The effect of breastfeeding on postpartum fructosamine and HbA1c values after normal pregnancy

Abstract

Introduction

Breastfeeding can lower postpartum oral glucose tolerance test results by 5%. Similar data do not exist regarding fructosamine and HbA1c. The primary outcome was to determine if breastfeeding would lower fructosamine values by 5%.

Methods

At the 4–8 week postpartum visit, women with uncomplicated pregnancies were given a questionnaire and had blood drawn for fructosamine and HbA1c.

Results

Breastfeeding (n = 22) and non-breastfeeding women (n = 28) were demographically similar, including postpartum weight loss. The respective values among breastfeeding and non-breastfeeding women were: fructosamine 2.20 versus 2.21 mmol/L; HbA1c 5.2% versus 5.2%. Only two of the seven women with an HbA1c of 5.7% or more had an abnormal fructosamine.

Conclusion

After uncomplicated pregnancies, breastfeeding was not associated with lower levels of postpartum fructosamine or HbA1c. Future research to improve screening for persistent postpartum dysglycemia in high-risk populations can utilize these tests without concern that results will be confounded by breastfeeding.

Introduction

Thirty percent of women with gestational diabetes mellitus (GDM) will have persistent postpartum dysglycemia, and up to 70% will develop overt diabetes mellitus (DM) within 10 years.¹ Both the American Diabetes Association (ADA) and American College of Obstetrics & Gynecology (ACOG) recommend a 2-h oral glucose tolerance test (OGTT) for women with GDM, but the average compliance rate is 35%, largely related to women perceiving the test as inconvenient.^1–6 Breastfeeding has benefits for the mother and newborn, including preventing or delaying onset of overt DM among women with GDM who breastfeed for at least three months.⁷ Breastfeeding improves glycemic control, but can confound postpartum testing as OGTT results are 5% lower among women who breastfeed during the test compared to those who did not.⁸ Other tests for dysglycemia and DM include serum markers of glycosylated proteins such as fructosamine and HbA1c, and evidence is emerging that postpartum HbA1c testing is more convenient and potentially more sensitive than the OGTT.^9,10 HbA1c reflects glycemic control over the past 12 weeks, and fructosamine levels are closely associated with the HbA1c. Fructosamine reflects glycemic control over the past 2–3 weeks, making it potentially attractive for use shortly after delivery, but fructosamine does not accurately reflect antepartum glycemic control, and due to high intra- and interindividual variability there are no published criteria to diagnose DM using fructosamine values.^11–14

Unlike the OGTT, the relationship between breastfeeding and postpartum fructosamine and HbA1c levels has not been evaluated. The objective of this study was to evaluate the relationship between breastfeeding, postpartum fructosamine, and HbA1c levels in women with normal pregnancies.

Methods

This study enrolled participants at the Women’s Care Center (WCC), an affiliate clinic of Drexel University College of Medicine. The primary outcome was to assess the difference in fructosamine values in the breastfeeding (BF) group versus the non-breastfeeding (NBF) group with our hypothesis that the BF group would have a value 5% lower than the NBF group. HbA1c levels were compared between the BF and NBF groups as a secondary endpoint. A post-hoc analysis was performed evaluating the sensitivity of abnormal fructosamine results using the HbA1c as the gold standard. The participants were patients at WCC at their 4–8 week postpartum visit. Identification of the participants was done by the WCC providers. Inclusion criteria: at least 18 years old, had a delivery of a live infant in the past 4–8 weeks, delivered at Hahnemann University Hospital so that delivery information would be available, and English as their primary language. Immediately following the provider visit, patients were approached for informed consent. After consent, blood obtained for fructosamine and HbA1c testing was sent to the local Quest Diagnostics laboratory, and a brief questionnaire was administered regarding demographics, education, and the question “What is the type of feeding you are using for your infant at this time?” with the following potential responses: “ONLY breastfeeding”; “Breastfeeding and giving formula a maximum of 3 times a day”; “Breastfeeding and giving formula 4 or more formula times a day”; “ONLY Formula feeding”. Women who reported any breastfeeding were grouped together for the analysis and compared to those who reported ONLY Formula feeding.

Abnormal results for the respective tests were defined as a HbA1c of 5.7% or more, or elevated fructosamine of 2.86 mmol/L or more. HbA1c values of 5.7% or more prompted a referral to the medical clinic or their primary care provider for follow-up. Per a commercial lab, the low normal fructosamine for healthy individuals is 2.05 mmol/L.¹⁵ Presuming that the non-breastfeeding women had a mean fructosamine value at the lower end of normal it would require 22 women to prove that breastfeeding would be associated with an absolute value 5% lower with a standard deviation of 10 and power of 90%. IRB approval was obtained. Mann–Whitney U test was used to compare non-parametric datasets and t test to compare mean values for normally distributed sets. SPSS Version 24 (owned by IBM) was used for the analysis.

Results

Demographic data are presented in Table 1. Comparing breastfeeding to non-breastfeeding mothers, there were no statistically significant differences in age, body mass index (BMI), gestational age at time of delivery, or smoking status. The amount of postpartum weight loss in the two groups was not significantly different (p = 0.82). The group that did breastfeed was more likely to have completed some trade school or higher (40.9%) compared to only 14.3% of those who did not breastfeed (p = 0.005).

Table 1.

Patient demographics.

Mean value ± standard deviation	Not breast feeding (n = 28)	Breastfeeding (n = 22)
Age (years)	27.5 ± 6.1	29.7 ± 5.5
Gravida	3.4 ± 3.2	3.8 ± 2.0
Living	2.1 ± 1.5	2.6 ± 1.3
BMI (kg/m2)	28.8 ± 8.9	30.2 ± 8.1
Gestational age at delivery (weeks)	38.0 ± 1.6	38.8 ± 2.3
Spontaneous vaginal delivery (%)	16 (57%)	15 (68%)
Caesarean section delivery (%)	9 (32%)	5 (23%)
Other (VBAC or operative)	3 (11%)	2 (9%)
Weight loss between last antepartum visit and postpartum visit (lbs)	18 ± 9.9	21.5 ± 10.9
Cigarette smoking (%)	4 (14%)	0
Some high school education (%)	9 (32%)	2 (9%)
Completed high school (%)	12 (43%)	6 (27%)
Some trade school (%)	3 (11%)	5 (23%)
College (%)	4 (14%)	9 (41%)

BMI: body mass index; VBAC: vaginal birth after cesarean.

Table 2 shows results of the primary analysis: measures of glycemic control in relation to breastfeeding versus non-breastfeeding. The values for fructosamine and HbA1c were nearly identical between the BF and NBF groups, and the 95% confidence intervals for the mean differences were not significant, demonstrating that breastfeeding was not associated with lower test values.

Table 2.

Fructosamine and HbA1c values by breastfeeding status.

	Non-breastfeeding	Breastfeeding	Mean difference(95% CI)
Fructosamine(mmol/L mean ± SD)	2.2 ± 0.05	2.2 ± 0.05	(−9.5,10.7)
HbA1c (%)	5.2 ± 0.4	5.2 ± 0.3	(−0.2,0.2)

CI: confidence interval; SD: standard deviation.

Table 3 shows the post-hoc analysis evaluating the sensitivity of fructosamine values using the HbA1c as the gold standard. As the HbA1c is an accepted test to diagnose dysglycemia (pre-DM or DM), and the fructosamine has greater variability, for this exploratory analysis we considered the HbA1c as the test to which we would compare fructosamine values.¹⁶ Seven women had dysglycemia based on HbA1c testing, two of whom also had dysglycemia by fructosamine value, for a fructosamine sensitivity of 29% and a false negative rate of 71%.

Table 3.

Post-hoc comparison of abnormal fructosamine values to HbA1c values.^a

	HbA1c
	≥5.7%	≤5.6%	Row totals
Fructosamine ≥286 µmol/L	2	1	3 (6%)
Fructosamine <286 µmol/L	5	43	48 (94%)
Column totals	7 (14%)	44 (86%)

^aResults of a post-hoc analysis comparing fructosamine values to HbA1c. As the HbA1c is an accepted test to diagnose diabetes mellitus in the non-pregnant population, it was considered the gold standard. Among the seven (14%) women with abnormal HbA1c results, two (29%) also had elevated fructosamine values, for a fructosamine sensitivity of 29% and a false negative rate of 71%.

Discussion

This comparative study demonstrated that the BF group did not have lower fructosamine levels compared to those who did not breastfeed (Table 3). Previous studies suggest breastfeeding for three or more months will improve postpartum glycemic control and lower HbA1c levels.⁷ We hypothesized that because fructosamine levels reflect the previous 2–3 weeks of glycemic control, breastfeeding over the prior 4–8 weeks would result in lower mean postpartum values, similar to the effect on OGTT results. While postpartum weight loss could result in lower fructosamine levels, the mean fructosamine and HbA1c values in the groups were the same and the change in weight was not significantly different between the two groups. It is therefore not surprising that a post-hoc regression analysis did not find a relationship between fructosamine levels and weight loss. The only significant demographic difference between the two groups was the highest level of education noted in the BF group (Table 1), which has been described previously.¹⁷ With hindsight one can attribute the similar laboratory values between the two groups to the lack of an effect of breastfeeding on the results in a cohort of pregnancies uncomplicated by GDM, but to our knowledge ours is the first study to report this relationship. A post-hoc calculation for HbA1c with power of 80% and the observed standard deviation would have required 56 women to disprove the null hypothesis for HbA1c as well.¹⁸ The finding that the mean HbA1c values were nearly identical certainly suggests that breastfeeding is unlikely to decrease postpartum HbA1c values, but due to the short time-frame of follow-up and sample size, we cannot conclusively state that.

This study was initiated in an effort to add data to the literature in the context of identifying postpartum tests that will be accepted by women and thus improve the rates of postpartum screening for dysglycemia in high risk women. In both non-pregnant and peripartum women, a single test such as a fructosamine or HbA1c has distinct advantages in terms of logistics and patient convenience compared to the fasting plasma glucose (FPG) or OGTT, but the HbA1c has lower variability, improved sample stability, and reliability.¹⁹ While the HbA1c and FPG can both be completed during an office visit, the interlaboratory variability for the HbA1c is less than 1% compared to the FPG (8%) and OGTT (17%).²⁰ Additionally, a pilot demonstrated that, among women with a recent diagnosis of GDM, an office HbA1c at the time of the postpartum visit facilitated a 100% testing rate, versus 53% of those sent to an outside lab.⁹

Postpartum testing for dysglycemia in the high-risk GDM population is of paramount importance, and because the compliance rate with the OGTT averages only 35%, alternatives that will be accepted by women should be developed.¹ All three approved tests for dysglycemia (FPG, HbA1c, and OGTT) predict the risk of future microvascular disease, but it is not practical to follow women for the 10 years necessary to observe that clinical endpoint.¹⁶ While fructosamine reflects glycemic control over a shorter timeframe and correlates well with HbA1c values, fructosamine is not approved to diagnose diabetes, and our findings suggest that it had a high false-negative rate in this population. While convenient, early postpartum testing with HbA1c is not currently endorsed by ADA and ACOG, and the National Institute for Clinical Excellence only recommends it after 13 weeks postpartum.^3,6,21 The HbA1c, while convenient, is not yet recommended due to concerns that postpartum blood loss/turnover could artifactually lower levels and the recent pregnancy-related increase in counterregulatory hormones could increase postpartum values. However, those same counterregulatory hormones could also affect OGTT results obtained 6–12 weeks postpartum and there is one report that postpartum HbA1c levels were the same in those with and without anemia.²² Those concerns support the need for additional research to compare six-week postpartum testing results with those after 12 weeks.

Strengths of this study include that it had 90% power to detect a 5% difference in fructosamine values and the similar mean fructosamine values and standard deviation are not surprising in this population of women with normal pregnancies. Due to the testing being relatively close to delivery we did not expect to demonstrate a difference in HbA1c values, therefore a limitation is that the sample size does not allow us to conclude definitively that breastfeeding did not have an effect on HbA1c values. However, as the mean HbA1c values and standard deviations were narrow, it is probable that future studies will eventually confirm this finding. This study was performed in women without GDM in order to determine the effect of breastfeeding on these test results in the normal population that can serve as the baseline and from a practical standpoint, the volume of patients in our practice facilitated recruitment. Glycated albumin is another test that reflects short-term glycemic control better than the HbA1c, appears to predict diabetes better than fructosamine, and therefore is a test with tremendous potential for future evaluation.¹³

In summary, in this study powered to detect a 5% absolute difference, breastfeeding was not associated with lower fructosamine values in women after normal pregnancies. Fructosamine is not yet approved to diagnose DM, and HbA1c values were nearly identical in the two groups, therefore it is reasonable to consider future research utilizing fructosamine and HbA1c as screening for postpartum dysglycemia with confidence that the results will not be confounded by breastfeeding status.