DISCUSSION
In this study of 424 pairs of consecutive GDM pregnancies, an ADO or ANO in the index GDM pregnancy conveyed a greatly increased risk of the same outcome in the subsequent GDM pregnancy. While these risks have been described in the general antenatal population, they have not been previously quantitated in GDM.
Compared to index GDM pregnancies, the rates of instrumental delivery and emergency Caesarean section were more than halved in subsequent pregnancies, with correspondingly increased rates of elective Caesarean section, lower rates of vaginal delivery and induction of labour. This could be explained by a greater consideration of elective Caesarean in women with a previous Caesarean section, and also be influenced by a history of ADO or LGA in the index pregnancy. But while ADOs were improved in subsequent pregnancies, the risk of having an ADO was still far greater in women with a history of the same ADO in the index pregnancy, with a RR of 3.09 for instrumental delivery and 2.20 for emergency Caesarean. These risks may justify a lower threshold for elective Caesarean in women with recurrent GDM and history of instrumental delivery or emergency Caesarean.
While delivery outcomes were improved in subsequent GDM pregnancies, ANO rates were unchanged in index versus subsequent pregnancies, with LGA rates of ~16%, SGA rates of ~8% and overall composite ANO rates of ~26%. Given that women with subsequent GDM pregnancies were older, had a higher BMI and were more likely to require medication, it could be hypothesised that they should have had a higher rate of adverse outcomes, which was not the case. One explanation could be that women were diagnosed earlier due to earlier screening which may have affected ANO rates.
Three retrospective studies have examined the comparative rates of LGA in first and second GDM pregnancies(10-12), although none have analyzed detailed individual-level data across consecutive pregnancies. Similar to our study, a study of 389 predominantly Mexican-American women found no difference in rates of LGA(10) with a 15.6% rate of LGA in the first GDM pregnancy compared to 19.9% in the second GDM pregnancy. Another retrospective study of pregnancy-pairs (12). also found that LGA and SGA rates were not significantly different between pregnancies with first time GDM and those with recurrent GDM. However, the authors also did not quantitate the risk of recurrent adverse outcomes from one GDM pregnancy to the next.
Only one study has quantitated the risk of recurrent adverse outcome in recurrent GDM pregnancy pairs(11). In contrast to our study, the LGA rate increased in the second GDM pregnancy (22.4% vs 13.8%, p < 0.05). The risk of recurrent LGA was 55.7%, comparable to our rate of 45.1%. While this population-based study had a large of number of pregnancy pairs, it did not examine other ANOs such as SGA and fetal or neonatal death, and detailed clinical information such as timing of diagnosis of GDM, medications, results of the GTT, maternal BMI and interpregnancy interval, were not included in the analyses. Thus, they were not able to evaluate for effects of other factors associated with increased risk of recurrent LGA.
Our study lends a new perspective by tracking the incidence of ANOs in individual women over consecutive GDM pregnancies. The RR of repeat outcome for women with LGA, SGA or any ANO in their GDM pregnancy was 4.5 fold, 5.0 and 2.1 respectively. Put another way, nearly half of women with LGA, 70% of women with SGA and 44% of women with the composite ANO in their subsequent pregnancy had the same outcome in their index pregnancy. Thus while ANO rates were similar in index and subsequent pregnancies as a group, a substantial proportion of adverse outcomes were occurring in the same women. Of additional interest is the very low risk of SGA in women with prior LGA, and the low risk of LGA in women with prior SGA.
Multivariate analysis of ANO in the subsequent pregnancy showed that having the same outcome in the index pregnancy was by far the strongest risk factor, with a 3.1-fold for LGA, 4.7-fold for SGA and 2-fold for the composite ANO. In LGA, this risk far outweighed that of maternal BMI, a well-established risk factor for LGA (13, 14). In SGA, this risk far outweighed that associated with increasing interpregnancy interval.
The risks of recurrent LGA or SGA have not been previously described in GDM. Our calculated risks are similar in magnitude to the five-fold risk observed in general obstetric cohorts for LGA (15)(16) as well as for SGA (17, 18). Moreover, severity of GDM based on the GTT results, need for medication and timing of diagnosis were not associated with subsequent pregnancy outcomes. While on the surface these data may suggest that GDM does not impact greatly on risk of recurrent ANOs, we were not able to include the modifiable factors of gestational weight gain and a measure of glycaemia such as HbA1c in our model, and cannot discount the importance of weight and glycemic management.
Limitations of this study include unavailable data on maternal smoking status, gestational weight gain and hypertensive disorders. There were slight differences in glucose targets between centres and slight differences in population demographics although reassuringly, interpregnancy changes did not differ between centres. We relied on medication requirement as a surrogate marker of glycaemia. It is possible some of the participants may have had undiagnosed type 2 diabetes.
Strengths of this study included the inclusion of consecutive GDM pregnancy pairs and the analysis of longitudinal data in individual patients that allowed us to assess risk of adverse outcomes in the context of previous complications. We were able to adjust for relevant clinical covariates including interpregnancy duration and interpregnancy weight gain, both pertinent to recurrent GDM. The definitions of LGA and SGA were based on customised centiles for an Australian population.
According to current standards, diagnostic criteria, glucose targets and weight gain targets are applicable to all GDM women, irrespective of their history of ADO/ANO. Given the high frequency of repeat complications, should these criteria be tightened for women with prior LGA, or relaxed for women with a history of SGA? Would early detection of GDM be effective in prevention of LGA, or could it be detrimental in those with prior SGA? Further studies are required to provide evidence-based guidelines for managing recurrent GDM.