Elliott Main

Neonatal morbidity in pregnancy complicated by diabetes mellitus: Predictive value of maternal glycemic profiles

The relationship between glycemic control and perinatal outcome was assessed in a relatively uniform population of 75 White Class B through D pregnant diabetic women. All patients used glucose reflectance meter self-monitoring and performed a minimum of four determinations daily. Mean capillary blood glucose was calculated from a minimum of 16 weeks of determinations. Regression analysis confirmed a correlation between these values and third-trimester hemoglobin A1 (p less than 0.001). The study population was divided into two groups on the basis of mean capillary blood glucose values: group I, mean capillary blood glucose less than 110 mg/dl (43 patients) (mean = 96.8 +/- 7.1); group II, mean capillary blood glucose greater than 110 mg/dl (32 patients) (mean = 126 +/- 9.0). Of the 32 patients in group II, eight had mean capillary blood glucose greater than or equal to 130 mg/dl. The degree of maternal glycemic control appeared to affect perinatal outcome. At least one form of infant morbidity was present in 33% of group I infants compared with 53% of group II. Significant differences were observed for the incidence of hypoglycemia (p less than 0.05), macrosomia (p less than 0.05), and respiratory distress syndrome (p less than 0.01). One of six group I infants delivered at 35 to 36 weeks developed respiratory distress syndrome, compared with four of seven group II patients. The appearance of phosphatidylglycerol in amniotic fluid appeared delayed in group II patients at term. These data suggest that maintaining mean capillary blood glucose values less than 110 mg/dl may serve to reduce several major forms of morbidity in the infant of the diabetic mother. This information is helpful in establishing objectives for glycemic control in pregnant women using self-monitoring techniques.

CreatingaPublicAgendaforMaternitySafety and Quality in Cesarean Delivery

Cesarean delivery rates in California and the United States rose by 50% between 1998 and 2008 and vary widely among states, regions, hospitals, and health care providers. The leading driver of both the rise and the variation is first-birth cesarean deliveries performed during labor. With the large increase in primary cesarean deliveries, repeat cesarean delivery now has emerged as the largest single indication. The economic costs, health risks, and negligible benefits for most mothers and newborns of these higher rates point to the urgent need for a new approach to working with women in labor. This commentary analyzes the high rates and wide variations and presents evidence of costs and risks associated with cesarean deliveries (complete discussion provided in the California Maternal Quality Care Collaborative White Paper at www.cmqcc.org/white_paper). All stakeholders need to ask whether society can afford the costs and complications of this high cesarean delivery rate and whether they can work together toward solutions. The factors involved in the rise in cesarean deliveries point to the need for a multistrategy approach, because no single strategy is likely to be effective or lead to sustained change. We outline complementary strategies for reducing the rates and offer recommendations including clinical improvement strategies with careful examination of labor management practices; payment reform to eliminate negative or perverse incentives; education to recognize the value of vaginal birth; and full transparency through public reporting and continued public engagement.

HLA antigen expression and induction by γ-interferon in cultured human trophoblasts

The expression and regulation of HLA antigens were examined in isolated human trophoblasts. Immunocytochemical studies that used monoclonal antibodies against class I (HLA-A, B, and C) antigens revealed that both cytotrophoblasts and syncytiotrophoblasts can express HLA heavy chains and β 2 -microglobulin. Expression of these antigens increased with time in culture. The addition of recombinant γ-interferon (1000 U/ml) to the cultures significantly increased cellular staining for these antigens over controls throughout the 72-hour time course studied. In addition, we noted that gene expression for HLA class I heavy chain was also markedly augmented by the addition of γ-interferon. Expression of class II (HLA-DR) antigens was not detected in any of the experiments. These results suggest that during in vitro differentiation, cytotrophoblasts can express class I HLA antigens and the genes controlling their production can be regulated. Alterations in the expression or suppression of these antigens during pregnancy could be responsible for some pregnancy complications.

Abnormalities in platelet antiglobulin tests in preeclamptic mothers and their neonates

We prospectively studied 40 women with preeclampsia and 26 women with normal pregnancy for the presence of platelet-bound and circulating platelet-bindable immunoglobulin and complement. Although only 12 patients with preeclampsia had a platelet count less than 150,000/mm3, 36 of 40 demonstrated an abnormal direct antiglobulin test, compared with only three of 26 control subjects (p less than 10(-8]. An abnormal indirect test was also detected in 30 of 40 patients with preeclampsia compared with five of 26 healthy pregnant control women (p = 9.3 X 10(-6]. Abnormal antiglobulin tests persisted for 2 to 6 weeks after delivery. Although each neonate had a platelet count greater than 200,000/mm3 at the time of delivery, 10 of 18 had an abnormal direct antiglobulin test compared with one of 14 control subjects (p = 0.0049). The high frequency of abnormal platelet antiglobulin tests in women with preeclampsia and their neonates may indicate an immune cause of certain aspects of the syndrome or may reflect the extent of platelet activation.

The origin of increased serum iron in pregnancy- induced hypertension

Serum iron was measured in 30 patients with pregnancy-induced hypertension and 24 normal pregnant women. The mean iron concentration was significantly higher in the group with pregnancy-induced hypertension (111 ± 26 μg/ml) than in the controls (69 ± 17 μg/ml) (p

Evaluation of maternal fluid dynamics during tocolytic therapy with ritodrine hydrochloride and magnesium sulfate

OBJECTIVE The purpose of the study was to observe and compare the effects of ritodrine hydrochloride and magnesium sulfate on maternal fluid dynamics. STUDY DESIGN Fourteen women in preterm labor were prospectively studied during tocolytic therapy with either ritodrine hydrochloride or magnesium sulfate. The cardiovascular and renal effects of a pretreatment crystalloid infusion were compared with those observed during tocolytic therapy. Profile analysis and repeated measures of variance were used to analyze the data. RESULTS Ritodrine hydrochloride was associated with decreased colloid osmotic pressure, hematocrit, and serum proteins and increased maternal and fetal heart rates. Arginine vasopressin levels increased during the first 2 hours of therapy, then returned to baseline. Sodium excretion was reduced and there was marked fluid retention. Intravenous magnesium sulfate also resulted in a reduction of colloid osmotic pressure, but hematocrit, serum protein concentration, arginine vasopressin, maternal and fetal heart rates, and mean arterial pressure were minimally affected. Sodium excretion increased to a maximum at 6 to 8 hours of treatment, then returned to baseline. A positive fluid balance was also noted in magnesium sulfate-treated patients but to a lesser degree than with ritodrine. CONCLUSIONS Sodium retention appears to be the primary cause of plasma volume expansion in ritodrine-treated patients, whereas volume expansion during magnesium sulfate therapy is probably related to intravenous overhydration. In the absence of risk factors for pulmonary capillary membrane injury, available evidence supports volume overload as the principal mechanism for pulmonary edema during tocolytic therapy.

Lymphocyte function-associated antigen 1 (LFA-1) and natural killer (NK) cell activity: LFA-1 is not necessary for all killer:Target cell interactions

A panel of five monoclonal antibodies detecting human lymphocyte function-associated antigen 1 (LFA-1) was generated and shown by competitive binding studies to react with at least four distinct epitopes on this molecule. The antibodies were then tested for their ability to inhibit the lytic activity of a variety of different human natural killer (NK) populations on a panel of four NK-susceptible target cells (K562, MOLT-4, HSB-2, and Jurkat). When heterogeneous NK populations derived from fresh peripheral blood and mixed-lymphocyte culture (MLC)-generated lines were used, these anti-LFA-1 monoclonal antibodies (MAbs) inhibited lysis of all four NK targets; this finding supports the notion that LFA-1 molecules play an important role in NK-mediated lysis. When tested on a cloned line of NK cells (NK 3.3), lysis of K562 was inhibited by these MAbs, but lysis of the other three targets was not affected. This represents an instance where a MAb specific for LFA-1 inhibits the lytic activity of NK cells against some but not all targets; thus the LFA-1 molecule cannot be considered under all circumstances to be an absolute requirement in NK-mediated lysis.

Chronic oral terbutaline tocolytic therapy is associated with maternal glucose intolerance

Plasma glucose determinations were performed 1 hour after a 50 gm oral glucose load in 30 patients receiving long-term terbutaline therapy (20 to 40 mg/day for at least 1 week) and 247 normal control patients. A total of 63% of patients receiving terbutaline had an abnormal 1-hour value (greater than or equal to 140 mg/dl), an incidence much higher than that of control subjects (17.8%) (p less than 0.0001) for a relative risk of 3.54 (95% confidence intervals of 2.29 to 5.42). Mean 1-hour values were 112.1 mg/dl for control subjects and 149.8 mg/dl in the terbutaline group (p less than 0.0001). All abnormal values were followed by a 3-hour 100 gm oral glucose tolerance test. A total of 15.9% of the glucose tolerance tests performed in the control group (2.8% overall) were abnormal as opposed to 52.6% (33.1% overall) in patients receiving terbutaline (p less than 0.01). Nine patients were studied before and after terbutaline therapy. Results obtained during administration of terbutaline were significantly higher (102.2 mg/dl before therapy versus 145.2 mg/dl during therapy). We conclude that treatment with oral terbutaline appears to be associated with impairment of glucose tolerance in pregnancy.

The effect of oral ritodrine therapy on glucose tolerance in pregnancy

Intravenous ritodrine therapy can cause significant deterioration of maternal glucose homeostasis. We investigated the effect of full maintenance oral ritodrine therapy (120 mg/day) on glucose tolerance in the early third trimester with the use of 50 gm 1-hour screens followed by 100 gm 3-hour oral glucose tolerance tests if the screen level was greater than or equal to 140 mg/dl. Four hundred ninety-one patients were studied, 42 of whom were receiving oral ritodrine therapy. Twenty-one percent of the ritodrine-treated women had an abnormal 1-hour screen, which was not different from the 20% observed in women not receiving therapy. None of the treated group and 13% of the untreated group who had abnormal screens had abnormal oral glucose tolerance tests. The probability of an abnormal test after an abnormal 1-hour screen was also determined.

HLA antigen expression and induction by gamma‐interferon in cultured human trophoblast

The expression and regulation of HLA antigens were examined in isolated human trophoblasts. Immunocytochemical studies that used monoclonal antibodies against class I (HLA-A, B, and C) antigens revealed that both cytotrophoblasts and syncytiotrophoblasts can express HLA heavy chains and beta 2-microglobulin. Expression of these antigens increased with time in culture. The addition of recombinant gamma-interferon (1000 U/ml) to the cultures significantly increased cellular staining for these antigens over controls throughout the 72-hour time course studied. In addition, we noted that gene expression for HLA class I heavy chain was also markedly augmented by the addition of gamma-interferon. Expression of class II (HLA-DR) antigens was not detected in any of the experiments. These results suggest that during in vitro differentiation, cytotrophoblasts can express class I HLA antigens and the genes controlling their production can be regulated. Alterations in the expression or suppression of these antigens during pregnancy could be responsible for some pregnancy complications.