Can metformin (biguanide oral hypoglycemic) use during pregnancy cause low birth weight babies?

Metformin During Pregnancy Can Cause Small-for-Gestational-Age Babies

Yes, metformin use during pregnancy is associated with smaller neonatal birth weights and an increased risk of small-for-gestational-age babies. 1

Evidence on Metformin and Birth Weight

Direct Effects on Birth Weight

• Metformin readily crosses the placenta, resulting in umbilical cord blood levels as high or higher than maternal levels 1
• Randomized controlled trials have consistently shown that neonatal birth weights are smaller in metformin-treated groups compared to insulin-treated groups 1
• One study demonstrated a doubling of small-for-gestational-age neonates in the metformin group 1
• A meta-analysis confirmed that metformin exposure resulted in smaller neonates with subsequent acceleration of postnatal growth 1

Specific Populations at Risk

• Metformin should not be used in pregnant women with hypertension, preeclampsia, or those at risk for intrauterine growth restriction due to the potential for further growth restriction 1
• The risk of small-for-gestational-age infants appears to be higher when metformin is used in women with preexisting type 2 diabetes compared to gestational diabetes 1

Long-Term Growth Patterns After Metformin Exposure

Interestingly, while metformin leads to smaller birth weights, follow-up studies reveal a concerning pattern:

• Despite lower birth weights, metformin-exposed infants experience accelerated postnatal growth 2
• By 18-24 months, metformin-exposed infants are significantly heavier than insulin-exposed infants (mean difference 440g) 2
• By mid-childhood (5-9 years), children exposed to metformin in utero have higher BMI (mean difference 0.78 kg/m²) 2
• Some studies show higher waist-to-height ratios and waist circumferences in metformin-exposed children 1

Clinical Implications and Recommendations

First-Line Treatment Recommendations

• Insulin remains the first-line agent recommended for treatment of diabetes during pregnancy according to the American Diabetes Association 1
• Unlike metformin, insulin does not cross the placenta in significant amounts, ensuring no direct fetal exposure 3

When Metformin Might Be Considered

• Metformin may be considered in milder forms of gestational diabetes where glycemic goals are not attained by lifestyle modification 4
• In situations where insulin cannot be used safely or effectively due to cost, language barriers, or cultural influences, metformin may be an alternative after discussing known risks 1

Predictors of Treatment Failure with Metformin

• Higher failure rates are likely in women with:
  • Earlier diagnosis of gestational diabetes
  • Higher blood glucose levels
  • Higher BMI
  • Previous history of gestational diabetes 4

Important Caveats and Monitoring

• Metformin should be avoided in pregnant women with hypertension, preeclampsia, or risk factors for intrauterine growth restriction 1
• Regular fetal growth monitoring is essential when using metformin during pregnancy to detect growth restriction early
• The pattern of lower birth weight followed by accelerated postnatal growth is concerning as it has been associated with adverse long-term cardio-metabolic outcomes 2
• There is no evidence-based need to continue metformin in women with polycystic ovary syndrome during pregnancy 1

The evidence clearly shows that metformin use during pregnancy is associated with smaller birth weights and increased risk of small-for-gestational-age infants, with potential long-term metabolic consequences for the offspring. This risk must be carefully weighed against any potential benefits when considering metformin use in pregnant women.