Pregnancy

Cuddly cats, toxoplasma and pregnancy

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DCF 1.0
DCF 1.0

A recent case of severe toxoplasma infection in pregnancy at one of my institutions reinforces the need for preconception and early pregnancy hygiene advice.

What is toxoplasma infection?

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. The parasite may be found in raw and cured meat, raw eggs, unpasteurised milk and cat faeces. It can also be found in soil contaminated with cat faeces. This means cat owners need to be careful when they handle kitty litter and should wear gloves when they garden in areas where the soil may be contaminated.

Clinical consequences of toxoplasma infection

Outside of pregnancy, toxoplasmosis results in a mild flu-like illness or a subclinical infection with no symptoms.

However, toxoplasma infection acquired in the period from three months prior to conception and during pregnancy, is more significant.  The parasite can cross the placenta and infect the developing baby who has an immature immune system. The consequences can be serious and include miscarriage, brain damage, blindness and death.

Why the timing of the infection is important

The timing of the infection in pregnancy influences the risk of the baby acquiring the infection. It also impacts on the severity of the sequelae of the infection in the baby.

In early pregnancy, less than 5% of babies are infected. This is because the placenta is too immature for transplacental infection.

However, in late pregnancy, 65% of babies can acquire the infection, as the placenta is mature and rates of transplacental infection are higher.

Even though infection caught late in pregnancy is more likely to result in fetal infection, the consequences of the infection are usually less severe.

In contrast,  infection caught by the mother early in her pregnancy results in a lower fetal infection rate but has far more significant consequences for her baby.

Most of the advice on toxoplasma in pregnancy comes from a few landmark research papers. It is worth looking at the findings from these papers to help guide pregnancy advice and management.

 

 

Landmark research papers

1. Pregnancy outcomes

The first landmark paper on toxoplasma in pregnancy was published in the New England Journal of Medicine in 1974 (1).

The researchers reported on the pregnancy outcomes of two groups of women. One group had evidence of toxoplasmosis prior to pregnancy and the other group acquired toxoplasmosis during pregnancy.

The key findings were:

  • Mothers who acquired toxoplasmosis prior to pregnancy did not infect their baby. No babies in this group had toxoplasmosis.

However;

  • In the 77 women who acquired toxoplasma infection during pregnancy:
    • 11 women miscarried;
    • 7 women suffered fetal death in utero and delivered a stillborn baby;
    • 2 newborns died soon after delivery;
    • 7 babies had severe effects of congenital toxoplasmosis and had cerebral and ocular complications;
    • 11 babies had  only mild illness requiring treatment:
    • 39 babies had subclinical illness with no long term problems.
  • Severe outcomes were only detected when the maternal toxoplasma infection occured during the first two trimesters (up to 27 weeks pregnancy).
  • Acquiring the toxoplasma infection in the third trimester resulted in subclinical infection or in no fetal infection.

2. Risk factors

The largest published research paper on risk factors comes from France (2), which has one of the highest rates of toxoplasma infection in pregnancy in the world. The authors reported that there were approximately 4900 cases of primary Toxoplasma infection in pregnant women in France each year.

Since 1992, France has had a policy that all pregnant women at risk of Toxoplasma infection undergo monthly serological testing. This research paper reported on 80 pregnant women who seroconverted to Toxoplasma in pregnancy and compared their risk factors against 80 pregnant women who had repeatedly negative tests.

After performing a multivariate statistical analysis to ensure differences between the two groups of women were accounted for, they found the risk factors for Toxoplasma infection were:

  • Poor hand hygiene increased risk by almost 10 fold (OR=9.9; 95%CI: 0.8-125);
  • Consumption of undercooked beef increased risk by almost 6 fold (OR=5.5; 95%CI: 1.1-27);
  • Having a pet cat increased risk by almost 5 fold (OR=4.5; 95%CI: 1.0-19.9);
  • Frequent consumption of raw vegetables outside the home increased risk by 3 fold (OR=3.1; 95%CI: 1.2-7.7);
  • Consumption of undercooked lamb increased risk by 3 fold (OR=3.1; 95%CI: 0.85-14).

The researchers noted that when women were provided with documentary advice on how to prevent toxoplasma infection, they had a lower risk of infection. They concluded that all  pregnant women should be given information on their eating habits, hand hygiene and cats in order to reduce the risk of acquiring toxoplasma infection in pregnancy.

3. Treatment of toxoplasma infection in pregnancy

The third landmark paper addressed the treatment of toxoplasma infection in pregnancy (3).

This treatment study was conducted across 5 major centres that specialised in the management of toxoplasma infection in pregnancy. The aim of the study was to determine if prenatal antibiotic therapy could reduce the rate of mother to baby transmission of Toxoplasma gondii and reduce the risk of severe consequences in infected babies as measured when they were one year old.

The study followed 144 women and considered key factors such as the gestational age at which the infection was acquired, the administration of antibiotic therapy, duration of antibiotic therapy, and time lapse between infection and the start of antibiotic therapy.

The authors reported that 64 of the 144 infected women (44%) gave birth to a congenitally infected infant.

After performing a multivariate analysis they concluded that the rate of transmission from the mother to the baby was not affected by the administration of antibiotics. The only factor that affected the rate of transmission was the gestational age at which the mother developed the infection in pregnancy (P < .0001).

However, antibiotic administration significantly reduced the risk of serious sequelae in the babies (P = 0.026, odds ratio 0.30, 95% confidence interval 0.104-0.863).

Of particular note, severe sequelae were significantly reduced when the mother was administered antibiotics (P = .007, odds ratio 0.14, 95% confidence interval 0.036-0.584). The sooner antibiotics were given after the infection, the less frequently sequelae were seen (P = 0.021).

The results were consistent with the earlier New England Journal of Medicine paper which also reported that treatment of infected mothers with the antibiotic Spiramycin reduced the impact of fetal infection (1).

What is the current pregnancy advice for preventing toxoplasmosis in pregnancy?

In Australia, the risk of toxoplasma infection is low. Therefore routine screening for the infection is not performed.

The main method to prevent infection is through education on strategies to reduce the risk of becoming infected.

The Australian Government’s Pregnancy, Birth and Baby website outlines strategies to reduce the risk of infection (4). These are:

  • Wear gloves when gardening, particularly when handling soil;
  • Wash your hands thoroughly after handling soil, using soap and hot water;
  • Do not eat raw or undercooked meat;
  • Cook all red meat until no trace of pinkness remains and the juices run clear;
  • Do not eat cured meats (e.g. Parma ham, salami);
  • Do not taste meat before it is fully cooked;
  • Wash your hands thoroughly after handling raw meat;
  • Wash all kitchenware thoroughly after preparing raw meat;
  • Always wash fruit and vegetables before cooking and eating;
  • Avoid drinking unpasteurised goat’s milk or eating products that are made from it;
  • Do not handle or adopt stray cats;
  • Keep animals, especially cats, away from areas that you prepare/store food;
  • Wash your hands and other exposed body parts with soap and running water after touching animals, their enclosures or food containers;
  • Avoid cat faeces in cat litter or soil – wear gloves if you are changing a cat’s litter tray and wash your hands thoroughly afterwards. If you are pregnant or immune deficient, ask someone else to change it for you and empty the litter tray daily;
  • Feed your cat dried or canned cat food rather than raw meat;
  • Cover children’s outdoor sand boxes to prevent cats using them as litter boxes;
  • Avoid contact with sheep and newborn lambs during the lambing season.

Management if infection is suspected

If a pregnant woman is concerned that she may have acquired toxoplasmosis in pregnancy, she should immediately see her doctor or midwife to discuss her concerns and be referred for an antibody test.

If the test demonstrates the presence of IgG antibodies, she can usually be reassured that she has already had the infection and is immune.

If the test demonstrates IgM antibodies, or no antibodies but the clinical suspicion of infection is high, the pregnancy should be managed by an obstetrician with expertise in this area.

Many cases are not detected until an ultrasound examination is performed and is noted to be abnormal.

Once maternal infection is diagnosed, or an ultrasound examination is suspicious of features of toxoplasma infection in the fetus, a tertiary level ultrasound, blood tests and amniocentesis to diagnose fetal infection are indicated. Antibiotic therapy needs to be commenced as soon as possible to reduce the impact of the fetal infection.

All cases should be managed in a tertiary obstetric hospital and advice and management will be individualised to each woman.

Babies should be enrolled in a follow up service to ensure any sequelae are diagnosed and managed as soon as possible.

Summary

Toxoplasma infection in pregnancy resulting in severe consequences for the baby is rare. However it can be prevented with good hygiene practices and managed with expert interventions by specialist teams.

The most important message is to be aware of good hand hygiene practices.

References

  1. Dismounts G, Couvreur J. Congenital Toxoplasmosis — A Prospective Study of 378 Pregnancies.N Engl J Med 1974; 290:1110-1116May 16, 1974. DOI: 10.1056/NEJM197405162902003
  2. Baril L, Ancelle T, Goulet V, Thulliez P, Tirard-Fleury V, Carme B. Risk Factors for Toxoplasma Infection in Pregnancy: A Case-Control Study in France. 
    Scandinavian Journal of Infectious Diseases 1999; 31(3): 305-309. 
    doi.org/10.1080/00365549950163626

  3. Foulon W, Villein I, Stray-Pedersen B, et al. Treatment of toxoplasmosis during pregnancy: A multicenter study of impact on fetal transmission and children’s sequelae at age 1 year. Am J Obstet Gynecol 1999; 180(2): 410-415.

    4. Department of health. Toxoplasmosis. Pregnancy, Birth and Baby. Australian Government 2016. Accessed on 31 December 2016 at http://www.pregnancybirthbaby.org.au/toxoplasmosis

When having a baby can kill you

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Pregnancy is usually a happy time with the outcome being a healthy baby. However, some complications in pregnancy can be serious. Over the years I have cared for many couples with molar pregnancy (technically known as gestational trophoblast disease). This terrible complication of pregnancy not only results in grief from the “lost baby”, but can also have lasting physical, social and psychological consequences for both the mother and father (1,2,3,4). Untreated, molar pregnancy can cause death of the mother (1,2).

Of note, our research into molar pregnancy revealed that many fathers experienced lasting social and psychological symptoms following molar pregnancy (4). One reason for this is due to the origins of the disease.

Origins of molar pregnancy

There are two types of molar pregnancy, a complete mole and a partial mole. In both cases, the male sperm plays a key role.

In a complete molar pregnancy, sperm (one or two) fertilize an egg that has lost its female genetic material (DNA). Therefore all the genetic material in the fertilized egg arises from the male and none from the female.

In a partial molar pregnancy, a single egg is fertilized by two sperm causing an excess of male genetic material within the fertilised egg.

The incidence of molar pregnancy varies around the globe, from 1 in 200 to 1 in 2000 pregnancies (1,2).

Impact on pregnancy

Sadly, molar pregnancy never results in a normal baby except for the extraordinarily rare cases of twinning where one twin is a molar pregnancy and the other a normal pregnancy. Instead, the usual situation is that the uterus becomes full of abnormal placental tissue and no baby is present (complete mole) or some fetal development occurs, but the fetus  is  malformed and not viable (partial mole).

The abnormal placental tissue causes bleeding and can metastasis around to body to other organs such as the lungs, in the same way an untreated cancer may spread around the body.

Impact on women

Most molar pregnancies present with abnormal vaginal bleeding between 8 and 16 weeks of pregnancy. Initially most women are concerned about miscarriage.

The diagnosis may be strongly suspected following an ultrasound, where a characteristic pattern called a “snowstorm” may be seen within the uterus. However, the condition is not definitively diagnosed until a sample of the tissue within the uterus is sent for analysis (histopathology) and tissue that looks like a cluster of grapes (abnormal chorionic villi) are seen under the microscope.

Some women may present with signs of thyroid disease, as the abnormal placental tissue can produce thyroid-like hormones. Women may also present with excessive nausea and vomiting of pregnancy (hyperemesis) and rarely may present with abnormally high blood pressure readings under 20 weeks of pregnancy.

Management of molar pregnancy

Once a molar pregnancy is confirmed, management involves surgery, follow up surveillance and possibly chemotherapy.

The initial management is uterine suction curettage. This surgical procedure is necessary to confirm the diagnosis and exclude an even rarer form of gestational trophoblastic disease called choriocarcinoma. The surgery carries more risk than a usual suction curettage, as the abnormal placental tissue is very vascular, and therefore the risk of heavy bleeding is higher. This means that the attending gynaecologist will often cross match blood and organise an anaesthetic consultation to plan the safest time to perform surgery. Medication may be required following surgery to help contract the uterus and reduce post operative bleeding.

Following surgery, women receive a “risk rating” that is determined on a number of factors such as their levels of pregnancy hormone, blood group, the presence of metastatic disease and the histopathology of the molar pregnancy.

Based on the “risk rating” results, women enter a follow up surveillance program that involves monitoring with serial blood or urine pregnancy hormone levels.

If a women had a high initial risk score, or her pregnancy hormone levels rose or failed to fall during her surveillance period, then she will require chemotherapy. This is usually Methotrexate, but in some case will be combined chemotherapy.

The impact of molar pregnancy on women is often profound. This is particularly true as the risk of molar pregnancy increases as women become older. Some women may have been trying to conceive for many years and then discover their pregnancy is a molar pregnancy. Not only do they not have the baby they desire, they face surgery, prolonged surveillance during which pregnancy is contraindicated, and possible chemotherapy. They must defer trying to have a child until they have been cleared (3,4).

Impact on partners

Partners of affected women can also suffer due to delayed childbearing, prolonged stress and a feeling of guilt related to the male role in the origins of molar pregnancy (4,5,6).

In our research, we contacted 158 former patients in our service with molar pregnancy and through these women, interviewed  41 partners. We found many partners were as emotionally fragile as the woman. For full results click here.

In a thematic analysis we found several themes related to anxiety and fear, sadness and depression, and guilt.

Anxiety

Anxiety was the dominant theme, rather than depression. Anxiety arose in male partners from a sense of frustration consequent to experiencing loss of control over their fertility, particularly their anxiety that they, as a couple, may never have a child.

‘Wouldn’t have occurred to us before when we were just worried about possible health of a baby’

‘Words cannot describe how emotionally stressful it was… I witnessed my partner being torn apart emotionally.’

‘Almost given up hope/plans of having a child at our age (maybe still some fear that another pregnancycould go awry).’

‘My world came crashing down.’

Guilt and blame

Partners felt guilty or blamed themselves for the occurrence of the molar pregnancy. Factors such as the male contribution in conception and individual genetic structures impacted on male participant’s view of cause and effect.

‘I somehow feel responsible in a way that it may have been my fault that it had something to do with my (works) my body that wasn’t right that caused this unusual pregnancy.’

Medical care

Themes relating to medical care centred around the actual treatment of molar pregnancy and the constant reminder of the diagnosis during the prolonged follow up perios that meant couples relived the experience. This delayed emotional recovery. The lack of clear information added to confusion and uncertainty.

‘…we are constantly reminded of our ‘failure’ through monthly urine samples, etc.’

‘I didn’t know as a individual at the time what was going on with my partner because we didn’t have enough information.’

Male partners’ displacement of feelings

Male partners felt a sense of indirect involvement in the management of the molar pregnancy. A new unfamiliar distancing occurred in a small percentage of couple relationships because of withdrawal from communication with partners during this time. This left partners feeling hopeless, unable to initiate appropriate actions to help their partner cope with trauma resulting from the diagnosis.

Partners felt they had to manage other financial and social matters additionally during this period of time. The male partner viewed himself largely as a supporter and made a distinction from being the patient.

‘I still cannot imagine what it would be like for my partner as she was the one carrying the pregnancy.’

‘It is hard for the husband to feel the same sense of loss as the wife because he has not had any physical contact with the “baby”.’

‘I felt very detached from it because it wasn’t my body going through the miscarry.’

Sexual function

Some men reported disparity in sexual functioning with their partner and described sexual tensions in their relationship.

‘My partner seems a little numb now, compared with before, and that makes it harder to feel good about sex and being close. I’m still keen but she seems less so…’

‘With all this happening inside her, she now seems less interested in sex, maybe that’s normal, but when I try she looks almost scared.’

‘…reduced desire by wife/apprehension re. sexual, even sensual contact…’

Positive role of children

The protective effect of children came through in our research. Subsequent delivery of a healthy child overcame the sense of loss.  This was reported both as an actual experience and as a hypothetically positive experience.

‘The scars only really started healing once we were given the gift of a beautiful baby boy nearly 2 years later.’

Summary

Most of the time pregnancy is a happy event, but occasionally things go wrong. It is important to remember that both mother and father may be deeply impacted and to provide support and follow up when things don’t go to plan.

Ultimately, providing support to ensure the couple are able to help each other through a sad and frightening experience is as important as getting the actual medicine right.

 References

  1. Berkowitz RS, Goldstein DP. Gestational trophoblastic diseases. In Principles and Practice of Gynecologic Oncology, Hoskins WJ, Perez CA, Young RC (eds.), Lippincott Williams & Wilkins: Philadelphia, PA, 2000; pp 1117–1137.
  2. Feltman CM, Growden WB, Wolfberg AJ et al. Clinical characteristics of persistent gestational trophoblastic disease after partial hydatidiform molar pregnancy. J Reprod Med 2006;51:902–906.
  3. Berkowitz RS, Marean AR, Hamilton N et al. Psychological and social impact of gestational trophoblastic neoplasia. J Reprod Med 1980;25:14–16.
  4. Quinlivan JA, Ung KA, Petersen RW. The impact of molar pregnancy on the male partner.Psychooncology. 2012 Sep;21(9):970-6. doi: 10.1002/pon.1992. Epub 2011 May 24.
  5. Wenzel L, Berkowitz RS, Robinson S, Bernstein M, Goldstein D. The psychological, social, and sexual consequences of gestational trophoblastic disease. Gynecol Oncol 1992;46:74–81.
  6. Wenzel L, Berkowitz RS, Robinson S, Goldstein DP, Bernstein MR. Psychological, social and sexual effects of gestational trophoblastic disease on patients and their partners. J Reprod Med 1994;39(3):163–167.