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Pre-pregnancy weight and excess weight gain are risk factors for macrosomia in women with gestational diabetes

Abstract

Objective:

To determine whether women with gestational diabetes mellitus (GDM) whose weight gain exceeded the 2009 Institute of Medicine (IOM) recommendations were more likely to have macrosomia.

Study Design:

Retrospective cohort study of the association of weight gain in women with Class A1 GDM, with term (37 weeks) singleton liveborns and macrosomia (birthweight 4000 g). Multivariate logistic regression models were used to adjust for covariates and test for interactions.

Result:

Of 1502 women studied, pre-pregnancy body mass index (BMI) categories were: normal (39.6%), overweight (28.5%) and obese (31.9%). The mean (±standard deviation ) weight gain (lbs) for these groups was: 27.6±10.9, 24.2±13.0 and 18.8±16.3 (P<0.0001), whereas the occurrence of macrosomia was 7.4, 11.4 and 19.0%, respectively. Women with an obese BMI were twice as likely to have a macrosomic infant compared with women in the normal BMI group (odds ratio, OR 2.0; 95% CI 1.4–3.0; P=0.0005). Independently, women who exceeded the IOM guidelines were three times more likely to have a macrosomic infant (OR 3.0, 95% CI 2.2–4.2, P<0.0001).

Conclusion:

Maternal pre-pregnancy weight and weight gain during pregnancy appear to be significant and independent risk factors for macrosomia in women with GDM.

Introduction

Gestational diabetes mellitus (GDM) complicates approximately 7% of pregnancies in the United States1 and is associated with an increased risk for adverse perinatal outcomes.2 In particular, women with GDM historically have been reported to have an increased risk for fetal macrosomia, which in turn can be associated with higher rates of shoulder dystocia, abnormal labor and other complications.3, 4 Historic risk factors for macrosomia have included increased maternal weight and excessive weight gain,5, 6, 7, 8 but they are also associated with the occurrence of GDM in and of itself.9, 10, 11, 12, 13 As such, the quantitative relationship and interaction between these various attributes has remained elusive.

Frequently, women begin their pregnancy either overweight or obese and then gain excess weight during the pregnancy.14 Clinically, optimizing weight gain to minimize fetal risk without jeopardizing maternal health is especially challenging in patients with GDM. The American Congress of Obstetricians and Gynecologists classifications of maternal weight and optimal weight gain during pregnancy are based on recommendations from the Institute of Medicine (IOM).14 In 2009, the IOM released revised guidelines with specified weight-gain thresholds related to pre-pregnancy body-mass index (BMI).15

Although reduced compliance with the IOM-stipulated weight-gain targets has resulted in higher rates of fetal macrosomia in non-diabetic women,7, 15, 16, 17, 18, 19 adherence to the guidelines has been shown to actually reduce the risk for GDM itself.13, 20, 21, 22 However, among women with GDM, the relationships between maternal weight, weight gain and fetal macrosomia remain unclear. Thus, in the present study, our objective was to determine whether weight gain exceeding the IOM guidelines in women with GDM was associated with macrosomia or other pregnancy complications.

Methods

We conducted a retrospective cohort study of all women with Class A1 GDM who delivered during calendar years 2000 to 2006 at a single institution. Women with term (37 and <42 weeks gestational age), singleton, liveborn fetuses were included in the analysis. The study was approved by the Institutional Review Board and complied with all patient protection criteria stipulated therein.

All patients with GDM had a multidisciplinary care plan including visits, with a diabetes case manager, dietician, obstetrician and perinatologist, as necessary. Patients were started on a regimen of diet and exercise pursuant to standard American Diabetes Association guidelines.23, 24 Patients with poor compliance with diet and exercise or inadequate glycemic control were started on insulin and excluded from this study. Maternal weight was documented at each prenatal visit and women were stratified according to their prepregnancy BMI. Women were excluded if they did not have documentation regarding BMI, maternal weight gain or neonatal birthweight. The BMI was calculated as weight in kilograms divided by height in meters squared. Using the criteria set forth by the National Institutes of Health (NIH), the normal group was defined with a BMI of <25 kg/m2, the overweight group with a BMI of 25 to 29.9 kg/m2, and the obese group with a BMI of 30 kg/m2.25 Because of the extremely low prevalence of underweight women in the study population (<2%), these women were categorized with the normal group.

The 2009 IOM guidelines were used to determine excess weight gain thresholds: a weight gain >35 pounds for the normal group, >25 pounds for the overweight group and >20 pounds for the obese group.15

Macrosomia was defined as birthweight 4000 g. An alternative definition for macrosomia with birthweight 4500 g was included for descriptive purposes only. The associations between macrosomia and maternal characteristics, including weight gain and BMI group, were tested. A multivariable logistic regression model was created to quantify the association of maternal weight gain and maternal BMI with macrosomia. Parameters included in the model were: BMI for both the overweight and obese groups (reference=normal BMI), multiparity with and without a history of GDM (reference=nulliparity), maternal weight gain over the IOM recommendations, maternal age 35 and history of macrosomia. Interaction terms were included for BMI groups1 and whether weight gain exceeded IOM recommendations,2 and history of macrosomia. An additional interaction term was tested for weight gain exceeding IOM recommendations and history of macrosomia. Upon derivation of the final model, gestational age categories were tested using those delivering between 37 weeks and 0 days through 37 weeks and 6 days as a reference, and comparing with similar categories for 38, 39, 40 and 41+ weeks, to account for increased weight gain associated with longer gestations.

For comprehensiveness, there were sufficient data to evaluate whether excess weight gain during pregnancy was associated with several other delivery outcome characteristics in addition to macrosomia. These included cesarean delivery, shoulder dystocia, neonatal hypoglycemia, respiratory distress syndrome and the occurrence of congenital anomalies.

Statistical methods used included: χ2-tests with Yates correction for categorical variables, Kruskal–Wallis one-way analysis of variance for continuous data and multivariable logistic regression analyses. Means are expressed as ±the standard deviation. A P-value <0.05 was considered statistically significant. All calculations were performed using SAS statistical software v.9.1 (Cary, NC, USA).

Results

During the study period, 1577 women with Class A1 GDM delivered term singleton neonates, and of these, 1502 (95.2%) had complete information and were included in the analysis. The majority of women were Latina (59.5%) or Asian (22.4%). The mean maternal age was 32.1±5.3 years (range 15.7–52.0). The mean prepregnancy BMI was 28.7±7.0 (range 15.4–58.5). BMI categories were distributed as follows: normal 595 (39.6%), overweight 428 (28.5%) and obese 479 (31.9%). Only 27 women (1.8%) were classified as ‘underweight’ and for the purposes of this study, they were combined with patients in the ‘normal’ category.

The mean birthweight for all patients was 3482±499 g (median 3470, range 1950–6150), and macrosomia was noted in 185 (12.3%) patients. Compared with women in the normal BMI group, women in the overweight and obese BMI groups had a lower mean maternal weight gain, but they were more likely to exceed the IOM weight gain recommendations (Table 1). These patients also appeared more likely to have a macrosomic infant, both at the 4000 and 4500 g thresholds. For each BMI category, women who exceeded the IOM recommendations were more likely to have a macrosomic newborn (Table 2). Women with and without macrosomia did not differ with regard to age, history of stillbirth, history of earlier GDM or early prenatal care. Women with subsequent fetal macrosomia were more likely to have an earlier history of macrosomia and be multiparous (P<0.0001 and P=0.0016, respectively). Categorization of women by BMI groups was so highly associated with the Latina segment of the study population that the relationship between Hispanic ethnicity and macrosomia could not be evaluated independently. The percent of study patients that were Latina by BMI group was: normal (41.8%), overweight (69.4%) and obese (72.7%), P<0.0001.

Table 1 Relationship of maternal weight gain, weight gain over IOM thresholds and macrosomia by BMI category
Table 2 Prevalence of macrosomia (birthweight 4000 g) with respect to maternal weight gain

Using multivariable logistic regression models, our data demonstrated that obese BMI, weight gain exceeding IOM guidelines and an earlier history of macrosomia were independently and strongly associated with the occurrence of macrosomia in the current pregnancy (P<0.001 for all categories, see Table 3). Interaction terms were non-contributory. Adjustment for gestational age did not affect these results and odds ratio (OR) for overweight BMI, obese BMI, exceeding IOM recommendations and history of macrosomia remained essentially unchanged (OR±95% CI, respectively): 1.11 (0.71–1.74), 1.94 (1.29–2.91), 2.99 (2.13–4.19) and 3.89 (2.55–5.93). Note that these findings were consistent at both the 4000 and 4500 g macrosomia thresholds.

Table 3 Multivariable logistic regression equation results for patient characteristics associated with macrosomia

Various outcomes are summarized in Table 4. Of the 1174 women giving birth vaginally (78.2%), those with weight gain exceeding IOM recommendations were 2.8 times more likely to experience a shoulder dystocia than those who met the recommendations (OR 2.78, 95% CI 1.10–6.98, P=0.0301, adjusted for BMI category). This difference became insignificant when also adjusted for birthweight, which improved the c statistic from 0.69 to 0.83. An interaction term for the group exceeding IOM recommendations and birthweight was non-contributory. Of the entire study population, women exceeding IOM recommendations were 1.6 times more likely to have a cesarean delivery compared with those who met the recommendations (OR 1.59, 95% CI 1.19–2.11, P=0.0015, adjusted for BMI category and history of an earlier cesarean delivery). This result was unaffected by birthweight adjustment, and the c statistic remained at 0.72. No differences were noted between those who did and did not exceed IOM weight gain guidelines for the outcomes of hypoglycemia (overall rate 3.1%), respiratory distress syndrome (overall rate 0.9%) or congenital anomalies (overall rate 2.3%).

Table 4 Calculated OR for various pregnancy outcomes among women who did and did not exceed IOM weight gain recommendations, adjusted for BMI categories

Multivariable logistic regression modeling results for the combined effects of macrosomia with BMI, excess weight gain and earlier history of macrosomia are summarized in Table 5. For example, an obese woman with GDM with excess weight gain and a history of macrosomia is 24 times more likely to deliver a macrosomic infant compared with a woman with GDM who is of normal weight and who does not have these risk factors. In our population, half of the women with this combination of risk factors (51.9%) delivered a macrosomic infant.

Table 5 Relationship of maternal characteristics and risk for macrosomia

Discussion

In the present study, we have shown that both maternal prepregnancy weight and weight gain during pregnancy in excess of the IOM recommendations appear to be independent and important risk factors for the development of macrosomia in women with GDM. Although earlier studies have demonstrated similar associations of maternal BMI and excess gestational weight gain to increased birthweight in normal pregnant women, (1316 to 1 92 627) to our knowledge, our results are the first to demonstrate such a link in women with GDM.

Even though obese women had the lowest mean weight gain in the study group, almost half of them (44%, see Table 1) exceeded the IOM weight gain guidelines, and this group had the highest incidence of macrosomia. Obesity and weight gain above the IOM threshold increased the risk for macrosomia six-fold above that for women with normal weight who met IOM recommendations (see Table 5). A history of earlier macrosomia was also an important risk factor for recurrent macrosomia (Table 3). As such, the presence of such a history in women with GDM may represent an additional clinical opportunity to optimize maternal weight and weight gain.

Recent studies have shown the significance of maternal weight and weight gain on fetal growth in nondiabetic women. Hedderson et al.13 showed that high rates of maternal weight gain, especially early in pregnancy, may lead to an increased incidence of GDM, whereas Fleten et al.26 demonstrated that maternal prepregnancy BMI was strongly associated with birthweight. Others have reported similar findings.27, 28, 29, 30 All of these studies were analyses of women without GDM. The results of our study provide additional support to the significance of maternal weight and weight gain as it relates to birthweight, but more importantly demonstrate that the relationship exists in women with GDM. As these women are inherently at increased risk for macrosomia, our findings may be even more clinically compelling.

Our results also demonstrate that other delivery outcomes may be affected by excess weight gain in this population of women with GDM. Over and above the risks associated with maternal obesity, exceeding IOM weight gain recommendations initially appeared to contribute independently to shoulder dystocia (Table 4). However, the increased shoulder dystocia risk for women who exceeded IOM weight gain guidelines disappeared after adjustment for BMI category and birthweight, indicating that fetal size is the predominant risk factor. However, cesarean risk for women who exceeded IOM guidelines did not change when adjusted by birthweight, indicating that causal factors for cesarean delivery remain more complex.

Strengths of this study include the large sample size and results from a single institution with a comprehensive and consistent perinatal care program. Moreover, all maternal and neonatal weights were recorded objectively, whereas in other studies, weights have been self-reported.13 In addition, the quantitative relationship of maternal weight and birthweight described in women with GDM has not been reported previously. Limitations of the study include its retrospective design and the predominance of Latina and Asian patients in the cohort. Because of the extremely low prevalence of underweight patients, and the association between obesity and Hispanic ethnicity in our population, caution may be necessary in extrapolating these results to other demographic groups. Furthermore, management of the timing of delivery can affect the occurrence of macrosomia, and although our findings did not differ when adjusted for gestational age at delivery, we could not fully account for management differences that might affect the occurrence of cesarean delivery or shoulder dystocia in this retrospective study. Finally, our assessment of the degree of ‘independence’ of weight gain and BMI category was limited by the size of our cohort. Although interaction terms were non-contributory in our models, larger numbers of patients may indeed allow for the discovery of more complex relationships between these clinical risk factors.

In summary, our results have demonstrated a strong relationship between maternal pre-pregnancy weight and weight gain to the occurrence of macrosomia in women with GDM. These findings may represent opportunities for early and, if necessary, aggressive intervention before and during pregnancy to help optimize neonatal birthweight. Whether or not such intervention programs will have a measurable effect on outcomes requires further investigation in prospective clinical trials.

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Correspondence to J G Ouzounian.

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Ouzounian, J., Hernandez, G., Korst, L. et al. Pre-pregnancy weight and excess weight gain are risk factors for macrosomia in women with gestational diabetes. J Perinatol 31, 717–721 (2011). https://doi.org/10.1038/jp.2011.15

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Keywords

  • gestational diabetes
  • obesity
  • macrosomia

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