Natural high-order multiple pregnancies (i.e. pregnancies with more than two foetuses in-utero) are uncommon. The reported incidence ranges from 1 - 7 per 10,000 of all pregnancies. Worldwide, Nigeria is recognized to have the highest incidence of multiple births, including high-order births     . In Nigeria, about 35% of institutional deliveries occur in private medical institutions  and there has been an increase in the incidence of multiple births and HOM pregnancy in current day obstetric practice. The increase in the incidence of high-order multiple pregnancies is estimated to be over ten folds that of previous occurrences and has been attributed to several factors. The factors include the use of ovulation-inducing agents and assisted reproductive technologies to treat infertility as well as a shift towards late childbearing in women when multiple gestations are naturally more likely to occur   . Infertility may induce the desire to have multiple pregnancies in women having such challenges. In Nigeria, the desire for multiple pregnancies, in infertile women, has been documented  and fertility practitioners readily transfer over two embryos during in vitro-fertilization and embryo transfer (IVF-ET) treatment cycles with attendant increase in multiple pregnancies  .
Multiple pregnancies including HOM pregnancies are associated with adverse pregnancy outcomes in the mother such as increase in spontaneous miscarriages, preterm term labour, preterm drainage of liquor, hypertensive diseases in pregnancy, caesarean section, antepartum and postpartum haemorrhage. These invariably increase hospital admissions causing dislocations in family, social and economic life of the woman and her family . Several interventions such as prophylactic cervical cerclage, prolonged hospital admissions with bed rest or the use of progestogens, have been instituted to improve the pregnancy outcome of multiple pregnancies with no clear evidence of the efficacy of these interventions, which may sometimes be harmful  . The best intervention, therefore, lies with preventing the HOM pregnancies.
The proliferation of fertility clinics within our environment, the high incidence of HOM pregnancies following fertility treatments, as well as the associated high maternal morbidity and sometimes mortality from the HOM pregnancies is the reason for initiating this study which aims to evaluate adverse pregnancy outcomes in women with HOM pregnancies at a specialist private health care facility.
2. Materials and Methods
This study was a descriptive retrospective study of all the higher-order multiple births managed and delivered in Prime Medical Consultants between January 2004 and December 2013.
Prime Medical Consultants is a private health care facility situated in Port Harcourt city, Rivers State, Nigeria, with 24-hours-coverage by consultant obstetricians and neonatologists. It has fully functional obstetric and special care baby units. We retrieved information from antenatal clinic records, labour ward records, theatre records, and case files of women with high-order multiple pregnancies, for various maternal data. The data collected were age, parity, educational status, gestational age at delivery, hospital admissions, use of prophylactic cerclage, preterm labour (defined as uterine contractions that caused progressive cervical dilatations before at 37 weeks gestation), premature rupture of fetal membranes (drainage of amniotic fluid before 37 weeks gestation). Others are gestational hypertension (defined as an elevation of blood pressure greater than or equal to 140/90 mmHg on two consecutive readings, 4 hours apart, occurring with or without proteinuria), anaemia (defined as haemoglobin concentration of <10.0 g/dl) and antepartum haemorrhage, primary postpartum haemorrhage (defined as blood loss above 500 mls following vaginal delivery; or above 1000 mls following caesarean delivery). Data analysis was carried out using SPSS version-15 software and the results presented as frequencies, percentages, mean and standard deviation.
There were a total of 7634 deliveries during the study period. Eighteen of the deliveries were high-order multiple pregnancy, comprising 14 triplets and four quadruplet pregnancies. The overall incidence of high-order pregnancy was 0.24% of all deliveries in this hospital. A set of triplets and another set of quadruplets were through natural conception and ovulation induction with clomiphene citrate respectively. The other 16 sets (89%) of HOM pregnancy were through fertility treatment with in-vitro fertilization and embryo transfer. The mean maternal age was 35.1 ± 4.81 years. Majority of the women (66.7%) were nulliparous with tertiary education (78%). See Table 1. The mean gestational age at delivery was 31 ± 1.5 weeks, as 83.3% of the deliveries were preterm. See Table 2.
Table 1. Demographic characteristics of mothers.
Table 2. Adverse outcomes during antenatal care.
All the prophylactic cerclage were inserted between 12 and 14 weeks. One cerclage was inserted in a referral hospital, and three patients registered late for antenatal care and two of them did not have any cerclage. Sixteen of these women had micro-ionized vaginal progesterone treatment for early pregnancy support. Five of them continued progesterone treatment to 12 weeks while others discontinued at confirmation of pregnancy. Two patients had spontaneous first trimester miscarriages, and there was no recorded case of antepartum haemorrhage in these women (Table 3).
Table 3. Indications and methods of delivery.
Two women referred to the clinic after 20 weeks had anaemia in pregnancy and postpartum anaemia. They also received blood transfusion in the postpartum period. There were frequent intermittent hospital admissions amongst these women. Cumulative admission periods for eleven mothers were between 7 to 14 days while in 2 mothers, cumulative admissions were over 21 days (Table 3).
Table 3 and Table 4 show that 77.8% of the pregnancies were delivered by caesarean sections and 68.75% by emergency caesarean section. Preterm labour (62.5%) was the most frequent indication for delivery.
Table 4. Intrapartum and puerperal complications.
Primary postpartum haemorrhage (PPH) occurred in 22.2% of these women and was the leading maternal adverse outcome in the postpartum period.
The incidence of high-order multiple pregnancies in this hospital over the period under study was 0.24%. This incidence represents an increase of 4 to 24 times over the natural rates of high-order multiple pregnancies of 0.01% to 0.07% in the literature     . This incidence of 0.24% is higher than 0.1% to 0.13% recently reported in the eastern part of Nigeria but lower than 0.72% published in the western part of Nigeria   . The increase in the incidence of high-order multiple pregnancies in this study is mainly from infertility treatments using IVF-ET. Fertility treatment with IVF-ET contributed 88.9% of these high-order pregnancies, which is similar to other reports in many recent studies from Nigeria     . In this study, about 87% of women with the high-order multiple pregnancies had preterm deliveries. The mean gestational age at delivery was 31 ± 1.5 weeks. The gestational age at delivery is similar to other reports around the globe and consistent with a report from America Society of Reproductive Medicine (ASRAM) showing that the risk of birth before 32 weeks of gestation for singleton, twin, triplet, and quadruplet pregnancies was 2, 8, 26, and >95 per cent, respectively . The presence of prophylactic cerclage in over 75% of the patients and frequent hospital admissions for bed rest did not seem to prolong the gestational age in these patients. These interventions could not prolong HOM pregnancies in other studies as well  . Premature rupture of fetal membranes (38.8%) and Preterm labour (62%) with consequent early deliveries were significant problems in these women. The excessive and rapid distension of the uterus in multifetal pregnancies could trigger preterm labour which could account for the high proportion of preterm births (87%) in these pregnancies.
The incidence of caesarean section (87%) amongst mothers with high-order multiple pregnancy was very high. The primary reason for these caesarean sections was infant survival. Caesarean section has higher morbidity than vaginal deliveries and did contribute to the adverse outcomes observed in these mothers. The high occurrence of other maternal adverse outcomes also noted in these mothers includes primary postpartum haemorrhage (22.2%). Primary postpartum haemorrhage from uterine atony was the most frequent maternal complication in these women following delivery. The high occurrence of primary PPH has also been reported in other studies as well  . Severe pre-eclampsia was uncommon because majority of the pregnancies ended around 30 weeks when pre-eclampsia begins to manifest in pregnant women. No antepartum haemorrhage was reported in these women. Traditionally, the incidence of antepartum haemorrhage is thought to increase in women with multiple pregnancies; however, the absence of antepartum haemorrhage may be due to the small study population.
Mothers with high-order pregnancies also had high cumulative admission periods in the hospital (see Table 3). Their frequent admissions, no doubt, would have caused unanticipated dislocations in family’s financial and socioeconomic life as has been reported in a previous study .
The practice of multiple embryo transfers (>2 embryos) amongst invitro-fertilization practitioners in Nigeria is accountable for the high occurrence of high-order multiple pregnancies  . It is reported that Nigerian mothers welcome and anticipates multifetal pregnancies from invitro-fertilization treatments . However, in wishing multiple pregnancies, these women may not have experienced the adverse medical, financial and socioeconomic effects associated with high-order multiple pregnancies. Recent studies show that transfer of numerous embryos in an IVF treatment cycle does not significantly increase pregnancy rates or take home babies, as initially thought, but substantially increases the occurrence of high-order multiple pregnancy and the adverse effects thereof   . To reduce multifetal pregnancies, women undergoing in-vitro fertilization treatment in Nigeria should undergo counselling aimed at reducing the number of embryos transferred to less than three. This reduction is also possible by enacting regulatory laws protecting against the transfer of over two embryos per cycle in a patient. Reducing the number of embryos transferred in a treatment cycle would check the high incidence of high-order multiple pregnancies and the associated adverse outcomes. The overall effect of high-order multiple pregnancy is that it increases morbidity and even mortality to the mothers. Most practitioners agree to elective single embryo transfer as the first step towards reducing the incidence of high-order multiple pregnancies and fetal reduction if the first step of elective single embryo transfer fails. Fetal reduction is an option to bring triplets and quadruplets to twin gestation to reduce the morbidity and mortality generally associated with multifetal pregnancies  .
This study shows that high-order multiple pregnancies have become commoner and are associated with high preterm births and maternal adverse pregnancy outcomes such as high caesarean section rate and primary postpartum haemorrhage. Effort to reduce the incidence of high-order multiple births should start with electively decreasing the number of embryos transferred at each IVF treatment cycle to less than three.
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