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Trial record 35 of 35 for:    fetal alcohol children

Macrolide in Pregnancy and Adverse Child Outcomes

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ClinicalTrials.gov Identifier: NCT03948620
Recruitment Status : Completed
First Posted : May 14, 2019
Last Update Posted : May 15, 2019
Sponsor:
Information provided by (Responsible Party):
Institute of Child Health

Brief Summary:

Over the last 20 years, concerns have been raised about rare but serious adverse outcomes associated with macrolide use during pregnancy. The strongest evidence comes from a large randomised controlled trial (RCT, ORACLE Child Study II) of women with spontaneous preterm labour (SPL), which reported an increased risk of cerebral palsy in children whose mothers received erythromycin compared with no erythromycin. A recent systematic review on macrolides prescription during pregnancy showed consistent associations with miscarriage, and less consistent associations with adverse child outcomes such as congenital malformations, cerebral palsy and epilepsy. In this study, the investigators will evaluate associations between macrolide antibiotics prescription during pregnancy and a range of adverse child outcomes.

The investigators compare children whose mothers were prescribed an only monotherapy of macrolides or penicillins during pregnancy (from 5 gestational week (GW) to delivery and by trimesters). The investigators estimate the risk ratios of major malformation (overall and five system-specific) and hazard ratios of four neurodevelopmental disorders (cerebral palsy, epilepsy, attention-deficit/hyperactivity disorder, and autism spectrum disorder) with control for potential confounders. The associations will also be examined by subtype of macrolides and treatment duration.

Mother-child pairs will be analysed in a cohort selected from the UK Clinical Practice Research Database (CPRD) between 1990 and 2016.


Condition or disease Intervention/treatment
Infection Drug: Macrolides Drug: Penicillins

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Study Type : Observational
Actual Enrollment : 726274 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Associations Between Macrolide Antibiotics Prescribed During Pregnancy and Adverse Child Outcomes
Actual Study Start Date : January 1, 1990
Actual Primary Completion Date : June 30, 2016
Actual Study Completion Date : June 30, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics
Drug Information available for: Penicillins

Group/Cohort Intervention/treatment
Children whose mother prescribed antibiotics during pregnancy

Children whose mother were prescribed an only monotherapy of macrolides or penicillins from 5 gestational weeks (GW) to delivery. A monotherapy is defined as one or more consecutive prescriptions for a single antibiotic (i.e. same drug substance) separated by no more than 30 days and uninterrupted by prescriptions for other antibiotic drug substances.

The investigators will also build a negative control cohort which includes children whose mother were prescribed an only monotherapy of macrolides or penicillins from 50 to 10 weeks before conception.

Drug: Macrolides
Macrolide antibiotics, including erythromycin, clarithromycin and azithromycin. Prescriptions of macrolides will be identified using a drug code list based on the British National Formulary (chapter 5.1.5) and the date of the first prescription was used as the index date of exposure.

Drug: Penicillins
The comparison group consists of children whose mother were prescribed penicillins during pregnancy. Prescriptions of penicillins will be identified using a drug code list based on the British National Formulary (chapter 5.1.1) and the date of the first prescription will be used as the index date of exposure.




Primary Outcome Measures :
  1. Number of major malformation overall [ Time Frame: From birth up to 4 years after birth. ]
    Major malformation overall will be defined as any of the 11 major system-specific malformations defined in the European Surveillance of Congenital Anomalies (EUROCAT)(Congenital heart defect, nervous system, eye, ear/face/neck, respiratory tract, oro-facial cleft, digestive system, abdominal wall defect, urinary tract, genital tract, and other malformations). The investigators exclude musculoskeletal malformations which are not reliably recorded in general practice (GP) records, and malformation with known cause such as malformation resulted from maternal infections, fetal alcohol syndrome and chromosomal malformations. The malformations will be identified in the children's medical records using Read codes mapped from the tenth edition of the International Classification of Diseases (ICD-10) code lists provided by EUROCAT.

  2. Number of cardiovascular malformation [ Time Frame: From birth up to 4 years after birth. ]
    The malformations will be identified in the children's medical records using Read codes mapped from the tenth edition of the International Classification of Diseases (ICD-10) code lists provided by EUROCAT (ICD Q20-Q26; exclude Q2111, Q250 if gestational age (GA) <37 weeks, Q2541, Q256 if GA<37 weeks, and Q261).

  3. Number of nervous system malformation [ Time Frame: From birth up to 4 years after birth. ]
    The malformations will be identified in the children's medical records using Read codes mapped from the tenth edition of the International Classification of Diseases (ICD-10) code lists provided by EUROCAT (Q00-Q07, exclude Q0461, Q0782).

  4. Number of gastrointestinal system malformation [ Time Frame: From birth up to 4 years after birth. ]
    The malformations will be identified in the children's medical records using Read codes mapped from the tenth edition of the International Classification of Diseases (ICD-10) code lists provided by EUROCAT (Q38-Q45, Q790, exclude Q381, Q382, Q3850, Q400, Q401, Q4021, Q430, Q4320, Q4381, Q4382).

  5. Number of genital malformation [ Time Frame: From birth up to 4 years after birth. ]
    The malformations will be identified in the children's medical records using Read codes mapped from the tenth edition of the International Classification of Diseases (ICD-10) code lists provided by EUROCAT (Q50-Q52, Q54-Q56; exclude Q523, Q525, Q527, Q5520, Q5521).

  6. Number of urinary malformation [ Time Frame: From birth up to 4 years after birth. ]
    The malformations will be identified in the children's medical records using Read codes mapped from the tenth edition of the International Classification of Diseases (ICD-10) code lists provided by EUROCAT (Q60-Q64, Q794; exclude Q610, Q627, Q633).

  7. Rate of cerebral palsy [ Time Frame: From birth up to 15 years after birth. ]
    The investigators identify children with cerebral palsy using informative Read codes or prescription codes (selected by the Random Forest approach) and validated by a paediatric neurologist (FC) and a clinical epidemiologist with paediatrics expertise (RG) blinded to their prenatal exposure (A machine learning approach to identify cases of cerebral palsy using the UK primary care database.Fan, Heng et al.The Lancet , Volume 392 , S33).

  8. Rate of epilepsy [ Time Frame: From birth up to 15 years after birth. ]
    The investigators identify epilepsy by 2 prescriptions of antiepileptic drug (AED, identified based on British National Formula Chapter 4.8) within 4 months or >= 1 diagnosis in children's GP records.

  9. Rate of attention-deficit/hyperactivity disorder (ADHD) [ Time Frame: From birth up to 15 years after birth. ]
    The investigators identify ADHD by >= 2 occurrence of prescriptions for ADHD ( identified based on British National Formula Chapter 4.4) or diagnoses (attention deficit hyperactivity disorder, hyperkinetic disorders, hyperkinetic syndrome, hyperkinetic reaction of childhood or adolescence, overactive child syndrome and disturbance of activity and attention) in children's GP records.

  10. Rate of autism spectrum disorder (ASD) [ Time Frame: From birth up to 15 years after birth. ]
    The investigators identify ASD by at least 1 diagnostic code ((infantile or childhood) autism, Asperger's syndrome, Rett's syndrome, Heller's syndrome, Autistic spectrum disorder, disintegrative disorder, and other pervasive developmental disorders) in children's GP records.



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Ages Eligible for Study:   up to 14 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
The study population will consist of all eligible children from the source population where the mother was prescribed an only monotherapy of macrolides or penicillins during pregnancy. The source population will be all mother-baby pairs identified from CPRD Mother-baby linkage where the children were born from Jan 1st 1990 to June 30th 2016.
Criteria

Inclusion Criteria:

  • Children whose mother was prescribed an only monotherapy of macrolides or penicillins during pregnancy (between 5 GW and delivery).
  • Children born from Jan 1st 1990 to June 30th 2016 in the CPRD Mother Baby Link.
  • Children who registered with the GP within 6 months of birth
  • Children whose mother was aged 14 to 50 years and had been registered with GP at least 50 weeks before estimated conception date until after delivery

Exclusion Criteria:

  • Children with known chromosomal abnormalities and pregnancies with exposure to known teratogenic medications (warfarin, angiotensin-converting enzyme (ACE) inhibitors, antineoplastic agents, isotretinoin, misoprostol, and thalidomide)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03948620


Sponsors and Collaborators
Institute of Child Health
Investigators
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Study Director: Ruth Gilbert, MD Institute of Child Health, University College London
Study Director: Leah Li, PhD Institute of Child Health, University College London
  Study Documents (Full-Text)

Documents provided by Institute of Child Health:

Publications:
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Responsible Party: Institute of Child Health
ClinicalTrials.gov Identifier: NCT03948620     History of Changes
Other Study ID Numbers: Heng1
First Posted: May 14, 2019    Key Record Dates
Last Update Posted: May 15, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Anti-Bacterial Agents
Penicillins
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents