Small for gestational age: the familial perspective

Background: There are multiple etiologies for being born small for gestational age (SGA). However, extended familial data in idiopathic cases have been scarcely reported.

Objective: Our aim was to explore the familial history of SGA newborns and describe the proportion and distribution of SGA in their parents and parental siblings.

Methods: This was a retrospective study performed at an obstetrics clinic holding a detailed reliable electronic database. Between 2008 and 2017, data of 14,003 patients and 20,617 pregnancies were recorded. Parents of SGA infants were identified and extended familial history was obtained by questionnaires, including birth weights (BWs) and gestational age at birth of the parents and parents' siblings. SGA was defined as a BW below the 10th percentile. Proportions of maternal, paternal, and parental siblings' SGA were calculated. Chi-square test was performed to assess the relationship between SGA family member's gender and SGA infants' gender, and between the relative's gender and their family relationship to the infant.

Results: About 2100 women had a history of a previous infant born SGA, however, after exclusion the final cohort comprised 926 women with a previous SGA infant. In 473 cases there was at least one other family member of the infant born SGA: father, mother, aunt, or uncle of the infant, representing a prevalence of 51% (473/926) of familial SGA. Out of familial SGA cases, maternal SGA was found in 55% (260/473), and paternal SGA was found in 28.1% (133/473). 27.6% had more than one SGA relative. Eighteen infants had both an SGA father and an SGA mother (3.8%). A history of an SGA aunt or uncle was found in 44% (209/473) of familial SGA cases, which was 22.5% (209/926) of the entire cohort. Parental sibling SGA occurred almost twice in mother's siblings as compared to father's siblings. Chi-square test revealed no association between the SGA relative's gender and their family relationship to the infant. There was no association between the SGA infant's gender and the SGA relative's gender.

Conclusions: A family history of SGA is common in SGA infants, and occurs most often in mothers. This study found 22% SGA in parental siblings, in maternal siblings more than paternal siblings, supporting the possibility of a genetic component in SGA trait transmission. In clinical practice, when counseling parents with a growth-restricted fetus from an unknown etiology, extended familial birthweight history should be obtained and taken into account, which may be helpful in reducing parental anxiety.