Prepregnancy Weight in Women with Type I Diabetes Mellitus: Effect on Pregnancy Outcomes.

Objective This study aims to evaluate the association between prepregnancy body mass index (BMI) and adverse pregnancy outcomes in women with type 1 diabetes mellitus (DM). Methods This is a secondary analysis of a cohort of 426 pregnancies in women with type 1 DM recruited before 20 weeks gestation. Women were categorized according to prepregnancy BMI: low BMI (< 20 kg/m2), normal BMI (20 to < 25 kg/m2), and high BMI (≥ 25 kg/m2). The outcomes of interest were: spontaneous abortion (delivery < 20 weeks gestation); preeclampsia; emergent delivery for maternal indications (hypertension or placental abruption); and preterm delivery (< 37 weeks gestation). Analyses included proportional hazards and multiple logistic regression models with covariates: age, age at diagnosis of type 1 DM, previous spontaneous abortion, microvascular disease (nephropathy or retinopathy), and glycohemoglobin A1 concentrations. Results Low BMI was associated with preterm delivery. High BMI was associated with emergent delivery for maternal indications. Glycemic control as measured by glycohemoglobin A1 was associated with increased risk of spontaneous abortion, attenuating the association with low prepregnancy weight. Conclusion Prepregnancy BMI is a risk factor to be considered when caring for women with type 1 DM, in particular for preterm delivery (low BMI) and emergent delivery for maternal indications (high BMI).

Deficient counterregulation: a possible risk factor for excessive fetal growth in IDDM pregnancies.

OBJECTIVE: The rate of macrosomia in infants born to women with IDDM remains high despite intensive insulin therapy and good glycemic control. We hypothesized that one of the factors contributing to this high rate of macrosomia is deficient counterregulatory hormonal responses to hypoglycemia. RESEARCH DESIGN AND METHODS: Hypoglycemia was induced in 17 women with IDDM and 10 normal control subjects at 24-28 and at 32-34 weeks' gestation, using the hypoglycemic clamp technique. Plasma glucose concentrations were decreased to 3.3 mmol/l and maintained at this level for 1 h. Blood samples were drawn every 15 min for measurement of counterregulatory hormone concentrations. RESULTS: All 17 women with IDDM had diminished epinephrine responses to hypoglycemia, compared with control subjects. Eight of the women with IDDM (nonresponders) had minimal or no responses (< 165 pmol/l above baseline) and nine women (responders) had a moderate response (244-764 pmol/l). Of the eight nonresponders, seven had large infants (birth weight in the upper quartile), while only three of the nine responders had large infants (P < 0.05). CONCLUSIONS: Severely impaired counterregulatory epinephrine responses to hypoglycemia in pregnant women with IDDM may be a factor contributing to excessive fetal growth. We speculate that in these women, recurrent episodes of hypoglycemia may result in frequent bouts of increased caloric intake, with repeated episodes of transient hyperglycemia leading to fetal hyperinsulinism and excessive fetal growth.

Interaction of angiotensin II and brain natriuretic peptide in the placentas of normal and diabetic women.

OBJECTIVE: To evaluate the effects of angiotensin II and brain natriuretic peptide on the placental vasculature of diabetic women. METHODS: Term placentas from five diabetic women and five nondiabetic controls were collected. Isolated placental cotyledons were perfused dually with fetal perfusion pressure as an index of vascular response. The effect of angiotensin II (10(-10)-10(-5) mol/L bolus injection) was established in the fetal-placental vasculature of all placentas in the absence or presence of brain natriuretic peptide (10(-8) mol/L final concentration). Data were analyzed using repeated measures analysis of variance and paired t test where appropriate. RESULTS: A significant vasoconstrictor response to angiotensin II was achieved in placentas of both diabetic and nondiabetic women (P < .001); however, the angiotensin II-induced increase in perfusion pressure was significantly greater in the diabetic group (P < .01). Significant attenuation of vasoconstrictor response to angiotensin occurred in the presence of brain natriuretic peptide in placentas of both nondiabetic (P < .0025) and diabetic (P < .025) women, but the effect was more prominent in the diabetic group. CONCLUSION: The in vitro placental vasculature of diabetic women is more sensitive to angiotensin II than is the in vitro placental vasculature of nondiabetic women. The attenuation exerted by brain natriuretic peptide on angiotensin II-induced vasoconstriction is more prominent in placentas from diabetic women compared to those from nondiabetic women.

Hypertension during pregnancy in insulin-dependent diabetic women.

Insulin-dependent diabetic patients are at increased risk for hypertensive disorders of pregnancy. This study was designed to study prospectively the rate of pregnancy-induced hypertension (PIH) in 175 insulin-dependent diabetic pregnancies (88 White classes B-C, 87 classes D-RT). Pregnancy-induced hypertension was defined as two or more occurrences after 20 weeks' gestation of a mean arterial pressure (MAP) of 105 mmHg or greater or an increase of 20 mmHg or greater from the baseline MAP. The rate of PIH in the diabetic population was 15.4% and was significantly associated with nulliparity, poor glycemic control in the first and second trimesters, and advanced White class. Neonatal outcome was not significantly altered in the presence of PIH. We speculate that improved glycemic control throughout pregnancy might reduce the rate of this complication in diabetic patients.

Counterregulatory hormonal responses to hypoglycemia during pregnancy.

OBJECTIVE: To evaluate the counterregulatory responses to insulin-induced hypoglycemia in healthy women and in women with insulin-dependent diabetes during pregnancy and in the nonpregnant state. METHODS: Hypoglycemia was induced using the hypoglycemic clamp technique in 17 women with insulin-dependent diabetes and in ten healthy controls, both in the nonpregnant state (study 1), at 24-28 weeks' gestation (study 2), and at 32-34 weeks' gestation (study 3). Plasma glucose concentrations were decreased to 60 mg/dL and maintained at this level for 1 hour. Blood samples were drawn every 15 minutes to measure epinephrine, glucagon, growth hormone, and cortisol concentrations. Statistical analyses compared counterregulatory responses between women with and without diabetes, and between the pregnant and nonpregnant state. RESULTS: Women with diabetes had significantly diminished peak epinephrine responses to hypoglycemia compared with controls (mean +/- standard error of the mean [SEM]): 52 +/- 11 versus 191 +/- 42 pg/mL in study 1, 30 +/- 9 versus 102 +/- 47 pg/mL in study 2, and 38 +/- 10 versus 148 +/- 38 pg/mL in study 3 (P < .05). Their responses during pregnancy were also diminished compared with their own nonpregnant epinephrine responses. Women with diabetes also had no recognizable cortisol or glucagon responses to hypoglycemia, and in healthy controls the glucagon responses were significantly diminished during pregnancy compared with their own nonpregnant responses. In both groups, growth hormone responses (mean +/- SEM) diminished progressively during pregnancy from study 1 (14.6 +/- 2.5 and 12.5 +/- 5.2 ng/mL) to study 2 (4.4 +/- 1.1 and 7.3 +/- 2.7 ng/mL) to study 3 (2.5 +/- 0.9 and 4.4 +/- 2.3 ng/mL) in women with diabetes and in controls, respectively. CONCLUSION: Counterregulatory epinephrine and growth hormone responses to hypoglycemia are diminished in women with insulin-dependent diabetes during pregnancy. This may be due, in part, to an independent effect of pregnancy, contributing to the increased incidence of hypoglycemia in these patients during pregnancy.

Hypoglycemia: the price of intensive insulin therapy for pregnant women with insulin-dependent diabetes mellitus.

OBJECTIVE: To evaluate the risk of hypoglycemia associated with intensive insulin therapy of type I diabetes during pregnancy. METHODS: Eighty-four women with type I diabetes were recruited before 9 weeks' gestation and received intensive insulin therapy throughout pregnancy. Patients monitored glucose concentrations with memory glucometers, and insulin dosages were adjusted weekly accordingly. A detailed history of clinical hypoglycemic events was obtained at each weekly clinic visit. RESULTS: Clinically significant hypoglycemia requiring assistance from another person occurred in 71% of pregnant patients, with a peak incidence between 10-15 weeks. Severe hypoglycemia during the early weeks of embryogenesis was not associated with an increase in embryopathy. Glycemic control was similar in women with or without recurrent hypoglycemia, but glucose fluctuations were significantly greater in hypoglycemic women. CONCLUSION: Severe hypoglycemia is a significant maternal risk associated with intensive insulin therapy of pregnant women with type I diabetes. In women with recurrent episodes of hypoglycemia, the clear benefits of strict glycemic control must be weighed against the hazards of hypoglycemia.

Glycemic thresholds for spontaneous abortion and congenital malformations in insulin-dependent diabetes mellitus.

OBJECTIVE: To test the hypothesis that women with insulin-dependent (type I) diabetes have a threshold of glycemic control in early pregnancy for increased risks of spontaneous abortion and congenital malformations. METHODS: Receiver-operating characteristic (ROC) curves were formed for the occurrence of abortion and malformations as a function of the median first-trimester preprandial blood glucose concentration and the first measured glycohemoglobin concentration in pregnant women with type I diabetes. RESULTS: Fifty-two of the 215 women (24%) who enrolled before 9 weeks' gestation had spontaneous abortions. Six percent of the women enrolled before 14 weeks had infants with major congenital malformations. Thresholds for an increased risk of abortion and malformations were a median first-trimester blood glucose concentration of 120-130 mg/dL or an initial glycohemoglobin concentration of 12-13% (6.2-7.5 standard deviations above the normal mean). CONCLUSIONS: Type I diabetic women with initial glycohemoglobin concentrations in pregnancy above 12% or median first-trimester preprandial glucose concentrations above 120 mg/dL have an increased risk of abortion and malformations. Below these glycemic thresholds, the risks are comparable to those in nondiabetic women.

Patient experience in a diabetic program project improves subsequent pregnancy outcome.

There has been a notable improvement in the outcome of the pregnancies of insulin-dependent diabetics. This improvement has resulted from intensive health care programs and increased awareness among patients and health providers of the need for specialized prenatal care. We hypothesized that participation in a specialized program providing early glycemic control would benefit the patient's subsequent pregnancy, despite progression of the diabetic disease process. We prospectively studied 55 insulin-dependent diabetic patients enrolled before 9 weeks' gestation through two consecutive pregnancies: sequence 1 and sequence 2. A control group of 55 insulin-dependent diabetic patients, entering the program for the first time, were matched with the sequence 2 pregnancies of the study group by maternal age and year of pregnancy. Specific outcomes related to glycemic control in early gestation were significantly improved from sequence 1 to sequence 2 pregnancies: earlier week of entry (P = .0001), lower glycohemoglobin at 9 weeks (P = .005) and at 14 weeks (P = .02), and improved fetal outcome (decreased rate of spontaneous abortions or major malformations; P less than .01). Week of entry and glycohemoglobin at 9 and 14 weeks were also significantly improved compared with the control group. Seventy-three percent of the patients entered the program earlier in their sequence 2 pregnancies (P = .001) and had lower glycohemoglobin concentrations at 9 weeks (P = .005) compared with their sequence 1 pregnancies. Sixty-five percent of the patients in sequence 2 had advanced diabetic disease (White class D-RF), compared with 46% in sequence 1 (P less than .05) and 44% of the controls (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Human versus animal insulin in the management of insulin-dependent diabetes: lack of effect on fetal growth.

It is generally accepted that the human placenta is impermeable to free insulin and that insulin present in the fetus is entirely of fetal origin. A recent study suggested that antibody-bound animal insulin crosses the placental barrier and may exert direct effects on fetal growth. We hypothesized that mothers with insulin-dependent diabetes treated with animal insulin would have infants with higher birth weights and ponderal indices compared with mothers treated with human insulin. We studied 209 mothers with insulin-dependent diabetes who were enrolled in our program and who delivered after 28 weeks' gestation: 170 were treated with animal insulin and 39 with human insulin. There were no differences between the groups in the mean birth weight (adjusted by gestational age at delivery) or ponderal index of the infants. The rate of macrosomia (birth weight greater than the 90th percentile for gestational age or ponderal index above 2.85) was similar in both groups. The sample size was adequate to yield a power of 80% to detect a difference between groups of 179 g or more in birth weight and 0.1 g/cm3 in ponderal index. We suggest that the type of insulin (animal versus human) used by the pregnant insulin-dependent diabetic mother has no bearing on fetal weight gain.

Sonographic estimation of fetal weight based on a model of fetal volume.

OBJECTIVES: To derive a formula for sonographic estimated fetal weight (EFW) based on a two-compartment model of fetal volume and to test it against two widely used formulas, especially at the extremes of fetal weight for which existing formulas are generally inaccurate. METHODS: We analyzed 865 consecutive sonograms that met the following inclusion criteria: singleton pregnancy, normal anatomy, delivery within 3 days of sonography, and measurements of biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). The weight of the fetal head was modeled to be proportional to HC3, and the weight of the trunk proportional to AC2 x FL. The proportionality constants were found by multiple linear regression on 380 sonograms performed in 1990 (the "derivation set"). The new formula was tested for accuracy of prediction of actual birth weight against the formulas of Hadlock et al and Shepard et al using 485 sonograms from 1991-1992 (the "validation set"). RESULTS: In the derivation set, the formula EFW = (0.23718 x AC2 x FL) + (0.03312 x HC3) was fit; the correlation with actual birth weight had an r value of 0.996. In the validation set, the new formula produced smaller systematic errors and smaller absolute errors than either the Hadlock or Shepard formula both overall and in fetal weight strata from less than 1000 g to over 4000 g. CONCLUSION: The new formula makes geometric sense and provides accurate estimates of fetal weight across a broad range of weights.

Early-pregnancy proteinuria in diabetes related to preeclampsia.

OBJECTIVE: To test the hypothesis that the risk of preeclampsia in diabetic mothers is increased with incipient diabetic nephropathy as well as with overt nephropathy. METHODS: Pregnancy outcome was studied in 311 women with class B-RF diabetes from two institutions. Using 104 women without chronic hypertension followed at the University of California, San Francisco, we constructed a receiver-operating characteristic curve relating 24-hour urinary total protein before 20 weeks' gestation to the subsequent development of preeclampsia. From the curve, a predictive cutoff level of proteinuria was selected and tested in two validation groups not used to construct the curve: 158 women without chronic hypertension followed at the University of Cincinnati and 49 women with chronic hypertension from both institutions. RESULTS: The receiver-operating characteristic curve showed an increased risk of preeclampsia with early-pregnancy proteinuria of 190 mg/day or more. In the Cincinnati validation group, the rate of preeclampsia was 7% in women with early-pregnancy proteinuria of less than 190 mg/day, 31% with proteinuria of 190-499 mg/day, and 38% with proteinuria of 500 mg/day or more. In the chronic-hypertension validation group, the rates were 0, 50, and 58%, respectively. By multiple logistic regression, the increased risk of preeclampsia with proteinuria above 190 mg/day persisted after controlling for the effects of parity, chronic hypertension, retinopathy, and glycemic control. CONCLUSIONS: Diabetic gravidas with early-pregnancy proteinuria of 190-499 mg/day are at increased risk for preeclampsia. The risk is comparable to that in women with overt diabetic nephropathy and is independent of chronic hypertension. We speculate that diabetic women with proteinuria in this range have incipient or subclinical diabetic nephropathy.

The effect of early discharge after vaginal delivery on neonatal readmission rates.

OBJECTIVE: To determine the effect of a structured program for early neonatal discharge from a tertiary medical center on the risk of neonatal readmission. METHODS: An early-discharge program was instituted at our tertiary medical center in July 1993, with the objective of discharging mothers and infants within 24 hours after vaginal birth. The readmission rate of vaginally delivered infants during the early-discharge period (July 1, 1993, through March 31, 1995) was compared with the rate during a conventional-discharge period (January 1, 1992, through June 30, 1993). Analyses were performed to examine two groups within the early-discharge group: those discharged within 24 hours of vaginal delivery; and those discharged within 1 hospital day of vaginal delivery. RESULTS: During the early-discharge period, 1.24% of neonates were readmitted within 10 days of birth, compared with 1.35% during the conventional-discharge period. In the early-discharge period group, infants born vaginally and discharged within 24 hours of birth had a readmission rate of 1.46% compared with 1.14% for those who stayed longer than 24 hours after delivery. Similarly, the readmission rate was no different for infants who were discharged within 1 hospital day. The primary indications for readmission in both periods were infections and jaundice. CONCLUSION: Implementation of a structured program for early neonatal discharge does not have an association with increased risk of neonatal readmission to the hospital.

Minor congenital malformations in infants of insulin-dependent diabetic women: association with poor glycemic control.

A prospective study of 171 insulin-dependent diabetic pregnant women was undertaken to establish the relationship of glycemic control with minor congenital malformations. Each live-born infant was assessed systematically by two independent examiners using a standardized checklist. There were 32 infants with minor congenital malformations (18.7%). There were significant differences in mean glycohemoglobin A1 between the group with minor congenital malformations and the group without congenital malformations at 12, 16, and 20 weeks, but not at 8 or 24 weeks. Logistic regression analysis showed that maternal age, race, gravidity, White class, duration of diabetes, maternal vasculopathy, and cigarette smoking were not significant variables correlated with minor congenital malformations. Because glycohemoglobin levels from 12-20 weeks are believed to reflect glycemic control from approximately 6-20 weeks, we conclude that poor glycemic control during late embryogenesis and early fetal development is associated with an increased risk of minor congenital malformations. We speculate that improvement of glycemic control during this period should decrease the risk of minor congenital malformations.

Fetal weight and progression of diabetic retinopathy.

OBJECTIVE: To test the hypothesis that progression of diabetic retinopathy in pregnancy is associated with reduced fetal growth and related neonatal morbidity. METHODS: Women with type 1 diabetes (n = 205) were enrolled before 14 weeks' gestation in a prospective study of diabetes in pregnancy and treated with intensive insulin therapy. They had serial ophthalmologic evaluations before 20 weeks' gestation and in late gestation or postpartum. Subjects were divided into two groups based on whether retinopathy progressed (progression group) or remained unchanged (no progression group). RESULTS: Retinopathy progressed in 59 of 205 women (29%) and was associated with advanced White classification (P =.001): three (5%) were class B, 14 (23%) class C, 24 (41%) class D, and 18 (30%) class F-RF. Reduced fetal growth was associated with progression of retinopathy. Mean birth weight was lower (P =.02), and more infants were small for gestational age (P =.02) and had low birth weights (P =.02) in the progression group. More large-for-gestational-age infants were noted in the no-progression group (P =.04). Birth weight percentile distributions showed a shift of the curve to the left in the progression group (P =.03). There were no differences in gestational age at delivery, macrosomia, preterm delivery, respiratory distress syndrome, neonatal hypoglycemia, or neonatal death. Small for gestational age was associated with chronic hypertension (odds ratio [OR] 6.4; 95% confidence interval [CI] 1.5, 27.9) and retinopathy progression (OR 4.7; 95% CI 1.2, 23.8). CONCLUSION: Development and progression of diabetic retinopathy during pregnancy were associated with reduced fetal growth manifested as increased rate of small-for-gestational-age and low-birth-weight infants.

Maternal floor infarction of the placenta: prenatal diagnosis and clinical significance.

OBJECTIVE: To determine whether maternal floor infarction can be diagnosed prenatally. METHODS: We reviewed the charts of 13 patients with maternal floor infarction confirmed histopathologically to determine the frequency of increased placental echogenicity, fetal growth restriction (FGR), and oligohydramnios. Subsequently, we applied these criteria prospectively to diagnose maternal floor infarction in three cases. RESULTS: Twelve of the 13 pregnancies reviewed retrospectively resulted in small for gestational age infants, of which eight were stillbirths. Fetal growth restriction and oligohydramnios were evident on ultrasound in five pregnancies and a placental abnormality was noted in four; two patients exhibited this complete triad of sonographic abnormalities. Three patients were identified prospectively with maternal floor infarction based on sonographic findings and electively delivered live preterm infants. CONCLUSIONS: Maternal floor infarction is a placental condition with profound risk for FGR and stillbirth. Antenatal diagnosis may improve the perinatal outcome with this condition.

The hormonal response of patients with polycystic ovarian disease to subcutaneous low frequency pulsatile administration of luteinizing hormone-releasing hormone.

Four patients with oligoamenorrhea manifesting hormonal and clinical features of polycystic ovarian disease (PCOD) were selected for treatment. All patients had high luteinizing hormone (LH) levels and a basal LH/follicle-stimulating hormone (FSH) ratio of greater than 3. Three of them had high androgen levels with normal adrenal cortical function. The four patients were treated for 12 cycles by pulsatile LH-releasing hormone (LH-RH) subcutaneously. Frequency of pulses varied between once in every 120 to once in every 400 minutes in consecutive cycles, in an attempt to reverse LH/FSH ratio. The dose of LH-RH varied between 20 and 40 micrograms/pulse. Treatment was monitored hormonally by the determinations of LH, FSH, 17 beta-estradiol, prolactin, progesterone, testosterone (T) (total and free), androstenedione (delta 4A), dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) every 2 days. The most striking change was the lowering of the LH/FSH ratio to the normal range, due to LH decrease and FSH increase with a pulse frequency of 180 to 240 minutes. DHEA-S levels reversed to normal in two patients and were reduced in one patient. T and delta 4A levels returned to normal with elevation to normal of SHBG. These hormonal improvements did not result in ovulation as expected (2 of 12 cycles). It may be assumed that either subcutaneous administration is inadequate in PCOD patients or that the frequency of pulses needed to correct the hormonal disturbances in PCOD patients differs from that needed for ovum maturation and ovulation.

Progesterone enhancement of prostaglandin E2 production by fetal placental macrophages.

The role of progesterone in immunoregulation at the fetomaternal interface at physiological concentrations (2-6 micrograms/ml) is controversial. This study examines the effect of progesterone on maternal lymphocyte proliferation in a one-way mixed lymphocytic reaction (MLR) stimulated by allogenic lymphocytes as well as on prostaglandin production and secretion by fetal placental macrophages. No suppressive effect on maternal lymphocyte proliferation was found at progesterone levels of up to 20 micrograms/ml. However, physiological concentrations of progesterone were found to induce a significant increase in the fetal macrophage release of PGE2, which is well known as a strong immunosuppressant. PGI2 production and secretion by these cells, measured by the appearance of its 6-keto-PGF1 alpha product, was not affected by incubation with progesterone. Enhancement of PGE2 secretion by progesterone may partly explain the roles of progesterone and fetal placental macrophages in immunosuppression at the fetomaternal interface.

Normalization of blood glucose in insulin-dependent diabetic pregnancies and the risks of hypoglycemia: a therapeutic dilemma.

Intensive insulin therapy delays the onset and progression of microvascular complications in insulin-dependent diabetes mellitus (IDDM). Such therapy, however, is associated with an increased risk of potentially life-threatening hypoglycemia due to the loss of normal counterregulatory hormonal responses to hypoglycemia and to the syndrome of hypoglycemia unawareness. Current standards for glycemic control during pregnancy in IDDM women require intensive insulin therapy to optimize pregnancy outcome. Therefore, obstetricians and gynecologists providing prenatal care for women with IDDM should be aware that intensive insulin therapy predisposes these patients to the significant risks of severe hypoglycemia. It often becomes necessary to individualize the optimal balance between glycemic control during pregnancy and the risks of hypoglycemia.

The effects of maternal diabetes on the fetus and neonate.

The outlook for the fetus and infant of the diabetic mother has changed remarkably over the past 70 years. Following the discovery of insulin in 1922, young diabetic women who were previously practically infertile, were introduced to the option of conceiving and bearing children. Pregnancy-related maternal mortality, which had previously been extremely high in this group of patients, fell dramatically after the advent of exogenous insulin. Nevertheless, perinatal morbidity and mortality remained unacceptably high. Over the past 20 years, there has been growing understanding of the pathophysiology of the diabetic pregnancy, development of specialized health care centers for pregnant diabetic women, and remarkable improvements in neonatal care. All these have conjointly resulted in a markedly improved prognosis for the infant of the diabetic mother. Despite these optimistic undertones, it is prudent to bear in mind that these unborn infants developing in the sweet maternal environment are set out for a bitter struggle against some rather unfavorable odds.