Health of Pessary Versus Progesterone Supplement for Preventing Preterm Birth Children

Study Overview
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Brief Summary
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To give strong recommendations on the efficacy and safety of vaginal progesterone versus cervical cerclage, we conduct this study to investigate the physical and mental development of children from vaginal progesterone versus cervical cerclage. Based on our research (Dang et al., 2019), the twin pregnancies with cervical lengths less than 38mm were randomly assigned to receive vaginal progesterone or cervical cerclage, which leads to the similarity in characteristics of these two groups. Hence, the result of analyzing these offsprings would be preciously valuable.

Detailed Description
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Preterm birth (PB) is the leading cause of neonatal morbidity and mortality. Twin pregnancies and short cervical length are two high-risk factors of PB. Generally, in singleton pregnancies with short cervical length below 25 mm, or with a history of preterm birth, preventive measures of PB are vaginal progesterone and cervical cerclage. The cervical pessary is also being investigated for effectiveness in PB prevention in different populations. However, the effective preventive methods for PB has not been identified up to now in twin pregnancies with short cervical length. In our research, the results showed that the preterm birth rate before 34 weeks in the cervical pessary group was lower than the progesterone group (16% vs 22%, RR 0.73; 95% CI 0.46 - 1.18). The perinatal outcomes were also better in the cervical pessary group than in the progesterone group (19% vs 27%, RR 0.70; 95% CI 0.43 - 0.93). The cost of the cervical pessary method was also significantly lower than the vaginal progesterone method cost. Pessary insertion was also more convenient since it was only inserted once during pregnancy, compared to daily vaginal progesterone. Therefore, the cervical pessary may be an appropriate option for preventing preterm birth in twin pregnancies with a short cervix. However, besides these short-term outcomes, we need to pay more attention to the longer-term issues of both mothers and infants. Some evidence up to now has demonstrated that both these two methods are safe with no impact on physical, mental, and motor development of children up to 3 years old and even in older children. However, such evidence is still rare. Also, there hasn't been any study evaluating the impact, if any, of these two PB preventive methods.

Official Title
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Physical, Mental and Motor Development of Children Born to Mothers Treated With Pessary or Progesterone Supplement for Preventing Preterm Birth

Conditions
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Preterm Birth

Intervention / Treatment
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* Other: Developmental score according to The Ages & Stages Questionnaires®, Third Edition - ASQ®-3
* Other: Physical development and General Health
* Other: Developmental Red flags


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Live babies born from The pessary versus vaginal progesterone in women with a twin pregnancy and a cervix <38 mm study (NCT02623881) Parents agree to participate in the study. Exclusion Criteria: Babies died after the perinatal period.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 66 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cervical pessary<br>Cervical pessary (Arabin) will be inserted to participants at 16-22 weeks and removed at 37 weeks of pregnancy or in case of premature rupture of membranes, signs of preterm labour or patient severe discomfort. | Other: Developmental score according to The Ages & Stages Questionnaires®, Third Edition - ASQ®-3<br>* Ages & Stages Questionnaires®, Third Edition (ASQ®-3) is a developmental screening tool designed for use by early educators and health care professionals. It relies on parents as experts, is easy-to-use, family-friendly and creates the snapshot needed to catch delays and celebrate milestones.<br>Other: Physical development and General Health<br>* Physical development and General health examination<br>Other: Developmental Red flags<br>* Developmental Red flags Questionnaires<br>|
| Vaginal Progesterone<br>Vaginal progesterone (Cyclogest 200 mg) once a day will be used, from 16-22 to 37 weeks of pregnancy or in case of premature rupture of membranes, signs of preterm labour or patient severe discomfort. | Other: Developmental score according to The Ages & Stages Questionnaires®, Third Edition - ASQ®-3<br>* Ages & Stages Questionnaires®, Third Edition (ASQ®-3) is a developmental screening tool designed for use by early educators and health care professionals. It relies on parents as experts, is easy-to-use, family-friendly and creates the snapshot needed to catch delays and celebrate milestones.<br>Other: Physical development and General Health<br>* Physical development and General health examination<br>Other: Developmental Red flags<br>* Developmental Red flags Questionnaires<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The average total ASQ-3 score | ASQ-3 (Ages and Stages Questionaires®) has 5 aspects: Communication, Gross motor, Fine motor, Problem solving and Personal-Social Each aspect has 6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. ASQ-3 average = average score of 5 aspects. | Up to 66 months after birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score of Communication | 6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspects in each stages has alternative threshold | Up to 66 months after birth | 
| Score of Gross motor | 6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspects in each stages has alternative threshold | Up to 66 months after birth | 
| Score of Fine motor | 6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspects in each stages has alternative threshold | Up to 66 months after birth | 
| Score of Problem solving | 6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspects in each stages has alternative threshold | Up to 66 months after birth | 
| Score of Personal-Social | 6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspects in each stages has alternative threshold | Up to 66 months after birth | 
| The rate of children who have at least one red flag sign | He or she has at least one red flag sign by age From 2 to < 3 year-old: Has very unclear speech Doesn't understand simple instruction • Doesn't speak in sentences Doesn't make eye contact Loses skills he/she once had From 3 to < 4 year-old: Can't jump in place Doesn't play pretend or make-believe • Speaks unclearly Can't retell a favorite story Doesn't use me and you correctly Loses skills he/she once had From 4 to < 5.5 year-old: Is easily distracted, has trouble focusing on one activity for more than 5 minutes • Doesn't talk about daily activities or experiences Shows extreme behavior Loses skills he/she once had | From 2 to 5.5 years after birth | 
| Duration of breast-feeding | Duration of breast-feeding | Up to 24 months after birth | 
| Infant age at which weaning starts | Infant age at which weaning starts | Up to 24 months after birth | 
| Name of diseases that lead to hospital admission | Name of diseases that lead to hospital admission | Up to 66 months after birth | 
| Number of hospital admission | Number of hospital admission | Up to 66 months after birth | 
| Weight | Weight on the examination date | Through study completion, an average of 1.5 months | 
| Height | Height on the examination date | Through study completion, an average of 1.5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pesary, Progesterone, ASQ-3, Health of children