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Published on: November 3, 2016
A sibling study of the prenatal and perinatal risks for cerebral palsy
Haoran Zhuo1,2, Tormod Rogne2,3, Zeyan Liew4,5
1Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Insights
Adverse perinatal factors like preterm birth and low Apgar scores are strongly linked to childhood cerebral palsy (CP). However, the connection between pregnancy complications and CP risk may be influenced by confounding factors.
Area of Science:
- Obstetrics and Gynecology
- Pediatrics
- Epidemiology
Background:
- Childhood cerebral palsy (CP) is a complex condition with multifactorial etiology.
- Understanding the influence of prenatal and perinatal factors is crucial for prevention strategies.
Purpose of the Study:
- To investigate the associations between various prenatal and perinatal factors and the risk of developing CP.
- To utilize a statewide sibling-comparison design to control for unmeasured familial confounding.
Main Methods:
- A large cohort of over 4 million singleton births in California (2007-2015) was analyzed.
- Sibling-comparison methodology identified families with CP and non-CP siblings.
- Odds ratios (OR) and 95% confidence intervals (CI) were estimated for factors including preterm birth, small for gestational age, Apgar score, maternal complications, and lifestyle factors.
Main Results:
- Perinatal factors such as preterm birth and low Apgar scores remained significantly associated with CP risk, though estimates were attenuated in the sibling design.
- Associations between maternal pregnancy complications (e.g., infection, preeclampsia) and pre-pregnancy overweight with CP risk were nullified in the sibling analysis.
- Maternal cigarette smoking showed a stronger association with CP in the sibling design, with potential bias from carryover effects noted.
Conclusions:
- Adverse perinatal factors are confirmed as strong risk factors for childhood CP.
- The sibling-comparison design suggests that confounding bias may explain the previously observed associations between certain maternal pregnancy complications and CP.
- This study highlights the value of sibling-comparison designs in CP etiology research while emphasizing the need for careful interpretation.
Background:
To evaluate the associations between prenatal and perinatal factors and CP risk using a statewide sibling-comparison design.
Methods:
We established a cohort of over 4 million singleton births in California during 2007-2015, and we identified families with outcome-discordant siblings of 1213 CP and 1544 non-CP. We estimated odds ratio (OR) and 95% confidence interval (CI) for CP according to perinatal factors including preterm birth (PTB), small for gestational age, low Apgar score, and prenatal factors including maternal pregnancy complications (perinatal infection, gestational diabetes, preeclampsia) and lifestyle-related factors (cigarette smoking, pre-pregnancy overweight).
Results:
The perinatal factors remained strongly associated with CP using sibling design, although the point estimates were smaller for PTB (cohort OR = 4.72, 95%CI 4.42-5.04, sibling OR = 3.49, 95%CI 2.74-4.46) and low Apgar score (cohort OR = 19.62, 95%CI 17.99-21.41, sibling OR = 8.79, 95%CI 5.49-14.08). In sibling design, the associations between maternal pregnancy complications or pre-pregnancy overweight and CP risk were attenuated to null. We observed stronger effects between maternal cigarette smoking and CP in the sibling design, however sensitivity tests indicated possible bias from carryover effects.
Conclusion:
Adverse perinatal factors remained strongly associated with childhood CP, while uncontrolled confounding bias required considerations for pregnancy complications and CP development.
Impact:
We conducted a population-based sibling comparison study to evaluate the associations between several prenatal and perinatal factors and cerebral palsy (CP). Preterm birth, small for gestational age, and low Apgar score at birth remained strongly associated with CP using the sibling comparison design. The associations between several maternal pregnancy complications and CP were close to null in the sibling comparison design, raising the possibility of uncontrolled confounding bias in the cohort analyses. We demonstrated that a sibling comparison design can provide valuable information to triangulate research evidence for CP etiology, but a careful implementation and interpretation of findings is warranted.
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