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Developmental biology - Pre-mature Babies

A Test to Predict Preterm Birth

Identifying women at risk in second trimester could lead to early treatment, maybe prevention...

Scientists at the University of California at San Francisco (UCSF) have developed a test to predict a woman's risk of preterm birth when she is between 15 and 20 weeks pregnant. It may enable doctors to treat mothers early and prevent severe complications later in her pregnancy.
Preterm birth is the leading cause of death for children under five in the United States, but rates are increasing in the USA and around the world. Often associated with inflammation, it has many potential causes including a mother's acute infection, her exposure to environmental toxins, or chronic conditions like hypertension and diabetes.

The new test screens for 25 biomarkers of inflammation and activation of a mother's immune system, as well as for protein levels important for placental development. Combined with information on other risk factors, such as her age and income, the test can predict a woman's risk for preterm birth at more than 80 percent accuracy.
In the highest risk pregnancies — preterm births occurring before 32 weeks or in women with preeclampsia, a potentially fatal pregnancy complication marked by high blood pressure in the mother — the test predicted nearly 90 percent of cases.

In the study, published Thursday, May 24, 2018, in the Journal of Perinatology, the researchers built a comprehensive test to capture both spontaneous preterm births — which occur when the amniotic sac breaks or contractions begin — and "indicated" preterm birth, where a physician induces labor or performs a cesarean section because the health of the mother or baby is in jeopardy. Researchers also wanted to be able to identify risk for preeclampsia, which is not included in current tests for preterm birth.
"There are multifactorial causes of preterm birth, and that's why we felt like we needed to build a model that took into account multiple biological pathways. The model works especially well for early preterm births and preeclampsia, which suggests that we're effectively capturing severe types of preterm birth."

Laura Jelliffe-Pawlowski PhD, Associate Professor, Epidemiology and Biostatistics, Director of Precision Health and Discovery, Preterm Birth Initiative, UCSF, USA.

The researchers developed the screen using blood samples from 400 women as part of routine prenatal care during their second trimester, comparing women who went on to give birth before 32 weeks, between 32 and 36 weeks, and after 38 weeks (full-term). They first tested the blood for more than 60 different immune and growth factors, ultimately narrowing the test down to 25 factors that altogether could help predict risk for preterm birth. When other data, including whether or not the mother was over 34 years old, or if she qualified as low income (indicated by Medicaid eligibility), improved the accuracy of the test by an additional 6 percent.

• Based on a woman's probability of preterm birth derived from the test, she could now discuss with her clinician how best to follow-up and try to lower her risk. Some cases of preterm birth, including those caused by preeclampsia, can be prevented or delayed by taking aspirin, but treatment is the most helpful if started before 16 weeks.

• Physicians could also evaluate high-risk women for underlying infections that may have gone undetected but could be treated. For others, close monitoring by their doctor could help flag early signs of labor like cervical shortening that can be slowed with progesterone treatment.
"We hope that this test could lead to more education and counseling of women about their level of risk so that they know about preterm birth and know what preeclampsia or early signs of labor look like. If we can get women to the hospital as soon as possible, even if they've gone into labor, we can use medications to stave off contractions. This might give her some additional days before she delivers, which can be really important for the baby."

Laura Jelliffe-Pawlowski PhD.

A currently used test for preterm birth, though available, is expensive and only screens for spontaneous preterm birth, not for signs indicating preterm births or preeclampsia. Jelliffe-Pawlowski adds that the new screen would likely be a fraction of the cost, making it more accessible to women at most risk.
"One of the reasons we're most excited about this test is that we see some potential for it addressing preterm birth in those most at risk, including low-income women, women of color, and women living in low-income countries. We want to make sure that we're developing something that has the potential to help all women, including those most in need."

Laura Jelliffe-Pawlowski PhD.

To evaluate if mid-pregnancy immune and growth-related molecular factors predict preterm birth (PTB) with and without (±) preeclampsia.

Study design:
Included were 400 women with singleton deliveries in California in 2009–2010 (200 PTB and 200 term) divided into training and testing samples at a 2:1 ratio. Sixty-three markers were tested in 15–20 serum samples using multiplex technology. Linear discriminate analysis was used to create a discriminate function. Model performance was assessed using area under the receiver operating characteristic curve (AUC).

Twenty-five serum biomarkers along with maternal age <34 years and poverty status identified >80% of women with PTB ± preeclampsia with best performance in women with preterm preeclampsia (AUC = 0.889, 95% confidence interval (0.822–0.959) training; 0.883 (0.804–0.963) testing).

Together with maternal age and poverty status, mid-pregnancy immune and growth factors reliably identified most women who went on to have a PTB ± preeclampsia.

Authors: Laura L. Jelliffe-Pawlowski, Larry Rand, Bruce Bedell, Rebecca J. Baer, Scott P. Oltman, Mary E. Norton, Gary M. Shaw, David K. Stevenson, Jeffrey C. Murray and Kelli K. Ryckman

Data from the California Prenatal Screening Program was obtained through the California Biobank Program (Screening Information System request no. 476). Data were obtained with an agreement that the California Department of Public Health is not responsible for the results or conclusions drawn by the authors of this publication.

Supported by the Bill and Melinda Gates Foundation (OPP52256), NIH/NHLBI (RC2 HL101748, RO1 HD-57192, and R01 HD-52953), the March of Dimes Prematurity Center at Stanford University School of Medicine, the Stanford Child Health Research Institute at Stanford University School of Medicine, the Stanford Clinical and Translational Science Award CTSA to Spectrum (UL1 TR001085), the March of Dimes Prematurity Center—Ohio Collaborative, March of Dimes (6-FY11-261 and FY10-180), and the California Preterm Birth Initiative (PTBi-CA) at the University of California San Francisco Benioff Children’s Hospital.

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