Pregnancy has a profound effect on the human body, particularly the musculoskeletal system. Hormonal changes cause ligamentous joint laxity, weight gain, and a shift in the center of gravity that leads to lumbar spine hyperlordosis and anterior tilting of the pelvis. In addition, vascular changes may lead to compromised metabolic supply in the low back. The most common musculoskeletal complaints in pregnancy are low back pain and/or pelvic girdle pain. They can be diagnosed and differentiated from each other by history taking, clinical examination, provocative test maneuvers, and imaging. Management ranges from conservative and pharmacologic measures to surgical treatment. Depending on the situation, and given the unique challenges pregnancy places on the human body and the special consideration that must be given to the fetus, an orthopaedic surgeon and the obstetrician may have to develop a plan of care together regarding labor and delivery or when surgical interventions are indicated.

ABSTRACT:Our objective was to evaluate the pharmacokinetics of metformin during pregnancy. Serial blood and urine samples were collected over one steady-state dosing interval in women treated with metformin during early to late pregnancy (n ‫؍‬ 35) and postpartum (n ‫؍‬ 16). Maternal and umbilical cord blood samples were obtained at delivery from 12 women. Metformin concentrations were also determined in breast milk samples obtained over one dosing interval in 6 women. Metformin renal clearance increased significantly in mid (723 ؎ 243 ml/min, P < 0.01) and late pregnancy (625 ؎ 130 ml/min, P < 0.01) compared with postpartum (477 ؎ 132 ml/min). These changes reflected significant increases in creatinine clearance (240 ؎ 70 ml/min, P < 0.01 and 207 ؎ 56 ml/min, P < 0.05 versus 165 ؎ 44 ml/min) and in metformin net secretion clearance (480 ؎ 190 ml/min, P < 0.01 and 419 ؎ 78 ml/min, P < 0.01 versus 313 ؎ 98 ml/min) in mid and late pregnancy versus postpartum, respectively. Metformin concentrations at the time of delivery in umbilical cord plasma ranged between nondetectable (<5 ng/ml) and 1263 ng/ml. The daily infant intake of metformin through breast milk was 0.13 to 0.28 mg, and the relative infant dose was <0.5% of the mother's weight-adjusted dose. Our results indicate that metformin pharmacokinetics are affected by pregnancy-related changes in renal filtration and net tubular transport and can be roughly estimated by the use of creatinine clearance. At the time of delivery, the fetus is exposed to metformin concentrations from negligible to as high as maternal concentrations. In contrast, infant exposure to metformin through the breast milk is low.

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