Elevated maternal glycohemoglobin in early pregnancy and spontaneous abortion among insulin-dependent diabetic women

Insulin-dependent diabetic women without adequate glucose control have a higher rate of spontaneous abortions than does the general population of pregnant women. The present study examined whether insulin-dependent diabetic women who experienced spontaneous abortions had higher levels of glycohemoglobin in the first trimester than did insulin-dependent diabetic women who had normal pregnancy outcomes. Measurement of glycohemoglobin during the first trimester provides an integrated, retrospective index of glucose control during the phase of organogenesis. This study evaluated 116 pregnancies in 75 insulin-dependent diabetic women. Ninety pregnancies progressed beyond 20 weeks, with normal outcome. Twenty-six pregnancies terminated in spontaneous abortions before 20 weeks. The mean gestational ages for sampling of glycohemoglobin for the women who experienced spontaneous abortion and those for the women with pregnancies of more than 20 weeks were not significantly different. The mean level of glycohemoglobin for the women who experienced spontaneous abortions was significantly greater than that for the women with pregnancies of more than 20 weeks (p less than 0.05). Individual levels of glycohemoglobin of less than 12% at 8 to 9 weeks' gestation were associated with favorable outcomes, whereas levels of glycohemoglobin of more than 12% were predictive of a greater incidence of spontaneous abortions (p less than 0.05). These data suggest that the poorly controlled pregnant diabetic patient, as reflected by high levels of glycohemoglobin early in pregnancy, has an increased risk of spontaneous abortion.     

Pregnancy outcome in patients with insulin-dependent diabetes mellitus with preconceptional diabetic control: a comparative study

Forty-four of 75 pregnant women with juvenile-onset insulin-dependent diabetes, who attended a preconceptional clinic, were seen regularly by a diabetologic team. Glycemic control was obtained by intensified insulin therapy and monitored by blood glucose self-monitoring. When these patients were compared with a group of 31 nonattenders of the preconceptional clinic, in the former normoglycemia and normal hemoglobin A1 values were achieved before conception, whereas in the latter good control was reached by the second trimester. This group had also more maternal complications, such as preeclampsia, and higher cesarean section rates. Congenital anomalies were 9.6% among offspring of nonattenders, while none occurred in those with preconceptional counseling. We confirm the evidence accumulated in the recent literature that congenital malformations in pregnancy complicated by diabetes may be linked to disturbances in maternal metabolism during the period of embryogenesis. Consequently we concur with the recommendation that tight diabetic control is required before the patient attempts to conceive.     

NK cell activity and subsets in women with a history of spontaneous abortion. Cause, number of abortions, and subsequent pregnancy outcome

OBJECTIVE: The aim of this study was to assess the role of NK cells in nonpregnant women with a history of spontaneous abortion. STUDY DESIGN: 113 nonpregnant women with a history of spontaneous abortion were assessed for peripheral NK cell activity and percentage of NK cell subsets, in relation to the cause of abortions, the number of spontaneous abortions, and subsequent pregnancy outcome (n = 56). RESULTS: Neither NK cell activity nor subsets showed a significant difference in relation to the cause or number of spontaneous abortions. NK cell activity in nonpregnant women who later experienced subsequent abortion with normal chromosomes (n = 10) (mean +/- SD: 42.8 +/- 15.8%) was relatively higher than that in women with subsequent live birth (control, n = 39) (32.1 +/- 13.7%) (p = 0.099). NK cell activity in women who later experienced subsequent abortion with abnormal chromosomes (n = 7) (28.7 +/- 21.4%) was the same as the level in the control. CONCLUSION: Peripheral NK cell activity or subsets during nonpregnant status were not related to the cause or number of previous spontaneous abortions. A relation between preconceptional NK cell activity and later experiencing abortion with normal chromosomes should be further studied.     

Influence of pre-conception pregnancy planning in women with diabetes mellitus I on the number of spontaneous abortions and major congenital malformations in their children

OBJECTIVE: The study assesses the relationship between pre-conception pregnancy planning and number of spontaneous abortions and major congenital malformations in their children. MATERIALS AND METHODS: 138 pregnancies in women with type 1 diabetes without complications or only with simple retinopathy (White B, C, D) were analyzed. Women were treated in the Outpatient Family Planning Center in Warsaw between 1988 and 1998. Thirty women were planning the pregnancy prior to conception, 108 registered already when pregnant. The groups compared did not differ statistically in age, duration of diabetes or diabetic angiopathy. Mean values of HbA1C in consecutive trimesters were: 6.40%, 5.84%, 5.67% in the group of patients planning the pregnancy and 6.99%, 6.29%, 6.15% in the non-planning group. The differences were statistically significant (p < 0.05, p < 0.05, p < 0.01). RESULTS: In the pre-conception group there were no spontaneous abortions and no and major congenital malformations. Mean value of HbA1C in early pregnancy was significantly higher in women with spontaneous abortions than in the remaining women in the non-planning group (respectively 7.9% and 6.9%). Also, mean value of HbA1C in early pregnancy was significantly higher in women who gave birth to children with major congenital malformations than in women had healthy children (respectively 8.23% and 6.81%, p < 0.05). CONCLUSION: Pre-conception pregnancy planning improves metabolic control during pregnancy and decreases the rate of spontaneous abortions and major congenital malformations.     

Predictive value of early pregnancy glycohemoglobin in the insulin-treated diabetic patient

The influence of early pregnancy glycemic control as measured by hemoglobin A1c concentration and the incidence of congenital anomalies and spontaneous abortions were evaluated in women presenting for prenatal care with insulin-treated diabetes in a population whose glycemic control was poor. Thirty-one abnormal outcomes were seen in 83 pregnancies (37%). There were 22 spontaneous abortions and nine major congenital anomalies. No woman with an early pregnancy hemoglobin A1C value less than 9.5% had an infant with a congenital anomaly and a single woman experienced a spontaneous abortion (4%). Conversely, in women with an early pregnancy hemoglobin A1C value greater than or equal to 9.5%, congenital anomalies occurred in 24% and spontaneous abortion in 35%. Outcomes of pregnancies in type 1 and type 11 diabetic women were comparable. A strong statistical relationship between hemoglobin A1C and adverse pregnancy outcomes was demonstrated. These results strongly suggest that poor glycemic control during early pregnancy adversely influences pregnancy outcomes; the greater the degree of poor control, the greater the impact on pregnancy outcome. The data further justify the need for preconceptional control in diabetic woman and for careful evaluation of the fetus during pregnancy in the woman with insulin-treated diabetes.     

Early complications after induced first-trimester abortion

Complications subsequent to 5,851 consecutively induced first-trimester abortions during the period 1980-85 were analysed. Three hundred and fifty-six abortions (6.1%) led to complications requiring hospital admission. According to bivariable analysis, women below 25 years of age, women with parity 0, women with no spontaneous and with no induced abortions, and women in gestational week 8 had significantly higher postabortal complication rates than women 25 years of age and older (p less than 0.001), women with previous births (p less than 0.0001), women with spontaneous abortions (p less than 0.005), women with induced abortions (p less than 0.005), and women in other gestational age groups (p less than 0.0005). The mean stay in hospital per complicated abortion was 5.3 days. It was discussed whether the administration of prophylactic antibiotics to women with a history of pelvic inflammatory disease and young women completing their first pregnancy could reduce the complication rate.     

The role of leiomyomas in infertility.

STUDY OBJECTIVE: To assess the role of leiomyomas and their surgical removal on pregnancy rates. DESIGN: (Canadian Task Force classification II-1). Setting. Academic center. PATIENTS: Two hundred twelve women who were investigated for infertility. INTERVENTION: Laparoscopic myomectomy. MEASUREMENTS and MAIN RESULTS: Patients were divided according to case control criteria as those who underwent laparoscopic removal of myomas (106) and those who did not (106); both groups were compared with 106 women with unexplained infertility without myomas. Of the 318 women, 83 (26%) became pregnant and delivered live infants. The 44 (42%) who underwent surgical removal of leiomyomas had higher delivery rates than 12 (11%) who did not undergo surgery (p <0.001) and 27 (25%) who did not have myomas (p <0.001). Patients whose myomas were not surgically treated had fewer deliveries than women who did not have myomas (12 vs 27, p <0.002). Fifteen women had spontaneous abortions before week 12: 3 (3%) who had surgery, 10 (9%) who did not have surgery, and 2 (2%) who did not have myomas. CONCLUSION: Laparoscopic myomectomy improved pregnancy rates over nonsurgical management of myomas.     

The implications of hypozincemia in pregnancy

Leukocyte zinc levels were significantly higher in normal pregnant women than in normal controls (p less than 0.001). There were inverse correlations between plasma zinc and leukocyte zinc (r = -0.76, p less than 0.001) and between plasma zinc and placental zinc (r = -0.88, p less than 0.0001) in normal pregnancies. When compared with infants borne by some pre-eclamptic subjects, there were significant increases in cord plasma zinc of infants borne by normal pregnant subjects (p less than 0.001). Plasma zinc concentrations were lower in normal pregnant subjects and in pre-eclamptics who gave birth to infants with normal birthweight than in pre-eclamptics who delivered infants with lower birthweight (p less than 0.005). When compared with normal pregnant women and pre-eclamptics who gave birth to infants with normal birthweight, total plasma estrogens were decreased in pre-eclamptics who delivered infants with lower birthweights (p less than 0.001). The data from this study suggest that in human pregnancy, zinc and estrogens compete for common binding sites on the plasma proteins and zinc plays an important role in the course and eventual outcome of human pregnancy.     

Glutathione S-transferase alpha levels in epileptic and healthy women preconceptionally and throughout pregnancy.

We studied plasma GSTA1-1 concentrations in preconceptionally recruited epileptic women who received antiepileptic drugs (n = 99) and a control group of healthy women (n = 106). Mean plasma GSTA1-1 concentrations in the control group did not show significant changes preconceptionally and throughout pregnancy. Six weeks postpartum, however, a significant increase in the mean plasma GSTA1-1 concentration (p < 0.001) was found as compared to preconceptional levels and levels during pregnancy. The mean plasma GSTA1-1 concentration in epileptic women was significantly higher in the 4th gestational week compared to those determined in healthy pregnant women (1.68 versus 1.08 microg/l, p < 0.001). Values between the groups in the second and third trimester and postpartum period showed no significant differences.     

Glycemic control and spontaneous abortion in insulin-dependent diabetic women

Insulin-dependent diabetic women without adequate glucose control have a higher spontaneous abortion rate when compared with the general population. The present study examined whether the increased rate of spontaneous abortions in insulin-dependent diabetic women was associated with poor glycemic control in the early postconceptional period or close to the abortive event itself. Measurements of glycohemoglobin A1 at eight to nine weeks' gestation provide retrospective indexes of glucose control during the early postconceptional period, whereas measurement of glycosylated serum albumin and serum protein at the same time reflects short-term glycemic control before the abortive event. This study evaluated 84 consecutive pregnancies occurring in 68 insulin-dependent diabetic women; 66 pregnancies progressed beyond 20 weeks with no malformation or death, and 18 pregnancies terminated in spontaneous abortions before 20 weeks' gestation. The mean glycohemoglobin A1 concentrations of women experiencing spontaneous abortions were significantly greater than that of women who did not abort (P less than .05). In contrast, maternal glycosylated proteins and glycosylated albumin concentrations did not differ between groups. The authors suggest that poor control of diabetes in the early conceptional period, rather than that just before abortion, increases the risk of spontaneous abortion.     

Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of habitual abortion

A diagnostic screening program was applied to 195 couples with a prior history of habitual abortion (i.e., three or more consecutive abortions). Abnormalities were identified in 110 (56%) of the couples. Such identification was significantly more frequent in couples with primary habitual abortion than in couples with secondary habitual abortion (p less than 0.001) and also more frequent in couples with second-trimester abortions than in those with first-trimester abortions (p approximately equal to 0.01). The abnormalities most commonly observed were anomalies of the uterine body (15%), endometrial infections (15%), and cervical incompetence (13%). Hormonal dysfunctions were detected in 5%, and there were chromosomal aberrations in 3% of the couples. The women in the group showing abnormalities were offered surgical or medical treatment, and 80% of those who subsequently conceived carried their pregnancies to term. Among the couples with no abnormal findings, women receiving specific antenatal counseling and psychological support had a pregnancy success rate of 86%, as compared to a success rate of 33% observed in women who were given no specific antenatal care (p less than 0.001).     

Outcome of subsequent pregnancies following antibiotic therapy after primary or multiple spontaneous abortions

The course of the subsequent pregnancy and the maternal and fetal complications were evaluated in 254 couples who were seen in an infertility clinic after primary or multiple spontaneous abortions. The 100 couples who were treated with antibiotics after pregnancy loss showed a significantly better chance of achieving a subsequent pregnancy. The outcome of pregnancy was significantly better in the antibiotic treated group and the rate of spontaneous abortion recurrence was significantly lower (10 versus 38 per cent). The number of maternal complications was significantly less in the treated group--premature rupture of membranes, three (4 per cent) versus 30 (46 per cent), and postpartum fever, three (4 per cent) versus 23 (35 per cent), respectively. The untreated group experienced a significantly lower percentage of vaginal delivery (56 versus 69 per cent) (p less than 0.001). In the antibiotic treated group, there were significantly lower rates of fetal complications, including fetal distress, meconium, respiratory distress syndrome, neonatal infection and hyperbilirubinemia. The mean birth weight of infants in the antibiotic treated group was significantly higher (3,529 versus 3,090 grams; p less than 0.001). Prematurity and postdatism were significantly less frequent in the antibiotic treated group, and the corresponding Apgar scores were significantly better. We, thus, postulate that certain spontaneous abortions may be caused by bacteria present in the genital tract at the time of conception. These bacteria may have an adverse effect on the course of pregnancy and result in increased maternal and fetal complications.     

Spontaneous abortion--an infectious aetiology?

The role of Chlamydia trachomatis, genital mycoplasmas, Campylobacter spp. and other aerobic and anaerobic bacteria in the aetiology of spontaneous abortion was investigated prospectively in 241 pregnant women at a community hospital. Sixteen women who had threatened abortions were a little younger, of lower social class and had had more previous spontaneous abortions than the 76 women who aborted or the 149 women whose pregnancies were not complicated in the early stages by haemorrhage. The demographic characteristics of the latter two groups of women were similar. C. trachomatis was isolated from the cervix of only one woman and she had no genital-tract bleeding at any stage in her pregnancy. Mycoplasma hominis was isolated most often from the women who had threatened abortions but otherwise the prevalence of the other various micro-organisms was similar in women who had spontaneous abortions, threatened abortions, and in those who had pregnancies uncomplicated by vaginal bleeding. It was clear, therefore, that C. trachomatis played no role in the aetiology of spontaneous abortion in the population studied and there was no suggestion that any of the other micro-organisms were involved either.     

Spontaneous abortion-an infectious aetiology?

Summary. The role of Chlamydia trachomatis , genital mycoplasmas, Campylobacter spp. and other aerobic and anaerobic bacteria in the aetiology of spontaneous abortion was investigated prospectively in 241 pregnant women at a community hospital. Sixteen women who had threatened abortions were a little younger, of lower social class and had had more previous spontaneous abortions than the 76 women who aborted or the 149 women whose pregnancies were not complicated in the early stages by haemorrhage. The demographic characteristics of the latter two groups of women were similar. C.trachomatis was isolated from the cervix of only one woman and she had no genital-tract bleeding at any stage in her pregnancy. Mycoplasma hominis was isolated most often from the women who had threatened abortions but otherwise the prevalence of the other various micro-organisms was similar in women who had spontaneous abortions, threatened abortions, and in those who had pregnancies uncomplicated by vaginal bleeding. It was clear, therefore, that C.trachomatis played no role in the aetiology of spontaneous abortion in the population studied and there was no suggestion that any of the other micro-organisms were involved either.     

Pre-conception management of insulin-dependent diabetes: improvement of pregnancy outcome

Poor glycemic control in early pregnancy in insulin-dependent diabetes is associated with an increased risk for spontaneous abortions and congenital malformations. Strict glycemic control from the initial stages of embryogenesis is one of the major goals of management in these pregnancies. We hypothesized that insulin-dependent diabetic patients attending a pre-conception program would have improved glycemic control compared with insulin-dependent diabetic patients who enrolled after conception and would have better pregnancy outcome, with fewer spontaneous abortions and fewer major malformations. Ninety-nine pregnant insulin-dependent diabetic patients were recruited before reaching 9 weeks' gestation and were followed prospectively throughout pregnancy. Twenty-eight had attended a pre-conception clinic to optimize glycemic control (study group) and 71 had enrolled after conception (control group). Early glycemic control was significantly better in the study group: Glycohemoglobin values at the first prenatal visit and at 9 and 14 weeks' gestation were significantly lower than in the control group. The rate of spontaneous abortion was significantly lower in the study group (7%) than in the controls (24%). There was one major malformation in the control group and none in the study group. We conclude that patients with insulin-dependent diabetes attending a pre-conception program have a decreased rate of early pregnancy loss compared with those receiving prenatal care early in pregnancy.     

The effect of abortion on the incidence of pre-eclampsia

The incidence of pre-eclampsia was studied in 9771 women that were pregnant for the first or second time. The protection offered by a previous pregnancy which ended in abortion was compared to that provided by a first pregnancy that proceeded to term. The rate of pre-eclampsia was 2.9% for primigravid women and was significantly lower (1.5%, p less than 0.001) for women giving birth for the second time. Adjusting by multiple regression for confounding factors (e.g., maternal age, social class, ethnic origin and smoking), the incidence of pre-eclampsia was also significantly lower (p = 0.038) following an induced abortion, but not following a spontaneous abortion.     

Spontaneous abortion after amniocentesis in women with a history of spontaneous abortion

The incidence of spontaneous abortion after amniocentesis (19 to 28 weeks gestation) in women who have had previous spontaneous abortions is compared with the rate in women who have not had previous spontaneous abortions. The outcome of the pregnancy after amniocentesis and the previous history of spontaneous abortion is reported for 691 pregnancies. The rate of spontaneous abortion after amniocentesis was found to be significantly higher in women who had one or more previous spontaneous abortions, 12/238 (5 per cent), than in women who did not, 6/453 (1.3 per cent). In women who reported two or more previous spontaneous abortions, the rate was 7/81 (8.6 per cent). No statistically significant effect of maternal age or gravidity was detected. The incidence of spontaneous abortion after amniocentesis was greater in the three weeks following the procedure (three for each of the three weeks) than in the subsequent seven weeks (nine for seven weeks).     

Sequelae of induced first-trimester abortion. A prospective study assessing the role of postabortal pelvic inflammatory disease and prophylactic antibiotics

A follow-up study was undertaken in 493 women who had participated in a clinical, controlled trial with the object of assessing the role of postabortal pelvic inflammatory disease and prophylactic antibiotics in the development of sequelae. Information about dysmenorrhea, dyspareunia, chronic pelvic pain, episodes of pelvic inflammatory disease, infertility, births, induced and spontaneous abortions, and ectopic pregnancies were obtained from 382 of the women and from 38 of 40 women who had contracted postabortal pelvic inflammatory disease during the previous study. Significantly elevated rates in women with postabortal pelvic inflammatory disease compared with women without this disease were found for spontaneous abortion (22% versus 5%, p less than 0.0005), secondary infertility (10% versus 2%, p less than 0.05), dyspareunia (20% versus 5%, p less than 0.005), and chronic pelvic pain (14% versus 2%, p less than 0.001). Nonsignificant differences were observed for ectopic pregnancy and dysmenorrhea. A new episode of pelvic inflammatory disease within the first year after abortion was observed more often in women with postabortal pelvic inflammatory disease than in women without infection (41% versus 5%, p less than 0.0001). Prophylactic antibiotics decreased the rates of spontaneous abortion and dyspareunia (p less than 0.05 in both instances).     

Reproductive history and intrapartum fever

Washington State Birth Registry data of the years 1980-1982 of 803 women with intrapartum fever, who gave birth to a singleton, and of 1,714 control women without such diagnosis selected at random from the child-bearing population were studied for risk factors and maternal and neonatal outcome variables. Cases were significantly more often less than 21 years old, nonwhite, unmarried, nulligravid, and nulliparous than controls, and had significantly shorter gestational ages and longer birth intervals. The risk of intrapartum fever was higher in nulliparous than in nulligravid women [adjusted odds ratio (OR) 4.0 and 2.3, respectively]. This risk difference led to the discovery of increased fetal and perinatal losses prior to the pregnancy under study: cases lost 160 of 390 (41%) previous pregnancies while controls lost 142 of 1,180 (12%; OR = 5.1; p less than 0.001). In a matched analysis, spontaneous abortions (less than 20 weeks gestation) immediately preceding the pregnancy under study were found to increase the risk of intrapartum fever by 2.7 times.     

Pregnancy-associated mortality after birth, spontaneous abortion, or induced abortion in Finland, 1987-2000

OBJECTIVE: To test the hypothesis that pregnant and recently pregnant women enjoy a "healthy pregnant women effect," we compared the all natural cause mortality rates for women who were pregnant or within 1 year of pregnancy termination with all other women of reproductive age. STUDY DESIGN: This is a population-based, retrospective cohort study from Finland for a 14-year period, 1987 to 2000. Information on all deaths of women aged 15 to 49 years in Finland (n=15,823) was received from the Cause-of-Death Register and linked to the Medical Birth Register (n=865,988 live births and stillbirths), the Register on Induced Abortions (n=156,789 induced abortions), and the Hospital Discharge Register (n=118,490 spontaneous abortions) to identify pregnancy-associated deaths (n=419). RESULTS: The age-adjusted mortality rate for women during pregnancy and within 1 year of pregnancy termination was 36.7 deaths per 100,000 pregnancies, which was significantly lower than the mortality rate among nonpregnant women, 57.0 per 100,000 person-years (relative risk [RR] 0.64, 95% CI 0.58-0.71). The mortality was lower after a birth (28.2/100,000) than after a spontaneous (51.9/100,000) or induced abortion (83.1/100,000). We observed a significant increase in the risk of death from cerebrovascular diseases after delivery among women aged 15 to 24 years (RR 4.08, 95% CI 1.58-10.55). CONCLUSION: Our study supports the healthy pregnant woman effect for all pregnancies, including those not ending in births.