Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04866277 |
| Other study ID # |
CE20140 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 2, 2021 |
| Est. completion date |
January 31, 2022 |
Study information
| Verified date |
April 2021 |
| Source |
Instituto de Saude Publica da Universidade do Porto |
| Contact |
Ines Baia, Phd |
| Phone |
+351965418274 |
| Email |
ines.baia[@]ispup.up.pt |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Introduction: Low birthweight (LBW) is associated with a wide range of short- and long-term
consequences and is related to a complex set of maternal psychosocial and behavioural
determinants. The objective of this study is to assess the effect of implementing fast-track
referral for early intervention on psychosocial and behavioural risk factors - smoking,
alcohol consumption, depression and interpersonal violence - on reducing the incidence of
LBW.
Methods and analysis: Parallel superiority pragmatic clinical trial randomized by clusters.
Primary health care units (PHCU) located in Portugal will be randomized (1:1) to intervention
or control groups. Pregnant women over 14 years of age attending these PHCU will be eligible
to the study. Risk factors will be assessed through face-to-face interviews. In the
intervention group, women who report at least one risk factor will have immediate access to
referral services. The comparison group will be the local standard of care for these risk
factors. The investigators will use intention-to-treat analyses to compare intervention and
control groups. A sample size of 2,832 pregnant women was estimated to detect a 30% reduction
in the incidence rate of LBW (primary outcome) between the control and intervention groups.
Secondary outcomes are the reduction of preterm births and reduction of risk factors targeted
by the intervention.
Description:
The investigators will conduct a parallel superiority pragmatic clinical trial randomized by
clusters.
The study will be conducted in Primary Health Care Units (PHCU) located in the metropolitan
regions of Porto and Lisbon, in Portugal. All 236 PHCU, nested in 13 Primary Care Centres
(PCC), will be considered eligible to inclusion (109 PHCU in 7 PCC in Porto; 127 PHCU in 6
PCC in Lisbon).
The investigators will use the PHCU as units of randomization and pregnant/newborn dyads as
the unit of analysis. In each of the 13 Primary Care Centres, all PHCU that adhere to the
study will be randomized in a 1: 1 ratio for the intervention or control group and will
belong to that group until the end of the study. A research team statistician will generate
the randomization sequence through Excel Office 365 and implement the random allocation
sequence using sequentially numbered, opaque, sealed envelopes.
At each PHCU, all pregnant women, of any gestational age, over the age of 14, who are
attending their first prenatal care visit during the study period, that currently reside in
Portugal and plan to have a birth in Portugal will be considered eligible and invited to
participate in the study.
Health professionals providing prenatal care will be responsible for recruiting pregnant
women at their first prenatal visit at the PHCU. Participation in the study is voluntary and
non-participation in the study does not affect the routine healthcare provided. The
recruitment of participants will last until the planned sample is reached (estimated period
of one year).
After being informed of the objectives of the study and giving informed and written consent,
pregnant women who agree to participate will answer a face-to-face questionnaire. Data
collection will take place in a private environment, that is, in a medical or nursing office,
without the presence of other pregnant women, partners or family members, to ensure
confidentiality, using an online link.
The electronic questionnaire includes sociodemographic characteristics (date of birth,
nationality, marital status, education level, type of work) and risk assessment (smoking,
alcohol consume, depression and physical abuse). Considering the particular context of the
SARS-CoV-2 pandemic, which can affect intrauterine development of the foetus, the
questionnaire also includes information on COVID-19 tests and contact with positive cases.
Pregnant women with at least one of the psychosocial or behavioural risk factors will be
asked about chronic conditions, medication use, obstetric history, characteristics of the
current pregnancy and anthropometry. To assess smoking during pregnancy, the investigators
will use a set of questions including pre-pregnancy smoking and smoking during pregnancy
(frequency, number of cigarettes per day, gestational month). In women who report smoking
during pregnancy, the investigators will assess smoking addiction using the Fagerström
nicotine addiction test, validated in Portugal in an academic community of teachers and
staff. For alcohol consumption screening, the investigators will use the Alcohol Use
Disorders Identification Test - Consumption (AUDIT-C), a scaled-down version of the Alcohol
Use Disorders Identification Test (AUDIT), which has a good performance in detecting risky
consumption of alcohol during pregnancy. To assess depression, the investigators will use the
Portuguese version of the Edinburgh Postpartum Depression Scale (EPDE) with a 9-point
cut-off. To assess physical violence against pregnant women the investigators will use the
Abuse Assessment Screen (AAS) instrument due to its reliability, validity and easiness of
application by clinicians in the context of healthcare provision.
Women who present at least one of the risk factors will be eligible to receive the
intervention. The intervention will be the activation of fast-track referral for specialized
units and care programs for the four psychosocial and behavioural risk factors under study.
All pregnant women referred by the "STOP LBW project" would have access to consultations or
other health activities, such as counselling and group meetings, within a maximum of seven
days, in reference services available in each metropolitan area. The activation of the
fast-track referral will be the responsibility of the doctor/nurse who applies the
questionnaires to identify the risk factors. The intervention ends with childbirth, abortion
or if the participant decides to abandon the study.
The intervention will have the following process:
i. Any tobacco use during pregnancy = Activation of fast-track referral for smoking cessation
consultation in Health Centre Units, Hospitals or other; and/or ii. Risk alcohol consumption
(score ≥4 on the test AUDIT-C) = Activation of fast-track referral for consultation in
support services for the cessation of alcoholic consumption in Health Centre Units,
Hospitals, Division of Intervention in Addictive Behaviours and Dependencies (DICAD), social
service or other; and/or iii. Risk of depression (score ≥9 on the EPDE scale) = Activation of
fast-track referral for psychology consultation at Health Centre Units, Hospital Psychiatry
or other; and/or iv. Physical Violence (affirmative answer to the physical violence question
in the AAS) = Activation of the fast-track referral for social service and/or psychological
consultation in Health Centre Units, Psychiatry Hospitals, or other.
The control group will be the standard of care currently existing in each PHCU. The standard
of care varies across the various PHCU and may include several approaches: routine screening
with care by the antenatal care provider; routine screening with referral to other health
professional in the same health unit; and routine screening with referral to other health
services, with the time elapsed for consultation depending on the health resources available
in each area. In each PHCU, different standards of care may exist for each of the four risk
factors.
The primary outcome is the incidence of LBW (objective of 30% reduction in the incidence of
low birthweight, from 9.0% to 6.5%). The secondary outcomes are: a) the prevalence of each of
the four psychosocial and behavioural risk factors (smoking, alcohol consumption, depression
and physical violence) at the first prenatal visit and after birth; b) the incidence of
preterm births (live births with less than 37 weeks of gestation); and c) the proportion of
pregnant women with adherence to care programs targeted at psychosocial and behavioural risk
factors and description of the determinants of adherence.
Information on birthweight, gestational age and type of delivery will be obtained from the
child health records at the first appointment of the newborn at the PHCU (the moment of the
first vaccination will be used whenever possible). The research team will conduct a telephone
interview in the first month after birth, using the same screening questionnaire used in the
first interview, to assess tobacco and alcohol consumption, the presence of depressive
symptoms and exposure to interpersonal violence. The investigators will also measure
adherence to care programs aimed at the four risk factors and the determinants of adherence
and other strategies used by the pregnant woman to control these risk behaviours.
The sample size was calculated considering the use of bilateral tests, for a significance
level of 5% and statistical power of 80%, in order to compare the intervention and control
groups in relation to the primary outcome defined in the main objective of the study. It was
assumed that the intervention can reduce the incidence of LBW by about 30%, that is, from
9.0% to 6.5%. Estimating an institutional adherence rate of 50%, using an intracluster
correlation coefficient of 0.01 (estimated from perinatal health studies in primary health
care) 60 and estimating a size variation of 20% in clusters (variation in the number of
eligible pregnant women in each PHCU), a sample size of 1,416 participants per intervention /
control group was estimated, in a total of 2,832 participants.
Due to the nature of the study, there will be no blinding of pregnant women, health
professionals or members of the research team after assignment of the intervention. However,
those involved in the outcome assessment and data analysis will be blinded as there will be
no identification of the intervention group.
Adherence to the study protocol will be fostered using different strategies including
information to pregnant women, project communication through the creation and maintenance of
a website, involvement of health professionals during the planning and monitoring phases, and
close monitoring of the intervention by the research team. Data collection will be weekly
monitored comparing women attended in the first prenatal consultation, women invited to
participate and women included in the study. This efforts aim to prevent empty clusters and
ensure that the inclusion process of pregnant women is independent of the allocation process.
All questionnaires will be coded using an alphanumeric unique code to ensure confidentiality
and anonymity. Clinical and sociodemographic data will be stored in a Limesurvey server from
the Institute of Public Health of the University of Porto, to which only two members of the
research team will have access (IB and PP). The access to the dataset is private and will
only be available by using a specific user account and password. This repository uses digital
certificates that guarantee the security of all the communications and traceability. Datasets
will be extracted to a SPSS software version 26.0 for analysis and report.
The investigators will conduct an intention-to-treat analysis to compare the results between
the intervention and control groups using random effects models that take into account the
cluster effect. Pregnant women who have miscarriages; stillbirths; early neonatal deaths
without information on birthweight; and pregnant women included in the study who decided to
leave the study or who became inaccessible by the research team will be classified as losses
to follow-up. The missing data for individual variables will be described and multiple
imputation methods used if the missing data is >5%. Characteristics of included women versus
losses to follow-up and potential impact on results will be described, with use of
statistical techniques, if necessary, to address selection bias. Differences in LBW incidence
between the intervention group and the control group clusters will be tested using the
chi-square test (χ2) or Fisher's exact test, as appropriate. Adjusted analysis will be
conducted to control the effect of potential confounders if maternal characteristics such as
age, education, chronic conditions, marital status, type of pregnancy (single or multiple),
type of delivery, among others are misbalanced between groups.
A pilot study was conducted from January 8 to June 18, 2020 in ten PHCU including 142
pregnant women (1 refusal, 0.7%). The average gestational age was 19 weeks and 28.2% had at
least one of the four risk factors: 14.8% reported smoking during pregnancy, 0.7% had high
alcohol consumption, 16.9% had depressive symptoms and 1.4% reported at least one episode of
physical abuse during pregnancy.
The investigators had planned to start the clinical trial immediately after the pilot study
but it had to be stopped because of the covid-19 pandemic. The study will be resumed in 2021.
Patients and public were not involved in the definition of research questions, outcome
measures and design of the study. During the interviews, women will be asked about the burden
of the intervention and their acceptance.The investigators intend to involve patients and the
public in the plan to disseminate the study results.
All women who agree to participate will sign a written and informed consent. Participants can
refuse to participate in the study or withdraw their consent at any time. Refusal or
abandonment does not affect the right to receive medical treatment or medical assistance, now
or in the future. There is no reason to believe that the intervention will harm the
participants. However, all cases of miscarriage, stillbirths, neonatal death, birth defects
or maternal death will be recorded. Any potential damage resulting from the investigation
will lead to the immediate suspension of part or all of it. The data will be stored
electronically on a secure server of the Public Health Institute of the University of Porto
(ISPUP), with access only by the research team. All information in the database will be
anonymized, using a unique identifier. The key to link the database records and the
identification of the participants will be kept by the health professionals of the PHCU.
The results will be disseminated to all health professionals and health service managers in
Portugal through meetings and reports. The results will also be made available to pregnant
women and the general population through the study website and the press. The main results
will be published in scientific journals.
