Lisa Mele

The relationship between maternal glycemia and perinatal outcome.

OBJECTIVE: To examine the relationship between varying degrees of maternal hyperglycemia and pregnancy outcomes. METHODS: This was a secondary analysis of a treatment trial for mild gestational diabetes including four cohorts: 1) 473 women with untreated mild gestational diabetes; 2) 256 women with a positive 50-g screen and one abnormal oral glucose tolerance test (OGTT) value; 3) 675 women with a positive screen and no abnormal OGTT values; and 4) 437 women with a normal 50-g screen. Groups were compared by test of trend for a composite perinatal outcome (neonatal hypoglycemia, hyperbilirubinemia, elevated cord C-peptide level, and perinatal trauma or death), frequency of large for gestational age neonates, shoulder dystocia, and pregnancy-related hypertension. Three-hour OGTT levels (fasting, 1-, 2-, and 3-hour) levels were divided into categories and analyzed for their relationship to perinatal and maternal outcomes. RESULTS: There were significant trends by glycemic status among the four cohorts for the composite and all other outcomes (P<.001). Analysis for trend according to OGTT categories showed an increasing relationship between fasting and all postload levels and the various outcomes (P<.05). Fasting glucose 90 mg/dL or greater and 1 hour 165 mg/dL or greater were associated with an increased risk for the composite outcome (odds ratios and 95% confidence intervals of 2.0 [1.03–4.15] and 1.46 [1.02–2.11] to 1.52 [1.08–2.15] for the fasting and 1 hour, respectively). A 1 hour glucose 150 mg/dL or greater was associated with an increased risk for large for gestational age (odds ratios, 1.8 [1.02–3.18] to 2.35 [1.35–4.14]); however, 2- and 3-hour glucose levels did not increase the risk for the composite or large for gestational age until well beyond current gestational diabetes diagnostic thresholds. CONCLUSION: A monotonic relationship exists between increasing maternal glycemia and perinatal morbidity. Current OGTT criteria require reevaluation in determining thresholds for the diagnosis and treatment of gestational diabetes. LEVEL OF EVIDENCE: II

Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: has the dose been too low?

OBJECTIVE Inconsistent effects of vitamin A supplementation on prevention of bronchopulmonary dysplasia have been reported. Meta-analysis of these reports resulted in a relative risk of 0.69-1.02 for death or bronchopulmonary dysplasia associated with vitamin A supplementation. Effective dosage regimens or serum retinol concentrations have not been determined in previous reports. The purpose of this pilot study was to define a vitamin A regimen that produces serum retinol concentrations of 25-55 micrograms/dl. STUDY DESIGN In this three-phase study, 91 infants (mean birth weight 799-864 g) were enrolled. Vitamin A was administered three times/week for 4 weeks at an average daily dose of 986-2143 IU/day. Physical examinations were performed and serum retinol specimens were collected weekly to assess clinical signs of toxicity. RESULTS The majority of serum retinol concentrations remained < 25 micrograms/dl until an intramuscular vitamin A dose of 5000 IU/dose three times/week was used. No clinical signs of toxicity were associated with the higher dosage and higher serum concentrations of vitamin A. CONCLUSION A large clinical trial of vitamin A supplementation with 5000 IU/dose three times/week (25-114% more than the dose used in the three published clinical trials) is needed to assess whether vitamin A supplementation safely reduces the risk of bronchopulmonary dysplasia in very-low-birth-weight infants.

The national institute of child health and human development maternal-fetal medicine unit network randomized clinical trial in progress : Standard therapy versus no therapy for mild gestational diabetes

It is recognized that women with gestational diabetes mellitus (GDM) who have significantly elevated fasting blood glucose levels are at increased risk for fetal macrosomia and perinatal morbidity if treatment is not provided (1,2). The association of milder forms of GDM with perinatal morbidity and mortality remains unclear, primarily because the condition is often confounded with other risk factors such as maternal obesity, age, and parity. Screening for GDM is recommended for most pregnant women, yet it is unknown whether there is a benefit to the identification and treatment of mild carbohydrate intolerance during pregnancy (3,4). The present report is an update of our previous description of a current ongoing randomized treatment trial for mild GDM (5). A randomized clinical trial of women with mild GDM (fasting glucose <95 mg/dl) is being undertaken that compares perinatal outcomes in those receiving diet therapy and insulin as required versus those randomized to no specific treatment. This study aims to clarify whether there is utility in identifying and treating women with a normal fasting glucose level who meet standard criteria for GDM. We plan to compare perinatal outcomes in women who have been randomized to diet and/or insulin therapy with women who have been randomized to no specific treatment. A randomized treatment trial of mild GDM will clarify whether identification and treatment of mild GDM reduce perinatal morbidity. This information will assist in determining appropriate thresholds for the treatment of GDM. Overall, with broader identification and aggressive treatment, perinatal mortality rates associated with GDM appear to be similar to the nondiabetic population (1). Several analyses of 20 years ago did document an increased stillbirth rate for GDM pregnancies that would qualify as preexisting diabetes according to World Health Organization criteria (6–9). Below this threshold, the extent to …

Placental villous hypermaturation is associated with idiopathic preterm birth.

Abstract Objective: Pregnancy complications such as intra-amniotic infection, preeclampsia, and fetal intrauterine growth restriction (IUGR) account for most cases of preterm birth (PTB), but many spontaneous PTB cases do not have a clear etiology. We hypothesize that placental insufficiency may be a potential cause of idiopathic PTB. Methods: Secondary analysis of 82 placental samples from women with PTB obtained from a multicenter trial of repeat versus single antenatal corticosteroids. Samples were centrally reviewed by a single placental pathologist masked to clinical outcomes. The histopathologic criterion for infection was the presence of acute chorioamnionitis defined as neutrophils marginating into the chorionic plate. Placental villous hypermaturation (PVH) was defined as a predominance of terminal villi (similar to term placenta) with extensive syncytial knotting. Idiopathic PTB comprised a group without another known etiology such as preeclampsia, IUGR or infection. Results: Acute chorioamnionitis was observed in 33/82 (40%) cases. Other known causes of PTB were reported in 18/82 (22%). The remaining 31/82 (38%) were idiopathic. The frequency of PVH in idiopathic PTB (26/31 = 84%) was similar to cases with IUGR or preeclampsia (16/18 = 89%), but significantly more common than PVH in the group with acute chorioamnionitis (10/33 = 30%) (p < 0.001). Conclusions: PVH, which is a histologic marker of relative placental insufficiency, is a common finding in idiopathic PTB.

Serum bilirubin levels at 72 hours by selected characteristics in breastfed and formula‐fed term infants delivered by cesarean section

The present multicenter study analysed the relative impact of maternal and infant factors on serum bilirubin levels at 72 ± 12 h in exclusively breastfed vs formula‐fed term infants. End‐tidal carbon monoxide levels corrected for ambient air (ETCOc), an index of bilirubin production, were measured in exclusively breastfed (B = 66) or formula‐fed (F = 210) term infants at 2–8 h of age. Inclusion criteria included cesarean section to ensure a 3 d hospitalization, birthweight ±2500 g, gestational age ±37 wk and absence of any illness. The ETCOc for B infants and F infants did not differ significantly (1.3 ± 0.7 ppm vs 1.3 ± 0.8 ppm). The serum bilirubin level at 72 ± 12 h was significantly higher in B infants than in F infants (8.5 ± 3.4mg dl−1 vs 6.7 ± 3.4 mg d l−1, p < 0.001), as was the percentage weight loss from birthweight. Serum bilirubin levels were significantly higher in infants who were male, who did not have meconium‐stained amniotic fluid, and in those whose mothers were insulin‐dependent diabetics or hypertensive. There was no difference between groups in the need for phototherapy or exchange transfusion.

Umbilical cord serum interleukin-6, C-reactive protein, and myeloperoxidase concentrations at birth and association with neonatal morbidities and long-term neurodevelopmental outcomes

OBJECTIVE The aim of the study is to determine if umbilical cord serum concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and myeloperoxidase (MPO), in pregnancies at risk for preterm birth (PTB), are associated with neonatal morbidities and/or altered neurodevelopmental outcomes in the children. STUDY DESIGN Umbilical cord serum samples were collected at birth from 400 newborns delivered within a multicenter randomized controlled trial of repeated versus single course of antenatal corticosteroids (ACs), in women at increased risk for PTB. Newborns were followed through discharge and were evaluated between 36 and 42 months corrected age with neurological examination and Bayley Scales of Infant Development. Umbilical cord serum concentrations of IL-6, CRP, and MPO were determined using enzyme-linked immunoassays. Multivariate logistic regression analyses explored the relationship between umbilical cord serum IL-6, CRP, and MPO levels, adverse newborn outcomes, and PTB < 32 weeks of gestational age (GA). RESULTS Univariate analysis revealed that umbilical cord IL-6 above the 75th percentile was associated with increased respiratory distress syndrome (RDS) and chronic lung disease (CLD), but not with necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), or neonatal sepsis; however, this association was not significant after adjusting for GA at delivery and treatment group. No significant associations between CRP or MPO and RDS, CLD, NEC, sepsis, or IVH were evident. Regression analysis revealed that CRP above the 75th percentile was associated with a decreased risk of CLD (odds ratio, 0.10; 95% confidence interval, 0.02-0.41). No associations between umbilical cord IL-6, CRP, or MPO and MDI < 70 or PDI < 70 were evident. Umbilical cord serum concentrations of IL-6, CRP, and MPO, above the 75th percentile, were associated with more frequent PTB < 32 weeks of GA. CONCLUSION Elevated umbilical cord serum concentration of CRP is associated with reduced risk for CLD even after adjusting for GA at delivery. Occurrence of levels > 75th percentile of IL-6, CRP, and MPO in umbilical cord serum was associated with PTB < 32 weeks of GA. Elevated umbilical cord serum concentrations of IL-6, CRP, and MPO at birth were not associated with poor neurodevelopmental outcomes.

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

Glycemic characteristics and neonatal outcomes of women treated for mild gestational diabetes

OBJECTIVE: To estimate the association between fasting and 2-hour postprandial blood glucose levels and neonatal outcomes in women treated for mild gestational diabetes. METHODS: In this secondary analysis of a multicenter randomized treatment trial of mild gestational diabetes, the median fasting and 2-hour postprandial glucose levels were analyzed in 2-week intervals and change over time (slope) was calculated for women with gestational diabetes (abnormal oral glucose tolerance test) and a fasting glucose less than 95 mg/dL who received nutritional management with self blood glucose monitoring and insulin as needed. Regression analyses were performed to estimate the relationship between median fasting and postprandial glucose and neonatal fat mass, cord blood C-peptide, birth weight, large-for-gestational-age neonates, macrosomia (greater than 4,000 g), and neonatal hypoglycemia. RESULTS: Among 460 women with gestational diabetes, median fasting (P<.001), postprandial breakfast (P<.001), and postprandial lunch (P<.001) glucose values declined over the treatment period, whereas postprandial dinner values remained stable (P=.83). Higher median fasting glucose during the first 2 weeks of treatment was significantly associated with increased odds ratios for neonatal fat mass (1.35; 95% CI 1.09–1.66; P=.006) and elevated C-peptide (1.29; CI 1.09–1.52; P=.003). Higher median fasting glucose during the last 2 weeks before delivery was associated with higher rates of large-for-gestational-age neonates (1.27; CI 1.05–1.53; P=.01), macrosomia (1.32; CI 1.04–1.65; P = .02), and elevated C-peptide (1.19; CI 1.03–1.38; P=.02). CONCLUSION: In women treated for mild gestational diabetes, higher fasting glucose during initiation of diet therapy was associated with increased neonatal fat mass and elevated C-peptide and during the last 2 weeks before delivery with macrosomia, large-for-gestational age, and elevated C-peptide. LEVEL OF EVIDENCE: II

Neurodevelopmental and Functional Outcome of Extremely Low Birth Weight(ELBW) Infants. † 1362

Neurodevelopmental and Functional Outcome of Extremely Low Birth Weight(ELBW) Infants. † 1362

Fetal male gender and the benefits of treatment of mild gestational diabetes mellitus

OBJECTIVE We evaluated whether improvements in pregnancy outcomes after treatment of mild gestational diabetes mellitus differed in magnitude on the basis of fetal gender. STUDY DESIGN This is a secondary analysis of a masked randomized controlled trial of treatment for mild gestational diabetes mellitus. The results included preeclampsia or gestational hypertension, birthweight, neonatal fat mass, and composite adverse outcomes for both neonate (preterm birth, small for gestational age, or neonatal intensive care unit admission) and mother (labor induction, cesarean delivery, preeclampsia, or gestational hypertension). After stratification according to fetal gender, the interaction of gender with treatment status was estimated for these outcomes. RESULTS Of the 469 pregnancies with male fetuses, 244 pregnancies were assigned randomly to treatment, and 225 pregnancies were assigned randomly to routine care. Of the 463 pregnancies with female fetuses, 233 pregnancies were assigned randomly to treatment, and 230 pregnancies were assigned randomly to routine care. The interaction of gender with treatment status was significant for fat mass (P = .04) and birthweight percentile (P = .02). Among women who were assigned to the treatment group, male offspring were significantly more likely to have both a lower birthweight percentile (50.7 ± 29.2 vs 62.5 ± 30.2 percentile; P < .0001) and less neonatal fat mass (487 ± 229.6 g vs 416.6 ± 172.8 g; P = .0005,) whereas these differences were not significant among female offspring. There was no interaction between fetal gender and treatment group with regard to other outcomes. CONCLUSION The magnitude of the reduction of a newborns birthweight percentile and neonatal fat mass that were related to the treatment of mild gestational diabetes mellitus appears greater for male neonates.