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Maternal Hypertension and Adverse Neurodevelopment in a Cohort of Preterm Infants
Shipra Jain1,2,3, Ting Ting Fu1,2, Maria E Barnes-Davis1,2,3
1The Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Insights
Maternal hypertensive disorders of pregnancy (HDP) are linked to poorer cognitive and language development in preterm infants. Preeclampsia exposure showed even greater negative impacts on neurodevelopmental outcomes.
Area of Science:
- Neonatal neurodevelopment
- Pregnancy complications
- Perinatal medicine
Background:
- Maternal hypertensive disorders of pregnancy (HDP) are common and may impact preterm infant neurodevelopment.
- Previous research has been limited by confounding factors and biases.
- The independent neurodevelopmental risks associated with HDP in premature infants remain controversial.
Purpose of the Study:
- To investigate the association between maternal HDP, particularly preeclampsia, and neurodevelopmental outcomes in preterm infants.
- To assess cognitive, language, and motor development at 2 years' corrected age.
- To control for confounding variables in the analysis.
Main Methods:
- Prospective cohort study of 395 preterm infants (≤32 weeks' gestation).
- Maternal HDP status determined by diagnosis during pregnancy.
- Neurodevelopment assessed using Bayley Scales of Infant and Toddler Development (BSID) at corrected age.
- Structural brain MRI performed at term-equivalent age.
- Multivariable regression and mediation analyses were employed.
Main Results:
- HDP exposure was associated with lower cognitive and language scores in preterm infants.
- Preeclampsia exposure showed stronger negative associations with cognitive and language development.
- Brain abnormalities partially mediated the association between HDP and cognitive scores.
Conclusions:
- Maternal HDP is an independent risk factor for adverse cognitive and language development in preterm infants.
- Preeclampsia exposure exacerbates these neurodevelopmental deficits.
- Recognizing HDP as a risk factor is crucial for targeted monitoring and early intervention strategies.
Importance:
Whether maternal hypertensive disorders of pregnancy (HDP) confer independent neurodevelopmental deficit risks in premature infants is controversial. Previous studies are limited by inadequate confounding variable control and other biases.
Objective:
To evaluate the associations between maternal HDP, especially preeclampsia, and neurodevelopmental outcomes of preterm infants at 2 years' corrected age.
Design, Setting, And Participants:
Regional prospective cohort study of 395 preterm infants (≤32 weeks' gestation) from 5 level III and IV southeast Ohio neonatal intensive care units from September 2016 to November 2019. Data analysis was conducted in August 2022.
Exposure:
HDP, defined by maternal diagnosis of chronic or gestational hypertension or preeclampsia during pregnancy.
Main Outcomes And Measures:
Structural brain magnetic resonance imaging was performed at term-equivalent age. Neurodevelopment was assessed by Bayley Scales of Infant and Toddler Development (BSID), Third Edition, between 22 and 26 months' corrected age. Multivariable regression was used to identify the independent association of HDP and preeclampsia on cognitive (primary outcome), language, and motor development, controlling for several confounders. Mediation analyses were performed to understand if the association with HDP was mediated by its association with birth weight or brain abnormalities.
Results:
In a cohort of 395 infants, the median (IQR) gestational age was 29.6 (27.6-31.4) weeks, birth weight was 1230 (950-1628) g, and 210 (53.2%) were male. Of these, 170 (43%) were HDP-exposed, of which 104 of 170 (61%) were exposed to preeclampsia. A total of 341 children (87%) completed the BSID. In adjusted analyses, HDP exposure was negatively associated with BSID cognitive scores (-3.69; 95% CI, -6.69 to -0.68; P = .02) and language scores (-4.07; 95% CI, -8.03 to -0.11; P = .04). Preeclampsia exposure showed similarly negative but greater associations for BSID scores (-4.85; 95% CI, -8.63 to -1.07; P = .01 for cognitive and -6.30; 95% CI, -11.49 to -1.09; P = .02 for language scores). Mediation analysis revealed that the association between HDP and cognitive scores was partially mediated by its adverse association with brain abnormalities at term-equivalent age (24% of the total effect; -0.82; 95% CI, -1.72 to -0.13; P = .02).
Conclusions And Relevance:
In this preterm cohort study, maternal HDP was independently associated with adverse cognitive and language development, with accentuated associations observed in preeclampsia-exposed preterm infants, emphasizing the clinical importance of recognizing HDP as a risk, enabling targeted risk management strategies for closer monitoring and aggressive early intervention in affected populations.
