Maternal hemoglobin associates with preterm delivery and small for gestational age in two Finnish birth cohorts

Abstract

Objective

To test whether maternal hemoglobin during pregnancy associates with offspring perinatal outcomes in a developed country. Changes in maternal hemoglobin concentration during pregnancy are partly physiological phenomena reflecting alterations of maternal blood volume. Especially hemoglobin measures outside the physiological range may influence maternal health and fetal growth with long-lasting consequences.

Study design

We studied an unselected sample drawn from two regional birth cohorts born 20 years apart: The Northern Finland Birth Cohorts 1966 and 1986. These are two mother-and-child population-based birth cohorts together comprising 21,710 mothers and their children. After exclusions, the sample size of the current study was 20,554. Concentrations of maternal hemoglobin at first and last antenatal visits were categorized as low (lowest 10%), medium (reference) or high (highest 10%). Multinomial logistic regression analyses for categories of maternal hemoglobin and perinatal outcomes such as preterm delivery and full-term small and large for gestational age were conducted with adjustments for maternal cofactors.

Results

Low maternal hemoglobin at early pregnancy associated with decreased risk of full-term small for gestational age (adjusted OR 0.73, 95% CI [0.58, 0.93], p = 0.010). At late pregnancy, low maternal hemoglobin associated with increased risk of preterm delivery (adjusted OR 1.60, 95% CI [1.26, 2.02], p < 0.0005) whereas high maternal hemoglobin associated with increased risk of full-term small for gestational age (adjusted OR 1.29, 95% CI [1.07, 1.56], p = 0.009). Maternal hemoglobin did not show constant association with risk of large for gestational age.

Conclusion

The results from this study support evidence that both low and high maternal hemoglobin associate with adverse perinatal outcomes. Low maternal hemoglobin associated with preterm delivery and high with full-term small for gestational age. Association was mainly present when maternal hemoglobin was measured during the third trimester. These results indicate that it is important to monitor both extremes of maternal hemoglobin throughout the pregnancy.

Introduction

Both low and high maternal hemoglobin (mHb) concentration has been consistently associated with adverse perinatal outcomes such as preterm birth and fetal growth restriction [[1], [2], [3], [4], [5], [6], [7]] and in our own data with later developmental indices [8]. Low hemoglobin and anemia (generally defined as mHb < 110 g/l) are global problems affecting both the mother and the developing child. In 2011, the global prevalence of anemia among pregnant women was 38%, which translated to 32 million mothers [9]. Regionally, the prevalence of maternal anemia vary substantially from 22% in European and North American countries to 56% in Central and West Africa [10].

Several environmental and behavioral maternal factors affect mHb and the developing child. Smoking during pregnancy has been associated with placental defects, prematurity and growth restriction (reviewed in [11]). Furthermore, smoking associates with increased mHb levels, which may contribute to increased risk of adverse perinatal outcomes [7,12]. Low maternal BMI is associated with increased risk of spontaneous preterm birth whereas some studies report obesity to have a protective effect [13]. However, obese mothers are in risk for hypertensive disorders, which associate with increased risk of medically indicated preterm birth [13]. Mother’s low education was associated with prematurity and small for gestational age (SGA) in recent meta-analysis comprising of 12 European countries, although there were differences between countries [14]. Nulliparous mothers are at increased risk of preterm delivery and SGA specifically if the mother is under 18 years old and maternal age 35 or more is associated with increased risk of SGA but not prematurity [15].

In the current study, we study the association between mHb and adverse perinatal outcomes within two study populations located in Finland. These populations are highly homogenous due to standardized antenatal care and pregnancy counselling, which contributes to fewer environmental confounders than in more diverse settings. Association between mHb at different time points of pregnancy and such outcomes as prematurity and small and large for gestational age (SGA and LGA) are studied.