Doppler studies in small for gestational age pregnancies and the influence of perinatal variables on postnatal outcomes

Abstract

Background, hypotheses and aims Poor fetal growth is associated with increased perinatal morbidity and mortality. Recently the topic of poor fetal growth has generated considerable research interest, as numerous epidemiological studies have demonstrated that small size at birth is also associated with increased risks of adult cardiovascular diseases and non-insulin dependent diabetes Antenatal treatment aimed at improving fetal growth might therefore reduce perinatal morbidity, as well as later complications of being born small for gestational age (SGA). SGA fetuses with abnormal umbilical artery Doppler studies have placental vascular pathology. Low dose aspirin, which inhibits the production of the powerful vasoconstrictor thromboxane, might therefore increase placental blood flow and fetal growth. The hypothesis in the first antenatal study was that treatment of SGA pregnancies, with abnormal umbilical artery Doppler studies, with aspirin (100 mg) for ≥14 days, would increase fetal weight. As perinatal morbidity and mortality are increased in SGA pregnancies most obstetricians advocate a programme of regular fetal surveillance. Outpatient management with twice weekly fetal surveillance has been usual practice in our hospital in uncomplicated SGA pregnancies. These frequent checks may be unnecessary when umbilical artery Doppler studies are normal as the risk of serious perinatal morbidity is low. More conservative management in SGA pregnancies with normal umbilical artery Doppler studies has been suggested by several authors but has only been evaluated in one previous trial, where hospitalisation was usual practice. In the second antenatal study we therefore wished to test the hypothesis that the frequency of fetal surveillance could be reduced from twice weekly to fortnightly, in SGA pregnancies with normal umbilical artery Doppler studies, without increasing maternal or perinatal morbidity. Abnormal umbilical artery Doppler studies have been shown in a number of reports to be associated with increased perinatal mortality and morbidity, in SGA pregnancies. Previous investigators have not considered the potential confounding effects of both gestational age at delivery and birthweight in relation to umbilical artery Doppler status. SGA babies with normal umbilical artery Doppler studies, have a low risk of complications and have been called ‘small normal babies’ although there is little data to support this claim. In the third antenatal study the following hypotheses were tested: that abnormal umbilical artery Doppler studies would predict newborn morbidity in SGA babies, independent of birthweight and gestational age; that compared with SGA babies with abnormal umbilical artery Doppler studies, SGA babies with normal umbilical artery Doppler studies would have low rates of newborn morbidity and malnutrition; and that their mothers would be smaller, have different ethnic distribution, and have lower rates of vascular problems in pregnancy than mothers of SGA babies with abnormal umbilical artery Doppler studies. After birth approximately 20% of SGA babies fail to show catchup growth and remain short at two years of age. Persisting short stature has been associated with later psychological difficulties, abnormal neurodevelopmental testing in childhood, poor school performance and hypertension in childhood and adult life. Most catchup growth occurs in the first six months after birth and most children who are small at six months will not show further catchup growth. Early identification of children who will remain small may enable interventions aimed at improving later outcomes. There are no previous reports of the influence of perinatal variables on size at six months. In the first postnatal study in this thesis we therefore chose to investigate the perinatal factors associated with small size at six months of age. We tested the hypotheses that children who were small at six months would: have been diagnosed SGA earlier in pregnancy; be more likely to have abnormal umbilical artery Doppler studies; have smaller body proportions at birth; and be more likely to have normal ponderal indices at birth. Previous studies, mostly of children born in the 1960s and 1970s, have reported more abnormal neurodevelopmental test results in children who were SGA at birth compared with appropriate weight for gestational age children. There are very few published studies of neurodevelopmental outcome in SGA children born in the 1990s, who have had the advantage of recent advances in antenatal and especially newborn care. The aims of the second postnatal study were therefore to: assess neurodevelopmental outcome in a cohort of SGA children at 18 months and compare results to a reference population; determine whether one or more of the following perinatal variables might be predictive of abnormal neurodevelopmental test results: early recognition of SGA antenatally, abnormal antenatal Doppler results, lack of participation in the antenatal studies in SGA pregnancies, gestation at delivery, head size at birth, head growth from birth to six months, and ponderal index at birth.