The twinning rate was moderately high, i.e. 18/1000 at community level and 28/1000 at the hospital. The MZ rate was 3.4/1000 in the community. Perinatal twin mortality was very high with community and hospital rates of 218/1000 and 237/1000, respectively. In the community the RR of perinatal death among twins vs. singletons was 2.71 (CI: 1.93-3.80).
Newborn twins had on average 791g lower birth weight than singletons. VLBW was the strongest risk factor for perinatal twin death. Maternal unawareness of twin pregnancy was common, and only a fraction of the twin mothers had been registered as high risk pregnancies antenatally.
Strengths and weaknesses
Considering that newborn twins constitute a substantial and very vulnerable group in Sub-Saharan Africa, a surprisingly small number of twin studies are available. A literature search revealed only few other prospective mortality datasets
[2, 10]. Most twin studies are based on retrospective analyses of hospital records and hence do not report community data. To our knowledge, this is the first cohort study to specifically target twin mortality; it has a large sample size and presents both community and hospital data. It is also one of the first to genetically determine the zygosity distribution.
The study has a number of limitations. Follow-up was only carried out within Bissau and is therefore missing for twins from the interior of the country. This could underestimate the hospital perinatal mortality. However, only very few deaths were registered immediately after discharge.
The zygosity sub-study was only done on live pairs. Hence, we have no zygosity status of same-sex pairs with one or both twins dead. MZ twins, who are often monochorionic, are at higher risk of death in utero[3, 30]. We may therefore have underestimated the MZ rate. Furthermore, for VLBW twins blood collection was postponed until follow-up. As LBW twins are more often MZ
[3, 31] and some twins were either dead or not located upon follow-up, this could mean that more MZ pairs were missed.
We did not monitor antenatal consultations in detail. Apart from the pregnancy cards, we have limited data on the nurses’ and midwives’ abilities to identify and monitor twin pregnancies.
At the hospital, twin mothers came from both inside and outside the study area, while the singleton controls were selected from the study area only. This could bias comparisons of clinical characteristics (Table
2). Though smaller differences were observed, most variables showed no significant differences. Hence, the bias is probably small.
Gestational age was calculated by the last menstrual date. This method is considered somewhat imprecise
, and the prematurity estimates should therefore be interpreted cautiously. Consequently, maturity was also assessed using the Ballard score. As gestational age was often unavailable, we did not include prematurity in the multivariate analysis. This is an important limitation. However, due to a presumed overlap between LBW and prematurity
 we believe that the multivariate analysis still provides important information.
We excluded children who were only registered after birth in the study area. This was done to avoid the bias of retrospective registration of stillbirths and early neonatal deaths, which is often unreliable and may result in the underestimation of the true mortality. The perinatal mortality was much lower in the excluded group.
Unfortunately, no distinction was made between “fresh” and “macerated” stillbirths. This limits our ability to distinguish between intra-partum and ante-partum deaths. It is, however, likely that many stillbirths were fresh and therefore labor related
Birth weight was often missing in the community data. The main reason was birth at home. This could bias the comparison of twin vs. singleton mortality by birth weight (Table
1), as it would predominantly include children born in health institutions
Though the cost of delivery in itself is quite small (~3 USD), costs can rapidly accumulate if medicine, utensils or in particular a cesarean section (~100 USD) are needed. Hence, financial constraints in emergency situations are likely to cause a mortality increase.
Consistency with previous findings
The community twinning rate of 18/1000 was similar to neighboring Gambia, Burkina Faso and Senegal
[10, 15, 33]. The hospital rate of 28/1000 probably reflects an overestimation due to selective referral of twin mothers
, a fact which is also illustrated in the community data by more twin (63%) than singleton (46%) mothers giving birth at the hospital. It should be emphasized that the estimates represent the “natural twinning rate” as in vitro fertilization is very uncommon in Guinea-Bissau.
Twinning refers to two separate phenomena
. While MZ twinning is the result of one fertilized egg dividing into two identical embryos, DZ twins are caused by the fertilization of two ova in the same cycle. The MZ rate is fairly constant around the world and independent of maternal age and parity. From Sub-Saharan Africa this has however mainly been theoretically confirmed by Weinberg’s differential rule, where the frequency of DZ twins is twice the number of opposite-sexed pairs
. Thus, in our study, the proportion of DZ twins at the hospital would be (2*140/326) * 100% = 86% and the MZ proportion would only be 14%, which is somewhat different from the genetic estimate of 19% MZ twins. A 19% MZ proportion would confirm a MZ rate of 3-4/1000 (0.19*18/1000)
. Studies from the Gambia and Burkina Faso have estimated MZ proportions of around 30%
Unlike the MZ rate, DZ twinning varies globally, with the highest rate observed in Sub-Saharan Africa. It is dependent on age, parity and ethnicity
. Genetic disposition also seems important since twinning was eightfold more likely among previous twin mothers in our study. This raises the question why DZ twinning is so common in Africa? Given the high mortality, fewer children may actually result from twin pregnancies. This should, at least in theory, cause a gradual genetic selection against twinning. Since this is not the case, there may be important health benefits associated with DZ twinning
, as recently confirmed in the Gambia
This study found perinatal twin mortality to be very high. Other African studies from Burkina Faso, the Gambia, Congo and Malawi have found overall perinatal mortality rates of 64-79/1000
, while WHO’s regional estimate is 56/1000
. In Europe and North America, much lower average rates are observed, i.e. 7-8/1000
. Hence, a community perinatal mortality of 218/1000 for twins in our setting is disturbing and demands attention. Twin studies from Nigeria have reported perinatal mortality rates between 155-186/1000
[8, 9], while in rural Gambia an early neonatal twin mortality of 114/1000 is described
. A small study from rural Malawi found a perinatal twin mortality of 248/1000
Likewise, it is worrying that the twin mortality rates at the hospital (237/1000) and in the community (218/1000) were almost similar, as one would expect a lower mortality given hospital delivery. A possible explanation is that in Guinea-Bissau twin pregnancies often remain unrecognized until delivery. Furthermore, many mothers give birth at home or in health centers with limited obstetrical expertise. This may cause delays in the referral of complicated twin deliveries, causing many twin mothers to arrive too late at the hospital. Transportation issues (especially at night), lack of money and delays due to availability of hospital staff may aggravate this
It should be noted that while the RR of 2.71 for twin vs. singleton death is actually lower than in some high-income countries, e.g. 4.22 in the US
, the high “background” singleton mortality (80/1000) makes newborn twins very vulnerable in Guinea-Bissau. Thus, in absolute terms (deaths per thousand twin and singleton births), the difference is much higher.
Clinically, twins were smaller and more premature than singletons
[2, 10, 15] and discharged later. Twin mothers were older and had higher parity
[1, 3]. Ethnicity was also important
, as twinning was more prevalent among the Balantas. Twin mothers were more ill during pregnancy, including suffering from hypertensive disorders
The strongest predictor for perinatal twin death was VLBW
[2, 10], which was associated with a fourfold increase in mortality. As twins account for 20-31% of all LBW newborns in West Africa
[26, 36], this has considerable impact on the overall perinatal mortality. Prematurity is another well described risk factor among twins
[2, 10]. The univariate analysis revealed a more than threefold increase in perinatal mortality.
Maternal unawareness of twin pregnancy tended to be a risk factor. This is worrying given the large number of women (65% of twin mothers), and it suggests gaps in proper health examinations during antenatal care. Even if a twin pregnancy was in fact noted, the mother may not have been properly counseled or referred to hospital birth. The fact that 20% of twin mothers arrived with hypertension could also indicate problems in diagnosing and treating common pregnancy disorders. Hypertension during pregnancy tended to confer a higher risk of perinatal twin death, presumably due to pre-eclampsia
Caesarean section was associated with nearly twofold higher twin mortality. This may be due to the fact that the caesarean sections were mainly emergency procedures in case of serious fetal or maternal distress
. However, fatal delays are also likely to play a role. Delays may exist in getting to the hospital, finding the means to pay for a caesarean section and in hospital staff realizing the problem and taking appropriate action
The tendency for higher mortality among male twins could reflect increased early neonatal mortality among males in general
. Surprisingly, maternal HIV infection was not a risk factor though this has been reported by others
Finally, a previous study by our group found that twins are more likely to suffer from hypothermia during the first day of life
. It is therefore possible that newborn twins do not always receive adequate monitoring of adverse conditions such as hypothermia, septicemia and signs of prematurity in our setting.
The very high perinatal twin mortality in Guinea-Bissau calls for immediate action. At hospital level, specialized training in handling twin deliveries has proved effective
, both intra-partum and post-partum. Though hospital resources are scarce, training in simple neonatal resuscitative procedures can lower death rates markedly
Although antenatal care was not the focus, our data suggest that better identification and monitoring of twin pregnancies are needed. Sixty-five percent of the mothers reported to be unaware of their twin pregnancy. Of those where pregnancy cards were available, only 6% of the twin mothers had been classified as high risk pregnancies. Limiting premature twin births should be a key priority
, and previous studies show that clinical examination alone can detect the majority of twin pregnancies
There are several reasons why twins should receive particular attention, apart from being a high risk group. First, provided the antenatal and hospital services gradually improve, the relative proportion of twin deaths in overall perinatal mortality is likely to increase
, as mortality in twins is more difficult to prevent
. Secondly, due to fetal distress and other adverse perinatal outcomes, newborn twins are at high risk of long term sequelae (e.g. neurological) even if they survive
. As systematic follow-up is difficult in low-income countries, improved management of twin pregnancies is essential. Thirdly, twins can be used as a proxy of antenatal care, e.g. the percentage of twin pregnancies recognized prior to delivery. This is important in settings where simple monitoring tools are needed.