Description of the condition

Multiple pregnancies occur when two or more fetuses are present in the uterus; this can be a result of implantation of two genetically different fertilised eggs by two different sperm (dizygotic twins), or due to the division of one fertilised egg (monozygotic). Monozygotic twins can share the same placenta (monochorionic) or have separate placentas (dichorionic) (Fox 2006).

Multiple pregnancies can be diagnosed by an ultrasound scan as early as six weeks. Women with multiple pregnancies may have more severe nausea and vomiting than those with singleton pregnancies, as a result of higher levels of human chorionic gonadotropin (hCG) (Rao 2004).

Since the 1970s there has been a steady increase in the number of twin pregnancies; from 9.6 per 1000 maternities in England and Wales (ONS 2006) in 1976 to 15.5 in 2008 (ONS 2009); in the USA, 18.8 per 1000 were twins in 1975 (Taffel 1992) rising to 32.1 per 1000 in 2006 (Martin 2009), while in Australia in 2010 multiple births accounted for 3.1% of all births (Umstad 2013). These trends have been reflected in many settings across the globe. This rise has been attributed to the increase in the use of assisted reproductive technology, and to some women deciding to have children later in life. An increase in maternal age increases the chances of multiple pregnancy. In the USA it was found that 20% of twin pregnancies from 1980 to 1997 were due to spontaneous conception, 40% due to in vitro fertilisation and 40% due to ovulation induction (Nakhuda 2005). In Europe, spontaneously conceived twins comprise 1% of all deliveries; 20% to 30% of all twins are due to assisted reproductive technology (Hansen 2009), although recent policies to restrict the number of embryos transferred during assisted conception may reverse the upward trend in multiple pregnancies (Collins 2007; Umstad 2013).

Multiple pregnancies are associated with higher rates of complications for both the mother and the fetuses. Gestational hypertension and pre‐eclampsia are twice as likely to occur with twins as in singleton pregnancies with risk ratios of 2 and 2.6 respectively (Siddiqui 2007). There is a higher incidence of antepartum and postpartum haemorrhage, with the average blood loss after delivery being 500 mL higher than after a singleton birth (Rao 2004).

Mulitple births have a substantial perinatal mortality rate (PMR) compared to singletons. In England and Wales, in 2006, there was an overall PMR of 8.2 per 1000 births, with twins having a rate of 27.2 per 1000, and triplets and higher order births 81.8 per 1000 (CEMACH 2008). When infants are born long before term they are functionally immature, and are usually admitted to neonatal intensive care units. They have poor thermoregulatory mechanisms, which are worsened by low brown fat levels and heat loss. Respiratory distress syndrome occurs as a result of lack of surfactant, and may be associated with chronic lung disease (bronchopulmonary dysplasia) (Keeling 2000). Multiple pregnancies have a strong association with preterm deliveries (before 37 weeks), ranging from 48.2% in Ireland to 68.4% in Austria; between 39.1% and 47.1% occur at 32 to 36 weeks, and 8.1% to 12.7% before 32 weeks (Blondel 2006).

Fifty per cent of twins are small‐for‐gestational age (SGA) by 39 weeks using the 1991 US singleton live birth values. Ten per cent to 15% of multiple pregnancies (twins and triplets) are SGA by 22 to 30 weeks' gestation (Alexander 1998).

Cerebral palsy is also eight times more likely to occur in twins, and has a greater prevalence when the birthweight is less than 1000 g (Pharoah 2002). When infants are below 1500 g, 30% to 65% will have neurological problems ranging from motor to cognitive/behavioural deficits. Other severe neurological concerns are intraventricular haemorrhage and periventricular leukomalacia. Necrotising enterocolitis also affects low birthweight infants, and there is a high risk of infection due to an immature immune system. Prematurity is a risk factor for retinopathy of prematurity; the retina is vascularly immature as there is insufficient vascularisation due to poor production of angiogenic factors (Keeling 2000).

Depending on the chorionicity of the twins, there are specific complications. For example, 10% to 15% of monochorionic twins have twin‐twin transfusion syndrome which can result in fetal death if left untreated. This occurs as a result of anastomoses (a connection between two blood vessels) on the placenta, resulting in a compromise of blood flow to one of the twins, which results in poor growth while the other twin receives the redirected blood from the placenta (Rao 2004).

The risk to mother and fetus is increased even more when the number of fetuses increases. High order pregnancies such as triplets and quadruplets have higher rates of perinatal mortality and have an earlier gestation at delivery; the average gestation for triplets is 33.4 weeks. High order births are more likely to deliver earlier on in the pregnancy than twins; 16.9% of triplets and 29.2% of quadruplets were born before 29 weeks compared to 5.6% of twins. The risk of complications is also greatly increased for higher order births with rates of cerebral palsy of 31/1000 reported for triplets (Bromer 2011).The number of fetuses also impacts on the chances of survival for both twins, with 6.3% of triplet and 8.0% of quadruplet pregnancies having one or more fetal deaths compared to 2.4% of twins (Luke 2008).

In one series, 100% of triplets were admitted to the neonatal intensive care unit, and 54% had a major morbidity (retinopathy of the newborn, necrotising enterocolitis, ventilator support or intraventricular haemorrhage) (Luke 2006).

Description of the intervention

It has been suggested that improved diets may lead to improved outcomes in multiple pregnancies. This is based on observations that a particular range of maternal weight gain is optimally associated with good fetal outcome (Goodnight 2009). However, the converse is not necessarily true ‐ that outcome can be improved by boosting maternal weight gain through improved diet.

Dietary input consists of many different components that may be relevant to multiple pregnancy. These include quantity of calorific intake, the source of calories such as a fat or proteins, micronutrients such as vitamin C, vitamin E, thiamine, magnesium, calcium and zinc, as well the inclusion of certain nutrients such as omega fats. The balance and amount of these components have the potential to impact on the health of the mother and fetuses.

Detailed dietary advice has been popular in the US. For example, Luke et al recommend a calorie intake of 4000 kcal for underweight mothers (body mass index (BMI) 19.8) with a total weight gain of 50 lbs to 62 lbs (23 to 28 kg); 3500 kcal for normal weight (BMI 19.8 to 26.0) with a weight gain of 40 lbs to 54 lbs (18 to 25 kg); 3250 kcal for overweight (BMI  26.1 to 29.0) 38 lbs to 47 lbs (17 to 21 kg); and 3000 kcal for obese mothers (BMI greater than 29.0) with a weight gain of 29 lbs to 38 lbs (13 to 17 kg) (Luke 2005).

The Institute of Medicine in the US has produced guidelines recommending a weight gain of 37 lbs to 54 lbs (17 to 25 kg) for normal weight, 31 lbs to 50 lbs (14 to 23 kg) for overweight, and 25 lbs to 42 lbs (11 to 19 kg) for obese women (Rasmussen 2009).

Published work also discusses the importance of a high carbohydrate diet as it has been linked to unwanted weight gain, poor glycaemic control and poor fetal growth, whereas a diet consisting of 20% protein, 40% carbohydrate, and 40% fat was found to have better fetal growth (Luke 2005).

Haematinic supplements such as folic acid and iron will not be considered in this review, as they are assessed elsewhere (Peña‐Rosas 2015a; Peña‐Rosas 2015b).

How the intervention might work

In multiple pregnancies, the metabolic rate of the mother is 10% greater than in women with singleton pregnancies (Shinagawa 2005), as a result of an increasing demand on the mother’s energy expenditure due to a larger placenta producing higher quantities of hormones, and two fetuses requiring a continuous nutrient supply for growth (Goodnight 2009). As a result of the increased energy use, fasting glucose levels are lower with a resulting depletion of glycogen reserves. Fats are broken down as an alternative energy source (Luke 2005).

The theoretical basis for recommending high‐calorie diets is to increase the provision of nutrients to prevent the likelihood of poor fetal growth. Poor fetal growth may have a number of adverse consequences and can also be associated with preterm birth. A high‐calorie diet may also help maintain the mother's nutritional state, which otherwise may be depleted by the needs of the babies, resulting in impaired maternal sense of well being. A retrospective study has shown that women with normal weights at the start of twin pregnancies are more likely to have larger neonates and less likely to deliver preterm if their weight gain during pregnancy met US Institute of Medicine recommendations (Fox 2010).

Although the focus has been on high‐calorie diets, any trial of any nutritional intervention (e.g. overall better quality) specifically tailored for women with multiple pregnancies would be of interest.

Why it is important to do this review

Some recommended diets for women with multiple pregnancies have calorific contents similar or greater than those for frontline troops (e.g. 4000 kcal daily for British troops in Afganistan; HM Forces 2011). As some women with multiple pregnancies are more sedentary than they would be when not pregnant, these diets have the potential to be associated with substantial weight gain. Excess weight gain is associated with increased complications in labour and higher rates of caesarean births, gestational diabetes, pre‐eclampsia and anaesthesia‐related risks (Reece 2008). Obese mothers have higher rates of fetal macrosomia, as well as increased chance of infection post surgery. By advocating a high‐calorie diet and a high weight gain it is important to consider the psychological impact this might have on the mother as well as future implications for her health. The mother will then have to face the difficulty of losing her extra weight postpartum, as obesity is linked to type 2 diabetes, cardiovascular disease, and thromboembolism (Castro 2002). It therefore needs to be established whether special diets do lead to improved outcomes for the babies and whether these cause unwanted weight gain in the mother.

In addition, a woman might experience anxiety if she were unable to follow specific nutritional advice, because of worry about resulting harm to her babies.

It is also important to consider the financial implications, as a high‐calorie diet may be expensive.