With limited sun exposure, an intake of 400 IU/day vitamin D(3) did not sustain circulating maternal 25(OH)D levels, and thus, supplied only extremely limited amounts of vitamin D to the nursing infant via breast milk. Infant levels achieved exclusively through maternal supplementation were equivalent to levels in infants who received oral vitamin D supplementation. Thus, a maternal intake of 6400 IU/day vitamin D elevated circulating 25(OH)D in both mother and nursing infant.
Objective
To determine the pharmacokinetics (PK) and placental transfer of intravenous (IV) N-acetylcysteine (NAC) in mothers with a clinical diagnosis of chorioamnionitis and determine the PK of IV NAC in their infants.
Study design
In this prospective, double blind study IV NAC 100 mg/kg/dose or saline was administered within 4 hours of CA diagnosis to pregnant women ≥24 weeks gestation and then every 6 hours until delivery. Maternal PK and placental transfer were determined with maternal blood and matched maternal and cord venous blood. Neonatal PK estimates were determined from IV NAC (12.5 – 25 mg/kg/dose) administered every 12 hours for 5 doses. Noncompartmental analyses were performed for maternal and neonatal PK estimates.
Results
Eleven mothers (5 preterm, 6 near-term) and 12 infants (1 set of twins) received NAC. Maternal clearance (CL) of NAC was faster than in non-pregnant adults, with a t1/2 of 1.2 ± 0.2 hours. The NAC cord to maternal ratio was 1.4 ± 0.8 suggesting rapid placental transfer and slower rate of fetal CL. Neonatal PK estimates for near-term compared with preterm infants showed a significantly shorter t1/2 (5.1 vs.7.5 hours, respectively) and higher CL (53.7 vs. 45.0 mL/hr/kg, respectively).
Conclusions
Maternal CL and placental transfer of NAC was rapid with umbilical cord concentrations frequently exceeding maternal concentrations. NAC administration to mothers with CA achieves predictable NAC plasma concentrations in the fetus, indicating that antenatal neuroprotection may be possible for these newborns at high risk for neuroinflammation.
Differences in vitamin D status occurred between black and white infants and were significant through the first 2 weeks after delivery. Infants receiving predominantly breast milk did not have significantly worse vitamin D status than those receiving formula. The significant decline in serum 25(OH)D status observed in 28% of the infants was not related to breast milk intake.
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