The mnemonic code of pregnancy: Comparative analyses of pregnancy success and complication risk in first and second human pregnancies

Obstetrical complications such as spontaneous abortion/miscarriage, fetal growth restriction, preeclampsia or preterm birth occur in approx. 15% of human pregnancies. Clinical experts often state that a previous uncomplicated pregnancy reduces the risk for complications in subsequent pregnancies. Vice versa, a prior pregnancy affected by obstetrical complications increases the risk for reoccurrence. However, published evidence directly underpinning these clinical statements is sparse. Considering that the maternal immune adaptation may be causally involved in determining the outcome of subsequent pregnancies, a comprehensive analysis of clinical data was long overdue. We here present a systematic analysis of clinical data using a PubMed-based approach to identify human studies with relevant information on birth weight and incidences of pregnancy complications in first and second pregnancies. From initially 18,592 publications, 37 studies were included in the quantitative data analysis. Women with a previous pregnancy affected by complications where a derailed immune response can be inferred have a 2.2-3.2-fold increased risk to be affected again in a subsequent pregnancy. Conversely, a normally progressing primary pregnancy reduced the risk for complications in a subsequent pregnancy by 35-65%. Moreover, an uncomplicated primary pregnancy was associated with a 4.2% increased birth weight in a following pregnancy without a difference in gestational age at delivery. In conclusion, the increased birth weight after previously uncomplicated pregnancies suggests that an immune memory is mounted during primary pregnancies. This immune memory may promote the successful outcome of subsequent pregnancies or - if missing or compromised - account for a risk perpetuation of pregnancy complications.