Inflammation Before Birth: What Doctors Can and Cannot Tell From the Placenta

Four recent studies from Italy, Romania, Greece and China, and what they say about the diagnosis families hear in the delivery room

Chorioamnionitis is inflammation of the membranes and placenta that surround a baby before birth. It is one of the commonest reasons babies are born early, and four studies published between 2025 and 2026 found that the diagnosis doctors make during labour often does not match what the placenta actually shows — sometimes over-calling the problem at full term, and badly under-calling it in the most premature babies.

If you have been told during labour that you have chorioamnionitis, the word usually arrives quickly and without much explanation. You may have had a fever, the baby's heart rate may have been fast, and antibiotics will have been started. What the word means is that the tissues around your baby — the membranes, and often the placenta itself — appear to be inflamed. Sometimes that inflammation is caused by bacteria that have travelled upwards from the birth canal. Sometimes there is no infection at all, and the inflammation has another cause. Either way, the concern is the same: inflammation can bring on labour early, and doctors have long suspected it can also affect the baby's developing organs directly.

Why this question has been hard to answer for so long

For much of the twentieth century, chorioamnionitis was thought of as a maternal problem — an infection in the mother that happened to end the pregnancy sooner than expected. That changed in the late 1990s, when researchers described what they called the fetal inflammatory response syndrome: evidence that the baby, too, mounts a whole-body inflammatory reaction before birth, measurable in the baby's blood and involving several organs at once [1]. Shortly afterwards, a large review pooling many earlier studies reported that premature babies exposed to chorioamnionitis were roughly twice as likely to develop cerebral palsy, a disorder of movement and posture, and three times as likely to show a particular pattern of injury to the brain's white matter [2].

Those findings changed how doctors thought, but they did not settle how doctors should act, because two different things were being called by the same name. One is the diagnosis made during labour, based on the mother's temperature and a small number of other signs. The other is what a pathologist sees weeks later when the placenta is examined under a microscope. An expert workshop in the United States tried to reduce the confusion by recommending that the vague word be replaced with a clearer description — inflammation, infection, or both [3] — and professional guidance set out exactly which signs during labour should trigger the diagnosis and treatment [4]. Pathologists, separately, agreed on how to sample the placenta and how to describe what they find [5], including a system that separates how far the inflammation has spread from how intense it is [6]. What nobody had tested carefully was how well the labour-room diagnosis and the microscope actually agree.

What the four new studies did

A team in Verona, Italy, reviewed the records of 12,332 women who gave birth at full term over five years and found 171 — about 1 in 70 — diagnosed with chorioamnionitis during labour. Every one of those placentas was sent for examination [7]. A team in Cluj-Napoca, Romania, looked at 80 babies born extremely early, between 23 and 28 weeks of pregnancy [8]. A team in Thessaloniki, Greece, followed 91 babies born before 32 weeks, scanning their brains and checking their development at two years of age [9]. And a team working across six hospitals in Shenzhen, China, studied 650 very premature or very small babies to see whether inflammation before birth was linked to a serious bowel illness called necrotising enterocolitis [10].

All four looked back at records that already existed rather than testing a treatment, which is an important limitation: studies of this kind can show that two things occur together, but cannot prove that one caused the other. This is a particularly awkward problem here, because inflammation before birth is itself one of the main causes of premature delivery — and being born early is, by itself, the single biggest risk to a baby's brain, lungs and bowel. Untangling what the inflammation does from what the prematurity does is the central difficulty in this whole field, and none of these four studies could fully solve it. Three of the four were also carried out in a single hospital, and two followed fewer than 100 babies, so their findings need confirming in larger groups before anyone treats them as settled.

The diagnosis is often wrong — in both directions

In the Italian study, only just over half of the women diagnosed during labour — 96 of 171, or 56% — turned out to have severe inflammation when the placenta was examined [7]. In other words, roughly two in five full-term babies were treated as though they had been exposed to significant inflammation when the placenta suggested otherwise. Two clues helped tell the difference: thick, heavily meconium-stained amniotic fluid (meconium is a baby's first stool, which is sometimes passed before birth), and older maternal age. Babies whose mothers did have confirmed severe inflammation were more likely to need intensive care (39% compared with 21%) and stayed there longer — a median of six days rather than two.

The Romanian study found the opposite error among the most premature babies. Only 15% had been diagnosed during labour, but 81% showed inflammation under the microscope [8]. Almost every labour-room diagnosis was correct; the problem was that the great majority of cases were never diagnosed at all. For families of very premature babies, this is worth knowing: not being told about chorioamnionitis does not mean it was absent.

What it seems to do to the baby

The three studies of premature babies looked at different organs and, honestly, did not entirely agree. In Romania, most differences between exposed and unexposed babies faded once the researchers accounted for the fact that exposed babies were born earlier and smaller — with one exception, severe breathing difficulty in the first days of life, which remained strongly linked [8]. The number of babies was small, so this finding, while striking, is imprecise.

In Greece, four links survived the same kind of statistical adjustment: bleeding into the brain's fluid spaces, chronic lung disease of prematurity, eye disease of prematurity, and an abnormal result on a two-year screening questionnaire for autism [9]. These are the kinds of associations that earlier large reviews have also reported for bleeding in the brain [11] and for chronic lung disease [12]. Two cautions matter for families. Most of the brain bleeds in this study were the mildest kind, which usually resolve without lasting effects. And a screening questionnaire is not a diagnosis — it flags children who should be looked at more carefully, and most children flagged this way do not turn out to have autism.

In China, exposure to inflammation was not linked to necrotising enterocolitis on its own — a reassuring result, and one that differs from some older pooled analyses [13]. It was linked to a combined measure of "serious bowel illness or death," particularly when both the labour-room diagnosis and the placenta agreed, though only seven babies fell into that group [10].

It is also worth knowing that the most carefully designed brain-imaging study in this field, published several years earlier, found no clear link between placental inflammation and brain injury once other risks were taken into account [14]. The honest summary is that the evidence points in a worrying direction without being conclusive.

What this means for families

If you are told you have chorioamnionitis during labour, antibiotics are the right response, and the caution is appropriate even though the diagnosis is imperfect. What these studies suggest is that the placenta should be examined afterwards in every case, and that the result is worth asking about — it is more reliable than the label given during labour. If your baby was very premature and no one mentioned chorioamnionitis, it is still reasonable to ask whether the placenta was examined and what it showed.

For babies who were exposed, the practical message is about follow-up rather than alarm. Keep developmental appointments, and mention the exposure to the clinicians who see your child; it is a reason for closer watching, not a prediction of how your child will do. Nothing in these studies says that an exposed baby will have problems — most will not.

What researchers are working on next

The clearest problem these four studies expose is that the four teams were not measuring quite the same thing. The fever threshold for making the diagnosis ranged from 37.5 °C to 39 °C between studies, and what counted as a "positive" placenta ranged from any inflammation at all to only the most severe. Until everyone measures it the same way, studies will keep producing different answers. The next generation of research is likely to record how far and how intensely the placenta was inflamed, rather than simply yes or no, and to follow exposed children with full developmental assessments rather than brief screening questionnaires. In[Neo]Sight also covers related questions, including preventing serious bowel illness in premature babies and protecting the premature brain before birth.

References

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  2. Wu YW, Colford JM Jr. Chorioamnionitis as a risk factor for cerebral palsy: a meta-analysis. JAMA. 2000;284(11):1417–1424. doi:10.1001/jama.284.11.1417 ↩
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