Confounding variables

There are many confounding variables that can contribute to birth weight and early neonatal outcomes in multifetal pregnancies. All multifetal pregnancies can be considered high risk because of the increase of many obstetrical complications, compared with those of singleton pregnancies. Maternal complications include preeclampsia, hypertension, gestational diabetes, placenta previa, abruptio placenta, cesarean birth, and maternal mortality. For the fetuses, the risks include prematurity, low birth weight, birth asphyxia, cerebral palsy, and neonatal death.

These complications associated with multifetal pregnancies should be considered when examining pregnancy outcomes. Some other important variables can contribute to the outcome of a multifetal pregnancy.

First, pregnancy complications such as preeclampsia, hypertension, diabetes, abruptio placenta, or placenta previa can be very problematic for the clinician and can result in medical or surgical interventions or even early delivery [34]. Some of these pathologic conditions are known to influence intrauterine growth. Would bed rest with reduced maternal activity and stress reduction alter interuterine fetal growth? Can overdistension of the uterus or an increased amniotic fluid precipitate early labor and delivery? All of these maternal factors and pregnancy complications need to be considered if birth weight is considered as a crude marker for nutrition.

Second, discordancy could account for a difference in fetal growth and birth weights with multifetal pregnancy. Growth discordancy, usually more than 20 or 25%, offers a unique challenge for clinicians. Discordancy occurs at a higher frequency and severity in triplet pregnancies [35]. Fetal growth, discordant or not, depends on many factors. One factor relates to the function of the placenta or uteroplacental unit, as nutrients cross from the mother to the fetus [36]. Umbilical cord insertion and fusion of the placentas has been shown to influence birth weight in twin gestation [37]. Fetal growth also seems to be influenced by plurality, that is, the mean birth weight decreases as the number of fetuses increases [38]. Fetal intrauterine growth depends on the time in gestation, as "growth curves" for singletons, twins, and triplets are similar until 28 weeks' gestation. After 28 weeks, the curves of the multifetal pregnancies deviate from the singleton pregnancy. Uterine adaptation and volume also may influence fetal growth [39, 40]. Therefore, when considering fetal growth or neonatal birth weight as a marker for nutrition, not only is the length of gestation critical, but pregnancy complications and other factors that influence fetal growth also must be considered. In fact, the monochorionic type of placentation in multifetal pregnancies has been reported as a risk factor for increased discordance [41, 42]. Nutritional status of multifetal pregnancies and outcome has not been well evaluated by the type of placentation or the other placental complications that occur more frequently in multifetal pregnancies.

Third, second-born twins have a greater risk for perinatal morbidity than first-born twins [43, 44]. Is this finding due to difference in mode of delivery, intrauterine or neonatal growth, or perinatal nutrition? The author was unable to find any literature that evaluates or links nutrition to the birth order.

Finally, carbohydrate metabolism in pregnancy can be characterized by the phenomenon of accelerated starvation; that is, the fasting glucose decreases as pregnancy advances with an accelerated insulin response to meals [45]. Pregnant women with twin gestation have an accelerated response compared with singleton pregnancy [46]. This indicates that lower glucose in the fasting state can increase the depletion of glycogen stores resulting in metabolism of fat. Ketones may result, and ketonuria has been associated with preterm delivery. Compared with the recommended diet for women whose pregnancies are complicated by carbohydrate intolerance (diabetes), changes in diet composition for women with multiple pregnancies would be a lowering (40%) of the carbohydrates to avoid more hyperglycemic peaks and an increase in the percent of fats (40%) to provide more substrate. This adjustment in the distribution of the macronutrients may be important not only for nutritional value, but also for prevention of preterm labor. Carbohydrate intolerance, particularly in the absence of longstanding vascular disease, is a well-recognized risk factor for fetal or neonatal macrosomia.

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