Nearly two-thirds of RhD-negative pregnant women who received routine anti-D at 28 weeks lost detectable antibody protection by birth, raising concerns about a possible gap in preventing hemolytic disease of the fetus and newborn (HDFN), according to a study published recently in The Journal of Maternal-Fetal and Neonatal Medicine.
This finding relates to HDFN because anti-D immunoglobulin is the cornerstone medication that protects a fetus from red blood cell destruction when the mother is RhD-negative and the fetus is RhD-positive. For patients, the results highlight that current dosing works well overall but may not last all the way to delivery in many pregnancies.
This study reviewed 915 singleton pregnancies cared for at Kayseri City Hospital between January 2023 and January 2025. All mothers were RhD-negative and had a negative antibody screen at 24 weeks, then received the standard 300 µg dose of Rhesus immune globulin at about 28 weeks.
“Beyond 10 weeks after a single 28-week dose, two-thirds of RhD-negative women had anti-D undetectable at term by automated microcolumn (gel) IAT [indirect antiglobulin test],” stated this study’s authors. They continued, “This is a detection signal, not evidence of protection or harm.”
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The women delivered at around 38 weeks, which was about 69 days after receiving the injection. When researchers checked antibody levels within 72 hours before birth, only 286 women (33 percent) still had detectable anti-D, while 629 (67 percent) did not.
The biggest factor that explained whether anti-D remained detectable was timing. Women who still had detectable anti-D had received their dose about one week later, at approximately 29 weeks, and gave birth sooner after the injection, at around 63 days instead of 72 days. Maternal age, body mass index, and newborn RhD status did not change the likelihood of antibody persistence, meaning most of the difference came down to how long the dose had been in the body.
For families, the absence of detectable anti-D does not necessarily mean the medication stopped working. The study measured whether the antibody could still be found in blood tests, not whether it continued to provide immune protection. Even so, the findings point to a stretch late in pregnancy when the anti-D level may drop below what routine tests can see. Since HDFN risk rises if a mother becomes newly sensitized, experts say strengthening late pregnancy coverage could matter.
Researchers noted that other countries already use a second dose at 34 to 36 weeks, and some adjust dosing based on body size or fetal RhD status determined by genetic testing. Patients may eventually see updated guidelines that test antibody levels later in pregnancy or add a booster dose to ensure continuous protection through birth.
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