adverse perinatal outcomes increase with disease severity, particularly with laboratory abnormalities and severe clinical signs. CONCLUSION: The frequency of abnormal laboratory values in women with pregnancy-associated hypertension increases with disease severity. Adverse perinatal outcomes increase in the presence of abnormal laboratory values, particularly in those with clinical signs, likely atttributable in part to the decision to deliver early. LEVEL OF EVIDENCE: II

Relationship between Excessive Gestational Weight Gain and Neonatal Adiposity in Women with Mild Gestational Diabetes Mellitus

OBJECTIVE: To evaluate the relationships among excessive gestational weight gain, neonatal adiposity, and adverse obstetric outcomes in women with mild gestational diabetes mellitus. METHODS: This is a secondary analysis of a multicenter randomized clinical trial of women with mild gestational diabetes mellitus. Based on self-reported prepregnancy body weight, gestational weight gain was categorized as excessive if it was greater than 2009 Institute of Medicine guidelines. Maternal outcomes and neonatal anthropomorphic characteristics were compared between women with excessive weight gain and those without excessive weight gain. Multiple linear and logistic regression analyses were performed to adjust for confounding factors. RESULTS: We studied 841 women who participated in the main trial and had prepregnancy body mass index (BMI) and delivery information available (n=431 treatment group, n=410 no treatment). After adjustment for factors including treatment and prepregnancy BMI, excessive weight gain remained associated with large for gestational age (adjusted odds ratio [OR] 2.94, 95% confidence interval [CI] 1.81–4.93), birth weight greater than 4,000 g (adjusted OR 2.56, 95% CI 1.54–4.40), preeclampsia (adjusted OR 2.96, 95% CI 1.35–7.03), and cesarean delivery for labor arrest (adjusted OR 2.37, 95% CI 1.30–4.44). In addition, excessive weight gain was independently associated with increased total neonatal fat (P<.001) and birth weight (P<.001). CONCLUSION: In women with both treated and untreated mild gestational diabetes mellitus, excessive gestational weight gain was independently associated with both greater birth weight and adiposity.

Carpenter-Coustan Compared With National Diabetes Data Group Criteria for Diagnosing Gestational Diabetes.

OBJECTIVE: Use of Carpenter-Coustan compared with National Diabetes Data Group criteria increases the number of women diagnosed with gestational diabetes mellitus (GDM) by 30–50%, but whether treatment of this milder GDM reduces adverse outcomes is unknown. We explored the effects of the diagnostic criteria used on the benefits of GDM treatment. METHODS: This was a secondary analysis of a randomized trial for treatment of mild GDM diagnosed using Carpenter-Coustan criteria. We evaluated the effect of treatment within two mutually exclusive diagnostic groups: 1) women who met the stricter National Diabetes Data Group as well as Carpenter-Coustan criteria (National Diabetes Data Group), and 2) those diagnosed by Carpenter-Coustan but not meeting National Diabetes Data Group criteria (Carpenter-Coustan only). Maternal outcomes examined were pregnancy-induced hypertension, shoulder dystocia, maternal weight gain, and cesarean delivery. Neonatal outcomes were large for gestational age, macrosomia (greater than 4,000 g), fat mass, small for gestational age, and a composite outcome of perinatal death, birth injury, hypoglycemia, hyperbilirubinemia, and hyperinsulinemia. Analysis of variance or the Breslow-Day test, as appropriate, was used to test for the interaction between diagnostic criteria and GDM treatment on the outcomes of interest. RESULTS: Of 958 patients, 560 (58.5%) met National Diabetes Data Group criteria and 398 (41.5%) met Carpenter-Coustan only. Compared with untreated women, the direction of treatment effect did not differ by diagnostic criteria used and was consistent with the original trial. The P value for interaction between diagnostic criteria and treatment status was not significant for any outcome. CONCLUSION: The overall beneficial treatment effect on pregnancy-induced hypertension, shoulder dystocia, cesarean delivery, and macrosomia was seen in patients diagnosed by the higher National Diabetes Data Group and by the lower thresholds of the Carpenter-Coustan criteria.

Pregnancy-associated hypertension in glucose-intolerant pregnancy and subsequent metabolic syndrome

OBJECTIVE: To evaluate whether pregnancy-associated hypertension (preeclampsia or gestational hypertension) among women with varying degrees of glucose intolerance during pregnancy is associated with maternal metabolic syndrome 5–10 years later. METHODS: This was an observational cohort study of women previously enrolled in a treatment trial of mild gestational diabetes mellitus or an observational study of lesser degrees of glucose intolerance evaluated 5–10 years after their index pregnancy. At follow-up, women underwent anthropometric and blood pressure measurements and analysis of fasting glucose and serum lipids. RESULTS: A total of 825 women (47% of eligible women from the original study) were included in this analysis and evaluated at a median 7 years after their index pregnancy at a median age of 35 years. Overall, 239 (29%) had subsequent metabolic syndrome. The frequency of metabolic syndrome and its components was highest in the women who had pregnancy-associated hypertension and delivered preterm. After adjusting for confounding factors, pregnancy-associated hypertension in women who delivered preterm was associated with subsequent hypertension (130/85 mm Hg or greater; relative risk 3.06, 95% confidence interval [CI] 1.95–4.80, P<.001), high triglycerides (150 mg/dL or greater; relative risk 1.82, 95% CI 1.06–3.14, P=.03), and metabolic syndrome (per the American Heart Association and National Heart Lung and Blood Institute Scientific Statement; relative risk 1.78, 95% CI 1.14–2.78, P=.01) compared with women who remained normotensive throughout their index pregnancy and were delivered at term. CONCLUSION: Women with varying degrees of glucose intolerance who experienced pregnancy-associated hypertension and then delivered preterm had a higher frequency of subsequent hypertension, high triglycerides, and metabolic syndrome 5–10 years later.

Association of Recorded Estimated Fetal Weight and Cesarean Delivery in Attempted Vaginal Delivery at Term

OBJECTIVE: To evaluate the association between documentation of estimated fetal weight, and its value, with cesarean delivery. METHODS: This was a secondary analysis of a multicenter observational cohort of 115,502 deliveries from 2008 to 2011. Data were abstracted by trained and certified study personnel. We included women at 37 weeks of gestation or greater attempting vaginal delivery with live, nonanomalous, singleton, vertex fetuses and no history of cesarean delivery. Rates and odds ratios (ORs) were calculated for women with ultrasonography or clinical estimated fetal weight compared with women without documentation of estimated fetal weight. Further subgroup analyses were performed for estimated fetal weight categories (less than 3,500, 3,500–3,999, and 4,000 g or greater) stratified by diabetic status. Multivariable analyses were performed to adjust for important potential confounding variables. RESULTS: We included 64,030 women. Cesarean delivery rates were 18.5% in the ultrasound estimated fetal weight group, 13.4% in the clinical estimated fetal weight group, and 11.7% in the no documented estimated fetal weight group (P<.001). After adjustment (including for birth weight), the adjusted OR of cesarean delivery was 1.44 (95% confidence interval [CI] 1.31–1.58, P<.001) for women with ultrasound estimated fetal weight and 1.08 for clinical estimated fetal weight (95% CI 1.01–1.15, P=.017) compared with women with no documented estimated fetal weight (referent). The highest estimates of fetal weight conveyed the greatest odds of cesarean delivery. When ultrasound estimated fetal weight was 4,000 g or greater, the adjusted OR was 2.15 (95% CI 1.55–2.98, P<.001) in women without diabetes and 9.00 (95% CI 3.65–22.17, P<.001) in women with diabetes compared to those with estimated fetal weight less than 3,500 g. CONCLUSION: In this contemporary cohort of women attempting vaginal delivery at term, documentation of estimated fetal weight (obtained clinically or, particularly, by ultrasonography) was associated with increased odds of cesarean delivery. This relationship was strongest at higher fetal weight estimates, even after controlling for the effects of birth weight and other factors associated with increased cesarean delivery risk.

Pregnancies after the diagnosis of mild gestational diabetes mellitus and risk of cardiometabolic disorders

OBJECTIVEnTo assess the association of subsequent pregnancy with subsequent metabolic syndrome and type II diabetes mellitus after a pregnancy complicated by mild gestational diabetes mellitus (GDM).nnnMETHODSnWe conducted a prospective observational follow-up study of women with mild GDM randomized from 2002 to 2007 to usual care or dietary intervention and glucose self-monitoring. Women were evaluated 5-10 years after the parent study. Participants were grouped according to the number of subsequent pregnancies (group A, none [reference]; group B, one; group C, two or greater). Serum triglycerides, glucose tolerance, high-density lipoprotein cholesterol, blood pressure, and waist circumference were assessed. Metabolic syndrome was diagnosed by American Heart Association and National Heart Lung and Blood Institute criteria. Multivariable regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs).nnnRESULTSnOf 905 eligible women from the original trial, 483 agreed to participate, 426 of whom were included in this analysis. Groups A, B, and C consisted of 212, 143, and 71 women, respectively. Of women with subsequent pregnancies, 32% (69/214) had another pregnancy complicated with GDM. No difference between groups was observed for metabolic syndrome (group A, 34%; group B, 33%; group C, 30%). Subsequent pregnancies were associated with diabetes mellitus outside of pregnancy (group A, 5.2%; group B, 10.5%, RR 2.62, 95% CI 1.16-5.91; group C, 11.3%, RR 2.83, 95% CI 1.06-7.59), and if complicated with GDM (no subsequent GDM pregnancy, RR 1.99, 95% CI 0.82-4.84; subsequent GDM pregnancy, RR 3.75, 95% CI 1.60-8.82).nnnCONCLUSIONnIn women with prior mild GDM, subsequent pregnancies did not increase the frequency of metabolic syndrome, but subsequent pregnancies with GDM increased the risk of diabetes mellitus outside of pregnancy.

Association of Cervical Effacement With the Rate of Cervical Change in Labor Among Nulliparous Women.

OBJECTIVE: To assess the association of cervical effacement with the rate of intrapartum cervical change among nulliparous women. METHODS: We conducted a secondary analysis of a prospective trial of intrapartum fetal pulse oximetry. For women who had vaginal deliveries, interval-censored regression was used to estimate the time to dilate at 1-cm intervals. For each given centimeter of progressive cervical dilation, women were divided into those who had achieved 100% cervical effacement and those who had not. The analysis was performed separately for women in spontaneous labor and those who were given oxytocin. RESULTS: A total of 3,902 women were included in this analysis, 1,466 (38%) who underwent labor induction, 1,948 (50%) who underwent labor augmentation (combined for the analysis), and 488 (13%) who labored spontaneously. For women in spontaneous labor, the time to dilate 1 cm was shorter for those who were 100% effaced starting at 4 cm of cervical dilation (P=.01 to <.001). For women who received oxytocin, the time to dilate 1 cm was shorter for those who were 100% effaced throughout labor (P<.001). CONCLUSION: The rate of cervical dilation among nulliparous women is associated with not only the degree of cervical dilation, but also with cervical effacement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00098709.