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AGA-Primed Uteri Compared With SGA-Primed Uteri and the Success of Subsequent In Utero Fetal Programming

OBJECTIVE: To assess whether risk for early mortality is increased with recurrent small for gestational age (SGA) compared with nonrecurrent SGA. METHODS: We used the Missouri maternally linked cohort data containing births from 1978–1997. We identified mothers according to four categories: 1) appropriate for gestational age (AGA)–AGA: both first and second pregnancies were AGA; 2) AGA–SGA: first pregnancy was AGA, second pregnancy outcome changed to SGA (a switch); 3) SGA–AGA: first pregnancy was SGA, second pregnancy outcome AGA (a switch); 4) SGA–SGA: both first and second pregnancies were SGA. We then compared the success of fetal programming in the second pregnancy with a switch compared with a pregnancy without a switch (AGA–SGA compared with SGA–SGA; and SGA–AGA compared with AGA–AGA). We used neonatal mortality as primary outcome with infant and postneonatal mortality as secondary outcomes. RESULTS: Appropriate for gestational age infants from a SGA-primed uterus (SGA–AGA switch) had a 19% (odds ratio 1.19; 95% confidence interval 1.11–1.28) and 29% (odds ratio 1.29; 95% confidence interval 1.17–1.42) greater likelihood of infant and neonatal mortality, respectively, when compared with AGA infants from AGA-primed uterus (AGA–AGA; nonswitch). Approximately the same magnitude of risk elevation for neonatal and infant mortality was noted among SGA infants resulting from AGA-primed uterus (a switch) as among SGA infants from SGA-primed uterus (a nonswitch). Overall, the greatest risk of neonatal, infant, and postneonatal mortality was associated with an AGA–SGA switch. CONCLUSION: Fetal programming switch in subsequent gestation adversely affects early survival of affected infants compared with those with no change in fetal growth pattern. LEVEL OF EVIDENCE: II