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(Hypertension. 2000;35:662.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Blood Pressure Is Related to Placental Volume and Birth Weight

Minerva Thame; Clive Osmond; Rainford J. Wilks; Franklyn I. Bennett; Norma McFarlane-Anderson; Terrence E. Forrester

From the Medical Research Council Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.

Correspondence to Prof Terrence Forrester, Tropical Metabolism Research Unit, University of the West Indies, Mona, Kingston 7, Jamaica. E-mail tmru{at}infochan.com

	Abstract

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Abstract—The objective of this study was to determine whether maternal nutrition and fetal and placental size program blood pressure. A longitudinal study linking the maternal anthropometric measurements of the first antenatal visit, ultrasound data of placental and fetal size, anthropometry at birth, and childhood growth and blood pressure was performed. The subjects were 428 women who attended the antenatal clinic at the University Hospital of the West Indies, Kingston, Jamaica, and their children, who were subsequently followed up. Systolic blood pressure at ages 1, 2, 2.5, 3, and 3.5 years was the main outcome measure. Pooling the data across ages, systolic blood pressure fell by 1.4 mm Hg for every 1-kg increase in birth weight (95% CI 0.2 to 2.7, P=0.02) and by 1.2 mm Hg for every 100-mL increase in placental volume at 20 weeks of gestation (95% CI 0.4 to 2.0, P=0.004). Blood pressure was also negatively associated with placental volume at 17 weeks and fetal abdominal circumference at 20 weeks. Measures of maternal nutritional status were strongly related to birth weight and placental volume but not directly to childhood blood pressure at these young ages. In conclusion, blood pressure is associated with fetal size in this population, as previously described among Europeans. We found associations between placental volume and abdominal circumference in the second trimester and childhood blood pressure, suggesting that the initiating events of blood pressure programming occur early in pregnancy. Measures of maternal nutritional status were not directly related to childhood blood pressure at these young ages but were strong predictors of both birth weight and placental volume, suggesting an indirect relation.

Key Words: blood pressure • body weight • fetus • placenta • pregnancy

	Introduction

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There is a growing body of evidence that birth weight and body proportions at birth are important risk factors for hypertension, diabetes, and coronary heart disease.¹ The prevalence of hypertension in the Caribbean is high and contributes significantly to morbidity and mortality.² However, only 2 of 34 recently reviewed studies linking birth weight to blood pressure³ were performed in black populations.^{4 5} One of these was a retrospective cohort sample of 1610 Jamaican children aged 6 to 16 years, which showed a significant fall in blood pressure of 2.6 mm Hg for every 1-kg increase in birth weight.⁴

In animals, malnutrition during critical periods of gestation programs changes in the fetus that may affect the anatomy, physiology, and metabolism of the animal.^{6 7} In humans, maternal nutritional status strongly influences birth weight and body proportions at birth,^{8 9} and there is evidence that it may influence blood pressure in their children. Blood pressure in Jamaican children was 2.6 mm Hg higher for each 1-g/dL fall in the mother’s lowest hemoglobin during pregnancy and was 0.6 mm Hg higher for each 1-kg decrease in weight gained by the mothers between the 15th and 35th week of gestation.⁵

Blood pressure is thought to follow the same course from birth through childhood to adulthood, raising the possibility that children who were small at birth and had higher blood pressure in childhood are at increased risk of hypertension in adult life.^{10 11} Therefore, this prospective study investigated the relation between maternal anthropometry, fetal size, birth weight, and childhood blood pressure.

	Methods

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Subjects and Data
Seven hundred twelve women attending their first antenatal clinic visit at the University Hospital of the West Indies, Kingston, Jamaica, were invited to join the study. Recruitment was restricted to women who were aged between 15 and 40 years, were sure of the dates of their last menstrual period, which was confirmed by the 14-week ultrasound, and did not have systemic illnesses or genetic abnormalities, eg, sickle cell disease. After delivery, they and their children were recruited into a longitudinal study of postnatal growth in which we planned to measure blood pressure annually from age 2. After the study had begun, we decided to extend the measurement of blood pressure to half yearly from age 1.

This sample size provided 88% power to detect a difference of 2.0 mm Hg in systolic blood pressure per kilogram change in birth weight by using a test at the 5% level of statistical significance.

Each mother’s weight was measured to the nearest 0.01 kg by use of a Weylux beam balance (CMS Weighing Equipment Ltd); height to the nearest 0.1 cm, by use of a stadiometer (CMS Weighing Equipment Ltd); triceps skinfold thickness, with a Harpenden skinfold caliper (Holtain Ltd); hemoglobin, with a Coulter counter (Coulter Electronics, Inc); and blood pressure, with an oscillometric sphygmomanometer (Dinamap TM monitor model 8100, Critikon Inc). Each woman was interviewed, and a measure of her socioeconomic status was derived on the basis of amenities and crowding in the home, her own and the father’s educational level, and occupation. A high total score corresponded to high socioeconomic status.

Abdominal ultrasound was performed (linear probe, ATL Ultramark IV) on the women at 14, 17, 20, 25, 30, and 35 weeks of gestation to determine placental and fetal growth. Placental volume was measured at the first 3 visits, and fetal biparietal diameter, femoral length, and head and abdominal circumference were measured at all 6 visits. The average of 3 repeats was used for each measurement. Placental volume was measured by identifying and recording on videotape the long axis of the placenta. A continuous recording of the image of the placenta orthogonal to the axis was made by sweeping the probe along the axis at constant velocity. This axis was divided into 6 sections of equal length; the 5 interior cross-sectional areas were measured and integrated to estimate the placental volume. This method was developed and validated by Howe et al¹² (1994).

Birth and placental weight were measured with an electronic balance (Soehnle, CMS Weighing Equipment Ltd); head, chest, and mid upper arm and abdominal circumference were measured with a fiberglass measuring tape; crown rump and crown heel lengths were measured with a length board (Holtain Ltd); and gestational age was determined by using the date of the last menstrual period, which was validated by ultrasound scan at 14 weeks of gestation.

Blood pressure in the children was measured twice by using an oscillometric sphygmomanometer, and the average value was used in the analysis. Weight was measured with an electronic balance (F150S, Sartorius, GMBH). Height was measured with a length board (Holtain Ltd) for children 2 years; thereafter, height was measured with a standing stadiometer (Holtain Ltd).

The reliability of measurements within and between 4 trained observers was assessed by making measurements on 20 subjects before the study began and again at 3-month intervals throughout the study.

Statistical Methods
Multiple linear regression and tabulation of means were used to analyze the data. In regression models in which blood pressure was the dependent variable, we controlled for gender, age, and weight. Placental volumes were right-skewed, transformed to normality by taking square roots, and adjusted for gestational age. We have used the methods of repeated measures and longitudinal analysis described by Diggle et al¹³ for such data. In this context, when the number of measurements per subject is very small relative to the number of subjects, the averaging process that we have chosen is only slightly less efficient and is more widely accessible. Our main hypothesis is that systolic blood pressure in childhood is associated with birth weight and second trimester placental volume. Other reported associations should be interpreted as secondary, bearing in mind the large number of possible comparisons.

	Results

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One thousand one hundred twenty-three systolic blood pressures were measured on 428 children at ages 1, 2, 2.5, 3, and 3.5 years. Twenty-three children (5%) were measured at all 5 ages, 102 (24%) were measured 4 times, 109 (25%) were measured 3 times, 79 (18%) were measured twice, and 115 (27%) were measured just once. For each of the ages, Table 1 shows the number of children measured, the number of males, and their mean weight, height, and blood pressure. One hundred ninety of the children (44%) were male. The variability in the exact age of measurement was small. Their mean weight and height corresponded closely to the median values in the National Center for Health Statistics standards.¹⁴

View this table: [in this window] [in a new window]   Table 1. Childhood Measurements

Table 2 shows descriptive data for the 428 mothers obtained at the first antenatal visit (mean±SD gestational age 63±8 days, maximum 99 days). Table 2 also shows characteristics of these 428 children at birth. Mean birth weight, length, and head circumference corresponded closely to values obtained from a sample of Jamaican births studied in the 1970s.¹⁵ Three hundred ninety-eight (93%) babies were born at term (259 days of gestation). Table 2 shows placental volume as measured by ultrasound at 20 weeks of gestation (mean±SD 142±5 days).

View this table: [in this window] [in a new window]   Table 2. Maternal and Newborn Measurements

By the method of Law and Shiell,³ we regressed systolic blood pressure at each of the 5 ages for the child’s gender, age, current weight, and birth weight. Blood pressure was not associated with gender at any age. It was only associated with current age in the measurements made at 1 year, when blood pressure decreased with age. At each of the 5 ages, blood pressure was strongly and positively associated with the child’s current weight, increasing by 2.0, 1.5, 1.5, 1.5, and 1.1 mm Hg for every kilogram respectively (P<0.0001 in each case). Table 3 shows the regression coefficients for birth weight. Those at ages 2.5 and 3 are significantly negative. To display these associations, we used multiple regression to generate a new systolic blood pressure variable at each age, controlling for the child’s gender, age, and current weight. Table 3 includes mean values of these variables according to birth weight grouped into 250-g intervals. There was little variation in the mean systolic blood pressure across the 5 age groups, so we generated for each child an average of all the available gender-, age-, and weight-adjusted blood pressures and tabulated this average in Table 3. This summary blood pressure decreased by 1.4 mm Hg for every kilogram of birth weight (P=0.02). In analyses restricted to term babies, the regression coefficients for birth weight were -3.0, 0.4, -3.0, -2.2, and -1.3. Thus, 4 became more negative, and that the regression coefficient at age 1 became statistically significant.

View this table: [in this window] [in a new window]   Table 3. Influence of Birth Weight on Systolic Blood Pressure by Age, Controlling for Gender and Current Weight

The same approach was used to assess the effect of other newborn measurements on childhood blood pressure. None was as consistently associated with blood pressure as was birth weight, although chest circumference was weakly associated (P=0.04). There was no association with crown-heel and crown-rump length, head, mid upper arm, and abdominal circumference, placental weight, gestational age, or any of the ratios defined in Table 2.

The same strategy was used with the ultrasound measurements. There was a consistent pattern with placental volume measured at 20 weeks of gestation. The regression coefficients at each of the 5 ages were negative (Table 4). Those at 1, 2, and 3.5 years are statistically significant. Table 4 also shows mean systolic blood pressure adjusted for gender, age, and current weight according to placental volume in 50-mL intervals. By using the mean of all ages, blood pressure decreased by 1.2 mm Hg for every 100-mL increase in placental volume (P=0.004). Table 4 also shows that placental volume is a powerful predictor of subsequent birth weight, although, paradoxically, placental volume and birth weight predict blood pressure most strongly at different ages. Placental volume at 17 weeks of gestation was also associated with blood pressure. By using 50-mL intervals, the mean adjusted systolic pressure taken across all ages fell from 93.6 mm Hg in those whose volume was <150 mL, through 92.7, 92.5, 90.9, and 91.4 mm Hg, to 89.9 mm Hg in those whose volume was >350 mL (P=0.004). There was no significant association with placental volume at 14 weeks of gestation.

View this table: [in this window] [in a new window]   Table 4. Influence of Birth Weight on Systolic Blood Pressure According to Placental Volume by Age, Controlling for Gender and Current Weight

Abdominal circumference at 20 weeks of gestation was the fetal measurement most strongly associated with childhood blood pressure. Systolic blood pressure fell by 0.85 mm Hg for every 10-mm increase in abdominal circumference (standard error 0.34, P=0.01). Fetal head circumference, biparietal diameter, or femoral length measurements were not associated with childhood blood pressure. Abdominal circumference was also the fetal measurement most strongly associated with placental volume.

The same regression strategy was used to assess the strength of association between the maternal variables listed in Table 2 and subsequent childhood systolic blood pressure. Only maternal blood pressure at the first antenatal visit was statistically significantly associated. Childhood systolic blood pressure increased by 1.3 mm Hg for every 10-mm Hg increase in the mother’s systolic blood pressure (standard error 0.3, P=0.0001). Childhood blood pressure at any age was not associated with socioeconomic status. Adjusting for the mother’s systolic blood pressure and socioeconomic status did not change the strength of the associations between birth weight, placental volume, and blood pressure.

Because birth weight and placental volume predict childhood blood pressure, their maternal determinants were explored. Table 5 shows mean maternal measurements at the first antenatal visit according to birth weight grouped into seven 250-g intervals and placental volume grouped into seven 50-mL intervals. Birth weight was positively associated with all the maternal anthropometric measurements but not associated with hemoglobin or systolic blood pressure. Placental volume was positively associated with weight, body mass index, and hemoglobin but was not associated with height, triceps skinfold thickness, or systolic blood pressure.

View this table: [in this window] [in a new window]   Table 5. Maternal Measurements at First Antenatal Visit According to Birth and Placental Weight

The mean birth weight and socioeconomic status scores of those who did and did not provide a blood pressure measurement at each of the 5 ages were compared. Those who were studied showed nonsignificant differences; they were 51 g heavier, 30 g lighter, 29 g lighter, 92 g heavier, and 109 g heavier at 1, 2, 2.5, 3, and 3.5 years, respectively. Their socioeconomic status scores did not differ by >0.5 U.

	Discussion

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Blood pressure was studied in 5 age groups of children aged <4 years. Systolic blood pressure was negatively associated with birth weight at ages 2.5 and 3 years but not at the other ages. Pooling the data across ages, blood pressure fell by 1.4 mm Hg for every 1-kg increase in birth weight (95% CI 0.2 to 2.7, P=0.02). These results parallel those of a longitudinal study¹⁶ in Farnborough, England, of 1895 children aged 0 to 10 years. Those authors described the gradual development of a negative association between birth weight and blood pressure and proposed that the underlying mechanism, whatever it may be, was established in utero and amplified throughout life. The children in the present study are not yet old enough for us to detect amplification. However, the size of the programming effects reported here, as measured by birth weight, are consistent with those found in the studies of white populations reviewed by Law and Shiell.³ Childhood systolic blood pressure was also analyzed in relation to placental volume at 20 weeks of gestation. Systolic blood pressure was always negatively associated with placental volume, an association that was statistically significant at ages 1, 2, and 3.5 years. Pooling the data across ages, blood pressure fell by 1.2 mm Hg for every 100-mL increase in placental volume (95% CI 0.4 to 2.0, P=0.004). A similar association was found with placental volume at 17 weeks (P=0.004), and a negative association was found with abdominal circumference at 20 weeks (P=0.001). These associations between blood pressure and measurements made in the second trimester suggest that the initiating event in the programming of blood pressure occurs early in pregnancy and is associated with placental growth and that abdominal circumference may be the most sensitive of the fetal ultrasound measurements as an indicator of the programming process. Birth weight and placental volume appear to predict blood pressure at complementary ages, but this may be the result of chance.

The data show that systolic blood pressure is positively associated with current weight at each age and that this association is stronger than that between systolic blood pressure and birth weight. This is a recurring observation.³ Longitudinal studies in children are required to identify the phases of infant and childhood growth that are critical for subsequent blood pressure, although the data on placental volume suggest that the initiating events occur early in pregnancy

Values of body mass index and triceps skinfold thickness were compared with those reported for black women aged 25 to 29 years in the NHANES II survey.¹⁷ Fewer Jamaican women were obese, although the median body mass index was similar. No direct association was found between measures of maternal nutrition, including triceps skinfold thickness, weight gain during pregnancy, and hemoglobin concentration, and blood pressure of the child. It is possible that such associations may emerge as the children age. The mother’s systolic blood pressure did predict the child’s systolic blood pressure, but multiple regression analyses with birth weight and placental volume suggested that this was not the pathway for programming. Measures of maternal nutrition did predict birth weight and placental volume; thus, indirectly they determine the blood pressure of the child. Hemoglobin concentration at the first antenatal visit was directly associated with placental volume at 20 weeks but not with birth weight.

Mothers attending the antenatal clinics of the University Hospital of the West Indies are not representative of the Jamaican population. They are more likely to have a history of previous fetal losses or complications in pregnancy, to be more motivated, to have booked early and remained in the study, and to be better educated. At each follow-up age, not all of those who were available provided a blood pressure measurement, although failure to do so was not related to birth weight or socioeconomic status. Such biases and selection effects would be a particular problem for the present study if they were also related to the degree of association between birth weight and blood pressure, but there is no evidence that this might be the case.

In conclusion, we have described, for the first time, associations between placental volume and abdominal circumference in the second trimester and childhood blood pressure, which suggests that the initiating events of programming occur early in pregnancy. Measures of maternal nutritional status were not directly related to childhood blood pressure at these young ages but were strong predictors of both birth weight and placental volume, suggesting an indirect relation.

	Acknowledgments

 
This study was supported by a grant from the Wellcome Trust.

Received April 23, 1999; first decision May 25, 1999; accepted September 14, 1999.

	References

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This Article Abstract Full Text (PDF) Correction (v35,p1016) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thame, M. Articles by Forrester, T. E. Search for Related Content PubMed PubMed Citation Articles by Thame, M. Articles by Forrester, T. E. Related Collections Other etiology Epidemiology