• During pregnancy,many physiological changes take place.Changes in metabolism can be seen.
• Insulin function may not be as effective during pregnancy
• The palcenta makes certain hormones that may prevent insulin from working the way that it should.
• The body has to make three times more insulin than normal to offset the hormones made by the pacenta since a growing fetus is dependent on the mother's nutrient supply of glucose,amino acids, and lipids.
• About 5 % of prgenant women are unable to produce enough insulin
• When this condition happens,it is referred to as insulin resistance.

With each feeding, the pregnant woman undergoes a complex series of maternal hormonal actions (ie, a rise in blood glucose; the secondary secretion of pancreatic insulin, glucagon, somatomedins, and adrenal catecholamines). These adjustments ensure that an ample, but not excessive, supply of glucose is available to the mother and fetus. The key features of this complex interaction include the following:

• Compared to nonpregnant subjects, pregnant women tend to develop hypoglycemia (plasma glucose mean = 65-75 mg/dL) between meals and during sleep. This occurs because the fetus continues to draw glucose across the placenta from the maternal bloodstream, even during periods of fasting. Interprandial hypoglycemia becomes increasingly marked as pregnancy progresses and the glucose demand of the fetus increases.
• Levels of placental steroid and peptide hormones (eg, estrogens, progesterone, and chorionic somatomammotropin) rise linearly throughout the second and third trimesters. Because these hormones confer increasing tissue insulin resistance as their levels rise, the demand for increased insulin secretion with feeding escalates progressively during pregnancy. Twenty-four–hour mean insulin levels are 50% higher in the third trimester compared to the nonpregnant state.
• If the maternal pancreatic insulin response is inadequate, maternal and, then, fetal hyperglycemia results. This typically manifests as recurrent postprandial hyperglycemic episodes. These postprandial episodes are most significantly accountable for the accelerated growth exhibited by the fetus.
• Surging maternal and fetal glucose levels are accompanied by episodic fetal hyperinsulinemia. Fetal hyperinsulinemia promotes excess nutrient storage, resulting in macrosomia. The energy expenditure associated with the conversion of excess glucose into fat causes depletion in fetal oxygen levels.
• These episodes of fetal hypoxia are accompanied by surges in adrenal catecholamines, which, in turn, cause hypertension, cardiac remodeling and hypertrophy, stimulation of erythropoietin, red cell hyperplasia, and increased hematocrit. Polycythemia (hematocrit >65%) occurs in 5-10% of newborns of diabetic mothers. This finding appears to be related to the level of glycemic control and is mediated by decreased fetal oxygen tension. High hematocrit values in the neonate lead to vascular sludging, poor circulation, and postnatal hyperbilirubinemia.

During a healthy pregnancy, mean fasting blood sugar levels decline progressively to a remarkably low value of 74 � 2.7 (SD) mg/dL. On the other hand, peak postprandial blood sugar values rarely exceed 120 mg/dL. Meticulous replication of the normal glycemic profile during pregnancy has been demonstrated to reduce the macrosomia rate. Specifically, when 2 hour postprandial glucose levels are maintained less than 120 mg/dL, approximately 20% of fetuses demonstrate macrosomia. Conversely, if postprandial levels range up to 160 mg/dL, macrosomia rates rise to 35%.

• Fetal morbidity with diabetes during pregnancy
• • Miscarriages
  • • In all women with preexisting diabetes mellitus, there is a 9-14% rate of miscarriage.
    • Current data suggest a strong association between degree of glycemic control prior to pregnancy and miscarriage rate. Suboptimal glycemic control has been shown to double the miscarriage rate in women with diabetes. A correlation also exists between more advanced diabetes and miscarriage rates. Patients with long-standing (>10 y) and poorly controlled (glycohemoglobin exceeding 11%) diabetes have been shown to have a miscarriage rate of up to 44%. Conversely, reports demonstrate a normalization of miscarriage rate with excellent glycemic control.
  • Birth defects
  • • Among the general population, major birth defects occur in 1-2% of the population. In women with overt diabetes and suboptimal glycemic control prior to conception, the likelihood of a structural anomaly is increased 4- to 8-fold.
    • Although initial reports demonstrated anomaly rates as high as 18% in women with preexisting diabetes mellitus,more recent reports with more aggressive preconception and first trimester management report anomaly rates between 5.1 and 9.8%.
    • Two-thirds of anomalies involve the cardiovascular and central nervous systems. Neural tube defects occur 13-20 times more frequently in diabetic pregnancy. Genitourinary, gastrointestinal, and skeletal anomalies are also more common.
    • The fact that no increase in birth defects occurs among the offspring of fathers who are diabetic and women who develop gestational diabetes after the first trimester is notable. This suggests that periconceptional glycemic control is the main determinant of abnormal fetal development in diabetic women.
    • When the frequency of congenital anomalies in patients with normal or high first-trimester maternal glycohemoglobin values was compared to the frequency in healthy patients, the rate of anomalies was only 3.4% with glycosylated hemoglobin values (HbA1C) of less than 8.5%, whereas patients with poorer glycemic control in the periconceptional period (HbA1C >8.5%) had a 22.4% rate of malformations. An overall malformation rate of 13.3% was reported in 105 patients with diabetes, but the risk of delivering a malformed infant was comparable to a normal population when the glycosylated hemoglobin (HbA1c ) was less than 7%. More recently, in a review of 7 cohort studies, researchers found that patients with a normal glycohemoglobin (0 SD above normal), the absolute risk of an anomaly was 2%. At 2 SD above normal, this risk was 3%, with an odds ratio of 1.2 (1.1- 1.4). As the glycohemoglobin increased so did the risk for malformation in a direct relationship.
    • Because birth defects occur during the critical 3-6 weeks after conception, nutritional and metabolic intervention must be initiated well before pregnancy begins. Clinical trials of intensive metabolic care have demonstrated that malformation rates similar to those in the nondiabetic population can be achieved with meticulous preconceptional glycemic control. Subsequent trials comparing a preconceptional intensive metabolic program to standard treatment over 15 years duration have demonstrated lowered perinatal mortality (0% vs 7%) and reduced congenital anomaly rate (14% to 2%). In addition, when the preconceptional counseling program was discontinued, the congenital anomaly rate increased by over 50%.
  • Growth restriction
  • • Although most fetuses of diabetic mothers exhibit growth acceleration, growth restriction occurs with significant frequency in pregnancies in women with preexisting type 1 diabetes.
    • The most import predictor of fetal growth restriction is underlying maternal vascular disease. Specifically, pregnant patients with diabetes-associated retinal or renal vasculopathies and/or chronic hypertension are most at risk for growth restriction.
  • Growth acceleration
  • • Excessive body fat stores, stimulated by excessive glucose delivery during diabetic pregnancy, often extends into childhood and adult life.
    • Approximately 30% of fetuses of women with diabetes mellitus in pregnancy are large for gestational age (LGA). In preexisting diabetes mellitus this incidence appears slightly higher, 38%.
    • Maternal obesity, common in type 2 diabetes, appears to significantly accelerate the risk of infants being LGA.
  • Fetal obesity
  • • Macrosomia is typically defined as a birthweight above the 90th percentile for gestational age or greater than 4000 grams. In pregnant diabetic women, macrosomia occurs in 15-45% of cases, a 3-fold increase from normoglycemic controls.
    • Newborns with macrosomia experience excessive rates of neonatal morbidity, as illustrated by a study by Hunter et al in 1993, which compared the neonatal morbidity among infants of 230 women with insulin-dependent diabetes and infants of 460 women without diabetes. The infants of diabetic mothers (IDMs) had 5-fold higher rates of severe hypoglycemia, a 4-fold increase in macrosomia, and a doubled increase in neonatal jaundice.
    • Birth injury, including shoulder dystocia and brachial plexus trauma, are more common among infants of diabetic mothers, and macrosomic fetuses are at the highest risk.
    • The macrosomic fetus in diabetic pregnancy develops a unique pattern of overgrowth, involving central deposition of subcutaneous fat in the abdominal and interscapular areas. Skeletal growth is largely unaffected. Neonates of diabetic mothers have a larger shoulder and extremity circumference, a decreased head-to-shoulder ratio, significantly higher body fat and thicker upper extremity skin folds compared to nondiabetic control infants of similar weights. Since fetal head size is not increased during poorly controlled diabetic pregnancy but shoulder and abdominal girth can be markedly augmented, the risk of injury to the fetus after delivery of the head (eg Erb palsy) is significantly increased.
    • When serial ultrasound examination findings from diabetic fetuses are plotted, the growth velocity of the abdominal circumference is often well above the growth centiles seen in nondiabetic fetuses and is higher than the fetal head and femur centiles. The accelerated growth of the abdominal circumference begins to rise significantly above normal after 24 weeks.
  • Metabolic syndrome
  • • The adverse downstream effects of abnormal maternal metabolism on the offspring have been documented well into puberty. Glucose intolerance and higher serum insulin levels are more frequent in children of diabetic mothers as compared to normal controls. By age 10-16 years, offspring of diabetic pregnancy have a 19.3% rate of impaired glucose intolerance.
    • The childhood metabolic syndrome includes childhood obesity, hypertension, dyslipidemia, and glucose intolerance. A growing body of literature supports a relationship between intrauterine exposure to maternal diabetes and risk of a metabolic syndrome later in life.
    • Fetuses of diabetic women that are born large for gestational age appear to be at the greatest risk.
  • Role of glucose levels
  • • Excess nutrient delivery to the fetus causes macrosomia and truncal fat deposition, but whether fasting or peak glucose values are more correlated with fetal overgrowth is less clear.
    • Data from the Diabetes in Early Pregnancy project indicate that fetal birthweight correlates best with second- and third-trimester postprandial blood sugar levels and not with fasting or mean glucose levels.¹⁷
    • More recent data from the ACHOIS trial demonstrated a positive relationship between severity of maternal fasting hyperglycemia and risk of shoulder dystocia, with a 1 mmol increase in fasting glucose leading to a relative risk for shoulder dystocia of 2.09 (1.03- 4.25).¹⁸
    • When postprandial glucose values average 120 mg/dL or less, approximately 20% of infants can be expected to be macrosomic. When postprandial levels range as high as 160 mg/dL, macrosomia rates can reach 35%.
    • In addition, there appears to be a role for excessive fetal insulin levels in mediating accelerated fetal growth. In the study by Simmons et al which compared umbilical cord sera in infants of diabetic mothers newborns and controls, the heavier, fatter babies from diabetic pregnancies were also hyperinsulinemic.¹⁹
  • Role of maternal obesity
  • • Maternal obesity has a strong and independent effect on fetal macrosomia. Birthweight is largely determined by maternal factors other than hyperglycemia, with the most significant influences being gestational age at delivery, prepregnancy maternal body mass index (BMI), maternal height, pregnancy weight gain, the presence of hypertension, and cigarette smoking.
    • When women who are very obese (weight >300 lb) were compared to women of normal weight, the obese women had more than double the risk of macrosomia compared to the women who were of normal weight. This may explain the failure of glycemic control to completely prevent fetal macrosomia in several series.
• Perinatal morbidity and birth injury
• • Perinatal mortality
  • • In diabetic pregnancy, perinatal mortality has decreased 30-fold since the discovery of insulin in 1922 and intensive obstetrical and infant care in the 1970s. Nevertheless, the current perinatal mortality rates among women who are diabetic remain approximately twice those observed in the nondiabetic population.
    • Congenital malformations, respiratory distress syndrome (RDS), and extreme prematurity account for most perinatal deaths in contemporary diabetic pregnancies.

• • Birth injury
  • • Injuries of birth, including shoulder dystocia and brachial plexus trauma, are more common among infants of diabetic mothers, and macrosomic fetuses are at the highest risk.
    • Most of the birth injuries occurring to infants of diabetic mothers are associated with difficult vaginal delivery and shoulder dystocia. While shoulder dystocia occurs in 0.3-0.5% of vaginal deliveries among healthy pregnant women, the incidence is 2- to 4-fold higher in women with diabetes. With strict glycemic control, the birth injury rate has been shown to be only slightly higher than controls (3.2 vs 2.5%).
    • Currently, clinical ability to predict shoulder dystocia is poor. Warning signs during labor (labor protraction, suspected fetal macrosomia, need for operative vaginal delivery) successfully predict only 30% of these events.
    • Common birth injuries associated with diabetes are brachial plexus, facial nerve injury, and cephalohematoma.
  • Polycythemia
  • • A central venous hemoglobin concentration greater than 20 g/dL or a hematocrit value greater than 65% (polycythemia) is not uncommon in infants of diabetic mothers and is related to glycemic control.
    • Hyperglycemia is a powerful stimulus to fetal erythropoietin production mediated by decreased fetal oxygen tension.
    • Untreated neonatal polycythemia may promote vascular sludging, ischemia, and infarction of vital tissues, including the kidneys and central nervous system.
  • Hypoglycemia
  • • Approximately 15-25% of neonates delivered from women with diabetes during gestation develop hypoglycemia during the immediate newborn period.²⁰ Neonatal hypoglycemia is less frequent when tight glycemic control is maintained during pregnancy²¹ and in labor.
    • Unrecognized postnatal hypoglycemia may lead to neonatal seizures, coma, and brain damage.
  • Neonatal hypocalcemia
  • • Up to 50% of infants of diabetic mothers have low levels of serum calcium (<7>
    • These changes in calcium appear to be attributable to a functional hypoparathyroidism, though the exact pathophysiology is not well understood.
  • Postnatal hyperbilirubinemia
  • • Hyperbilirubinemia occurs in approximately 25% of infants of diabetic mothers, a rate approximately double that in a healthy population. The causes of hyperbilirubinemia in infants of diabetic mothers are multiple, but prematurity and polycythemia are the primary contributing factors. Increased destruction of red blood cells contributes to the risk of jaundice and kernicterus.
    • Treatment of this complication is usually by phototherapy, but exchange transfusions may be necessary if bilirubin levels are markedly elevated.
  • Respiratory problems
  • • Until recently, neonatal respiratory distress syndrome (RDS) was the most common and serious morbidity in infants of diabetic mothers. In the 1970s, improved prenatal maternal management for diabetes and new techniques in obstetrics for timing and mode of delivery resulted in a dramatic decline in its incidence from 31% to 3%.²² Nevertheless, respiratory distress syndrome continues to be a relatively preventable complication.
    • The majority of the literature indicates a significant biochemical and physiological delay in infants of diabetic mothers. Tyden²³ and Landon²⁴ and colleagues reported that fetal lung maturity occurred later in pregnancies with poor glycemic control regardless of class of diabetes when infants were stratified by maternal plasma glucose levels.
    • The nondiabetic fetus achieves pulmonary maturity at a mean gestational age of 34-35 weeks. By 37 weeks’ gestation, more than 99% of healthy newborn infants have mature lung profiles as assessed by phospholipid assays. However, in a diabetic pregnancy, presuming that the risk of respiratory distress has passed is unwise until after 38.5 gestational weeks have been completed.
    • Prior to contemplating any delivery before 38.5 weeks for other than the most urgent fetal and maternal indications, perform an amniocentesis to document pulmonary maturity.
• Maternal morbidity
• • Diabetic retinopathy
  • • This is the leading cause of blindness in women aged 24-64 years. Some form of retinopathy is present in virtually 100% of women who have had type 1 diabetes for 25 years or more; of these women, approximately 1 in 5 is legally blind.
    • A prospective study showed that while half the patients with preexisting retinopathy experienced deterioration during pregnancy, all the patients had partial regression following delivery and returned to their prepregnant state by 6 months postpartum.
    • Other studies have suggested that rapid induction of glycemic control in early pregnancy stimulates retinal vascular proliferation.²⁵ However, when the total effect of pregnancy on ophthalmologic status was considered, women with pregnancies had a slower progression of retinopathy than nonpregnant women, probably because the modest deterioration in retinal status during rapid improvement in control is offset by the excellent control during the remainder of the pregnancy.
    • Current management recommendations include baseline ophthalmology referral for pregnant patients with diabetes, with follow-up according to degree of retinopathy.
  • Renal function
  • • In general, patients with underlying nephropathy can expect varying degrees of deterioration of renal function during a pregnancy. As renal blood flow and glomerular filtration rate increase 30-50% during pregnancy, the degree of proteinuria will also increase.
    • The most recent studies indicate that pregnancy does not measurably alter the time course of diabetic renal disease, nor does it increase the likelihood of progression to end stage renal disease. The progression to renal disease in diabetic patients appears to be related to duration of diabetes and degree of glycemic control.
    • Patients using the subcutaneous insulin pump have lower mean glucose levels than those using intermittent injections. The effect on progression of nephropathy of 2 years of strict metabolic control showed that none of the patients managed on the insulin pump progressed to clinical nephropathy, while 5 patients with conventional treatment did.
    • Perinatal complications are greatly increased in patients with diabetic nephropathy. Preterm birth, intrauterine growth restriction, and preeclampsia are all significantly more common in women with diabetic nephropathy during pregnancy.
  • Chronic hypertension
  • • This complicates approximately 1 in 10 diabetic pregnancies overall. Patients with underlying renal or retinal vascular disease are at a substantially higher risk, with 40% having chronic hypertension.
    • Patients with chronic hypertension and diabetes are at increased risk of intrauterine growth restriction, superimposed preeclampsia, abruptio placentae, and maternal stroke.
    • Baseline renal function determination is recommended in all patients with preexisting diabetes. Renal function assessments in each trimester should be performed in those with overt vascular disease or who have had diabetes for more than 10 years.
  • Preeclampsia
  • • Consists of abrupt elevation in blood pressure, significant proteinuria, plasma uric acid levels greater than 6 mg/dL or evidence of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome.
    • Preeclampsia is more frequent among women with diabetes, occurring in approximately 12% as compared to 8% of the nondiabetic population. The risk of preeclampsia is also related to maternal age and the duration of preexisting diabetes. In patients who have chronic hypertension coexisting with diabetes, preeclampsia may be difficult to distinguish from near-term blood pressure elevations.
    • The rate of preeclampsia has been found to be related to the level of glycemic control, with fasting plasma glucose (FPG) less than 105, the rate of preeclampsia was 7.8%, if FPG was greater than 105, the rate of preeclampsia was 13.8%.²⁶
    • In this same study, pregravid body mass index was also significantly related to the development of preeclampsia.

• A family history of diabetes in parents or brothers and sisters.
• Gestational diabetes in a previous pregnancy
• the presence of o birth defect in a previous pregnancy
• obesity in the women.BMI greather than 29
• older mathernal age(over the age of 30)
• previous delivery of large baby(4 kg or more)
• A history of pregnancy induced high blood pressure,urinary tract infections,hydramnions(extra amniotic fluids)
• Race :women of hispanic ,asian,african-american decent.