Long-term Follow-up of Children Born in the PETN Studies

Official title

Langzeiteffekt Einer Pentaerithrityltetranitrat (PETN)-Behandlung in Der Schwangerschaft - Nachbeobachtung Der Kinder Der PETN-Studien

Overview

In every 10th pregnancy, the child in the uterus is insufficiently nourished, a so-called growth retardation. This occurs when the child cannot reach its growth potential due to an undersupply in the uterus. This inadequate supply is considered a developmental cause for the later development of physical diseases like cardiovascular diseases, sugar metabolism disorders and obesity as well as mental developmental problems (for example problems in cognitive skills, deficits in language development, concentration and attention). From 2002 to 2008, 111 patients with impaired placental blood flow were included in a small study and treated with Pentalong or placebo. From 2017 to 2022, the positive effects of the study treatment were tested on a larger number of patients. A total of 317 pregnant women were included at 14 participating study centers in Germany. In this follow-up study, the development of the children born in the two studies will be examined. The study consists of two independent parts: firstly, questionnaires are answered by the former participants and secondly, an on-site visit is carried out to check the physical and mental health of the child.

Detailed description

Pregnancies in which impaired uterine blood flow is detected by Doppler measurements during routine examinations in the second trimester are at high risk of developing fetal growth restriction (FGR). FGR affects 10% of pregnancies and is the leading cause of perinatal mortality and morbidity. In addition, intrauterine growth restriction places a lifelong burden on the physical and mental health of affected children. Epidemiological studies have shown that children with FGR have an increased risk of developing type 2 diabetes mellitus, hypertension, dyslipidemia and a high BMI. In addition, the affected children show disorders in hormonal balance and pubertal development as well as specific impairments of various cognitive and neurocognitive functions. There is also a link between FGR and lower cognitive ability in preschool children, school-age children and young adults, as well as lower communication, language and reading skills in school-age children. Neuronal development (e.g. EEG frequency spectra, resting-state networks) and executive functions are also impaired by FGR.

In the follow-up study, the children will be examined from the age of 6. Here, the effects of PETN on the development of children of women with high-risk pregnancies can be further investigated and a comparative study of growth-retarded and normal-growth children can also be carried out.

Interventions

• Behavioral Questionnaire Child Behaviour Checklist
  The Child Behavior Checklist comprises items assigned to 8 subscales describing various behavioral areas. These subscales can be summed up to scores for internalizing and externalizing problems as well as a total score. Checklist scores are reported on a T-scale. Range of T-scale from scores 20 to 100 (average performance between scores 40 and 60). Higher scores mean higher amount of problems.
• Behavioral Questionnaire Young Self Report
  The Questionnaire Young Self Report comprises items assigned to 8 subscales describing various behavioral areas. These subscales can be summed up to scores for internalizing and externalizing problems as well as a total score.
• Diagnostic test physical examination
  physical development examination including height (in cm), weight (in g) and tanner states
• Diagnostic test metabolic examination
  metabolic development using blood analysis including blood components, metabolic parameters (Glucose, HbA1c, cholestrol)
• Behavioral Questionnaire Reynolds Intellectual Assessment Scales and Screening
  The RIAS is standardized intelligence test. The RIAS provides an "Total Intelligence Index" (GIX, estimate of the general intelligence/g-factor), Verbal Intelligence Index (VIX) and the Nonverbal Intelligence Index (NIX). Test scores are reported on a T-scale. Range of T-scale from scores 20 to 100 (average performance between scores 40 and 60). Higher scores mean better cognitive performance.
• Diagnostic test electroencephalogram
  neurocognitive development
• Other Questionnaire Movement Assessment Battery for Children
  The M-ABC-2 is an standardized test to assess the motoric development. Adding up subscores addressing manual dexterity, aiming and catching, and balance delivers a total score of the motoric performance. Test scores are reported on a T-scale. Range of T-scale from scores 20 to 100 (average performance between scores 40 and 60). Higher scores mean better performance.
• Other Questionnaire Continuous Performance Test
  The CPT measures selective attention, sustained attention as well as impulsive behavior. Checklist scores are reported on a T-scale. Range of T-scale from scores 20 to 100 (average performance between scores 40 and 60). Higher scores mean worse performance.
• Other Questionnaire Diagnostic System for Mental Disorders
  The FBB-ADHS assesses a total score for ADHD-like behavior and subscores for the symptom trias of ADHD (attention deficit, motoric hyperactivity as well as impulsive behavior, Questionnaire scores are reported on a T-scale. Range of T-scale from scores 20 to 100 (average performance between scores 40 and 60). Higher scores mean higher amount of symptoms.
• Diagnostic test kidney function tests
  urine examination (proteomics, cytokines, lipidomics)

Primary outcome measures

• childrens behaviour [Time frame: up to 2 years after study inclusion]

Secondary outcome measures (12)

• physical development height [Time frame: up to 2 years after study inclusion]
• physical development weight [Time frame: up to 2 years after study inclusion]
• age appropriate development [Time frame: up to 2 years after study inclusion]
• cognitive, motoric, and exectuve function [Time frame: up to 2 years after study inclusion]
• physical development [Time frame: age above 10 years]
• cardiovascular development [Time frame: age of 6 to 8 years]
• IQ development [Time frame: age of 6 to 8 years]
• motoric development [Time frame: age of 6 to 8 years]
• attention behaviour [Time frame: age of 6 to 8 years]
• symptoms of attention and activity disorders [Time frame: age of 6 to 8 years]
• neurocognitive development [Time frame: age of 6 to 8 years]
• neurocognitive development [Time frame: age of 6 to 8 years]

Eligibility criteria

Inclusion criteria

• mothers participation in one of the PETN studies
• age above 5 years
• completion of questionnaires for self reported data
• written consent for physical examination

Exclusion Criteria - only physical examination:

• physical and mental states preventing physical examination

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Germany · 13 centers

• Universitäts-Frauenklinik Tübingen — Tübingen
• Universitätsklinikum Ulm — Ulm
• Klinikum der Universität München — München
• Städtisches Klinikum München — München
• Medizinische Hochschule Hannover — Hanover
• Universitätsklinikum Bonn — Bonn
• Universitätsklinikum Dresden — Dresden
• Uniklinikum Leipzig — Leipzig
• … and 5 more centers

Identifiers

NCT: NCT06534307 · ZKSJ0133

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗