It’s well known that pregnancy and delivery dramatically affect virtually all systems of the woman’s body. But until now, these changes have not been systematically analyzed in a large human population.

In a first-of-its-kind study, researchers in Prof. Uri Alon’s lab at Israel’s Weizmann Institute of Science have provided a comprehensive portrait of the huge physiological load of pregnancy and childbirth — and how long it takes the mother’s systems to return to pre-pregnancy conditions.

Using Clalit Health Services’ database of about 44 million measurements from 313,501 women – who accounted for approximately half of all pregnancies in Israel between 2003 and 2020 — Alon’s group assessed weekly fluctuations in 76 different lab test results from 20 weeks before conception to 80 weeks after delivery.

The extensive results, published in Science Advances, show that in about half of the lab tests, values returned to pre-pregnancy baseline only three months to a year after childbirth. 

This is a more gradual process than previously assumed.

Massive changes

The researchers, led by Dr. Alon Bar and Ron Moran in collaboration with Dr. Yoel Toledano from the Division of Maternal Fetal Medicine at Beilinson Medical Center’s Helen Schneider Women’s Hospital, outline the many maternal physiological changes that support fetal growth and development.

“During pregnancy, the [mother’s] cardiovascular, respiratory, renal, gastrointestinal, skeletal, metabolic, endocrine, and immune systems are all affected by fetal demand and massive endocrine secretion by the placenta,” they write.

In addition, elevated demand for oxygen and nutrients during pregnancy causes an increase in cardiac output and up to 50 percent growth in blood volume. The mother’s kidneys work harder and produce more urine; the immune system adapts to prevent rejection of the fetus; coagulation and red blood cells “show marked changes” and the placenta secretes hormones that alter metabolism.

Delivery of the fetus and placenta bring an abrupt end to these effects. 

“The mother undergoes a series of adaptations in which various physiological systems recover with different timescales—from hours to months,” they write.

“During gestation, all tests show sizable changes, and about half show large overshoots after delivery.”

The precision of the dataset allowed them to detect intricate dynamic changes, including the impact of nutritional supplements (such as folic acid) taken before conception, and deviations from healthy pregnancy including preeclampsia, gestational diabetes, and postpartum bleeding. 

The researchers could actually see signs of these future complications months before conception, as shown by abnormal blood test results. This finding could be key in developing a way to assess a woman’s risk for complications before she gets pregnant.

Why this study is important

The researchers explain that understanding healthy physiology and pathology is essential both for advancing basic science and as a baseline for treatment approaches before, during and after pregnancy.

This unique study identifies “global dynamical trends in healthy pregnancies and in pregnancy complications” and “greatly expands our knowledge of the postpartum period because most postpartum studies considered only one or a few time points,” write the authors. 

Supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program, the Weizmann study “thus provides a resource for understanding pregnancy and the postpartum period and demonstrates how it may be used to understand mechanisms in systems physiology.”