Paul Speer

Elevated asymmetric dimethylarginine concentrations precede clinical preeclampsia, but not pregnancies with small-for-gestational-age infants.

OBJECTIVE The purpose of this study was to investigate maternal plasma concentrations of asymmetric dimethylarginine (ADMA) in mid pregnancy and at the time of disease in women who experience preeclampsia, compared with women with uncomplicated pregnancies and women with small-for-gestational-age infants. STUDY DESIGN Plasma samples were collected at mid-pregnancy and at the time of delivery from 31 women with uncomplicated pregnancies, from 12 women with small-for-gestational-age infants, and from 15 women with preeclampsia. ADMA and L-arginine concentrations were measured using high-pressure liquid chromatography. RESULTS Maternal ADMA concentrations were elevated at mid pregnancy and remained elevated at delivery in women who later experienced preeclampsia (0.45 +/- 0.09 micromol/L) compared with women with uncomplicated pregnancies (0.34 +/- 0.08 micromol/L; P < .01) and with women with small-for-gestational-age infants (0.33 +/- 0.06 micromol/L; P < .01). CONCLUSION Maternal ADMA concentrations are higher in mid pregnancy in women who experience preeclampsia, compared with women with uncomplicated pregnancies and small-for-gestational-age infants. Elevated ADMA concentration before clinical onset of preeclampsia suggests a role of this nitric oxide synthase inhibitor in the pathophysiologic condition of preeclampsia.

A customized standard of large size for gestational age to predict intrapartum morbidity

OBJECTIVE The purpose of this study was to determine whether a customized standard of large-for-gestational age (LGA) identifies pregnancies with increased perinatal risk. STUDY DESIGN We evaluated 7510 estimates of fetal weight to generate a fetal growth curve. Next, we analyzed the gestational age at delivery, physiologic and pathological variables from 5072 pregnancies to predict birthweight, and calculated a customized ideal birthweight and cutoff for LGA. In a separate analysis of 32,271 pregnancies, rates of macrosomia-related adverse outcomes were compared in pregnancies that had been identified as LGA by a customized standard (LGA(cust)) and those pregnancies that had been identified as LGA or macrosomic by conventional standards. RESULTS LGA(cust) pregnancies carried increased risk of shoulder dystocia, third- or fourth-degree laceration, and cephalopelvic disproportion. LGA(cust) pregnancies that did not meet conventional criteria for LGA/macrosomia were at increased risk of all measured outcomes. CONCLUSION A customized standard of LGA identifies a previously unrecognized population that is at increased risk of perinatal morbidity.

Risk of morbid perinatal outcomes in small-for-gestational-age pregnancies: customized compared with conventional standards of fetal growth.

OBJECTIVE: To estimate and compare the risk of morbid perinatal outcomes in pregnancies identified as small for gestational age (SGA) with customized compared with conventional standards of fetal growth. METHODS: Ultrasound-derived estimates of fetal weight were used to generate a fetal growth trajectory (N=7,510). The gestational age at delivery and pathologic and physiologic variables from 5,072 pregnancies were used to calculate a customized threshold for SGA. In a separate analysis of 32,070 pregnancies, rates of morbid outcomes were compared in participants classified as SGA according to a population-based birth weight standard only (SGApop only), a customized standard only (SGAcust only), and both methods (SGAboth). RESULTS: Eight-hundred seventy-five (2.7%) participants were SGApop only, 1,970 (6.1%) participants were SGAboth, and 609 (1.9%) participants were SGAcust only. The odds ratios of neonatal death in SGApop only and SGAcust only pregnancies were 1.78 (95% confidence interval [CI] 0.2–13.1) and 54.6 (95% CI 29.0–102.8), respectively. Rates of prematurity in the SGApop only and SGAcust only cohorts were 4.8% and 64.5%, respectively. After adjustment for the effect of prematurity, odds ratios of neonatal death in the SGApop only and SGAcust only cohorts were 4.8 (95% CI 0.6–37.0) and 2.9 (95% CI 1.4–6.1), respectively. CONCLUSION: After adjustment for confounding stemming from premature delivery, there is little difference in the risk of adverse outcomes between SGAcust only and SGApop only participants. Adoption of customized fetal growth standards into clinical practice may not improve the ability to identify pregnancies with increased risk of perinatal morbidity. LEVEL OF EVIDENCE: II

Large-for-Gestational-Age Ultrasound Diagnosis and Risk for Cesarean Delivery in Women With Gestational Diabetes Mellitus.

OBJECTIVE: To assess the accuracy of a large-for-gestational-age (LGA) ultrasound diagnosis and the subsequent risk for cesarean delivery associated with ultrasound diagnosis of LGA among women with gestational diabetes mellitus. METHODS: This was a retrospective cohort study of 903 women with GDM who delivered after 36 weeks of gestation with an ultrasound-estimated fetal weight within 31 days of delivery. Delivery outcomes were compared between women with an ultrasound diagnosis of LGA and a non-LGA ultrasound diagnosis. RESULTS: Based on ultrasound assessments, we identified 248 women with an LGA fetus and 655 women with a non-LGA fetus. Among women with an LGA ultrasound diagnosis, 56 of 248 (22.6%) delivered an LGA neonate, whereas, of women with a non-LGA ultrasound diagnosis, 18 of 655 (2.8%) delivered an LGA neonate. Ultrasound diagnosis of LGA was associated with increased risk for cesarean delivery (adjusted odds ratio [OR] 3.13, 95% confidence interval [CI] 2.10–4.67, P<.001) after adjusting for relevant covariates. Stratified analyses demonstrated that ultrasound diagnosis of LGA was associated with an increased risk for cesarean delivery whether the birth weight was between 2,500 and 3,499 g (OR 2.82, 95% CI 1.62–4.84, P<.001) or between 3,500 and 4,500 g (OR 3.47, 95% CI 2.06–5.88, P<.001). CONCLUSION: Ultrasonography significantly overestimates the prevalence of LGA in women with gestational diabetes mellitus, and an ultrasound diagnosis of LGA is associated with an increased risk for cesarean delivery independent of birth weight. LEVEL OF EVIDENCE: II