Rayburn W F, Gonzalez C L, Christensen H D, Kupiec T C, Jacobsen J A, Stewart J D
Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
J Matern Fetal Med. 2000 Mar-Apr;9(2):136-41. doi: 10.1002/(SICI)1520-6661(200003/04)9:2<136::AID-MFM10>3.0.CO;2-Q.
Our purpose was to determine, in a placebo-controlled manner, whether antenatal exposure to paroxetine affected long-term growth and physical maturation of mice offspring.
Forty-one CD-1 mice consumed paroxetine (n = 21) or a placebo (n = 20) for 2 weeks before conception and throughout gestation. The daily dose of paroxetine (Paxil; 30 mg/kg/d) was known to achieve concentrations in the serum equivalent to the upper therapeutic level in humans and in the fetal brain equivalent to that of the adult mouse. Growth and physical maturation of the offspring were compared by paired t-test, Welch's corrected test, and Fisher's exact test.
The maternal weight gain, litter sizes, number of fetal resorptions, and gestational age at delivery were not different between the paroxetine and the placebo-exposed offspring. Newborn pups exposed to paroxetine were more likely to have low birthweights (1.65 gm vs. 1.70 gm; P < 0.05) and narrower heads (7.7 mm vs. 8.1 mm; P < 0.05). Body weight, body length, and head circumference measurements increased in a manner that was indistinguishable between the two groups of offspring, regardless of gender. No differences in achievement of physical milestones (lower incisor eruption, eye opening, and development of external genitalia) were noted between the two groups. The reproductive capability and the perinatal outcomes of the second-generation offspring were unaffected by paroxetine exposure.
A clinically relevant dose of paroxetine, when given throughout gestation, did not affect long-term growth and physical maturation of mice offspring.
我们旨在以安慰剂对照的方式，确定孕期接触帕罗西汀是否会影响小鼠后代的长期生长和身体发育。
41只CD-1小鼠在受孕前2周及整个妊娠期服用帕罗西汀（n = 21）或安慰剂（n = 20）。已知帕罗西汀（帕罗西汀；30毫克/千克/天）的每日剂量可使血清浓度达到相当于人类治疗上限的水平，在胎儿脑中的浓度相当于成年小鼠的浓度。通过配对t检验、韦尔奇校正检验和费舍尔精确检验比较后代的生长和身体发育情况。
帕罗西汀组和安慰剂组后代的母体体重增加、窝仔数、胎儿吸收数和分娩时的孕周没有差异。接触帕罗西汀的新生幼崽更有可能出生体重低（1.65克对1.70克；P < 0.05）且头部较窄（7.7毫米对8.1毫米；P < 0.05）。两组后代的体重、体长和头围测量值的增加方式无明显差异，无论性别如何。两组在身体发育里程碑（下门齿萌出、睁眼和外生殖器发育）的达成方面没有差异。帕罗西汀暴露对第二代后代的生殖能力和围产期结局没有影响。
在整个妊娠期给予临床相关剂量的帕罗西汀，不会影响小鼠后代的长期生长和身体发育。
