Arch Gynecol Obstet (2012) 286:283–286

DOI 10.1007/s00404-012-2287-5

MATERNAL-FETAL MEDICINE

Cancer during pregnancy: perinatal outcome after in utero exposure to chemotherapy

El-Said Abdel-Hady · Reda Abdel-Hady Hemida · Anas Gamal · Maha El-Zafarany · Eman Toson · Mohammed Attia El-Bayoumi

Received: 25 January 2012 / Accepted: 1 March 2012 / Published online: 13 March 2012© Springer-Verlag 2012

AbstractObjectives To study the outcome of pregnancies compli-cated by malignant disease, in particular neonatal morbidityand mortality after in utero exposure to chemotherapy.Methods This prospective study included 118 patientsdiagnosed with malignant disease for the Wrst time duringpregnancy over an 8-year period (March 2003–March2011). Outcome of neonates born to mothers who receivedchemotherapy during pregnancy was studied and comparedwith a control group.Results The commonest cancer type diagnosed during preg-nancy (56/118 = 47.45 %) was breast carcinoma followed bylymphoma/leukemia (32 = 27.12 %). Gynecological tumors(all ovarian) represented 10.16 %, soft tissue tumors 5.08 %,colorectal 4.23 %, thyroid 2.54 % and others 3.38 %.

Sixty-one (51.64 %) women received chemotherapy(average 3 § 2 cycles) during the second and third trimes-ters. The incidence of neonatal survival, preterm birth,small for gestational age and congenital malformations wasnot signiWcantly diVerent between women who receivedchemotherapy during pregnancy and the control group.

Five (4.23 %) women with advanced disease died during orshortly after termination of pregnancy.Conclusion In utero exposure to chemotherapy during thesecond and third trimesters of pregnancy carries minimalmorbidity to the unborn fetus.

Keywords Obstetric outcome · Malignant disease during pregnancy · Chemotherapy during pregnancy · Maternal outcome · Perinatal outcome

Introduction

Cancer during pregnancy complicates approximately 1 in1,000 pregnancies [1]. The incidence is increasing as morewomen chose to delay pregnancy. The most frequent malig-nancies encountered during pregnancy are cervical andbreast carcinoma, melanoma and Hodgkin lymphoma [2].There is no evidence that pregnancy increases the incidenceof cancer and no evidence of an adverse eVect of pregnancyupon the prognosis or biology of cancer [3].

The lines of treatment of cancer during pregnancy areessentially the same as in the non-pregnant state, namelysurgery and chemotherapy. Pregnancy is not a contraindica-tion to surgery as surgical intervention is least likely toaVect pregnancy especially if done during the second andthird trimesters [4–6].

The eVect of cytotoxic drugs upon the fetus and neonatedepends upon the type of cytotoxic drug, time of exposure,duration of exposure, and dose of the drug [7, 8]. Radio-therapy is contraindicated during pregnancy because itposes risks of teratogenicity and induction of childhoodmalignancies. Pregnancy should be delayed 2–3 years aftersuccessful treatment for cancer. This gives time for earlydetection of metastasis or recurrence [9].

E.-S. Abdel-Hady (&) · R. A.-H. Hemida · A. GamalDepartment of Obstetrics and Gynecology, Mansoura University, Mansoura, Egypte-mail: elsaidhady@yahoo.co.uk

M. El-ZafaranyDepartment of Medical Oncology, Mansoura University, Mansoura, Egypt

E. TosonDepartment of Clinical Oncology and Nuclear Medicine, Mansoura University, Mansoura, Egypt

M. A. El-BayoumiDepartment of Pediatrics, Mansoura University, Mansoura, Egypt

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The current study prospectively analyzed the maternaland perinatal outcome of 118 patients presented withmalignant disease during pregnancy at Mansoura Univer-sity Hospitals in Egypt.

Patients and methods

This prospective study included 118 patients diagnosed forthe Wrst time with a malignant disease during pregnancyover an 8-year period (March 2003–March 2011). Amultidisciplinary team of Obstetricians and Gynecologists,Surgical, Medical and Radiation Oncologists and Neonatol-ogists were involved in the management of pregnantwomen and their neonates. This study had ethical approvalfrom the research ethics committee of Mansoura Faculty ofmedicine. Patients and their family were counseled by asenior staV member involved in patient’s care. A writtenconsent was signed by the patient and in case of terminationof pregnancy by her husband as well.

Inclusion criteria included women diagnosed with can-cer for the Wrst time during pregnancy. The managementoptions discussed depended upon the gestational age atdiagnosis, histological type and stage of cancer andpatient’s wishes to continue pregnancy.

Four lines of treatment were discussed with each patient,namely termination of pregnancy, surgical intervention dur-ing pregnancy, neoadjuvant or adjuvant chemotherapy dur-ing pregnancy, or delivery if the diagnosis was made at orbeyond 34 completed gestational weeks. Chemotherapywas given during the second and third trimesters, the regi-mens most commonly used were as follows:

For pregnancy associated breast cancer, the followingregimen was used an adjuvant treatment [10]. AC (Doxoru-bicin 60 mg/m2 IV d1, Endoxan 600 mg/m2 IV d1) 2 cyclesto be repeated every 3 weeks followed by Paclitaxel175 mg/m2 4 cycles repeated every 3 weeks +G-CSF.For locally advanced breast cancer, the following protocolwas used [11] Doxorubicin 60 mg/m2, Docetaxel 75 mg/m2

(6 cycles).Treatment of Hodgkin lymphoma (HL) during preg-

nancy: the ABV (Adriamycin, Bleomycin, Vinblastin) regi-men was used [12–14]. (Doxorubicin 25 mg/m2 IV d1, 15),(Vinblastin 6 mg/m2 IV d1, 15) and Bleomycin 5–10 mg/m2

IV d1, 15).Treatment of Non Hodgkin lymphoma during preg-

nancy: the CVP protocol was used during the second andthird trimester of pregnancy [15]. (Cyclophosphamide750 mg/m2 IV d1), (Vincristine 1, 2 mg/m2 IV d1), (Predni-sone 40 mg/m2 d1-5 p.o).

Delivery was planned at 34–35 gestational weeks andnot less than 2 weeks from the last cycle of chemotherapy.Perinatal outcome of neonates born to mothers who

received chemotherapy (either neoadjuvant or adjuvant)during pregnancy was studied and compared with a controlgroup of neonates born to healthy women delivered at thesame gestational age (34–35 weeks) due to preterm deliv-ery.

The primary outcome measure included the eVect of inutero exposure to chemotherapy on neonatal survival. Sec-ondary outcome measures included assessment of birthweight, presence of congenital anomalies, neonatal Apgarscores at 1, 5 and 10 min, length of admission (in days) tospecial care baby units and neonatal survival.

Statistical analysis was carried out using the statisticalpackage SPSS 15.0 for Windows (SPSS, Chicago, IL,USA). The medians and standard deviations (SD) were cal-culated for continuous variables. An independent samplet test was used to evaluate the associations between contin-uous variables. Two-sided p values were considered statis-tically signiWcant at p < 0.05.

Results

The commonest cancer type diagnosed during pregnancy(56/118 = 47.45 %) was breast carcinoma followed by lym-phoma (15.25 %) and leukemia (11.86 %). 12 gynecologi-cal tumors (all ovarian, 8 germ cell and 4 epithelial tumors)represented 10.16 %, soft tissue sarcomas 5.08 %, colorec-tal 4.23 %, thyroid 2.54 % and 4 other tumors 3.38 % ateach of tongue, bronchus, brain and kidney. The medianage at diagnosis was 33 § 4 years (range 18–42 years), andthe median parity was 1 § 0 as given in Table 1.

Chemotherapy (average 3 § 2 cycles) was given duringthe second and third trimesters to 61 patients (51.69 %). 32patients with locally advanced breast carcinoma receivedneoadjuvant chemotherapy and 2 other patients receivedadjuvant chemotherapy following surgery for breast carci-noma as given in Table 2.

Table 1 Cancer type, age and parity of the studied group

a Other tumors included: tongue carcinoma, brain tumor, broncho-genic carcinoma and renal cell carcinoma

Type Number (%) Age (years) Parity

Breast carcinoma 56 (47.45%) 33 § 3 2 § 1

Lymphoma 18 (15.25%) 21 § 2 1 § 0.5

Leukemia 14 (11.86%) 20 § 2 1 § 0.5

Ovarian tumors 12 (10.16%) 29 § 4 1 § 1

Soft tissue sarcoma 6 (5.08%) 26 § 4 1 § 1

Colorectal carcinoma 5 (4.23%) 27 § 3 1 § 1

Thyroid carcinoma 3 (2.54%) 35 § 5 2 § 1

Othera 4 (3.38%) 37 § 4 3 § 1

Total 118 (100%) 33 § 4 1 § 1

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Arch Gynecol Obstet (2012) 286:283–286 285

Perinatal outcome of neonates born to mothers whoreceived chemotherapy during pregnancy was studied andcompared with 60 controls born prematurely during thesame period as seen in Table 3. There was no statisticallysigniWcant diVerence between the 2 groups regarding neo-natal survival (p = 0.711), birth weight (p = 0.260), oradmission to special care baby unit (p = 0.510). There was,however, a statistically signiWcant diVerence in Apgarscores at 1 (p = 0.03) and 5 (p = 0.02) min in favour of thecontrol group. This diVerence was non-signiWcant(p = 0.510) at 10 min. There were no identiWed congenitalmalformations either in study or in the control group. Five(4.23 %) women with advanced bronchogenic carcinoma,brain tumor, soft tissue sarcoma, breast carcinoma and leu-kemia died during or shortly after termination of preg-nancy.

Discussion

To the best of our knowledge, this is the largest single insti-tution experience on perinatal outcome in pregnancies asso-ciated with malignant disease. Mansoura Oncology center

is the only tertiary care center within Dakahlia Governoratewith a population of over 6 million persons. Many referralsfrom nearby governorates were also seen over the 8-yearstudy period.

The most common cancer type diagnosed during preg-nancy in this study was breast carcinoma (47.45 %), fol-lowed by hematological malignancies (lymphoma andleukemia), which together represented 27.12 %. Ovariantumors (10.16 %) were the only diagnosed gynecologicalmalignancies. There were no cases of cervical carcinomaencountered during this study. This may be explained bydiVerent socio-cultural factors and the lack of routinescreening for cervical carcinoma in Egypt [16].

In this study, 22 % of pregnant women diagnosed withmalignant disease had decided to terminate their pregnancy.In the majority of these cases (16 out of 26 women), thedecision of the multidisciplinary team was in favour ofpregnancy continuation, yet the patient and her family haddecided to terminate pregnancy.

During the Wrst 4 years (2003–2007) of the study, therewas a profound concern among patients and their familiesthat when cancer is diagnosed in a pregnant woman, life-saving chemotherapy for the mother poses life-threateningcomplications for the developing fetus. This concernbecame less profound during the second half of the study(2007–2011), when many women who have received che-motherapy during pregnancy and had healthy babies wereinvolved in the counseling of new patients and their fami-lies.

The perinatal outcome in neonates delivered to patientswho received chemotherapy during pregnancy was notdiVerent from the control group except in Apgar scores at 1and 5 min as seen in Table 3. Apgar scores at 10 min,which indicate future neurobehavioral development, werenot diVerent from the control group. These Wndings werereported before [17–19].

The main limitation of the current study is the lack oflong-term follow-up of infants and children who wereexposed to chemotherapy during pregnancy. The current

Table 2 Cancer management during pregnancy

Type Chemotherapy Surgery TOP Delivery Total

Breast carcinoma 32 5a 11 8 56

Lymphoma 16 0 2 0 18

Leukemia 13 0 1 0 14

Ovarian tumors 0 8 0 4 12

Soft tissue sarcoma 0 0 2 4 6

Colorectal carcinoma 0 0 3 2 5

Thyroid carcinoma 0 0 3 0 3

Other 0 0 4 0 4

Total 61 13 26 18 118

% 51.69 11.02 22.03 15.25 100

Delivery = nothing but delivery at 34–35 weeks (average 34 weeks § 5 days)

TOP termination of pregnancya Two out of these Wve patients received adjuvant chemotherapy during pregnancy

Table 3 Perinatal outcome in neonates born to mothers who receivedchemotherapy during pregnancy

Control group: healthy women who delivered prematurely during thesame period

SCBU special care baby unit, gm gram, min minute

Outcome Chemotherapy Control p

(n = 61) (n = 60)

Birth weight (gm) 2,100 § 100 2,300 § 150 0.260

Apgar score at 1 min 4 § 1 5 § 1 0.03

Apgar score at 5 min 5 § 1 6 § 1 0.02

Apgar score at 10 min 7 § 2 8 § 1 0.51

Admission to SCBU (days) 4 § 3 3 § 3 0.510

Neonatal survival 56 57 0.711

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health system in Egypt makes it very diYcult to follow-upsuch children. Similar reports from developed countries[20] have indicated that there is no serious health-relatedmorbidities or malignancies following exposure to chemo-therapy during the second and third trimesters of preg-nancy.

In view of the increasing incidence of malignant diseasediagnosed during pregnancy, clinical guidelines and algo-rithms have recently been established for diagnosis andtherapy [21, 22]. More studies are needed to assess thewell-being of the expectant mother against the well-beingof the unborn neonate in these ethically and scientiWcallychallenging situations.

Conclusion

In this study, chemotherapy for malignant disease was usedduring the second and third trimesters of pregnancy withminimal morbidity to the unborn fetus.

ConXict of interest There was no conXict of interest during thisstudy.

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