Mark B. Landon

Frequency of congenital varicella syndrome in a prospective cohort of 347 pregnant women

OBJECTIVE To estimate the rate of congenital varicella zoster virus syndrome in neonates born to women developing varicella zoster virus infections during pregnancy. METHODS Pregnant women with clinical varicella zoster virus infection were enrolled at ten perinatal centers. Maternal and fetal immunoglobulin (Ig) G and IgM by fluorescent antibody confirmed 74.3% of cases. Specialists examined neonates at 0–6 months, 7–18 months, and 19–30 months after delivery to detect abnormalities of their eyes, hearing, and physical and developmental features. A hierarchical set of criteria was used to define congenital varicella syndrome. A jury of four investigators assigned the classification of all findings. RESULTS In 362 women enrolled from 1993 to 1996, 15 had herpes zoster, and 347 had primary varicella zoster virus infection. Varicella zoster virus affected 140 women (38.7%) in the first trimester, 122 (33.7%) in the second trimester, and 100 (27.6%) in the third trimester. Five twin pairs were included. Only one case (0.4%) of definite congenital varicella syndrome was found, a 3360‐g female infant having a left retinal macular lesion with typical skin scars after maternal varicella at 24 weeks. The maternal blood sample at birth was negative for IgG antibodies to toxoplasmosis and cytomegalovirus. Two cases involved fetal death at 20 weeks and fetal hydrops at 17 weeks after maternal varicella at 11 and 5 weeks, respectively. We found no cases of limb hypoplasia, microcephalus, or cataract. CONCLUSION The frequency of congenital varicella syndrome is very low (0.4%) in a prospectively studied cohort. Eye examinations of exposed infants had a low yield.

The preterm prediction study: Patterns of cervicovaginal fetal fibronectin as predictors of spontaneous preterm delivery

OBJECTIVEnOur purpose was to determine how various temporal patterns of fetal fibronectin positivity from 24 to 30 weeks predict subsequent fetal fibronectin test results and spontaneous preterm delivery.nnnSTUDY DESIGNnA total of 2929 women had vaginal and cervical fetal fibronectin tests obtained at least once at 24, 26, 28, or 30 weeks, and 1870 women had tests performed at all four gestational ages. Fetal fibronectin values > or = 50 ng/ml were considered positive. Various patterns of positive and negative tests were evaluated for prediction of (1) whether the next fetal fibronectin test would be positive or negative and (2) the percent of women with a spontaneous preterm delivery > or = 4 weeks after the last fetal fibronectin test at < 30, < 32, < 35, and < 37 weeks gestational age.nnnRESULTSnWomen with previous negative test results had only a 3% chance of a subsequent positive test result; however, if the last test result was positive, 29% of the next tests were positive. Of the 1870 women with tests at 24, 26, 28, and 30 weeks, 89% had all negative results, 8.4% had one positive result, 1.8% had two positive results, and 0.8% had three or four positive results. The higher the percent of positive tests at 24 to 26 weeks, at 28 to 30 weeks, or at 24 to 30 weeks, the greater the risk of subsequent spontaneous preterm birth. As an example, the risk of spontaneous preterm birth at < 30 weeks for women with two negative fetal fibronectin test results at 24 and 26 weeks was 0.3% versus 16% for women with two positive results.nnnCONCLUSIONnThe presence of a positive cervical or vaginal fetal fibronectin test result predicts subsequent positive fetal fibronectin positivity and subsequent spontaneous preterm birth. The greater the percent of positive results, the higher is the risk of spontaneous preterm birth. After a positive test result, two negative results are required before the risk of spontaneous preterm birth returns to baseline.

Timing of Delivery and Adverse Outcomes in Term Singleton Repeat Cesarean Deliveries

OBJECTIVE: To compare the maternal and neonatal risks of elective repeat cesarean delivery compared with pregnancy continuation at different gestational ages, starting from 37 weeks. METHODS: We analyzed the composite maternal and neonatal outcomes of repeat cesarean deliveries studied prospectively over 4 years at 19 U.S. centers. Maternal outcome was a composite of pulmonary edema, cesarean hysterectomy, pelvic abscess, thromboembolism, pneumonia, transfusion, or death. Composite neonatal outcome consisted of respiratory distress, transient tachypnea, necrotizing enterocolitis, sepsis, ventilation, seizure, hypoxic–ischemic encephalopathy, neonatal intensive care unit admission, 5-minute Apgar of 3 or lower, or death. Outcomes after elective repeat cesarean delivery without labor at each specific gestational age were compared with outcomes for all who were delivered later as a result of labor onset, specific obstetric indications, or both. RESULTS: Twenty-three thousand seven hundred ninety-four repeat cesarean deliveries were included. Elective delivery at 37 weeks of gestation had significantly higher risks of adverse maternal outcome (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.06–2.31), whereas elective delivery at 39 weeks of gestation was associated with better maternal outcome when compared with pregnancy continuation (OR 0.51, 95% CI 0.36–0.72). Elective repeat cesarean deliveries at 37 and 38 weeks of gestation had significantly higher risks of adverse neonatal outcome (37 weeks OR 2.02, 95% CI 1.73–2.36; 38 weeks OR 1.39 95% CI 1.24–1.56), whereas delivery at 39 and 40 weeks of gestation presented better neonatal outcome as opposed to pregnancy continuation (39 weeks OR 0.79, 95% CI 0.68–0.92; 40 weeks OR 0.57, 95% CI 0.43–0.75). CONCLUSION: In women with prior cesarean delivery, 39 weeks of gestation is the optimal time for repeat cesarean delivery for both mother and neonate. LEVEL OF EVIDENCE: II

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.

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

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

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.