George Kazzi

Identifying the pregnancy at risk for intrauterine growth retardation: Possible usefulness of the intravenous glucose tolerance test☆

Antenatal detection of intrauterine growth retardation (IUGR) remains problematic. Previous animal and human studies have documented a relationship between increased substrate delivery to the fetus, e.g., in diabetes mellitus, and the birth of large-for-gestational age infants. The purpose of the study of 55 pregnancies, in which intravenous glucose tolerance tests (IVGTTs) were performed during the third trimester, was to examine the hypothesis that evidence of decreased availability of substrates for fetal growth precedes the birth of small-for-gestational age (SGA) infants; hence, the IVGTT might be useful for the detection of pregnancies complicated by IUGR. Increased glucose utilization rates (kt) and 10-minute plasma glucose concentrations and decreased plasma glucose concentrations at fasting and 60 minutes were found to be significantly associated with decreased infant birth weight, adjusted for gestational age. The Kt and 10- and 60-minute glucose values together could account for 40% of the variance in age-adjusted birth weight (r = 0.63, p less than 0.01). The IVGTTs in the pregnancies resulting in the birth of SGA infants were characterized by kt greater than 2 and plasma glucose levels at fasting of less than 64 mg/dl, at 10 minutes of greater than 193 mg/dl, and at 60 minutes of less than 82 mg/dl. When the kt was greater than 2, six (30%) of 20 infants were SGA; when the kt was less than or equal to 2, none (0%) of the 35 infants was SGA. These results suggest that, regardless of the underlying reason for the association, parameters of maternal glucose metabolism may be useful in detecting the pregnancy at risk for IUGR.

The relationship of placental grade, fetal lung maturity, and neonatal outcome in normal and complicated pregnancies

Ultrasonically diagnosed maturity changes in the placenta, Grades 0 to III, have been previously shown to correlate with fetal lung maturity. In a prospective study of 230 term and preterm complicated pregnancies, we compared the relationship between sonographic placental grading, amniotic fluid phospholipids, and neonatal outcome. The frequencies of gestational age less than 38 weeks, lecithin/sphingomyelin (L/S) ratio less than 2.0, negative phosphatidylglycerol, and neonatal hyaline membrane disease were found to decrease as placental grade advanced from 0 to III. Patients were divided into subgroups on the basis of maternal complications. In patients with Grade III placentas, the frequencies of gestational age less than 38 weeks and L/S ratio less than 2.0 were significantly increased when the subgroup of patients with chronic hypertension was compared individually to both of the subgroups, repeat cesarean section deliveries, and Classes A, B, and C diabetes mellitus (both with p less than 0.05) All three infants who developed hyaline membrane disease in association with Grade III placentas were from pregnancies of less than 38 weeks complicated by chronic hypertension. These findings suggest that the presence of a Grade III placenta is affected by both gestational age and pregnancy complications. Hence, when an elective cesarean section delivery is being planned near term gestation, a Grade III placenta is a reliable predictor of lung maturity. In preterm complicated pregnancies, an ultrasound-diagnosed Grade III placenta may still be associated with hyaline membrane disease.

Noninvasive prediction of hyaline membrane disease: An optimized classification of sonographic placental maturation

Accurate prediction of fetal pulmonary maturity by means of a less invasive procedure than amniocentesis would be desirable. Sonographic diagnosis of a Grade III placenta has been reported to be an excellent predictor of fetal lung maturity. The standard classification of placental grading assigns grade according to the most advanced portion of the placenta. Using this classification, we studied 230 patients. In 80 pregnancies with Grade III placenta, three of the neonates developed respiratory distress syndrome. With reclassification of the placentas as immature, (no Grade III areas), intermediate, (only a portion of the placenta being Grade III), or mature, (Grade III placenta throughout), it was found that no neonatal hyaline membrane disease occurred in the 41 pregnancies with mature placentas, whereas 12% of the neonates in the immature group and 8% in the intermediate group developed hyaline membrane disease. These findings suggest that when sonographic examination of the placenta shows both Grade III and non-Grade III sections, there is still a risk for an immature amniotic fluid lecithin/sphingomyelin ratio and neonatal hyaline membrane disease. The placentas should be considered mature only when Grade III changes are present in all sections examined by ultrasound.

When is an amniocentesis for fetal maturity unnecessary in nondiabetic pregnancies at risk

For several years standard obstetric practice has been to perform an amniocentesis for evaluation of fetal maturity. In order to provide a more definitive answer as to which pregnancies need an amniocentesis, a group of 294 nondiabetic pregnant women in whom an amniocentesis for the evaluation of fetal maturity had been performed for clinical indications were evaluated. Three predictors of fetal maturity--obstetric estimate of gestational age, fetal biparietal diameter, and ultrasonic determination of placental maturation--were evaluated for their ability to predict three outcomes of fetal maturity, including positive amniotic fluid phosphatidylglycerol, pediatric estimate of gestational age greater than or equal to 38 weeks, and absence of hyaline membrane disease. A fetal biparietal diameter of greater than or equal to 90 mm was present in 36% of the total population and was associated with 97% term delivery, 87% positive amniotic fluid phosphatidylglycerol, and 0% hyaline membrane disease. The results associated with an obstetric estimate of gestational age of greater than or equal to 38 weeks were similar. In the present data set over one third of clinically indicated amniocenteses could potentially be avoided without losing any predictive capability for fetal maturity.

Neonatal Complications Following in Utero Exposure to Intravenous Ritodrine

Intravenous administration of ritodrine for tocolysis has been associated with maternal cardiovascular and metabolic changes. Studies with other tocolytic agents, such as isoxsuprine, have shown an increased neonatal morbidity among infants born soon after failure of such therapy. We examined the potential side effects of maternal intravenous ritodrine therapy in 58 neonates born within 12 h following discontinuation of maternal medication. ‘Low dextrostix’ was significantly greater in the ritodrine exposed neonates (p<0.05) than in the controls. It occurred within a mean 1.0±0.5 h following birth. The mean 1 min and 5 min Apgar scores, neonatal pH, bicarbonate levels, hypotension and neonatal mortality were comparable in the ritodrine‐exposed and control groups of neonates. The occurrence of any of the neonatal morbidity variables, including ‘low dextrostix’ was not related either to the total dose of ritodrine used or to the interval between drug discontinuation and delivery. Administration of ritodrine by the standard protocol to stop preterm labor is not associated with any significant increase in neonatal morbidity.

Preterm Birth Rate Following Surgical Correction of Uterine Septum/Arcuate Uterus in Singleton Gestations [30E]

INTRODUCTION: This study compared preterm birth rate, gestational age at delivery and neonatal birth weights in singleton gestations, in a cohort of women with primary infertility and a surgically corrected uterine anomaly to those with normal uterine cavity. METHODS: This retrospective cohort study included 265 patients between 1992–2011. The study group (106 patients) had primary infertility patients with hysteroscopically corrected incomplete uterine septum or arcuate uterus. The control group (159 patients) had primary infertility with normal uterine cavity by hysteroscopic evaluation. All patients conceived a singleton gestation via spontaneous conception (SC), or intrauterine insemination after controlled ovarian stimulation (IUI+COS), or in vitro fertilization and embryo transfer (IVF-ET). RESULTS: There was no significant difference in patient age, BMI, day 3 FSH levels, the incidence of male factor infertility or ovulatory disorders between the two groups. There was significantly lower duration of infertility (P<.01), incidence of tubal factors (P<.001) and endometriosis (P<.001) in the study group compared to the control group. There was no statistically significant differences in the incidence of preterm birth (17.9% vs 22.6%), mean gestational age at delivery in weeks (37.6±5.3 vs 37.9±3.8) and birth weight in kg (3.2+0.6 vs 3.3±0.6) between the study group and the control group respectively. CONCLUSION: Our data suggest that in patients with primary infertility and hysteroscopically corrected incomplete uterine septum or arcuate uterus, the incidence of preterm birth, gestational age, and birth weight appear to be similar to those patients with normal uterine cavities.

Preterm Birth Rate in Twin Gestation After Hysteroscopic Septoplasty of Incomplete Uterine Septum/Arcuate Uterus [27G]

INTRODUCTION: The purpose of this study was to evaluate the risk of PTD in primary infertility patients who underwent hysteroscopic septoplasty and had a subsequent twin gestation. METHODS: This retrospective cohort study included 265 patients between 1992–2011. The study group (36 patients) were primary infertility patients who underwent hysteroscopic septoplasty for either an incomplete uterine septum or an arcuate uterine anomaly. The control group (50 patients) had primary infertility and a normal uterine cavity by hysteroscopic evaluation. All patients conceived twin gestations via spontaneous conception (SC), or intrauterine insemination after controlled ovarian stimulation (IUI+COS) or in vitro fertilization and embryo transfer (IVF-ET). RESULTS: There was no significant difference in age, duration of infertility, day 3 FSH levels, or incidence of male factor infertility between the two groups. There was a significantly higher BMI kg/m2 (30.1+6.9 vs 24.7+5.0; P<.03) and incidence of ovulatory disorders (P<.05). There was significantly lower incidence of tubal factors (P<.001) and endometriosis (P<.01) in the study group compared to the control group. The incidence of PTD in the study group (77.8%) was significantly higher compared to the control group (52.0%), P<.05. There were no differences in gestational ages or neonatal birth weights. CONCLUSION: This study suggests that the risk of PTD in patients with hysteroscopic correction of uterine anomalies may be compounded in twin gestations. Therefore, every effort should be made to achieve a singleton pregnancy in these patients. These patients may require increased surveillance, while future studies regarding possible interventions to reduce the incidence of PTD may be warranted.

Preterm Birth and IVF-ET in Singleton Pregnancy After Hysteroscopic Correction of Uterine Septum [27H]

INTRODUCTION: The purpose of this study is to compare preterm birth rate in a cohort of women with primary infertility, and hysteroscopically corrected incomplete uterine septum or arcuate uterine anomaly, who subsequently conceived singleton gestation via spontaneous conception (SC), or intrauterine insemination after controlled ovarian stimulation (IUI+COS) or IVF-ET. METHODS: This retrospective study included women with primary infertility and incomplete uterine septum or arcuate uterine anomaly. All patients underwent successful hysteroscopic septoplasty that resulted in a normal uterine cavity postoperatively between 1992–2011. Subsequently all patients conceived singleton gestation by SC, IUI+COS, or IVF-ET. The study included 106 patients, 45 conceived spontaneously, 11 with IUI+COS, and 50 with IVF-ET. The primary outcome was the preterm birth rate. Secondary outcomes were gestational age at delivery and neonatal birth weight. RESULTS: There was a significant difference in age, but no significant differences in duration of infertility, BMI, day 3 FSH levels or underlying etiology among the three groups. There was no statistical difference in preterm birth rates (17.8% vs 27.3% vs 16%), mean gestational age at delivery in weeks (38.6±2.5 vs 37.6±3.6 vs 36.6±7.0), and birth weight in Kg (3.3±0.6 vs 3.1±0.8 vs 3.2±0.7) between SC, IUI+COS, and IVF-ET groups respectively. CONCLUSION: Our data suggest that in patients with incomplete uterine septum or arcuate uterine anomaly, who underwent successful hysteroscopic correction, IVF-ET treatment per se is not associated with increased risk of preterm birth and/or low birth weight.