For decades, pregnant women in regions where schistosomiasis is common were routinely left out of treatment programmes. They were excluded not because the drug, praziquantel, was known to harm them, but because nobody had proven it did not. This article explains why the World Health Organization moved from exclusion to inclusion, first in a 2002 expert consultation and later in formal guidance that endorses treatment after the first trimester. It also sets out what the only placebo-controlled trial of praziquantel in pregnancy for Schistosoma japonicum, conducted in the Philippines, actually found about mothers and their babies. It is also plain about what that trial could not answer.

The disease, the drug, and why pregnancy matters

Schistosomiasis is caused by parasitic flatworms (blood flukes) whose larvae penetrate the skin during contact with infested fresh water. Adult worms live for years in the veins around the intestines or bladder. Most of the harm comes from their eggs, which lodge in tissues and provoke chronic inflammation. Over time this can cause anaemia, liver fibrosis, bladder disease and, in women, female genital schistosomiasis, a frequently missed condition affecting the cervix and vaginal wall. More than 200 million people are infected worldwide, most of them in sub-Saharan Africa. S. japonicum, the species found in parts of the Philippines, China and Indonesia, is generally regarded as one of the more aggressive forms.

Praziquantel was developed in the 1970s by German pharmaceutical researchers. Unlike many older antiparasitic medicines, it is a synthetic compound, not one derived from a plant or soil organism. It is effective against all major schistosome species, usually as a single day's treatment. It is inexpensive and has a long safety record across hundreds of millions of doses. It appears on the WHO Model List of Essential Medicines. In the United States it is approved for schistosomiasis and certain liver fluke infections. Older US labelling placed it in pregnancy category B, meaning animal studies had not shown fetal harm but adequate human studies were lacking.

Pregnancy matters here for two opposite reasons. The developing child deserves protection from any avoidable drug exposure, and caution is a proper instinct. Yet the mother's infection is not harmless either. Chronic schistosomiasis is associated with maternal anaemia and systemic inflammation. Observational studies have linked it with low birthweight and other adverse outcomes, though such studies cannot fully separate the infection from the poverty and malnutrition that accompany it. A woman of childbearing age in an endemic village may spend a large share of her reproductive years pregnant or breastfeeding. Excluding pregnant and lactating women can therefore mean leaving her untreated for years at a stretch.

Why WHO changed its position

In 2002 WHO convened an informal expert consultation on the use of praziquantel during pregnancy and lactation. The experts weighed the available evidence:

The consultation concluded that pregnant and lactating women should be offered praziquantel, either individually or during community treatment programmes, rather than being automatically excluded. Uptake was uneven. Many national programmes continued to exclude pregnant women, in part because no randomised trial had yet tested the question directly.

WHO's 2022 guideline on the control and elimination of human schistosomiasis made the position more specific. It recommends preventive treatment for affected populations from age two upward, including pregnant women after the first trimester and breastfeeding women. The first-trimester exclusion reflects ordinary prudence, not evidence of harm. The early weeks are when the baby's organs are forming, and human data from that window remain thin. Delaying treatment by a matter of weeks costs little when the infection is chronic. By the time of the 2022 guideline, randomised evidence from later pregnancy had become available, and that evidence came largely from the Philippines.

The Philippines trial: design

The trial was a collaboration between investigators at Brown University and the Research Institute for Tropical Medicine in Manila, led by Remigio Olveda and Jennifer Friedman. It was conducted in Leyte, an island where S. japonicum is endemic. The results were published in The Lancet Infectious Diseases in 2016 as a phase 2, randomised, double-blind, placebo-controlled trial. This is the strongest kind of design for separating a drug's effects from chance and from the many other influences on pregnancy outcomes.

Ethically, this was a carefully considered study. Offering a placebo to infected women was justified by genuine uncertainty about whether treating during pregnancy helped or harmed. The women in the placebo group were not denied treatment; it was deferred until after birth.

What the trial found for mothers and babies

On safety, the findings were reassuring. Rates of miscarriage, fetal death, preterm delivery and congenital anomalies did not differ meaningfully between the praziquantel and placebo groups. Neither did serious adverse events overall. The study was not large enough to detect rare harms. What it did show is that a pattern of common harm, had one existed, would very likely have appeared, and it did not.

Mothers who received praziquantel experienced more of the expected short-lived side effects than those given placebo. These typically include headache, dizziness, abdominal discomfort and nausea, and are familiar to anyone who has treated schistosomiasis outside pregnancy. They generally resolve within a day.

On benefit, the findings were neutral. Average birthweight was essentially the same in both groups. Treatment did not measurably improve the rate of low birthweight, and the trial did not demonstrate improvements in maternal anaemia or other secondary measures of maternal and newborn health. In short, praziquantel at this point in pregnancy did no detectable harm, but it also did not deliver the improvements in birth outcomes that observational studies had hoped for.

The investigators and later commentators have offered several possible explanations, none proven:

An earlier trial in Uganda, the Entebbe Mother and Baby Study, published in Clinical Infectious Diseases in 2010, reached broadly similar conclusions. In that much larger study, predominantly involving S. mansoni, treatment with praziquantel during pregnancy did not affect birthweight, maternal anaemia or perinatal mortality, and no safety concern emerged. The two trials involved different parasite species, populations and study designs. That they arrived at the same pattern of findings, safe but without detectable benefit to birth outcomes, makes each more credible.

What remains uncertain

Honest reporting requires noting the limits of what is known:

It is also worth stating clearly that the trials studied women with confirmed infection. They provide no rationale for taking praziquantel in pregnancy "just in case," and outside endemic settings the drug should be used only for diagnosed infection.

Weighing two lives with care

The question of treating schistosomiasis in pregnancy is, at its heart, a question of caring well for two people at once. A mother's health and her unborn child's health are not rivals. The intricate design of pregnancy, in which the placenta nourishes and protects a developing child, is a reminder that the two are bound together. Untreated chronic infection is not a neutral choice for either of them.

The evidence now available gives families and clinicians a reasonable basis for that decision. After the first trimester, praziquantel has been studied directly against placebo and has not been shown to harm the pregnancy or the newborn. It should not be presented as a means of improving birthweight, because the trials did not show that it does. The case for treatment rests mainly on the mother's own health and on preventing the slow damage of long-term infection. Not leaving her untreated for years is part of honouring the value of her life alongside her child's.

Every pregnancy is different. Infection intensity, symptoms, gestational age, breastfeeding plans and access to follow-up all matter. A woman who is pregnant or planning pregnancy and lives in, or has travelled from, an endemic area is best served by an open conversation with her own physician or midwife. She should understand both what the evidence shows and where it falls silent, and the decision about timing should be one she makes with them.

Key takeaway: WHO now supports praziquantel for schistosomiasis after the first trimester because randomised trials, including the Philippines placebo-controlled trial, found no safety concerns for mothers or babies, though they also showed no improvement in birthweight, and first-trimester use remains insufficiently studied.