Do parental heights influence pregnancy length?: a population-based prospective study, HUNT 2

The mechanisms that trigger onset of delivery and determine pregnancy length are poorly understood. Offspring sex, fetal growth, parity, and genetic factors may influence biological variation of pregnancy length, and various obstetric complications, including maternal and fetal disease may shorten length of pregnancy [1‐4]. It is not clear if maternal height is a determinant of the length of pregnancy, and studies of maternal height and pregnancy length have shown conflicting results [5, 6].

Nonetheless, it has been suggested that women of short stature are at increased risk of preterm births and other pregnancy complications that may shorten pregnancy length [5, 7‐13]. Short women are also at increased risk of cardiovascular disease later in life, and an unfavorable cardiovascular risk profile prior to pregnancy (increased blood pressure and body mass index (BMI), and unfavorable serum lipids and glucose) have been associated with increased risk of preterm birth, low offspring birth weight and preeclampsia [14‐17]. Thus, factors associated with cardiovascular risk may underlie a possible association between maternal height and pregnancy length.

Among men, short stature is also associated with increased risk of cardiovascular disease [17], but in contrast to the risk among women [14], it is not known whether unfavorable and common paternal cardiovascular risk factors may influence length of the fathered pregnancy. Neither is it known whether paternal height per se is associated with length of pregnancy. Still, results of large intergenerational studies suggest that paternal factors may contribute to the variation in pregnancy length [1, 2, 18, 19].

Therefore, the main aims of this study were to assess maternal and paternal height in relation to pregnancy length, and to examine whether parental height is associated with risk for pre- or post-term birth. We have also assessed whether any association of parental height could be attributed to cardiovascular risk factors, and whether common paternal cardiovascular risk factors, including blood pressure, BMI, serum glucose and lipids, are associated with pregnancy length.

Data on parental height and cardiovascular risk factors were retrieved from the second wave of a large population based study in Norway (HUNT 2) that was conducted between 1995 and 1997. By individual linkage to the Medical Birth Registry of Norway, we identified all births that occurred between 1997 and 2005 and had been parented by participants in the HUNT 2 Study.

The primary aim of the HUNT 2 Study was related to major public health issues, such as cardiovascular disease, diabetes, obstructive lung disease, osteoporosis and mental health. The HUNT 2 Study has been described in detail elsewhere [20]. Briefly, all residents of Nord-Trøndelag County 20 years or older were invited, and 66 140 of the 94 194 eligible adults (71%) attended the study, that included a clinical examination carried out by specially trained nurses and technicians. Standardized measurements of height, weight, waist circumference, blood pressure, and non-fasting serum lipids and glucose were performed. Additionally, the participants responded to a comprehensive medical and life style-related questionnaire.

Body height was measured to the nearest 1.0 cm and weight to the nearest 0.5 kg. Body-mass index (BMI) was calculated as weight in kilograms (kg) divided by the squared value of height in meters (m2). Blood pressure measurements were repeated three times with one minute intervals and measured by an automatic oscillometric method (Dinamap 845 XT; (Critikon, Tampa, Florida). The mean of the second and third measurements was recorded and cuff size was adjusted to arm circumference. Venous blood sampling was done non-fasting at attendance, but with the registration of time since last meal. Serum lipids were analyzed on a Hitachi 911 Auto analyzer (Hitachi,Mito,Japan) with reagents from Boehringer Mannheim (Mannheim,Germany). Total cholesterol and HDL cholesterol were measured by an enzymatic colorimetric cholesterolerase method, and HDL cholesterol was measured after precipitation with phosphortungsten and magnesium ions. Triglycerides were also measured with an enzymatic colorimetric method, and glucose was measured by an enzymatic hexokinase method.

All live- and stillbirth after 16 weeks of gestation are compulsory notified to the Medical Birth Registry (MBR) of Norway. The registration is based on a standardized form completed by midwives or doctors at the delivery units, and contains information related to maternal health before and during pregnancy, complications of pregnancy and delivery and perinatal data of the newborn.

Last menstrual period (LMP) was used to estimate expected date of delivery (EDD) from 1967 until ultrasound (US) became the national standard dating method in 1999. LMP has still been recorded for all women after 1999 and is used when ultrasound data is missing. In the current study, LMP was available for nearly all births and ultrasound data was available for more than 80% of the births.

In Norway, one routine ultrasound examination is offered to all pregnant women between 17–19 weeks of gestation, and the offer accepted by more than 98% of the women [21]. In 1997–2005 EDD was based on measurement of the outer-outer border of fetal biparietal diameter (BPD). Preterm deliveries were defined as occurring before 259 days (< 37 +0 weeks) of gestation, and post-term pregnancies as lasting 294 days or more (≥ 42 +0 weeks). The proportion of post-term pregnancies will be influenced by hospital guidelines for induction of labor. During the study period, the Norwegian official guidelines recommended assessment of all pregnancies at 296 days (42+2 weeks). Women at high risk of complications were offered induction of labor, whereas low-risk women were subject to expectant management until spontaneous delivery or induction at 43 +0 weeks.

We calculated z-scores of birth weight according to sex and gestational age, using estimated standards from births registered in MBR [22]. Estimates of gestational age were based on LMP [22]. Z-scores indicate the standard deviations of the offspring’s birth weight above or below the expected mean for gestational age and sex. In this study, small for gestational age offspring (SGA) was defined as z-score of birth weight adjusted for gestational age and sex below the 2.5 percentile. Diagnoses of preeclampsia were based upon hospital medical records noted in the MBR, using the following diagnostic criteria: The onset of blood pressure increase to 140/90 mm Hg in combination with proteinuria (protein excretion of ≥ 0.3 grams per 24 hours or ≥ + on dip stick) after 20 weeks of gestational age.

Onset of labour was categorized as either spontaneous or induced. Induction of labour was either by medication or by caesarian section. Induced caesarian sections included all elective sections (planned and performed more than 8 hours after the decision was made), and acute sections (planned and performed less than 8 hours after the decision was made) performed before labour. In 1997–2005 elective caesarian sections in Norway were recommended to be performed around 38 gestational weeks Data on indications for caesarian sections are insufficient in the MBR of Norway.

Among women who participated in HUNT 2, a total of 6 122 births were recorded in MBR (gestational age > 22.0 weeks and birth weight > 425 grams) from 1995 to 2005. Among these births, 1 022 were excluded from the analysis because of either multiple pregnancies (n=252) or possible ongoing pregnancies at the time of data collection (n=770). In addition, 90 were excluded due to missing data on the following variables: maternal height (n=5), information on social benefits (n=49), information on diabetes or chronic hypertension prior to pregnancy (n=7), and information on cardiovascular risk factors prior to pregnancy (n=29). Thus, the main analyses included 5 010 births among 3 497 mothers.

For the paternal analyses, 2 210 of 5 010 pregnancies were excluded because the father did not participate in HUNT 2, and 2 births had missing data on paternal height, thus leaving a total of 2 798 fathered pregnancies among 2 005 men to be analyzed.

Descriptive characteristics of the parents participating in HUNT 2 are presented in Table 1. Mean maternal age at participation was 25.9 years. Pregnancy length was associated with maternal age at delivery, maternal smoking and maternal systolic blood pressure, whereas no association with pregnancy length was found for parity, maternal educational status, maternal BMI, paternal BMI and paternal systolic blood pressure (Table 1).

Table 2 describes pregnancy and offspring characteristics, stratified by quintiles of maternal height. Information on LMP was available for nearly 97% of the pregnant women, and 81% had EDD based on ultrasound. Shorter maternal height was associated with lower mean birth weight, lower frequency of spontaneous onset of labour, and higher frequency of onset of labour by caesarian section (elective and acute caesarian sections before onset of labour). Shorter women also had higher frequency of total number of caesarian sections, including acute caesarian sections after onset of labour. Shorter women had higher rates of SGA offspring below the 2.5 percentile than taller women.

Table 3 shows age-adjusted and multivariable adjusted differences in mean pregnancy length according to quintiles of maternal height. In the age-adjusted analyses gestational age increased by increasing maternal height, and women in the upper quintile (≥ 173 cm) had on average 4.3 days longer pregnancies than women in the reference group (< 163 cm) when EDD was based on ultrasound, and 2.7 days longer when EDD was LMP based. Additional adjustments for obstetric and socioeconomic measures (maternal age at delivery, time between baseline at HUNT 2 and delivery, parity, offspring sex, maternal smoking, educational status, and receiving social benefits or not) did not influence the effect estimates. Neither did additional adjustment for levels of maternal cardiovascular risk factors prior to pregnancy (systolic and diastolic blood pressure, BMI, concentration of glucose and lipids, hypertension, diabetes mellitus, kidney disease and coronary artery disease (Table 3). Additional adjustment for paternal height did not change the results (results not shown).

Table 4 shows age-adjusted and multivariable adjusted differences in pregnancy length according to quintiles of maternal height after restriction of the analysis to births with spontaneous onset of delivery. For deliveries with spontaneous onset, the difference in pregnancy length between the upper and lower maternal height group was reduced from 4.3 days (95% CI 3.0, 5.7) to 3.5 days (95% CI 2.2, 4.8), according to ultrasound dating, and from 2.8 days (95% CI 1.4, 4.2) to 1.9 days (95% CI 0.4, 3.4) according to LMP dating (Table 4). Additional exclusion of pregnancy complications (SGA, preeclampsia, and stillbirth) did not substantially change these results (results not shown).

Paternal height showed no association with pregnancy length of the partner in age-adjusted and fully adjusted models (Table 5). Neither did we find any association with pregnancy length for common paternal cardiovascular risk factors, including levels of blood pressure, BMI, serum lipids and glucose (results not shown).

The risk of post-term deliveries (≥ 42.0 weeks) increased with maternal height (Table 6). In the crude analysis, taller women (≥ 173 cm) had 90% higher odds of post-term pregnancy compared to the reference group when gestational age was estimated by ultrasound (OR 1.9, 95% CI 1.3, 2.9), and 50% higher when gestational age was based on LMP (OR 1.5, 95% CI 1.0,1.9). The risk was slightly increased after adjustment for obstetric factors, socioeconomic measures and cardiovascular risk factors prior to pregnancy. The risk of preterm delivery was lower in taller women when gestational length had been estimated by ultrasound, whereas only weak associations were observed when EDD was determined by LMP.

After restricting the analysis of maternal height with risks of pre- and post-term birth to deliveries with spontaneous onset (Table 7), the effect estimates were not substantially changed in relation to preterm births, but precision was lower due to the fewer numbers of pregnancies. The associations with post-term delivery were slightly weaker for deliveries with spontaneous onset than for unselected deliveries.

We found no association between paternal height and risks of pre- or post-term births (Table 8). Paternal height was, however, positively associated with z-score of fetal birth weight (Table 9), and the strength of the association among fathers was similar to the corresponding association for the mothers.

In separate analyses, we assessed potential effect modification between maternal height and cardiovascular risk factors, but found no consistent evidence of any interaction (all P-values above 0.10, except for HDL cholesterol with p=0.03) (results not shown).

We found a positive association of maternal height with pregnancy length per se, and the effect was stronger when EDD was estimated by ultrasound than by LMP. Women with shorter stature had lower risk of post-term deliveries, and when EDD was based on ultrasound, they also had higher risk of preterm births. Paternal height and common cardiovascular risk factors of the father showed no association with length of pregnancy or with the risk of pre-and post-term births.

A Norwegian study among women with low risk pregnancies, spontaneous start of delivery, and EDD estimated by LMP found no association of maternal height with length of pregnancy [4]. However, the authors of a Swedish study among 952 630 unselected pregnant women whose gestational length was estimated by ultrasound in early second trimester, reported that unadjusted mean gestational length was 2 days shorter in mothers of short stature (< 160 cm) compared to those who were taller than 160 cm [5].

We assessed paternal height and levels of paternal cardiovascular risk factors such as blood pressure, BMI, serum glucose and lipids, in relation to pregnancy length and risk of pre- and post-term birth. In contrast to previously reported associations between unfavorable cardiovascular risk factors among mothers and pregnancy length [14], no such associations were observed for the fathers. Intergenerational studies have suggested that fathers may be of importance in determining pregnancy length in term and post-term pregnancies [2, 18, 19], but there has been little evidence for a paternal contribution to the risk of preterm birth [24, 25]. In this study, paternal height was neither associated with pregnancy length nor with the risk of pre- and post-term birth. To our knowledge, these relations have not been reported previously. In line with a recent review [26], however, we found a positive association of paternal height with offspring birth weight.

The population based prospective design of the present study makes it unlikely that selection or recall bias can explain our findings. The attendance to HUNT 2 was 71%, and in a follow-up study of 685 (2.5%) non-responders it was concluded that practical reasons such as time constraints and moving out of the county were the main reasons for young people not to attend [20]. Thus, the participants at fertile age in our study are likely to be representative for the source population. The relatively large sample size and the standardized measurements of height and other clinical measures in HUNT 2 ensure high precision of the effect estimates, and comprehensive information from self-administered questionnaires provides access to a range of possible confounders. By combining data from the HUNT 2 Study and the MBR it was possible to control for metabolic factors and other known risk factors on an individual basis. A potential limitation in this study is that smoking status was sampled before rather than during pregnancy. This was due to lack of registration of smoking status in MBR until 1999. We performed sensitivity analyses restricted to pregnancies with available information on smoking during pregnancy from 1999 to 2005, and the estimates did not differ substantially from the main results.

The MBR in Norway is a nationwide registry that includes information about virtually all births that have occurred in the country since 1967. Almost all pregnant women in Norway receive antenatal care, and hospital deliveries are free of charge, which minimizes any potential selection bias [21]. EDD was estimated by two different methods for most of the women (ultrasound and last menstrual period), and the use of both methods was standardized throughout the study period. The internal validity of our results is regarded as good. Generalization of the results to other populations must still be done with caution, since the population under study was rather homogenous with less than 3% of Caucasian women.

The LMP method is limited by inaccurate maternal recall, uncertain time of conception and implantation, irregular menses/oligomenorrea and pre-pregnancy use of hormonal contraceptives. If shorter women have higher risk of hormonal disturbances with delayed ovulation, this could have biased our findings by underestimating EDD in LMP-based analyses. Adjustment for menstrual disturbances in the statistical analyses did not, however, substantially alter the results.

It is generally agreed that ultrasound biometry in early second trimester gives a more accurate prediction of date of delivery (EDD) and reduces the rate of post-term deliveries compared to LMP dating [27]. However, the ultrasound method is based on the assumption that the size of all fetuses is similar at a given gestational age during the first half of pregnancy, whereas several studies suggest that fetal size (BPD) may differ substantially during the first half of pregnancy according to fetal sex, fetal growth restriction, and maternal smoking [28‐30]. If fetal size (BPD) in early second trimester also differ according to maternal height, ultrasound dating may induce a biased estimate of EDD [31]. Femur length of the fetus at 18–19 gestational weeks has been reported to correlate with maternal height, [32]maternal height is a known determinant of offspring birth weight [5, 33, 34],and fetal size in early second trimester is positively associated with offspring birth weight [35, 36]. Thus, it is not unlikely that ultrasound in 17–19 weeks of gestation may underestimate the true gestational age of a short woman and shift the EDD to a later date due to her smaller than average sized fetus, and vice versa for taller women. As a result, shorter women may have more severe post-term pregnancies than taller women and may therefore be at higher risk of adverse perinatal outcomes as well [31]. Taller women, on the other hand, may risk labor inductions on false post-term indications. A large population-based study reported that the replacement of LMP-dating with second trimester ultrasound dating in Sweden resulted in an increased risk of post- term perinatal morbidity and mortality for female fetuses [37]. The smaller size of female fetuses compared to males at time of ultrasound measurement most likely resulted in an underestimation of the true gestational age and more severely post term pregnancies among mothers of female fetuses. Whether the rate of post-term adverse perinatal outcomes may differ between short and tall women is not known, and unfortunately we did not have sufficient analytical power to investigate this in our data.

The observation that small fetuses grow slower and have longer pregnancies than average-sized fetuses, and vice versa for large fetuses, applies to low risk/non-pathological pregnancies for humans, and are also observed for some other mammals [2, 4, 38, 39]. The opposite is documented for pathological pregnancies; i.e. women with slow intrauterine fetal growth have increased risk of both spontaneous and iatrogenic preterm births compared to other women [40, 41]. Since maternal height is a predictor of offspring birth size [33, 34] and fetal growth may influence pregnancy length, fetal growth could be an intermediate factor for the association of maternal height with gestational length. We did not have access to data on serial ultrasound measurements of fetal size to assess fetal growth. Offspring birth weight could serve as an indicator of fetal growth. However, birth weight was not regarded as a confounder, but as an intermediate factor or a common consequence of maternal height and gestational length. Thus, to avoid introducing a bias to the results, we chose not to adjust the analyses for birth weight. As an alternative approach, we separately assessed associations of parental heights with birth weight z-scores, and found that paternal height was positively associated with offspring birth weight. The association of paternal height with birth weight was of similar strength to that of maternal height, and contrasted the finding of no association between paternal height and pregnancy length. This different effect of parental height may suggest that gestational length and offspring birth weight are determined by different parental factors, and that the positive association of maternal height with gestational length cannot solely be explained by fetal growth.

Short women are at increased risk of cardiovascular disease compared to tall women, and length of pregnancy tends to be shorter in women who are at increased cardiovascular risk [14, 17]. According to the fetal origins hypothesis, poor nutritional conditions in utero may program both slow intrauterine growth and increased risk of later cardiovascular disease [42]. If the short stature of the woman has an intrauterine origin, their higher cardiovascular risk may also have originated in utero, and could possibly explain the observed association of short maternal height with short gestational length. However, adjustment for maternal cardiovascular risk factors did not change the effect estimates in the present study, and is therefore an unlikely explanation of the results. Possible effect modification of cardiovascular risk factors was also assessed, but we found no evidence of any interaction. Similarly, unfavorable socioeconomic conditions of the mother could be a common cause for short maternal stature and short pregnancy length, but adjustment for socioeconomic measures did not influence the results.

In line with other research, our descriptive data suggest that shorter women experience pregnancy complications more frequently than taller women, including SGA offspring, and acute and elective Caesarian section [5, 7]. Preeclampsia, stillbirth and perinatal deaths have also been reported to be associated with short stature of the mother [5, 8, 10]. After excluding induced births (by medication or by caesarian sections), and preeclampsia, SGA and stillbirths, the associations between maternal height and length of pregnancy became weaker in our study. This indicates that some of the association between maternal height and gestational length may be explained by a higher incidence of pregnancy complications and caesarian sections before labour among shorter women than among taller. The higher frequency of elective caesarian sections among shorter women may further reflect their higher risk of previous complications, such as previous caesarian section and/or traumatic labour experience [12, 43].

We cannot rule out that the observed association of maternal height with gestational length may have some biological basis. Blacks and Asians have shorter average gestational length and higher risk of preterm birth than white Americans and Europeans, and teenage mothers have shorter length of pregnancy and higher risk of preterm birth compared to adult mothers [44, 45]. A smaller or more constricted female pelvis of teenage and Asian mothers has been suggested to facilitate shorter duration of pregnancy to minimize complications from cephalopelvic disproportion. In evolutionary terms similar mechanisms may explain that shorter women benefit from shorter duration of pregnancy [44]. The population in the present study is ethnically fairly homogenous and without teenage pregnancies [20].

Women with shorter stature had shorter pregnancy length and lower risk of post-term pregnancies than taller women. The associations were stronger when pregnancy length was based on ultrasound, and shorter women also had increased risk of preterm births in ultrasound-based analyses. The associations between maternal height and pregnancy length could partly be explained by a higher risk of elective caesarian sections and more pregnancy complications among shorter women. Cardiovascular risk factors did not explain the associations.

Early second trimester ultrasound is the method of choice for estimating EDD in many areas of the world and gestational age is a crucial determinant of perinatal outcome. Thus, it remains to be clarified whether the observed association between maternal height and gestational length may have any clinical consequences.