A landmark analysis says biomarkers may be present pre-conception, and finds recovery from childbirth takes far longer than women are told.
The most comprehensive analysis of pregnancy data to date has captured the profound physiological changes experienced during gestation and postpartum recovery.
Not only has it concluded that recovery is far longer than the six weeks many women are promised, but researchers also suggest it could disprove the long-held theory that preeclampsia is an issue arising from placental implantation.
Data from over 300,000 pregnancies, showing weekly test results between 20 weeks preconception and 80 weeks postpartum, has identified trends in both healthy pregnancies and pregnancies experiencing complications.
It is an unprecedented number of participants, time intervals, and major laboratory tests, with more than 43 million measurements taken via 76 lab tests. Authors suggest that existing studies have limited participation and a narrow scope, for example only including one time point per trimester or one time point to cover the entire postpartum period.
Clalit Healthcare, the largest HMO in Israel, provided data for roughly half of the country’s pregnancies between 2003 and 2020 with a broad socioeconomic and ethnic demographic. Women were aged 20-35 with no chronic disease. Pregnancies that resulted in stillborn birth, multiples, or pre-term deliveries were excluded, as were women who fell pregnant again within the postpartum period.
The true scale of recovery
Pregnancy has a profound impact on oxygen demand, insulin resistance, lipid production, glomerular filtration rate, cardiac output, blood volume and other factors. At delivery, many metabolic and endocrine processes that our body has adapted to over the better part of a year abruptly cease.
Recovery from this is a distinct process and not a simple reversal of pregnancy dynamics, researchers concluded.
Professor Uri Alon, co-author of the study, told New Scientist that the usual postpartum recovery timeline of six to eight weeks was clearly not accurate.
They found that in 31 of the 76 tests, recovery to pre-pregnancy levels took between 10 and 50 weeks, indicating that postpartum recovery is on an entirely different trajectory from changes during pregnancy.
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They found two stereotypical profiles of postpartum recovery: a smooth rise and fall, where changes revert to baseline after delivery, and a “jump-like” profile, where recovery is a far more jagged line.
Some physiological changes hadn’t even returned to baseline at the end of the study period, a full 80 weeks after birth. Compared to preconception baseline, they found that inflammation marker CRP stayed elevated and mean corpuscular haemoglobin and iron stayed low, no doubt contributing to the lasting physiological effects of pregnancy.
The study also looked at the time it took for postpartum fluctuations to settle and remain within a small margin. Almost half of the tests settled within a month after delivery, and 12% took between a month and 10 weeks.
However, more than 40% had a settling time exceeding 10 weeks. These included liver function tests such as AST and ALT, which took about half a year to recover, while cholesterol and ALP took about a year.
Preconception biomarkers and pregnancy outcomes
Conditions such as preeclampsia and gestational diabetes are diagnosed during pregnancy, but findings from this study suggest that some markers of these conditions may also be present both before and after gestation.
In cases of preeclampsia, elevated platelets and ALT were seen prior to conception.
“For decades, the idea has been that the placenta doesn’t implant properly, and if it doesn’t implant properly, the blood supply is disrupted, it releases hormones and substances that lead to the mother getting high blood pressure,” Professor Alon said.
However, the finding of preconception biomarkers adds weight to the alternate theory that preeclampsia could be associated with a different cardiovascular function prior to pregnancy.
Associate Professor Michelle Oyen of Wayne State University in Detroit said in a recent article about this research that pregnancy health is an established marker for future health.
“A fundamental question arises about complications in pregnancy: Was the pregnancy the source of the problem, or did pregnancy just stress the body sufficiently to reveal an underlying pathology that would have otherwise eventually emerged?”
Professor Oyen wrote that women who experience cardiovascular complications in pregnancy carry increased cardiovascular risks for decades postpartum, and that pregnancy is an important window into women’s health.
The study also found elevated gestational uric acid, high systolic and diastolic blood pressure throughout the study period, and elevated postpartum triglycerides in women with preeclampsia.
For those with gestational diabetes, high glucose, HbA1c, triglycerides and elevated GGT liver damage test were present both before and after pregnancy.
Postpartum haemorrhage (PPH) was associated with mildly reduced platelets, suggesting altered blood clotting even prior to pregnancy, although other coagulation markers weren’t significantly altered. They also saw a distinctive pattern of decreased mean corpuscular haemoglobin concentration and elevation mean corpuscular volume before conception and during pregnancy. Previous studies have shown that these markers towards the end of pregnancy is associated with higher likelihood of PPH, but not that they may be present prior to conception.
“Without firm underlying mechanistic understanding, clinicians are missing tools for improving diagnosis, prevention, and treatment of pregnancy complications,” Professor Oyen said.
Professor Alon hopes that further research in this area could lead to targeted pre-pregnancy interventions to reduce risk of developing these complications.
