Clinical trial NCT03844490: Timing of Umbilical Cord Clamping: One to Three Minutes vs. After Cessation of Cord Pulsation
Official title: Timing of Umbilical Cord Clamping and Maternal and Neonatal Outcomes, Comparing One to Three Minutes vs. After Cessation of Cord Pulsation: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Umbilical Cord
Keywords: Postpartum Hemorrhage
Neonatal jaundice
Umbilical cord
Lead sponsor: Instituto Materno Infantil Prof. Fernando Figueira
Sponsor class: OTHER
Collaborators: name: Hospital Da Mulher do Recife
First posted: 2019-02-18
Enrollment: 580
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The timing of umbilical cord clamping has been widely discussed in the scientific community.

As part of the worldwide strategies to reduce childhood iron deficiency anemia, the incorporation of late clamping (at least one minute after delivery), has been adopted as an effective and low-cost measure for health services.

The optimal timing for clamping, ( if until 3 minutes of delivery, or later, when the cord stops spontaneous pulse), still remains controversial.

Also, doubts remain about the effect of late clamping of the umbilical cord on maternal outcomes.

This study has the hypothesis that waiting for the cessation of the cord pulsation will not bring harm to the newborn or the mother.

Detailed description: Due to several studies showing the advantages of late clamping of the umbilical cord for the newborn child. Delayed clamping from one, up to three minutes has been associated with better adaptation of the neonate to extrauterine life, with increased supply of oxygen, iron reserve in childhood, and benefits in the neuropsychic and motor development of children. It is considered a safe technique, recommended and has been recommended by obstetrics and neonatologists throughout the world, although the exact moment for its accomplishment is not aligned between countries.

Early clamping was one of the strategies of active management in the third period of delivery in order to prevent postpartum hemorrahge (PPH), which is considered a major cause of maternal mortality worldwide. Studies have not confirmed this initial hypothesis and the balancing between the advantages for the newborn, and no evidence of advantage fot he mother has shifted the management to late cord clamping, which for most professionals consists of clamping the cord from one to three minutes after birth.

On the other hand, there are still questions regarding the possibility of prolonging the cord clamping time, for an even longer time, or even stopping the cord's pulsations, as a way to favor placental drainage, reduce the time of placental detachment and consequently decrease bleeding events. It is believed that delayed clamping after pulsations cease may contribute to the increase in the blood volume transferred to the neonate, thus increasing its iron stores without any additional harm to the health of the woman and the newborn.

The subject is new, in order to verify the impact on the occurrence of neonatal jaundice and the blood loss when the cord is clamped after the pulsations cease, since there is no detailed report in any other study on this practice. Thus, it can contribute to the available evidence on the subject, and can be included in a systematic review and enable the elucidation of questions that still need to be clarified.

The study is relevant, since the conclusions may be of great use for clinical conduct, since it is a non-invasive and cost-free method that can contribute to reduce the occurrence of iron deficiency anemia in early childhood and postpartum haemorrhage.

General objective To determine the effects of late clamping of the umbilical cord with one to three minutes vs. after pulsations on maternal and neonatal outcomes ceased.

Specific objectives

In neonates and women undergoing delayed clamping with one to three minutes and after ceasing the cord pulsations, compare:

Primary Outcomes Rate of neonatal hyperbilirubinemia, requiring phototherapy is equivalent in both groups.

Neonatal hemoglobin between 24-48 hours postpartum is higher in the intervention group.

Secondary Outcomes Neonatal Weight at birth; Apgar score in the first minute and fifth minute; Skin-to-skin contact in the first hour of life; Duration of skin-to-skin contact; Breastfeeding in the first hour; Breastfeeding until discharge; Concentration of Ht at birth and between 24-48 hours after birth; Need for admission to neonatal neonatal intensive care unit (ICU); Hyperbilirubinemia requiring exchange transfusion; Neonatal polycythemia. Maternal Postpartum blood loss; PPH (blood loss\> 1,000ml); Hemoglobin (HG) and (Hematocrit) Ht levels in 24 hours postpartum; Hemoglobin levels lower than 8 g / dl in 24 hours postpartum; Time of detention less than 30 minutes; Uterine manual cleaning, uterine curettage, and manual removal of the placenta; Treatment for PPH in the first hour up to 24 hours postpartum; Hemotransfusion after delivery; Maternal death; Level of maternal satisfaction. Study design=\> open randomized clinical trial The study will be conducted in Instituto de Saude Integral Prof Fernando Figueira (IMIP) and Hospital da Mulher do Recife (HMR). Sample will be composed of normal risk women, live fetus at term, hospitalized in labor and by their newborns attended during the study period in the hospitals involved in the research.

Sample size calculation The sample was calculated using the online public domain calculator, Sealed Envelope 2012, considering data from a study in which 4.36% of newborns submitted to umbilical cord clamping at three minutes presented hyperbilirubinemia requiring phototherapy, with the maximum tolerable frequency of 5.36%, to show that there is no superiority between the two ducts, with a power (1-error beta) of 90% and a level of bilateral significance of (1-alpha error) of 95% 526 patients were needed, a number that was increased to 580 patients, 290 in each group, and possible losses were predicted.

After consenting to participate a blood sample will be collected from the pregnant woman by the laboratory professional, at the obstetric screening or at the PP, immediately before delivery, and sent to the laboratory for analysis of hemoglobin and hematocrit levels. All participants will be assisted in labor and delivery performed according to the routine of the service. Only after birth, if the newborn meets the eligibility criteria, will the allocation be made to one of the two previously randomized groups, with opening of the sealed envelopes.

Data collection will be performed by the assistant researchers and professionals on duty (nurse obstetrician, obstetrician and / or nursing residents) during the daytime and night shift on weekends and holidays, filling in the 24 hours of the shift. Within 24 hours of delivery, a new blood sample from the puerperium will be collected by the laboratory employee to evaluate hemoglobin and hematocrit levels; and the newborn for evaluation of hemoglobin, hematocrit and total bilirubin levels.

Data processing and analysis The analysis of the data will be performed by a blind statistic collaborator of the test, using the statistical program Epi-Info 3.5.4. The analysis will be done by intention to treat the data and performed with the groups identified as A or B. Only at the end of the analysis, already prepared the tables, is that you will know about which group will correspond each letter.

To evaluate the association between the independent variable or predictor (clamping of the umbilical cord with one to three minutes vs. clamping after the pulsations cease) and the dependent variables (outcomes) will be constructed double-entry tables. For the primary outcome, we will work with the equivalence hypothesis and for the secondary outcomes with the hypothesis of superiority.

For the continuous numerical variables of normal distribution, Student's t-test will be used, if the normality of the distribution is not verified (Kolmogorov-Smirnov test), the Mann-Whitney test will be used. For categorical variables, the Chi-square test of association (Pearson) and Fisher's exact test, when applicable, will be used. All adopted p values will be counted. The Risk Ratio (RR) will be calculated as a measure of the relative risk, as well as the 95% Confidence Interval (95% CI). The default value of 1.0 will be assigned to the reference category.

Eligibility criteria: Inclusion Criteria:

(pregnant women)

* Low risk pregnancy;
* Full-term pregnancy (37 to 42 weeks);
* Single fetus;
* Cephalic presentation;
* Normal birth;
* Euthocic delivery. (newborns)
* Live birth;
* Apgar\> 7 in the first minute and fifth minutes.

Exclusion Criteria:

Early clamping for any reason (indicated by assistant);

* Instrumental delivery (forceps);
* Chorioamnionitis;
* Placental abruption;
* Prolapse of umbilical cord;
* Congenital anomaly;
* Labor analgesia.

Primary outcomes:
measure: Neonatal Hyperbilirubinemia requiring phototherapy
timeFrame: 24 to 7 days after birth
measure: Neonatal hemoglobin concentration 24-48 h postpartum
timeFrame: 24 to 48 hours after birth
Secondary outcomes:
measure: Weight of the newborn
timeFrame: 1 hour postpartum
measure: Apgar Score in the first and fifth minutes
timeFrame: 5 minutes
measure: Skin-to-skin contact
timeFrame: 5 hours
measure: Duration of skin-to-skin contact
timeFrame: 5 hours
measure: Breastfeeding in the first hour after birth
timeFrame: 1 hour
measure: Breastfeeding until discharge
timeFrame: 15 days
measure: Hematocrit concentration 24-48 hours
timeFrame: 24-48 hours
measure: Need of ICU or NICU
timeFrame: 28 days
measure: Hyperbilirubinemia requiring exchange transfusion
timeFrame: 7 days
measure: Blood loss at birth
timeFrame: 3 hours
measure: Postpartum haemorrhage
timeFrame: 24 hours
measure: maternal hemoglobin 24 hours postpartum
timeFrame: 24 hour
measure: HG < 8 g / dL
timeFrame: 24 hours
measure: Third period duration
timeFrame: 3 hours
measure: Uterine curage
timeFrame: 3 hours
measure: Uterine curettage
timeFrame: 3 hours
measure: Manual removal of the placenta
timeFrame: 3 hours
measure: Treatment of PPH
timeFrame: 24 hours
measure: Blood transfusion
timeFrame: 24 hours
measure: Maternal death
timeFrame: 42 days
measure: Maternal satisfaction
timeFrame: 24 hours
Other outcomes:
Locations:
city: Recife
country: Brazil
facility: Instituto Materno Infantil Prof. Fernando Figueira
state: Pernambuco
Study officials:
affiliation: IMIP
name: LEILA KATZ, MD, PhD
role: STUDY_DIRECTOR
References: