perinatology.com



Home > perinatology > Big Babies


 By David A Sacks MD
Department of Research, Southern California Permanente Medical Group Pasadena, California
 

The relationship between large birth weight and maternal glucose intolerance has been acknowledged for decades. Imprecision of definition and a lack of understanding of the components of the maternal and fetal metabolic milieus have, at least in part, hampered attempts to reduce this adverse perinatal outcome. With the advent of the worldwide epidemic of obesity, research has focused on overweight and obesity, particularly in women of reproductive age. Together with studies of the pathophysiology of diabetes during pregnancy and of fetal and neonatal body composition, much has been learned about how big babies develop. This paper will endeavor to summarize what is known about the development of large newborns in pregnancies complicated by diabetes, as well as reviewing attempts at decreasing their prevalence.


Definition

     There is no universally accepted definition of a large baby. The entity may be defined nominally by such terms as “macrosomic” “large for gestational age” (LGA), or “oversized”. Macrosomia is defined by an absolute birth weight, usually 4000 or 4500 grams [1]  A single birthweight carries with it the ease of memorization and application. However, it fails to consider the influence of gestational age. For example, a baby delivered at 34 weeks and weighing 4000 grams is biologically and physiologically very different from one delivered at 40 weeks. Identifying a baby as “large for gestational age” (LGA), usually defined as weighing more than the 90th percentile for gestational age and gender, eliminates confounding by duration of pregnancy, but does not consider the influences of other variables such as geography and ethnicity. Thus the numerical standards used to define LGA should be derived from a population similar to that of the baby being assessed [2]

     Likely macrosomia and LGA are the two terms most commonly used to define a larger than average-weight baby. However, neither measure offers commentary on body composition. Two studies from the same institution measured fat and lean tissue by a non-invasive device (TOBEC) using measurement of electrical conductivity in the newborn. Given that, because of its electrolyte content, lean tissue is a better conductor of electricity than is fat mass, estimation of lean body mass is achieved by comparison of electrical conductivity of the baby with a standard curve derived from carcass conductivity. After weighing the baby, lean body mass is subtracted from the baby’s weight to obtain an estimate of fat mass. Using TOBEC, a comparison of LGA neonates found relatively less lean body mass and relatively more fat mass in LGA neonates of women who had gestational diabetes (GDM), compared with LGA neonates of mothers who were normoglycemic [3]. Even among appropriate for gestational age babies, those of diabetic mothers were found to have greater fat content and percent of body weight that is fat than those of non-diabetic women [4]. Fat deposition in upper body subcutaneous tissue may, in part, explain the finding that for every 250 gram increment in birth weight above 3750 grams, infants of diabetic women were significantly more likely to experience shoulder dystocia than were infants of non-diabetic women of comparable weight [5]. These observations raise the possible need of the expression of birthweight to include fat mass. Universal application of this concept awaits the development of an easily applied tool for measuring this parameter.


Maternal Factors Associated With Large Babies

Elucidating the causal factors or those which are associated with increased fetal growth is not an easy task. This is of particular concern in infants of diabetic women. A number of demographic confounders are associated with fetal growth [Table 1]. All except smoking and hypertension have a positive relationship with birth weight.

Table 1. Variables which may contribute to fetal growth.

  • Maternal age
  • Ethnicity
  • Parity
  • Prepregnancy BMI
  • Weight gain during pregnancy
  • Smoking []
  • Hypertension []
  • Fetal gender
  • Gestational age at birth


Few studies have been performed controlling for each of these factors to determine the independent relationship between each and birth weight. In studies which have investigated this question, different definitions were used for independent and dependent variables (e.g. for hyperglycemia, big babies). Not all studies controlled for the same variables [Table 2]. Despite these differences, the maternal factors that most consistently emerge as being independently associated with birth weight are prepregnancy weight and maternal glucose concentrations during pregnancy, Table 2 [6-10].

 (Click image to enlarge)
 

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]

Category BMI (kg/m2) Total pounds Pounds per week
Underweight < 18.5 28 -40 1
Normal 18.5 -24.9 25 - 35 1
Overweight 25 - 29.9 15 -25 0.6
Obese > 30 11 -20 0.5


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.
 


References


1. Modanlou HD, Dorchester WL, Thorosian A, Freeman RK. Macrosomia--maternal, fetal, and neonatal implications. Obstet Gynecol 1980;55:420-4. PMID: 7366896
2. Williams RL, Creasy RK, Cunningham GC, Hawes WE, Norris FD, Tashiro M. Fetal growth and perinatal viability in California. Obstet Gynecol 1982;59:624-32.PMID:7070736
3. Durnwald C, Huston-Presley L, Amini S, Catalano P. Evaluation of body composition of large-for-gestational-age infants of women with gestational diabetes mellitus compared with women with normal glucose tolerance levels. Am J Obstet Gynecol 2004;191:804-8. PMID: 15467545
4. Catalano PM, Thomas A, Huston-Presley L, Amini SB. Increased fetal adiposity: a very sensitive marker of abnormal in utero development. Am J Obstet Gynecol 2003;189:1698-704. PMID: 14710101
5. Langer O, Berkus MD, Huff RW, Samueloff A. Shoulder dystocia: should the fetus weighing greater than or equal to 4000 grams be delivered by cesarean section? Am J Obstet Gynecol 1991;165:831-7. PMID: 1951539
6. Ehrenberg HM, Mercer BM, Catalano PM. The influence of obesity and diabetes on the prevalence of macrosomia. Am J Obstet Gynecol 2004;191:964-8. PMID: 15467573
7. Cundy T, Gamble G, Manuel A, Townend K, Roberts A. Determinants of birth-weight in women with established and gestational diabetes. Aust N Z J Obstet Gynaecol 1993;33:249-54. PMID: 8304885
8. Stotland NE, Caughey AB, Breed EM, Escobar GJ. Risk factors and obstetric complications associated with macrosomia. Int J Gynaecol Obstet 2004;87:220-6. PMID: 15548393
9. Surkan PJ, Hsieh CC, Johansson AL, Dickman PW, Cnattingius S. Reasons for increasing trends in large for gestational age births. Obstet Gynecol 2004;104:720-6. PMID: 15458892
10. Sacks DA, Liu AI, Wolde-Tsadik G, Amini SB, Huston-Presley L, Catalano PM. What proportion of birth weight is attributable to maternal glucose among infants of diabetic women? Am J Obstet Gynecol 2006;194:501-7. PMID: 16458653
11. Yogev Y, Ben-Haroush A, Chen R, Rosenn B, Hod M, Langer O. Diurnal glycemic profile in obese and normal weight nondiabetic pregnant women. Am J Obstet Gynecol 2004;191:949-53. PMID: 15467570
12. Ben-Haroush A, Yogev Y, Chen R, Rosenn B, Hod M, Langer O. The postprandial glucose profile in the diabetic pregnancy. Am J Obstet Gynecol 2004;191:576-81. PMID: 15343240
13. Standards of medical care in diabetes--2010. Diabetes Care;33 Suppl 1:S11-61. PMID: 20042772
14. de Veciana M, Major CA, Morgan MA, et al. Postprandial versus preprandial blood glucose monitoring in women with gestational diabetes mellitus requiring insulin therapy. N Engl J Med 1995;333:1237-41. PMID: 7565999
15. Peck RW, Price DE, Lang GD, MacVicar J, Hearnshaw JR. Birthweight of babies born to mothers with type 1 diabetes: is it related to blood glucose control in the first trimester? Diabet Med 1991;8:258-62. PMID: 1828742
16. Hackmon R, Le Scale KB, Horani J, Ferber A, Divon MY. Is severe macrosomia manifested at 11-14 weeks of gestation? Ultrasound Obstet Gynecol 2008;32:740-3. PMID: 18570208
17. Kerssen A, de Valk HW, Visser GH. Increased second trimester maternal glucose levels are related to extremely large-for-gestational-age infants in women with type 1 diabetes. Diabetes Care 2007;30:1069-74. PMID: 17468376
18. Bo S, Menato G, Signorile A, et al. Obesity or diabetes: what is worse for the mother and for the baby? Diabetes Metab 2003;29:175-8. PMID: 12746640
19. Ouzilleau C, Roy MA, Leblanc L, Carpentier A, Maheux P. An observational study comparing 2-hour 75-g oral glucose tolerance with fasting plasma glucose in pregnant women: both poorly predictive of birth weight. CMAJ 2003;168:403-9. PMID: 12591779
20. Ray JG, Vermeulen MJ, Shapiro JL, Kenshole AB. Maternal and neonatal outcomes in pregestational and gestational diabetes mellitus, and the influence of maternal obesity and weight gain: the DEPOSIT study. Diabetes Endocrine Pregnancy Outcome Study in Toronto. QJM 2001;94:347-56. PMID: 11435630
21. Cheng YW, Chung JH, Kurbisch-Block I, Inturrisi M, Shafer S, Caughey AB. Gestational weight gain and gestational diabetes mellitus: perinatal outcomes. Obstet Gynecol 2008;112:1015-22. PMID: 18978100
22. Rasmussen KM, Catalano PM, Yaktine AL. New guidelines for weight gain during pregnancy: what obstetrician/gynecologists should know. Curr Opin Obstet Gynecol 2009;21:521-6. PMID: 19809317
23. Weight Gain During Pregnancy: Reexamining the Guidelines.Institute of Medicine (US) and National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines; Rasmussen KM, Yaktine AL, editors. National Academies press 2009. PMID: 20669500
24. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005;352:2477-86. PMID: 7366896
25. Landon MB, Spong CY, Thom E, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009;361:1339-48. PMID: 19797280
26. Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005;115:e290-6. PMID: 15741354
27. Jarvie E, Hauguel-de-Mouzon S, Nelson SM, Sattar N, Catalano PM, Freeman DJ. Lipotoxicity in obese pregnancy and its potential role in adverse pregnancy outcome and obesity in the offspring. Clin Sci (Lond);119:123-9. PMID: 20443782
28. Cogswell ME, Scanlon KS, Fein SB, Schieve LA. Medically advised, mother's personal target, and actual weight gain during pregnancy. Obstet Gynecol 1999;94:616-22. PMID: 10511369
29. Stotland NE, Haas JS, Brawarsky P, Jackson RA, Fuentes-Afflick E, Escobar GJ. Body mass index, provider advice, and target gestational weight gain. Obstet Gynecol 2005;105:633-8. PMID: 15738036
30. Claesson IM, Sydsjo G, Brynhildsen J, et al. Weight gain restriction for obese pregnant women: a case-control intervention study. BJOG 2008;115:44-50. PMID: 17970795
31. Callaway LK, Colditz PB, Byrne NM, et al. Prevention of gestational diabetes: feasibility issues for an exercise intervention in obese pregnant women. Diabetes Care;33:1457-9. PMID: 20357374
32. Kinnunen TI, Pasanen M, Aittasalo M, et al. Preventing excessive weight gain during pregnancy - a controlled trial in primary health care. Eur J Clin Nutr 2007;61:884-91. PMID: 17228348
33. Olson CM, Strawderman MS, Reed RG. Efficacy of an intervention to prevent excessive gestational weight gain. Am J Obstet Gynecol 2004;191:530-6. PMID: 15343232

 

Home | About | Disclaimer | Privacy | Contact
Copyright © 2010 by Focus Information Technology.
All rights reserved