毒理性
◉ 母乳喂养期间的用途总结：催产素是在哺乳期间释放的一种重要哺乳激素，它会导致乳汁排出，并对母亲产生镇静作用。对于哺乳困难的母亲，给予外源性催产素并未被明确显示对哺乳成功或治疗乳房充血有益。它可能对那些失去乳房和下丘脑之间神经元连接的女性有益。在哺乳期间给予催产素对婴儿的影响不大。
多项研究表明，在分娩期间给予催产素可能会负面影响哺乳，可能是通过以剂量依赖的方式减少新生儿的吸吮行为，或者通过减少产后催产素的释放，尽管研究方法和一致性有很大差异。这种效果在开始哺乳时可能最为重要，但在哺乳建立后可能不会持续。一项研究发现，只有催产素结合硬脊膜外麻醉会减少哺乳，单独使用催产素则不会。另一项研究发现，所有节律性反射、抗重力反射和全部原始新生儿反射都被产程中催产素的使用抑制，这与剂量无关，可能不利于哺乳。一些证据表明，围产期使用催产素可能会增加产后抑郁症的风险。
◉ 对哺乳婴儿的影响：截至修订日期，未找到相关的已发布信息。
◉ 对哺乳和母乳的影响：鼻喷剂。据报道，瑞士的一些助产士将鼻内催产素作为催乳剂使用。它已被采用母亲希望哺乳的方案中使用。
一项小型研究发现，皮下注射2.5国际单位催产素每日与安慰剂治疗乳房充血3天后，症状没有差异。
一项早期的随机、安慰剂对照试验使用了催产素鼻喷剂于新生儿的母亲，但哺乳管理远远达不到现在认为可接受的标准。研究发现，这种喷剂可能有助于略微减少足月婴儿母亲的乳房充血，但在催产素和安慰剂组别中，出生到第4天的婴儿平均体重下降没有差异。
两项设计相似的研究调查了早产新生儿母亲的催产素鼻喷剂使用情况，这些母亲正在用吸奶器为她们的婴儿泵奶。第一项研究了对出生前38周的婴儿的母亲，每次泵奶前使用总共3单位鼻内催产素（Syntocinon-Sandoz，40单位/mL），每天四次，每次泵奶10分钟。在初产妇中，产后2至5天的乳汁产量为使用催产素的1964毫升，而接受安慰剂喷剂的母亲为510毫升。由于催产素在初产妇中的效果大且具有统计学意义，因此在只有8位初产妇被研究后，试验就被停止了。在4位首次尝试哺乳的多产妇中，催产素和安慰剂之间没有发现统计学上的显著差异。该论文没有报告给母亲任何哺乳技术的指导。
研究了51位分娩小于35周胎龄婴儿的母亲。27位母亲使用了4单位鼻内催产素（Syntocinon-Novartis，40单位/mL），24位母亲在用吸奶器泵奶前接受了相同的安慰剂喷剂。所有母亲都接受了使用手按摩的指导，并建议每3小时泵一次奶。在产后前5天内，接受催产素（中位数667毫升）和安慰剂（中位数530毫升）的母亲之间没有发现乳汁产量的差异，尽管在研究第2天，接受催产素的女性产生的乳汁略多。在这项研究中，生育次数没有影响。
几个因素可能解释研究之间的差异。由于最近研究中记录的母亲之间乳汁产量的大变异性和第一项研究中患者数量少，早期研究的结果可能是由偶然因素造成的。第一项研究中使用的催产素剂量高出50%，这可能导致了更大的效果。另一个合理的解释是，最近的大型研究中给予母亲的良好哺乳支持在早期研究中似乎缺乏。
两份病例报告表明，催产素鼻喷剂可能有助于让失去乳头和下丘脑之间神经元连接的四肢瘫痪女性实现乳汁排出。
在分娩期间。一项对在分娩期间接受催产素的母亲的研究发现，在产后第二天，催产素输注以剂量依赖的方式降低了内源性催产素水平。硬脊膜外麻醉结合催产素输注对内源性催产素水平产生了负面影响。催产素输注还增加了血清催乳素。
对585位在分娩期间接受硬脊膜外麻醉的母亲的数据进行逻辑回归分析发现，接受外源性催产素的母亲比未接受催产素的母亲延迟哺乳的风险高出3.3倍。
一项对20位初产妇的观察性研究发现，在3个月时（63%）完全哺乳的母亲在分娩期间接受的催产素剂量低于未完全哺乳的母亲（平均总剂量1363毫单位与3088毫单位）。这一结果归因于催产素对婴儿吸吮行为的抑制作用。
一项小型、非随机队列研究发现，接受合成催产素诱导或维持分娩的母亲的新生儿在出生后一小时内预喂养组织水平降低。
在西班牙进行的一项回顾性队列研究比较了在
◉ Summary of Use during Lactation:Oxytocin is an essential lactation hormone released during breastfeeding that causes milk ejection and appears to have calming effect on the mother. Administration of exogenous oxytocin to mothers having difficulty in breastfeeding has not been clearly shown to have a beneficial effect on lactation success or in the treatment of breast engorgement. It might be of benefit in women who have lost the neuronal connection between the breast and hypothalamus. Effects on the infant are unlikely when given during breastfeeding.
Numerous studies suggest that oxytocin given during labor can negatively affect breastfeeding, possibly by reducing sucking behavior in the newborn in a dose-dependent manner, or by decreasing postpartum oxytocin release although study methodology and consistency has varied considerably. This effect might be most important during the initiation of breastfeeding, but may not persist after lactation is established. One study found that only oxytocin in conjunction with epidural analgesia reduced breastfeeding, but not oxytocin alone. Another study found that all rhythmic reflexes, the antigravity reflex, and total primitive neonatal reflexes were inhibited by intrapartum oxytocin administration, unrelated to dose, which could adversely affect breastfeeding. Some evidence exists that peripartum oxytocin administration might increase the risk of postpartum depression.
◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk:Nasal spray. Intranasal oxytocin is reportedly used by some midwives in Switzerland as a galactogogue. It has been used as part of regimens used by adoptive mothers who wish to breastfeed.
A small study found no difference in symptoms between subcutaneous oxytocin 2.5 international units daily and placebo after 3 days of treatment for breast engorgement.
An early randomized, placebo-controlled trial used oxytocin nasal spray in the mothers of newborns, but lactation management fell far short of what is considered acceptable nowadays. The study found that the spray might be useful in decreasing breast engorgement slightly in the mothers of fullterm infants, but no difference was found in the average infant weight loss between birth and day 4 in the oxytocin and placebo groups.
Two similarly designed trials studied oxytocin nasal spray in mothers of preterm newborns who were pumping milk for their infants. The first studied mothers of infants born before 38 weeks and used a total of 3 units of intranasal oxytocin (Syntocinon-Sandoz, 40 units/mL) before pumping each breast for10 minutes a breast pump four times daily. Among primiparous mothers, milk production during days 2 to 5 days postpartum was 1964 mL in those who used oxytocin and 510 mL in those who received placebo spray. Because of the large and statistically significant effect of oxytocin among primiparous women, the trial was stopped after only 8 primiparous mothers had been studied. No statistically significant difference was found between oxytocin and placebo among 4 multiparous women who were attempting to breastfeed for the first time. The paper did not report giving the mothers any instructions in lactation technique.
Fifty-one mothers who delivered an infant of less than 35 weeks gestation were studied. Twenty-seven mothers used 4 units of intranasal oxytocin (Syntocinon-Novartis, 40 units/mL), and 24 mothers received an identical placebo spray before pumping with a breast pump. All mothers were given instructions on using hand massage before pumping and advised to pump every 3 hours. No difference in milk production over the first 5 days postpartum was found between mothers who received oxytocin (median 667 mL) and placebo (median 530 mL), although women receiving oxytocin produced slightly more milk on day 2 of the study. Parity had no effect in this study.
Several factors might explain the differences in findings between the studies. Because of the great interpatient variability in milk production documented in the recent study and the small number of patients in the first study, the finding in the earlier study may have been due to chance. A 50% higher dose of oxytocin was used in the first study, which may have caused a greater effect. Another plausible explanation is the good lactation support given to mothers in the recent larger study that seemed to be lacking in the early study.
Two case reports indicate that oxytocin nasal spray may facilitate letdown in tetraplegic women who have lost the neuronal connection between the nipple and the hypothalamus.
During labor. A study of mothers who received oxytocin during labor found that on the second day postpartum, oxytocin infusion decreased endogenous oxytocin levels dose-dependently. Epidural analgesia in combination with oxytocin infusion influenced endogenous oxytocin levels negatively. Oxytocin infusion also increased serum prolactin.
Logistic regression of data from 585 mothers who had epidural analgesia during labor found that mothers who had received exogenous oxytocin had a 3.3 times greater risk of delayed onset of lactation than women who did not.
An observational study of 20 primiparous women found that those who were exclusively breastfeeding at 3 months (63%) had received a lower dose of oxytocin during labor (mean total dosage 1363 milliIunits) than those who were not exclusively breastfeeding (mean total dosage 3088 milliIunits). This result was attributed to an inhibitory effect on neonatal sucking by the infant caused by oxytocin.
A small, nonrandomized cohort study found that the newborn infants whose mothers received synthetic oxytocin to induce or maintain labor had a decreased level of prefeeding organization one hour after birth.
A retrospective cohort study in Spain compared breastfeeding outcomes between mothers who received oxytocin during labor (n = 189) and mothers who did not, including those who delivered via elective Cesarean section (n = 127). Mothers who received oxytocin during the first and second stages of labor had a 45% increased risk of bottle feeding and a 129% increased risk of breastfeeding discontinuation by 3 months of age. Effects were most pronounced in women under 27 years of age.
A small prospective study in California compared women who received an epidural infusion of fentanyl and ropivacaine to mothers who did not receive an epidermal during labor. All mothers had normal vaginal deliveries and their infants had 1 uninterrupted hour of skin-to-skin contact immediately postpartum. The study found inverse relationships between the amount of fentanyl and the amount of oxytocin received during labor and the time of the first suckling. Because women who received more fentanyl also tended to receive more oxytocin, the study could not clearly separate the effects of the two drugs.
A small prospective cohort study in Spain followed mothers by telephone postpartum to determine their breastfeeding status. Mothers who had received oxytocin during labor were breastfeeding at a similar rate as those who had not at 1, 3 and 6 months postpartum.
A nonblinded, nonrandomized study compared breastfeeding among the infants of mothers who received oxytocin during delivery (n = 70) and those who did not (n = 90) in two Iranian hospitals. Mothers were primiparous and infants were full term. Infant breastfeeding behavior was assessed to be either successful or unsuccessful within 2 hours of delivery. Infants whose mothers received oxytocin were judged to successfully breastfeed 48.6% compared to 82.2% among the infants of mothers who did not receive oxytocin. Use of opiate pain relievers in the two groups was not stated.
A retrospective cohort study compared breastfeeding results between women who did and did not receive oxytocin during labor. After correcting for confounding factors, the study found that exogenous oxytocin impaired breastfeeding during the first hour postpartum, but not at 3 months postpartum. High pregestational body mass index was the best predictor of an impaired third month's postpartum breastfeeding.
A retrospective case-control study conducted in two hospitals in central Iran compared breastfeeding behaviors in the first 2 hours postdelivery by infants of 4 groups of primiparous women with healthy, full-term singleton births who had vaginal deliveries. The groups were those who received no medications during labor, those who received oxytocin plus scopolamine, those who received oxytocin plus meperidine, and those who received oxytocin, scopolamine and meperidine. The infants in the no medication group performed better than those in all other groups, and the oxytocin plus scopolamine group performed better than the groups that had received meperidine.
A prospective cohort study in Spain found no relationship between oxytocin dose during labor or postpartum with the duration of breastfeeding. However, elective cesarean section without oxytocin resulted in the greatest risk of stopping exclusive breastfeeding.
An observational study in Sweden compared nursing behaviors of the infants of mothers who received intravenous oxytocin or intramuscular oxytocin with or without receiving epidural analgesia with sufentanil and bupivacaine. Infants of mothers who received oxytocin infusions alone during labor breastfed as well as those of mothers who had no interventions during labor. Mothers who received oxytocin plus epidural analgesia had reduced breastfeeding behaviors and more weight loss at 2 days postpartum than those who did not receive epidural analgesia. The mothers of infants who breastfed well had greater variability in serum oxytocin than those whose infants did not breastfeed well.
A study examined the effects of low, medium and high doses of intrapartum synthetic oxytocin administered to that in mothers who received no oxytocin. A dose-related decrease in several infant breastfeeding behaviors and the number of exclusive nursing bouts at 24, 48 and 72 hours was found, but there was no difference in the rate of exclusive breastfeeding at 3 months postpartum.
来源:Drugs and Lactation Database (LactMed)
