The aim
To investigate the effects of different methods of breast milk expression on breastfeeding initiation, efficacy of breast milk extraction, and as a consequence, on the rate of exclusive breastfeeding at 6 months.
Design and setting of the study
In this open-label, randomized controlled trial, the participants were recruited at Xinhua Hospital affiliated to Shanghai Jiaotong University, a hospital certified as a Baby Friendly Hospital. This is a tertiary general hospital with a 75-bed obstetrics unit and approximately 3300-3500 deliveries annually. Being the Shanghai Critical Maternal Transfer Center, Shanghai Prenatal Diagnosis Center, and Shanghai Premature Birth Center, it is also a referral centre for high-risk pregnancies from other hospitals in Shanghai City and surrounding provinces.
Participants
The participants were recruited from Sept. 2018 to Sept. 2019 through posters at an Obstetrics unit and in a delivery room of the hospital. Mother-neonate dyads were potentially eligible if the mother was aged 20-40 years, had attended antenatal education course in the hospital, committed to direct breastfeeding for at least 4 months in her maternity leave and were willing to express breast milk if required. The neonates had to have been delivered at gestational age ≥34 weeks and body weight ≥2000 gram with 1-minute Apgar score ≥7. Dyads in which the woman had a history of smoking or regular alcohol drinking, or contraindications (such as human immunodeficiency virus infectious diseases) to direct breastfeeding, or the infant had congenital anomalies or was unsuitable for direct breastfeeding, were excluded. Ethical approval of this trial was obtained from the Institutional Review Board of Shanghai Jiaotong University School of Medicine. All participants provided written informed consent before any trial-related procedures, first during antenatal preparation classes in the 30th-37th weeks of gestation, and then if the mother-infant dyads matched the eligibility criteria, just before delivery or within 2 hours after delivery, depending on the clinical situation of the baby. Since participants recruitment the principles of quality control were followed. This trial is registered with Chinese Clinical Trial Registry (http://www.chictr.org.cn), code ChiCTR1800018193. The reporting of the trial is guided by the extension to the CONSORT statement for multi-arm parallel-group randomized trials.47
Randomization and masking
Participants were randomly assigned into three groups (1:1:1) through a simple “lottery drawing” process without replacement. The lottery of grouping information, pre-sealed in 155 opaque envelops, was opened in the face of two investigators. The three groups were defined according to the methods of breast milk expression in the absence of infant sucking, namely hand expression, sequential pumping (Avent SCF902/11 single electric breast pump, Philips Invest, China) and simultaneous pumping (Avent SCF303/01 bilateral electric breast pumps, Philips Invest, China) in the first 6 months after birth.
This is an open-label trial. The diary check, coding, questionnaire information collection will be conducted by two nurses who did not know the allocation. The groups are coded that will not suggest any clue for electric breast pump usage and the statistician will not know the information of groups in prior.
Procedures
Participants were interviewed face-to-face during antenatal preparation classes before recruitment. Actual recruitment and simple randomization occurred immediately (<30 min) after birth at bedside of delivery/recovery room that the decision was made based on whether the neonates should be separated from their mothers for ≥6 hours. The common causes of mother and infant separation include preterm birth, neonatal asphyxia, maternal or neonatal suspicious infections (such as maternal fever before delivery, meconium-stained amniotic fluid) and complications of delivery. Physical examination and laboratory tests in pregnancy were carried out and demographic data were obtained.
All participants were trained in three manual expression of breast milk during mother-baby separation, according to guidelines for initiating milk supply in the absence of infant suction.48 Women were asked to begin breast milk expression at 2 hours after birth and continue with an interval of 2-3 hours between subsequent sessions (each comprising10 min of pumping per breast per session) until initiation of direct breastfeeding. After the infants were able to suck, the usage of breast pump was restricted to remove excessive breast milk, to alleviate the fullness of breast milk, to donate breast milk, or to discard breast milk likely to be contaminated with medications. The number of sessions of breast pumping per day was expected to decrease gradually as lactation became established in healthy mother-infant dyads.
The 10-minute expression volume of breast milk per breast at 3 days and at 6 weeks postpartum were recorded, and the mother-infant dyads were followed up at 4 and 6 months after birth (Figure 1).
All women in this study would be at hospital more than 48 hrs after delivery and discharge at the 3rd day. At the 3rd day, the two breasts were sequentially or simultaneously pumped for 10 minutes. This was repeated 2-3 hours later, using the same type of pumping (Figure 1).
On a follow-up about day 6 weeks postpartum, the mothers were asked to breastfeed directly first, and one hour later each breast was pumped for 10 minutes. After a clinical review, the mothers were asked to breastfeed their infants directly again, and then have milk pumped with the type of breast pump crossed over one hour after second direct breastfeeding.
The participants also joined an online trial member group through WeChat (Tencent, China), a mobile phone App that facilitates instant communication between participants and investigators. One investigator was assigned to answer questions from the trial group and provide professional advice. The information on breastfeeding at 4 and 6 months were collected through online questionnaire.
Outcomes and data collection
The two primary outcomes were (1) Time for lactation initiation: also known as time for breastfeeding initiation, defined as the time of the infant was provided successfully direct breastfeeding or with expressed breast milk between delivery and hospital discharge and (2) Volume or weight of expressed breast milk in 20 min (10 min per breast) at three days or six weeks postpartum. To assess the effects of manual breast expression, milk transfer was measured at 3 days and at 6 weeks postpartum. The infants were weighed just before and after breastfeeding to determine milk transfer to the infant in the obstetrician ward. This method had been validated and was used in lactogenesis research23,49. Test weights of infants in cradle were obtained in duplicate using an electronic scale (accuracy=0.1 g). Each weight was recorded when the measurement was stable for 10 seconds. A density factor of 1.03 g/ml was used in conversion between weight and volume of breast milk.
The secondary outcomes were the rates of exclusive breastfeeding at 4 and 6 months. (1) times of milk ejection during a expressing session (counted by mothers and nurse); [time frame: 6 weeks] (2) Breast milk production and mode of breastfeeding; the mode of breastfeeding divided into direct breastfeeding; direct breastfeeding+expressed breast milk; direct breastfeeding+expressed breast milk+formula milk powder; direct breastfeeding+formula milk powder; merely expressed breast milk; expressed breast milk+formula milk powder; totally formula milk powder; these data will be collected online; [time frame: six months]. Breastfeeding initiation was defined as the appearance of colostrum following breast expression or infant's sucking, and thus the time between delivery and colostrum appearance was defined to be the time required for breastfeeding initiation.
The reported adverse events during breast pumping include those from mothers and from device. General adverse events are those which patients or trial participants have complained about or clinicians have observed.
Statistical analysis
According to unpublished data from a pilot comparison between two groups of lactation-established women that each applied one of the two types of breast pumps, there was a difference in breast milk volume of around 15 ml with a standard deviation of 40 ml. The sample size was then estimated to be 90 participants in each group with statistical power of 0.8 and significant level of 0.05. Considering the limit of eligible participants, the sample size was adjusted to 50 participants in each group, and a cross over design of breast pump types was used at 6 weeks.
The data were analysed according to intention-to-treat (ITT). The continuous data were presented with mean±SD and the categorical data were presented as count and percentage. To compare baseline characteristics, two-tailed one-way ANOVA was conducted for variables with a normal distribution or the Wilcoxon signed rank (Mann-Whitney U) test for those not. Among three trial groups, nonparametric Kruskal-Wallis rank sum test and chi-squared test were applied for continuous and categorical data, respectively. Tukey honest significant differences were calculated in multiple comparison adjusted with p value. Paired student’s t test was applied to compare the milk volume between left and right breast or between two breast pumps. The log-rank test was applied to compare the time required for breastfeeding initiation (event=1). Linear mixed-effect modelling (lme4 package) was used to analyze the association between the expressed milk volume and co-variates. p<0.05 was considered statistically significant. Statistical analyses were done with R(version 3.3.3).50