Fetal sex-specific differences in gestational age at delivery in pre-eclampsia: a meta-analysis.
: Pre-eclampsia (PE) is a major pregnancy disorder complicating up to 8% of pregnancies. Increasing evidence indicates a sex-specific interplay between the mother, placenta and fetus. This may lead to different adaptive mechanisms during pregnancy.



We performed an individual participant data meta-analysis to determine associations of fetal sex and PE, with specific focus on gestational age at delivery in PE. This was done on 219 575 independent live-born singleton pregnancies, with a gestational age at birth between 22.0 and 43.0 weeks of gestation, from 11 studies participating in a worldwide consortium of international research groups focusing on pregnancy.



Of the women, 9033 (4.1%) experienced PE in their pregnancy and 48.8% of the fetuses were female versus 51.2% male. No differences in the female/male distribution were observed with respect to term PE (delivered ≥ 37 weeks). Preterm PE (delivered < 37 weeks) was slightly more prevalent among pregnancies with a female fetus than in pregnancies with a male fetus [odds ratio (OR) 1.11, 95% confidence interval (CI) 1.02-1.21]. Very preterm PE (delivered < 34 weeks) was even more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus (OR 1.36, 95% CI 1.17-1.59).



Sexual dimorphic differences in the occurrence of PE exist, with preterm PE being more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus and with no differences with respect to term PE.
Erasmus Medical Centre, Department of Obstetrics and Gynecology, Rotterdam, The Netherlands.
Sarah
S
Schalekamp-Timmermans
Institute of Psychology, and Department of Pedagogical Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands, and Erasmus Medical Centre, Department of Biostatistics, Rotterdam, The Netherlands.
Lidia R
LR
Arends
Norwegian Institute of Public Health, Oslo, Norway.
Elin
E
Alsaker
Women's Health Academic Centre, King's College London and King's Health Partners, London, UK.
Lucy
L
Chappell
Lund University, Department of Clinical Sciences, Obstetrics and Gynecology, Lund, Sweden, and Skåne University Hospital, Perinatal Unit, Malmo, Sweden.
Stefan
S
Hansson
Oslo University Hospital, Department of Obstetrics, Oslo, Norway.
Nina K
NK
Harsem
Lund University, Department of Clinical Sciences, Obstetrics and Gynecology, Lund, Sweden, and Skåne University Hospital, Department of Obstetrics and Gynecology, Malmo, Sweden.
Maya
M
Jälmby
University of Pittsburgh School of Medicine, Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Pittsburgh, PA, USA.
Arundhathi
A
Jeyabalan
Medical and Clinical Genetics and Obstetrics and Gynecology, and Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Hannele
H
Laivuori
MRC Integrative Epidemiology Unit at the University of Bristol, School of Social and Community Medicine, Bristol, UK.
Debbie A
DA
Lawlor
MRC Integrative Epidemiology Unit at the University of Bristol, School of Social and Community Medicine, Bristol, UK.
Corrie
C
Macdonald-Wallis
Norwegian Institute of Public Health, Oslo, Norway.
Per
P
Magnus
Maternal & Fetal Health Research Centre, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Jenny
J
Myers
Aarhus University, Institute of Clinical Epidemiology, Aarhus, Denmark, and UCLA Los Angeles, Los Angeles, CA, USA.
Jørn
J
Olsen
Women's Health Academic Centre, King's College London and King's Health Partners, London, UK.
Lucilla
L
Poston
Nuffield Department of Obstetrics and Gynecology, John Radcliffe Hospital, Oxford, UK.
Christopher W
CW
Redman
Oslo University Hospital, Department of Obstetrics and Department of Gynecology, University of Oslo, Oslo, Norway.
Anne C
AC
Staff
Obstetrics and Gynecology, and Clinical Graduate School in Pediatrics and Obstetrics/Gynecology, University of Helsinki, Helsinki, Finland.
Pia
P
Villa
Department of Obstetrics, Gynecology and Reproductive Sciences, Epidemiology and Clinical and Translational Research University of Pittsburgh, Pittsburgh, PA, USA.
James M
JM
Roberts
Erasmus Medical Centre, Department of Obstetrics and Gynecology, Rotterdam, The Netherlands.
Eric A
EA
Steegers
D000328:Adult; D036861:Delivery, Obstetric / Q000706:statistics & numerical data; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000453:epidemiology; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011225:Pre-Eclampsia / Q000453:epidemiology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology*; D012737:Sex Factors; D055815:Young Adult
ALSPAC; Sexual dimorphism; placenta; pre-eclampsia; sex ratio