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Diabetes and Prepregnancy weight

Much attention has been paid to the relationship between measures of maternal glycemia and birth weight. A critical starting point is to determine what a normal 24-hour glucose profile in a metabolically normal pregnant woman looks like. One study used continuous subcutaneous glucose monitoring to compare glucose values of non-obese and obese non-diabetic women throughout the day. Though the respective fasting glucose values of both groups were not statistically significantly different (72 mg/dl and 73 mg/dl), the respective one-hour post-prandial glucose values (103 mg/dl and 112 mg/dl, p=0.04); peak glucose values (106 mg/dl and 118 mg/dl) and time to peak glucose values (71 and 88 minutes, p= 0.03 minutes) were statistically significantly different. The lack of uniformity in post-meal and peak results as well as in time to peak value call into question the appropriateness of a “one size fits all” approach to glycemic targets during pregnancy [11]. Among women who underwent 24 hour continuous glucose monitoring who had gestational diabetes (GDM) treated with diet, GDM treated with insulin, and type 1 diabetes, there were statistically significant differences in peak post-meal glucose values (respectively 131 mg/dl, 148 mg/dl, and 182 mg/dl), but the time to peak glucose (mean 85 minutes) was not significantly different among the three groups [12]. Cumulatively, these studies demonstrate that the time to peak glucose concentration in non-diabetic pregnant women differs between obese and non-obese gravidas, but that there is no difference in time to peak glucose for women who have different types of diabetes; that peak glucose concentrations for women who have gestational diabetes approximates the 130-140 mg/dl post-meal targets recommended by some diabetes associations [13], but that these peaks are achieved later in women both with and without diabetes. than the 1-hour post-meal interval used by many as a yardstick to measure glycemic control

Which maternal glucose value relative to a meal is most closely related to birth weight is another area of contention. Likely the only randomized controlled trial to address this issue found that the 1-hour post-meal glucose value best identified women at increased risk of having a large baby. However, an underlying assumption in that study was the equivalence in predictive value for fetal macrosomia of a fasting glucose of 60 to 90 mg/dl and a postprandial glucose concentration of less than 140 mg/dl. While patients managed on the basis of their post-meal glucose had significantly fewer large babies than did those whose management was based on pre-meal glucose results, the question of whether respectively lowering or raising pre-prandial and/or post-prandial glucose targets would have changed the outcome of the study remains unresolved [14]

Yet another area of inquiry is the question of when in gestation maternal glycemic control is most important in affecting fetal growth. One study reported that among mothers who had type 1 diabetes and whose babies were LGA hemoglobin A1c in first, but not third trimester was greater than that of women who had non-LGA babies [15]. This has biological plausibility, in that other investigators reported a positive correlation between the birth weight ratio (birth weight /birth weight at the 50th percentile for gestational age) and the difference between actual and expected crown-rump length in first trimester. However, no such correlation was found in appropriate weight for gestational age neonates [16]. Finally, among diabetic women who had serial ultrasound estimates of fetal weight, those who developed sonographically-detected LGA before 30 weeks gestation had higher maternal glucose concentrations in second trimester than in first or third. Those whose fetal LGA had been detected after 30 weeks and those whose babies were appropriate for gestational age (AGA) had no significant differences in glucose throughout all three trimesters, suggesting that early excessive fetal growth in infants of diabetic women may be more closely related to hyperglycemia in second trimester than earlier or later in gestation [17].

As previously mentioned, in multivariable analyses of the nature of the relationship between diabetic women’s demographics, laboratory findings, and large babies, maternal prepregnancy weight and glucose concentrations are more often found to be independently associated with large babies than are other variables [18, 19]. A few reports have attempted to analyze which of these two variables have a stronger relationship with large birth weight [6,10]. Although pregestational and gestational diabetes appear to have a stronger independent relationship with fetal macrosomia than does maternal obesity, a far greater proportion of the obstetric population is obese than is diabetic. Thus the proportion of large babies in a given patient population which may be attributed to maternal obesity is greater than that which may be attributed to maternal glucose intolerance [6].


Weight Gain

An independent positive relationship between maternal weight gain during pregnancy and birth weight has been reported among women who have pregestational and gestational diabetes [7, 20, 21]. Obesity and overweight in general, and in reproductive age women in particular, have become international problems. Data collected from 1993 to 2003 in the US demonstrates a progressive annual increase in the amount of weight gained during pregnancy. Furthermore, weight gain among overweight and obese women appears to be proportionately greater than among those who have normal and underweight prepregnancy body mass indices (BMIs) [22, 23]
 

Preventing Large Birth Weight Babies

Of the three elements associated with birth weight: prepregnancy BMI, maternal glycemia, and maternal weight gain during pregnancy, only the latter two are amenable to interventions. While much attention has been paid to control of maternal glycemia, attention to restriction of maternal weight gain has only relatively recently attracted interest from the scientific community. That restriction of weight gain during pregnancy is of benefit was demonstrated in two blinded randomized controlled trials of women with gestational diabetes [24, 25]. The treatment modalities employed in the study groups were limited to diet and exercise. Insulin was added only for the minority of women who failed to achieve glycemic control with diet and exercise alone. Both studies found a reduction in maternal weight gain and birth weight. Neither study reported daily measures of maternal glycemia. However, one of the two studies additionally measured neonatal fat mass, and found this parameter to be decreased in the intervention group. That this is of clinical importance is indicated by emerging data demonstrating a relationship between excessive weight at birth-likely consisting of central adipose- and subsequent development of the metabolic syndrome, from childhood [26] to adulthood [27].

Based on reviews of studies relating maternal weight gain to both maternal weight retention following delivery and birth weight, as well as to other maternal and perinatal outcomes, in 2009 the Institute of Medicine (IOM) modified its 1990 guidelines for weight gain, dependent upon maternal prepregnancy BMI [Table 3]. The greater the prepregnancy BMI, the less the weight gain per pregnancy recommended [23].
 

Table 3. IOM Suggested total pregnancy weight gain, by BMI categories [23]

A first step in attempting control of maternal weight gain is the education of caregivers. Two studies published since 1990 (the year that the first iteration of the IOM guidelines were released) found that one-third of caregivers to pregnant women gave no weight gain advice to their patients. Only 37 to 49 percent of pregnant women were advised to gain weight within the IOM guidelines [28, 29]. That patients follow physicians’ advise regarding weight gain was demonstrated by the finding that a significantly greater proportion of women advised to gain more than the IOM guidelines did so than did not. The same was true of women advised by their physicians to gain less than that suggested by the guidelines.

While no single program has had universal success in achieving appropriate weight gain in pregnant women, tools are available that may be of use to motivated women who are supported in their efforts by medical staff, family, and friends. The United States Department of Agriculture maintains a website (www.mypyramid.gov/mypyramidmoms) on which information regarding diet and exercise, divided into segments for patients and for professionals may be found. Besides instruction and monitoring of food intake and exercise, other modifiable potential barriers to achieving these goals should be frankly discussed. Smokers and those abusing alcohol and/or recreational drugs should be encouraged to discontinue their habits. Referral to therapists or to programs dealing with these problems seems prudent. Marginal income may pose a barrier to buying appropriate food. Information about federal and state programs providing funding for healthy eating may be obtained through local social service agencies. Walking is likely the most common form of exercise utilized by pregnant women. However, women who live in unsafe neighborhoods may be reluctant to walk in those neighborhoods. Problem solving regarding these barriers to achieving a healthy lifestyle requires the incorporation of social service workers, nutritionists, physical therapists, psychologists and psychiatrists, all of whom ideally should be available during the course of a woman’s pregnancy. Programs limiting maternal weight gain and/or large babies have met with mixed success. Unique features of each include the incorporation of water aerobics [30], individualized exercise regimens [31] frequent office visits [32], and frequent mailings of supportive and instructive material [33]. While further study is needed, making pregnant women aware of the guidelines for weight gain for pregnancy and of the resources available to assist these women to achieve their goals is a reasonable starting point.
 

Conclusions

Though imperfect, defining a large baby as one whose birth weight is ≥ the 90th percentile for the population of which (s)he is a member allows comparison between babies from different populations. Consideration should be given to devising a method to easily measure neonatal fat mass, and perhaps incorporating the latter in classifying birth weight. Both maternal glycemia and maternal weight gain are modifiable factors associated with birth weight in women who have diabetes. Further study is needed to better define appropriate maternal glycemic targets and appropriate maternal weight gain to minimize maternal obesity and fetal overgrowth in pregnancies complicated by diabetes mellitus.