Breast Milk Hormones and Early Infant Growth of Women With Gestational Diabetes Mellitus

Sponsor

Peking Union Medical College Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT03145649

Collaborator

(none)

Enrollment

18.1

Actual Duration (Months)

Study Details

Study Description

Brief Summary

Background: Breastfeeding has been associated with attenuated risk of obesity and type 2 diabetes in children born to women with diabetes. However, breast milk (BM) components responsible for the protective effects remain to be unveiled.

Objective: To evaluate the hormone concentrations in BM of women with gestational diabetes mellitus (GDM) and their influence on early infant growth.

Design: The investigators followed nulliparous women with and without GDM and their breastfed term singletons. Women diagnosed with GDM received dietary therapy or insulin injection to maintain euglycemia during pregnancy. Hormone concentrations in BM (i.e., adiponectin, leptin, insulin, and ghrelin) were tested and infant growth was evaluated on days 3, 42 and 90. The investigators compared the hormone concentrations between the GDM and healthy groups, and tested the associations of hormone concentrations with maternal factors (i.e., BMI, plasma glucose concentration, gestational age, and delivery mode) and early infant growth.

Hypothesis: Hormone concentrations in BM could be determined by multiple maternal factors, including metabolic and obstetrical factors. GDM should be a significant influencing factor for hormone concentrations in BM.

Condition or Disease	Intervention/Treatment	Phase
Gestational Diabetes	Other: Dietary therapy or insulin injection

Detailed Description

Subjects Nulliparous women with GDM and healthy women, who intended to exclusively breastfeed their singletons, were recruited consecutively from the obstetric wards at the Peking Union Medical College Hospital and the Beijing Obstetrics and Gynecology Hospital during the 37th gestational week. The exclusion criteria were: pre-pregnancy diabetes, fetal anomaly, gestational hypertension, preeclampsia, fetal growth restriction, ruptured membranes, postpartum glucose abnormalities (see below), and introduction of formula feeding during the follow-ups. Women with plasma glucose>7.8mmol/L in the 1-hour 50g glucose load test (GLT) during the 24th-28th gestational weeks underwent a 3-hour 100g diagnostic oral glucose tolerance test (OGTT) following a 12-hour overnight fast. GDM was diagnosed if two or more plasma glucose reads in the OGTT equaled or exceeded the threshold according to Carpenter and Coustan. All subjects diagnosed with GDM initially received dietary therapy to attain glycemic targets: 3.3-5.6 mmol/L at fasting, 3.3-5.8 mmol/L pre-prandially, 4.4-6.7 mmol/L 2-hours post-prandially, and 4.4-6.7 mmol/L at night. The participants were followed by dietitians to ensure euglycemia, appropriate weight gain, and adequate nutritional intake. The participants who did not attain glycemic targets in 2 weeks after starting the dietary therapy were given insulin via injection. As macronutrients in BM were mainly determined by the maternal glucose metabolic status, the investigators excluded women with postpartum glucose abnormalities, i.e., impaired glucose tolerance (IGT) with the 2-hour plasma glucose between 7.8 and 11.0 mmol/l and type 2 diabetes with the 2-hour plasma glucose ≥11.1 mmol/l in the 75g OGTT on postpartum day 42.

Anthropometric measurements Data was recorded using customized case report forms. Obstetric data, such as glycemic tests, gestational age, and mode of delivery, were retrieved from the medical records. Pre-pregnancy weight was self-reported. Mothers' height was measured twice to the nearest 0.1 cm with a wall-mounted stadiometer. Mothers' weight was measured twice to the nearest 0.1 kg with a medical balance scale before delivery, on postpartum days 42 and 90. The weight, length, and head circumference of the infants were measured at birth, on days 42 and 90. The infants were weighed twice in nude using a precision scale (Seca, CA, USA). Body length and head circumference were measured twice to the nearest 0.1 cm with a length board and non-stretchable measuring tapes (Seca, CA, USA). The mean values of the two readings were used for data analysis.

Milk sample collection, processing, and laboratory tests Colostrum samples were collected between 8 a.m. and 9 a.m. before infant feeding on the third day after delivery. Mature milk, including both foremilk and hindmilk, was delivered and collected from one breast before infant feeding using an electric pump (Medela, Baar, Switzerland) between 2 p.m. and 4 p.m. on days 42 and 90 in the clinics. The milk samples were frozen immediately in sterilized plastic tubes at -80°C. Before quantifying the hormones in BM, the samples were thawed at 4°C, sonicated, and centrifuged. The samples were sonicated using a sonicator (Braun-sonic sonicator, B. Braun, Melsungen, Germany) at 50 watts for 3 bursts with 10-second intervals, and centrifuged at 100,000g for 1 hour at 4°C. The supernatant fat was discarded and the skim milk was used for quantifying adiponectin, leptin, insulin, and ghrelin by ELISA at the Key Laboratory of Endocrinology in the Peking Union Medical College Hospital. The assay had an intra- and inter-assay CV of <5.4 and <8.5% for adiponectin, and <7.4% and <9.3% for leptin, respectively. The insulin assay had no cross-reactivity to proinsulin (<0.05%), and had sensitivity of 0.5 mU/L and an inter-assay CV of <9.0%. Total ghrelin was tested using the total human ghrelin ELISA kit (Millipore, USA). The intra- and inter-assay CVs for the ghrelin assay were <1.9% and <7.7%.

Study Design

Study Type:

Observational

Actual Enrollment :

96 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Breast Milk Hormones and Early Infant Growth of Women With Gestational Diabetes Mellitus

Actual Study Start Date :

Jan 12, 2010

Actual Primary Completion Date :

Oct 21, 2010

Actual Study Completion Date :

Jul 16, 2011

Arms and Interventions

Arm	Intervention/Treatment
Gestational diabetes mellitus Women with gestational diabetes mellitus and their infants. The blood glucose of women with gestational diabetes mellitus was controlled by dietary therapy or insulin injection.	Other: Dietary therapy or insulin injection
Healthy Healthy mother-infant dyads

Arm

Intervention/Treatment

Gestational diabetes mellitus

Women with gestational diabetes mellitus and their infants. The blood glucose of women with gestational diabetes mellitus was controlled by dietary therapy or insulin injection.

Other: Dietary therapy or insulin injection

Healthy

Healthy mother-infant dyads

Outcome Measures

Primary Outcome Measures

Adiponectin in the colostrum [Day 3 after delivery]
Adiponectin concentration in the colostrum
Leptin in the colostrum [Day 3 after delivery]
Leptin concentration in the colostrum
Insulin in the colostrum [Day 3 after delivery]
Insulin concentration in the colostrum
Ghrelin in the colostrum [Day 3 after delivery]
Ghrelin concentration in the colostrum
Adiponectin in the early mature milk [Day 42 after delivery]
Adiponectin concentration in the mature milk of day 42
Leptin in the early mature milk [Day 42 after delivery]
Leptin concentration in the mature milk of day 42
Insulin in the early mature milk [Day 42 after delivery]
Insulin concentration in the mature milk of day 42
Ghrelin in the early mature milk [Day 42 after delivery]
Ghrelin concentration in the mature milk of day 42
Adiponectin in the mature milk [Day 90 after delivery]
Adiponectin concentration in the mature milk of day 90
Leptin in the mature milk [Day 90 after delivery]
Leptin concentration in the mature milk of day 90
Insulin in the mature milk [Day 90 after delivery]
Insulin concentration in the mature milk of day 90
Ghrelin in the mature milk [Day 90 after delivery]
Ghrelin concentration in the mature milk of day 90
Infant birth weight [At birth]
Infants' weight at birth
Infant birth height [At birth]
Infants' height at birth
Infant birth head circumference [At birth]
Infants' head circumference at birth
Infant weight at day 42 [Day 42]
Infants' weight at day 42
Infant height at day 42 [Day 42]
Infants' height at day 42
Infant head circumference at day 42 [Day 42]
Infants' head circumference at day 42
Infant weight at day 90 [Day 90]
Infants' weight at day 90
Infant height at day 90 [Day 90]
Infants' height at day 90
Infant head circumference at day 90 [Day 90]
Infants' head circumference at day 90

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Nulliparous women with GDM and healthy women, who intended to exclusively breastfeed their singletons, were recruited consecutively from the obstetric wards at the Peking Union Medical College Hospital and the Beijing Obstetrics and Gynecology Hospital during the 37th gestational week.

Exclusion Criteria:

Pre-pregnancy diabetes, fetal anomaly, gestational hypertension, preeclampsia, fetal growth restriction, ruptured membranes, postpartum glucose abnormalities, and introduction of formula feeding during the follow-ups.