Please select the eligibility criteria that correspond to the clinical trial below.
Title: Metformin to Augment Low Milk Supply in Pre-diabetic Mothers, a Phase I/II Randomized Clinical Trial
Brief Summary: Most new mothers in the United States will start off breastfeeding. For some mothers, despite following best practices, they are not able to meet their breastfeeding goals due to unexplained low milk supply. At the same time, nearly 1 in 4 new mothers are pre-diabetic (elevated blood sugar, but not yet diabetic). My progression of research suggests that the same metabolic factors causing pre-diabetes may also be causing low milk supply. Metformin is a widely prescribed drug to treat high blood sugar. This study is a preliminary, small scale randomized trial designed to test for a trend in the hypothesis that metformin is safe and potentially effective in treating low milk supply in insulin resistant and pre-diabetic mothers.


Options:
A: Inclusion Criteria:

* Women between the ages of 18 and 45 years
* Good general health
* Lactating
* Singleton birth
* Two to twelve weeks postpartum
* Have a full term (\>37 weeks gestation) healthy infant
* Is successfully fully breastfeeding at the time they enter the study
* Intend to fully breastfeed their infants for the following 4 weeks at the time of enrollment.

Exclusion Criteria:

* Chronic illnesses (e.g. diabetes, hypertension, bronchial asthma, Gastroesophageal Reflux Disease (GERD), atopic dermatitis, celiac disease or gluten sensitivity, Crohn's Disease, ulcerative colitis, eating disorders, breast cancer, blood disorder, psychiatric)
* Pre-pregnant BMI (\>50)
* History of alcohol, drug abuse or cigarette smoking
* Currently using the following pharmaceuticals: diuretics, pseudoephedrine, anticholinergics, and an estrogen-containing birth control pill or using an estrogen-containing device
* Currently consuming other drugs/herbals used to induce milk production including metoclopramide, domperidone, or other drugs/herbals (i.e. fenugreek capsules, goat's rue products, or "More Milk" capsules or tinctures)
* Sensitivity or known allergies to peanuts, soybeans, or chick peas
* Sensitivity or known allergies to plants in the Apiaceae/carrot plant family (e.g. anise, celery, coriander, fennel) or the compound anethole
* Sensitivity or known allergies to plants in the Asteraceae/daisy family (e.g. blessed thistle, echinacea, or calendula)
* Taking a selective serotonin reuptake inhibitor (SSRI)
B: Inclusion Criteria:

* singleton, term delivery
* \>2.5 kg newborn weight
* lactation-deficiency

Exclusion Criteria:

* Neonatal Intensive Care Unit admission
* use of galactagogue drugs
* allergy
C: Inclusion Criteria among mother-infant dyads:

Stage 1 Criteria (for participation in baseline measurement phase):

* identified with low milk supply by a Cincinnati-area IBCLC
* mother denies obvious cause of low milk supply such as pituitary disorder, breast surgery, severe lack of breast emptying (\< 4 times per day), or failure to show any signs of lactogenesis
* mother at least 20 years of age
* infant is between 1 week and 2 calendar months old
* mother gave birth to a single, healthy, term (\>37 weeks gestation) infant
* mother free of breast and nipple infections
* mother lives within study catchment area
* mother has not been diagnosed with Type 1 or Type 2 Diabetes Mellitus
* mother willing to sustain consistent use of herbal galactogogues (such as fenugreek) during follow up measurements (2-4 weeks) as was consumed during the baseline measurements
* mother not currently taking a prescription medication that may affect the hormones of lactation and not planning to initiate any such drug for at least the next 2-4 weeks.
* mother has established pediatric care for the infant

Stage 2 maternal inclusion criteria (among those who meet Stage 1 criteria, to continue with enrollment into randomized controlled trial, goal, N=30 with replacement for non-completers to at least two weeks):

* successful completion of baseline measurements (involving 24-hour test weighing of milk output and undergoing baseline measurements at the clinical research center, including providing fasting blood samples)
* body mass index is \>19.0 kg/m2 (i.e., not underweight)
* evidence of likely insulin resistance, based on at least one of the following: mean fasting plasma glucose between 95.0 - 125.0 g/dL, inclusive; abdominal obesity; history of polycystic ovary syndrome; or history of gestational diabetes
* estimated glomerular filtration rate \> 60 mL/min
* liver function in normal range (AST \<= 37 U/L, ALT \< 87 U/L, and total bilirubin \<= 1.1 mg/dL
* willingness to continue trying to lactate for the next 2-4 weeks
* health history does not reveal illness/treatments for which metformin is contraindicated
* participant is not currently being treated with metformin

Eligibility criteria for enrollment into abundant milk supply comparison group (goal, N=30, will be compared in baseline measurements).

Inclusion criteria:

* exclusively feeding mother's own milk to infant, and presenting to Cincinnati area IBCLC with breastfeeding question or problem unrelated to milk supply
* mother at least 20 years of age
* infant is between 1 week and 2 calendar months old
* mother gave birth to a single, term infant
* mother free of breast and nipple infections
* mother lives within study catchment area
* mother has not been diagnosed with Type 1 or Type 2 Diabetes Mellitus
* mother willing to sustain consistent use of herbal galactogogues (such as fenugreek) during baseline measurements
* mother willing to avoid prescription medication that may affect the hormones of lactation
D: Inclusion Criteria:

* Mothers 2-12 weeks postpartum
* Mothers with term infants 37 weeks gestation or older
* Mothers with poor milk supply documented by professional lactation consultants
* Mothers whose milk supply is less than 600 cc per 24 hours
* Mothers who agree not to breastfeed or provide their milk to their infants during this study

Exclusion Criteria:

* Mothers with documented mastitis
* Mothers with breast engorgement
* Mothers with inverted nipples
* Maternal BMI greater than 35
* Mothers currently consuming Reglan, Domperidone or other drugs/herbals used to induce milk production
* Mothers who are clinically ill or hospitalized, or taking the following medications:

  1. Diuretics
  2. Pseudoephedrine
  3. Anticholinergics
  4. Warfarin or any anticoagulant
  5. An estrogen-containing birth control pill
* Mothers with Diabetes mellitus
* Mothers who have had breast surgery that could alter milk synthesis or production
* Mothers diagnosed with Polycystic ovary syndrome
* Mothers with tubular breasts or breasts with insufficient glandular tissue
* Mothers diagnosed with Asthma or atopic disease
* Mothers who are known to be allergic to peanuts or soybeans
* Mothers who are pregnant
* Mothers whose milk supply per 24 hours exceeds 600 mL
* Mothers with Obstetrical evaluation recommending exclusion

Answer: C