*3.3.4. Microbiological issues*

McMullen et al. [26] in 2006 characterized health outcomes in CF pregnant women, comparing them with a group of never-pregnant CF population: this large observational study showed a nonsignificant difference in terms of FEV1 decline between the two groups (6.8% in pregnant group and 4.7% in never-pregnant, *P*=0.61). Respiratory exacerbations and hospitalizations were increased during pregnancy, as well as the number of outpatient visits and administered

The risk for congenital anomalies in the fetus is not increased in CF gravidas and breastfeeding

The pregravid pulmonary function is clearly the greatest outcome predictor in CF women, but there are multiple clinical prognostic markers to consider. Women with poor nutritional status, pulmonary hypertension, and relevant decrease in pulmonary function during the first 3 months of gestation have to be informed about the high risk of maternal mortality and should

FEV1% predicted, PO2, and PCO2 are important predictors of pregnancy outcomes. In 1995, Edenborough et al. [28] reported that a pregravid FEV1 <60% caused greater pulmonary function decrease, a higher frequency of preterm infants, and also a higher mortality. However, successful pregnancies have been reported also in CF patients with compromised lung function (FEV1 < 50% of that predicted), and most patients seem to return to baseline pulmo‐

The only absolute contraindication to pregnancy in CF is represented by pulmonary hyper‐ tension, which is correlated with higher rates of mortality in pregnancy. An echocardiogram performed before pregnancy can be useful to individuate underlying pulmonary hypertension and cor pulmonale, in order to advise the patient about the high mortality risk in case of

In old literature, pancreatic insufficiency was considered as a major risk factor in pregnancy outcomes. Actually, with the modern pancreatic enzymes supplementations, it is a nonsigni‐

CF women planning pregnancy have to be tested for glucose intolerance before conception and the test has to be repeated at 20 weeks of gestational age. Insulin therapy is indicated in

Clinician should advise to reach a pregravid weight before conception up to 90% of the ideal body weight. Poor nutritional status is without any doubt one of the most relevant risk factor

therapies.

**3.3. Risk factors**

*3.3.1. Lung function*

pregnancy [24].

is possible without complications.

120 Cystic Fibrosis in the Light of New Research

consider therapeutic abortion [27].

nary status after pregnancy.

ficant issue in CF pregnancies.

*3.3.3. Nutritional status*

*3.3.2. Pancreatic insufficiency and diabetes mellitus*

case of abnormalities in blood glucose monitoring.

*Burkholderia cepacia* complex has been considered for several years a relative contraindication for pregnancy in CF, because this infection seemed to be related with a higher maternal mortality [30]. *B. cepacia* (particularly *B. cenocepacia* and *B. multivorans*) is also considered related to preterm delivery, weight loss, and rapid pulmonary function decline [31], but further studies are needed to better define its role in CF pregnancies.

### *3.3.5. Pulmonary transplantation*

Limited cases of pregnancy after lung transplantation have been reported; most experience comes from renal transplantation. Compared to other solid organ transplants, lung recipients experience more frequent rejections during pregnancy and also a higher rate of graft loss postpartum [32]. Graft dysfunction is unpredictable and may occur anytime during pregnancy, leading to progressive decline and also eventual death after delivery. However, further studies are necessary to determine long-term maternal survival.

Prematurity and neonatal complications in these pregnancies are very high (56% and 33%, respectively), but no long-term consequences on children are reported [33].

### **3.4. Management of pregnancy in CF women**

The management of pregnancy in CF requests necessarily a multidisciplinary approach. Most of the literature on pregnancy in CF is constituted by case reports and a few national centre based reviews. Unfortunately, at the moment, we have no available trials about any aspect of pregnancy management in CF. In 2008, Edenborough et al. [34] published the guidelines for the management of pregnancy in women with CF, based on the review of the literature and experience of pediatricians, adult and transplant physicians, nurses, physiotherapists, dietitians, pharmacists and psychologists experienced in CF, and also anesthetists and obstetricians with experience of CF pregnancy.

### *3.4.1. Counselling*

Counselling consists in helping the CF patient planning pregnancy and her partner to explain the risks of their decision, such as medical implications, treatment options, and also the impact of a toddler on the everyday life of a CF woman.

Genetic features, such as the risk of recurrence of the disease, have also to be discussed with the couple. CF genotype, if not already known, have to be defined and the partner should also be tested before conception. Genetic counsellors should be involved in order to discuss these delicate issues with the couple.

Genetic tests have a sensitivity <100% with detection rates from 70% to 95% of CFTR mutations. If the partner has not been tested, given a CF carrier frequency of 1:25, the risk of an affected infant is 1:50; while if the partner is a CF carrier, the risk is 1:2.

When the partner is a known carrier or if he has not been tested, clinicians should suggest to perform prenatal genetic diagnosis to the couple, with the analysis of chorionic villus sample (CVS) within the first trimester of gestation. This procedure includes technical risks that should be discussed with the couple.

Psychological counselling is also an important part of the counselling activities: CF team should provide information about sexual health and reproduction to all of their patients, particularly teenage girls. Psychologists and clinicians play an important role also in psycho‐ logical counselling for CF women who want to become pregnant, even if women with advanced disease with a very strong wish to have a child may proceed whatever the advices.

### *3.4.2. Medications during pregnancy*

Most drugs have not been tested on pregnant women. Relevant issues about their use in pregnancy are timing of exposure (periconception, first, second, third trimester, or perinatally), systemic availability of the drug, and its ability to cross the placenta. Side effects can consist in teratogenesis, growth retardation, death, renal insufficiency, neurological disorders, stillbirth, etc.

Many pregnancies are unplanned and drugs could have been taken at the time of conception and continued in the first weeks of pregnancy, and many women with serious illnesses required treatment to be continued. Even if nowadays there is experience to guide prescribing in pregnancy, the principle remains to avoid drug use where possible, except when the risk of the drug is outweighed by the risk of the condition being treated.

The Swedish FASS information catalog provides information on the risks of drugs to the fetus during pregnancy and to the infant during lactation. Each drug is classified to one category of safety:


Patient's therapy should be reviewed during the discussion of a potential pregnancy, even if most of the routine CF medications are safe and could be continued. Contraindicated drugs have to be discontinued. β-lactams are safe in pregnancy and aminoglycosides at conventional doses have not showed toxic results. Once-daily tobramicin has been tested in second and third trimesters, showing safe results. Ciprofloxacin has been widely used during pregnancy with no certain side effects, but its use is indicated only if vital for the mother.
