Table 3.
Studies assessing the impact of preeclampsia exposure on infant neurodevelopment in infancy (birth – 2 years)
| First Author (Year) | Study Type | Exposure (Number) | Tool | Main Findings at 2 Yearsa (PE versus NTP-exposed infants) | Adjusted Confounders | Comments |
|---|---|---|---|---|---|---|
| Szymonowicz (1987) [23] | Case–control |
PE (35) NTP (35) |
BSID |
MDI: PE lower PDI: ND |
Nil |
Cohort: preterm, VLBW infantsb ROB: Low |
| Spinillo (1994) [148] | Case–control |
PE (68) NTP (184) |
BSID |
MDI: PE lower PDI: PE lower |
Maternal age, SES, education |
Cohort: preterm infants, PE group had expectant management ROB: Low |
| McCowan (2002) [153] | Prospective cohort |
PE/GH (88) NTP (131) |
BSID-II |
MDI: PE/GH higher PDI: ND ND between < 32 weeks and > 32 weeks |
Infant sex, GA, hospital stay, breastfeeding status, perinatal complications Maternal age, parity, ethnicity, smoking, education |
Cohort: SGA infantsb Grouped PE and GH Assessed 18-month outcomes ROB: Low |
| Cheng (2004) [25] | Retrospective cohort |
PE (25) NTP (54) |
BSID-II |
MDI: PE lower (mild delay from -1 to -2 SDs), ND (severe delay), ND between SGA PE and SGA NTP PDI: ND |
Infant sex, GA, birthweight, lack of prenatal steroid, PPROM, intraventricular haemorrhage Maternal/paternal education, chronic lung disease |
Cohort: VLBW, very preterm (< 32 weeks) infantsb. Small sample ROB: Low |
| Silveria (2007) [26] | Prospective cohort |
PE (40) NTP (46) |
BSID-II |
MDI: ND PDI: PE higher |
Nil |
Cohort: VLBW infantsb Small sample. Assessed 12, 18-month outcomes ROB: Low |
| Spinillo (2009) [154] | Prospective cohort |
PE (185) NTP (596) |
BSID-II | MDI: PE higher (female higher than male), SGA lower than non-SGA |
Infant sex, GA, proportion of expected birthweight, SGA status, antenatal steroids, placental abruption, praevia, PPROM, non-reassuring fetal heart rate, chorioamnionitis, caesarean section, year of birth, umbilical artery pH = < 7.2 Maternal age, parity, education, SES, smoking |
Cohort: preterm infantsb ROB: Low |
| Schlapbach (2010) [152] | Case–control |
PE (33) NTP (33) |
BSID-II |
MDI: ND PDI: ND |
Infant GA, birthweight, 2-year body weight, bronchopulmonary dysplasia, mechanical ventilation | Cohort: very preterm (< 32 weeks) infantsb |
| Matić (2017) [28] | Retrospective cohort |
PE/GH (261) NTP (1212) |
Griffiths MDS, BSID-II |
ND Long-term functional disability: SGA status, earlier GA and male sex were significant |
Infant sex, GA, birthweight, surfactant therapy Maternal parity |
Grouped PE and GH Cohort: infants aged 2–3 years, born very preterm (< 29 weeks). Powered to assess chronic lung disease, not just neurodevelopment ROB: Low |
| Degirmenci-oglu (2018) [155] | Retrospective cohort |
PE (120) NTP (251) |
BSID-II |
MDI: PE higher PDI: ND Overall neurodevelopmental index: ND |
Infant GA, birthweight, asphyxia, sepsis, intraventricular haemorrhage, necrotising enterocolitis Maternal hypothyroidism |
Cohort: VLBW, very preterm (< 32 weeks) infants, but FGR infants were excludedb Assessed 18- 24-month outcomes ROB: Low |
|
Martikainen (1989) [24] |
Prospective cohort |
GH (14 preterm, 60 term) PE (31 preterm, 40 term) NTP (128 preterm, 175 term) |
Denver |
Term: PE/GH higher motor performance, visuo-auditory perception, and social abilities Preterm: PE lower fine motor and visuo-auditory perception, SGA lower than non-SGA |
Infant sex, GA |
Also assessed other HDPs. Cohort stratified by hypertension exposure, prematurity and SGA statusb. Assessed 18-month outcomes ROB: Low |
| Gray (1998) [151] | Prospective cohort |
GH (14) PE (79) NTP (107) |
Griffiths-II, NSMDA |
ND | Nil |
Cohort: very preterm (24–32 weeks) infantsb ROB: Low |
| Johnson (2015) [149] | Prospective cohort |
Preterm (638) Term (765) |
PARCA-R | Preterm: PE was independent risk factor for cognitive impairment, preterm lower than term |
Infant sex, SGA status Maternal ethnicity, SES |
Cohort: late preterm infants (32–36 weeks)b Assessed other perinatal variables, including PE ROB: Low |
| Wade (2016) [156] | Prospective cohort |
HDP (23) NTP (478) |
Many tools- see study | Social cognition: HDP lower |
Infant age, sex, GA, birthweight Maternal age, gestational diabetes mellitus, thyroid problems, SES, smoking status |
Grouped PE with other HDPs. Small sample Assessed 18-month outcomes ROB: Low |
| Warshafsky (2016) [80] | Prospective cohort |
Mild PE (34) Severe PE (46) NTP (103) |
ASQ | Severe PE was protective, higher GA reduced risk and FGR increased risk in both groups |
Infant sex, GA, SGA status breastfeeding status, MgSO4 usage Maternal age, parity, ethnicity, smoking, SES, education |
Cohort: FGR infants below 5th centile Removed the mild PE subgroup due to poor numbers. Assessed 12, 24-month outcomes ROB: Low |
| Bharadwaj (2018) [157] | Case–control |
PE (56) NTP (61) |
DASII | Motor and mental development quotients: PE lower, maternal total antioxidant status was an independent motor development quotient predictor (PE group) |
Infant GA, early onset sepsis, respiratory distress syndrome, necrotising enterocolitis Maternal total antioxidant status, Maternal and cord/baby protein carbonyl levels |
No adjustment for SGA or prematurity status Assessed 12-month outcomes ROB: Low |
| Chen (2020) [158] | Prospective cohort |
GH (233) PE (41) NTP (3669) |
GDS |
Social Behaviour Development Quotient: GH lower Neurodevelopmental delay: ND |
Infant sex, GA, birthweight, mode of delivery, asphyxia neonatorum Maternal age, smoking, drinking, education, folic acid supplementation |
Also studied chronic hypertension Assessed 6-month outcomes ROB: Low |
| Maher (2020) [159] | Prospective cohort |
PE (709) NTP (10,425) |
ASQ | ASQ failure: ND, ND between preterm vs term |
Infant sex, SGA, prematurity Maternal age, ethnicity, BMI, gestational diabetes mellitus, education, SES |
PE status determined by maternal recall. Assessed 9-month outcomes ROB: Low |
Abbreviations: ASQ Ages and Stages Questionnaire [125], BSID-II Bayley Scales of Infant Development (2nd edition) [138], C-HTN† Complicated hypertension, DASII Developmental Assessment Scale for Indian Infants [160], Denver The Denver Developmental Screening Test [161], FGR Fetal growth restriction, GA gestational age at birth, GDS Gesell Developmental Schedules [162, 163], GH Gestational hypertension, HDP Hypertensive disorder of pregnancy, HTN, Hypertension, MDI Mean developmental index (BSID), MDS Griffiths Mental Development Scale [141], ND No difference, NSMDA Neurosensory Motor Developmental Assessment [164], NTP Normotensive pregnancy, PARCA-R Parent Report of Children’s Abilities- Revised [132], PDI Psychomotor development index (BSID), PE Preeclampsia, PRROM Preterm premature rupture of the membranes, ROB Risk of bias, SES Socioeconomic status, SGA Small for gestational age, VLBW Very low birth weight
aAll results in the ‘Main Findings’ column are of infant developmental outcomes at 2 years, unless specified in the ‘Comments’ column
bPreterm birth was defined as birth < 37 weeks’ gestation. VLBW was defined as birthweight < 1500 g. SGA birth was defined as birthweight corrected for gestational age < 10th centile. Study-specific definitions of ‘very preterm’ are specified in the ‘Comments’ column